The term ataxia denotes disturbances in the fine control of posture and movement. The cerebellum and its major input systems from the frontal lobes and the posterior columns of the spinal cord provide this control. The initial and most prominent feature is usually an abnormal gait. The ataxic gait is wide-based, lurching, and staggering, and it provokes disquiet in an observer for fear that the patient is in danger of falling. One observes a similar gait in people who are attempting to walk in a vehicle that has several directions of motion at once, such as a railroad train.
When an abnormality occurs in the vermis of the cerebellum, the child cannot sit still but constantly moves the body to-and-fro and bobs the head (titubation). In contrast, disturbances of the cerebellar hemispheres cause a tendency to veer in the direction of the affected hemisphere, with dysmetria and hypotonia in the ipsilateral limbs. Bifrontal lobe disease may produce symptoms and signs that are indistinguishable from those of cerebellar disease.
Loss of sensory input to the cerebellum, because of peripheral nerve or posterior column disease, necessitates constant looking at the feet to know their location in space (due to loss of proprioception). The gait is also wide-based, but is not so much lurching as careful. The foot raises high with each step and slaps down heavily on the ground. Station and gait are considerably worse with the eyes closed, and the patient may actually fall to the floor (Romberg sign). Sensory ataxia is more likely to cause difficulty with fine finger movements than with reaching for objects.
Other features of cerebellar disease are a characteristic speech that varies in volume and has an increased separation of syllables (scanning speech), hypotonia, limb and ocular dysmetria, and tremor. The differential diagnosis of a child with acute ataxia or recurrent attacks of ataxia ( Box 10-1 ) are quite different from that of a child with chronic static or progressive ataxia ( Box 10-2 ). Therefore, the discussion of these two presentations is separate in the text. However, one may “suddenly” become aware of what had been a slowly progressive ataxia, and children with recurrent ataxia may never recover to baseline function after each attack. Progressive ataxia superimposes on the acute attacks.
Conversion reaction ∗
∗ Denotes the most common conditions and the ones with disease modifying treatments
Dominant recurrent ataxia
Episodic ataxia type 1
Episodic ataxia type 2
Maple syrup urine disease
Pyruvate dehydrogenase deficiency
Benign paroxysmal vertigo ∗
Acute postinfectious cerebellitis
Miller Fisher syndrome ∗
Multiple sclerosis ∗
Myoclonic encephalopathy and neuroblastoma ∗
Progressive cavitating leukoencephalopathy
Cerebellar astrocytoma ∗
∗ Denotes the most common conditions and the ones with disease modifying treatments
Cerebellar hemangioblastoma ∗ (Von Hippel-Lindau disease)
Cerebellar hemisphere aplasia
Chiari malformation ∗
Dandy-Walker malformation (see Chapter 18 )
Autosomal dominant inheritance (see Table 10-1 )
Autosomal recessive inheritance
Ataxia without oculomor apraxia
Ataxia with episodic dystonia
Juvenile GM 2 gangliosidosis
Juvenile sulfatide lipidoses
Maple syrup urine disease
Pyruvate dehydrogenase deficiency
Ramsay Hunt syndrome
Refsum disease (HSMN IV) (see Chapter 7 )
Respiratory chain disorders (see Chapter 8 )
Adrenoleukodystrophy (see Chapter 5 )
Leber optic neuropathy (see Chapter 16 )
With adult-onset dementia
With deafness and loss of vision
Acute and Recurrent Ataxias
The two most common causes of ataxia among children who were previously healthy and then suddenly have an ataxic gait are drug ingestion and acute postinfectious cerebellitis. Migraine, brainstem encephalitis, and an underlying neuroblastoma are the next considerations.
Primary brain tumors ordinarily cause chronic progressive ataxia and their discussion is later in this chapter. However, ataxia may be acute if the brain tumor bleeds or causes hydrocephalus. In addition, early clumsiness may not become apparent until it becomes severe enough to cause an obvious gait disturbance. Brain imaging is therefore a recommendation for most children with acute cerebellar ataxia.
Psychogenic gait disturbances are relatively common in children, especially girls between 10 and 15 years of age. Psychogenic symptoms are involuntary and usually protective against an overwhelming stressor. In contrast, malingering is a voluntary act. Psychogenic gait disturbances are often extreme. The child appears to sit without difficulty but when brought to standing immediately begins to sway from the waist. Stance is not wide to improve stability as it would occur in an organic ataxia. Instead, the child lurches, staggers, and otherwise travels across the room from object to object. The lurching maneuvers are often complex and require extraordinary balance. Strength, tone, sensation, and tendon reflexes are normal.
