SEIZURES
DEFINITION
Symptom of brain dysfunction (not an etiologic diagnosis).
A paroxysmal electrical discharge of neurons in the brain resulting in an alteration of function or behavior.
The most common neurologic disorder in children:
4–10% of children
1% of all ED visits
Highest incidence: < 3 yr.
The diagnosis of clinical epilepsy requires two or more unprovoked seizures.
ETIOLOGY
Multiple etiologies have been identified for seizures. Provoked causes include:
Fever.
Metabolic:
Hypoglycemia
Hyponatremia
Hypocalcemia
Inborn errors of metabolism
Medications and illegal drugs.
Trauma (intracranial hemorrhage).
Infections (encephalitis, meningitis, abscess).
Vascular events (strokes).
Hypoxic ischemia encephalopathy.
Recurrence risk after a first unprovoked episode is 45% (27–52%).
The risk of epilepsy is > 70% after two unprovoked episodes.
In most children with seizures, an underlying cause cannot be determined and a diagnosis of idiopathic epilepsy is given.
Types of Seizures
See Table 17-1.
Partial seizures: Onset in one brain region. Generalized seizures: Onset simultaneously in both cerebral hemispheres.
PARTIAL (FOCAL) SEIZURES
Begin in one brain region.
1. Simple partial seizures:
Average duration is 10–20 sec.
Restricted at onset to one focal cortical region.
Aura: Abnormal perception or hallucination that precede seizures.
TABLE 17-1. Types of Seizures
Consciousness is not altered.
Tend to involve the face, neck, and extremities.
Patients may complain of preictal aura, which is characteristic for the brain region involved in the seizure (ie, visual aura, auditory aura, etc.).
Seizures can also be somatosensory/visual or auditory.
In seizure, as opposed to migraine, the aura is part of the seizure.
2. Complex partial seizures:
Average duration is 1–2 min.
Hallmark feature is alteration or loss of consciousness.
Automatisms are seen in 50–75% of cases (psychic, sensory, or motor phenomena carried out while unconscious and not recalled postic-tally).
May begin as a simple partial seizure and progress until consciousness is affected.
Both simple and complex partial seizures may become generalized.
GENERALIZED SEIZURES
Begins simultaneously in both cerebral hemispheres. Consciousness is impaired from seizure onset.
1. Typical absence seizures (formerly “petit mal”):
Generalized seizure.
Characterized by sudden cessation of motor activity or speech.
Brief stares (usually < 10 sec), rarely longer than 30 sec.
More common in girls. Male-to-female ratio: 2:1.
Onset 2–6 yr.
Frequency: Dozens/day.
There is no aura.
There is no postictal state.
Childhood absence epilepsy is associated with characteristic 3-Hz spike-and-wave pattern (Figure 17-1) on EEG.
The first step in evaluating any seizure disorder is determining the type of seizure.
Motor activity is the most common symptom of simple partial seizures.
FIGURE 17-1. Absence seizure EEG.
Characteristic 3-Hz spike and wave pattern.
2. Generalized tonic-clonic (GTC, formerly “grand mal”) seizures:
Extremely common and may follow a partial seizure with focal onset.
Patients suddenly lose consciousness, their eyes roll back, and their entire musculature undergoes tonic contractions, rarely arresting breathing.
Gradually, the hyperextension gives way to a series of rapid clonic jerks.
Finally, a period of flaccid relaxation occurs, during which sphincter control is often lost (incontinence).
Prodromal symptoms (not aura) often precede the attack by several hours and include mood change, apprehension, insomnia, or loss of appetite. (Unclear if these are warning signs or part of the cause).
The presence of an aura always indicates a focal onset of the seizure. Physiologically, an aura is simply the earliest conscious manifestation of a seizure and corresponds with area of brain involved.
ABSENCE VERSUS COMPLEX PARTIAL SEIZURES
While examining an 8-year-old girl in your office, the child suddenly develops a blank stare and flickering eyelids. Twenty seconds later she returns to normal and acts as if nothing out of the ordinary has occurred. Think: Absence seizure.
Automatisms are a common symptom of complex partial seizures.
You are reviewing the history before seeing a patient. She is a 7-year-old bright girl with no significant past medical history. The schoolteacher noted that she sometimes does not respond when her name is called. Also, she stares in space with a blank look momentarily. Think: Absence seizures.
Absence seizures are the second most common type of generalized seizure in children. Common age of presentation is between 4 and 12 yr. Since these seizures develop in childhood, schoolteachers are often the first to notice. There is no aura and no postictal symptoms. It may be accompanied by brief eye blinking or myoclonic movement. Electroencephalogram (EEG) shows spike-and-wave activity at 3/sec. These seizures are not associated with progressive neurologic disease.
Absence Seizures
Shorter (seconds)
Automatism –
More frequent (dozens)
Quick recovery
Hyperventilation +
EEG: 3/sec spikes and waves
Complex Partial Seizures
Longer (minutes)
Automatism +
Less frequent
Gradual recovery
Hyperventilation –
EEG: Focal spikes
Pediatric Seizure Disorders
SIMPLE FEBRILE SEIZURE
The most common seizure disorder during childhood. Occur in 2–5% of children 6 months to 6 years of age.
Present as a brief tonic-clonic seizure associated with a fever.
Risk of recurrence is 30% after first episode and 50% after second episode.
Highest recurrence before 1 year of age (50%).
There are no long-term sequelae, and children will outgrow by age 6.
Risk of epilepsy (1–2% as opposed to 0.5–1% in the general population) not statistically significant.
↑ risk of epilepsy (up to 13%) in the presence of:
Abnormal neurologic examination.
Complex febrile seizure.
Family history of epilepsy.
An autosomal-dominant inheritance pattern with incomplete penetrance is demonstrated in some families (19p and 8q13–21).
Complex febrile seizure:
15 min
Focal motor
Recurrent seizures in < 24 hr
Benign neonatal familial convulsions (“fifth day fits”) are a brief self-limited autosomal-dominant condition with generalized seizures beginning in the first week of life and subsiding within 6 weeks. There is a normal interictal EEG. There is a 10–15% chance of future epilepsy, but otherwise carries an excellent prognosis. Always elicit a family history in neonatal seizures usually revealed after interviewing grandparents.
NEONATAL SEIZURE
The most common neurologic manifestation of impaired brain function.
Occurs in 1.8–3.5 of every 1000 newborns.
Higher incidence in low-birth-weight infants.
Metabolic, toxic, hypoxic, ischemic, and infectious diseases are commonly present during the neonatal period, placing the child at an ↑ risk for seizures.
Myelination is not complete at birth; thus, GTC seizures are very uncommon in the first month of life.
May manifest as tonic, myoclonic, clonic, or subtle (prolonged nonnutritive sucking, nystagmus, color change, autonomic instability).
EEG may show burst suppression (alternating high and very low voltages), low-voltage invariance, diffuse or focal background slowing, and focal or multifocal spikes.
Neonatal seizures are typically treated acutely with phenobarbital (drug of choice), fosphenytoin, or benzodiazepines.
Phenytoin not a first-line agent due to depressive effect on the myocardium and variable metabolism in newborns.
Prophylaxis usually with phenobarbital, but also topiramate or levetiracetam.
INFANTILE SPASM
Onset: 4–8 months.
Clusters of brief symmetric flexor/extensor contractions of the neck, trunk, and extremities up to 100/day.
Symptomatic type is most commonly seen with central nervous system (CNS) malformations, brain injury, tuberous sclerosis, or inborn errors of metabolism, and typically has a poor outcome.
Cryptogenic type has a better prognosis and children typically have an uneventful birth history and reach developmental milestones before the onset of the seizures.
Treated with adrenocorticotropic hormone (ACTH) in the United States.
Vigabatrin (equally as effective as ACTH therapy).
EEG has characteristic hypsarrhythmia pattern: Large amplitude chaotic multifocal spikes and slowing (see Figure 17-2).
Immature neonatal brain is more excitable than older children.
Epilepsy
DEFINITION
A history of two or more unprovoked seizures.
After a nebulous period (on the order of 5–10 yr) of seizure freedom without the aid of antiepileptic medications or devices, the epilepsy can be considered to have resolved, particularly if the patient fits an epilepsy syndrome that is known typically to resolve.
If you are present during a tonic–clonic seizure:
Keep track of the duration.
Place the patient between prone and lateral decubitus to allow the tongue and secretions to fall forward.
Hyperextend the neck and jaw to enhance breathing.
Loosen any tight clothing or jewelry around the neck.
Do not try to force open the mouth or teeth!
EPIDEMIOLOGY
Epilepsy occurs in 0.5–1% of the population and begins in childhood in 60% of the cases.
A febrile seizure lasting > 15 min suggests an organic cause such as meningitis or toxin exposure. Always get cerebrospinal fluid (CSF) if suspicion of infection.
FIGURE 17-2. EEG demonstrating hypsarrhythmia pattern.
Often seen in tuberous sclerosis, for example.
If the seizure is brief with fever and immediate complete recovery consistent with febrile seizure, then only good examination and laboratory evaluation to find the cause of fever. CT/EEG is not indicated.
SIGNS AND SYMPTOMS
Vary depending on the seizure pattern. See above discussion of types of seizures.
A seizure is defined electrographically as a hypersynchronous, hyper-rhythmic, high-amplitude signal that evolves in both frequency and space.
An aura is a stereotyped symptom set that immediately precedes the onset of a clinical seizure and does not affect consciousness.
Physiologically, the aura is the true beginning of the seizure, and as such its character can be quite useful for localizing seizure onset.
A seizure prodrome is a set of symptoms, much less stereotyped than an aura, that precedes a seizure by hours to days. Symptoms such as headache, mood changes, and nausea are reported by over 50% of patients in some series.
Etiologies of neonatal seizure:
Hypoxic-ischemic encephalopathy (35– 42%)
Intracranial hemorrhage/infarction (15–20%)
CNS infection (12–17%)
Metabolic and inborn errors of metabolism (8–25%)
CNS malformation (5%)
TREATMENT
Therapy is directed at preventing the attacks.
See Table 17-2 for current pharmacologic treatments for epilepsy.
Unprovoked seizure: Unrelated to current acute CNS insult such as infection, ↑ intracranial pressure (ICP), trauma, toxin, etc.
Common Epilepsy Syndromes
See Table 17-3 for localizing/lateralizing seizure semiologies.
