Rehabilitation in LMICs is more important than in HICs due to the lack of access to acute stroke interventions (thrombolysis, endovascular thrombectomy, and stroke unit care) in most treated patients which leads to worse long-term outcomes, and thereby greater disability and functional impairment, therefore requiring specialized rehabilitation. The are barriers to rehabilitation in LMICs. These can be considered under healthcare- and patient-related factors. Healthcare factors include limited skilled rehabilitation specialists, negligible stroke unit care, lack of government policies, insurance for rehabilitation and adequate infrastructure for rehabilitation. Patient-related factors include lack of awareness about the benefits of rehabilitation, financial constraints and belief in alternate systems of care. The barriers to rehabilitation in LMICs can be overcome with LMIC specific solutions like community-based rehabilitation, task shifting, stroke unit care, telerehabilitation, offering integrated models of care and increased recruitment and training of rehabilitation professionals.
Traumatic brain injury (TBI) is still a leading cause of death and disability worldwide, with a disproportionate burden in low- and middle-income countries (LMICs) where access to imaging, invasive intracranial pressure (ICP) monitoring, and neurosurgical care is limited. This review examines recent advances in TBI management in austere environments, where standard high-resource paradigms are frequently impractical, and analyzes the quality of evidence supporting context-adapted approaches. Recent literature highlights the growing role of protocolized care pathways, noninvasive neuromonitoring adjuncts such as optic nerve sheath diameter ultrasonography, quantitative pupillometry, transcranial Doppler, and selected serum biomarkers, as well as alternative surgical strategies including hinge craniectomy. Emerging physiological frameworks, including stage-based models of intracranial decompensation, offer structured decision-making support when numeric ICP thresholds are unavailable. However, most supporting evidence remains observational, heterogeneous, and frequently extrapolated from high-income settings, with major limitations in external validation and implementation science. Enhancing outcomes in austere TBI care will depend less on technological development than on rigorous implementation science, context-specific validation, and sustainable health system strengthening to bridge the gap between evidence and clinical delivery.
Computed tomography perfusion (CTP) has become an important tool for tissue-based assessment in acute ischemic stroke, particularly in patients considered for reperfusion therapy beyond conventional time windows. This review summarizes common pitfalls, diagnostic blind spots, and adjunctive uses of CTP. Although CTP supports patient selection for endovascular thrombectomy in the extended window, automated core-penumbra estimates are vulnerable to technical and interpretive error. Major pitfalls include overestimation of ischemic core (ghost infarct core) and underestimation of core (perfusion scotoma). Negative automated maps do not exclude small deep infarcts or posterior circulation stroke, and perfusion abnormalities may also occur in stroke mimics. CTP should not be interpreted in isolation. Its greatest clinical value lies in integration with non-contrast CT, CT angiography, perfusion parameter maps, and clinical assessment.
This review synthesizes the mechanisms, applications, and evidence gaps regarding pulsed radiofrequency (PRF) in the rehabilitation of post-stroke complications to guide its standardized integration. PRF, a minimally invasive neuromodulation technique, modulates neuronal excitability without thermal damage. Emerging evidence highlights multi-target effects, including improved microcirculation, suppressed neuroinflammation, and regulated neurotrophic factors. Clinically, PRF effectively alleviates refractory post-stroke pain and may indirectly ameliorate post-stroke depression while facilitating motor recovery. Image-guided procedures targeting specific nerves demonstrate favorable safety profiles. Despite promising outcomes for stroke rehabilitation, current evidence relies primarily on small case series and preclinical studies. Significant gaps remain in standardized protocols and high-quality randomized controlled trials. Further validation of long-term efficacy and safety is essential to establish PRF’s definitive role in comprehensive post-stroke management.
