INTRODUCTION: Carbon dioxide is a key determinant of cerebral blood flow and its regulatory mechanisms. Previous work has shown patients with acute ischemic stroke (AIS), including lacunar stroke syndromes (LSS), are mor...INTRODUCTION: Carbon dioxide is a key determinant of cerebral blood flow and its regulatory mechanisms. Previous work has shown patients with acute ischemic stroke (AIS), including lacunar stroke syndromes (LSS), are more likely to be spontaneously hypocapnic. We aimed to estimate the prevalence of hypocapnia in AIS and determine the association between end-tidal CO (EtCO) and patient characteristics, dynamic cerebral autoregulation (dCA) parameters, and modified Rankin Score (mRS). METHODS: Participating centers were identified through systematic literature search and direct invitation. Data on dCA measures were derived from transfer function analysis at low frequency (LF) and very low frequency (VLF). Bivariate analyses were conducted at each time point separately using mixed effects models, with the participating center as a random effect. RESULTS: Prevalence of hypocapnia (EtCO < 35 mmHg) was highest at <24 h (43%), decreasing at 24-72 h (31%), and 3 months (27%). Non-lacunar stroke had lower EtCO compared to LSS (t = 2.16,df = 62.2,p = 0.035) and higher prevalence of hypocapnia (FET, p = 0.029) at <24 h. At <24 h, reduced EtCO was associated with higher phase at LF (β = -0.01,SE = 0.006,p = 0.029) but was not present at 24-72 h or 3 months. Lower EtCO was associated with greater likelihood of poor mRS [3-6] at 24-72 h. CONCLUSION: Hypocapnia at <24 h post-stroke is associated with improved dCA (through higher phase). Beyond 24 h this association is lost and hypocapnia becomes predictive of poorer clinical outcome. Hypocapnia was prevalent in LSS but to a lesser extent than non-lacunar AIS. Future work should affirm the value of capnography in acute stroke care.
Nair S, Kinkata M, Asukile M
… +20 more, Awraris M, Braun S, Chishimba L, Bwalya M, Chilando M, Chomba M, Luchembe M, Mortel D, Munkombwe D, Mwamba J, Mwendaweli N, Mutete F, Namangala C, Nassoro D, Nutakki A, Peloso A, Simushi F, Yankae L, Zimba S, Saylor D
J Neurol Sci
· 2026 May · PMID 41830669
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BACKGROUND: The modified Rankin Scale (mRS) is widely used to assess functional status after stroke, yet prior work in Zambia has shown low agreement between clinician assessments and patient-reported scores. OBJECTIVE:...BACKGROUND: The modified Rankin Scale (mRS) is widely used to assess functional status after stroke, yet prior work in Zambia has shown low agreement between clinician assessments and patient-reported scores. OBJECTIVE: To identify cultural, linguistic, and other factors contributing to discrepancies between clinician-determined and self-reported mRS scores among adults with stroke in Zambia. METHODS: Consecutive adults hospitalized with stroke were recruited into a mixed-methods cross-sectional study. A neurologist assigned an in-person mRS score. Within seven days, a verbal mRS questionnaire was administered in the participant's preferred language (English, Nyanja, or Bemba). Semi-structured interviews explored how respondents interpreted and justified their answers. Transcripts were analyzed for themes related to comprehension, health perceptions, and observed behavior. RESULTS: Among 51 participants, in-person and self-reported mRS scores matched in 51% of cases (weighted kappa = 0.548). Self-reported scores were 1 point higher in 19% and 1 point lower in 11% of cases; 8% reported scores 2 points higher. Agreement for dichotomized outcomes (good <2; poor >3) was moderate (k = 0.60). Discrepancies arose from translation challenges, caregiver responses based on incomplete knowledge, patients' fear of attempting tasks such as sitting or walking, underestimation of non-motor deficits, and mismatches between patient and clinician interpretations of mRS criteria. CONCLUSION: Clinician and patient-reported mRS scores aligned for only half of participants. Improving translations and better understanding how patients perceive their abilities may enhance interpretation of both clinician-assigned and self-reported mRS scores in this setting.
