First Aid for the Pediatrics Clerkship, 3 Ed.

Neurologic Disease




Image Symptom of brain dysfunction (not an etiologic diagnosis).

Image A paroxysmal electrical discharge of neurons in the brain resulting in an alteration of function or behavior.

Image The most common neurologic disorder in children:

Image 4–10% of children

Image 1% of all ED visits

Image Highest incidence: < 3 yr.


The diagnosis of clinical epilepsy requires two or more unprovoked seizures.


Multiple etiologies have been identified for seizures. Provoked causes include:

Image Fever.

Image Metabolic:

Image Hypoglycemia

Image Hyponatremia

Image Hypocalcemia

Image Inborn errors of metabolism

Image Medications and illegal drugs.

Image Trauma (intracranial hemorrhage).

Image Infections (encephalitis, meningitis, abscess).

Image Vascular events (strokes).

Image Hypoxic ischemia encephalopathy.


Image Recurrence risk after a first unprovoked episode is 45% (27–52%).

Image 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.


Begin in one brain region.

1. Simple partial seizures:

Image Average duration is 10–20 sec.

Image Restricted at onset to one focal cortical region.


Aura: Abnormal perception or hallucination that precede seizures.

TABLE 17-1. Types of Seizures


Image Consciousness is not altered.

Image Tend to involve the face, neck, and extremities.

Image Patients may complain of preictal aura, which is characteristic for the brain region involved in the seizure (ie, visual aura, auditory aura, etc.).

Image 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:

Image Average duration is 1–2 min.

Image Hallmark feature is alteration or loss of consciousness.

Image Automatisms are seen in 50–75% of cases (psychic, sensory, or motor phenomena carried out while unconscious and not recalled postic-tally).

Image May begin as a simple partial seizure and progress until consciousness is affected.


Both simple and complex partial seizures may become generalized.


Begins simultaneously in both cerebral hemispheres. Consciousness is impaired from seizure onset.

1. Typical absence seizures (formerly “petit mal”):

Image Generalized seizure.

Image Characterized by sudden cessation of motor activity or speech.

Image Brief stares (usually < 10 sec), rarely longer than 30 sec.

Image More common in girls. Male-to-female ratio: 2:1.

Image Onset 2–6 yr.

Image Frequency: Dozens/day.

Image There is no aura.

Image There is no postictal state.

Image 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:

Image Extremely common and may follow a partial seizure with focal onset.

Image Patients suddenly lose consciousness, their eyes roll back, and their entire musculature undergoes tonic contractions, rarely arresting breathing.

Image Gradually, the hyperextension gives way to a series of rapid clonic jerks.

Image Finally, a period of flaccid relaxation occurs, during which sphincter control is often lost (incontinence).

Image 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.



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

Image Shorter (seconds)

Image Automatism –

Image More frequent (dozens)

Image Quick recovery

Image Hyperventilation +

Image EEG: 3/sec spikes and waves

Complex Partial Seizures

Image Longer (minutes)

Image Automatism +

Image Less frequent

Image Gradual recovery

Image Hyperventilation –

Image EEG: Focal spikes

Pediatric Seizure Disorders


Image The most common seizure disorder during childhood. Occur in 2–5% of children 6 months to 6 years of age.

Image Present as a brief tonic-clonic seizure associated with a fever.

Image Risk of recurrence is 30% after first episode and 50% after second episode.

Image Highest recurrence before 1 year of age (50%).

Image There are no long-term sequelae, and children will outgrow by age 6.

Image Risk of epilepsy (1–2% as opposed to 0.5–1% in the general population) not statistically significant.

Image ↑ risk of epilepsy (up to 13%) in the presence of:

Image Abnormal neurologic examination.

Image Complex febrile seizure.

Image Family history of epilepsy.

Image An autosomal-dominant inheritance pattern with incomplete penetrance is demonstrated in some families (19p and 8q13–21).


Complex febrile seizure:

Image 15 min

Image Focal motor

Image 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.


Image The most common neurologic manifestation of impaired brain function.

Image Occurs in 1.8–3.5 of every 1000 newborns.

Image Higher incidence in low-birth-weight infants.

Image Metabolic, toxic, hypoxic, ischemic, and infectious diseases are commonly present during the neonatal period, placing the child at an ↑ risk for seizures.

Image Myelination is not complete at birth; thus, GTC seizures are very uncommon in the first month of life.

Image May manifest as tonic, myoclonic, clonic, or subtle (prolonged nonnutritive sucking, nystagmus, color change, autonomic instability).

Image EEG may show burst suppression (alternating high and very low voltages), low-voltage invariance, diffuse or focal background slowing, and focal or multifocal spikes.

Image Neonatal seizures are typically treated acutely with phenobarbital (drug of choice), fosphenytoin, or benzodiazepines.

Image Phenytoin not a first-line agent due to depressive effect on the myocardium and variable metabolism in newborns.

Image Prophylaxis usually with phenobarbital, but also topiramate or levetiracetam.


Image Onset: 4–8 months.

Image Clusters of brief symmetric flexor/extensor contractions of the neck, trunk, and extremities up to 100/day.

Image 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.

Image Cryptogenic type has a better prognosis and children typically have an uneventful birth history and reach developmental milestones before the onset of the seizures.

Image Treated with adrenocorticotropic hormone (ACTH) in the United States.

Image Vigabatrin (equally as effective as ACTH therapy).

Image 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.



Image A history of two or more unprovoked seizures.

Image 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:

Image Keep track of the duration.

Image Place the patient between prone and lateral decubitus to allow the tongue and secretions to fall forward.

Image Hyperextend the neck and jaw to enhance breathing.

Image Loosen any tight clothing or jewelry around the neck.

Image Do not try to force open the mouth or teeth!


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.


Image Vary depending on the seizure pattern. See above discussion of types of seizures.

Image A seizure is defined electrographically as a hypersynchronous, hyper-rhythmic, high-amplitude signal that evolves in both frequency and space.

Image An aura is a stereotyped symptom set that immediately precedes the onset of a clinical seizure and does not affect consciousness.

Image Physiologically, the aura is the true beginning of the seizure, and as such its character can be quite useful for localizing seizure onset.

Image 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:

Image Hypoxic-ischemic encephalopathy (35– 42%)

Image Intracranial hemorrhage/infarction (15–20%)

Image CNS infection (12–17%)

Image Metabolic and inborn errors of metabolism (8–25%)

Image CNS malformation (5%)


Image Therapy is directed at preventing the attacks.

Image 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



Image Seizures secondary to a focal CNS lesion, not necessarily visible on imaging, best candidates for epilepsy surgery.

Image Common examples include masses (particularly cortical tubers of tuberous sclerosis [TS]), cortical dysplasia, postencephalitic gliosis, and arteriovenous malformations (AVMs).



