桑原 聡

OBJECTIVES: To elucidate current epidemiological, clinical, and immunological profiles, and the treatment of Isaacs syndrome in Japan. METHODS: We conducted a nationwide survey using established methods. Questionnaires were sent to neurological facilities throughout Japan to identify Isaacs syndrome patients seen between April 2018 and March 2021. RESULTS: The estimated total number of Isaacs syndrome patients was 114 (95 % confidence interval [CI]: 89.63-138.91), and the estimated prevalence was 0.091 per 100,000 population. Detailed clinical data were available for 44 patients. The median age at onset was 40 (range, 17-78 years), and 55 % were female. The median time from symptom onset to diagnosis was 24 months (range, 1-372 months). Electrodiagnostic studies showed evidence of nerve hyperexcitability in 90 % (myokymic discharges in 50 % and stimulus-induced repetitive discharges in 32 %). Of the 28 patients examined in the cell-based assay, 22 % tested positive (11 % for both leucine-rich glioma-inactivated 1 [LGI1] and contactin-associated protein-like 2 [CASPR2] antibodies and 11 % for LGI1 antibodies only). The median modified Rankin Scale (mRS) score was 2 at diagnosis and 1.5 at the last visit. A high mRS score (mRS ≥4) at baseline was an independent risk factor for poor outcomes (mRS ≥3) (Odds ratio, 20.7; 95 % CI, 2.90-209.18; p < 0.001). CONCLUSION: We elucidated the current epidemiological and clinical characteristics of Isaacs syndrome in Japan. Isaacs syndrome is a rare neuromuscular disorder. Electrophysiologic abnormalities were frequent, and serum antibodies were not detectable in the majority of patients. A high mRS score before treatment was a risk factor for poor outcomes.

OBJECTIVES: Intrathecal baclofen (ITB) therapy is well documented as an effective treatment option for severe spasticity. Before ITB implantation, trials are conducted to evaluate efficacy, safety, and candidate suitability. While many centers conduct ITB trials, appropriate physical assessment has not been fully established. This study aimed to identify useful physical assessments for ITB trials in spastic paraparesis. MATERIALS AND METHODS: Patients with spasticity who experienced paraplegia for at least 12 months and underwent ITB trials in Chiba University Hospital were included. Physical functions were assessed before ITB administration and 4 hours after ITB injection on each day of the ITB trial. Physical assessments included targeted neurological and musculoskeletal tests (modified Ashworth scale, deep tendon reflexes, clonus, active range of motion, and manual muscle test) and mobility tests (Berg Balance Scale, Timed Up and Go Test [TUG], 10-Meter Walk Test, and step length). RESULTS: A total of 22 patients underwent ITB trials. Among the physical assessments, the Modified Ashworth Scale, reflexes, clonus, active range of motion at hip abduction and ankle dorsiflexion, TUG, and step length showed significant differences between the assessments conducted before and during ITB trials. Conversely, active range of motion in most joints, the manual muscle test, and the 10-Meter Walk Test did not show significant differences. The total score of the Berg Balance Scale did not show significant differences, whereas only the item of "placing alternate foot on stool" was significantly different. CONCLUSIONS: Spasticity assessments, including the Modified Ashworth Scale and reflexes, and mobility assessments such as TUG and step length, were useful for detecting the effectiveness of ITB screening for spastic paraparesis. The TUG may be particularly suitable for detecting effects, as it is a quantitative and reliable measure that reflects actual movement in daily living activities.

OBJECTIVES: This study aimed to investigate cerebrospinal fluid (CSF) adenosine deaminase (ADA) levels in various neurological disorders and examine the relationships between CSF ADA levels and immunological parameters. METHODS: Overall, 276 patients whose CSF ADA levels were measured for suspected tuberculous meningitis (TBM) were evaluated. Data on baseline characteristics, final diagnoses, CSF ADA levels, and other laboratory parameters were collected. Thereafter, CSF ADA levels were compared based on final diagnoses, and correlations between CSF ADA levels and other CSF and blood laboratory parameters were evaluated. RESULTS: Five diseases exhibited a significant increase in CSF ADA levels relative to the noninflammatory disease control group (n = 40): (1) TBM (n = 15, p < 0.0001), (2) fungal meningitis (n = 7, p = 0.0400), (3) autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A, n = 7, p < 0.0001), (4) neurosarcoidosis (n = 7, p = 0.0028), and (5) lymphoproliferative disorders (n = 18, p = 0.0001). Strong positive correlations were observed between CSF ADA and CSF parameters, including soluble IL2 receptor (rs = 0.7566, p < 0.0001), albumin (rs = 0.6693, p < 0.0001), lactate dehydrogenase (rs = 0.6452, p < 0.0001), white blood cell count (rs = 0.6035, p < 0.0001), protein (rs = 0.6334, p < 0.0001), and lymphocytes (rs = 0.5954, p < 0.0001). DISCUSSION: CSF ADA levels were elevated in various inflammatory neurological diseases, especially in TBM, fungal meningitis, GFAP-A, neurosarcoidosis, and lymphoproliferative disorders. CSF ADA levels may reflect T-cell hyperactivation in the central nervous system.