Journal of Neurotrauma

Traumatic brain injury (TBI), particularly sports- and recreational activity related mild TBI (mTBI), is common in young adults and can be followed by persistent attentional and executive complaints. This study investigated chronic ([≥]6 months post-injury) structural brain alterations in gray matter (GM) and white matter (WM) and their associations with self-reported inattentive and hyperactive/impulsive symptoms, with a focus on sex-differentiated patterns. Structural brain properties in gray matter (GM) and white matter (WM) were acquired from 44 subjects with TBI and 45 matched controls, by utilizing structural MRI and diffusion tensor imaging techniques. Behavioral measures assessing severities of post TBI inattentive and hyperactive/impulsive symptoms were collected from each participant. Between-group and sex-specific differences of these brain and behavioral measures were conducted. Interactions among the TBI-induced significant brain- and behavioral-alterations, and their sex-specific patterns, were assessed as well. Male-dominated pattern of increased cortical thickness in superior parietal lobule (SPL) and female-dominated pattern of higher superior longitudinal fasciculus and superior fronto-occipital fasciculus (sFOF) fractional anisotropy (FA) were observed in the TBI group, when compared to controls. In males with TBI, greater SPL cortical thickness was significantly correlated with increased inattentive behaviors. In females with TBI, higher FA of sFOF was significantly correlated with decreased hyperactive/impulsive behaviors. Findings suggest that TBI-induced superior parietal cortical GM abnormalities may significantly cause attention deficits in patients with TBI, especially in males; while optimal post-TBI WM recovery in sFOF significantly contributes to maintenance of inhibitive control in patients with TBI, especially in females.

BackgroundTraumatic spinal cord injury (SCI) is a major cause of long-term neurological disability, with limited pharmacological therapies targeting secondary inflammatory and neurodegenerative injury mechanisms. Minocycline, a tetracycline derivative with anti-inflammatory and neuroprotective properties, has been investigated in both experimental and clinical settings; however, its therapeutic efficacy in acute traumatic SCI remains uncertain. MethodsA systematic review was conducted in accordance with PRISMA 2020 guidelines. Major electronic databases were comprehensively searched to identify preclinical animal studies and human clinical studies evaluating minocycline, alone or in combination therapies, for acute traumatic SCI. Risk of bias was assessed using Joanna Briggs Institute (JBI) critical appraisal tools tailored to study design. Qualitative synthesis included all eligible studies, while quantitative synthesis was restricted to clinical studies reporting extractable effect estimates for neurological improvement. ResultsA total of 11 studies met inclusion criteria for qualitative synthesis, including experimental animal studies and human clinical investigations. Preclinical studies demonstrated consistent biological effects of minocycline on inflammatory markers, oxidative stress, and histopathological outcomes, particularly in combination therapies, although functional recovery with minocycline monotherapy was inconsistent. Clinical studies indicated that minocycline was generally well tolerated; however, most trials did not demonstrate statistically significant improvements in neurological or functional outcomes. Only two clinical studies provided suitable data for meta-analysis, yielding a pooled odds ratio of 1.70 (95% CI 0.95-3.06) for neurological improvement, which did not reach statistical significance. ConclusionCurrent evidence suggests that while minocycline exhibits promising biological activity and an acceptable safety profile in acute traumatic SCI, robust clinical efficacy has not been conclusively demonstrated. Well-designed, adequately powered randomized controlled trials with standardized outcome reporting are required to determine whether these biological effects translate into meaningful functional recovery.

Repetitive head impacts (RHI) from contact and collision sports have been associated with later-life cognitive and neurobehavioral impairments, as well as neurodegenerative conditions such as chronic traumatic encephalopathy (CTE). RHI-associated clinical sequelae among female former soccer players, specifically, are not well understood. This cross-sectional study aimed to examine the relationship of RHI exposure proxies (e.g., total years of soccer play, highest level of play, and estimated cumulative heading frequency) with clinical measures (e.g., subjective cognitive complaints, objective cognitive performance, behavioral dysregulations, and depressive symptoms) among 3,174 women, aged 40 years or above, enrolled in the Head Impact and Trauma Surveillance Study (HITSS), all of whom played organized soccer. HITSS participants completed an online battery that elicited self-reported cognitive and behavioral complaints and depressive symptoms, and that assessed cognitive performing via computerized tests. Multivariable linear and logistic regression models estimated associations between soccer-related RHI proxies and outcome measures, adjusting for age and education. Among the former soccer players, longer duration of soccer play, higher level of play, and greater estimated cumulative heading frequency were significantly associated with worse self-reported cognitive functioning, greater behavioral dysregulation, and elevated depressive symptom severity (range of significant unstandardized B coefficients: 0.02 to 0.52). Higher estimated cumulative heading exposure was associated with higher odds of clinically meaningful elevations on subjective measures (OR range: 1.05 to 1.13) There were no associations between any of the RHI proxies and performance on the objective computerized cognitive assessments. Among middle-aged women who played organized soccer, cumulative RHI exposure was associated with small but statistically significant effects for measures of subjective cognitive complaints, behavioral functioning, and depressive symptoms. We found no associations for objective outcomes of cognitive function. Continued monitoring of this large cohort of female former soccer players will improve understanding of long-term consequences of soccer play.