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.

Image Most common partial epilepsy.

Image Onset 3–13 years.

Image Particularly nocturnal (early morning hours before awakening).

Image EEG: Central temporal spikes (Figure 17-3).

Image Excellent prognosis; most resolve by age 16 yr.

Image Treatment: Carbamazepine, phenytoin, and valproic acid.

TABLE 17-3. Localizing/Lateralizing Seizure Semiologies




Epilepsy History

Image Age, sex, handedness

Image Seizure semiology (what the seizures look like, details about right/left). If more than one type, the pattern of progression (if any)

Image Seizure duration/history of status epilepticus

Image Postictal lethargy or focal neurologic deficits

Image Current frequency/tendency to cluster

Image Age at onset

Image Date of last seizure

Image Longest seizure-free interval

Image Known precipitants (don’t forget to ask if the seizures typically arise out of sleep)

Image History of head trauma, difficult birth, intrauterine infection, hypoxic/ischemic insults, meningoencephalitis, or other CNS disease

Image Developmental history (delay strongly correlated with poorer prognosis)

Image Family history of epilepsy, febrile seizures

Image Psychiatric history

Image Current AEDs

Image AED history (maximum doses, efficacy, reason for stopping)

Image Previous EEG, MRI findings


FIGURE 17-3. EEG demonstrating central temporal spikes characteristic of benign Rolandic epilepsy.


Image Two percent of childhood epilepsies, but 25% of epilepsy with onset in the first year of life.

Image Onset is at age 4–8 months.

Image Triad: Infantile spasms, mental retardation (MR), and hypsarrhythmia.

Image Boys are more commonly affected but not significantly; generally poor prognosis.

Image Differential includes TS (largest group), CNS malformation, intrauterine infection, inborn metabolic disorders, and idiopathic. Idiopathic group fares the best.

Image Treatment in the United States is restricted to ACTH.


Image Onset: 12–16 yr.

Image Characteristic history: Usually early morning on awakening, while hair combing and tooth brushing.

Image Seizures: Myoclonus, absence, GTC.

Image EEG: 4- to 6-Hz irregular spike-and-wave pattern (Figure 17-4 and Table 17-4).

Image Treatment: Valproate, lamotrigine.

Image Prognosis: Good Rx response but lifelong.

Image High rate of recurrence if antiepileptic drug (AED) discontinued.


Image See absence seizures above. GTC seizures often develop in adolescence; spontaneous resolution is the rule, however.

Image 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.


Image A generalized epilepsy syndrome.

Image Multiple seizure types (tonic, atonic, absence, and myoclonic seizures).

Image EEG: 1.5- to 2.5-Hz spike-and-wave pattern.

Image Cognitive impairment.

Image Infantile spasms may evolve to LGS (30%).

Image Seizures are frequent and resistant to treatment with AEDs.


Image Language regression.

Image Aphasia (primarily receptive or expressive).

Image Seizures of several types (focal or GTC, atypical absence, partial complex).

Image EEG: High-amplitude spike-and-wave discharges. Obtain EEG during sleep (more apparent during non–rapid eye movement sleep).

Image Differential diagnosis: Autism.

Image Treatment: Valproic acid.


Loss of language skills in a previously normal child with seizure disorder. Think: LKS.


Image 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.

Image 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




Image Gliotic scarring and atrophy of the hippocampal formation, creating a seizure focus. Abnormality is often apparent on high-resolution magnetic resonance imaging (MRI).

Image Rhythmic, 5–7 Hz, sharp theta activity.

Image Phenytoin, phenobarbital, carbamazepine, and valproate are equally effective. Curative resection is often possible if refractory to treatment.



A neurodegenerative disorder of unknown cause.


Image 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.

Image Prevalence: 1 in 15,000 to 1 in 22,000.


Image Most cases result from defect in MECP2. Gene testing available.

Image 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.


Image Normal development until 12–18 months (can appear as early as 5 months)

Image The first signs are deceleration of head growth, lack of interest in environment, and hypotonia, followed by a regression of language and motor milestones.

Image Ataxia, hand-wringing, reduced brain weight, and episodes of hyperventilation are typical.

Image Autistic behavior.


Image After the initial period of regression, the disease appears to plateau.

Image Death occurs during adolescence or the third decade of life (cardiac arrhythmias).


Dermato-oculo-neural syndrome.


Occurs sporadically in 1 in 50,000.


Image Abnormal development of the meningeal vasculature, resulting in hemispheric vascular steal phenomenon and resultant hemiatrophy.

Image Facial capillary hemangioma usually accompanies in V1 distribution.


If you see “port-wine stain,” think: Sturge-Weber syndrome.


Image Cutaneous facial nevus flammeus (distribution of the trigeminal nerve) → port-wine stain.

Image Ipsilateral diffuse cavernous hemangioma of the choroid → glaucoma.

Image Ipsilateral meningeal hemangiomatosis (seizures and mental retardation).

Image The lesions in the eye, skin, and brain are always present at birth.

Image Contrast-enhanced MRI to look for meningeal angioma.

Image Seizures are usually refractory, and hemispherectomy improves the prognosis.

Image 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.



Any seizure or recurrent seizures without return to baseline lasting 20 min.


Image Febrile seizures, idiopathic status epilepticus, and symptomatic SE.

Image 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.


Prolonged neural firing may result in neuronal cell death, called excitotoxicity.


Image Initial treatment includes assessment of the respiratory and cardiovascular systems (ABCs).

Image 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.


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:

Image Load with phenobarbital 20 mg/kg IV or

Image 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.


Obstructive Sleep Apnea (OSA)

Image Occurs in 2–5 % of children, most often between ages 2 and 6.

Image Characterized by chronic partial airway obstruction with intermittent episodes of complete obstruction during sleep, resulting in disturbed sleep.

Image Snoring is the most common symptom, occurring in most of them (12% of general pediatric population has snoring without OSA).

Image Symptoms: Fatigue/hyperactivity, headache, daytime somnolence.

Image Signs: Narrow airway, tonsillar hypertrophy, often obese.

Image 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


Image 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.

Image 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.


Occur in 1–3% of the population, primarily in boys between ages 5 and 7.


Image Fifty percent complete recovery by age 8.

Image Fifty percent are also sleepwalkers.

Image Often, incontinence and diaphoresis.

Image Occurs in stage 4 (deep) sleep.


PSG (polysomnography).


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)

Image Occurs during slow-wave sleep.

Image Occurs during first third of the night.

Image Onset: 8–12 yr.

Image Awakened only with difficulty and may be confused when awakened.

Image 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).


Image Affects 10–20% of adolescents.

Image Depression is a common cause and should be ruled out.


