BMC Neurology

BACKGROUND: Previously published studies have reported that up to 43% of patients with disorders of consciousness are erroneously assigned a diagnosis of vegetative state (VS). However, no recent studies have investigated the accuracy of this grave clinical diagnosis. In this study, we compared consensus-based diagnoses of VS and MCS to those based on a well-established standardized neurobehavioral rating scale, the JFK Coma Recovery Scale-Revised (CRS-R). METHODS: We prospectively followed 103 patients (55 +/- 19 years) with mixed etiologies and compared the clinical consensus diagnosis provided by the physician on the basis of the medical staff's daily observations to diagnoses derived from CRS-R assessments performed by research staff. All patients were assigned a diagnosis of 'VS', 'MCS' or 'uncertain diagnosis.' RESULTS: Of the 44 patients diagnosed with VS based on the clinical consensus of the medical team, 18 (41%) were found to be in MCS following standardized assessment with the CRS-R. In the 41 patients with a consensus diagnosis of MCS, 4 (10%) had emerged from MCS, according to the CRS-R. We also found that the majority of patients assigned an uncertain diagnosis by clinical consensus (89%) were in MCS based on CRS-R findings. CONCLUSION: Despite the importance of diagnostic accuracy, the rate of misdiagnosis of VS has not substantially changed in the past 15 years. Standardized neurobehavioral assessment is a more sensitive means of establishing differential diagnosis in patients with disorders of consciousness when compared to diagnoses determined by clinical consensus.

BACKGROUND: stroke is the main cause of disability in high-income countries, and ranks second as a cause of death worldwide. Patients with acute stroke are at risk for infections, but reported post-stroke infection rates vary considerably. We performed a systematic review and meta-analysis to estimate the pooled post-stroke infection rate and its effect on outcome. METHODS: MEDLINE and EMBASE were searched for studies on post-stroke infection. Cohort studies and randomized clinical trials were included when post-stroke infection rate was reported. Rates of infection were pooled after assessment of heterogeneity. Associations between population- and study characteristics and infection rates were quantified. Finally, we reviewed the association between infection and outcome. RESULTS: 87 studies were included involving 137817 patients. 8 studies were restricted to patients admitted on the intensive care unit (ICU). There was significant heterogeneity between studies (P < 0.001, I(2) = 97%). The overall pooled infection rate was 30% (24-36%); rates of pneumonia and urinary tract infection were 10% (95% confidence interval [CI] 9-10%) and 10% (95%CI 9-12%). For ICU studies, these rates were substantially higher with 45% (95% CI 38-52%), 28% (95%CI 18-38%) and 20% (95%CI 0-40%). Rates of pneumonia were higher in studies that specifically evaluated infections and in consecutive studies. Studies including older patients or more females reported higher rates of urinary tract infection. Pneumonia was significantly associated with death (odds ratio 3.62 (95%CI 2.80-4.68). CONCLUSIONS: Infection complicated acute stroke in 30% of patients. Rates of pneumonia and urinary tract infection after stroke were 10%. Pneumonia was associated with death. Our study stresses the need to prevent infections in patients with stroke.

BACKGROUND: The Patient Determined Disease Steps (PDDS) is a promising patient-reported outcome (PRO) of disability in multiple sclerosis (MS). To date, there is limited evidence regarding the validity of PDDS scores, despite its sound conceptual development and broad inclusion in MS research. This study examined the validity of the PDDS based on (1) the association with Expanded Disability Status Scale (EDSS) scores and (2) the pattern of associations between PDDS and EDSS scores with Functional System (FS) scores as well as ambulatory and other outcomes. METHODS: 96 persons with MS provided demographic/clinical information, completed the PDDS and other PROs including the Multiple Sclerosis Walking Scale-12 (MSWS-12), and underwent a neurological examination for generating FS and EDSS scores. Participants completed assessments of cognition, ambulation including the 6-minute walk (6 MW), and wore an accelerometer during waking hours over seven days. RESULTS: There was a strong correlation between EDSS and PDDS scores (ρ = .783). PDDS and EDSS scores were strongly correlated with Pyramidal (ρ = .578 &ρ = .647, respectively) and Cerebellar (ρ = .501 &ρ = .528, respectively) FS scores as well as 6 MW distance (ρ = .704 &ρ = .805, respectively), MSWS-12 scores (ρ = .801 &ρ = .729, respectively), and accelerometer steps/day (ρ = -.740 &ρ = -.717, respectively). CONCLUSION: This study provides novel evidence supporting the PDDS as valid PRO of disability in MS.