AIMS: Fatigue is a pervasive feature of multiple sclerosis (MS) and its interaction with other MS symptoms is complex. These interactions were explored over time in a large cohort of adults with MS, using a measure refle...AIMS: Fatigue is a pervasive feature of multiple sclerosis (MS) and its interaction with other MS symptoms is complex. These interactions were explored over time in a large cohort of adults with MS, using a measure reflecting a patient-based definition of MS fatigue. METHODS: Participants were recruited across the UK to complete a questionnaire pack, measuring fatigue and associated demographic, clinical and symptom factors, repeated serially over up to 54 months. Following conversion to interval-level estimates, data were analysed by regression, structural equation and trajectory modelling, and Classification and Regression Tree Analysis. RESULTS: In 6356 people with MS, the prevalence of moderate/severe fatigue was 565.4/1000 (95% CI: 553.0-577.8), with no difference between sexes but significantly higher in progressive subtypes. Peak prevalence was from age 50-64. Spasticity-related pain, physical/cognitive function, anxiety, visual problems and non-restorative sleep were associated with increased fatigue. Self-efficacy had strong influences to reduce fatigue. Use of disease modifying treatment was associated with worse fatigue. Trajectory analysis showed four groups, 28.9% have ongoing severe fatigue, 66.3% fall into two worsening fatigue groups with different inception points. Only 4.9% had low, stable fatigue. These four groups varied significantly by MS subtype, EDSS, symptoms, comorbidity, and employment. The risk of fatigue worsening to moderate/severe over the ensuing 27 months could be predicted by sex, EDSS, vision and self-efficacy. CONCLUSIONS: The factors interacting with MS fatigue need consideration when managing this prevalent symptom. In addition, their effect should be accounted for in any MS trial where fatigue is an outcome.
Multiple sclerosis (MS) arises from the convergence of polygenic immune susceptibility, environmental exposures, and infectious determinants, none of which alone is sufficient for disease expression. More than 200 geneti...Multiple sclerosis (MS) arises from the convergence of polygenic immune susceptibility, environmental exposures, and infectious determinants, none of which alone is sufficient for disease expression. More than 200 genetic variants contribute to MS risk, with the HLA-DRB115:01 haplotype providing the strongest effect within a broader network of immune-regulatory loci. Functional genomic evidence shows that these variants primarily influence antigen presentation and lymphocyte activation, creating an immune landscape that can be further shaped by external factors. This review integrates epidemiological, genomic, and mechanistic data to outline the main determinants of MS susceptibility. Epstein-Barr virus infection emerges as the dominant infectious driver, with seroconversion preceding early neuroaxonal injury and clinical onset. In contrast, cytomegalovirus infection appears protective, likely through immune imprinting that counterbalances EBV-driven B-cell and T-cell activation. Environmental factors including cigarette smoking, adolescent obesity, vitamin D deficiency, circadian disruption, and gut microbiota dysbiosis further modify susceptibility by promoting proinflammatory immune programs and reducing regulatory stability. Many of these exposures interact synergistically with HLA-DRB115:01, amplifying risk beyond additive expectations. These determinants influence shared immunological pathways regulating antigen presentation, lymphocyte differentiation, and immune tolerance. Clarifying these biological interfaces highlights actionable domains including smoking avoidance, metabolic health optimization, vitamin D sufficiency, viral prevention strategies, circadian alignment, and microbiome-targeted interventions that may inform risk-reduction and early identification efforts.
