使用改进的德尔菲法来培养神经学家完成>为期一年的高级全球神经病学培训的能力。半岛投注体育官网

从美国神经病学学会全球健康科和美国神经病学协会国际外展委员会招募了19名美国神经病学专家组成的全球健康专家小组。半岛投注体育官网通过对全球卫生课程的审查，产生了一份广泛的全球卫生能力清单，并将其用于全球神经病学培训。半岛投注体育官网利用改进的德尔菲法，美国的神经学家参与了一项调查的三轮投票，以4分的李克特量表对潜在能力进行评分。为了达成一致意见，举行了最后一次小组讨论。随后，来自低收入和中等收入国家(LMICs)的七名神经病学专家对所建议的能力进行了正式审查，这些专家具有与来自高收入国家(HICs)的神经学学员一起工作的经验，他们对所建议的能力的潜在差距、可行性和当地实施挑战发表了评论。半岛投注体育官网这个反馈被用来修改和最终确定胜任力。

利用三轮调查、与美国专家的电话会议、半结构化问卷和与LMIC专家的焦点小组讨论来讨论并就最终能力达成共识。这就形成了一个由八个领域的47项能力组成的能力框架:(1)文化背景、健康的社会决定因素和获得保健的机会;(2)临床和教学技能及神经医学知识; (3) Team-Based Practice; (4) Developing Global Neurology Partnerships; (5) Ethics; (6) Approach to Clinical Care; (7) Community Neurological Health; (8) Health Care Systems and Multinational Health Care Organizations.

These proposed competencies can serve as a foundation on which future global neurology training programs can be built and trainees evaluated. It may also serve as a model for global health training programs in other medical specialties as well as a framework to expand the number of neurologists from HICs trained in global neurology.

图书馆员在Medline Ovid、Embase、PsycINFO、Web of Science和Cochrane Library中创建了搜索标准。两位医生使用PRISMA指南独立完成了系统评价/荟萃分析的剩余部分。在系统综述/荟萃分析之外，我们对具有昼夜节律表达模式的基因(时钟控制基因或CCGs)进行了遗传分析，方法是交叉参考头痛的全基因组关联研究(GWAS)、各种组织中CCGs的非人类灵长类动物研究以及最近对头痛疾病相关脑区域的综述。总的来说，这使我们能够在行为水平(昼夜节律时间、一天中的时间、一年中的时间和生物钟类型)、系统水平(ccg活跃的相关大脑区域、褪黑激素和皮质类固醇水平)和细胞水平(核心昼夜节律基因和ccg)上对昼夜节律特征进行分类。

在系统评价和荟萃分析中，共发现1513项研究，其中72项符合纳入标准;在遗传分析方面，我们找到了16个GWAS, 1个非人灵长类动物研究和16个成像综述。行为学上，荟萃分析显示，16项研究中70.5%(3490/4953)的参与者具有发作的昼夜节律模式，在21:00-03:00之间有明显的昼夜节律高峰，春季和秋季为一年一次的高峰。不同研究的时型差异很大。在系统水平上，褪黑激素水平降低，皮质醇水平升高。 At the cellular level, cluster headache was associated with core circadian genes CLOCK and REV-ERBα, and five of the nine cluster headache susceptibility genes were CCGs.

Behaviorally, meta-analyses showed a circadian pattern of attacks in 50.1% (2698/5385) of participants across eight studies, with a clear circadian trough between 23:00-07:00 and a broad circannual peak between April-October. Chronotype was highly variable across studies. At the systems level, urinary melatonin levels were lower in migraine participants and even lower during an attack. At the cellular level, migraine was associated with core circadian genes CK1 and RORα, and 110 of the 168 migraine susceptibility genes were CCGs.

Cluster headache and migraine are highly circadian at multiple levels, reinforcing the importance of the hypothalamus. This review provides a pathophysiological foundation for circadian-targeted research into these disorders.

The study was registered with PROSPERO (registration number CRD42021234238).

这项前瞻性队列研究招募了2014年8月至2019年11月在新生儿重症监护室出生的36周PMA约6小时的新生儿。参与者进行了至少48小时的连续脑电图检查，3-5天内进行了脑MRI检查，并在18个月时进行了结构化随访。电图癫痫发作由委员会认证的神经生理学家确定，并量化为总癫痫发作负担和最大每小时癫痫发作负担。根据新生儿重症监护病房入院期间给予的所有抗癫痫药物计算药物暴露评分。基于基底节区和分水岭评分对脑MRI损伤严重程度进行分类。发育结果采用Bayley婴儿发育量表，3^和版。进行多变量回归分析，调整显著的潜在混杂因素。

在108例入组的受试者中，收集了98例脑电图和MRI数据，其中5例失访，6例在18个月前死亡。 All subjects with moderate-severe encephalopathy completed therapeutic hypothermia. cEEG-confirmed neonatal seizures occurred in 21(24%) newborns, with a total seizure burden mean of 12.5 ± 36.4 minutes, and a maximum hourly seizure burden mean of 4 ± 10 min/hr. After adjusting for MRI brain injury severity and medication exposure, total seizure burden was significantly associated with lower cognitive (-0.21, 95%CI -0.33 – -0.08, p=0.002) and language (-0.25, 95%CI -0.39 – -0.11, p=0.001) scores at 18 months. Total seizure burden of 60 minutes was associated with 15-point decline in language scores, and 70 minutes for cognitive scores. However, seizure burden was not significantly associated with epilepsy, neuromotor score, or cerebral palsy (p>0.1).

Higher seizure burden during neonatal encephalopathy was independently associated with worse cognitive and language scores at 18 months, even after adjusting for exposure to anti-seizure medications and severity of brain injury. These observations support the hypothesis that neonatal seizures occurring during neonatal encephalopathy independently contribute to long-term outcomes.

成年IIH患者，并记录手术过程和医院特征。评估并比较VSS、脑脊液分流术和视神经鞘开窗术手术次数的时间趋势。

46,065例[95%CI: 44,710-47,420] IIH患者，其中7,535例[95%CI: 6,982-8,088]患者接受手术IIH治疗。VSS手术增加了80%(每年150例[95%CI: 55-245]至270例[95%CI: 162-378]， p<0.001)。同时，脑脊液分流术的数量减少了19%(每年1365例[95%CI: 1,126-1,604]至1105例[95%CI: 900-1,310]， p<0.001)， ONSF手术减少了54%(每年65例[95%CI: 20-110]至30例[95%CI: 6-54]， p<0.001)。

美国IIH手术治疗的实践模式正在迅速发展，VSS正变得越来越普遍。这些发现强调了随机对照试验的紧迫性，以研究VSS、CSF分流术、ONSF和标准医学治疗的相对有效性和安全性 昆特，M.，陈，H.，科拉苏尔多，M.，查图维迪，S.，马尔霍特拉，A.，甘地，D.。 2023 - 03 - 29 - t12:45:38 07:00 信息:doi 10.1212 / / WNL.0000000000207245 hwp: master-id半岛投注体育官网:神经病学;WNL.0000000000207245 美国神经病学学会半岛投注体育官网 特发性颅内高压，其他脑血管疾病/脑卒中 脑静脉窦支架置入术治疗特发性颅内高压的全国趋势 2023-03-29 临床/科学报告 hw_mjid:半岛投注体育官网神经病学;WNL.0000000000207245v1 http://n.半岛投注体育官网neurology.org/cgi/content/short/WNL.0000000000207262v1?rss=1 背景:

急性缺血性卒中(AIS)晚期(6-24小时)行血管内取栓(EVT)治疗的患者可通过计算机断层扫描灌注(CTP)或仅通过非对比计算机断层扫描(NCCT)进行评估。结果是否取决于影像学选择的类型是未知的。我们进行了系统回顾和荟萃分析，比较了CTP和NCCT在治疗后期选择EVT的结果。

本研究根据PRISMA 2020指南报道。使用Web of Science、Embase、Scopus和PubMed数据库对英语文献进行了系统的文献综述。本文收录了通过CTP和NCCT对晚期AIS进行EVT成像的论文。数据采用随机效应模型汇总。主要观察指标为功能独立性，定义为修正Rankin量表(mRS) 0-2。次要结局包括成功再灌注率(定义为脑梗死(TICI)溶栓2b-3)、死亡率和症状性颅内出血(sICH)。

我们的分析纳入了5项研究，共3384例患者。功能独立性的可比率(OR= 1.03, 95% CI, 0.87-1.22;p值= 0.71)和sICH (OR= 1.09, 95% CI, 0.58-2.04; P-value= 0.80) between the two groups. Patients imaged with CTP had higher rates of successful reperfusion (OR= 1.31, 95% CI, 1.05-1.64; P-value= 0.015) and lower rates of mortality (OR= 0.79, 95% CI, 0.65-0.96; P-value= 0.017).

Although recovery of functional independence after late window EVT was not more common in patients selected by CTP as compared to patients selected by NCCT only, patients selected by CTP had lower mortality.

在这项准实验性卫生服务研究干预研究中，我们在全省实施了TIA管理算法，以24小时医生TIA热线以及公共和卫生提供者TIA教育为中心。从行政数据库中，我们将急诊科出院摘要与医院出院摘要联系起来，通过单一付款人系统识别90天内的偶发tia和复发性卒中，并验证复发性卒中事件。主要结局是卒中复发;继发复合结局为卒中复发、急性冠状动脉综合征和全因死亡。我们使用中断时间序列回归分析TIA后年龄和性别调整的卒中复发率，包括两年实施前(2007-2009年)、15个月实施期和两年实施后(2010-2012年)。Logistic回归用于检验不符合时间序列模型的结果。

我们评估了实施前6 715例患者和实施后6 956例患者。 The 90-day stroke recurrence rate in the pre-ASPIRE period was 4.5% compared to 5.3% during the post-ASPIRE period. There was neither a step change (estimate 0.38; p=0.65) nor slope change (parameter estimate 0.30; p=0.12) in recurrent stroke rates associated with the ASPIRE intervention implementation period. Adjusted all-cause mortality (OR 0.71 95%CI [0.56, 0.89]) was significantly lower following the ASPIRE intervention.

