ID: 36428088
Title: Modified Erasmus GBS Respiratory Insufficiency Score: a simplified clinical tool to predict the risk of mechanical ventilation in Guillain-Barré syndrome.
Abstract: This study aimed to determine the clinical and diagnostic factors associated with mechanical ventilation (MV) in Guillain-Barré syndrome (GBS) and to simplify the existing Erasmus GBS Respiratory Insufficiency Score (EGRIS) for predicting the risk of MV. Data from the first 1500 patients included in the prospective International GBS Outcome Study (IGOS) were used. Patients were included across five continents. Patients <6 years and patients from Bangladesh were excluded. Univariable logistic and multivariable Cox regression were used to determine which prespecified clinical and diagnostic characteristics were associated with MV and to predict the risk of MV at multiple time points during disease course. 1133 (76%) patients met the study criteria. Independent predictors of MV were a shorter time from onset of weakness until admission, the presence of bulbar palsy and weakness of neck flexion and hip flexion. The modified EGRIS (mEGRIS) was based on these factors and accurately predicts the risk of MV with an area under the curve (AUC) of 0.84 (0.80-0.88). We internally validated the model within the full IGOS cohort and within separate regional subgroups, which showed AUC values of 0.83 (0.81-0.88) and 0.85 (0.72-0.98), respectively. The mEGRIS is a simple and accurate tool for predicting the risk of MV in GBS. Compared with the original model, the mEGRIS requires less information for predictions with equal accuracy, can be used to predict MV at multiple time points and is also applicable in less severely affected patients and GBS variants. Model performance was consistent across different regions.

ID: 37512077
Title: An Analysis of Respiratory Muscle Paralysis of Adult Patients in Guillain-Barré Syndrome: A Retrospective Analysis.
Abstract: Respiratory muscle paralysis is known as a very common complication of Guillain-Barré syndrome (GBS). However, most research has focused on its later stages rather than its earlier stages, including the prognosis of patients with this condition, or factors that act as early predictors of risk. Therefore, our study aimed to identify early predictors of respiratory muscle paralysis in patients with GBS and determine the short-term prognosis of such patients. We recruited 455 GBS patients (age ≥ 18) who had been hospitalized in the First Affiliated Hospital of Harbin Medical University between 2016 and 2021, retrospectively. We recorded clinical and laboratory data and used linear and logistic regression analysis to investigate the relationship between early clinical, examination results, and subsequent respiratory muscle paralysis. Among the 455 patients, 129 were assigned to a respiratory muscle paralysis group and 326 were assigned to a non-respiratory muscle paralysis group. Compared with the non-affected group, the time from onset to admission was shorter (p = 0.0003), and the Medical Research Council (MRC) score at admission and discharge was smaller in the affected group (p < 0.0001). Compared with the non-affected group, the affected group had higher Hughes and Erasmus GBS Respiratory Insufficiency Score (EGRIS) scores at admission and longer hospital stays (p < 0.0001). Patients in the affected group were more likely to have bulbar palsy and lung infections (p < 0.0001). To conclude, bulbar palsy, a higher EGRIS score and Hughes score at admission, a lower MRC score, and a shorter time between onset and admission, are all predictive risk factors for respiratory muscle paralysis in patients with GBS. An increase in any of these factors increases the risk of muscle paralysis. Patients with respiratory muscle paralysis have a poorer short-term prognosis than those without respiratory muscle paralysis. Therefore, we should attempt to identify patients with one or more of these characteristics in the early stages of admission, provide ventilation management, and administer IMV treatment if necessary.

ID: 38511308
Title: Effect of Intermittent Oro-Esophageal Tube Feeding in Bulbar Palsy After Ischemic Stroke: A Randomized Controlled Study.
Abstract: Nasogastric tube feeding (NG) has been widely used in patients with bulbar palsy after ischemic stroke but is associated with a significant risk of complications including malnutrition and pneumonia. Intermittent oro-esophageal tube feeding (IOE) can help alleviate these concerns. This study explored the clinical effect of IOE versus NG on nutritional status, swallowing function, stroke-associated pneumonia, and depression in patients with bulbar palsy after ischemic stroke. This randomized controlled study included 148 patients with bulbar palsy after ischemic stroke who underwent routine treatment and swallowing rehabilitation training in the Department of Rehabilitation Medicine between July 2017 and July 2019 in China. The participants were randomly divided into the IOE group (n=74) and NG group (n=74) with IOE and NG as nutritional supports, respectively. The primary outcome was nutritional status including (1) body mass index (kg/m2), (2) serum ALB (albumin, g/L), and (3) PA (prealbumin, mg/L). The secondary outcomes were (1) swallowing function including (i) Functional Oral Intake Scale (FOIS) and (ii) Penetration-Aspiration Scale, (2) pneumonia, (3) depression, and (4) adverse events. Statistical analyses for continuous outcomes were performed using t test, Mann-Whitney U test and Wilcoxon signed-rank test and categorical variables using χ2 test. SPSS 21.0 was used for all analysis. There were no significant baseline differences between the 2 groups. After the treatment, the IOE group demonstrated significantly better results compared with the NG group in ALB ([32.71±0.94] versus [32.28±0.81] g/L; P=0.003), PA ([278.15±13.81] versus [270.31±15.08] mg/L; P=0.001], body mass index ([19.77±1.03] versus [19.41±0.98] kg/m2; P=0.002], FOIS (P<0.001), Penetration-Aspiration Scale (P<0.001), stroke-associated pneumonia ([1, 4.05%] versus [26, 35.14%]; P<0.001), depression ([1, 1.35%] versus [44, 59.46%]; P<0.001) and overall less adverse events (reflux, fever, discomfort in the throat; P<0.001). In patients with dysphagia with bulbar palsy after ischemic stroke who received routine treatment and swallowing rehabilitation training, IOE is safer and more conducive to the improvement of nutritional status, swallowing function, stroke-associated pneumonia, and depression than NG. URL: https://www.chictr.org.cn; Unique identifier: ChiCTR-INC-17011741.

