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BMC Neurology

Springer Science and Business Media LLC

Preprints posted in the last 30 days, ranked by how well they match BMC Neurology's content profile, based on 12 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.

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Variation in Haemostasis and VTE Prophylaxis in Elective Adult Cranial Neurosurgery: A Global Survey of Perioperative Practice

Pandit, A. S.; Chaudri, T.; Chaudri, Z.; Vasilica, A. M.; Dhaliwal, J.; Sayar, Z.; Cohen, H.; Westwood, J. P.; Toma, A. K.

2026-04-16 surgery 10.64898/2026.04.14.26350905 medRxiv
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Background Venous thromboembolism (VTE) remains a major cause of perioperative morbidity in cranial neurosurgery, yet clinical practice varies widely, and formal guidelines are inconsistent. Understanding internationally sampled neurosurgical practice is essential for informing consensus and future trials. Methods An international, 2-stage cross-sectional, internet-based survey was conducted. Practising neurosurgeons performing elective adult cranial surgery were eligible. Descriptive statistics were used to summarise practice. Responses covered patterns of pre-operative haemostasis decision making, use and timing of mechanical and/or chemical prophylaxis, use of perioperative imaging prior to anticoagulation, and frequency of clinical assessment for VTE. Associations with geographical income status, subspecialty, and years post-certification were statistically tested. Practice heterogeneity was quantified and contextual influence was summarised using mean effect sizes across stratifying variables in order to determine domains of true equipoise. Results Of 585 responses, 456 (78%) met criteria for inclusion: representing 322 units across 78 countries (71% high-income). Thirteen per cent reported no departmental VTE plan; 23% followed no guidelines and 12% used multiple. Routine pre-operative testing almost universally included haemoglobin/platelets/haematocrit, with fibrinogen more common in high-income settings. Compared with high-income country respondents, low- and middle-income respondents reported higher haemoglobin transfusion thresholds (>90 g/dL; p<0.001) and shorter antiplatelet interruption (p[&le;]0.03), and less frequent outpatient VTE assessment (p<0.001). Mechanical prophylaxis was common (TEDs 81%, IPC 62%), typically started pre- or intra-operatively. Among those completing the chemoprophylaxis section (n=310), 57% required a CT or MRI scan before LMWH which was then initiated on average 31.4 hours after surgery. 1% of respondents did not routinely use LMWH. Many clinical decisions demonstrated statistical equipoise ie. high heterogeneity with low contextual influence. Conclusion Peri-operative haemostasis and VTE prophylaxis practices in adult elective cranial neurosurgery vary substantially worldwide, with some decisions reflecting geographical or socioeconomic differences and many others reflecting true clinical equipoise rather than contextual determinants. By mapping contemporary real-world practice across diverse health-system contexts, this study provides a necessary empirical foundation for rational trial design and future guideline development.

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The MIND Study: Design, Feasibility, and Baseline Characteristics of a Smartphone-Based Migraine Cohort

Khorsand, B.; Teichrow, D.; Lipton, R. B.; Ezzati, A.

2026-04-21 neurology 10.64898/2026.04.14.26350866 medRxiv
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ObjectiveTo describe the design, feasibility, and baseline characteristics of the Migraine Impact on Neurocognitive Dynamics (MIND) study, a 30-day smartphone-based cohort for high-frequency assessment of cognition and symptoms in adults with migraine. BackgroundCognitive symptoms are an important component of migraine burden, but they are difficult to measure using single-visit testing or retrospective questionnaires. Repeated smartphone-based assessment may better capture real-world variability in cognition and symptoms. MethodsAdults meeting International Classification of Headache Disorders, 3rd edition, criteria for migraine were enrolled remotely and completed 30 days of once-daily ecological momentary assessments and mobile cognitive tasks delivered through the Mobile Monitoring of Cognitive Change platform. Baseline measures assessed demographics, migraine characteristics, disability, mood, stress, and treatment patterns. Feasibility was evaluated using enrollment, completion, and retention metrics. ResultsA total of 177 participants enrolled (mean age 38.8 {+/-} 11.9 years; 79.7% female), including 80/177 (45.2%) with chronic migraine. Across the 30-day protocol, 3688 daily assessments were completed, representing 70.8% of all possible study days, and 70.6% of participants completed at least 20 days of monitoring. Completion remained above 60% across study days. At baseline, chronic migraine was associated with greater burden than low-frequency and high-frequency episodic migraine, including higher MIDAS scores (98.6 vs. 38.7 and 70.3), more days with concentration difficulty (16.0 vs. 7.9 and 11.5), and more days with functional interference (18.5 vs. 7.6 and 13.0). ConclusionsThe MIND study demonstrates the feasibility of high-frequency smartphone-based assessment of cognition and symptoms in migraine and provides a methodological foundation for future analyses of within-person cognitive and symptom dynamics across the migraine cycle.

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Characteristic resting state facial expressions in older adults with mild cognitive impairment level

Miyayama, M.; Sekiguchi, T.; Sugimoto, H.; Kawagoe, T.; Tripanpitak, K.; Wolf, A.; Kumagai, K.; Fukumori, K.; Miura, K. W.; Okada, S.; Ishimaru, K.; Otake-Matsuura, M.

