Clinical manifestations

Presentation and course

Acute cerebellar ataxia is a clinical syndrome defined by the rapid onset of cerebellar dysfunction, most commonly manifesting as ataxic gait and incoordination. Although gait ataxia is the most prominent sign (92% of patients in some studies) (51), appendicular ataxia and nystagmus may also occur. Truncal ataxia is often seen but is worse during standing than sitting, representing a component of gait ataxia (15). The child will often veer toward the affected side when walking (69). The ataxia appears anywhere from immediately to weeks after the illness, although the latency is most commonly around 10 to 15 days (15; 62; 77). The ataxia is often “explosive” in that the child is often acutely ataxic, although the ataxia may continue to worsen over the first several days and then gradually improve (29). Vomiting, horizontal nystagmus (usually gaze-paretic), and dysarthria may initially occur. Cranial nerve dysfunction and corticospinal tract signs can also be seen (15). Headache, photophobia, and lightheadedness are common (62). Other associated symptoms include somnolence, dizziness, choreoathetosis, diplopia, blurred vision, and head tilt (97). Typically, there are no features of meningitis or encephalopathy, and if these are present, a search for other conditions such as intracranial hemorrhage, meningitis, drug ingestion, and others is warranted (see Differential diagnosis section).

Acute cerebellar ataxia usually occurs in children between 2 and 5 years of age and is rare in adolescents and adults (29; 85), although it has been reported even in children less than 1 year old (56). There is a slight male predominance to acute cerebellar ataxia (28). Postinfectious cerebellar ataxia accounts for 30% to 50% of all acute ataxia in children (80). With widespread international vaccination programs, although varicella remains a common cause (occurring in 1 in 4000 children with varicella and often seen in younger patients), it is likely decreasing. In a cohort of children identified in the Australian Childhood Encephalitis study in a country with very high varicella vaccination rates, none of the 20 individuals had evidence of varicella infection via serological or PCR evaluation (36). Epstein-Barr virus infection and immunizations are the most common causes in older patients (15; 62; 77). All children present with signs of ataxia, including 20% to 50% of patients who cannot walk due to gait instability. Finger dysmetria is seen in two thirds of these children but is strikingly mild compared with gait ataxia (15). Transient behavioral alterations and school difficulties are seen in at least one third of children with acute cerebellar ataxia, although these usually resolve over time (15). Cerebellar mutism has been reported, which evolved into dysphonic and dysarthric speech, suggesting that the mutism is a severe form of cerebellar dysarthria/anarthria (68; 23; 27). A case of cerebellar cognitive affective syndrome was reported in a 12-year-old boy with postinfectious ataxia in 2016. Since that time, a more extensive study evaluating three children with acute postinfectious cerebellar ataxia through a comprehensive neuropsychologic and logopedic assessment revealed that all three patients met the criteria for cerebellar cognitive affective syndrome (28). In addition, the severity of cognitive and affective cerebellar symptoms corresponded with the severity of acute cerebellar ataxia. Symptoms of cerebellar cognitive affective syndrome include disturbances in executive function, personality changes, linguistic difficulties, and visuospatial difficulties (55).

Prognosis and complications

Greater than 90% of children will completely recover from the ataxia, typically within the first few weeks to months after the disease onset (15; 19; 62; 29). Supportive therapy is needed to ensure adequate hydration and safety. One fifth of children experience transient behavioral or intellectual problems, but less than 10% demonstrate sustained learning problems (15). Similar to the motor symptoms of acute cerebellar ataxia, cognitive and affective symptoms remit over time (28). In rare cases without complete recovery, atrophy of the cerebellar hemispheres is seen on repeat imaging (73; 09; 23). This is especially true in cases of acute cerebellitis, and the atrophy can be bilateral in patients who presented initially with hemicerebellitis (97). An unusual, potentially life-threatening complication seen in acute cerebellitis is hydrocephalus and possible cerebellar herniation secondary to cerebellar swelling (see Management section). These patients also had a higher proportion of long-term neurologic sequelae; more than half have been reported to be associated with severe manifestations, and predictors for worse outcomes were more severe initial presentation and length of hospitalization (39).

Clinical vignette

A 4-year-old girl was previously healthy until she developed a varicella infection, with resolution of the skin lesions by 5 days. Several days later, she developed progressive unsteadiness and difficulty walking.