BACKGROUND: The aim was to collate all myasthenia gravis (MG) epidemiological studies including AChR MG and MuSK MG specific studies. To synthesize data on incidence rate (IR), prevalence rate (PR) and mortality rate (MR) of the condition and investigate the influence of environmental and technical factors on any trends or variation observed. METHODS: Studies were identified using multiple sources and meta-analysis performed to calculate pooled estimates for IR, PR and MR. RESULTS: 55 studies performed between 1950 and 2007 were included, representing 1.7 billion population-years. For All MG estimated pooled IR (eIR): 5.3 per million person-years (C.I.:4.4, 6.1), range: 1.7 to 21.3; estimated pooled PR: 77.7 per million persons (C.I.:64.0, 94.3), range 15 to 179; MR range 0.1 to 0.9 per millions person-years. AChR MG eIR: 7.3 (C.I.:5.5, 7.8), range: 4.3 to 18.0; MuSK MG IR range: 0.1 to 0.32. However marked variation persisted between populations studied with similar methodology and in similar areas. CONCLUSIONS: We report marked variation in observed frequencies of MG. We show evidence of increasing frequency of MG with year of study and improved study quality. This probably reflects improved case ascertainment. But other factors must also influence disease onset resulting in the observed variation in IR across geographically and genetically similar populations.

Substances cross the blood-brain barrier (BBB) by a variety of mechanisms. These include transmembrane diffusion, saturable transporters, adsorptive endocytosis, and the extracellular pathways. Here, we focus on the chief characteristics of two mechanisms especially important in drug delivery: transmembrane diffusion and transporters. Transmembrane diffusion is non-saturable and depends, on first analysis, on the physicochemical characteristics of the substance. However, brain-to-blood efflux systems, enzymatic activity, plasma protein binding, and cerebral blood flow can greatly alter the amount of the substance crossing the BBB. Transport systems increase uptake of ligands by roughly 10-fold and are modified by physiological events and disease states. Most drugs in clinical use to date are small, lipid soluble molecules that cross the BBB by transmembrane diffusion. However, many drug delivery strategies in development target peptides, regulatory proteins, oligonucleotides, glycoproteins, and enzymes for which transporters have been described in recent years. We discuss two examples of drug delivery for newly discovered transporters: that for phosphorothioate oligonucleotides and for enzymes.

BACKGROUND: As greater numbers of us are living longer, it is increasingly important to understand how we can age healthily. Although old age is often stereotyped as a time of declining mental abilities and inflexibility, cognitive neuroscience reveals that older adults use neural and cognitive resources flexibly, recruiting novel neural regions and cognitive processes when necessary. Our aim in this project is to understand how age-related changes to neural structure and function interact to support cognitive abilities across the lifespan. METHODS/DESIGN: We are recruiting a population-based cohort of 3000 adults aged 18 and over into Stage 1 of the project, where they complete an interview including health and lifestyle questions, a core cognitive assessment, and a self-completed questionnaire of lifetime experiences and physical activity. Of those interviewed, 700 participants aged 18-87 (100 per age decile) continue to Stage 2 where they undergo cognitive testing and provide measures of brain structure and function. Cognition is assessed across multiple domains including attention and executive control, language, memory, emotion, action control and learning. A subset of 280 adults return for in-depth neurocognitive assessment in Stage 3, using functional neuroimaging experiments across our key cognitive domains.Formal statistical models will be used to examine the changes that occur with healthy ageing, and to evaluate age-related reorganisation in terms of cognitive and neural functions invoked to compensate for overall age-related brain structural decline. Taken together the three stages provide deep phenotyping that will allow us to measure neural activity and flexibility during performance across a number of core cognitive functions. This approach offers hypothesis-driven insights into the relationship between brain and behaviour in healthy ageing that are relevant to the general population. DISCUSSION: Our study is a unique resource of neuroimaging and cognitive measures relevant to change across the adult lifespan. Because we focus on normal age-related changes, our results may contribute to changing views about the ageing process, lead to targeted interventions, and reveal how normal ageing relates to frail ageing in clinicopathological conditions such as Alzheimer's disease.

