Kenji Sekiguchi

Introduction/Aims: Fasciculations are a hallmark of amyotrophic lateral sclerosis (ALS), yet quantitative description of individual events on muscle ultrasound (MUS) is limited. We characterized the spatiotemporal kinematics of individual fasciculations to determine whether they differ between ALS and other neurogenic conditions. Methods: We retrospectively analyzed biceps brachii MUS recordings from 680 examinations (January 2020–June 2025), identifying 74 ALS and 40 non‐ALS neurogenic recordings with fasciculations (167 and 62 segments). After propensity score matching for age and muscle strength, 62 matched pairs were analyzed. The Lucas‐Kanade optical flow algorithm, which estimates frame‐to‐frame displacement vectors from local intensity gradients, was applied at 1‐pixel intervals (57,600 points per 240 × 240 region; ≈60 μm) to quantify twitch durations, peak displacement velocity, and directional anisotropy as a measure of spatial movement coherence. Results: ALS fasciculations showed prolonged total duration (582.8 ± 112.8 ms vs. 489.2 ± 128.7 ms, p < 0.001), reduced directional anisotropy (0.534 ± 0.245 vs. 0.627 ± 0.215, p = 0.028), and lower peak displacement velocity (6.55 ± 6.56 vs. 9.53 ± 9.07 μm/ms, p = 0.039). MANOVA showed significant multivariate differences (Pillai's trace = 0.317 ± 0.030, p < 0.001) with moderate group separation (Mahalanobis distance = 1.10 ± 0.05). Discussion: ALS fasciculations showed spatially heterogeneous and temporally prolonged contraction patterns, suggesting motor units in a transitional state of incomplete reinnervation, distinct from the more stable architecture of chronic neurogenic disorders. This framework may complement existing ultrasound assessment and aid the study of motor unit pathology in ALS.

Background: Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP‐A) is an inflammatory neurological disease of the CNS characterized by GFAP antibody positivity. Cognitive impairment is a common feature of this disease; however, its long‐term outcomes remain unclear. Case 1: A 74‐year‐old Japanese man was admitted to our hospital for examination and treatment of progressive cognitive impairment that had developed 9 months before admission. At the time of admission, his FAB score was eight and cerebrospinal fluid (CSF) IgG index was 0.91. The patient tested positive for GFAP antibodies in CSF and was diagnosed with GFAP‐A. Intravenous methylprednisolone (IVMP) was administered 28 days after admission. After treatment, the FAB score improved to 12. However, 117 days after the initial treatment, the cognitive function deteriorated again, requiring another course of IVMP. Despite these treatments, the patient experienced repeated relapses with progressive cognitive decline and brain atrophy. Case 2: A 66‐year‐old man was admitted with cognitive impairment and abnormal behavior that began 60 days prior to admission. His FAB score was six and CSF IgG index was 1.5. After admission, his cognitive function showed slight improvement; however, the CSF IgG index remained high. The diagnosis was confirmed by a positive CSF GFAP antibody test, and IVMP was administered from day 109 after admission. After IVMP treatment, the FAB score improved to 15. Conclusion: In patients with GFAP‐A, delayed treatment initiation may result in irreversible cognitive impairment. GFAP‐A should be included in the differential diagnosis of treatable dementia, and early therapeutic intervention is recommended.

The significance of anti-contactin-associated protein 1 (Caspr1) antibodies in autoimmune nodopathies (ANs) has not been fully established. The aim of this study was to elucidate the clinical profiles of Caspr1 AN. Consecutive serum samples were included from patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) nationwide who were referred to our laboratory for antibody testing with questionnaires as part of routine clinical practice and who fulfilled definite European Federation of Neurological Societies and Peripheral Nerve Society electrodiagnostic criteria. Anti-Caspr1 immunoglobulin (Ig) G was screened using in-house ELISA and confirmed using immunohistochemistry and Western blotting. Clinical data, electrophysiologic findings, and treatment responses were retrospectively collected. The pathologic features of sural nerves were also examined. Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores, antibody titers, and serum neurofilament light chain (NfL) levels were analyzed at baseline and follow-up. Of 559 screened serum samples from patients with CIDP (median age at onset 54 years, 35% female), 19 cases with anti-Caspr1 IgG were identified; the main subclass was IgG4 (17 cases). Patients with IgG4 Caspr1 AN cases exhibited an older age at disease onset (median 67 years); male predominance (82%); high proportions of limb weakness (100%), gait disturbance (100%), tremor (65%), and sensory ataxia (82%); and very high CSF protein levels (249 mg/dL). Nerve conduction studies showed prolonged F-wave and distal motor latencies and reduced sensorimotor conduction velocities in all nerves tested. Light microscopy findings of sural nerve biopsy specimens from 4 patients with Caspr1 AN indicated a loss of myelinated fiber density and myelin ovoids without macrophage-mediated demyelination or onion bulbs. Electron microscopic evaluation demonstrated axo-glial detachment. Patients with IgG4 Caspr1 AN showed a poor response to IVIg (31%) and needed combined immunotherapies. Even after correcting for age, serum NfL levels were higher in patients with IgG4 Caspr1 AN than in healthy controls (p = 0.0609) and correlated with INCAT scores (p = 0.0143). In the 7 patients with 2 consecutive serum samples, antibody titers decreased with clinical improvement. IgG4 Caspr1 AN presents with a similar clinical phenotype to other nodopathies (e.g., neurofascin 155 and contactin 1), but with an older age at onset. Changes in antibody titers may be a potential biomarker for monitoring disease activity.