2026-04-11 geriatric medicine 10.64898/2026.04.10.26350581 medRxiv
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Background: For early detection of Alzheimer's disease, it is essential to identify individuals showing cognitive performance consistent with the mild cognitive impairment (MCI) range during preliminary screening, ideally using methods that extend beyond conventional cognitive assessments. Non-invasive, easily accessible screening tools applicable in daily life are increasingly needed. Facial expressions, particularly during rest, may offer promising biomarkers for MCI level detection. This study aimed to identify specific facial features associated with MCI level during rest to inform development of facial expression-based screening tools. Methods: Participants were classified into an MCI level group and a healthy control (HC) group based on the Montreal Cognitive Assessment (MoCA) scores. Facial Action Units (AUs) were extracted from video recordings of resting-state facial expressions in 31 individuals with MCI level and 14 HC. Two statistical models were employed: a multilevel zero-inflated beta regression model for intensity of 17 AUs and a multilevel logistic regression model for presence or absence of 18 AUs. Results: In the zero-inflated beta regression, the AU relates to upper lip raiser showed a significant group effect (MCI level vs. HC; p <0.001), remaining significant after multiple comparison correction. The logistic regression revealed significant group differences for the AUs related to lip tightener (p <0.001) and lip suck (p <0.001), both remained significant after multiple comparison correction. Conclusions: Distinctive facial action patterns during rest were observed in individuals with MCI level. These findings highlight the potential of resting-state facial expressions as a basis for novel, unobtrusive screening tools for early MCI level detection.

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Predicting long term clinical outcomes in Parkinson's Disease using short term rating scales

Burnell, M.; Gonzalez-Robles, C.; Zeissler, M.-L.; Bartlett, M.; Clarke, C. S.; Counsell, C.; Hu, M. T.; Foltynie, T.; Carroll, C.; Lawton, M.; Ben-Shlomo, Y.; Carpenter, J.

2026-03-30 neurology 10.64898/2026.03.27.26349548 medRxiv
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Background: Most trials of Parkinson's disease (PD) measure progression over a short to medium time-period using continuous rating scales that may be hard to interpret and less meaningful for patients. There is a lack of evidence connecting changes in these scales to changes in outcomes important to patients. Objectives: We present causal modelling to translate the causal, short-term disease-modifying treatment effects on functional rating scales to the 10-year risk of serious clinical progression milestones. Methods: We selected four important clinical milestones of disease progression from the Oxford Parkinson's Disease Centre "Discovery" cohort: dementia, any falls, frequent falls, and mortality. We proposed a causal framework for our research objectives so we could model the potential impact of a 30% reduction in disease progression slopes ("treatment effect") using the summation of parts I and II of the Movement Disorders Society Unified Parkinson's Disease Rating Scale (UPDRS12). This outcome was regressed on time to milestone using flexible parametric survival models. Marginal predictions of survival and survival difference at year 10 were then calculated for the Discovery cohort, and a counterfactual cohort applying the treatment effect to estimate the relative and absolute reductions for the four clinical milestones. Results: The model increase in risk for each unit change in the UPDRS12 were as follows: dementia hazard ratio (HR)=1.52 (95% Confidence Interval (CI) 1.36-1.70), any falls HR=1.37 (95% CI 1.29-1.46), frequent falls HR=1.68 (95% CI 1.49-1.89), mortality=1.29 (95% CI 1.17-1.42). These models led to marginal predictions of absolute reductions, when the progression was reduced by 30%, between 4.0% (mortality) and 7.5% (frequent falls) at 10 years follow up. Conclusions: We have demonstrated how a treatment effect in a trial specified in terms of a progression change of a rating scale can be contextualised into a long-term reduction in the probability of clinically relevant milestones. Whilst we have used PD as our exemplar, we believe this methodological approach is generalisable to other chronic progressive diseases where trials are often limited to a relatively short follow-up period and use some scalar measure of progression, but significant clinical milestones usually take longer to be observed. Keywords: Clinical trials; disease modifying therapies; causal estimation; prediction models

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Individualized Forecasting of Headache Attack Risk Using a Continuously Updating Model

Houle, T. T.; Lebowitz, A.; Chtay, I.; Patel, T.; McGeary, D. D.; Turner, D. P.