BACKGROUND: There are a number of instruments that describe severity and progression of multiple sclerosis and they are increasingly used as endpoints to assess the effectiveness of therapeutic interventions. We examined to what extent the psychometric properties of two accepted instruments--EDSS and MSFC--meet methodological standards and the value they have in clinical trials. METHODS: We conducted a systematic literature search in relevant databases [MEDLINE (PubMed), ISI Web of Science, EMBASE, PsycINFO & PSYNDEX, CINAHL] yielding 3,860 results. Relevant full-text publications were identified using abstract and then full-text reviews, and the literature was reviewed. RESULTS: For evaluation of psychometric properties (validity, reliability, sensitivity of change) of EDSS and MSFC, 120 relevant full-text publications were identified, 54 of them assessed the EDSS, 26 the MSFC and 40 included both instruments. The EDSS has some documented weaknesses in reliability and sensitivity to change. The main limitations of the MSFC are learning effects and the z-scores method used to calculate the total score. However, the methodological criterion of validity applies sufficiently for both instruments.For use in clinical studies, we found the EDSS to be preferred as a primary and secondary outcome measure in recent studies (50 EDSS, 9 MSFC). CONCLUSIONS: Recognizing their strengths and weaknesses, both EDSS and MSFC are suitable to detect the effectiveness of clinical interventions and to monitor disease progression. Almost all publications identify the EDSS as the most widely used tool to measure disease outcomes in clinical trials. Despite some limitations, both instruments are accepted as endpoints and neither are discussed as surrogate parameters in identified publications. A great advantage of the EDSS is its international acceptance (e.g. by EMA) as a primary endpoint in clinical trials and its broad use in trials, enabling cross-study comparisons.

BACKGROUND: The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood. METHODS: Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/- 11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/- 11.8 yrs.) who fulfilled criteria for fibromyalgia. RESULTS: Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post- SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms. CONCLUSIONS: The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.

BACKGROUND: Multiple sclerosis (MS) is the most common cause of neurological disability in young adults worldwide and approximately half of those affected are in Europe. The assessment of differential incidence and prevalence across populations can reveal spatial, temporal and demographic patterns which are important for identifying genetic and environmental factors contributing to MS. However, study methodologies vary and the quality of the methods can influence the estimates. This study aimed to systematically review European studies of incidence and prevalence of MS and to provide a quantitative assessment of their methodological quality. METHODS: A comprehensive literature search was performed to obtain all original population-based studies of MS incidence and prevalence in European populations conducted and published between January 1985 and January 2011. Only peer-reviewed full-text articles published in English or French were included. All abstracts were screened for eligibility and two trained reviewers abstracted the data and graded the quality of each study using a tool specifically designed for this study. RESULTS: There were 123 studies that met the inclusion criteria. The study estimates were highly heterogeneous, even within regions or countries. Quality was generally higher in the more recent studies, which also tended to use current diagnostic criteria. Prevalence and incidence estimates tended to be higher in the more recent studies and were higher in the Nordic countries and in northern regions of the British Isles. With rare exceptions, prevalence and incidence estimates were higher in women with ratios as high as 3:1. Few studies examined ethnicity. Epidemiological data at the national level was uncommon and there were marked geographical disparities in available data, with large areas of Europe unrepresented and other regions well-represented in the literature. Only 37% of the studies provided standardized estimates. CONCLUSIONS: Despite the breadth of the literature on the epidemiology of MS in Europe, inter-study comparisons are hampered by the lack of standardization. Further research should focus on regions not yet studied and the evaluation of ethnic differences in MS prevalence and incidence. National-level studies using current diagnostic criteria, validated case definitions and similar age- and sex-standardization would allow better geographical comparisons.