PURPOSE OF REVIEW:To examine sex differences in Alzheimer's disease and cognition with a focus on hormonal transitions, biomarker trajectory, and implications for diagnosis and treatment. RECENT FINDINGS:Women account for nearly two-thirds of individuals with Alzheimer's disease and demonstrate important biological and clinical differences compared with men. APOE ε4 confers greater risk in women, while menopause, depression, chronic stress, adverse pregnancy outcomes, and metabolic dysfunction may further increase vulnerability. Biomarker studies suggest that amyloid trajectories are broadly similar between sexes, but women exhibit earlier or greater tau accumulation once amyloid pathology is present. Women may maintain verbal memory performance longer than men despite underlying pathology, potentially delaying diagnosis. Emerging plasma biomarkers, particularly p-tau217, may improve early detection, monitoring, and treatment. Alzheimer's disease in women reflects a complex interaction between sex-specific biology, hormonal transitions, psychosocial factors, and neurodegenerative processes. Recognizing these differences has important implications for cognitive assessment, biomarker interpretation, diagnosis, and application of disease-modifying therapies.
Menopause is a neuroendocrine process with important implications for neurological health. This review examines the complex, multidirectional relationships between menopause and major central nervous system conditions, including stroke, migraine, epilepsy, multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. Menopause may mark an inflection point for vascular injury, neurodegeneration, and disability accumulation in several neurological conditions. Perimenopausal hormonal fluctuations may exacerbate migraines and seizures in susceptible women. Research increasingly supports the critical window hypothesis for estrogen therapy and highlights the importance of distinguishing reproductive and chronological aging when interpreting neurologic trajectories. Menopause represents an important transition for many conditions. Hormone therapy has heterogenous effects with cognitive benefit in premature ovarian insufficiency, harm related to stroke risk in older women, and greater uncertainty in other conditions. Therefore, individualized risk-benefit assessment is essential. Research gaps remain significant, and menopause should be a priority area for neurologic research.
This review examines challenges in post-stroke dysphagia management, including access to swallowing imaging, enteral feeding decisions, and barriers to reassessment and rehabilitation. It evaluates how healthcare systems and practice patterns influence swallowing outcomes and stroke recovery. Recent literature emphasizes that post-stroke dysphagia is a dynamic condition requiring longitudinal management rather than a temporary acute complication. Evidence supports validated dysphagia screening followed by clinical swallowing evaluation and swallowing imaging for accurate diagnosis and treatment planning. Studies highlight variability in gastrostomy tube practices, post-acute access to swallowing imaging, continuity of care, and the psychosocial burden of oral restriction and feeding decisions after stroke. Dysphagia management systems remain fragmented, contributing to inconsistent diagnosis, reassessment, access to intervention, and prolonged unnecessary oral intake restrictions. Future efforts should prioritize rehabilitation pathways that support recovery-oriented dysphagia management.
To examine sex differences in Alzheimer’s disease and cognition with a focus on hormonal transitions, biomarker trajectory, and implications for diagnosis and treatment. Women account for nearly two-thirds of individuals with Alzheimer’s disease and demonstrate important biological and clinical differences compared with men. APOE ε4 confers greater risk in women, while menopause, depression, chronic stress, adverse pregnancy outcomes, and metabolic dysfunction may further increase vulnerability. Biomarker studies suggest that amyloid trajectories are broadly similar between sexes, but women exhibit earlier or greater tau accumulation once amyloid pathology is present. Women may maintain verbal memory performance longer than men despite underlying pathology, potentially delaying diagnosis. Emerging plasma biomarkers, particularly p-tau217, may improve early detection, monitoring, and treatment. Alzheimer’s disease in women reflects a complex interaction between sex-specific biology, hormonal transitions, psychosocial factors, and neurodegenerative processes. Recognizing these differences has important implications for cognitive assessment, biomarker interpretation, diagnosis, and application of disease-modifying therapies.
