Clinical and Translational Neuroscience

Non-organic (muscle) weakness (NOw) is proposed as a distinct pathological entity characterized by maladaptive neuroplasticity (learning) affecting motor control. Functional deficits are most directly revealed through the manual muscle testing (MMT) break test, which uniquely exposes a muscle’s ability to adapt to increasing external load, potentially serving as an index of motor control integrity. We advance the “muscle-motor-movement PTSD” (mPTSD) model in which learning during pain or stress (trauma) yields chronic avoidance (inhibition) of the associated muscles. In a second stage, compensatory synergies develop, overriding attempts at hypertrophy-oriented training. This non-systematic, integrative review synthesizes clinical reports, learning theories, motor control and pain literature, and objective tests of force and movement over time during MMT. Predictive processing and reinforcement learning offer complementary accounts of how hyper-precise priors and passive avoidance may maintain NOw beyond functional recovery. Unexplained muscle weakness is found in non-specific musculoskeletal disorders and functional motor disorder (functional weakness), but may also contribute to other conditions, such as kinesiophobia. Effective alternative treatments for NOw may act by updating or erasing maladaptive motor learning by disrupting memory reconsolidation, allowing immediate restoration of function. Analogous to psychoneuroimmunology’s role in immune function, we propose “psychoneurokinesiology”, the study of how maladaptive learning affects movement. Full article

Mild traumatic brain injury (mTBI) in adults is extremely common worldwide, but only a small fraction of these patients harbor clinically significant intracranial injuries. Computed tomography (CT) of the head is the standard diagnostic tool to detect traumatic brain hemorrhages or lesions, yet indiscriminate CT scanning of all mTBI patients is inefficient, costly, and exposes patients to ionizing radiation. To optimize patient care, numerous clinical decision rules and guidelines have been developed internationally to identify which adult patients with mTBI should undergo head CT. This review provides a global perspective on the indications for head CT in adult mTBI, comparing key decision rules including the Canadian CT Head Rule, New Orleans Criteria, UK NICE Head Injury Guidelines, and others. Methods: We conducted a comprehensive analysis of major international guidelines and decision rules for head CT in adult mTBI, focusing on their inclusion criteria, risk factors, and diagnostic performance. Results: All the examined rules prioritize near-100% sensitivity for identifying patients who need neurosurgical intervention, but they differ greatly in specificity and recommended CT utilization rates. North American rules such as the New Orleans Criteria tend to favor higher sensitivity, scanning almost all patients with any symptom, whereas the Canadian CT Head Rule and certain European guidelines (NICE, Scandinavian) are more selective, significantly reducing CT usage while maintaining safety. Discussion: We discuss how these variations reflect different healthcare settings and risk tolerances, and we examine the implications for neurosurgical practice. We also highlight challenges in guideline implementation, the impact on global CT utilization, and emerging approaches (such as biomarker-assisted triage) that may further refine decision-making. In conclusion, appropriate use of clinical decision rules for head CT in mTBI can safely minimize unnecessary imaging, but local adaptation and clinician judgment remain crucial to ensure that no significant injuries are missed while avoiding over-scanning. Full article

Electroencephalogram (EEG) methods for the diagnosis of Benign Epilepsy with Centrotemporal Spikes (BECTS) are reviewed. The focus is on procedures reported for EEG analysis and diagnosis in BECTS, since some recent and potential applications of artificial intelligence (AI) aim to enhance the diagnostic accuracy and time reduction process, thereby moving a step closer to advancing our knowledge of the electrical nuclei sources and dynamics of energy distribution through the scalp in patients with epilepsy. The advantages of AI classification techniques have an increasing publication rate in the specialist literature, with no clear agreement on methodology. Hence, a better understanding of the procedures, arguments, and achievements is needed. To achieve this goal, (1) we review the background knowledge of the clinical characteristics of BECTS, (2) we analyze the results and advantages of computational processing methods for source and connectivity analyses of EEG in BECTS, and finally, (3) we explore the AI methods published in specialized journals for BECTS analysis. In conclusion, we argue in favor of the combined use of a priori information, which is the basis of the clinical visual analysis of EEG, as a potential feature to be included in AI methods for the classification of epileptiform graphoelements in EEG in BECTS diagnosis. Full article