BACKGROUND: While multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are primarily inflammatory and degenerative disorders respectively, there is increasing evidence for shared cellular mechanisms that may affect disease progression, particularly glial responses. Cyclooxygenase 2 (COX-2) inhibition prolongs survival and cannabinoids ameliorate progression of clinical disease in animal models of ALS and MS respectively, but the mechanism is uncertain. Therefore, three key molecules known to be expressed in activated microglial cells/macrophages, COX-2, CB2 and P2X7, which plays a role in inflammatory cascades, were studied in MS and ALS post-mortem human spinal cord. METHODS: Frozen human post mortem spinal cord specimens, controls (n = 12), ALS (n = 9) and MS (n = 19), were available for study by immunocytochemistry and Western blotting, using specific antibodies to COX-2, CB2 and P2X7, and markers of microglial cells/macrophages (CD 68, ferritin). In addition, autoradiography for peripheral benzodiazepine binding sites was performed on some spinal cord sections using [3H] (R)-PK11195, a marker of activated microglial cells/macrophages. Results of immunostaining and Western blotting were quantified by computerized image and optical density analysis respectively. RESULTS: In control spinal cord, few small microglial cells/macrophages-like COX-2-immunoreactive cells, mostly bipolar with short processes, were scattered throughout the tissue, whilst MS and ALS specimens had significantly greater density of such cells with longer processes in affected regions, by image analysis. Inflammatory cell marker CD68-immunoreactivity, [3H] (R)-PK11195 autoradiography, and double-staining against ferritin confirmed increased production of COX-2 by activated microglial cells/macrophages. An expected 70-kDa band was seen by Western blotting which was significantly increased in MS spinal cord. There was good correlation between the COX-2 immunostaining and optical density of the COX-2 70-kDa band in the MS group (r = 0.89, P = 0.0011, n = 10). MS and ALS specimens also had significantly greater density of P2X7 and CB2-immunoreactive microglial cells/macrophages in affected regions. CONCLUSION: It is hypothesized that the known increase of lesion-associated extracellular ATP contributes via P2X7 activation to release IL-1 beta which in turn induces COX-2 and downstream pathogenic mediators. Selective CNS-penetrant COX-2 and P2X7 inhibitors and CB2 specific agonists deserve evaluation in the progression of MS and ALS.

Demyelinating disorders are among the neurological complications following COVID-19 vaccination; however, the magnitude and consistency of this association are debated. An umbrella review of systematic reviews and meta-analyses on COVID-19 vaccination and demyelinating diseases was conducted following PRISMA. PubMed/MEDLINE, Google Scholar and Scopus were searched. Overlap of primary studies was quantified using a citation matrix and the corrected covered area (CCA). Ten artificial intelligence (AI) tools were prompted with the same questions, and their outputs appraised against a pre-specified rubric verifying every supplied reference. Thirty eligible reviews fulfilled the inclusion criteria, addressing new-onset disease and relapse. Overlap was slight overall (CCA 3.7%) but moderate-to-high for Guillain-Barre syndrome (10.5%) and acute disseminated encephalomyelitis (8.6%). The evidence suggests a possible association with both new-onset and relapsing disease; however, the absolute risk appears very low, approximately 1.4 Guillain-Barre cases per million doses in the only review reporting a denominator. All 28 AI outputs matched the manual synthesis in direction, but only 65% of 167 supplied references could be verified and 9% were fabricated. Previously reported relative risk estimates, considered together, suggest that demyelinating events occur more frequently following SARS-CoV-2 infection than after vaccination. Current evidence supports a low risk of demyelinating disease onset or exacerbation following COVID-19 vaccination, whereas the risk after COVID-19 infection is substantially higher; benefits clearly outweigh potential risks. Because the underlying evidence derives overwhelmingly from case reports and series without unexposed comparators, causality cannot be established. AI tools may support rapid synthesis but cite unreliably.