Image Consciousness refers to the state of awareness of self and environment.

Image Pediatric evaluation of consciousness is dependent on both age and developmental level.


Pathologic cause of loss of normal consciousness.


Image Consciousness is the result of communication between the cerebral cortex and the ascending reticular-activating system.

Image Coma can be caused by:

Image One medial cerebral hemisphere with ispilateral, striatum, thalamus, and tegmentum of midbrain and rostral pons.

Image Bilateral medial hemispheres, striatum, thalami, tegmentum of rostral pontomesencephalic tegmentum impairs consciousness.

Image Lesions of the medullary reticular-activating system or its ascending projections. Ventral pontine lesions can → the locked-in syndrome, which is not coma.


Image Structural causes include trauma, vascular conditions, and mass lesions involving directly or mass effects.

Image Metabolic and toxic causes include hypoxic-ischemic injury, toxins, infectious causes, and seizures.


Herniation syndromes that may result in coma:

Image Ipsilateral oculomotor dysfunction. Think: Uncal herniation.

Image Cheyne-Stokes respirations. Think: Transtentorial (central) herniation.


Image Administer glucose via IV line so that the brain has an adequate energy supply.

Image Treat underlying cause (toxin antidote, reduce ICP, antibiotics, etc.).


Image Overall, children tend to do better than adults.

Image 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)



Image 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!




Image Diffuse inflammation of the meninges, particularly arachnoids and pia mater.

Image Bacteria:

Image < 3 months: Group B streptococci and gram-negative organisms, Escherichia coli, Listeria.

Image > 3 months: Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis (two life-threatening clinical syndromes: meningococcemia and meningococcal meningitis).

Image Virus: The term aseptic meningitis is used to describe the syndrome of meningism and CSF leukocytosis usually caused by viruses or bacteria.


If immunocompromised, these signs and symptoms will be not prominent.

Image Fever, headache, and nuchal rigidity (most important features).

Image Photophobia or myalgia may be present.

Image Meningism (Brudzinski’s and Kernig’s signs) (see Figures 17-5 and 17-6).

Image 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.


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 17-7You will be asked this!


Image See Table 17-7 for common meningitis-causing bacteria.

Image 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


Image 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


Image Enterovirus (85%): Echovirus, coxsackievirus, and nonparalytic poliovirus.

Image Other classic causes are herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV), mumps, influenza, arboviruses, and adenoviruses.

Image Clinical presentation is similar but symptoms are less severe than that of bacterial meningitis.

Image Children are not toxic looking.

Image Children show typical viral-type infectious signs (fever, malaise, myalgia, nausea, and rash) as well as meningeal signs.

Image Typically is a self-limited process with complete recovery, and treatment is supportive.


Image Although relatively uncommon, the classic organism is Cryptococcus.

Image Encountered primarily in the immunocompromised patient (with transplants, AIDS, or on chemotherapy).

Image May be rapidly fatal (as quickly as 2 weeks) or evolve over months to years.

Image Tends to cause direct lymphatic obstruction, → hydrocephalus.


Treat all acute cases of meningitis as if they are bacterial until cultures return.


Image Third-generation cephalosporin (cefotaxime/ceftriaxone).

Image Add ampicillin for Listeria in neonates. Neonates can be treated with ampicillin + gentamicin or ampicillin + cefotaxime.

Image Add vancomycin, considering the increasing resistance of pneumococci to cephalosporins and carbapenems until the sensitivities are known.

Image 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.

Image Steroid use is controversial.


Nuchal rigidity. Think: Meningitis.



Image A disease process in the brain primarily affecting the brain parenchyma.

Image 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:

Image Interstitial keratitis

Image Peg-shaped incisors

Image Deafness (cranial nerve [CN] VIII)


Chronic Bacterial Meningoencephalitis.

1. Mycobacterium tuberculosis, M bovis, and M avium-intracellulare.

Image Nonspecific features develop over days to weeks. Patients have generalized complaints of headache, malaise, and weight loss initially.

Image This is followed by confusion, focal neurological signs, cranial nerve palsies, and seizures or, in advanced cases, hemiparesis, hemiplegia, or coma.

Image Serious complications include arachnoid fibrosis, → hydrocephalus, and arterial occlusion, → infarcts.

Image M avium-intracellulare is common in AIDS patients.


Argyll Robertson pupil is discrepancy in pupil size seen in neurosyphilis.

2. Neurosyphilis (tabes dorsalis).

Image Causative organism is Treponema pallidum.

Image May present with aseptic meningitis only.

Image Tertiary syphilis (late-stage syphilis) manifests with neurologic, cardiovascular, and granulomatous lesions.

Image Congenital syphilis presents with a maculopapular rash, lymphadenopathy, and mucopurulent rhinitis.

Image 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:

Image HSV-1: Most cases after the neonatal period.

Image 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:

Image Can occur after primary infection or as a result of reactivation later in life.

Image Usually with a rash, but outcome is poor in those without a rash.

Image 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.

Image In immunocompromised hosts, the dormant virus causes small-vessel vasculitis and results in hemorrhagic infarcts of gray and white matter.

Image EEG will show diffuse slowing and periodic lateralizing epileptiform discharges (PLEDs).

3. Rabies:

Image Causes severe encephalitis, coma, and death due to respiratory failure.

Image Transmitted via bite from an infected animal, usually associated with dogs, bats, skunks, raccoons, or squirrels.

Image The virus travels up the peripheral nerves from the bite site and enters the brain.

Image 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.

Image Hydrophobia is a classic, late finding but is not consistently present.



Image 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.

Image It is a neurological emergency and requires prompt diagnosis and treatment to prevent permanent damage.


Image Fever, lethargy, malaise, muscle pains.

Image Begins acutely and progresses within 1–2 days.

Image Back pain at the level of the involved cord and paresthesias of the legs are common.

Image Anterior horn involvement may cause lower motor neuron dysfunction.

Image Bladder and bowel dysfunction is present.


Image MRI: Enhanced T2 signals.

Image CSF: Pleocytosis.

Image Electromyogram (EMG): Anterior horn cell dysfunction in involved segments.


IV steroids, intravenous immune globulin (IVIG), may require surgical intervention.


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.



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.


Image An acute illness with painful muscle spasms and hypertonia caused by the neurotoxin produced by Clostridium tetani.

Image These symptoms usually starts in the jaw and facial muscles and progressively involve other muscle groups.


Image Trismus (masseter muscle spasm) is the characteristic sign and is present in 75% of cases.

Image Risus sardonicus, a grin caused by facial spasm, is also classic.

Image Dysphagia due to pharyngeal spasm develops over a few days; laryngospasm may result in asphyxia.

Image 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.

Image 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.

Image The development of seizures is associated with poor prognosis.