To synthesize recent evidence on how environmental exposures influence stroke risk, with emphasis on air pollution, thermal stress, circadian and occupational disruption, built and social environments, and selected toxicants. Long-term and episodic air pollution, especially fine particulate matter with aerodynamic diameter ≤ 2.5 μm (PM₂.₅) and wildfire smoke, remain most consistently associated with stroke risk. Extreme heat combined with heat-humidity metrics is emerging as an important acute stroke trigger. Noise, artificial light at night, shift work, and long working hours show smaller but plausible associations, while greener and more walkable environments may be modestly protective. Social and structural disadvantage clusters, multiple exposures and inequities play an integrated role in risk and prevention. Environmental determinants are increasingly relevant to stroke risk. The strongest current links are realted to pollution, heat, sleep, and work disruption, as well as environmental inequity. Future research should move beyond single-exposure models toward combined-exposure as well as intervention-focused approaches.
Moderate to severe traumatic brain injury (TBI) requiring intensive care is associated with high morbidity, mortality and long-term disability. In addition to neurologic sequelae, TBI causes a systemic disease with associated injury to other organ systems, including the gastrointestinal (GI) tract. Here, we review the evidence that GI tract dysfunction occurs after TBI and discuss the clinical implications of GI tract dysfunction on the clinical care of TBI patients, including inadequate nutritional support, elevated risk of pneumonia, and a hyperactive inflammatory response. We highlight recent findings that highlight putative mechanisms through which GI tract pathology may arise after TBI, including vagal nerve and enteric nervous system dysfunction, gut microbiome dysbiosis, sympathetic hyperactivity and iatrogenic injury. Finally, we highlight future approaches to target the GI tract that could improve outcomes in this critically ill patient population. In summary, we review the evidence supporting a role for GI tract dysfunction in the pathophysiology of critically ill TBI patients and highlight potential mechanisms through which GI tract dysfunction may worsen outcomes in this population.
This narrative review synthesizes emerging evidence on experience-dependent myelin plasticity and its relevance for neurorehabilitation in persons with multiple sclerosis (MS). Building on foundational work demonstrating motor learning–induced neuroplasticity, we highlight growing recognition that myelination remains adaptable across the lifespan and may be harnessed to support motor relearning, neuroprotection, and remyelination in MS. Preclinical and human studies demonstrate that neuronal activity, especially that induced by motor learning, regulates oligodendrocyte behavior and myelin remodeling. Rodent models show that skilled training enhances oligodendrocyte precursor cell proliferation and myelin thickness, while human neuroimaging confirms training-related increases in myelin-sensitive metrics within task-relevant systems. In MS, early evidence from exercise and motor training studies suggests task-specific white matter plasticity, though sample sizes remain small and imaging outcomes heterogeneous. Additional work points to synergistic potential between behavioral training, neuromodulation, and pharmacologic remyelinating agents. Notably, the combination of exercise and clemastine produces robust remyelination in preclinical models. With MS patients now living longer, aging introduces additional vulnerabilities—including inflammation, microglial dysfunction, and reduced regenerative capacity—but myelin retains responsiveness to behavioral and environmental enrichment. Experience-dependent myelin plasticity represents a promising but underexplored mechanism for enhancing neurorehabilitation outcomes. Motor learning, physical exercise, and multimodal interventions may support adaptive myelination, though optimized dosing, timing, and biomarkers remain undefined. Future research should employ targeted, multimodal imaging approaches and integrate behavioral, neuromodulatory, and pharmacologic strategies, in addition to following patients longitudinally post-intervention, to clarify the therapeutic potential of activity-driven remyelination.