ID: 38522911
Title: The clinical practice guideline for the management of amyotrophic lateral sclerosis in Japan-update 2023.
Abstract: Amyotrophic lateral sclerosis (ALS) is an adult-onset intractable motor neuron disease characterized by selective degeneration of cortical neurons in the frontotemporal lobe and motor neurons in the brainstem and spinal cord. Impairment of these neural networks causes progressive muscle atrophy and weakness that spreads throughout the body, resulting in life-threatening bulbar palsy and respiratory muscle paralysis. However, no therapeutic strategy has yet been established to halt ALS progression. Although evidence for clinical practice in ALS remains insufficient, novel research findings have steadily accumulated in recent years. To provide updated evidence-based or expert consensus recommendations for the diagnosis and management of ALS, the ALS Clinical Practice Guideline Development Committee, approved by the Japanese Society of Neurology, revised and published the Japanese clinical practice guidelines for the management of ALS in 2023. In this guideline, disease-modifying therapies that have accumulated evidence from randomized controlled trials were defined as "Clinical Questions," in which the level of evidence was determined by systematic reviews. In contrast, "Questions and Answers" were defined as issues of clinically important but insufficient evidence, according to reports of a small number of cases, observational studies, and expert opinions. Based on a literature search performed in February 2022, recommendations were reached by consensus, determined by an independent panel, reviewed by external reviewers, and submitted for public comments by Japanese Society of Neurology members before publication. In this article, we summarize the revised Japanese guidelines for ALS, highlighting the regional and cultural diversity of care processes and decision-making. The guidelines cover a broad range of essential topics such as etiology, diagnostic criteria, disease monitoring and treatments, management of symptoms, respiration, rehabilitation, nutrition, metabolism, patient instructions, and various types of care support. We believe that this summary will help improve the daily clinical practice for individuals living with ALS and their caregivers.

ID: 38536565
Title: AI-assisted automatic MRI-based tongue volume evaluation in motor neuron disease (MND).
Abstract: Motor neuron disease (MND) causes damage to the upper and lower motor neurons including the motor cranial nerves, the latter resulting in bulbar involvement with atrophy of the tongue muscle. To measure tongue atrophy, an operator independent automatic segmentation of the tongue is crucial. The aim of this study was to apply convolutional neural network (CNN) to MRI data in order to determine the volume of the tongue. A single triplanar CNN of U-Net architecture trained on axial, coronal, and sagittal planes was used for the segmentation of the tongue in MRI scans of the head. The 3D volumes were processed slice-wise across the three orientations and the predictions were merged using different voting strategies. This approach was developed using MRI datasets from 20 patients with 'classical' spinal amyotrophic lateral sclerosis (ALS) and 20 healthy controls and, in a pilot study, applied to the tongue volume quantification to 19 controls and 19 ALS patients with the variant progressive bulbar palsy (PBP). Consensus models with softmax averaging and majority voting achieved highest segmentation accuracy and outperformed predictions on single orientations and consensus models with union and unanimous voting. At the group level, reduction in tongue volume was not observed in classical spinal ALS, but was significant in the PBP group, as compared to controls. Utilizing single U-Net trained on three orthogonal orientations with consequent merging of respective orientations in an optimized consensus model reduces the number of erroneous detections and improves the segmentation of the tongue. The CNN-based automatic segmentation allows for accurate quantification of the tongue volumes in all subjects. The application to the ALS variant PBP showed significant reduction of the tongue volume in these patients and opens the way for unbiased future longitudinal studies in diseases affecting tongue volume.

ID: 40413968
Title: Clinical and electrophysiological characteristics and blood markers for short-term prognosis prediction in severe Guillain-Barré syndrome: a retrospective cohort study.
Abstract: This study aimed to investigate the clinical, electrophysiological characteristics and blood inflammatory markers in severe Guillain-Barré syndrome (GBS) and their correlation with short-term prognosis. Data from 95 patients with severe GBS were classified into two groups based on the Hughes functional grading scale (HFGS) on day 28: those with poor prognosis (>3) and those with prognosis (≤3). Clinical characteristics, nerve conduction studies and blood parameters were compared at admission between the two groups. Logistic regression analysis identified predictive factors for GBS, and receiver operating characteristic (ROC) curves were used to evaluate the predictive efficacy. A nomogram model combining these predictive factors was constructed and evaluated using ROC and calibration curves and Hosmer⁃Lemeshow goodness-of-fit test. The poor prognosis group exhibited bulbar paralysis and an elevated modified Erasmus GBS Outcome Score (mEGOS) (P < 0.05). Nerve conduction studies revealed increased numbers of inexcitable motor nerves (IMN) in the poor prognosis group. Blood analysis showed significantly elevated neutrophil-to-lymphocyte ratio (NLR) during acute disease stage (P < 0.05) compared with the good prognosis group. ROC curve analysis indicated that mEGOS, NLR value, IMN number, and their combination had area under the curve (AUC) values of 0.818, 0.757, 0.870, and 0.947, with sensitivities of 78.4 %, 76.5 %, 75.0 %, and 92.2 %, and specificities of 77.3 %, 77.3 %, 61.3 %, and 86.4 % respectively, for short-term prognosis prediction. The nomogram model demonstrated an area under the ROC curve of 0.990, reflecting good potential clinical effect. The calibration curve showed good agreement between actual observations and nomogram predictions. The findings indicate that early assessment of the occurrence of bulbar palsy, mEGOS, IMN numbers, and NLR value can predict poor prognosis, with their combination providing improved accuracy for short-term prognosis in patients with severe GBS.

ID: 40567532
Title: West Nile neuroinvasive disease with poliomyelitis syndrome: A grave phenomenon.
Abstract: West Nile virus infection poses a significant threat, especially during the warmer months when mosquitoes are abundant. Clinicians must remain vigilant for neuroinvasive illness in patients presenting with febrile symptoms and malaise following mosquito exposure. While magnetic resonance imaging and cerebrospinal fluid analysis aid in differential diagnosis, detecting West Nile immunoglobulin M in serum is crucial for definitive diagnosis. Treatment primarily involves supportive care due to the absence of established regimens, though promising outcomes have been reported with plasma exchange and intravenous immunoglobulin. We present the case of an 83-year-old resident of Alabama, an avid gardener living near a pond, who initially exhibited symptoms of productive cough, diarrhea, fever, and generalized malaise. However, within 48 h, he developed hypoxemia, functional quadriplegia, and bulbar palsy necessitating intubation. Diagnostic evaluations, including magnetic resonance imaging and positive West Nile virus immunoglobulin M in serum, confirmed West Nile virus-associated poliomyelitis viral syndrome, prompting intravenous immunoglobulin therapy. This case highlights the importance of promptly identifying and managing West Nile virus infection, especially in regions susceptible to mosquito-borne diseases, and being vigilant of the disease in non-endemic regions. The case also begs the question of the timing and efficacy of intravenous immunoglobulin and plasma exchange in West Nile virus infection and the fact that more data should be collected on these therapies.