On examination, she was afebrile. There were no signs of meningismus. She was alert and awake. Cranial nerve examination was normal other than some mild horizontal nystagmus occurring throughout all parts of gaze. There was no papilledema. Motor examination showed good strength. There were no sensory deficits, reflexes were present, and plantar responses were down-going. Her gait was wide-based and unsteady, and she needed to hold on to her mother’s hand to walk. There was mild finger-to-nose ataxia as well.

Routine labs and brain MRI were normal. A lumbar puncture showed a mild pleocytosis of 11 white blood cells with normal protein and glucose.

She was diagnosed with acute cerebellar ataxia. One-month follow-up revealed almost complete resolution of her symptoms, although she was still slightly unsteady on complex gait maneuvers. Follow-up at 12 months revealed no residual symptoms and a normal examination.

Biological basis

Etiology and pathogenesis

Acute cerebellar ataxia usually develops days to weeks after an illness. Varicella infection is the most common, although in the age of varicella vaccination, studies have shown a predominance of acute cerebellar ataxia after respiratory illnesses (80). In the largest series (15), 26% of patients had chickenpox, 3% had Epstein-Barr virus infection, 49% had other viral illnesses, 19% had no prodrome, and 3% developed acute cerebellar ataxia after immunizations. Other preceding viral infections previously identified include measles, mumps, herpes simplex virus, coxsackievirus, enterovirus, respiratory syncytial virus, + Coxiella burnetti, human herpes virus, West Nile virus, enteric fever, echovirus, poliovirus, typhoid fever, parvovirus B19, hepatitis A, malaria, adenovirus, influenza, rotavirus, cytomegalovirus, and SARS-CoV2 (15; 22; 60; 26; 97; 64). Other infectious agents documented include M pneumoniae, Streptococcus pneumonia, mycoplasma, Lyme, Salmonella typhi, dengue fever, malaria, scrub typhus, toxoplasmosis, and legionella. Vaccinations can also cause acute cerebellar ataxia, including H1N1 and meningococcal group C (18; 52). However, acute cerebellar ataxia is a diagnosis of exclusion, and other etiologies must be considered, especially if there is no clear prior infection (see Differential diagnosis section).

Two prominent hypotheses exist regarding the pathophysiology of acute cerebellar ataxia (26). The first theory is that there is direct invasion of a pathogen into the CNS that may be due to disruption of the blood-brain barrier during initial infection. However, Emelifeonwu and colleagues argue that a direct invasion hypothesis does not explain the specificity for the cerebellum or the latency often seen between infection and cerebellar symptoms (26). In addition, it is rare for pathogens to be found in CSF analysis of patients with acute cerebellar ataxia. Therefore, the preferred hypothesis is of an immuno-inflammatory process, which many studies have since supported. For example, some reports have identified antineuronal antibodies in the disorder following Epstein-Barr virus and varicella infections (42; 01; 90). Anticentriolar antibodies have been reported after mycoplasma (13). Antibodies directed against centromeres were seen in children with post-varicella ataxia (31). Glutamate receptor delta2 autoantibody has been detected in children who develop chronic cerebellitis (82) and was reported in a patient who developed acute cerebellar ataxia post-EBV infection (58). Antibodies against glutamic acid decarboxylase were reported in a child with acute cerebellar ataxia and mutism who responded to treatment with IVIG (65). These glutamic acid decarboxylase antibodies could be related to diabetes mellitus or thyroid disorders such as Hashimoto encephalopathy, although thyroid disorders in children are rare (69). Homer-3 autoantibodies have been reported in two adult patients with subacute cerebellitis (40). Anti-leucine-rich glioma-inactivated protein (LGI-1) has been detected in children with acute cerebellar ataxia (93). Evidence of inflammation may be detected in cerebrospinal fluid. Viral antibodies and nucleic acids have rarely been isolated from the CSF of patients (77). CSF pleocytosis ranging from 0 to 107/μl occurs in 25% to 50% of children (15). Signs of inflammation based on IgG index and oligoclonal bands can also be seen. The CSF IgG index is elevated in 50% of these children with pleocytosis evaluated by Connolly and colleagues, and oligoclonal bands are present in 10% to 17%. A study demonstrated the positive predictive value of oligoclonal and mirror bands in numerous inflammatory CNS disorders found oligoclonal bands in one of four children with acute cerebellar ataxia (84).

