Neurology International最新文献

The journal retracts the article, "Effect Comparison of E-Cigarette and Traditional Smoking and Association with Stroke-A Cross-Sectional Study of NHANES" [...].

Movement disorders comprise a heterogeneous group of neurological conditions shaped by a complex interplay of genetic and environmental factors [...].

Background/objectives: Scheie syndrome is the attenuated phenotype of mucopolysaccharidosis type I (MPS I), a lysosomal storage disorder resulting from partial deficiency of α-L-iduronidase. The attenuated clinical spectrum and absence of cognitive impairment often delay recognition. Early manifestations may mimic common pediatric conditions, leading to repeated evaluations without a definitive diagnosis.

Methods: We describe a 12-year-old girl who presented with slowly progressive bilateral hand stiffness, weak grip strength, and intermittent sensory symptoms over one year. Her initial investigations-including laboratory studies, electrophysiology, imaging, and multispecialty evaluations-were unremarkable.

Results: The gradual progression of symptoms involving joints, motor function, and vision prompted metabolic testing. Whole exome sequencing revealed a homozygous IDUA variant, and enzymatic testing confirmed markedly reduced α-L-iduronidase activity, establishing the diagnosis of Scheie syndrome. Early initiation of enzyme replacement therapy was pursued.

Conclusions: This case emphasizes that children with unexplained musculoskeletal and sensory symptoms should be evaluated for attenuated MPS I, especially when routine studies are inconclusive. Heightened clinical suspicion can reduce diagnostic delay and improve long-term outcomes.

Background: The leptomeninges, comprising the arachnoid and pia mater, serve essential roles in protecting the brain and facilitating cerebrospinal fluid (CSF) circulation. Their significance extends beyond structural support, affecting brain development and function.

Methods: This study synthesizes findings from various anatomical, embryological, and neuroimaging research to elucidate the complexities of the leptomeninges. Key methodologies include historical anatomical analysis, contemporary imaging techniques, and examination of pathological states.

Results: The review highlights the role of leptomeningeal structures in CSF dynamics, neurovascular interactions, and their involvement in conditions such as hydrocephalus and neurodevelopmental disorders. These insights underscore the leptomeninges' critical involvement in both normal physiology and disease states.

Conclusions: Understanding the intricacies of leptomeningeal anatomy and function is vital for advancing diagnostic and therapeutic approaches in neurodegenerative disorders. This knowledge may facilitate better management strategies in clinical practice, particularly concerning conditions that disrupt CSF flow and brain health.

Brain aging is a progressive process marked by cellular dysfunction, chronic inflammation, and increased susceptibility to neurodegenerative diseases. A growing body of evidence identifies cellular senescence, the accumulation of non-dividing, metabolically active cells with a pro-inflammatory secretory profile (SASP), as a key contributor to cognitive decline and brain aging. This review explores the emerging field of senotherapeutics, which includes senolytics (agents that eliminate senescent cells) and senomorphics (agents that suppress SASP without killing cells), as potential strategies to manage brain aging. We summarize recent preclinical studies demonstrating that senotherapeutics can reduce neuro-inflammation, improve synaptic plasticity, and enhance cognitive function in aged animal models. Additionally, we highlight early-phase clinical trials investigating senolytic compounds in Alzheimer's disease and discuss key challenges, including the delivery of drugs to the brain, biomarker development, and long-term safety. The review concludes that senotherapeutics, particularly when combined with personalized and multimodal approaches, represent a promising avenue for mitigating age-related cognitive decline and promoting healthy brain aging.

