Topical Review

Acute in Childhood

Monique M. Ryan, MBBS, MMed; Elizabeth C. Engle, MD

ABSTRACT

Acute childhood ataxia is a common cause of presentation to the pediatric emergency room or child neurologist. The pri- mary concern on initial assessment is to exclude serious causes of this clinical syndrome, including infections and mass lesions, while recognizing the essentially benign nature of acute ataxia in most children. Childhood ataxia can be diagnostically approached by consideration of the temporal course and presence or absence of associated neurologic abnormalities. In all forms of childhood ataxia, outcome is largely determined by etiology. In this review, the various causes and syndromes of acute ataxia in childhood are described, with discussion of diagnostic considerations and an approach to investigation, treatment, and prognosis. (J Child Neurol 2003;18:309–316).

The word “ataxia” (Greek: ataktos, lacking order) refers to ious causative disorders are discussed, followed by an a pathologic abnormality of organization or modulation of overview of investigation, treatment, and prognosis in the movement. Although ataxia is most commonly attributable acute ataxic syndromes of childhood. to cerebellar dysfunction, lesions at almost all levels of the nervous system can result in motor incoordination. CLINICAL EVALUATION OF ACUTE ATAXIA IN Acute ataxia is a common cause of presentation to the CHILDHOOD pediatric emergency room or child neurologist. Childhood ataxia is best approached diagnostically by determination of Most children with acute ataxia are seen within several days the temporal course and the presence or absence of asso- of symptom onset, usually because of refusal to walk or the ciated neurologic abnormalities. Ataxia may be congenital sudden development of a wide-based, “drunken” gait. Care- or acquired. Congenital ataxia is usually associated with givers less commonly remark on unsteadiness of arm move- central nervous system malformations. Acquired ataxia can ments, truncal titubation, and . At presentation, the be classified as acute, episodic, or chronic. Episodic and primary concern is to exclude serious causes of acute ataxia, chronically progressive are uncommon in childhood including central nervous system infections and mass lesions and are usually caused by inherited metabolic or genetic dis- (Table 1), while recognizing the essentially benign nature of orders. In all forms of childhood ataxia, outcome is largely this clinical syndrome in most children. The history should determined by etiology. This review is confined to a discus- therefore include inquiry as to antecedent or current symp- sion of the causes, investigation, and outcome of acute child- toms of systemic infection, including fever, rash, and gas- hood ataxia, which may be defined as unsteadiness of walking trointestinal upset. Recent immunizations should be noted, or of fine motor movement, of less than 72 hours’ duration, as should the child’s general state of health in the weeks and in a previously well child. The symptoms and signs of the var- months prior to presentation. Recurrent or persistent headache and vomiting or diplopia suggests an intracranial mass lesion and possible elevation of intracranial pressure. A common cause of acute ataxia is inadvertent or deliber- Received Dec 26, 2002. Received revised Jan 21, 2003. Accepted for publi- cation Jan 21, 2003. ate drug ingestion. The child’s activities should be reviewed From the Department of Neurology (Drs Ryan and Engle), Children’s Hospital with respect to possible exposure to medications, alcohol, Boston, Boston, MA. and household chemicals. Recent head or neck trauma Presented in part at the Michael J. Bresnan Child Neurology Course, should prompt consideration of vertebral artery dissection. Children’s Hospital, Harvard Medical School, Boston, September 26, 2002. A history of previous similar episodes in the patient or other Address correspondence to Dr Monique M. Ryan, Department of Neurology, family members should also be identified if present. Fegan 11, Children’s Hospital Boston, 300 Longwood Avenue, Boston MA 02115. Tel: 617-355-2067; fax: 617-264-9691; e-mail: [email protected] Specific details regarding physical findings in the var- vard.edu. ious forms of acute ataxia are discussed in detail below. In

