BACKGROUND:Following mechanical thrombectomy for acute ischemic stroke due to anterior-circulation large-vessel occlusion, early neurological deterioration (END) continues to be a clinically consequential complication. Computed tomography perfusion (CTP)-derived mismatch volume estimates the amount of hypoperfused tissue that is not part of the ischemic core, but its value for END stratification at different time points has not been clarified. We therefore examined the relationship between mismatch volume and END and constructed risk models anchored to clearly specified temporal windows. METHODS:Consecutive patients treated with mechanical thrombectomy between January 2021 and December 2024 were retrospectively included. END encompassed either a ≥4-point increase from the preprocedural National Institutes of Health Stroke Scale (NIHSS) score or death from any cause during the first 72 h after thrombectomy; deaths occurring within 72 h were analyzed as END events. Potential nonlinearity was examined using restricted cubic spline (RCS) analysis. Only information known before thrombectomy was entered into the preprocedural baseline model. For the 24-h landmark analysis, patients who remained free of END through 24 h formed the reassessment cohort; successful recanalization status and hemorrhagic transformation subtypes were added to predict delayed END arising after >24-72 h. Discrimination, calibration, clinical utility, and internal validity were evaluated by receiver operating characteristic (ROC) analysis, calibration assessment, decision curve analysis (DCA), and 1000 bootstrap resamples, respectively. RESULTS:END occurred in 87 of 438 patients (19.9%): 78 experienced neurological worsening and 9 died within 72 h. The association between mismatch volume and END departed from linearity (p for nonlinearity = 0.023). Observed END frequencies were 33.0%, 18.9%, and 12.5% for mismatch volumes <75 mL, 75-105 mL, and >105 mL, respectively (p for trend <0.001). Mismatch volume, ischemic core volume, admission NIHSS score, and collateral score constituted the preprocedural model, which produced an area under the ROC curve (AUC) of 0.789 (95% confidence interval [CI], 0.735-0.843) and a bootstrap-corrected AUC of 0.774. END occurred in 8.0%, 20.7%, and 38.5% of patients assigned to the low-, intermediate-, and high-risk categories of the simplified preprocedural score. Among 387 patients eligible for 24-h reassessment, 36 developed delayed END; the corresponding model yielded an AUC of 0.838 (95% CI, 0.773-0.903). Delayed END was associated with parenchymal hematoma but not with hemorrhagic infarction. CONCLUSIONS:CTP mismatch volume was related to END following mechanical thrombectomy. The preprocedural and 24-h reassessment models, each defined by its prediction time, retained acceptable discrimination after internal validation; independent external validation remains necessary.
BACKGROUND:Post-stroke gait dysfunction may involve impaired integration of motor commands, somatosensory feedback, and phase-dependent peripheral sensory input during locomotion. Transcutaneous electrical nerve stimulation (TENS) combined with gait training may provide additional sensory input, but the relevance of different temporal stimulation profiles remains unclear. OBJECTIVE:To evaluate the feasibility, safety, and preliminary clinical signals of continuous and gait-synchronized TENS during gait training in individuals with chronic stroke. METHODS:Twenty-four participants with chronic stroke were randomized to continuous stimulation (CS), gait-synchronized stimulation (GS), or sham stimulation during standardized gait training. Participants received 12 intervention sessions over 4 weeks. CS delivered non-phase-specific stimulation, whereas GS delivered stimulation according to stance and swing phases. Outcomes were assessed at baseline, post-intervention, and 8-week follow-up. The primary longitudinal analysis was conducted in the modified intention-to-treat (mITT) population using baseline-adjusted linear mixed-effects models, with false discovery rate correction applied to group × time interaction p-values across estimable outcomes. RESULTS:One participant withdrew before intervention without baseline assessment; therefore, 23 participants were included in the mITT analysis. Intervention adherence was high, with 99% of scheduled sessions completed, and no intervention-related adverse events were reported. Comfortable gait speed showed no significant group × time interaction. Maximal gait speed and Berg Balance Scale showed nominal group × time interaction effects before correction, but these did not remain significant after false discovery rate correction. No robust group × time interaction effects were observed after correction. Exploratory per-protocol analyses were unadjusted for baseline imbalance and were interpreted as supportive only. CONCLUSIONS:Continuous and gait-synchronized TENS combined with standardized gait training were feasible and well tolerated in individuals with chronic stroke. The adjusted analysis did not provide robust evidence of differential clinical effects among stimulation-timing groups after correction for multiple outcome testing. Larger, adequately powered trials are needed to determine whether continuous or gait-synchronized TENS provides clinically meaningful benefits during post-stroke gait rehabilitation. CLINICAL TRIAL REGISTRATION:No: KCT0008481. Registered 17 May, 2023, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24719&search_page=L.
