Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

CHAPTER 8 – Neurologic Diseases

Dimitry Baranov, MD,
Tom Kelton, MD,
Heather McClung, MD,
Keith Scarfo, DO,
James G. Hecker, PhD, MD

  

 

Basal Ganglia and Cerebellar Disorders

  

 

Parkinson's Disease (Paralysis Agitans)

  

 

Sydenham's Chorea (Rheumatic Chorea)

  

 

Huntington's Chorea

  

 

Spasmodic Torticollis and Other Focal Dystonias

  

 

Motor Neuron Degeneration

  

 

Amyotrophic Lateral Sclerosis

  

 

Friedreich's Ataxia

  

 

Spinal Muscular Atrophy

  

 

Peripheral Nerve Disease and the Polyneuropathies

  

 

Guillain-Barré Syndrome

  

 

Abnormalities of Metabolism and Circulation of the CSF Pathways

  

 

Hydrocephalus

  

 

Pseudotumor Cerebri

  

 

Syringomyelia and Syringobulbia

  

 

Spinal Cord Injury

  

 

Demyelinating Diseases

  

 

Multiple Sclerosis

  

 

Mucopolysaccharidoses

  

 

Hereditary Peripheral Neuropathies

  

 

Hereditary Primary Motor Sensory Neuropathies, Including Charcot-Marie-Tooth Disease

  

 

Hereditary Sensory and Autonomic Neuropathies

  

 

Neurodegenerative Disorders with Autonomic Failure

  

 

Multiple System Atrophy

  

 

Pure Autonomic Failure

  

 

Neuroectodermal Disorders

  

 

Neurofibromatoses

  

 

Von Hippel-Lindau Disease

  

 

Tuberous Sclerosis

  

 

Sturge-Weber Syndrome

  

 

Posterior Fossa Anomalies and Arnold-Chiari Malformations

  

 

Chiari I Malformation

  

 

Chiari II Malformation, Myelomeningocele, and Hydrocephalus

  

 

Klippel-Feil Syndrome and Other Cervical Spine Disorders of Childhood

Over the past decade there have been advances in the diagnosis and treatment of neurologic diseases, in part from information gleaned from genetics.

BASAL GANGLIA AND CEREBELLAR DISORDERS

Disorders of the basal ganglia and cerebellum are linked by motor signs and symptoms and by location of pathology in the extrapyramidal motor system. The extrapyramidal system consists of the basal ganglia, striatum (caudate, putamen), globus pallidus, subthalamic nucleus, and substantia nigra ( Fig. 8-1 ).[1] Motor functions are coordinated through the nuclei of the basal ganglia and cerebellum via the cortical/brain stem/spinal system.[2] Damage to elements of this system, or to the extrapyramidal tracts, can lead to movement disorders, commonly negative symptoms or signs (e.g., akinesia, bradykinesia, loss of reflexes) or positive symptoms or signs (e.g., chorea, athetosis, ballismus, dystonia), and contraction abnormalities.[2]

 
 

FIGURE 8-1  Elements of the extrapyramidal system.

 

 

Extrapyramidal disorders can be divided into loss of function due to deficits and symptoms due to loss of inhibitory inputs. Impairments in patient-initiated movements are described as hypokinesia, bradykinesia, or akinesia, depending on rapidity of voluntary movements. Muscle tone, is defined as resistance to passive movement. Rigidity, refers to a constant resistance to passive movement, whereascogwheel rigidity, (Parkinson's disease) is jerky resistance. Chorea, refers to involuntary, rapid, widespread, jerky, arrhythmic movements that are slower than myoclonic jerks. Ataxia, is cerebellar incoordination of voluntary movements. Ataxia is usually thought of as purely loss of motor coordination, but it may result from profound sensory loss as well. Athetosis, an inability to maintain any part of the body in a voluntary muscle position, is slower than chorea and is most often found in the hands. Dystonia, is a persistent increase of muscle tone, most often involving the trunk rather than extremity muscle groups, which results in a fixed or shifting abnormal postures. Focal dystonias include spastic torticollis. Hemiballismus, is used to describe violent, unilateral, proximal limb movements on one side only. Double athetosis, is a combination of athetosis and chorea in all four limbs.

Damage to extrapyramidal tracts can occur as a result of central nervous system (CNS) trauma, chronic neurodegenerative disease, stroke, ischemic CNS disease, drug therapy, or hypoxic encephalopathies. The neurotransmitters most involved in basal ganglia function include acetylcholine, inhibitory γ-aminobutyric acid (GABA) projection neurons, and glutamate, as well as the neuromodulators substance P, enkephalins, somatostatins, and neuropeptide Y. Catecholamines probably also act as neuromodulators with modest effects, with the exception of dopamine in the substantia nigra and striatum, where it plays a critical role in Parkinson's disease. The motor strip in the cerebral cortex receives both inhibitory and excitatory modulation from the basal ganglia, with feed-forward and feed-back connections to the basal ganglia/thalamus/corticospinal system. Table 8-1 compares several of the more common bradykinesias and hyperkinetic movement disorders and contrasts them to other neurologic diseases that can also manifest as movement disorders. The most common of the movement disorders is Parkinson's disease (PD).


TABLE 8-1   -- Comparison of Movement Dysfunction Disorders

Rights were not granted to include this content in electronic media. Please refer to the printed book.

Adapted from Adams RD, Victor M, Ropper AH (eds): Principles of Neurology. New York, McGraw-Hill, 1997, pp 1048, 1081.

 

 

 

Parkinson's Disease (Paralysis Agitans)

Pathology and Diagnosis.

Parkinson's disease is characterized by the loss of pigmented cells in the substantia nigra and pigmented nuclei, as well as by a neurotransmitter imbalance caused by a relative dopamine deficiency in the caudate nucleus and putamen. An as yet unidentified environmental agent has been postulated as causative for PD.[2] Experimentally, a Parkinson's model can be created by ablation (surgical or 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine [MPTP]) of pigmented cells of the substantia nigra. MPTP is degraded by monoamine oxidase B (MAO-B), causing a toxic metabolite and destruction of the substantia nigra. The remaining pigmented cells in the substantia nigra contain eosinophilic inclusions called Lewy bodies, which are also seen in all cases of idiopathic PD. These inclusions are characteristic of numerous neurodegenerative diseases. The inhibitory effects of dopamine in the basal ganglia are normally opposed by the excitatory modulation by acetylcholine. The etiology can also be due to manganese poisoning, encephalitis, CNS trauma (pugilistica), carbon monoxide exposure, or chronic reserpine, phenothiazine, or butyrophenone use. In the United States the incidence is approximately 1% in those older than age 65 years. The incidence is highest in the 40- to 70-year age group, with peak onset in the sixth decade. Diagnosis is made on the basis of the characteristic stooped posture, axial instability, shuffling, unsteady gait, expressionless face (hypokinetic dysarthria), rigidity, paucity of movement (bradykinesia), and pill-rolling tremor. Up to one third of PD patients develop dementia as well. Tremors are dampened with intentional movement or with complete relaxation.

Treatment of PD is based on achieving a balance between cholinergic and striatal dopaminergic activity. Levodopa (l-dopa) crosses the blood-brain barrier and is the mainstay of treatment. It is converted in the CNS by dopa-decarboxylase to dopamine, which does not appreciably cross the blood-brain barrier. L-Dopa is co-administered with carbidopa or benserazide decarboxylase inhibitors to minimize the systemic dopamine effects. Other therapies used for treatment of PD include selegiline and rasagiline (second generation), MAO-B inhibitors are used to block the degradation of dopamine, which often delays the need for L-dopa. Dopamine agonists (i.e., bromocriptine, ropinirole, pergolide, apomorphine, and pramipexole) or catechol-o,-methyl transferase (COMT) inhibitors (i.e., tolcapone, entacapone) are used early in the disease or in combination with L-dopa to minimize the dose of L-dopa.

Common side effects of chronic dopamine delivery include nausea and vomiting, myocardial irritability, decreased intravascular volume, and orthostatic hypotension due to suppression of the renin-angiotensin axis, confusion, psychiatric symptoms and depression, and the classic “on-off” phenomenon seen with rapid shifts from mobility to immobility and involuntary movements. Dyskinesias are the limiting factor in therapy and are treated by decreasing the dose of L-dopa and adding the anticholinergics trihexyphenidyl (Artane) and benztropine mesylate (Cogentin) or by using the dopaminergics bromocriptine, lisuride, or pergolide or the antiviral amantadine, which releases presynaptic dopamine. Clozapine is sometimes effective for treatment of drug-induced psychosis. Stereotactic lesions in the globus pallidus have been tried to alleviate the tremors and rigidity. Adrenal medullary grafts and, more recently, stem cell transplants have shown progress in animal models of PD.

Preoperative Assessment and Perioperative Considerations.

Preoperative assessment should focus on the effectiveness of treatment. Hypotension due to relative hypovolemia, autonomic dysfunction, and depleted norepinephrine stores is possible. Treatment of hypotension should be with volume as needed and with direct-acting agents such as phenylephrine, rather than ephedrine.

Therapeutic drugs should be continued through the morning of surgery. Medications that could cause extrapyramidal symptoms (e.g., phenothiazines, butyrophenones [Droperidol]), and metoclopramide (Reglan) should be held. One should be aware of the potential for increased catecholamine-induced tachyarrhythmias with L-dopa and Halothane (rarely used in the United States anymore). Ketamine has the potential for a hypertensive response but has been used without incident, and opioids such as fentanyl have a potential for an exacerbation of muscle rigidity. Morphine was reported to decrease dyskinesia in low doses but to increase dyskinesias at high doses.[3] Use of inhaled anesthetics has been associated with an increase in rigidity postoperatively. Propofol blocks the tremors of PD in the immediate postoperative period.[4] Although there is no contradiction to regional anesthesia, there was one report of increased potassium after succinylcholine use that was most likely related to denervation.[5] Most reports indicate that the use of succinylcholine or nondepolarizing neuromuscular blockers is acceptable. [6] [7] Diphenhydramine (Benadryl), a centrally acting anticholinergic, can be used for control of tremor in the awake patient.

The patient's routine doses should be resumed as soon as possible in the postoperative period. There is an increased incidence of laryngospasm and respiratory failure and obstructive ventilation in the postoperative period.[1]

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Sydenham's Chorea (Rheumatic Chorea)

Pathology and Diagnosis.

Rheumatic chorea is a movement disorder often seen in female children with a prior exposure to β-hemolytic streptococci. It persists despite improvements in medical care, even in the developed world. Females are affected more than males, and children have a higher incidence than adults. [8] [9] There also appears to be a familial predisposition to the disease.[10] The choreatic movements occur more often in the upper extremities and tend to cease during sleep. The pathology of chorea is uncertain, with degeneration in the cortex, basal ganglia, substantia nigra, and cerebellum, and sometimes including arteritis.

Symptoms include emotional lability, irritability, and occasional severe mental retardation. Diagnosis is based on observation of the characteristic choreiform movements in a child. The differential diagnosis includes any of the other basal ganglia diseases that have choreiform signs (e.g., Huntington's disease, neuroleptics, phenytoin, oral contraceptives, lupus, thyrotoxicosis, polycythemia vera, hyperosmolar nonketotic hyperglycemia, and chorea gravidarum).

Perioperative Considerations.

Diagnostic workup includes electrocardiographic (ECG) and cardiac evaluation, as well as antibiotic prophylaxis for β-streptococcal rheumatic heart disease. Although rarely fatal, ECG abnormalities and endocarditis are seen at increased frequency in asymptomatic siblings. Treatment is symptomatic, and the mainstays have been corticosteroids, barbiturates, and phenothiazines; levodopa is used for the Parkinson-like features. Because of an extremely limited anesthetic experience, there are few anesthetic contraindications other than potential interactions with the drugs used for symptomatic therapy. As in the treatment of PD, propofol will likely decrease choreiform movements in the postoperative period.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Huntington's Chorea

Pathology and Diagnosis.

Huntington's disease (Huntington's chorea) is a monohybrid autosomal dominant disease (chromosome 4, CAG repeat) with complete penetrance. It is another example of polyglutamine expansion diseases and is related to the cerebellar ataxias.[11] It has an incidence of 4 per 1 million and is characterized by severe atrophy of the caudate nucleus and putamen bilaterally, less atrophy of the globus pallidus and basal ganglia, and diffusely enlarged ventricles. The mutant Huntington protein interacts with both transcription factors and the ubiquitin-proteasome pathway, [12] [13] but pathology seems to be limited to the CNS. Increases in somatostatin and dopamine and decreases in GABA are seen in these brain regions. Onset occurs between ages 35 and 40, with earlier onset in successive generations, known as anticipation. Clinically, the disease is marked by chorea, athetosis, dysarthria, ataxia, and dementia. Mood, cognitive, and self-control changes may occur much earlier, correlating with increases in the motor components.[2] Although butyrophenones and phenothiazines help suppress movement, therapies are limited. Delivery of brain-derived neurotrophic factor (BDNF), glial cell line–derived neurotrophic factor (GDNF), or ciliary derived neurotrophic factor (CDNF) to lateral ventricles has shown promise in animals. [14] [15]

Perioperative Considerations.

One case of delayed recovery from thiopental has been described,[16] although other case reports document no problems with thiopental or propofol for induction or with the use of inhaled anesthetics and nondepolarizing neuromuscular blockage (NDNMB). [17] [18] [19] [20] [21] [22] [23] Decreased pseudocholinesterase activity is seen; and although only a single case of delayed recovery from succinylcholine has been reported,[24] one should be aware of the potential for a delayed recovery from succinylcholine.[20] Neither nondepolarizing nor depolarizing muscle relaxants are contraindicated,[25] although there is a potential for delayed recovery from pseudocholinesterase-dependent NDNMB. Butyrophenones and phenothiazines may alleviate choreiform movements. Because anticholinergic effects may worsen choreiform movements, glycopyrrolate should be used instead of atropine to avoid central CNS effects.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Spasmodic Torticollis and Other Focal Dystonias

Pathology and Diagnosis.

Also known as craniocervical spasms, spasmodic torticollis belongs to a group of restricted dyskinesias and dystonias in which only one or a few muscle groups are primarily affected. Spasmodic torticollis consists of contractile spasms of the scalene, sternocleidomastoid (SCM), and upper trapezius muscles, and secondary dystonia of the arm, trunk, neck, and facial musculature, with rotation and partial extension of the head (torticollis).[2] No neuropathologic changes have been found, and these disorders may be related to an imbalance in the dopamine pathway in the striatum. Other restricted dyskinesias include Meige's syndrome (blepharospasm), oromandibular dystonia (lip retraction and pursing), and spasmodic dysphonia (spasm with attempted speech). Symptoms begin in early adulthood and can be easily diagnosed by abnormal electromyographic (EMG) activity in the sternocleidomastoid, trapezius, and posterior cervical muscles. The disorder is characterized by simultaneous activation of both agonist and antagonist muscles in the same muscle group. Surgical treatments to transect the SCM or spinal accessory nerves and the first three cervical motor roots have been used to alleviate symptoms, but complications can include phrenic nerve injury and dysphagia owing to an inability to lift the chin. EMG-guided botulism toxin injections every 3 to 4 months have been shown to be effective in up to 90% of patients. Treatments may lose efficacy if antibodies to the toxin develop. There are no contraindications to anesthetics. Spasms are relieved with muscle relaxants, whereas N2O at concentrations above 50% relieves dystonia.[26] There is one case report of spastic torticollis during general anesthesia in a patient who was receiving chlorpromazine (Thorazine) preoperatively.[27]

Torsion dystonia (Oppenheim's disease or dystonia musculorum deformans) is an autosomal dominant disease most often seen in adulthood, although forms of this disorder with variable penetrance are occasionally seen. An autosomal recessive form is seen occasionally in children of Jewish ancestry.[2]

Clinically the disease is characterized by torsion spasms, involuntary twisting, and vertebral column movements, with possible lordosis, scoliosis, or a fixed cervical spine. Treatment attempts have includedL-dopa, bromocriptine, carbamazepine, diazepam, tetrabenazine, trihexyphenidyl, and clonazepam, with limited improvements in symptoms. Although there are no contraindicated anesthetic agents, awake fiberoptic techniques may be indicated for airway control. Symptoms are relieved during sleep or heavy sedation.[28] Other forms of hereditary and nonhereditary dystonias include Wilson's disease (inherited error in copper transport, with absent ceruloplasmin globulin), Creutzfeldt-Jakob disease (prion, with earlier onset variant), double athetosis (status marmoratus), and Hallervorden-Spatz (globus pallidus pigmentary degeneration).

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

MOTOR NEURON DEGENERATION

Motor neuron diseases are characterized by variable, progressive, degenerative loss of motor neurons in the frontal cortex, the ventral horn of the spinal cord, and lower cranial nerve medullary nuclei, leading to muscle weakness, atrophy, corticospinal tract signs, and wasting in the spinal cord, brain stem, and motor cortex, with intact intellect and sensory system.[29] Pathology shows loss of anterior horn cells in the spinal cord and lower brain stem, in which loss of large fibers precedes that of small fibers. Astrocytes and lipofuscin fill in for the deleted neurons. In addition to the depleted large motor nerve fibers, there is a loss of muscarinic, cholinergic, glycinergic, and benzodiazepine receptors, up to and including the motor cortex. Recently, superoxide dismutase (SOD) mutations have been found in these patients, leading to the possibility that increased free radicals may contribute significantly to disease progression. We will consider several representatives of the motor neuron diseases,[29] including amyotrophic lateral sclerosis (ALS) (mixed upper and lower motor neuron disease), Friedreich's ataxia (mixed), and spinal muscle atrophy (lower motor neurons), before we consider polyneuropathies. Because the classification of these diseases is uncertain, mixed upper and lower motor neuron diseases with sensory involvement could also be considered in the general category of polyneuropathies as well ( Table 8-2 ).

TABLE 8-2   -- Degenerative Motor Neuron Diseases

  

 

Amyotrophic lateral sclerosis (ALS)

  

 

Progressive muscular atrophy

  

 

Primary lateral sclerosis

  

 

Pseudobulbar palsy

  

 

Inherited motor neuron diseases

  

 

Autosomal-recessive spinal muscular atrophy

  

 

Type I: Werdnig-Hoffman, acute

  

 

Type II: Werdnig-Hoffmann, chronic

  

 

Type III: Kugelberg-Welander

  

 

Type IV: Adult-onset disease

  

 

Familial ALS

  

 

Familial ALS with dementia or Parkinson's disease (Guam)

  

 

Other

  

 

Arthrogryposis multiplex congenita

  

 

Progressive juvenile bulbar palsy (Fazio-Londe)

  

 

Neuroaxonal dystrophy

  

 

Associated with other degenerative disorders

  

 

Olivopontocerebellar atrophies

  

 

Peroneal muscle atrophy

  

 

Friedreich's ataxia

  

 

Guillain-Barré syndrome

  

 

Baló's disease

  

 

Acute disseminated encephalomyelitis following measles, chickenpox, smallpox, and (rarely) mumps, rubella, or influenza

  

 

Acute and subacute necrotizing hemorrhagic encephalitis

  

 

Acute encephalopathic form (Hurst's disease)

  

 

Subacute necrotic myelopathy

  

 

Acute brain purpura

 

 

Amyotrophic Lateral Sclerosis

Pathophysiology and Diagnosis.

The most common example of a motor neuron disease is ALS, a progressive degeneration of both lower motor neurons, leading to amyotrophy, and upper motor neurons, leading to hyperreflexia and spasticity (due to “laterally sclerotic” corticospinal tracts). Primary disease is limited to the motor cortex and efferent pathways.[2] If motor nuclei of the lower brain stem are most affected, it is termedprogressive bulbar palsy., Weakness and atrophy in the absence of corticospinal tract signs is termed progressive spinal muscle atrophy., The selective motor neuron death of ALS spares intellect, voluntary movement, and the sensory system. The extraocular and sacral parasympathetic neurons for bowel and bladder are also spared. It is autosomal dominant with an age-dependent penetrance, and the gene defect appears to map to chromosome 21 in some cases. This relentlessly progressive disease attacks both upper and lower motor neurons. The incidence is about 2 per 100,000. Onset is highest in the 40- to 50-year age group, and men are affected more frequently than women. Sporadic forms account for 90% of the cases, whereas familial forms account for the rest. Onset at an earlier age is seen in rare familial autosomal dominant and recessive forms. By far the highest incidence is found in the Mariana and Guam Islands, in three clusters that are associated with Parkinson's dementia.[2] ALS is also sometimes associated with malignancy.

Pathologic examination reveals that astrocytic gliosis has replaced the lost motor neurons, and neurofilament, intracellular, and ubiquinated inclusions are also common in pathologic examination. Diagnosis is made with magnetic resonance spectroscopy, EMG, and nerve conduction studies, with a decrease in the number of motor units but an increase in the size of single motor action potentials. EMG shows fasciculations, fibrillations, and denervation, but conduction is only slightly delayed. Interestingly, sensory evoked potentials are abnormal. Clinically, fine motor awkwardness and early spastic weakness is seen, with atrophy, hyperreflexia, mild spasticity, fasciculations and involvement of the limbs gradually progressing to all extremities and motor neurons. Bulbar symptoms are seen in striated muscles, thereby affecting speech, swallowing, and facial spasms with emotional responses. Fasciculations may be visible under the skin owing to contractions of muscle fiber bundles and may worsen with exercise and fatigue. Dementia is rare. Over 100 mutations in the SOD1, gene have been reported in familial ALS.[30] Besides SOD mutations,[31] other proposed causes include excitotoxicity, mitochondrial dysfunction, apoptosis, heavy metal exposure, and GM2 ganglioside accumulation. There are no effective therapies, although Storkebaum[32] reported improvements in an animal model of ALS after intracerebroventricular vascular endothelial growth factor (VEGF) delivery.

Perioperative Considerations.

Supportive treatment includes respiratory support, aspiration precautions, feeding tubes, and walkers. Because of the involvement of respiratory function and bulbar muscles, particular care must be given to prevention of aspiration and the need for ventilatory support. Succinylcholine should be avoided owing to the potential for hyperkalemic response from denervated muscle.[33] Case reports also indicate an increased sensitivity to NDNMB.[34] Successful epidural and general anesthesia without NDNMBs has been reported. [35] [36] Cyclophosphamide, interferon, minocycline, and tyrosine-releasing hormone (TRH) infusion have all been tried, with limited improvement in motor function. Gabapentin has shown some promise in animal studies, and more recently the antiglutamate drug riluzole has slowed disease progression. [37] [38] [39]

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Friedreich's Ataxia

Pathophysiology and Diagnosis

Friedreich's ataxia is a prototype of a progressive ataxia involving the spinal cord, peripheral nerves, heart, and pancreas. Incidence is 1 per 50,000 in whites, and the disorder accounts for one half of all hereditary ataxia.[40] Other similar lesions include cerebellar lesions such as familial cortical cerebellar atrophy, brain stem lesions such as familial cerebellar and olivopontocerebellar degeneration, and olivopontocerebellar atrophy. These are autosomal recessive (GAA repeat, mapping to chromosome 9q13) with an autosomal dominant subset (with four distinct chromosomal loci), with onset from 10 to 30 years of age. Pathology is caused by a loss of function in the frataxin gene, which encodes for a mitochondrial protein, presumably leading to increased oxidative stress. [41] [42] Gross pathology is characterized by degeneration of long descending and ascending fibers in the spinal cord, posterior columns, corticospinal and spinocerebellar tracts, with fibrosis, gliosis, and atrophy of the dorsal root ganglions. This is a mixed upper and lower motor neuron disease with predominantly cerebellar atrophy. Clinically, patients exhibit ataxia, nystagmus, absent lower limb reflexes, spasticity, weakness, dysarthria, and, finally, atrophy. Friedreich's ataxia is associated with diabetes mellitus, cardiomyopathy, pes cavus, kyphoscoliosis, restrictive respiratory function, and hypertrophic cardiomyopathy with myocardial muscle degeneration and a potential for congestive heart failure. The ECG often shows sinus tachycardia and arrhythmias and is abnormal in 95% of cases. Diagnosis is by genetic testing, magnetic resonance imaging (MRI), and electrophysiologic studies (EPS). The differential diagnosis for ataxia includes alcoholic-nutritional, drug abuse, ataxia-telangiectasia, autosomal dominant Roussy-Levy variant of hereditary neuropathy type I idiopathic atrophy, neoplasm, or cerebellar stroke. Whereas 5-hydroxytryptophan (serotonin) seems to improve cerebellar symptoms, there are no treatments.

Perioperative Considerations.