The ASPIRE TIA triaging and management interventions did not further reduce stroke recurrence in the context of an organized stroke system. The apparent lower mortality post intervention may be related to improved surveillance following events identified as TIAs but secular trends cannot be excluded.

A meta-analysis on the highest dose of each trial on hippocampus, ventricle, and whole brain revealed drug-induced acceleration of volume changes that varied by anti-Aβ drug class. Secretase inhibitors accelerated atrophy to the hippocampus (mean difference: -37.1 µL [-19.6% relative to change in placebo]; 95% confidence interval: -47.0 to -27.1) and whole brain (-3.3mL [-21.8% relative to change in placebo]; 95% confidence interval: -4.1 to 2.5). Conversely, ARIA-inducing monoclonal antibodies accelerated ventricular enlargement (mean difference: +2.1mL [+38.7% relative to change in placebo]; 95% confidence interval: 1.5 to 2.8) where a striking correlation between ventricular volume and ARIA frequency was observed (r=0.86, p=6.22x10^-7). Mild Cognitively Impaired participants treated with anti-Aβ drugs were projected to have a material regression toward brain volumes typical of Alzheimer’s dementia ~8 months earlier than if they were untreated.

These findings reveal the potential for anti-Aβ therapies to compromise long-term brain health by accelerating brain atrophy, and provide new insight into the adverse impact of ARIA. Six recommendations emerge from these findings.

40例ANAN患者中，21例有酒精使用障碍，10例厌食症，9例近期接受过减肥手术。纯感觉神经病变14例(低硫胺素7例)，感觉运动神经病变23例(低硫胺素8例)，纯运动神经病变3例(低硫胺素1例)。维生素B1含量最低(85%)，其次是维生素B6(77%)和叶酸(50%)。危险因素和神经病变类型与特定微量营养素缺乏无关。在随访的37例患者中，只有13例(35%)独立行走，只有8例(22%)在发病后平均22个月(范围:2-88个月)的最后一次随访时无疼痛。

The spectrum of ANAN is wide ranging from: 1) a pure sensory neuropathy with areflexia, limb and gait ataxia, neuropathic pain and unevocable sensory responses to 2) a motor axonal neuropathy with low-amplitude motor responses without conduction slowing, block, or dispersion, and 3) a mixed sensorimotor axonal polyneuropathy. Specific micronutrient deficiencies or risk factors do not predict neuropathy subtype. The sub-group of ANAN patients with documented thiamine deficiency also range from pure sensory to pure motor, and only a minority have Wernicke’s encephalopathy. We do not know whether co-existent micronutrient deficiencies may help explain the wide clinical spectrum of thiamine-deficient ANAN. The prognosis of ANAN is guarded due to residual neuropathic pain and slow recovery of independent ambulation. Therefore, early recognition of patients at risk is important.

这是一项基于国际脑卒中灌注成像登记(INSPIRE)的回顾性队列研究。选取脑卒中发病4.5小时内接受灌注CT的急性缺血性脑卒中患者。将直接进行EVT的患者与在EVT之前接受EVT桥接治疗的患者进行比较。缺血核生长速率是在假定缺血核呈线性增长模式的基础上，用灌注CT显示的急性缺血核体积除以卒中发生到灌注CT的时间来估算。根据其与桥接IVT在预测主要预后方面的相互作用，将核心生长速率分为快速(15mL/小时)和慢速(15mL/小时)。3个月时的主要指标为0-2的改良Rankin量表。次要结局包括通过改良的脑梗死溶栓评分为2b-3来定义的成功取栓再灌注，以及从腹股沟穿刺到再灌注的时间。

在INSPIRE的1221例EVT患者中，选取323例，其中直接EVT 82例，桥接IVT 241例。 Bridging IVT was associated with a higher rate of good clinical outcome amongst patients with fast core growth (39% vs 7% for direct EVT, odds ratio=8.75 [1.96-39.1], p=0.005), but the difference was not significant for patients with slow core growth (55% vs 55% for direct EVT, odds ratio=1.00 [0.53-1.87], p=0.989). In patients with fast core growth, the bridging and direct EVT patients showed no difference in the reperfusion rate (80% vs. 76%, p=0.616). However, patients who received bridging IVT were more likely to achieve reperfusion earlier (the median groin to reperfusion time of 63.0 vs 94.0 minutes p=0.005).

Patients with fast core growth were more likely to benefit from bridging intravenous thrombolysis. This is likely because prior intravenous thrombolysis facilitates clot removal and thus reduces time to reperfusion.

和目的

糖尿病(DM)是代谢综合征和心血管事件的重要因素，可能是癫痫的合并症。本研究的目的是调查长期使用抗癫痫药物(ASM)是否与发生2型糖尿病的风险相关。

方法

我们分析了长庚研究数据库的数据。年龄;确定了2001年1月至2019年5月接受ASM治疗的45例患者。排除患有dm相关疾病和短期使用ASM的患者。将患者分为非酶相互作用组、酶诱导组、酶抑制组和混合ASM组。进一步分析与个体ASM相关的糖尿病发生率。倾向得分加权来平衡组间差异。采用Cox比例回归模型和稳定处理权重逆概率(IPTW)进行分析。在指标日期后3年、4年、6年和9年及随访结束时计算风险比(HR)。

Results

A total of 5,103 patients were analyzed, of whom 474 took non-enzyme interaction ASMs, 1,156 took enzyme-inducing ASMs, 336 took enzyme-inhibiting ASMs, and 3,137 took mixed ASMs. During follow-up (39,248 person-years), 663 patients developed new-onset DM, and the prevalence was 13.0%. The incidence of DM plateaued at 6-9 years after ASM initiation. Enzyme-inhibiting ASMs were significantly associated with a higher HR starting at the 3^rd year and then throughout the study period. The HRs were 1.93 (95% CI, 1.33-2.80), 1.85 (95% CI, 1.24-2.75), and 2.08 (95% CI, 1.43-3.03) in unadjusted, adjusted, and stabilized IPTW models, respectively, at the end of follow-up. The dosing of ASM did not increase the risk of DM, and none of the individual ASM analyses reached statistical significance.

Discussion

The long-term use of enzyme-inhibiting ASMs was associated with an increased risk of incident DM, and the risk increased with the duration of treatment. These findings may guide the choice of drugs in those requiring long-term ASM therapy, particularly in high-risk individuals.

Classification of Evidence:

This study provides Class IV evidence that enzyme-inhibiting anti-seizure medications were associated with an increased risk of developing diabetes mellitus compared with non-enzyme interaction anti-seizure medications.

颅侧脑电图在多大程度上能准确预测耐药癫痫术前评估中脑内癫痫发作的定位，目前尚不清楚。在这项研究中，我们的目的是定义均匀的头峰脑电图(基于他们的第一个头峰异常)，并评估他们的定位价值，同时记录头皮脑电图和立体脑电图。

我们回顾性地纳入了在法国Nancy的癫痫科同时有至少一次癫痫发作的立体脑电图和头皮脑电图记录的连续的耐药局灶性癫痫患者。我们分析了每位患者的一次癫痫发作，并使用分层聚类分析对头皮脑电图上相似的癫痫发作特征进行分组，然后对其脑内相关性进行描述性分析。

我们入组了129例患者。分层聚类分析得到头皮脑电首次修改后的6个特征。没有一个特定于单一的脑内定位。“正常脑电图”和“模糊脑电图”集群(早期肌肉伪影)各只有5名患者，并且没有优先的脑内定位。“颞放电”簇(n=46)的特征是同侧颞前部头皮电极上的θ波或δ波放电，与颞内侧脑内优先定位相对应。“后侧放电”簇(n=42)的特征是后侧或对侧有节奏的α放电或头皮慢波，对应于优先的颞部定位。然而，这是统计上最常见的枕骨和顶骨癫痫相关的头皮脑电图。 The "diffuse suppression" cluster (n=9) was characterized by a bilateral and diffuse background activity suppression on scalp and corresponded to mesial, and particularly insulo-opercular, localization. Finally, the "frontal discharge" cluster (n=22) was characterized by bilateral frontal rhythmic fast activity or pre-ictal spike on scalp and corresponded to preferential ventrodorsal frontal intra-cerebral localizations.

Hierarchical cluster analysis identified six seizure profiles regarding the first abnormality on scalp EEG. None of them was specific of a single intra-cerebral localization. Nevertheless, the strong relationships between the "temporal", "frontal", "diffuse suppression" and "posterior" profiles and intra-cerebral discharges localizations may contribute to hierarchize hypotheses derived from ictal scalp EEG analysis regarding intra-cerebral seizure onset.

在3,651名参与者中(中位年龄72.3 + 10.0岁，57.9%为女性)，688名(18.8%)在中位11.1年期间发生了偶发性痴呆，其中528名(76.7%)发生了阿尔茨海默病。在整个随访期间，股骨颈骨密度较低的参与者(每SD降低)更容易发生全因痴呆(风险比[HR] _总随访: 1.12, 95%可信区间[CI]: 1.02-1.23)和阿尔茨海默病(HR _总随访: 1.14, 95% CI: 1.02-1.28)。在基线后的前10年内，骨密度最低的组发生痴呆的风险最大(股骨颈骨密度，HR_0-10年 2.03;95% CI, 1.39–2.96; total body bone mineral density, HR_0-10years 1.42; 95% CI, 1.01–2.02; trabecular bone score, HR_0-10years 1.59; 95% CI, 1.11–2.28).

In conclusion, participants with low femoral neck and total body bone mineral density and low trabecular bone score were more likely to develop dementia. Further studies should focus on the predictive ability of bone mineral density for dementia.