OBJECTIVE:To identify distinct long-term functional recovery trajectories among intensive care unit (ICU)-treated patients with spontaneous intracerebral hemorrhage (ICH) and to evaluate whether trajectory-based classification improves prediction of long-term quality of life (QoL) compared with conventional single time-point functional assessment. METHODS:We conducted a prospective longitudinal cohort study of consecutive adult patients with spontaneous ICH admitted to a tertiary ICU between January 2024 and January 2025. Survivors to hospital discharge were followed for 12 months. Functional status was assessed using the modified Rankin Scale (mRS) at hospital discharge, 90 days, 6 months, and 12 months. Latent class mixed modeling (LCMM) was used to identify distinct recovery trajectories. Health-related QoL at 12 months was measured using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) instrument. Multinomial logistic regression was performed to evaluate associations between early clinical characteristics and trajectory membership. Receiver operating characteristic curve analysis was conducted to compare the predictive performance of trajectory membership and 90-day mRS for 12-month QoL. RESULTS:Among 196 patients (mean age 61.7 ± 12.4 years; 60.2% male), three distinct functional recovery trajectories were identified: good, moderate, and poor recovery. Twelve-month QoL demonstrated a graded decline across trajectory groups. Older age, lower admission Glasgow Coma Scale scores, and larger hematoma volume were independently associated with both moderate and poor recovery trajectories, while intraventricular hemorrhage, mechanical ventilation, and prolonged sedation (>48 hours) were specifically associated with the poor recovery trajectory. Trajectory-based classification demonstrated superior predictive performance for 12-month QoL compared with 90-day mRS (area under the curve [AUC], 0.81 vs 0.72; p = 0.003), with significant improvement in risk discrimination. Trajectory-based classification also improved risk reclassification (net reclassification improvement (NRI) = 0.27; integrated discrimination improvement (IDI) = 0.09). CONCLUSION:ICU-treated patients with intracerebral hemorrhage exhibit distinct long-term recovery trajectories that are strongly associated with quality of life. Importantly, trajectory-based classification provides incremental prognostic value beyond conventional single time-point functional assessment, supporting a shift toward dynamic outcome modeling for long-term prognostication in ICH.
The 18th edition of the post-European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting was held on 17-18 October 2025 in Madrid, bringing together Spanish neurologists specialising in multiple sclerosis (MS), who presented the most relevant advances discussed at the ECTRIMS congress held a few days earlier in Barcelona. The aim of the meeting was to summarise the latest developments in the pathogenesis, new diagnostic criteria and biomarkers of MS. This article is the first of a two-part series (I and II) that reviews recent data on cell trafficking into the central nervous system, highlighting the functional heterogeneity of the brain endothelium, the molecular mechanisms regulating leukocyte infiltration and the differential role of macrophages and resident microglia in tissue damage and chronic inflammation. The evidence supporting the role of Epstein-Barr virus as a necessary risk factor in MS is presented, together with the therapeutic and preventive implications from studies of antiviral therapies, cell-based therapies and vaccines. Regarding diagnosis, the new criteria for neuromyelitis optica spectrum disorders are addressed, with particular attention to the molecular heterogeneity of double-seronegative forms, as well as the update of the magnetic resonance imaging (MRI) guidelines following the 2024 revision of the McDonald criteria. Advances in the neuroimaging of chronic active inflammation, quantitative spinal cord imaging and the concept of spinal cord reserve are highlighted. The growing role of artificial intelligence applied to MRI for the early prediction of progression and treatment response is also reviewed. Finally, advances in remyelination mechanisms and in biomarkers are presented, underscoring the value of multimodal and longitudinal approaches for prognostic stratification and treatment monitoring. Overall, the data reviewed reflect a change into a more integrated and predictive understanding of MS, with direct implications for early diagnosis, treatment personalisation and the design of future clinical trials.