2026-04-22 neurology 10.64898/2026.04.20.26350119 medRxiv
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ImportanceMigraine attacks often occur unpredictably, limiting the ability of individuals to initiate timely preventive or preemptive treatment. Short-term probabilistic forecasting of migraine risk could enable more targeted management strategies. ObjectiveTo externally validate the previously developed Headache Prediction Model (HAPRED-I), evaluate an updated continuously learning model (HAPRED-II), and assess the feasibility and short-term safety of delivering individualized probabilistic migraine forecasts directly to patients. Design, Setting, and ParticipantsProspective 8-week cohort study conducted remotely at two academic medical centers in the United States (Massachusetts General Hospital and Wake Forest Health Sciences) between 2015 and 2019. Adults with recurrent migraine or tension-type headache completed twice-daily electronic diaries. A total of 230 participants contributed 23,335 diary entries across 11,862 participant-days of observation. Main Outcomes and MeasuresOccurrence of a headache attack within 24 hours following each evening diary entry. Model performance was evaluated using discrimination (area under the receiver operating characteristic curve [AUC]) and calibration. ResultsExternal validation of HAPRED-I demonstrated modest discrimination (AUC, 0.59; 95% CI, 0.57-0.61) and poor calibration, with predicted probabilities consistently exceeding observed headache risk. In contrast, the continuously updating HAPRED-II model demonstrated progressive improvement in predictive performance as participant-specific data accumulated. Discrimination increased from an AUC of 0.59 (95% CI, 0.57-0.61) during the first 14 days to 0.66 (95% CI, 0.63-0.70) after the first month, accompanied by improved calibration across predicted risk levels. Over the study period, 6999 individualized forecasts were delivered directly to participants. No evidence suggested that receipt of forecasts was associated with increasing headache frequency or worsening predicted headache risk trajectories. Conclusions and RelevanceA static migraine forecasting model demonstrated limited transportability to new individuals. In contrast, models that continuously update within individuals may improve predictive accuracy over time and enable real-time delivery of personalized migraine risk forecasts. Further work incorporating richer physiologic and contextual predictors will likely be necessary before such systems can reliably guide clinical treatment decisions.

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Cognitive Profiling and Validation of a Digital Cognitive Assessment Tool in Post-COVID-19 Condition: Protocol for a Single-Center, Cross-Sectional Study (DigiCog Study)

Lacomba-Arnau, E.; Da Rocha Oliveira, R.; Monteiro, S.; Pauly, C.; Vaillant, M.; Celebic, A.; Bulaev, D.; Fischer, A.; Fagherazzi, G.; Fernandez, G.; Shulz, M.; Perquin, M.

2026-04-16 neurology 10.64898/2026.04.14.26350862 medRxiv
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Methods: DigiCog is a single-center cross-sectional study conducted within the Luxembourgish Predi-COVID cohort (NCT04380987). Participants aged 25-65 years, with and without persistent COVID-19 symptoms, are invited to participate. Cognitive assessments are performed during face-to-face sessions by trained nurses and neuropsychologists using both the VMTech device and standardized neuropsychological tests. Additional data on PCC symptom status, CR, sociodemographic characteristics, fatigue, and psychological factors are also collected. Agreement between digital and standard cognitive assessments will be evaluated using Cohen's kappa coefficient, with sensitivity, specificity, and receiver operating characteristic analyses as secondary measures. Cognitive performance will be compared between participants with and without PCC, and associations with CR proxies will be explored.

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Digital Assessment of Objective and Patient-Reported Cognition Across Migraine Phases: Results from the MIND Cohort

Khorsand, B.; Teichrow, D.; Jicha, C. J.; Minen, M. T.; Seng, E.; Lipton, R. B.; Ezzati, A.

2026-04-16 neurology 10.64898/2026.04.14.26350892 medRxiv
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Objective: Migraine attacks are frequently accompanied by patient-reported subjective cognitive symptoms, but objective findings have been inconsistent. We used high-frequency, smartphone-based cognitive testing to assess within-person changes in subjective and objective cognition across migraine phases using daily diaries. Methods: Adults with migraine were recruited through social media. Eligible participants met ICHD-3 migraine criteria and had 3 to 22 monthly headache days. For 30 days, they completed daily smartphone-based reports on headache features, cognitive symptoms, and three smartphone-based objective cognitive tasks. Objective tests included Symbol Search (processing speed/visual search), Color Dots (visual working memory/attention), and Grid Memory (visuospatial working memory). Primary analyses contrasted assessments on current headache days (ictal) versus days with no headache (nonictal). When possible, non-ictal days were subclassified using information from adjacent days as pre-ictal, post-ictal, and interictal days. Outcomes included subjective cognition, reaction time (mean across correctly scored trials), accuracy, and a speed-accuracy composite (Reaction Time/Accuracy). Mixed-effects models adjusted for age, sex, and practice effects. Results: The 139 eligible participants (84.9% female; mean age 38.2 years) contributed 3,014 person-days for ictal versus nonictal comparisons (2,097 nonictal; 917 ictal); for 1,828 person-days precise phase classification was possible. Subjective cognitive symptoms were worse on ictal days, with higher odds of more severe brain fog (OR=3.39, 95% CI 2.70-4.27) and task forgetting (OR=2.82, 95% CI 2.29-3.49). In adjusted models, reaction times were slower on ictal days for Symbol Search (reaction time ratio =1.043, 95% CI 1.028-1.059) and Color Dots (ratio=1.015, 95% CI 1.003-1.026) but not Grid Memory (reaction time ratio =1.006, 95% CI 0.985-1.028). Grid Memory accuracy was lower on ictal days (OR=0.867, 95% CI 0.823-0.914). In analyses based on phase, most nonictal phases showed faster reaction time and lower subjective symptom burden relative to ictal days, with limited differentiation among preictal, postictal, and interictal periods. Conclusions: In persons with migraine, daily smartphone assessments revealed subjective cognitive impairment on ictal vs nonictal days in brain fog and forgetfulness. Objective testing revealed slowing in processing speed and attention and modest differences in the accuracy of working-memory. High-frequency digital cognition appears feasible and may provide scalable functional endpoints for real-world monitoring and treatment evaluation.