TABLE 17-2. Epilepsy Drugs and Their Use in Different Seizure Types
LOCALIZATION-RELATED EPILEPSY
Seizures secondary to a focal CNS lesion, not necessarily visible on imaging, best candidates for epilepsy surgery.
Common examples include masses (particularly cortical tubers of tuberous sclerosis [TS]), cortical dysplasia, postencephalitic gliosis, and arteriovenous malformations (AVMs).
BENIGN ROLANDIC EPILEPSY
A 5-year-old boy was noted to have facial twitching and facial drooling noted at a day care center during a nap followed by generalized shaking of the body lasting 1–2 min. The mother also reported noticing facial twitching during sleep. In the ED, he is awake and his neurological examination is normal. You order an EEG, which shows centrotemporal spikes. Think: Benign rolandic epilepsy.
Benign rolandic epilepsy is partial epilepsy of childhood. The usual age of presentation is 3–13 years. Typical presentation: seizure occurs during sleep (nighttime) with facial involvement. EEG shows central temporal spikes. Seizures typically resolve spontaneously by early adulthood.
Most common partial epilepsy.
Onset 3–13 years.
Particularly nocturnal (early morning hours before awakening).
EEG: Central temporal spikes (Figure 17-3).
Excellent prognosis; most resolve by age 16 yr.
Treatment: Carbamazepine, phenytoin, and valproic acid.
TABLE 17-3. Localizing/Lateralizing Seizure Semiologies
Epilepsy History
Age, sex, handedness
Seizure semiology (what the seizures look like, details about right/left). If more than one type, the pattern of progression (if any)
Seizure duration/history of status epilepticus
Postictal lethargy or focal neurologic deficits
Current frequency/tendency to cluster
Age at onset
Date of last seizure
Longest seizure-free interval
Known precipitants (don’t forget to ask if the seizures typically arise out of sleep)
History of head trauma, difficult birth, intrauterine infection, hypoxic/ischemic insults, meningoencephalitis, or other CNS disease
Developmental history (delay strongly correlated with poorer prognosis)
Family history of epilepsy, febrile seizures
Psychiatric history
Current AEDs
AED history (maximum doses, efficacy, reason for stopping)
Previous EEG, MRI findings
FIGURE 17-3. EEG demonstrating central temporal spikes characteristic of benign Rolandic epilepsy.
WEST SYNDROME
Two percent of childhood epilepsies, but 25% of epilepsy with onset in the first year of life.
Onset is at age 4–8 months.
Triad: Infantile spasms, mental retardation (MR), and hypsarrhythmia.
Boys are more commonly affected but not significantly; generally poor prognosis.
Differential includes TS (largest group), CNS malformation, intrauterine infection, inborn metabolic disorders, and idiopathic. Idiopathic group fares the best.
Treatment in the United States is restricted to ACTH.
JUVENILE MYOCLONIC EPILEPSY (JME)
Onset: 12–16 yr.
Characteristic history: Usually early morning on awakening, while hair combing and tooth brushing.
Seizures: Myoclonus, absence, GTC.
EEG: 4- to 6-Hz irregular spike-and-wave pattern (Figure 17-4 and Table 17-4).
Treatment: Valproate, lamotrigine.
Prognosis: Good Rx response but lifelong.
High rate of recurrence if antiepileptic drug (AED) discontinued.
CHILDHOOD ABSENCE EPILEPSY (CAE; PYKNOLEPSY)
See absence seizures above. GTC seizures often develop in adolescence; spontaneous resolution is the rule, however.
Juvenile absence epilepsy (JAE): Similar to CAE except beginning in adolescence and have more GTC seizures, sexes affected equally, EEG spike and wave often faster than 3 Hz.
FIGURE 17-4. EEG demonstrating characteristic pattern of juvenile myoclonic epilepsy.
LENNOX-GASTAUT SYNDROME (LGS)
A generalized epilepsy syndrome.
Multiple seizure types (tonic, atonic, absence, and myoclonic seizures).
EEG: 1.5- to 2.5-Hz spike-and-wave pattern.
Cognitive impairment.
Infantile spasms may evolve to LGS (30%).
Seizures are frequent and resistant to treatment with AEDs.
LANDAU-KLEFFNER SYNDROME (LKS; ACQUIRED EPILEPTIC APHASIA)
Language regression.
Aphasia (primarily receptive or expressive).
Seizures of several types (focal or GTC, atypical absence, partial complex).
EEG: High-amplitude spike-and-wave discharges. Obtain EEG during sleep (more apparent during non–rapid eye movement sleep).
Differential diagnosis: Autism.
Treatment: Valproic acid.
Loss of language skills in a previously normal child with seizure disorder. Think: LKS.
PROGRESSIVE MYOCLONIC EPILEPSIES
This group of diseases includes Unverricht-Lundborg disease, myoclonic epilepsy with ragged-red fibers (MERRF), Lafora disease, neuronal ceroid lipofuscinosis, and sialidosis/mucolipidosis, and Ramsay Hunt syndrome.
Begin in late childhood to adolescence, and entail progressive neurologic deterioration with myoclonic seizures, dementia, and ataxia. Death within 10 yr of onset is common, but survival to old age occurs.
Evaluate patients following their first seizure (for mass, lesion, etc.) prior to diagnosing and treating epilepsy.
TABLE 17-4. Characteristic EEG Patterns in Various Seizure Conditions
MESIAL TEMPORAL SCLEROSIS/TEMPORAL LOBE EPILEPSY
Gliotic scarring and atrophy of the hippocampal formation, creating a seizure focus. Abnormality is often apparent on high-resolution magnetic resonance imaging (MRI).
Rhythmic, 5–7 Hz, sharp theta activity.
Phenytoin, phenobarbital, carbamazepine, and valproate are equally effective. Curative resection is often possible if refractory to treatment.
RETT SYNDROME
DEFINITION
A neurodegenerative disorder of unknown cause.
EPIDEMIOLOGY
X-linked recessive with MECP2 gene mutation occurs almost exclusively in females. Rett syndrome does exist in males with 47,XXY and MEP2 gene mutation. However, males with 46,XY and MECP2gene mutation do not survive.
Prevalence: 1 in 15,000 to 1 in 22,000.
ETIOLOGY
Most cases result from defect in MECP2. Gene testing available.
CDKL5 gene mutations can also cause Rett syndrome.
The hallmark of Rett syndrome is repetitive hand-wringing and loss of purposeful and spontaneous hand movements.
SIGNS AND SYMPTOMS
Normal development until 12–18 months (can appear as early as 5 months)
The first signs are deceleration of head growth, lack of interest in environment, and hypotonia, followed by a regression of language and motor milestones.
Ataxia, hand-wringing, reduced brain weight, and episodes of hyperventilation are typical.
Autistic behavior.
PROGNOSIS
After the initial period of regression, the disease appears to plateau.
Death occurs during adolescence or the third decade of life (cardiac arrhythmias).
STURGE-WEBER SYNDROME
Dermato-oculo-neural syndrome.
EPIDEMIOLOGY
Occurs sporadically in 1 in 50,000.
ETIOLOGY
Abnormal development of the meningeal vasculature, resulting in hemispheric vascular steal phenomenon and resultant hemiatrophy.
Facial capillary hemangioma usually accompanies in V1 distribution.
If you see “port-wine stain,” think: Sturge-Weber syndrome.
SIGNS AND SYMPTOMS
Cutaneous facial nevus flammeus (distribution of the trigeminal nerve) → port-wine stain.
Ipsilateral diffuse cavernous hemangioma of the choroid → glaucoma.
Ipsilateral meningeal hemangiomatosis (seizures and mental retardation).
The lesions in the eye, skin, and brain are always present at birth.
Contrast-enhanced MRI to look for meningeal angioma.
Seizures are usually refractory, and hemispherectomy improves the prognosis.
It is very unlikely to have meningeal involvement without port-wine stain, but most children with a facial port-wine nevus do not have an intracranial angioma.
STATUS EPILEPTICUS (SE)
DEFINITION
Any seizure or recurrent seizures without return to baseline lasting 20 min.
ETIOLOGY
Febrile seizures, idiopathic status epilepticus, and symptomatic SE.
Febrile SE accounts for 5% of febrile seizures and one-third of all episodes of SE.
In children under age 3, febrile seizures are the most likely etiology of status epilepticus.
PATHOPHYSIOLOGY
Prolonged neural firing may result in neuronal cell death, called excitotoxicity.
TREATMENT
Initial treatment includes assessment of the respiratory and cardiovascular systems (ABCs).
Obtain rapid bedside glucose level.
Neonatal status that is refractory to the usual measures may respond to pyridoxine. This is seen in pyridoxine dependency (due to diminished glutamate decarboxylase activity, a rare autosomal-recessive condition) or pyridoxine deficiency in children born to mothers on isoniazid.
PROTOCOL
1. Airway, breathing, circulation (ABCs); give O2.
2. Vitals, particularly blood pressure (BP).
3. Intravenous (IV) access.
4. Obtain rapid bedside glucose level.
5. Labs: Basic metabolic panel, ammonia (NH3), aspartate transaminase (AST), alanine transaminase (ALT), AED levels, toxicology screen, blood cultures, complete blood count (CBC). Obtain blood cultures if febrile (consider lumbar puncture).
6. If seizing for > 5 min: Lorazepam 0.1 mg/kg IV (benzodiazepines #1).
7. If lorazepam fails, fosphenytoin 20 mg/kg IV (doses of fosphenytoin are in “phenytoin equivalents” by convention).
8. If fosphenytoin fails, give a second dose of 5 mg/kg IV.
9. If second fosphenytoin fails, either:
Load with phenobarbital 20 mg/kg IV or
Load with midazolam 0.1 mg/kg IV and start drip at 2 µg/kg/min and titrate to effect.
10. Consider EEG and computed tomography (CT) head in case of new-onset SE in otherwise stable child.
SLEEP DISORDERS
Obstructive Sleep Apnea (OSA)
Occurs in 2–5 % of children, most often between ages 2 and 6.
Characterized by chronic partial airway obstruction with intermittent episodes of complete obstruction during sleep, resulting in disturbed sleep.
Snoring is the most common symptom, occurring in most of them (12% of general pediatric population has snoring without OSA).
Symptoms: Fatigue/hyperactivity, headache, daytime somnolence.
Signs: Narrow airway, tonsillar hypertrophy, often obese.
Diagnosis: History and physical examination, polysomnography (> 1 apnea/hypopnea per hour).