BACKGROUND: The relationship between menopause-related hormonal changes and disease outcomes in women with multiple sclerosis (WwMS) is still debated. We investigated whether natural estrogen exposure during reproductive...BACKGROUND: The relationship between menopause-related hormonal changes and disease outcomes in women with multiple sclerosis (WwMS) is still debated. We investigated whether natural estrogen exposure during reproductive years and its decrease at menopause correlate with disease outcomes in WwMS. METHODS: Thirty-two perimenopausal WwMS participated in a two-phase study. In the first cross-sectional phase, we calculated the cumulative lifetime estrogen exposure (CLEE) and examined its associations with physical and cognitive disability, as well as optical coherence tomography and magnetic resonance imaging metrics, comparing individuals with long versus short CLEE. In the second longitudinal phase, 21 WwMS returned for follow-up at 6, 12 and 18 months. The cohort was divided into menopause-positive (M+) and menopause-negative (M-) groups, and group differences were analyzed. RESULTS: WwMS with longer CLEE had lower baseline Expanded Disability Status Scale scores (p = 0.03), a thicker optic nerve head (p = 0.04), and a thicker macular retinal nerve fiber layer (p = 0.03). They also performed better on the 9-Hole Peg Test (p = 0.018) and scored lower on the MS Impact Scale-29 (p = 0.002). After 12 months, longer CLEE correlated inversely with loss of the macular ganglion cell-inner plexiform layer (r = -0.532, p = 0.04). Additionally, M+ WwMS experienced greater brain volume loss compared with M- WwMS (p = 0.029). DISCUSSION: A longer duration of CLEE is associated with better outcomes in WwMS, while menopause appears to be linked to increased brain atrophy. Larger clinical studies are warranted to further explore these findings and clarify the relationships between CLEE, menopause and MS outcomes.
OBJECTIVE: Cerebral sinus venous thrombosis (CSVT) is a rare stroke subtype and data regarding the impact of ethnicity on its presentation and outcomes are limited. METHODS: The Israeli CSVT cohort, which includes databa...OBJECTIVE: Cerebral sinus venous thrombosis (CSVT) is a rare stroke subtype and data regarding the impact of ethnicity on its presentation and outcomes are limited. METHODS: The Israeli CSVT cohort, which includes databases from six academic medical centers, was retrospectively studied. Demographics, clinical presentations, risk factors, radiological findings, and outcome parameters were compared between Jewish and Arab Israeli patients. RESULTS: The study included 554 patients with CSVT, of whom 71 (13%) were of Arab ethnicity and 483 (87%) were Jewish. Arab patients were younger (mean age 38.4 ± 15.8 vs. 42.8 ± 10.1 years, p = 0.027), and more frequently male (48% vs. 33%, p = 0.013). Rates of Behcet's disease (BD) were higher among Arabs patients (13% vs. 3%, p < 0.001), antiphospholipid syndrome (23% vs. 10%, p = 0.002) and any coagulopathy (48% vs. 35%, p = 0.04), but lower rates of hypertension (4% vs. 15%, p = 0.016), and use of oral contraceptives (9% vs. 26%, p = 0.002). Differences in clinical presentation included higher rates of headache (90% vs. 74%, p = 0.004) and vomiting (39% vs. 15%, p < 0.001) in the Arab patient group. Arab ethnicity was associated with lower rates of any recanalization (aOR 0.346 [0.172-0.695], p = 0.003), and complete recanalization (aOR 0.408 [0.209-0.795], p = 0.008). Despite these differences, rates of favorable outcomes, mortality, and CSVT recurrence were similar between the groups. CONCLUSIONS: The findings highlight notable ethnic variations in the risk factors and clinical manifestations of CSVT between Arab and Jewish populations living in the same physical surroundings. Understanding these ethnic differences is crucial for creating targeted prevention and treatment strategies that cater to the specific needs of these diverse groups.