The diagnosis of psychogenic gait disturbances is by observation; laboratory tests or imaging studies are not ordinarily required to exclude other possibilities.
Determination of the precipitating stress is important. Conversion may represent a true call for help in a desperate situation such as sexual or physical abuse. Such cases require referral to a multispecialty team able to deal with the whole family. Fortunately, most children with psychogenic gait disturbances are responding to an immediate and less serious life stress. Identifying possible stressors, modifying surrounding circumstances and activities, and improving copying mechanisms are necessary for improvement and prevention of further psychogenic symptoms.
Dominant Recurrent Ataxias
At least two distinct genetic defects are recognized that cause episodic ataxia: episodic ataxia type 1 (EA-1) and episodic ataxia type 2 (EA-2). Both are the result of ion channel mutations. Mutations in a potassium channel gene underlie EA-1 and mutations in a voltage-dependent calcium channel underlie EA-2 ( ).
Episodic Ataxia Type 1 (Paroxysmal Ataxia and Myokymia)
EA-1 results from a mutation of the potassium channel gene KCNA1 on chromosome 12p. The additional feature of continuous motor unit activity (see Chapter 8 ) suggests a defect in membrane stability affecting the central and peripheral nervous systems.
The onset of attacks is usually between 5 and 7 years of age. Abrupt postural change, startle, exercise, and stress may provoke an attack. The child becomes aware of attack onset by the sensation of spreading limpness or stiffness lasting for a few seconds. Incoordination, trembling of the head or limbs, and blurry vision often follow. Some children feel warm and perspire. Some can continue standing or walking, but most sit down. Attacks usually last for less than 10 minutes but can be as long as 6 hours. Myokymia of the face and limbs begins at about age 12 years. Physical findings include large calves, normal muscle strength, and widespread myokymia of face, hands, arms, and legs, with a hand posture resembling carpopedal spasm. Electromyography (EMG) at rest shows continuous spontaneous activity ( )
The basis for clinical diagnosis is the history of typical attacks and the family history. EMG confirms the diagnosis by showing continuous motor unit activity, most often in the hands but also in the proximal arm muscles and sometimes in the face.
Some patients respond to daily antiepileptic drugs. When these fail, a trial of daily acetazolamide is reasonable.
Episodic Ataxia Type 2 (Acetazolamide-Responsive Ataxia)
EA-2, one form of spinocerebellar ataxia (SCA6), and one type of familial hemiplegic migraine all represent allelic mutations in the same calcium channel gene CACNA1A on chromosome 19p. About half of patients have migraine headaches; some episodes may be typical of basilar migraine ( ).
Clinical heterogeneity is considerable despite genetic localization to the 19p site. The onset is generally during school age or adolescence. The child first becomes unsteady and is then unable to maintain posture because of vertigo and ataxia. Vomiting is frequent and severe. Jerk nystagmus, sometimes with a rotary component, occurs during attacks. One to three attacks may occur each month, with symptoms lasting from 1 hour to 1 day. Attacks become milder and less frequent with age. Slowly progressive truncal ataxia and nystagmus may persist between attacks. In some patients ataxia is the only symptom, others have only vertigo, and still others have only nystagmus. Most affected individuals are normal between attacks, but some are phenotypically indistinguishable from those with SCA6 (see discussion on Progressive Hereditary Ataxias later in this chapter).
The clinical features and the family history are the basis for diagnosis. Molecular diagnosis is available on a research basis. Magnetic resonance imaging (MRI) may show selective atrophy of the cerebellar vermis. Basilar artery migraine and benign paroxysmal vertigo can be distinguished from dominant recurrent ataxia because in these conditions, older family members have migraine but do not have recurrent ataxia. Further, attacks of benign paroxysmal vertigo rarely last more than a few minutes.
Daily oral acetazolamide prevents recurrence of attacks in almost every case. The mechanism of action is unknown. The dose is generally 125 mg twice a day in young children and 250 mg twice a day in older children. Flunarizine, 5–10 mg/day, may serve as an alternative therapy for children with acetazolamide intolerance. Antiepileptic and antimigraine medications are without value.
Other Episodic Ataxias
Episodic ataxia type 3 (EA-3), EA-4, EA-5 and EA-6 are described. These ataxias are even less frequent and well described. EA-6 was identified as a more severe phenotype of episodic and progressive ataxia, seizures, alternating hemiplegia, and migraine headache associated with a mutation of the SLC1A3 gene, which encodes the glial excitatory amino acid transporter EAAT1 involved in glutamate removal from the synaptic cleft ( ).
