Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder in which dysphagia progressively worsens over time. We report a 70-year-old man with MSA who had previously undergone laryngeal suspension and tracheostomy, allowing continued oral intake while preserving phonation. However, disease progression led to recurrent aspiration pneumonia, severe secretion retention, and transient ventilatory dependence. Reassessment revealed severe saliva pooling, silent aspiration, impaired laryngeal sensation, and upper esophageal sphincter (UES) dysfunction on high-resolution manometry. Given the patient's frailty, colonization with extended-spectrum beta-lactamase-producing organisms, and strong desire to resume oral intake, subglottic laryngeal closure combined with bilateral cricopharyngeal myotomy was performed through a minimally invasive surgical field. Postoperatively, aspiration was successfully prevented, UES opening improved, and partial oral intake was resumed without recurrent aspiration pneumonia. This case highlights the importance of individualized and stage-specific surgical decision-making for severe dysphagia in progressive neurodegenerative disease.

Magnetoencephalography (MEG) inverse problem is a method that estimates neural currents from the magnetic field measured outside the head, which is essentially used in the diagnosis of epilepsy. Although a single equivalent current dipole (ECD) fitting is usually used in clinical practice, the localization result is incorrect if multiple foci and/or background activities exist other than epileptic discharges. In this paper, we propose a heterogeneous source model that combines two models to distinguish multiple foci from the background activities: one model expresses the localized and multiple foci using Poisson wavelets mapped from a sphere to a cortical surface, and the other model consists of the elemental dipoles on a mesh grid for the background activities. We applied the proposed method to clinical data from an epilepsy patient and showed that multiple sites with spatial extent and temporal changes of the current moments can be stably identified.

BACKGROUND:Dual antiplatelet therapy (DAPT) is more effective than aspirin alone in preventing early recurrences of non-cardioembolic strokes. In Japan, DAPT is often combined with argatroban, a direct thrombin inhibitor, for treating acute atherosclerotic stroke. However, the safety and effectiveness of this combination compared with those of DAPT alone remains unclear. METHODS:We identified patients with acute atherothrombotic stroke treated with DAPT between April 2016 and March 2022, using the Diagnostic Procedure Combination database, a large national inpatient database in Japan. Patients were divided into two groups: those receiving DAPT plus argatroban and those receiving DAPT alone. We compared 7-day mortality, hemorrhagic complications, and readmission for stroke recurrence within 90 days between the groups using propensity-score overlap weighting analyses. RESULTS:Of 59,983 eligible patients, 47,213 received DAPT plus argatroban, while 12,770 received DAPT alone. In the propensity-score overlap weighting analyses, no significant differences in 7-day mortality (0.2% vs 0.2%; adjusted risk ratio [aRR], 0.77; 95% confidence interval [CI], 0.49-1.21), the proportions of hemorrhagic complications (2.3% vs 2.1%; aRR, 1.12; 95% CI, 0.99-1.27), or 90-day readmission for stroke recurrence (1.2% vs 1.2%; aRR, 0.99; 95%CI, 0.84-1.17) were observed between the DAPT plus argatroban and DAPT alone groups. CONCLUSIONS:The outcomes did not differ significantly between DAPT alone and argatroban combined with DAPT for acute atherothrombotic stroke.

Background:Gait-induced seizures are a rare manifestation of reflex epilepsy. Pathophysiology of this phenomenon has not been fully understood. Case presentation:A 28-year-old woman presented with a long history of "falls" following paroxysmal bilateral leg stiffness triggered by walking. Scalp electroencephalogram (EEG) revealed low-amplitude rhythmic beta activity, maximal at the Cz electrode, during these events. Magnetoencephalography demonstrated repetitive sharp waves source-localized to the right primary motor cortex. Multiple anti-seizure medications failed to improve her symptoms; however, the clinical manifestation was consistent with epilepsy with gait-induced seizures. Intracranial subdural EEG recording was performed and confirmed ictal activity originating from the right supplementary motor area. Resection of this area resulted in complete resolution of her symptoms. Discussion:This is the first reported case of successful resective surgery for epilepsy with gait-induced seizure. Brain networks involving cortical regions responsible for the initiation or execution of walking presumably played a key role in the generation of gait-induced seizures. Careful assessment using non-invasive neurophysiological studies facilitated accurate diagnosis, successful intracranial recordings, and effective resective surgery.