Obstructive sleep apnea due to adenotonsillar hyperplasia is an indication for tonsillectomy and adenoidectomy.
Night Terrors
DEFINITION
Transient, sudden-onset episodes of terror in which the child cannot be consoled and is unaware of the surroundings, usually lasting for 5–15 min.
There is total amnesia following the episodes.
Since obstructive sleep apnea causes hypoxia, it may be associated with polycythemia vera, growth failure, and serious cardiorespiratory pathophysiology.
EPIDEMIOLOGY
Occur in 1–3% of the population, primarily in boys between ages 5 and 7.
PATHOPHYSIOLOGY
Fifty percent complete recovery by age 8.
Fifty percent are also sleepwalkers.
Often, incontinence and diaphoresis.
Occurs in stage 4 (deep) sleep.
DIAGNOSIS
PSG (polysomnography).
TREATMENT
Reassurance; usually self-limited and resolve by age 6.
Night terrors, sleepwalking, and nightmares are associated with disturbed sleep, but have no known neurologic disorder.
Somnambulance (Sleepwalking)
Occurs during slow-wave sleep.
Occurs during first third of the night.
Onset: 8–12 yr.
Awakened only with difficulty and may be confused when awakened.
Fifty percent also have night terrors.
Sleep deprivation causes attention deficit, hyperactivity, and behavior disturbances in children—often mistaken for attention deficit/hyperactivity disorder (ADHD).
Insomnia
Affects 10–20% of adolescents.
Depression is a common cause and should be ruled out.
COMA
Consciousness refers to the state of awareness of self and environment.
Pediatric evaluation of consciousness is dependent on both age and developmental level.
DEFINITION
Pathologic cause of loss of normal consciousness.
PATHOPHYSIOLOGY
Consciousness is the result of communication between the cerebral cortex and the ascending reticular-activating system.
Coma can be caused by:
One medial cerebral hemisphere with ispilateral, striatum, thalamus, and tegmentum of midbrain and rostral pons.
Bilateral medial hemispheres, striatum, thalami, tegmentum of rostral pontomesencephalic tegmentum impairs consciousness.
Lesions of the medullary reticular-activating system or its ascending projections. Ventral pontine lesions can → the locked-in syndrome, which is not coma.
ETIOLOGY
Structural causes include trauma, vascular conditions, and mass lesions involving directly or mass effects.
Metabolic and toxic causes include hypoxic-ischemic injury, toxins, infectious causes, and seizures.
Herniation syndromes that may result in coma:
Ipsilateral oculomotor dysfunction. Think: Uncal herniation.
Cheyne-Stokes respirations. Think: Transtentorial (central) herniation.
EVALUATION
Administer glucose via IV line so that the brain has an adequate energy supply.
Treat underlying cause (toxin antidote, reduce ICP, antibiotics, etc.).
PROGNOSIS
Overall, children tend to do better than adults.
Several measurement scales have been published attempting to predict outcome. The most widely accepted is the Glasgow Coma Scale (see Table 17-5).
TABLE 17-5. Glasgow Coma Scale (GCS)
Another scale that you should know exists is the Pediatric Cerebral Performance Category Scale, which, unlike the Glasgow, was specifically designed for pediatric patients.
Prognosis depends on the etiology of the insult and the rapid initiation of treatment!
CNS INFECTION
Meningitis
DEFINITION
Diffuse inflammation of the meninges, particularly arachnoids and pia mater.
Bacteria:
< 3 months: Group B streptococci and gram-negative organisms, Escherichia coli, Listeria.
> 3 months: Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis (two life-threatening clinical syndromes: meningococcemia and meningococcal meningitis).
Virus: The term aseptic meningitis is used to describe the syndrome of meningism and CSF leukocytosis usually caused by viruses or bacteria.
SIGNS AND SYMPTOMS
If immunocompromised, these signs and symptoms will be not prominent.
Fever, headache, and nuchal rigidity (most important features).
Photophobia or myalgia may be present.
Meningism (Brudzinski’s and Kernig’s signs) (see Figures 17-5 and 17-6).
Altered consciousness, petechial rash, seizures, cranial nerve, or other abnormal neurological findings.
FIGURE 17-5. Kernig’s sign.
Flex patient’s leg at both hip and knee, and then straighten knee. Pain on extension is a positive sign.
FIGURE 17-6. Brudzinski’s sign.
Involuntary flexion of the hips and knees with passive flexion of the neck while supine.
DIAGNOSIS
Analysis of the CSF is not always predictive of viral or bacterial infection since there is considerable overlap in the respective CSF findings, especially at the onset of the disease (Table 17-6).
Take some time to familiarize yourself with Tables 17-6 and 17-7: You will be asked this!
BACTERIAL MENINGITIS
See Table 17-7 for common meningitis-causing bacteria.
Associated with high rate of complications and chronic morbidity.
TABLE 17-6. Cerebrospinal Fluid (CSF) Findings in Meningitis
TABLE 17-7. Common Causes of Pediatric Bacterial Meningitis
Pathogenesis: 95% blood-borne. Organism enters the CSF, multiplies, and stimulates an inflammatory response. Direct toxin from organism, hypotension, or vasculitis → thrombotic event; vasogenic/cytotoxic edema causes ↑ ICP and ↓ blood flow, which all may contribute to further damage.
Chronic meningitis: Bacterial: TB, Lyme, syphilis Viral: Cryptococcus, histoplasmosis, coccidioidomycosis, and Nocardia Noninfectious: Cardiovascular disease
VIRAL MENINGITIS
Enterovirus (85%): Echovirus, coxsackievirus, and nonparalytic poliovirus.
Other classic causes are herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV), mumps, influenza, arboviruses, and adenoviruses.
Clinical presentation is similar but symptoms are less severe than that of bacterial meningitis.
Children are not toxic looking.
Children show typical viral-type infectious signs (fever, malaise, myalgia, nausea, and rash) as well as meningeal signs.
Typically is a self-limited process with complete recovery, and treatment is supportive.
FUNGAL MENINGITIS
Although relatively uncommon, the classic organism is Cryptococcus.
Encountered primarily in the immunocompromised patient (with transplants, AIDS, or on chemotherapy).
May be rapidly fatal (as quickly as 2 weeks) or evolve over months to years.
Tends to cause direct lymphatic obstruction, → hydrocephalus.
Treat all acute cases of meningitis as if they are bacterial until cultures return.
TREATMENT
Third-generation cephalosporin (cefotaxime/ceftriaxone).
Add ampicillin for Listeria in neonates. Neonates can be treated with ampicillin + gentamicin or ampicillin + cefotaxime.
Add vancomycin, considering the increasing resistance of pneumococci to cephalosporins and carbapenems until the sensitivities are known.
If viral etiology is suspected or CSF is not clearly differentiating between bacterial and viral etiologies, consider adding acyclovir until viral polymerase chain reaction (PCR) comes back negative.
Steroid use is controversial.
Nuchal rigidity. Think: Meningitis.
ENCEPHALITIS
DEFINITION
A disease process in the brain primarily affecting the brain parenchyma.
Because patients often have symptoms of both meningitis and encephalitis, the term meningoencephalitis is often applied.
Congenital syphilis may manifest around age 2 with Hutchinson’s triad:
Interstitial keratitis
Peg-shaped incisors
Deafness (cranial nerve [CN] VIII)
ETIOLOGY
Chronic Bacterial Meningoencephalitis.
1. Mycobacterium tuberculosis, M bovis, and M avium-intracellulare.
Nonspecific features develop over days to weeks. Patients have generalized complaints of headache, malaise, and weight loss initially.
This is followed by confusion, focal neurological signs, cranial nerve palsies, and seizures or, in advanced cases, hemiparesis, hemiplegia, or coma.
Serious complications include arachnoid fibrosis, → hydrocephalus, and arterial occlusion, → infarcts.
M avium-intracellulare is common in AIDS patients.
Argyll Robertson pupil is discrepancy in pupil size seen in neurosyphilis.
2. Neurosyphilis (tabes dorsalis).
Causative organism is Treponema pallidum.
May present with aseptic meningitis only.
Tertiary syphilis (late-stage syphilis) manifests with neurologic, cardiovascular, and granulomatous lesions.
Congenital syphilis presents with a maculopapular rash, lymphadenopathy, and mucopurulent rhinitis.
Routine prenatal screening for syphilis is now mandatory in most states to prevent congenital syphilis.
Pupil reacts poorly to light but accommodation is normal.
Viral Meningoencephalitis.
1. Herpes simplex virus:
HSV-1: Most cases after the neonatal period.
HSV-2: Usually blood-borne and results in diffuse meningoencephalitis and other organ involvement. It is the congenitally acquired form, transmitted to 50% of babies born to a mother with active vaginal lesions.
The transmission rate of syphilis from infected mother to infant is nearly 100%. Treat infant with IV penicillin G.
2. Herpes zoster virus:
Can occur after primary infection or as a result of reactivation later in life.
Usually with a rash, but outcome is poor in those without a rash.
In immunocompetnt hosts, after 2–6 months of primary infection, the dormant virus in the ganglia becomes activated in and causes large-vessel vasculitis → infarcts.
Acyclovir is the treatment of choice for herpetic meningitis.
In immunocompromised hosts, the dormant virus causes small-vessel vasculitis and results in hemorrhagic infarcts of gray and white matter.
EEG will show diffuse slowing and periodic lateralizing epileptiform discharges (PLEDs).
3. Rabies:
Causes severe encephalitis, coma, and death due to respiratory failure.
Transmitted via bite from an infected animal, usually associated with dogs, bats, skunks, raccoons, or squirrels.
The virus travels up the peripheral nerves from the bite site and enters the brain.
Nonspecific symptoms (fever, malaise) and paresthesia around the bite site are pathognomonic. This is followed by more specific neurologic symptoms of hydrophobia, aerophobia, agitation, hypersalivation,and seizures. This proceeds to coma and death.
Hydrophobia is a classic, late finding but is not consistently present.
TRANSVERSE MYELITIS
DEFINITION
An acute focal infectious or immune-mediated illness causing swelling and demyelination of the spinal cord. This most commonly affects the thoracic spinal cord (80%) followed by cervical cord.
It is a neurological emergency and requires prompt diagnosis and treatment to prevent permanent damage.
SIGNS AND SYMPTOMS
Fever, lethargy, malaise, muscle pains.
Begins acutely and progresses within 1–2 days.
Back pain at the level of the involved cord and paresthesias of the legs are common.