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Assessing medication-related burden and medication adherence among older patients from Central Nepal: A machine learning approach

Giri, R.; Agrawal, R.; Lamichhane, S. R.; Barma, S.; Mahatara, R.

2026-04-23 geriatric medicine 10.64898/2026.04.22.26351447 medRxiv
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We are pleased to submit our Original article entitled "Assessing medication-related burden and medication adherence among older patients from Central Nepal: A machine learning approach" for consideration in your esteemed journal. In this paper, we assessed medication burden using validated Living with medicines Questionnaire (LMQ-3) and medication adherence using Adherence to Medication refills (ARMS) Scale. In this paper we analysed our result through machine learning approach in spite of traditional statistical approach to identify the complex factors influencing both. Six ML architectures (Ordinary Least Square, LightGBM, Random Forest, XGBoost, SVM, and Penalized linear regression) were employed to predict ARMS and LMQ scores using various socio-demographic, clinical and medication-related predictive features. Model explainability was provided through SHAP (Shapley Additive exPlanations). Our study identified the moderate medication burden with moderate non-adherence among older adults. Requiring assistance for medication and polypharmacy were the strongest drivers for the medication burden and non-adherence. The high predictive accuracy by ML suggests the appropriate clinical intervention like deprescribing to cope with the high prevalent medication burden and non-adherence among older adults in Nepal.

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Self-reported sleep problems are associated with impaired daily-life gait quality and increased fall risk in older people

van Schooten, K. S.; Vakulin, A.; Khanal, R.; Sansom, K.; Bletsas, J.; Delbaere, K.

2026-04-06 geriatric medicine 10.64898/2026.03.30.26349800 medRxiv
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Background: Sleep problems are common in older people and have been associated with increased fall risk, but the mechanisms underlying this relationship remain unclear. Gait quality reflects balance control and neurological function and may provide insight into pathways linking sleep health and falls. Methods: Data from 758 community-dwelling older people ([&ge;]65 years; mean age 75.8 years, 69.3% women) were analysed. Sleep problems were assessed at baseline using a self-reported item (Patient Health Questionnaire-9, question 3). Daily-life gait quality and habitual walking speed were derived from one week of wearable sensor monitoring. Falls and injurious falls were prospectively recorded over 12 months. Associations between sleep problems, gait quality, and fall incidence were examined using regression models adjusted for demographic, pain and cognitive factors, and use of sleeping medication. Results: Sleep problems were reported by 43.9% of participants. Sleep problems were not associated with habitual walking speed, but were associated with lower gait quality in daily life (adjusted {beta} = -0.15, 95% CI -0.27 to -0.03). Participants reporting sleep problems had higher incidence rates of total falls (adjusted IRR = 1.42, 95% CI 1.07 to 1.90) and injurious falls (adjusted IRR = 1.50, 95% CI 1.07 to 2.10). Conclusions: Self-reported sleep problems were associated with impaired real-world gait quality and substantially higher rates of falls and injurious falls in older people. These findings suggest that sleep problems may increase fall risk by altering balance control rather than by reducing walking speed. Sleep should be considered when managing fall risk, and fall risk should be considered in older people with sleep complaints.

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PainWaive: A Consumer-grade Digitally Delivered EEG Neurofeedback Intervention for Chronic Low Back Pain

Hesam-Shariati, N.; Ermolenko, E.; Chowdhury, N.; Zahara, P.; Chen, K. Y.; Lin, C.-T.; Newton-John, T.; Gustin, S.

2026-04-01 pain medicine 10.64898/2026.03.26.26349247 medRxiv
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Chronic low back pain (CLBP) is persistent and refractory, affecting 20-30% of population worldwide. Neurofeedback has been explored as a potential non-pharmacological intervention for chronic pain, although evidence in CLBP remains limited. This study evaluated PainWaive, a consumer-grade digitally-delivered neurofeedback intervention targeting multiple pain-related frequency bands recorded over the sensorimotor cortex in individuals with CLBP. In a multiple-baseline experimental design, four participants completed daily assessments of pain severity and pain interference during randomly-assigned baseline phases of 7, 10, 14, and 20 days, followed by 20 sessions of the PainWaive intervention over four weeks. Daily pain assessments continued during the post-intervention and follow-up phases. Participants rated PainWaive's usability and acceptability at post-intervention. Anxiety, depression, wellbeing, and sleep disturbance were assessed at three timepoints. Aggregated Tau-U analyses indicated a large effect (-0.67) on pain severity from baseline to intervention and very large from baseline to post-intervention (-0.92) and follow-up (-0.92) phases. Large effects (-0.63, -0.62, and -0.70) were also observed for pain interference. Individual-level analyses showed significant reductions across all participants, with visual inspection confirming progressive decreases over time. The intervention was rated usable and acceptable by all participants, while psychological outcomes were mixed and varied across participants. The findings provide promising evidence that the PainWaive neurofeedback intervention may reduce pain severity and pain interference in some individuals with CLBP. By prioritising accessibility, usability, and self-administration, PainWaive supports a foundation for more patient-centred, technology-enabled approaches to chronic pain management. Further evaluation of this approach in randomised trials is required to establish efficacy.