Reading engages complex neural networks integrating visual, phonological, and semantic information. The dual-stream model posits ventral and dorsal pathways for lexical and sublexical processing in the left hemisphere and is well-supported in alphabetic languages. However, its applicability to non-alphabetic scripts remains unclear. The Japanese writing system, comprising Kana (syllabograms) and Kanji (morphograms) with distinct orthographic, phonological, and semantic properties, provides a unique framework to investigate neural dissociation between phonological and orthographic-semantic processing. Previous studies suggest that Kanji relies on the ventral route for whole-word recognition and semantic processing, whereas Kana depends mainly on the dorsal route for phonological decoding via grapheme-to-phoneme conversion; however, their spatiotemporal dynamics remain unknown. Using high-gamma power analysis from electrocorticography recordings in 14 patients with epilepsy and subdural implants, we examined the spatiotemporal neural dynamics of Kana and Kanji reading. Participants completed a visual lexical decision task with Kana and Kanji words and pseudowords. Across 912 electrodes, differential high-gamma power analysis showed that Kanji activated bilateral occipitotemporal fusiform regions early (120-550 ms) and the left inferior temporal gyrus (150-240 ms). Conversely, Kana showed prolonged late activation (270-750 ms) in the left-lateralised superior temporal, supramarginal, and inferior frontal gyri, especially during pseudoword processing. These findings indicate that Kanji relies on bilateral ventral stream earlier, while Kana depends on the left dorsal stream, with slower processing reflecting the extra grapheme-to-phoneme conversion. This underscores the value of non-alphabetic languages in elucidating both universal and script-specific neural mechanisms, advancing a cross-linguistic understanding of the reading network.

This guideline summarizes updated safety data (2017-2025) and provides expert recommendations on the use of low intensity transcranial electrical stimulation (tES) in humans. tES encompasses several techniques including transcranial direct current stimulation (tDCS), oscillatory transcranial direct current stimulation (otDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS), transcranial temporal interference stimulation (tTIS), and their combinations or variations. Across over 300,000 sessions involving healthy individuals, patients with neuropsychiatric conditions, and other clinical populations, no tES-related serious adverse events (AEs) have been reported. Moderate AEs are rare and limited to a small range of specific applications. Mild AEs are common and include transient symptoms such as localized sensations (e.g., tingling or burning), headaches, and fatigue. Similar mild AEs are also reported by individuals receiving placebo stimulation. The frequency, magnitude, and type of AEs are comparable across healthy, clinical, and vulnerable groups, including children, elderly, or pregnant women. Combined interventions (e.g., co-application with EEG, TMS, or neuroimaging) have not shown increased safety risks. Safety is well-established for both bipolar and multichannel tES when applied up to 4 mA and up to 60 min per day. Higher intensities and longer stimulation durations may also be safe. Nevertheless, the number of studies using intensities above 4 mA or stimulating longer than 60 min is low. Home-based use of treatments is growing rapidly, leveraging remote supervision to provide patients with greater access and enable repeated, sustained dosing paradigms. We recommend using screening and AE questionnaires in future controlled studies, in particular when planning to extend the stimulation parameters applied. We discuss recent regulatory and ethical issues.

OBJECTIVES:Transcranial magnetic stimulation (TMS) is used widely to explore human motor function. This study was conducted to investigate the differences between contralateral and ipsilateral cortical control on trunk muscles for eliciting contralateral and ipsilateral motor evoked potentials (MEPs) in the external oblique muscles. METHODS:Twenty healthy participants were examined: 10 younger and 10 older adults. They underwent TMS to locate contralateral and ipsilateral hot spots. For the identified hot spots in the younger group, the coil was positioned in eight orientations, each separated by 45 degrees, to measure active motor threshold (AMT) and onset latencies. RESULTS:Contralateral MEPs were obtained from all participants, whereas ipsilateral MEPs were detected in 14 out of 20 participants. The ipsilateral hot spots were located more laterally from Cz (p < 0.05). Coil orientation that induced an antero-medially directed current in the brain produced the shortest onset latency and lowest AMT for both stimulations. However contralateral MEPs required lower AMT and exhibited shorter onset latency than ipsilateral MEPs (p < 0.05). CONCLUSIONS:Ipsilateral motor pathways of the external oblique muscles have physiological features unlike those of contralateral motor pathways. SIGNIFICANCE:These findings suggest differential cortical control between contralateral and ipsilateral pathways in trunk muscles and provide bases for additional investigations into ipsilateral motor control.

