Subarachnoid hemorrhage (SAH) disproportionately affects young adults aged 15–49 years, yet prior global studies have rarely focused on this population and may obscure age-specific patterns by combining all-age data. We therefore quantified the global burden of SAH in young adults and explored disparities by sex and socio-demographic index (SDI) level. Using Global Burden of Disease 2021 data from 204 countries (1990–2021), we estimated the age-standardized incidence rates (ASIR), age-standardized prevalence rates, age-standardized death rates, and age-standardized disability-adjusted life-year (DALY) rates. Temporal trends were assessed using estimated annual percentage changes and age-period-cohort models. We further evaluated cross-country disparities by SDI, examined risk attribution using population attributable fractions, projected future burden to 2050 using Bayesian age-period-cohort models, and conducted an exploratory machine learning analysis with SHapley Additive exPlanations. In 2021, SAH caused 55,012 deaths and 3.19 million DALYs among young adults globally. Although the ASIR declined over time, the absolute burden remained substantial. High-SDI regions showed higher incidence, whereas lower-SDI regions bore a greater mortality and DALY burden. Males had a higher DALY burden, whereas females had higher prevalence. Metabolic risks were the leading contributors globally, while environmental and occupational risks remained more prominent in low-SDI settings. Projections suggested a continued decline in burden through 2050, although uncertainty widened after 2040. SAH in young adults represents a non-uniform burden-transition pattern, with declining age-standardized rates but persistent premature mortality and DALYs, higher incidence in high-SDI settings, and greater fatal and disabling burden in lower-resource settings. These findings support stronger metabolic-risk reduction in high-SDI settings and improved blood pressure screening, referral, and acute-care access in lower-resource regions. Age-stratified global assessment of SAH in 15-49-year-olds across 204 countries (1990-2021). Young-adult SAH showed a burden-transition pattern: declining age-standardized rates but persistent premature deaths and DALYs. High-SDI regions typically exhibit higher incidence but lowest mortality; metabolic risks account for ≈ 45
This study aimed to investigate the frequency of Restless Legs Syndrome (RLS) in pregnant women and its relationship with sleep quality and the questionnaire-defined risk of obstructive sleep apnea syndrome (OSAS). This cross-sectional study included 208 pregnant women, and RLS was diagnosed according to the International Restless Legs Syndrome Study Group criteria. RLS severity and disease-specific quality of life were evaluated using the International Restless Legs Syndrome Rating Scale (IRLS) and the Restless Legs Syndrome Quality of Life (RLS-QoL) questionnaire. Sleep quality and daytime sleepiness were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS), while the risk of OSAS was evaluated using the STOP-Bang and Berlin questionnaires. RLS was identified in 69 women (33.2
PHACE syndrome is a rare neurocutaneous disorder defined by the association of large segmental infantile hemangiomas of the head and neck with malformations of the posterior fossa, cerebral and cervical arteries, heart, eyes, and ventral midline structures. Although facial hemangiomas are often the presenting feature, the cerebrovascular, neurodevelopmental, and airway manifestations are responsible for the greatest long-term morbidity. A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Web of Science, EMBASE, and PsycINFO. After removal of duplicates and screening of 308 records, five studies meeting the inclusion criteria were retained for qualitative synthesis. We additionally present the case of a now 12-year-old girl with PHACE syndrome characterized by a left V1-distribution facial hemangioma, ocular abnormalities, multiple cerebrovascular venous and arterial malformations, neonatal intraventricular hemorrhage with hydrocephalus, and a subsequently diagnosed dural arteriovenous fistula requiring repeated embolization. The five included studies collectively describe epidemiology and early supportive care needs, long-term health outcomes and quality of life into adulthood, airway hemangioma prevalence and management, and the clinical spectrum of infantile hemangiomas with minimal or arrested growth (IH-MAG) as a cutaneous marker of PHACE syndrome. Across studies, cerebrovascular arteriopathy (72–91
Whether spontaneous cervical artery dissection (sCeAD), the leading cause of ischemic stroke in young adults, represents the manifestation of unrecognized hereditary connective tissue disorders (HCTDs) and whether HCTDs have a major impact in the epidemiology of the disease is a matter of ongoing debate. We aimed at determining the frequency of clinically relevant genetic variants (CRGVs) in a cohort of unselected sCeAD patients by targeted next-generation sequencing (NGS) approach. We designed a high-throughput sequencing panel to identify variants in 38 candidate genes associated with arterial dissection or aneurysm and screened patients with apparently sporadic sCeAD, consecutively referred to one comprehensive stroke center from August 2020 to December 2025. The frequency of known disease-causing and pertinent variants of uncertain significance (VUS) was calculated. Then, we performed a systematic review of all studies evaluating the prevalence of monogenic disorders among sCeAD patients up to December 2025. Among 183 patients (males, 51.3