ObjectiveCognitive motor dissociation (CMD) is associated with long-term recovery in acute brain injury, but CMD testing is only available in few centers. Our objective was to identify surface EEG patterns with high sensitivity or positive predictive value (PPV) for CMD in patients with acute disorders of consciousness to refine allocation of this resource-intensive test. MethodsIn this observational cohort study, we enrolled clinically unresponsive, acutely brain injured patients who underwent continuous surface EEG and CMD assessments. CMD was detected by applying a machine learning algorithm to EEG acquired during a motor command paradigm presentation. Electroencephalographers blinded to CMD test results applied standardized ACNS criteria to the EEGs acquired during CMD assessments. We calculated accuracy measures of surface EEG findings for CMD test results using generalized estimating equations, with an exchangeable matrix and accounting for repeated measures per patient. ResultsWe included 185 patients (mean age: 62 {+/-} 17; 85 [46%] female) and 282 CMD assessments. CMD testing was positive in 39 (14%) assessments. Sensitivity and PPV of normal background voltage, symmetry and continuity were respectively 77% (95%-CI: 60-88%) and 19% (95%-CI: 13-26%), 74% (95%-CI: 58-86%) and 14% (95%-CI: 10-20%), and 74% (95%-CI: 58-86%) and 14% (95%-CI: 9-19%). All EEGs with burst suppression, suppression, sporadic epileptiform discharges, lateralized periodic discharges, bilateral independent periodic discharges, electrographic seizures and brief potentially ictal rhythmic discharges had negative CMD tests. InterpretationSurface EEG findings are not reliable to screen for CMD or to identify patterns conferring higher CMD pretest probability.

BackgroundTraumatic brain injury (TBI) remains a major cause of morbidity, yet U.S. comparisons of injury mechanisms in diverse urban settings are limited. We examined differences across motorized road injuries, non-motorized road injuries, and falls. MethodsWe performed a retrospective study of consecutive TBI admissions to an ACS-verified trauma center from 2017 to 2022. Mechanisms were categorized as motorized, non-motorized, or falls. Outcomes included mortality, ICU and ventilator use, and hospital length of stay (LOS). Secondary measures included GCS-based TBI severity and orthopedic injury. Group differences were evaluated using chi-square/Fisher exact and Kruskal-Wallis tests; motorized versus non-motorized road injuries were compared with Wilcoxon rank-sum tests. ResultsAmong 1,131 TBI admissions, falls predominated (90.2%), followed by non-motorized (5.5%) and motorized (4.3%) injuries. Fall-related TBI occurred in older adults (mean age 71.2 vs 49.6 non-motorized and 45.6 motorized). Road injuries affected more frequently male ({approx}75 to 80% vs 61%; p=0.005) and Hispanic patients, who comprised 37.1% of non-motorized and 36.7% of motorized injuries versus 23.8% of falls. Mean Injury Severity Score (ISS) was 11.9 (non-motorized), 15.1 (motorized), and 14.1 (falls); ICU days were 1.7, 4.7, and 2.2; LOS 5.4, 8.4, and 8.3 respectively. Ventilator use differed across mechanisms (p=0.02), as did orthopedic injury (p=0.009). Mortality was highest after motorized injuries (14.3%) compared with falls (7.5%) and non-motorized injuries (3.2%). In pairwise comparisons, motorized injuries showed higher ISS, greater ICU and ventilator needs, and longer LOS (all p{approx}0.01 to 0.02), with a trend toward lower GCS (p=0.058). ConclusionsFalls accounted for most TBIs and primarily affected older adults, whereas motorized road injuries, though less frequent, produced the greatest severity, resource utilization, and mortality. The elevated representation of Hispanic patients in road-related mechanisms highlights a need for targeted prevention in urban communities.

ObjectiveTo examine the association between lumbo-pelvic angles (LPAs) and Magnetic Resonance Imaging (MRI) detected discopathy in adults with low back pain (LBP) in the Gaza Strip and to establish local reference values for LPA measurements. MethodologyProspective cross-sectional study, 200 adults with LBP referred for lumbosacral MRI at two major hospitals in Gaza Strip. 1.5T MRI scanners were used, and Lumbar lordosis angle (LLA), sacral kyphosis angle (SKA) and sacral table angle (STA) were measured on mid-sagittal T2 images. Discopathy characteristics were recorded, and disability was assessed using the Oswestry Disability Index. ResultOf the 200 participants (mean age 45.7{+/-}13.6 years; 52.5% male), discopathy was most common at L4/L5 (89.5%), L5/S1 (67%) and L3/L4 (40.5%). LPAs were not significantly associated with discopathy involvement, type or severity, except for SKA discopathy severity at L3/4 (p=0.044). LPA measures were consistent across age groups, though LLA and STA were lower in males (p<0.001 and p=0.008), and obese individuals had higher LLA than those of normal weight (p=0.004). Reference LPA values were established stratified by LBP duration, in acute, subacute and chronic LBP, indicating a negative correlation between LLA and SKA in moderate and chronic duration. ConclusionIn adults with LBP in Gaza Strip, MRI-derived LPA showed limited association with lumbar discopathy characteristics, pain duration or disability. Although small differences related to gender, BMI and a single disc level were observed, overall associations were weak. The study establishes population-specific reference values for LPAs, which should be interpreted cautiously within a broader clinical context.

