Clinical and Radiological Characterization of Progressive Multifocal Leukoencephalopathy in HIV-Infected Patients: A Retrospective Analysis and Review of the Literature

Abstract

Acta Med Port 2015 May-Jun;28(3):286-296 RESUMOIntrodução: A leucoencefalopatia multifocal progressiva é uma patologia desmielinizante causada pelo vírus John Cunningham, geralmente associada a estados de imunodepressão, em particular a infeção pelo vírus da imunodeficiência humana. Pode apresentar múltiplas manifestações clínicas e tem habitualmente um padrão imagiológico típico. A evolução clínica é geralmente progressiva, podendo ocorrer uma melhoria do prognóstico associada à recuperação imunológica. Results: Twenty-one patients were included in our study, mostly men (n = 20, 95.2%). Mean age at diagnosis was 39 years. Motor deficits were the most common clinical finding. John Cunningham virus-DNA was detected in the cerebral spinal fluid in 20 patients (95.2%). Brain imaging studies most commonly disclosed bilateral supratentorial, asymmetric lesions. Four (19%) patients developed immune reconstitution inflammatory syndrome in the follow-up. Therapeutic approach included initiation and continuation/optimization of antiretroviral therapy, with adjunctive therapy with corticosteroids in four patients. Seventeen (81%) patients died during the study period; median survival time following progressive multifocal leukoencephalopathy diagnosis was 3 months (range 1 -13). Discussion:The results of our study are in accordance with the data previously published on progressive multifocal leukoencephalopathy in human immunodeficiency virus patients. Progressive multifocal leukoencephalopathy is predominantly associated with severe immunosuppression, particularly in patients who are not under anti-retroviral therapy, and usually presents with motor and cognitive symptoms and signs. A typical bilateral asymmetric pattern in conventional magnetic resonance imaging is present in the majority of the patients. There is no specific therapy for progressive multifocal leukoencephalopathy and it is usually fatal, although outcomes can improve with highly active anti-retroviral therapy. Immune reconstitution inflammatory syndrome is also an important complication related with progressive multifocal leukoencephalopathy, usually associated with anti-retroviral therapy. Progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome presents with different imaging characteristics from progressive multifocal leukoencephalopathy and treatment with steroids can improve survival. Conclusion:The mortality rate and long-term neurological morbidity associated with progressive multifocal leukoencephalopathy are quite high. These data should increase clinician awareness to the occurrence of progressive multifocal leukoencephalopathy among human immunodeficiency virus patients and highlight the important role of magnetic resonance imaging, as early diagnosis may be associated with better outcome.

Sequelae and mortality in patients with HIV/AIDS and Progressive Multifocal Leukoencephalopathy: Systematic review and case series in the Brazilian Amazon

“…In our case series, 72,2% (13/18) were immunosuppressed, 33% (6/18) were severely immunosuppressed (CD4+ < 100 cells/mm3), and 61% (11/18) were on regular ART use. These findings differ little from what has been shown in a series of 20 PML/HIV cases in Portugal, where patients were also suppressed and on irregular use of ART, evidencing a high death rate (81%) (36). Here, a lower death rate was evidenced both in our case series (44%) and in our systematic review (47%).…”

“…It is known that the treatment of HIV patients with continuous ART and obtaining undetectable levels of viral load are good predictors of survival (14,15,39,40). Thus, the therapeutic approach may include initiating ART in untreated patients or optimizing previous ART regimens (36). Some factors were associated with an improved outcome of PML.…”

“…Some factors were associated with an improved outcome of PML. Better chances of survival have been correlated with (i) higher CD4+ cell counts at disease onset, (ii) immunological responsiveness, (iii) particularly an improvement in CD4 lymphocyte counts and (iv) reduced JCV load in the CSF (36,41). Baseline CD4+ count is considered a prognostically significant variable.…”

Multiple sclerosis: Diagnosis and Differrential Diagnosis

“…Motor or cognitive symptoms would arise according to the involved site of the CNS. The characteristic radiological manfestations are bilateral, mostly large, diffuse, asymmetric, supratentorial T2 and FLAIR hyperintense lesions (46,47). Any hematological disease, malignancy, history of chemotherapy, or other immunosuppression, or HIV seropositivity should be questioned.…”

“…Any hematological disease, malignancy, history of chemotherapy, or other immunosuppression, or HIV seropositivity should be questioned. Both radiologically the presence of bilateral widespread large white matter lesions with poor or no contrast enhancement, and clinically the findings of encephalopathy, seizures, aphasia with rapid progression could be the clues for atypical MS features (47).…”