Acute cerebellar ataxia in children

INTRODUCTION — Acute cerebellar ataxia is a syndrome that occurs in previously well children, often presenting as a postinfectious disorder [1-5]. The pathogenesis, clinical presentation, evaluation, and prognosis of acute cerebellar ataxia will be reviewed here. The differential diagnosis and evaluation of children presenting with acute ataxia, as well as diagnostic considerations in adults with ataxia, are discussed separately. (See "Approach to the child with acute ataxia" and "Overview of cerebellar ataxia in adults".)

EPIDEMIOLOGY — Acute cerebellar ataxia accounts for 35 to 60 percent of all cases of pediatric ataxia and usually occurs in children under six years of age, although older children and adolescents can also be affected [1,5,6]. The incidence of this disorder in the pediatric age group is at least 1 in 100,000 to 500,000, making it the most common cause of ataxia in children [2,7].

PATHOGENESIS — Acute cerebellar ataxia usually occurs after an acute febrile illness, though it may occur unheralded [5,8]. Varicella infection-induced cases, once the most common single postinfectious cause, has diminished due to vaccination [7,9]. (See "Clinical features of varicella-zoster virus infection: Chickenpox", section on 'Neurologic complications'.)

Numerous other infectious agents have been implicated in the pathogenesis of acute cerebellar ataxia, including coxsackievirus, echovirus, enteroviruses, Epstein-Barr virus, hepatitis A, herpes simplex virus I, human herpesvirus 6, measles, mumps, parvovirus B19, Borrelia burgdorferi (Lyme disease), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), malaria, Mycoplasma pneumoniae, and typhoid fever [10-15]. The syndrome has been anecdotally reported following vaccination for varicella, hepatitis B, rabies, meningococcal group C, and human papillomavirus, all without evidence of systemic infection [1,16-19]. However, rates after vaccination are much lower than in association with infection: For example, the association of acute cerebellar ataxia with varicella infection is at least 35 times higher than after vaccination [7].

The pathogenic mechanisms that underlie acute cerebellar ataxia have not been definitively established but are believed to be autoimmune [1]. Antiviral antibodies and autoantibodies against centrosomes, glutamate receptor delta 2, myelin-associated glycoprotein, neurons, and triosephosphate isomerase have been isolated from serum and/or cerebrospinal fluid (CSF) in affected patients [1,11,20-23]. However, in other case reports, viral nucleic acids have been identified in the CSF, suggesting that infection of brain tissue may contribute.

Radiologic studies in patients with recent onset of acute cerebellar ataxia generally are normal; if lesions are seen, they are usually limited to the cerebellum [1,9].

CLINICAL PRESENTATION — Acute cerebellar ataxia typically occurs in children under six years of age, although older children and adolescents can also be affected. It is characterized by rapid onset and progression of symptoms, typically developing over a few hours to one or two days. In cases associated with a prodromal illness, the ataxia typically follows it within days to three weeks [1-5]. Gait disturbance is the primary symptom in most patients, but in other patients, the cerebellar dysfunction may be limited to fine motor control problems or tremor [1,9].

Associated symptoms may include nystagmus (present in approximately one-half of cases reported), slurred or garbled speech, vomiting, irritability, dysarthria, or, in older children, headache. Fever, meningismus, and seizures are absent [2,3].

EVALUATION — Acute cerebellar ataxia should be suspected in a child presenting with the sudden onset of ataxia. The evaluation is directed toward exclusion of other potentially more serious illnesses [2]. (See 'Differential diagnosis' below.)

History — The history should explore the nature of any neurologic symptoms and timing of their onset, including whether there have been any chronic or episodic neurologic symptoms in the past. In children with acute cerebellar ataxia, the degree of ataxia and gait disturbance varies widely but generally has rapid onset. Mild acute manifestations may be overlooked by caregivers (leading to underreporting of the syndrome), but symptoms can be sufficiently severe to lead to an emergency department visit. By contrast, mild chronic manifestations may also be overlooked, leading to underrecognition of the slow evolution of a more ominous chronic condition.