OBJECTIVE: To characterize the phenotypes and prevalence of status epilepticus (SE) in idiopathic generalized epilepsy (IGE) through a case series in an epilepsy center and a literature review. METHODS: In this study, we...OBJECTIVE: To characterize the phenotypes and prevalence of status epilepticus (SE) in idiopathic generalized epilepsy (IGE) through a case series in an epilepsy center and a literature review. METHODS: In this study, we evaluated a cohort of IGE patients aged 18 years or older with EEG-confirmed SE at Beaumont Hospital between 2005 and 2023. A scoping review was also performed by searching PubMed/Medline and SCOPUS between January 1983 and December 2023. RESULTS OF THE CASE SERIES: Eleven out of 443 adult IGE patients (2.5%) at our center had EEG-confirmed status epilepticus, all presenting as absence status epilepticus (ASE). All patients had a prior diagnosis of epilepsy; four were initially misdiagnosed with focal epilepsy. We identified two clinical presentations: ASE in isolation and associated with a GTCS. Most cases resolved with benzodiazepine therapy. RESULTS OF THE SCOPING REVIEW: Seventy-three studies were included, encompassing 204 adult patients who experienced SE. ASE accounted for 84.8% of cases. Common triggers included sodium channel blockers and poor antiseizure medication adherence. Benzodiazepines were the primary first-line treatment for SE, with valproate often used as a second-line option. Despite several studies not including clinical follow-up, around 40% of patients achieved seizure freedom. SIGNIFICANCE: ASE appears to be the most commonly reported type of SE in IGE, yet it is often not suspected clinically. The clinical presentation of ASE is wide, mainly characterized by confusion and altered awareness, and often accompanied by subtle motor and/or psychiatric symptoms. The response to benzodiazepines is generally favorable.
BACKGROUND: The optimal antithrombotic strategy for secondary prevention in patients with atrial fibrillation (AF) and concomitant atherosclerotic cardiovascular disease (ASCVD) following acute ischemic stroke (IS) remai...BACKGROUND: The optimal antithrombotic strategy for secondary prevention in patients with atrial fibrillation (AF) and concomitant atherosclerotic cardiovascular disease (ASCVD) following acute ischemic stroke (IS) remains undefined. This network meta-analysis aimed to compare the efficacy and safety of oral anticoagulant (OAC) monotherapy, antiplatelet therapy (APT), and their combination in this population. METHODS: We systematically searched major electronic databases through October 2025 for relevant randomized and non-randomized studies. A frequentist network meta-analysis was performed using random-effects models to calculate pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Treatment hierarchies were ranked using P-scores. The primary outcome was a composite of all-cause mortality, major bleeding, and any ischemic event. RESULTS: Ten studies (1 randomized trial, 9 observational) involving 14,104 patients were included. Compared to combination therapy, OAC monotherapy ranked most favorable for the primary composite endpoint (HR 0.82, 95% CI: 0.53-1.27; P-score: 0.90) and for recurrent IS (HR 0.77, 95% CI: 0.50-1.20; P-score: 0.88). Regarding major bleeding, both APT (HR 0.64, 95% CI: 0.28-1.46; P-score: 0.75) and OAC monotherapy (HR 0.74, 95% CI: 0.35-1.55; P-score: 0.57) showed a trend toward reduced major bleeding compared to combination therapy, though neither reached statistical significance. For mortality, OAC monotherapy was comparable to combination therapy (HR 1.11, 95% CI: 0.66-1.87), whereas APT showed a trend toward higher risk (HR 1.78, 95% CI: 0.97-3.29; P-score: 0.05). CONCLUSION: In patients with IS, AF, and ASCVD, OAC monotherapy appears to be the most favorable strategy for secondary prevention, offering an optimal balance between efficacy and safety. Adding APT confers no additional clinical benefit while potentially increasing bleeding risk. However, given the predominance of observational data, these findings should be interpreted with caution and confirmed through dedicated randomized controlled trials. PROSPERO ID: CRD420251182535.