Image Autonomic dysfunction may be seen as ↑ sweating, heart rate, blood pressure, and temperature.

Image Can also present with localized spasms at the site of infection or with abdominal pain mimicking acute abdomen.

Image Incubation period varies from 2 to 14 days (average 7 days).


Image Diagnosis is clinical, with the presence of trismus, dysphagia, ↑ rigidity, and muscle spasms.

Image Laboratory studies are usually normal, but a moderate leukocytosis may be present.

Image CSF is normal.

Image Gram stain is positive in only one-third of cases.


Image Admit to ICU for prophylactic intubation.

Image Rapid administration of human tetanus immune globulin.

Image 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.

Image Surgical excision and debridement of the wound.

Image Muscle relaxants such as diazepam, phenobarbital should be used to promote relaxation and seizure control. Neuromuscular blocking agents like vecuronium are also used.


Image Mortality rate: 5–35%.

Image Neonatal tetanus mortality ranges from 10% to 75%, depending on quality of care received.



A syndrome of generalized dysfunction of the brain.


Two main groups:

1. Progressive encephalopathies with onset before age 2 years.

Image If other systems are involved in addition to nervous system then it is lysosomal, peroxisomal, or mitochondrial disorders.

Image If peripheral nervous system and muscles involved in addition to central nervous system is likely lysosomal or mitochondrial.

Image Gray matter or white matter disease.

2. Encephalopathies that begin during childhood after age 2 years.

Image Lysosomal disorders: Gaucher’s type 3, late onset Krabbe disease, juvenile Tay-Sachs disease, Niemann-Pick disease type C.

Image Infectious disease: AIDS, congenital syphilis, subacute sclerosing panencephalitis.

Image 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):

Image The most common of mitochondrial encephalopathies.

Image Onset between ages 2 and 10 yr; initial development normal, but short stature is present.

Image The most initial feature is GTC seizure (often associated with hemiparesis and cortical blindness), recurrent headache, and vomiting.

Image The neurologic abnormalities are transient initially, but later become progressive and → coma and death.

Image 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):

Image Onset may be in childhood or adult life.

Image Four cardinal features are myoclonus, myoclonic epilepsy, ataxia, and ragged-red fibers on muscle biopsy.

Image 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.

Image 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:

Image A disorder of mitochondrial dysfunction associated with viral infection and aspirin ingestion.

Image Sporadic syndrome can occur with varicella-zoster or influenza B infection.

Image 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.

Image 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

Image 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).

Image In children, most commonly related to fulminant viral hepatitis (50–75%).

Image Early symptoms are malaise, lethargy, jaundice, dark urine, and abnormal liver function tests (LFTs). The encephalopathy can be acute or chronic.

Image Other features include, sleep disturbance, change in affect, drowsiness, asterixis (flapping tremor). Decerebrate posturing may occur in the terminal stages.

Image 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:

Image Ammonia level (↓ dietary protein, stop gastrointestinal [GI] bleed, treat constipation).

Image Cerebral edema with fluid restriction and the use of hyperosmolar agents (mannitol).

Image Patients who recover typically have no long-term sequelae.

HIV/AIDS Encephalopathy

Image There is a 40–90% incidence of CNS involvement in perinatally infected children.

Image Ninety percent of infected infants are symptomatic by 18 months of age.

Image Develops 2–5 months after infection.

Image Commonly presents with progressive encephalopathy and hepatosplenomegaly, → failure to meet developmental milestones, impaired brain growth, and symmetrical motor dysfunction.

Image Imaging techniques reveal cerebral atrophy in 85% of children and ventricular enlargement.

Image Basal ganglia calcifications may be present.

Image Opportunistic infections such as toxoplasmosis typically occur later in adolescence.

Image PCR analysis of HIV DNA or RNA is used to detect HIV infection in infants < 18 months.

Image Diagnosis: Via immunoglobulin G (IgG) antibody to HIV for patients > 18 months and a confirmatory test HIV DNA PCR.

Image Treatment: Highly active antiretroviral therapy (HAART).

Image 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

Image There is no direct correlation to the level of lead and clinical manifestations. Lead interferes with porphyrin metabolism in red blood cells (RBCs).

Image Acute: Vomiting, abdominal pain, seizures, impaired consciousness, and respiratory arrest are common.

Image 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.

Image Pica is common in these children (eg, eating paint chips).

Image Diagnosis is made primarily through history and also via blood lead testing. Microcytic hypochromic anemia, basophilic stippling, and azotemia also present.

Image 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

Image Rapid, brief, unsustained, nonstereotypical movements of the body.

Image Autoimmune mediated.

Image Twice as common in females.

Image Onset: Age 3–17 yr.

Image Postinfectious chorea appearing 4–8 weeks after a group A streptococcal pharyngitis.

Image Resolves after 8–9 months; 50% have persistent chorea.

Image Diagnosis: Recent throat infection (anti-streptolysin O, DNase B), ↑ T2 signals in basal ganglia.

Image Treatment:

Image Valproate: First choice.

Image Dopamine-blocking agents: Second choice.

Image 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.


Image A progressive disease, characterized by demyelination of the CNS and peripheral nerves and adrenal insufficiency.

Image X-linked recessive, peroxisomal disorder, defect in the ability to catabolize long-chain fatty acids (LCFAs).

Image It presents between 4 and 10 yr with behavioral and cognitive decline with visual loss, followed by motor symptoms.

Image Diagnosis: White matter abnormality on MRI, ↑ serum very-long-chain fatty acids (VLCFA), labs for adrenal insufficiency.

Image 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

Image A lifelong condition affecting 1 in 2000 that presents before age 15.

Image Diagnostic criteria: Multiple motor and vocal tics for > 1 year with tic-free period not more than 3 consecutive months.

Image Often associated with other conditions like obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder (ADHD).

Image Symptoms are enhanced by stress and anxiety.

Image Treatment with medications should be avoided.

Image Treat when tics interfere with child’s developmental learning or cause undue social stress. Also treat comorbid conditions.



Image A nonprogressive disorder of movement and posture resulting from damage to the developing brain prior to or surrounding birth. If progressive, consider another diagnosis.

Image Most cases occur in the absence of identifiable causes.


Image Prematurity with intraventricular hemorrhage.

Image Birth or other asphyxia.

Image Intrauterine growth retardation (IUGR), placental insufficiency.

Image Infection: Prenatal/postnatal.

Image Twin pregnancy.

Image Chromosomal and genetic disorders.

Image Head trauma.


CP is a static disorder, meaning that it does not result in the loss of previously acquired milestones.


Image Prenatal and perinatal history.

Image Delayed motor, language, or social skills.

Image Not losing skills previously acquired.

Image Feeding difficulties.

Image Late-onset dystonia (age 7–10).


