JC Virus Granule Cell Neuronopathy and Lymphoma.

Neurological opportunistic infections are going to increase. Clinicians should be aware of the neurological spectrum of JC virus manifestations, including granule cell neuronopathy. Detection of JC virus DNA by polymerase chain reaction in cerebrospinal fluid should be realized in the assessment of a progressive cerebellar ataxia in an immunocompromised patient.

A 79-year-old woman was hospitalized for subacute cerebellar ataxia. Indolent B-cell lymphoma (splenic marginal zone lymphoma) was diagnosed 6 years earlier. Surveillance was recommended.

She described progressive gait instability associated with dysarthria, worsening over 2 months.

On admission, she was found to have severe cerebellar ataxia. She required a rollator to mobilize and had a cerebellar dysarthria, swallowing problems, and occulomotor involvement (square wave jerks).

Brain imaging demonstrated diffuse cerebellar atrophy, hyperintense areas in the cerebellar cortex, and bilateral middle cerebellar peduncles on diffusion, T2 and FLAIR-weighted imaging, and T1 hypointensities (Figure 1). There was no gadolinium enhancement.

Figure 1.

Axial magnetic resonance image (MRI) (A, B) showing, respectively, bilateral hyperintensity in the middle cerebellar peduncle (arrows) and cerebellar vermis cortex hyperintensities (FLAIR-weighted image). Sagittal MRI (C) showing cerebellar cortex hyperintensities (FLAIR-weighted image).

Blood test revealed cytopenias with thrombocytopenia (116 G/L) and T lymphopenia (0.766/µL, normal count 1–2.2/µL) with selective TCD8 lymphopenia (0.168/µL, 0.330–0.920/µL). Lymphocytes and TCD4 counts were normal. The CD4/CD8 ratio was elevated (3.25; range, 1.20–2.20). Severe hypogammaglobulinemia was associated (3 g/L; normal range, 8–13 g/L). The HIV test was negative.

Cerebrospinal fluid (CSF) analysis showed a normal cell count (1 white cell) and normal protein (0.21 g/L) with no malignant cells on cytology. Detection of JC virus (JCV) DNA by polymerase chain reaction (PCR) was positive in the CSF (5000 copies per mL).

After discussion, chemotherapy was not given because of the risk of worsening lymphopenia and progression of JCV infection. She was treated with intravenous immunoglobulin. Correction of immunoglobulin G subclass occurred, without clinical improvement. Interleukin-7 therapy was also discussed but rejected given the risk of lymphoma progression.

She deteriorated rapidly, becoming bed bound, and she died due to recurrent aspiration pneumonia. A post mortem examination was not carried out.

The cause of death was JC virus granule cell neuronopathy (JCV-GCN) associated with cerebellar peduncle progressive multifocal leukoencephalopathy (PML). This is a newly described complication of JCV [1-3], reported in the context of immunosuppression and chronic lymphopenia. The most common association is with HIV infection [4], but it has also been reported in sarcoidosis and with immunosuppressive treatments such as natalizumab and rituximab [5, 6]. JCV-GCN corresponds to specific lytic infection of cerebellar granule cell neurons, classically resulting in a chronic progressive ataxia [7]. It is associated with a JCV variant, with mutations in the DNA at the c-terminus of the VP1 capsid gene [5, 6].

Given the development of immunosuppressive treatments, particularly in the era of monoclonal antibodies, clinicians should be aware of the neurological spectrum of JCV manifestations, including JCV-GCN. We report the first case of JCV-GCN in a patient with untreated lymphoma. We also provide new clinico-radiological features of JCV-GCN with subacute and lethal evolution. Clinicians should consider CSF analysis for JCV DNA by PCR in the assessment of progressive cerebellar ataxia in immumocompromised patients.