New type of encephalomyelitis responsive to trimethoprim/sulfamethoxazole treatment in Japan.

OBJECTIVE: To determine the causative pathogen and investigate the effective treatment of a new type of encephalomyelitis with an unknown pathogen in Japan and report the preliminary ultrastructural and genomic characterization of the causative agent. METHODS: From 2005 to 2012, we treated 4 Japanese patients with geographic clustering and comparable clinical features, serum/CSF cytology, and radiologic findings. Brain biopsy was conducted in all patients to analyze neuropathologic changes by histology, and electron microscopy was applied to reveal the features of the putative pathogen. Genomic DNA was obtained from the affected brain tissues and CSF, and an unbiased high-throughput sequencing approach was used to screen for specific genomic sequences indicative of the pathogen origin. RESULTS: All patients exhibited progressive dementia with involuntary tongue movements. Cytologic examination of CSF revealed elevated mononuclear cells. Abnormal MRI signals were observed in temporal lobes, subcortical white matter, and spinal cord. Biopsied brain tissue exhibited aggregated periodic acid-Schiff-positive macrophages and 2-7 µm diameter round/oval bodies without nuclei or cell walls scattered around the vessels. Unbiased high-throughput sequencing identified more than 100 archaea-specific DNA fragments. All patients were responsive to trimethoprim/sulfamethoxazole (TMP-SMX) plus corticosteroid therapy. CONCLUSIONS: We report 4 cases of encephalomyelitis due to an unknown pathogen. On the basis of ultrastructural and genomic studies, we propose a new disease entity resulting from a causative pathogen having archaeal features. TMP-SMX therapy was effective against this new type of encephalomyelitis.

[A case of Lyme neuroborreliosis coexistent with T-cell lymphoma].

An 80-year-old Japanese man developed sensory disturbance of his extremities. One week after the onset of sensory disturbance, he also developed bilateral facial nerve palsy, weakness of the extremities, vesicorectal disturbance, general fatigue, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). His symptoms worsened gradually. Despite the absence of apparent tick bite and characteristic skin lesions, we suspected Lyme neuroborreliosis (LNB) because of pleocytosis and elevated protein levels in the cerebrospinal fluid (CSF), in addition to the aforementioned symptoms. After combined administration of antibiotics and steroids, his symptoms improved rapidly. CSF showed highly elevated levels of the chemokine CXCL-13 and his serum was positive for IgM against Borrelia afzelii. Therefore, we diagnosed him as having LNB. He developed an exacerbation of SIADH and generalized fatigue during the course of LNB. His condition deteriorated despite further administration of antibiotics and steroids. Bone marrow aspiration revealed the presence of medium- to large-sized atypical lymphoma cells and lymphoma cells positive for CD8 but negative for CD45. Therefore, we diagnosed T-cell lymphoma. In recent years, an association between Borrelial infection and lymphoma development has been suspected. Borrelia afzelii infection may have been involved in the development of T-cell lymphoma in this case.

Comparative electrophysiological study of response to botulinum toxin type B in Japanese and Caucasians.

Ethnic differences in the muscle-relaxing effect of botulinum toxin type B (BTX-B) were examined by means of electrophysiological measurements in Japanese and Caucasian volunteers. This was a randomized, single-blinded, single-center study of 24 Japanese and 24 Caucasian healthy adult male subjects in Japan. BTX-B (20 U, 100 U, or 500 U/0.2 mL) or placebo was administered to the extensor digitorum brevis (EDB) muscle in the left lower limb as a single dose (in each dose group, 6 subjects received the test drug and two received placebo). The inhibitory effect of BTX-B on the M wave amplitude of EDB muscle generated by stimulation of the deep peroneal nerve was measured frequently during 2 weeks after administration, and then at weeks 4 (day 28) and 12 (day 84). The inhibitory effect of BTX-B on the M wave amplitude of EDB muscle was dose-dependent in both Japanese and Caucasian subjects, and the dose-response curves were similar. These findings demonstrate that the muscle-relaxing effect of BTX-B in Japanese subjects is electrophysiologically similar to that in Caucasians.