OBJECTIVE:Status epilepticus (SE) is a neurological emergency requiring immediate treatment. Although intravenous lacosamide (LCM) is used for the management of epilepsy, its effectiveness in treating SE remains unclear. We aimed to compare the in-hospital outcomes between intravenous LCM and levetiracetam (LEV) as an early adjunctive therapy for SE using a nationwide inpatient Japanese database. METHODS:We conducted an observational study using data extracted from the Japanese Diagnosis Procedure Combination database. Patients admitted for SE who received intravenous diazepam or lorazepam on the day of admission and were discharged between April 2019 and March 2023 were enrolled. Patients were categorized into those who received intravenous LCM or LEV on the day of admission. We compared the in-hospital outcomes (in-hospital mortality, length of hospital stay, total hospitalization costs, and proportion of patients with a Glasgow Coma Scale score [GCS] ≤9 at discharge) between the groups using propensity score overlap weighting. RESULTS:Among the 4605 eligible patients, 227 received LCM and 4378 received LEV. In the propensity score overlap-weighted cohort, in-hospital mortality (4.0% vs. 4.6%, adjusted risk difference [aRD], -0.28%; 95% confidence interval [CI], -3.3% to 2.7%), length of hospital stay (22.4 vs. 22.3 days; difference, 0.011; 95% CI, -3.9 to 3.9), and total hospitalization costs (1 167 798 JPY vs. 1 177 497 JPY; difference, 9699 JPY; 95% CI, -196 269 to 176 872 JPY) did not differ significantly between the LCM and LEV groups. The proportion of patients with GCS scores ≤9 at discharge was lower in the LCM group than in the LEV group (0.6% and 2.4%; aRD, -2.1%; 95% CI, -3.3% to -0.9%). SIGNIFICANCE:LCM and LEV did not yield significantly different in-hospital mortality rates when used for early adjunctive treatment of SE. However, LCM may reduce poor neurological status at discharge. These results highlight the potential utility of LCM in the early management of SE. PLAIN LANGUAGE SUMMARY:This study compared two intravenous antiseizure medications, levetiracetam (LEV) and lacosamide (LCM), as early add-on therapy for status epilepticus (SE), using data from a large Japanese inpatient database. The in-hospital mortality, length of hospital stay, or total medical costs did not differ significantly between the groups. However, patients treated with LCM had a lower chance of having a poor neurological status at discharge. While LEV is a well-established treatment for SE, this study suggests that LCM may be similarly effective and could offer an advantage, although more research is needed.

INTRODUCTION:Miller Fisher syndrome (MFS) is typically associated with a benign course and spontaneous recovery. However, immunotherapies such as intravenous immunoglobulin (IVIG) and plasma exchange (PE) are often administered for this condition because of the potential for clinical deterioration. We aimed to evaluate the real-world use of immunotherapies in MFS management using a nationwide Japanese database. METHODS:We conducted a retrospective cohort study between April 2014 and March 2020 using the Japanese Diagnosis Procedure Combination database. Patient demographics and treatment modalities were described. Outcomes included length of hospital stay, in-hospital mortality, hospitalization cost, and activities of daily living defined by the Barthel index score. RESULTS:We identified 1,595 patients with MFS. Of these, 999 (62.6%) received immunotherapy (including IVIG for 908 [56.9%] patients, intravenous methylprednisolone for 219 [13.7%] patients, and PE for 18 [1.8%] patients). In patients with and without immunotherapy, the median length of hospital stay was 18 and 12 days, in-hospital mortality was 0.7% and 0.2%, median total hospitalization costs were ¥1,660,200 and ¥549,375, and the proportions of Barthel index score of 95-100 at discharge were 75.3% and 75.2%, respectively. CONCLUSION:Our findings highlight the widespread use of immunotherapies for MFS in Japan despite its generally favorable natural course.

Objective:The technique combining a stent retriever (SR) and contact aspiration (CA) has been widely used in mechanical thrombectomy for acute ischemic stroke. However, advancements in large-bore aspiration catheters suggest that CA alone may achieve comparable therapeutic outcomes, while streamlining the procedure. Nevertheless, real-world evidence directly comparing these approaches is limited. Methods:We identified patients hospitalized for ischemic stroke who underwent mechanical thrombectomy between April 2020 and March 2023 from the Japanese national inpatient Diagnosis Procedure Combination database. Patients treated with CA or CA combined with SR (CA + SR) were enrolled. Propensity score overlap weighting was performed to adjust for confounders. The outcomes were intracranial hemorrhage (ICH), functional independence at discharge, in-hospital mortality, and total hospitalization cost. Results:Among 17589 eligible patients, 14892 underwent CA + SR and 2697 received CA. The adjusted proportions of ICH were comparable between the groups (1.4% vs. 1.3%; adjusted risk difference [aRD], 0.1%; 95% confidence interval [CI], -0.5% to 0.5%). The CA + SR group had a lower proportion of functional independence at discharge (28.7% vs. 36.2%; aRD, -7.5%; 95% CI, -9.5% to -5.4%) and higher in-hospital mortality (11.4% vs. 9.2%; aRD, 2.2%; 95% CI, 1.0%-3.5%). The total hospitalization costs (USD) were higher in the CA + SR group than in the CA group (21687 vs. 18317; difference, 3370; 95% CI, 2976-3764). Conclusions:The proportion of patients with ICH did not differ significantly between the CA + SR group and CA groups. CA + SR was associated with worse functional outcomes, higher in-hospital mortality, and higher costs.

