Resident Rounds

April 2008

A previously healthy 22-month-old girl presented to the pediatric emergency department with complaints of worsening gait and progressive jerky movements of the upper and lower extremities for the past 10 days.

The patient developed cough and nasal congestion two weeks prior to this admission and was seen by her pediatrician.

She was diagnosed with bilateral otitis media and placed on 10 days of amoxicillin. There was no history of fever, vomiting, diarrhea or generalized rash. Three days later, the upper respiratory infection symptoms resolved but the mother noticed feet shaking and later shaking of her arms and strange movements of the eyes. She was seen at another emergency department, requiring admission. A computed tomography scan of the brain was negative. With subsidence of symptoms and tests done on admission including complete blood count, electrolytes, liver enzymes and spinal tap being negative, the patient was discharged from the hospital after 96 hours with instructions to complete her course of antibiotics. The gait worsened during the next 24 hours and the parents brought her to our county hospital.

In the ED, the patient was afebrile and had no nausea, vomiting, diarrhea or skin rash. She was unable to walk, stand without support or stand up from a sitting position. Her speech was dysarthric. She was extremely irritable and consolable only by her parents.

The parents denied any recent travel history, head injury, ingestion of canned food or honey or lead exposure risks.

Developmental milestones were appropriate for her age. She had completed her 10-day course of amoxicillin and was not on any chronic medications.

The girl’s history was up-to-date with her immunizations and she had no history of vaccination, nor any family history of consanguinity, epilepsy, convulsion disorder or any joint diseases.

On examination, the patient was alert, irritable and crying yet consolable by her mother. She had persistent high blood pressures. On physical examination she was noted to have rapid, involuntary, multivectorial (horizontal and vertical), and unpredictable, conjugate fast eye movements intermixed with small amplitude movements, appearing as tiny deviations from primary position. Her pupils were round and equally reactive to light. No photophobia was noted. The patient had an upper lip hemangioma since birth, no evidence of cafe-au-lait macules or ash leaf spots on skin. Her heart and lung examinations were normal.

Neurological exam was limited in lieu of patient’s irritability. She had a supple neck, good muscle tone, hyper reflexic ankle jerks and negative Babinski reflex.

Following admission she had numerous episodes of gait unsteadiness and rolling of her eyes; each lasted for only a few seconds coupled with episodes of hypotonicity and hyporeflexia followed by complete recovery. Dysmetria was clinically evident when she tried to reach out for toys and she was unable to sit or stand unsupported during these episodes. Between the episodes there was complete resolution of symptoms with normal physical examination and vital signs.

Toxicology screen was negative and CBC, basic metabolic panel, liver function tests and creatinine kinase were all within normal limits for age. Vitamin B12 level was normal. Urine was negative for amino acids.

Urine culture for cytomegalovirus was negative.

Lumbar tap performed at admission had normal cell count, glucose and protein. Culture for herpes simplex virus type 1 and 2 immunoglobulin G, CMV IgG, Lyme, and myelin basic protein were conducted. Serum was negative result for monospot, rapid plasma reagin and varicella zoster virus. Immunoglobulins G and M for VZV, HSV 1 and 2 and mycoplasma were within normal limits. Lyme titer was positive on initial serology but with negative on Western blot confirmatory test. Iron, unsaturated iron-binding capacity, total iron-binding capacity, transferrin, ferritin, C-reactive protein, erythrocyte sedimentation rate, and, hemoglobin electrophoresis were within normal limits.

CT scan of the brain was negative and magnetic resonance imaging of the brain with contrast was also negative with no meningeal enhancement.

Further studies were ordered to rule out neuroblastoma including 24 hour urine for vanillylmandelic acid, which was negative. MRI of the cervical spine and chest, and CT scans of the thorax, abdomen and pelvis were normal. Repeat lumbar tap was negative as well.

The patient remained afebrile and showed no meningeal manifestations throughout the hospitalization. Only supportive care and close monitoring were provided during her hospitalization and her symptoms improved on the 10th day of admission. There was decrease in the frequency of episodes, decreased irritability, improved oral intake and normal reflexes in all four extremities. She verbalized better compared with the day of admission and was ambulating with support.

The patient was discharged on the 15th day of admission to be followed by her pediatrician. The patient was readmitted for similar complaints to another medical facility and received supportive care and was discharged within a few days. Repeat imaging and labs were negative as well. What do you think is the diagnosis?

Answer

Acute cerebellar ataxia has been referred to in the literature as acute cerebellitis and cerebellar encephalitis. Some investigators have suggested the pathophysiology of acute cerebellar ataxia to involve edematous cerebellitis, based on magnetic resonance imaging and single-photon emission computed tomography findings.

The diagnosis is based on: acute onset of ataxia with or without nystagmus; absence of known genetic predisposing factors, such as familial degenerative disorders; and absence of drug intoxication, bacterial meningitis and metabolic disorders. It is a diagnosis of exclusion and postulated to result from viral and/or autoimmune etiologies.

Acute cerebellar ataxia has a rapid onset, reaching maximum severity in a period of hours to several days. The two most common childhood causes are drug intoxication and acute postinfectious cerebellitis. Rarely, bacterial meningitis may present with ataxia. Many recent reports of acute cerebellitis with a critical or potentially critical course have changed the conception of the disease from an acute cerebellar ataxia with a benign course to a notable disease entity with a heterogeneous pathogenesis. Acute post infectious cerebellitis is a self-limiting condition, usually seen in children aged between 2 and 7 years with sudden onset ataxia, maximum at the onset, non-progressive, with complete recovery. Cerebellar ataxia may be present at diagnosis or appear during follow-up and may be progressive or static.