Accurate diagnosis of urinary tract infection (UTI) in individuals with neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury or disease (SCI/D) remains a major clinical challenge. Standard diagnostic tools--including urine dipstick, urinalysis, and culture--lack population-specific reference ranges, and existing criteria are often insufficient to distinguish infection from background variability. To address this gap, we conducted a longitudinal study to define the range of "normal" variability in common urinary biomarkers among individuals with SCI/D who manage their bladders using intermittent catheterization (IC). Participants with NLUTD due to SCI/D who manage their bladders with IC provided urine samples at least two weeks apart, while asymptomatic. We assessed urinary white blood cell count, nitrite, leukocyte esterase, culture-based findings, and urine neutrophil gelatinase-associated lipocalin (uNGAL) to characterize intra-individual stability and inter-individual variation in biomarker profiles. Findings demonstrate that urine parameters exhibit measurable but bounded variability in the absence of UTI, and that deviations beyond these thresholds may support more accurate and individualized UTI diagnosis. By defining the normal range within which values vary without the emergence of symptoms, we hope to further inform clinical and researcher decision-making around variability that moves an individual beyond their normal range of variation in these urinary markers. Operationalizing biologic variability can reduce diagnostic uncertainty and improve antimicrobial stewardship in this frequently overtreated population.

BACKGROUNDThe recovery from sport-related concussion (SRC) is highly heterogenous, with many individuals experiencing symptoms that persist beyond typical recovery timeframes. The early identification of individuals at risk of prolonged symptoms is therefore critical to inform timely interventions and set realistic recovery expectations. Although acute symptom burden is one predictor of future symptom burden, reliance on self-reported measures may limit objectivity and reduce clinical utility in settings where symptom evaluation may be unreliable. In this prospective cohort study, we evaluated the discriminatory accuracy of the CogState Brief Battery, alone and in combination with the Sport Concussion Assessment Tool (SCAT), to classify Australian football players with SRC from Australian footballers without SRC at 24-hours post-injury/match. Furthermore, we examined whether CogState performance and symptom severity at 24 hours were associated with symptom outcomes at one-week post-injury. Adult amateur Australian football players (n=181) were recruited following SRC (n=109 SRC, 86% male) or after a non-injured match (n=72, 90% male). Participants completed the CogState Brief Battery, SCAT and Rivermead Post Concussion Questionnaire (RPQ) at 24-hours and one-week post-injury or match. Area under the receiver operating characteristic (AUC) analyses quantified the ability of 24-hour CogState task performance and SCAT symptom severity to distinguish SRC from controls. Linear regression models examined associations between CogState performance and symptom severity (SCAT and RPQ), within and across the 24-hour and one-week time points. Additional models evaluated whether combining 24-hour symptom severity assessments with CogState performance improved prediction of one-week symptom burden and symptomatic status. SCAT symptom severity demonstrated excellent discriminatory classification accuracy for SRC versus controls at 24-hours post-injury (AUC [95% CI]: 0.949 [0.916 - 0.981]). CogState task performance showed lower discriminatory accuracy but demonstrated fair classification and prognostic utility (e.g., Identification task AUC [95% CI]: 0.666 [0.582 - 0.750]). CogState performance at 24-hours was significantly associated with overall symptom severity at both 24-hours and one-week, as well as with symptom severity across individual symptom domains. In combined models, 24-hour symptom severity and CogState performance independently contributed to the prediction of symptomatic from asymptomatic individuals at one-week post-SRC (e.g., Identification task AUC [95% CI]: 0.721 [0.606 - 0.835] for classification based on <4 versus [&ge;]4 symptoms). These findings indicate that CogState performance at 24-hours post-SRC may serve as an objective adjunct to subjective symptom-based reporting, supporting both diagnosis and early prognostication in the clinical evaluation of SRC.