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Table 1. Causes of Acute Ataxia in Childhood ETIOLOGY OF ACUTE ATAXIA IN CHILDHOOD Infectious/immune-mediated cerebellar disorders Acute * Cerebellar Disorders Acute demyelinating encephalomyelitis* Acute ataxia secondary to cerebellar dysfunction is char- Systemic infections acterized by hypotonia, gait abnormalities (wide based, Multiple sclerosis lurching, possibly staggering), poor maintenance of truncal Toxic: alcohol and drug related* position (titubation), and speech abnormalities (fluctua- Mass lesions tions in clarity, rhythm, tone, and volume). Poor coordina- Tumors tion of voluntary movements (dysmetria) results in Vascular lesions Abscesses , under- or overshooting of limb movements (best seen on finger-nose or toe-target testing), and difficulty Trauma with rapid alternating movements (), Cerebellar contusion or hemorrhage which may be associated with (which is Posterior fossa hematoma oscillatory, to and fro in a plane perpendicular to the object Postconcussion syndrome Vertebrobasilar dissection being approached). The deep tendon reflexes can be pen- dular, with slowed contraction and relaxation phases, Vertebrobasilar dissection or thromboembolism although this is often difficult to appreciate. Cerebellar hemorrhage Some clue to localization of the lesion within the cere- Paraneoplastic disorders bellum can be apparent on examination: vermal (midline) Opsoclonus-myoclonus syndrome lesions cause dysarthria, truncal titubation, and gait abnor- Sensory ataxia Guillain-Barré syndrome malities, whereas lesions of the cerebellar hemispheres Miller Fisher syndrome spare speech but result in ipsilateral limb hypotonia, dys- Paretic ataxia metria, and tremor. When walking, patients tend to veer in Upper motoneuron Lesions of , the direction of the affected cerebellar hemisphere. Lesions corticospinal pathways Lower motoneuron : transverse of the deep cerebellar nuclei cause resting tremor, myoclonus myelitis, vascular lesions, of the extremities and palate, and opsoclonus. Findings in cord compression cerebellar ataxia remain unchanged in severity whether Peripheral nerve: Guillain-Barré syndrome, the eyes are open or closed. Miller Fisher syndrome, tick paralysis Infectious or Immune Mediated Other neurologic disorders Inborn errors of metabolism (see Table 3)* Basilar migraine, benign paroxysmal vertigo Acute Cerebellar Ataxia Nonconvulsive seizures The most common cause of childhood ataxia, accounting Central pontine myelinolysis for about 40% of all cases, is acute cerebellar ataxia.1 Acute Wernicke’s encephalopathy cerebellar ataxia usually results from postinfectious cere- Functional ataxia bellar demyelination, less commonly occurring as a result *Most common. of direct infection of the . Postinfectious cere- bellar demyelination is thought to be an autoimmune phe- general, the physical examination can be difficult as sig- nomenon incited by infection or immunization, with nificantly ataxic children are often hesitant and irritable, subsequent cross-reaction of antibodies against cerebellar necessitating prolonged observation to differentiate poor epitopes, although specific autoantibodies have only rarely coordination from weakness. The mental state is impor- been identified.2 tant. Children with postinfectious cerebellar ataxia are nor- Acute cerebellar ataxia is most common in younger mally alert and interactive. Abruptly altered responsiveness children (2–4 years) but may be seen in older children suggests an ingestion, acute disseminated encephalomyelitis, and adolescents.1,3 Boys are more commonly affected.3 A or stroke. Extreme irritability and decreased speech output history of antecedent illness in the 5 to 21 days before pre- can be seen in the opsoclonus-myoclonus syndrome. sentation is obtained in about 70% of patients. Numerous Nystagmus is common to disorders affecting the cere- infectious agents have been implicated in the pathogene- bellar hemispheres. Additional abnormalities of cranial sis of this condition (Table 2). As many as 26% of cases