Image Hypertonia.

Image Hyperreflexia.

Image Posture and movement: May be spastic, ataxic, choreoathetoid, and dystonic.

Image Abnormal primitive reflexes.

Image Abnormal gait.

Image Impaired growth of affected extremity.


Image Seizure disorder

Image Mental retardation

Image 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.


Image Hemiplegic cerebral palsy: Upper limb involvement > lower limb; many walk before 2 years.

Image Diplegic cerebral palsy.

Image Quadriplegic cerebral palsy: Majority does not walk.

Image Dystonic/athetoid cerebral palsy.

Image Ataxic cerebral palsy.

Image Monoplegic cerebral palsy: Usually lower limb and appears late.


Image Multidisciplinary approach with goals of maximizing function and minimizing impairment.

Image Team includes general pediatrician, physiotherapist, occupational therapist, language therapist, neurologist, and social and educational support services.

Image 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.



Image Below average intellectual functioning in association with deficits in adaptive behavior prior to 18 years of age.

Image Intelligence quotient (IQ) or developmental quotient (DQ) < 70 or < 2 standard deviations (SDs).


Image Affects 1–3% of the population.

Image Approximately 75% are mild cases.

Image Males are affected more than females.


Image Significant delay in reaching developmental milestones.

Image Delayed speech and language skills in toddlers with less severe MR.

Image 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.


Classification is based on IQ:

Image Mild: IQ 55–70, 85% of cases.

Image Moderate: IQ 40–55, 10% of cases.

Image Severe: IQ 25–40, 3–5% of cases.

Image Profound: IQ < 25, 1–2% of cases.


Earlier classification:

Image Moron: IQ 51–75

Image Imbecile: IQ 26–50

Image Idiot: IQ ≤ 25

This is no longer considered politically correct.


Image Significant discrepancy between a person’s intellectual ability and academic achievement.

Image Often learn best in unconventional ways.

Image Often restricted to a particular realm such as reading or mathematics with correspondingly discrepant scores on standardized measures of intelligence or academic achievement.

Image 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.


Inability to coordinate muscle activities to regulate posture and also strength and direction of extremity movements (see Table 17-8).



Image A diagnosis of exclusion occurring in children 2–7 years old.

Image Often follows viral infection by 2–3 weeks; thought to be autoimmune response and has been seen with live inactivated vaccines like varicella vaccine.

Image Sudden onset of severe truncal ataxia; often, the child cannot stand or sit.

Image Severity is maximum at the onset with clear sensorium.

Image Horizontal nystagmus in 50%.

Image Diagnosis: Diagnosis of exclusion; exclude other serious causes first.

Image Treatment: Self-limited disease.

Image Prognosis: Complete recovery typically occurs within 2 months (1–5 months).

TABLE 17-8. Ataxias



Image Autosomal-recessive mutation (usually a triplet expansion) in Frataxin gene on chromosome 9.

Image Degeneration of the dorsal columns and rootlets, spinocerebellar tracts, and, to a lesser extent, the pyramidal tracts and cerebellar hemispheres.

Image Onset before age 10 (2–16 yr).

Image 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.

Image Romberg test is positive.

Image Associated abnormalities include skeletal abnormalities (scoliosis), cardiomyopathy, and optic atrophy.

Image Elevated α-fetoprotein (AFP).

Image 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.


Image Autosomal-recessive disorder of nervous and immune system due to gene mutation at chromosome 11.

Image The most common degenerative ataxia.

Image A slowly progressive ataxia beginning during first year of life resulting in inability to walk by adolescence.

Image Oculomotor apraxia is a present in 90% of the patients.

Image 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.

Image Sinopulmonary infection is another important feature. ↓ or absent IgA, IgE, and especially IgG2 subclass. IgM may be ↑.

Image ↑ AFP and peripheral acanthocytes.

Image Have a 50- to 100-fold greater chance of brain tumors and lymphoid tumors, so avoid radiation exposure by limiting imaging studies.


Image Injuries to the peripheral nerves may be either:

Image Demyelinating (injury to Schwann cells).

Image Degenerating (injury to the nerve or axon).

Image Peripheral neuropathy is the most common cause of progressive distal weakness.

Image Most common are hereditary causes and slow progression.

Image The most common acquired cause is Guillain-Barré syndrome (GBS) with rapid progression.




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).

Image A postinfection demyelinating neuropathy affecting predominantly the motor neurons.

Image 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.

Image Weakness begins in the legs and progresses symmetrically upward to the trunk, arms, then bulbar and ocular muscles.

Image Tendon reflexes are absent.

Image Respiratory muscles in 50%, autonomic dysfunction, pain, paresthesias can be present.

Image ↑ proteins in CSF with no ↑ in lymphocytes.

Image Nerve conduction will be slow with conduction blocks, and enhancement of nerve roots can be seen on MRI.

Image 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.


Image 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.

Image Infant botulism: The first sign is usually absence of defecation. The head control is lost and the weakness descends.

Image Most dreaded complication is respiratory paralysis, and approximately 50% of patients are intubated.

Image Prognosis is good in noncomplicated cases.

Image Antibiotics and blocking antibodies have not been shown to affect the course of the disease.

Image 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).


Image ↓ in postsynaptic acetylcholine receptors due to autoimmune degradation, resulting in rapid fatigability of muscles.

Image Ptosis and extraocular eye weakness are the earliest and most diagnostic symptoms.

Image Onset usually after age 8, as early as 6 months. Prepubertal male bias, postpubertal female bias.

Image 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.

Image Cholinesterase drugs are the mainstay of treatment, with oral steroids used as needed for immune suppression (initially may exacerbate the disease).

Image Prognosis varies, with some children undergoing spontaneous remission, while in others the disease persists into adulthood.


Image Passive transfer of antibodies from myasthenic mothers (10–15% incidence).

Image 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.

Image 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.


Image Rare disorder.

Image Collection of autosomal-recessive seronegative disorders of the neuro-muscular junction. Most defects are postsynaptic, but presynaptic forms are described.

Image Onset can be neonatal. Diagnosis by EMG with repetitive stimulation, response to edrophonium, specialized testing for identification of the specific defect.

Image 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.


See Table 17-9 for common electrolyte imbalances affecting the nervous system.



The most common type of headache in the pediatric population with female predominance.

TABLE 17-9. Electrolyte Disturbances and the Nervous System



A recurrent headache with symptom-free intervals and associated with the following:

Image Abdominal pain.

Image Nausea and/or vomiting.

Image Throbbing headache.

Image Often bilateral (vs. unilateral in adults).

Image Associated aura.

Image Relieved by sleep.

Image Family history of migraines.


Migraines may be classified into the following subgroups:

Image 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.