我们对2002年至2018年在单一一级创伤中心治疗的严重TBI患者的前瞻性数据库进行了回顾性分析。于伤后3、6、12和24个月收集格拉斯哥预后量表(GOS)。我们使用重复测量逻辑回归预测GOS，分为有利(GOS 4-5)和不利(GOS 1-3)，并使用单独的逻辑模型预测两年后的死亡率。我们使用国际TBI临床试验预后和分析任务(IMPACT)基础模型定义的预测因子(即年龄、瞳孔反应性和GCS运动评分)、PTE状态和时间。

392例存活至出院的患者中，98例(25%)发展为PTE, 3个月预后良好的患者比例在有PTE和没有PTE的患者中没有差异(23%[95%置信区间[CI]: 15%-34%]对32% [95% CI: 27%-39%];p=0.11)，但显著低于6- (33% [95% CI: 23-44%] vs. 46%;(95%置信区间CI: 39 - 52%] p = 0.03), 12(41%(95%置信区间CI: 30 - 52%)和54% (95% CI: 47 - 61%); p=0.03), and 24-months (40% [95% CI: 47-61%] vs. 55% [95% CI: 47-63%]; p=0.04). This was driven by higher rates of GOS 2 (vegetative) and 3 (severe disability) outcomes in the PTE group. By two years, the incidence of GOS 2 or 3 was double in the PTE group (46% [95% CI: 34-59%]) compared to non-PTE group (21% [95% CI: 16-28%]; p<0.001), while mortality was similar (14% [95% CI: 7-25%] vs. 23% [95% CI: 17-30%]; p=0.28). In multivariate analysis, patients with PTE had lower odds of favorable outcome (odds radio [OR] 0.1; 95% CI: 0.1-0.4; p<0.001), but not mortality (OR 0.9; 95% CI: 0.1-1.9; p=0.46).

Post-traumatic epilepsy is associated with impaired recovery from severe TBI and poor functional outcomes. Early screening and treatment of PTE may improve patient outcomes.

我们使用国家健康保险数据库与国家死亡登记册进行了一项基于全国人群的回顾性队列研究。纳入2008 - 2016年通过抗癫痫药物处方和癫痫/发作诊断代码确定的新治疗的PWE，并观察至2017年。我们评估了全因和特定病因的粗死亡率和标准化死亡率(SMRs)。

在138,998例PWE中，确定了20,095例死亡，平均随访时间为4.79年。整体PWE组SMR为2.25，诊断时年龄越小SMR越高，诊断后时间间隔越短。单药组的SMR为1.56,4次及以上asm组的SMR为4.93。无合并症的PWE的SMR为1.61。农村居民PWE的SMR高于城市居民(分别为2.47和2.03)。 The causes of death among PWE were cerebrovascular disease (18.9%, SMR 4.50), malignant neoplasms outside the central nervous system (CNS) (15.7%, SMR 1.37), malignant neoplasms of the CNS (6.7%, SMR 46.95), pneumonia (6.0%, SMR 2.08), and external causes (7.2%, SMR 2.17), including suicide (2.6%, SMR 2.07). Epilepsy itself and status epilepticus accounted for 1.9% of the overall death. The excess mortality associated with pneumonia and external causes was persistently high, whereas the excess mortality associated with malignancy and cerebrovascular diseases tended to decrease with increasing time since diagnosis.

This study showed excess mortality in PWE, even in those without comorbidities and those receiving monotherapy. Regional disparities and sustained risks of deaths from external causes over ten years imply potential points of intervention. In addition to active control of seizures, education about injury prevention, monitoring for suicidal ideation and efforts to improve accessibility to epilepsy care are all required to reduce mortality.

本研究纳入435例患者，其中71.5%为男性。年龄中位数为65岁(四分位数范围为56& & 72)，美国国立卫生研究院卒中量表中位数为14岁(四分位数范围为10& & 19)。替罗非班组患者在90天的功能独立性比安慰剂组患者高(校正优势比，1.68;95%置信区间为1.11& 2.56，P = 0.02)，未增加死亡或症状性颅内出血的风险。替罗非班与较少的取栓次数相关(中位数[四分位数范围]，1 [1–2] vs 1 [1–2]， < 1 >P = 0.004)，这是功能独立性的独立预测因子。 Mediation analysis showed tirofiban-reduced thrombectomy passes explained 20.0% (95% confidence interval, 4.1%–76.0%) of the effect of tirofiban on functional independence.

In this post hoc analysis of the RESCUE BT trial, tirofiban was an effective and well-tolerated adjuvant medication of endovascular thrombectomy for patients with large vessel occlusion due to intracranial atherosclerosis. These findings need to be confirmed in future trials.

临床和神经病理数据来自美国国家阿尔茨海默病协调中心(NACC)。死亡时75岁以上无额颞叶退行性变神经病理指征的个体的基线数据纳入分析。病理定义组反映LATE, AD和合并症LATE+AD被确定。通过使用统一数据集测量的方差分析和卡方分析，探讨临床特征和认知的组间差异。病理组包括31例LATE患者(M_年龄: 80.6±5.4)， 393例AD患者(M_年龄: 77.8±6.4)， 262例LATE+AD患者(M_年龄: 77.8±6.6)，性别、教育程度和种族均无显著差异。与AD和LATE+AD病理的参与者相比，LATE病理的参与者寿命明显更长(M_次: LATE=7.3±3.7;广告= ± 5.8; 3.0;晚+广告= 5.8 ± 3.0;F(2,683)=3.7, p< 0.05)，报告晚发性认知衰退(M_发病: LATE=78.8±5.7; AD=72.5±7.0; LATE+AD=72.9±7.0; F(2,516)=6.2, p<.01), and were more likely to be diagnosed as cognitively normal at baseline (LATE=41.9%; AD=25.4%; LATE+AD=12%; ²=38.7, p<.001). Individuals with LATE (45.2%) also reported fewer memory complaints than those with AD (74.4%) or LATE+AD (66.4%; ²=13.3, p=.001) and were less likely to be classified as Impaired on the Mini Mental State Exam (LATE=6.5%; AD=24.2%; LATE+AD=40.1%; ²=29.20, p<.001). Across all neuropsychological measures, participants with LATE+AD pathology performed significantly worse than the AD and LATE groups.

Those with LATE pathology were older when cognitive symptoms began and lived longer than participants with AD or LATE+AD pathology. Participants with LATE pathology were also more likely to be classified as "cognitively normal" based on objective screening and self-report measures, and they had higher scores on neuropsychological testing. Consistent with prior literature, comorbid pathologies led to more significant cognitive and functional impairment. Early disease characteristics based on clinical presentation alone were insufficient for differentiating LATE from AD, reiterating the need for a validated biomarker.

我们对2008年1月至2020年1月期间新诊断为ATTRv的患者进行了回顾性病例系列研究，以表征突出的US变异体的特征。我们描述了神经学(检查、肌电图、皮肤活检)、心脏(回声)和实验室评估(proBNP、可逆性神经病变筛查)。

纳入56例伴有周围神经病变或心肌病症状/体征的治疗naiv ATTRv患者，确认基因检测为Val122Ile (N=31)，迟发性Val30Met (N=12)和Leu58His ATTRv (N=13)。发病年龄和性别分布相似(V122I: 71.5±8.0, V30M: 64.8±2.6, L58H: 62.4±9.8岁;26,25,31%为女性)。只有10%的V122I患者和17%的V30M患者知道ATTRv家族史，而69%的L58H患者知道ATTRv家族史。尽管神经损伤评分不同，但三种变异在诊断时均存在周围神经病变(90,100,100%):V122I: 22±16, V30M: 61±31和L58H: 57±25。大多数分数(缺分)是由于体力的丧失。腕管综合征(CTS)和Romberg阳性征象在所有组中都很常见(V122I: 97%， 39%; V30M: 58%, 58%; L58H: 77%, 77%).

ProBNP levels and interventricular septum thickness were highest among patients with V122I (5939±962pg/mL, 1.70±0.29cm) followed by V30M (796±970pg/mL, 1.42±0.38cm) and L58H (404±677pg/mL, 1.23±0.36cm). Atrial fibrillation was present among 39% of V122I cases and only 8% of V30M and L58H cases. Gastrointestinal symptoms were rare (6%) among patients with V122I and common in patients with V30M (42%) and L58H (54%).

Important clinical differences exist between ATTRv genotypes. While V122I is perceived to be a cardiac disease, peripheral neuropathy is common and clinically relevant. Most patients with V30M and V122I were diagnosed de-novo and therefore require clinical suspicion for diagnosis.A history of CTS and a positive Romberg sign are helpful diagnostic clues.

横断面研究，连续的多导睡眠图证实的IRBD患者和年龄匹配的没有RBD的对照组同一天接受皮肤活检和腰椎穿刺。双侧颈区C7和C8皮节背侧及小腿远端均行3毫米皮肤穿刺活检。RT-QuIC评估了这六个皮肤部位和CSF中错误折叠的& α;-synuclein

Our study in IRBD shows that 1) RT-QuIC detects misfolded α-synuclein in skin and CSF with similar high sensitivity, specificity, and agreement, 2) α-synuclein RT-QuIC positivity is associated with supportive features and biomarkers of synucleinopathy, and 3) skin punch biopsy and lumbar puncture have comparable mild adverse effects, tolerance, and acceptance. α-synuclein RT-QuIC in skin or CSF might represent a patient selection strategy for future neuroprotective trials targeting α-synuclein in IRBD.

This study provides Class III evidence that RT-QuIC detected misfolded α-synuclein in the skin and CSF distinguishes patients with IRBD from controls.

We included up to 19,152 participants (mean age 59 years, 57% women). Higher mtDNA CN was cross-sectionally associated with better general cognitive function (Beta=0.04; 95% CI 0.02, 0.06) independent of age, sex, batch effects, race/ethnicity, time between blood draw and cognitive evaluation, cohort-specific variables, and education. Additional adjustment for blood cell counts or cardiometabolic traits led to slightly attenuated results. We observed similar significant associations with cognition in prospective analyses, although of reduced magnitude. We found no significant associations between mtDNA CN and brain MRI measures in meta-analyses. MR analyses did not reveal a causal relation between mtDNA CN in blood and cognition.

Discussion:

Higher mtDNA CN in blood is associated with better current and future general cognitive function in large and diverse communities across the US. Although MR analyses did not support a causal role, additional research is needed to assess causality. Circulating mtDNA CN could serve nevertheless as a biomarker of current and future cognitive function in the community.