Introduction: Percutaneous pulsed radiofrequency (PPRF) is a minimally invasive neuromodulation technique used in chronic pain management. Our aim was to evaluate its effectiveness and safety in refractory cases of trigeminal neuralgia (TN) and chronic cluster headache (CH). Methods: We conducted a retrospective study of patients with TN and CH diagnosed according to the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria and treated with PPRF (Gasserian ganglion for TN and sphenopalatine ganglion for CH) over an 8-year period. Effectiveness at 3 months was assessed by evaluating reduction in the number of pain days in TN and number of attacks in CH, ≥50% response rate, visual analogue scale (VAS), Patient Global Impression of Improvement (PGI-I), and pain recurrence. Results: Twenty-five patients met the inclusion criteria, including 19 with TN and 6 with CH, with a mean age of 76 and 52 years, respectively. Clinical improvement was observed in 14/19 (73.6%) patients with TN and 5/6 (83.3%) patients with CH. A ≥50% response rate was achieved in 11/14 (78.6%) patients with TN and 4/6 (66.7%) patients with CH. VAS scores decreased at 3 months in both groups (p < 0.0001 in TN; p = 0.06 in CH). PGI-I was rated as “better” or “much better” in 10/19 (52.6%) patients with TN and 5/6 (83.3%) patients with CH. Pain recurrence occurred in 13/14 (92.8%) patients with TN and 5/5 (100%) patients with CH, mainly after 1 year following the first procedure (7/13 TN and 2/5 CH). No major adverse events were reported. Conclusions: In our series, PPRF appears to be an effective and safe treatment for refractory TN and CH. Although the study is retrospective and the sample size is limited, particularly in CH, these findings should be considered preliminary but clinically relevant. Despite the high recurrence rate, given its low complication profile, it may represent a treatment option for patients who are not candidates for surgical procedures.
Background: Spinocerebellar ataxia (SCA) is a rare group of hereditary degenerative disorders with major symptoms such as unsteady gait, dysarthria, and finger-nose instability. At present, the Berg Balance Scale (BBS) is a widely utilized balance assessment tool for SCA patients, exhibiting high reliability. The objective of this study was to ascertain whether the Semans Scale and the Balance Coordination Test can also be utilized for balance assessment in SCA patients.Methods: A total of 32 patients with SCA who had been diagnosed according to previously reported molecular criteria were recruited between 2021 and 2022. In addition, all patients completed assessments for all three scales.Results: The results of the study demonstrated a moderate positive correlation between the BBS and both the Semans Scale and Balance Coordination Test scores (BBS versus Semans: r = 0.568, p < 0.001; BBS versus Balance Coordination Test: r = 0.625, p < 0.001). However, the Wilcoxon signed-rank test showed statistically significant differences between BBS and both Semans Scores (Z = -2.955, p = 0.003) and Balance Coordination Test scores (Z = -3.666, p < 0.001).Conclusions: The Semans Scale and Balance Coordination Test reflect the balance function of SCA patients to a certain extent and can be used as valid complements to the BBS, providing additional information for clinical treatment and rehabilitation.
BACKGROUND:Central sleep apnea (CSA) syndromes and acute ischemic stroke are linked by a complex, bidirectional relationship. After ischemic stroke, CSA prevalence rises markedly compared with the general population, in which it is usually below 1%. In stroke cohorts, CSA frequencies of around 8%-12% have been reported, although estimates are heterogeneous owing to differing diagnostic criteria. In this scoping review we map the evidence on CSA syndromes during sleep in patients with stroke, summarizing prevalence, mechanisms, clinical correlates, and prognostic implications. METHODS:The Medline (PubMed), Scopus, Cochrane Reviews, and Web of Science databases were searched for observational and interventional studies published from inception to August 31 2025 in English and Spanish assessing CSA syndromes in adults with ischemic stroke. Two reviewers independently screened records, selected studies, and extracted data on study design, stroke characteristics, CSA definitions, comorbidities, and clinical outcomes; disagreements were resolved by consensus with a third reviewer. RESULTS:Fifty-five studies including several thousand patients with ischemic stroke were identified. Across studies, post-stroke CSA prevalence ranged from approximately 8% to 12%, clearly exceeding rates in the general population. CSA was often reported in the absence of overt cardiac comorbidities, and patients with CSA tended to have lower body mass index and fewer classic cardiovascular risk factors than those typically described with obstructive sleep apnea. Pathophysiological analyses emphasized disturbed central ventilatory control after cerebral ischemia; however, several studies did not show a consistent association between specific lesion locations and CSA occurrence, suggesting that stroke may unmask CSA in predisposed individuals rather than cause it solely through focal damage. In older adults, CSA appeared as an independent correlate of ischemic stroke and a potential marker of silent cerebral injury or impaired central respiratory regulation. CONCLUSIONS:Available evidence indicates that CSA syndromes during sleep are substantially more frequent in patients with ischemic stroke than in the general population and may be associated with increased cerebrovascular risk and subclinical brain injury. Heterogeneity in CSA definitions, diagnostic protocols, and outcome measures limits firm conclusions. Standardized criteria and adequately powered prospective studies are needed to clarify the mechanistic and prognostic role of CSA in stroke.
