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Abstract Background The syndrome defined by cerebellar ataxia, neuropathy, and vestibular areflexia (CANVAS) has been previously described as a cause of late-onset ataxia. With the discovery of biallelic expansion in the replication factor C subunit 1 (RFC1) gene as its underlying genetic cause, this syndrome and the broader gene disease became more clinically heterogeneous and one of the most common genetic causes of ataxia in adults. Objective To characterize the phenotypic spectrum of RFC1 expansion using a multidisciplinary approach combining neurological, otoneurological, and neuroimaging assessments. Methods A retrospective cohort study comprising patients with a genetically confirmed diagnosis of biallelic RFC1 repeat expansions was conducted. Data related to neurological examination, video head impulse test (vHIT), caloric tests, posturography, electromyography/nerve conduction studies and brain magnetic resonance imaging (MRI) were considered. Results We included 15 patients, of whom 10 (66.7%) presented with the complete clinical triad. At neurological examination, 13 patients showed signs of peripheral neuropathy. Cerebellar dysfunction was observed in 12, whereas postural instability was seen in 11. Electromyography/nervous conduction studies revealed peripheral neuropathy in all of the cases, while bilateral vestibular dysfunction was confirmed in approximately half of them. The mean balance values from the posturography were lower in the majority (n = 14). In the imaging assessment (n = 11), 6 patients displayed significant vermian atrophy, predominantly in the anterior/dorsal regions, while the other 5 patients showed moderate atrophy. Conclusion This study underscores the clinical importance of comprehensive phenotyping and multimodal diagnostic approaches—including neurological, otoneurological, electrophysiological, and imaging assessments—in enhancing diagnostic precision, especially when neurological examination findings are inconclusive or in atypical/incomplete clinical presentations.

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Abstract Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to progressive muscle weakness and paralysis. Approximately 10% of ALS cases are familial (FALS), with the VAPB gene's P56S pathogenic variant being notably prevalent in Brazilian families, contributing to the rare ALS8. This variant progresses more slowly than typical ALS, with distinct clinical features. Objective To identify VAPB gene pathogenic variants in Brazilian FALS patients, particularly the P56S pathogenic variant associated with ALS8 and explore its clinical presentation and progression. Methods Twelve FALS patients from 12 unrelated families in Rio de Janeiro were included in the study between 2023 and 2024. Clinical, laboratory, and electrophysiological data were reviewed. Collection of DNA samples happened via oral swabs, and VAPB gene sequencing was performed to identify pathogenic variants, specifically the P56S variant linked to ALS8. Results There were 3 cases of the P56S pathogenic variant, all presenting ALS8 with symptom onset in the lower limbs and slower disease progression. A family with 11 affected members across four generations showed an autosomal dominant inheritance pattern, with varying survival rates, highlighting its clinical variability. Conclusion The present study underscores the importance of genetic screening for ALS subtypes, particularly ALS8, in Brazil. Identifying the P56S pathogenic variant enhances our understanding of ALS's genetic diversity and clinical presentation, offering a foundation for improved diagnostic practices and personalized care.

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Abstract Background Stroke is a major cause of mortality and disability globally. Dysphagia is a frequent complication that increases the risk of aspiration pneumonia, a key contributor to stroke-related deaths. Early screening is essential for improving outcomes. Objective To identify clinical indicators that can help prioritize swallowing assessments in the emergency room, enabling faster and safer resumption of oral feeding. Methods A prospective cohort of 134 postacute ischemic stroke patients admitted to the emergency room was assessed. Patients were divided into 2 groups: G1 (at risk of dysphagia) and G2 (no risk). Swallowing function was evaluated using the Dysphagia Risk Evaluation Protocol (DREP) and the American Speech-Language-Hearing Association National Outcomes Measurement System (ASHA-NOMS) scale. A subset (n = 15) underwent videofluoroscopic swallowing study (VFSS). Stroke severity was measured using the National Institutes of Health (NIH) stroke scale (NIHSS). Statistical analyses included t-tests, Chi-squared test, Pearson's correlation, and Cochran's Q test (p < 0.05). Results Patients from G1 were older (mean: 69.1 vs. 63.0 years, p = 0.023), had more severe strokes (NIHSS ≥ 9.8, p = 0.002), and were more likely to require alternative feeding methods. Older age and longer hospital stays correlated with increased dysphagia risk. Coughing during the 50-ml water swallow test was a strong predictor of aspiration. Conclusion Key indicators of aspiration risk in postacute ischemic stroke patients include age ≥ 69, NIHSS score ≥ 9, and the need for alternative feeding. Coughing during the water swallow test is a valuable clinical predictor. Early identification can support targeted interventions and reduce complications.