于2022年6月1日使用Medline、Embase、NHS经济评估数据库和Cost-Effectiveness Analysis数据库进行系统文献检索。纳入的研究包括成人DRE队列的经济评估;比较手术和神经刺激治疗(迷走神经刺激(VNS)、反应性神经刺激(RNS)和深部脑刺激(DBS))与单纯药物治疗;并报告成本效益分析、成本效用或成本效益。排除标准是儿科队列研究和以非英语语言发表的研究。三名独立审稿人根据综合卫生经济评估报告标准(CHEERS)清单筛选、提取和评估数据，第四名审稿人裁定差异。

10项研究符合纳入标准。7项研究评估癫痫手术，3项研究评估神经刺激治疗。所有相关研究都表明，与单纯的医疗管理相比，癫痫手术是一种具有成本效益的干预措施，涉及到质量调整生命年(QALYs)和2岁和5岁时的癫痫发作自由度。 All relevant studies found neurostimulator treatments to be potentially cost-effective. The incremental cost-effectiveness ratio (ICER), with lower ICER indicating greater cost-effectiveness, was reported for nine studies, and varied between GBP £3,013 and US $61,333. Cost adaptation revealed ICERs from US $170 to US $121,726. Key model determinants included, but were not limited to, improved surgical outcomes and quality of life, reduced surgical and presurgical evaluation costs, higher rates of surgical eligibility after referral and evaluation, epilepsy subtype, less expensive neurostimulator devices with improved longevity, and cost analysis strategy used in the analysis.

There is consistent evidence that epilepsy surgery is a cost-effective treatment for eligible candidates with DRE. Limited evidence suggests that VNS, RNS, and DBS may be cost-effective therapies for DRE, although more health economic evaluations alongside prospective clinical trials are needed to validate these findings.

本研究采用经验方法表征颞叶切除术后儿童的记忆结局。 Provided online calculator and nomograms may be used by clinicians to estimate the risk of postoperative memory decline for individual patients prior to surgery.

这是一项回顾性队列研究，研究对象是连续住进三级神经危重症监护病房的自发性脑出血成年患者。排除继发性脑出血患者和72小时前限制护理的患者。对于每个ICH评分，检查30天和90天死亡率，以及修改的Rankin量表(mRS)。开颅术/开颅术的疗效观察血肿清除对幕上脑出血结果的影响采用倾向评分匹配法。出院后中位随访时间为2.2年[IQR, 0.4-4.4]年。结果:319例自发性脑出血患者(中位年龄69岁[IQR, 60-77]岁，60%为男性)中，30天和90天死亡率分别为16%和22%，在脑出血后中位3.1个月时，不良功能结局(mRS 4-6)为50%。入院死亡率预测因子反映了原始ICH评分。 Unfavorable outcomes for ICH score 3 and 4 were 73% and 86%, respectively. The most common adjudicated primary causes of mortality were direct effect or progression of the ICH (54%), refractory cerebral edema (21%), and medical complications (11%). In matched analyses, lifesaving surgery for supratentorial ICH did not significantly alter mortality or unfavorable functional outcome in patients overall. In subgroup analyses restricted to (1) surgery with hematoma evacuation, and (2) ICH score 3 and 4 patients, the odds of 30-day mortality were reduced by 71% (OR, 0.29, 95% CI, 0.09-0.9, p=0.032) and 80% (OR, 0.2, 95% CI, 0.04-0.91, p=0.038), respectively, but no difference was observed for 90-day mortality or unfavorable functional outcome.

This study demonstrates that poor outcomes after ICH prevail despite aggressive treatment. Unfavorable outcomes appear related to direct effects of the primary injury and not to premature care limitations. Lifesaving surgery for supratentorial lesions delayed mortality but did not alter functional outcomes.

我们选取并回顾性分析umn -综合征患者的临床资料。在第一次评估时，使用超灵敏单分子阵列测量血清生物标志物。

研究人群包括55例PLS和50例ALS患者。PLS患者首次神经学评估时间较长(PLS: 35.0个月，IQR: 17.0 ~ 38.0;ALS: 12.5个月，IQR: 7.0-21.3;p<0.01)和较低水平的神经丝轻链(NfL) (PLS: 81.8 pg/mL, IQR: 38.4-111.1;半岛中国官网ALS: 155.9 pg/mL, IQR: 85.1-366.4; p=0.01). Two PLS and three ALS patients carried the C9orf72 expansion. NfL resulted an independent predictor of final diagnosis (OR: 1.01, 95%CI: 1.00-1.02; p=0.04) and an independent prognostic factor (HR: 1.01, 95%CI: 1.00-1.01; p<0.01).

NfL might help to differentiate PLS from ALS patients and to predict prognosis in patients with an UMN-syndrome.

纳入2011-2019年在瑞士学术护理中心接受麻醉治疗的RSE患者。评估临床资料和半定量脑电图分析。爆发抑制分为不完全爆发抑制(≥20%和<50%抑制比例)和完全爆发抑制(≥50%抑制比例)。诱导发作抑制的频率以及发作抑制与结局(持续发作终止、住院生存和恢复发病前神经功能)的关联是终点。

我们确定了147例接受IVAD治疗的RSE患者。在102例无脑缺氧的患者中，14例(14%)患者实现了不完全爆发抑制，中位数为23小时(四分位间距[IQR] 1-29)， 21例(21%)患者实现了完全爆发抑制，中位数为51小时(IQR 16-104)。年龄、Charlson合并症指数、伴有运动症状的RSE和癫痫持续状态严重程度评分(ess)在有和没有突发抑制的患者之间的单变量比较中被确定为潜在的混杂因素。多变量分析显示，任何突发抑制与预定义终点之间没有关联。然而，在45例脑缺氧患者中，诱导的突发抑制与持续发作终止(72%无发作抑制vs. 29%发作抑制，p=0.004)和生存(50% vs. 14% p=0.005)相关。

在接受IVAD治疗的成年RSE患者中，发作抑制达到50%的抑制比例，且与持续发作终止、住院生存或恢复病前神经功能无关 nger, A. L, Baumann, s.m, Semmlack, S.， De Marchis, g.m, Hunziker, S.， RüeggFAES, S.， Marsch, S.， Sutter, R.。 2023 - 03 - 08 - t12:45:24喂饲 信息:doi 10.1212 / / WNL.0000000000207129 hwp: master-id半岛投注体育官网:神经病学;WNL.0000000000207129 美国神经病学学会半岛投注体育官网 预后，重症监护，癫痫持续状态，癫痫监测 难治性癫痫持续状态患者诱导爆发抑制与临床结果的关系:一项为期9年的队列研究 2023-03-08 半岛体育app苹果下载 hw_mjid:半岛投注体育官网神经病学;WNL.0000000000207129v1 http://n.半岛投注体育官网neurology.org/cgi/content/short/WNL.0000000000207136v1?rss=1 背景与目的:原发性进行性失语(PPA)是一种进行性语言能力下降的神经退行性综合征。PPA有3个主要的子类型:逻辑类型、语义类型和语法类型。观察性研究表明，语言相关的神经发育表型与PPA风险增加之间存在关联。我们试图通过孟德尔随机化(MR)方法来评估这种关系，该方法可以提示潜在的因果关系。方法:采用与阅读障碍(42个snp)、发育性语言障碍(29个snp)和左撇子(41个snp)相关的全基因组显著单核苷酸多态性(snp)作为暴露的遗传指标。左撇子的18/41 snp与大脑皮层的结构不对称有关。GWAS的汇总统计数据来自公开的数据库，包括语义PPA(308例/ 616例对照)和语法PPA(269例/ 538例对照)。语言缺失性PPA(324例/ 3444例对照)通过“临床诊断为阿尔茨海默病伴显著语言障碍”的标题进行代理近似。反向加权方差MR是检验暴露与结果之间关系的主要分析方法。完成敏感性分析以检验结果的稳健性。

Dyslexia, developmental speech disorders and left-handedness were not associated with any PPA subtype (P > 0.05). The genetic proxy of cortical asymmetry in left handedness was significantly associated with agrammatic PPA (beta = 4.3, P= 0.007), but not with other PPA subtypes. This association was driven by microtubule-related genes, primarily by a variant that is in complete linkage disequilibrium with MAPT gene. Sensitivity analyses were overall consistent with the primary analyses.

Our results do not support a causal association between dyslexia, developmental speech disorders, or handedness with any of the PPA subtypes. Our data suggests a complex association between cortical asymmetry genes and agrammatic PPA. Whether the additional association with left handedness is necessary remains to be determined but is unlikely given the absence of association between left handedness and PPA. Genetic proxy of brain asymmetry (regardless of handedness) was not tested as an exposure due to lack of suitable genetic proxy. Furthermore, the genes related to cortical asymmetry associated with agrammatic PPA are implicated in microtubule-related proteins (TUBA1B, TUBB, and MAPT), which is keeping with the association of tau-related neurodegeneration in this PPA variant.

和目的

抑郁症已被报道为急性卒中的危险因素，主要基于高收入国家的研究。在INTERSTROKE研究中，我们探讨了抑郁症状对世界各地区急性卒中风险和1个月预后的影响，在亚人群中，按卒中类型

方法

INTERSTROKE是一项在32个国家进行的首次急性卒中危险因素的国际病例对照研究。病例为经CT或MRI证实的急性住院卒中患者，对照组根据年龄、性别和部位进行匹配。记录了有关过去12个月自我报告的抑郁症状和处方抗抑郁药物使用的标准化问题。采用多变量条件logistic回归来确定卒中前抑郁症状与急性卒中风险的关系。采用调整有序逻辑回归探讨脑卒中前抑郁症状与脑卒中后功能结局的关系，脑卒中后1个月采用修正rankin量表测量。

结果

在26,877名参与者中，40.4%为女性，平均年龄为61.7岁;13.4年。在过去12个月内，病例中抑郁症状的患病率高于对照组(18.3%vs.14.1%，p <p_相互作用 <0.001)，中国的患病率最低(对照组为6.9%)，南美洲的患病率最高(对照组为32.2%)。 In multivariable analyses pre-stroke depressive symptoms were associated with greater odds of acute stroke (OR 1.46, 95%CI 1.34–1.58), which was significant for both intracerebral hemorrhage (OR 1.56, 95%CI 1.28–1.91) and ischemic stroke (OR 1.44, 95%CI 1.31–1.58). A larger magnitude of association with stroke was seen in patients with a greater burden of depressive symptoms. While pre-admission depressive symptoms were not associated with a greater odds of worse baseline stroke severity (OR 1.02, 95%CI 0.94–1.10), they were associated with a greater odds of poor functional outcome at 1-month after acute stroke (OR 1.09, 95%CI 1.01–1.19).