are nerve examination, such as papilledema and cranial nerve preceded by varicella.3 Rarely, the development of ataxia palsies, suggest an intracranial focal lesion or hydrocephalus. precedes the eruptive phase of varicella infection.4 The Pupillary abnormalities can be seen with mass lesions, introduction of universal immunization against varicella is raised intracranial pressure, stroke, or intoxication. Asym- likely to render varicella-related cerebellar ataxia uncom- metries of limb tone, power, and the deep tendon reflexes mon. To date, only one case of acute cerebellar ataxia are uncommon in acute cerebellar ataxia and should prompt temporally related to varicella vaccination has been consideration of other conditions. Truncal ataxia is easier described.5 Although cerebellar ataxia has long been tem- to appreciate when the child sits unsupported. porally linked to childhood immunizations (most com- Acute Ataxia in Childhood / Ryan and Engle 311

Table 2. Reported Causes of Infectious/Postinfectious Cerebellitis in Childhood Infections Associated With Direct Infection Post- or Parainfectious Cerebellitis Systemic Infections Echovirus type 9 Varicella zoster Typhoid fever Coxsackie B Epstein-Barr virus Scarlet fever Varicella zoster Mumps Mycoplasma pneumoniae Bacterial (pneumococcal, meningococcal) Legionella pneumophilia Diphtheria Hepatitis A Leptospirosis Influenza A and B Herpes simplex virus I Coxsackie A Echovirus type 6 Enterovirus type 71 Malaria Poliovirus type 1 Japanese B encephalitis Parvovirus B19 Measles Mycoplasma pneumoniae

monly the initial measles vaccination), a causal relation- encephalitis and Miller Fisher syndrome (see below) can be ship has not been proven.3,6 difficult. Mental state changes, cerebrospinal fluid pleocy- Postinfectious cerebellitis presents with the explosive tosis, and abnormal electroencephalography (EEG) are onset of gait abnormalities, ranging in severity from unsteadi- more common in brainstem encephalitis, whereas areflexia ness and a wide-based stance to complete inability to walk. is usually present in Miller Fisher syndrome. Symptoms are maximal at onset and may be more severe in Systemic infections not directly involving the cerebel- cases following varicella infection.3 The extremities are less lum or other parts of the central nervous system can also affected than the trunk. Associated findings can include trun- cause ataxia, the pathophysiology of which is poorly under- cal instability, head titubation, intention tremor, dysmetria, stood (see Table 2). and nystagmus. Abnormalities of ocular movement, includ- ing ocular flutter (horizontal) and opsoclonus (multidirec- Toxic Cerebellar Syndromes tional), are occasionally seen. A small minority of patients has In as many as 32.5% of cases, acute childhood ataxia is attrib- associated cranial nerve palsies or long-tract signs.3 Mental utable to drug ingestion.1 Cerebellar symptomatology com- status is normal. “Pure” acute cerebellar ataxia is not asso- monly follows ingestion of anticonvulsants, benzodiazepines, ciated with fever, seizures, or other systemic upset. alcohol, and antihistamines. Less often, ataxia develops after exposure to organic chemicals and heavy metals. Acute Postinfectious Demyelinating Encephalomyelitis Accidental poisoning in children aged less than 6 years Ataxia is a common feature of acute postinfectious demyeli- is the most common form of toxic ingestion. There is a sec- nating encephalopathy, a multifocal immune-mediated ond peak in adolescence, when intoxication occurs as a encephalomyelopathy. Acute postinfectious demyelinating result of substance abuse.1 A high index of suspicion should encephalopathy also develops during the recovery phase always be maintained as a history of ingestion or exposure from viral illness or vaccination7,8 but is distinguished from might not be forthcoming. After ingestion, ataxia is often acute cerebellar ataxia by alteration of consciousness or the accompanied by mental status changes such as lethargy, con- fulminant onset of multifocal neurologic deficits. Seizures fusion, inappropriate speech, or behavior. Nystagmus can are common, as are cranial neuropathies, , and be present. transverse