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Development and Evaluation of iSupport-Malaysia: A Multimedia Web-Based Psychoeducational Intervention for Dementia Caregivers

Loh, K. J.; Lee, W. L.; Ng, A. L. O.; Chung, F. F. L.; Renganathan, E.

2026-04-21 geriatric medicine 10.64898/2026.04.14.26350743 medRxiv
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BackgroundCaring for people with dementia can impose a considerable psychological burden on caregivers, yet access to caregiver support in Malaysia remains limited. The World Health Organizations iSupport for Dementia program provides dementia education via textual, e-learning format. However, a culturally adapted Malaysian version has not been available. ObjectiveThis study aimed to develop and gather user feedback on a culturally adapted, multimedia version of iSupport tailored for Malaysia (iSupport-Malaysia). MethodsGuided by a four-phase cultural adaptation framework, the generic iSupport content was translated into Bahasa Malaysia, adapted to local customs, and transformed into multimedia lessons on an e-learning platform. A mixed-methods design was used to explore user perceptions and evaluate usability through four homogeneous focus group discussions and 15 individual usability test sessions with informal caregivers (FG: n=9; UT: n=9) and healthcare professionals (FG: n=11; UT: n=6). Focus groups examined aesthetics, ease of use, clarity, cultural relevance, comprehensiveness, and satisfaction. Usability testing involved Think Aloud tasks, post-test questionnaires, and brief interviews. Qualitative data was analysed thematically, and descriptive statistics summarised usability performance. ResultsiSupport-Malaysia demonstrated good usability (M=74.3{+/-}18.0), with most tasks completed without assistance. Strengths included interactive learning activities, peer discussion features, and flexible self-paced learning. Content was viewed as culturally appropriate, credible, and useful. Suggested improvements included enhancing visual aesthetics, shortening videos, refining quizzes, and increasing practical relevance. ConclusionUser insights indicate that iSupport-Malaysia is usable and culturally appropriate. These findings will inform refinement of the platform prior to the pilot feasibility study and provide recommendations for future multimedia-based caregiver interventions.

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A Modified Percutaneous Spinal Cord Stimulation Implant Approach to Target the Ventral Spinal Cord

Valestrino, K. J.; Ihediwa, C. V.; Dorius, G. T.; Conger, A. M.; Glinka-Przybysz, A.; McCormick, Z. L.; Fogarty, A. E.; Mahan, M. A.; Hernandez-Bello, J.; Konrad, P. E.; Burnham, T. R.; Dalrymple, A. N.

2026-04-13 surgery 10.64898/2026.04.06.26350176 medRxiv
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ObjectivesEpidural spinal cord stimulation (SCS) is an emerging therapy for motor rehabilitation following spinal cord injury (SCI) and other motor disorders. Conventionally, SCS leads are placed along the dorsal spinal cord (SCSD), where stimulation activates large diameter afferent fibers, which indirectly activate motoneurons through reflex pathways. This leads to broad activation of flexor and extensor muscles and limited fine-tuned control of motor output. Targeting the ventral spinal cord (SCSV) may enable more direct activation of motoneuron pools, potentially improving the specificity of muscle activation; however, there is currently no established method to place leads ventrally. To address this, we evaluated the feasibility of four modified percutaneous implantation techniques to target the ventrolateral thoracolumbar spinal cord. Materials and methodsPercutaneous SCSV implantation was performed in three human cadaver torso specimens under fluoroscopic guidance. The following approaches were evaluated: sacral hiatus, transforaminal, interlaminar contralateral, and interlaminar ipsilateral. The leads in the latter 3 approaches were inserted between L1 and L5. Eighteen implants were attempted, with nine leads retained for analysis. Lead and electrode position were assessed using computed tomography (CT) with three-dimensional reconstruction, along with anatomical dissection to verify lead and electrode placement within the epidural space. ResultsSuccessful ventral epidural lead placement was achieved using all four implantation approaches. The sacral hiatus (16/16 electrodes) and transforaminal (8/8 electrodes) approaches resulted in exclusively ventrolateral placement. The interlaminar contralateral approach led to 27/32 electrodes positioned ventrolaterally and 5/32 dorsally. The interlaminar ipsilateral implantation approach led to 14/32 electrodes positioned ventrolaterally and 18/32 positioned ventromedially. ConclusionsThese findings demonstrate that ventral epidural SCS lead placement can be achieved using modified percutaneous implant techniques. The four approaches outlined here provide a clinically feasible pathway to SCSV and establishes a foundation for future clinical studies investigating SCSV for motor rehabilitation following SCI.