Discussion

In this global study we recorded that depressive symptoms are an important risk factor for acute stroke, including both ischemic and hemorrhagic stroke. Pre-admission depressive symptoms were associated with poorer functional outcome, but not baseline stroke severity, suggesting an adverse role of depressive symptoms in post-stroke recovery.

我们的研究参与者(N=581，死亡年龄:91.0 ±6.3年;首次饮食评估的平均年龄:84.2岁;73%的女性; 6.8 ± 3.9 years of follow-up) dietary patterns were associated with lower global AD pathology (MIND: β= -0.022, p=0.034, standardized β=-2.0; Mediterranean: β=-0.007, p=0.039, standardized β=-2.3) and specifically less beta-amyloid load (MIND: β=-0.068, p=0.050, standardized β=-2.0; Mediterranean: β=-0.040, p=0.004, standardized β=-2.9). The findings persisted when further adjusted for physical activity, smoking, and vascular disease burden. The associations were also retained when participants with mild cognitive impairment or dementia at the baseline dietary assessment were excluded. Those in the highest tertile of green leafy vegetables intake had less global AD pathology when compared to those in the lowest tertile (Tertile-3 vs. Tertile-1: β= -0.115, p=0.0038).

The MIND and Mediterranean diets are associated with less postmortem AD pathology, primarily beta-amyloid load. Among dietary components, green leafy vegetables inversely correlate with AD pathology.

目的

小血管病变(SVD)和神经炎症均发生在阿尔茨海默病(AD)和其他神经退行性疾病中。目前尚不清楚这些过程在阿尔茨海默病中是相关的还是独立的机制，特别是在疾病的早期阶段。因此，我们研究了白质病变(WML;神经炎症的脑脊液生物标志物及其对无痴呆人群认知的影响(SVD最常见的表现)。

方法

纳入瑞典BioFINDER研究中无痴呆的个体。分析CSF的促炎标志物(白介素[IL] 6、IL-8)、细胞因子(IL-7、IL-15、IL-16)、趋化因子(干扰素诱导蛋白10 [IP-10]、单核细胞趋化蛋白1、血管损伤标志物(可溶性细胞间黏附分子1、可溶性血管黏附分子1)、血管新生标志物(胎盘生长因子[PlGF]、可溶性纤维相关酪氨酸激酶1 [sFlt-1]、血管内皮生长因子[VEGF-A、vegf - d])和a & β;42。a & β;40和P-tau 217。在基线和6年内纵向测定WML体积。在基线和8年的随访中测量认知能力。线性回归模型用于检验相关性。结果

纳入495例认知功能未受损(CU)老年人和247例轻度认知功能障碍(MCI)患者。 There was significant worsening in cognition over time, measured by MMSE, CDR and mPACC in CU and MCI, with more rapid worsening in MCI for all cognitive tests. At baseline, higher levels of PlGF (β=0.156, p<0.001), lower levels of sFlt-1 (β=-0.086, p=0.003), and higher levels of IL-8 (β=0.07, p=0.030) were associated with more WML in CU. In MCI, higher levels of PlGF (β=0.172, p=0.001), IL-16 (β=0.125, p=0.001), IL-8 (β=0.096, p=0.013), IL-6 (β=0.088, p=0.023), VEGF-A (β=0.068, p=0.028), and VEGF-D (β=0.082, p=0.028) were associated with more WML. PlGF was the only biomarker that was associated with WML independent of Aβ status and cognitive impairment. Longitudinal analyses of cognition showed independent effects of CSF inflammatory markers and WML on longitudinal cognition, especially in people without cognitive impairment at baseline.

Discussion

Most neuroinflammatory CSF biomarkers were associated with WML in individuals without dementia. Our findings especially highlight a role for PlGF, which was associated with WML independent of Aβ status and cognitive impairment.

替奈普酶治疗串联性脑卒中患者的安全性和有效性尚不清楚。我们对串联病变患者使用替奈普酶和阿替普酶进行了比较分析。方法:

我们首先比较了tenecteplase和alteplase在串联病变患者中的治疗效果，使用的是EXTEND-IA TNK试验的个体患者数据。我们使用有序逻辑模型和Firth回归模型评估初始血管造影评估和90天mRS时的颅内再灌注。由于在EXTEND-IA TNK试验中接受阿替普酶治疗的患者中，死亡率和症状性颅内出血这两个关键结果很少，因此我们通过对系统评价中确定的研究进行荟萃分析获得的发生率估计来补充试验数据，从而对这些结果进行汇总估计。然后，我们计算未调整的风险差异，以比较接受阿替普酶的患者的汇总估计值与接受替尼替普酶的患者在试验中观察到的发生率。

在EXTEND-IA TNK试验中，483例患者中有71例(15%)具有串联病变。在串联病变患者中，11/56(20%)的替奈普酶治疗患者与1/15(7%)的阿替普酶治疗患者出现颅内再灌注(aOR: 2.19;95%置信区间:0.28—-17.29)。90天mRS差异无统计学意义(经校正的普通OR: 1.48;95% ci: 0.44-5.00)。 A pooled study-level proportion of alteplase associated mortality and symptomatic intracranial hemorrhage was 0.14 (95% CI: 0.08-0.21) and 0.09 (95% CI: 0.04-0.16), respectively. Compared to a mortality rate of 0.09 (95% CI: 0.03-0.20) and a symptomatic intracranial hemorrhage rate of 0.07 (95% CI: 0.02-0.17) in tenecteplase treated patients, no significant difference was observed.

Functional outcomes, mortality, and symptomatic intracranial hemorrhage did not significantly differ between tenecteplase and alteplase treated tandem lesion patients.

This study provides Class III evidence that tenecteplase is associated with similar rates of intracranial reperfusion, functional outcome, mortality, and symptomatic intracranial hemorrhage compared with alteplase, in patients with acute stroke due to tandem lesions. However, the confidence intervals do not rule out clinically important differences.

SPaRCNet在基于校准和判别指标的IIIC事件分类方面匹配或超过大多数专家。对于SZ、LPD、GPD、LRDA、GRDA和“其他”类，SPaRCNet超过了以下20位专家的百分比–Roc: 45%、20%、50%、75%、55%、40%; PRC: 50%, 35%, 50%, 90%, 70%, 45%; and calibration: 95%, 100%, 95%, 100%, 100%, 80%, respectively.

SPaRCNet is the first algorithm to match expert performance in detecting seizures and other seizure-like events in a representative sample of EEGs. With further development, SPaRCNet may thus be a valuable tool for expedited review of EEGs.

评估癫痫发作危重症成人患者癫痫持续状态(SE)的发生频率，探讨重症监护病房(ICU)孤立性癫痫发作患者与SE患者的临床差异。方法:

从2015-2020年，通过筛选所有数字医疗、ICU和脑电图记录，确定瑞士三级保健中心ICU中由重症医师和/或咨询神经科医师报告的所有连续发生的孤立性癫痫发作或SE的成人患者。排除18岁及脑电图无癫痫发作的缺氧缺血性脑病所致肌阵挛患者。孤立性癫痫发作和SE的频率以及癫痫发作时与SE相关的临床特征是主要结局。采用单变量和多变量logistic回归来确定与SE出现的关联。

404例癫痫患者中，51%发生SE。与孤立性癫痫发作患者相比，SE患者的Charlson共病指数(CCI)中位数较低(3比5,p=0.039)，致死性病因较少(43.6%比80.5%，p= 0.001)，格拉斯哥昏迷评分中位数较高(7比5,p= 0.001)，发热频率较高(27.5%比7.5%，p=0.039)，中位数ICU和住院时间较短(ICU: 4比5天，p=0.039;住院时间:13天对15天，p=0.045)，恢复到病前功能的频率更高(36.8%对17%，p= 0.001)。多变量分析显示，随着CCI (OR=0.91, 95%可信区间[CI] 0.83-0.99)、致死性病因(OR=0.15, 95%CI 0.08-0.29)和癫痫(OR=0.32, 95%CI 0.16-0.63)的增加，SE的优势比(OR)降低。在排除癫痫发作患者作为入院ICU的原因后，全身性炎症是与SE的另一个关联(CRP OR _{=1.01, 95%CI 1.00-1.01;OR =7.35, 95%CI)。 While fatal etiologies and increasing CCI remained associated with low odds for SE after excluding anesthetized patients and hypoxic-ischemic encephalopathy, inflammation remained associated in all subgroups except patients with epilepsy.}

Among all ICU patients with seizures, SE emerged frequently and seen in every second patient. Besides the unexpected low odds for SE with higher CCI, fatal etiology, and epilepsy, the association of inflammation with SE in the critically ill without epilepsy represents a potential treatment target and deserves further attention.

