BMC Neurology

BACKGROUND: Myofascial Pain Syndrome (MPS) is a common musculoskeletal pain condition associated with myofascial trigger points that has been reported to occur in 30-93% of patients who present with musculoskeletal pain. The current pharmacologic treatments (such as nonsteroidal anti-inflammatory drugs [NSAIDs], muscle relaxants, and tricyclic antidepressants) are only partially effective and have side effects. Shilajit, a mineral-organic exudate from the Himalayas, has antioxidant, anti-inflammatory, mitochondrial bioenergetic, and central analgesic effects and has not previously been examined as an analgesic in any musculoskeletal pain condition. METHODS: This was an exploratory pilot clinical trial with open-label design in a single arm for an 18-month period at All India Institute of Medical Sciences (AIIMS), Rishikesh, India. Patients aged 18 to 65 years with clinically diagnosed MPS (Simons et al. 1999 criteria) and a baseline visual analog scale (VAS) score >4 were enrolled. Native Himalayan Shilajit 250 mg daily was administered as add-on therapy for 49 days. The main outcome was the percentage of participants with more than or equal to 30% VAS reduction at Day 49. The intensity of pain, the dose of analgesics consumed, and the number of trigger points were evaluated at five time points (Day 0, 12, 24, 36, 49). Throughout, adverse events were monitored. RESULTS: Of 80 enrolled participants, 76 (95.0%) completed the per-protocol analysis. Mean age was 41.25 (SD 9.05) years; 52.6% were male. A total of 56 of 76 participants (73.7%; 95% CI: 62.1-82.8%) achieved the primary endpoint. Mean VAS score declined from 6.63 (SD 1.08) at baseline to 3.63 (SD 1.72) at Day 49 (mean reduction 45.3%; Friedman Chi-square= 278.5, p<0.001). The first signs of pain reduction were seen at Day 24. The number of analgesic doses consumed decreased by 75.5% during the study period (chi-square = 126.1, p<0.001). There was a significant reduction in trigger point count from baseline to Day 49 (p=0.031) of 23.4%. One Grade 2 adverse event (gastrointestinal irritation, Day 28, resolved within 24 hours, no drug discontinuation) occurred; no serious adverse events were reported. Trial registration: CTRI/2025/06/088636. The study was not funded by any external sources. CONCLUSIONS: Native Himalayan Shilajit 250 mg/day for 49 days was associated with clinically and statistically significant reductions in pain intensity, analgesic consumption, and trigger-point burden in patients with MPS, with a favorable safety profile. These findings warrant confirmation in a larger, randomized, placebo-controlled trial.

Objective: To map, using the Hyperhidrosis Disease Severity Scale (HDSS), the preoperative distribution and six-month regional evolution of sweating severity across 20 anatomical sites after dominant-side unilateral versus one-stage bilateral R4 video-assisted thoracoscopic sympathectomy for primary palmar hyperhidrosis. Methods: This was a secondary complete-case, site-level analysis of a prospective multicenter randomized trial. Adults undergoing one-stage bilateral thoracic sympathectomy (BTS) or dominant-side unilateral sympathectomy (UniS) were eligible when baseline and six-month HDSS data were complete for all 20 prespecified sites. HDSS was grouped as 1, 2, or 3-4. Regional outcomes were classified as improvement, stability, or worsening and were stratified by baseline HDSS. Results: Ninety-two patients were included: 36 BTS and 56 UniS. Before surgery, severe sweating was present in 182 of 184 hand-site observations, 168 of 184 foot-site observations, and 75 of 184 axillary-site observations. At six months, improvement was more frequent after BTS than UniS in the hands (88.9% vs 52.7%) and axillae (72.2% vs 29.5%). Worsening was concentrated mainly in abdominal, hemidorsal, and thoracic sites. Among observations that were normal at baseline, progression to HDSS 3-4 occurred in 10.8% after BTS and 7.7% after UniS. Among observations with baseline HDSS 3-4, complete resolution to HDSS 1 occurred in 47.2% after BTS and 21.8% after UniS. Conclusion: Baseline-stratified 20-site HDSS mapping may improve preoperative counseling and postoperative outcome assessment by distinguishing true new-onset compensatory hyperhidrosis from worsening or persistence of pre-existing sweating.