The incidence of accidental drug ingestion is greatest between ages 1 and 4 years.
An overdose of most psychoactive drugs causes ataxia, disturbances in personality or sensorium, and sometimes seizures. Toxic doses of antiepileptic drugs, especially phenytoin, may cause marked nystagmus and ataxia without an equivalent alteration in sensorium. Excessive use of antihistamines in the treatment of an infant or young child with allergy or an upper respiratory tract infection may cause ataxia. This is especially true in children with otitis media, who may have underlying unsteadiness because of middle-ear infection and possible inner ear dysfunction.
Carefully question the parents or care providers of every child with acute ataxia concerning drugs intentionally administered to the child and other drugs accessible in the home. Specific inquiry concerning the use of anticonvulsant or psychoactive drugs by family members is mandatory. Screen urine for drug metabolites, and send blood for analysis when suspecting intoxication with a specific drug.
Treatment depends on the specific drug ingested and its blood concentration. In most cases of ataxia caused by drug ingestion, the drug can be safely eliminated spontaneously if vital function is not compromised, if acid–base balance is not disturbed, and if liver and kidney function is normal. In life-threatening situations, dialysis may be necessary while supporting vital function in an intensive care unit. Gastric emptying has limited value when ataxia is already present.
Ataxia may be the initial feature of viral encephalitis affecting primarily the structures of the posterior fossa. Potential etiological agents include echoviruses, coxsackieviruses, adenoviruses, and Coxiella burnetti ( ).
Cranial nerve dysfunction is often associated with the ataxia. Generalized encephalitis characterized by declining consciousness and seizures may develop later. Meningismus is sometimes present. The course is variable, and, although most children recover completely, some suffer considerable neurological impairment. Those who have only ataxia and cranial nerve palsies, with no disturbance of neocortical function, tend to recover best. Such cases are indistinguishable from the Miller Fisher syndrome on clinical grounds alone.
Diagnosis requires showing a cellular response, primarily mononuclear leukocytes, in the cerebrospinal fluid, with or without some elevation of the protein content. Prolonged interpeak latencies of the brainstem auditory evoked response are evidence of an abnormality within the brainstem parenchyma and not the peripheral sensory input system. The electroencephalogram (EEG) is usually normal in children with brainstem encephalitis who have a normal sensorium.
No specific treatment is available for the viral infection.
Inborn Errors of Metabolism
Hartnup disease is a rare disorder transmitted by autosomal recessive inheritance. The abnormal gene localizes to chromosome 5p15 ( ). The basic error is a defect of amino acid transport in kidney and small intestine. The result is aminoaciduria and the retention of amino acids in the small intestine. Tryptophan conversion is to nonessential indole products instead of nicotinamide.
Affected children are normal at birth but may be slow in attaining developmental milestones. Most achieve only borderline intelligence; others are normal. Affected individuals are photosensitive and have a severe pellagra-like skin rash after exposure to sunlight. Nicotinamide deficiency causes the rash. Many patients have episodes of limb ataxia, sometimes associated with nystagmus. Mental changes, ranging from emotional instability to delirium or states of decreased consciousness, may occur. Examination reveals hypotonia and normal or exaggerated tendon reflexes. Stress or intercurrent infection triggers the neurological disturbances, which may be due to the intestinal absorption of toxic amino acid breakdown products. Most patients have both rash and neurological disturbances, but each can occur without the other. Symptoms progress over several days and last for a week to a month before recovery occurs.
The constant feature of Hartnup disease is aminoaciduria involving neutral monoaminomonocarboxylic amino acids. These include alanine, serine, threonine, asparagine, glutamine, valine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan, histidine, and citrulline.
Daily oral administration of nicotinamide, 50–300 mg, may reverse the skin and neurological complications. A high-protein diet helps make up for the amino acid loss and the disease is rare in populations with a super- adequate diet.
Maple Syrup Urine Disease (Intermittent)
Maple syrup urine disease is a disorder of branched-chain amino acid metabolism caused by deficiency of the enzyme branched-chain keto acid dehydrogenase. The result of the deficiency is a neonatal organic acidemia. Transmission of the defect is by autosomal recessive inheritance. Three phenotypes are associated, depending on the percentage of enzyme deficiency. The classic form begins as seizures in the newborn (see Chapter 1 ), the intermediate form causes progressive mental retardation (see Chapter 5 ), and the intermittent form causes recurrent attacks of ataxia, and encephalopathy.