myelitis.7–10 Systemic symptoms such as fever, headache, and meningism can be seen.8,9 Repeated episodes Mass Lesions of demyelination raise concern as to multiple sclerosis, Forty-five to sixty percent of all childhood brain tumors arise which occasionally presents in childhood with ataxia aris- in the brain stem or cerebellum.15 Posterior fossa tumors ing from lesions within the cerebellum or its major con- usually present with slowly progressive ataxia and symp- nections. Associated findings include optic neuritis and toms of increased intracranial pressure. Acute decompen- long-tract signs.11 sation can be related to the development of hydrocephalus or, less commonly, hemorrhage into the lesion. Other clin- Brainstem Encephalitis ical features can include headache, personality change, Brainstem encephalitis can involve the inflow and outflow and focal abnormalities on neurologic examination (eg, tracts of the cerebellum, resulting in ataxia in association papilledema, cranial nerve palsies, and hemiparesis). A with cranial neuropathies, hemiparesis, and respiratory minority of supratentorial tumors produce ataxia, usually irregularities. Causative agents include Epstein-Barr virus,12 those in the midline. Parenchymal lesions of the frontal Listeria monocytogenes,13 and, in recent epidemics, lobes can cause ataxia owing to involvement of fronto- enterovirus type 71.14 Differentiation between brainstem cerebellar associative fibers.16 312 Journal of Child Neurology / Volume 18, Number 5, May 2003

Hydrocephalus Sensory Ataxia Ataxia arising from acute hydrocephalus owing to mass Ataxia can result from loss of sensory input to the cerebellum lesions or hemorrhage from vascular lesions (such as arte- owing to lesions in the posterior column of the spinal cord, riovenous malformations) is usually accompanied by other spinal nerve roots, or peripheral nerves. Sensory ataxias are symptoms such as headache and vomiting. Clinical signs can characterized by a positive Romberg’s sign and decreased include papilledema and of lateral gaze. deep tendon reflexes. Loss of posterior column sensory functions ( and vibration sense) causes Trauma pseudoathetosis of the hands and a wide-based, “steppage” Head injuries sometimes cause ataxia owing to cerebellar gait. These findings worsen with the eyes closed. contusion or hemorrhage or because of extraparenchymal Sensory ataxia is present in as many as 15% of pediatric posterior fossa hematoma. Occasionally, ataxia accompa- cases of Guillain-Barré syndrome, usually in association with nies concussion. In younger children with postconcussive neuropathic weakness (which can initially be relatively sub- syndromes, gait unsteadiness is more marked than nystag- tle) and pain.1,31 Pure sensory postinfectious neuropathies mus or appendicular dysmetria; older children also complain have also been reported in childhood.32 The Miller Fisher of headache and dizziness.17 Magnetic resonance imaging variant of Guillain-Barré syndrome commonly follows 5 to 10 scans can be normal or demonstrate foci of high signal on days after an infectious illness (often Campylobacter gas-

T2-weighted sequences, lesions that are felt to demonstrate troenteritis) and is defined by the triad of ataxia, areflexia, and areas of diffuse axonal injury.18 After neck injuries, ataxia ophthalmoplegia.33 Vertical gaze is most commonly affected, can be a pointer to vertebral artery dissection. horizontal gaze usually being preserved, although nystagmus of the abducting eye is often present. Ptosis can develop, Stroke pupillary abnormalities and facial weakness are not uncom- Posterior circulation are rare in young children19 mon, and there can be mild proximal limb weakness.33 Ataxia but should be considered after neck trauma (causing ver- is often more marked in the extremities. This postinfectious tebral artery dissection) or in those predisposed to immune-mediated phenomenon is related to antibodies to thromboembolic disease.20 In such cases, cerebellar deficits the GQ1b myelin ganglioside in more than 90% of cases.34 are often asymmetric and evolve in association with deficits Sensory ataxia can also be seen with acute postinfec- attributable to