Objective: To describe the self-reported effects of incobotulinumtoxinA treatments on migraine-like headache in participants who experienced traumatic brain injury versus Anomalous Health Incidents. Background: Persistent headache attributed to traumatic injury to the head has been widely recognized as among the most common sequelae of concussion/mild traumatic brain injury. Such persistent headaches often have migraine-like characteristics and are typically treated similarly to idiopathic migraine. Patients who have experienced Anomalous Health Incidents have also commonly reported migraine-like headaches, but to our knowledge, no reports describing treatment for persistent headaches attributed to Anomalous Health Incidents have been published. Methods: We describe the self-reported effects of incobotulinumtoxinA treatments on headache with migraine-like characteristics in 19 participants with traumatic brain injury and 11 who had experienced Anomalous Health Incidents from a single center. Results: Self-reported benefits from incobotulinumtoxinA treatments were generally similar and statistically indistinguishable between groups. The Headache Impact Test-6 score decreased by a mean of 12 points in the traumatic brain injury group and 9.5 points in the Anomalous Health Incidents group from baseline to peak efficacy (p = 0.43), with concomitant reductions in work/school hours lost (62% vs. 50%) and family/leisure hours lost (75% vs. 33%). Furthermore, reductions in headache frequency (67% for the traumatic brain injury group vs. 57% for the Anomalous Health Incidents group), headache severity (36% vs. 23%), headache duration (37% vs. 50%), nausea/vomiting (50% vs. 25%), photophobia (34% vs. 29%), phonophobia (30% vs. 37%), visual aura (50% vs. 29%), vestibular aura (50% vs. 33%), and other aura (21% vs. 25%) from baseline to peak efficacy were similar in both groups. Likewise, time from treatment to response (6.5 vs. 7 days), duration of response (10.2 vs. 9.1 weeks), adverse effects (3/19 for the traumatic brain injury group, 3/11 for the Anomalous Health Incidents group), and improved efficacy of concomitant abortive treatments (30% vs. 50% for pain, 50% vs. 55% for aura) did not differ between groups. Osmophobia and cogniphobia, when present, did not improve on average in either group. Notably, the mean duration of response was less than 12 weeks in both groups, with only 3 participants with traumatic brain injury and 1 participant who had experienced Anomalous Health Incidents reporting benefit beyond the typical 12-week incobotulinumtoxinA treatment interval. Conclusion: Overall, these findings provisionally indicate that at least some patients who have experienced Anomalous Health Incidents may subjectively benefit from incobotulinumtoxinA treatment for persistent migraine-like headaches similarly to patients with traumatic brain injury. Limitations include the open-label, single-center, primarily retrospective design; small sample size; and limited representativeness. Further prospective controlled studies are needed to determine whether these groups truly respond similarly to incobotulinumtoxinA and other standard treatments.

Post-stroke depression affects approximately 30% of patients after stroke and is associated with delayed recovery in activities of daily living, reduced rehabilitation effectiveness, and poorer quality of life. Attentional bias modification may provide a low-burden, nonpharmacological approach for patients in the acute phase of stroke. However, before such an intervention can be implemented in clinical practice, it is necessary to clarify whether attentional bias is present in patients with acute stroke and depressive symptoms, whether cognitive function influences the manifestation of this bias, and which task and stimulus formats are most appropriate for assessment. This multicenter, cross-sectional observational study will enroll patients with acute stroke between 7-30 days after stroke onset. Depressive symptoms will be assessed using the depression subscale of the Hospital Anxiety and Depression Scale. Attentional bias will be measured under four task conditions based on the dot-probe task and the cue-target task, using face and word stimuli. Secondary assessments will include cognitive function, anxiety symptoms, activities of daily living, health-related quality of life, and clinical background variables. The aims of this study are to investigate the association between depressive symptoms and attentional bias in patients with acute stroke, compare attentional bias characteristics across task and stimulus types, and examine the potential influence of cognitive function on this association. The findings are expected to provide an empirical basis for designing future attentional bias modification protocols targeting post-stroke depression in the acute phase. This study has been registered with the UMIN Clinical Trials Registry (UMIN000059166).