Anesthetic considerations are similar to those of the motor neuron degenerative diseases: regional anesthesia is not contraindicated, and care should be taken with onset and recovery of NDNMB, with particular attention to bulbar and respiratory function. Cardiomyopathy and bulbar dysfunction are implicated most often as the cause of death. One recent case report described general anesthesia with endotracheal intubation, a propofol/alfentanil infusion, and no use of muscle relaxants, without complication.[43]

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Spinal Muscular Atrophy

Pathophysiology and Diagnosis.

Spinal muscular atrophy (SMA) is characterized by peripheral motor nerves without involvement of upper motor neurons. Some types are more frequent in infancy and childhood, but all types appear to map to chromosome 5 and appear to be autosomal recessive. They are a leading cause of heritable infant deaths, trailing only cystic fibrosis in the category of autosomal recessive disease. SMA may also be seen in other diseases, such as Friedreich's ataxia.

Infantile SMA, also known as Werdnig-Hoffman disease or SMA type I, is a rapid, progressive disease of infancy, causing hypotonic weakness and usually death within the first year of age. SMA type II is a slightly slower form of SMA; it is also progressive but can be seen in adolescents or young adults. SMA type III (Kugelberg-Welander disease) is a more indolent variant with prominent spastic weakness manifested in late childhood and affecting muscles of the trunk and proximal limbs. SMA type IV is a slowly progressive adult-onset variant.

Perioperative Considerations.

The etiology of the impaired neuromuscular transmission is not yet known. Decreases in choline acetyltransferase, part of the ACh synthesis pathway, are seen secondary to degeneration of the anterior horn cells, and the decreased acetylcholine leads to an increased sensitivity to NDNMB. One should avoid succinylcholine because of the increased potassium release and myotonia-like contractions. Because of the potential for aspiration and respiratory weakness, careful dosing and attention to reversal of neuromuscular blockade (NMB) are important. Likewise, high blocks with regional anesthetics may exacerbate the respiratory and/or bulbar muscle weakness but regional anesthesia is not absolutely contraindicated. Case reports describe both regional[44] and general anesthesia [45] [46] for SMA II and III patients. Watts[47] used total intravenous (IV) anesthesia and a laryngeal mask airway (LMA), while Habib and colleagues[48] described the use of alfentanil and propofol, without NMB, for direct laryngoscopy and intubation for an abdominal procedure.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

PERIPHERAL NERVE DISEASE AND THE POLYNEUROPATHIES

Peripheral nerve disease covers a wide variety of causation and clinical entities ( Table 8-3 ). The peripheral nervous system (PNS), which encompasses all neural structures outside of the spinal cord and brain stem, includes a broad variety of cell types, nerve fibers, anatomic variability, and function. Likewise, the pathologic conditions capable of affecting the PNS at multiple points are also incredibly variable. Signs and symptoms of polyneuropathies can therefore include impaired motor function, spasm and fasciculations, reflex changes, sensory loss, pain and paresthesia, dysesthesias, ataxia, tremor, trophic changes, and autonomic dysfunction. These can all have acute or chronic onset and duration.

TABLE 8-3   -- Principal Neuropathic Syndromes

  

I.   

Syndrome of Acute Motor Paralysis with Variable Disturbance of Sensory and Autonomic Function

  

A.   

Guillain-Barré syndrome (GBS; acute inflammatory polyneuropathy; acute autoimmune neuropathy)

  

B.   

Acute axonal form of GBS

  

C.   

Acute sensory neuro(no)pathy syndrome

  

D.   

Diphtheritic polyneuropathy

  

E.   

Porphyric polyneuropathy

  

F.   

Certain toxic polyneuropathies (thallium, triorthocresyl phosphate)

  

G.   

Rarely, paraneoplastic

  

H.   

Acute pandysautonomic neuropathy

  

I.   

Tick paralysis

  

J.   

Critical illness polyneuropathy

  

II. 

Syndrome of Subacute Sensorimotor Paralysis

  

A.   

Symmetrical polyneuropathies

  

1.   

Deficiency states: alcoholism (beriberi), pellagra, vitamin B12 deficiency, chronic gastrointestinal disease

  

2.   

Poisoning with heavy metals and solvents: arsenic, lead, mercury, thallium, methyl n-butyl ketone, n-hexane, methyl bromide, ethylene oxide, organophosphates (TOCP, etc.), acrylamide

  

3.   

Drug toxicity: isoniazid, ethionamide, hydralazine, nitrofurantoin and related nitrofurazones, disulfiram, carbon disulfide, vincristine, cisplatin, paclitaxel, chloramphenicol, phenytoin, pyridoxine, amitriptyline, dapsone, stilbamidine, trichloethylene, thalidomide, clioquinol, amiodarone, adulterated agents such as L-tryptophan, etc.

  

4.   

Uremic polyneuropathy

  

5.   

Subacute inflammatory polyneuropathy

  

B.   

Asymmetrical neuropathies (mononeuropathy multiplex)

  

1.   

Diabetes

  

2.   

Polyarteritis nodosa and other inflammatory angiopathic neuropathies (Churg-Strauss, hypereosinophilic, rheumatoid, lupus, Wegener granulomatosis, isolated peripheral nervous system vasculitis)

  

3.   

Mixed cryoglobulinemia

  

4.   

Sjögren-sicca syndrome

  

5.   

Sarcoidosis

  

6.   

Ischemic neuropathy with peripheral vascular disease

  

7.   

Lyme disease

  

C.   

Unusual sensory neuropathies

  

1.   

Wartenberg migrant sensory neuropathy

  

2.   

Sensory perineuritis

  

D.   

Meningeal-based nerve root disease (polyradiculopathy)

  

1.   

Neoplastic infiltration

  

2.   

Granulomatous and infectious infiltration: Lyme, sarcoid, etc.

  

3.   

Spinal diseases: osteoarthritic spondylitis, etc.

  

4.   

Idiopathic polyradiculopathy

  

III. 

Syndrome of Chronic Sensorimotor Polyneuropathy

  

A.   

Less chronic, acquired forms

  

1.   

Paraneoplastic: carcinoma, lymphoma, myeloma, and other malignancies

  

2.   

Chronic inflammatory demyelinating polyneuropathy (CIDP)

  

3.   

Paraproteinemias

  

4.   

Uremia (occasionally subacute)

  

5.   

Beriberi (usually subacute)

  

6.   

Diabetes

  

7.   

Connective tissue diseases

  

8.   

Amyloidosis

  

9.   

Leprosy

  

10. 

Hypothyroidism

  

11. 

Benign sensory form in the elderly

  

B.   

Syndrome of more chronic polyneuropathy, genetically determined forms

  

1.   

Inherited polyneuropathies of predominantly sensory type

  

a.   

Dominant mutilating sensory neuropathy in adults

  

b.   

Recessive mutilating sensory neuropathy of childhood

  

c.   

Congenital insensitivity to pain

  

d.   

Other inherited sensory neuropathies, including those associated with spinocerebellar degenerations, Riley-Day syndrome, and the universal anesthesia syndrome

  

C.   

Inherited polyneuropathies of mixed sensorimotor t ypes

  

1.   

Idiopathic group

  

a.   

Peroneal muscular atrophy (Charcot-Marie-Tooth; hereditary motor-sensory neuropathy [HMSN], types I and II)

  

b.   

Hypertrophic polyneuropathy of Dejerine-Sottas, adult and childhood forms

  

c.   

Roussy-Levy polyneuropathy

  

d.   

Polyneuropathy with optic atrophy, spastic paraplegia, spinocerebellar degeneration, mental retardation, and dementia

  

e.   

Hereditary liability to pressure palsy

  

2.   

Inherited polyneuropathies with a recognized metabolic disorder

  

a.   

Refsum's disease

  

b.   

Metachromatic leukodystrophy

  

c.   

Globoid-body leukodystrophy (Krabbe's disease)

  

d.   

Adrenoleukodystrophy

  

e.   

Amyloid polyneuropathy

  

f.    

Porphyric polyneuropathy

  

g.   

Anderson-Fabry disease

  

h.   

Abetalipoproteinemia and Tangier disease

  

IV. 

Neuropathy Associated with Mitochondrial Disease

  

V.   

Syndrome of Recurrent or Relapsing Polyneuropathy

  

A.   

Guillain-Barré syndrome

  

B.   

Porphyria

  

C.   

Chronic inflammatory demyelinating polyneuropathy

  

D.   

Certain forms of mononeuritis multiplex

  

E.   

Beriberi or intoxications

  

F.   

Refsum's disease, Tangier disease

  

VI. 

Syndrome of Mononeuropathy or Plexopathy

  

A.   

Brachial plexus neuropathies

  

B.   

Brachial mononeuropathies

  

C.   

Causalgia

  

D.   

Lumbosacral plexopathies

  

E.   

Crural mononeuropathies

  

F.   

Migrant sensory neuropathy

  

G.   

Entrapment neuropathies

From Adams RD, Victor M, Ropper AH (eds): Principles of neurology. New York, McGraw-Hill, 1997.

 

 

 

Guillain-Barré syndrome (GBS) is an example of a polyneuropathy with motor, sensory, and autonomic components. The anesthetic considerations of the polyneuropathies in general will be discussed using GBS as an illustrative example. In actuality, diagnosis of a specific etiology for a mixed polyneuropathy can be challenging. In large studies a sizable fraction of patients remain without a specific diagnosis of causative agent. Polyneuropathies that might be encountered frequently by anesthesia providers include those due to ischemia, diabetes, drugs, rheumatoid arthritis, lupus, sarcoid, Sjögren's disease, paraneoplasm, acquired metabolic syndrome, uremia, and alcohol. Of particular interest are the polyneuropathy of critical illness [49] [50] and a report of acute quadriplegia and myopathy attributed to prolonged NMB and corticosteroid use.[51] The inherited polyneuropathies are covered later in this chapter. Individual neuropathies due to trauma, radiation, reflex sympathetic dystrophy (RSD), or inflammation of individual peripheral nerves are not covered here.

Guillain-Barré Syndrome

Pathology and Diagnosis

Guillain-Barré syndrome, also known as acute idiopathic polyneuritis or acute inflammatory polyneuropathy, is a cell-mediated immunologicresponse against peripheral nerves, with a number of variant forms ( Table 8-4 ). [52] [53] [54] [55] [56] [57] It is found worldwide, in both sexes and all ages, with an incidence of about 1.5 per 100,000. Pathologic examination demonstrates perivascular lymphocytic and inflammatory cell infiltration, segmental demyelination, and wallerian degeneration along entire peripheral nerves and scattered throughout the PNS. Damage is primarily axonal and is thought to be due to an immune-mediated response to myelin proteins.[58] In 60% to 70% of cases, GBS is preceded by a mild gastrointestinal or respiratory influenza-like illness by 1 to 3 weeks, with Campylobacter jejuni,Epstein-Barr virus (EBV), or cytomegalovirus (CMV) most frequently identified.[59] Other preceding events that have been statistically associated with GBS include surgery, other viral illness, vaccination, and lymphomatous disease. GBS is characterized by paresthesias, numbness, and progression to weakness that is mostly symmetrical. Distal extremities are affected first, followed by proximal upper extremities and cranial muscles in 50% of cases. Pain and aches accompany variable sensory loss and areflexia.


TABLE 8-4   -- Guillain-Barré Syndrome and Its Variant Forms

Form of Guillain-Barré Syndrome

Incidence/Occurrence

Motor or Sensory

Characteristic Signs

Suspected Etiology

Acute inflammatory demyelinating polyneuropathy

Most common in developed countries of Europe and North America

Both motor and sensory

85%–90% of cases; peripheral nerve demyelination

Cell-mediated immune, and humoral, attacks myelin and Schwann cells

Acute motor axonal neuropathy

Mainly northern China;

Motor only; axonal damage

Seasonal; higher incidence of respiratory failure

Immune, motor axons; higher association withCampylobacter jejuni

Acute motorsensory neuropathy

Prolonged course

Resembles pure variant but with some sensory

Axonal damage of both motor and sensory

 

Miller-Fisher variant

 

No significant weakness, but can involve cranial nerves

Ataxia, ophthalmoplegia, areflexia

Often Campylobacter jejuni also, antibodies to cranial nerve myelin

Data from references 54-59.

 

 

 

Signs and symptoms can be limited solely to lower extremities or can lead to total muscular paralysis with paresthesias and autonomic dysfunction (hypotension and hypertension, sinus tachycardia or bradycardia, diaphoresis or loss of sweating, and orthostatic hypotension). Hyponatremia, the syndrome of inappropriate antidiuretic hormone (SIADH), and diabetes insipidus can also occur. Nerve conduction studies show reduced amplitude of motor evoked potentials, slowed conduction, prolonged latency, and prolonged F waves. Diagnosis is made with an increased finding of protein in the cerebrospinal fluid (CSF) with a normal cell count. The differential diagnosis includes the muscular dystrophies, acute spinal cord injury, transverse myelitis or myelopathy, renal failure, polyneuropathy of critical illness, prolonged corticosteroid use, chronic neuromuscular blockade, and acute hyperphosphatemia. Treatment consists of symptomatic support of respiration and hemodynamics, as well as aspiration precautions. Corticosteroids have not proven efficacious, but plasmapheresis within the first 2 weeks after onset has been useful.[60] Recovery is usually spontaneous and full.

Perioperative Considerations

The anesthetic management is the same as that for motor neuron degeneration. Succinylcholine should be avoided because of the potential for potassium release, and there should be increased awareness of the potential for increased sensitivity to NDNMB. An arterial line may be useful for patients with autonomic dysfunction, and postoperative ventilation may be necessary because of reduced respiratory function. Regional anesthesia is controversial owing to a limited number of case reports claiming an association with onset of disease, although use for obstetrics has also been reported.[61] Both general anesthesia with limited or no use of NDNMBs [62] [63] [64] and regional anesthesia have been reported for poly(dermato)myositis, which has proximal muscle weakness and myalgias similar to GBS.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

ABNORMALITIES OF METABOLISM AND CIRCULATION OF THE CSF PATHWAYS

The balance between CSF formation, intracranial pressure (ICP), circulation, and absorption determines CSF hydrostatic pressure and the distribution of CSF within the CNS. There is 50 to 150 mL of CSF in the adult, and it is divided into two main compartments: an intracranial compartment, consisting of primarily lateral ventricles and the third ventricle, and the spinal subarachnoid space. CSF is generated primarily in the choroid plexus at a rate of 21 to 22 mL/hr. In the absence of pathologic or vascular changes, CSF production, flow, and uptake determine CSF pressure and ventricular volume. CSF production occurs mainly in the choroid plexus in the ventricles at a rate of 500 to 600 mL/day and is due to a combination of active transport and passive filtration from blood plasma. CSF formation is affected by numerous drugs and conditions, including temperature, CSF pressure, hypocapnia, and venous pressure. Electrolytes and glucose equilibrate with CSF in the ventricles and subarachnoid space. Ionized drugs enter the CSF slowly, except for those taken up by a facilitated diffusion membrane transport. Diffusion of water, sodium, and hypotonic or hypertonic fluids occurs rapidly, and the CSF is in dynamic equilibrium with blood and intracellular fluid in the brain.

CSF bulk flow occurs from the lateral ventricles through the foramina of Monro to the third ventricle, through the aqueduct of Silvius to the fourth ventricle. CSF exits the fourth ventricle through the two lateral foramina of Luschka and the foramen of Magendie (medially) into the perimedullary and perispinal subarachnoid spaces, then to the brain stem, basal cistern, and cerebral hemispheres. CSF bathes the intracranial and spinal subarachnoid spaces from the cisterna magna, with considerable to and fro bulk flow across the various foramina as a result of cardiac oscillations and movement. A pressure gradient with arterial pulsations is observed to fall with direction of CSF flow, from 60 mm Hg in the lateral ventricles to 50 mm Hg in the cistern to 30 mm Hg in the lumbar subarachnoid space. CSF is taken up by bulk filtration at several sites, primarily the arachnoid villa in the sagittal sinus. Each ventricle normally contains 25 to 40 mL. Obstruction of the foramina or increased production can lead to hydrocephalus.

The blood-brain barrier is made up of both blood-CSF and brain-CSF barriers of varying “barrier” effectiveness and includes capillary endothelium, plasma membrane adventitia, and pericapillary foot processes of astrocytes. Drugs that affect CSF production include digoxin, furosemide, corticosteroids, and acetazolamide. Aminophylline increases CSF production by increasing the Na+,K+-ATPase active transport. The effects of most opioids are modest, and the effects of anesthetic agents on the balance between production and absorption is usually small. Artru, [65] [66] [67] in a series of classic studies in dogs, showed little effect of isoflurane, halothane, or fentanyl on CSF production, although ketamine and enflurane increased CSF production. More recently, Sugioku[68] showed decreased CSF production in rabbits with sevoflurane anesthesia, confirmed an increase in production with enflurane, and showed increased CSF absorption with N2O. Artru[69] showed no significant alterations in CSF production or absorption by sevoflurane or remifentanil.

Hydrocephalus

Pathophysiology and Diagnosis

Hydrocephalus is defined as excessive ventricular CSF, most commonly due to foraminal obstruction (noncommunicating), but it can also be due to overproduction or impaired absorption (communicating). Congenital hydrocephalus is seen in 0.3% due to Arnold-Chiari malformation, Dandy-Walker cysts, myelomeningocele, aqueductal stenosis, arachnoid cysts, neoplasms, and vascular malformations. Acquired hydrocephalus can result from meningitis, intraventricular or subarachnoid hemorrhage, trauma, or neoplasm.[2]

Hydrocephalus may be acute or chronic in onset, and diagnosis is most commonly made by computed tomography (CT) or MRI. Chronic hydrocephalus may present as headache and nausea, whereas the rapid increase in CSF pressure in acute hydrocephalus can also cause vomiting, confusion, and lethargy. Signs include irregular respiration, papilledema, decorticate or decerebrate posturing, bradycardia, hypertension, and ECG changes due to brain stem compression and transtentorial herniation. Ventricular hydrocephalus is treated with an intraventricular catheter or surgical correction of a physical obstruction, whether due to neoplasm, malformation, or clot. Ventricular catheters are most commonly shunted to peritoneal, pleural, or, less commonly, atrial, choledochal, or vesicular spaces.[70]

Perioperative Considerations.

Anesthetic considerations are similar to other neurosurgical procedures, with particular attention to the potential for increased ICP and avoidance of abrupt or severe changes in CSF pressures or volumes due to the abnormal drainage. One of the rare case reports in a small series of patients described a variable response of ICP after induction of anesthesia with ketamine.[71] Oversedation, hypercarbia, hypoxia, anxiety, and hyperventilation should be avoided. Rapid decompression can cause subdural hematoma secondary to bridging veins from the dura or upward herniation of the brain stem, causing bradycardia, irregular respiration, or ECG changes.

Normal-Pressure Hydrocephalus

Pathophysiology and Diagnosis.

Normal-pressure hydrocephalus is common in the elderly and is associated with hypertension and atherosclerotic heart disease.[72] The exact incidence in the United States is not known, but as many as 1 in 25,000 people worldwide may have this disorder and as many as 6% of patients with dementia appear to have it. It may be seen occasionally in pediatric patients as well. Symptoms include forgetfulness, inattention, impaired thought process, and memory difficulty. Signs include ataxia, urinary incontinence, and cognitive dysfunction.[73] CT or MRI shows ventricular enlargement with normal to low lumbar opening CSF pressures. Pathology is due to hydrocephalic compression, periventricular (especially frontal subcortical) hypoperfusion, and secondary stretching of periventricular vascular and white matter structures.[74] CSF shunting is only beneficial in less than 50% of patients. [75] [76] [77] The differential diagnosis includes all of the other causes of dementia in the elderly.[78] Anesthetic management is similar to that for hydrocephalus.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Pseudotumor Cerebri

Pathophysiology and Diagnosis.

Pseudotumor cerebri or idiopathic intracranial hypertension (previously also called “benign” intracranial hypertension) is defined as an increased ICP with normal CSF composition, normal CNS imaging studies, and no known etiology. The pathology that has been proposed to account for pseudotumor cerebri is probably due to increased CSF production or increased cerebral venous pressure; increased sagittal sinus pressure, leading to low conductance CSF outflow, extracellular edema; and increased brain volume, with the resultant compression of venous sinuses and decreased CSF absorption. [79] [80]The increased CSF and intracranial pressures may be a compensatory increase in an attempt to restore CSF bulk absorption.[81] Incidence is about 0.9 per 100,000. In children, both males and females are affected equally, but in adults more women are diagnosed. In adults, pseudotumor cerebri presents as a throbbing or episodic headache, nausea, vomiting, or blurred vision. Headaches are most often worst in the morning and are exacerbated by Valsalva maneuvers and movement. Visual changes are manifested as a blind spot, field cuts with inferonasal field cut, diplopia, or blindness. This diagnosis is most common in obese women and can be self-limited. Signs include papilledema, abnormal third or lateral ventricles, effaced cerebral sulci, and elevated ICP pressures (as high as 300 to 600 mm Hg). CSF composition is normal, and, remarkably, consciousness is not altered. The diagnosis is one of exclusion, and the differential diagnosis includes cerebral venous thrombosis, increased ICP due to neoplasm, infection, or inflammatory process.

Perioperative Considerations.

Multiple causes are associated with pseudotumor cerebri. Treatment is initially medical therapy ( Table 8-5 ), mainly with diuretics, but serial lumbar punctures with drainage may also be used. If medical management fails or visual changes progress, CSF shunts, usually lumboperitoneal, may be attempted but have a high failure and complication rate. [82] [83]

TABLE 8-5   -- Causes Associated with Pseudotumor Cerebri

  

 

Endocrine

  

 

Addison's disease, menarche, pregnancy, hypo/hyperthyroid, hypoparathyroidism, pseudohypoparathyroidism, empty sella syndrome

  

 

Dietary

  

 

Obesity, hypo-/hypervitaminosis A, vitamin D deficiency,

  

 

Drugs

  

 

Corticosteroid withdrawal, estrogen, oral contraceptives, lithium, tetracycline, trimethoprim-sulfamethoxazole, nitrofurantoin, nalidixic acid, thyroid supplements, danazol

  

 

Impaired Cerebral Venous Drainage

  

 

Otitis media, mastoiditis, idiopathic cerebral venous/dural sinus thrombosis, superior vena cava syndrome, arteriovenous malformation, right-sided heart failure, jugular vein ligation, subclavian vein, thrombosis

  

 

Others

  

 

AIDS, systemic lupus erythematosus, polyarteritis nodosa, polycythemia vera, anemia (pernicious, iron deficiency), Guillain-Barré syndrome, thrombocytopenia

 

 

Optic nerve decompression is sometimes used to salvage visual loss[84] and can attenuate headaches. [85] [86] [87] Anesthetic management is the same for hydrocephalus, but regional anesthesia is not absolutely contraindicated.[88]

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Syringomyelia and Syringobulbia

Pathophysiology and Diagnosis.

Syringomyelia is an enlarged CSF-filled cavity in the spinal cord, whereas syringobulbia is a comparable cavity in the brain stem. Hydromyelia refers to a cavity in the central canal. Syringomyelia can be communicating, often in conjunction with Chiari malformations, or noncommunicating. Syringomyelia is progressive, with loss of pain and temperature sensation in the upper extremities, with preserved touch and proprioception, possible hyporeflexia, and extremity atrophy.[2] Deep tendon reflexes can be lost, and loss of paraspinous muscles can result in scoliosis.

Syringobulbia most commonly presents as a throbbing occipital headache and can lead to lower cranial nerve dysfunction, including motor and sensory changes of the tongue, vocal cords, and sensation of the face. Traumatic syrinx formation can manifest itself as pain radiating to the neck and upper extremities.[89] Diagnosis is by CT with contrast medium enhancement, or by MRI, although it may be found after a failed subarachnoid block.[90] Pathologic examination shows a syrinx cavity filled with CSF and reactive gliosis histology, but without inflammation or ischemia. Noncommunicating syringomyelia can be the result of spinal cord trauma, tumor, or arachnoiditis.

Perioperative Considerations.

Surgery is intended to drain the syrinx cavity and to relieve the spinal cord compression, either by craniocervical decompression, in the case of communicating syringomyelia, or with laminectomy and shunting, in the case of noncommunicating syringomyelia. Patients should be treated as if they have an acute spinal cord injury, because they can exhibit autonomic hyperreflexia, impaired sympathetic responses, impaired temperature regulation, and respiratory difficulty. Succinylcholine is contraindicated, and the response to NDNMBs can be variable.[91] Syringobulbia involvement of the cranial nerves may lead to impaired airway protection.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

SPINAL CORD INJURY

Pathophysiology and Diagnosis.