Introduction: There is no consensus on the optimal management of intracranial aneurysms in patients with moyamoya disease. Here, we report a case of a patient in the subacute hemorrhagic stage of moyamoya disease with a presumed pseudoaneurysm detected on interval imaging, who was treated with aneurysm resection combined with superficial temporal artery (STA)-middle cerebral artery (MCA) bypass. This report illustrates a feasible individualized surgical approach for similar cases. Case Report: A 27-year-old male without a prior history of cerebrovascular disease was admitted for a right temporal intracerebral hemorrhage following external ventricular drainage. Initial computed tomography angiography (CTA) at admission showed no aneurysm. One week later, follow-up CTA revealed a newly developed 10 × 9 mm aneurysm in the right MCA region. Subsequent digital subtraction angiography (DSA) demonstrated occlusion of the right MCA M1 segment with the development of characteristic moyamoya collateral networks. The patient underwent microsurgical resection of the aneurysmal lesion, combined with a right STA-MCA bypass. Postoperative imaging demonstrated complete obliteration of the aneurysm, patency of the bypass, and a reduction in moyamoya collateral vessels. Histopathological examination revealed a red blood cell clot surrounded by fibrous connective tissue without definitive evidence of a preserved arterial wall, consistent with a presumed pseudoaneurysm. The patient recovered well, with improved neurological function on follow-up imaging. Conclusions: In patients with moyamoya disease, a peripheral aneurysmal lesion may become detectable on interval imaging after an initially negative CTA and may represent an unstable hemorrhage-related vascular lesion. In carefully selected cases, lesion resection combined with STA-MCA bypass during the subacute phase may be a feasible individualized treatment strategy, particularly when direct lesion treatment and hemodynamic revascularization are both required. However, longer clinical and imaging follow-up is needed before any firm conclusions can be drawn regarding outcome improvement, or prevention of rebleeding.
Introduction: Developmental and epileptic encephalopathy (DEE) is a group of severe neurological disorders characterized by early-onset epilepsy and developmental delay, often caused by genetic variants. Cdc42 Guanine Nucleotide Exchange Factor 9 (ARHGEF9) gene variants have been linked to DEE, yet novel variants and their phenotypic presentations remain incompletely characterized.Clinical Cases: Herein, we describe two siblings with DEE caused by a novel deletion variant in the ARHGEF9 gene. Both patients presented with early-onset epilepsy and developmental delay. Whole-exome sequencing identified a hemizygous c.1037_1045del variant in the ARHGEF9 gene (NM_015185.2) in both brothers, which is reported here for the first time. Notably, the two siblings exhibited a marked difference in outcomes: the elder brother achieved good seizure control with anti-epileptic drugs, while the proband, despite multidrug therapy and vagus nerve stimulation (VNS), exhibited a limited response and continued to experience frequent seizures.Conclusions: These cases expand the genotypic spectrum of ARHGEF9-related disorders and underscore the intrafamilial phenotypic variability associated with this gene. These findings emphasize the significance of early genetic testing for establishing a diagnosis, assessing prognosis, and facilitating genetic counseling.
BACKGROUND:Neurological and neuropsychiatric disorders constitute a major global health challenge. The P300 event-related potential, an electroencephalography-derived measure of cognitive processing, has emerged as a promising biomarker for diagnosis, treatment monitoring, and outcome prediction. This systematic review examines P300's role across neurological and neuropsychiatric disorders, evaluating how P300 latency (processing speed) and amplitude (attentional resource allocation) may reflect neurocognitive dysfunction. METHODS:Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we searched PubMed, Scopus, and Web of Science for randomized controlled trials and controlled studies published January 2020-August 2025. Six research domains were examined: dementia spectrum disorders (Research Question, RQ1), acquired brain injury and disorders of consciousness (RQ2), mood and anxiety disorders (RQ3), neurodevelopmental disorders (RQ4), psychotic disorders and addiction (RQ5), and chronic neurological conditions (RQ6). Risk of bias was assessed using a modified Cochrane tool. Of 125 records identified, 52 studies met the inclusion criteria. RESULTS:P300 emerged as a promising transdiagnostic biomarker. Prolonged latency and reduced amplitude consistently characterized clinical populations versus controls (pooled standardized mean difference [SMD] = -0.72, 95% confidence interval [CI]: -0.89 to -0.55; I2 = 67.3%). In dementia spectrum disorders, P300 latency distinguishes mild cognitive impairment from healthy aging. In disorders of consciousness, the emergence of the P300 waveform provided objective indices of residual cognitive capacity. In mood disorders, baseline amplitude predicted therapy outcomes. In addition, P300 correlated with craving severity. Neuromodulation (transcranial direct current stimulation [tDCS], repetitive transcranial magnetic stimulation [rTMS]) produced the most robust normalization effects across categories. P300 changes occurred within 3 days to 6 weeks of treatment, potentially enabling earlier detection of response than conventional assessments. Portable electroencephalography (EEG) systems demonstrated adequate sensitivity for clinical applications. CONCLUSIONS:P300 shows promise as a non-invasive biomarker for cognitive dysfunction across neuropsychiatric disorders. Its diagnostic utility, treatment responsiveness, and prognostic potential support clinical translation. Near-term applications include consciousness assessment, cognitive screening in dementia, and treatment monitoring. However, standardization of protocols, multi-site validation, and scalable technologies require further development. Advancing P300 research through interdisciplinary collaboration may contribute to precision psychiatry and population-level mental health strategies.