ObjectiveDespite substantial variability in the severity of post-anoxic encephalopathy, all comatose patients after cardiac arrest are usually treated according to the same standardized intensive care protocol, including sedation, mechanical ventilation, and targeted temperature management (TTM). We hypothesize that patients with a favourable EEG pattern (continuous EEG within 12 hours after cardiac arrest) may not benefit from prolonged sedation and TTM. We studied the feasibility and safety of early cessation of sedation and TTM in this subgroup. MethodsWe conducted a non-randomized, controlled intervention study including 40 adult patients admitted to the ICU with postanoxic encephalopathy after cardiac arrest and an early (< 12 hours) favourable EEG pattern. The control group received standard care with sedation and TTM for at least 24-48 hours, whereas the intervention group underwent early cessation of sedation and TTM as soon as possible after establishing a favourable EEG, followed by weaning from mechanical ventilation. The primary outcome was duration of mechanical ventilation. Secondary outcomes included ICU length of stay, total sedation time, number of ICU complications, and neurological outcomes at 3 and 6 months. ResultsDuration of mechanical ventilation was significantly shorter in the intervention than in the control group (median 12 vs 28 h, p < 0.001). Median ICU length of stay and median total sedation time were also reduced by more than 50% in the intervention group, from respectively 2.5 to 1.2 days (p = 0.001) and 27 to 12 h (p < 0.001). There was no increase in ICU complications in the intervention group. No statistically significant differences in neurological outcomes at 3 or 6 months were observed. ConclusionEarly withdrawal of sedation is feasible and safe in patients with an early favourable EEG following cardiac arrest. The study was underpowered to detect possible differences in long-term neurological recovery. SignificanceShortening sedation and mechanical ventilation is likely to result in direct reductions in healthcare costs and contribute to more appropriate care. Larger studies are needed to evaluate the impact on long-term neurological outcomes.

BackgroundDisc degeneration is the primary cause of low back pain, although the disc itself is not usually the source of the pain. Instead, it can lead to various clinically significant conditions that cause pain. However, there are no objective measures of the disc degeneration. PurposeLack of objective measures of disc degeneration may sometimes cause uncertainties in treatment decisions. Currently disc degeneration is graded by visual assessment of MRI, which often leads to uncertainty and disagreements. Therefore, the objective of this study was to develop a simple, efficient, accurate, and objective diagnostic tool for assessing disc degeneration. Study typeProspective (data acquired on site) and retrospective (data from online repository). PopulationLumbar spine MRI data from 277 participants are used. 208 of those were from an online repository and 69 were from our site. Field strength/Sequence3.0T; T2 weighted 2D and 3D fast spin echo pulse sequences. AssessmentA fully automated method is implemented where selected radiomics features are calculated from T2 weighted MRI and used for classification of the disc degeneration grade. Binary disc masks are generated using nnU-Net and radiomics features are extracted using Pyradiomics. Optimal preprocessing approaches are explored to obtain reliable feature calculations from repeated scans. Several advanced decision tree classification methods were also tested. Statistical testsF1 accuracy score, Area Under the Curve, confidence interval. ResultsXGBoost was in good agreement with the rater and the important features used in classification were in accord with expected changes in discs. Data conclusionAutomated evaluation of disc degeneration streamlines the physicians workflow and reduces uncertainties. Using radiomics features enables explainability and provides simple and robust training for machine learning approaches. Level of evidence2 Technical Efficacy3

BackgroundInvasive intracranial pressure (ICP) monitoring is the reference standard for detecting intracranial hypertension but requires neurosurgical expertise and carries procedural risks. Non-invasive methods with high negative predictive value (NPV) could serve as screening tools to rule out dangerous ICP elevations and guide decisions about invasive monitoring. We conducted a pilot evaluation to assess whether a smartphone-based, lighting-invariant quantitative pupillometry platform achieves the high NPV needed for clinical screening. MethodsThis prospective single-center pilot study in neuro-ICU enrolled adults with acute neurological emergencies who underwent serial bilateral pupillometry alongside clinically indicated intraparenchymal ICP monitoring. The primary outcome was diagnostic performance of the Pupil Reactivity (PuRe) Score for identifying intracranial hypertension (ICP [&ge;] 20 mmHg), with emphasis on NPV. Secondary analyses examined PuRe Score correlations with ICP, clinical phenotypes across reactivity strata, ambient lighting invariance, and subgroup performance by Glasgow Coma Scale (GCS). ResultsNineteen patients contributed 731 pupillometry recordings, of which 634 (87%) had concurrent invasive ICP measurements; 112 recordings (18%) showed elevated ICP. PuRe Score exhibited a significant inverse correlation with ICP (Spearman{rho} =- 0.17, p<0.001). At the screening threshold (PuRe [&le;]1.3), sensitivity was 85.7% (95% CI: 78.0-91.0%) and specificity 61.3% (95% CI: 57.1-65.4%), yielding a negative predictive value of 95.2% (95% CI: 92.4-97.0%) with AUC of 0.72 (95% CI: 0.68-0.77). Mean ICP differed significantly across PuRe groups: unreactive pupils (PuRe=0) showed 18.3 {+/-}1.3 mmHg versus 8.2 {+/-} 0.5 mmHg in brisk reactivity (PuRe 3; [&ge;] ANOVA F=24.27, p<0.001). The PuRe Score maintained stable discrimination across ambient lighting conditions (ANOVA p=0.91), whereas traditional constriction metrics showed significant lighting dependence (CAMP p=0.04, DELTA p=0.03). ConclusionsIn this pilot cohort, smartphone-based, lighting-invariant pupillometry demonstrated high negative predictive value for ruling out intracranial hypertension. A PuRe Score above the screening threshold may provide bedside reassurance that dangerous ICP elevation is unlikely, suggesting potential for a two-tier neuromonitoring strategy in which high-frequency non-invasive screening identifies patients who require targeted invasive monitoring. Larger validation studies are needed to confirm these findings.