Pathologic studies have been conducted on patients with acute cerebellitis who have required neurosurgical resection or undergone autopsy after fatal cerebellitis. Microscopic examination of a cerebellar biopsy section from a patient with acute near-fatal cerebellar swelling demonstrated intense T-cell infiltration in the molecular layer and marked evacuation at the interface of the molecular and granular layers (04). Neuropathological examination of a child who died from diffuse cerebellar swelling demonstrated leptomeningeal exudates of lymphoplasmacytic and mononuclear cells in the molecular layer (74). Another child with fatal cerebellar swelling showed similar microscopic findings and identified a prominent loss of Purkinje cells, suggesting this may be the target of the inflammatory response (53). This inflammation has been noted to spare the cerebellar white matter (26).

Overall, the data to date demonstrate a postinfectious autoimmune etiology for acute cerebellar ataxia. The fact that immunocompetent, rather than immunocompromised, children more commonly develop acute cerebellar ataxia after varicella infection supports this conclusion (71). Additionally, postinfectious cerebellitis rates are decreasing with widespread vaccination, especially for varicella (91; 21; 80).

Epidemiology

Postinfectious or acute cerebellar ataxia occurs sporadically. Factors that account for increased susceptibility to the development of postinfectious cerebellar ataxia in infected children are unknown. It is estimated that 1 in 4000 children with varicella will develop acute cerebellar ataxia (51). The incidence of acute cerebellar ataxia is estimated at 1:100,000 to 1:500,000 children per year, and it is the most common cause of childhood ataxia, representing approximately 50% to 60% of total cases (26). It accounts for approximately 0.02% of pediatric emergency room visits (32).

Acute cerebellitis is thought to be a small percentage of acute cerebellar ataxia cases, with a meta-analysis estimating that it is 2.5% of acute ataxia in children (26). Larger prospective studies with strict inclusion criteria are needed to determine the true incidence of acute cerebellitis in the general pediatric population.

Prevention

Because postinfectious cerebellar ataxia is the most common etiology of acute ataxia in children, strategies for reducing infection are the mainstay of prevention. In the era of widespread childhood vaccinations including varicella, the incidence of acute cerebellar ataxia is thought to be decreasing, although large studies are still needed (91; 71). A small cohort of children in Israel (n=58) was evaluated retrospectively for acute cerebellar ataxia and revealed that respiratory infections were most likely to be the antecedent infections, given that 83% of the cohort was vaccinated for varicella (80). In contrast, acute cerebellar ataxia after varicella vaccination is estimated at 1.5 in 1,000,000 doses (91). In areas where varicella vaccination is not routinely performed, chickenpox is still the most common cause of acute cerebellar ataxia (07). Because most cases of acute cerebellar ataxia are presumed to be postinfectious, hand washing, good hygiene, and other methods to reduce transmission of infections may be helpful.

Differential diagnosis

Confusing conditions

In a previously healthy child who becomes acutely ataxic, major considerations in the differential diagnosis include Guillain-Barre syndrome (Miller-Fisher variant), drug intoxication, acute disseminated encephalomyelitis, infectious encephalitis, or acute decompensation of a more indolent neurologic disorder such as a posterior fossa mass lesion (75; 29; 76; 85; 30; 70; 86; 10).

The incidence of drug ingestion is greatest in children between 1 and 4 years old (accidental) or adolescents (intentional) and is often associated with disturbances in personality or sensorium (29; 70). Common medications include antiepileptic drugs, antineoplastic or immunosuppressive agents, antihistamines, benzodiazepines, and psychoactive drugs (85; 10; 80). In addition, two cases of HIV-positive children presenting with ataxia were found to be caused by the antiretroviral efavirenz (37). Other toxic agents that can cause acute cerebellar ataxia include alcohol, ethylene glycol, lead, mercury, thallium, lithium, and toluene (80). Unintentional marijuana ingestion presents as ataxia in 14% of people (72). Urine toxicology screens are helpful even in patients denying drug exposure (33). For children exposed to alcohol prenatally, ataxia may present as a neurodevelopmental symptom due to cerebellar damage (08).