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The relationship between limb dystonia severity and functional impact in children with cerebral palsy

Lott, E.; Kim, S.; Blackburn, J. S.; Gelineau-Morel, R.; Mingbunjerdsuk, D.; O'Malley, J.; Tochen, L.; Waugh, J.; Wu, S.; Aravamuthan, B. R.

2026-04-13 neurology 10.64898/2026.04.11.26350684 medRxiv
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Dystonia treatment evaluation in cerebral palsy (CP) is limited by the lack of clinician-assessed scales linking dystonia severity to functional impact. We asked 7 pediatric movement disorder specialists to review videos of 27 children with CP while performing an upper extremity task and while walking. Experts rated arm and leg dystonia severity using the Global Dystonia Severity Rating Scale (GDRS) and task-specific functional impact on a five-point scale adapted from the Dyskinetic Cerebral Palsy Functional Impact Scale. Arm GDRS scores correlated with functional impact on the upper extremity task (linear regression R^2=0.48, p=0.0005). Leg GDRS scores correlated with gait impact (R^2=0.43, p=0.001). A four-point increase in total GDRS corresponded to a one-point worsening in combined functional impact. By demonstrating how expert-rated limb dystonia severity correlates with task-specific functional impact in children with CP, these results could help clinically identify functionally-meaningful differences in dystonia severity.

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Dual Nanoparticle-Driven Therapeutics for Leishmaniasis: A Mathematical Model of Targeted Macrophage and Parasite Elimination

Arumugam, D.; Ghosh, M.

2026-03-30 immunology 10.64898/2026.03.27.714640 medRxiv
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BackgroundTo control leishmaniasis, chemotherapy drugs are currently under development. However, these drugs often exhibit poor efficacy and are associated with toxicity, adverse effects, and drug resistance. At present, no specific drug is available for the treatment of leishmaniasis. Meanwhile, vaccine research is ongoing. Recent studies have analysed some experimental vaccines using mathematical models. AimIn previous work, drug targeting was focused on the entire human body rather than specifically addressing infected macrophages and parasites. In our current approach, we aim to eliminate infected macrophages and parasites through nano-drug design. Specifically, we utilise two types of nanoparticles: iron oxide and citric acid-coated iron oxide. Moving forward, we plan to advance this strategy using mathematical modelling of macrophage-parasite interactions. MethodsWe design PDE-based models of macrophages and parasites, incorporating cytokine dynamics, to support nano-drug development. Drug efficacy is estimated using posterior distributions to analyse phenotypic fluctuations of macrophages and parasites during the design phase. We investigate implicit and semi-implicit treatment schemes, focusing on energy decay properties. To model drug flow during treatment, we introduce a three-phase moving boundary problem. Comparative analyses are conducted to evaluate macrophage and parasite behaviour with and without treatment. Finally, the entire framework is implemented within a virtual lab environment. ResultsThe results show that the nano-drug exhibits better efficacy compared to combined drug doses. We analysed and compared two types of nano-drug particles: iron oxide and citric acid-coated iron oxide. We discuss how the drug effectively targets and eliminates infected macrophages and parasites. ConclusionOur models results and simulations will support researchers conducting further studies in nano-drug design for leishmaniasis. These simulations are performed within a virtual lab environment.

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Recovering Clinical Detail in AI-Generated Responses for Low Back Pain Through Prompt Design

Basharat, A.; Hamza, O.; Rana, P.; Odonkor, C. A.; Chow, R.

2026-04-23 pain medicine 10.64898/2026.04.21.26351437 medRxiv
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Introduction Large language models are increasingly being used in healthcare. In interventional pain medicine, clinical reasoning is essential for procedural planning. Prior studies show that simplified prompts reduce clinical detail in AI-generated responses. It remains unclear whether this reflects knowledge loss or simply prompt-driven suppression of information. Methods We performed a controlled comparative study using 15 standardized low back pain questions representing common interventional pain questions. Each question was submitted to ChatGPT under three conditions, professional-level prompt (DP), fourth-grade reading-level prompt (D4), and clinician-directed rewriting of the D4 response to a medical level (U4[-&gt;]MD). No follow-up prompting was allowed. Three physicians independently rated responses for accuracy using a 0-2 ordinal scale. Clinical completeness was determined by consensus. Word count and Flesch-Kincaid Grade Level (FKGL) were also measured. Paired t-tests compared conditions. Results Accuracy was highest with professional prompting (1.76). Accuracy declined with the fourth-grade prompt (1.33; p = 0.00086). When simplified responses were rewritten for clinicians, accuracy returned to baseline (1.76; p {approx} 1.00 vs DP). Clinical completeness followed the same pattern showing DP 80.0%, D4 6.7%, U4[-&gt;]MD 73.3%. Fourth-grade responses were shorter and less complex. Upscaled responses were more complex and similar in length to professional responses. Inter-rater reliability was low (Fleiss {kappa} = 0.17), but trends were consistent across conditions. Conclusions Reduced clinical detail under simplified prompts appears to reflect constrained output rather than loss of knowledge. Clinician-directed reframing restores omitted content. LLM performance in interventional pain depends strongly on prompt design and intended audience.

