Progressive multifocal leukoencephalopathy in idiopathic CD4⁺ lymphocytopenia: A case report and review of literature

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease due to a lytic infection of oligodendrocytes caused by polyoma virus (JC virus) infection. PML usually occurs in a setting of severe immunosuppression and is most commonly associated with human immunodeficiency virus (HIV) infection. Idiopathic CD4 + lymphocytopenia is a very rare cause of PML and only a few cases have been reported in the literature. We present a case of a 45-year-old man who presented with behavioral alteration followed by progressive weakness of right side of the body. Contrast-enhanced magnetic resonance imaging of the brain revealed confluent irregular areas of T2-weighted/fluid-attenuated inversion recovery hyperintensities in left frontoparietal and right temporoparietal regions. His hematological work up showed a decreased absolute CD4 + count of 217 per microliter, but was negative for HIV serology. Keeping a differential diagnoses of central nervous system lymphoma, brain biopsy was performed. Histopathology revealed demyelination with presence of intranuclear inclusions in the oligodendrocytes, which were positive for SV40 immunostain. Adjacent areas showed reactive gliosis with hypertrophic astrocytes, hence a diagnosis of PML was made. The patient died due to aspiration pneumonia. PML can occur very rarely in association with idiopathic CD4 + lymphocytopenia in the absence of other immunosuppressive illnesses. This report highlights the importance of high index of clinical suspicion and need for a careful histological examination for diagnosis of PML to facilitate adequate patient management.

Characteristics of Progressive Multifocal Leukoencephalopathy Associated With Sarcoidosis Without Therapeutic Immune Suppression

“…Only 11% to 13% of these patients have CD4 + counts above 200/μL at time of PML diagnosis . In published cases of PML associated with idiopathic CD4 + lymphopenia, the median CD4 + count was 119/μL, with CD4 + counts greater than 200/μL in 4 of 20 patients (20%) . Our findings suggest that even patients with moderate rather than severe CD4 + lymphopenia may be at risk of S-PML.…”

“Burnt‐out” progressive multifocal leukoencephalopathy in idiopathic CD4+ lymphocytopenia

“…10,11 Indeed, there have been some reports of PML patients with ICL who survived for a considerably long period of time, despite experiencing a significant depletion of CD4 + cells. 12,13 This suggests that the longterm survival of our patient has been supported not only by tube feeding and tracheotomy but also by some favorable immunoreaction that is unique to a subgroup of ICL that enables the elimination of viral particles, probably independent of the number of CD4 + cells. We postulate the hypothesis that the immune system in some patients with ICL may be slightly below the threshold of development of immunodeficiency, and that endogenous or exogenous factors may trigger opportunistic infections.…”

Progressive multifocal leukoencephalopathy in a patient with systemic sclerosis treated with methotrexate: A case report and literature review

“…8 Among primary immunodeficiency disorders, idiopathic CD4+ T-cell cytopenia is the most common disorder associated with PML. 11 The monoclonal antibodies efalizumab and natalizumab that target cell adhesion molecules, and rituximab that targets B cells have most commonly been associated with PML. Efalizumab, a humanized monoclonal antibody against the human CD11a subunit of the lymphocyte function-associated antigen 1 (LFA-1), used to treat severe plaque psoriasis, has been withdrawn from the market due to its high incidence of PML (1/500 cases).…”