IntroductionIdiopathic normal pressure hydrocephalus (iNPH) is a partially reversible neurological disorder in which imaging biomarkers support diagnosis and surgical decision-making. The callosal angle (CA) is one of the most robust radiological markers of iNPH and has also been associated with postoperative shunt outcome. However, several manual measurement variants exist and artificial intelligence (AI)-based tools now enable automatic CA measurement. Materials and MethodsIn total 71 patients (40 with confirmed iNPH and 31 controls) were included. Six predefined manual methods for measuring CA were applied to preoperative 3D T1-weighted MRI and evaluated for diagnostic performance and interobserver agreement. An AI-derived automatic CA (cMRI from Combinostics) was included as a seventh method and compared with the traditional manual method (perpendicular to the bicommissural plane and through the posterior commissure). Automatic measurements were additionally assessed in pre- and postoperative scans to evaluate robustness against shunt-related artifacts. ResultsAll seven CA variants significantly differentiated iNPH patients from controls (p < 0.05). The traditional method showed the highest discriminative performance (AUC = 0.986, SE = 0.012), while alternative planes demonstrated slightly lower accuracy (AUC range = 0.957-0.978). Interobserver agreement for manual measurements was good to excellent (ICC = 0.687-0.977). Automatic CA measurements showed excellent correlation with the traditional method, preoperative ICC = 0.92; postoperative ICC = 0.96. ConclusionAlthough several CA positions perform comparably, the traditional method remains marginally superior and is best supported by the literature. Automated CA measurements closely match expert manual assessment in pre- and postoperative imaging, supporting clinical implementation.

ObjectiveTo evaluate whether novice, non-specialist operators can rapidly learn to use a handheld near-infrared (NIR) head scanner and maintain scan quality after brief training, supporting its use for point-of-care triage when computed tomography is unavailable or delayed. MethodsThirty-two right-handed adults with no prior NIR experience received a brief standardized training session ([~]2 minutes) on the ArcheOptix NIRD(R) device, which detects intracranial hemorrhage by tracking hemoglobin absorption during guided scalp scans. Operators then completed two full-head scans on a healthy volunteer: an initial competency assessment (Scan 1) and a follow-up assessment after one day without refresher training (Scan 2). Performance metrics included total scan time, frequency of repeat scans prompted by loss of contact or light leaks, and mean scanpath time as an index of handling efficiency and consistency. Scan quality was evaluated using Lift on dark and Noise on dark indices. User experience was measured after each scan with the 10-item System Usability Scale (SUS, 0-100). Within-participant changes were analyzed with paired t tests or Wilcoxon signed-rank tests. ResultsAll operators completed both sessions. Median performance improved from Scan 1 to Scan 2, with total scan time decreasing from 5 min 27 s to 2 min 53 s. The proportion of "Excellent" scans (<5 minutes) increased from 50% to 84%, and "Poor" scans (>10 minutes) fell to zero. Repeat scans per session declined from 38 to 24, and mean scanpath time shortened while becoming more consistent. Lift on dark and Noise on dark remained stable, indicating no degradation in signal quality as operators worked faster. SUS scores improved from 69.4 to 76.5, reflecting higher perceived ease of use and confidence. ConclusionsAfter minimal training, novice operators achieved rapid, reliable NIR scans with faster performance, fewer repeat scans, stable signal quality, and improved usability ratings. This work shows that portable NIR can practically complement CT by helping prioritize transport and focus scarce imaging resources in emergency, sideline, and remote head trauma triage.

INTRODUCTIONCore cognitive deficits in iNPH include slowed information processing, psychomotor slowing and executive dysfunction. However, the cognitive benefits of iNPH treatment with shunt surgery are not well understood. This review synthesised evidence on cognitive assessment methods and outcomes following shunt surgery in iNPH. METHODSPubMed, Scopus, PsycINFO and Web of Science were searched for peer-reviewed studies including adults with iNPH who underwent shunt surgery and had within-subject cognitive evaluations pre- and post-operatively. Key data were extracted and study quality was assessed. Random-effects meta-analyses were performed on pooled baseline and post-shunt difference scores for frequently reported cognitive tests with comparable data. RESULTSOf 1,876 records, 195 met the inclusion criteria, comprising 11,445 patients. Cognitive evaluation methods ranged from subjective reports and NPH grading scales to brief screening tools and comprehensive test batteries. Over 193 distinct tests were reported and 54.4% of studies did not formally assess any core iNPH cognitive deficits. Post-shunt improvement rates, follow-up times and criteria for defining improvement varied widely. Eighty-five studies contributed data to meta-analyses of ten outcomes. Pooled estimates indicated post-shunt cognitive improvement, with Trail Making Test-A, Grooved Pegboard-Dominant and Trail Making Test-B showing changes exceeding thresholds for clinically significant improvement. CONCLUSIONSCognitive assessment in iNPH is highly heterogeneous and frequently omits core domains, limiting detection of treatment effects. When domain-relevant cognitive measures are used, shunt surgery is associated with statistically and clinically significant cognitive improvement. These findings highlight the need for standardised iNPH-specific cognitive evaluation tools with validated criteria for detecting clinically meaningful change and have direct implications for clinical assessment, interpretation of shunt response and the selection of cognitive endpoints in future interventional studies. Summary BoxO_ST_ABSWhat is already known on this topicC_ST_ABSCognitive outcomes after shunt surgery for idiopathic normal pressure hydrocephalus (iNPH) have been inconsistently reported, with cognitive improvement reported less reliably than gait outcomes, in the context of highly variable assessment practices across centres. What this study addsThis systematic review of 195 studies (11,445 patients) shows substantial heterogeneity in iNPH cognitive assessment and demonstrates that when tests sensitive to frontal-subcortical dysfunction are used, shunt surgery is associated with statistically and clinically meaningful cognitive improvement. Widely used dementia screening tools, including the MMSE and MoCA, show changes largely within expected practice-effect ranges and do not adequately capture core iNPH cognitive deficits. How this study might affect research, practice or policyThese findings demonstrate the need to standardise cognitive assessment in iNPH using appropriate iNPH-specific tools with validated metrics for determining clinically meaningful improvement. This will enable robust trial endpoints and accurate evaluation of cognitive benefits of shunting in routine clinical practice.