Acute spinal cord injury (SCI) affects some 220,000 individuals in the United States each year. The majority are young adult males, and the injuries are commonly associated with alcohol or other substances of abuse and with motor vehicle accidents. Acute trauma resuscitation is covered in Chapter 17 , and we only briefly review specific neurologic considerations after acute and chronic SCI here.

Anesthetic Management of Acute SCI.

Any trauma patient should be considered to be at risk for brain or spinal cord injury and treated appropriately with cervical spine precautions and examination for head or neck injuries that might possibly have been overlooked while treating other life-threatening injuries. Rarely, vertebral artery injuries can occur in conjunction with cervical spine injuries and should be in the differential diagnosis in patients with CNS trauma and signs and symptoms consistent with cerebellar or brain stem injury (e.g., gait, balance, nausea/vomiting, hemodynamics, respiration, cranial nerve dysfunction).[92] Elderly trauma patients are at increased risk for flexion and extension injuries, which can lead to central cord syndrome, with symptoms of variable sensory loss below the level of spinal cord injury, lower extremity weakness, and urinary dysfunction. Acute SCI can lead to loss of sympathetic and autonomic reflexes, responses, and tone (spinal shock). This is manifested as cardiovascular and autonomic instability, loss of reflexes, and flaccid paralysis.[93] Symptomatic inotropic, chronotropic, and respiratory support is indicated. These patients are at risk for possible neurogenic pulmonary edema, myocardial irritability and arrhythmias, hypoactive and hyperactive sympathetics and autonomics. Risks of abdominal atony and ileus, distention, malfunction of the diaphragm, and increased risks of aspiration should all be considered. Ongoing secondary injury after trauma to the spinal cord may cause extension of the initial injury, with further loss of function and increased respiratory or cardiovascular compromise. Quadriplegia may be associated with hyperdynamic vagal responses owing to loss of sympathetic or cardioaccelerator fibers. Bronchi may be hyperresponsive from increased tone after SCI as well.

Anesthetic Management of Chronic SCI.

Unfortunately, patients with a chronic SCI are not uncommon and frequently present for urologic or orthopedic procedures. Multiple organ systems can be affected by the injury, and the level of SCI determines organ system involvement. Higher lesions (those above T4 to T6) can cause significant impairment of hemodynamics and cardiovascular reflexes.[94] These changes are due to damage to the sympathetic chain, chronic loss of cardiovascular and cerebrovascular tone, increased renin-angiotensin activity, and resultant changes in intravascular volume. Respiratory function may be impaired because of diaphragmatic and chest wall mechanics and ventilation-perfusion mismatch. Patient positioning for optimal spontaneous respiration must be balanced with the potential for orthostatic hypotension. Other common coexisting diseases include renal dysfunction (i.e., infection, stones, insufficiency, failure), anemia, pressure necrosis and sores, osteoporosis, pain, and lack of temperature regulation.

Autonomic hyperreflexia is found in the majority of SCI patients with lesions above T6. It is defined as a generalized autonomic overactivity in response to stimuli, out of proportion to the intensity of the stimulus. Common stimuli include bladder or intestinal distention, but it may also include uterine contractions or surgical skin incision. Signs and symptoms include hypertension, bradycardia, headache, visual changes, sweating, piloerection below the level of the lesion with vasodilation above the level of the lesion, and cardiac arrhythmias.[94] Untreated autonomic hyperreflexia can lead to hypertensive crisis, stroke, seizures, and death. The pathology involves the unopposed sympathetic thoracolumbar tract, with impaired descending spinal inhibitory pathways. Anesthesia can be regional or general, and the key is effective anesthesia, regardless of the technique chosen. Treatment of hypertensive crisis should include calcium channel blockade (nicardipine, nifedipine), vasodilators (nitroprusside, hydralazine), or α-adrenergic antagonists (phentolamine, phenoxybenzamine). Centrally acting antihypertensives (clonidine, methyldopa) are not as effective in acute treatment, and β blockers alone are contraindicated due to the resultant unopposed α-adrenergic activity. Epidural anesthesia has been used to treat autonomic hyperreflexia in a quadriplegic patient.[95]

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

DEMYELINATING DISEASES

The most common demyelinating diseases are classified into two groups, multiple sclerosis and diffuse cerebral sclerosis. Multiple sclerosis has three subtypes that include chronic relapsing encephalomyopathy, neuromyelitis optica, and the acute form of multiple sclerosis. Diffuse myelinoclastic cerebral sclerosis, also known as Schilder's disease, usually has a relapsing remitting course and affects primarily children, but it can present in young adulthood and may mimic intracranial neoplasm or abscess.[15] Definitive pathologic findings include neuronal myelin sheath destruction, perivascular inflammatory infiltration, which is mainly perivenular in white matter, and a lack of fiber tract wallerian or secondary degeneration. Although similar in pathology, the leukodystrophies and Krabbe's disease primarily affect infants and involve abnormal myelin production, or dysmyelination. In addition, with recent advances in genomics, the etiology for several of these leukodystrophies has been genetically linked to transport proteins and enzymes responsible for myelin production.[96]

Multiple Sclerosis

Pathophysiology and Diagnosis.

Multiple sclerosis (MS) is an autoimmune disorder mediated by inducible T cells and autoantibodies that target CNS myelin. In the United States roughly 400,000 men and women are diagnosed with MS, with a twofold to threefold higher prevalence in women.[97] There is a well-established geographic correlation in the incidence of MS, with the highest rates (30 to 80/100,000) found in Northern Europe and northern climates in North America, followed by southern regions of Europe and the United States (6 to 14/100,000). The lowest incidence (1 in 100,000) is seen in equatorial latitudes. There is a bimodal distribution of MS patients, with one third presenting between 45 and 60 years of age and the majority between 20 and 40 years of age. Despite extensive epidemiologic studies, it appears that MS is influenced by unknown environmental factors and familial genetics rather than ethnicity or comorbidities. First-degree relatives demonstrate up to 14 times the incidence of MS. In this group there has been a remarkable similarity between HLA-B7 and HLA-Dw2 antigens. Many researchers and clinicians believe that there is an underlying autoimmune component to MS in light of the fact that the diagnostic criteria include evidence of CSF antibodies of the IgG type.

The typical MS patient experiences unpredictable bouts of neurologic deficits, secondary to random CNS sclerotic lesions, followed by variable periods of latency, hence the chronic relapsing clinical course. These nonspecific sclerotic lesions can present acutely over several hours or chronically over months to years with evolving motor, neurologic and cognitive deficits depending on the location and size of the lesion(s). At the cellular level the clinical symptoms are thought to be secondary to circulating activated myelin-reactive T cells with locally associated edema. This theory is further supported by the often rapid response to immunosuppression to decrease inflammation and edema.[97]

Research is currently focused on identifying genetic loci that are linked to MS and could potentially lead to diagnostic and therapeutic advances. Genetic testing research for diagnostic and treatment purposes has not been conclusive to date, because demyelinating diseases have been linked to several enzyme cascades and antigenic expression in the HLA groups. Several genomic screens have been undertaken to locate such genes but have not provided consistent gene localization, except for the major histocompatibility complex on chromosome 6p21 and a locus on chromosome 19q13.[98] A T-cell β chemokine known as the RANTES (r, egulated upon activation, normal T-cell expressed and secreted) gene has been found in sclerotic lesions in the CNS of MS patients post mortem. There appears to be a significant correlation with certain polymorphisms of this gene and its relation to onset and mortality.[99] The Multiple Sclerosis Genetics Group, which is a multicenter research consortium, has multiple studies underway trying to identify inherited and inducible genetic loci for MS.

Common clinical manifestations include paresthesias, weakness, bulbar deficits affecting cranial nerve function, abnormal extremity tone, cerebellar ataxia or diplopia, and bladder or bowel dysfunction; however, the severity and multitude of symptoms depends on the gross burden of sclerotic lesions in the CNS.

Factors that have been clinically established as exacerbating MS include stressful events such as emotional and physical trauma, infections, surgery, and the peripartum period. Hormonal and temperature fluctuations appear to have a clinical correlation with exacerbations as well. Davis[99a] demonstrated that a temperature rise of 0.5°F blocks nerve conduction in previously demyelinated nerve fibers. Previously, Edmund and Fog documented clinical deterioration with temperature elevations in 75% of MS patients.[100]

Diagnostic criteria for MS are based on clinical, laboratory, and radiologic findings. The most useful appear to be MRI evidence of CNS plaques (typically periventricular) that are separate in time and space and are supported by abnormal evoked potentials of the somatosensory, visual, and auditory type. CSF may show abnormal oligoclonal antibodies. Current therapies for MS are not curative but attempt to ameliorate acute exacerbations and prevent future recurrences. Most MS flares respond to glucocorticoid therapy in the early phases, but many patients fail to respond to corticosteroids as their number of exacerbations increases. Patients with optic neuritis respond to oral and intravenous adrenocorticotropic hormone and prednisone in the acute phases and experience fewer relapses. Other immunosuppressive agents, such as cyclophosphamide, cytarabine, and azathioprine, have shown intermittent success at preventing the number and severity of relapses but are not without side effects. Patients with severe motor spasticity and bladder dysfunction are treated with antispastic medications, which provide some relief. Alternative therapies that are not clinically proven but that have been tried in severely resistant cases include plasmapheresis, hyperbaric oxygen therapy, linoleate supplementation, and interferons.

Perioperative Considerations.

Although not directly correlated with anesthetic medications, the clinical course of MS may fluctuate in the perioperative period. Periods of stress, whether emotional or physical, often coincide with a deterioration of MS symptoms. There have been no randomized studies that implicate general anesthesia as an exacerbating factor for MS flares; however, there are rare case reports of disease exacerbation associated with perioperative fevers.

Anesthetic induction agents and inhaled gases have no demonstrable adverse effects on nerve conduction and have not been definitively implicated in the literature as contributing to progression of any neurodegenerative disorders. However, several agents used commonly during general anesthesia might affect nerve conduction and thus affect MS patients. Temperature fluctuations have been implicated in nerve conduction inhibition in demyelinated nerve fibers. Drugs that are commonly administered under anesthesia include the anticholinergics atropine and glycopyrrolate. At the doses used during surgery these drugs have not been shown to significantly raise temperatures enough to elicit symptoms or predict exacerbations. An earlier account of sodium thiopental being deleterious for MS patients undergoing surgery or sedation has now been discounted. [102] [103] [104] [105] The use of depolarizing muscle relaxants also carries theoretical risks in MS patients, more specifically those with profound neurologic deficits that often cause upregulation of motor end plate acetylcholine receptors and the hyperkalemic response to depolarization. We have not found any studies that implicate nondepolarizing muscle relaxants in neurologic sequelae perioperatively; thus, their use appears to be safe.

Local and regional anesthesia remains a controversial topic in MS patients because of their pharmacodynamics on nerve conduction. In clinical practice it is common for clinicians to perform lumbar puncture for diagnosis and clinical response to therapies, and there are no significant data to suggest an exacerbation of symptoms with said procedure.[105] With the pathology of demyelination in MS one might expect that the potential for neurotoxicity with local anesthetics administered in the epidural or intrathecal space would be higher. However, several retrospective studies have not demonstrated a significant increase in MS exacerbations with either epidural or spinal local anesthetic administration. [107] [108] [109] [110] [111] [112] Although unproven, many clinicians believe that repeated doses of local anesthetics for regional anesthesia carry a potentially increased risk for neurotoxicity, both locally and centrally, because the blood-brain barrier may be more permeable owing to chronic inflammatory changes. In light of this concept, many believe that lower concentrations of local anesthetics should be utilized and combined with narcotics, because there have been no reports of significant adverse events with epidural or intrathecal opioids. Regardless of the technique utilized, MS patients should be informed of the potential side effects and risks of perioperative exacerbations.

Based on the historical and clinical data available there appear to be no absolute contraindications for general or regional anesthesia in the MS population. As a standard preoperative assessment these patients should have a well-documented neurologic examination, as well as a postoperative assessment for any new findings. During surgery there should be close attention to thermoregulation, because pyrexia has been described to elicit MS exacerbations in a perioperative setting. Chronic immunosuppressive therapy should be maintained or continued; however, there is no clinical evidence to support the use of stress doses of corticosteroids perioperatively.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Mucopolysaccharidoses

Pathophysiology and Diagnosis.

The mucopolysaccharidoses (MPS) are hereditary lysosomal storage disorders caused by the deficiency of various enzymes necessary for the metabolism of glycosaminoglycans (GAG), previously called mucopolysaccharides. Excess accumulation of partially degraded glycosaminoglycans within cells causes cellular dysfunction. The faulty metabolism results in serious structural and functional abnormalities in a wide variety of tissues, particularly bone and cartilage. There are now 9 MPS disorders, classified as types I through IX, based on enzyme deficiency and severity of the phenotype. With the exception of Hunter's syndrome (MPS II), which is an X-linked disorder, the MPS are inherited in an autosomal recessive pattern. The cumulative incidence is estimated at 1 in 20,000 live births. Table 8-6 outlines the classification system and summarizes the associated clinical features.

TABLE 8-6   -- Classification of Mucopolysaccharidoses[*],[†]

Syndrome

MPS Type

Incidence

Clinical Features

Hurler

IH

1/100,000

Severe skeletal and cardiac abnormalities, coarse facies, airway obstruct hepatosplenomegaly, hydrocephalus, mental retardation, corneal opac and hearing loss

Hurler-Scheie

IH/IS

1/115,000

Intermediate in severity with significant joint involvement, hepatosplenomegaly, micrognathia, and near-normal mentation.

Scheie

IS

1/500,000

Mildest MPS I with life span of several decades

 

 

 

Aortic valve disease common

 

 

 

Normal facies and intelligence

Hunter

II

1/100,000

Mild to severe forms

 

 

 

Physical disease similar to MPS I with slower progression

 

 

 

Less mental retardation but aggressive behavior

Sanfillippo A-D

III A-D

1/30,000

Primarily central nervous system involvement with progressive mental retardation and aggressive behavior

 

 

 

Each subtype is the result of a different enzyme deficiency.

 

 

 

III C is the mildest form.

Morquio

IV A and B

Rare

Skeletal disease and ligament laxity with high incidence of odontoid dysplasia and atlantoaxial instability

 

 

 

Normal intelligence and survival to middle age

 

 

 

Both types have severe and mild forms.

Maroteaux-Lamy

VI

Rare

Severe skeletal disease similar to MPS I but normal intelligence Severity variable

Sly

VII

Rare

Variable physical presentation with psychomotor retardation

Hyaluronidase deficiency[‡]

IX

Very rare

Short stature, acetabular erosion, periarticular masses

*

MPS V and VIII no longer in use.

Goetz C (ed): Textbook of clinical neurology, 2nd ed. Philadelphia, Saunders, 2003, pp. 611–612.

Natowicz MR, Short MP, Wang Y, et al: Clinical and biochemical manifestations of hyaluronidase deficiency. N Eng J Med 1996; 335(14):1029–1033.

 

Diagnosis is made by elevated GAG concentration in urine or demonstration of enzyme deficiency in leukocytes. Treatment options include enzyme replacement, bone marrow transplantation, and cord blood transplantation. These therapies are symptomatic and may alter the natural progression of the disease but do not preventeventual decline in function. The MPS continue to worsen as the patient grows older, and most patients will die of pulmonary or cardiac complications.

Perioperative Considerations.

The anesthetic implications of this disease are extensive and relate to the end organ dysfunction and anatomic distortions experienced by this patient population. Complications with general anesthesia are common, and morbidity and mortality are primarily due to airway issues. Upper airway abnormalities such as macroglossia, hypertrophic tonsils and adenoids, patulous lips, micrognathia, friable tissues, copious secretions, and restrictive temporomandibular joint movement can hinder adequate ventilation. Many patients have obstructive breathing at baseline, with sleep apnea and need for continuous positive airway pressure. Bone marrow transplant can reverse upper airway obstruction.[112] Lower airway abnormalities from deposition of GAG in the epiglottis and tracheal wall distort the airway, and difficulties with intubation can increase with age as this process continues.[113] A short neck with a narrow, anterior larynx accompanied by possible cervical instability or history of cervical fusion offer additional airway challenges, particularly in those with Hurler's syndrome (MPS I). Incidence of difficult and failed intubations is reported as 54% and 23%, respectively. [115] [116] Tracheotomy is also technically difficult, owing to a large mandible, short neck, and retrosternal trachea and was impossible even post mortem in one case report. [117] [118]

Cardiac abnormalities also result from MPS. Mitral and aortic valves thicken, causing insufficiency that may progress to cardiomyopathy.[118] Deposition of GAG in the walls of arterial blood vessels causes systemic hypertension and coronary artery disease. Coronary lesions are diffuse and can lead to ischemia or sudden death. Coronary angiography may not predict the severity of the diseases. [113] [120] Pulmonary hypertension secondary to chronic hypoxemia of pulmonary disease and airway obstruction can lead to right-sided heart failure.

Pulmonary dysfunction is another frequent complication. Kyphoscoliosis causes a restrictive disease with recurrent pneumonia and ventilation-perfusion mismatch, resulting in chronic hypoxemia and hypercarbia. Patients with Morquio's syndrome (MPS IV) are also prone to atlantoaxial instability and odontoid dysplasia. This can lead to central apnea from cord compression.[120]

Neurologic complications of MPS vary depending on the particular classification. Developmental delay and sleep disturbance are common. Vertebral subluxation can occur at any level of the spinal column and compromise the spinal cord. Communicating hydrocephalus frequently develops and can cause increased ICP. Seizures are uncommon in most of these patients.

Patients with MPS present for surgery frequently, most commonly for ear, nose, and throat procedures and hernia repairs. Anesthetic management should begin with a preoperative evaluation that establishes which type of MPS is involved and what components of the disease are present.[115] Careful review of cardiac, pulmonary, and neurologic function are paramount, and workup may include an electrocardiogram, chest radiograph, neck films, pulmonary function tests, and echocardiogram, as indicated. Preoperative flexion-extension films to evaluate stability of the cervical spine are recommended in those with Morquio's syndrome.[121] Detailed inspection of the airway, review of old anesthesia records, and neck imaging can help predict airway difficulties.[115] However, the airway can worsen with time and disease progression. Age and level of mental retardation are also important considerations in planning an anesthetic. Premedication with benzodiazepines can be helpful in the uncooperative patient but should be avoided in those with an airway prone to obstruction. An antisialagogue should be administered to decrease secretions but used cautiously in patients with heart disease.

Because most reported anesthetic complications in this population involve airway or positioning difficulties, regional anesthesia may be a safer option. [123] [124] [125] Regional technique may prove problematic if the patient cannot lie flat because of skeletal pain or respiratory compromise or is unable to cooperate because of mental retardation.[121] If general anesthesia is required, the airway can be secured before induction with topicalization of the airway and awake fiberoptic intubation. A reverse guidewire technique is also possible after appropriate sedation.

When inducing general anesthesia before securing the airway, inhalation induction with spontaneous ventilation is recommended. [124] [126] For those unable to cooperate with inhalation induction, intravenous induction with ketamine has been used successfully.[123] Intravenous access should be established before induction, and difficult airway equipment should be immediately available. Nasotracheal intubation is discouraged because of anatomically altered nasal passages and friable tissues. Recent literature has shown that the laryngeal mask airway can be used successfully in this population for maintenance of adequate ventilation during general anesthesia and for assistance with fiberoptic intubation through the laryngeal mask airway.[126] Limited use of the angulated video-intubation laryngoscope has also facilitated intubation in MPS patients with cervical spine instability.[127] Intraoperative considerations include careful positioning to avoid cervical subluxation and arterial cannulation in patients with severe pulmonary or cardiac dysfunction.[120] Narcotics should be titrated carefully to avoid respiratory depression. There are no reported abnormal responses to muscle relaxants or anesthetic agents. Extubation should be performed with caution in these patients, because they have increased incidence of atelectasis and airway obstruction secondary to traumatic tissue edema.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

HEREDITARY PERIPHERAL NEUROPATHIES

Inherited disorders of peripheral nerves are a part of a much larger group of inherited or acquired polyneuropathies that often coexist with systemic, infectious, and metabolic diseases (e.g., diabetes mellitus, thyroid disease, neoplastic syndromes) or are caused by exposure to various agents (e.g., heavy metals, alcohol, certain medications). As such, the hereditary neuropathies are a common and very diverse group of genetically determined neurologic diseases. They are primarily characterized by a dysfunction of peripheral sensory neurons in the presence of additional muscle weakness or autonomic system dysfunction. However, a dysfunction of the central nervous and other organ systems is more prominent in some types of hereditary neuropathies, which is of special relevance to the anesthesiologist treating these patients. Historically, classification of these disorders was primarily based on clinical manifestations and eponyms were used to designate a specific combination of clinical symptoms (e.g., Riley-Day syndrome, Charcot-Marie-Tooth disease). However, significant phenotypic variability led to nosologic confusion. Modern classification of hereditary neuropathies is based on clinical and electrophysiologic characteristics, modes of inheritance, and underlying genetic mutations. The hereditary neuropathies are usually divided into three major groups according to their main clinical manifestation—predominantly motor involvement, predominantly sensory or autonomic involvement, or neither. These major groups are further divided into types (usually based on differences in clinical presentation, pathology, nerve conductivity studies) and subtypes (based on genetic characteristics). Table 8-7 provides information about some of the more prevalent hereditary types of polyneuropathies; a comprehensive description can be found in a recent review.[128]

TABLE 8-7   -- Hereditary Peripheral Neuropathies

Hereditary Peripheral Neuropathies

Clinical Manifestations and Underlying Pathologic Process

Inheritance Patterns

Electrophysiologic Findings

Hereditary Primary Motor Sensory Neuropathies (HMSN)

HMSN type 1 (Charcot-Marie-Tooth disease type 1 or CMT 1)–five identified subtypes

Demyelinating disorder, distal weakness, onset in first or second decade of life, slow-progressing, onion bulbs

Autosomal dominant

Moderate to severe reduction in nerve conduction velocities

HMSN type 2 (Charcot-Marie-Tooth disease type 2 or CMT 2)–eight identified subtypes

Neuroaxonal (not demyelinating) disorder, distal weakness, slow progressing

Autosomal dominant

Normal to mildly reduced nerve conduction

HMSN type 3 (Dejerine-Sottas or congenital hypomyelinating neuropathy)—three identified subtypes

Demyelinating disorder, severe hypotonia in early childhood or at birth, onion bulbs

Autosomal dominant

Very severe reduction in nerve conduction velocities

HMSN type 4–seven identified subtypes)

Large group of disorders with typically early severe presentation and rapidly progressing, demyelinating, sometimes prominent sensory deficit

Autosomal recessive

Very severe reduction or absent nerve conduction velocities

Hereditary Primary Sensory Autonomic Neuropathies (HSAN)

HSAN type 1 (hereditary sensory radicular neuropathy)

Small axon loss, acromutilation

Autosomal dominant

HSAN type 2 (congenital sensory neuropathy)

Large and small axon loss

Autosomal recessive

HSAN type 3 (Riley-Day syndrome or familial dysautonomia)

Large and small axon loss, with dysautonomic crises, lack of lacrimation

Autosomal recessive

HSAN type 4 (congenital insensitivity to pain with anhidrosis)

Congenital sensory neuropathy with anhidrosis, C-axon loss

Autosomal recessive

Other Hereditary Neuropathies

Hereditary neuropathy with pressure palsy

 

 

 

Hereditary brachial plexopathy

 

 

 

Giant axonal neuropathy

 

 

 

 

 

In the previous edition of this textbook, traditional eponymic classification was used. This approach is still used in many, even most, recent anesthesia textbooks. However, we believe that use of the modern classification with cross-referencing to traditional eponyms iswarranted in this edition. All major medical reference databases use this classification, and patients seen in clinical anesthesia practice will be increasingly likely to have a diagnosis defined by this new terminology, which is widely accepted in the mainstream neurologic practice.

Hereditary Primary Motor Sensory Neuropathies, Including Charcot-Marie-Tooth Disease

The hereditary motor sensory neuropathies (HMSNs) represent a spectrum of disorders caused by a specific mutation in one of several myelin genes that results in defects in myelin structure, maintenance, and formation. The association of different mutations within the same gene with various clinical phenotypes is a common finding in this group of peripheral neuropathies. This variability suggests that these disorders represent a spectrum of related phenotypes caused by an underlying defect in peripheral nervous system myelination. The HMSNs, otherwise known as Charcot-Marie-Tooth disease (CMTD), have been classified as types 1 through 7, which are further subdivided, thus consisting of close to 30 clinical syndromes. The vast majority of these syndromes are very rare and have never been reported in the anesthesia literature. The space limitations of this text, in addition to the paucity of relevant anesthesia references, do not allow a detailed description of all currently identified phenotypes. Therefore, only types 1 and 2 (CMT1 and CMT2), and 3, which together are the most common hereditary peripheral neuropathies,[129] will be discussed. Combined prevalence in the population is close to 40 per 100,000.