Frontotemporal dementia (FTD) is a leading cause of early-onset dementia in individuals under 65. Despite its significant burden, a comprehensive synthesis of its global prevalence is lacking. We conducted a systematic review and meta-analysis to estimate the worldwide prevalence of FTD. We systematically searched multiple databases for epidemiological studies on FTD prevalence published up to October 31, 2025. Meta-analysis was performed using a random-effects model. Subgroup analyses were conducted by geographic region, age range, and diagnostic criteria era. We systematically searched multiple databases for epidemiological studies on FTD prevalence published up to October 31, 2025. Meta-analysis was performed using a random-effects model. Subgroup analyses were conducted by geographic region, age range, and diagnostic criteria era. A total of 21 studies, encompassing 38,656, 516 individuals, were included. The pooled global prevalence of FTD was 30 cases per 100,000 population (0.03
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with a complex etiology involving genetic and environmental factors. Maternal diabetes during pregnancy has been hypothesized to influence offspring MS risk through intrauterine metabolic programming, yet the evidence remains inconclusive. To systematically review and meta-analyze the association between maternal diabetes and the risk of MS in offspring. A systematic literature search was conducted across PubMed, Scopus, Web of Science, and Embase, identifying 427 records. After removing 188 duplicates, 239 records were screened, 38 full-text reports were assessed for eligibility, and 4 studies met the inclusion criteria. Pooled risk ratios (RR) were calculated using both common-effect and random-effects models. Heterogeneity was assessed using the I² statistic, and publication bias was evaluated using Egger’s and Begg’s tests. The studies, published between 2009 and 2026, were conducted in Denmark, the USA (two studies), and Norway, utilizing diverse designs including nationwide register-based cohorts and a case-control study. The common-effect model yielded a pooled RR of 1.42 (95
Smoking is a well-established environmental risk factor for multiple sclerosis (MS), yet its impact on disability progression remains incompletely understood, with conflicting evidence across studies. This review evaluated smoking and clinical outcomes in MS. Disability progression was the primary outcome; disability severity, imaging, relapse recovery, functional status, and patient-reported outcomes were secondary outcomes. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, Scopus, Web of Science, and the Cochrane Library were searched from inception through the 4th of March 2026. Eighteen studies were included. Smoking was not significantly associated with increased EDSS (SMD = 0.09, 95
Subjective cognitive decline (SCD) is a transitional state between objective cognitive impairment and cognitively intact mental status, providing a critical window for implementing preventive interventions to delay objective cognitive decline. We aimed to develop a predictive model for SCD progression in older adults with mild cognitive impairment (MCI). This model will facilitate the identification of risk factors and establishment of targeted interventions for community-based SCD management. Data from the China Health and Retirement Longitudinal Study (CHARLS) was utilized in this study, extracting 18 indicators. Potential predictors selected through univariate Cox regression and LASSO regression analyses were sequentially incorporated into a multivariable Cox regression model. A nomogram was constructed to establish a predictive model. Model validation encompassed Area Under Curve (AUC) metrics for discriminative capacity, complemented by quantitative assessments using calibration curve analysis for precision verification and decision curve analysis (DCA) for clinical utility evaluation. A total of 1099 older adults with SCD were included in the final analysis, of whom 114 (10.3
Cryptococcal meningitis (CM) is one of the most devastating opportunistic infections in people living with HIV and typically occurs in patients with advanced immunosuppression. Ischemic stroke is an uncommon manifestation and rarely represents the initial presentation. We report a 28-year-old man with an 11-year history of HIV infection who presented with acute right-sided hemiparesis despite a relatively preserved CD4 count (302 cells/mm³). Brain magnetic resonance imaging demonstrated an acute infarction of the left internal capsule with communicating hydrocephalus. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis, elevated protein, low glucose, positive cryptococcal antigen, and culture-confirmed Cryptococcus neoformans. The patient was treated with amphotericin B and fluconazole, resulting in marked clinical improvement. This case demonstrates that CM may present as acute ischemic stroke in HIV-infected patients despite a relatively preserved CD4 count and the absence of classical meningeal manifestations. Early cerebrospinal fluid evaluation and prompt antifungal therapy are essential to avoid delayed diagnosis and improve neurological outcomes.