Objective:To investigate precision, accuracy, and reliability of a threshold hunting method to estimate resting motor threshold (RMT) using parameter estimation by sequential testing and maximum likelihood estimation (PEST-MLE). Methods:In 53 healthy participants, single pulse transcranial magnetic stimulation was delivered to estimate RMT with cutoff values of 0.05 mV and 0.2 mV. RMT was inferred from 30-trial PEST-MLE algorithm for at maximum two days with two estimation sessions per day, comprising Sessions 1 to 4. Precision and accuracy were assessed within each session. Repeatability was assessed using intraclass correlation coefficient (ICC), reproducibility coefficient (RC), and standard error of measurement (SEM). Results:For both 0.05 mV and 0.2 mV, 18 trials were needed to have good accuracy. ICC greater than 0.8 was achieved for within-day comparison but the ICC of between-day comparison was lower. RC and SEM were around 10 % and 5 %, respectively. Conclusions:At 18th trial the estimations were converged in terms of precision and accuracy, and good reliability was achieved at that stage. Significance:RMT estimation with the PEST-MLE is a rapid and reliable approach that can be implemented for future clinical and scientific studies.

OBJECTIVES:Infarctions of the posterior limb of the internal capsule (plIC) typically cause contralateral motor deficits. Cases with pure agraphia, writing impairments alone, are rare. We present a case of agraphia as the sole symptom after a small infarction in the anterior portion of the left plIC, which facilitates understanding of the interplay between the subcortical and cortical networks controlling writing. METHODS:This study evaluated a 62-year-old right-handed Japanese man presenting with difficulties in typing and writing. In addition to neuropsychological assessments, diffusion tensor tractography and brain perfusion scintigraphy were used to analyze subcortical-cortical network disruptions. RESULTS:Neuropsychological tests revealed selective agraphia in Kana and Romaji, characterized by phonological errors, but intact Kanji writing. Neuroimaging revealed disrupted neural fibers connecting the thalamus to the superior and middle frontal gyri and mild hypoperfusion in the middle frontal cortex. DISCUSSION:Selective impairment of thalamic radiation projecting to the left frontal cortex due to the plIC infarction can result in pure agraphia. Our findings suggest a specific role of the left anterior plIC in writing Kana and Romaji, specifically in sound-to-letter conversion and postorthographic processes. This case underscores the importance of evaluating writing ability in patients with plIC infarctions to avoid overlooking agraphia.

We have briefly reviewed the transcranial magnetic stimulation (TMS) method, which has been widely used as one of the noninvasive brain stimulation techniques in humans in the field of basic neuroscience or clinical neurology. Four topics are summarized. Basic mechanism of action: Which part of the brain is activated and how it is stimulated are discussed mainly based on the results of motor cortical stimulation in single-pulse TMS. Single-pulse and paired-pulse TMS: Motor cortical (M1) output function is studied with a single-pulse TMS. The M1 excitability changes produced by inputs from within M1 or from other parts of the brain are studied by a paired-pulse TMS. Repetitive TMS (rTMS): The long-term effects induced by rTMS, which continue after the intervention and sometimes are used as treatment, are summarized. Variability, safety, and others: These issues are summarized based on previous works.