brainstem ischemia. Cerebellar hemorrhage tious demyelinating encephalopathy or multiple sclerosis, is rare in childhood and, in the absence of a bleeding other forms of sensory ataxia usually presenting less acutely. diathesis, is most commonly associated with arteriovenous malformations.21 Motor (Paretic) Ataxia Weakness from focal cerebral (commonly frontal or pari- Paraneoplastic Cerebellar Syndromes etal)16 or corticospinal tract lesions can present with a Acute ataxia is occasionally associated with rapid chaotic “paretic” ataxia, possibly associated with sensory loss, multidirectional conjugate eye movements (opsoclonus); altered deep tendon reflexes, and impaired sphincter con- myoclonic jerks of the extremities, head, trunk, and face; trol. Ataxia is proportional to the degree of weakness. More and encephalopathy in opsoclonus-myoclonus syndrome. peripherally, weakness, presenting as ataxia, can develop in This develops as a postviral phenomenon in a minority of Guillain-Barré syndrome and with tick paralysis.35 cases.22–24 In at least 50% of children, however, opsoclonus- myoclonus syndrome is the presenting manifestation of an Other Neurologic Disorders occult neuroblastoma or ganglioneuroblastoma, usually Ataxia is common in basilar migraine, in which it can be asso- sited in the mediastinum or abdomen, in which case ataxia ciated with vertigo, hemiparesis and cranial nerve dys- is thought to arise as a paraneoplastic autoimmune phe- function, nausea, vomiting, and headache.36 The initial nomenon involving cross-reactivity of tumor and cerebel- episode should cause concern as to a focal (vascular or lar antigens.25,26 other) lesion, although description of positive visual phe- Opsoclonus-myoclonus syndrome is seen in young chil- nomena—commonly blobs or flashes of light rather than dren (6 months to 3 years), with a trend to earlier onset in well-defined fortification spectra—suggest the migrainous infants with occult neoplasms.25 There can be associated nature of the episode. Subsequent episodes are often stereo- extreme irritability and recurrent vomiting.22,25 Opsoclonus typed and respond to standard migraine therapies.36 can be temporally distinct from myoclonus and can be fleet- Ataxia can be prominent during the ictal or postictal ing. It is accentuated by agitation and visual saccades and phases of seizures. Nonconvulsive seizures can also mani- persists during sleep. Ataxia in this disorder can be of sub- fest with ataxia with or without alteration of consciousness acute onset and can fluctuate. Isolated ataxia, without in the absence of clonic movements but possibly with minor abnormal eye movements or myoclonus, has also been myoclonus and atonic episodes.37 Nonconvulsive seizures reported as the presenting sign of neuroblastoma.25, 27 are more common in children with cognitive impairment and Ataxia has also been described as a paraneoplastic preexisting mixed seizure disorders. phenomenon in isolated pediatric cases of Hodgkin’s disease, Many inborn errors of metabolism can present with Langerhans’ cell histiocytosis, and hepatoblastoma.28–30 ataxia (Table 3), which could develop acutely or intermittently Acute Ataxia in Childhood / Ryan and Engle 313

Table 3. Causes of Episodic or Intermittent Ataxia in Childhood aim of laboratory and radiologic investigations in children Recurrence of acute cerebellar ataxia* with acute ataxia is identification of serious conditions Migraine or migraine equivalents mimicking postviral cerebellitis. In practice, a thorough Basilar migraine* history and physical examination are far more likely to Benign paroxysmal vertigo* Benign paroxysmal torticollis of infancy identify the etiology of acute ataxia than is a battery of Alternating hemiplegia of childhood “screening” investigations. Metabolic disorders Of all investigations performed in the diagnostic work- Mitochondrial disorders up of acute cerebellar ataxia, the urine and/or serum drug Pyruvate decarboxylase deficiency Pyruvate dehydrogenase deficiency screen are most likely to prove diagnostic, even where a Leigh disease source of ingestion is not immediately apparent.1 Drug lev- Amino acidopathies els should be determined where a specific