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Abstract Background Timely identification of large-vessel occlusion (LVO) in ischemic stroke is essential for optimizing prehospital triage and enabling rapid mobilization of thrombectomy-capable teams. Traditional LVO screening tools are often lengthy and reliant on neurological examination skills that may be inaccessible to nonspecialists. Objective To assess the ability of large language models (LLMs) to detect LVO using only free-text summaries, with or without National Institutes of Health Stroke Scale (NIHSS) data, in a national teleneurology service. Methods We conducted a retrospective analysis of 2,887 suspected stroke cases across 21 spoke hospitals within a national TeleStroke network. Neurologist-authored case summaries were processed using natural language processing techniques, including text embedding and supervised machine learning classification. Contextual LLMs (BERTimbau, BioBERTpt, GPorTuguese-2) were evaluated with five algorithms. The Bootstrap method was employed to mitigate class imbalance, with performance averaging over 100 iterations. Results Of 1,060 cases included in the final dataset, 143 had confirmed proximal occlusions. Median Alberta Stroke Program Early CT Score (ASPECTS) was 9 and mean National Institutes of Health Stroke Scale (NIHSS) was 5.4 ± 2. AdaBoost paired with BioBERT yielded the highest accuracy (89.82%), precision (98.37%), and AUC (89.86%). Incorporating NIHSS as a numerical feature improved recall (87.60% with multilayer perceptron) and F1-score (89.05% with Dense Neural Network). BioBERT consistently outperformed other models, regardless of NIHSS inclusion. Conclusion The LLM-based models demonstrated strong performance in identifying LVO using routine clinical narratives. These findings support the integration of NLP and ML in TeleStroke systems and underscore the need for further validation across larger, multilingual datasets to ensure generalizability and clinical applicability.

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Abstract Background Pituitary macroadenomas (PMAs) are frequently encountered tumors, predominantly characterized as soft and easily resectable during neurosurgery. In contrast, fibrous PMAs present difficulties during surgical removal. Therefore, the ability to predict the consistency of PMAs preoperatively could enhance surgical planning. Objective To evaluate the ability of conventional T2-weighted imaging (T2WI) to predict PMA consistency by comparing isolated tumor signal intensity with the adenoma-to-middle cerebellar peduncle (ACP) ratio. Methods Magnetic resonance imaging (MRI) scans from 45 patients with PMAs were independently reviewed by 3 blinded radiologists. For each case, the signal intensity (SI) of the adenoma and of the middle cerebellar peduncle was measured, and the ACP ratio (SIadenoma/SIpeduncle) was calculated. Tumor consistency (soft or fibrous) was determined intraoperatively by a single neurosurgeon. Results Intraoperative assessment classified 29 PMAs (64.4%) as soft and 16 (35.6%) as fibrous. Isolated adenoma SI on T2WI differed significantly between soft and fibrous tumors (p = 0.013), while the ACP ratio demonstrated stronger discriminatory power (p < 0.0001). The receiver operating characteristic (ROC) curve yielded an area under the curve of 0.939 for the ACP ratio. Threshold values > 1.59 were highly predictive of soft tumors (sensitivity 72.4%; specificity 100.0%), whereas values < 1.27 were associated with fibrous tumors (sensitivity 100.0%; specificity 37.5%). Conclusion Although isolated adenoma SI on T2WI showed statistical significance, it was not sufficient for consistent preoperative prediction of tumor consistency. The ACP ratio provided superior accuracy and clinical utility, supporting its role as a noninvasive imaging biomarker to enhance preoperative assessment and surgical planning in patients with pituitary macroadenomas.

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Abstract Background Cisplatin, a potent platinum-based chemotherapeutic, effectively treats various cancers. However, it is limited by cisplatin-induced peripheral neuropathy (CIPN), driven by oxidative stress and neuroinflammation. Objective The present study investigates the neuroprotective potential of Taraxacum officinale L. leaf extract (TOE), rich in polyphenols such as luteolin and quercetin, known for their antioxidant and antiinflammatory properties. Methods Molecular docking of 10 polyphenols against NF-κB1 revealed that luteolin and quercetin outperform synthetic inhibitors, forming strong interactions with key residues. These compounds exhibited favorable pharmacokinetics, including high gastrointestinal absorption and nontoxicity. The CIPN was induced in male Wistar albino mice (3 mg/kg cisplatin, i.p., weekly for 5 weeks), with TOE (500 mg/kg, intragastric, daily) or saline administered concurrently. A TOE-only group served as a control. Behavioral assessments (rotarod, hot plate, cold plate, tail flick) evaluated sensory and motor function, while biochemical assays measured antioxidant enzymes (CAT, GPx1, SOD2), oxidative stress markers (MDA, TOS, IMA), and proinflammatory cytokines (NF-κB, TNF-α, IL-6) in serum and sciatic nerve tissues. Results Cisplatin induced significant behavioral deficits, reduced antioxidant capacity, and elevated oxidative and inflammatory markers. The TOE significantly ameliorated these effects, restoring behavior, enhancing antioxidant status, and reducing inflammation, consistent with the in silico predictions of NF-κB1 inhibition. Conclusion These findings highlight T. officinale as a promising, safe, complementary therapy for CIPN, warranting further clinical exploration.