Acute cerebellitis is one of the main causes of acute cerebellar dysfunction in children. It is either infectious, usually viral or postinfectious, or postvaccinal in etiology. Varicella zoster, Epstein-Barr, measles, pertussis, diphtheria, coxsackie, mumps, herpes simplex virus I, parvovirus, typhoid fever and Mycoplasma pneumonia viruses are the most frequently involved agents.

Varicella is involved in more than one-fourth of cases. Acute cerebellar ataxia usually develops as the result of post-infectious cerebellar demyelination, but it may also occur with direct infection of the cerebellum. Post varicella cerebellitis usually affects preschool and elementary school-aged children. It begins about two weeks after the onset of the viral illness, often after the vesicles begin to clear, and evolves rapidly over two to three days. Rarely, ataxia may be concomitant with or precede a skin rash. Gait is prominently affected and ataxia varies from mild unsteadiness to complete inability to stand or walk; the child is otherwise normal.

Acute childhood ataxia is a common cause of presentation to the pediatric emergency room or child neurologist. The primary concern on initial assessment is to exclude serious causes of this clinical syndrome, including central nervous system infections and mass lesions, while recognizing the benign nature of acute ataxia in most children. The clinical manifestations cause concern because they must be differentiated from other causes of cerebellar ataxia with more serious prognostic implications. The etiology is apparently varied and has often gone unexplained.

Childhood ataxia can be diagnostically approached by consideration of the temporal course and presence or absence of associated neurological abnormalities. In all forms of childhood ataxia, outcome is largely determined by etiology. Diagnosing of acute cerebellitis can sometimes be difficult because the patient may present only mild cerebellar signs and the examination of cerebrospinal fluid may be normal.

A thorough history, physical examination and drug screen should be performed prior to admission and also prior to other costly and invasive tests. This approach may eliminate the need for hospitalization of some patients with postinfectious acute cerebellar ataxia and ingestion. Neuroimaging studies should be used judiciously in the evaluation of acute ataxia, considering their low yield. Neuroimaging studies and hospitalization are needed only in case of atypical presentation, asymmetric neurological examination and prolonged ataxia.

Onset of ataxia is typically sudden, usually five to 10 days after the beginning of the precipitating infection. Symptoms are generally maximal at onset. Truncal ataxia can be severe, leading to complete inability to walk. Vomiting, horizontal nystagmus and dysarthria may initially occur. Mental status should be normal for children with acute cerebellar ataxia. Fever, meningismus and seizures are absent. There is one reported case of sudden death from acute fulminant cerebellitis in a 13-year-old ballet dancer supported by serial CT and MRI, which demonstrated rapid progression of the disease.

Areflexia and a mild degree of ataxia may be present in children with Guillain-Barré syndrome. Ataxia is a major feature of the Miller-Fisher variant of the Guillain-Barré syndrome that typically occurs 10 to 15 days following a viral illness. Miller-Fisher syndrome is characterized by areflexia, ataxia and ophthalmoplegia that commonly affects vertical gaze, especially upward gaze. Horizontal gaze is usually preserved. Elevation of cerebral spinal fluid protein is seen in both disorders. Other conditions that may mimic the syndrome should be excluded.

Clinical features do not distinguish acute cerebellar ataxia from many other causes of acute ataxia in children. Therefore, it is a diagnosis of exclusion for a toddler or young child presenting with acute onset of ataxia. Symptoms usually take several weeks to resolve, and the prognosis for complete recovery is usually excellent.

The investigations for acute cerebellar ataxia are:

• MRI to rule out mass lesions, infarcts, white matter disease for chronic ataxias.
• Wilson’s disease screen (24-hour urinary copper, ceruloplasmin, slit-lamp examination).
• Genetic testing for spino cerebellar ataxias (especially SCA1, 2 and 3), Friedrich’s ataxia (FRDA gene), dentatorubral-pallidoluysian atrophy, and myoclonus epilepsy associated with ragged-red fibers if appropriate family history or clinical features are present.

The patient in our report had a history of upper respiratory infection, followed by acute onset of truncal and limb ataxia with inability to walk and talk. Her eye changes resembled opsoclonus and not nystagmus. Features that were against the diagnosis of encephalitis included absence of meningeal enhancement on the MRI. However, the patient demonstrated a degree of irritability that was consistent clinically with encephalitis.

Myoclonic encephalopathy/Dancing Eye syndrome, an idiopathic encephalopathy and a diagnosis of exclusion, was not part of our working diagnosis. Our patient had similar symptoms as in Dancing Eye syndrome but her eye findings were not persistent and there were periods of spontaneous recovery between episodes.

One common differential diagnoses included an occult neuroblastoma. Each child with prolonged or recurrent acute cerebellar ataxia should be extensively investigated for the presence of neuroblastoma, even in the absence of opsoclonus. If ataxia is associated with chaotic eye movements or worsens and persists for more than a week without apparent cause, neuroblastoma should be suspected.

Our working diagnosis was acute cerebellar ataxia, rule out neuroblastoma. With all the serology and culture as well as imaging studies being normal/negative, with exacerbations of symptoms and periods of spontaneous recovery, we concluded this case to be one of an atypical presentation of post infectious cerebellitis

For more information:

• Anish Ray, MD is currently a resident in pediatrics at Nassau University Medical Center, Long Island, NY and a keen follower of applied neurology. Brinda Doraiswamy, MD is in the Department of Infectious Diseases and Satish Kadakia, MD is with pediatric neurology.
• Ashwal S, Swaiman KF (eds). Pediatric Neurology: Principles and Practice. 3rd ed. St. Louis, MO: Mosby-Year Book Inc.;1999.
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