Progressive Multifocal Leukoencephalopathy with Balanced CD4/CD8 T-Cell Infiltration and Good Response to Mefloquine Treatment

Abstract

A 53-year-old man was admitted for sub-acute progressive dementia and Gerstmann syndrome. MRI demonstrated lesions in the white matter involving the left parietal lobe, accompanied by speckled or faint linear peripheral enhancement. Brain biopsy revealed JC virus infection in oligodendrocytes and balanced infiltration of CD8+ and CD4+ T lymphocytes. We diagnosed progressive multifocal leukoencephalopathy (PML) with controlled inflammation. The finding of CD4/CD8 T cells in the infected PML brain suggested therapeutically valuable immune system involvement, which we decided to preserve by withholding corticosteroids. We treated the patient with risperidone, cytarabine and mefloquine to suppress virus replication, but not with the corticosteroid that is conventionally used in inflammatory PML cases. The patient was discharged three months after admission, and one year later, his score on the Mini-Mental State Examination had recovered to 26/30, from 5/30 on admission.

Inflammatory Cerebellar PML with a CD4/CD8 Ratio of 2.9 Showed a Favorable Prognosis in a Patient with Rheumatoid Arthritis

“…In the post-mortem brain, fatal PML-IRIS is characterized by excessive CD8 + T-cell infiltration without CD4 + T-cells, even with the clearance of JCV antigen (5-7). In contrast, in biopsied cases, pathological examinations revealed T-cell infiltration with a well-balanced CD4/CD8 ratio in the presence of plasma cells (8). Quantitative polymerase chain reaction (qPCR) detects a relatively low, but distinct, JCV titer.…”

The Use of Antimalarial Drugs against Viral Infection

“…Again, the outcome was variable, and the contribution of the single drugs was difficult to determine [118,119]. Lack of differences: study ended prematurely [129] MQ has also been combined with risperidone [75] or risperidone and cytarabine [120], and the final outcomes were opposing, either death or recovery of the patient.…”

“…Herpesviridae HCMV Artesunate [12,13,[46][47][48] Artesunate-amodiaquine [49] Arthemeter-lumefantrine [64] HHV6 Artesunate [52] Polyomaviridae JCPyV Artesunate [54,55] Mefloquine [72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][122][123][124][125][126] Mefloquine and mirtazapine [86,87,127,128] Mefloquine, mirtazapine and a third drug [118,119] Mefloquine and risperidone [75] Mefloquine, risperidone and cytarabine [120] Mefloquine and cidofovir [121] Mefloquine and PML standard of care [129] Filoviridae EBOV Artesunate-amodiaquine [58,60] Nevertheless, some drugs have already been used in several clinical trials, as summarized in Table 1. Most of them regard the use of antimalarial drugs against HIV infection, but some of them failed, and...…”

<p>Progressive Multifocal Leukoencephalopathy: Current Insights</p>

“…Two types of inflammation have been reported in PML: fatal IRIS type and anti-JCPyV immunoreaction type. The latter is associated with good prognosis 86…”