Anterior horn involvement may cause lower motor neuron dysfunction.
Bladder and bowel dysfunction is present.
DIAGNOSIS
MRI: Enhanced T2 signals.
CSF: Pleocytosis.
Electromyogram (EMG): Anterior horn cell dysfunction in involved segments.
TREATMENT
IV steroids, intravenous immune globulin (IVIG), may require surgical intervention.
PROGNOSIS
Most make good recovery; however, it is slow.
Numerous viruses as well as the rabies vaccination and smallpox vaccination have been linked to transverse myelitis.
TETANUS
A 1-week-old child born to an immunocompromised mother presents with difficulty feeding, trismus, and other rigid muscles. Think: tetanus.
Tetanus is a toxin-mediated disease characterized by severe skeletal muscle spasms. It is a serious infection in neonatal life. Initial symptoms can be nonspecific. Inability to suck and difficulty in swallowing are important clinical features followed by stiffness and seizures. Neonatal tetanus can be prevented by immunizing mothers before or during pregnancy and providing sterile care throughout the delivery.
DEFINITION
An acute illness with painful muscle spasms and hypertonia caused by the neurotoxin produced by Clostridium tetani.
These symptoms usually starts in the jaw and facial muscles and progressively involve other muscle groups.
SIGNS AND SYMPTOMS
Trismus (masseter muscle spasm) is the characteristic sign and is present in 75% of cases.
Risus sardonicus, a grin caused by facial spasm, is also classic.
Dysphagia due to pharyngeal spasm develops over a few days; laryngospasm may result in asphyxia.
The muscles are involved in a descending order and once the paralysis involves the trunk and thigh, the patient may exhibit an arched posture in which only the head and heels touch the ground.
Late stages manifest with recurrent seizures consisting of sudden severe tonic contractions of the muscles with fist clenching, flexion, and adduction of the upper limb and extension of the lower limb.
The development of seizures is associated with poor prognosis.
Autonomic dysfunction may be seen as ↑ sweating, heart rate, blood pressure, and temperature.
Can also present with localized spasms at the site of infection or with abdominal pain mimicking acute abdomen.
Incubation period varies from 2 to 14 days (average 7 days).
DIAGNOSIS
Diagnosis is clinical, with the presence of trismus, dysphagia, ↑ rigidity, and muscle spasms.
Laboratory studies are usually normal, but a moderate leukocytosis may be present.
CSF is normal.
Gram stain is positive in only one-third of cases.
TREATMENT
Admit to ICU for prophylactic intubation.
Rapid administration of human tetanus immune globulin.
IV penicillin G, metronidazole, or doxycycline.
Tetanic contractions can be triggered by minor stimuli, such as a flashing light. Patients should be sedated, intubated, and put in a dark room in severe cases.
Surgical excision and debridement of the wound.
Muscle relaxants such as diazepam, phenobarbital should be used to promote relaxation and seizure control. Neuromuscular blocking agents like vecuronium are also used.
PROGNOSIS
Mortality rate: 5–35%.
Neonatal tetanus mortality ranges from 10% to 75%, depending on quality of care received.
ENCEPHALOPATHIES
DEFINITION
A syndrome of generalized dysfunction of the brain.
TYPES
Two main groups:
1. Progressive encephalopathies with onset before age 2 years.
If other systems are involved in addition to nervous system then it is lysosomal, peroxisomal, or mitochondrial disorders.
If peripheral nervous system and muscles involved in addition to central nervous system is likely lysosomal or mitochondrial.
Gray matter or white matter disease.
2. Encephalopathies that begin during childhood after age 2 years.
Lysosomal disorders: Gaucher’s type 3, late onset Krabbe disease, juvenile Tay-Sachs disease, Niemann-Pick disease type C.
Infectious disease: AIDS, congenital syphilis, subacute sclerosing panencephalitis.
Grey matter disorders: Ceroid lipofuscinosis, Huntington disease, mitochondrial disorders (late-onset poliodystrophy, myoclonic epilepsy, and ragged-red fibers), xeroderma pigmentosa.
Tetanus is an entirely preventable disease via immunization.
Mitochondrial Encephalopathy
A group of disorders that can be caused by mutations in either nuclear or mitochondrial DNA, resulting in a variety of symptoms:
1. Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS):
The most common of mitochondrial encephalopathies.
Onset between ages 2 and 10 yr; initial development normal, but short stature is present.
The most initial feature is GTC seizure (often associated with hemiparesis and cortical blindness), recurrent headache, and vomiting.
The neurologic abnormalities are transient initially, but later become progressive and → coma and death.
MRI shows multiple strokes not in vascular distribution pattern. ↑ lactic acid in blood and CSF. Muscle biopsy is diagnostic (ragged-red fibers).
2. Myoclonic epilepsy with ragged-red fibers (MERRF):
Onset may be in childhood or adult life.
Four cardinal features are myoclonus, myoclonic epilepsy, ataxia, and ragged-red fibers on muscle biopsy.
The initial feature is progressive insidious decline in school performance. GTC seizures or myoclonus is usually the first symptom to seek medical attention. Later, they develop progressive epilepsy, cerebellar ataxia, and dysarthria. Clinical myopathy may not be present.
Diagnosis is by gene testing and muscle biopsy.
MELAS and MERRF are caused by point mutations in transfer RNA (tRNA) in mitochondrial DNA.
MELAS = leucine
MERRF = lycine
MERRF is often confused with Friedreich’s ataxia.
3. Reye syndrome:
A disorder of mitochondrial dysfunction associated with viral infection and aspirin ingestion.
Sporadic syndrome can occur with varicella-zoster or influenza B infection.
Recurrent Reye-like syndrome is seen in children with inborn errors of metabolism, medium-chain acyl Co-A dehydrogenase (MCAD) deficiency, urea cycle disorders, pyruvate metabolism disorders.
Diagnosis: Liver biopsy is diagnostic. ↓ blood glucose, ↑ ammonia and liver enzymes without jaundice.
In general, salicylates should be avoided in children to prevent Reye syndrome.
Hepatic Encephalopathy
Acute hepatic failure caused by viral hepatitis, drugs, toxins, or Reye syndrome results in altered consciousness (due to cerebral edema and accumulation of toxins, ammonia).
In children, most commonly related to fulminant viral hepatitis (50–75%).
Early symptoms are malaise, lethargy, jaundice, dark urine, and abnormal liver function tests (LFTs). The encephalopathy can be acute or chronic.
Other features include, sleep disturbance, change in affect, drowsiness, asterixis (flapping tremor). Decerebrate posturing may occur in the terminal stages.
Hepatic encephalopathy is reversible with treatment, and most therapies are aimed at controlling the cerebral, renal, and cardiovascular functions until the liver regenerates or liver transplantation can be done. These are achieved by lowering:
Ammonia level (↓ dietary protein, stop gastrointestinal [GI] bleed, treat constipation).
Cerebral edema with fluid restriction and the use of hyperosmolar agents (mannitol).
Patients who recover typically have no long-term sequelae.
HIV/AIDS Encephalopathy
There is a 40–90% incidence of CNS involvement in perinatally infected children.
Ninety percent of infected infants are symptomatic by 18 months of age.
Develops 2–5 months after infection.
Commonly presents with progressive encephalopathy and hepatosplenomegaly, → failure to meet developmental milestones, impaired brain growth, and symmetrical motor dysfunction.
Imaging techniques reveal cerebral atrophy in 85% of children and ventricular enlargement.
Basal ganglia calcifications may be present.
Opportunistic infections such as toxoplasmosis typically occur later in adolescence.
PCR analysis of HIV DNA or RNA is used to detect HIV infection in infants < 18 months.
Diagnosis: Via immunoglobulin G (IgG) antibody to HIV for patients > 18 months and a confirmatory test HIV DNA PCR.
Treatment: Highly active antiretroviral therapy (HAART).
All pregnant mothers are tested for HIV infection and are treated to ↓ the transmission.
Old lead paint is the number one cause of lead toxicity.
Lead Encephalopathy
There is no direct correlation to the level of lead and clinical manifestations. Lead interferes with porphyrin metabolism in red blood cells (RBCs).
Acute: Vomiting, abdominal pain, seizures, impaired consciousness, and respiratory arrest are common.
Chronic: Gradual confusion, behavior changes, sleep problems, seizures, ataxia. Peripheral neuropathy, while common in adults, is rarely seen in children unless they also have sickle cell anemia.
Pica is common in these children (eg, eating paint chips).
Diagnosis is made primarily through history and also via blood lead testing. Microcytic hypochromic anemia, basophilic stippling, and azotemia also present.
Treatment: Removing the source of lead, and chelation therapy.
PANDAS (pediatric autoimmune neuropsychiatric disorder) has been suggested for the syndrome of behavioral problems, obsessive-compulsive behavior, and tics with an antecedent group A β-hemolytic streptococcal infection.
Sydenham’s Chorea
Rapid, brief, unsustained, nonstereotypical movements of the body.
Autoimmune mediated.
Twice as common in females.
Onset: Age 3–17 yr.
Postinfectious chorea appearing 4–8 weeks after a group A streptococcal pharyngitis.
Resolves after 8–9 months; 50% have persistent chorea.
Diagnosis: Recent throat infection (anti-streptolysin O, DNase B), ↑ T2 signals in basal ganglia.
Treatment:
Valproate: First choice.
Dopamine-blocking agents: Second choice.
Also treat primary infection.
Posited to fall in a disease spectrum including Syndenham’s chorea, in which there is an autoimmune attack of the basal ganglia triggered by a group A strep infection.
Adrenoleukodystrophy
A progressive disease, characterized by demyelination of the CNS and peripheral nerves and adrenal insufficiency.
X-linked recessive, peroxisomal disorder, defect in the ability to catabolize long-chain fatty acids (LCFAs).
It presents between 4 and 10 yr with behavioral and cognitive decline with visual loss, followed by motor symptoms.
Diagnosis: White matter abnormality on MRI, ↑ serum very-long-chain fatty acids (VLCFA), labs for adrenal insufficiency.
Treatment: Bone marrow transplantation if only radiological changes are present and no appearance of the neurological symptoms.
Methylphenidate may unmask Tourette syndrome but does not cause it.
Tourette Syndrome
A lifelong condition affecting 1 in 2000 that presents before age 15.
Diagnostic criteria: Multiple motor and vocal tics for > 1 year with tic-free period not more than 3 consecutive months.
Often associated with other conditions like obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder (ADHD).