Pathophysiology and Diagnosis.

HMSN type 1, or CMT1, is a demyelinating disorder of peripheral nerves, which most often presents in the first or early second decade of life, although infants can also be affected.[130] Significant family history is typical. Diffuse slowing of nerve conduction velocity and gradually progressing distal muscle weakness and early loss of coordination characterize CMT1. It is associated with loss of reflexes, pes cavus foot deformity, and hammertoes. Later, distal calf atrophy develops (classic “stork leg deformity”), in combination with gradual loss of proprioception and sense of vibration. Abnormal concentric myelin formations are called onion bulbs and are found around the peripheral axons. These are a characteristic feature of CMT1, usually revealed by the sural nerve biopsy. The CMT1A subgroup of patients may present with proximal muscle wasting and weakness. Dematteis and colleagues also observed obstructive sleep apnea in this subtype of patients, with a high degree of correlation between the severity of neuropathy and degree of obstruction.[131] Even later changes include atrophy of the intrinsic hand and foot muscles, footdrop, palpable hypertrophy of the peripheral nerves, and possible development of scoliosis and kyphosis. Disease exacerbation may occur in pregnancy.[132] Life expectancy is unaffected.

HMSN type 2, or CMT2, also called axonal CMT, is a heterogeneous disorder with normal or borderline nerve conduction velocity. It is primarily an axonal, and not a demyelinating, disorder, with neuropathy being a result of neuronal death and wallerian degeneration (no onion bulbs on biopsy). The clinical course is similar to that of CMT1, but sensory symptoms predominate over motor symptoms and peripheral nerves are not palpable. Patients with CMT2C subtype display significant degree of vocal cord and diaphragm weakness, resulting in obstructive sleep apnea, which is of interest to the anesthesiologist.[133]

Onset is usually in the second or third decades of life but can be in early childhood with rapid clinical progression.

HMSN type 3 includes two syndromes: Dejerine-Sottas syndrome and congenital hypomyelinating neuropathy (CHM). Both of these syndromes are characterized by profound hypotonia, presenting in early infancy or at birth, in the case of CHM. Dejerine-Sottas syndrome is clinically similar to CMT1, although its manifestations are more severe and appear in early childhood.

The preoperative preparation of HMSNs may be complicated owing to similarity in clinical presentation with other genetic or acquired polyneuropathies ( Table 8-8 ).


TABLE 8-8   -- Differential Diagnosis of Hereditary Motor Sensory Neuropathies

  

 

Genetic Neuropathies

  

 

Refsum's disease

  

 

Metachromatic leukodystrophy

  

 

Familial brachial plexus neuropathy

  

 

Adrenomyeloneuropathy

  

 

Pelizaeus-Merzbacher disease

  

 

Amyloid neuropathies

  

 

Acquired Neuropathies

  

 

Metabolic Disease

  

 

Diabetes mellitus

  

 

Thyroid disease

  

 

Vitamin B12deficiency

  

 

Infectious

  

 

Neurosyphilis

  

 

Leprosy

  

 

Human immunodeficiency virus

  

 

Others

  

 

Chronic alcoholism

  

 

Heavy metal intoxications

  

 

Vasculitis

  

 

Neoplastic syndromes

  

 

Chronic inflammatory demyelinating polyneuropathy

 

 

No specific treatments for HMSNs are available. Symptomatic supportive care consists of orthopedic corrective joint procedures for pes cavus and scoliosis deformities and physical and occupational therapy. Orthopedic procedures are usually staged, ranging from soft tissue procedures and osteotomies to triple arthrodesis. Multiple administrations of general or regional anesthesia might be required.

Preoperative preparation of patients with HMSNs is dictated by the extent of clinical involvement and coexisting morbidities.

The degree of motor neurologic involvement should be evaluated, and affected muscle groups should be noted. Atrophic denervated muscles usually display significant resistance to nondepolarizing muscle relaxants and are unreliable for monitoring of neuromuscular blockade.

The CMT1 and CMT2C patients should be evaluated for restrictive pulmonary disease related to scoliosis and diaphragmatic weakness and potential obstructive sleep apnea. Respiratory insufficiency has been described in patients with CMT. [135] [136] [137] Careful planning for extubation and a possible need for postoperative respiratory support may be necessary in these patients.

Patients with HMSNs may have undetected cardiac conduction abnormalities. [138] [139] Although this association is not strong, all patients with an HMSN should have a preoperative ECG.

Pregnancy often leads to exacerbation of the symptoms of CMTD and, in combination with diaphragmatic splitting, can lead to respiratory compromise.[136]

Intraoperative Considerations.

The anesthetic experience for HMSN types 1, 2, and 3 is limited to a number of case reports [137] [138] [140] [141] [142] [143] [144] [145] [146] and retrospective reviews. [147] [148] Despite the absence of strong evidence advocating for or against the use of specific anesthetic agents or particular anesthetic techniques, a number of important concerns have been raised in the literature regarding anesthetic management of these patients.

Malignant Hyperthermia.

Although drugs triggering malignant hyperthermia (MH) have been used in patients with CMTD without complication, [147] [148] there are two reports of MH during general anesthesia in patients with CMTD.[142] In these reports the authors advocate against the use of succinylcholine and volatile agents. Furthermore, an approach postulating that any patient with a neuromuscular disease should be considered to be at increased risk for MH adds to this controversy. The review of the available literature describing anesthesia management in patients with HMSNs indicates that the majority of authors prefer to avoid administering MH-triggering agents in patients with HMSN types 1, 2, and 3, in part owing to medicolegal considerations.

Succinylcholine use in these patients is associated with increased risk of malignant arrhythmias secondary to exaggerated hyperkalemic response.[148] Although succinylcholine has been used in CMTD without untoward effects, [147] [148] it seems appropriate to avoid its use in any patient with suspected muscular denervation.

Nondepolarizing, muscle relaxants, have been used successfully in patients with HMSNs without indications of prolonged duration of action. [147] [148] [150] [151] However, some authors express reasonable concern that adequate monitoring of neuromuscular blockade could be complicated due to altered responses on the affected muscles, which are not always obvious during clinical assessment.[151]Additionally, there is at least one case report of prolonged neuromuscular block with vecuronium.[152] Inadequate reversal of neuromuscular blockade in patients with preexisting respiratory compromise can lead to serious complications. It is advocated by some authors to avoid the use of nondepolarizing muscle relaxants in such patients whenever possible. [140] [142] [146]

Neuroaxial anesthetic techniques, have been successfully used in patients with HMSNs without untoward effects, including for vaginal delivery and cesarean section. [137] [145] [146] [154] [155] However, some authors correctly point out that medicolegal concerns have to be taken into considerations when designing anesthesia plans for these patients. [137] [146] Despite lack of evidence that anesthesia affects the course of preexisting neuromuscular disease, regional anesthesia may be erroneously blamed for any subsequent deterioration in sensory or motor deficits. This is especially true in pregnancy, which, as pointed out earlier, is associated with exacerbation of neurologic symptoms in women with CMTD. Additionally, the choice between general or regional/neuraxial anesthesia in patients with CMTD complicated by respiratory compromise is guided by the preservation of respiratory function in the perioperative period. In patients with phrenic nerve involvement, whose respiration depends on accessory muscles, regional block involving intercostal muscles can lead to acute respiratory failure.[136] On the other hand, there are case reports of patients with CMTD who required prolonged respiratory support after general anesthesia. [156] [157]

Hypnotic Anesthetic Agents.

Patients with CMT1 have been reported to demonstrate increased sensitivity to thiopental, correlating with the degree of motor and sensory deficit.[157] However, propofol and total intravenous anesthesia have been successfully used in these patients without untoward effects. [141] [144]

In summary, anesthetic management in the vast majority of patients with HMSNs appears to be uncomplicated and should be directed to accommodate any coexisting systemic conditions.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Hereditary Sensory and Autonomic Neuropathies

The hereditary sensory and autonomic neuropathies (HSANs) are a diverse and constantly expanding group of disorders affecting the development of autonomic and sensory neurons. Until recently, seven such disorders have been described, with familial dysautonomia (HSAN type III), also known as Riley-Day syndrome, and HSAN type IV, also known as congenital insensitivity to pain with anhidrosis (CIPA), being by far the most recognized and well understood. All HSANs are manifested by both sensory and autonomic dysfunction present at variable degree, with a unique feature for all types being absence of a normal axon flare response after intradermal injection of histamine phosphate. The reported anesthetic experience for HSANs is limited to anesthesia management of patients with familial dysautonomia (HSAN III) and CIPA (HSAN IV). The clinical presentation, diagnosis, and management of other HSANs have been reviewed.[158]

Familial Dysautonomia (HSAN Type III, or Riley-Day Syndrome)

Pathophysiology and Diagnosis.

Familial dysautonomia (FD) is a rare genetic disorder that affects, almost exclusively, persons of Ashkenazi Jewish extraction. It is the most prevalent and well studied of all HSANs. Development of autonomic and sensory neurons is impaired, resulting in reduced population of nonmyelinated and small-diameter myelinated axons. The sympathetic neurons are primarily affected, and sympathetic ganglia are small. The parasympathetic neurons and large axons are generally spared. FD presents at birth and progresses with age. In the past, more than 50% of patients died before 5 years of age. Today, due to improvements in diagnosis and treatment, newborns diagnosed with FD have more than a 50% chance to live past 30 years of age.

Although FD has close to 100% penetrance, the presentation of the disease at different life stages is highly variable. Autonomic dysfunction is the most prominent feature of this disease, presenting the most impediment to normal functioning, and usually overshadows thesensory deficits. The clinical diagnosis is usually established soon after birth by demonstrating the presence of the following main criteria: absence of tears with emotional crying, absence of lingual fungiform papillae, hypotonic or absent patellar reflexes, and absence of axon flare to intradermal injection of histamine in children of Ashkenazi Jewish descent. Many other systems are affected at various stages in life, and the myriad of clinical manifestations of FD can be divided into two main groups: sensory dysfunction and autonomic dysfunction ( Table 8-9 ).

TABLE 8-9   -- Familial Dysautonomias: Sensory and Autonomic Dysfunction

Sensory System

 

Decreased pain sensation, often with hypersensitivity of palms, sole, neck, and genital areas; decreased temperature sensation

Syncopal episodes produced by various stimuli (e.g., full bladder, large bowel movement)

Visceral sensation intact

Postural hypotension (can develop in older patients)

Sense of vibration and proprioception affected in older individuals; ataxia

Dysautonomic Crisis

Hypotonia in younger children, often disappears with age; decreased tendon reflexes

Episodes of severe nausea and vomiting associated with agitation, hypertension, tachycardia, excessive sweating and salivation; easily triggered by emotional or physical stress, arousal from sleep

Prone to self-injury; unrecognized fractures; scoliosis and joint deformities

Other Manifestations

Autonomic System

Renal System

Gastrointestinal System

Dehydration azotemia

Impaired oropharyngeal coordination; impaired swallowing, resulting in dysphagia and frequent aspirations in newborns and infants

Progressive loss of renal function with age

Abnormal esophageal motility; decreased lower esophageal sphincter pressure; esophageal reflux

Central Nervous System and Developmental

Gastrointestinal dysmotility, complicated by cyclical vomiting (part of dysautonomic crisis)

Emotional lability, probably related to catecholamine imbalance

Respiratory System

Prolonged breath holding with crying, decerebrate posturing, syncope, cyanosis; may be misinterpreted as seizures

Recurrent pneumonias due to aspirations

Normal intelligence

Insensitivity to hypoxia and hypercapnia (no ventilatory response)

Delayed development

Low tolerance for hypoxia; profound hypotension and bradycardia in response to hypoxia

Ocular Manifestations

Cardiovascular System

Absence of overflow tears with emotional crying in all patients

Rapid severe orthostatic hypotension without compensatory tachycardia

Corneal insensitivity; abrasions and spontaneous injuries; ulcers

Episodes of severe hypertension and tachycardia as part of dysautonomic crisis

Optic neuropathy increasing with age

 

Laboratory Findings

 

Elevated blood urea nitrogen

 

Hyponatremia associated with excessive sweating

 

Catecholamine imbalance—elevated DOPA:DHPG ratio

 

 

Differential diagnosis typically does not present a problem, considering availability of genetic testing and the fact that this disease is restricted to Ashkenazi Jews. However, many other conditions have some similar symptoms of autonomic and sensory dysfunction. All HSANs, cranial nerve and/or nuclear dysplasias, cri du chat syndrome, and Möbius syndrome can have some of the features found in FD. Many eye conditions share similar ocular manifestations with those of FD.

Treatment in FD is symptomatic. Diazepam is the most effective treatment for dysautonomic crisis with vomiting. It also normalizes blood pressure and heart rate in these patients. Increased salt and fluid intake is used to treat dehydration and hyponatremia and associated postural hypotension. Fludrocortisone and midodrine are also used for this purpose. Surgical procedures performed on these patients include gastrostomies in majority of patients before 5 years of age to provide fluids and alimentations in patients with dysphagia; fundoplication for treatment of gastroesophageal reflux and associated pneumonia; and spinal fusions for severe scoliosis.

Preoperative Preparation.

Anesthesia for surgical procedures had been associated with great risks in patients with FD. [160] [161] [162] Recent progress in the understanding of existing risks and improved preoperative preparation resulted in significantly improved perioperative outcomes. [163] [164] [165] [166] Good working knowledge of FD manifestations and a systematic approach to preoperative assessment is essential for successful anesthetic management of these patients.

The respiratory system should be evaluated for signs of chronic or acute infections due to repeated aspirations. Chest radiography is warranted in all patients. In patients with restrictive pulmonary disease due to chronic pneumonias and scoliosis arterial blood gas analysis is included.

Severe intraoperative hypotonia is a well-recognized risk of general anesthesia. [160] [161] [162] Cardiac output is dependent on preload due to lack of compensatory sympathetic response to hypotonia. Correction of existing dehydration and hyponatremia is essential for intraoperative hemodynamic stability in these patients. Intravenous prehydration with crystalloids is often recommended to achieve euvolemic status preoperatively. [166] [167]

Patients are evaluated for the presence and severity of gastroesophageal reflux. Antacids need to be administered preoperatively to affected patients.

Renal function is assessed to rule out significant renal failure, which can affect the choice of muscle relaxants.

Patients with FD are prone to anticipation anxiety that can trigger dysautonomic crisis. Preoperative medication with benzodiazepines is recommended. Preoperative medication with opioids is contraindicated owing to the concern of increased sensitivity to the agents.

Intraoperative Considerations.

Intraoperative management of FD patients is directed toward better cardiovascular stability, prevention of pulmonary aspiration, prevention of postoperative respiratory compromise, and adequate postoperative pain control. Invasive hemodynamic monitoring (intra-arterial line and central venous catheters) has been advocated in the past but was not used in one reported series without untoward effects. [163] [166] It appears reasonable to use it in patients with postural hypotension and for extensive surgery with large fluid shifts. Immediate preinduction administration of fluid bolus can reduce blood pressure variation. Blood pressure instability intraoperatively is treated by additional fluid boluses and direct-acting vasopressors, if the patient is unresponsive to administration of fluids. Any episodes of desaturation are promptly addressed by increased oxygen concentration to avoid profound hypotension and bradycardia owing to lack of hypoxic compensatory responses.

Rapid-sequence induction with cricoid pressure should be considered in patients with gastroesophageal reflux and a history of repeated aspirations.

Careful planning for extubation, postoperative ventilatory support, and weaning from the respirator in the ICU should be part of the routine postoperative management for these patients. In the past, FD patients frequently required prolonged ventilation in the ICU setting after general anesthesia. Reports indicate that with alternative techniques, such as epidural[162] or local anesthesia, or deep propofol sedation with spontaneous ventilation,[165] these patients can recover from anesthesia very quickly without need for postoperative respiratory support.

Although patients with FD have decreased perception of pain and temperature, their visceral perception is intact and they need sufficient levels of anesthesia and postoperative pain control. Postoperative pain should be promptly treated to avoid dysautonomic crisis. Nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol will suffice in the many cases. Opioids should be used cautiously to avoid respiratory depression. Regional techniques can be useful.[162]

There have been no reports of adverse or prolonged responses to any specific anesthetic agents or muscle relaxants. For appropriate surgical procedures, regional anesthesia is well tolerated.[162] Use of deep propofol sedation for endoscopic outpatient procedures has been reported, with excellent results.[165]

Body temperature needs to be carefully monitored owing to impaired temperature control in these patients. The eyes should be lubricated and protected at all times.

In conclusion, FD is a serious anesthetic challenge that can be hazardous in these patients without proper preoperative preparations and intraoperative management. However, current approaches have resulted in significantly reduced mortality and morbidity in these patients.

Congenital Insensitivity to Pain with Anhidrosis (CIPA, or HSAN type IV)

Pathophysiology and Diagnosis.

CIPA is a rare autosomal recessive neuropathy characterized by recurrent episodic fever, anhidrosis (absence of sweating), pain insensitivity, self-mutilating behavior, and mental retardation.[158] Death from hyperthermia has been reported in infants with CIPA. Besides anhidrosis, it differs from FD by complete insensitivity to superficial and deep painful stimuli and normal lacrimation, much milder autonomic dysfunction, with absent postural hypotension or dysphagia. Self-inflicted multiple injuries are typical for these patients. This is often accompanied by accidental trauma, burns, wound infections, skin ulcers, joint deformities, and osteomyelitis.

There is only limited anesthetic experience in patients with CIPA. [168] [169] [170] Okuda and associates[167] suggest three important considerations in the anesthesia management of patients with CIPA: anxiety alleviation, temperature control, and adequate pain control. Despite congenital insensitivity to pain, general anesthesia was found to be necessary. Overall requirements of general anesthetics necessary for maintaining stable hemodynamics have been found to be only slightly reduced. General anesthesia was used in all patients in these reports without any adverse reactions to the intravenous or inhalational anesthetic agents, opioids, and succinylcholine. In one report, a patient died following intraoperative cardiac arrest without clear cause, although the authors suspected that the high concentration of halothane used (2%) could be responsible.[168] Previous recommendations against the use of atropine (or other anticholinergic drugs) to avoid hyperpyrexia in these patients was not supported by the results reported in this series. Many patients received atropine without any untoward effects.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

NEURODEGENERATIVE DISORDERS WITH AUTONOMIC FAILURE

Autonomic failure (or dysautonomia), with its protean range of manifestations and symptoms, is a common part of an immensely diverse group of disorders in which some or all elements of the autonomic nervous system are affected. Autonomic failure to a various degree is a part of the presentation of many systemic diseases (e.g., diabetes mellitus, amyloidosis), infectious diseases (e.g., leprosy, human immunodeficiency virus, rabies), immune disorders (e.g., acute dysautonomia, Guillain-Barré syndrome), paraneoplastic disorders, hereditary autonomic disorders (e.g., all HSANs, dopamine β-hydroxylase deficiency), and neurodegenerative disorders, to name just a few. A comprehensive discussion on various aspects of autonomic dysfunction in these conditions can be found in most neurology and medical textbooks. In this chapter we discuss only the most prevalent neurodegenerative disorders in which autonomic failure plays a prominent role, presenting a significant anesthetic challenge.

Parkinson's disease (PD), dementia with Lewy-body disorder (DLB), multiple system atrophy (MSA), and pure autonomic failure disorder (PAF) are all neurodegenerative disorders of unclear etiology, presenting with variable degrees of autonomic dysfunction. Based on the differences in the neuropathology, these disorders can be divided into two subgroups: Lewy-body syndromes (PD, DLB, and PAF) and multiple system atrophy (MSA). All these disorders are characterized by the presence of α-synuclein (hence, these disorders are often called synucleinopathies) in the neuronal (Lewy bodies, as in Lewy body syndromes) or glial (GCIs, as in MSA) cytoplasmic inclusions. In PD, neurodegeneration is predominant in the substantia nigra and other brain stem nuclei and in peripheral autonomic neurons. Motor dysfunction is more prominent than autonomic failure in PD patients. Neuronal degeneration in PAF is restricted to peripheral autonomic neurons, hence the symptoms of pure autonomic failure without other manifestations. Extensive cortical involvement, in addition to degeneration of brain stem nuclei and peripheral autonomic neurons, is characteristic for DLB, which presents as severe dementia associated with parkinsonism and autonomic failure.

In MSA, cytoplasmic inclusions are found in the glial cells (GCIs) and not neurons (Lewy body). These are associated with degenerative changes in the central neurons in basal ganglia, cortex, and spinal cord but not in peripheral autonomic neurons. Two phenotypes of MSA are currently identified based on the predominant clinical picture of parkinsonism (MSA-P) or cerebellar dysfunction (MSA-C). In the past, the patients with a predominant picture of autonomic failure were diagnosed with Shy-Drager syndrome. Today this term is rarely used, because all patients with MSA have a significant degree of autonomic dysfunction.[170]

Autonomic failure in patients with Lewy body syndromes and MSA is typically manifested by orthostatic and postprandial hypotension, bladder dysfunction, gastrointestinal motility disorders, and erectile sexual dysfunction. Orthostatic and postprandial hypotension is often the most disabling and early aspect of dysautonomia in many of these patients. Many other symptoms of autonomic dysfunction described in the section on familial dysautonomia can be present. The differential diagnosis can be very difficult owing to frequent overlapping of the clinical picture between these conditions, especially in the initial stages of the disease process. Definitive diagnosis in some disorders could be established only on postmortem histopathologic examination. However, thorough clinical examination helps to distinguish between PD, LBD, MSA, and PAF ( Table 8-10 ). The subject of neurodegenerative disorders with autonomic failure has been reviewed. [171] [172]

TABLE 8-10   -- Differential Diagnosis of Multiple System Atrophy, Parkinson's Disease, Pure Autonomic Failure, and Dementia with Lewy Bodies

Characteristic

Multiple System Atrophy

Parkinson's Disease

Pure Autonomic Failure

Dementia with Lewy Bodies

Central nervous system involvement

Multiple involvements

Multiple involvements

Unaffected

Multiple involvements

Site of lesions

Mainly preganglionic, central; degeneration of interomediolateral cell columns

Peripheral autonomic postganglionic neurons

Mainly peripheral autonomic postganglionic neurons; loss of ganglionic neurons

Cortex, brain stem, peripheral autonomic postganglionic neurons

Progression

Fast, median survival 6-8 years after first symptoms

Slow

Slow, up to 15 years and longer

Slow

Prognosis

Poor

Good

Good

Moderate to poor

Autonomic dysfunction

Early onset, severe

Late onset, usually mild to moderate

Severe, usually the only manifestation

Unclear, but can be severe

Extrapyramidal involvement

Common

Common

Absent

Common

Cerebellar involvement

Common

Common

Absent

Common

Lewy bodies

Mostly absent

Primarily in substantia nigra

Present in autonomic neurons

Cortex, brain stem, hippocampus

Glial cytoplasmic inclusions (postmortem staining)

Present

Absent

Absent

Absent

Response to chronic levodopa therapy

Poor

Good

 

Moderate

Dementia

Uncommon

Usually not severe, in 25%-30%of patients

Uncommon

Early, severe, rapidly progressing dementia

Adapted from Marti MJ, Tolosa E, Campdelacreu J: Clinical overview of the synucleinopathies. Mov Disord 2003;18(Suppl 6):S21-S27; and Kaufmann H, Biaggioni I: Autonomic failure in neurodegenerative disorders. Semin Neurol 2003;23:351-363.

 

 

 

Anesthetic management of PD is described elsewhere in this chapter. Although DLB is the second most common cause of dementia after Alzheimer's disease, there are no reports of anesthetic management in the literature. It appears reasonable to assume that the principles of anesthetic management of patients with DLB are common to those in patients with other forms of dementia. In DLB patients with advanced dysautonomia the same precautions should be taken as in patients with MSA.

Multiple System Atrophy

In 1998, Consensus Committees representing the American Autonomic Society and the American Academy of Neurology defined MSA as a sporadic, progressive, neurodegenerative disorder of undetermined etiology, characterized by features in the three clinical domains of parkinsonism, autonomic failure, and cerebellar or pyramidal dysfunction. In the past, the terms' “striatonigral degeneration,” “olivopontocerebellar atrophy,” and “Shy-Drager syndrome” were used, depending on the predominance of clinical symptoms in any of these three domains.