Background: Post-stroke dysphagia (PSD) is a common and serious complication, yet conventional rehabilitation therapies have limited efficacy. Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment, but its optimal intervention strategy remains undetermined. Methods: Seventy-five PSD patients were randomly assigned in a 1:1:1 ratio to the sham rTMS group, affected rTMS group and bilateral rTMS group. All groups received the corresponding rTMS intervention and conventional rehabilitation therapy. Swallowing function was assessed at baseline (T0) and after treatment (T1) using the standardized swallowing assessment (SSA), penetration-aspiration scale (PAS), yale pharyngeal residue severity rating scale (YPR-SRS), and suprahyoid motor evoked potentials (MEP). Adverse reactions and dropouts were recorded. Results: After treatment, the SSA scores of all three groups were significantly improved. Bilateral rTMS showed significantly greater improvement in SSA and a higher treatment response rate (77.27%) compared to both the sham group and the affected rTMS group (p < 0.001). Mixed-effects model and intention-to-treat analyses both supported the optimal efficacy of bilateral rTMS (interaction effect p < 0.01). Regarding swallowing safety (PAS), the bilateral rTMS group's score was significantly lower than that of the sham group (p = 0.017). In terms of pharyngeal residue clearance (YPR-SRS), the bilateral rTMS group showed significantly greater improvement in the piriform sinuses compared to the other two groups, and superior improvement in the vallecula compared to the sham group (p < 0.05). After treatment, MEP amplitudes increased in all groups. Notably, only the bilateral rTMS group not only significantly increased MEP amplitudes on both sides (p < 0.01) but also significantly shortened the latency on the contralesional side (p = 0.046). The bilateral rTMS group achieved a "large effect size" in improving SSA scores, increasing MEP amplitudes, and shortening latency on the contralesional side, with the SSA effect size (D = 2.339) far exceeding that of the other groups. All treatment regimens were well-tolerated, with only 5 cases of transient scalp discomfort reported and no serious adverse events. Conclusions: Conventional rehabilitation combined with 10 Hz rTMS targeting the swallowing cortex can effectively improve swallowing function in PSD patients. Bilateral rTMS is a superior strategy. Its therapeutic advantage may stem from the synergistic modulation of bilateral cortical excitability and neural conduction efficiency, providing a better multi-target neuromodulation option for clinical practice. Clinical Trial Registration: No: ChiCTR2300068730. https://www.chictr.org.cn/showproj.html?proj=182568.