Physical examination — Cerebellar signs in acute cerebellar ataxia include abnormalities in gait (gait ataxia), speech, eye movements, and coordination of voluntary movement.

The range of findings includes the following (see "Approach to the child with acute ataxia"):

●The gait is typically wide based, unsteady, lurching, or staggering.

●Speech abnormalities such as fluctuations in clarity, rhythm/fluency, tone, and volume may occur.

●Posture while sitting unsupported may be difficult to maintain, with corrections and oscillations (titubation).

●Coordination and targeting of voluntary movements may be impaired, as seen on finger-nose testing (dysmetria) and during rapid alternating movements (dysdiadochokinesia).

●Hypotonia, action tremor, and end-gaze nystagmus may also occur.

The neurologic evaluation of a child with acute ataxia and the general neurologic examination in children are described in detail separately. (See "Approach to the child with acute ataxia", section on 'Neurologic examination' and "Detailed neurologic assessment of infants and children".)

Features suggestive of other diagnoses — When evaluating a child with suspected acute cerebellar ataxia, it is important to look for findings that may point to another more serious condition.

Features that should raise concern for other illnesses in the differential diagnosis include [2] (see 'Differential diagnosis' below):

●Altered consciousness/somnolence

●Extreme irritability

●Unremitting headaches

●Fever

●Seizures

●Meningismus

●Opsoclonus

●Multifocal myoclonus

●Acquired ocular malalignment

●Weakness

●Focal or asymmetric neurologic findings

●Abnormal reflexes

●Sensory loss

●Insidious onset of ataxia

●Recent history of trauma, unusual bruising pattern, or other findings raising concern for inflicted injury

Laboratory evaluation — The diagnostic evaluation for children presenting with ataxia should include toxicology screening, including blood alcohol level [24]. Other laboratory tests are appropriate in selected children, depending on the presenting symptoms:

●Children with opsoclonus or myoclonus should have abdominal imaging performed to look for neuroblastoma, which in this condition can be very small. (See "Clinical presentation, diagnosis, and staging evaluation of neuroblastoma".)

●Children with fever, meningismus, seizures, or altered mental status should undergo lumbar puncture to exclude possible central nervous system infection (meningitis, encephalitis, or acute cerebellitis). In the absence of such findings, cerebrospinal fluid (CSF) examination is usually not necessary [24]. (See "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Lumbar puncture' and "Acute viral encephalitis in children: Clinical manifestations and diagnosis", section on 'Cerebrospinal fluid analysis'.)

Among children with acute cerebellar ataxia who undergo lumbar puncture, the CSF can be normal or it may show mild lymphocytic pleocytosis with elevated protein (seen in approximately 25 to 50 percent of cases) [1]. Other CSF abnormalities may include increased CSF immunoglobulin G (IgG) index (seen in approximately 50 percent of cases) and/or oligoclonal bands (10 to 17 percent of cases) [1]. These findings are nonspecific. One study identified neuron-specific enolase levels in the CSF as a possible prognostic marker, although further studies are necessary to verify this finding [25].

Neuroimaging — Neuroimaging is not necessary in all cases of acute cerebellar ataxia. Close clinical follow-up without imaging is reasonable for children with highly suggestive clinical features.

Neuroimaging is indicated in patients with atypical features, including any of the following [26]:

●Altered consciousness

●Asymmetric focal weakness, sensory loss, or hyperreflexia on examination

●Acquired ocular malalignment

●Atypical disease course (previous episodes of ataxia, worsening ataxia, additional neurologic symptoms/signs, etc)

●New unremitting headache and vomiting, particularly if worse with lying flat or with Valsalva and improved with vomiting

●When there is concern for the possibility of head or neck trauma

In the absence of these findings, the yield of neuroimaging is low [4,5,24].