我们从ADNI数据库中估计，在0.05水平下，80%的功率测试25%的药物效应对降低CU参与者血浆标志物变化所需的样本量。

共纳入257例CU个体[45.5%男性;平均年龄73(6)岁;32%淀粉样蛋白(a & β;)阳性]。血浆NfL的变化与年龄有关，血浆p-tau181的变化与进展为遗忘性轻度认知障碍有关。与12个月的随访相比，使用p-tau181和NfL的临床试验需要的样本量分别减少85%和63%。利用中间水平A和β的种群富集策略正电子发射断层扫描(Centiloid 20-40)进一步减少了使用p-tau181(73%)和NfL(59%)作为替代的24个月临床试验的样本量。

血浆p-tau181/NfL可用于监测CU个体的大规模人群干预。中级a、β级大学的招生;对于测试药物对血浆p-tau181和NfL变化的影响的试验而言，水平是具有最大效应量和最具成本效益的替代方案。

入选梅奥诊所衰老研究的2239名妇女(中位年龄73岁)，均有病历摘录妊娠信息。每15个月进行9项认知测试。整体认知和特定领域的z分数(记忆，执行/注意，视觉空间，语言)是结果。线性混合效应模型评估妊娠史(所有血压正常，任何HPD, HPD亚型[GH/CH, PE/E]或未分娩)与年龄和教育调整后认知能力下降之间的关系。其他模型调整为APOE、吸烟、高血压、血脂异常、体重指数(BMI)、糖尿病、中风和心脏病。研究了妊娠史与年龄或教育程度对认知能力的影响。

在2,239名妇女中，1,854名(82.8%)至少有一次妊娠(1,607名血压正常，100 GH/CH, 147 PE/E);385例(17.2%)未生育。 Cognitive performance did not cross-sectionally differ for women with a history of any HDP, GH/CH, or PE/E versus women with a history of all normotensive pregnancies; women who were nulliparous had lower global and domain-specific cognition (all p<0.05) in age- and education-adjusted models. There was an interaction (p=0.015) between nulliparity and education such that the lower cognitive performance was most pronounced among nulliparous women with ≤12 years of education (beta = -0.42, p<0.001) versus 12+ years (b = -0.11, p=0.049). Longitudinally, women with any HDP had greater declines in global cognition and attention/executive z-scores compared to women with all normotensive pregnancies. When stratified by HDP type, only women with PE/E had greater declines in global cognition (beta = -0.04, p<0.001), language (beta = -0.03, p=0.001), and attention (beta = -0.04, p<0.001) z-scores. Adjustment for vascular risk factors, BMI, smoking, and APOE did not attenuate results.

Women with a history of HDP, especially PE/E, are at greater risk of cognitive decline in later life.

共纳入29名双语和88名单语TLE患者，并纳入81名年龄匹配的健康对照。在全球范围内，语言状态和癫痫发作侧侧之间的显著相互作用表明，双语者比单语者有更高的网络组织，但仅在左TLE (LTLE)。 Locally, bilinguals with LTLE showed higher efficiency in frontal-executive, but not in perisylvian networks compared to LTLE monolinguals. Improved whole-brain network organization was associated with better executive function performance in bilingual but not monolingual LTLE.

Higher structural network organization in bilingual individuals with LTLE suggests a neuromodulatory effect of bilingualism on whole-brain connectivity in epilepsy, providing evidence for neural reserve. This may reflect attenuation of or compensation for epilepsy-related dysfunction of the left hemisphere, potentially driven by increased efficiency of frontal-executive networks that mediate dual-language control. This highlights a potential role of bilingualism as a protective factor in epilepsy, motivating further research across neurological disorders to define mechanisms and develop interventions.

分析样本包括9,396个人(5,336名女性，4,060名男性)，年龄在50-95岁之间，主要是白人，非西班牙裔美国居民。UPSIT百分位数分别为女性和男性的7个年龄段(50-54岁、55-59岁、60-64岁、65-69岁、70-74岁、75-79岁和80岁)推导并提供;相对于现有的标准，分组参与者的数量增加了2.4-20倍。嗅觉功能随年龄增长而下降，女性优于男性;因此，一个给定的原始分数所对应的百分位数随着年龄和性别的不同而显著变化。 UPSIT performance was comparable among individuals with vs without first-degree family history of PD. Comparisons of self-reported hyposmia vs UPSIT percentiles indicated a strong association (chi-squared P<0.0001), but minimal agreement (Cohen’s simple kappa [95% CI]: = 0.32 [0.28-0.36] for females; 0.34 [0.30-0.38] for males).

Updated age/sex-specific UPSIT percentiles are provided for ≥50-year-old adults who reflect a population likely to be recruited into studies of prodromal neurodegenerative diseases. Our findings highlight the potential advantages of evaluating olfaction relative to age and sex instead of in absolute terms (e.g., based on raw UPSIT scores) or based on subjective (i.e., self-reported) measures. This information addresses the need to support studies of disorders including PD and Alzheimer’s disease by providing updated normative data from a larger sample of older adults.

性激素可能调节三叉神经血管系统中CGRP的释放。我们研究了患有发作性偏头痛(EM)和月经周期正常(RMC)的女性受试者、患有EM和联合口服避孕药(COC)的女性受试者以及绝经后患有EM的女性受试者血浆和泪液中的CGRP浓度。作为对照，我们分析了三组相应的年龄匹配的无EM的女性参与者。

RMC参与者有两次就诊:月经周期第2天及之后;第2天和第13天及以上的排卵期;2.COC患者在第4天及以后接受检查;无激素间隔(HFI)的第2天和激素摄入(HI)的第7-14天。绝经后参与者在随机时间点评估一次。每次就诊时收集血浆和泪液样本，用酶联免疫吸附法测定CGRP水平。

共有180名女性参与者(每组30人)完成了研究。与没有偏头痛的女性参与者相比，偏头痛和RMC参与者在月经期间血浆和泪液中的CGRP浓度在统计学上显着更高[血浆:5.95 pg/ml (IQR 4.37 – 10.44) vs. 4.61 pg/ml (IQR 2.83 – 6.92), p=0.020 (Mann-Whitney U test); tear fluid: 1.20 ng/ml (IQR 0.36 – 2.52) vs. 0.4 ng/ml (IQR 0.14 – 1.22), p=0.005 (Mann-Whitney U test)]. In contrast, female participants with COC and in the postmenopause had similar CGRP levels in the migraine and the control groups. In migraine participants with a RMC, tear fluid but not plasma CGRP concentrations during menstruation were statistically significantly higher compared to migraine participants under COC (p=0.015 vs. HFI and p=0.029 vs. HI, Mann-Whitney U test).

Different sex hormone profiles may influence CGRP concentrations in people, with current or past capacity to menstruate, with migraine. Measurement of CGRP in tear fluid was feasible and warrants further investigation.

使用OTC泻药在一般人群中很常见。微生物群-肠-脑轴假说表明，使用泻药与痴呆有关。我们的目的是检查在英国生物银行参与者中定期使用泻药和痴呆发病率之间的关系。

这项前瞻性队列研究基于英国生物银行参与者，年龄40至69岁，无痴呆史。常规使用泻药被定义为在基线(2006-2010)的最后4周内每周大多数天自我报告使用泻药。结果是全因痴呆、阿尔茨海默病和血管性痴呆，从相关的医院入院或死亡登记中确定(截至2020年)。在多变量Cox回归分析中调整了社会人口统计学特征、生活方式因素、医疗条件、家族史和常规用药情况。

在基线时平均年龄为56.5 (SD=8.1)的502,229名参与者中，273,251名(54.4%)为女性，18,235名(3.6%)报告定期使用泻药。在平均9.8年的随访中，218名(1.3%)经常使用泻药的参与者和1969名(0.4%)不经常使用泻药的参与者患上了全因痴呆。多变量分析显示，经常使用泻药与全因痴呆风险增加相关(风险比[HR] 1.51; 95% confidence interval 1.30-1.75) and vascular dementia (HR 1.65; 1.21-2.27), with no significant association observed for Alzheimer’s disease (HR 1.05; 0.79-1.40). The risk of both all-cause dementia and vascular dementia increased with the number of regularly used laxative types (P-trend 0.001 and 0.04, respectively). Among the participants who clearly reported that they were using just one type of laxative (n=5800), only those using osmotic laxatives showed a statistically significantly higher risk of all-cause dementia (HR 1.64 [1.20-2.24]) and vascular dementia (HR 1.97 [1.04-3.75]). These results remained robust in various subgroup and sensitivity analyses.

Regular use of laxatives was associated with a higher risk of all-cause dementia, particularly in those who used multiple laxative types or osmotic laxative.

该研究纳入了1,179例脑脓肿30天幸存者，其中323例(27%)在中位0.76年后发生新发癫痫(四分位数间距[IQR] 0.24-2.41)。脑脓肿入院时，癫痫患者的中位年龄为46岁(IQR 32-59)，而非癫痫患者的中位年龄为52岁(IQR 33-64)。女性在癫痫患者和非癫痫患者中的比例相似(37%)。脑脓肿抽吸或切除对癫痫的hrr为2.44 (95% CI 1.89-3.15)，酒精滥用为2.37(1.56-3.60)，既往神经外科或头部创伤为1.75(1.27-2.40)，卒中为1.62(1.17-2.25)，20-39岁年龄组为1.55(1.04-2.32)。酒精滥用(52%对31%)、脑脓肿抽吸或切除(41%对20%)、既往神经外科手术或头部创伤(41%对31%)和中风(46%对31%)患者的累积发病率增加。 Analysis using clinical details from medical record review of patients from 2007 through 2016 demonstrated adj. HRRs of 3.70 (2.24-6.13) for seizures at admission for brain abscess and 1.80 (1.04-3.11) for frontal lobe abscess. In contrast, adj. HRR was 0.42 (0.21-0.86) for occipital lobe abscess.

Using the entire registry-based cohort, patients with epilepsy had an adj. MRR of 1.26 (1.01-1.57).

Important risk factors for epilepsy were seizures during admission for brain abscess, neurosurgery, alcoholism, frontal lobe abscess, and stroke. Epilepsy was associated with increased mortality. Anti-epileptic treatment may be guided by individual risk profiles and specialized follow-up is highlighted by increased mortality in survivors with epilepsy.

对45例

的早期ALS患者进行双盲、随机、假对照试验。参与者被随机分为12周的主动rst(30%负荷，n=23)或假rst(0%负荷，n=22)。进行意向治疗分析。以小组地位和前试成绩为预测因子，对前后变化进行线性回归。主要结局包括最大呼气和吸气压(MEP, MIP)，次要结局是咳嗽肺活量测定和用力肺活量。探索性随访结果包括一年的全球和球衰退(ALS功能评定量表-修订版- ALSFRS-R总分和球亚量表斜率)、口服摄入状况和无创通气(NIV)时间。

RST完成率为91%，无RST相关不良事件。12周RST计划导致MEP升高(p=0.004)，但MIP未升高(p=0.33)。主动rst后MEP平均增加20.8 cmH 0 (95% CI: +7.6， +33.9)，假rst后MEP平均下降1.0 cmH 0 (95% CI: -9.1， +7.2)。活跃组和假手术组的平均MIP分别增加了8.9 cmH 0 (95% CI: +1.5， +16.3)和4.8 cmH 0 (95% CI: -0.6， +10.2)。次要结局: RST导致咳嗽峰值吸气流量显著增加(p=0.02)，但不影响咳嗽呼气流量(p= 0.06)或FVC (p=0.60)。 Twelve-Month Outcomes: A significant difference in ALSFRS-R Bulbar subscale slope was observed across treatment groups, with a more than two-fold faster rate of bulbar decline in the sham versus active-RST groups observed (-0.29 vs. -0.12 points/month, p=0.02). Total ALSFRS-R slope, feeding status, and time to NIV did not differ across treatment groups (p >0.05).

