蓄積症モデル動物としての運動神経変性マウス : レクチン結合性による蓄積物質についての検討

取得学位：博士(医学), 学位授与番号：医博乙第1461号，学位授与年月日：平成10年9月16日,学位授与年：199

Reversible cortical lesions in primary Sjögren\u27s syndrome presenting with meningoencephalitis as an initial manifestation

金沢大学医学部附属病院放射線部We report a 50-year-old woman with primary Sjögren\u27s syndrome (SjS) who initially showed forgetfulness, and later developed disturbance of consciousness. In addition to aseptic meningoencephalitis revealed by cerebrospinal fluid examination and magnetic resonance imaging (MRI), the presence of serum anti-SS-A and anti-SS-B antibodies and inflammatory findings in lip biopsy indicated primary SjS. Fluid attenuated inversion recovery (FLAIR) of MRI revealed well defined small, high signal intensity areas in the cortex involving the subcortical white matter. Corticosteroid therapy resulted in rapid and nearly complete resolution of the cortical lesions with marked improvement of the clinical manifestations. Memory disturbance is a rare initial manifestation in meningoencephalitis associated with SjS. Our patient with SjS showed inflammatory cortical lesions on MRI, which were reversed by corticosteroid therapy. © 2005 Elsevier B.V. All rights reserved

Phenotypic heterogeneity in a family with FAP due to a TTR Leu58Arg mutation: A clinicopathologic study

金沢大学医学部附属病院神経内科A family with familial amyloid polyneuropathy (FAP) due to a transthyretin (TTR) Leu58Arg mutation was investigated clinicopathologically. The proband presented with sensorimotor-autonomic polyneuropathy and autopsy demonstrated massive amyloid deposition in the peripheral nerves and heart. However, the mother was characterized by carpal tunnel syndrome and ocular vitreous opacities. Thus, there was considerable phenotypic heterogeneity among family members despite the identical TTR genotype. © 2007 Elsevier B.V. All rights reserved

発症早期ALS患者に対する超高用量メチルコバラミンの有効性・安全性について : ランダム化比較試験

Importance: Post hoc analysis in a phase 2/3 trial indicated ultra-high dose methylcobalamin slowed decline of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score at week 16 as well as at week 182, without increase of adverse events, in patients with amyotrophic lateral sclerosis (ALS) who were enrolled within 1 year from onset. Objective: To validate the efficacy and safety of ultra-high dose methylcobalamin for patients with ALS enrolled within 1 year of onset. Design: A multicenter, placebo-controlled, double-blind, randomized phase 3 trial with 12-week observation and 16-week randomized period, conducted from October 2017 to September 2019. Setting: Twenty-five neurology centers in Japan. Participants: Patients 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 ALSFRS-R total score, a percent forced vital capacity over 60%, no history of noninvasive respiratory support and tracheostomy, and being ambulant. The target number was 64 in both methylcobalamin and placebo groups. Of 203 patients enrolled in the observation, 130 patients (age, 61.0 ± 11.7 years; female, 56) met the criteria and were randomly assigned through an electronic web-response system to methylcobalamin or placebo (65 for each). Of these, 129 patients were eligible for the full analysis set, and 126 completed the double-blind stage. Interventions: Intramuscular injection of methylcobalamin 50 mg or placebo twice weekly for 16 weeks. Main outcomes and measures: The primary endpoint was change in ALSFRS-R total score from baseline to week 16 in the full analysis set. Results: The least-squares mean difference in ALSFRS-R total score at week 16 of the randomized period was 1.97 points greater with methylcobalamin than placebo (−2.66 versus −4.63; 95% CI, 0.44–3.50; P = 0.012). The incidence of adverse events was similar between the two groups. Conclusions and relevance: Ultra-high dose methylcobalamin was efficacious in slowing functional decline and safe in the 16-week treatment period in ALS patients in the early stage and with moderate progression rate. Trial registration: UMIN-CTR Identifier: UMIN000029588 (umin.ac.jp/ctr); ClinicalTrials.gov Identifier: NCT03548311 (clinicaltrials.gov

Hereditary inclusion body myopathy with a novel mutation in the GNE gene associated with proximal leg weakness and necrotizing myopathy [10]

金沢大学医学部附属病院神経内科全文公開20080