intoxicant is Maple syrup urine disease, intermittent form Hartnup disease identified. -Glutamylcysteine synthetase deficiency Neuroimaging is often obtained in the emergency room Urea cycle disorders to exclude a mass lesion. In the absence of altered con- Carbamoyl phosphate synthetase type 1 deficiency Ornithine transcarbamylase deficiency sciousness, focal neurologic signs, or marked asymmetry of Citrullinemia ataxia, the yield of such scans is low. Computed tomogra- Arginosuccinic aciduria phy (CT) and magnetic resonance imaging (MRI) of the Organic acidopathies Holocarboxylase deficiency brain are normal in most children with postinfectious Biotinidase deficiency ataxia.1,3 Lesions suggestive of focal cerebellar or cerebel- Isovaleric acidemia lopontine demyelination are occasionally identified.5,38,39 Carnitine acetyltransferase deficiency Very rarely, cerebellitis is acutely complicated by obstruc- Recurrent genetic ataxias Episodic ataxia type 1 (paroxysmal ataxia with tive hydrocephalus, necessitating urgent posterior fossa myokymia) decompression.40,41 Episodic ataxia type 2 (acetazolamide responsive) CT scans are often normal in acute postinfectious Episodic ataxia types 3 and 4 9 Episodic ataxia with paroxysmal dystonia demyelinating encephalopathy, although acutely useful to CAPOS syndrome (cerebellar ataxia, areflexia, exclude mass effect, which can contraindicate lumbar punc- pes cavus, optic atrophy, sensorineural ture. MRI in acute postinfectious demyelinating encephalo- hearing loss) pathy demonstrates multiple asymmetrically located foci of Nonconvulsive seizures demyelination within the cerebral white matter and deep Drug ingestion* gray nuclei.7–10 Acute lesions often enhance after adminis- Paroxysmal tonic upgaze of childhood tration of gadolinium contrast, reflecting local breakdown Cogan’s syndrome of the blood–brain barrier.8–10 Brainstem encephalitis is *Most common. associated with areas of increased signal intensity within the 14 brain stem and cerebral peduncles on T2-weighted MRIs. because of decompensation triggered by dietary intake or Neuroimaging is usually normal at presentation of opso- intercurrent illness. The first presentation of such disorders clonus-myoclonus syndrome.25,27, 42 Variable degrees of cere- in childhood can mimic acute cerebellar ataxia. Detailed dis- bellar atrophy can be seen on follow-up imaging, independent cussion of these conditions is beyond the scope of this of corticosteroid therapy and of neurobehavioral outcome.43 review, but they should be suspected where there is coex- Posterior fossa tumors and strokes can be difficult to visu- isting developmental delay, a family history of similarly alize on CT scans, where artefacts sometimes obscure sub- affected relatives or of consanguinity, or where ataxia is tle hypodensities within the brain stem and cerebellum. accompanied by significant lethargy, overt encephalopa- MRI (with diffusion-weighted imaging where acute ischemia thy, excessive vomiting and diarrhea, or unusual body odor. is suspected) is the imaging modality of choice for such lesions. Functional Ataxia Cerebrospinal fluid examination is commonly normal Hysterical gait disorders are not uncommon, especially in in postinfectious acute cerebellar ataxia and acute postin- female adolescents. In such cases, although the patient fectious demyelinating encephalopathy, with mild pleocy- lurches and appears to stagger, the gait is often not wide tosis and elevation of cerebrospinal fluid protein being based, and falls are rare. Clinical signs are inconsistent present in 26 to 50% of cases.1,3,8,25 In postinfectious ataxia, and often fail to conform to recognized neuroanatomic identification of mild cerebrospinal fluid lymphocytosis distributions. provides evidence of an inflammatory process. Significant pleocytosis and elevation of cerebrospinal fluid protein, INVESTIGATION OF ACUTE ATAXIA IN with or without hypoglycorrachia, suggest meningitis or CHILDHOOD encephalitis and should prompt further investigation. A mild lymphocytic pleocytosis is identified in fewer than Acute postinfectious cerebellar ataxia, an essentially benign 20% of cases of opsoclonus-myoclonus syndrome and does