Background: Sialorrhea, caused by various neurological diseases, impairs patient health and quality of life. After the results of a randomized controlled trial, incobotulinumtoxinA was approved for the treatment of chronic sialorrhea in the United States and Europe; however, no pharmacotherapy has been approved in Japan. Objective: The aim was to evaluate the efficacy and safety of incobotulinumtoxinA treatment for chronic sialorrhea in a single‐arm phase 3 study in Japan. Methods: Patients with chronic sialorrhea caused by neurological diseases (Parkinson's disease, atypical parkinsonism, and stroke, group A) and broader diseases (eg, muscular dystrophy and amyotrophic lateral sclerosis, group B) were enrolled. IncobotulinumtoxinA 100 U was injected into the salivary glands once every 16 weeks for 48 weeks. A primary endpoint was assessed in group A, whereas secondary endpoints and safety were assessed in both groups. Results: From November 2021 to August 2023, 92 patients (58 and 34 in groups A and B, respectively) received incobotulinumtoxinA at 28 institutions. The primary endpoint, the least square mean (standard error) of change in unstimulated salivary flow rate from baseline to 4 weeks, was −0.08 (0.009, 95% confidence interval [CI]: −0.10, −0.06) g/min, achieving the prespecified efficacy criteria (upper limit of the 95% CI <−0.04). The secondary endpoints were consistent across efficacy measures, indicating that reduced salivary secretion and improved drooling symptoms persisted for 48 weeks. The most common adverse events were dry mouth and dysphagia. Conclusions: The first study in Japan confirmed the efficacy of incobotulinumtoxinA treatment for chronic sialorrhea with good patient tolerability and no new safety concerns.

Background: Although neurology department ward rounds are among the most important medical education exercises in Japan, they have several issues. Patients may find it unpleasant to undergo repeated neurological tests, especially when in the presence of several students. Only the front row of students can closely observe the examination findings; moreover, students were prohibited from contacting patients altogether during the COVID-19 pandemic. One possible solution is to use commercial videoconferencing systems. However, Japanese patients are reluctant to have their medical information or video footage of them sent outside of the hospital via the internet. Objective: The study aimed to confirm the feasibility of conducting remote teaching rounds using an in-house web conferencing system in which the patients’ personal data are securely protected. This study also explored whether using remote rounds alongside face-to-face participation would enhance learning. Methods: We created an on-premises videoconferencing system using an open-source app. To perform video ward rounds, the professor wore a wireless microphone while leading routine in-person rounds and the attending physician carried a tablet device linked to a web conference, allowing students in another room to watch the rounds on a live stream. In total, 112 of 5th-year students who entered their 1-week neurology rotation between 2021 and 2022 were instructed to participate in 1-hour in-person and remote rounds. Students were given questionnaires to evaluate their satisfaction and the educational effects of the remote rounds. Results: The remote ward rounds were conducted easily with no interference with the in-person rounds, nor any complaints from the patients. Each examination technique was explained by another teacher to the students who participated in remote rounds in the conference room. Characteristic neurological findings, such as plantar reflexes (Babinski sign), which are usually seen only by close observers during in-person rounds, could be visualized under magnification by all students. The postexperience survey (82/112, 73% response rate) showed that the mean score of participants’ satisfaction was 3.94 (SD 0.83; excellent 5 and poor 1). No participant scoring 1 was noted. The proportion of students who observed 6 representative abnormal neurological findings (Babinski sign, hyperreflexia, cerebellar ataxia, involuntary movement, muscular weakness, and abnormality in sensory examination) increased by 22% (18/82, range 13-24) compared to in-person rounds alone. When self-rating the learning value, 43% (35/82) of the students answered that remote rounds are equally as valuable as in-person rounds, while 32% (26/82) preferred remote rounds. Conclusions: Live-streaming of neurology ward rounds using a secure in-house web conferencing system provides additional learning experience without concerns regarding leakage of patient information. This initiative could enhance neurology learning before entering a clinical clerkship.

[This corrects the article DOI: 10.3389/fneur.2023.1259887.].