ID: 40701363
Title: Syringobulbia and Syringomyelia Associated with Intramedullary Ependymoma.
Abstract: No cases of bulbar palsy secondary to hemorrhage from intramedullary ependymoma into the peritumoral cavity have been reported. A 23-year-old man presented with persistent hiccups, pneumonia, and progressively worsening respiratory dysfunction. Clinical course and imaging findings raised strongly suggested bulbar palsy from a C4-5 intramedullary hemorrhagic lesion. Computed tomography and magnetic resonance imaging of the brain and cervical spine revealed an intramedullary mass at C4-5, accompanied by syringobulbia and syringomyelia, with signals extending from the lower medulla oblongata to the T1 spinal level. The patient underwent laminectomy, myelotomy, and microsurgical mass excision with intraoperative neurophysiological monitoring. Postoperative pathology confirmed the lesion as an ependymoma. Neurologic function improved steadily after surgery. Thus, central respiratory dysfunction should be considered in patients with severe pneumonia without underlying disease. Additionally, contrast-enhanced magnetic resonance imaging is essential for differential diagnosis in bulbar palsy cases.

ID: 40802071
Title: Biallelic variants in DNAJC7 cause familial amyotrophic lateral sclerosis with the TDP-43 pathology.
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. ALS pathology primarily involves the failure of protein quality control mechanisms, leading to the accumulation of misfolded proteins, particularly TAR DNA-binding protein 43 (TDP-43). TDP-43 aggregation is a central pathological feature of ALS. Maintaining protein homeostasis is critical and facilitated by heat shock proteins (HSPs), particularly the HSP40 family, which includes co-chaperones such as DNAJC7. Here, we report a family with three siblings affected by ALS who carry a homozygous c.518dupC frameshift variant in DNAJC7, a member of the HSP40 family. All three patients exhibited progressive muscle weakness, limb atrophy, bulbar palsy, and respiratory failure. Pathological examination revealed degeneration of both upper and lower motor neurons, with phosphorylated TDP-43-positive neuronal cytoplasmic inclusions in the frontal and temporal cortices. Immunoblot analysis were consistent with a type B pattern of phosphorylated TDP-43 in the precentral gyrus. Immunohistochemistry and RNA sequencing analyses demonstrated a substantial reduction in DNAJC7 expression at both the protein and RNA levels in affected brain regions. In a TDP-43 cell model, DNAJC7 knockdown impaired the disassembly of TDP-43 following arsenite-induced stress, whereas DNAJC7 overexpression suppressed the assembly and promoted the disassembly of arsenite-induced TDP-43 condensates. Furthermore, in a zebrafish ALS model, dnajc7 knockdown resulted in increased TDP-43 aggregation in motor neurons and reduced survival. To the best of our knowledge, this study provides the first evidence linking biallelic loss-of-function variants in DNAJC7 to familial ALS with TDP-43 pathology.

ID: 40957031
Title: Intrathecal Baclofen to Improve Functional Status in ALS: A Case Report.
Abstract: Intrathecal pumps are well known to benefit patients with chronic pain as well as spasticity. Intrathecal baclofen (ITB) can offer doses 100-1000 times smaller with similar efficacy, compared to oral baclofen. Only 2 previous reports detailed improvement in functional status after patients with amyotrophic lateral sclerosis (ALS) received ITB. Our patient presented with progressive bulbar palsy, further progressing to ALS. His lower extremity spasticity and tremors continued to progress over 3 years despite increased baclofen. At the time of implant, he expressed whole body tremors and spasticity to bilateral lower extremities, complicated by falls. Prior to the trial, the patient ambulated 50 feet. ITB was started at a rate of 100 mcg/day. After the implant, the patient's ambulation distance increased to 100 feet. The patient and his wife reported resolution of his tremors and improvement in spasticity. This report details the functional improvement obtained from ITB in a patient with ALS.

ID: 41004918
Title: Tongue shear wave elastography for bulbar dysfunction in amyotrophic lateral sclerosis.
Abstract: Amyotrophic lateral sclerosis (ALS) often manifests with tongue involvement, leading to dysarthria and dysphagia. While current diagnostic methods are invasive or qualitative, the development of non-invasive quantitative assessments of tongue function is essential. A prospective study (March 2022 - March 2024) included 38 ALS patients (categorized by bulbar or spinal onset) and 12 controls. Clinical symptoms were evaluated using the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). Tongue muscle elasticity was measured using shear wave elastography (LOGIQ® E9, 9 MHz). Median shear modulus of the genioglossus (GG) muscle was significantly lower in bulbar-onset ALS (7.80 kPa, range 5.41-10.08) compared to spinal-onset ALS (12.48 kPa, range 8.50-21.42) and controls (14.16 kPa, range 11.37-20.21). The geniohyoid (GH) muscle showed similar patterns. Both muscles showed significantly reduced elasticity in bulbar-onset ALS compared to controls (p < 0.05). The GG muscle elasticity showed strong positive correlation with bulbar symptom severity on the ALSFRS-R. Reduced tongue muscle elasticity in bulbar-onset ALS, along with its correlation with bulbar symptoms, suggests the potential utility of this technique for both diagnosis and prognosis. These findings indicate that shear wave elastography is a promising noninvasive tool for the quantitative assessment of tongue dysfunction in ALS.

ID: 41063391
Title: Familial ALS With p. L127S (L126S) Variant of the Cu/Zn SOD1 Gene: A Report of Two New Cases and Literature Review.
Abstract: Herein, we report two autopsy cases of familial ALS with a p. L127S (L126S) SOD1 variant. Case 1 involved a 62-year-old woman who presented with lower-extremity muscle weakness with lower motor neuron signs. The patient developed bulbar palsy and died of respiratory failure 9 years after onset. Case 2 (the second son of Case 1) presented with lower-extremity muscle weakness at the age of 38 years, with upper and lower motor neuron signs and died of respiratory failure 8 years after onset. The pathological findings in both cases predominantly consisted of lower motor neuron loss and degeneration of the lateral and posterior funiculi. Numerous conglomerate hyaline inclusions (CHIs) were observed in the remaining motor neurons. Vacuole formation was observed inside the inclusions, sometimes with granular structures. Some inclusions were positive for ubiquitin, p62, and SOD1. Electron microscopy revealed that CHIs were composed of neurofilaments and expanded mitochondria. By literature review, ALS with p. L127S disclosed a male-dominant incidence rate, a variety of ages at onset, and low penetrance. The initial symptom was exclusively lower limb weakness. One-third of the patients only showed lower motor neuron signs and half did not present with bulbar symptoms. The neuropathological findings commonly observed in ALS with p. L127S variants were mainly the degeneration of lower motor neurons and the sensory system, including the posterior column, Clarke's nucleus, and the associated cerebellar system. The formation of intracytoplasmic hyaline inclusions was also a prominent feature. ALS with p. L127S variant should be included in the possible diagnosis of slowly progressive muscle weakness in the lower extremities, with or without family history or upper motor neuron signs. The loss of lower motor neurons and the accumulation of neurofilaments in the remaining neurons are key to the pathological diagnosis for ALS with p. L127S variant.