Abstract Background Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy associated with substantial morbidity, but contemporary data on post-discharge readmission remain limited. We characterized 90-day readmission timing, causes, associated factors, and procedure coding after GBS. Methods We analyzed an unweighted cohort of adults with a principal diagnosis of GBS in the 2020 Nationwide Readmissions Database. The primary outcome was all-cause readmission within 90 days after discharge. Readmission causes were classified using principal readmission diagnoses mapped to Clinical Classifications Software Refined categories, and procedure coding was descriptively assessed using ICD-10 procedure codes and procedure-day variables. Logistic regression models were used to identify factors associated with readmission. Results Among 2,587 adults eligible for 90-day follow-up, 364 (14.1%) were readmitted. Readmissions clustered early, with 170 (46.7%) occurring within 15 days and 241 (66.2%) within 30 days. Separately, GBS was the principal diagnosis in 170 of 364 readmissions (46.7%), representing the largest grouped cause followed by septicemia (9.6%) and cardiovascular or thromboembolic conditions (6.9%). In adjusted analyses, discharge disposition was the most consistent marker of readmission risk: compared with routine home discharge, facility discharge was associated with higher odds of 90-day readmission (odds ratio 1.70, 95% confidence interval 1.27–2.28). Procedure-code timing suggested that diagnostic evaluation and immunotherapy were administered early, whereas plasma exchange, tracheostomy, gastrostomy, and rehabilitation-related procedures were performed at later stages. Conclusions Readmission after GBS is frequent, early, and clinically heterogeneous, supporting its interpretation as a marker of residual neurological disability, systemic complications, and care-transition vulnerability rather than recurrent GBS alone.

Current classifications of Guillain-Barré syndrome (GBS) cannot adequately predict the prognosis and response to immunotherapy of patients, leading to treatment uncertainty and suboptimal outcomes. This study aimed to establish a novel, data-driven classification to identify clinically distinct GBS subtypes and improve outcome prediction. Clinical, laboratory, and electrodiagnostic data from 155 patients with GBS who underwent plasmapheresis were retrospectively analyzed. A clustering algorithm, mixture model, was applied to identify distinct patient subgroups. Subsequently, a streamlined, interpretable decision tree model was developed using the most crucial features. Three distinct clusters were identified. Cluster 1 ( n = 39) represented the most severe presentation, with a median admission GBS disability scale of 5 and the lowest rate of post-treatment independent ambulation at 30 days after symptom onset (12.8%). Cluster 2 ( n = 61) demonstrated the baseline severity (median of GBS disability scale: 3) at admission and the most favorable prognosis, with 54.1% having independent ambulation. Cluster 3 ( n = 55), characterized by prominent demyelinating features, showed a notably higher response rate to plasmapheresis (85.5% of patients improving by ≥ 1 GBS disability scale), despite presenting with intermediate severity (median of GBS disability scale: 4). The decision tree model, incorporating five common clinical and electrophysiological variables, achieved excellent classification fidelity to practically approximate the clusters (accuracy: 0.877). Machine learning identified three GBS subtypes with distinct prognoses and clinical trajectories to plasmapheresis. Derived from these findings, a simple five-variable decision tree provides a practical tool for early prognostic stratification, facilitating early prognostic outcome estimation and risk-adapted clinical monitoring.

