桑原 聡

BACKGROUND: Acute intermittent porphyria (AIP) is a rare but treatable disease. COVID-19 has various possible complications including posterior reversible encephalopathy syndrome (PRES). COVID-19 was reported to trigger an acute attack in patients with acute hepatic porphyria (AHP). The pathophysiology of AHP-associated PRES is not fully elucidated. CASE PRESENTATION: A 31-year-old Vietnamese female initially presented with seizures, severe hyponatremia, and hypertension after COVID-19. Despite the initial treatment, she had recurrent seizures and developed PRES as confirmed by magnetic resonance imaging. Further investigations revealed a genetic mutation of c.517 C > T in HMBS, leading to a diagnosis of AHP. Treatment with hemin significantly improved her symptoms and corrected her electrolyte imbalance. CONCLUSIONS: This case highlights the potential for COVID-19 to trigger acute attacks in patients with underlying porphyria, potentially leading to complications such as PRES. Also, we observed elevated catecholamine levels during an acute porphyria attack and PRES, suggesting their involvement in the pathogenesis of AIP-associated PRES. Clinicians should consider the possibility of porphyria in patients with COVID-19-associated PRES, especially when they present with gastrointestinal and neuropsychiatric symptoms.

Rigidity, a cardinal symptom of Parkinson's disease (PD), remains challenging to assess objectively. A torque-angle instrument was developed to quantify muscle tone, providing two parameters: bias difference and elastic coefficient. This study aimed to investigate the association of the instrument-measured rigidity with clinical assessments and brain function. In 30 patients with PD, the muscle tone in both arms was evaluated. Ten with wearing-off phenomenon were assessed twice, off and on condition. Twentynine patients underwent brain perfusion single-photon emission computed tomography (SPECT), and expression of PD-related covariance pattern (PDRP) was computed. Bias difference and elastic coefficient showed positive correlations with physician-rated rigidity (P < 0.002). Bias difference decreased after dopaminergic medication (P = 0.022) and was associated with lower body mass index (P = 0.012). Elastic coefficient positively correlated with the Unified PD Rating Scale Part III and PDRP scores (P < 0.044). Furthermore, the higher bias difference correlated with decreased sensory-motor cortex and increased substantia nigra perfusion (P < 0.001). The Torque-angle instrument is a viable tool for quantifying rigidity in PD. The bias difference reflects treatment responsiveness and is associated with the function in the sensory-motor cortex and substantia nigra. The elastic coefficient is indicative of overall Parkinsonism severity.

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.