Hot cross bun sign in JC-Virus Granule cell neuronopathy in HIV infected patient - a case report.

BACKGROUND: John Cunningham virus related granule cell neuronopathy (JCV-GCN) is a rare manifestation of the reactivation of infection of the cerebellar granule cells by the JCV, mostly in immunocompromised individuals. The "hot cross bun" (HCB) sign is a cruciform hyperintensity seen in the midpons on T2-weighted and fluid attenuated inversion recovery (FLAIR) sequences on magnetic resonance imaging (MRI) of the brain. An index sub-Saharan Africa report of a case of JCV-GCN with HCB sign follows. CASE PRESENTATION: A 27-year-old HIV positive female with JCV-GCN was re-evaluated for chronic ataxia complicated by subacute progressive horizontal diplopia. Cerebrospinal fluid (CSF) had trace Mycobacterium tuberculosis (MTB) detected by GeneXpert Mycobacterium Tuberculosis/Rifampicin resistance (MTB/RIF) assay test. Brain MRI revealed diffuse severe cerebellar atrophy with a hot cross bun sign and patchy enhancement contiguous to the cerebellar dentate nuclei bilaterally. She continued Highly Active Antiretroviral Therapy (HAART) pending CSF HIV viral load counts and started standard brain TB local treatment regimen protocols with progressive improvement in limb ataxia. CONCLUSIONS: In conclusion, finding of the HCB sign may be indicative of and aid diagnosis of JCV-GCN in the right clinical context. This could be an important neuroimaging marker in this context, that may radiologically be more evident in later stages of the condition.

Infratentorial onset of progressive multifocal leukoencephalopathy in a patient with systematic lupus erythematosus complicated with lymphoma: a case report.

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system caused by reactivation of JC virus (JCV). Typical PML shows confluent, bilateral but asymmetric, subcortical lesions in the supratentorial white matter on magnetic resonance imaging (MRI). We report here a 50-year-old woman with systemic lupus erythematosus complicated with lymphoma who developed PML with atypical brain MRI findings limited to the infratentorial area at presentation. She presented with numbness on the right side of the face, including her tongue, clumsiness of the right hand, and gait disturbance, after completion of remission induction therapy for lymphoma, including rituximab. Brain MRI demonstrated a solitary lesion limited to the cerebellum and brainstem, but a definitive diagnosis could not be made from cerebrospinal fluid study or tentative histologic evaluation of brain biopsy specimens. Despite methylprednisolone pulse therapy, her neurological deficits progressively worsened. One month later, in-depth analysis of her cerebrospinal fluid and brain biopsy specimens confirmed the presence of JCV. Eventually, the localised unilateral crescent-shaped cerebellar lesions on MRI expanded to the contralateral cerebellum, middle cerebellar hemisphere, pons, and midbrain and finally developed multifocal invasion into the white matter of the cerebral hemispheres. Our case suggests that PML could first present with a solitary infratentorial lesion in immunocompromised patients.

JC Virus Granule Cell Neuronopathy as AIDS-Presenting Illness.

JC virus is the etiological agent of progressive multifocal leukoencephalopathy, a white matter demyelinating disease that mostly affects immunocompromised patients. JC virus can also infect neurons and meningeal cells and cause encephalitis, meningitis and granule cell neuronopathy. We report a patient with JC virus granule cell neuronopathy, without concomitant progressive multifocal leukoencephalopathy, presenting as inaugural acquired immune deficiency syndrome-related illness. This patient's human immunodeficiency virus infection remained undiagnosed for several months after neurological symptoms onset. We review JC virus pathophysiology, clinical manifestations, treatment and prognosis, and emphasize the importance of considering human immunodeficiency virus infection and related opportunistic infections in the differential diagnosis of new-onset isolated cerebellar disease.

JC virus granule cell neuronopathy onset two months after chemotherapy for low-grade lymphoma.

BACKGROUND: Granule cell neuronopathy (GCN) is a rare disease caused by the JC virus, leading to degeneration of cerebellar granule cell neurons. Primarily described in patients with AIDS, it has also been diagnosed in patients with lymphoproliferative diseases and after long-term treatment with immune-suppressing medications such as natalizumab. CASE PRESENTATION: A 69 year old woman presented with progressive ataxia which began 2 months after initiation of treatment for follicular low-grade B cell lymphoma with rituximab/bendamustine, and progressed for 2 years prior to admission. Extensive prior evaluation included MRI that showed atrophy of the cerebellum but normal CSF analysis and serum studies. Neurologic exam on admission was notable for severe appendicular ataxia and fatigable end-gaze direction-changing horizontal nystagmus. FDG-PET/CT scan was unremarkable and repeat lumbar puncture revealed 2 WBCs/mm3, 148 RBCs/mm3, glucose 70 mg/dL, protein 37.7 mg/dL and negative flow cytometry/cytopathology. Standard CSF JC virus PCR testing was negative, but ultrasensitive TaqMan real-time JC virus PCR testing was positive, consistent with JC virus-related GCN. CONCLUSIONS: Because of the diagnostic challenges in identifying GCN, a high threshold of suspicion should be maintained in patients with an immune-suppressing condition such as lymphoma or on immune-suppressing agents such as rituximab, even shortly after initiation of therapy.

JC virus granule cell neuronopathy in the setting of chronic lymphopenia treated with recombinant interleukin-7.