Chorea is a symptom of numerous pathophysiologically and clinically heterogeneous genetic conditions. A number of developments have been made in this field over the last years linked to improved genomic testing, large cohort collaborations and improved understanding of the molecular mechanisms. This review aims to provide an update on the new genetic conditions and phenotypes linked to chorea disorders, their modification factors and pathophysiological background. Several novel genetic conditions have been linked to chorea over the last 3 years, including mutations in FTH1, NAA60, ACBD6 or TOR1AIP2. Also, novel phenotypes have been established and linked to chorea, such as Adult-onset Neurodegeneration in Nucleotide Excision Repair Disorder (NERD-ND). Major advances have been made in understanding of the pathophysiological role of somatic instability in HD. Striatal pallidal neurons (SPNs) with 150–500 + CAG repeats seem to lose positive and then negative features of neuronal identity, de-repress senescence/apoptosis genes, ultimately leading to cell death. Improved recognition of the genetic background of chorea leads to more effective diagnostic processes, better prognostication and improved personalized treatment. The findings on somatic instability in HD suggest that neurodegeneration in HD is an asynchronous DNA process for >95
Cerebral noradrenergic activity modulates physiological functions of behaviour, cognition, movement, arousal and sleep. This review aims to provide an accurate summary of the current knowledge on the involvement of the noradrenergic system in Parkinson’s Disease (PD) and its clinical correlations based on neuroimaging studies. Studies in PD highlight neuromelanin MRI signal loss in the locus coeruleus (LC), and positron emission tomography shows noradrenergic denervation across subcortical and cortical areas. More severe phenotypes of PD, manifesting with cognitive decline, apathy, REM sleep behaviour disorder and autonomic dysfunction, are associated with more severe noradrenergic dysfunction. Conversely more preserved noradrenergic transmission is common in tremulous PD. Furthermore, noradrenergic dysfunction, is also involved in transient motor manifestations such as tremor and freezing of gait. Recent neuroimaging advances greatly expanded the knowledge about noradrenergic dysfunction pathophysiology in PD. However, pharmacological treatment of its several associated manifestations is still lacking and needs further investigation.
The main unmet need of Parkinson’s disease (PD) is the lack of a therapy able to slow progression. The field is shifting from syndromic diagnosis toward biologically anchored definitions and staging, enabling PD identification before motor onset. In this context, imaging biomarkers provide in vivo measures to identify subtypes, enrich cohorts, and track changes in disease-modifying trials. This review focuses on the role of monoaminergic imaging for preclinical intervention. Monoaminergic imaging captures both the core substrate of motor phenoconversion and extranigral mechanisms underlying early non-motor symptoms. Presynaptic dopaminergic imaging remains the most robust marker of conversion risk in prodromal cohorts, while noradrenergic and serotonergic imaging delineate early brainstem and limbic involvement. Peripheral autonomic imaging further extends biomarker coverage, with cardiac sympathetic imaging detecting early extracerebral denervation in prodromal stages. Together, harmonised monoaminergic imaging provides a unifying framework for staging and clinical trial readiness.
Functional movement disorder (FMD) is a biopsychosocially-complex condition with diverse neurologic, physical, and psychiatric manifestations. Converging neuroimaging evidence demonstrates abnormalities in networks supporting self-agency, attention, sensorimotor processing, multimodal integration, salience/threat detection, and interoception. This review summarizes recent work on the prognostic and therapeutic relevance of these findings. Baseline functional neuroimaging predictors of outcome implicate cingulo-insular, frontolimbic, and subcortical circuits involved in attention, emotion regulation, and salience processing. Clinical improvement has been associated with activity changes in frontal premotor and regulatory regions, as well as in paralimbic areas. Preliminary studies of transcranial magnetic stimulation, transcranial direct-current stimulation, and neurofeedback suggest that targeted modulation of dysfunctional networks may alleviate symptoms. Neuroimaging features in FMD may inform outcome prediction, elucidate treatment-response mechanisms, and guide neuromodulation strategies. However, the field remains early in development, and larger, longitudinal studies are needed to translate these insights into routine clinical care.