ID: 41090254
Title: A Case of Miller-Fisher Overlap Syndrome With Positive Anti-GM4 Antibody and Atypical Symptoms.
Abstract: Miller-Fisher syndrome (MFS) is a recognized clinical variant of Guillain-Barré syndrome (GBS), characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia. When accompanied by additional symptoms such as bulbar palsy, limb weakness, or lethargy, it is termed MFS overlap syndrome. This report describes a male patient diagnosed with MFS overlap syndrome, presenting with ophthalmoplegia, ataxia, bulbar palsy, numbness in both arms, positive GM4 IgG antibodies, a persistent, intractable headache, and a delayed onset of left-sided peripheral facial palsy. The patient had a preceding suspected case of chlamydial pneumonia before symptom onset, and his condition improved significantly following treatment with intravenous immunoglobulin. This case suggests that chlamydial pneumonia might predispose individuals to GBS. Patients with MFS/pharyngeal-cervical-brachial (PCB) overlap syndrome may exhibit atypical symptoms, including persistent, intractable headaches, and delayed peripheral facial paralysis. Atypical symptoms should not delay the diagnosis and treatment of GBS once other conditions have been adequately excluded. The presence of anti-GM4 antibodies, often found alongside other anti-ganglioside antibodies, may serve as a critical immunological factor in MFS/PCB overlap syndrome.

ID: 41241894
Title: Rapid Bolus Inflow into the Esophagus in a Patient with a Tracheostomy after Surgical Treatment for Dysphagia.
Abstract: This report describes a case in which a patient with an open tracheostomy, following surgery for severe dysphagia, acquired vacuum swallowing and exhibited rapid bolus inflow into the esophagus. A 39-year-old man with bulbar palsy caused by medullary surgery demonstrated impaired pharyngeal contraction and upper esophageal sphincter opening. After undergoing laryngeal suspension and cricopharyngeal myotomy, videofluoroscopic evaluation of swallowing revealed rapid passage of the bolus from the pharynx into the esophagus. High-resolution manometry demonstrated markedly negative intraesophageal pressure accompanied by simultaneous elevation of lower esophageal sphincter pressure during swallowing. These findings suggest that the patient had spontaneously acquired vacuum swallowing despite the presence of a tracheostoma communicating with the atmosphere. Recognition of this compensatory mechanism is important because it may facilitate bolus transport in individuals with tracheostomy. Increased awareness of this swallowing pattern may prevent underdiagnosis and offer new insights into rehabilitation strategies for dysphagia.

ID: 41366746
Title: Safety and efficacy of botulinum toxin injection for sialorrhea in amyotrophic lateral sclerosis: a systematic review and meta-analysis.
Abstract: INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, with 80% of ALS patients experiencing bulbar weakness at some stage of the disease. ALS patients with bulbar weakness often suffer from troublesome sialorrhea. Botulinum toxin injection, as a neuromuscular blocker, has been widely used in the treatment of sialorrhea. This paper evaluates the safety and efficacy of botulinum toxin injections for the treatment of sialorrhea in ALS patients through a systematic review and meta-analysis. METHODS: A systematic review and meta-analysis was conducted by searching eight databases, including PubMed, EMBASE, and CNKI, up to April 13, 2025. Eligible randomized controlled trials and quasi-experimental studies were analyzed using Review Manager 5.4 and Stata software. RESULTS: Thirteen studies (2 RCTs, 11 quasi-experimental studies) with 130 ALS patients were included. Botulinum toxin significantly reduced sialorrhea and improved quality of life (Z = 10.98, p < 0.00001; RD = 0.82, 95% CI: 0.67–0.97). The treatment effect was independent of toxin type (p = 0.48), injection site (p = 0.17), and ultrasound guidance use (p = 0.44). CONCLUSION: Botulinum toxin appears to be a safe and effective option for managing sialorrhea in ALS patients, regardless of injection technique. However, given that most included studies were observational, further validation through high-quality RCTs is warranted. TRIAL REGISTRATION: This meta-analysis has been registered with Prospero, and the registration number is CRD420251029441. The registration period is April 9, 2025.

ID: 41612234
Title: Clinical profile and predictors of guillain-barre syndrome associated pneumonia: a retrospective cohort study.
Abstract: BACKGROUND: Pneumonia is a serious complication in Guillain-Barre syndrome (GBS) patients, associated with increased mortality, yet its risk factors remain underexplored. METHODS: Our study analyzed clinical factors linked to pneumonia in GBS patients through a retrospective review of 101 individuals admitted to Tianjin Huanhu Hospital between January 2020 and December 2023. Patients were divided into two groups based on pneumonia development after admission: GBS with pneumonia (n = 19) and GBS without pneumonia (n = 82). Clinical and blood parameters were compared between the groups. Logistic regression analysis identified predictive factors for pneumonia in these GBS patients. RESULTS: Significant associations were found between pneumonia and older age (P = 0.01), bulbar palsy (P = 0.017), mechanical ventilation (MV) support (P < 0.01), hypoalbuminemia (P < 0.01), hyponatremia (P < 0.01), and underlying conditions (P = 0.008). Multivariate logistic regression identified bulbar palsy, MV support and hyponatremia as significant independent risk factors for pneumonia. Finally, GBS patients with pneumonia experienced longer hospital stays and worse functional outcomes. CONCLUSIONS: We initially identified key risk factors for pneumonia in GBS, highlighting its association with poorer prognoses.