RST was well tolerated and led to improvements in some, but not all, short- and long-term outcomes. RST represents a proactive rehabilitative intervention that could increase physiologic capacity of specific breathing and airway clearance functions during the early stages of ALS. Further work is needed to determine optimal training intensity, resistance load specifications, and potential long-term functional outcomes.

我们招募了病理ATXN1或ATXN3扩增和对照的携带者，来自18个美国和两个欧洲的失调转诊中心。突变携带者与对照组的临床、认知、定量运动、神经心理测量和血浆神经丝轻链(NfL)测量进行了比较。

我们招募了200名参与者:45名病理性ATXN1扩展携带者(31名患有失调(中位SARA: 9[7;10])， 14名无失调突变携带者(1[0;2])，116名病理性ATXN3扩展携带者(80名患有失调(7[6;9])，36名无失调突变携带者(1[0;2]))。此外，我们招募了39名对照组，他们没有在ATXN1或ATXN3中携带病理性扩张。尽管平均年龄相似(对照组:5.7 pg/mL, SCA1: 18.0 pg/mL (P<0.0001)， SCA3: 19.8 pg/mL (P<0.0001)，但无失调突变携带者的血浆NfL水平显著高于对照组。无共济失调的突变携带者与对照组相比，上肢运动体征明显增加(SCA1 P=0.0003, SCA3 P=0.003)， SCA3中存在传感器损伤和复视(P分别为0.0448和0.0445)。功能量表、疲劳和抑郁评分、吞咽困难和认知障碍在突变携带者中有共济失调比无共济失调者更差。 Ataxic SCA3 subjects showed extrapyramidal signs, urinary dysfunction and lower motor neuron signs significantly more often than mutation carriers without ataxia.

READISCA showed the feasibility of harmonized data acquisition in a multi-national network. NfL alterations, early sensory ataxia and corticospinal signs were quantifiable between preataxic participants and controls. Patients with ataxia differed in many parameters from controls and mutation carriers without ataxia, with a graded increase of abnormal measures from control to preataxic to ataxic cohorts.

目的

大血管闭塞缺血性卒中的血管内血栓切除术(EVT)既可以在全身麻醉(GA)下进行，也可以采用非全身麻醉技术，如清醒镇静(CS)或局部麻醉(LA)单独进行。先前的小型荟萃分析表明，与非GA技术相比，GA技术具有更高的再通率和改善的功能恢复。进一步的随机对照试验的发表可以为在遗传和非遗传技术之间的选择提供最新的指导。方法

在Medline、Embase和Cochrane Central Register of Controlled trials中对卒中EVT患者随机分为GA组或非GA组的试验进行了系统检索。采用随机效应模型进行系统评价和荟萃分析。

结果

系统评价和荟萃分析共纳入7项rct。这些试验共纳入980名受试者(GA, N=487;non-GA, N = 493)。GA提高了9.0%的再通率(GA为84.6%，非GA为75.6%;OR=1.75, 95% CI 1.26 ~ 2.42, P=0.0009)，功能恢复的患者比例提高了8.4% (GA 44.6% vs非GA 36.2%; OR=1.43, 95% CI 1.04 to 1.98, P=0.03). There was no difference in hemorrhagic complications or 3 month mortality.

Conclusions

In ischemic stroke patients treated with EVT, general anesthesia (GA) is associated with higher recanalization rates and improved functional recovery at 3 months compared with non-GA techniques. Conversion to GA and subsequent intention to treat analysis will underestimate the true therapeutic benefit. GA is established as effective in improving recanalization rates in EVT (7 Class 1 studies) with a high GRADE certainty rating. GA is established as effective in improving functional recovery at 3 months in EVT (5 Class 1 studies) with a moderate GRADE certainty rating. Stroke services need to develop pathways to incorporate GA as the first choice for most endovascular thrombectomy procedures in acute ischemic stroke with a level A recommendation for recanalization and level B recommendation for functional recovery.

这是一项2017-2019年全国医疗保险索赔的回顾性研究。我们根据诊断相关组(DRG)纳入了65岁以上住院的患者，分为以下大类:多发性硬化症和小脑性共济失调[DRG 058-060];中风(061 - 072);退行性神经系统疾病[056-057];癫痫(100 - 101);创伤性昏迷[082-087]和非创伤性昏迷[080-081]。暴露感兴趣的是社区社会经济地位，通过区域剥夺指数(ADI)来衡量，该指数使用社会经济指标，如受教育程度、失业、基础设施获取、收入等来估计人口普查街区群体层面的区域社会经济剥夺。根据ADI百分位数将患者分为高、中、低邻里水平SES。 Adjustment covariates included age, comorbidity burden, race/ethnicity, individual socioeconomic status, and sex.

After exclusions, 905,784 patients were included in the mortality analysis and 915,993 were included in the readmission analysis. After adjustment for age, sex, race/ethnicity, comorbidity burden, and individual socioeconomic status, patients from low SES neighborhoods had higher 30-day mortality rates compared to patients from high SES neighborhoods for all disease categories except for multiple sclerosis: magnitudes of the effect ranged from an adjusted odds ratio (aOR) of 2.46 (95% Confidence Interval [CI] 1.60-3.78) for the non-traumatic coma group to 1.23 (95% CI 1.19-1.28) for the stroke group. After adjustment, no significant differences in readmission rates were observed for any of the groups.

Neighborhood socioeconomic status is strongly associated with 30-day mortality for many common neurological conditions even after accounting for baseline comorbidity burden and individual socioeconomic status. Strategies to improve health equity should explicitly consider the effect of neighborhood environments on health outcomes.

脑白质健康状况可通过mri衍生的微结构指标来评估。白质功能障碍越来越被认为是影响认知和中风后功能结局的神经退行性疾病的一个因素。脑卒中幸存者的脑白质微观结构指数在横切面上比无脑卒中患者有所降低，但脑卒中后脑白质结构的纵向变化在很大程度上仍未被研究。我们的目的是表征脑卒中后3年的白质微观和宏观结构，并研究白质指标和认知功能之间的关系。方法:

将任何血管区域的任何病因的首次或复发性缺血性卒中患者与无卒中年龄和性别匹配的对照组进行比较。那些诊断为出血性中风、短暂性脑缺血发作、静脉梗死、或显著的医学合并症、精神和神经退行性疾病、药物滥用或痴呆史的患者被排除在外。3、12和36个月的弥散加权MRI数据使用纵向“固定”为基础的分析，对体素内纤维束特异性差异敏感。它被用来检查中风患者与对照组相比的全脑白质退化。我们研究了与认知表现有关的纤维密度的微观结构差异和纤维束截面的宏观结构变化。对年龄、颅内容量和教育程度进行控制分析(fwe校正p<0.05，超过5000个排列的非参数检验)。

我们纳入了71名卒中患者(年龄66±12, 22名女性)和36名对照受试者(年龄69±5, 13名女性)。 We observed extensive white matter structural degeneration across the whole brain, particularly affecting the thalamic, cerebellar, striatal, and superior longitudinal tracts, and corpus callosum. Importantly, follow up regression analyses in 72 pre-defined tracts showed that the decline in fiber density and cross-section from 3 months to 3 years was associated with worse cognitive performance at 3 years after stroke, especially affecting visuospatial processing, processing speed, language, and recognition memory.

We conclude that white matter neurodegeneration in ipsi- and contra-lesional- thalamic, striatal and cerebellar tracts continues to be greater in stroke survivors compared to stroke-free controls. White matter degeneration persists even years after stroke and is associated with post-stroke cognitive impairment.

既往研究报道了吡格列酮对2型糖尿病(DM)患者痴呆的保护作用。最近的研究表明，吡格列酮还可以降低原发性和复发性中风的风险。了解患者的特点，特别是与吡格列酮的益处相关的特点，将有助于在常规临床护理中通过指定亚群来个性化使用吡格列酮。本研究的目的是在考虑卒中发生的情况下，研究吡格列酮对痴呆的影响。方法:

使用韩国国民健康保险服务糖尿病队列(2002–2017)的全国糖尿病患者纵向数据，我们研究了吡格列酮使用与新发2型糖尿病患者发生痴呆的关系。采用探索性分析来检验治疗效果的异质性。使用多状态模型，我们评估了意外中风对吡格列酮使用与痴呆之间关系的影响程度。

使用吡格列酮与痴呆风险降低相关(校正风险比(HR) = 0.84, 95% CI, 0.75-0.95);在糖尿病发病前有缺血性心脏病或中风病史的患者中，痴呆的风险降低更大(调整HR = 0.46, 95% CI, 0.24-0.90，调整HR = 0.57, 95% CI, 0.38-0.86)。使用吡格列酮也可降低卒中的发生率(调整后HR = 0.81, 95% CI, 0.66-1.00)。然而，在使用吡格列酮的观察期内发生卒中时，未观察到痴呆风险降低(调整后HR = 1.27, 95% CI, 0.80-2.04)。

Pioglitazone use is associated with a lower risk of dementia in DM patients, particularly in those with a history of stroke or ischemic heart disease, suggesting the possibility of applying a personalized approach when choosing pioglitazone to suppress dementia in DM patients.