Background: Migraine is a highly prevalent neurological disorder and a leading cause of disability, particularly among working-age adults. Although the Work Productivity and Activity Impairment (WPAI) questionnaire is widely used to assess the functional impact of health conditions, no validated Arabic version specific to migraine is currently available. This study was conducted to validate the Arabic version of the WPAI:Migraine questionnaire among Arabic-speaking migraine patients in Saudi Arabia. Methods: A cross-sectional psychometric validation study was conducted at a tertiary headache clinic between June 2023 and January 2024. Adult patients diagnosed with episodic or chronic migraine, based on the International Classification of Headache Disorders, 3rd edition (ICHD-3), completed the Arabic version of the WPAI:Migraine and the validated Arabic version of the Migraine Disability Assessment Scale (MIDAS). Test-retest reliability was assessed after two weeks. Psychometric properties, including reliability, criterion validity, and known-group validity, were evaluated using intraclass correlation coefficients (ICCs), Pearson's and Spearman's correlations, and one-way ANOVA. Results: Eighty-two patients completed the study (76.8% female; mean age 38 ± 11 years). The Arabic WPAI:Migraine questionnaire demonstrated substantial-to-almost-perfect test-retest reliability (ICC range: 0.68-0.84). WPAI:Migraine domain scores correlated significantly with MIDAS scores-particularly for activity impairment (r = 0.576), presenteeism (r = 0.526), and absenteeism (r = 0.522)-and increased consistently across MIDAS disability grades, supporting validity. Conclusions: The Arabic WPAI:Migraine questionnaire is a valid and reliable instrument for assessing work productivity and activity impairment among Arabic-speaking migraine patients, suitable for clinical and research use.

Background/objectives: Atrophy of the thenar muscles (abductor pollicis brevis [APB], opponens pollicis [OP], and flexor pollicis brevis [FPB]) is most commonly caused by carpal tunnel syndrome (CTS). It may also occur following injury to the recurrent motor branch of the median nerve, proximal median nerve neuropathy, medial cord/lower trunk plexopathy, T1 radiculopathy, ventral horn cell disorder at C8 or T1, disuse atrophy, or congenital aplasia. Clinical observation of flattening of the thenar eminence coupled with electrodiagnostic (EDX) and ultrasound (US) studies is valuable in determining the etiology of thenar atrophy. This study describes clinical, EDX, and US findings in a large cohort of patients with thenar muscle atrophy.

Methods: This is a review of 197 patients (226 hands) with thenar atrophy who underwent EDX and US studies. Patients were divided into those with total thenar atrophy (all three thenar muscles were atrophic) or partial thenar atrophy (atrophy of one or two thenar muscles) based on clinical and US findings.

Results: Of the 226 hands, 174 (77.0%) had partial thenar atrophy, 217 (96.0%) had sensory loss, and all hands demonstrated weakness of the APB and OP muscles on examination. A total of 220 (97.3%) hands had EDX evidence of severe median nerve entrapment at the carpal tunnel. The compound muscle action potentials (CMAPs) of the APB muscle and sensory nerve action potentials (SNAPs) were absent in 186 (82.3%) and 212 (93.8%) hands, respectively. US study showed hyperechoic APB and OP muscles in 225 (99.6%) hands. The Heckmatt grade, determined by US, was 3 in 152 (67.3%) hands, showing increased muscle echogenicity with loss of architecture and reduced bone reflection.

Conclusions: In patients with thenar muscle atrophy, EDX studies were not always conclusive for confirming CTS due to an absence of SNAP and CMAP over the APB and second lumbrical muscles. In these cases, US is important to confirm the cause of thenar atrophy.

Background: Neuromyelitis optica spectrum disorder (NMOSD) involves demyelinating astrocytopathy. Most cases have autoantibodies against aquaporin-4 (AQP4 ab), but AQP4 ab-negative patients may also meet NMOSD criteria. Overlapping clinical phenotypes of CNS inflammatory demyelinating diseases (IDDs) complicate understanding NMOSD mechanisms.

Objectives: Investigate molecules related to neuroinflammation and astrocyte function as potential biomarkers of NMOSD and other IDDs by using clinical data and in vitro assays.

Methods: Subjects (176) with different IDDs (NMOSD (37), MS (125), MOGAD (3), ADEM (3) and eight radiologic isolated syndromes (RIS)) were studied. Plasma concentrations of TGF-β and other cytokines were measured by single molecule array (SIMOA), Luminex and ELISA assays. Functional assays used in vitro cultured human astrocytes exposed to NMOSD subjects' serum, followed by immunolabeling.