Affected individuals are normal at birth. Between 5 months and 2 years, minor infections, surgery, or a diet rich in protein provokes episodes of ataxia, irritability, and progressive lethargy. The length of an attack is variable; most children recover spontaneously, but some die of severe metabolic acidosis. Psychomotor development remains normal in survivors.
The urine has a maple syrup odor during the attack, and the blood and urine have elevated concentrations of branched-chain amino acids and ketoacids. Between attacks, the concentrations of branched-chain amino acids and ketoacids are normal in both blood and urine. Establishing the diagnosis requires showing the enzyme deficiency in cultured fibroblasts.
Children with intermittent maple syrup disease need a protein-restricted diet. Some have a thiamine-responsive enzyme defect, and 1 g of thiamine a day treats the acute attacks. If this is successful, a recommended maintenance dose is 100 mg/day. The main objective during an acute attack is to reverse ketoacidosis. Allow no protein ingestion and peritoneal dialysis may be helpful in life-threatening situations.
Pyruvate Dehydrogenase Deficiency
The pyruvate dehydrogenase (PDH) complex is responsible for the oxidative decarboxylation of pyruvate to carbon dioxide and acetyl-coenzyme A (acetyl-CoA). Disorders of the complex are associated with several neurological conditions, including subacute necrotizing encephalomyelopathy (Leigh syndrome), mitochondrial myopathies, and lactic acidosis. The complex contains three main components that are termed E1, E2, and E3. E1 consists of two alpha subunits encoded on the X chromosome and two beta subunits. Episodes of intermittent ataxia and lactic acidosis characterize the X-linked form of PDH-E1 deficiency ( ). E1 deficiency is the most common form of PDH deficiency.
The clinical features range from severe neonatal lactic acidosis and death to episodic ataxia with lactic and pyruvic acidosis and spinocerebellar degeneration. Most patients show mild developmental delay during early childhood. Episodes of ataxia, dysarthria, and sometimes lethargy usually begin after 3 years of age. In more severely affected patients, episodes may begin during infancy and are associated with generalized weakness and states of decreased consciousness. Some attacks are spontaneous, but intercurrent infection, stress, or a meal high in carbohydrate provokes others. Attacks recur at irregular intervals and may last for periods ranging from 1 day to several weeks.
The severity of neurological dysfunction in any individual probably reflects the level of residual enzyme activity. Those with generalized weakness are also areflexic and have nystagmus or other disturbances in ocular motility. Ataxia is the predominant symptom. Intention tremor and dysarthria may be present. Hyperventilation is common and metabolic acidosis may be the cause. Patients with almost complete PDH deficiency die of lactic acidosis and central hypoventilation during infancy.
PDH deficiency should be suspected in children with lactic acidosis, hypotonia, progressive or episodic ataxia, the Leigh disease phenotype, and recurrent polyneuropathy. The pyruvic acid concentration is elevated, and the lactate-to-pyruvate ratio is low. The blood concentration of lactate may be elevated between attacks; lactate and pyruvate concentrations are always elevated during attacks. Some children have hyperalaninemia as well. Analysis of enzyme activity in cultured fibroblasts, leukocytes, or muscle establishes the diagnosis.
The ketogenic diet is a rational treatment for PDH complex deficiency ( ). Patients are usually treated with thiamine (100–600 mg/day) and a high-fat (>55 %), low-carbohydrate diet. Unfortunately, current treatments do not prevent disease progression in most patients. In addition, daily oral acetazolamide, 125 mg twice a day in small children and 250 mg twice a day in older children, may significantly abort the attacks. The treatment of several patients with biotin, carnitine, coenzyme Q10, and thiamine supplements has not established efficacy.
The term basilar (artery) migraine characterizes recurrent attacks of brainstem or cerebellar dysfunction that occur as symptoms of a migraine attack. Children who experience basilar artery migraine have typical migraine with aura at other times ( ). Girls are more often affected than are boys. The peak incidence is during adolescence, but attacks may occur at any age. Infant-onset cases are more likely to present as benign paroxysmal vertigo.
Gait ataxia occurs in approximately 50 % of patients. Other symptoms include visual loss, vertigo, tinnitus, alternating hemiparesis, and paresthesias of the fingers, toes, and corners of the mouth. An abrupt loss of consciousness may occur, usually lasting for only a few minutes. Cardiac arrhythmia and brainstem stroke are rare life-threatening complications. A severe, throbbing, occipital headache usually follows the neurological disturbances. Nausea and vomiting occur in less than one-third of cases.