ID: 41714394
Title: [Motor neuron diseases from a radiological perspective : Focus on amyotrophic lateral sclerosis].
Abstract: Motor neuron diseases (MND) affect the upper and/or lower motor neurons. Radiological diagnostics primarily serve to systematically exclude treatable mimics and support the clinical and electrophysiological diagnosis. The focus is on amyotrophic lateral sclerosis (ALS); supplementary progressive muscular atrophy (PMA, purely lower motor neuron, LMN disease) and spinal muscular atrophy (SMA). Which imaging signs support the diagnosis of ALS, how do electromyography/magnetic resonance imaging (EMG/MRI) fit into the Gold Coast criteria and which other motor neuron diseases are relevant? Overview of clinical criteria (Gold Coast), genetics and typical MRI findings of the brain, spinal cord and musculature. Gold Coast core: progressive motor deterioration, upper motor neuron (UMN) and LMN signs in ≥ 1 region or LMN in ≥ 2 regions and exclusion of alternative causes. susceptibility-weighted imaging (SWI) motor band sign as UMN marker; T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities along the corticospinal tract with low sensitivity, moderate specificity; T1 bright tongue as an indication of chronic denervation in bulbar involvement. EMG: detection of subclinical LMN involvement, sometimes limited in UMN-dominant/bulbar courses. PMA: Pure purely LMN symptoms, often continuum to ALS. SMA: Autosomal autosomal recessive (SMN1 deletion). The diagnosis remains primarily clinical; EMG and MRI are supportive. The radiological priority is the exclusion of mimics. The UMN markers increase diagnostic certainty in the context of clinical/EMG findings but do not replace them. Clear findings facilitate classification according to Gold Coast. The PMA and SMA require careful differential diagnostics; characteristic MRI patterns support progression and treatment planning. HINTERGRUND: Motoneuronerkrankungen (MNE) betreffen das obere (UMN) und/oder untere (LMN) Motoneuron. Die radiologische Diagnostik dient primär dem strukturierten Ausschluss behandelbarer Mimics und der Unterstützung der klinischen und elektrophysiologischen Diagnose. Fokus: amyotrophe Lateralsklerose (ALS); ergänzend progressive Muskelatrophie (PMA) und spinale Muskelatrophie (SMA). Welche bildgebenden Zeichen stützen die ALS-Diagnose, wie ordnen sich Elektromyographie (EMG)/Magnetresonanztomographie (MRT) in die Gold-Coast-Kriterien ein, und welche weiteren MNE sind relevant? Übersicht klinischer Kriterien (Gold-Coast), Genetik und typischer MRT-Befunde von Gehirn, Rückenmark und Muskulatur. Gold-Coast-Kern: progrediente motorische Verschlechterung, UMN- und LMN-Zeichen in ≥ 1 Region oder LMN in ≥ 2 Regionen, Ausschluss alternativer Ursachen. Als Bildgebungsverfahren kommen die MRT („motor-band sign“) in der Suszeptibilitätswichtung (SWI) als UMN-Marker; T2/FLAIR-Hyperintensitäten entlang des kortikospinalen Trakts mit geringer Sensitivität und moderater Spezifität; „T1-Bright-Tongue“ als Hinweis auf chronische Denervation bei bulbärer Beteiligung. EMG: Nachweis subklinischer LMN-Beteiligung, bei UMN-dominanten/bulbären Verläufen teils limitiert. PMA: reine LMN-Symptomatik, häufig Kontinuum zur ALS. SMA: autosomal-rezessiv (SMN1-Deletion). Die Diagnose bleibt primär klinisch; EMG und MRT sind unterstützend. Radiologische Priorität ist der Ausschluss von Mimics. UMN-Marker erhöhen im Kontext von Klinik/EMG die diagnostische Sicherheit, ersetzen diese jedoch nicht. Klare Befundformulierung erleichtern die Zuordnung nach Gold-Coast. PMA und SMA erfordern differenzialdiagnostische Sorgfalt; charakteristische MRT-Muster unterstützen Verlauf und Therapieplanung.

ID: 41782152
Title: Effects of ultrasound-guided stellate ganglion block in poststroke bulbar palsy: a double-blind placebo-controlled trial.
Abstract: Bulbar palsy typically causes severe dysphagia. Based on rehabilitation interventions, stellate ganglion block (SGB) might improve swallowing function by regulating sympathoexcitation and cerebral perfusion. This study explored the short- and long-term effects of SGB on swallowing function, anxiety, and cerebral blood flow in patients with bulbar palsy after ischemic stroke. This randomized double-blind placebo-controlled trial included 124 participants in rehabilitation departments from March 2024 to July 2025 in China. The participants were randomized 1:1 to SGB or placebo groups, and all received routine treatment for 10 consecutive days. The SGB group received SGB with lidocaine hydrochloride, whereas the placebo group received block with normal saline. The primary outcome was the clinical severity of dysphagia. The secondary outcomes were airway protection, forward and upward movement distances of the hyoid bone, accumulation of secretions, pharyngeal residue, anxiety, and mean blood flow velocity (Vm) and internal diameter of the vertebral artery. The Vm and internal diameter were additionally assessed one hour after the first SGB. Repeated measures ANOVA and generalized estimating equations were used to explore time, group, and their interaction effects. There were no significant baseline inter-group differences. After treatment, significant (P < 0.001) interaction effects were observed for dysphagia severity (η2 > 0.06), movement distances of the hyoid bone (η2 > 0.19), airway protection (β = - 0.774), pharyngeal residue (β < - 0.54), accumulation of secretions (β = - 0.371), and anxiety (η2 = 0.462). These effects remained significant at follow-up. After the first SGB, the Vm and internal diameter of the vertebral artery on the SGB side significantly increased (P < 0.001) in the SGB group, but the inter-group differences were non-significant after the intervention period. In patients with bulbar palsy after ischemic stroke who receive routine treatment, SGB is safe and can effectively improve swallowing function, airway protection, and anxiety. The effects of SGB on vertebral artery blood flow are temporary, but the functional impacts are long-term. ClinicalTrials.gov. (Unique identifier: NCT06319534, 20/03/2024).

ID: 41795250
Title: Deciphering the Breathless Future: A Novel Approach to Predicting Respiratory Failure in Children With Guillain-Barré Syndrome.
Abstract: The applicability and utility of clinical predictive models for respiratory failure in the pediatric Guillain-Barré syndrome (GBS) and Asian population are significantly constrained. Therefore, we aim to develop and validate a clinical prediction model to predict respiratory failure risk in pediatric GBS patients in China, alongside the economic immunological biomarkers in decision-making, and evaluate the Erasmus GBS Respiratory Insufficiency Score (EGRIS)-Kids score's efficacy. The retrospective study originated from our pediatric GBS cohort at Children's Hospital of Chongqing Medical University during 2014-2022. We utilized logistic regression to identify predictors and construct a nomogram and web-based dynamic nomogram. The net reclassification index and integrated discriminant improvement index were used to compare models after incorporating new indices, with bootstrapping validation. Our study included 175 children, among which 23 (13%) patients have developed respiratory insufficiency. Variables included in our score were: age (odds ratio [OR] 1.23), bulbar palsy (OR 23.17), bilateral hip flexion (OR 0.75), and platelet-to-lymphocyte ratio (PLR; OR 2.47). The area under the receiver operating characteristic curve of the nomogram was 0.899 (95% confidence interval 0.839-0.960). The calibration plots showed an adequate consistency between the reported and predicted occurrence. The EGRIS-Kids model yielded an area under the receiver operating characteristic curve of 0.849 (95% confidence interval 0.754-0.944) in our cohort and the incorporation of PLR exhibited an incremental value of 12.51% (P = 0.03). We performed the first external validation of the EGRIS-Kids score in Chinese children with GBS. Furthermore, we developed a new predictive model incorporating the PLR, which shows promise and additional value but requires further external validation.