Image Diagnosis of migraine is clinical and no neuroimaging is necessary unless it is persistently occipital or with abnormal neurologic examination.


Image The most prevalent type of migraine in children.

Image Intense nausea and vomiting are classic.

Image Aura is absent.

Image Family history is present in 80%, most often on the maternal side.


Image An aura precedes the headache by 5–20 min and nearly always disappears before the headache begins.

Image 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.


Transient neurologic signs develop during a headache and persist after the resolution of the headache for a few hours to days.


Image 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.

Image Consider nonpharmacologic treatment with biofeedback techniques in chronic stress headache.

Image For acute attacks:

Image Dark, quiet environment and sleep.

Image Adequate fluid intake.

Image Pharmacologic therapy: Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are first line.

Image Second-line drugs include triptans, caffeine, and ergot alkaloids (status migrinosus).

Image Antiemetics are helpful at the start of headache.

Image 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.


Image Antiepileptic drugs, such as topiramate, valproate, levetiracetam.

Image Tricyclic antidepresssants such as amitriptyline.

Image β blockers such as propranolol.

Cluster Headache

Image Brief, severe, unilateral stabbing headaches that occur multiple times daily over a period of several weeks and tend to be seasonal.

Image Onset after 10 yr of age.

Image Male predominance.

Image Conjunctival injection, tearing, rhinorrhea.

Image Prophylaxis with lithium or calcium channel blocker.

Image 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.


Image Most often occur with a stressful situation, such as an exam.

Image Described as “hurting” but not “throbbing.”

Image It presents like a band around the head. It is present most of the times of the day.

Image Unlike migraines and ↑ intracranial pressure, tension headaches are not associated with nausea and vomiting,

Image However, it is sometimes difficult to differentiate them from migraine.


Image Diagnosis of exclusion.

Image EEG or CT is not necessary.

Image 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.


Steps should be taken to minimize anxiety and stress:

Image Mild analgesics often are ample.

Image Other options include counseling and biofeedback.

Image 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.


Image It usually presents as headache, nausea, vomiting, diplopia, personality changes.

Image It can present as bulging fontanelle, impaired upward gaze in infants.

Image 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.

Image Coughing or Valsalva’s maneuver tends to make the pain worse by increasing ICP further.


Any time you see papilledema, think ↑ ICP.


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.


Image Thorough history and physical exam are vital.

Image Papilledema (if ↑ pressure is present for some time) and nuchal rigidity are helpful signs.

Image Obtain CBC, erythrocyte sedimentation rate (ESR), and CT/MRI to narrow the differential.

Image 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%)


Image Varies with particular diagnosis, and should be directed at the underlying etiology.

Image 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.


Image 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.

Image Most common in internal carotid artery followed by middle cerebral artery, anterior communicating artery, and basilar artery.

Image Saccular aneurysms are the most common type and often at bifurcation of the internal carotid artery.

Image Early warning signs are headaches or localized cranial nerve compression.

Image Most common presentation is subarachnoid hemorrhage (SAH).

Image More likely to rupture in patients < 2 years of age or > 10 years.

Image More common in males 2:1.

Image 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.


Image Most often are related to a congenital diseases:

Image Ehlers-Danlos syndrome.

Image Marfan syndrome, tuberous sclerosis.

Image AVMs.

Image Coarctation of the aorta.

Image Polycystic kidney disease (likely develop secondary to hypertension in this condition); called berry aneuryms.

Image Acquired aneurysms are most often related to bacterial endocarditis:

Image Embolization of bacteria results in mycotic aneurysms in the cerebral vasculature.

Image 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.


Image Angiography is the gold standard for aneurysms in both children and adults.

Image 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%).


Image Surgical clipping or endovascular coiling is the treatment of choice.

Image Risk for rebleeding.


Image 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.

Image It grows in size with time and varies in size from several millimeters to several centimeters.

Image The larger ones create a significant atrioventricular (AV) shunt (steal phenomenon) and considerable damage if they rupture.

Image Supratentorial (90%).


Image Small unruptured malformations present with headache or seizures.

Image Larger malformations may present with progressive neurologic deficit.

Image Hemorrhage is most often presentation (subarachnoid or intraparenchymal).


Image Angiography is the test of choice and is required to direct the future therapy. MRA is also available.

Image MRI or CT with contrast can demonstrate an AVM but provide less information than angiography.

Image Photon knife is the treatment.

Common AVM Variants


Image Normal vein of Galen does not develop from its primitive vein, which persists and communicates with superior saggital sinus.

Image Typically present during infancy with high-output congestive heart failure (CHF), failure to thrive, or enlarging head size.

Image Mortality is 50%.

Image Treatment is difficult embolization is preferred over surgery.

Image A cranial bruit is often present with vein of Galen malformations.


Image Low-flow AVM with tendency to leak (cause seizure) but usually do not result in massive intracerebral hemorrhage.

Image Retinal cavernous hemangiomas may be also present.

Image Surgical resection is indicated if symptomatic.


Image Rarely symptomatic (seizures are the most common presenting sign).

Image Surgery is not indicated unless complications arise.


Image Treatment consists of surgical resection or embolization.

Image Focused gamma knife radiation has some benefit in smaller lesions.


Image Transient ischemic attacks (TIAs): Neurologic deficits that resolves in < 24 hr.

Image Stroke: Neurological deficits persists beyond 24 hr.


Image 2.6–13 cases per 100,000 per yr.

Image Hemorrhagic stroke 1.5–5 per 100,000 children per yr.

Image 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.


Image Sudden onset of neurologic deficit or seizures in neonates.

Image Headache, neck pain, and visual symptoms.


Image Pediatric causes of stroke differ from those in the adult population.

Image Types of stroke include:

Image Ischemic: Thrombosis (both arterial and venous) or embolic (arterial).

Image Hemorrhage.

Image A variety of conditions or risk factors exist for stroke, including:

Image AVMs.

Image Antiphospholipid antibodies/lupus anticoagulant.

Image Congenital coagulopathies such as factor V Leiden and deficiencies of protein C, S, and antithrombin III.

Image Hemoglobinopathies, sickle cell disease (SCD).

Image Sickle cell anemia at risk for ischemic stroke (sickling RBCs may → thrombosis or endothelial injury).

Image Cardiac conditions: Arrhythmias, myxoma, paradoxical emboli through a patent foramen ovale, and septic emboli from bacterial endocarditis.

Image Blunt trauma to the head and neck → arterial dissection.

Image Vasculitis, such as Kawasaki, hemolytic-uremic syndrome, systemic lupus erythematosus (SLE), meningitis.

Image Mitochondrial diseases.

Image 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


Image Intracerebral arterial dissection after trivial trauma to head and neck due to a tear in the intima.