When neuroimaging is performed, magnetic resonance imaging is vastly superior to computed tomography, both because of the information gained and the avoidance of radiation exposure. In patients with acute cerebellar ataxia, magnetic resonance imaging may reveal bilateral diffuse abnormalities of the cerebellar hemispheres, which are not pathognomonic and probably have no prognostic value [19,27]. Computed tomography is of limited value, given the difficulty of imaging the posterior fossa with this modality; when obtained, it is most often normal [1,9,24].

DIAGNOSIS — The diagnosis of acute cerebellar ataxia is made clinically after excluding other potentially more serious illnesses, which are reviewed below. (See 'Differential diagnosis' below.)

Features that help establish the diagnosis are [26]:

●Rapid onset of symptoms.

●History of a prodromal illness during the previous two to three weeks.

●Absence of signs or symptoms that might suggest an alternative diagnosis (eg, altered consciousness, somnolence, extreme irritability, unremitting headaches, fever, seizures, meningismus, opsoclonus, multifocal myoclonus, acquired ocular malalignment, weakness, focal or asymmetric neurologic findings, abnormal reflexes, sensory loss, recent history of trauma, or concern for inflicted injury). (See 'Features suggestive of other diagnoses' above.)

In most cases with typical presenting symptoms, the diagnosis can be made with a focused history, detailed general and neurologic examination, and toxicology screen (algorithm 1). In patients with atypical presenting features or findings, more extensive evaluation may be required, including neuroimaging and/or lumbar puncture.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis includes the following categories (table 1) [1-3]:

●Toxic ingestions – Toxic ingestions are the second most common cause of acute ataxia in childhood. Ataxia can be seen with ingestion of alcohol, benzodiazepines, or other antiseizure medications or exposure to environmental toxins such as mercury or lead. In most cases, there are additional findings that suggest occult ingestion (eg, depressed consciousness). A thorough history may identify potential exposure to intoxicating agents. Ultimately, the diagnosis requires toxicology testing. (See "Approach to the child with occult toxic exposure".)

●Infections – Meningitis, encephalitis, and labyrinthitis can manifest with ataxia as presenting symptoms. Fever is a key feature that distinguishes these acute infections from acute cerebellar ataxia. In addition, unlike acute cerebellar ataxia, children with acute central nervous system infections are often ill appearing. Children with fever, meningismus, seizures, or altered mental status should undergo lumbar puncture for examination of the cerebrospinal fluid (CSF) and microbiologic testing, which will distinguish central nervous system infection from acute cerebellar ataxia. (See "Bacterial meningitis in children older than one month: Clinical features and diagnosis" and "Acute viral encephalitis in children: Clinical manifestations and diagnosis".)

●Postinfectious and autoimmune conditions – Postinfectious and autoimmune conditions that can present with acute ataxia include:

•Opsoclonus-myoclonus syndrome (OMS) – Opsoclonus, multifocal myoclonus, and extreme behavioral irritability are characteristic of OMS. It is important to note that opsoclonus may be present transiently and multifocal myoclonus can be difficult to distinguish clinically from truncal titubation, and thus this important diagnosis may be delayed. Clinicians should always be vigilant for the possibility of this diagnosis when making a diagnosis of acute cerebellar ataxia. Approximately one-half of children with OMS have underlying neuroblastoma. OMS is a clinical diagnosis, and there is no specific test that confirms the diagnosis. However, children with concerning findings should undergo neuroimaging and evaluation for neuroblastoma, as discussed separately. (See "Opsoclonus-myoclonus-ataxia syndrome", section on 'Pediatric syndrome' and "Clinical presentation, diagnosis, and staging evaluation of neuroblastoma".)

•Acute cerebellitis – Acute cerebellitis is a rare postinfectious condition sometimes included under the heading of acute cerebellar ataxia; however, it has distinctive clinical and imaging features [28-30]. It can occur following a variety of infections, including SARS-CoV-2 [31]. (See "COVID-19: Neurologic complications and management of neurologic conditions", section on 'Other acute neurologic manifestations'.)

Altered mental status and cerebellar abnormalities on brain magnetic resonance imaging, particularly leptomeningeal enhancement and/or diffuse bihemispheric signal change or swelling, are the key elements that distinguish acute cerebellitis from acute cerebellar ataxia [27,28].