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Systematic Review of Population-Based Studies of Prevalence and Incidence of Aging-Associated Neurodegenerative Diseases in Russia

Okhotion, A.; Gorbunova, I.; Bolshakov, A.

2026-04-06 geriatric medicine 10.64898/2026.04.03.26350047 medRxiv
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Purpose: To systematically review population-based studies reporting the prevalence and incidence of neurodegenerative diseases among adults aged 50 and older in Russia Methods: We searched Medline, Scopus, Embase, and eLibrary from inception to January 2025. Cross-sectional and cohort studies were eligible if they reported community-based prevalence or incidence of dementia, cognitive impairment, or Parkinson's disease in adults aged 50 and older in Russia. Healthcare and institutionalised populations were excluded. Risk of bias was assessed using the RoB-PrevMH tool, and dementia prevalence from screening tools was adjusted for test sensitivity and specificity. Prevalence estimates were pooled using random- and fixed-effects meta-analysis, stratified by age group and assessment method. Results: Twenty studies met the inclusion criteria. Dementia prevalence ranged from 0.5% to 81.6%, with the lowest estimates from administrative data and the highest from Mini-Cog screening in adults aged 85 and older. Cognitive dysfunction was reported in 12 studies (prevalence 3.1-81.5%). Nine studies reported Parkinson's disease prevalence (0.017-0.31%), with the highest estimate from the only neurologist-assessed population-based study. Conclusion: Prevalence of dementia and Parkinson's disease in Russia varies widely depending on diagnostic method, age group, and study design. Most studies lacked representative sampling and used non-standardised diagnostic criteria. Population-based longitudinal research using validated tools is urgently needed to support public health planning in Russia.

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Identifying trial-relevant concepts of interest in HSP: insights from an international patient-voice study in >600 individuals

Ademi, M.; Morales Saute, J. A.; Dubec-Fleury, C.; Greenfield, J.; Wallis, R.; Gobeil, C.; Linton, L. R.; Nadke, A.; Horvath, R.; Klebe, S.; Santorelli, F.; Vural, A.; van de Warrenburg, B.; Gagnon, C.; Synofzik, M.; PROSPAX Consortium, ; Tezenas du Montcel, S.; Schuele, R.

2026-04-10 neurology 10.64898/2026.04.09.26350392 medRxiv
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As therapeutic options emerge for hereditary spastic paraplegias (HSP), clinical trials require outcome measures that reflect disease aspects most important to patients. Patient priorities in HSP remain poorly defined. This study aimed to develop a regulatory-compliant framework of patient-prioritised health domains to evaluate treatment response in clinical trials. Patient-reported data on health impacts were collected via two multinational, multilingual online surveys conducted sequentially, including 616 and 504 patients across the clinical and genetic spectrum of HSP. Using a staged approach, we examined prevalence, relevance, and severity, focusing on health impacts that were (i) common (ii) sensitive to disease progression, (iii) highly relevant to patients, and (iv) showed strong severity-relevance correlation. Patient representatives contributed centrally to study design and prioritisation. Our patient-focused analysis yielded five highly prevalent and relevant core health domains: mobility, lower body function, autonomic dysregulation, pain, and psychosocial aspects. Ambulation and lower body function ranked highest across all disease stages. Among non-motor impacts, reduced ability to work, bladder incontinence, and fatigue were most relevant. In mild disease stages, reduced walking distance, reduced walking speed, and the urgency to empty the bladder were the most frequent and most relevant health impact. This work provides the most comprehensive patient-reported and disease stage specific profiling of HSP health impacts to date. It lays the necessary groundwork for developing patient-focused outcome tools capable of capturing treatment effects in future trials.

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Elder-Sim: A Psychometrically Validated Platform for Personality-Stable Elderly Digital Twins

Wang, J.; Yang, Z.; Zhu, Z.; Zhu, X.; Huang, Z.; Wang, H.; Tian, L.; Cao, Y.; Qu, X.; Qi, X.; Wu, B.