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Abstract Background Migraine is a common neurological disorder associated with an increased risk of cardiovascular conditions, including arrhythmias. Although autonomic dysfunction is considered a key mechanism linking migraine and cardiac abnormalities, its impact during pain-free intervals remains unclear. Objective To investigate the association between migraine and cardiac arrhythmias, focusing on the prevalence of premature ventricular contractions (PVCs) and autonomic dysfunction during pain-free periods. Methods A total of 50 migraine patients and 51 age- and sex-matched healthy controls were enrolled in the present observational, cross-sectional study. All participants underwent 24-hour Holter monitoring, standard electrocardiographic and echocardiographic evaluation. The frequencies of PVCs, PR interval, QT interval (QTc), heart rate variability, and sinus tachycardia prevalence were compared between groups. Migraine-related disability was assessed using the Migraine Disability Assessment Scale (MIDAS) and the Headache Impact Test-6 (HIT-6). Results At least 1 PVC was detected in 40% of migraine patients, although no significant difference was observed compared with controls (p > 0.05). However, migraine patients showed a significantly higher prevalence of sinus tachycardia (p < 0.05). Additionally, a positive correlation was found between PVC burden and MIDAS scores, suggesting a potential link between migraine severity and arrhythmia risk. No significant differences were observed in QTc intervals or other major arrhythmic parameters. Conclusion Migraine patients may exhibit increased sinus tachycardia and subtle electrocardiographic changes even during pain-free intervals, possibly reflecting underlying autonomic dysfunction.

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Abstract Background White matter hyperintensities (WMH) are commonly detected on brain magnetic resonance imaging (MRI) scans of migraine patients, but their clinical relevance and underlying mechanisms remain uncertain. Objective To systematically review the relationship between WMH and migraine, focusing on prevalence, progression, and associations with clinical and demographic characteristics. Methods We conducted a systematic review of observational studies published between 1990 and May 2025, including adult patients with migraine (with or without aura) who underwent brain MRIs with at least 1.5T scanners. Data extraction was performed by two independent reviewers, with disagreements resolved by a third. Study quality was assessed using the Newcastle-Ottawa scale for observational studies. Results A total of 25 studies were included, comprising approximately 3,600 participants, of whom 1,725 had migraine. Most participants were women and reported age means or medians typically between 30 and 60 years. Frequently, WMHs were observed in migraine patients, particularly in those with aura, longer disease duration, and higher headache frequency. No consistent association was found between WMH and comorbidities. Significant heterogeneity in imaging protocols, lesion quantification methods, and study design limited data comparability and precluded meta-analysis. Conclusion Migraine patients often present with WMHs, but their clinical significance remains unclear. Future studies should employ standardized MRI protocols, volumetric lesion quantification, and consistent migraine phenotyping to clarify its pathophysiological role in migraine and potential implications for diagnosis and management.

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Abstract Background Deep brain stimulation (DBS) is a treatment for dystonia, with most trials conducted in developed countries. Data from developing countries like Brazil are limited. Objective To evaluate the landscape of DBS for dystonia in Brazil, assessing motor outcomes compared with the existing literature. Methods A retrospective multicenter cohort study was conducted via medical record review. Demographics and motor outcomes were collected and analyzed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) from patients across four of Brazil's five macro-regions. Results The cohort included 60 patients (44.3% female), with DBS primarily targeting the globus pallidus internus (73.3%) or subthalamic nucleus (18.3%). The BFMDRS motor scores decreased from 63.0 ± 26.2 (n = 24) at baseline to 36.7 ± 24.6 at 1-year post-DBS (n = 22, p = 0.0018) and 43.6 ± 35.0 at the last assessment (n = 13, p = 0.0327). Conclusion The use of DBS yielded significant, sustained motor improvements, consistent with developed countries, highlighting its feasibility and effectiveness in Brazil within diverse healthcare settings.