Treatment is the same as that for acute disseminated encephalomyelitis (ADEM) and typically consists of high-dose glucocorticoids and close monitoring. Patients are at risk for malignant cerebellar edema and obstructive hydrocephalus requiring urgent measures to lower intracranial pressure that may include osmotic therapy, temporary CSF diversion, and rarely decompressive craniectomy. (See "Acute disseminated encephalomyelitis (ADEM) in children: Treatment and prognosis", section on 'Management of malignant edema'.)

•Acute disseminated encephalomyelitis – ADEM (also known as postinfectious encephalomyelitis) is a demyelinating disease that typically presents with multifocal neurologic symptoms and encephalopathy. Affected children often have somnolence, weakness, and focal abnormalities on neurologic examination. If such features are present, neuroimaging and lumbar puncture should be performed, which will distinguish ADEM from acute cerebellar ataxia. (See "Acute disseminated encephalomyelitis (ADEM) in children: Pathogenesis, clinical features, and diagnosis".)

•Autoimmune encephalitis – The autoimmune encephalitis syndromes, of which anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is the best characterized, have a wide clinical spectrum. While ataxia and abnormal movements can occur in these syndromes, most affected patients have other accompanying symptoms, particularly psychiatric and behavioral manifestations and seizures, which are generally not present in acute cerebellar ataxia. (See "Autoimmune (including paraneoplastic) encephalitis: Clinical features and diagnosis".)

•Guillain-Barré syndrome (GBS) – GBS most commonly presents as subacute ascending weakness, though there are a number of variant forms with ataxia. Sensory abnormalities (eg, paresthesias, loss of peripheral sensation) and loss of reflexes are key features that distinguish GBS from acute cerebellar ataxia. (See "Guillain-Barré syndrome in children: Epidemiology, clinical features, and diagnosis".)

●Structural abnormalities – Structural causes of ataxia typically present with associated focal neurologic findings. Neuroimaging can distinguish these from acute cerebellar ataxia. Structural lesions that can cause ataxia in children include the following:

•Traumatic brain injury (see "Child abuse: Evaluation and diagnosis of abusive head trauma in infants and children" and "Severe traumatic brain injury (TBI) in children: Initial evaluation and management")

•Posterior fossa tumor (see "Clinical manifestations and diagnosis of central nervous system tumors in children")

•Stroke (see "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis")

●Metabolic and neurodegenerative diseases – Metabolic disorders such as maple syrup urine disease (branched-chain amino aciduria), Hartnup disease, hyperammonemia, biotinidase deficiency, mitochondrial disorders, and pyruvate dehydrogenase complex deficiency can present with acute bouts of ataxia. However, these disorders generally have a more chronic or recurrent course, which usually can be elicited with a detailed history. (See "Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features" and "Overview of the hereditary ataxias".)

A stepwise diagnostic approach to the child with acute ataxia is described separately. (See "Approach to the child with acute ataxia".)

TREATMENT AND MONITORING — Treatment for acute cerebellar ataxia is supportive. Children should be clinically reevaluated two to three weeks after the initial presentation. If the symptoms persist or worsen, or if new symptoms appear (eg, focal neurologic deficits, opsoclonus, myoclonus), the patient should be further evaluated for other causes of ataxia. (See 'Laboratory evaluation' above and 'Neuroimaging' above.)

There are scattered case reports of treatment of refractory cases with glucocorticoids [32] or intravenous immune globulin [14,33,34]. Prospective clinical trials are lacking. When such therapy has been provided, a beneficial response has been noted anecdotally within days.

Based on the limited available evidence, treatment with antiviral medications does not appear to alter disease course or outcome [35]. This is consistent with the hypothesis that the illness represents a postinfectious autoimmune process rather than acute infection. (See 'Pathogenesis' above.)