Shaban N, Shawkat AM, Jain AK
… +12 more, Gadelmawla AF, Kaddoura R, Gozum N, Feldstein E, Elfil M, Elmashad A, Albanna AJ, Khandelwal P, El-Ghanem M, Kaur G, Gandhi CD, Al-Mufti F
BACKGROUND: Despite the fact that a large proportion of patients with acute ischemic stroke (AIS) who undergo endovascular thrombectomy (EVT) for large vessel occlusion (LVO) achieve successful recanalization, they conti...BACKGROUND: Despite the fact that a large proportion of patients with acute ischemic stroke (AIS) who undergo endovascular thrombectomy (EVT) for large vessel occlusion (LVO) achieve successful recanalization, they continue to experience poor functional outcomes due to microvascular failure. Adjunctive intra-arterial tenecteplase (IA-TNK) has been proposed as a promising strategy to address this phenomenon of futile recanalization. OBJECTIVE: To evaluate the effectiveness and safety of intra-arterial tenecteplase (IA-TNK) after successful EVT in ischemic stroke. METHODS: We performed a comprehensive search of seven databases for clinical trials of IA-TNK after successful EVT for AIS. Eligible studies compared combined IA-TNK and EVT versus EVT only. Data were pooled using random-effects models, risk of bias was assessed with RoB-2 and RoB-1, and certainty of evidence was graded using GRADE. RESULTS: Overall analysis showed that IA-TNK administered after successful EVT was associated with significantly higher rates of mRS 0-1 compared to control (risk difference [RD] = 0.08, 95% CI [0.02, 0.14], p = 0.004; I = 0%). The number needed to treat was 13. Subgroup analysis revealed some benefits across different TNK dosing strategies. There was no significant increase in symptomatic intracranial hemorrhage (sICH) (RD = 0.02, 95% CI [-0.01, 0.05], p = 0.13) or mortality (RD = -0.02, 95% CI [-0.07, 0.02], p = 0.36). CONCLUSION: Adjunctive IA-TNK after successful EVT is associated with significant improvement in functional outcomes without increasing the risk of sICH or mortality. These findings suggest that IA-TNK may be considered as promising therapy to overcome microvascular failure in patients achieving successful EVT.
BACKGROUND: Odorant-binding protein IIa (OBPIIa) gene variants are linked to Parkinson's disease (PD)-related olfactory loss, but their role in clinical subtypes and mechanisms remains unclear. This study examined associ...BACKGROUND: Odorant-binding protein IIa (OBPIIa) gene variants are linked to Parkinson's disease (PD)-related olfactory loss, but their role in clinical subtypes and mechanisms remains unclear. This study examined associations with clinical scales, neuroimaging, and cerebrospinal fluid (CSF) biomarkers. METHODS: Data from the Parkinson's Progression Markers Initiative (PPMI) cohort were analyzed. Multinomial logistic regression was employed to investigate the role of OBPIIa SNPs in PD prodromal or clinically established PD status. Additionally, the associations of OBPIIa SNPs with clinical scales, neuroimaging, and CSF biomarkers were evaluated using multiple linear or logistic regression models. RESULTS: Among the 1079 subjects (195 Healthy controls, 287 prodromal PD, and 597 clinically established PD), rs2590499 and rs2853652 were significantly associated with prodromal PD status, but not with clinically established PD diagnosis. Dopamine transporter (DAT)-SPECT imaging revealed divergent associations: rs3178137 was strongly linked to a higher DAT binding in the caudate, while rs504061 and rs2853652 exhibited a trend toward lower DAT binding. Concurrently, rs72766539 and rs3178137 were statistically significantly correlated to elevated levels of CSF DOPAC in females. In males, rs3178137 showed a trend toward milder non-motor symptoms, higher DAT binding, and higher levels of CSF tau proteins. No significant associations were found between OBPIIa variants and PD severity (H&Y stage). OBPIIa showed no longitudinal association with DAT or CSF progression. CONCLUSION: Our study showed that OBPIIa variants are associated with prodromal phenotypes and dopaminergic-related biomarker characteristics. These findings supported a potential link to early non-motor and biomarker features rather than clinically established PD.
The characteristic MRI findings in AESD emerge 3-14 days post-onset according to international consensus definitions, creating a temporal mismatch whereby MRI-based prognostic classification may not be available within t...The characteristic MRI findings in AESD emerge 3-14 days post-onset according to international consensus definitions, creating a temporal mismatch whereby MRI-based prognostic classification may not be available within the critical 24-48 h therapeutic window for neuroprotective interventions such as edaravone.