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by both motor and non-motor symptoms. The home-based wearable sensor monitoring Parkinson’s KinetiGraph (PKG) evaluates clinical efficacy, caregiver satisfaction, and cost-effectiveness in the clinical management of Parkinson’s disease (PD) compared to prior usual standard care. Methods: We analyzed 50 patients with Parkinson’s disease, comparing baseline clinical outcomes, healthcare utilization, and caregiver burden without PKG to follow-up data after 12 months with PKG. We used IBM SPSS Statistics for the analysis. Statistical significance was set at p < 0.05 for hypothesis testing. We employed the Wilcoxon signed-rank test to evaluate differences between the two time points, while exploratory bivariate associations between caregiver burden (Zarit score) and various outcomes were examined using Spearman’s rank correlation. Results: Over a 12-month period following the implementation of PKG-guided care, significant improvements were observed in various clinical, functional, and economic areas for the patients. Key findings include the following: motor function improved, with UPDRS Part III scores showing a 20% median reduction (from 25 to 20); medication adjustments decreased by 40% (from 5 to 3); outpatient visits were reduced by 60% (from 5 to 2); hospital admissions decreased by 100% (from 1 to 0); caregiver burden, as measured using the Zarit caregiver burden score, declined by 37.5% (from 48 to 30); and total direct medical costs decreased by 17.9% (from AED 261,800 to AED 215,000). Conclusions: These findings indicate substantial reductions in healthcare utilization, costs, and caregiver burden following the integration of PKG monitoring into clinical practice. Full article

The National Institutes of Health (NIH) Toolbox cognition battery and Trail Making Tests (TMT) are widely used to quantify cognitive aging and to detect early cognitive vulnerability in Alzheimer’s disease and related conditions. However, these tests are often treated as interchangeable markers of global cognition, despite likely differences in their dependence on specific brain systems, limiting interpretability across studies and clinical contexts. To address this gap, we examined associations between four commonly used cognitive measures—fluid cognition, crystallized cognition, TMT-A, and TMT-B—and multimodal MRI metrics in 725 healthy volunteers aged 36 to 100 years from the Human Connectome Project–Aging. Voxel-wise diffusion MRI and vertex-wise cortical thickness and volume analyses were adjusted for age, sex, and years of education. Higher crystallized and fluid cognition scores and faster TMT-A/B completion times were generally associated with greater white matter integrity. TMT-B showed the most extensive diffusion and cortical associations, involving major projection, commissural, and association pathways and frontoparietal and temporo-occipital cortices. TMT-A and crystallized cognition demonstrated intermediate, overlapping patterns, whereas fluid cognition showed only focal brainstem and limited cortical correlates. These findings demonstrate systematic differences in the neuroanatomical substrates underlying commonly used cognitive tests and provide normative structure–cognition reference maps that can improve test selection, mechanistic interpretation, and sensitivity to brain health in studies of aging, vascular risk, and preclinical neurodegenerative disease. Full article

Background: Recent studies have highlighted the significant impact of combined thermal and lighting conditions on human comfort. However, there is limited understanding of how these factors influence cognitive performance in older adults. This study explored the effects of complex thermal and lighting conditions on various cognitive functions and physiological responses in older adults. Additionally, a predictive cognitive model was developed using physiological indicators as well as demographic factors. Methods: Twenty-two older adults participated in a within-subject design experiment under different thermal and lighting combinations. The study focused on two temperature conditions, 18 °C and 28 °C, and two lighting conditions, 480 nm with 5500 K and 644 nm with 3200 K. Conclusions: The finding showed that males significantly performed better at 18 °C under 480 nm lighting, while females excelled at 28 °C under 644 nm lighting. Electrodermal activity (EDA) increased in warmer conditions with warmer lighting, and pupil size expanded similarly but decreased under cooler conditions. Males’ EDA was negatively correlated with cognitive performance, while females’ pupil size and BMI were positively correlated. Using the classification and regression tree (CART) algorithm, predictive model demonstrated 89.7% accuracy. These findings emphasize the potential of optimizing thermal and lighting conditions to enhance cognitive functions and predict performance in older adults Full article