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Abstract Idiopathic spinal cord herniation (ISCH) is a rare condition caused by a defect in the dura mater, resulting in ventral displacement of the spinal cord. Its etiology is not fully understood, but it mainly affects middle-aged women and manifests as progressive myelopathy. Surgical treatment is the best option to avoid neurological worsening. This report presents a case of spinal cord herniation in a 45-year-old man, complaining of numbness for 4 months, with paraparesis that progressed to gait disorder. This condition was diagnosed by magnetic resonance imaging and computed tomography. The patient underwent T2 to T3 laminectomy, hernia reduction, and duroplasty, with successful resolution of the condition.

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Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is a debilitating recurrent inflammatory disease of the central nervous system. Establishing management guidelines is essential to optimize patient care in Brazil. Objective To combine the Delphi and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approaches to validate evidence-based guideline statements for NMOSD treatment. Methods These guidelines focused on providing recommendations for different scenarios: general management and diagnosis of NMOSD; acute and preventive treatments (including systemic immunosuppressants and anti-B cell, anti-interleukin-6, and anti-complement monoclonal antibodies); and therapeutic approaches in special groups (such as the pediatric population and pregnant women). A literature review based on the Population, Intervention, Comparator, and Outcome (PICO) framework was performed, and studies were evaluated using the GRADE system. An initial questionnaire containing 19 statements was sent to 44 specialists from all regions of Brazil. Results Three voting rounds were necessary to reach consensus in all statements. After the first voting round, 17 statements reached consensus (level of agreement > 70%). Two statements failed to reach consensus and were, thus, revised. One of them was segmented into three different statements. After the second voting round, three out of the four revised statements reached consensus. Upon further revision, the last statement was again submitted to voting, reaching consensus in this third round. Overall, agreement was achieved on the 21 proposed statements. Conclusion The primary objective in the management of NMOSD is to mitigate the severity of the attacks and prevent relapses, thereby minimizing the risk of irreversible neurological deficits. The statements in the current guideline offer evidence-based recommendations for such management within the Brazilian context.

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Abstract Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune demyelinating disease characterized by a high risk of relapse and disability. In cases positive for aquaporin 4-immunoglobulin G (AQP4-IgG), long-term immunosuppression is the established standard. However, the management of double-seronegative NMOSD remains controversial due to limited data. Although some authors propose treatment discontinuation in patients with prolonged remission, there are no reliable predictors of sustained disease inactivity. Given the unpredictability and severity of the relapses, even after a decade of stability, and the lack of robust evidence supporting safe cessation, we argue that maintenance immunotherapy should remain the standard of care in most cases. The risks of disease reactivation outweigh the potential benefits of treatment withdrawal. Until validated biomarkers or clinical tools for individualized risk stratification emerge, the default approach should prioritize sustained disease suppression.

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Abstract Double-seronegative neuromyelitis optica spectrum disorder (DS-NMOSD) encompasses a heterogeneous spectrum, including monophasic and relapsing phenotypes. While 1/3 patients may follow a monophasic course, lifelong immunotherapy remains common practice due to the fear of relapse. However, this strategy may unnecessarily expose stable patients to long-term adverse effects and economic burden. The condition lacks the relapse-associated mechanisms observed in aquaporin 4 (AQP4)-positive disease, questioning the generalizability of prior treatment-withdrawal studies. Although predictive markers for relapse are still lacking, the median time to relapse is of approximately 3.4 (range: 0-7) years; hence, sustained remission beyond 10 years may indicate a subgroup of patients with low relapse risk. Until prospective data are available, individualized, cautious treatment interruption should be considered, guided by shared decision-making.

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Abstract As we near the bicentenary of his birth, Jean-Martin Charcot (1825-1893) is remembered not only as the founder of modern neurology but also as a uomo universale. His multidisciplinary approach transcended 19th-century medicine, establishing neurology as a distinct discipline while integrating art, psychology, and philosophy into his study of the nervous system. His work laid foundations for neurodegenerative diseases (amyotrophic lateral sclerosis [ALS], Parkinson's disease, multiple sclerosis [MS]), functional neurological disorders (FNDs), and psychoanalysis, foreshadowing neuroplasticity and the mind-body connection. His innovative teaching at Salpêtrière—merging anatomy with artistic documentation—revolutionized medical education, inspiring figures from Freud to modern neuroscientists. Two centuries later, Charcot's legacy endures not just in eponyms but in his unifying vision of brain, mind, and art - a timeless model for interdisciplinary medicine. The present paper explores his impact on neurodegenerative research, functional disorders, medical pedagogy, and the humanities.