Unawareness of chorea is well-known in Huntington’s disease (HD). This study investigated unawareness for the whole gamut of motor impairments in daily life, which has not been explored previously. Data from 71 consecutive patients with stage I or II HD were assessed retrospectively. The motor section of UHDRS; the total functional capacity; a short battery of cognitive tests; the SANS and SAPS scales for negative and positive psychiatric symptoms; the Hamilton scales for depression (HAM-D) and anxiety (HAM-A); and a semi-structured questionnaire to assign motor anosognosia on a scale from 0 (fully aware) to 3 (severely unaware), were administered. Twenty-seven (38
Holmes tremor is a low-frequency movement disorder combining rest, postural and intention tremor, developing weeks to months after lesions involving the brainstem, thalamus, or cerebellothalamic pathways. We report an acute-onset Holmes-like tremor following an isolated precentral cortical ischemic stroke. A 68-year-old man presented with acute right-sided facial and upper limb weakness and aphasia, with rapid clinical improvement. Within 24 hours, he developed rhythmic low-frequency pronation–supination movements of the right hand and forearm, present at rest and enhanced during posture and voluntary movement. EEG showed no epileptiform discharges or cortical correlates, and lacosamide produced no clinical benefit. Multichannel surface polygraphy and accelerometry demonstrated relatively regular oscillations at approximately 3 Hz at rest and 3.5–4 Hz during action, supporting a Holmes-like tremor phenotype. Brain MRI revealed acute ischemic lesions confined to the left precentral cortex, without involvement of the thalamus, brainstem, basal ganglia, or cerebellum. The tremor resolved within days and did not recur at 1-month follow-up. This case is unusual because of the acute onset, isolated precentral cortical lesions, distal predominance of tremor, and spontaneous remission. The absence of prior tremor, the close temporal relationship with the new infarct, and complete recovery suggest that the acute cortical lesion was the most likely trigger. The cortical localization is consistent with network-based models suggesting that Holmes tremor may arise from disruption of a distributed motor circuit rather than a single anatomical structure. The rapid resolution supports the hypothesis of a transient functional network disturbance rather than a stable oscillatory circuit dysfunction.
Spontaneous intracranial hypotension (SIH) is caused by spinal cerebrospinal fluid (CSF) leakage leading to intracranial CSF hypovolemia and orthostatic headache. Diagnostic and therapeutic strategies remain heterogeneous across institutions. We report the outcomes of a structured stepwise diagnostic and therapeutic pathway applied in a tertiary referral center. We performed a retrospective analysis of 106 consecutive patients treated for SIH between 2020 and 2025. All patients were managed according to a standardized escalation protocol including conservative treatment, non-targeted epidural blood patch (nt-EBP), advanced spinal leak localization with dynamic CT myelography, and etiology-directed surgical or endovascular treatment when indicated. Initial nt-EBP resulted in complete clinical resolution in 64 patients. Forty-two patients with persistent or recurrent symptoms underwent advanced spinal imaging. Among them, 8 patients were diagnosed with lateral nerve root sleeve leaks and 4 with ventral dural tears related to osteophytes, all treated surgically, while 10 patients were diagnosed with CSF-venous fistulas and underwent transvenous embolization. All patients receiving etiology-directed surgical or endovascular treatment achieved complete clinical and radiological resolution. The remaining 20 patients without identifiable focal leak sites were managed with repeated nt-EBP, achieving partial clinical improvement and remaining under follow-up. A structured stepwise management strategy improves diagnostic efficiency and therapeutic outcomes in SIH. Non-targeted epidural blood patch remains an effective first-line intervention. Early escalation to targeted spinal imaging in refractory cases enables etiology-directed surgical or endovascular treatment, which can provide definitive clinical and radiological cure in selected patients.