clinical syndrome, is a diagnosis of exclusion. The primary not predict etiology.24,27,42,43 Cerebrospinal fluid examina- 314 Journal of Child Neurology / Volume 18, Number 5, May 2003 tion can demonstrate cytoalbuminologic dissociation in TREATMENT AND PROGNOSIS OF ACUTE ATAXIA Guillain-Barré and Miller Fisher syndromes, but the cere- IN CHILDHOOD brospinal fluid protein is normal in as many as 20% of chil- dren within a week of onset of Guillain-Barré syndrome.44 Most children with acute cerebellar ataxia recover com- Assays for the anti-GQ1b antibody should be obtained if pletely. Improvement usually begins within a week of symp- Miller Fisher syndrome is suspected.34 Oligoclonal bands and tom onset. Recovery is full within 3 months of onset in at elevation of the serum:cerebrospinal fluid immunoglobulin least 50% of children45 but remains incomplete in a minor- index and myelin basic protein level can be present in acute ity of cases. cerebellar ataxia, acute postinfectious demyelinating In the first major review of outcome in acute cerebel- encephalopathy, and multiple sclerosis7 and do not differ- lar ataxia, 6 of 18 children were felt to have permanent entiate between these disorders. These investigations are neurologic sequelae in the form of persistent gait distur- therefore not generally indicated at the initial presentation bance, ataxia, and delayed speech development.45 More of acute ataxia. recently, Connolly and associates reported a series of 73 chil- EEG is indicated in those with altered consciousness and dren treated in St. Louis between 1967 and 1989. Fifty-five fluctuating clinical signs. Epileptiform discharges or slow- of 60 children (91%) for whom 4-month outcome data were ing is seen on EEG in as many as two thirds of children with available recovered completely, including all 16 children acute cerebellar ataxia45 and is even more frequently abnor- with postvaricella cerebellitis. Recurrences occurred in mal in acute postinfectious demyelinating encephalopa- four patients, usually after a second viral infection. The thy.8,10 EEG is normal in opsoclonus-myoclonus syndrome.42 only clinical feature distinguishing children with recur- With nonconvulsive seizures, EEG commonly reveals gen- rences from those with a monophasic illness was a longer eralized spike-wave complexes (spike-wave stupor).37 latency between the prodrome and development of the ini- Electromyography is indicated where sensory ataxia is tial attack of ataxia. Behavioral or learning difficulties were suspected. In Guillain-Barré syndrome, diagnostic abnor- present in 20% of children during the recovery phase from malities can be identified on neurophysiologic examina- acute cerebellar ataxia but resolved in most within 6 months.3 tion in over 90% of children within a week of symptom There is no evidence that immunosuppressive therapies onset.31 In Miller Fisher syndrome, electromyography is improve outcome in acute cerebellar ataxia. less frequently diagnostic but might demonstrate abnor- Foci of demyelination seen on acute MRI in childhood mal sensory potentials and delayed late responses.46 acute cerebellar ataxia can resolve completely,52 can persist,53 A number of further investigations should be under- or can evolve into cerebellar atrophy.54 Most patients make taken on suspicion of neuroblastoma. Urinary excretion of full recoveries even in the face of persisting neuroradiologic catecholamine metabolites is increased in only 47 to 60% of abnormalities.53 patients with paraneoplastic opsoclonus-myoclonus syn- Recovery from acute postinfectious demyelinating drome,47,48 in comparison with children with uncomplicated encephalopathy is typically somewhat slower than that from neuroblastoma (> 95%).48 Identification of small tumors acute cerebellar ataxia and can be hastened by treatment with could require CT or MRI of the chest and abdomen or scintig- corticosteroids.8 Although most patients recover completely, raphy with I123 metaiodobenzylguanidine scanning. Whole- a minority have significant sequelae.7–10 Single relapses can body metaiodobenzylguanidine scintigraphy has been shown occur in as many as 10% of affected children,8 multiple to have a sensitivity