ID: 41820716
Title: Free-hand electrode placement for intraoperative monitoring of extraocular cranial nerves in skull base surgery: preliminary experience and feasibility assessment.
Abstract: Postoperative dysfunction of the oculomotor (CN III) and abducens (CN VI) nerves remains a major determinant of disability after skull base surgery for tumors. This study assessed the feasibility, safety, and diagnostic performance of a surgeon-controlled, free-hand extraocular muscle electrode placement for corticobulbar motor evoked potentials (cb-MEPs) and direct nerve stimulation (DNS). This monocentric, observational, retrospective study enrolled 40 patients scheduled for skull base tumor surgery, with planned intraoperative monitoring of CN III and/or VI. Curved needle electrodes were placed free-hand by the neurosurgeon at the scleral–muscular junction of the medial and/or lateral rectus, and cb-MEPs and DNS were recorded; evaluability required reproducible baselines. Primary endpoint was 3-month cranial nerve palsy. Diagnostic accuracy was calculated, and Spearman correlations tested the relationship between intraoperative percentage amplitude change and postoperative deficit severity. Placement succeeded in all cases (mean 10 min) with one transient conjunctivitis (2.5%). Stable baseline cb-MEPs occurred in 20/37 (CN III) and 18/31 (CN VI). For CN III, cb-MEPs showed sensitivity 66.7% and specificity 100%; amplitude reduction correlated with postoperative severity (ρ = 0.94, p < 0.001). DNS was evaluable in 22/26, with sensitivity 83.3% and specificity 100%. For CN VI, cb-MEPs showed sensitivity 75.0% and specificity 96.8%, with correlation to severity (ρ = 0.88, p < 0.001). DNS elicited responses in 15/22, with sensitivity 75.0% and specificity 100%. This neurosurgeon-performed, free-hand technique enabled rapid, safe, and reproducible electrode placement for extraocular cranial nerve monitoring during skull base surgery. When baselines are obtainable, cb-MEPs and DNS provide highly specific, actionable feedback aligned with postoperative outcomes. These findings support pragmatic adoption and prospective multicenter validation.

ID: 41837970
Title: Safety and Efficacy of PrimeC in Amyotrophic Lateral Sclerosis: The PARADIGM Randomized Clinical Trial.
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. PrimeC is a fixed-dose oral combination of celecoxib and ciprofloxacin designed to target ALS-related mechanisms, including neuroinflammation, iron homeostasis, and dysregulated microRNAs. To evaluate the safety, tolerability, and potential efficacy of PrimeC in people living with ALS. This was a randomized, double-blind, placebo-controlled, phase 2b trial conducted at 4 ALS referral centers from May 2022 to November 2023 and followed by 12-month open-label extension. Adults with definite or probable ALS and disease duration of 30 months or less were eligible. Of 73 screened, 69 were randomized and 68 were included in the intent-to-treat population. Participants were randomized 2:1 to receive PrimeC or placebo for 6 months, followed by open-label extension PrimeC for all. The primary outcome was safety and tolerability. The prespecified primary biomarker outcome was plasma neuron-derived-exosomal TAR DNA-binding protein 43 (TDP-43) or prostaglandinJ2. Secondary outcomes included change in ALS Functional Rating Scale-Revised (ALSFRS-R) score at 6 and 18 months, survival, and time-to-composite events. Exploratory biomarkers included neurofilament light chains, iron-regulatory proteins, and circulating microRNAs. The 68 participants were well balanced in age at entry and sex. In the PrimeC group, the mean (SD) age was 59.1 (9.1) years, and 27 of 45 participants were male. In the placebo group, the mean (SD) age was 55.0 (13.0) years, and 14 of 23 participants were male. PrimeC was well tolerated, with a safety profile comparable to placebo (adverse event rate, 66.7% PrimeC vs 65.2% placebo). Drug-related adverse events were more frequent with PrimeC (20.0% vs 4.3%), mostly mild to moderate, and transient. At month 6, the mean ALSFRS-R difference was 2.23 points between PrimeC and placebo (95% CI, -0.61 to 5.07; P = .12). At month 18, ALSFRS-R scores in participants continuously treated with PrimeC maintained a difference (7.92 points; 95% CI, 2.25 to 13.60; P = .007), with significant bulbar difference (3.18 points; 95% CI, 1.32 to 5.04; P = .001). Continuous treatment was associated with lower risk of ALS complications, including hospitalization, respiratory failure, or death (HR, 0.36; 95% CI, 0.15-0.85; P = .02). In the double-blind period, transferrin levels were preserved with PrimeC (1.90 μmol/L difference; P = .03), the negative ferritin-ALSFRS-R correlation observed in placebo (ρ = -0.50; P = .02) was abolished, and ALS-associated microRNAs were downregulated (log2 fold change: miR-199a-3p, -1.87; false discovery rate [FDR] P = .004; miR-199a-5p, -2.23; FDR P < .001; miR-181a-5p: -1.89; FDR P = .001; miR-181b-5p, -1.62; FDR P = .005). Prespecified neuron-derived exosome TDP-43/PgJ2 analyses will be reported separately following completion of development and analyses. PrimeC was safe and well tolerated over 18 months. Although not powered for efficacy, functional and biomarker findings support a confirmatory trial. ClinicalTrials.gov Identifier: NCT05357950.

ID: 41892827
Title: Biomechanical Voice Parameters as Potential Biomarkers for Phenotype Differentiation in Amyotrophic Lateral Sclerosis: A Cross-Sectional Study.
Abstract: Background/Objectives: Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous neurodegenerative disease in which bulbar involvement frequently affects speech and voice production. Although acoustic voice analysis can detect phonatory alterations in ALS, its ability to differentiate clinical phenotypes remains limited. This study investigated whether biomechanical voice parameters provide complementary information for characterizing bulbar involvement across bulbar-onset ALS (ALS-B) and spinal-onset ALS (ALS-S) and explored their association with clinical and functional measures. Methods: This cross-sectional observational study included 50 patients with ALS (20 ALS-B, 30 ALS-S) and 50 controls with non-neurological voice disorders. Sustained vowel phonation was analyzed using acoustic measures and biomechanical voice parameters derived from a standardized model of vocal fold vibration. Perceptual voice severity was assessed using the GRBAS scale, while functional status was evaluated with the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Barthel Index. Associations with clinical measures were explored in secondary analyses. Results: Compared with controls, ALS patients showed significant differences in acoustic measures and several biomechanical parameters related to glottal closure and vibratory stability. Biomechanical analysis revealed significant differences between ALS-B and ALS-S, particularly in parameters reflecting vibratory asymmetry, glottal tension and cycle-to-cycle instability. Unexpectedly, ALS-B showed greater perceptual voice severity and higher Barthel Index scores than ALS-S, while no differences were observed in global ALSFRS-R total scores. Conclusions: Biomechanical voice analysis appears to capture physiologically meaningful alterations in vocal fold function in ALS and provides complementary information for characterizing bulbar motor involvement across clinical phenotypes, particularly ALS-B disease. When combined with acoustic and clinical assessments, this approach may enhance the evaluation of bulbar involvement and functional status in ALS.