2026-03-30 geriatric medicine 10.64898/2026.03.25.26349036 medRxiv
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Background: LLMs enable patient-facing conversational agents, creating a pathway toward digital twins that capture older adults' lived experiences and behavioral responses across time. A central barrier is personality drift---inconsistent trait expression across repeated interactions---which undermines reliability of generated trajectories and intervention-response simulation in geriatric care. Objective: To develop ELDER-SIM, a multi-role elderly-care conversational platform for building personality-stable digital twin agents, and to propose a psychometric validation framework for quantifying personality consistency in LLM-based agents. Methods: ELDER-SIM was implemented via n8n workflow orchestration with local LLM inference (Ollama/vLLM), integrating (1) Big Five (OCEAN) trait specifications, (2) a Cognitive Conceptualization Diagram (CCD) grounded in Beck's CBT framework, and (3) a MySQL-based long-term memory module. Ablation studies across four conditions---Baseline, +Memory, +CCD, and +LoRA (fine-tuned on 19,717 instruction pairs from CHARLS)---were evaluated via Cronbach's $\alpha$, ICC, and role discrimination accuracy. Results: Personality measurement reliability was acceptable to excellent across conditions (Cronbach's : 0.70-0.94), with consistently high test-retest stability (ICC: 0.85- 2 0.96). Role discrimination improved stepwise from 83.3% (Baseline) to 88.9% (+Memory), 94.4% (+CCD), and 97.2% (+LoRA). CCD produced the largest gain in internal consistency (mean 0.702[-&gt;]0.892), while LoRA achieved the highest overall internal consistency ( 0.940) and ICC (0.958). Conclusions: ELDER-SIM provides a psychometrically validated approach for constructing personality-consistent elderly digital twin agents. Structured cognitive modeling and domain adaptation reduce personality drift, supporting reliable longitudinal simulation for elderly mental health care and reproducible in silico evaluation before clinical deployment.

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The burden of neurogenic orthostatic hypotension in patients with multiple system atrophy: a real-world study

Kmiecik, M. J.; O'Brien, L.; Szpyhulsky, M.; Iodice, V.; Freeman, R.; Jordan, J.; Biaggioni, I.; Kaufmann, H.; Vickery, R.; Miller, A.; Saunders, E.; Rushton, E.; Valle, L.; Norcliffe-Kaufmann, L.

2026-04-22 neurology 10.64898/2026.04.20.26351214 medRxiv
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BackgroundAlthough neurogenic orthostatic hypotension (nOH) is a common and debilitating feature of multiple system atrophy (MSA), little is known about the burden of symptoms in the real world. ObjectivesTo design and conduct a cross-sectional community-based research survey targeting patients with MSA, with and without nOH. MethodsWe recruited patients with MSA to complete an anonymous online survey covering three core themes: 1) timely diagnosis, 2) nOH pharmacotherapy and refractory symptoms, and 3) confidence in physician knowledge. Responses were grouped by pre-specified diagnostic certainty levels. Relationships between symptoms, function, and pharmacotherapy were assessed using univariate and multivariate methods. ResultsWe analyzed 259 respondents with a self-reported diagnosis of MSA (age: M=64.38, SD=8.09 years; 44% female). In total, 42% also had a diagnosis nOH; 40% had symptoms highly suspicious of nOH, but no diagnosis; and 21% reported having never had their blood pressure measured in the standing position at a clinical visit. Treatment with a pressor agent was independently associated with the presence of other symptoms of autonomic failure. Each additional nOH symptom reported increased the odds of requiring pharmacotherapy by 18%. Yet, despite anti-hypotensive medication use, 97% of patients reported limitations in their ability to bathe, cook, or arise from a chair/bed with 76% needing caregiver support for refractory nOH symptoms. ConclusionsThis cross-sectional representative sample shows nOH is underrecognized and undertreated in MSA patients, leading to substantial functional limitations. It is our hope that these findings are leveraged for planning future trials and advocating for better treatments.

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AENEAS Project: First real-time intraoperative application of machine vision-based anatomical guidance in neurosurgery

Sarwin, G.; Ricciuti, V.; Staartjes, V. E.; Carretta, A.; Daher, N.; Li, Z.; Regli, L.; Mazzatenta, D.; Zoli, M.; Seungjun, R.; Konukoglu, E.; Serra, C.

2026-04-11 surgery 10.64898/2026.04.09.26348607 medRxiv
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Background and Objectives: We report the first intraoperative deployment of a real-time machine vision system in neurosurgery, derived from our previous anatomical detection work, automatically identifying structures during endoscopic endonasal surgery. Existing systems demonstrate promising performance in offline anatomical recognition, yet so far none have been implemented during live operations. Methods: A real-time anatomy detection model was trained using the YOLOv8 architecture (Ultralytics). Following training completion in the PyTorch environment, the model was exported to ONNX format and further optimized using the NVIDIA TensorRT engine. Deployment was carried out using the NVIDIA Holoscan SDK, the system ran on an NVIDIA Clara AGX developer kit. We used the model for real-time recognition of intraoperative anatomical structures and compared it with the same video labelled manually as reference. Model performance was reported using the average precision at an intersection-over-union threshold of 0.5 (AP50). Furthermore, end-to-end delay from frame acquisition to the display of the annotated output was measured. Results: A mean AP50 of 0.56 was achieved. The model demonstrated reliable detection of the most relevant landmarks in the transsphenoidal corridor. The mean end-to-end latency of the model was 47.81 ms (median 46.57 ms). Conclusion: For the first time, we demonstrate that clinical-grade, real-time machine-vision assistance during neurosurgery is feasible and can provide continuous, automated anatomical guidance from the surgical field. This approach may enhance intraoperative orientation, reduce cognitive load, and offer a powerful tool for surgical training. These findings represent an initial step toward integrating real-time AI support into routine neurosurgical workflows.