Symptoms are enhanced by stress and anxiety.
Treatment with medications should be avoided.
Treat when tics interfere with child’s developmental learning or cause undue social stress. Also treat comorbid conditions.
CEREBRAL PALSY (CP)
DEFINITION
A nonprogressive disorder of movement and posture resulting from damage to the developing brain prior to or surrounding birth. If progressive, consider another diagnosis.
Most cases occur in the absence of identifiable causes.
ETIOLOGY
Prematurity with intraventricular hemorrhage.
Birth or other asphyxia.
Intrauterine growth retardation (IUGR), placental insufficiency.
Infection: Prenatal/postnatal.
Twin pregnancy.
Chromosomal and genetic disorders.
Head trauma.
CP is a static disorder, meaning that it does not result in the loss of previously acquired milestones.
SIGNS AND SYMPTOMS
Prenatal and perinatal history.
Delayed motor, language, or social skills.
Not losing skills previously acquired.
Feeding difficulties.
Late-onset dystonia (age 7–10).
EXAMINATION
Hypertonia.
Hyperreflexia.
Posture and movement: May be spastic, ataxic, choreoathetoid, and dystonic.
Abnormal primitive reflexes.
Abnormal gait.
Impaired growth of affected extremity.
ASSOCIATED PROBLEMS
Seizure disorder
Mental retardation
Developmental disorders
When there are no risk factors, family history of neurologic disease, presents late infancy or early childhood, ataxic CP, or atypical features, then consider other diagnosis.
Extensor plantar response (presence of Babinski sign) can be present up to 1 year of age, but should be present symmetrically.
CLASSIFICATION
Hemiplegic cerebral palsy: Upper limb involvement > lower limb; many walk before 2 years.
Diplegic cerebral palsy.
Quadriplegic cerebral palsy: Majority does not walk.
Dystonic/athetoid cerebral palsy.
Ataxic cerebral palsy.
Monoplegic cerebral palsy: Usually lower limb and appears late.
TREATMENT
Multidisciplinary approach with goals of maximizing function and minimizing impairment.
Team includes general pediatrician, physiotherapist, occupational therapist, language therapist, neurologist, and social and educational support services.
Orthopedic interventions are sometimes helpful.
DQ is often used as a rough estimator of IQ in infants and younger children. It is simply the mental age (estimated from historical milestones and exam) divided by the chronologic age, × 100.
MENTAL RETARDATION (MR)
DEFINITION
Below average intellectual functioning in association with deficits in adaptive behavior prior to 18 years of age.
Intelligence quotient (IQ) or developmental quotient (DQ) < 70 or < 2 standard deviations (SDs).
EPIDEMIOLOGY
Affects 1–3% of the population.
Approximately 75% are mild cases.
Males are affected more than females.
SIGNS AND SYMPTOMS
Significant delay in reaching developmental milestones.
Delayed speech and language skills in toddlers with less severe MR.
The child will continue to learn new skills depending on severity of MR.
The IQ is scaled such that the mean is 100 and the standard deviation (SD) is 15. So MR is simply defined as an IQ two SDs below the mean.
DIAGNOSIS
Classification is based on IQ:
Mild: IQ 55–70, 85% of cases.
Moderate: IQ 40–55, 10% of cases.
Severe: IQ 25–40, 3–5% of cases.
Profound: IQ < 25, 1–2% of cases.
Earlier classification:
Moron: IQ 51–75
Imbecile: IQ 26–50
Idiot: IQ ≤ 25
This is no longer considered politically correct.
LEARNING DISABILITY (LD)
Significant discrepancy between a person’s intellectual ability and academic achievement.
Often learn best in unconventional ways.
Often restricted to a particular realm such as reading or mathematics with correspondingly discrepant scores on standardized measures of intelligence or academic achievement.
Significant improvement with appropriate interventions.
Titubations are a disturbance of body equilibrium in standing or walking, resulting in an uncertain gait and trembling, especially resulting from diseases of the cerebellum.
ATAXIAS
Inability to coordinate muscle activities to regulate posture and also strength and direction of extremity movements (see Table 17-8).
Types
ACUTE CEREBELLAR ATAXIA
A diagnosis of exclusion occurring in children 2–7 years old.
Often follows viral infection by 2–3 weeks; thought to be autoimmune response and has been seen with live inactivated vaccines like varicella vaccine.
Sudden onset of severe truncal ataxia; often, the child cannot stand or sit.
Severity is maximum at the onset with clear sensorium.
Horizontal nystagmus in 50%.
Diagnosis: Diagnosis of exclusion; exclude other serious causes first.
Treatment: Self-limited disease.
Prognosis: Complete recovery typically occurs within 2 months (1–5 months).
TABLE 17-8. Ataxias
FREIDREICH’S ATAXIA
Autosomal-recessive mutation (usually a triplet expansion) in Frataxin gene on chromosome 9.
Degeneration of the dorsal columns and rootlets, spinocerebellar tracts, and, to a lesser extent, the pyramidal tracts and cerebellar hemispheres.
Onset before age 10 (2–16 yr).
Slow progression of ataxia involving the lower limbs > upper limbs associated with dysarthria, ↓ tendon reflexes, positive Babinki’s sign, high-arch foot with loss of dorsal column sensations.
Romberg test is positive.
Associated abnormalities include skeletal abnormalities (scoliosis), cardiomyopathy, and optic atrophy.
Elevated α-fetoprotein (AFP).
Clinical features establish the diagnosis, which is confirmed with genetic testing. There is no curative treatment available but symptomatic treatment to improve quality of life.
Myoclonic epilepsy with ragged-red fibers (MERRF) is often confused with Friedreich’s ataxia.
ATAXIA-TELANGIECTASIA
Autosomal-recessive disorder of nervous and immune system due to gene mutation at chromosome 11.
The most common degenerative ataxia.
A slowly progressive ataxia beginning during first year of life resulting in inability to walk by adolescence.
Oculomotor apraxia is a present in 90% of the patients.
Telangiectasia becomes evident after 2 yr or in the teenage years and is most prominent on the bulbar conjunctiva (first), bridge of nose, and exposed surfaces of the extremities. Sun exposure exacerbates the telangiectasia.
Sinopulmonary infection is another important feature. ↓ or absent IgA, IgE, and especially IgG2 subclass. IgM may be ↑.
↑ AFP and peripheral acanthocytes.
Have a 50- to 100-fold greater chance of brain tumors and lymphoid tumors, so avoid radiation exposure by limiting imaging studies.
PERIPHERAL NEUROPATHIES
Injuries to the peripheral nerves may be either:
Demyelinating (injury to Schwann cells).
Degenerating (injury to the nerve or axon).
Peripheral neuropathy is the most common cause of progressive distal weakness.
Most common are hereditary causes and slow progression.
The most common acquired cause is Guillain-Barré syndrome (GBS) with rapid progression.
Types
GUILLAIN-BARRé SYNDROME
A 6-year-old boy with no significant past medical history presents to the ED with difficulty walking for past few days and is now unable to walk. He also has some weakness in his upper extremities but he does not have any respiratory distress. There is no clear history of any recent illness, vaccination, or sick contacts. He had upper respiratory infection symptoms a few weeks ago. On examination, he is weaker more in the lower extremities than upper, and deep tendon reflexes are absent at knee and ankle. Think: Guillain-Barré syndrome (GBS).
GBS is an ascending paralysis. History of prior upper respiratory tract or viral infection or recent vaccination may be present. Initial symptoms are pain, numbness, paresthesia, or weakness in the lower extremities, which rapidly progresses to bilateral and relatively symmetric weakness. ↓ or absent deep-tendon reflexes are often present. Lumbar puncture typically shows ↑ protein with normal CSF and white cell count (cyto-albuminologic dissociation).
A postinfection demyelinating neuropathy affecting predominantly the motor neurons.
It is due to immune cross-reactivity to a secondary illness within 4 weeks. Most commonly seen after upper respiratory infection (URI), Campylobacter jejuni, Mycoplasma pneumoniae, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella, influenza, hepatitis A and B infection.
Weakness begins in the legs and progresses symmetrically upward to the trunk, arms, then bulbar and ocular muscles.
Tendon reflexes are absent.
Respiratory muscles in 50%, autonomic dysfunction, pain, paresthesias can be present.
↑ proteins in CSF with no ↑ in lymphocytes.
Nerve conduction will be slow with conduction blocks, and enhancement of nerve roots can be seen on MRI.
Treatment includes close monitoring for respiratory weakness and IVIG or plasmapheresis in more severe cases.
It is not possible to have botulism without having multiple cranial nerve palsies.
BOTULISM
Botulinum toxin is disseminated through the blood and, due to the rich vascular network in the bulbar region, symmetric flaccid paralysis of the cranial nerves is the typical manifestation.
Infant botulism: The first sign is usually absence of defecation. The head control is lost and the weakness descends.
Most dreaded complication is respiratory paralysis, and approximately 50% of patients are intubated.
Prognosis is good in noncomplicated cases.
Antibiotics and blocking antibodies have not been shown to affect the course of the disease.
Electromyogram (EMG) with high frequency (20–50 Hz) reverses the presynaptic blockade and produces an incremental response.
Infantile botulism is associated with ingestion of honey (honey contains botulism spores).
MYASTHENIA GRAVIS
↓ in postsynaptic acetylcholine receptors due to autoimmune degradation, resulting in rapid fatigability of muscles.
Ptosis and extraocular eye weakness are the earliest and most diagnostic symptoms.
Onset usually after age 8, as early as 6 months. Prepubertal male bias, postpubertal female bias.
Diagnosis is made by EMG with repetitive stimulation, edrophonium (Tensilon) test, a quick test (acetylcholinesterase inhibitor). Acetylcholine receptor-binding or -blocking antibodies are detected in the sero-positive forms and are an indication for thymectomy. May be associated with autoimmune thyroid disease and seizures.
Cholinesterase drugs are the mainstay of treatment, with oral steroids used as needed for immune suppression (initially may exacerbate the disease).
Prognosis varies, with some children undergoing spontaneous remission, while in others the disease persists into adulthood.
TRANSITORY NEONATAL MYASTHENIA
Passive transfer of antibodies from myasthenic mothers (10–15% incidence).
Self-limited disease consisting of generalized weakness and hypotonia for 1 week to 2 months. Symptoms develop a few hours after birth. If develop after 3 days, then are unlikely.
Poor suck and respiratory problems are addressed with supportive care. Neostigmine or exchange transfusion can be used in more severe cases.
