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Monday

 

FOR NEUROLOGISTS: (TYSABRI) Newly Recognized JC Virus Syndrome with Pure Cerebellar Degeneration

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Robert T. Naismith, MD

 Robert T. Naismith, MD Reviewing Schippling S et al., Ann Neurol

Newly Recognized JC Virus Syndrome with Pure Cerebellar Degeneration

A case of cerebellar granule cell neuronopathy with progressive ataxia and  cerebellar atrophy in the setting of natalizumab treatment for multiple sclerosis.
This case report describes a patient with multiple sclerosis (MS) who, after being treated with TYSABRI (natalizumab) for more than 4 years, developed progressive gait ataxia and appendicular signs over 4 months.

MRI did not show any new T2 or gadolinium-enhancing lesions but did demonstrate cerebellar atrophy. Cerebrospinal fluid (CSF) was positive for JC virus by PCR testing, natalizumab was stopped, and plasma exchange promptly removed circulating natalizumab. The patient continued to worsen over 2 months, prompting a cerebellar biopsy establishing severe destruction of the granule cells in the cortical structure, with immunohistochemistry detecting JC virus within the nucleus of remaining granule cells.

Progressive multifocal leukoencephalopathy is the protypical presentation of JC virus cerebral infection, and it is always associated with T2 lesions on magnetic resonance imaging (NEJM JW Neurol April 8 2013). A cerebellar degeneration syndrome has been described in the setting of HIV that may be due to a genetic variation in the JC virus.

COMMENT

Clinicians prescribing natalizumab for MS patients who are JC virus serum antibody–positive need to know about this progressive ataxia with cerebellar atrophy syndrome. Because MS also causes ataxia, the syndrome may be underappreciated and erroneously attributed to MS progression. Instead, CSF should be obtained, and if it is positive for JC virus, natalizumab should be withdrawn and plasma exchange initiated. Treatment beyond that is supportive, with the hope that the immune reconstitution will limit ongoing granule cell damage.

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