PROGNOSIS — Acute cerebellar ataxia typically resolves without sequelae within two to three weeks of presentation, with a median duration of symptoms between 10 and 12 days [1,4,5]. Rarely, symptoms persist for several weeks without improvement [1]. If worsening of symptoms or relapse occurs, the diagnosis should be reconsidered and other causes of ataxia carefully excluded. (See 'Differential diagnosis' above and "Approach to the child with acute ataxia".)

Up to 10 percent of children with acute cerebellar ataxia may have some long-term neurologic sequelae [1]. Older age at diagnosis and associated Epstein-Barr virus infection (which, coincidentally, is more common in older patients as compared with younger patients) appear to confer a worse prognosis [1].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)

●Basics topic (see "Patient education: Acute cerebellar ataxia in children (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Acute cerebellar ataxia is a clinical syndrome characterized by the sudden onset of ataxia, usually manifested as gait disturbance. Associated symptoms may include nystagmus, slurred or garbled speech, vomiting, irritability, dysarthria, or headache. Fever, meningismus, and seizures are absent. Most cases occur in toddlers or school-aged children; in many cases, the symptoms develop a few days or weeks after a viral illness. (See 'Pathogenesis' above and 'Clinical presentation' above.)

●Acute cerebellar ataxia should be suspected in a child presenting with the sudden onset of ataxia, especially if there was an associated prodromal illness within the previous few weeks. The evaluation is aimed at excluding other causes of acute ataxia including toxic ingestion, head trauma, and infections or structural lesions of the brain. Ataxia may also be caused by metabolic, oncologic, or neurodegenerative processes, which often have gradual or intermittent onset of symptoms (table 1). (See 'Evaluation' above and 'Differential diagnosis' above and "Approach to the child with acute ataxia".)

●The history should include questions about antecedent illness, prior vaccinations, head trauma, potential exposure to intoxicating agents, and whether there have been any chronic or episodic neurologic symptoms in the past. The physical examination should assess for unusual signs such as fever, altered mental status, asymmetric and/or focal neurologic deficits, weakness, or areflexia. Any of these findings should raise concern for other illnesses in the differential diagnosis. (See 'History' above and 'Physical examination' above.)

●Cerebrospinal fluid (CSF) should be obtained whenever unusual features such as fever, meningismus, loss of reflexes, weakness, or altered mental status raise concern for central nervous system infection or Guillain-Barré syndrome (GBS). CSF analysis in acute cerebellar ataxia is typically normal or shows a mild lymphocytic pleocytosis, with or without elevations in protein. (See 'Laboratory evaluation' above.)

●Neuroimaging is not necessary for children with typical features; however, brain imaging should be performed if there are atypical findings (eg, altered consciousness, asymmetric focal weakness, sensory loss, abnormal reflexes, acquired ocular malalignment, atypical disease course [eg, previous episodes of ataxia, worsening ataxia, additional neurologic symptoms/signs], new unremitting headache, or recent history of head or neck trauma). When imaging is indicated, magnetic resonance imaging is the preferred method. (See 'Neuroimaging' above.)

●The diagnosis of acute cerebellar ataxia is made clinically after excluding other potentially more serious illnesses. In most cases with typical presenting symptoms, this can be accomplished with a focused history, detailed general and neurologic examination, and toxicology screen (algorithm 1). (See 'Diagnosis' above and 'Differential diagnosis' above.)

●Treatment for acute cerebellar ataxia is supportive. Children should be clinically reevaluated two to three weeks after the initial presentation. If the symptoms persist or worsen, or if new symptoms appear (eg, focal neurologic deficits, opsoclonus, myoclonus), the patient should be further evaluated for other causes of ataxia. (See 'Treatment and monitoring' above.)

●The prognosis for children with typical features of acute cerebellar ataxia is good. Approximately 90 percent of patients have complete resolution of symptoms within a few weeks without specific treatment, while up to 10 percent have some long-term neurologic sequelae. (See 'Prognosis' above.)

ACKNOWLEDGMENTS — The editorial staff at UpToDate acknowledge Steve Maricich, PhD, MD, and Mark Helm, MD, who contributed to an earlier version of this topic review.