Peripheral neuropathy or degeneration of the spinal cord posterior column can result in sensory ataxia due to loss of proprioceptive information to the cerebellum. Causes include diabetes mellitus, B12 deficiency (pernicious anemia), neurosyphilis (Tabes dorsalis), porphyria, diphtheria, and others (29; 85; 17). In addition, low levels of thiamine, vitamin E, zinc, and folate may be seen in neglected children and present as ataxia (69).

Posterior fossa mass lesions that occur in children include tumors or, rarely, cerebellar hemorrhages or abscesses (57; 75; 85; 38). Approximately 85% of all brain tumors in children between the ages of 2 and 12 years occur in the posterior fossa, which encompasses the age when acute cerebellar ataxia is most common (29). The four major types of posterior fossa tumors are cerebellar astrocytoma, brainstem glioma, ependymoma, and primitive neuroectodermal tumor (medulloblastoma). Furthermore, up to one quarter of children with supratentorial tumors may present with ataxia. Cerebellar hemangioblastomas can occur in children with von Hippel-Lindau disease (29). Cerebellar tumors often cause progressive ataxia and can have preceding symptoms of headache, nausea, morning vomiting, vision changes, and seizures (69).

Other neurologic deficits may sometimes be difficult to distinguish from ataxia in young children, particularly acute weakness such as that seen in Guillain-Barré, tick paralysis, or myositis. In such cases, ataxia is proportional to the degree of weakness, and there may be other associated findings such as areflexia or muscle tenderness, elevated CK, or a tick (75).

Posterior circulation strokes are extremely rare in young children. In children with neck trauma (that could cause vertebral artery dissection) or in those predisposed to thromboembolic disease (eg, with certain types of cardiac or vascular disease), the possibility of an ischemic lesion should be considered in the differential diagnosis. In such cases, cerebellar deficits would more likely be asymmetric and evolve in association with deficits attributable to brainstem ischemia (75; 54). Cerebellar hemorrhage is rare in the absence of coagulopathy, although it can be associated with an arteriovenous malformation or underlying cavernous angioma (75; 29; 10).

Autoimmune etiologies of ataxia can also present similarly to acute cerebellar ataxia (69; 80). When opsoclonus and myoclonus are additionally present, the opsoclonus-myoclonus-ataxia syndrome should be considered. The etiology can be postinfectious or paraneoplastic, most commonly secondary to a neuroblastoma (85; 67). Paraneoplastic acute ataxia has also been reported with Hodgkin lymphoma, Langerhans cell histiocytosis, hepatoblastoma, and ganglioneuroma (75; 47; 61; 67). Gluten ataxia has been coined due to an association between antigliadin antibodies and ataxia (80). These children often have associated neuropathy and nystagmus. Symptoms resolve when the child is placed on a gluten-free diet. Despite the association between antigliadin antibodies and ataxia, data are mixed, and patients with true celiac disease are not more likely to have ataxia in follow-up studies (69).

Neoplastic and bacterial meningitis has also been reported to present as acute ataxia (10). Rarely, vasculitic disorders such as Sjögren syndrome (95), lupus (12), and Kawasaki disease (29) have been reported to present as acute cerebellar ataxia. It was reported in a child with familial hemophagocytic lymphohistiocytosis (02).

Acute disseminated encephalomyelitis (ADEM) can also present with ataxia associated with mental status changes, multiple neurologic deficits, and multiple grey and white matter changes on MRI. Multiple sclerosis most often presents in female children as ataxia, encephalopathy, seizures, or other neurologic deficits associated with periventricular white matter demyelination noted on brain MRI (29; 85; 03; 10). Miller-Fisher syndrome is defined by the triad: ataxia, ophthalmoplegia, and areflexia. It is classified as a variant of Guillain-Barré syndrome or brainstem encephalitis (10). Labyrinthitis (vestibular ataxia) is occasionally misdiagnosed as acute ataxia because of the child's unsteadiness and refusal to sit up or walk. Complaints of vertigo, associated nausea and vomiting, and the absence of appendicular ataxia may be helpful distinguishing features. Like acute cerebellar ataxia, this is most commonly a postinfectious inflammatory condition.