There is an increasing number of single case reports describing patients with findings compatible with thiamine deficiency, in whom rapid replacement of thiamine fails to induce improvement. Further work-up identifies positive aquaporin-4 antibodies (AQP-4) leading to a final diagnosis of neuromyelitis optica spectrum disorder (NMOSD). Occasionally, NMOSD is the initial diagnosis, but it turns out that the patient has thiamine deficiency. Similarly, these two diagnoses may overlap, particularly with area postrema lesions and in other cases of protracted vomiting. We reviewed the literature to attempt further clarification for this clinical overlap. The common denominator is the astrocyte, as cytotoxic edema due to impaired mitochondrial dysfunction and lactic acidosis in instances of thiamine deficiency causes downregulation of the AQP-4 receptor leading to vasogenic edema and breakdown of the blood-brain-barrier (BBB). Similar dysfunction of the AQP-4 receptor occurs because of IgG binding antibodies in NMOSD. Impaired glutamate transport in the astrocytic podocytes regardless of the AQP4 receptor etiologic mechanism causes excitotoxicity. Awareness of this clinical overlap is critical to initiate timely treatment in thiamine deficiency states and NMOSD
The McDonald criteria assist neurologists in making accurate and timely diagnoses of multiple sclerosis (MS). The 2024 revision of these criteria aims to enable a more timely diagnosis by including additional biomarkers and alternative diagnostic approaches. They also extend to individuals with MRI findings typical of multiple sclerosis that lack classic MS symptoms, as they would previously have been classified as having radiologically isolated syndrome (RIS). This review examines the scientific foundation of the novel biomarkers used and how the revised criteria influence individuals undergoing diagnostic evaluation, clinical practice, and society. Most research concentrates on the scientific foundation for the updates rather than their impact. Benefits and potential disadvantages of the revised criteria can be identified for individuals undergoing diagnostic evaluation, clinical practice, and society. Additional guidelines for real-life application to guide management decisions are advisable.
The goal of this narrative review is to provide a comprehensive analysis of Post-Traumatic Headache (PTH), addressing its epidemiology, pathophysiology, and multidisciplinary management. The paper seeks to explore the diagnostic controversies surrounding the timing of symptom onset and evaluates current assessment methods and treatment paradigms for this prevalent sequela of traumatic brain injury. Recent research highlights that while current diagnostic criteria require headache onset within seven days of injury, delayed-onset symptoms are common, creating a significant diagnostic dilemma. Pathophysiologically, PTH is understood to be multifaceted, driven by neuroinflammation, neurometabolic cascades, and central sensitization. These processes result in clinical phenotypes that often mirror primary migraine or tension-type headaches. Additionally, while clinical history remains the gold standard for assessment, emerging blood biomarkers are showing promise as objective tools for evaluation. The review concludes that PTH management currently requires a multimodal approach, combining non-pharmacological interventions with pharmacological treatments adapted from primary headache protocols. A major takeaway is the lack of high-quality, PTH-specific randomized controlled trials, which currently forces a reliance on expert opinion rather than robust clinical evidence. To improve patient outcomes, future research must shift toward a more multi-disciplinary, patient-centered paradigm and focus on generating high-quality data to move beyond diagnostic controversies and empiric treatment.
This review aims to provide an overview of how artificial intelligence (AI) is being integrated into stroke care across the full clinical spectrum with emphasis on its applications in diagnosis, management, and rehabilitation. The focus is on recent advances (2020–2025), addressing key questions on clinical utility and implementation challenges. AI has shown promise in enhancing stroke diagnosis through imaging analysis, wearable sensors, and remote monitoring. In stroke management, it supports decision-making and therapy optimization. AI-enabled tools are also improving rehabilitation via robotics and computer vision, and aid prevention through risk prediction and community screening. However, challenges remain in model generalizability, acceptance by the community, and ethical concerns. AI is reshaping stroke care by enabling personalized, timely, and data-driven approaches which can significantly improve quality of life. Future progress will depend on transparent multimodal, globally validated models, supported by interdisciplinary collaboration.