BACKGROUND/OBJECTIVES: Parkinson's disease patients (PD) display changes in the levels of circulating peripheral immune cells. A declining lymphocyte count and a raised neutrophil-to-lymphocyte ratio (NLR) may result fro...BACKGROUND/OBJECTIVES: Parkinson's disease patients (PD) display changes in the levels of circulating peripheral immune cells. A declining lymphocyte count and a raised neutrophil-to-lymphocyte ratio (NLR) may result from an impaired adaptive response and increased levels of inflammation. This study sought to identify circulating peripheral immune cell changes in PD patients. METHODS: PD and healthy controls (HC) were recruited from the East London Parkinson's Disease (ELPD) project. Numbers of immune cells from peripheral blood samples were cross-sectionally analysed across three (pre-, within 6 months of PD diagnosis, and post-PD diagnosis) or two (pre- and post-PD diagnosis) time points and compared with HC. RESULTS: The study included 145 (85 male (M), 60 female (F)) PD and 73 (47 M, 26 F) HC. The two-time point analysis included all participants, whereas the three-time point analysis included 41 (25 M, 16 F) PD and 55 (36 M, 19 F) HC. Lymphocyte count and NLR were not significantly different between PD and HC. There was a non-significant trend towards lower lymphocyte count in PD following diagnosis in an unadjusted model for both the two-time point (OR = 0.76; CI = 0.56-1.02, p = 0.069) and three-time point (OR = 0.62; CI = 0.37-1.30, p = 0.064) analyses, but in both analyses this trend disappeared when adjusting for confounding factors. Levodopa equivalent daily dose was not significantly associated with lymphocyte count or NLR. CONCLUSION: Our study revealed no significant difference in lymphocyte count or NLR between PD and HC. There was a non-significant trend towards lower lymphocyte count following diagnosis in PD.
Belgrado E, Tuniz F, Piccolo D
… +10 more, Bagatto D, De Colle C, D'Agostini S, Fabris M, Cifù A, Gigli GL, Merlino G, Vindigni M, Valente M, Tereshko Y
AIMS: AQP4 is involved in regulating brain water homeostasis and in the function of the glymphatic system. In iNPH there is an altered parenchymal expression of AQP4, contributing to glymphatic dysfunction. This study ai...AIMS: AQP4 is involved in regulating brain water homeostasis and in the function of the glymphatic system. In iNPH there is an altered parenchymal expression of AQP4, contributing to glymphatic dysfunction. This study aimed to test AQP4 and AQP1 levels in cerebrospinal fluid from iNPH, NOT-NPH, and control subjects to evaluate their diagnostic utility and their correlation with clinical parameters. METHODS: CSF samples were collected from probable iNPH patients during the Tap test (TT). Patients who responded to the TT or with a R ≥ 12 mmHg/mL/min, performed ventriculoperitoneal shunting (VPS); patients with a negative response to the TT and with a R < 12 mmHg/mL/min did not perform surgery (NOT-iNPH group). Ten CSF samples from healthy Controls were collected from our biobank. We conducted an ELISA test to measure levels of Aquaporin 1 and Aquaporin 4. Clinical parameters were collected before and after the TT. A total of 16 iNPH patients, 10 NOT-iNPH patients, and 10 controls were involved in this study. RESULTS: AQP1 levels were higher in iNPH versus NOT-NPH and controls (p < 0,005); AQP4 levels were similar in the three groups. In iNPH patients only, there was a significant correlation between AQP4 CSF levels and MDS-UPDRS-III (r 0.76, p < 0.001), TUG (Time Up-and-Go) (r 0.58, p < 0.05), and MMSE (r - 0.55, p = 0.05). CONCLUSIONS: AQP-4 CSF levels may correlate with the severity of Parkinsonian signs in iNPH patients, while AQP1 CSF levels may reflect the downregulation of CSF production.