Background: The management of asymptomatic lumbosacral lipomas remains controversial, with studies reporting both prophylactic surgery and conservative management. This review compares conservative and surgical treatment approaches for asymptomatic lumbosacral lipomas in children, analyzing outcomes, complications and secondary treatment. Methods: A systematic literature review was conducted using PubMed, Cochrane, and Web of Science databases. Data were extracted and analyzed based on demographic characteristics, lipoma classification, treatment modality, complications and secondary treatment. Results: A total of 22 retrospective studies comprising 1215 patients were included. The mean age was 1.87 years, with a 1.12:1 female-to-male ratio. Dorsal lipomas were the most common subtype (31.6%). At first, a total of 1017 (83.7%) patients underwent surgery, whereas 198 (16.3%) patients had conservative management. Total resection was achieved in 422 (41.9%) patients, whereas subtotal resection and partial resections were performed in 261 (25.9%) and in 334 (33.29%) patients, respectively. Neurological worsening occurred in 17.2% of patients treated conservatively at first diagnosis, with urological dysfunction being the most common symptoms reported (15.2%), followed by neurological deficit to the lower limbs (12.6). Conservative management following prior surgical intervention was performed in 2.6% of cases. A favorable outcome was observed in 88.7% of patients following surgical resection and in 81.8% of patients who were not treated surgically. Conclusion: While surgical intervention is associated with operative risk, it provides a lower risk of long-term neurological deterioration compared to conservative management. The decision to operate should be individualized, considering patient age, anatomical complexity and based on risk of progression. Full article

Objective: Alzheimer’s disease (AD) and other forms of dementia are a heterogeneous group of neurodegenerative diseases characterized by progressive cognitive decline. Differential diagnosis between AD and other dementias is crucial for choosing the optimal treatment strategy. Currently, cerebrospinal fluid (CSF) analysis remains the most accurate diagnostic method, but its invasiveness limits its use. In this regard, the search for reliable biomarkers in the blood is an urgent task. Methods: The study included 31 dementia patients (23 women and 8 men) diagnosed via interdisciplinary consultations and neuropsychological testing (MMSE ≤ 24). CSF and blood plasma samples were collected and analyzed using Luminex technology. Biomarker concentrations were measured, and statistical analyses (ANOVA, Kruskal–Wallis, and Pearson correlation) were performed to compare groups and assess correlations. Results: Levels of Aβ40 and Aβ42 in CSF were significantly lower in patients with AD compared with non-AD dementia (p = 0.02 and p < 0.001, respectively). The Aβ42/40 ratio in CSF was higher in patients with non-AD dementia (p = 0.048). The concentration of Aβ42 in blood plasma was increased in patients with AD (p = 0.001). Positive correlations were found between Aβ42 in CSF and TDP-43 in plasma in non-AD dementia (r = 0.97, p < 0.001), as well as between neurogranin and TDP-43 in plasma in AD (r = 0.845, p < 0.001). Conclusions: The study demonstrates the potential of blood biomarkers, in particular Aβ42, for the differential diagnosis of AD and other forms of dementia. The discovered correlations between CSF and plasma biomarkers deepen the understanding of neurodegenerative processes and contribute to the development of noninvasive diagnostic methods. Full article

Down Syndrome Regression Disorder (DSRD) is a rare but severe neuropsychiatric condition characterized by abrupt loss of speech, autonomy, and cognitive abilities in individuals with Down syndrome, often associated with immune dysregulation and gut–brain axis dysfunction. We report the case of an 11-year-old girl with Down syndrome who developed developmental regression at age five, in temporal proximity to a family transition (the birth of a younger sibling), with loss of continence, language, and comprehension, alongside persistent behavioral agitation and gastrointestinal symptoms. Laboratory assessment revealed Giardia duodenalis infection, elevated fecal calprotectin and secretory IgA, and microbial imbalance with overgrowth of Streptococcus anginosus and S. sobrinus. The patient received a single oral dose of tinidazole (2 g), daily folinic acid (1 mg/kg), and a 90-day course of transcranial and abdominal photobiomodulation (PBM) (1064 nm, 10 min per site). Post-treatment, stool analysis showed normalized inflammation markers and restoration of beneficial bacterial genera (Bacteroides, Bifidobacterium, Lactobacillus) with absence of Enterococcus growth. Behaviorally, she exhibited marked recovery: CARS-2-QPC decreased from 106 to 91, ABC from 63 to 31, and ATEC from 62 to 57, alongside regained continence, speech, and fine-motor coordination. These outcomes suggest that abdominal and transcranial PBM, by modulating mitochondrial metabolism, mucosal immunity, and microbiota composition, may facilitate systemic and neurobehavioral recovery in DSRD. This translational case supports further investigation of PBM as a non-invasive, multimodal therapy for neuroimmune regression in genetic and developmental disorders including validation through future randomized controlled clinical trials. Full article