BACKGROUND:Anxiety symptoms in elderly patients with cognitive impairment (CI) often reflect shared neurobiological processes rather than distinct psychiatric disorders. Current diagnostic approaches lack objective biomarkers for early identification. This study investigated the association between serum biomarkers and anxiety disorder status in elderly men with CI and to evaluate the exploratory discriminative ability of cognitive domains and biomarker profiles in differentiating CI patients with and without comorbid anxiety. METHODS:This cross-sectional retrospective study analyzed 86 elderly male CI patients (Group A: CI alone, n = 41; Group B: CI with anxiety, n = 45) at Jiangsu Rongjun Hospital (June-December, 2024). Anxiety disorder diagnosis was established through structured clinical interviews based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria conducted by two independent psychiatrists, with the Hamilton Anxiety Scale (HAMA) serving as an initial severity screening instrument. The Montreal Cognitive Assessment (MOCA) was used to evaluate cognitive function. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum Tau protein (Tau), β-amyloid (Aβ), visinin-like protein 1 (VILIP-1), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6); reverse transcription-polymerase chain reaction (RT-PCR) quantified microRNA-34c (MiR-34c). Patients with acute inflammation (C-reactive protein [CRP] >10 mg/L) were excluded. Bonferroni correction was used to address multiple comparisons across 25 simultaneous tests, and multivariate regression analysis was controlled for demographic and clinical confounders. Receiver operating characteristic (ROC) analysis was used to determine the discriminative ability. RESULTS:Group B showed worse cognitive performance across the MOCA domains, with attention (area under the curve [AUC] = 0.738) and delayed recall (AUC = 0.742) demonstrating the strongest discriminative ability. Biomarker analysis revealed elevated Tau (AUC = 0.957), MDA (AUC = 0.941), and VILIP-1 (AUC = 0.914) in anxiety patients. Within-group analyses showed that anxiety severity correlated negatively with MiR-34c and positively with Tau, Aβ, MDA, IL-6, and VILIP-1. Under the Bonferroni-adjusted threshold (p < 0.002), only MDA in Group B (r = 0.478, p = 0.001) and MiR-34c in Group B (r = -0.523, p < 0.001) remained significant. Multivariate analysis identified these factors as independently associated with the outcome after controlling for demographics and comorbidities. However, given the substantial baseline imbalances between the groups, these associations should be interpreted with caution. CONCLUSION:Combined cognitive assessment (attention, delayed recall) and serum biomarkers (Tau, MDA, VILIP-1, MiR-34c) demonstrate promising discriminative ability for identifying anxiety in elderly male patients with CI. These findings are exploratory and derived from a single-center cohort of retired male military veterans with pronounced baseline group imbalances, which substantially limits generalizability to the broader elderly CI population. The identified markers may reflect shared neuroinflammatory and oxidative stress pathways underlying both cognitive and emotional dysfunction, warranting further investigation as potential targets for integrated therapeutic approaches. Validation in prospective, multicenter, sex-inclusive cohorts with balanced comparison groups is essential before any clinical application can be considered.
BACKGROUND:Cognitive reserve (CR) may help mitigate cognitive decline in people with multiple sclerosis (PwMS); however, few interventions have targeted CR enhancement, and none have focused on individuals without baseline cognitive impairment. The EM Reserva program is a multimodal intervention that combines cognitive leisure activities, aerobic exercise, and structured social engagement and is designed to strengthen CR in individuals with relapsing-remitting MS (RRMS). METHODS:This pragmatic, single-center, observer-blinded randomized controlled trial included PwMS aged 18-55 years with RRMS and no cognitive impairment. Participants were randomized in a 1:1 ratio to either the EM Reserva program or usual cognitive care. Outcomes were assessed at baseline and at 6-month and 12-month time points. The primary endpoint was the change in Symbol Digit Modalities Test (SDMT) scores at 6 months. Secondary outcomes included additional neuropsychological measures, Modified Fatigue Impact Scale-5 (MFIS-5), Perceived Deficits Questionnaire-5 (PDQ-5), and Multiple Sclerosis Quality of Life‑54 (MSQOL-54). Analyses followed a modified intention-to-treat approach. RESULTS:Forty-five participants completed follow-up. At 6 months, the EM Reserva group showed a significant improvement in SDMT scores compared with controls (mean difference -4.23, p < 0.022) and higher Controlled Oral Word Association Test (COWAT) scores. These cognitive gains were not sustained at 12 months. Fatigue improved in both groups at 6 months but remained significantly lower only in the EM Reserva group at 12 months. No between-group differences were observed in PDQ-5, MSQOL-54, or other neuropsychological measures. CONCLUSION:The EM Reserva program produced short-term improvements in processing speed and verbal fluency in cognitively preserved PwMS, along with sustained reductions in fatigue. However, cognitive benefits were not maintained at 12 months, and subjective cognitive functioning remained unchanged. These findings suggest that multimodal CR-oriented interventions may offer temporary cognitive advantages, but long-term maintenance strategies are likely required to sustain gains. CLINICAL TRIAL REGISTRATION:No: NCT05546424. https://clinicaltrials.gov/study/NCT05546424.