Children with myasthenic syndromes cannot tolerate neuromuscular blocking drugs, such as succinylcholine, and various other drugs. Most offenders are in the antibiotic, cardiovascular, and psychotropic categories.
FAMILIAL INFANTILE MYASTHENIA
Rare disorder.
Collection of autosomal-recessive seronegative disorders of the neuro-muscular junction. Most defects are postsynaptic, but presynaptic forms are described.
Onset can be neonatal. Diagnosis by EMG with repetitive stimulation, response to edrophonium, specialized testing for identification of the specific defect.
Long-term treatment with neostigmine or pyridostigmine useful in some forms (acetylcholinesterase inhibitors). Thymectomy and immunosuppression are of no benefit.
Remember, rapid correction of hyponatremia can result in cerebellar pontine myelinosis.
ELECTROLYTE IMBALANCES
See Table 17-9 for common electrolyte imbalances affecting the nervous system.
HEADACHES
Migraine
The most common type of headache in the pediatric population with female predominance.
TABLE 17-9. Electrolyte Disturbances and the Nervous System
DEFINITION
A recurrent headache with symptom-free intervals and associated with the following:
Abdominal pain.
Nausea and/or vomiting.
Throbbing headache.
Often bilateral (vs. unilateral in adults).
Associated aura.
Relieved by sleep.
Family history of migraines.
CLASSIFICATION
Migraines may be classified into the following subgroups:
The diagnosis of migraine in children is based on clinical symptoms, and usually we do not follow the International Headache Society criteria in young children.
Diagnosis of migraine is clinical and no neuroimaging is necessary unless it is persistently occipital or with abnormal neurologic examination.
COMMON MIGRAINE
The most prevalent type of migraine in children.
Intense nausea and vomiting are classic.
Aura is absent.
Family history is present in 80%, most often on the maternal side.
CLASSIC MIGRAINE
An aura precedes the headache by 5–20 min and nearly always disappears before the headache begins.
The auras most often manifest as paresthesias and visual disturbances such as flashing lights, black dots, zig-zag lines.
Common migraines may present with vomiting, abdominal pain, and fever, and should be included in the differential of ↑ ICP diseases.
COMPLICATED MIGRAINE
Transient neurologic signs develop during a headache and persist after the resolution of the headache for a few hours to days.
TREATMENT
Avoid the possible triggers: Often, migraines occur in response to specific triggers, such as psychological stress, strenuous exercise, sleep deprivation, cheese, chocolate, processed meat, or moving vehicles, and minimizing these factors may have great therapeutic effect.
Consider nonpharmacologic treatment with biofeedback techniques in chronic stress headache.
For acute attacks:
Dark, quiet environment and sleep.
Adequate fluid intake.
Pharmacologic therapy: Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are first line.
Second-line drugs include triptans, caffeine, and ergot alkaloids (status migrinosus).
Antiemetics are helpful at the start of headache.
Treatment should be instituted as early as possible in an attack.
Prophylaxis should be offered to children with two or more migraines per month that interfere with activities such as school or recreation.
PROPHYLAXIS
Antiepileptic drugs, such as topiramate, valproate, levetiracetam.
Tricyclic antidepresssants such as amitriptyline.
β blockers such as propranolol.
Cluster Headache
Brief, severe, unilateral stabbing headaches that occur multiple times daily over a period of several weeks and tend to be seasonal.
Onset after 10 yr of age.
Male predominance.
Conjunctival injection, tearing, rhinorrhea.
Prophylaxis with lithium or calcium channel blocker.
Acute treatment with 100% oxygen or sumatriptan and dihydroergotamine (DHE).
Tension Headache
Tension or stress headaches are rare in children prior to puberty and are often difficult to differentiate from migraines.
PRESENTATION
Most often occur with a stressful situation, such as an exam.
Described as “hurting” but not “throbbing.”
It presents like a band around the head. It is present most of the times of the day.
Unlike migraines and ↑ intracranial pressure, tension headaches are not associated with nausea and vomiting,
However, it is sometimes difficult to differentiate them from migraine.
DIAGNOSIS
Diagnosis of exclusion.
EEG or CT is not necessary.
A poor self-image, fear of failure, and low self-esteem are common factors.
Headaches can occur in children secondary to refractive errors. It is therefore imperative to perform a visual acuity determination.
TREATMENT
Steps should be taken to minimize anxiety and stress:
Mild analgesics often are ample.
Other options include counseling and biofeedback.
Sedatives or antidepressants are rarely necessary.
Normal ICP
Newborns: 6 mmHg Children: 6–13 mmHg Adolescents/adults: 0–15 mmHg
Increased Intracranial Pressure (ICP)
Headache due to tension of the blood vessels or dura may be the first symptom of an ↑ in intracranial pressure.
SYMPTOMS
It usually presents as headache, nausea, vomiting, diplopia, personality changes.
It can present as bulging fontanelle, impaired upward gaze in infants.
The presentation depends also on rate at which the ICP increases. If it increases slowly, then the intracranial structures have time to accommodate for the change.
Coughing or Valsalva’s maneuver tends to make the pain worse by increasing ICP further.
Any time you see papilledema, think ↑ ICP.
ETIOLOGY
Common causes include posterior fossa brain tumors (and other brain tumors), obstructive hydrocephalus, hemorrhage, meningitis, venous sinus thrombosis, pseudotumor cerebri, abscesses, and chronic lead poisoning.
DIAGNOSIS
Thorough history and physical exam are vital.
Papilledema (if ↑ pressure is present for some time) and nuchal rigidity are helpful signs.
Obtain CBC, erythrocyte sedimentation rate (ESR), and CT/MRI to narrow the differential.
If CT/MRI is negative, consider lumbar puncture (LP).
A classic textbook finding due to compression of the brain stem is Cushing’s triad:
1. ↓ respiratory rate
2. ↓ heart rate
3. ↑ BP (actually seen in 20–30%)
TREATMENT
Varies with particular diagnosis, and should be directed at the underlying etiology.
Techniques to lower ICP acutely are as follows:
1. Intubation and subsequent hyperventilation results in cerebral vasoconstriction, effective for about 30 min.
2. Elevating the head 30 degrees facilitates venous return.
3. Hyperosmolar agents such as mannitol (osmotic diuretic), avoid hypovolemia.
4. Extraventricular drain provides temporary relief and can provide continuous monitoring of ICP.
5. Surgical decompression if persistently remains ↑.
MRI is the best test for a posterior fossa tumor.
ANEURYSMS
The pathogenesis of the aneurysms is multifactorial and controversial; however, it is believed that focal congenital weakness of the internal elastic lamina and muscular layers in the cerebral arteries → to aneurysmal formation.
Most common in internal carotid artery followed by middle cerebral artery, anterior communicating artery, and basilar artery.
Saccular aneurysms are the most common type and often at bifurcation of the internal carotid artery.
Early warning signs are headaches or localized cranial nerve compression.
Most common presentation is subarachnoid hemorrhage (SAH).
More likely to rupture in patients < 2 years of age or > 10 years.
More common in males 2:1.
Familial occurrence is common.
Never perform an LP if papilledema is present.
Must obtain CT before LP if suspicion of ↑ ICP.
Subarachnoid hemorrhage can present as subacute or repeated headaches.
ETIOLOGY
Most often are related to a congenital diseases:
Ehlers-Danlos syndrome.
Marfan syndrome, tuberous sclerosis.
AVMs.
Coarctation of the aorta.
Polycystic kidney disease (likely develop secondary to hypertension in this condition); called berry aneuryms.
Acquired aneurysms are most often related to bacterial endocarditis:
Embolization of bacteria results in mycotic aneurysms in the cerebral vasculature.
Twenty-five percent present with bleeding, such as a subarachnoid or intraparenchymal hemorrhage.
CT reveals hemorrhage in two-thirds of patients. LP reveals ↓ RBCs in tube 4 and xanthochromia.
DIAGNOSIS
Angiography is the gold standard for aneurysms in both children and adults.
Magnetic resonance angiography (MRA) may also be used and is becoming more reliable.
Relatively more children have aneurysms in the vertebrobasilar circulation (23%) compared to adults (12%).
TREATMENT
Surgical clipping or endovascular coiling is the treatment of choice.
Risk for rebleeding.
ARTERIOVENOUS MALFORMATIONS (AVMs)
True AVMs consist of an abnormal communication of arteries and veins without intervening capillaries that arises during development in prenatal period or just after birth.
It grows in size with time and varies in size from several millimeters to several centimeters.
The larger ones create a significant atrioventricular (AV) shunt (steal phenomenon) and considerable damage if they rupture.
Supratentorial (90%).
PRESENTATION
Small unruptured malformations present with headache or seizures.
Larger malformations may present with progressive neurologic deficit.
Hemorrhage is most often presentation (subarachnoid or intraparenchymal).
DIAGNOSIS
Angiography is the test of choice and is required to direct the future therapy. MRA is also available.
MRI or CT with contrast can demonstrate an AVM but provide less information than angiography.
Photon knife is the treatment.
Common AVM Variants
VEIN OF GALEN MALFORMATIONS
Normal vein of Galen does not develop from its primitive vein, which persists and communicates with superior saggital sinus.
Typically present during infancy with high-output congestive heart failure (CHF), failure to thrive, or enlarging head size.
Mortality is 50%.
Treatment is difficult embolization is preferred over surgery.
A cranial bruit is often present with vein of Galen malformations.
CAVERNOUS HEMANGIOMAS
Low-flow AVM with tendency to leak (cause seizure) but usually do not result in massive intracerebral hemorrhage.
Retinal cavernous hemangiomas may be also present.
Surgical resection is indicated if symptomatic.
VENOUS ANGIOMAS
Rarely symptomatic (seizures are the most common presenting sign).
Surgery is not indicated unless complications arise.
TREATMENT
Treatment consists of surgical resection or embolization.
Focused gamma knife radiation has some benefit in smaller lesions.
STROKE
Transient ischemic attacks (TIAs): Neurologic deficits that resolves in < 24 hr.
Stroke: Neurological deficits persists beyond 24 hr.
EPIDEMIOLOGY
2.6–13 cases per 100,000 per yr.
Hemorrhagic stroke 1.5–5 per 100,000 children per yr.
Ischemic stroke 1.2 and 8 per 100,000 children per yr.
Gamma knife radiation typically takes up to 2 yr to see resolution of the AVM, during which time the patient is at risk for hemorrhage; thus, surgery is the treatment of choice.