The high attrition rates in glioblastoma (GB) therapeutic development stem largely from preclinical models that fail to adequately recapitulate the dynamic tumor–host ecosystem. Unlike previous reviews that characterize glioma cell lines in isolation, this article integrates tumor biology with the distinct neuro-immune–endocrine landscapes of major laboratory rat strains. We critically evaluate standard rat malignant glioma cell lines (C6, F98, RG2, 9L) alongside transplantable tissue models (GB 101.8, GB 15/47), which offer enhanced translational relevance, demonstrating that the predictive value of any model is contingent upon the specific “glioma model and host strain” pairing and the individual physiological characteristics of the host. We provide evidence that strain-specific hypothalamic–pituitary–adrenal (HPA) axis reactivity (e.g., hyper-reactive Fischer 344 versus normo-reactive Wistar) acts as a decisive, yet often overlooked, modulator of the tumor microenvironment and therapeutic response. The review delineates the utility and limitations of these models, specifically addressing the MHC incompatibilities of the widely used C6 model in immunotherapy research, while contrasting it with the immune-evasive phenotypes of RG2 and the GB 101.8 tissue model. Furthermore, we highlight the superiority of tissue transplants in preserving cellular polyclonality and diffuse infiltration patterns compared to the circumscribed growth often observed in cell line-derived tumors. Consequently, we propose a strategic selection paradigm wherein immunogenic models serve as bioindicators of host immunocompetence, while invasive, non-immunogenic systems (F98, RG2, and GB 101.8) are utilized to investigate therapeutic resistance and systemic host-tumor interactions. Full article

Considering the prevalence of migraine and its impact on everyday living, its evolutionary persistence remains puzzling. This essay reviews recent literature and conceptual perspectives that frame migraine attacks as a possible side-effect of prolonged stress and unmet needs. To illustrate this, the article compares the antithetical relationship of triggers and migraine symptoms: During the early phase of the attack, many eat, drink, rest and sleep more and tolerate less nuisance compared to the hours and days before; previously, however, there was too little time to eat, drink, rest, and sleep, and the nuisance had to be tolerated. A relevant characteristic of many migraineurs is that they are prone to stress, e.g., because of a character trait, an impaired adaptation to stress, the lack of habituation to sensory stimuli, and disturbances of the energy supply. In that way, the appearance of the attack during fading stress makes sense: the body seizes the opportunity and communicates its needs when circumstances permit. In this context, the concept of pain as an imperative—a signal designed to enforce behavioural change—provides an insightful framework. Understanding migraine in this way may help reframe its pathophysiology and its clinical and translational significance. Full article

Brain Health has become a global public health priority, driven mainly by the rapid aging of populations and the increasing burden of neurological and psychiatric disorders. This report presents the first activities of the Bern Brain Health Working Group, established to implement the Swiss Brain Health Plan (SBHP), published in 2023. The aim is to describe the development and initial outcomes of regional initiatives promoting Brain Health in Switzerland. Specifically, we outline the structure and objectives of the Bern Brain Health Consultation, the development process and conceptual framework of the Swiss Brain Health Questionnaire, and additional educational and research activities supporting the SBHP. By summarizing these first steps, this report provides a model for regional implementation of a national Brain Health strategy and contributes to building a foundation for broader national and international Brain Health efforts. Full article

Working memory training (WMT) has promising effects on cognitive and clinical outcomes in children with attention deficit hyperactivity disorder (ADHD). However, few studies have explored the effectiveness of such programs in developing countries with different populations and sociocultural backgrounds. This study aimed to pilot Cogmed WMT (CWMT) and examine its impact on clinical and cognitive outcomes in children diagnosed with ADHD in Saudi Arabia. We assessed 34 children with ADHD assigned to either a CWMT or standard-of-care group. Both groups were evaluated at baseline and five weeks for ADHD symptoms and cognitive function, including working memory (WM), sustained attention, and impulsivity. Compared with the baseline and the control group, the intervention group demonstrated improved parent ratings of ADHD clinical symptoms and cognitive function scores, including WM, sustained attention, and impulsivity. CWMT improved cognitive and clinical measures in our sample of Saudi children with ADHD and is a promising non-pharmacological therapy for treating children with ADHD in developing countries. Full article

