Neurology

Severe WMH identifies patients harmed by intensive BP lowering after thrombectomy

In this OPTIMAL-BP secondary analysis, 271 EVT-treated ischemic stroke patients were stratified by Fazekas-defined WMH severity. Among those with severe WMH, intensive systolic BP control <140 mm Hg for 24 hours reduced functional independence vs 140–180 mm Hg (29.9% vs 51.3%; adjusted OR 0.36). In patients with mild WMH, intensive BP control did not significantly change 3‑month functional independence (adjusted OR 0.77; wide CI). Rates of symptomatic intracerebral hemorrhage and stroke-related death were similar across BP strategies, regardless of WMH burden. These data support avoiding aggressive post‑EVT BP lowering in patients with substantial WMH and tailoring BP targets to pre-existing small‑vessel disease. 1

Lobar and mixed microbleed patterns substantially increase dementia risk

This ARIC-Neurocognitive Study analysis followed 1,583 community participants (mean age 76 years) without prior ICH or dementia after 3T MRI. Over a long follow-up, cumulative dementia incidence was 24.7%, and 361 participants had CMBs at baseline. Compared with no CMBs, mixed and lobar±cSS patterns nearly doubled dementia risk (HR ~2), whereas subcortical-only CMBs carried no excess risk. Cortical superficial siderosis alone also conferred higher dementia risk (HR 2.57), and greater CMB counts across subtypes further increased risk. Clinically, lobar or mixed CMB patterns and high CMB burden should trigger heightened dementia surveillance and careful counseling about future cognitive decline. 2

Proteomic atlas links small-vessel disease manifestations to shared and distinct pathways

This study profiled plasma and CSF proteins in 1,670 patients to map signatures of WMLs, microbleeds, and infarcts. Across cSVD phenotypes, extracellular matrix and vascular remodeling proteins, particularly MMP12, were consistently elevated, implicating endothelial and smooth muscle dysfunction. These protein signatures were validated in CSF cohorts, and a plasma subset better predicted incident cerebrovascular events than standard risk scores in the UK Biobank. Microglial-associated proteins tracked faster WML progression, while neuron-derived proteins mediated WML–cognitive decline links. Findings point toward blood- and CSF-based risk stratification tools that may eventually complement MRI in cSVD management and trial enrichment. 3

CSF proteomics yields a 22‑protein panel that improves MS diagnosis and staging

Using high-throughput mass spectrometry, investigators quantified about 1,500 CSF proteins in 5,000 patients with diverse neurologic disorders. An intensified workflow in MS quantified 2,100 proteins per sample and revealed disease-specific signatures beyond generic blood–CSF barrier and demographic effects. A 22‑protein CSF panel outperformed established biomarkers in distinguishing MS from related inflammatory disorders, including diagnostically challenging cases. Targeted mass spectrometry with isotope-labeled standards validated this panel in an independent cohort, making clinical implementation feasible. Proteome-based staging along the relapsing–progressive spectrum correlated with outcomes, suggesting utility for prognosis and treatment monitoring in MS clinics. 4