INTRODUCTION:Migraine aura status is a complication of migraine. It is characterised by the presence of at least 3 episodes of migraine aura within a 3-day period. The pain and/or associated symptoms are often debilitating. Cortical laminar necrosis (CLN) is a gyriform brain lesion caused by insufficient oxygen and glucose supply, resulting in the loss of cortical neurons, often due to cardiac arrest, global hypoxia, and hypoglycaemia. Metabolic disorders, hypoglycaemia, renal and hepatic dysfunction, and immunosuppressive chemotherapy. In children, cortical laminar necrosis has been linked to the subacute or chronic phase of brain damage due to hypoxic-ischaemic encephalopathy. Metabolic disorders, hypoglycaemia, renal and hepatic dysfunction, and immunosuppressive chemotherapy are included as other possible aetiologies. CLN has also been reported in patients with encephalitis, but it is extremely rare in migraine with or without aura. CLINICAL CASE:We describe a 14-year-old boy with no previous neurological problems who was admitted to our unit due to the onset of acute and persistent symptoms characterised by headache, confusion, dysarthria, aphasia and visual disturbances. An initial emergency brain neuroimaging scan revealed edema localised in the supramarginal gyrus of the left cerebral hemisphere, with possible vascular etiology. A control magnetic resonance imaging revealed laminar necrosis of the cortico-pial area located in the same region. CONCLUSIONS:This clinical case is interesting due to the uncommon correlation between cortical laminar necrosis and migraine with aura (MA), the pediatric presentation, the location of hypoperfusion and the atypical progression of the migraine aura. We have reported a narrative review of the two disorders.
Introduction: In countries with a low incidence of human rabies, this lethal virus is rarely considered in the differential diagnosis of acute flaccid paralysis.Clinical Case: A young woman presented with fever and progressive weakness that evolved into flaccid quadriparesis, associated with neuropsychiatric symptoms, multiple cranial neuropathy, and dysautonomia. The complementary tests and the unusual reflexes that accompanied the diagnosis of brain death are described. The diagnosis was confirmed postmortem by compatible histopathological findings.Conclusions: Human rabies should be considered in cases of flaccid paralysis with encephalitis due to its implications for preventing further deaths through public health measures.
Sudden Unexpected Death in Epilepsy (SUDEP) is the leading cause of death in patients with epilepsy (PWE), although the mechanisms are unclear. Early studies have shown that abnormal cardiopulmonary function plays a key role in SUDEP. Cardiopulmonary activity is regulated by the autonomic nervous system. Serotonin (5-hydroxytryptamine or 5-HT) neurons significantly influence respiration and are also closely related to epilepsy. Therefore, serotonin is hypothesized to be involved in SUDEP, and a substantial amount of research has focused on it. Notably, serotonin signals through at least 14 known receptor subtypes, with preclinical data suggesting a particular involvement of the 5-HT2, 5-HT3, and 5-HT4 receptors in SUDEP. Dilute Brown Non-Agouti (DBA)/1 and DBA/2 mice, which often die of seizure-induced respiratory arrest (S-IRA) following audiogenic seizures (AGS), are the most commonly used animal models for studying SUDEP. Increased serotonin reduces S-IRA, activating serotonin neurons prevents SUDEP, abnormalities in serotonin receptors are associated with SUDEP, and selective serotonin reuptake inhibitors (SSRIs) affect electroencephalogram (EEG) activity. Other studies have found that serotonin protects against S-IRA in PWE. Pathological studies in patients with SUDEP have also revealed that, in comparison with controls, the axonal length (AL) of serotonin transporter (SERT)-positive axons is longer and the level of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin synthesis, is lower. Consequently, serotonin is possibly a potential target for preventing SUDEP. However, most of the results are from animal studies, while the experimental data in PWE are limited. More human studies are needed in the future.
Background: Neurovascular conflict (NVC) is a rare but often overlooked cause of oculomotor cranial nerve (OCN) palsy. In this study, we aimed to enhance understanding of NVC as a potential cause of cranial nerve palsies by summarizing the characteristics of eight OCN palsy cases associated with NVC and reviewing previously reported cases.Methods: A retrospective case series of eight patients with OCN palsy due to NVC was analyzed. Diagnosis was made using 3.0 Tesla magnetic resonance imaging (MRI) with 3D-fast imaging with steady-state acquisition (3D-FIESTA) sequences. Differential diagnoses like myasthenia gravis, inflammatory diseases, and aneurysms were excluded.Results: The study involved eight patients (six males, two females), aged 34-78 years (average 58.4 years). Six had abducens nerve palsy, and two had partial oculomotor nerve palsy, all exhibiting painless partial ophthalmoplegia. Imaging revealed OCN compression by various arteries: abducens nerve palsy was due to the basilar artery (three patients), vertebral artery (one patient), and anterior inferior cerebellar artery (two patients); two cases of partial oculomotor nerve palsy were caused by compression of the superior cerebellar artery and the posterior cerebral artery, respectively.Conclusion: NVC should be considered in patients with abducens nerve palsy, particularly those with intermittent symptoms and painless ophthalmoplegia, especially if they have atherosclerotic risk factors; in this descriptive single-center cohort, diagnosis was supported by high-resolution MRI, including 3D-FIESTA and magnetic resonance angiography.