Background: Traumatic Brain Injury (TBI) represents a growing cause of medical emergencies globally. Objective: This study evaluates whether healthcare outcomes for TBI patients differ between daytime and on-call (after-hours) admissions. Methods: A retrospective analysis was conducted using data from a hospital database spanning January 2015 to December 2019. Of the 670 cases reviewed, 45 patients over the age of 65 were admitted with head trauma. Data were analyzed using SPSS. Results: Surgical interventions were significantly less frequent during on-call hours. Admission type (elective vs. emergent) showed a statistically significant difference (p < 0.05). Postoperative ICU length of stay (LOS) was markedly longer for on-call admissions (p = 0.002). Due to a controlled sample size, p-value interpretations would need some discretion. TBI patients admitted during on-call hours had a 9.9-fold increase in ICU stay, a 2.5-fold increase in total hospital LOS, and a 475% higher complication rate compared to daytime admissions. Complication rates were 20% for daytime admissions versus 92% for on-call admissions. Furthermore, patients treated during on-call hours were 11 times more likely to be discharged in an unconscious state (GCS < 8). Conclusions: TBI outcomes are significantly worse during on-call hours. Enhancing imaging availability and staffing during these periods may help improve patient outcomes. Full article

Background: Severe traumatic brain injury (TBI) often leads to elevated intracranial pressure (ICP) that requires aggressive management. Inducing burst suppression with deep sedation is an established therapy for refractory intracranial hypertension. Traditionally, barbiturate coma has been used to achieve burst-suppression EEG in TBI patients, but alternative sedative agents (propofol, midazolam, ketamine, dexmedetomidine) are increasingly utilized in modern neurocritical care. This review compares barbiturates with these alternatives for inducing burst suppression in adult TBI, focusing on protocols, mechanisms, efficacy in controlling ICP, safety profiles, and impacts on neurological outcomes. Methods: A search of the literature was performed, including clinical trials, observational studies, and guidelines on deep sedation for ICP control in adult TBI. Studies comparing high-dose barbiturates to other sedatives (propofol, midazolam, ketamine, dexmedetomidine) in the context of burst suppression or severe TBI management were included. Data on sedative protocols (dosing and EEG targets), mechanisms of action, ICP-lowering efficacy, complications, and patient outcomes were extracted and analyzed qualitatively. Results: High-dose barbiturates (e.g., pentobarbital or thiopental) and propofol are both effective at inducing burst-suppression EEG and reducing ICP via cerebral metabolic suppression. Barbiturate coma remains a third-tier intervention reserved for ICP refractory to other treatments. Propofol infusion has become first-line for routine ICP control due to rapid titratability and shorter half-life, though it can also achieve burst suppression at high doses. Midazolam infusions provide sedation and seizure prophylaxis but yield less metabolic suppression and ICP reduction compared to barbiturates or propofol, and are associated with longer ventilation duration and delirium. Ketamine, once avoided for fear of raising ICP, has shown neutral or lowering effects on ICP when used in ventilated TBI patients, thanks to its analgesic properties and maintenance of blood pressure; however, ketamine alone does not reliably produce burst-suppression patterns. Dexmedetomidine offers sedative and anti-delirium benefits with minimal respiratory depression, but it is generally insufficient for deep burst-suppressive sedation and has only a modest effect on ICP. In comparative clinical evidence, propofol and barbiturates both effectively lower ICP, but neither has demonstrated clear improvement in long-term neurological outcome when used prophylactically. Early routine use of barbiturate coma may increase complications (hypotension, immunosuppression), and thus, current practice restricts it to refractory cases. Modern sedation protocols emphasize using the minimal necessary sedation to maintain ICP < 22 mmHg, with continuous EEG monitoring to titrate therapy to a burst-suppression target (commonly 2–5 bursts per minute) when deep coma is employed. Conclusions: In adult TBI patients with intracranial hypertension, propofol-based sedation is favored for first-line ICP control and can achieve burst suppression if needed, whereas high-dose barbiturates are reserved for ICP crises unresponsive to standard measures. Compared to barbiturates, alternative agents (propofol, midazolam, ketamine, dexmedetomidine) offer differing advantages: propofol provides potent, fast-acting metabolic suppression; midazolam adds anticonvulsant sedation for prolonged use at the cost of slower wake-up; ketamine supports hemodynamics and analgesia; dexmedetomidine aids lighter sedation and delirium control. The choice of agent is guided by the clinical scenario, balancing ICP reduction needs against side effect profiles. While all sedatives can transiently reduce ICP, careful monitoring and a tiered therapy approach are essential, as no sedative has conclusively improved long-term neurological outcomes in TBI. EEG monitoring for burst suppression and meticulous titration is required when employing barbiturate or propofol coma. Ongoing research into optimal combinations and protocols may further refine sedation strategies to improve safety and outcomes in severe TBI. Full article