Individuals with NF2-related schwannomatosis (NF2-SWN) experience a complex constellation of physical, emotional, and social symptoms that substantially impact quality of life (QoL). Although disease-specific patient-reported outcome measures are increasingly important for evaluating treatment benefit in clinical trials, existing NF2-SWN QoL measures have limitations in content coverage and sensitivity to change. This study describes the development and initial validation a new disease-specific QoL assessment -- the Quality of Life Evaluation in NF2-related Schwannomatosis Trials (QUEST). Using a three-phase, mixed-methods approach, items were generated through concept elicitation interviews with individuals with NF2-SWN and clinicians, prioritized via patient survey data, and refined through iterative cognitive debriefing procedures. The resulting 21-item QUEST assesses the extent to which NF2-SWN has negatively impacted a persons daily life over the past seven days. Initial psychometric evaluation was conducted in an international sample of 174 individuals with NF2-SWN aged 15 years and older (117 women (67%), 158 White individuals (89%)). Exploratory factor analysis supported a four-factor structure, and the total score demonstrated excellent internal consistency and strong test-retest reliability. Evidence of construct validity was demonstrated through hypothesized associations with disease-specific, generic, and domain-specific QoL measures, as well as known-groups validity based on self-reported disease severity and number of prior surgeries. Incremental validity analyses indicated that QUEST explained unique variance beyond existing measures. Together, findings support the QUEST as a reliable and valid disease-specific QoL measure with strong content validity and feasibility for use as a clinical trial endpoint in NF2-SWN.

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is frequently complicated by delayed cerebral ischaemia (DCI), for which current therapies incompletely target the underlying multifactorial pathophysiology. Transauricular vagus nerve stimulation (taVNS) modulates inflammatory, vasoactive and autonomic pathways and may attenuate secondary brain injury after aSAH. Methods: We conducted a prospective, single-centre, single-blind, randomised, sham-controlled pilot trial in adults within 5 days of aneurysm securing for non-traumatic aSAH. Participants were allocated 1:1 to active taVNS (left tragus) or sham (left earlobe) using a portable device delivered for 45 minutes twice daily over 5 days. Primary outcomes were safety (taVNS-related serious adverse events), acceptability, and compliance; secondary outcomes included inflammatory biomarkers, DCI, in-hospital complications, and functional outcomes to 1 month. Results: Thirty patients were randomised (16 taVNS, 14 sham), with numerically more severe aSAH at baseline in the taVNS arm. No taVNS-related serious adverse events occurred; side effects were generally mild and transient, and over 80% of planned sessions were completed. TaVNS produced greater reductions in serum tumour necrosis factor- and trends towards reductions in interleukin-1{beta} and interleukin-10, with numerically fewer DCI events (6.6% vs 35.7%) and neurological impairments (16.7% vs 53.8%), although functional outcomes were not statistically different at 1 month. Conclusions: Early taVNS after aSAH is safe, acceptable, and feasible in the neurocritical care setting and shows biologically plausible signals warranting evaluation in larger multi-centre trials.

Objective: To evaluate the clinical efficacy of non-invasive electrical pulsed radiofrequency (PRF) stimulation on diagnostic thresholds and subjective pain in chronic, pedal diabetic peripheral neuropathy (DPN). Methods: A randomized, single-blind, placebo-controlled trial (ClinicalTrials.gov: NCT07725419) enrolled 92 patients with pedal DPN naive to PRF and scoring [&ge;] 4/10 on the Douleur Neuropathique 4 (DN4) test. Participants received either active PRF stimulation (n = 46) or a non-stimulating placebo (n = 46) applied bilaterally to the sciatic nerve in the popliteal fossa for 10 minutes per limb, once weekly for three weeks. The primary outcome was clinical neuropathic resolution (DN4 < 4). Secondary outcomes included subjective pain tracking via the Brief Pain Inventory-Short Form (BPI-SF) Worst Pain scale over a 6-month follow-up window. Missing data were handled via Non-Responder Imputation (NRI). Longitudinal continuous trajectories were modeled using Linear Mixed-Effects Models (LMMs) adjusted for age, gender, and baseline medication use. Results: In the Intention-to-Treat population (N = 92), a significant diagnostic responder effect occurred at 3 months, with 39.1% of active patients dropping below the diagnostic threshold for neuropathy (DN4 < 4) versus 19.6% of placebo controls (p = 0.039). For subjective pain, 47.7% of active patients achieved a Minimally Clinically Important Difference ([&ge;] 3-point reduction) in BPI Worst Pain at 1 month compared to 19.4% of placebo controls (p = 0.008). Multivariable logistic regression identified active treatment as a significant independent predictor of clinical response (Adjusted OR = 4.86; 95% CI: 1.56 to 17.53; p = 0.010). Continuous LMM tracking confirmed a statistically significant treatment-by-timepoint interaction for BPI Worst Pain at 1 month (p = 0.046). Conclusion: A brief, three-week course of non-invasive PRF stimulation serves as a safe, effective, non-pharmacological adjunct that aids in managing the diagnostic presentation of neuropathic pain and mitigates worst pain experiences in patients suffering from pedal DPN.