Children may have repeated basilar migraine attacks, but, with time, the episodes evolve into a pattern of classic migraine. Even during attacks of classic migraine, the patient may continue to complain of vertigo and even ataxia.
EEG distinguishes basilar migraine from benign occipital epilepsy. The EEG shows occipital intermittent delta activity during and just after an attack in basilar migraine and occipital sharp and spike and wave discharges in epilepsy.
Treatment of basilar artery migraine is the same as for other forms of migraine (see Chapter 3 ). Frequent attacks require a prophylactic agent.
Benign Paroxysmal Vertigo
Benign paroxysmal vertigo is primarily a disorder of infants and preschool children but may occur in older children.
Recurrent attacks of vertigo are characteristic. Vertigo is maximal at onset. True cerebellar ataxia is not present, but vertigo is so profound that standing is impossible. The child either lies motionless on the floor or wants holding. Consciousness maintains throughout the event and headache is not associated. The predominant symptoms are pallor, nystagmus, and fright. Episodes last only for minutes and may recur at irregular intervals. With time, attacks decrease in frequency and stop completely or evolve into more typical migraines. Migraine develops in 21 % ( ).
The diagnosis is primarily clinical, and laboratory tests are useful only to exclude other possibilities. A family history of migraine, though not necessarily paroxysmal vertigo, is positive in 40 % of cases. Some parents indicate that they experience vertigo with their attacks of migraine. Only in rare cases does a parent have a history of benign paroxysmal vertigo.
The attacks are so brief and harmless that treatment is not required. Migraine prophylaxis may be considered when the attacks are frequent.
In many conditions discussed in this section, the underlying cause of cerebellar dysfunction and some other neurological deficits is an altered immune state. Preceding viral infections are usually incriminated but documentation is limited to only half of cases. Natural varicella infections and the varicella vaccine are definite preceding causes. No other vaccine links to acute cerebellar ataxia.
Acute Cerebellar Ataxia
Acute cerebellar ataxia usually affects children between 2 and 7 years of age, but it may occur as late as 16 years. The disorder affects both genders equally, and the incidence among family members is not increased. In the past, acute cerebellar ataxia occurred most often following varicella infection. The widespread use of varicella vaccine has made the syndrome uncommon. However, it is a complication of live-inactivated vaccine administration.
The onset is explosive. A previously healthy child awakens from a nap and cannot stand. Ataxia is maximal at onset. Some worsening may occur during the first hours, but a longer progression, or a waxing and waning course, negates the diagnosis. Ataxia varies from mild unsteadiness while walking to complete inability to stand or walk. Even when ataxia is severe, sensorium is clear and the child is otherwise normal. Tendon reflexes may be present or absent; their absence suggests the Miller Fisher syndrome . Nystagmus, when present, is usually mild. Chaotic movements of the eyes (opsoclonus) should suggest the myoclonic encephalopathy-neuroblastoma syndrome.
Symptoms begin to remit after a few days, but recovery of normal gait takes 3 weeks to 5 months. Patients with pure ataxia of the trunk or limbs and only mild nystagmus are likely to recover completely. Marked nystagmus or opsoclonus (see the section on Myoclonic Encephalopathy/Neuroblastoma Syndrome later in this chapter), tremors of the head and trunk, or moderate irritability are usually followed by persistent neurological sequelae.
The diagnosis of acute postinfectious cerebellitis is one of exclusion. Every child should have drug screening, and most will have a brain imaging study. The necessity of imaging the brain in typical cases, especially those with varicella infection, is debatable. Lumbar puncture is indicated when encephalitis is suspected.
Acute postinfectious cerebellitis is a self-limited disease. Treatment is not required. Occupational therapy may facilitate activities during the recovery phase.
Miller Fisher Syndrome
Ataxia, ophthalmoplegia, and areflexia characterize the Miller Fisher syndrome. A similar disorder with ataxia and areflexia but without ophthalmoplegia is acute ataxic neuropathy . Some believe that Miller Fisher syndrome is a variant of Guillain-Barré syndrome; others believe that it is a form of brainstem encephalitis. In support of the hypothesis of a Guillain-Barré-like, immune-mediated hypothesis is the finding that Campylobacter jejuni serotype O:19 is a causative agent in both Miller Fisher syndrome and Guillain-Barré syndromes ( ).