Results: TGF-β levels were higher in NMOSD patients during attacks compared to inactive phases. AQP4+ groups in inactive phases had lower TGF-β levels than AQP4- groups. No significant difference was found for IL-1β, IL-8, IL-10, IL-17A and Thrombospondin plasma concentrations, with a minor difference for VEGF in the AQP4+ group. Astrocytes exposed to NMOSD AQP4+ and AQP4- subjects serum, with or without TGF-β1, showed no changes in C3, NFkB and HMGB1. However, the content of GLT-1 decreased in AQP4+ serum-treated astrocytes, reversed by TGF-β1.

Conclusions: TGF-β may be a potential NMOSD activity biomarker, indicating different disease mechanisms based on AQP4 ab presence.

Introduction: Autoimmune encephalitis (AE) is a neurological disorder caused by immune responses targeting neuron-surface or synaptic proteins. While its immunological mechanisms have been studied, the genetic underpinnings remain unclear. This study investigates whether rare deleterious variants (RDVs) in immunological genes contribute to AE susceptibility.

Method: We enrolled 36 patients with AE and 407 healthy controls without autoimmune diseases. Whole-exome sequencing was performed to identify RDVs, including start-loss, stop-gain, frameshift, splice-site variants, and deleterious missense mutations. We analyzed the distribution of RDVs in an immunological gene set and its subsets. A burden test was used to identify genes significantly associated with AE.

Results: Overall, RDVs in the full immunological gene set did not differ between AE patients and controls. However, the T cell receptor signaling pathway subset showed a significantly higher RDV burden in AE patients. Within this pathway, PDK1 was significantly associated with AE. Two additional genes, CAT and MIA, also showed strong associations, although their broader gene subset, cytokines, did not display differential RDV distribution.

Discussion: Our findings suggest that RDVs in specific immunological pathways, particularly the T cell receptor signaling pathway, may play a role in AE pathogenesis. The significant associations of PDK1, CAT, and MIA with AE highlight potential genetic contributors to the disease. Further functional studies are necessary to validate these associations and explore their biological relevance, potentially paving the way for improved understanding and future therapeutic targets in AE.

Background/objectives: The optimal timing for initiating oral anticoagulants (OACs) after acute ischemic stroke (AIS) in patients with atrial fibrillation (AF) remains uncertain due to potential risks of recurrent stroke and bleeding. This meta-analysis compares early versus late OAC initiation for recurrent ischemic stroke, major bleeding, intracranial hemorrhage (ICH), systemic embolism, and all-cause mortality.

Methods: We conducted a meta-analysis of randomized controlled trials (RCTs), prospective, and retrospective observational studies. Data were pooled using random-effects models, and subgroup analyses were performed to assess outcomes by study design. Heterogeneity was quantified using I² statistics.

Results: A total of 17 studies were included. Early OAC initiation was associated with a significantly lower risk of recurrent ischemic stroke compared to late initiation (OR = 0.74, 95% CI [0.58, 0.95], p = 0.02), with moderate heterogeneity (I² = 36%, p = 0.08). No significant difference was observed in ICH rates (OR = 0.74, 95% CI [0.41, 1.33], p = 0.32), major bleeding (OR = 1.48, 95% CI [0.51, 4.30], p = 0.47), or systemic embolism (OR = 0.65, 95% CI [0.33, 1.25], p = 0.20). All-cause mortality showed no difference between early and late initiation (OR = 1.00, 95% CI [0.72, 1.39], p = 0.99). Subgroup analyses were consistent with overall findings, and heterogeneity ranged from low to moderate across outcomes.

Conclusions: Early initiation of OACs post-AIS in AF patients significantly reduces ischemic stroke recurrence without increasing risks of ICH, major bleeding, systemic embolism, or mortality. These findings support early anticoagulation strategies for selected patients.