Background: Neuropathic pain (NP) remains a therapeutic challenge, with conventional repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) yielding a response rate of approximately 40%. Personalised targeting based on dysfunctional neurocircuitry offers a promising strategy to enhance efficacy, yet its application in NP is unexplored. This open-label trial investigated a novel targeting approach guided by the recently described cingulo-opercular and somato-cognitive action (CON-SCAN) network, a circuit integrating cognitive and affective dimensions of pain. Methods: Twenty patients with NP received 10 sessions of M1-rTMS over two weeks, with the stimulation site individually localised based on maximal functional connectivity to a CON template. Results: Increased CON-SCAN connectivity from baseline to post-treatment was associated with reduction in pain interference, anxiety and depression scores. The response rate was 50% post-treatment, which was maintained at the 1-month follow-up. Improvements were also observed in neuropathic pain symptoms, negative affect, and overall health. Conclusions: As the first connectivity-guided rTMS trial for NP, this study provides preliminary evidence that personalised targeting of the CON-SCAN network is feasible and associated with the analgesic effects of M1-rTMS, supporting further investigation in randomised controlled trials. Trial registration: Chinese Clinical Trial Registry, ChiCTR2500104679. Registered 20 June 2025, http://www.chictr.org.cn. Chinese Clinical Trial Registry, ChiCTR2400094568. Registered 24 December 2024, http://www.chictr.org.cn. Keywords: Personalised TMS; Pain; M1; CON; SCAN

Background: The relative merits of infrainguinal bypass and primary major lower limb amputation (MLLA) for chronic limb-threatening ischaemia (CLTI) remain uncertain, and the baseline profiles of patients selected for each strategy are poorly described. Methods: A systematic review and meta-analysis were undertaken in accordance with PRISMA 2020 and prospectively registered (PROSPERO: CRD42022356094). MEDLINE, Embase, CENTRAL, and CINAHL were searched from inception to March 2025. Prospective studies of adults with CLTI undergoing primary infrainguinal bypass or primary MLLA were eligible. Mortality, major adverse cardiovascular events (MACE) and subsequent amputation outcomes were synthesised using random-effects meta-analysis of proportions. Baseline comorbidity profiles were also extracted. Results: Twenty-seven studies involving 6,576 patients were included: 5,779 underwent infrainguinal bypass and 797 underwent MLLA. After bypass, pooled mortality was 3.7% at 30 days (95% CI 2.8%-4.9%, I2 = 49.4%), 18.5% at 1 year (95% CI 15.6%-21.9%, I2 = 62.3%), and 54.3% at 5 years (95% CI 50.5%-58.0%, I2 = 0%). After MLLA, pooled mortality was 9.2% at 30 days (95% CI 4.1%-19.3%, I2 = 73.5%), 28.5% at 1 year (95% CI 13.3%-51.0, I2 = 70.8%), and 39.9% at 2 years (95% CI 0.3%-99.3, I2 = 90.5%), although longer-term estimates were limited by sparse data and marked heterogeneity. Thirty-day MACE was 6.5% (95% CI 4.3%-9.7, I2 = 63.5%) after bypass and 2.8% after MLLA (95% CI 0.1%-37.6%, I2 = 0%). Early subsequent major amputation after bypass occurred in 3.9% of patients (95% CI 2.0%-7.7%, I2 = 91.2%), rising to 16.2% at 1 year (95% CI 12.6%-20.5%, I2 = 82.0%) and 33.3% at 3 years (95% CI 20.1%-49.8%, I2 = 0%). Early re-amputation after MLLA occurred in 10.9% of patients (95% CI 4.5%-24.4%, I2 = 40.3%). Baseline comorbidity burden was high in both groups, with substantial heterogeneity across studies. Conclusions: CLTI carries a poor prognosis regardless of treatment strategy. Infrainguinal bypass is associated with lower early mortality and better early limb preservation than primary MLLA, but long-term survival remains poor and later limb failure is common. Primary MLLA is not a low-risk alternative. Better contemporary comparative evidence utilising modern causal inference approaches is needed to support individualised decision-making.