Early and accurate prediction of outcome in acute ischemic stroke (AIS) is important for clinical management. We aimed to develop and validate a clinical-radiomics nomogram to predict clinical outcomes in patients with AIS. A total of 214 AIS patients were retrospectively included, which were assigned to a training ( n = 105), validation ( n = 43), internal test ( n = 33), and external test cohorts ( n = 33). All patients underwent baseline multi-parametric MRI (mp-MRI) scans. According to the 90-day modified Rankin Scale (mRS) after discharge, the patients were stratified into good (mRS ≤ 2) and poor (mRS > 2) prognosis subtypes. A total of 1130 radiomic features were extracted from diffusion-weighted imaging, apparent diffusion coefficient, and cerebral blood flow images generated from arterial spin labeling data, respectively. The clinical, radiomics, and clinical-radiomics models were constructed for predicting AIS prognosis. The model discrimination, calibration, and clinical usefulness were evaluated using the area under the curve (AUC), calibration curves, and decision curve analysis (DCA), respectively. The clinical-radiomics nomogram, which integrates the multi-parametric MRI-based (mp-MRI) radiomics signature and diabetes, demonstrated higher AUCs (0.796 and 0.741) compared to the clinical model (0.787 and 0.670) and the mp-MRI radiomics model (0.783 and 0.682) in the internal and external test cohorts, respectively. The nomogram showed strong goodness-of-fit in both training and validation cohorts. DCA further indicated the clinical utility of the integrated model. The clinical-radiomics model is effective in predicting clinical outcomes of AIS patients, which can be used to guide personalized treatment strategies.

Drug resistance occurs in a clinically important subgroup of children with childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE), but early risk stratification remains difficult. We investigated clinical and video-electroencephalography (video-EEG) features associated with drug resistance and assessed the internal validity of an exploratory three-variable model. In this single-centre retrospective cohort, we analysed 61 children with CAE or JAE treated at the Affiliated Hospital of Qingdao University between January 2022 and January 2025. Drug resistance was defined as failure of adequate trials of two tolerated and appropriately chosen antiseizure medication schedules. Candidate variables included epilepsy syndrome, pretreatment seizure burden and quantitative video-EEG measures. Exploratory logistic-regression models were developed, and discrimination was quantified using the area under the receiver operating characteristic curve (AUC). The final combined model was internally validated with 2,000 bootstrap resamples to estimate optimism-corrected AUC, calibration intercept and slope, and Brier score. Of 61 children, 41 had a favourable seizure outcome and 20 met the criteria for drug resistance. Drug-resistant patients had higher pretreatment seizure frequency and greater interictal sleep generalized spike-wave discharge (GSWD) density. In the adjusted exploratory model, JAE versus CAE (odds ratio [OR] 10.219, 95% confidence interval [CI] 1.499–69.657), log-transformed pretreatment seizure frequency (OR 2.002, 95% CI 1.105–3.628) and log-transformed interictal sleep GSWD density (OR 13.793, 95% CI 1.846-103.056) remained associated with drug resistance; the wide CIs indicated substantial uncertainty. The apparent AUC was 0.868. After correction for bootstrap optimism of 0.025, the AUC was 0.843. The optimism-corrected calibration intercept and slope were − 0.110 and 0.784, respectively, and the optimism-corrected Brier score was 0.143. In this single-centre cohort, JAE syndrome, higher pretreatment seizure frequency and greater interictal sleep GSWD density were associated with drug resistance. Internal validation showed overfitting; the model should therefore be considered hypothesis-generating until it has undergone independent validation.

Abstract Background Sudoscan measures electrochemical skin conductance (ESC) at the hands and feet, but its role in focal radiculopathy is uncertain. We evaluated region-appropriate ESC in patients with electromyography/nerve conduction study (EMG/NCS)-confirmed radiculopathy, focusing on values below device-defined thresholds displayed on the Impeto Medical SUDOSCAN result page that might indicate coexisting distal sudomotor dysfunction rather than radiculopathy itself. Methods This cross-sectional study included 177 participants contributing 200 EMG/NCS-confirmed radiculopathy-region observations; 23 participants contributed both upper- and lower-region observations. Sudoscan and EMG/NCS were performed concurrently. For unilateral radiculopathy, affected-side hand ESC (upper region) or foot ESC (lower region) was used; for bilateral radiculopathy, left and right values were averaged. Below-threshold ESC was defined using device-defined boundaries of < 60 µS for hands and < 70 µS for feet. These boundaries were not derived or validated for radiculopathy. Regression used participant-clustered robust standard errors. Results Mean region-specific ESC was 63.2 ± 15.9 µS overall, 51.9 ± 15.1 µS for upper-region observations, and 68.1 ± 13.6 µS for lower-region observations. ESC was below the limb-specific threshold in 108/200 observations (54.0%; participant-clustered 95% CI 46.5–61.5%) and in at least one region in 99/177 participants (55.9%; 95% CI 48.6–63.0%). Rates were 70.5% for upper and 46.8% for lower observations. In the multivariable model (170 observations from 154 participants), older age (adjusted β = −0.29 µS/year, 95% CI − 0.51 to − 0.08; p = 0.007) and upper/hand measurement (adjusted β = −16.50 µS vs. lower/foot, 95% CI − 20.86 to − 12.14; p < 0.001) were associated with lower ESC. Among 51 unilateral observations from 50 participants, affected-side ESC was 1.78 µS lower than contralateral ESC (participant-clustered 95% CI − 3.16 to − 0.41; exploratory p = 0.012). Conclusions ESC was below the device-defined limb-specific threshold displayed on the Impeto Medical SUDOSCAN result page in 54.0% of EMG/NCS-confirmed radiculopathy-region observations. The upper–lower difference cannot be separated from the inherent hand–foot measurement-site difference. These findings do not support Sudoscan for diagnosing or localizing radiculopathy. Any adjunctive role in identifying coexisting distal sudomotor dysfunction remains hypothesis-generating and requires prospective validation.

