Neurology最新文献

Background and objectives: Ischemic stroke remains a leading cause of death and disability worldwide, with large vessel occlusion (LVO) accounting for a disproportionate share of poststroke morbidity. Early identification of LVO is essential for timely intervention with endovascular thrombectomy; however, the clinical scales currently used for triage vary widely in their application and accuracy. This study assesses the diagnostic performance of clinical stroke scales in predicting LVO.

Methods: A systematic review was conducted to identify studies evaluating the diagnostic accuracy of prehospital stroke scales for detecting LVO. Pooled sensitivity and specificity were estimated using a bivariate random-effects model, with diagnostic performance further assessed through summary receiver operating characteristic (ROC) curves and area under the curve (AUC) analysis. A Bayesian network meta-analysis was conducted to rank the scales using surface under the cumulative ranking (SUCRA) probabilities, and post hoc analyses were performed to evaluate publication bias.

Results: A total of 58 studies comprising 58,381 patients and 33 unique stroke scales were included in the final analysis. The studies, published between 2014 and 2023, were primarily conducted in North America (50%) and Europe (26%), with a median sample size of 473 participants. Pooled sensitivity ranged from 0.30 (HEMIPARESIS) to 0.99 (LARIO) while specificity varied from 0.34 (FANG) to 0.94 (HEMIPLEGIA). Among the highest-performing scales overall were LARIO (AUC = 0.983), FPSS (AUC = 0.896), FACE2AD (AUC = 0.876), and ACT-FAST (AUC = 0.873). In prehospital settings, FPSS (AUC = 0.896), FAST VAN (AUC = 0.878), and FACE2AD (AUC = 0.876) demonstrated strong performance while LARIO (AUC = 0.983) and ACT-FAST (AUC = 0.883) showed the highest accuracy in hospital settings. Bayesian network meta-analysis identified POMONA (SUCRA = 0.877), NIHSS (0.856), sNIHSS EMS (0.854), G-FAST (0.823), and SAFE (0.788) as the top-ranked scales. Funnel plot analysis revealed minimal publication bias among the most frequently evaluated tools, including RACE, CPSS, and NIHSS.

Discussion: Numerous clinical scales are available for detecting LVO in the prehospital setting. While several demonstrate strong performance in specific contexts, there remains a clear need for a simple, accurate, and generalizable tool to reliably identify patients with LVO across diverse clinical environments.

Background and objectives: Valproate (VPA) use during pregnancy is associated with a wide range of structural birth defects, but not all exposed children are affected and there is evidence for a genetic predisposition. The development of a pharmacogenomic biomarker test that can be used for preconception counseling, allowing access to women unnecessarily denied VPA treatment because of concern about teratogenic risks if they were to become pregnant, is challenged by a poor understanding of how variation in maternal DNA could modify the risk. We hypothesized that genomic variants that affect the binding affinity of transcription factors (TFs), key regulators of gene expression, are integral to VPA-associated teratogenicity and a plausible explanation for both variance in interindividual risk and the wide range of birth defect types.

Methods: We interrogated genomic variants within maternal exomes from women recruited through international epilepsy pregnancy registries and genomics consortia. We applied a network-based approach that contextualized the variant spectra to genes associated with diverse birth defect types, gene burden tests, and evidence from multiple modalities to identify variant-sensitive TFs.

Results: Sixty-six pregnancies were exposed to VPA as monotherapy or polytherapy, leading to 28 cases with birth defects, and 184 were exposed to other antiseizure medications (ASMs), leading to 20 cases with birth defects. The variant burden within genes associated with 32 different birth defect types was higher for those exposed to VPA compared with those exposed to other ASMs (OR 1.73 [95% CI 1.39 to 2.13], p < 0.0001). Variants in a network comprising significant genes from VPA-exposed mothers were predicted to modify the binding affinity of 359 TFs. These variant-sensitive TFs formed a highly connected protein-protein interaction network, among which the acetyltransferase EP300 connected to 41% (147/359) of all proteins. Profiling of coexpression between EP300 and other TFs in an embryonic stem cell (hESC) model showed that VPA exposure alters EP300-TF interactions.

Discussion: These findings suggest that VPA-induced disruption of EP300-related gene regulation is a teratogenic mechanism that is common to heterogeneous birth defect types and sensitive to genetic variation. This has implications for the development of pharmacogenomic risk biomarkers and safer drugs for women of childbearing potential.

Progressive myelopathy in immunocompromised patients presents a broad differential diagnosis and requires careful localization, imaging interpretation, and correlation with clinical context. A 66-year-old man with human immunodeficiency virus and diabetes mellitus developed vertigo, followed by asymmetric limb weakness beginning in the right leg and later progressing to the left leg, trunk, and upper extremities; gait imbalance with falls; paresthesias; and urinary urgency approximately 3 months after restarting antiretroviral therapy and 4 weeks after receiving a COVID-19 booster shot. Neurologic examination revealed mild symmetric quadriparesis, brisk reflexes, and impaired proprioception in the lower limbs. CSF analysis demonstrated elevated protein, oligoclonal bands, and an elevated immunoglobulin G index. Magnetic resonance imaging demonstrated longitudinally extensive tract-specific spinal cord abnormalities, which resolved spontaneously after several months without immunotherapy. This report illustrates the stepwise approach to myelopathy in immunocompromised patients, emphasizing the differential diagnosis for tract-specific imaging findings, clinical localization, and the role of immune reconstitution in neurologic disease.