MSA is a fatal disease that typically presents in the fourth to sixth decade of life with a mean disease duration of 6 years from the onset of symptoms. Because of the significant similarity of clinical presentation to other neurodegenerative disorders, it is often not diagnosed until later stages. Parkinsonism is a predominant symptom in 80%, and cerebellar dysfunction is seen in 20% of all patients. Parkinsonism is usually not responsive to antiparkinsonian medications, which helps to differentiate it from PD. The most common and early presentation of autonomic dysfunction is urinary incontinence and erectile dysfunction (in male patients). Orthostatic hypotension is found in half of these patients and is usually mild. Reduced heart rate variability and absence of compensatory tachycardia during hypotension is characteristic. Paradoxically, supine hypertension is present in more than half of patients with MSA and complicates their management. Recurrent syncopes are signs of severe orthostatic hypotension. Severe constipation, fecal incontinence, and decreased sweating are other signs of autonomic dysfunction in MSA.

Obstructive sleep apnea or central sleep apnea and sleep-related inspiratory stridor associated with bilateral vocal cord paresis or dysfunction have been reported in MSA patients.[172]

There are no currently available treatments that can modify the clinical course or address the underlying pathologic process. All the treatments are symptomatic, intended for improving the quality of life in these patients. Orthostatic hypotension is treated with administration of fludrocortisone or milrinone (oral adrenergic vasoconstrictor). The presence of significant supine hypertension limits the use of vasopressors. Erythropoietin has been reported to be useful in the treatment of patients with associated anemia and severe hypotension. Tracheostomy and respiratory support is reserved for the patients with stridor and central sleep apnea.

Intraoperative Considerations.

Perioperative management of patients with MSA is a formidable challenge, owing to potential hemodynamic instability and possible respiratory compromise in the postoperative period. A few case reports in the literature indicate no adverse effects to most commonly used anesthetic agents. [174] [175] [176] [177] [178] [179] [180] [181] [182] [183] [184] The management is directed at ensuring hemodynamic stability by the use of invasive hemodynamic monitoring, adequate preoperative hydration, and maintenance of normovolemia with fluid replacement intraoperatively. Preoperative optimization of fludrocortisone therapy is recommended. There is some controversy in the literature regarding the potentially unpredictable response to vasopressor amines due to sympathetic hypersensitivity caused by autonomic denervation. [176] [185] Therefore, it is recommended to administer vasoactive medications very cautiously in much smaller doses than usual. However, vasopressors have been used without any adverse effects for treatment of hypotension intraoperatively, when titrated judiciously. [177] [178] [184]

Significant intraoperative supine hypertension has been reported with minimal response to labetalol but a profound hypotension after hydralazine administration.[185] The hypotension responded only to vasopressin infusion. It appears that short-acting vasodilators such as sodium nitroprusside may be a better choice for the treatment of intraoperative supine hypertension. The hypertensive episodes in autonomic failure are particularly responsive to transdermal nitroglycerin.[186]

Neuraxial anesthesia techniques have been successfully employed in patients with MSA, including for labor and delivery, with a greater degree of hemodynamic stability, also avoiding possible difficulties with extubation in these patients. [175] [180] [181] [183] [188] It is speculated that patients with autonomic failure are less likely to respond with hypotension to sympathectomy caused by neuraxial block because they are already sympathectomized. The data in the literature support this hypothesis.

When general anesthesia is opted for, careful planning for extubation and postoperative monitoring of the respiration in the ICU setting is warranted, especially in patients with a history of stridor or central or obstructive sleep apnea.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Pure Autonomic Failure

Pure autonomic failure (PAF) is a sporadic, slow-progressing neurodegenerative disorder of the autonomic nervous system that typically affects individuals in their sixth decade of life. It is characterized by an isolated impairment of the peripheral and central autonomic nervous system. No symptoms of parkinsonism, cerebellar dysfunction, or dementia are typically present. The orthostatic hypotension in this syndrome is typically very severe and more disabling than in other neurodegenerative disorders with autonomic failure. Other symptoms of autonomic failure are similar to those seen in MSA. The prognosis, however, is much better.

There is only one case report in the literature of general anesthesia without complications in a patient with PAF.[188] It is not very clear from the abstract provided whether the patient also had epidural anesthesia performed. However, the authors advocate the use of epidural anesthesia and invasive hemodynamic monitoring for greater hemodynamic stability.

It seems that the same principles of anesthetic management that are used for patients with MSA should be applied when managing PAF patients.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

NEUROECTODERMAL DISORDERS

Neuroectodermal disorders belong to a group of congenital malformations affecting structures of ectodermal origin and are characterized by coexistent skin and nervous system lesions. Neurofibromatosis types I (von Recklinghausen's disease) and II, von Hippel-Lindau disease (VHL), tuberous sclerosis, and Sturge-Weber syndrome are of particular interest to anesthesiologists, owing to the multiple anesthetic challenges that patients with these disorders may present. Patterns of inheritance, genetic characteristics, and encoded proteins associated with identified genetic mutations are provided in Table 8-11 . Neurofibromatoses, von Hippel-Lindau disease, and tuberous sclerosis are also often called phakomatoses on the basis of the patchy ophthalmologic manifestations observed in these disorders. There has been significant progress in the understanding of the pathogenesis of phakomatoses, which is characterized by loss of function of various tumor suppressor genes, which, in turn, leads to the development of benign or malignant tumors in many tissues.[189] Although the inheritance patterns and pathogenesis of Sturge-Weber are unknown, it is usually discussed together with phakomatoses, owing to the similarity of the clinical manifestations and to the distribution of lesions observed in these disorders.[190] All these disorders are chronic conditions, in which there is increasing pathology over the patient's lifetime.

TABLE 8-11   -- Patterns of Inheritance, Genetic Characteristics and Encoded Proteins Associated with Identified Genetic Mutations in Neuroectodermal Disorders

Disorder

Pattern of Inheritance

Genetic Mapping and Protein Product

Neurofibromatosis I (von Recklinghausen's disease)

Autosomal dominant trait, familial transmission in 50%; the rest are spontaneous mutations

NF1 gene on chromosome 17, truncated (nonfunctional) neurofibromin

 

Complete penetrance, variable expression

 

Neurofibromatosis II

 

NF2 tumor suppressor gene on chromosome 22, truncated merlin

Von Hippel-Lindau disease

Autosomal dominant trait with variable high penetrance

VHL gene on chromosome 3, VHL protein

 

 

Other genes may be involved.

Tuberous sclerosis

Autosomal dominant trait; 1 in 3 familial transmission, the rest spontaneous mutations or mosaicism

TSC1 gene on chromosome 9 and TSC2 on chromosome 16, encoding for hamatrin and tuberin, respectively

 

Complete penetrance, variable expression

 

Sturge-Weber syndrome

Not inherited

Unknown

 

 

Neurofibromatoses

Pathophysiology and Diagnosis.

Neurofibromatoses are genetic disorders of the nervous system primarily affecting the development and growth of neural tissues and causing subsequent growth of neural tumors. They are divided into type I, or NF1, also known by its eponym as von Recklinghausen's disease, and type II, or NF2. The former is much more common and accounts for 90% of all neurofibromatoses. These two types have different causes, and their clinical manifestations and diagnostic criteria differ significantly ( Table 8-12 ). Other rare forms of neurofibromatosis have been defined and reviewed.[191]


TABLE 8-12   -- Pathologic Findings, Clinical Manifestations, and Diagnosis of Neurofibromatosis Types 1 and 2

 

Type 1

Type 2

Neural Tissue Tumors

Neurofibromas (major feature) of the skin, peripheral nerves, and along nerve roots; plexiform neurofibromas (can become malignant), astrocytomas (not malignant), optic nerve gliomas

Vestibular (often called acoustic neuromas) or other cranial nerve schwannomas (main feature), spinal schwannomas, astrocytomas, meningiomas, ependymomas

Cutaneous Manifestations

Café-au-lait spots (usually the first symptom), cutaneous neurofibromas

Rare

Ocular Manifestations

Pigmented iris hamartomas or Lisch nodules

None

Central Nervous System (Besides Tumors)

Epilepsy, hydrocephalus, mild mental retardation more frequent than in general population

Intracerebral calcifications

Cardiovascular Involvement

Essential hypertension, renovascular (renal artery stenosis) hypertension, pheochromocytoma-related hypertension, vascular neurofibromatosis, aortic and cerebral aneurysms, obstruction of major thoracic vessels by neurofibromas

None

Pulmonary Involvement

Fibrosing alveolitis

None

Osseous Involvement

Many bone abnormalities, including chest deformities, kyphoscoliosis, sphenoid and occipital bone dysplasia, long-bone deformities, etc.

None

Other Systems

Neurofibromas of gastrointestinal system, intestinal carcinoid tumors, association with multiple endocrine neoplasia type III, which includes pheochromocytoma, NF1, and medullary thyroid carcinoma

None

Diagnostic Criteria

Cutaneous (95% of adult patients), nodular (peripheral nerves) and plexiform (30%) neurofibromas, café-au-lait spots, Lisch nodules (95%), optic nerve glioma

Bilateral acoustic neuromas or first-degree relative with NF2 in combination with unilateral acoustic neuroma, meningioma, glioma, or schwannoma

Symptoms

Symptomatic picture of NF1 is immensely diverse and determined by degree of involvement of various systems in the body. Severity of symptoms varies widely between patients

Tinnitus, poor balance caused by eighth nerve tumors

 

 

Headache, facial pain, facial numbness and other symptoms related to pressure effect of growing neural lesions

 

 

Preoperative Preparation.

While evaluating a patient diagnosed with neurofibromatosis for surgery and anesthesia, it is important to make a distinction between NF1 and NF2. Unlike patients with NF1, in which associated pathology may involve all systems in the body, relevant clinical manifestations of NF2 are largely limited to intracranial pathology.[192] It is worth mentioning that although NF2 is much less prevalent in the general population (1:210000) than NF1 (1:5000), most of the patients with NF2 will require surgical removal of cranial nerve schwannomas, an NF2 primary manifestation. As a result, anesthesiologists in neurosurgical practice frequently see these patients whereas in general practice the likelihood of seeing patients with NF2 is very low. To date, most anesthetic and medical literature concerned with management of neurofibromatosis is limited to NF1. Here, we cover mainly the issues related to the perioperative management of NF1 patients. The specifics of NF2 anesthetic management are addressed when relevant.

The severity of clinical manifestations of NF1 varies greatly between patients and usually increases over the patient's lifetime. NF1 might involve multiple organ systems, thus presenting a formidable challenge to an anesthesiologist. Familiarity with the clinical manifestations of NF1 and a systematic approach to preoperative assessment of these patients are essential to successful anesthetic management.[192]

Airway Assessment.

Thorough assessment of the airway is important in NF1 patients. Neurofibromas associated with NF1 can affect any segment of the airway. Intraoral lesions have been reported in up to 5% of patients with NF1, involving the tongue and the laryngeal and pharyngeal structures, leading to obstruction and dyspnea.[192] Plexiform and major subcutaneous neurofibromas are commonly found in the cervical region and parapharyngeal spaces. Large lesions can cause significant airway distortion and/or obstruction. Unanticipated sudden airway obstruction following induction of general anesthesia has been reported requiring emergency tracheostomy. [194] [195] Large neurofibromas originating in the posterior mediastinum, retroperitoneal space, or cervical paraspinal areas can lead to progressive compression of the distal airway. [196] [197] Additionally, involvement of the recurrent laryngeal nerve can result in unilateral vocal cord paralysis.[197] Cranial nerve involvement due to the large intracranial tumors found in neurofibromatosis can lead to impairment and loss of effective gag reflex and swallowing mechanisms,[192] which can leave the airway unprotected after extubation in these patients.

Additionally, some NF1 patients can have macrocephaly, mandibular abnormalities, and undiagnosed cervical spine instability, further complicating airway management. Patients with neurofibromas involving the cervical spine should be evaluated for cervical instability, including radiography, neck CT, or MRI as needed.

Cardiovascular Assessment.

All NF1 patients should be screened for hypertension, which is common, and is caused by renal artery stenosis, catecholamine-secreting nodular plexiform neurofibroma, or pheochromocytoma (found in up to 1% of patients).[198] In patients with hypertension that is paroxysmal or resistant to routine treatment, it is essential to exclude pheochromocytoma, which is associated with high intraoperative morbidity and may lead to death if not detected preoperatively.[192] All patients with NF1 should be questioned for the presence of brief headaches, anxiety attacks, palpitations, and night sweats, which are common for pheochromocytoma. Coarctation of the abdominal or thoracic aorta is another rare cause of hypertension in NF1.

Other cardiovascular pathologic processes associated with NF1 include vena caval obstruction by mediastinal tumors, generalized vasculopathy caused by vascular nodular proliferation, and potential association with hypertrophic cardiomyopathy.[192]

Pulmonary Assessment.

Pulmonary function should be evaluated for the presence of restrictive lung disease, which can be caused by kyphoscoliosis, intrapulmonary neurofibromas, and progressive pulmonary fibrosis associated with NF1.[192] Patients are questioned for the presence of cough or dyspnea. Chest radiography and arterial blood gas analysis are ordered if pulmonary involvement is suspected. It will help evaluate the need for postoperative ventilation and admission to an intensive care unit.

CNS Assessment.

CNS tumors are major manifestations of both NF1 and NF2. Therefore, all patients must be evaluated for undiagnosed CNS tumors and increased ICP. Absence of intracranial or intraspinal tumors on earlier examinations cannot be relied on, because new asymptomatic tumors in different locations can appear over time. Also, new neurologic symptoms should not be ascribed to the preexisting CNS lesions and the possibility of new pathology should be explored.

Additionally, these patients should be assessed for the presence of epilepsy and questioned for the nature of their seizures and type of anticonvulsant therapy. The possibility of cerebral aneurysms or intracranial internal carotid artery stenosis should be investigated if the patient is symptomatic.[199] The brain stem structures can also be affected by neurofibroma or gliomas, which can lead to central hypoventilation, requiring ventilation support with prolonged weaning after surgery.[200] Mild mental retardation may be present in these patients, and the degree of the patient's cooperation should be evaluated.

Other Systems.

Patients with NF1 may have carcinoid tumors, especially in the duodenum,[192] and present with carcinoid syndrome and significant risk of perioperative morbidity and mortality. Symptoms of carcinoid syndrome include flushing, bronchoconstriction, diarrhea, and right-sided heart lesions. Perioperative management of patients with carcinoid syndrome has been reviewed.[201] The association of NF1, carcinoid tumor, and pheochromocytoma would make the correct diagnosis especially difficult.[202]

NF1 in pregnancy presents an increased risk of severe hypertension, potentially rapid growth of CNS lesions, and intracranial hypertension. Patients should be assessed for the presence of an intraspinal tumor before the decision to employ neuraxial anesthesia is made. The association of pregnancy, NF1 and pheochromocytoma carries very high risks.[192]

Intraoperative Considerations.

Anesthetic experience in patients with neurofibromatosis is limited to few case reports. The anesthetic challenges in these patients are many, and anesthetic management should be designed, based on the existing pathology and its severity.

Awake fiberoptic intubation is the preferred approach in patients with airway lesions, although even elective awake fiberoptic intubation can fail when gross anatomic distortion is present.[203] In pediatric or mentally impaired patients, an asleep fiberoptic intubation in a spontaneously breathing patient should be considered. Sevoflurane induction followed by fiberoptic intubation in spontaneously breathing patients has been successfully employed.[204] In all NF1 patients with complicated airway, advanced planning as outlined in the American Society of Anesthesiologists' guidelines for the difficult airway management[205] is advised. A difficult airway cart and possibly equipment for emergency tracheostomy should be immediately available, depending on the severity of airway distortion.

The severity of the cardiovascular or cerebrovascular pathology will dictate the extent of hemodynamic monitoring. An intra-arterial catheter is advised in all patients with severe hypertension and associated cerebrovascular pathology to ensure appropriate cerebral perfusion pressure. Use of central venous and/or pulmonary artery catheter should be reserved for patients with active pheochromocytoma, carcinoid syndrome, and cardiac lesions with advanced cardiac disease.

Neuraxial anesthesia should not be performed in patients with increased intracranial pressure or intraspinal lesions. The presence of significant kyphoscoliosis might also complicate conduction of neuraxial anesthesia. If it is perceived that neuraxial anesthesia is preferable because of the high risk of general anesthesia, spinal cord neurofibromas and intracranial hypertension need to be ruled out using CT or MRI.[206]

Although there have been many reports of altered response to nondepolarizing muscular blockers and succinylcholine, the results of a large retrospective study indicate that the response to various muscular blockers is unchanged in patients with neurofibromatoses. [193] [208] However, neuromuscular blockade should be monitored, especially in NF1 patients with renal impairment or those receiving anticonvulsant therapy. Succinylcholine should be avoided in the presence of neurologic deficit.

There are no contraindications to any specific anesthetic agents. Potent inhalational agents and nitrous oxide should be used with caution in patients with large intracranial tumors and increased ICP.

Positioning of NF1 patients may be complicated by gross deformities of the chest, spine, or the neck. Potential cervical instability should be considered when positioning these patients. The combination of chest deformities and intrathoracic neurofibromas can lead to severe hemodynamic compromise caused by the sternal compression of the heart in the prone position.[208]

Careful planning for extubation is warranted in patients with difficult airway. Postoperative respiratory support and slow weaning may be necessary in patients with restrictive lung disease of hypoventilation syndromes due to the brain stem involvement.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Von Hippel-Lindau Disease

Pathophysiology and Diagnosis.

Von Hippel-Lindau disease (VHLD) is an autosomal dominant neoplastic syndrome of variable expression. It is characterized by the development of various benign or malignant tumors and cystic lesions in many organ systems.[209] Whereas hemangioblastomas of the retina and the CNS are the most typical lesions found in VHLD patients, lesions of many other visceral organs are frequently found. Organ distribution of the lesions associated with VHLD, their frequency, mean age at onset, and relevant clinical symptoms can be found in Table 8-13 . It is important to understand that the clinical presentation of VHLD is highly variable and progressive. Various tumors can affect multiple organs at the same time. Penetrance of VHLD increases with age, reaching 90% by the age of 60.[210] In the past, the majority of patients with VHDL died of complications of the renal cell carcinoma and CNS hemangioblastomas. With improvements in the treatment and diagnosis of VHDL, including serial screening and a multidisciplinary approach to management of these patients, their life expectancy has significantly improved.[209] Over their lifetime, the majority of patients with VHLD require surgical treatment under general anesthesia for the CNS hemangioblastomas, sometimes preceded by embolization, pheochromocytomas, and renal cell carcinoma.

TABLE 8-13   -- Von Hippel-Lindau Disease: Distribution of Lesions by Organs, Frequency, Age at Onset and Clinical Symptomatology

 

Frequency in Patients

Mean Age at Onset (yr)

Clinical Symptoms

CNS

Retinal hemangioblastoma

25%–60%

25

Glaucoma, vision loss, blindness

CNS hemangioblastomas

 Cerebellum

44%–72%

33

Headache, nausea, ataxia, motor and sensory deficits, hearing loss; pain syndromes

 Brainstem

10%–25%

32

 

 Spinal cord

13%–50%

33

 

 Lumbosacral nerve roots

<1%

Unknown

 

Supratentorial

<1%

Unknown

 

Endolymphatic sac tumors (petrous bone papillary adenoma)

11%

22

Hearing loss, tinnitus, vertigo, facial paresis

Syringomyelia

80% (in patients with CNS lesions)

 

 

Visceral

Renal cell carcinoma or cysts

25%–60%

39

Hematuria, flank pain

Pheochromocytoma

10%–20%

30

Often asymptomatic, with sudden hypertensive crisis

Pancreatic tumor or cysts

35%–70%

36

Abdominal pain, jaundice

Epididymal cystadenoma

25%–60%

Unknown

 

Broad ligament cystadenoma

Unknown

Unknown

 

 

 

Preoperative Preparation.

There are a number of serious anesthetic concerns in patients with VHLD that need to be considered during preoperative evaluation. These patients need to be evaluated for the presence of pheochromocytomas, CNS lesions, and renal function impairment due to renal cell carcinoma.

Pheochromocytomas, in, VHLD can be multiple, bilateral, and, in some patients, the only manifestation of the disease, with 5% of the tumors being malignant. Although pheochromocytomas are found only in 10% to 20% of VHLD patients, the recent preoperative screening for hidden pheochromocytomas is essential because of the high potential for perioperative hypertensive crisis, and potential mortality associated with undiagnosed pheochromocytoma, especially in pregnancy.[211] The subject of anesthesia for a patient with pheochromocytoma has been reviewed and covered in Chapter 13 .[212] Definitive diagnosis is based on demonstrating excessive production of catecholamines, by measuring urine and blood levels of catecholamines and urinary metanephrines, and supported by imaging tests (CT and MRI).[210]

CNS Hemangioblastomas.

Patients with VHLD should be evaluated for the presence, distribution, and size of the CNS lesions. Symptoms of increased ICP or local mass effect can be present in these patients, as described in Table 8-13 . The postoperative central hypoventilation syndrome and bulbar palsy with impairment of swallowing mechanisms have been reported after removal of brain stem hemangioblastomas.[213]Postoperative respiratory support and careful planning for extubation is warranted.

Intraoperative Considerations.

The experience of anesthetic management of patients with VHLD is limited to a few case reports in the literature. [215] [216] [217] [218] [219] [220] [221] [222] [223] The choice of anesthesia and monitoring in these patients is dictated by the type of surgery performed and the extent of the existing pathology. For example, the anesthetic management for a patient undergoing posterior fossa decompression in the sitting position for the excision of intramedullary hemangioblastoma is very different from what it would be for nephrectomy for renal cell carcinoma. There is no contraindication to use of any specific anesthetic agents.

The use of an intra-arterial catheter is indicated for craniotomy and pheochromocytoma removal. Use of a central venous and/or pulmonary artery catheter is warranted for the removal of pheochromocytoma.

Neuraxial anesthesia has been successfully used for cesarean section or delivery in patients with VHLD. [215] [217] [221] [223] However, risks related to use of neuraxial anesthesia in patients with an asymptomatic spinal cord and/or cerebellar hemangioblastomas should be carefully considered.[223]

Tuberous Sclerosis

Pathophysiology and Diagnosis.

Tuberous sclerosis (TS) complex is inherited as an autosomal dominant trait with a prevalence in the general population of 1 in 50,000 to 300,000 people. It is a multisystem disorder primarily characterized by cutaneous and neurologic involvement. However, cardiac, pulmonary, and renal involvement have also been reported.[189] The clinical picture of TS is determined by what organs are involved and the extent of that involvement. However, the most frequent clinical presentation of TS is generalized or partial seizures, which typically start in early childhood. The severity and onset of the seizure disorder correlate with degree of developmental problems.[189]

The characteristic skin lesions are usually the first evidence of TS, with the most common being hypopigmented macula in different shapes (90%), adenoma sebaceum (50%), “shagreen” patches, café-au-lait spots, fibromas, and angiomas. The CNS pathology consists of subependymal nodules or giant cell astrocytomas (90%) and hamartomatous regions in the cortex called tubers, which give the name to the disorder and are believed to be the cause of seizures (80% to 100%) and mental retardation (50%). Developmental delays, mental retardation, and behavioral problems are found in 45% to 70% of patients with TS. Cardiac rhabdomyomas are present in up to 50% of infants with TS and often regress with age.[224] A high incidence of congenital heart disease in patients with TS has been reported.[224]Cardiac abnormalities secondary to TS can lead to obstruction of flow, congestive heart failure, arrhythmias, conduction delays, and preexcitation. Renal lesions composed of primary renal cysts and angiomyolipomas are found in half of all patients with TS. Renal angiomyolipomas are associated with early-onset severe hypertension and may result in renal hemorrhage. Pulmonary cysts and lymphangiomyomatosis have been reported. Pleural thickening can lead to recurrent spontaneous pneumothorax. Upper airway fibromas and papillomas, involving the tongue, the palate, and, sometimes the larynx or the pharynx, have been reported in TS patients.

There is no specific treatment for the majority of TS manifestation, except for the standard medical anticonvulsant therapy. Based on the clinical series,[224] many of the patients with TS require general anesthesia for diagnostic or operative procedures in their childhood. The majority of them will do so for the surgical treatment of intractable seizures due to tuberous lesions.

Preoperative Preparation.

Preoperative evaluation of patients with TS should be directed toward determination of the extent of neurologic, cardiovascular, pulmonary/airway, and renal involvement.