Objective: To evaluate decision concordance between commercially available multimodal large language models (LLMs), resident doctors, and senior-surgeon ground truth for surgical indication and spinal level in degenerative lumbar spine disease. Methods: We retrospectively analyzed 147 consecutive patients. Each case included clinical documentation and MRI presented as two composite PNG images. Two resident doctors and three multimodal LLMs (GPT 5.5, Claude Sonnet 4.6, Gemini 3.1 Pro) independently assessed operative versus conservative management and, if operative, the surgical level. Analyses used Cochran's Q, McNemar tests with Holm correction, and Bayesian methods. Results: LLMs achieved higher therapy-decision accuracy (66.0%-68.0%; 97-100/147) than residents (54.4%; 80/147) but over-recommended surgery. Conditional level accuracy when surgery was correctly indicated was 71.4% (20/28) for residents versus 33.3%-41.1% for LLMs. Conclusion: Off-the-shelf multimodal LLMs approximate human performance for binary surgical indication but remain inferior for precise level localization. These results establish a practice-relevant baseline of spatial reasoning limitations for tools already used by patients and junior doctors.

Background: Detecting higher order relationships in datasets of complex traits, such as multiple sclerosis (MS), has been challenging. Conventional statistics largely rely on comparing averages across groups and thereby discard important information on the underlying distribution of datapoints. The Genomic Information Field Theory (GIFT) overcomes this limitation by ranking individuals based on linear measures, for example immunoglobulin titres. The exact role of humoral immune responses against several human herpes viruses in a sex-dependent manner in MS is currently unknown. Materials and methods: We compared the performance of GIFT with conventional statistical frameworks to detect differences in the humoral immune response against 4 highly prevalent herpes viruses linked to an individuals susceptibility to develop MS in 200 MS patients and 137 healthy controls. Results: GIFT validated the well-known association that the Epstein Barr Virus (EBV) protein EBNA1 is strongly linked to MS susceptibility in both sexes. In contrast to conventional statistics, GIFT also identified association between herpes simplex virus, varicella zoster virus and the EBV VCA protein and female susceptibility to develop MS, whereas male MS susceptibility was only linked to CMV immunoglobulin levels. None of these associations was observed using conventional statistical tools. Conclusion and discussion: We here show for the first time that GIFT is able to detect novel associations in human immunoglobulin data linked to MS susceptibility, which remained undetected by conventional statistical frameworks. This shows the power of GIFT to detect complex phenotype-trait associations and underlying subgroups within populations.