Abstract Background Robust predictors of death by neurologic criteria (DNC) after non-traumatic acute brain injury remain insufficiently defined. We therefore aimed to systematically synthesize the available evidence on prediction of DNC in non-traumatic brain injury. Methods We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines. MEDLINE, Embase, Scopus, the Cochrane Library and Web of Science were searched to August 31, 2026. Eligible studies included randomized controlled trials, observational studies, case series and registry data. Studies were included in the quantitative synthesis when sufficient comparable data for the same prognostic factor were available from at least two studies. Pooled effect estimates were calculated using random-effects models. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. The certainty of evidence was assessed using the GRADE approach. Results The database search identified 2,091 records. Eighteen studies comprising reported study cohorts of 9,070 participants were included. Quantitative synthesis included four studies ( n =1,738), comprising two post-cardiac arrest and two stroke cohorts. In stroke populations, CT markers of severe intracranial mass effect were associated with a more than threefold increased odds of DNC (pooled OR 3.14, 95%CI 1.98–4.96; p <0.0001; I2=0%), while in post-cardiac arrest cohorts lower gray-white matter ratio values were associated with progression to DNC (pooled mean difference -0.15, 95%CI -0.22 to -0.07; p <0.001; I2=72%). Conclusions Evidence on predictors of DNC after non-traumatic acute brain injury remains limited and methodologically heterogeneous, with only a small number of studies providing robust analyses. Across these studies, CT-based markers - particularly indicators of diffuse cerebral edema or intracranial mass effect - show the most reproducible associations with progression to DNC.

Post-stroke fatigue (PSF) is a highly prevalent and disabling symptom that significantly impairs quality of life and rehabilitation outcomes after stroke. Despite its clinical importance, the neural mechanisms underlying PSF remain poorly understood. Neuroimaging provides a means to identify structural and functional brain markers associated with PSF; however, existing findings are heterogeneous and inconclusive. Further, the role of individual characteristics in the PSF-neuroimaging marker association has not been systematically examined. This scoping review aimed to identify neuroimaging markers associated with PSF and to explore whether individual characteristics, including age, sex, stroke severity, and fatigue severity, account for the inconsistency in these associations across studies. Five electronic databases (Medline, CINAHL, EMBASE, PubMed, and PsycInfo) were searched from January 1980 to May 2025. Studies were included if they assessed adult-onset stroke, measured fatigue using any validated or non-validated tool, and examined associations between fatigue and neuroimaging markers using MRI, CT, DTI, PET, or functional MRI. Two reviewers independently screened and extracted data. Findings were mapped descriptively across imaging markers, and exploratory comparisons were conducted to examine whether demographic factors and symptom severity differ among studies. Thirty studies including 3,660 participants were included. Functional connectivity was the most consistently associated neuroimaging marker, with 67% of studies reporting significant associations between altered resting-state connectivity and PSF. Lesion location was associated with PSF in 45% of studies, particularly involving subcortical regions such as the basal ganglia, thalamus, and brainstem. Structural connectivity and brain atrophy were understudied, while lesion size, lesion laterality, number of lesions, and white matter lesions were generally not associated with PSF. Exploratory analyses suggested that older mean age, a lower proportion of females, and higher fatigue prevalence were associated with studies reporting significant relationship between neuroimaging markers and PSF. This scoping review suggests that altered functional connectivity and lesion location, particularly involving the fronto-striato-thalamic circuitry, are promising neuroimaging markers of PSF. The findings further indicate that demographic factors and symptom severity may account for the inconsistency in neuroimaging literature. Future studies should incorporate network-based imaging approaches, assess distinct domains of fatigue, and account for individual characteristics to better delineate the neural mechanisms of PSF and support personalized rehabilitation strategies.