Background and Objectives: The mechanisms of traumatic brain injury (TBI), patient characteristics, and long-term outcomes in elderly patients differ from those in other age groups. This study aims to evaluate the effectiveness of the Elderly Traumatic Brain Injury (eTBI) Scoring System, recently described in the literature, in predicting mortality, prognosis, and surgical indication. Materials and Methods: Patients diagnosed with TBI over the age of 65 between January 2017 and December 2024 were retrospectively analyzed, and their eTBI scores were calculated. Statistical analyses were conducted to assess mortality, prognosis, and surgical indication or benefit from surgery across low-, medium-, and high-risk groups. Results: In this cohort of 236 patients, the mortality rate was higher in the high-risk group according to the eTBI scoring system, compared to the medium- and low-risk groups. However, the scoring system does not appear to be effective in determining surgical indications. While the medium-risk group was most predictive of mortality, the low-risk group demonstrated better accuracy in predicting prognosis. Conclusions: The eTBI scoring system appears to be an effective tool for assessing mortality risk and predicting prognosis in specific subgroups of elderly TBI patients. Full article

Neuroradiology and neuro-oncology are rapidly emerging fields in the diagnosis and treatment of central nervous system (CNS) diseases, including brain tumors. This review presents a comprehensive look at the current imaging techniques, clinical applications, and therapeutic strategies, with a focus on gliomas, metastases, and functional brain mapping. Conventional modalities such as CT and MRI, as well as sophisticated approaches including functional MRI (fMRI), diffusion tensor imaging (DTI), MR spectroscopy, PET, and hybrid techniques, are discussed. On the therapeutic front, high-precision radiotherapy modalities such as stereotactic radiosurgery (SRS), stereotactic radiotherapy (SRT), and proton therapy are discussed, with a focus on radiation biology, dose planning, and the impact on neurocognitive outcomes. The interlink between neuroradiology and radiotherapy is highlighted through advanced image-guided treatment planning. Full article

Background: Neurorehabilitation plays a central role in restoring and maintaining brain health across lifespan. However, its contribution is often underestimated in public health policies. Aim: This paper aims to highlight the importance of neurorehabilitation within the brain health frameworks, advocating for its full integration into global and national health strategies. Main content: We discuss the unique characteristics of neurorehabilitation, including its interdisciplinary structure, long-term scope and role in prevention. We underline how the ICF model provides a bridge between clinical practice and public health policy. Key prevention strategies and the potential of digital technologies are also examined. Conclusion: A stronger integration of neurorehabilitation into brain health policy can yield individual and socio-economic benefits. We call for strategic political and structural efforts to expand its availability and recognition. Full article

Background: Deep vein thrombosis (DVT) is a serious thromboinflammatory complication of acute ischemic stroke (AIS). The true incidence, mechanistic risk factors, and optimal prophylactic strategies remain uncertain, particularly in the era of reperfusion therapy. Methods: This systematic review and meta-analysis (IRIS-DVT) searched PubMed, Embase, Cochrane, Scopus, and Web of Science for studies reporting DVT incidence, risk factors, or prophylaxis in AIS (2004–2025). Random-effects models were used to generate pooled prevalence and effect estimates, and the certainty of evidence was graded using the GRADE framework. Results: Forty-two studies (n = 6,051,729 patients) were included. The pooled prevalence of DVT was 7% (95% CI, 6–9%), approximately seventy-fold higher than in the general population, with wide heterogeneity influenced by screening timing and diagnostic modality. Pathophysiological risk factors included higher stroke severity (NIHSS; SMD 0.41; 95% CI, 0.38–0.43), older age (SMD 0.32; 95% CI, 0.18–0.46), elevated D-dimer (SMD 0.55; 95% CI, 0.38–0.72), female sex (OR 1.33; 95% CI, 1.19–1.50), and malignancy (OR 2.69; 95% CI, 1.56–5.22), supported by moderate-certainty evidence. Respiratory infection and admission hyperglycemia showed weaker, low-certainty associations. Traditional vascular risk factors (hypertension, diabetes, atrial fibrillation, dyslipidemia) were not significantly related to DVT risk. Evidence for prophylaxis with low-molecular-weight heparin, direct oral anticoagulants, or intermittent pneumatic compression was limited and graded very low certainty. Conclusions: DVT complicates approximately one in fourteen AIS cases, reflecting a distinct thromboinflammatory process driven more by acute neurological severity, systemic hypercoagulability, and malignancy than by conventional vascular risk factors. Early systematic screening (≤72 h) and consistent use of mechanical prophylaxis are warranted. Dedicated AIS-specific mechanistic and interventional trials are urgently needed to refine prevention strategies and improve post-stroke outcomes. Full article