ObjectivesTo validate whether cerebrospinal fluid oxyhaemoglobin (CSF-Hb), measured from external ventricular or lumbar drains, is associated with secondary brain injury (SAH-SBI) after aneurysmal subarachnoid haemorrhage (aSAH), and to assess its value as a real-time monitoring biomarker. DesignPreregistered multicentre prospective observational cohort study. SettingEight neurosurgical tertiary centres in Switzerland, Germany, and Austria, between August 2021 and June 2024. Participants366 patients with aSAH (mean age 58 years; 65% women). Of these, 260 provided cerebrospinal fluid (CSF) samples via external ventricular drain (EVD; 2,467 samples, median 10 days per patient) and 66 via lumbar drain (LD; 379 samples, median 6 days). InterventionsDaily CSF samples were collected via EVD or LD from day 1 to day 14 after haemorrhage; no therapeutic interventions were tested. Main outcome measuresCSF-Hb and its metabolites were analysed post hoc in a blinded manner. The primary outcome was SAH-SBI, defined as a composite of angiographic vasospasm (aVSP), delayed cerebral ischaemia (DCI), and delayed ischaemic neurological deficits (DIND), assessed daily over 14 days. Secondary outcomes included temporal CSF-Hb profiles and associations with aneurysm location, haematoma volume, intraventricular haemorrhage, chronic hydrocephalus, and 3-month functional outcome. ResultsCSF-Hb showed a delayed peak pattern: concentrations were low after aSAH, rose to a maximum on day 10 (EVD-derived CSF-Hb median 11.3 {micro}M, IQR 2.64 to 25.90), and then declined. Larger haematoma volume (p<0.001) and intraventricular haemorrhage (p<0.001) were associated with higher EVD-derived CSF-Hb. SAH-SBI occurred in 209/366 patients (57%). Daily EVD-derived CSF-Hb showed no association with SAH-SBI (p=0.25) and only poor prognostic potential of same-day SAH-SBI (area under the curve 0.59, 95% confidence interval 0.56-0.63), with substantial between-centre heterogeneity. The oxidised haemoglobin metabolite methaemoglobin was positively associated with SAH-SBI (p=0.023; odds ratio 1.18 per log[{micro}M], 95% confidence interval 1.02-1.36). Acute-phase EVD-derived CSF-Hb correlated with chronic hydrocephalus (p=0.012) and poor 3-month functional outcome (p=0.008). Catheter-related infection rates were low (2.2%). ConclusionsIn this preregistered multicentre validation study, EVD-derived CSF-Hb did not perform as a robust real-time monitoring biomarker for SAH-SBI, showing limited same-day discrimination and substantial between-centre heterogeneity. These findings argue against clinical implementation of CSF-Hb point-measurement as a single-parameter biomarker. In contrast, CSF methaemoglobin remained consistently associated with SAH-SBI, supporting the mechanistic relevance of haemolysis-related pathways. Future work using the HeMoVal biobank will apply multi-marker, pathway-level analyses to define haemolysis-related biomarker signatures and provide a platform for robust external validation of future candidates. Study registrationClinicalTrials.gov NCT04998370; date of registration 10 August 2021. Summary BoxesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIPreclinical animal models link cell-free haemoglobin in cerebrospinal fluid (CSF-Hb) to secondary brain injury after aneurysmal subarachnoid haemorrhage (SAH-SBI). C_LIO_LIA single-centre study reported strong associations between daily external ventricular drain (EVD) derived CSF-Hb levels and SAH-SBI, and suggested a strong predictive potential(area under the curve 0.89). C_LIO_LICSF-Hb monitoring has therefore been proposed as a bedside biomarker, but it has not undergone multicentre validation. C_LI What this study addsO_LIIn a preregistered multicentre cohort of 366 patients from eight neurosurgical centres, once-daily EVD-derived CSF-Hb measurements showed poor same-day discrimination for SAH-SBI (area under the curve 0.59) and substantial between-centre heterogeneity. C_LIO_LIIn contrast, CSF methaemoglobin was consistently associated with SAH-SBI, and higher acute-phase CSF-Hb was related to chronic hydrocephalus and worse 3-month functional outcome. C_LIO_LIThese findings argue against routine adoption of CSF-Hb point-measurements as bedside single-analyte, while supporting haemolysis-related pathways as mechanistic targets. C_LI