A viral illness precedes the neurological symptoms by 5 to 10 days in 50 % of cases. Either ophthalmoparesis or ataxia may be the initial feature. Both are present early in the course. The initial ocular motor disturbance is paralysis of upgaze, followed by loss of lateral gaze and then downgaze. Recovery takes place in the reverse order. Preservation of the Bell phenomenon sometimes occurs despite paralysis of voluntary upward gaze, suggesting the possibility of supranuclear palsy. Ptosis occurs but is less severe than the vertical gaze palsy.
Decreased peripheral sensory input probably causes areflexia and more prominent limb than trunk ataxia. Weakness of the limbs may be noted. Unilateral or bilateral facial weakness occurs in a significant minority of children. Recovery generally begins within 2 to 4 weeks after symptoms become maximal and is complete within 6 months.
The clinical distinction between the Miller Fisher syndrome and brainstem encephalitis can be difficult. Disturbances of sensorium, multiple cranial nerve palsies, an abnormal EEG, or prolongation of the interpeak latencies of the brainstem auditory evoked response should suggest brainstem encephalitis. The cerebrospinal fluid profile in Miller Fisher syndrome parallels that of Guillain-Barré syndrome. A cellular response occurs early in the course, and protein elevation occurs later.
Intravenous immunoglobulin to block antibodies and plasmapheresis to remove antibodies may be beneficial. The dose of immunoglobilin is 2 g/kg over 2 to 5 days. The outcome in untreated children is usually good.
Multiple sclerosis is usually a disease of young adults, but 3–5 % of cases occur in children less than 6 years of age ( ). The childhood forms of multiple sclerosis are similar to the adult forms. This section could just as well appear in several other chapters of the text. The advent of neuroimaging, especially magnetic resonance imaging (MRI), has heightened diagnostic accuracy ( ).
In a prospective study of 296 children with acute demyelination, 81 presented with focal involvement, 119 with acute disseminated encephalomyelitis (ADEM), and 96 with symptoms that suggest already established multiple sclerosis. Long-tract (motor, sensory, or sphincter) dysfunction was the commonest finding in 226 children (76 %), followed by symptoms localized to the brainstem in 121 children (41 %), optic neuritis in 67 children (22 %), and transverse myelitis in 42 children (14 %) (Mikaeloff, 2006). Monofocal presentation was more common in adolescents. Recovery from acute demyelination is variable: 85 % of children with optic neuritis recover full visual acuity ( ). In published reports of 250 children with transverse myelitis, 80 % were paraplegic or tetraplegic and had incontinence or severe urinary symptoms at onset, and 5 % died ( ). More than 30 % of survivors remain wheelchair dependent, and 70 % have residual bladder control problems ( ).
The female-to-male ratio varies from 1.5:1 to 3:1. Ataxia, concurrent with a febrile episode, is the most common initial feature in children, followed by encephalopathy, hemiparesis, or seizures. Intranuclear ophthalmoplegia, unilateral or bilateral, develops in one-third of patients (see Chapter 15 ).
The clinical features that occur in multiple sclerosis are sufficiently variable that no single prototype is valid. The essential feature is repeated episodes of demyelination in noncontiguous areas of the central nervous system. Focal neurological deficits that develop rapidly and persist for weeks or months characterize an episode. Afterward the child has partial or complete recovery. Months or years separate recurrences, which are often concurrent with fever, but not with a specific febrile illness. Lethargy, nausea, and vomiting sometimes accompany the attacks in children but rarely in adults. The child is usually irritable and shows truncal and limb ataxia. Tendon reflexes are generally brisk throughout. The long-term outcome is poor.
Multiple sclerosis may be the suspected diagnosis at the time of the first attack, but definitive diagnosis requires recurrence to establish a polyphasic course. Examination of the cerebrospinal fluid at the time of exacerbation reveals fewer than 25 lymphocytes/mm 3 , a normal or mildly elevated protein content, and sometimes the presence of oligoclonal bands.
MRI is the technique of choice for the diagnosis of multiple sclerosis and shows occult disease in up to 80 % of affected individuals at the time of first presentation ( Figure 10-1 ). The finding of three or more white matter lesions on a T 2 -weighted image MRI scan, especially if one of these lesions is in the perpendicular plane to the corpus callosum, is a sensitive predictor of definite multiple sclerosis ( ). However, the extent and severity of lesions may not correlate with the clinical syndrome. After repeated attacks, the MRI reveals thalamic grey matter loss ( ).