In some children with migraine, recurrent ataxia is a prominent feature; however, this migraine variant may be difficult to diagnose with confidence before excluding other possible causes of recurrent ataxia. Basilar migraine is most commonly seen in adolescent girls and can be associated with cranial nerve palsies and altered levels of consciousness. It is diagnosed by associated headache, positive family history, and normal brain imaging. Benign paroxysmal vertigo is primarily seen in infants and preschool children. However, it can be seen in older children, presenting with episodes of acute severe ataxia that make standing or walking impossible. It is sometimes associated with pallor, nystagmus, and fright. The attacks are brief, resolve with sleep, are associated with later development of migraine (20%) or positive family history for migraine (40%), and are not associated with altered consciousness or headache. Benign paroxysmal torticollis of infancy is similarly associated with migraine and presents as acute episodes of head tilt that may be confused with ataxia (75; 29; 85). In patients with these conditions, the interictal neurologic examination is normal (69).

Familial paroxysmal or episodic ataxia can include metabolic etiologies such as aminoacidopathies (eg, maple syrup urine disease and Hartnup disease), urea cycle disorders (eg, argininemia), organic acidopathies (eg, biotinidase deficiency), vitamin E deficiency, biotinidase deficiency, and mitochondrial disorders (eg, pyruvate dehydrogenase deficiency) (10). Furthermore, episodic ataxia type 1 (EA1) presents in childhood as brief bouts of dysarthria and ataxia and can be triggered by sudden movement, anxiety, excitement, fever, and others. Myokymia is usually seen between attacks, and the condition is due to mutations in the KCNA1 potassium channel. Episodic ataxia type 2 (EA2) is characterized by bouts of ataxia lasting hours to days, triggered by emotional upset, alcohol, caffeine, exercise, and phenytoin. Gaze-evoked nystagmus is often evident between attacks, and the condition is due to mutations in the CACNA1A calcium channel subunit gene (29; 85). Glucose transporter type 1 deficiency syndrome has also led to episodic ataxia in one reported case (63). A genetic etiology for ataxia is suggested by longer duration of symptoms, consanguinity, first-degree relative with similar symptoms, non-neurologic weakness or ataxia, or abnormal physical findings, which may include pes cavus, gait abnormalities, dysmetria, abnormal deep tendon reflexes, sensory loss, or abnormal motor examination (06).

Seizures (epileptic ataxia or pseudoataxia) can present as bouts of ataxia, manifesting as both acute limb incoordination and gait abnormalities. In children with epilepsy, high drug levels should be considered contributory, but if nystagmus is absent, ataxia may represent seizures, especially if the episode is associated with confusion or inattention. EEG monitoring may demonstrate 2 to 3 Hz spike-wave discharges. Furthermore, myoclonic jerks and atonic seizures may also be confused with ataxia (29; 70).

Ataxia after a closed head injury is common, and ataxia may occur after even minor head trauma. Most commonly, the ataxia is due to postconcussive syndrome and is associated with dizziness, headache, nausea, and vomiting, and the ataxia is most commonly axial. Symptoms can persist from several days to several months, and MRI may demonstrate T-2 hyperintensities in the white matter consistent with diffuse axonal injury. As mentioned above, vertebral dissection and brainstem or cerebellar infarct should be considered in children with a recent history of neck trauma (75; 29; 85; 70).

Congenital posterior fossa malformations can also sometimes present as acute ataxia, as the child begins to not meet motor milestones. Brain MRI may show “molar tooth sign,” which is consistent with Joubert syndrome, or cerebellar vermis atrophy with cystic dilation of the fourth ventricle as seen in Dandy-Walker malformations (85; 70). Chiari malformations have been reported as associated with ataxia, although their common incidental finding on brain MRIs confuses the issue. The presence of occipital headache, head tilt, neck or shoulder pain, lower cranial nerve dysfunction, arm weakness, nystagmus, or brisk reflexes associated with ataxia in the presence of brainstem or cerebellar distortion may benefit from posterior fossa decompression. Additionally, an asymptomatic Chiari malformation and basilar impression may become symptomatic after minor head trauma, warranting early surgical intervention for improved outcome (29; 96).

Conversion disorder can present as ataxia, most commonly in adolescent females. Typically, the child has no ataxia while sitting, but when standing, he sways wildly and lurches around the room; the gait is not wide-based, and the child does not fall. This is sometimes referred to as “astasia-abasia.” Because many of these children have a history of sexual or emotional abuse, early involvement in child psychiatry is essential to managing this involuntary but disabling condition (29; 85).