Data on the nature of seizure disorder, anticonvulsant medications and their effectiveness, degree of mental retardation, and behavioral problems should be collected. Patient cooperation is also assessed. Increased ICP due to intracranial lesions should be excluded.

Cardiovascular assessment includes an ECG and is performed in all patients to exclude arrhythmias, conduction defects, or preexcitation, which are often found in patients with rhabdomyomas. If heart involvement is suspected, an echocardiography and chest radiograph are performed to rule out congenital heart disease and congestive heart failure due to rhabdomyomas or TS pulmonary involvement.

The upper airway should be evaluated for the presence of TS nodular tumors. A history of spontaneous pneumothorax is noted, because it can recur and is associated with high mortality. Chest radiography and arterial blood gas analysis are ordered if pulmonary involvement is suspected. It will help evaluate the need for postoperative ventilation and admission to an intensive care unit.

Renal function should be assessed and associated hypertension ruled out.

Intraoperative Considerations.

The experience of anesthetic management of patients with TS is limited to a number of case reports and retrospective series reported in the literature. [225] [226] [227] [228] [229] [230] No specific anesthetic agents are contraindicated in TS, and the choice of anesthetic is determined by the magnitude of the surgical procedure and the severity of TS.

Airway management might be complicated in patients with airway lesions, and alternatives to direct laryngoscopy should be considered. Careful planning for extubation in these patients is warranted and is based on the size of the airway masses and extent of pulmonary involvement.

Anticonvulsant therapy should be optimized before surgery and continued throughout the perioperative period. Anesthetic management is tailored to prevent exacerbation of seizures.

Neuromuscular blockade should be monitored with a nerve stimulator. The patients on chronic anticonvulsive therapy may have higher requirements for nondepolarizing muscle relaxants.[230]

Regional anesthesia is not contraindicated in TS patients and has been safely employed.[226]

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Sturge-Weber Syndrome

Pathophysiology and Diagnosis.

Sturge-Weber syndrome (SWS) is a rare congenital (not heritable) vascular disorder of unknown etiology.[190] Its hallmark manifestations are a facial angioma (port-wine stain) and a leptomeningeal angioma. The facial angioma, besides presenting a serious aesthetic problem for the patient, can also involve the eye structures, leading to glaucoma. In cases of increased intraocular pressure refractory to medication, surgical intervention is recommended. The leptomeningeal angioma is associated with progressive neurologic symptoms, such as seizures (80%), hemiparesis, mental retardation (50% to 66%), behavioral problems, visual field defects, and hydrocephalus. Seizures are treated with anticonvulsant therapy but may be refractory in more than 50% of cases. In refractory cases, hemispherectomy or limited surgical excision of epileptogenic tissue has been performed successfully. Differential diagnosis of SWS is not problematic, because clinical features do not overlap with other disorders. Prognosis for SWS patients is determined largely by the severity of seizures and by the size of leptomeningeal angioma. However, the disease is typically not fatal. There is no specific treatment for SWS, although the cutaneous, ocular, and neurologic manifestations of SWS are managed medically or surgically with mixed success.

Preoperative Preparation.

Most of the patients with SWS requiring a surgical procedure will need it for the surgical treatment of facial or ocular angioma or removal of intracranial leptomeningeal angioma causing seizures that are refractory to medical therapy. Preoperative evaluation of patients with SWS should be directed toward determination of the extent of neurologic pathology and associated symptoms. Patients should be evaluated for signs of increased ICP and hydrocephalus. If the surgical procedure is not for the treatment of seizures, optimization of anticonvulsant therapy should be considered.

Intraoperative Consideration.

There is little evidence in the literature to support any particular anesthetic approach to these patients. Two case reports in the literature describing anesthetic management of patients with SWS [232] [233] do not provide information regarding adverse reactions to particular anesthetic regimens. Adverse outcomes related to use of general anesthesia are also not reported in the surgical literature concerned with the management of patients with SWS.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

POSTERIOR FOSSA ANOMALIES AND ARNOLD-CHIARI MALFORMATIONS

The Arnold-Chiari malformation is a somewhat archaic eponym that is often used in the anesthesia literature to denote a group of congenital posterior fossa anomalies. This group of disorders includes many other disorders besides Chiari type I (CM I) and type II (CM II) malformations, and the list grows every year ( Table 8-14 ). A great deal of semantic confusion, which exists in the literature regarding precise definition and classification of this group of disorders, can be explained by rapid progress being made in the neuroimaging characterization of existing pathology and in the understanding of brain stem and cerebellar development. However, the current lack of understanding of etiology and pathogenesis in most of these conditions precludes a complete classification that would be accepted in all the different fields of medicine involved with the management of these disorders. This topic has been reviewed.[233] It is out of the scope of this text to provide discussion about all of the posterior fossa anomalies. Therefore, we will limit ourselves to discussion of the CM I and CM II, which constitute the vast majority of all posterior fossa anomalies in the general population. The rest of these disorders, or at least some of them, and their characteristic features are presented in Table 8-14 . It is worth mentioning that in the past the term Arnold-Chiari malformation, was often used as a combined term for different types of posterior fossa abnormalities or used interchangeably with Chiari type I and II. To avoid this semantic confusion we use the Chiari I and II malformation definition, which is most commonly used in the modern literature.

TABLE 8-14   -- Pathophysiology, Clinical Features and Associated Pathology in the Posterior Fossa Anomalies

Malformation Type

Pathophysiology

Clinical Features

Associated Pathology

Chiari type I malformation

Cerebellar tonsils displaced into cervical spinal canal, small posterior fossa

Usually presents in late teens or adult years; wide variety of neurologic symptoms caused by the upper cervical canal compression

Syringomyelia, syringobulbia, scoliosis, skeletal anomalies

Chiari type II malformation

Cerebellar vermis and brain stem displaced into cervical spinal canal

Presents at birth or early infancy; lower brain stem and cranial nerves dysfunction; could be medical emergency

Myelomeningocele and other lumbosacral neural tube closure defects, hydrocephalus, syringomyelia

Chiari type III malformation (very rare)

Cerebellum displaced into large occipital encephalocele

Respiratory and swallowing disorders, cranial nerves deficits, dystonias; often fatal

Corpus callosum agenesis, tentorium dysplasia, midbrain deformities

Dandy-Walker malformation

Cyst-like dilation of the fourth ventricle, enlarged posterior fossa, hypoplasia and anterior rotation of cerebellar vermis

Very heterogeneous in presentation, depending on associated pathology; ataxia, brain stem dysfunction, mental retardation (varies), hydrocephalus

Corpus callosum agenesis, brain stem anomalies, hydrocephalus

Jourbet's syndrome (extremely rare)

Cerebellar vermis aplasia

Motor hypotonia, ataxia, behavioral delay

Occipital meningocele, scoliosis, hydrocephalus, hepatic fibrosis

Cerebellar disruptions (very rare)

Cerebellar tissue loss

Motor deficits, mental retardation, often early death

 

Pontocerebellar hypoplasia (very rare)

Pontine hypoplasia, cerebellar hypoplasia

Severe developmental disorders, seizures, often early death

-

Rhombencephalosynapsis (extremely rare)

Cerebellar hemispheres fusion, vermis agenesis, fusion of dentate nuclei and superior cerebellar peduncles

Variable presentation; mental retardation, epilepsy, spasticity common

Hydrocephalus, ventriculomegaly

 

 

Chiari I Malformation

Pathophysiology and Diagnosis.

CM I is anatomically defined as an extension of the cerebellar tonsils below the foramen magnum. It is not associated with caudal displacement of the medulla or supratentorial abnormalities. The etiology of CM I is not well established. The small size of the posterior fossa causing the cerebellar displacement is the most likely explanation. Downward tonsillar displacement is not associated with any actual malformations of the cerebellum or midbrain structures found in most other posterior fossa anomalies.

The CM I is associated with the various skeletal and CNS abnormalities listed in Table 8-15 . The diagnosis of the CM I in otherwise asymptomatic patients is made progressively more often during the investigation of these abnormalities with neuroimaging techniques.[234]


TABLE 8-15   -- Abnormalities Associated with Chiari Malformation Type 1

Associated Abnormality

Important Features

Skeletal

Basilar impression

Decreased overall cervical spine mobility combined with cervical spine instability, increased risk of neurologic injury from minor trauma

Atlanto-occipital fusion

Klippel-Feil syndrome

Atlantoaxial assimilation

Scoliosis

Common finding in patients with syringomyelia

Central Nervous System

Syringomyelia

Usually maximal in the cervical cord

 

 

The signs and symptoms of the CM I can be divided into those caused by the compression of dural or neural structure by the displaced cerebellar tonsils and those related to the progressive development of syringomyelia ( Table 8-16 ). The patients with CM I usually become symptomatic in the late teens. However, some may firstdisplay symptoms at a more advanced age, even in the presence of the syringomyelia.[235]


TABLE 8-16   -- Signs and Symptoms in Chiari Type 1 Malformation

Signs and Symptoms

Important Features

Caused by Compression at the Craniocervical Junction

Occipital/posterior cervical pain

Associated with Valsalva maneuver

Weakness

Typically caused by the distortion of the medulla

Sensory deficits

 

Hyperreflexia

 

Babinski response

 

Vocal cord paralysis, hoarseness, dysarthria

Typically caused by the involvement of the lower cranial nerves

Dysphagia, recurrent aspirations

 

Sleep apnea

 

Sinus bradycardia, syncope

 

Ataxia

Symptoms of the rare cerebellar syndrome

Nystagmus

 

Caused by Syringomyelia

Upper limb weakness with atrophy

Usually starts distally at the hand and spreads proximally

Suspended sensory loss

Pain and temperature loss; touch and position preserved

Progressive scoliosis

 

Lower motor neuron paralysis

 

 

 

The differential diagnosis in CM I with syringomyelia is complex owing to a wide range of neurologic symptoms and signs observed in this condition. Many neurologic diseases of the spinal cord and cerebellum, including MS, SMA, ALS, spinocerebellar ataxias, mononeuropathy multiplex, cervical disc degenerative disease, and others have similar clinical picture. However, use of the CNS and skeletal imaging studies resolves most of these difficulties. A paucity of imaging findings in the presence of a florid clinical neurologic picture might make it difficult to differentiate CM I from hematomyelia, astrocytoma, or ependymoma of the spinal cord, Leigh disease, or necrotizing myelopathy.

Preoperative Preparation.

The majority of situations in which patients with CM I will require anesthesia for a surgery fall under two categories:

  

1.   

Suboccipital craniectomy with or without cervical laminectomies for the decompression of neural structures trapped in the foramen magnum. Occasionally, decompression or shunting of the coexisting syrinx is required.

  

2.   

Anesthesia for labor and delivery and cesarean section in parturients with CM I.

Generally, both categories pose similar anesthetic risk, although their preoperative neurologic status typically differs. The patients scheduled for craniectomy already present with some degree of neurologic involvement, which indicates significant compression of the neural elementsin the craniocervical junction. Most pregnant patients diagnosed with CM I are either asymptomatic or have already undergone surgical correction.[236]

Neurologic assessment is directed toward evaluation of signs of brain stem compression or cranial nerve involvement: vocal cord dysfunction, ventilation disorders, swallowing control. It is important to determine whether any neurologic symptoms are exacerbated with laughing, coughing, or exertion or during flexion-extension of the neck. Symptoms of increased intracranial pressure are sought. Appropriate imaging studies should be performed in all patients with suspected CM I. The presence of syringomyelia is determined even in patients without a clinical picture of myelopathy, especially in parturients, in whom neuraxial anesthesia is considered. The presence and location of motor deficit is noted to avoid overdosing nondepolarizing muscle relaxants by monitoring neuromuscular blockade on denervated muscles.

Autonomic function should be evaluated in patients with significant brain stem involvement. Subclinical autonomic dysfunction, a well-recognized condition in CM I, can result in unstable hemodynamics, lack of compensatory responses to hypotension, hypoxia, and hypocarbia intraoperatively. [238] [239] The absence of heart rate beat-to-beat variability and lack of cardiac responses to postural maneuvers are good predictors of autonomic dysfunction.

Cervical spine assessment is directed toward evaluation of possible associated cervical spine abnormalities listed in Table 8-15 . Limited range of motion could be due to cervical spine fusion combined with hypermobility between fused segments. Therefore, lateral and anteroposterior flexion-extension cervical spine radiographs are recommended.

Intraoperative Considerations.

General Anesthesia for Neurosurgical Procedures.

There are a number of case reports in the literature regarding anesthetic management of these patients for suboccipital decompression. [239] [240] [241] [242] [243] There is no evidence that any particular anesthetic agents are contraindicated for these patients. Although in one case the patient developed asystole after dural incision and draining of CSF, the patient promptly responded to atropine and ephedrine administration without sequelae.[242]

During induction of anesthesia and positioning, flexion-extension of the neck should be limited to prevent further compression of the neural structures. Fiberoptic bronchoscopic intubation, awake or asleep, is recommended in patients with skeletal cervical spine abnormalities and unstable cervical spine.[243] Careful planning for extubation, and possibly postoperative respiratory support with slow weaning, is indicated in patients with pronounced brain stem compression and cranial nerve involvement, owing to increased risk of postoperative ventilatory failure[238] or compromised upper airway reflexes. [245] [246] [247] Use of invasive monitoring is usually limited to the arterial line for measuring blood pressure and blood gases analysis in the postoperative period, if needed. Although, in the past, suboccipital decompression was often performed in the sitting position and was associated with high risk of venous air embolism, it is routinely performed in the prone position today. For this reason there is no need for right atrial catheter placement.

Anesthesia for Labor and Delivery.

There are a number of case reports [248] [249] [250] [251] [252] [253] [254] and retrospective series[236] on anesthetic management in this group of patients. In patients without an elevated ICP or significant neurologic symptomatology at the time of delivery, it seems to be safe to employ epidural, spinal, or general anesthesia with inhalational agents, whether for vaginal delivery or cesarean section. In those patients with increased intracranial pressure and neurologic deficits associated with syringomyelia the risks and benefits for any form of anesthesia should be carefully weighed, bearing in mind that dural puncture may result in the sudden neurologic deterioration caused by further cerebellar herniation. [253] [254] For labor, a combination of cervical and pudendal blocks, supplemented by parenteral opioids, could be the safest approach.[236] For a cesarean delivery, general endotracheal anesthesia directed toward preventing ICP elevations should be considered. Other considerations mentioned in the section for decompressive suboccipital craniotomy are also valid in these patients.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Chiari II Malformation, Myelomeningocele, and Hydrocephalus

Pathophysiology and Diagnosis.

CM II is very distinct in its presentation, anatomy, prognosis, and outcomes from CM I. One of the most striking features of CM II is that it is present in practically every child born with meningomyelocele (MMC). Conversely, CM II is diagnosed only in children with MMC.[254] Additionally, hydrocephalus is found or will develop in more than 80% of children born with MMC and CM II and often presents as a medical emergency requiring urgent shunt placement. Therefore, we are going to discuss these conditions and their implications for anesthesia care together.

Although the etiology of the CM II is not well understood, one of the possible and most likely explanations has been proposed by McLone and Knepper.[255] According to their theory, both open neural tube defect and incomplete spinal occlusion lead to CSF leakage out of the fetal spinal canal and ventricular system. The lack of ventricular CSF distention precludes the full development of the normal size posterior fossa, which, in turn, leads to the caudal displacement of the rapidly developing cerebellum into the spinal canal along with the brain stem. Anatomically, CM II is characterized by the caudal displacement of the cerebellar vermis (not the cerebellar tonsils, as in CM I) below the foramen magnum. The vermis could reach as far down as the upper thoracic spinal canal as the child ages. Other neuroanatomic anomalies typically found in CM II include small upward rotated cerebellum, caudal displacement of the medulla (and sometimes the pons) into the spinal canal, small posterior fossa, multiple ventricular anomalies, and small fourth ventricle and the aqueduct. The foramen magnum is often enlarged. Additionally, hypoplasia or aplasia of cranial nerve nuclei is often present (20%). Other associated abnormalities of MMC and CM II include neurogenic bladder, neurogenic bowel, multiple orthopedic deformities, and lower extremity fractures. These latter conditions often require repeated corrective surgical procedures under general anesthesia.

It is important to understand that the first indication of possible CM II in the newborn is the presence of MMC, which will require urgent repair. However, these neonates must be evaluated for the signs and symptoms of CM II. Asymptomatic CM II is the most common cause of death in children with MMC younger than 2 years of age. Close to one third of patients with MMC will develop symptoms of brain stem compression, and one third of them will die[254] before the age of 5 years. Therefore, all symptomatic CM II patients should be aggressively evaluated for hydrocephalus and considered for CSF shunt placement. Symptomatic CM II in children younger than 2 years typically has a different presentation than in older children ( Table 8-17 ).

TABLE 8-17   -- Chiari Malformation Type II Clinical Presentation in Early and Late Childhood

 

Signs and Symptoms

Implications

Children ≤ 2 Yr

Increasing hydrocephalus

Inspiratory stridor due to vocal cords abduction paralysis/paresis, apneic episodes (including cyanotic expiratory apnea of central origin), swallowing difficulties, chronic aspirations, weak gag reflex, dysphagia, malnutrition

Often emergency presentation; life threatening; shunt placement is lifesaving (although not in all infants)

Brain stem dysfunction

Ninth and 10th cranial nerve dysfunction

Older Children

Cervical myelopathy

Weakness and spasticity of upper extremities, occipital headache, craniocervical pain, ataxia, sensory loss, scoliosis

Slowly progressing, rarely life threatening; decompressive surgery is often performed after normal cerebrospinal fluid shunt function confirmed

 

 

Preoperative Preparation.

Most children with CM II undergo MMC repair procedure in the first hours of their life. The principles of anesthetic management for MMC repair can be found in most pediatric anesthesia texts. All other procedures typically required by these patients during their lifetime can be divided into three categories: emergency decompressive surgery or CSF shunt placement in stridorous infants, elective decompressive procedure (e.g., cervical laminectomies), or corrective surgical procedures for associated pathology (e.g., bladder surgery, orthopedic procedures) in patients without obvious symptoms of CM II.

Emergency Procedures.

These patients should be evaluated for the signs of vocal cord dysfunction and breathing disorders. Patients with these symptoms may develop respiratory depression, such as apneic spells and vocal cord paralysis, even if the ICP is well controlled. [245] [257] They should be monitored postoperatively in the ICU for the signs of apnea and the compromised airway. Careful planning for extubation is recommended. Volemic status should be evaluated in patients with unrepaired MMC, with potentially significant loss of CSF.

Elective Procedures.

The most important step in the surgical and anesthetic preoperative evaluation of these patients is to rule out nonfunctioning shunt or latent hydrocephalus. Otherwise, the considerations are similar to those described in patients with CM I.

Intraoperative Considerations.

Anesthetic management in the literature on CM II is limited to two case reports and a series. There are no clear contraindications to any particular anesthetic agents. Positioning of the patient may be a challenge, especially in those cases when shunt placement is performed simultaneously with MMC repair. Extremes of the neck flexion or extension should be avoided to prevent further compression of neural structures in the upper cervical canal.

Inhalational mask induction, even in the asymptomatic child, can be complicated by apneic spells and laryngospasm.[257]

In the past, when suboccipital decompressive craniectomy and duraplasty was performed, an increased risk of inadvertent hemorrhage from the occipital or transverse sinuses had to be considered in these patients. This life-threatening complication was associated with venous airembolism and carried very high mortality. This surgery is rarely recommended today. However, invasive hemodynamic monitoring is indicated for decompressive cervical laminectomies.

Succinylcholine should be avoided in patients with motor deficits, which are typically present in these patients after MMC repairs or as a result of cervical myelopathies. Neuromuscular blockade should be monitored on the limbs not affected by motor deficits to avoid overdosing.

Intraoperative considerations for orthopedic, urologic, and other corrective procedures in asymptomatic patients are similar to those in patients with CM I.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

KLIPPEL-FEIL SYNDROME AND OTHER CERVICAL SPINE DISORDERS OF CHILDHOOD

Anesthetic care of patients with cervical spine disorders resulting from congenital or developmental alterations in childhood represent a unique and complex challenge. Increased susceptibility to cervical spine injury and subsequent neurologic deficit, often combined with anatomically difficult airway, are common for this diverse group of disorders of different etiology. Understanding of the anatomic and pathophysiologic features of these disorders, thorough preoperative evaluation, and appropriate early management are essential in prevention of neurologic injury and other anesthetic complications in these patients. [259] [260] Klippel-Feil syndrome is a member of this group and is often mentioned in the anesthetic literature. It also presents one of the most formidable anesthetic challenges. For simplicity of presentation, other disorders in this section are discussed in conjunction with the discussion of the preoperative evaluation and anesthetic management of this syndrome.

Pathophysiology and Diagnosis.

Klippel-Feil syndrome is a rare (1 in 42,000 births) congenital anomaly of the cervical spine typically characterized by fusion of two or more cervical vertebrae. It is unclear whether Klippel-Feil syndrome is a discrete entity with common genetic etiology or a phenotypic presentation of a heterogeneous group of congenital spinal deformities.[260] The classic triad of short neck, low posterior hairline, and limitations of cervical motion are found in less than half of patients with this condition. Other common associated findings include congenital scoliosis (50% of patients), renal abnormalities (one third of patients), the Sprengel deformity (congenital elevation of scapula), hearing impairment, posterior fossa dermoid cysts, and congenital heart disease (the most frequent being ventricular septal defect). Overall decreased neck mobility is the most common physical finding. This finding is often combined with hypermobility between fused vertebral segments, which puts these patients at high risk for either spontaneous neurologic injury, or neurologic injury as a result of minor trauma.[261] Many neurologic symptoms caused by cranial nerve abnormalities, cervical radiculopathy, or myelopathy are typically found in the second or third decade of life. Most neurologic manifestations are secondary to chronic compression of the cervical spinal cord, pons, medulla, and stretching of the cranial nerves. Sudden neck movement or minor falls can cause basilar artery insufficiency and syncope. Tetraplegia has been reported as a result of minor trauma in these patients.[261] This syndrome is often classified into three different types, depending on the location of the fused cervical vertebrae. The presentation of clinical and anatomic features of this syndrome varies widely, ranging from mild deformity to severe disability.

Alternative Conditions.

Cervical spine abnormalities similar to those observed in Klippel-Feil syndrome are frequently seen in other uncommon disorders listed in Table 8-18 .[258] Cervical instability, increased risk of severe neurologic injury from minor trauma, and difficult airway is common for all of these conditions. A full description of these disorders and relevant anesthetic issues can be found either in the subsequent sections of this chapter or other chapters of this book.

TABLE 8-18   -- Cervical Spine Disorders

Disorder

Cervical Spine Abnormalities

Symptoms

Down syndrome

Occipitocervical or atlantoaxial instability

Muscle weakness, gait abnormality, neck pain

Achondroplasia

Foramen magnum stenosis, lumbar spine stenosis, cervical instability is uncommon

Severe sleep apnea and sudden death in early childhood

Spondyloepiphyseal dysplasia

Odontoid hypoplasia and/or os odontoideum with atlantoaxial instability

Persistent hypotonia, motor developmental delay

Mucopolysaccharidoses, Morquio syndrome

Odontoid hypoplasia with atlantoaxial instability and progressive myelopathy, extradural soft tissue hypertrophy

Severe neurologic compromise secondary to upper cervical spinal cord compression, sudden death

Isolated odontoid anomalies: aplasia, hypoplasia, os odontoideum

Progressive atlantoaxial instability

Symptoms of upper cervical spinal cord injury, sudden death

 

 

Preoperative Preparation.

Preoperative assessment in patients with cervical spine disorders should primarily be directed at the evaluation of degree of cervical instability present, preexistent neurologic impairment, and the evaluation of airway. A previous uneventful anesthetic history is a poor predictor of difficult airway or neurologic complications in patients with Klippel-Feil syndrome, because cervical fusion becomes progressively worse with time.[262] Therefore, lateral and anteroposterior flexion-extension cervical spine radiographs are recommended. Cervical MRI is indicated to assess the degree of neurologic involvement, such as cord compression and myelopathy. Other perioperative considerations should include the following:

  

1.   

Congenital heart defects and cardiac conduction abnormalities. Preoperative ECG and echocardiography are indicated.

  

2.   

Assessment of pulmonary function, which could be severely compromised in patients with chest deformities and advanced scoliosis. Consider chest radiography and pulmonary function tests.

  

3.   

Renal function. Patients with Klippel-Feil syndrome should be evaluated for kidney anomalies and renal failure.

Intraoperative Considerations.

Anesthetic experience in Klippel-Feil syndrome patients is limited to a number of case reports. [244] [260] [264] [268] The main anesthetic challenge in these patients is airway management and positioning.