SIGNS AND SYMPTOMS
Sudden onset of neurologic deficit or seizures in neonates.
Headache, neck pain, and visual symptoms.
ETIOLOGY
Pediatric causes of stroke differ from those in the adult population.
Types of stroke include:
Ischemic: Thrombosis (both arterial and venous) or embolic (arterial).
Hemorrhage.
A variety of conditions or risk factors exist for stroke, including:
AVMs.
Antiphospholipid antibodies/lupus anticoagulant.
Congenital coagulopathies such as factor V Leiden and deficiencies of protein C, S, and antithrombin III.
Hemoglobinopathies, sickle cell disease (SCD).
Sickle cell anemia at risk for ischemic stroke (sickling RBCs may → thrombosis or endothelial injury).
Cardiac conditions: Arrhythmias, myxoma, paradoxical emboli through a patent foramen ovale, and septic emboli from bacterial endocarditis.
Blunt trauma to the head and neck → arterial dissection.
Vasculitis, such as Kawasaki, hemolytic-uremic syndrome, systemic lupus erythematosus (SLE), meningitis.
Mitochondrial diseases.
Extracorporeal membrane oxygenation (ECMO) is a risk for both intracranial hemorrhage and embolic ischemic stroke.
Cardiac abnormalities are the most common cause of thromboembolic stroke in children.
Clinically Relevant Types of Stroke
ARTERIAL THROMBOSIS/EMBOLISM
Intracerebral arterial dissection after trivial trauma to head and neck due to a tear in the intima.
The cerebral area supplied by the vessel distal to lesion undergoes infarction and produces symptoms (loss of functions)
Cerebral symptoms such as a progressive hemiplegia, lethargy, or aphasia result from the shedding of small emboli into the carotid circulation.
Seizures are the most common presenting symptom in neonates.
Cardiac source usually.
History and physical exam are critical to search for the etiology.
VENOUS THROMBOSIS
May be subdivided into septic and nonseptic causes.
Septic causes include bacterial meningitis, otitis media, and mastoiditis.
Aseptic causes are numerous and include severe dehydration, hypercoagulable states, congenital heart disease, and hemoglobinopathies (SCD).
Neonates present with diffuse neurologic signs and seizures.
In children, focal neurologic signs are more common.
A typical workup for a stroke syndrome will include head CT or MRI scan, followed by an angiogram (if the CT/MRI is nondiagnostic), and a cardiac echo to exclude cardiac causes.
CLOSED HEAD TRAUMA
See Table 17-10 for a comparison of subdural and epidural hematomas.
Subdural Hematoma (SDH)
EPIDEMIOLOGY
The most frequent focal brain injury in sports and the most common form of sports-related intracranial hemorrhage. Seen most often in infants, with a peak at 6 months.
Low-molecular-weight heparin has been shown to be safe, effective, and well tolerated in children.
ETIOLOGY
Occurs when a bridging vein is torn between the dura and the brain.
In neonates due to a tear in tentorium near its junction with the falx.
Trauma is usually the cause. Skull fracture is not seen commonly.
An SDH should be ruled out if changes in conscious level are present after head injury.
Typically frontoparietal location. It can be acute, subacute, or chronic.
The extent of brain damage directly attributable to impact is the most important prognostic factor.
SIGNS AND SYMPTOMS
These depend on age of the child and also severity of the SDH.
Neonates: Seizures, a bulging fontanelle, and ↓ activity.
Retinal and preretinal hemorrhages common in children, especially in abused children.
↑ ICP (irritability, lethargy, vomiting, papilledema, headache).
Subdural hematomas appear crescent shaped (concave) on CT and will not cross the midline, but will cross ipsilateral suture lines.
DIAGNOSIS
Gold standard is CT scan.
Epidural Hematoma
EPIDEMIOLOGY
Seen most often in children > 2 years of age.
ETIOLOGY
Most commonly results from a fracture in the temporal bone, lacerating the middle meningeal artery.
Can be acute (arterial bleed) or chronic (venous bleed).
Skull fracture is seen commonly.
Nearly always unilateral; however, bilateral case has been described.
Lucid interval. Think: Epidural hematoma.
SIGNS AND SYMPTOMS
Classic progression involves an initial loss of consciousness, followed by a lucid interval, and then abrupt deterioration and death (not as helpful in younger children).
Hemorrhage and acute brain swelling cause ↑ ICP that can result in herniation with ispilateral ptosis, dilated pupil, and ispilateral hemiparesis due to contralateral compression of crus cerebri.
Retinal and preretinal hemorrhages are not common.
↑ ICP is seen (irritability, lethargy, vomiting, papilledema, headache).
DIAGNOSIS
Gold standard is CT scan.
TREATMENT
Epidural hematomas may progress rapidly, and immediate neurosurgical treatment is indicated.
Epidural hematomas appear lens shaped (convex) on CT and will not cross the midline or other cranial sutures.
Coup/Contrecoup Injuries
Cerebral contusion injury mainly occurs when the head is subjected to a sudden acceleration or deceleration.
COUP INJURIES
Located directly at the point of impact.
More common in acceleration injuries such as being hit with a baseball bat.
Multiple microhemorrhages as blood leaks into the brain tissue.
Old contusions develop an orange color secondary to hemosiderin deposition and are referred to as plaques jaunes by pathologists.
TABLE 17-10. Features of Acute Epidural and Subdural Hematomas
CONTRECOUP INJURIES
Located opposite (180 degrees) from the point of impact.
More common in deceleration injuries, such as striking one’s head on the pavement after a fall.
Contrecoup injuries tend to be more severe than coup injuries.
Diffuse Axonal Injury
EPIDEMIOLOGY
Tissues with differing elastic properties shear against each other, tearing axons.
Caused by rapid deceleration/rotation of head.
Locations:
Cerebral hemispheres near gray-white junction.
Basal ganglia.
Corpus callosum, especially splenium.
Dorsal brain stem.
High morbitity and mortality—common cause of posttraumatic vegetative state.
Initial CT often normal despite poor GCS.
Lesions often nonhemorrhagic and seen only on MRI.
Survivors often have substantial long-term cognitive and behavioral morbidity.
Diffuse axonal injury is best visualized on a T2-weighted MRI.
HYDROCEPHALUS
Head circumference > 2 SD above the mean is macrocephaly, and if due to ↑ CSF in the CSF spaces, it is called hydrocephalus.
PHYSIOLOGY
CSF is made by the choroid plexus in the walls of the lateral, third, and fourth ventricles.
CSF flows in the following direction: lateral ventricles → foramen of Monro → third ventricle → cerebral aqueduct → fourth ventricle → foramina of Magendie and Luschka → subarachnoid space of spinal cord and brain → arachnoid villi.
CSF is absorbed primarily by the arachnoid villi through tight junctions.
Choroid plexus papilloma is the only rare cause of hydrocephalus from ↑ CSF production.
ETIOLOGY
Obstructive (noncommunicating) hydrocephalus:
Most commonly due to stenosis or narrowing of the aqueduct of Sylvius.
An obstruction in the fourth ventricle is a common cause in children, including posterior fossa brain tumors, Arnold-Chiari malformations (type II), and Dandy-Walker syndrome.
Also seen in brain abscess, hematoma, infectious, vein of Galen malformation.
Nonobstructive (communicating) hydrocephalus:
Most commonly follows a subarachnoid hemorrhage or meningitis.
Blood in the subarachnoid spaces may obliterate the cisterns or arachnoid villi and obstruct CSF flow.
Venous sinus thrombosis, meningeal malignancy, and intrauterine infections are other causes.
Ex vacuo: Hydrocephalus resulting from ↓ brain parenchyma.
Pneumococcal and tuberculous meningitis produce a thick exudate that can obstruct the basal cisterns, → communicating hydrocephalus.
CLINICAL MANIFESTATIONS
Infants:
Accelerated rate of enlargement of the head is most prominent sign.
Bulging anterior fontanelle (fontanelles can provide some pressure relief in infants, delaying symptoms of ↑ ICP). Widening of cranial sutures, sun-setting sign, and Parinaud syndrome.
Upper motor neuron signs such as brisk reflexes are common findings due to stretching of the descending cortical spinal tract.
↑ ICP signs (lethargy, vomiting, headache, etc.) may be present, especially acutely ↑ ICP.
Ocular bobbing.
Children and adolescents:
Signs are more subtle because the cranial sutures are partially closed.
↑ ICP signs may be present. Visual fields particularly peripheral fields are involved gradually. Papilledema can be present.
A gradual change in school performance may be the first clue to a slowly obstructing lesion.
DIAGNOSIS
A detailed history and physical exam is key to discovering the underlying etiology.
Ultrasound and head CT/MRI are the most important studies to identify the cause of hydrocephalus.
Familial cases of aqueductal stenosis have been reported and have an X-linked pattern of inheritance.
Neurofibromatosis and meningitis have also been linked to aqueductal stenosis.
Preemies with intraventricular hemorrhage frequently develop hydrocephalus.
TREATMENT
Medical management with acetazolamide (may ↓ CSF production) and furosemide may provide temporary relief.
Placement of an extraventricular drain (EVD) or ventriculoperitoneal shunt (VPS), if the etiology is permanent, may be required.
NEOPLASMS
Pediatric Brain Tumors
EPIDEMIOLOGY
Most common solid tumors of the childhood.
Third most common pediatric tumors (#1 leukemia, #2 lymphoma).
Supratentorial tumors are as common as infratentorial tumors.
Glial cell tumors are the most common tumors in childhood and consist of astrocytomas, ependymomas, olidodendrioglioma, and primitive neuroectodermal tumor (PNET).
Medulloblastoma is a common PNET only in childhood.
Glioblastoma multiforme (GBM) is a high-grade glioma common in adults but rare in children.
CLINICAL MANIFESTATIONS
Generally present with either signs and symptoms of ↑ ICP (infants) or with focal neurologic signs (adolescents).
Alterations in personality are often the first symptoms of a brain tumor.
Nystagmus is the classic finding in posterior fossa tumors.
Clinical signs depending on location of the tumor (loss/alteration in the functions of the brain area).
Tumors in the posterior fossa tend to result in hydrocephalus secondary to CSF flow obstruction.
CEREBELLAR ASTROCYTOMA
The most common posterior fossa tumor of childhood.
It is a slow-growing poilocytic astrocytoma and more benign than the adult-onset astrocytomas.