of 95% and a specificity of 100% for the relapses raise the possibility of multiple sclerosis. identification of neuroblastomas overall, but its ability to iden- Brainstem encephalitis should be treated with broad- tify tumors associated with the opsoclonus-myoclonus syn- spectrum antibiotics (including coverage for Listeria mono- drome has not specifically been studied.49 Newer imaging cytogenes) and acyclovir, pending identification of a techniques could increase the proportion of cases of opso- causative organism, but is commonly complicated by sig- clonus-myoclonus syndrome, which can be demonstrated to nificant neurologic sequelae in surviving patients.12–14 be paraneoplastic in origin, but a proportion of neuroblas- Treatment of ingestions depends on the nature and tomas undergo spontaneous involution and might not be amount of the ingested substance. Often no specific treat- identifiable even after extensive investigation.50,51 ment is available. In some cases, administration of an anti- Investigations indicated for work-up of a possible inborn dote, chelation, dialysis, or other therapies are required. error of metabolism include a complete blood count and liver Outcome in most other conditions associated with function tests; determination of blood ammonia, lactate, acute ataxia in childhood is dependent on the underlying dis- pyruvate, and ketone levels; and assessment of acid-base sta- ease process. Tumors, stroke, and are tus by blood gas determination. Additional screening tests commonly complicated by significant sequelae. possibly indicated include plasma and urinary amino acid Neuroblastoma, if found, should be removed surgically. assays, urine organic acids, serum biotinidase level, and cere- The underlying tumor is small and well differentiated in most brospinal fluid lactate and pyruvate assays. With the first pre- cases of paraneoplastic opsoclonus-myoclonus syndrome.25,27 sentation of acute ataxia and in the absence of developmental Systemic chemotherapy is not usually required. The neurologic delay, similar previous episodes, or a positive family history, syndrome of opsoclonus-myoclonus syndrome can remit par- such investigations are unlikely to be contributory.1 tially or completely over time but does not generally respond Acute Ataxia in Childhood / Ryan and Engle 315

to removal of the causative tumor. A majority of children with 14. Huang CC, Liu CC, Chang YC, et al: Neurologic complications in opsoclonus-myoclonus syndrome have long-term neurologic children with enterovirus 71 infection. N Engl J Med 1999; 341:936–942. deficits related to persistence of their movement disorder or 27,43,55 15. Pollack IF: Brain tumors in children. N Engl J Med 1994; to cognitive and behavioral problems. Some response 331:1500–1507. might be seen to treatment with high-dose corticosteroids or 16. Freund H-J: Differential effects of cortical lesions in humans. intravenous immunoglobulin.27,43,55 There is inconclusive evi- Ciba Foundation Symposium 1987;132:269–281. dence that neurologic outcome can be improved in children 17. Katz DI, Alexander MP: Traumatic brain injury, in Good DC, receiving chemotherapy for their neuroblastoma.43 Couch JR (eds): Handbook of Neurorehabilitation. New York, Children with Guillain-Barré and Miller Fisher syn- Marcel Dekker, 1994, 493–549. dromes should be admitted to hospital, with careful moni- 18. Snow RB, Zimmerman RD, Gandy SE, Deck MDF: Comparison of magnetic resonance imaging and computed tomography in the toring of their respiratory and autonomic function, until evaluation of . Neurosurgery 1986;18:45–52. their clinical nadir is reached.56 Pain is common in childhood 19. Echenne B, Gras M, Astruc J, et al: Vertebro-basilar arterial occlu- Guillain-Barré syndrome and should be treated aggres- sion in childhood—Report of a case and review of the literature. sively.31,44 Specific treatments for Guillain-Barré and Miller Brain Dev 1983;5:577–581. Fisher syndromes include intravenous immunoglobulin and 20. Garg BP, Ottinger CJ, Smith RR, Fishman MA: Strokes in children plasmapheresis, which are presumed to act by reducing due to vertebral artery trauma. 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