Neurology最新文献

Background and objectives: The residual recurrence risk after atrial fibrillation (AF)-related stroke is high despite anticoagulation, thereby necessitating new therapies. The importance of inflammation in AF is increasingly recognized. However, patients with AF-related stroke were excluded from recent trials of anti-inflammatory therapies. It is uncertain whether associations between IL-6/high-sensitivity C-reactive protein (hsCRP) and poststroke recurrence are modified by AF status. In this study, we aimed to analyze the association between IL-6/hsCRP and recurrence according to AF history.

Methods: We leveraged individual participant data from studies identified by systematic review. We analyzed associations between IL-6/hsCRP and recurrent stroke/major adverse cardiovascular events (MACEs) (defined as fatal or nonfatal recurrent stroke or major coronary events) using multivariable Cox regression analyses (conditional logistic regression for 1 study) adjusted for age, sex, index event, cardiovascular risk factors, and medication use, stratified by AF status.

Results: Data from 11 prospective studies with 10,080 patients (2,134 with AF, mean age 70 years, 59.3% male) were included. During 21,080 person-years of follow-up, 1,677 patients had MACEs and 1,342 had recurrent stroke. Inflammatory markers were higher in patients with AF, irrespective of stroke severity and timing of measurement, with elevated levels persisting well beyond the acute phase. hsCRP was associated with recurrent MACEs in patients with AF (adjusted risk ratio [aRR] 1.14, 95% CI 1.04-1.25, per log_e-unit increase) and without AF (aRR 1.08, 1.03-1.13) (P_interaction 0.30). There were similar associations on per-quarter analysis in patients with AF (aRR 1.51, 1.04-2.18) and without AF (aRR 1.32, 1.10-1.59) (Q4 vs Q1). No association was observed between hsCRP and recurrent stroke in either group. For IL-6, there was no evidence of interaction according to AF status for MACEs (P_interaction 0.57) or recurrent stroke (P_interaction 0.82). The aRR per log_e unit for MACE was 1.17 (1.07-1.27) in patients without AF and 1.10 (0.91-1.34) in those with AF. The corresponding aRR for recurrent stroke was 1.15 (1.05-1.25) and 1.12 (0.91-1.37) in patients without and with AF, respectively.

Discussion: These data highlight the importance of inflammatory mechanisms in vascular recurrence irrespective of AF, provide rationale for the inclusion of patients with AF in trials of anti-inflammatory therapy, and support a selection approach in future trials based on elevated inflammatory marker levels, rather than stroke etiology alone.

Spinocerebellar ataxia type 27B (SCA27B) is a recently identified autosomal dominant form of late-onset cerebellar ataxia (LOCA) caused by a guanine-adenine-adenine (GAA) > 250 intronic repeat expansion in the fibroblast growth factor 14 (FGF14) gene. Recent studies suggest that SCA27B may account for 10%-60% of undiagnosed patients with LOCA. Age at onset ranges from 40s to 70s, and clinical features include slowly progressive pancerebellar syndrome with prominent gait ataxia and cerebellar oculomotor abnormalities. Positive family history may be absent, particularly given the characteristically late onset of this condition. It is important to note that up to half of the patients with SCA27B report episodic symptoms, including imbalance, vertigo, visual disturbances, or dysarthria, which might initially manifest without clear interictal clinical or radiologic features of cerebellar ataxia. These features can result in the misdiagnosis of SCA27B. We present 2 patients with LOCA. Both patients initially received alternative working diagnoses, which were re-examined several years later only after symptoms and imaging findings progressed. First-line genetic testing for both patients was unrevealing because of the deep intronic location of the causative variant. Ultimately, whole-genome-based testing in one case and targeted FGF14 trinucleotide repeat analysis in the other revealed the diagnosis of SCA27B. These cases highlight SCA27B as a cause of episodic neurologic symptoms in an older adult population. Furthermore, these cases demonstrate the potential pitfalls of panel and exome-based genetic testing, given the important role of pathogenic intronic variants in the spectrum of neurogenetic disorders.

Synaptic vesicle exocytosis and endocytosis are 2 fundamental processes that involve the coordinated and timely activity of many proteins and protein-lipid interactions. Alpha-synuclein (α-Syn) regulates several steps of these processes. Impaired exocytosis and endocytosis are important consequences of Parkinson disease (PD), reflecting both loss of function of normal α-Syn and toxic gain of function of abnormal α-Syn aggregates. Studies in familial forms of PD indicate that abnormal functions of other critical proteins such as leucine repeat rich kinase 2 also impair normal synaptic vesicular trafficking and contribute to synaptic dysfunction and secondary neurodegeneration.