ID: 41994699
Title: Botulinum Toxin Type A as an Early Intervention for Traumatic Oculomotor Nerve Palsy: A Pediatric Case Report.
Abstract: Traumatic third cranial nerve palsy is a rare complication of head injury, with an incidence of approximately 1% and a characteristically poor prognosis. Conventional management remains conservative, often yielding unsatisfactory outcomes. We report the case of a 13-year-old girl who developed complete right third cranial nerve palsy following a 15-meter fall, presenting with exotropia (35Δ), ptosis, complete ophthalmoplegia, and pupillary dysfunction. Brain CT revealed hemorrhage in the right cavernous sinus, and subsequent MRI demonstrated focal nerve damage. Thirty-eight days post-injury, a single botulinum toxin type A (BTX-A) injection (5 units) was administered to the right lateral rectus muscle. Progressive improvement in ocular alignment and motility was observed, with resolution of diplopia by 4.5 months and sustained orthotropia at 10 months post-injury. Although pupillary dilation persisted, functional recovery was substantial. This case demonstrates that early BTX-A intervention may prevent lateral rectus contracture and promote functional recovery in traumatic third cranial nerve palsy. BTX-A represents a promising minimally invasive therapeutic option that warrants further investigation in larger patient populations.

ID: 42040341
Title: Translation of surface electromyography into a clinically applicable objective bulbar assessment tool to improve measurement-based care in amyotrophic laterals sclerosis.
Abstract: This study aims to translate surface electromyography (sEMG) into a clinically applicable, objective tool for assessing bulbar involvement in amyotrophic lateral sclerosis (ALS). A clinically grounded sEMG framework was developed, integrating a standardized, repeatable protocol with a novel analytic pipeline, to automatically extract 60 features from six craniofacial muscle groups during a set of motorically demanding but cognitively and linguistically less challenging oral diadochokinetic (DDK) tasks. Using this framework, 104 oral DDK recordings were acquired from 16 individuals with ALS-nine with overt bulbar symptoms (ALS+B) and seven without (ALS-B)-and 10 healthy controls (HCs). The sEMG features were clustered into 10 interpretable composite measures and validated by evaluating their (1) internal consistency using Cronbach's α ; (2) associations with standardized functional outcomes and a biomechanical metric-stiffness-via mediation analysis; (3) discriminatory efficacy in distinguishing ALS+B and ALS-B from HC, as well as from each other, using machine learning classifications; and (4) robustness to common nonmotor confounders, including age, sex, and cognitive-linguistic impairments, through a comparison of discriminatory performance before and after adjustment for these factors. All composite measures exhibited (1) high internal consistency (Cronbach's α = 0.89 ± 0.071 ), (2) significant (or marginally significant) direct or stiffness-mediated indirect associations with the functional outcomes, and (3) consistently high discriminatory accuracy (0.82-0.85), both before and after adjustment for confounders. The sEMG framework demonstrates strong potential as a reliable, valid, and robust objective tool to detect subclinical neuromuscular changes throughout the prodromal and symptomatic phases of bulbar involvement in ALS, while remaining resistant against disease-related cognitive-linguistic impairments and disease-unrelated confounders. This tool may augment standard clinical evaluations, enabling earlier detection of bulbar involvement and measurement-based care in ALS.

ID: 42078235
Title: Systemic Barium Toxicity Manifesting As Acute Hypokalemic Paralysis and Respiratory Failure Following a Firework Injury.
Abstract: We present the case of a 63-year-old male who sustained a penetrating soft tissue injury to the right thigh from a commercial firework. Following uncomplicated surgical debridement and discharge, the patient returned within hours exhibiting rapidly progressive ascending paralysis, bulbar weakness, and respiratory failure requiring intubation. Laboratory evaluation revealed profound hypokalemia (1.4 mmol/L), hypophosphatemia, and rhabdomyolysis. The clinical presentation, coupled with the patient's report of the firework emitting a green flare, is most consistent with acute barium toxicity. Formal toxicologic confirmation was not available; however, the clinical constellation, mechanism of injury, and rapid response to electrolyte repletion strongly support this diagnosis. Barium salts, commonly used in pyrotechnics to produce green coloration, can induce systemic toxicity by competitively blocking potassium channels, causing a widespread intracellular shift of potassium. This case highlights the rare but life-threatening systemic toxicity associated with soluble barium salts and the importance of considering toxicologic etiologies in trauma patients presenting with unexplained neurological collapse.

ID: 42289571
Title: Multilevel surgical management for severe dysphagia due to lower cranial nerve palsy with multimodal functional assessment: a case report.
Abstract: Lower cranial nerve (LCN) palsy may develop following tumor resection in the cerebellopontine angle or jugular foramen, often resulting in dysphagia and dysphonia. Although many patients recover with rehabilitation, some exhibit persistent functional deficits. In such cases, detailed pathophysiologic evaluation may assist in guiding surgical intervention to improve outcomes. A 77-year-old woman presented with severe dysphagia and hoarseness after resection of a right cerebellopontine angle meningioma, which caused glossopharyngeal, vagus, and accessory nerve palsies. Despite initial recovery, she developed repeated aspiration pneumonia and malnutrition. Comprehensive reassessment using high-resolution manometry (HRM) and dynamic swallowing computed tomography (CT) revealed right-sided velopharyngeal insufficiency, pharyngeal constrictor dysfunction, vocal fold paralysis with paramedian fixation, and impaired upper esophageal sphincter relaxation. A tailored multi-procedural surgical approach was performed, including right pharyngeal flap, arytenoid adduction, right hypopharyngeal pharyngoplasty with expanded polytetrafluoroethylene mesh reinforcement, right cricopharyngeal myotomy, and tracheostomy. Postoperatively, swallowing and phonation significantly improved. The patient resumed oral intake, and tracheostoma closure was performed on postoperative day (POD) 25. Maximum phonation time improved sevenfold by POD 32. She was discharged on POD 33, and resumed a regular diet with some limitations by 3 months postoperatively. Intractable dysphagia due to complex LCN dysfunction requires individualized surgical strategies. Multimodal functional assessment, including dynamic swallowing CT and HRM, aids precise evaluation and helps refine surgical planning in selected complex cases, potentially leading to significant improvements in quality of life.