Histologically shows fibrillary astrocytes with dense cytoplasmic inclusions called Rosenthal fibers.
Associated with neurofibromatosis type 2 (NF2).
Good prognosis; 5-year survival > 90% after gross total resection which is achieved in 70% of the cases.
Treatment is surgical resection.
Rosenthal fibers are also seen in Alexander’s disease, a progressive leukodystrophy with mental retardation, spasticity, and megalencephaly.
MEDULLOBLASTOMA (PNET)
The second most common posterior fossa tumor and the most prevalent brain tumor in children under the age of 7 yr. More common in males.
Rapidly growing malignant tumor, arises from the undifferentiated neural cells in the region of cerebellar vermis.
Tends to invade the fourth ventricle and spread along CSF pathways and involves the spine, so consider imaging the spine.
Histologic analysis shows deeply staining nuclei with scant cytoplasm arranged in pseudorosettes.
Presents with intracranial hypertension and ataxia, symptoms evolving in few weeks; papilledema is absent.
MRI: Brightly enhancing mass with cystic lesion.
Treatment: Surgical resection followed by irradiation.
Prognosis: Dependent on size and dissemination of the tumor, 5-year survival rate is > 80%.
CRANIOPHARYNGIOMA
One of the most common supratentorial brain tumors of childhood which arises from cells in the Rathke’s pouch.
It is locally aggressive and recurs.
Short stature or other endocrine-associated problems are common initial signs.
Typically slow growing and benign.
The tumor may be confined to the sella turcica or extend through the diaphragma sellae and compress the optic nerve or, rarely, obstruct CSF flow.
Due to location, surgical resection is often subtotal.
DIAGNOSIS
Ninety percent of craniopharyngiomas show calcification on CT scan; MRI provides better images of surrounding structures.
Baseline endocrine studies and visual fields should be done prior to surgery.
NEUROBLASTOMA (NB)
EPIDEMIOLOGY
A common tumor of neural crest origin, representing the most common neoplasm in infants and 8% of all childhood malignancies.
Malignant tumor that arises from the neural crest cells.
Ninety percent are diagnosed before age 5, with a peak at 2 yr.
Infants tend to have localized NB in the cervical or thoracic region, whereas older children tend to have disseminated abdominal disease.
PATHOGENESIS
NB is a small, round blue cell tumor with varying degrees of neuronal differentiation.
CLINICAL PRESENTATION
The tumor may arise at any site of sympathetic nervous tissue.
The adrenals, retroperitoneal sympathetic ganglia, and abdomen are the most common sites.
Thirty percent arise in the cervical or thoracic region and may present with Horner syndrome.
Opsoclonus-myoclonus: “Dancing eyes, dancing feet”—the telltale symptom of this disease (secondary to paraneoplastic antibodies).
DIAGNOSIS
Typically, a mass is seen on CT or MRI.
Ninety-five percent of cases have elevated tumor markers, most often homovanillic acid (HVA) and vanillylmandelic acid (VMA) in the urine.
Metaiodobenzylguanidine (MIBG) radioisotope scan for detecting small primaries and metastases.
Stage 4: Infantile form, self-limited with good prognosis.
Unfavorable prognosis is associated with ↑ neuron-specific enolase and amplification of N-Myc gene.
Treatment is surgical resection followed by radio + chemotherapy.
von Hippel–Lindau Disease
DEFINITION
A neurocutaneous syndrome (usually no cutaneous involment) affecting many organs, including the cerebellum, spinal cord, medulla, retina, kidneys, pancreas, and epididymis.
SIGNS AND SYMPTOMS
The major neurologic manifestations are:
Cerebellar/spinal hemagioblastomas: Present in early adult life with signs of ↑ ICP.
Retinal angiomata: Small masses of thin-walled capillaries in the peripheral retina.
Multiple congenital cysts of the pancreas and polycythemia are also associated with it.
Early detection and resection is the best management.
Photocoagulation for retinal detachment.
Renal carcinoma is the most common cause of death associated with von Hippel– Lindau disease.
Neurofibromatosis (NF)
EPIDEMIOLOGY
Both types display autosomal recessive inheritance patterns.
Type 1: The most prevalent type (∼90%) with an incidence of 1 in 4000 (chromosome 17).
Type 2: Accounts for 10% of all cases of NF, with an incidence of 1 in 40,000 (chromosome 22).
About 50% of NF-1 results from new mutations. Parents should be carefully screened before counseling on the risk to future children.
CLINICAL MANIFESTATIONS
Type 1
Diagnosis is made by the presence of two or more of the following:
Six or more café-au-lait macules (must be > 5 mm prepuberty, > 15 mm postpuberty).
Axillary or inguinal freckling (Crowe sign).
Two or more iris Lisch nodules (melanocytic hamartomas).
Two or more cutaneous neurofibromas.
A characteristic osseous lesion (sphenoid dysplasia, thinning of long-bone cortex).
Optic glioma.
A first-degree relative with confirmed NF-1.
Learning disabilities, abnormal speech development, and seizures are common.
Patients are at a higher risk for other tumors of the CNS such as meningiomas and astrocytomas (optic nerve gliomas in 20%) (but not as significantly as in NF-2).
Risk of malignant transformation to neurofibrosarcoma is < 5%.
NF-1: Café-au-lait spots, childhood onset.
NF-2: Bilateral acoustic neuromas, teenage onset, multiple CNS tumors.
Café-au-lait is French for “coffee with milk,” which is the color of these lesions.
Type 2
Diagnosis is made when one of the following is present:
Bilateral CN VIII masses (most of the cases).
A parent or sibling with the disease and either a neurofibroma, meningioma, glioma, or schwannoma.
Café-au-lait spots and skin neurofibromas are not common findings.
Patients are at significantly higher risk for CNS tumors than in NF-1 and typically have multiple tumors.
TREATMENT
Treatment is mainly aimed at preventing future complications and early detection of malignancies. Resection of the schwanomas can be done to preserve hearing.
Prenatal diagnosis and genetic confirmation of diagnosis is available in familial cases of both NF-1 and NF-2, but not new mutations.
Tuberous Sclerosis
EPIDEMIOLOGY
Inherited as an autosomal-dominant trait, with a frequency of 1:6,000.
Two-third are new mutations.
PATHOLOGY
Characteristic brain lesions consist of tubers, which are located in the convolutions of the cerebrum, where they undergo calcification and project into the ventricles.
There are two recognized genes: TSC1 on chromosome 9, encoding a protein called hamartin; and TSC2 on chromosome 16, encoding a protein called tuberin.
Tubers may obstruct the foramen of Monro, → hydrocephalus.
In general, the younger that a child presents with signs and symptoms, the greater the likelihood of mental retardation.
CLINICAL MANIFESTATIONS
Hypopigmented macules (Ash leaf skin lesions) are seen in 90% and are best viewed under a Wood’s lamp (violet/ultraviolet light source).
CT scan shows calcified hamartomas (tubers) in the periventricular region.
Seizures and infantile spasms (IS) are common. Seizures usually present as IS before age 1 and are difficult to control. Children develop autistic features and have developmental disabilities and learning difficulties.
Adenoma sebaceum—small, raised papules resembling acne that develop on the face between 4 and 6 years of age, actually are small hamartomas.
A Shagreen patch (rough, raised lesion with an orange-peel consistency in the lumbar region) is also a classic finding; typically does not develop until adolescence.
Fifty percent of children also have rhabdomyomas of the heart, which may → CHF or arrhythmias. They can be found on prenatal ultrasonography but usually regress after birth.
Hamartomas of the kidneys and the lungs are also frequently present.
Tuberous sclerosis is the most common cause of infantile spasms, an ominous seizure pattern in infants.
DIAGNOSIS
A high index of suspicion is needed, but all children presenting with infantile spasms should be carefully assessed for skin and retinal lesions.
CT or MRI will confirm the diagnosis.
Genetic testing is available for mutations in TSC1 and TSC2.
Hamartoma: A tumor-like overgrowth of tissue normally found in the area surrounding it.
CONGENITAL MALFORMATIONS
Agenesis of the Corpus Callosum
Associated with numerous syndromes and several inborn errors of metabolism, including patients with lissencephaly, Dandy-Walker syndrome, Arnold-Chiari type 2 malformations, and Aicardi syndrome.
Imaging techniques reveal that the lateral ventricles are shifted laterally.
Normal intelligence is not unusual, and often only mild clinical signs are seen.
The severity of the disease varies greatly, from only mild deficits to marked retardation and severe epilepsy.
Syringomyelia
A teenage girl has a headache and a cape-like distribution of pain and temperature sensory loss that developed after a minor motor vehicle accident. Think: Cervical syringomyelia with undiagnosed Chiari I.
The Chiari type I malformation is characterized by herniation of the cerebellar tonsils through the foramen magnum and may → the development of syringomyelia. Common presentations include headache, neck pain, vertigo, sensory changes, and ataxia. Typical scenario is occipital pain precipitated by cough or Valsalva maneuver. MRI is the modality of choice.
A slowly progressive paracentral cavity formation within the brain or spinal cord, most often in the cervical or lumbar regions.
Thought to arise from incomplete closure of the neural tube during the fourth week of gestation.
MRI is the test of choice for diagnosis.
Often develops post-traumatically in the setting of an undiagnosed Chiari I malformation or tethered cord.
Symptoms include bilateral impaired pain and temperature sensation due to decussation of these fibers near the central canal. Also weakness of the hand muscles and progressive symptoms as the cavity enlarges. It contains a yellow fluid.
Called syringobulbia when present in brain stem.
Dandy-Walker Malformation
Results from a developmental failure of the roof of the fourth ventricle to form, resulting in a cystic expansion into the posterior fossa.
Ninety percent of patients have hydrocephalus.
Agenesis of the cerebellar vermis and corpus callosum is also common.
Infants present with a rapid ↑ in head size.
Management is via shunting of the cystic cavity to prevent hydrocephalus.
Arnold-Chiari Malformations
Four variations exist (see Figure 17-7), with type 2 being the most common, in which the cerebellum and medulla are shifted caudally, resulting in crowding of the upper spinal column.
Type 2 is also associated with meningomyelocele in > 95% of cases.
Syringomyelia is associated in 70% of type 1, and 20–50% overall.
Management includes close observation with serial MRIs and surgery as required.
FIGURE 17-7. The Chiari malformations.
Schematic representations of the Chiari malformations. Commonly associated hydrocephalus and syringomyelia not depicted.