In this review, different aspects of the use of clinical neurophysiology techniques for the treatment of movement disorders are addressed. First of all, these techniques can be used to guide neuromodulation techniques or to perform therapeutic neuromodulation as such. Neuromodulation includes invasive techniques based on the surgical implantation of electrodes and a pulse generator, such as deep brain stimulation (DBS) or spinal cord stimulation (SCS) on the one hand, and non-invasive techniques aimed at modulating or even lesioning neural structures by transcranial application. Movement disorders are one of the main areas of indication for the various neuromodulation techniques. This review focuses on the following techniques: DBS, repetitive transcranial magnetic stimulation (rTMS), low-intensity transcranial electrical stimulation, including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), and focused ultrasound (FUS), including high-intensity magnetic resonance-guided FUS (MRgFUS), and pulsed mode low-intensity transcranial FUS stimulation (TUS). The main clinical conditions in which neuromodulation has proven its efficacy are Parkinson’s disease, dystonia, and essential tremor, mainly using DBS or MRgFUS. There is also some evidence for Tourette syndrome (DBS), Huntington’s disease (DBS), cerebellar ataxia (tDCS), and axial signs (SCS) and depression (rTMS) in PD. The development of non-invasive transcranial neuromodulation techniques is limited by the short-term clinical impact of these techniques, especially rTMS, in the context of very chronic diseases. However, at-home use (tDCS) or current advances in the design of closed-loop stimulation (tACS) may open new perspectives for the application of these techniques in patients, favored by their easier use and lower rate of adverse effects compared to invasive or lesioning methods. Finally, this review summarizes the evidence for keeping the use of electromyography to optimize the identification of muscles to be treated with botulinum toxin injection, which is indicated and widely performed for the treatment of various movement disorders.

We have briefly reviewed the transcranial magnetic stimulation (TMS) method, which has been widely used as one of the noninvasive brain stimulation techniques in humans in the field of basic neuroscience or clinical neurology. Four topics are summarized. Basic mechanism of action: Which part of the brain is activated and how it is stimulated are discussed mainly based on the results of motor cortical stimulation in single-pulse TMS. Single-pulse and paired-pulse TMS: Motor cortical (M1) output function is studied with a single-pulse TMS. The M1 excitability changes produced by inputs from within M1 or from other parts of the brain are studied by a paired-pulse TMS. Repetitive TMS (rTMS): The long-term effects induced by rTMS, which continue after the intervention and sometimes are used as treatment, are summarized. Variability, safety, and others: These issues are summarized based on previous works.

A 35-year-old woman with no prior history of epilepsy developed status epilepticus (SE), which was highly resistant to multiple antiseizure medications and sedatives. The etiology of SE was not identified despite extensive investigation, and the patient was diagnosed with cryptogenic new-onset refractory status epilepticus (C-NORSE). Although first-line immunotherapies such as high-dose corticosteroids and plasma exchange were ineffective, the patient manifested a resolution of SE after the administration of tocilizumab, which inhibits interleukin-6. Non-antibody-mediated inflammation has been hypothesized to be a probable pathophysiology of C-NORSE in recent studies, and tocilizumab may be a plausible second-line treatment.

Anti-GM1 antibodies are associated with Guillain-Barr & eacute; syndrome (GBS), primarily peripheral neuropathy. However, there are cases of anti-GM1 IgG antibody-positive GBS with upper motor neuron (UMN) signs. We herein report a case of gastrointestinal infection followed by subacute gait disturbance with predominant signs of UMN on a neurological examination. The serum and cerebrospinal fluid tests were positive for antiGM1 and anti-asialo-GM1 IgG antibodies. An electrophysiological evaluation revealed normal nerve conduction and prolonged central motor conduction times. No MRI abnormalities were observed. The symptoms improved with treatment, which was accompanied by decreased antibody titers. This case highlights the fact that anti-GM1 IgG-associated disorders may present with predominant UMN involvement.

OBJECTIVE:Temporally extended signal space separation (tSSS) is a powerful method for artifact suppression in magnetoencephalography (MEG). Because tSSS first separates MEG signals coming from inside and outside a certain sphere, definition of the sphere origin is important. For this study, we explored the influence of origin choice on tSSS performance in spontaneous and evoked activity from epilepsy patients. METHODS:Interictal epileptiform discharges (IEDs) and somatosensory evoked fields (SEFs) were processed with two tSSSs: one with the default origin of (0, 0, 40 mm) in the head coordinate, and the other with an individual origin estimated using each patient's anatomical magnetic resonance imaging (MRI). Equivalent current dipoles (ECDs) were calculated for the data. The ECD location and quality of estimation were compared across conditions. RESULTS:MEG data from 21 patients revealed marginal differences in ECD location, but the estimation quality inferred from goodness of fit (GOF) and confidence volume (CV) was better for the tSSS with individual origins. This choice affected IEDs more than it affected SEFs. CONCLUSIONS:Individual sphere model resulted in better GOF and CV. SIGNIFICANCE:Application of tSSS using an individual origin would be more desirable when available. This parameter might influence spontaneous activity more strongly.