Ensuring they are actually ataxic and not just clumsy is important in evaluating children with ataxia. Many children with learning disabilities, ADHD, speech articulation disorders, or mild gross motor delays may demonstrate mild clumsiness and hypotonia and fall into the developmental disorders spectrum. These children are often labeled “clumsy child syndrome” or “mixed developmental disorder.” Weakness or involuntary movements such as tremors, tics, dystonia, or chorea should not be mistaken for ataxia (85).

Diagnostic workup

Details of the clinical presentation will influence the diagnostic evaluation, primarily looking for causes other than acute cerebellar ataxia. In a child recovering from varicella whose level of consciousness and cranial nerve examination (in particular optic discs) are normal, it is generally unnecessary to perform any neurodiagnostic studies, and their utility is debated due to variable published data (80). Similarly, reviews suggest that all children should undergo a urine drug screen to exclude unanticipated toxins and provide documentation of a presumed offending agent (10; 69). Evaluation of underlying toxic and metabolic abnormalities is important in a child with acute ataxia and associated mental status changes such as lethargy, confusion, or hallucinations. For patients with suspected underlying metabolic disorder or a history of poor nutrition or restrictive diet, metabolic screening labs, comprehensive metabolic profile, and complete blood count should be ordered. Altered ammonia and lactate levels can indicate mitochondrial disorders such as Leigh syndrome, pyruvate dehydrogenase deficiency, or errors in catabolism. Follow-up labs examining levels of pyruvate, urinary amino acids, organic acids, carnitine, and an acyl-carnitine profile may be necessary (29; 76; 85; 70; 10; 24; 69). Urinalysis may also be important to check for urine catecholamines to rule out neuroblastoma.

Neuroimaging should be obtained in patients with acute ataxia and additional signs of altered level of consciousness, signs of increased intracranial pressure, focal neurologic signs, asymmetry of ataxia, or history of trauma (80). Studies have shown that approximately 13% of patients with acute ataxia and additional clinical signs have diagnostic MRI findings such as tumors, infarct, or acute disseminated encephalomyelitis. One study of patients presenting to the emergency department showed that abnormal imaging was significantly more likely in those with a longer time from symptom onset (32). Additionally, when symptoms were scored in one study, they found that patients with a high clinical score (7 to 10 symptoms of cerebellar or extracerebellar symptoms) were more likely to have abnormalities seen on CT scan compared to those presenting with a low-to-moderate score (0 to 3 and 4 to 6 symptoms, respectively) (51). Pathologic CT scans also purported neurologic sequelae in these patients. In the absence of these associated systemic symptoms, some have argued that cranial imaging studies (such as MR imaging) may not be indicated (29). Nonetheless, cranial imaging is frequently performed in this setting because of the dramatic nature of the symptoms and the limitations often encountered in the clinical examination. Cranial imaging reveals no abnormalities in most children with postinfectious ataxia (75; 76; 80). Certainly, the risks and benefits of imaging should be discussed with the family, given that acute cerebellar ataxia occurs most commonly in young children who will likely require sedation for MRI and are more difficult to examine by those unfamiliar with children. If imaging is to be used, MRI is preferred over CT in most cases for superior detection of intracranial pathology and greater ability to resolve subtle areas of demyelination and cytotoxic edema. CT is more pertinent for emergencies to detect stroke, acute hydrocephalus, cerebellar edema, or brainstem compression if acute cerebellitis is suspected (10; 51).