Airway Management.

Awake fiberoptic intubation is the preferred approach whenever possible. [244] [264] [268] However, most pediatric and mentally impaired (Down syndrome) patients are not suitable candidates, and asleep fiberoptic intubation in a spontaneously breathing patient should be considered. Direct laryngoscopy is likely to be difficult owing to multiple facial, neck, and chest deformities. However, when direct laryngoscopy is chosen, a neutral neck axis needs to be maintained to avoid neurologic sequelae. The laryngeal mask airway can be used to ventilate these patients, although intubation via laryngeal mask may be technically difficult.[264]

Positioning.

Positioning of patients with Klippel-Feil syndrome may be difficult owing to multiple head, neck, and thoracic deformities. Great care must be taken to avoid any cervical tension or sudden neck movements while positioning these patients. It is important to understand that the risk of neurologic injury in these patients is not limited to laryngoscopy and intubation and may develop thereafter. [260] [264] [269]

Regional anesthesia has been successfully performed in these patients [266] [267] and might be preferable if indicated, to avoid potential neurologic and respiratory complications related to airway management. It can be difficult to perform considering various spine deformities associated with this condition.

Neuromuscular Blockade.

Succinylcholine should be avoided in the presence of neurologic deficit. In patients with associated renal anomalies accompanied by renal failure, the use of nondepolarizing muscle relaxants for which excretion is dependent on renal function is contraindicated.

Other Issues.

Careful planning for extubation is warranted in patients with significantly compromised pulmonary function and after very difficult intubation. There are no contraindications to any specific anesthetic drugs in these patients.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Acknowledgment

This chapter is based on the chapter on Neurologic Diseases in the third and fourth editions of Anesthesia and Uncommon Diseases, authored by Drs. Martz, Schreibman, and Matjasko, who provided a comprehensive approach. We have reorganized this chapter by sections, keeping some of the disease categories but changing others to reflect current neurology nomenclature.

Copyright © 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

References

  1. Nicholson G, Pereira AC, Hall GM: Parkinson's disease and anaesthesia.  Br J Anaesth2002; 89:904-916.
  2. In: Adams RD, Victor M, Ropper AH, ed. Principles of Neurology,  New York: McGraw-Hill; 1997.
  3. Berg D, Becker G, Reiners K: Reduction of dyskinesia and induction of akinesia induced by morphine in two parkinsonian patients with severe sciatica.  J Neural Transm1999; 106:725-728.
  4. Anderson BJ, Marks PV, Futter ME: Propofol: Contrasting effects in movement disorders.  Br J Neurosurg1994; 8:387-388.
  5. Gravlee GP: Succinylcholine-induced hyperkalemia in a patient with Parkinson's disease.  Anesth Analg1980; 59:444-446.
  6. Cooperman LH: Succinylcholine-induced hyperkalemia in neuromuscular disease.  JAMA1970; 213:1867-1871.
  7. Muzzi DA, Black S, Cucchiara RF: The lack of effect of succinylcholine on serum potassium in patients with Parkinson's disease.  Anesthesiology1989; 71:322.
  8. Veasy LG, Tani LY, Hill HR: Persistence of acute rheumatic fever in the intermountain area of the United States.  J Pediatr1994; 124:9-16.
  9. Carapetis JR, Currie BJ: Rheumatic chorea in northern Australia: A clinical and epidemiological study.  Arch Dis Child1999; 80:353-358.
  10. Aron, AM, Freeman, JM, Cavalcanti, F: The natural history of Sydenham's chorea: Review of the literature and long-term evaluation with emphasis on cardiac sequelae.  Am J Med1965; 38:83.
  11. Trottier Y, Lutz Y, Stevanin G, et al: Polyglutamine expansion as a pathological epitope in Huntington's disease and four dominant cerebellar ataxias.  Nature1995; 378:403-406.
  12. Schaffar G, Breuer P, Boteva R, et al: Cellular toxicity of polyglutamine expansion proteins: Mechanism of transcription factor deactivation.  Mol Cell2004; 15:95-105.
  13. Bence NF, Sampat RM, Kopito RR: Impairment of the ubiquitin-proteasome system by protein aggregation.  Science2001; 292:1552-1555.
  14. Kells AP, Fong DM, Dragunow M, et al: AAV-mediated gene delivery of BDNF or GDNF is neuroprotective in a model of Huntington disease.  Mol Ther2004; 9:628-682.
  15. Bloch J, Bachoud-Levi AC, Deglon N, et al: Neuroprotective gene therapy for Huntington's disease, using polymer-encapsulated cells engineered to secrete human ciliary neurotrophic factor: results of a phase I study.  Hum Gene Ther2004; 15:968-975.
  16. Davies DD: Abnormal response to anaesthesia in a case of Huntington's chorea.  Br J Anaesth1966; 38:490-491.
  17. Soar J, Matheson KH: A safe anaesthetic in Huntington's disease?.  Anaesthesia1993; 48:743-744.
  18. Farina J, Rauscher L: Anaesthesia and Huntington's chorea: A report of two cases.  Br J Anaesth1977; 49:1149-1167.
  19. Browne M: Anaesthesia in Huntington's chorea.  Anaesthesia1982; 38:65.
  20. Gupta K, Leng CP: Anaesthesia and juvenile Huntington's disease.  Paediatr Anaesth2000; 10:107-109.
  21. Gaubatz CL, Wehner RJ: Anesthetic considerations for the patient with Huntington's disease.  AANA J1992; 60:41-44.
  22. Cangemi Jr CF, Miller RJ: Huntington's disease: Review and anesthetic case management.  Anesth Progress1998; 45:150-153.
  23. Nagele P, Hammerle AF: Sevoflurane and mivacurium in a patient with Huntington's chorea.  Br J Anaesth2000; 85:320-321.
  24. Gualandi W, Bonfanti G: [A case of prolonged apnea in Huntington's chorea].  Acta Anaesth1968; 19(Suppl 6):235-238.
  25. Mitra S, Sharma K, Arora S, et al: Repeat anesthetic management of a patient with Huntington's chorea.  Can J Anaesth2001; 48:933-934.
  26. Gillman MA, Sandyk R: Nitrous oxide ameliorates spasmodic torticollis.  Eur Neurol1985; 24:292-293.
  27. Stemp LI, Taswell C: Spastic torticollis during general anesthesia: Case report and review of receptor mechanisms.  Anesthesiology1991; 75:365-366.
  28. Steen SN: Anesthetic management for basal ganglia surgery in patients with movement disorders.  Anesth Analg1965; 44:66-69.
  29. Worms PM: The epidemiology of motor neuron diseases: A review of recent studies.  J Neurol Sci2001; 191:3-9.
  30. Andersen PM, Sims KB, Xin WW, et al: Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: A decade of discoveries, defects and disputes.  Amyotroph Lateral Scler Other Motor Neuron Disord2003; 4:62-73.
  31. Turner JB, Atkin DJ, Farg AM, et al: Impaired extracellular secretion of mutant superoxide dismutase 1 associates with neurotoxicity in familial amyotrophic lateral sclerosis.  J Neurosci2005; 1:108-117.
  32. Storkebaum E: Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS.  Neuroscience2005; 8:85-92.
  33. Gronert GA, Lambert EH, Theye RA: The response of denervated skeletal muscle to succinylcholine.  Anesthesiology1973; 39:13-22.
  34. Rosenbaum KJ, Neigh JL, Strobel GE: Sensitivity to nondepolarizing muscle relaxants in amyotrophic lateral sclerosis: Report of two cases.  Anesthesiology1971; 35:638-641.
  35. Otsuka N, Igarashi M, Shimodate Y, et al: [Anesthetic management of two patients with amyotrophic lateral sclerosis (ALS)]. [Japanese].  Masui2004; 53:1279-1281.
  36. Hara K, Sakura S, Saito Y, et al: Epidural anesthesia and pulmonary function in a patient with amyotrophic lateral sclerosis.  Anesth Analg1996; 83:878-879.
  37. Lacomblez L, Bensimon G, Leigh PN, et al: Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II.  Lancet1996; 347:1425-1431.
  38. Mitsumoto H: Riluzole what is its impact in our treatment and understanding of amyotrophic lateral sclerosis?.  Ann Pharmacother1997; 31:779-781.
  39. Miller RG, Mitchell JD, Lyon M, Moore DH: Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND).  Cochrane Database Syst Rev2002;CD001447
  40. Labuda M, Labuda D, Miranda C: Unique origin and specific ethnic distribution of the Friedreich ataxia GAA expansion.  Neurology2000; 54:2322.
  41. Durr A, Cossee M, Agid Y, et al: Clinical and genetic abnormalities in patients with Friedreich's ataxia.  N Engl J Med1996; 335:1169-1175.
  42. Campuzano V, Montermini L, Molto MD, et al: Friedreich's ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion.  Science1996; 271:1423-1427.
  43. Levent K, Yavuz G, Kamil T: Anaesthesia for Friedreich's ataxia: Case report.  Min Anestesiol2000; 66:657-660.
  44. Buettner AU: Anaesthesia for caesarean section in a patient with spinal muscular atrophy.  Anaesth Intensive Care2003; 31:92-94.
  45. Kitson R, Williams V, Howell C: Caesarean section in a parturient with type III spinal muscular atrophy and pre-eclampsia.  Anaesthesia2004; 59:94-95.
  46. McLoughlin L, Bhagvat P: Anaesthesia for caesarean section in spinal muscular atrophy type III.  Int J Obstet Anesth2004; 13:192-195.
  47. Watts JC: Total intravenous anaesthesia without muscle relaxant for eye surgery in a patient with Kugelberg-Welander syndrome.  Anaesthesia2003; 58:96.
  48. Habib AS, Helsley SE, Millar S, et al: Anesthesia for cesarean section in a patient with spinal muscular atrophy.  J Clin Anesth2004; 16:217-219.
  49. De Jonghe B, Sharshar T, Lefaucheur JP, et al: Groupe de Reflexion et d'Etude des Neuromyopathies en Reanimation: Paresis acquired in the intensive care unit: A prospective multicenter study.  JAMA2002; 288:2859-2867.
  50. Deem S, Lee CM, Curtis JR: Acquired neuromuscular disorders in the intensive care unit.  Am J Respir Crit Care Med2003; 168:735.
  51. Larsson L, Li X, Edstrom L, et al: Acute quadriplegia and loss of muscle myosin in patients treated with nondepolarizing neuromuscular blocking agents and corticosteroids: Mechanisms at the cellular and molecular levels.  Crit Care Med2000; 28:34-45.
  52. Feasby TE, Gilbert JJ, Brown WF, et al: An acute axonal form of Guillain-Barré polyneuropathy.  Brain1986; 109:1115-1126.
  53. Yuki N, Yoshino H, Sato S, Miyatake T: Acute axonal polyneuropathy associated with anti-GM1 antibodies following Campylobacter enteritis.  Neurology1990; 40:1900-1902.
  54. McKhann GM, Cornblath DR, Griffin JW, et al: Acute motor axonal neuropathy: A frequent cause of acute flaccid paralysis in China.  Ann Neurol1993; 33:333-342.
  55. Visser LH, Van der Meche FG, Van Doorn PA, et al: Guillain-Barré syndrome without sensory loss (acute motor neuropathy): A subgroup with specific clinical, electrodiagnostic and laboratory features. Dutch Guillain-Barré Study Group.  Brain1995; 118:841-847.
  56. Ho TW, Mishu B, Li CY, et al: Guillain-Barré syndrome in northern China: Relationship to Campylobacter jejuni infection and anti-glycolipid antibodies.  Brain1995; 118:597-605.
  57. Fisher M: An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia).  N Engl J Med1956; 255:56-57.
  58. Hahn AF: Guillain-Barré syndrome.  Lancet1998; 352:635-641.
  59. Jacobs BC, Rothbarth PH, Van der Meche FG, et al: The spectrum of antecedent infections in Guillain-Barré syndrome: A case-control study.  Neurology1998; 51:1110-1115.
  60. Osterman PO, Fagius J, Lundemo G, et al: Beneficial effects of plasma exchange in acute inflammatory polyradiculoneuropathy.  Lancet1984; 2:1296-1299.
  61. Brooks H, Christian AS, May AE: Pregnancy, anaesthesia and Guillain-Barré syndrome.  Anaesthesia2000; 55:894-898.
  62. Ohta M, Nishikawa N, Kida H, Miyao S: [Anesthetic management of two patients with polymyositis].  Masui2000; 49:1371-1373.2000. Japanese
  63. Fujita A, Okutani R, Fu K: [Anesthetic management for colon resection in a patient with polymyositis].  Masui1996; 45:334-336.Japanese.
  64. Rockelein S, Gebert M, Baar H, Endsberger G: [Neuromuscular blockade with atracurium in dermatomyositis].  Anaesthesist1995; 44:442-444.German.
  65. Artru AA: Relationship between cerebral blood volume and CSF pressure during anesthesia with isoflurane or fentanyl in dogs.  Anesthesiology1984; 60:575-579.
  66. Artru AA: Effects of halothane and fentanyl on the rate of CSF production in dogs.  Anesth Analg1983; 62:581-585.
  67. Artru AA: Isoflurane does not increase the rate of CSF production in the dog.  Anesthesiology1984; 60:193-197.
  68. Sugioka S: [Effects of sevoflurane on intracranial pressure and formation and absorption of cerebrospinal fluid in cats].  Masui1992; 41:1434-1442.Japanese.
  69. Artru AA, Momota T: Rate of CSF formation and resistance to reabsorption of CSF during sevoflurane or remifentanil in rabbits.  J Neurosurg Anesth2000; 12:37-43.
  70. Walchenbach R, Geiger E, Thomeer RT, Vanneste JA: The value of temporary external lumbar CSF drainage in predicting the outcome of shunting on normal pressure hydrocephalus.  J Neurol Neurosurg Psychiatry2002; 72:503-506.
  71. Kaul HL, Jayalaxmi T, Gode GR, Mitra DK: Effect of ketamine on intracranial pressure in hydrocephalic children.  Anaesthesia1976; 31:698-701.
  72. Krauss JK, Regel JP, Vach W, et al: Vascular risk factors and arteriosclerotic disease in idiopathic normal-pressure hydrocephalus of the elderly.  Stroke1996; 27:24-29.
  73. Tsai TC, He CC, Wu SZ, et al: Normal pressure hydrocephalus found after anesthesia a case report.  Acta Anaesth Sin2003; 41:197-200.
  74. Kristensen B, Malm J, Fagerland M, et al: Regional cerebral blood flow, white matter abnormalities, and cerebrospinal fluid hydrodynamics in patients with idiopathic adult hydrocephalus syndrome.  J Neurol Neurosurg Psychiatry1996; 60:282-288.
  75. Vanneste JA: Three decades of normal pressure hydrocephalus: Are we wiser now?.  J Neurol Neurosurg Psychiatry1994; 57:1021-1025.
  76. Black PM: Idiopathic normal-pressure hydrocephalus: Results of shunting in 62 patients.  J Neurosurg1980; 52:371-377.
  77. Wikkelso C, Andersson H, Blomstrand C, et al: Normal pressure hydrocephalus: Predictive value of the cerebrospinal fluid tap-test.  Acta Neurol Scand1986; 73:566-573.
  78. Knopman DS: An overview of common non-Alzheimer dementias.  Clin Geriatr G Med2001; 17(2):281-301.
  79. Malm J, Kristensen B, Markgren P, Ekstedt J: CSF hydrodynamics in idiopathic intracranial hypertension: A long-term study.  Neurology1992; 42:851-858.
  80. Owler BK, Parker G, Halmagyi GM, et al: Pseudotumor cerebri syndrome: Venous sinus obstruction and its treatment with stent placement.  J Neurosurg2003; 98:1045-1055.
  81. Karahalios DG, Rekate HL, Khayata MH, Apostolides PJ: Elevated intracranial venous pressure as a universal mechanism in pseudotumor cerebri of varying etiologies.  Neurology1996; 46:198-202.
  82. Jain N, Rosner F: Idiopathic intracranial hypertension: Report of seven cases.  Am J Med1992; 93:391-395.
  83. Rosenberg ML, Corbett JJ, Smith C, et al: Cerebrospinal fluid diversion procedures in pseudotumor cerebri.  Neurology1993; 43:1071-1072.
  84. Spoor TC, McHenry JG: Long-term effectiveness of optic nerve sheath decompression for pseudotumor cerebri.  Arch Ophthalmol1993; 111:632-635.
  85. Kelman SE, Heaps R, Wolf A, Elman MJ: Optic nerve decompression surgery improves visual function in patients with pseudotumor cerebri.  Neurosurgery1992; 30:391-395.
  86. Corbett JJ, Thompson HS: The rational management of idiopathic intracranial hypertension.  Arch Neurol1989; 46:1049-1051.
  87. Kelman SE, Sergott RC, Cioffi GA, et al: Modified optic nerve decompression in patients with functioning lumboperitoneal shunts and progressive visual loss.  Ophthalmology1991; 98:1449-1453.
  88. Abouleish E, Ali V, Tang RA: Benign intracranial hypertension and anesthesia for cesarean section.  Anesthesiology1985; 63:705-707.
  89. Biyani A, el Masry WS: Post-traumatic syringomyelia: A review of the literature.  Paraplegia1994; 32(11):723-731.
  90. Adler R, Lenz G: Neurological complaints after unsuccessful spinal anaesthesia as a manifestation of incipient syringomyelia.  Eur J Anaesthesiol1998; 15:103-105.
  91. Agusti M, Adalia R, Fernandez C, Gomar C: Anaesthesia for caesarean section in a patient with syringomyelia and Arnold-Chiari type I malformation.  Int J Obstet Anesth2004; 13:114-116.
  92. Deen Jr HG, McGirr SJ: Vertebral artery injury associated with cervical spine fracture: Report of two cases.  Spine1992; 17:230-234.
  93. Atkinson PP, Atkinson JL: Spinal shock.  Mayo Clin Proc1996; 71:384-389.
  94. Hambly PR, Martin B: Anaesthesia for chronic spinal cord lesions.  Anaesthesia1998; 53:273-289.
  95. Murphy DB, McGuire G, Peng P: Treatment of autonomic hyperreflexia in a quadriplegic patient by epidural anesthesia in the postoperative period.  Anesth Analg1999; 89:148-149.
  96. Noetzel MJ: Diagnosing ‘undiagnosed’ leukodystrophies: The role of molecular genetics.  Neurology2004; 62:847-848.
  97. Kenealy SJ, Pericak-Vance MA, Haines JL: The genetic epidemiology of multiple sclerosis.  J Neuroimmunol2003; 143:7-12.
  98. Haines JL, Bradford Y, Garcia ME, et al: Multiple Sclerosis Genetics Group: Multiple susceptibility loci for multiple sclerosis.  Hum Mol Genet2002; 11:2251-2256.
  99. Gade-Andavolu R, Comings DE, MacMurray J, et al: RANTES: A genetic risk marker for multiple sclerosis.  Multiple Sclerosis2004; 10:536-539.

99A. Davis FA, Michael FA, Neer D: Serial hyperthermia testing in multiple sclerosis related to circadian temperature variations.  Acta Neurol Scand  1973; 49(1):63-74.