Background and objectives: Early exposure to lead has known neurocognitive impacts in childhood, but few studies have examined the long-term impacts extending into later adulthood. We estimated associations between prenatal and early postnatal lead exposure and later adulthood cognitive function and examined specific periods of exposure and effect modification by sex.

Methods: The St. Louis Baby Tooth-Later Life Health study (SLBT) is a prospective cohort study that re-enrolled participants of the Baby Tooth Survey, originally centered in St. Louis, MO, who had donated their deciduous teeth between 1958 and 1972. SLBT participants completed surveys and a battery of cognitive tests in later adulthood. Tooth dentin lead concentrations were assessed using laser ablation inductively coupled plasma mass spectrometry across prenatal (second and third trimesters) and early postnatal periods. Cognitive function was assessed using a computerized cognitive battery taken at home using computers or personal digital devices. We used weighted generalized estimating equations to estimate associations between lead exposure and a composite outcome of later adulthood cognitive function.

Results: A total of 715 participants (52% female, mean age at cognitive testing: 62 years) had completed tooth metals analysis. The association between lead and performance on the vocabulary test was positive and statistically significantly different from the other tests. For each part per million (ppm) higher second trimester tooth dentin lead concentration, performance on a composite of tests excluding vocabulary was 0.07 SDs lower (95% CI -0.15 to 0.02). This effect was similar when coadjusting for third trimester and postnatal lead. These findings were driven by females, among whom each 1 ppm higher second trimester lead concentration was statistically significantly associated with 0.16 SD worse cognitive function (95% CI -0.29 to -0.03), equivalent to a 3-year difference in age in the same model. The results were robust to adjustment for additional potential sources of confounding and alternate methods of averaging tooth lead concentrations.

Discussion: We found suggestive evidence for associations between early lead exposures and later adulthood cognitive function, although these only reached statistical significance for second trimester lead exposure among females. A coadjusted analysis suggested the second trimester may be most relevant for later cognitive function.

Background and objectives: Previous antiplatelet therapy (APT) may influence outcomes in patients undergoing direct endovascular therapy (EVT) for anterior circulation large vessel occlusion (LVO) stroke, but evidence on clinical benefits and safety is limited and inconsistent. We aimed to evaluate the effects of previous APT on the outcomes of direct EVT.

Methods: We conducted a retrospective analysis of consecutive patients treated at 20 high-volume stroke centers across 9 European countries and Israel (EVA-TRISP registry, 2015-2023). We included adults with anterior circulation LVO strokes, without previous use of IV thrombolysis (IVT) or anticoagulants. We compared outcomes of direct EVT patients stratified by previous APT regimen, using propensity score matching based on medical history and multilevel models to address confounders. The primary outcome was the 90-day modified Rankin Scale (mRS) score. The secondary efficacy outcomes were 90-day independence and the rate of successful reperfusion. The secondary safety outcomes were the rate of symptomatic intracranial hemorrhage (sICH) and mortality.

Results: Among 12,950 patients, 2,611 met the criteria and 1,308 were matched: 480 without previous APT and 828 with any previous APT, among whom 764 were on single APT and 64 on dual APT. The overall mean age was 75.8 ± 11.4 years, and 49.4% were female; the mean NIH Stroke Scale score was 13.1 ± 7.2 points, the successful reperfusion rate was 74.7%, and the median mRS score was 3 (interquartile range 2-4), with 38.8% of patients independent at 90 days. When compared with no previous APT, any previous APT was associated with a shift toward lower mRS scores at 90 days (odds ratio [OR] 1.30, CI 1.04-1.61, p = 0.018). Independence at 90 days was associated with any previous APT (OR 1.62, CI 1.22-2.16, p = 0.001). Any previous APT was not associated with successful reperfusion (OR 0.96, CI 0.69-1.35, p = 0.821), sICH (OR 1.06, CI 0.47-2.39, p = 0.880), or mortality (OR 0.89, CI 0.66-1.21, p = 0.821). There was no significant interaction between any previous APT and proximal/distal occlusion location (p = 0.213) or time-to-groin earlier/later than 6 hours (p = 0.743).

Discussion: In patients with anterior circulation LVO stroke treated with direct EVT and no previous anticoagulation, pretreatment with any APT was independently linked to better 90-day functional outcomes and higher independence, without increasing sICH risk.

Classification of evidence: This study provides Class III evidence that, in patients with anterior circulation LVO stroke treated with direct EVT, previous APT is associated with better 90-day functional outcomes compared with no previous APT.