To identify potentially useful objective indicators for early assessment of respiratory dysfunction in amyotrophic lateral sclerosis (ALS). Forty ALS patients were enrolled and followed every 3 months for one year. Baseline assessments included dyspnea complaints, ALSFRS-R, the ALS Respiratory Symptom Score (ARES), physical examination (including lower lung mobility), phrenic nerve conduction studies, diaphragm ultrasound, and multi-region ultrasound fasciculation detection. Forced vital capacity (FVC
The glymphatic system is a glial-dependent perivascular clearance pathway that maintains central nervous system homeostasis through cerebrospinal fluid and interstitial fluid exchange. Emerging evidence suggests that glymphatic dysfunction contributes to the pathophysiology of neurodegenerative disorders involving cerebellar networks. This review summarizes current evidence linking glymphatic dysfunction to cerebellar neurodegeneration, with a particular focus on spinocerebellar ataxia type 3, multiple system atrophy, progressive supranuclear palsy, and essential tremor. Mechanistic pathways involving aquaporin-4 mispolarization across astrocytic perivascular and Bergmann glial pial endfeet, neuroinflammation, vascular alterations, and sleep-dependent fluid dynamics are evaluated. Advanced neuroimaging approaches, including diffusion tensor image analysis along the perivascular space (DTI-ALPS), blood oxygen level-dependent–cerebrospinal fluid coupling, and structural perivascular space imaging, are reviewed as complementary surrogate markers of alterations in glymphatic-related fluid dynamics. Recent clinical studies indicate that these glymphatic-related imaging abnormalities correlate with clinical severity and, in specific disorders, may precede overt symptom onset. Collectively, current evidence supports glymphatic dysfunction as a contributor to cerebellar neurodegeneration and related movement disorders. A deeper understanding of glymphatic clearance dynamics may facilitate the development of novel imaging biomarkers and targeted therapeutic strategies addressing impaired protein clearance, reactive astrogliosis, vascular dysfunction, and sleep disturbances.
Autism Spectrum Disorder (ASD) is characterized by challenges in social interaction, communication, and restricted or repetitive behaviors, with motor abnormalities increasingly recognized as potential indicators for early identification. This paper presents a comprehensive review of recent advancements in ASD research, with particular emphasis on neuroimaging, artificial intelligence (AI), and machine learning (ML)-based diagnostic approaches. The review examines global and country-specific prevalence trends, current diagnostic methodologies, and existing therapeutic interventions. Through a critical analysis of the literature, including experimental and review studies, key challenges are identified, such as small sample sizes, limited population diversity, heterogeneous imaging protocols, restricted generalizability, and reliance on single-modal datasets. The review further summarizes publicly available ASD datasets and evaluates the strengths and limitations of contemporary AI-driven neuroimaging approaches for ASD diagnosis. The contributions of this study include a comprehensive synthesis of neuroimaging and AI-based diagnostic methods, an analysis of available datasets, and a critical evaluation of current methodological challenges and future research directions. The findings highlight the growing potential of AI-driven tools for supporting early ASD diagnosis while emphasizing the need for standardized protocols, external validation, explainable AI, and clinically translatable frameworks. Future research should focus on improving dataset diversity, conducting multicenter clinical validation studies, and integrating adaptive learning methodologies to enhance the reliability and applicability of ASD diagnostic systems. This study contributes to the growing body of multidisciplinary research aimed at advancing early diagnosis, personalized intervention, and evidence-based clinical decision support for individuals with ASD.
The expanding clinical use of immune checkpoint inhibitors (ICIs) has led to increased recognition of neurological immune-related adverse events, among which central nervous system demyelinating disease (ICI-CDD) represents a rare but clinically severe complication. Current evidence remains largely confined to case reports and small case series, highlighting the need for a comprehensive characterization of this condition. A systematic review and pooled analysis of published case reports and case series were conducted by searching English-language databases from inception to March 28, 2026, for literature related to ICI-CDD. A total of 60 patients with ICI-CDD from 39 publications were included, with a median age of 58.5 years (range: 9–81 years) and a slight male predominance (58.3