BackgroundStroke is the leading cause of adult-onset disability, with impairments across motor, language, cognitive, swallowing, mood, and gait domains. Non-invasive brain stimulation techniques like repetitive transcranial magnetic stimulation (rTMS) have emerged as promising tools to augment rehabilitation therapies to improve post-stroke impairments. This systematic review and meta-analysis will evaluate the efficacy of rTMS for post-stroke recovery across multiple functional domains and identify moderators of treatment response. MethodsWe systematically searched five databases for randomized controlled trials (RCTs) published from February 16, 2004 to July 1, 2024. Eligible studies compared active rTMS with sham rTMS in stroke survivors and reported validated outcomes. Risk of bias was assessed using the Cochrane Collaboration tool. Random-effects meta-analyses were conducted for each outcome domain. Subgroup analyses examined timing of intervention (acute/subacute, early chronic, late chronic). Meta-regression evaluated continuous moderators, including stimulation intensity (% resting motor threshold), number of sessions, age, and sex. ResultsFifty-two studies met inclusion criteria (2,472 participants, mean age 59.8 years; 35.1% female). rTMS was associated with significant improvements in motor function (UE-FMA, MD = 4.68, 95% CI [2.18, 6.54]), language (CCAT, MD = 0.62, 95% CI [0.22, 1.01]), cognition (MMSE, MD = 2.12, 95% CI [1.34, 2.92]), dysphagia (PAS, MD = -1.50, 95% CI [-2.40, -0.57]), and mood (HAMD-17, MD = -2.34, 95% CI [-4.38, -0.30]), but not gait. Subgroup analyses showed significantly larger treatment effects when rTMS was delivered within 3 months post-stroke, particularly for motor outcomes. Meta-regression indicated that stimulation intensity, number of sessions, and participant demographic distribution were not significant moderators. ConclusionsrTMS improves post-stroke outcomes across multiple functional domains, with the strongest evidence for motor recovery in the acute/subacute phase. Standardization of protocols and larger trials in understudied domains are needed to maximize therapeutic outcomes.

ObjectiveThis study aimed to characterize the activation of lower urinary tract (LUT) targets in response to pudendal nerve stimulation (PNS) in awake human participants. Materials and MethodsIn this single center study, recruited participants had an implanted pudendal neurostimulator for treatment of their symptoms including overactive bladder, incontinence, urinary retention, and/or pelvic pain. Participants came in for a modified urodynamic study where a multichannel manometry catheter was placed in the lower urinary tract alongside a dual sensor urodynamics catheter. The bladder was filled and after each participant expressed a strong desire to void, PNS was applied and LUT pressures were measured. Participants attempted voids with the catheters in place to characterize LUT behavior and voiding efficiency with and without stimulation. ResultsThe study consisted of 15 participants including 13 women. Across 133 total trials contractions were observed at the distal urethra 52 times (39%) and at the proximal urethra 46 times (35%). The maximum observed pressure change occurred significantly more often at the proximal urethra than the distal urethra (p = 0.007). There was a significantly higher maximum tolerable stimulation amplitude for low frequency stimulation (2-3.1 Hz) when compared to high frequency stimulation (30-33 Hz) (p = 0.041). In one participant there were four instances of stimulation driven bladder contractions with an average pressure change of 24.3 cmH2O (standard deviation = 10.5). There was not a significant difference in voiding efficiency or maximum flow rate with and without stimulation (p = 0.76 and p = 0.45, respectively). ConclusionsPNS can affect LUT pressures at tolerable stimulation amplitudes. The absence of an effect of PNS on voiding characteristics suggests a similar mechanism of action as sacral neuromodulation.

PurposeNeonatal imaging is particularly challenging because newborns have a high likelihood of head motion, which can degrade image quality and complicate interpretation. Improving MRI brain image quality may help reduce diagnostic uncertainty and facilitate the nuanced assessment of early myelinating structures in the neonatal brain. Although deep learning reconstruction algorithms designed to improve MRI image quality have been evaluated in pediatric imaging, they have not been specifically studied in exclusively neonatal populations. We sought to evaluate image quality improvement through the employment of a deep learning reconstruction algorithm in neonatal brain imaging. Methods3D T1-weighted brain MRIs were obtained in 15 neonates. A deep-learning reconstruction algorithm was applied to the image sets using low, medium, and high levels of denoising. Three radiologists qualitatively rated image quality (signal-to-noise ratio, presence of artifacts, and overall clarity) on a 4-point scale of eight early myelinating structures. Objective apparent signal-to-noise ratio (aSNR) and apparent contrast-to-noise ratio (aCNR), based on signal intensities of white-and gray-matter, was measured across all three denoising levels. ResultsEvaluation by radiologists indicated an overall increase in all image quality categories and increased conspicuity of the early myelinating structures as the level of denoising increased. Objective aSNR and aCNR values also increased progressively with denoising, with significant differences observed for nearly all pairwise comparisons. ConclusionOur findings suggest that the use of the proposed deep learning reconstruction algorithm improves image quality in 3D T1-weighted neonatal brain MRIs at 3T.