Image The cerebral area supplied by the vessel distal to lesion undergoes infarction and produces symptoms (loss of functions)

Image Cerebral symptoms such as a progressive hemiplegia, lethargy, or aphasia result from the shedding of small emboli into the carotid circulation.

Image Seizures are the most common presenting symptom in neonates.

Image Cardiac source usually.


History and physical exam are critical to search for the etiology.


Image May be subdivided into septic and nonseptic causes.

Image Septic causes include bacterial meningitis, otitis media, and mastoiditis.

Image Aseptic causes are numerous and include severe dehydration, hypercoagulable states, congenital heart disease, and hemoglobinopathies (SCD).

Image Neonates present with diffuse neurologic signs and seizures.

Image 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.


See Table 17-10 for a comparison of subdural and epidural hematomas.

Subdural Hematoma (SDH)


Image 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.


Image Occurs when a bridging vein is torn between the dura and the brain.

Image In neonates due to a tear in tentorium near its junction with the falx.

Image Trauma is usually the cause. Skull fracture is not seen commonly.

Image An SDH should be ruled out if changes in conscious level are present after head injury.

Image 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.


Image These depend on age of the child and also severity of the SDH.

Image Neonates: Seizures, a bulging fontanelle, and ↓ activity.

Image Retinal and preretinal hemorrhages common in children, especially in abused children.

Image ↑ 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.


Gold standard is CT scan.

Epidural Hematoma


Seen most often in children > 2 years of age.


Image Most commonly results from a fracture in the temporal bone, lacerating the middle meningeal artery.

Image Can be acute (arterial bleed) or chronic (venous bleed).

Image Skull fracture is seen commonly.

Image Nearly always unilateral; however, bilateral case has been described.


Lucid interval. Think: Epidural hematoma.


Image 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).

Image 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.

Image Retinal and preretinal hemorrhages are not common.

Image ↑ ICP is seen (irritability, lethargy, vomiting, papilledema, headache).


Gold standard is CT scan.


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.


Image Located directly at the point of impact.

Image More common in acceleration injuries such as being hit with a baseball bat.

Image 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



Image Located opposite (180 degrees) from the point of impact.

Image 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


Image Tissues with differing elastic properties shear against each other, tearing axons.

Image Caused by rapid deceleration/rotation of head.

Image Locations:

Image Cerebral hemispheres near gray-white junction.

Image Basal ganglia.

Image Corpus callosum, especially splenium.

Image Dorsal brain stem.

Image High morbitity and mortality—common cause of posttraumatic vegetative state.

Image Initial CT often normal despite poor GCS.

Image Lesions often nonhemorrhagic and seen only on MRI.

Image Survivors often have substantial long-term cognitive and behavioral morbidity.


Diffuse axonal injury is best visualized on a T2-weighted MRI.


Head circumference > 2 SD above the mean is macrocephaly, and if due to ↑ CSF in the CSF spaces, it is called hydrocephalus.


Image CSF is made by the choroid plexus in the walls of the lateral, third, and fourth ventricles.

Image 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.

Image CSF is absorbed primarily by the arachnoid villi through tight junctions.


Choroid plexus papilloma is the only rare cause of hydrocephalus from ↑ CSF production.


Image Obstructive (noncommunicating) hydrocephalus:

Image Most commonly due to stenosis or narrowing of the aqueduct of Sylvius.

Image 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.

Image Also seen in brain abscess, hematoma, infectious, vein of Galen malformation.

Image Nonobstructive (communicating) hydrocephalus:

Image Most commonly follows a subarachnoid hemorrhage or meningitis.

Image Blood in the subarachnoid spaces may obliterate the cisterns or arachnoid villi and obstruct CSF flow.

Image Venous sinus thrombosis, meningeal malignancy, and intrauterine infections are other causes.

Image Ex vacuo: Hydrocephalus resulting from ↓ brain parenchyma.


Pneumococcal and tuberculous meningitis produce a thick exudate that can obstruct the basal cisterns, → communicating hydrocephalus.


Image Infants:

Image Accelerated rate of enlargement of the head is most prominent sign.

Image 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.

Image Upper motor neuron signs such as brisk reflexes are common findings due to stretching of the descending cortical spinal tract.

Image ↑ ICP signs (lethargy, vomiting, headache, etc.) may be present, especially acutely ↑ ICP.

Image Ocular bobbing.

Image Children and adolescents:

Image Signs are more subtle because the cranial sutures are partially closed.

Image ↑ ICP signs may be present. Visual fields particularly peripheral fields are involved gradually. Papilledema can be present.

Image A gradual change in school performance may be the first clue to a slowly obstructing lesion.


Image A detailed history and physical exam is key to discovering the underlying etiology.

Image Ultrasound and head CT/MRI are the most important studies to identify the cause of hydrocephalus.

Image Familial cases of aqueductal stenosis have been reported and have an X-linked pattern of inheritance.

Image Neurofibromatosis and meningitis have also been linked to aqueductal stenosis.


Preemies with intraventricular hemorrhage frequently develop hydrocephalus.


Image Medical management with acetazolamide (may ↓ CSF production) and furosemide may provide temporary relief.

Image Placement of an extraventricular drain (EVD) or ventriculoperitoneal shunt (VPS), if the etiology is permanent, may be required.


Pediatric Brain Tumors


Image Most common solid tumors of the childhood.

Image Third most common pediatric tumors (#1 leukemia, #2 lymphoma).

Image Supratentorial tumors are as common as infratentorial tumors.

Image Glial cell tumors are the most common tumors in childhood and consist of astrocytomas, ependymomas, olidodendrioglioma, and primitive neuroectodermal tumor (PNET).

Image Medulloblastoma is a common PNET only in childhood.


Glioblastoma multiforme (GBM) is a high-grade glioma common in adults but rare in children.


Image Generally present with either signs and symptoms of ↑ ICP (infants) or with focal neurologic signs (adolescents).

Image Alterations in personality are often the first symptoms of a brain tumor.

Image Nystagmus is the classic finding in posterior fossa tumors.

Image Clinical signs depending on location of the tumor (loss/alteration in the functions of the brain area).

Image Tumors in the posterior fossa tend to result in hydrocephalus secondary to CSF flow obstruction.


Image The most common posterior fossa tumor of childhood.

Image It is a slow-growing poilocytic astrocytoma and more benign than the adult-onset astrocytomas.

Image Histologically shows fibrillary astrocytes with dense cytoplasmic inclusions called Rosenthal fibers.

Image Associated with neurofibromatosis type 2 (NF2).

Image Good prognosis; 5-year survival > 90% after gross total resection which is achieved in 70% of the cases.

Image Treatment is surgical resection.


Rosenthal fibers are also seen in Alexander’s disease, a progressive leukodystrophy with mental retardation, spasticity, and megalencephaly.