Background: Fluctuations in pain intensity are intrinsic to non-specific chronic low back pain (nsCLBP). Nevertheless, pain fluctuations have rarely been considered when investigating pathophysiological mechanisms. Therefore, a novel study protocol was developed and implemented to systematically assess the impact of fluctuating pain states on pain-related measures. Methods: The final study cohort consisted of 45 nsCLBP patients and 47 age- and sex-matched healthy controls (HCs). Patients participated in three visits, conducted during different pain states (i.e. clinically relevant pain, low-intensity clinical pain / pain-free, clinically irrelevant pain induced using a Qutenza 8% capsaicin patch). Pain fluctuations were monitored through online assessments every four days and guided the pseudorandomized visit scheduling. HCs participated in a single visit. Each study visit comprised a multimodal battery of pain-related measures. Results: 93.33% of patients completed all three visit types in a pseudorandomized order (chi-squared=1.50, p=0.826). Visit scheduling was possible due to the high self-report adherence (median=93.48%), unrelated to self-report burden (rho=-0.097, p=0.53). Study visits were conducted during different pain states, as indicated by: i) the significantly higher low back pain intensity in the clinically relevant pain visit (mean[SD]: 3.98[0.90]), compared to the low-intensity clinical pain (1.03[0.86]) and clinically irrelevant pain (1.13[0.82]) visits (p-values<0.001), as well as by ii) the successful induction of a moderate-to-high clinically irrelevant pain across assessments. Conclusion: Despite scheduling complexity and pain state transition uncertainty, a pain state-dependent pseudorandomized study design is feasible and could improve the understanding of nsCLBP mechanisms.

Introduction Post stroke dysphagia is common, associated with poor functional outcome and lacks treatment strategies beyond behaviour therapies delivered by speech & language therapists. Here, we present the statistical analysis plan for the ongoing pharyngeal electrical stimulation for acute stroke dysphagia trial (PhEAST). PES is a candidate treatment for dysphagia present in non-ventilated stroke patients. Methods PhEAST is an investigator-initiated international prospective randomised open-label blinded-endpoint phase-4 superiority trial involving 650 participants with tube-dependent post-stroke dysphagia. Consenting patients are randomised to PES versus no PES given on top of standard care with PES given daily for 6 days. The primary outcome is the dysphagia severity rating scale (DSRS), a measure of swallowing impairment, made at days 14 and 90 and analysed using repeated measures regression. Conclusion We present the statistical analysis plan for the main analyses based on data up to day 90 along with planned secondary analyses including presentation of baseline data, health economics, cognition and extended follow-up to 12 months.

Background: Endovenous techniques are considered the gold standard for treating great saphenous vein (GSV) insufficiency, but access remains limited in low- and middle-income countries. In such contexts, simplified conventional surgeries may represent viable alternatives. This study aimed to compare outcomes of isolated GSV stripping with conventional surgery (stripping plus varicose vein resection) in patients with varicose veins (VV) associated with GSV insufficiency. Methods: A prospective interventional study was conducted including 34 patients with VV (CEAP C2-C6), divided into two groups: Conventional (C, n=17) and Isolated Saphenectomy (IS, n=17). Quality of life was assessed preoperatively and at 2 and 6 months postoperatively using the Venous Clinical Severity Score (VCSS) and VEINES-QoL/Sym questionnaires. Varicose vein evolution in the IS group was quantified using a standardized visual scoring system. Statistical analyses included Students t-test, chi-square, and generalized estimating equations (p[&le;]0.05). Results: Both groups were demographically comparable. Surgical treatment significantly improved VCSS and VEINES scores in both groups (p<0.005), with no intergroup difference at 6 months. In the IS group, the mean reduction in visible VV was 46% (range 20-90%). CEAP classification improved in both groups, with migration toward less severe categories postoperatively. No major complications were reported. Conclusion: Isolated GSV stripping yields comparable short- and mid-term improvements in symptoms and quality of life to conventional surgery, while reducing operative extent. In resource-limited settings, this abbreviated technique may expand access to treatment for VV, improving patient outcomes and reducing healthcare costs without compromising clinical efficacy.

BACKGROUND Recruitment in stroke neurorehabilitation trials is often difficult, particularly in studies requiring MRI and repeated laboratory visits. The recruitment efficiency was analyzed to identify the major barriers to enrollment in a stroke neurorehabilitation trial. METHODS In this observational screening study, 1201 patients were screened at a neurological rehabilitation center in Germany between October 2023 and February 2026. Recruitment barriers were analyzed using a stepwise recruitment flow approach. RESULTS Of 678 patients with ischemic stroke, 13 were ultimately enrolled (1.9%; 1.1% of all 1201 screened rehabilitation patients). The most common exclusion reasons were strict clinical eligibility criteria (52.2%), travel distance to the study center (23.9%), and predefined age restrictions (17.9%). Recruitment losses occurred across multiple stages of the screening process. CONCLUSION Recruitment in stroke neurorehabilitation trials is strongly limited by restrictive study criteria and logistical barriers. More pragmatic and inclusive study designs may improve recruitment efficiency and better reflect real-world stroke populations.