Musical performances are generated through bodily movements; because they involve repetitive physical actions, there is a risk of developing playing-related physical problems (PRPPs). This study aimed to investigate PRPPs among amateur and professional drummers in Japan using an online survey, focusing on the differences between the four limbs. In addition, the study sought to compare the prevalence, affected body regions, and diagnoses of PRPPs between the two groups and identify factors associated with the development of PRPPs. The questionnaire included items regarding age, sex, handedness, musical genre, performance level, practice time, experience with PRPPs, affected body regions, and medical diagnoses. Data from 868 respondents (667 amateurs and 201 professionals) were analyzed. The self-reported prevalence of PRPPs was 33.4% and 66.2% in amateurs and professional, respectively. Among amateurs, the symptoms were most frequent in the right wrist, whereas among professionals, the right lower limb was most frequently affected. Regarding diagnosis, the most frequently reported condition was tenosynovitis among amateurs (2.10 %) and musicians dystonia among professionals (8.95%). Logistic regression analysis revealed that the risk factors for PRPPs included higher performance levels, more significant stress related to the use of the metronome click, perfectionism, and experience of altering playing technique. In contrast, increased stress resilience was significantly associated with a decreased risk of PRPP development. There was a significant interaction indicating that the protective effect of stress resilience weakened at higher performance levels. This study revealed that professional drummers exhibited a higher prevalence of PRPPs than did amateurs, with distinct patterns of affected regions and diagnoses. Additionally, the performance level, psychological factors, and playing environment may contribute to these problems. This study may provide evidence for the revision of practice and performance methods for injury prevention tailored to each performance level.

ImportanceTraumatic brain injury (TBI) is a risk factor for dementia and is known to impact levels of several Alzheimers disease (AD) blood biomarkers. Plasma pTau217/ A{beta}42 ratio has been reported to be 90% accurate for detection of brain amyloid in civilian cohorts. ObjectiveTo evaluate the accuracy of emerging AD blood biomarkers in Veterans with and without TBI history. DesignWe assessed the performance of the FDA-approved plasma pTau217/A{beta}42 ratio and plasma levels of pTau217 and A{beta}42/40 ratio for detecting brain amyloid-{beta} positivity (e.g., amyloid-PET consensus visual read). We compared biomarkers accuracy in Veterans with no TBI (N=93), TBI with loss of consciousness (LOC) 0-5 minutes (N=89), and TBI with LOC >5 minutes (N=90). SettingCross-sectional cohort study using existing data and banked plasma from the Alzheimers Disease Neuroimaging Initiative Department of Defense (ADNI-DOD) study. Participants272 older Vietnam Veterans without dementia (83% cognitively unimpaired, 17% mild cognitive impairment), median (IQR) age 69 (67,72) years, 270/272 male, who had amyloid-PET and concurrently collected banked plasma available for analysis. ResultsAmyloid-PET positivity prevalence was 30.5%. Plasma pTau217/A{beta}42 ratio was highly accurate (90%) in Veterans with no TBI, but not in Veterans with TBI with LOC 0-5 minutes (78% accuracy, P=0.027 vs no TBI) nor in Veterans with TBI with LOC>5 minutes (63% accuracy, P<0.001 vs no TBI). Results were similar for plasma pTau217 alone and plasma A{beta}42/40 ratio. Results were also similar after excluding Veterans with TBI within the past 10 years, or when amyloid-PET positivity was defined using a quantitative threshold rather than consensus visual read. DiscussionPrior TBI is a modifier of AD biomarkers accuracy in prediction of brain amyloid-PET positivity. Caution is advised in interpreting AD blood test results in this context. Further research is warranted to refine precision AD diagnosis in Veterans and civilians with TBI history. Key points QuestionWhat is the accuracy of the plasma pTau217/A{beta}42 ratio test for detecting amyloid-PET positivity for Alzheimers disease (AD) diagnosis in older Veterans with and without a history of traumatic brain injury (TBI)? FindingsIn this cross-sectional study (n=272), plasma pTau217/A{beta}42 ratio test accuracy was 90% in Veterans without TBI history, but was significantly lower (63-78% accuracy) in Veterans with TBI history, with lowest accuracy in those with greater TBI severity. MeaningTBI history and severity is a modifier of AD blood test accuracy in prediction of brain amyloid-PET positivity.AD blood tests should be interpreted with caution in Veterans and civilians with TBI history.