  1. Edmund J, Fog T: Visual and motor instability in multiple sclerosis.  Arch Neurol Psychiatry1955; 73:316-320.
  2. Siemkowicz E: Multiple sclerosis and surgery.  Anaesthesia1976; 31:1211-1216.
  3. Baskett PJ, Armstrong R: Anaesthetic problems in multiple sclerosis: Are certain agents contraindicated?.  Anaesthesia1970; 25:397-401.
  4. Bamford C, Sibley W, Laguna J: Anesthesia in multiple sclerosis.  Can J Neurol Sci1978; 5:41-44.
  5. Kytta J, Rosenberg PH: Anaesthesia for patients with multiple sclerosis.  Ann Chir Gynaecol1984; 73:299-303.
  6. Schapira K, Poskanzer DC, Miller H: Familial and conjugal multiple sclerosis.  Acta Neurol Scand1966; 42(Suppl 19):83-84.
  7. Warren TM, Datta S, Ostheimer GW: Lumbar epidural anesthesia in a patient with multiple sclerosis.  Anesth Analg1982; 61:1022-1023.
  8. Berger JM, Ontell R: Intrathecal morphine in conjunction with a combined spinal and general anesthetic in a patient with multiple sclerosis.  Anesthesiology1987; 66:400-402.
  9. Bader AM, Hunt CO, Datta S, et al: Anesthesia for the obstetric patient with multiple sclerosis.  J Clin Anesth1988; 1:21-24.
  10. Leigh J, Fearnley SJ, Lupprian KG: Intrathecal diamorphine during laparotomy in a patient with advanced multiple sclerosis.  Anaesthesia1990; 45:640-642.
  11. Crawford JS: Regional analgesia for patients with chronic neurological disease and similar conditions.  Anesthesia1981; 36:821-822.
  12. Abouleish E: Neurological diseases.   In: James FM, Wheeler AS, ed. Obstetric Anesthesia: The Complicated Patient,  Philadelphia: FA Davis; 1988:110-111.
  13. Belani KG, Krivit W, Carpenter BL, et al: Children with mucopolysaccharidosis: Perioperative care, morbidity, mortality, and new findings.  J Pediatr Surg1993; 28:403-408.
  14. Baines D, Keneally J: Anaesthetic implications of the mucopolysaccharidoses: A fifteen-year experience in a children's hospital.  Anaesth Intensive Care1983; 11:198-202.
  15. Walker RW, Darowski M, Morris P, Wraith JE: Anaesthesia and mucopolysaccharidoses: A review of airway problems in children.  Anaesthesia1994; 49:1078-1084.
  16. Herrick IA, Rhine EJ: The mucopolysaccharidoses and anaesthesia: A report of clinical experience.  Can J Anaesth1988; 35:67-73.
  17. Shinhar SY, Zablocki H, Madgy DN: Airway management in mucopolysaccharide storage disorders.  Arch Otolaryngol Head Neck Surg2004; 130:233-237.
  18. Hopkins R, Watson JA, Jones JH, Walker M: Two cases of Hunter's syndrome the anaesthetic and operative difficulties in oral surgery.  Br J Oral Surg1973; 10:286-299.
  19. Wippermann CF, Beck M, Schranz D, et al: Mitral and aortic regurgitation in 84 patients with mucopolysaccharidoses.  Eur J Pediatr1995; 154:98-101.
  20. Braunlin EA, Hunter DW, Krivit W, et al: Evaluation of coronary artery disease in the Hurler syndrome by angiography.  Am J Cardiol1992; 69:1487-1489.
  21. Morgan KA, Rehman MA, Schwartz RE: Morquio's syndrome and its anaesthetic considerations.  Paediatr Anaesth2002; 12:641-644.
  22. Tobias JD: Anesthetic care for the child with Morquio syndrome: General versus regional anesthesia.  J Clin Anesth1999; 11:242-246.
  23. Kempthorne PM, Brown TC: Anaesthesia and the mucopolysaccharidoses: A survey of techniques and problems.  Anaesth Intensive Care1983; 11:203-207.
  24. Sjogren P, Pedersen T, Steinmetz H: Mucopolysaccharidoses and anaesthetic risks.  Acta Anaesthesiol Scand1987; 31:214-218.
  25. King DH, Jones RM, Barnett MB: Anaesthetic considerations in the mucopolysaccharidoses.  Anaesthesia1984; 39:126-131.
  26. Diaz JH, Belani KG: Perioperative management of children with mucopolysaccharidoses.  Anesth Analg1993; 77:1261-1270.
  27. Walker RW: The laryngeal mask airway in the difficult paediatric airway: An assessment of positioning and use in fibreoptic intubation.  Paediatr Anaesth2000; 10:53-58.
  28. Dullenkopf A, Holzmann D, Feurer R, et al: Tracheal intubation in children with Morquio syndrome using the angulated video-intubation laryngoscope.  Can J Anaesth2002; 49:198-202.
  29. Klein CJ: Pathology and molecular genetics of inherited neuropathy.  J Neurol Sci2004; 220:141-143.
  30. Mersiyanova IV, Ismailov SM, Polyakov AV, et al: Screening for mutations in the peripheral myelin genes PMP22, MPZ and Cx32 (GJB1) in Russian Charcot-Marie-Tooth neuropathy patients.  Hum Mutat2000; 15:340-347.
  31. Roy III EP, Gutmann L, Riggs JE: Longitudinal conduction studies in hereditary motor and sensory neuropathy type 1.  Muscle Nerve1989; 12:52-55.
  32. Dematteis M, Pepin JL, Jeanmart M, et al: Charcot-Marie-Tooth disease and sleep apnoea syndrome: A family study.  Lancet2001; 357:267-272.
  33. Rudnik-Schoneborn S, Rohrig D, Nicholson G, Zerres K: Pregnancy and delivery in Charcot-Marie-Tooth disease type 1.  Neurology1993; 43:2011-2016.
  34. Yoshioka R, Dyck PJ, Chance PF: Genetic heterogeneity in Charcot-Marie-Tooth neuropathy type 2.  Neurology1996; 46:569-571.
  35. Eichacker PQ, Spiro A, Sherman M, et al: Respiratory muscle dysfunction in hereditary motor sensory neuropathy, type I.  Arch Intern Med1988; 148:1739-1740.
  36. Nathanson BN, Yu DG, Chan CK: Respiratory muscle weakness in Charcot-Marie-Tooth disease: A field study.  Arch Intern Med1989; 149:1389-1391.
  37. Reah G, Lyons GR, Wilson RC: Anaesthesia for caesarean section in a patient with Charcot-Marie-Tooth disease.  Anaesthesia1998; 53:586-588.
  38. Tetzlaff JE, Schwendt I: Arrhythmia and Charcot-Marie-Tooth disease during anesthesia.  Can J Anaesth2000; 47:829.
  39. Yim SY, Lee IY, Moon HW, et al: Hypertrophic neuropathy with complete conduction block hereditary motor and sensory neuropathy type III.  Yonsei Med J1995; 36:466-472.
  40. Ginz HF, Ummenhofer WC, Erb T, Urwyler A: [The hereditary motor-sensory neuropathy Charcot-Marie-Tooth disease: Anesthesiologic management case report with literature review].  Anaesthesist2001; 50:767-771.German.
  41. Gratarola A, Mameli MC, Pelosi G: Total intravenous anaesthesia in Charcot-Marie-Tooth disease: Case report.  Min Anestesiol1998; 64:357-360.
  42. Niiyama Y, Kanaya N, Namiki A: [Anesthetic management for laparoscopic surgery in a patient with Charcot-Marie-Tooth disease].  Masui2003; 52:524-526.Japanese.
  43. Roelofse JA, Shipton EA: Anaesthesia for abdominal hysterectomy in Charcot-Marie-Tooth disease: A case report.  S Afr Med J1985; 67:605-606.
  44. Sugino S, Yamazaki Y, Nawa Y, et al: [Anesthetic management for a patient with Charcot-Marie-Tooth disease using propofol and nitrous oxide].  Masui2002; 51:1016-1019.Japanese.
  45. Tanaka S, Tsuchida H, Namiki A: [Epidural anesthesia for a patient with Charcot-Marie-Tooth disease, mitral valve prolapse syndrome and IInd degree AV block].  Masui1994; 43:931-933.Japanese.
  46. Huang J, Soliman I: Anaesthetic management for a patient with Dejerine-Sottas disease and asthma.  Paediatr Anaesth2001; 11:225-227.
  47. Antognini JF: Anaesthesia for Charcot-Marie-Tooth disease: A review of 86 cases.  Can J Anaesth1992; 39:398-400.
  48. Greenberg RS, Parker SD: Anesthetic management for the child with Charcot-Marie-Tooth disease.  Anesth Analg1992; 74:305-307.
  49. Cooperman LH: Succinylcholine-induced hyperkalemia in neuromuscular disease.  JAMA1970; 213:1867-1871.
  50. Baraka AS: Vecuronium neuromuscular block in a patient with Charcot-Marie-Tooth syndrome.  Anesth Analg1997; 84:927-928.
  51. Naguib M, Samarkandi AH: Response to atracurium and mivacurium in a patient with Charcot-Marie-Tooth disease.  Can J Anaesth1998; 45:56-59.
  52. Fiacchino F, Grandi L, Ciano C, Sghirlanzoni A: Unrecognized Charcot-Marie-Tooth disease: Diagnostic difficulties in the assessment of recovery from paralysis.  Anesth Analg1995; 81:199-201.
  53. Pogson D, Telfer J, Wimbush S: Prolonged vecuronium neuromuscular blockade associated with Charcot-Marie-Tooth neuropathy.  Br J Anaesth2000; 85:914-917.
  54. Scull T, Weeks S: Epidural analgesia for labour in a patient with Charcot-Marie-Tooth disease.  Can J Anaesth1996; 43:1150-1152.
  55. Sugai K, Sugai Y: [Epidural anesthesia for a patient with Charcot-Marie-Tooth disease, bronchial asthma and hypothyroidism].  Masui1989; 38:688-691.Japanese.
  56. Brian Jr JE, Boyles GD, Quirk Jr JG, Clark RB: Anesthetic management for cesarean section of a patient with Charcot-Marie-Tooth disease.  Anesthesiology1987; 66:410-412.
  57. Byrne DL, Chappatte OA, Spencer GT, Raju KS: Pregnancy complicated by Charcot-Marie-Tooth disease, requiring intermittent ventilation.  Br J Obstet Gynaecol1992; 99:79-80.
  58. Kotani N, Hirota K, Anzawa N, et al: Motor and sensory disability has a strong relationship to induction dose of thiopental in patients with the hypertropic variety of Charcot-Marie-Tooth syndrome.  Anesth Analg1996; 82:182-186.
  59. Axelrod FB, Hilz MJ: Inherited autonomic neuropathies.  Semin Neurol2003; 23:381-390.
  60. Kritchman MM, Schwartz H, Paper EM: Experiences with general anesthesia in patients with familial dysautonomia.  JAMA1959; 170:529-533.
  61. McCaughey TJ: Familial dysautonomia as an anaesthetic hazard.  Can Anaesth Soc J1965; 12:558-568.
  62. Axelrod FB, Donenfeld RF, Danziger F, Turndorf H: Anesthesia in familial dysautonomia.  Anesthesiology1988; 68:631-635.
  63. Challands JF, Facer EK: Epidural anaesthesia and familial dysautonomia (the Riley Day syndrome): Three case reports.  Paediatr Anaesth1998; 8:83-88.
  64. Szold A, Udassin R, Maayan C, et al: Laparoscopic-modified Nissen fundoplication in children with familial dysautonomia.  J Pediatr Surg1996; 31:1560-1562.
  65. Udassin R, Seror D, Vinograd I, et al: Nissen fundoplication in the treatment of children with familial dysautonomia.  Am J Surg1992; 164:332-336.
  66. Wengrower D, Gozal D, Gozal Y, et al: Complicated endoscopic pediatric procedures using deep sedation and general anesthesia are safe in the endoscopy suite.  Scand J Gastroenterol2004; 39:283-286.
  67. Beilin B, Maayan C, Vatashsky E, et al: Fentanyl anesthesia in familial dysautonomia.  Anesth Analg1985; 64:72-76.
  68. Okuda K, Arai T, Miwa T, Hiroki K: Anaesthetic management of children with congenital insensitivity to pain with anhidrosis.  Paediatr Anaesth2000; 10:545-548.
  69. Rozentsveig V, Katz A, Weksler N, et al: The anaesthetic management of patients with congenital insensitivity to pain with anhidrosis.  Paediatr Anaesth2004; 14:344-348.
  70. Tomioka T, Awaya Y, Nihei K, et al: Anesthesia for patients with congenital insensitivity to pain and anhidrosis: A questionnaire study in Japan.  Anesth Analg2002; 94:271-274.
  71. Marti MJ, Tolosa E, Campdelacreu J: Clinical overview of the synucleinopathies.  Mov Disord2003; 18(Suppl 6):S21-S27.
  72. Kaufmann H, Biaggioni I: Autonomic failure in neurodegenerative disorders.  Semin Neurol2003; 23:351-363.
  73. Isono S, Shiba K, Yamaguchi M, et al: Pathogenesis of laryngeal narrowing in patients with multiple system atrophy.  J Physiol2001; 536:237-249.
  74. Dewhurst A, Sidebottom P: Anaesthetic management of a patient with multiple system atrophy (Shy-Drager syndrome) for urgent hip surgery.  Hosp Med1999; 60:611.
  75. Gomesz FA, Montell M: Caudal anaesthesia in the Shy-Drager syndrome.  Anaesthesia1992; 47:1100.
  76. Hack G, Engels K, Greve I, Rapp S: [Anesthesiologic implications in the Shy-Drager syndrome a case report].  Anasth Intensivther Notfallmed1990; 25:362-366.German.
  77. Harioka T, Miyake C, Toda H, et al: [Anesthesia for Shy-Drager syndrome; effects of elastic bandage, phenylephrine, and IPPV].  Masui1989; 38:801-804.Japanese.
  78. Hashimoto H, Nishiyama T, Nagase Y, et al: [Anesthesia for emergency surgery in a patient with Shy-Drager syndrome].  Masui2001; 50:40-41.Japanese.
  79. Hutchinson RC, Sugden JC: Anaesthesia for Shy-Drager syndrome.  Anaesthesia1984; 39:1229-1231.
  80. Malinovsky JM, Cozian A, Rivault O: Spinal anesthesia for transurethral prostatectomy in a patient with multiple system atrophy.  Can J Anaesth2003; 50:962-963.
  81. Niquille M, Van Gessel E, Gamulin Z: Continuous spinal anesthesia for hip surgery in a patient with Shy-Drager syndrome.  Anesth Analg1998; 87:396-399.
  82. Saarnivaara L, Kautto UM, Teravainen H: Ketamine anaesthesia for a patient with the Shy-Drager syndrome.  Acta Anaesthesiol Scand1983; 27:123-125.
  83. Tsen LC, Smith TJ, Camann WR: Anesthetic management of a parturient with olivopontocerebellar degeneration.  Anesth Analg1997; 85:1071-1073.
  84. Yazawa R, Kondo T, Miyashita T, et al: [Anesthetic management of a patient with olivopontocerebellar atrophy using heart rate variability (HRV)].  Masui2004; 53:55-58.Japanese.
  85. Bevan DR: Shy-Drager syndrome: A review and a description of the anaesthetic management.  Anaesthesia1979; 34:866-873.
  86. Vallejo R, DeSouza G, Lee J: Shy-Drager syndrome and severe unexplained intraoperative hypotension responsive to vasopressin.  Anesth Analg2002; 95:50-52.
  87. Shannon J, Jordan J, Costa F, et al: The hypertension of autonomic failure and its treatment.  Hypertension1997; 30:1062-1067.
  88. McBeth C, Murrin K: Subarachnoid block for a case of multiple system atrophy.  Anaesthesia1997; 52:889-892.
  89. Kida K, Mori M, Yoshitake S, et al: [Anesthetic management for a patient with pure autonomic failure].  Masui1997; 46:813-817.Japanese.
  90. Korf BR: The phakomatoses.  Clin Dermatol2005; 23:78-84.
  91. Baselga E: Sturge-Weber syndrome.  Semin Cutan Med Surg2004; 23:87-98.
  92. Ruggieri M: The different forms of neurofibromatosis.  Childs Nerv Syst1999; 15:295-308.
  93. Hirsch NP, Murphy A, Radcliffe JJ: Neurofibromatosis: Clinical presentations and anaesthetic implications.  Br J Anaesth2001; 86:555-564.
  94. Crozier WC: Upper airway obstruction in neurofibromatosis.  Anaesthesia1987; 42:1209-1211.
  95. Reddy AR: Unusual case of respiratory obstruction during induction of anaesthesia.  Can Anaesth Soc J1972; 19:192-197.
  96. Dodge TL, Mahaffey JE, Thomas JD: The anesthetic management of a patient with an obstructing intratracheal mass: A case report.  Anesth Analg1977; 56:295-298.
  97. el Oakley R, Grotte GJ: Progressive tracheal and superior vena caval compression caused by benign neurofibromatosis.  Thorax1994; 49:380-381.
  98. Rees G: Neurofibroma of the recurrent laryngeal nerve.  Chest1971; 60:414-418.
  99. Delgado JM, de la Matta MM: Anaesthetic implications of von Recklinghausen's neurofibromatosis.  Paediatr Anaesth2002; 12:374.
  100. Zhao JZ, Han XD: Cerebral aneurysm associated with von Recklinghausen's neurofibromatosis: A case report.  Surg Neurol1998; 50:592-596.
  101. Sforza E, Colamaria V, Lugaresi E: Neurofibromatosis associated with central alveolar hypoventilation syndrome during sleep.  Acta Paediatr1994; 83:794-796.
  102. Vaughan DJ, Brunner MD: Anesthesia for patients with carcinoid syndrome.  Int Anesthesiol Clin1997; 35:129-142.
  103. Wheeler MH, Curley IR, Williams ED: The association of neurofibromatosis, pheochromocytoma, and somatostatin-rich duodenal carcinoid tumor.  Surgery1986; 100:163-169.
  104. Wulf H, Brinkmann G, Rautenberg M: Management of the difficult airway: A case of failed fiberoptic intubation.  Acta Anaesthesiol Scand1997; 41:1080-1082.
  105. Wang CY, Chiu CL, Delilkan AE: Sevoflurane for difficult intubation in children.  Br J Anaesth1998; 80:408.
  106. Practice guidelines for management of the difficult airway: An updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway.  Anesthesiology2003; 98:1269-1277.
  107. Dounas M, Mercier FJ, Lhuissier C, Benhamou D: Epidural analgesia for labour in a parturient with neurofibromatosis.  Can J Anaesth1995; 42:420-422.
  108. Richardson MG, Setty GK, Rawoof SA: Responses to nondepolarizing neuromuscular blockers and succinylcholine in von Recklinghausen neurofibromatosis.  Anesth Analg1996; 82:382-385.
  109. Alexianu D, Skolnick ET, Pinto AC, et al: Severe hypotension in the prone position in a child with neurofibromatosis, scoliosis and pectus excavatum presenting for posterior spinal fusion.  Anesth Analg2004; 98:334-335.
  110. Lonser RR, Glenn GM, Walther M, et al: von Hippel-Lindau disease.  Lancet2003; 361:2059-2067.
  111. Hes FJ, van der Luijt RB, Lips CJ: Clinical management of Von Hippel-Lindau (VHL) disease.  Neth J Med2001; 59:225-234.
  112. Harrington JL, Farley DR, van Heerden JA, Ramin KD: Adrenal tumors and pregnancy.  World J Surg1999; 23:182-186.
  113. O'Riordan JA: Pheochromocytomas and anesthesia.  Int Anesthesiol Clin1997; 35:99-127.
  114. Wang C, Zhang J, Liu A, Sun B: Surgical management of medullary hemangioblastoma: Report of 47 cases.  Surg Neurol2001; 56:218-226.
  115. Berl M, Dubois L, Belkacem H, et al: [Von Hippel-Lindau disease and obstetric anaesthesia: 3 cases report].  Ann Fr Anesth Reanim2003; 22:359-362.French.
  116. Boker A, Ong BY: Anesthesia for Cesarean section and posterior fossa craniotomy in a patient with von Hippel-Lindau disease.  Can J Anaesth2001; 48:387-390.
  117. Demiraran Y, Ozgon M, Utku T, Bozkurt P: Epidural anaesthesia for Caesarean section in a patient with von Hippel-Lindau disease.  Eur J Anaesthesiol2001; 18:330-332.
  118. Ercan M, Kahraman S, Basgul E, Aypar U: Anaesthetic management of a patient with von Hippel-Lindau disease: A combination of bilateral phaeochromocytoma and spinal cord haemangioblastoma.  Eur J Anaesthesiol1996; 13:81-83.
  119. Gurunathan U, Korula G: Unsuspected pheochromocytoma: von Hippel-Lindau disease.  J Neurosurg Anesthesiol2004; 16:26-28.
  120. Joffe D, Robbins R, Benjamin A: Caesarean section and phaeochromocytoma resection in a patient with Von Hippel Lindau disease.  Can J Anaesth1993; 40:870-874.
  121. Matthews AJ, Halshaw J: Epidural anaesthesia in von Hippel-Lindau disease: Management of childbirth and anaesthesia for caesarean section.  Anaesthesia1986; 41:853-855.
  122. Mugawar M, Rajender Y, Purohit AK, et al: Anesthetic management of von Hippel-Lindau syndrome for excision of cerebellar hemangioblastoma and pheochromocytoma surgery.  Anesth Analg1998; 86:673-674.
  123. Wang A, Sinatra RS: Epidural anesthesia for cesarean section in a patient with von Hippel-Lindau disease and multiple sclerosis.  Anesth Analg1999; 88:1083-1084.
  124. Monge E, Botella M, Rueda ML, Navia J: [Anesthesia for cesarean section in a patient with von Hippel-Lindau disease].  Rev Esp Anestesiol Reanim2002; 49:377-380.Spanish.
  125. Shenkman Z, Rockoff MA, Eldredge EA, et al: Anaesthetic management of children with tuberous sclerosis.  Paediatr Anaesth2002; 12:700-704.
  126. Papaioannou EG, Staikou CV, Lambadarioui A, et al: Anesthetic management of a patient with tuberous sclerosis presenting for renal transplantation.  J Anesth2003; 17:193-195.
  127. Tsukui A, Noguchi R, Honda T, et al: Aortic aneurysm in a four-year-old child with tuberous sclerosis.  Paediatr Anaesth1995; 5:67-70.
  128. Ong EL, Koay CK: Tuberous sclerosis presenting for laparotomy.  Anaesth Intensive Care2000; 28:94-96.
  129. Nott MR, Halfacre J: Anaesthesia for dental conservation in a patient with tuberous sclerosis.  Eur J Anaesthesiol1996; 13:413-415.
  130. Lee JJ, Imrie M, Taylor V: Anaesthesia and tuberous sclerosis.  Br J Anaesth1994; 73:421-425.
  131. Soriano SG, Kaus SJ, Sullivan LJ, Martyn JA: Onset and duration of action of rocuronium in children receiving chronic anticonvulsant therapy.  Paediatr Anaesth2000; 10:133-136.
  132. Ceyhan A, Cakan T, Basar H, et al: Anaesthesia for Sturge-Weber syndrome.  Eur J Anaesthesiol1999; 16:339-341.
  133. Batra RK, Gulaya V, Madan R, Trikha A: Anaesthesia and the Sturge-Weber syndrome.  Can J Anaesth1994; 41:133-136.
  134. Boltshauser E: Cerebellum-small brain but large confusion: A review of selected cerebellar malformations and disruptions.  Am J Med Genet A2004; 126:376-385.
  135. Steinbok P: Clinical features of Chiari I malformations.  Childs Nerv Syst2004; 20:329-331.
  136. Takigami I, Miyamoto K, Kodama H, et al: Foramen magnum decompression for the treatment of Arnold Chiari malformation type I with associated syringomyelia in an elderly patient.  Spinal Cord2005; 43:249-251.
  137. Chantigian RC, Koehn MA, Ramin KD, Warner MA: Chiari I malformation in parturients.  J Clin Anesth2002; 14:201-205.
  138. Nogues MA, Newman PK, Male VJ, Foster JB: Cardiovascular reflexes in syringomyelia.  Brain1982; 105:835-849.
  139. Williams DL, Umedaly H, Martin IL, Boulton A: Chiari type I malformation and postoperative respiratory failure.  Can J Anaesth2000; 47:1220-1223.
  140. Kakinuma H, Saito Y, Sato H, Kobayashi T: [Blind orotracheal intubation using Trachilight in a pediatric patient with Arnold-Chiari malformation].  Masui1999; 48:1253-1254.Japanese.
  141. Keyaki A, Makita Y, Nabeshima S, et al: [Surgical management of syringomyelia associated with Arnold-Chiari malformation, primary IgA deficiency and chromosomal abnormality a case report].  Nippon Geka Hokan1990; 59:161-167.Japanese.
  142. Nakayama Y, Sonoda H, Namiki A: [Propofol anesthesia for a patient with Arnold-Chiari deformity].  Masui1998; 47:726-729.Japanese.
  143. Sellery GR: Intraoperative problem during surgery for Chiari malformation.  Can J Anaesth2001; 48:718.
  144. Daum RE, Jones DJ: Fibreoptic intubation in Klippel-Feil syndrome.  Anaesthesia1988; 43:18-21.
  145. Choi SS, Tran LP, Zalzal GH: Airway abnormalities in patients with Arnold-Chiari malformation.  Otolaryngol Head Neck Surg1999; 121:720-724.
  146. Ruff ME, Oakes WJ, Fisher SR, Spock A: Sleep apnea and vocal cord paralysis secondary to type I Chiari malformation.  Pediatrics1987; 80:231-234.
  147. Wynn R, Goldsmith AJ: Chiari type I malformation and upper airway obstruction in adolescents.  Int J Pediatr Otorhinolaryngol2004; 68:607-611.
  148. Agusti M, Adalia R, Fernandez C, Gomar C: Anaesthesia for caesarean section in a patient with syringomyelia and Arnold-Chiari type I malformation.  Int J Obstet Anesth2004; 13:114-116.
  149. Landau R, Giraud R, Delrue V, Kern C: Spinal anesthesia for cesarean delivery in a woman with a surgically corrected type I Arnold Chiari malformation.  Anesth Analg2003; 97:253-255.
  150. Nel MR, Robson V, Robinson PN: Extradural anaesthesia for caesarean section in a patient with syringomyelia and Chiari type I anomaly.  Br J Anaesth1998; 80:512-515.
  151. Semple DA, McClure JH: Arnold-Chiari malformation in pregnancy.  Anaesthesia1996; 51:580-582.
  152. Sicuranza GB, Steinberg P, Figueroa R: Arnold-Chiari malformation in a pregnant woman.  Obstet Gynecol2003; 102:1191-1194.
  153. Barton JJ, Sharpe JA: Oscillopsia and horizontal nystagmus with accelerating slow phases following lumbar puncture in the Arnold-Chiari malformation.  Ann Neurol1993; 33:418-421.
  154. Hullander RM, Bogard TD, Leivers D, et al: Chiari I malformation presenting as recurrent spinal headache.  Anesth Analg1992; 75:1025-1026.
  155. Stevenson KL: Chiari type II malformation: Past, present, and future.  Neurosurg Focus2004; 16:E5.
  156. McLone DG, Knepper PA: The cause of Chiari II malformation: A unified theory.  Pediatr Neurosci1989; 15:1-12.
  157. Nishino H, Kinouchi K, Fukumitsu K, et al: [Anesthesia and perioperative management in infants with Chiari type II malformation].  Masui1998; 47:982-986.Japanese.
  158. Shiraishi M, Minami K, Horishita T, Shigematsu A: [Difficult ventilation during induction of anesthesia in a patient with Arnold-Chiari malformation type II].  Masui2001; 50:776-778.Japanese.
  159. Herman MJ, Pizzutillo PD: Cervical spine disorders in children.  Orthop Clin North Am1999; 30:457-466.ix.
  160. Naguib M, Farag H, Ibrahim A: Anaesthetic considerations in Klippel-Feil syndrome.  Can Anaesth Soc J1986; 33:66-70.
  161. Tracy MR, Dormans JP, Kusumi K: Klippel-Feil syndrome: Clinical features and current understanding of etiology.  Clin Orthop2004;183-190.
  162. Nagib MG, Maxwell RE, Chou SN: Identification and management of high-risk patients with Klippel-Feil syndrome.  J Neurosurg1984; 61:523-530.
  163. Thompson E, Haan E, Sheffield L: Autosomal dominant Klippel-Feil anomaly with cleft palate.  Clin Dysmorphol1998; 7:11-15.
  164. Farid IS, Omar OA, Insler SR: Multiple anesthetic challenges in a patient with Klippel-Feil syndrome undergoing cardiac surgery.  J Cardiothorac Vasc Anesth2003; 17:502-505.
  165. Sakai H, Takizawa K, Miura N, Suzuki M: [Anesthetic management of a child with Klippel-Feil syndrome associated with severe scoliosis].  Masui2001; 50:645-647.Japanese.
  166. O'Connor PJ, Moysa GL, Finucane BT: Thoracic epidural anesthesia for bilateral reduction mammoplasty in a patient with Klippel-Feil syndrome.  Anesth Analg2001; 92:514-516.
  167. Dresner MR, Maclean AR: Anaesthesia for caesarean section in a patient with Klippel-Feil syndrome: The use of a microspinal catheter.  Anaesthesia1995; 50:807-809.
  168. Burns AM, Dorje P, Lawes EG, Nielsen MS: Anaesthetic management of caesarean section for a mother with pre-eclampsia, the Klippel-Feil syndrome and congenital hydrocephalus.  Br J Anaesth1988; 61:350-354.
  169. Hall JE, Simmons ED, Danylchuk K, Barnes PD: Instability of the cervical spine and neurological involvement in Klippel-Feil syndrome: A case report.  J Bone Joint Surg Am1990; 72:460-462.