JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML) in patients with decreased immune competence. To elucidate genetic changes in JCPyV associated with the pathogenesis of PML, multiple complete JCPyV DNA clones originating from the brains of three PML cases were established and sequenced. Although unique rearranged control regions occurred in all clones, a low level of nucleotide variation was also found in the coding region. In each case, a parental coding sequence was identified, from which variant coding sequences with nucleotide substitutions would have been generated. A comparison between the parental and variant coding sequences demonstrated that all 12 detected nucleotide substitutions gave rise to amino acid changes. Interestingly, seven of these changes were located in the surface loops of the major capsid protein (VP1). Finally, 16 reported VP1 sequences of PML-type JCPyV (i.e. derived from the brain or cerebrospinal fluid of PML patients) were compared with their genotypic prototypes, generated as consensus sequences of representative archetypal isolates belonging to the same genotypes; 13 VP1 proteins had amino acid changes in the surface loops. In contrast, VP1 proteins from isolates from the urine of immunocompetent and immunosuppressed patients rarely underwent mutations in the VP1 loops. The present findings suggest that PML-type JCPyV frequently undergoes amino acid substitutions in the VP1 loops. These polymorphisms should serve as a new marker for the identification of JCPyV isolates associated with PML. The biological significance of these mutations, however, remains unclear.

Segmental zoster paresis is still underrecognized by neurologists. Awareness of this disorder is important because it may eliminate unnecessary invasive investigations and lead to appropriate treatment. Further studies on the treatment are necessary.

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IMPORTANCEThe effectiveness of currently approved drugs for amyotrophic lateral sclerosis (ALS) is restricted; there is a need to develop further treatments. Initial studies have shown ultrahigh-dose methylcobalamin to be a promising agent.OBJECTIVE To validate the efficacy and safety of ultrahigh-dose methylcobalamin for patients with ALS enrolled within 1 year of onset. DESIGN, SETTING, AND PARTICIPANTSThis was a multicenter, placebo-controlled, double-blind, randomized phase 3 clinical trial with a 12-week observation and 16-week randomized period, conducted from October 17, 2017, to September 30, 2019. Patients were recruited from 25 neurology centers in Japan; those with ALS diagnosed within 1 year of onset by the updated Awaji criteria were initially enrolled. Of those, patients fulfilling the following criteria after 12-week observation were eligible for randomization: 1-or 2-point decrease in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score, a percent forced vital capacity greater than 60%, no history of noninvasive respiratory support and tracheostomy, and being ambulatory. The target participant number was 64 in both the methylcobalamin and placebo groups. Patients were randomly assigned through an electronic web-response system to methylcobalamin or placebo.INTERVENTIONS Intramuscular injection of methylcobalamin (50-mg dose) or placebo twice weekly for 16 weeks. MAIN OUTCOMES AND MEASURESThe primary end point was change in ALSFRS-R total score from baseline to week 16 in the full analysis set.RESULTS A total of 130 patients (mean [SD] age, 61.0 [11.7] years; 74 men [56.9%]) were randomly assigned to methylcobalamin or placebo (65 each). A total of 129 patients were eligible for the full analysis set, and 126 completed the double-blind stage. Of these, 124 patients proceeded to the open-label extended period. The least square means difference in ALSFRS-R total score at week 16 of the randomized period was 1.97 points greater with methylcobalamin than placebo (−2.66 vs −4.63; 95% CI, 0.44-3.50; P = .01). The incidence of adverse events was similar between the 2 groups.CONCLUSIONS AND RELEVANCE Results of this randomized clinical trial showed that ultrahigh-dose methylcobalamin was efficacious in slowing functional decline in patients with early-stage ALS and with moderate progression rate and was safe to use during the 16-week treatment period.

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In neuro-Behcet's disease (NBD)

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We herein report the rare case of a 56-year-old man who suffered from heat stroke. Although he was in a coma with convulsions on arrival and developed multiorgan failure, he recovered after two weeks of successful treatments. Hyperintense signals on the right temporoparietooccipital cortex, which disappeared within one week, were demonstrated on diffusion-weighted magnetic resonance images. A diagnosis of transient cortical injury caused by heat stroke was suggested. Although the cerebellum is most susceptible to lesion formation, the mechanisms underlying heat stroke are multifactorial and may result in a variety of brain lesions.