Background: Stroke remains a leading cause of death and disability worldwide. Matrix metalloproteinases (MMPs), particularly MMP-9 and MMP-12, contribute to early blood-brain barrier (BBB) disruption, neuroinflammation, haemorrhagic transformation, and intracerebral haemorrhage (ICH). Intravenous thrombolysis is the only widely used pharmacological therapy for acute ischaemic stroke, but its utility is limited by narrow eligibility criteria and haemorrhagic risk. Inhibition of MMPs in the acute phase may offer a complementary neurovascular protective strategy. Methods: AZD1236, a selective dual MMP-9/-12 inhibitor, was evaluated in transient and permanent middle cerebral artery occlusion models and in a collagenase-induced ICH model in young, aged, obese, and female mice. Drug or vehicle was administered 2-6 hours after stroke onset. Outcomes included infarct or haematoma volume, BBB integrity, neurological function, and pain-related behaviours. Results: AZD1236 given within 2-4 hours after ischaemic or haemorrhagic insult significantly reduced infarct and haematoma volumes, improved short- and long-term neurological scores, and preserved BBB integrity, whereas treatment at 6 hours was largely ineffective. AZD1236 also attenuated the development of post-stroke mechanical allodynia and thermal hyperalgesia. Mechanistically, treatment reduced MMP-9 and MMP-12 activity, increased tight junction protein expression, and dampened inflammatory responses. Conclusions: Dual inhibition of MMP-9/-12 with AZD1236 confers robust neurovascular protection and mitigates post-stroke pain across clinically relevant models of ischaemic and haemorrhagic stroke. These findings provide a strong preclinical rationale for clinical evaluation of dual MMP-9/12 inhibition as an adjunctive neuroprotective strategy for acute stroke.

Background: Chronic knee pain, primarily due to knee osteoarthritis, significantly impairs quality of life of the elderly by restricting mobility, reducing physical activity, and contributing to psychological distress such as depression and anxiety. The standard of care include pharmacological treatments (e.g., NSAIDs, analgesics), physical therapy, lifestyle modifications, and, in severe cases, surgical interventions, most of which often do not provide sustained relief, may carry adverse effects, and lead to poly-pharmacy, particularly in elderly patients with comorbidities. Ashwagandha is known to have Balya (strengthening) and Rasayana (adaptogenic/ rejuvenating) properties, pacifies Vata and thus may be helpful in mitigating chronic musculoskeletal pain. Objective: To evaluate the efficacy of oral Ashwagandha & Til Taila Abhyanga for six weeks on chronic knee pain, functionality, mobility, quality of life, general wellbeing, sleep quality of the older adults with knee osteoarthritis. Materials & Methods: Patients of any gender, above 60 years age and having pain in one or both knee joints since more than 3 months and average severity rated [&ge;]4 on the Wong-Baker Faces, due to knee osteoarthritis diagnosed as per the American College of Rheumatology Criteria are being included in the study. Medically unstable and non-ambulatory patients with severity Grade>4 of Kellgren and Lawrence scale for OA, BMI[&ge;]30 kg/m2, those on recent treatment with intra-articular injections or Ayurveda medications, having knee implant or fixed flexion deformity in knees, history of acute trauma, or with severe systemic/infectious ailments or other chronic conditions affecting the knee joint are excluded. Total 72 participants are enrolled and allocated randomly to either group. Participants are given either Ahwagandha Churna or Boswellia extract as oral medication for 45 days. Til Taila and standard operating procedure of Abhyanga (external oleation through massage) at the affected knee are given in both groups. The severity of pain is assessed by the numeric pain rating scale after every 15 days. Other outcomes are change in Knee Injury and Osteoarthritis Outcome Score, score of WHO Wellbeing Index -5, Global Sleep Assessment Questionnaire, Five Times Sit and Stand test and Time to Up and Go, after the intervention period. The need for conventional analgesics through the study duration is also observed and will be compared in both groups. Discussion: The outcomes of this double-blind randomized controlled trial will inform about the efficacy of Ashwagandha which is generally considered as Balya in alleviating chronic pain of knee osteoarthritis among elderly. This study can generate evidence and lead to larger effectiveness studies on role of adding Ashwagandha to the standard care for management of chronic musculoskeletal pain in older adults.

