We report herein the case of a 37-year-old man who developed probable progressive multifocal leukoencephalopathy (PML) following an umbilical cord blood transplant. The patient showed favorable clinical, neuroradiological and virological responses after treatment with mefloquine, an anti-malarial drug. Mefloquine may offer some benefits as a treatment for PML in patients with or without human immunodeficiency virus type-1 infection. This report highlights the need to gather sufficient data to confirm the efficacy of mefloquine against this devastating viral disease of the central nervous system.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease in the central nervous system caused by a ubiquitous human polyomavirus designated as JC virus (JCV). PML affects individuals with decreased immune competence and is now one of the common opportunistic infections in patients with AIDS. JCV DNAs in the brain of PML patients contain various PML-type regulatory regions that were generated from the archetypal regulatory region during persistence. Recently, many studies have suggested that detection of JCV DNA from the cerebrospinal fluid (CSF) may offer a tool for diagnosing PML. However, in all of these studies, coding sequences within the T antigen or capsid protein gene have been targeted for amplification. To amplify the JCV regulatory region, we established a nested PCR that could efficiently amplify the regulatory region from most JCV subtypes prevalent in the world. Using this PCR, we amplified JCV regulatory regions from the CSF samples from 4 patients strongly suspected of PML, whereas amplification was negative from 80 CSF samples from patients without PML. Sequencing of the amplified fragments revealed that they had unique deletions and/or duplications. Furthermore, in 3 PML patients, we analyzed the structures of regulatory regions derived from the brain as well as CSF. In each of these cases, the major regulatory sequence of both origins were identical. This finding indicates that JCV DNA in brain lesions is excreted in the CSF. Since the structures of PML-type JCV regulatory regions are unique to individual patients, the current PCR, if the amplified fragments are sequenced, can eliminate false positives that may arise from contaminations.

Progressive multifocal leukoencephalopathy (PML) is caused by JC polyomavirus (JCV) infection in the brain. JCV isolates from PML patients have variable mutations in the non-coding control region (NCCR) of the genome. This study was conducted to examine sequential changes in NCCR patterns of JCV isolates obtained from the cerebrospinal fluid (CSF) of PML patients. CSF specimens were collected from PML patients at different time points, the NCCR sequences were determined, and their compositions were assessed by computer-based analysis. In patients showing a marked increase in JCV load, the most frequent NCCR sequences in the follow-up specimens were different from those in the initial samples. In contrast, the dominant NCCRs in the CSF remained unaltered during the follow-up of individuals in whom the viral load decreased after therapeutic intervention. These data demonstrate that the majority of JCV variants emerge with the progression of PML and that these changes are suppressed when the viral load is decreased.

A 75-year-old man with hyperlipidemia suddenly presented with difficulty in lifting his left arm, despite the lack of shoulder pain. Moderate weakness restricted to the left shoulder with normal joint flexibility was observed, despite normal muscle strength in the elbow, wrist and fingers. There were no other neurologic abnormalities. Shoulder magnetic resonance imaging (MRI) findings were normal. Cranial MRI (Picture 1A, B: diffusion-weighted image, Picture 1C, D: T2-weighted image) demonstrated a small infarction in the right precentral gyrus (arrow). Electrocardiogram, echocardiogram, and carotid ultrasonography demonstrated normal findings. Because atherothrombosis was considered, intravenous ozagrel sodium was initiated. Thereafter, he became asymptomatic within 10 days.In the primary motor cortex, there is a broad somatotopic representation of the different body parts in an arranged order, and the area corresponding to the shoulder is very small. Therefore, to date there are only 2 reported cases of isolated shoulder palsy due to a cortical infarction detected by diffusion-weighted MRI (1, 2). The authors state that they have no Conflict of Interest (COI). References1. Nah HU, Park HK, Kang DW. Isolated shoulder weakness due to a small cortical infarction.

A 71-year-old man with hyperlipidemia abruptly developed left-sided isolated shoulder palsy. Cranial magnetic resonance imaging demonstrated infarction of the cortical branch of the right middle cerebral artery (MCA). In the primary motor cortex, there is broad somatotopic representation of various body parts in a particular arrangement, and the area corresponding to the shoulder is very small. Consequently, there have been only 3 reported cases of isolated shoulder palsy due to cerebral infarction, and its vascular supply remains uncertain. The present case indicates that the corresponding area to the shoulder receives its blood from the cortical branch of the MCA.