Patients presenting with signs of altered mental status should undergo neuroimaging to help diagnose acute cerebellitis. MRI is the preferred imaging modality in these cases as it is more sensitive for the cerebellum and brainstem (26). MRI findings in acute cerebellitis are categorized as one of three presenting patterns: bihemispheric lesions, hemicerebellitis, and acute cerebellitis with encephalitis demonstrating additional inflammation in extracerebellar areas. Contrast enhancement and diffusion restriction in the cerebellum are also common MRI findings. Kobayashi and colleagues also reported two cases of rotavirus encephalitis with cerebellar symptoms and demonstrated that reduced apparent diffusion coefficients (ADC) on diffusion-weighted imaging (DWI) might be useful for diagnosis (49). MRI imaging may help determine etiology with hyperintense brainstem lesions suggesting an immune-mediated cerebellitis and herniation suggestive of an acute infectious cerebellitis (81). MRI imaging may show changes in the cerebellum that correlate to disease severity. In one study, mild to moderate acute cerebellitis showed cerebellar cortex lesions, whereas more severe cases also demonstrated cerebellar white matter lesions (97). Involvement of the dentate nucleus appears to be variable in the literature. Yildrim and colleagues showed that the dentate nuclei were spared in their cases, which they argued may help to differentiate acute cerebellitis from metabolic disorders. However, Kubota and colleagues reported chronological changes on DWI with marked hyperintensity in the bilateral dentate nucleus followed by the vermis and cerebellar hemisphere, all associated with cerebellar mutism (50). A similar study found that the dentate nucleus lesions resolved over time, leaving only hemispheric inflammation in later imaging studies (26). The lesions may evolve over time. Acute cerebellitis appears to be predominantly monophasic radiologically; however, depending on the infectious organism (such as influenza), it may be multiphasic, with the second phases typically involving the dentate nucleus or corpus callosum (11). In cerebellitis secondary to rotavirus, the radiologic course is described as “a reversible splenial lesion in the acute phase, abnormal signal intensity in the cerebellar white matter/nuclei in the acute-to-subacute stages, followed by an increased signal intensity in the cerebellar cortex and finally cerebellar atrophy” (88). Atrophy can be seen with a normal neurologic examination on repeat imaging (97; 11). Additionally, the initially unaffected cerebellar hemisphere can show atrophy on follow-up imaging (97). Given the risk for cerebellar edema leading to hydrocephalus in acute cerebellitis, a rapid CT scan may be warranted to quickly identify these children for intervention.

Multiple case reports and series support the use of single-photon emission computed tomography (SPECT) imaging to show hypoperfusion (59) or hyperperfusion (35), especially in cases with normal MRI or CT findings. The largest cohort by Hung and colleagues examined 10 children with this condition; they found that several were abnormal (four with cerebellar hypoperfusion, five with unilateral cortical or subcortical hypoperfusion, and one with unilateral cortical hyperperfusion), whereas none of the MRI and CT imaging was abnormal (41). Furthermore, the extent of abnormality on SPECT imaging correlated with clinical severity and recovery time. Thus, the authors felt that brain SPECT may allow identification of children with acute cerebellar ataxia so that further diagnostic work-up can be avoided and may also assist with prognosis. In one case report, SPECT became positive for cerebellar hyperperfusion as the MRI findings resolved, suggesting not only that SPECT might be useful for diagnosis but also that the high percentage of normal MRI imaging in patients with cerebellar ataxia may be because the imaging abnormalities resolve early in the course of the syndrome (35).

If deep tendon reflexes are suppressed or absent, or if the examiner believes that weakness underlies observed ataxia, then electrodiagnostic studies may help diagnose polyradiculopathy or neuropathy. Although the results of these studies may be acutely normal in an affected child, neurophysiological abnormalities can be demonstrated in up to 90% of children with Guillain-Barré syndrome (75). EEG is indicated in those with fluctuating or altered levels of consciousness to evaluate for nonconvulsive seizures. Interestingly, EEG abnormalities can commonly be seen in children with acute cerebellar ataxia, including slowing and electrographic epileptogenic activity; however, none of the children with abnormal EEGs in two studies had seizures or required treatment with antiepileptic medications (15; 62). In patients with known epilepsy, checking drug levels is warranted to evaluate for medication-induced ataxia (29).

A common question in the emergency room is whether a lumbar puncture should be done in an acutely ataxic child. In a child with postinfectious ataxia, although the presence of mild CSF lymphocytosis provides some confirmatory evidence of an inflammatory process, this information is unlikely to influence management, and the procedure is rarely essential (15; 33; 75; 70). Abnormal lumbar punctures are seen in approximately 38% of acute cerebellar ataxia evaluations, with the most common findings a mild to moderate leukocytosis with or without elevated protein (80). In the emergency room, a lumbar puncture is often performed to rule out infection, whereas the use of a lumbar puncture in the inpatient setting is often to evaluate for inflammatory conditions. Based on clinical judgment, a lumbar puncture is warranted to evaluate for meningitis if a child presents acutely with ataxia and fever. A cautious approach is essential. It is generally prudent to perform a cranial imaging study (CT scan or MR imaging) first to exclude a posterior fossa mass or hydrocephalus (Fenichel 2010; 76; 10). Furthermore, CSF analysis may demonstrate cytoalbuminologic disassociation, as seen in Guillain-Barré/Miller-Fisher syndrome, or oligoclonal bands and elevation of serum: CSF immunoglobulin index as seen in multiple sclerosis (75; 43). Neuro-specific enolase in CSF was shown to be prognostic, with higher levels associated with longer times for recovery from ataxia (87). In patients with diagnostic uncertainty, lesions on MRI, and severe clinical course, biopsy of the cerebellum has been rarely utilized to assist in diagnosis (26).