Image 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.

Image Rapidly growing malignant tumor, arises from the undifferentiated neural cells in the region of cerebellar vermis.

Image Tends to invade the fourth ventricle and spread along CSF pathways and involves the spine, so consider imaging the spine.

Image Histologic analysis shows deeply staining nuclei with scant cytoplasm arranged in pseudorosettes.

Image Presents with intracranial hypertension and ataxia, symptoms evolving in few weeks; papilledema is absent.

Image MRI: Brightly enhancing mass with cystic lesion.

Image Treatment: Surgical resection followed by irradiation.

Image Prognosis: Dependent on size and dissemination of the tumor, 5-year survival rate is > 80%.


Image One of the most common supratentorial brain tumors of childhood which arises from cells in the Rathke’s pouch.

Image It is locally aggressive and recurs.

Image Short stature or other endocrine-associated problems are common initial signs.

Image Typically slow growing and benign.

Image 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.

Image Due to location, surgical resection is often subtotal.


Image Ninety percent of craniopharyngiomas show calcification on CT scan; MRI provides better images of surrounding structures.

Image Baseline endocrine studies and visual fields should be done prior to surgery.



Image A common tumor of neural crest origin, representing the most common neoplasm in infants and 8% of all childhood malignancies.

Image Malignant tumor that arises from the neural crest cells.

Image 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.


Image NB is a small, round blue cell tumor with varying degrees of neuronal differentiation.


Image The tumor may arise at any site of sympathetic nervous tissue.

Image The adrenals, retroperitoneal sympathetic ganglia, and abdomen are the most common sites.

Image Thirty percent arise in the cervical or thoracic region and may present with Horner syndrome.

Image Opsoclonus-myoclonus: “Dancing eyes, dancing feet”—the telltale symptom of this disease (secondary to paraneoplastic antibodies).


Image Typically, a mass is seen on CT or MRI.

Image Ninety-five percent of cases have elevated tumor markers, most often homovanillic acid (HVA) and vanillylmandelic acid (VMA) in the urine.

Image Metaiodobenzylguanidine (MIBG) radioisotope scan for detecting small primaries and metastases.

Image Stage 4: Infantile form, self-limited with good prognosis.

Image Unfavorable prognosis is associated with ↑ neuron-specific enolase and amplification of N-Myc gene.

Image Treatment is surgical resection followed by radio + chemotherapy.

von Hippel–Lindau Disease


A neurocutaneous syndrome (usually no cutaneous involment) affecting many organs, including the cerebellum, spinal cord, medulla, retina, kidneys, pancreas, and epididymis.


The major neurologic manifestations are:

Image Cerebellar/spinal hemagioblastomas: Present in early adult life with signs of ↑ ICP.

Image Retinal angiomata: Small masses of thin-walled capillaries in the peripheral retina.

Image Multiple congenital cysts of the pancreas and polycythemia are also associated with it.

Image Early detection and resection is the best management.

Image Photocoagulation for retinal detachment.


Renal carcinoma is the most common cause of death associated with von Hippel– Lindau disease.

Neurofibromatosis (NF)


Both types display autosomal recessive inheritance patterns.

Image Type 1: The most prevalent type (∼90%) with an incidence of 1 in 4000 (chromosome 17).

Image 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.


Type 1

Image Diagnosis is made by the presence of two or more of the following:

Image Six or more café-au-lait macules (must be > 5 mm prepuberty, > 15 mm postpuberty).

Image Axillary or inguinal freckling (Crowe sign).

Image Two or more iris Lisch nodules (melanocytic hamartomas).

Image Two or more cutaneous neurofibromas.

Image A characteristic osseous lesion (sphenoid dysplasia, thinning of long-bone cortex).

Image Optic glioma.

Image A first-degree relative with confirmed NF-1.

Image Learning disabilities, abnormal speech development, and seizures are common.

Image 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).

Image 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

Image Diagnosis is made when one of the following is present:

Image Bilateral CN VIII masses (most of the cases).

Image A parent or sibling with the disease and either a neurofibroma, meningioma, glioma, or schwannoma.

Image Café-au-lait spots and skin neurofibromas are not common findings.

Image Patients are at significantly higher risk for CNS tumors than in NF-1 and typically have multiple tumors.


Image 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


Image Inherited as an autosomal-dominant trait, with a frequency of 1:6,000.

Image Two-third are new mutations.


Image Characteristic brain lesions consist of tubers, which are located in the convolutions of the cerebrum, where they undergo calcification and project into the ventricles.

Image There are two recognized genes: TSC1 on chromosome 9, encoding a protein called hamartin; and TSC2 on chromosome 16, encoding a protein called tuberin.

Image 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.


Image Hypopigmented macules (Ash leaf skin lesions) are seen in 90% and are best viewed under a Wood’s lamp (violet/ultraviolet light source).

Image CT scan shows calcified hamartomas (tubers) in the periventricular region.

Image 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.

Image Adenoma sebaceum—small, raised papules resembling acne that develop on the face between 4 and 6 years of age, actually are small hamartomas.

Image 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.

Image 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.

Image 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.


Image A high index of suspicion is needed, but all children presenting with infantile spasms should be carefully assessed for skin and retinal lesions.

Image CT or MRI will confirm the diagnosis.

Image Genetic testing is available for mutations in TSC1 and TSC2.


Hamartoma: A tumor-like overgrowth of tissue normally found in the area surrounding it.


Agenesis of the Corpus Callosum

Image 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.

Image Imaging techniques reveal that the lateral ventricles are shifted laterally.

Image Normal intelligence is not unusual, and often only mild clinical signs are seen.

Image The severity of the disease varies greatly, from only mild deficits to marked retardation and severe epilepsy.



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.

Image A slowly progressive paracentral cavity formation within the brain or spinal cord, most often in the cervical or lumbar regions.

Image Thought to arise from incomplete closure of the neural tube during the fourth week of gestation.

Image MRI is the test of choice for diagnosis.

Image Often develops post-traumatically in the setting of an undiagnosed Chiari I malformation or tethered cord.

Image 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.

Image Called syringobulbia when present in brain stem.

Dandy-Walker Malformation

Image Results from a developmental failure of the roof of the fourth ventricle to form, resulting in a cystic expansion into the posterior fossa.

Image Ninety percent of patients have hydrocephalus.

Image Agenesis of the cerebellar vermis and corpus callosum is also common.

Image Infants present with a rapid ↑ in head size.

Image Management is via shunting of the cystic cavity to prevent hydrocephalus.

Arnold-Chiari Malformations

Image 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.

Image Type 2 is also associated with meningomyelocele in > 95% of cases.

Image Syringomyelia is associated in 70% of type 1, and 20–50% overall.

Image 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.

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