Infratentorial progressive multifocal leukencephalopathy in a patient with pulmonary sarcoidosis

Sirs, A 56-year-old woman was referred to our hospital in July 2007 because of cerebellar ataxia, tetraparesis, dysphagia and dysarthrophonia which had progressed over the last 9 months. In 1988 the patient was diagnosed with pulmonary sarcoidosis and since treated with varying doses of glucocorticoids. A magnetic resonance imaging (MRI) scan of the brain from February 2007 showed a left pontine T2 weighted hyperintense lesion (Fig. 1a). The patient was diagnosed with probable neurosarcoidosis and treated with a pulse of i.v. methylprednisolone (500 mg/day for 5 consecutive days) followed by oral prednisolone (40– 100 mg/day over the next weeks). However, despite treatment neurological symptoms further progressed and the patient was transferred to our neurological ward. Laboratory testing revealed lymphocytopenia in differential blood count (relative: 3%, absolute: 0.31/nl) with normal leukocyte levels. Serological tests for possible autoimmune and infective etiologies were negative. Cerebral spinal fluid (CSF) examination was normal besides detection of oligoclonal bands only in CSF. Molecular testing revealed a polyclonal Tand B-cell population. To exclude Whipple0s disease a biopsy of duodenal mucosa was performed and found normal. Thorax-CT was consistent with pulmonary sarcoidosis. MRI scans showed T2-weighted and fluid-attenuated inversion recovery hyperintensities in pons and cerebellum (Fig. 1b, c) without Gadolinium enhancement. Smaller (7 mm), similar signal intensities were found supratentorially in the frontal subcortical white matter on both sides (Fig. 1d). Intravenous methylprednisolone at 500 mg/day was administered for 5 consecutive days followed by administration of methotrexate at 10 mg orally once. Soon thereafter, the patient developed bacterial pneumonia, was transferred to the neurointensive care unit, antibiotically treated and mechanically ventilated. Stereotactic brain biopsy of the cerebellum showed areas of demyelination additionally marked by the presence of several foamy macrophages. JC virus (JCV) was detected in biopsy sample by immunohistochemistry (Fig. 2). In addition, JCV DNA was detected by polymerase chain reaction (PCR) in cerebellar tissue, CSF, serum and later in urine, establishing the diagnosis of progressive multifocal leukoencephalopathy (PML). Therapy with oral prednisolone was immediately stopped. Treatment with cidofovir 5 mg/kg plus probenicid was initiated and repeated 1 week later. However, the patient developed bacterial sepsis with multi-organ failure. She died of cardiovascular failure 11 months after first neurological symptoms occurred. This case shows a brainstem/cerebellar manifestation of PML in a patient with sarcoidosis. PML is a demyelinating CNS disease caused by re-activation of a latent JCV L. Neeb (&) L. Harms M. Endres Department of Neurology, Charite Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany e-mail: lars.neeb@charite.de