Abstract Background Caring for a child with epilepsy often causes a significant psychological burden on caregivers, leading to elevated stress levels that may affect both caregiver well-being and child care outcomes. In resource-limited settings like Sri Lanka, limited awareness, treatment challenges, and socioeconomic constraints may further intensify caregiver stress. Methods A descriptive cross-sectional study was conducted among 220 primary caregivers of epileptic children attending the Pediatric Neurology Clinic at National Hospital Galle, Sri Lanka. A validated Sinhala version of the Perceived Stress Scale (PSS) was used. The data were analyzed with SPSS 26 software, using descriptive statistics, Chi square test, independent sample t-test, and Pearson correlation. Ethical approval was obtained from the Ethics Review Committee of the Faculty of Allied Health Sciences, University of Ruhuna. Results The majority of the caregivers were female (68.2%), married (95.9%), and living in rural areas (80.5%). Mean (± SD) age was 39.3 (± 7.7) years. The PSS total score revealed that the majority ( n = 178, 80.9%) experienced a moderate level of stress. Significant associations were found between caregivers’ stress and residential area ( p = 0.007), awareness of sudden epileptic attacks management ( p = 0.023), child’s use of epilepsy medications ( p = 0.018), and monthly household income ( p = 0.002). Conclusions The study showed that the majority of caregivers of epileptic children experienced moderate to high stress. Significant associations were found with residential area, awareness of seizure management, the child’s medication use, and monthly income. Interventions focusing on caregiver education, psychosocial support, and assistance for rural and low-income families are recommended to reduce stress. Clinical trial number Not applicable.

Acute cerebrovascular disease (ACD) carries a high mortality rate despite advances in intensive care management. Glycemic variability (GV) and systolic blood pressure variability (SBPV) have been identified as prognostic indicators, but their combined and mediating effects on mortality remain unclear. This retrospective cohort study analyzed patients with cerebral infarction, intracerebral hemorrhage, or subarachnoid hemorrhage from the MIMIC-IV database. GV and SBPV were calculated using the coefficient of variation and stratified into tertiles. Logistic and Cox regression models were used to assess associations with 30-day, 1-year, and in-hospital mortality. Mediation analysis using the PROCESS macro with bootstrapping evaluated the interrelationship between GV and SBPV. Among 7,286 patients with ACD, both higher GV and SBPV were independently associated with increased 30-day, 1-year, and in-hospital mortality (all p < 0.001). A dose-response relationship was observed, with the combined elevation of GV and SBPV conferring the highest risk. For in-hospital mortality, SBPV showed the strongest predictive performance for in-hospital mortality (AUC = 0.672). Further exploratory analysis suggested a directional pathway, wherein the detrimental effect of GV on in-hospital mortality appeared to be partially dependent on the level of SBPV (proportion mediated = 18.0%, p < 0.001). Elevated GV and SBPV are independently associated with 30‑day, 1‑year, and in‑hospital mortality. Furthermore, higher combined variability scores are associated with a progressive increase in mortality risk. These findings suggest that concurrent monitoring of metabolic and hemodynamic fluctuations reflects physiological instability and may serve as supplementary markers alongside the assessment of absolute physiological levels.