JC virus (JCV) is a human polyomavirus that infects the central nervous system (CNS) of immunocompromised patients. JCV granule cell neuronopathy (JCV-GCN) is caused by infection of cerebellar granule cells, causing ataxia. A 77-year-old man with iatrogenic lymphopenia presented with severe ataxia and was diagnosed with JCV-GCN. His ataxia and cerebrospinal fluid (CSF) improved with intravenous immunoglobulin, high-dose intravenous methylprednisolone, mirtazapine, and mefloquine. Interleukin-7 (IL-7) therapy reconstituted his lymphocytes and reduced his CSF JCV load. One month after IL-7 therapy, he developed worsening ataxia and CSF inflammation, which raised suspicion for immune reconstitution inflammatory syndrome. Steroids were restarted and his ataxia stabilized.

JC Virus Infects Neurons and Glial Cells in the Hippocampus.

The human polyomavirus JC (JCV) infects glial cells and is the etiologic agent of the CNS demyelinating disease progressive multifocal leukoencephalopathy. JCV can infect granule cell neurons of the cerebellum, causing JCV granule cell neuronopathy and cortical pyramidal neurons in JCV encephalopathy. Whether JCV also infects neurons in other areas of the CNS is unclear. We determined the prevalence and pattern of JCV infection of the hippocampus in archival samples from 28 patients with known JCV infection of the CNS and 66 control subjects. Among 28 patients, 11 (39.3%) had JCV infection of hippocampus structures demonstrated by immunohistochemistry. Those included gray matter (dentate gyrus and cornu ammonis, subiculum) in 11/11 and afferent or efferent white matter tracts (perforant path, alveus, fimbria) in 10/11. In the hippocampus, JCV infected granule cell and pyramidal neurons, astrocytes, and oligodendrocytes. Although glial cells expressed either JCV regulatory T Antigen or JCV VP1 capsid protein, infected neurons expressed JCV T Antigen only, suggesting an abortive/restrictive infection. None of the 66 control subjects had evidence of hippocampal JCV protein expression by immunohistochemistry or JCV DNA by in situ hybridization. These results greatly expand our understanding of JCV pathogenesis in the CNS.

Concomitant granule cell neuronopathy in patients with natalizumab-associated PML.

Granule cell neuronopathy (GCN) is a rare JC virus infection of the cerebellar granule cell neurons in immunocompromised patients. On brain imaging, GCN is characterized by cerebellar atrophy which can be accompanied by infratentorial white matter lesions. The objective of this study is to investigate the prevalence of MRI findings suggestive of GCN in a large natalizumab-associated progressive multifocal leukoencephalopathy (PML) cohort. MRI scans from before, at the time of, and during follow-up after diagnosis of PML in 44 natalizumab-treated MS patients, and a control group of 25 natalizumab-treated non-PML MS patients were retrospectively reviewed for imaging findings suggestive of GCN. To assess and quantify the degree of cerebellar atrophy, we used a 4 grade rating scale. Three patients in the PML group showed imaging findings suggestive of GCN and none in the control group. In two of these PML patients, cerebellar atrophy progressed from grade 0 at the time of diagnosis of isolated supratentorial PML to grade 1 and 2 after 2.5 and 3 months, respectively, in the absence of infratentorial white mater lesions. The third patient had grade 1 cerebellar atrophy before diagnosis of infra- and supratentorial PML, and showed progression of cerebellar atrophy to grade 2 in the 3 months following PML diagnosis. None of the other eight patients with infratentorial PML lesions developed cerebellar atrophy suggestive of GCN. Three cases with imaging findings suggestive of GCN were detected among 44 natalizumab-associated PML patients. GCN may, therefore, be more common than previously considered in natalizumab-associated PML patients.

JC virus granule cell neuronopathy: A cause of infectious cerebellar degeneration.

JC virus (JCV) infection of glial cells can lead to progressive multifocal leukoencephalopathy (PML) in immunocompromised patients. A newly described phenotype of the infection is infection of neurons. This distinct clinical and radiological syndrome is named JCV granule cell neuronopathy, characterized by exclusive or predominant cerebellar atrophy. We report the clinical and radiological longitudinal findings of 5 HIV-infected patients referred to us between September 2004 and November 2011 who exhibited JCV granule cell neuronopathy (4 probable cases and 1 possible). The association of immunocompromised status, progressive cerebellar syndrome, MRI abnormalities with cortical cerebellar atrophy and cerebrospinal fluid positive for JCV on PCR allowed for a highly probable diagnosis. The reversal of the immunocompromised status is the only way to stop the disease evolution. Motor functioning can remain impaired, but the illness itself, unlike progressive multifocal leukoencephalopathy, does not seem to threaten life.

Infections of the cerebellum.

Although the cerebellum can be affected by any infection that also involves other parts of the brain parenchyma, cerebrospinal fluid, or nerve roots, a limited range of infections targets cerebellar structures preferentially. Thus, a primarily cerebellar syndrome narrows infectious differential diagnostic considerations. The differential diagnosis of rapidly evolving cerebellar signs suggesting infection includes prescription or illicit drug intoxications or adverse reactions, inflammatory pseudotumor, paraneoplastic processes, and acute postinfectious cerebellitis. This article discusses the diagnosis and differential diagnosis of viral, bacterial, fungal, and prion pathogens affecting the cerebellum in patterns predictable by pace of illness and by involved neuroanatomic structures.