Management

The treatment of acute cerebellar ataxia is largely supportive. This includes ensuring adequacy of hydration and protecting the child from injury. Because acute cerebellar ataxia is a self-resolving condition, no treatment is usually warranted (89). The role of steroids or antivirals is controversial and, in retrospective studies, is often utilized on a case-by-case basis (51). In one series, 66% of patients were given acyclovir despite VZV being identified in fewer patients. Treatment with acyclovir of patients with varicella-induced cerebellar ataxia has not been shown to affect outcomes (07; 51). Yet some authors, such as Heneinger and colleagues, suggest the use of acyclovir in all patients infected with VZV who have complications such as ataxia. Steroids are also frequently used in patients with acute cerebellar ataxia. In the group evaluated by Lancella and associates, 33% of patients received intravenous steroids (51). Despite it being a common practice, there is no consensus on the dose, length of administration, formulation, or mode of administration for steroid use. Once again, steroid use has not been shown to change patient outcomes.

In the setting of acute cerebellitis where there is evidence of inflammation on neuroimaging, steroids or immunomodulators are more commonly utilized despite little evidence (76; 85; 45; 26; 97). In one series, 43% received corticosteroids as either dexamethasone or prednisolone (26). Pulse methylprednisolone was utilized in 16% of these patients, and intravenous immunoglobulin was given to 7%. In another series, approximately half of the patients with acute cerebellitis were treated with IVIG with no additional benefit. Those patients with autoimmune etiologies for their acute cerebellitis were also treated with IVIG but continued to have long-term neurologic sequelae. A case of HSV-1 cerebellitis treated with IVIG in conjunction with acyclovir showed improvement but not full recovery following treatment (66).

Emergent surgical management, including shunting (external ventricular drains or ventriculoperitoneal shunts) or posterior fossa decompression, has been reported due to brainstem compression and hydrocephalus developing acutely and may occur in as high as a quarter of patients with acute cerebellitis (53; 78; 92; 20; 46; 83; 14; 26). One report suggested that children with acute cerebellar ataxia due to mycoplasma may be more prone to developing hydrocephalus (79). In some cases, the child died even with surgical intervention, but in all cases, there were more severe signs and symptoms such as papilledema, altered mental status, and imaging findings of obstructive hydrocephalus. In many cases, treatment with IV dexamethasone was attempted without success, and some cases underwent shunting initially and then later required decompression due to continued worsening. There are also a few reports of patients responding to intravenous steroids with resolution of cerebellar swelling and hydrocephalus and avoidance of neurosurgical intervention (98; 83; 97).

Outcomes

Acute cerebellar ataxia is typically a monophasic disease with few neurologic sequalae in most cases (26). Patients typically improve within 2 weeks, although ataxia can take months to fully resolve. Treatment has not been shown to change outcomes in the current literature. One study of neuropsychiatric outcomes in a small series of patients with prior acute postinfectious cerebellar ataxia did show that patients had comorbid cognitive and affective cerebellar symptoms (28). It is unclear if there will be long-term subtle executive functioning deficits in patients who recover from acute cerebellar ataxia, which has been seen with other neurologic injury such as traumatic brain injury.

Prompt medical treatment or neurosurgical intervention may prevent death in patients with acute cerebellitis with associated edema. One of the largest series of acute cerebellitis showed 27% of patients with neurologic sequelae (four cases) (97). This included continued dysmetria, ataxia, memory difficulties, and mild motor impairment. Long-term disability has been reported in some patients up to 2 years after illness and can include motor symptoms such as spastic paraplegias and neuropsychological symptoms (26).

Special considerations

Recommended reading

The reader is referred to two reviews on acute cerebellar ataxia evaluation and management (44; 86).