Background: Chronic migraine is a disabling and prevalent neurological disease that significantly impacts patients' quality of life. OnabotulinumtoxinA (OnabotA) is a safe and effective chronic migraine preventive treatment. The objective was to evaluate adherence to the recommended time interval between consecutive OnabotA injections according to the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) protocol, and to analyze changes in the interval adherence before and after the introduction of an Advanced Practice Nurse (APN) in a specialized Headache Unit of a tertiary hospital. Methods: This was a retrospective study performed in a Spanish specialized Headache Clinic. Patients diagnosed with chronic migraine and treated with OnabotA following the PREEMPT protocol were included, before and after the introduction of APNs. Treatment was considered interval-compliant if the injection interval ranged from 75 to 105 days. The data collected included three 18-month periods. Statistical analyses examined differences across periods using R-Studio. Results: A total of 2991 participants were included, of whom 83.8% (2507/2991) were women, with a median age [interquartile range (IQR)] of 48.0 [40.0-57.0] years old. A statistically significant association between the introduction of the APN and improved adherence to the PREEMPT protocol was observed over time (Z = -19.60, p < 0.001). Adherence rates increased from 52.1% in P1 to 76.1% in both P2 and P3. The median time between visits decreased from 105 days in P1 to 96 days in P2, with a slight increase to 98 days in P3. Conclusion: The involvement of advanced practice nurses in OnabotA administration decreased the time interval between infiltrations and improved adherence to the PREEMPT protocol. These findings highlight the APN's role in optimizing patient care.
INTRODUCTION:Gait training using robotic devices in stroke patients is a widely researched treatment modality. Therefore, there is a lot of heterogeneous information that needs to be synthesized, sorted, and classified. The aim of this work was to synthesize and analyze the scientific evidence on the application of robotic devices for gait training in people with stroke. METHODS:This overview of systematic reviews and meta-analysis was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Searches were performed in four electronic databases: PubMed, Scopus, Web of Science, and Cochrane Library Plus. Systematic reviews and meta-analyses that included randomized controlled trials (RCTs) that investigated the effects of robotic devices in combination or not with another physiotherapy treatment on gait recovery in stroke patients were included. RESULTS:Thirteen studies with a total of 101 RCTs were included. Data regarding the participants, outcome measures, training protocols and main results were extracted. The A Messurement Tool to Assess Systematic Review (AMSTAR-2) scale and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system of certainty of evidence were applied. Only one study had a high certainty of evidence; while four had a moderate certainty, six were classified as having a low certainty and two had a critically low quality. CONCLUSIONS:Robotic gait training combined with physiotherapy improves walking speed after stroke, especially with end-effector devices. However, benefits do not reach clinically meaningful functional thresholds, and applicability is limited due to insufficient evidence, high costs, and limited accessibility. The PROSPERO Registration: CRD42021237915, https://www.crd.york.ac.uk/PROSPERO/view/CRD42021237915.
Background: To evaluate the association of the purinergic receptor P2Y, G-protein coupled, 12 (P2Y12) gene polymorphisms with susceptibility to different etiological stroke subtypes. Methods: A total of 459 first-ever acute ischemic stroke patients were classified into large-artery atherosclerosis (LAA, n = 163), small-vessel occlusion (SVO, n = 204), and cardioembolism (CE, n = 92) based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Direct sequencing was used to screen these three stroke subtypes and non-stroke controls for P2Y12 polymorphisms: a T→C transition at 744 nucleotides (nt) downstream of intron 5's start site (i-T744C) and a C→T transition at 34 nt downstream of exon 2's start site (C34T). Based on the results of multivariate logistic analyses, a prediction model was established via a nomogram that incorporated genomic and clinical variables to quantify the risk of LAA stroke. Results: Significant differences in the P2Y12 i-T744C genotype and allele frequencies were observed between LAA patients and controls. After adjusting for confounding factors, the dominant model (p = 0.009) and additive model (p = 0.023) revealed that the i-T744C polymorphism was significantly associated with increased susceptibility to LAA. No significant associations were found for the SVO and CE stroke subtypes. Moreover, the C34T polymorphism was not an independent factor for any stroke subtype. We further constructed a nomogram prediction model for LAA stroke based on genomic and clinical variables, including age, hypertension, smoking, high-density lipoprotein cholesterol, and the i-T744C polymorphism. This nomogram exhibited satisfactory accuracy and predictive power for LAA stroke, as demonstrated by the area under the curve, calibration plot, and decision curve analysis. Conclusion: The P2Y12 i-T744C polymorphism may serve as a predictor for LAA stroke. Furthermore, we constructed a genomic-clinical nomogram that may be valuable for predicting LAA stroke risk in the study population.