Abstract Background: Disability prediction in elderly with cardiometabolic multimorbidity (CMM) is limited. We developed a dynamic nomogram and addressed three questions: predictive value of routine blood markers, depression vs. physical function, and plateau in CMM count.Methods: Using CHARLS data (46 predictors), disability defined as ADL/IADL impairment or self-report. LASSO and logistic regression built the nomogram, with mediation, RCS, trend tests, machine learning, and SHAP.Results: Six predictors (depression, cognition, stroke, CMM number, age, falls) formed a good-performing nomogram (https://xjbsashjtdx.shinyapps.io/DynamicNomogram/). Left-hand grip strength mediated 12.3% of strokes effect. Cognition showed an inverted U-shape (inflection point=12.043). CMM count plateaued after 3 diseases. Depression outranked grip strength and walking speed. SHAP identified HbA1c, creatinine, uric acid, hematocrit, fasting glucose, TyG, and CVAI as risk markers.Conclusions: The nomogram enables personalized risk stratification. Routine blood markers predict disability, depression dominates over physical function, and the CMM-disability relationship plateaus at CMM[&ge;]3.

INTRODUCTION Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are autoimmune diseases of the neuromuscular junction resulting in fatigable muscle weakness. Rituximab (RTX) is used to treat patients refractory to standard immunosuppression, but evidence for its efficacy remains inconsistent. Here, we analyzed real-world data on the clinical course and side effects of RTX in MG and LEMS patients. METHODS This was a single-center study of all patients diagnosed with MG (n=64) or LEMS (n=5) treated with RTX from 2011 until 2021. Outcomes of RTX treatment were recorded retrospectively with Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS), number of rescue therapies, myasthenic crises, and steroid dose at 1-year and 2-year follow-ups. RESULTS MGFA-PIS improved at both 1-year (y) and 2-y follow-up compared with baseline. Incidence rates of rescue therapies per 100 person-months (95% CI) decreased from 15.0 (11.8-18.8) at baseline to 7.5 (4.7-12.3) at 1-y and 4.3 (2.5-7.8) at 2y-follow-up. The number of patients without myasthenic crises within one year increased from baseline (49, 86.0%) to 1y-follow-up (55, 96.5%). Median (IQR) daily steroid dose decreased from 10 (5-22.5) mg/d at baseline to 4 (0-10) mg/d at 1y-follow-up, and to 2.5 (0-10) mg/d at 2y-follow-up. CONCLUSION This study indicates that RTX was associated with a stabilized clinical course and decreased steroid use in patients with autoimmune myasthenic syndromes, including those with thymoma-associated MG. Our data suggest that therapeutic benefit is apparent within the first year of treatment and is maintained through two years.

Background: Gait impairment is common among people with multiple sclerosis (PwMS) and is an important marker of disease progression. However, gait assessments typically require in-person evaluations. Objective: To describe the pose-estimation-based method for estimating spatiotemporal gait parameters from a single consumer-grade video, and evaluate the feasibility of home video collection by PwMS. Methods: In a single-center longitudinal digital phenotyping study, ambulatory adults with MS completed a standardized walking task recorded in the frontal plane. Pose estimation (MediaPipe Pose, Ultralytics) and custom scripts were used to estimate gait parameters from videos. Participants were invited to record walking videos at home using personal devices. Adoption and technical feasibility were evaluated across two home video data acquisition phases, with iterative protocol refinements. Results: The in-clinic study included 132 participants; 55 contributed home videos. In Phase I, while home video adoption was low (45% [30/66]), 87% [26/30] uploaded [&ge;]1 video of sufficient quality for gait analysis. After protocol refinements, 100% [25/25] uploaded [&ge;]1 high-quality video. Overall, high-quality frontal-plane videos were obtained at similar rates at home (92% [97/105]) and in-clinic (91% [423/467]). Conclusions: Home walking videos can feasibly be collected by PwMS to estimate gait parameters, providing an accessible approach for remote gait monitoring.