ID: 42293075
Title: Efficacy observation of electromyography-guided targeted injection of swallowing muscles for treating dysphagia resulting from medullary paralysis.
Abstract: To observe the clinical efficacy of electromyography (EMG)-guided targeted mecobalamin injections for treating dysphagia resulting from medullary paralysis and to investigate effective dysphagia management strategies. This study was a prospective randomized controlled trial. A total of 110 patients with dysphagia due to post-stroke bulbar palsy were enrolled at Baoding No.1 Central Hospital from February 2017 to December 2020. Patients were randomly assigned using a random number table to either a control group (n = 55) receiving conventional pharmacotherapy combined with rehabilitation training, or a treatment group (n = 55) receiving the same conventional therapy plus additional EMG-guided targeted injections of mecobalamin into the swallowing muscles. Swallowing function was assessed using the Wada water swallowing test (WST) and videofluoroscopic swallowing study (VFSS) after 2 weeks of treatment. The treatment group showed a significantly higher overall response rate on the WST than the control group (P < 0.05). Based on VFSS, the marked and overall effectiveness rates were 50.9% and 96.4% in the treatment group, respectively, significantly higher than the corresponding rates of 18.2% and 83.6% in the control group (both P < 0.05). The incidence of aspiration decreased significantly in both groups post-treatment (P < 0.05), with a more pronounced reduction observed in the treatment group (P < 0.05). EMG-guided targeted injection of mecobalamin into swallowing muscles is an effective adjunctive strategy for enhancing swallowing function in patients with dysphagia due to post-stroke medullary paralysis.

ID: 42318512
Title: Efficacy and safety of pyrimidine nucleos(t)ide therapy in thymidine kinase 2 deficiency.
Abstract: Thymidine kinase 2 deficiency (TK2d) (MIM 609560) is an ultra-rare, autosomal recessive mitochondrial myopathy caused by TK2 variants, leading to mitochondrial DNA depletion and/or multiple deletions. People with thymidine kinase 2 deficiency experience progressive myopathy, bulbar weakness and respiratory insufficiency, often losing the ability to walk, eat and breathe independently. Doxecitine and doxribtimine represents the first approved treatment for patients with thymidine kinase 2 deficiency with age of symptom onset ≤12 years by the US Food and Drug Administration and the European Medicines Agency; previously, disease management was limited to supportive care. We investigated the efficacy and safety of pyrimidine nucleos(t)ide therapy in thymidine kinase 2 deficiency. Patients treated with pyrimidine nucleos(t)ides were pooled from retrospective (NCT03701568, NCT05017818) and prospective (NCT03845712) studies and company-supported Expanded Access Programs. Untreated patients were pooled from literature reviews and a retrospective chart review study (NCT05017818). Patient subgroups were stratified by age of thymidine kinase 2 deficiency symptom onset (≤12 years and >12 years). The primary outcome was survival in 50th-percentile matched pairs of treated and untreated patients. Other outcomes included status of developmental motor milestones, ventilatory and feeding tube support, and safety. In total, 218 patients were included (treated: 104; untreated: 114). Baseline demographics and characteristics were comparable between subgroups. Most patients had an age of symptom onset ≤12 years [treated: 82/104 (78.8%); untreated: 93/114 (81.6%)]. In the age-of-symptom-onset-≤12-years subgroup, restricted mean survival time (95% confidence interval) was 29.2 (28.2, 30.3) years over the 30 years after symptom onset for treated patients and 14.4 (11.1, 17.6) years for untreated patients. Loss of ≥1 acquired motor milestone was more frequent before treatment start than after. Substantially more patients regained ≥1 lost motor milestone after treatment start than before. Ventilatory and feeding support were used across all age-of-symptom-onset subgroups, but some patients reduced or discontinued support after starting treatment and fewer patients initiated support after treatment start than before. Most treatment-emergent adverse events (TEAEs) did not lead to discontinuation. The most frequent TEAE was diarrhoea [43/50 patients (86.0%)], which was generally mild or moderate and resolved with dose reduction. Serious TEAEs occurred in 28/50 patients (56.0%); few were considered to be drug related [4/50 (8.0%)]. In total, 3/67 patients (4.5%) experienced a fatal serious TEAE, which were not considered to be drug related. These findings indicate that pyrimidine nucleos(t)ide therapy improves survival and functional outcomes in people with thymidine kinase 2 deficiency, especially those with age of symptom onset ≤12 years, and has an acceptable safety profile.

ID: 42404894
Title: FcRn antagonist and C5 complement inhibitor as early rescue strategies in severe Myasthenia Gravis: a two-case report.
Abstract: Myasthenia gravis (MG) is an autoimmune neuromuscular disorder in which approximately 10-15% of patients with generalized AChR antibody-positive MG develop refractoriness to standard immunosuppressive therapies. Advanced therapeutic strategies, including FcRn antagonists and C5 complement inhibitors, have demonstrated early and sustained clinical efficacy in pivotal phase 3 trials. However, evidence supporting their early use in complex clinical scenarios remains limited. We report two cases of severe generalized MG in which early initiation of advanced therapies was associated with rapid clinical stabilization. In the first case, a 75-year-old man with thymoma-associated MG and severe bulbar involvement refractory (MG-ADL: 11) to plasma exchange (PLEX) and intravenous immunoglobulins (IVIg), and unable to continue azathioprine due to adverse events, received off-label efgartigimod preoperatively. Near-complete resolution of bulbar symptoms was observed within 48 hours, enabling robot-assisted thymectomy on day 4 following the first infusion, with sustained neurological improvement at one-month follow-up (MG-ADL score: 2). In the second case, a 74-year-old man with severe refractory bulbar MG requiring nasogastric tube feeding (MG-ADL: 13) and subsequent percutaneous endoscopic gastrostomy (PEG) was treated with ravulizumab after an incomplete response to PLEX, IVIg, corticosteroids, and azathioprine. MG-ADL decreased from 9 at treatment initiation to 5 after two infusions of ravulizumab, and complete recovery of swallowing function allowed PEG removal at 18-week follow-up, with achievement of minimal symptom expression (MG-ADL score: 0). These cases highlight the potential role of early and targeted use of advanced immunotherapies in severe, refractory MG, including as a bridging strategy to thymectomy. Further prospective studies are needed to define optimal criteria and timing for early integration of these agents into the therapeutic algorithm.