我们纳入了连续的CCM患者。在长达5年的前瞻性随访中，我们通过多变量Cox比例风险回归比较了女性激素治疗与CCM所致颅内出血发生率之间的关系。我们通过Ovid MEDLINE和EMBASE进行了另外一项系统回顾，从开始到2021年11月2日，以确定比较研究，并根据女性激素治疗的使用评估其颅内出血发生率比。

在722例诊断为脑海绵状血管瘤时年龄≥10岁的女性患者中，有137例在随访期间任一时间点使用了女性激素治疗。女性激素治疗的使用(根据年龄、表现方式和CCM位置调整)与随后颅内出血的风险增加相关(46/137 [33·6%]对91/585 [15·6%]，调整后的风险比为1·56, 95% CI为1·09至2·24;p = 0压力;015)。经相同因素校正后，10-44岁女性患者口服避孕药的使用与随后颅内出血的高风险相关(校正风险比2 - 00,95% CI 1 - 26-3 - 17;p = 0压力;003)。我们系统的文献检索显示，没有研究报道女性激素治疗对随访期间颅内出血风险的影响。

女性激素治疗与脑海绵状畸形颅内出血的高风险相关。 These findings raise questions about the safety of female hormone therapy in clinical practice in patients with cerebral cavernous malformation. Further studies evaluating clinical factors raising risk of thrombosis may be useful to determine which patients may be most susceptible to intracranial hemorrhage.

This study provides Class III evidence that female hormone therapy increased the risk of intracranial hemorrhage in patients with CCM.

在277名被诊断为PCNST的参与者中，57%为男性，43%为女性。参与者报告他们的种族是白人，非西班牙裔(78%);白人、西班牙裔/拉丁裔(9%);亚洲(7%);黑色(4%);夏威夷原住民/太平洋岛民(1%); other (2%) with 8% missing. The median age of the overall cohort was 45 years (range 18-74). Hispanic participants in the overall sample were 2.3 times more likely, and in the brain tumor group 3.2 times more likely, to report unemployment (p=.043, OR=2.3, 95% CI [1.0, 5.4] and p=.008, OR=3.2, 95% CI [1.3, 7.9], respectively). The 77 (28%) individuals unemployed due to tumor reported more functional impairment with walking, washing, dressing, performing usual activities, and reduced HRQOL (p<.001). More unemployed participants in the total sample reported moderate-to-severe depressive symptoms (25%) than those employed (8%) (X²(1)=13.9, p<.001, OR=3.7, 95% CI [1.8, 7.8]) and more moderate-to-severe anxiety symptoms (30%) than those employed (15%) (X²(1)=7.8, p=.005, OR=2.4, 95% CI [1.3, 4.5]). Unemployed brain tumor participants reported on average 3 more symptoms as moderate-to-severe compared to those employed (t(83)=-4.0, 95% CI _difference [-5, -2], p<.001, Hedge’s g=.70).

Being unemployed due to a PCNST strongly correlated with high symptom burden, functional impairment, psychological distress and reduced HRQOL which may be impediments to returning to work that warrant intervention. Lack of employer-based health insurance and reduced earnings are financial sequelae of unemployment superimposed on the physical, social, and cognitive effects of living with a PCNST. Innovations to screen for and address financial toxicity and its contributing factors are needed.

在对遗传性DEE患者的回顾性分析中，我们估计了CSE、NCSE和SUDEP的比例以及每种遗传诊断的总体死亡率和SUDEP特异性死亡率。我们纳入了以下基因致病性变异的患者:SCN1A、SCN2A、SCN8A、SYNGAP1、NEXMIF、CHD2、PCDH19、STXBP1、GRIN2A、KCNT1、KCNQ2和Angelman综合征(AS)。

该队列包括510例遗传性DEE患者;其中CSE占47%，NCSE占19%。SCN1A相关dee患者发生CSE的比例最高，包括181/203 (89%;95%CI 84-93%)为Dravet综合征患者，8/15 (53%;95%CI 27-79%) non- draft SCN1A- des。 CSE was also notable in patients with pathogenic variants in KCNT1 (6/10; 60%; 95%CI 26-88%) and SCN2A (8/15; 53%; 95%CI 27-79%). NCSE was common in patients with non-Dravet SCN1A-DEEs (8/15; 53%; 95%CI 27-79%) and was notable in patients with CHD2-DEEs(6/14; 43%; 95%CI 18-71%) and AS (6/19; 32%; 95%CI 13-57%). There were 42/510 (8%) deaths amongst the cohort, producing a mortality rate of 6.1 per 1000 person years (95% CI 4.4 – 8.3). SUDEP cases accounted for 20/42 (48%) deaths. Four genes were associated with SUDEP: SCN1A, SCN2A, SCN8A and STXBP1. The estimated SUDEP rate was 2.9 per 1000 person years (95% CI 1.7 – 4.5).

We showed that proportions of patients with CSE, NCSE and SUDEP differ for commonly encountered genetic DEEs. The estimates for each genetic DEE studied will inform early diagnosis and management of status epilepticus and SUDEP and inform disease-specific counselling for patients and families in this high-risk group of conditions.

动脉瘤性蛛网膜下腔出血(aSAH)研究中预后指标的报道存在显著的异质性。改良Rankin量表(mRS)是最常报道的功能结果测量。mRS侧重于身体残疾，然而许多aSAH幸存者在其他领域经历了后遗症，因此mRS可能没有捕捉到对aSAH幸存者重要的结果。本研究的目的是评估mRS作为研究结果衡量的临床相关性。方法:

我们对355名aSAH幸存者、家庭成员和护理人员进行了一项国际横断面调查，以评估患者对mRS的感知结果。mRS使用先前验证的基于网络的工具进行评估。< / p > < /秒> <秒> <圣>结果:圣> < / p > <响应率为60%;来自七大洲的受访者包括86%的aSAH幸存者和14%的家庭成员/照顾者。自我评估结果与mRS之间的一致性较差(Kappa 0.26 (CI 0.14-0.39))。在172名自我评估为aSAH预后良好的受访者中，122名(71%)的mRS评分为0-2分，19%的受访者根据测量的mRS评分为0-2分，结果良好，自我评估为aSAH预后较差。当mRS评分被二分类为0-3表示预后良好时，评分与自评结果之间的一致性仍然很差，Kappa评分为0.40 (CI 0.20-0.60)。30%的回答者认为mRS不应作为未来aSAH试验的结果衡量标准。

The findings suggest that there is poor agreement between aSAH survivors’ self-assessed outcome, their actual mRS score and the dichotomization of the mRS score into good/poor outcomes. Patient-centered and -informed outcome measurement tools are needed to guide the aSAH research agenda.

一项前瞻性队列研究(IIH Life)在2012-2021年间招募了连续的IIH患者，评估结果包括:视力(LogMAR视力;汉弗莱视野周界平均偏差;光学相干断层扫描(OCT)成像)和头痛。评估了四个队列:怀孕期间首次诊断为IIH的患者;已确诊的IIH孕妇;诊断为IIH前已怀孕者;以及那些患有IIH但从未怀孕的人。

377 people with IIH agreed to participate in the IIH Life maternal health study. Mean follow up was 17.5 months (standard deviation (SD) 20.5). IIH diagnosed in pregnancy was rare. Patients diagnosed with IIH whilst pregnant had greater papilloedema (mean OCT total retinal thickness +11.59 µm/month (95% CI: 1.25, 21.93)), although they had comparable visual field and acuity measures compared to those with established IIH who became pregnant during their disease course (-1.2 µm/month (95% CI: -2.6, 0.21)). In those with established IIH, pregnancy did not adversely affect visual or headache outcomes over time and the trajectory was akin to those with IIH that never had a pregnancy. Headache outcomes showed variability reflecting the IIH cohort as a whole.

A diagnosis of IIH whilst pregnant was rare but associated with more severe papilloedema. Long term visual outcomes in IIH were analogous irrespective of the timing of the pregnancy. This data is reassuring however close vigilance of IIH clinical features during pregnancy is recommended.

在本队列研究中，参与者进行了详细的神经学检查、电生理、IENFD量化、CCM和定量感觉测试。DPN的定义依据多伦多糖尿病神经病变标准(不依赖于IENFD和热阈值)。

共纳入214例至少可能患有DPN的患者，63例无DPN的患者和97例无糖尿病的对照组。DPN患者的CCM指标(角膜神经纤维长度(CNFL)、神经纤维密度和分支密度)、IENFD、CDT和WDT均低于无DPN患者(p=<0.001， <0.001, 0.002, p<0.001, p=0.003和<0.005)，而对照组与无DPN的糖尿病患者之间无差异。所有三种CCM方法的诊断敏感性都很低，其中CNFL的诊断敏感性最高(14.4% (95% CI 9.8;18.4))，特异性为95.7%(88.0;99.1)。 In comparison, the sensitivity of abnormal CDT and/or WDT was 30.5% (24.4;37.0) with a specificity of 84.9% (74.6;92.2). The sensitivity of abnormal IENFD was highest among all measures with a value of 51.1% (43.7;58.5) and a specificity of 90% (79.5;96.2). CCM measures did not correlate with IENFD, CDT/WDT or neuropathy severity in the group of patients with DPN.

CCM measures showed the lowest sensitivity compared to other small fiber measures, in the diagnosis of DPN. This indicates that CCM is not a sensitive method to detect DPN in recently diagnosed type 2 diabetes.

This study provides Class III evidence that CCM measures aid in the detection of diabetic polyneuropathy in recently diagnosed type 2 diabetics, but with a low sensitivity when compared to other small fiber measures.

在美国，由于阿片类药物的流行，感染性心内膜炎相关卒中(IERS)的发病率正在上升。了解阿片类药物流行对IERS临床特征的影响，有必要进行当代流行病学描述。我们描述并分析了IERS的人口统计学趋势、危险因素和临床特征。

这是一项在大辛辛那提/北肯塔基地区130万双种族人群中进行的回顾性队列研究。使用ICD-9和-10代码对2005年、2010年和2015年的所有出血性或缺血性卒中住院患者进行识别和医生验证。IERS被定义为感染性心内膜炎引起的急性中风，符合可能或明确心内膜炎的修订Duke标准。在每个研究期间对IERS和non-IERS进行未经调整的人口统计学、危险因素、结局和临床特征的比较。比较趋势的调整模型对分类变量使用Cochran-Armitage检验，对数值变量使用一般线性模型或Kruskal-Wallis检验。使用一般线性或逻辑模型检查心内膜炎状态在趋势中的相互作用。

研究期间共发现54例ier患者和8204例非ier患者。 Between 2005 and 2015, there was a decline in rates of hypertension (91.7% vs 36.0%; p=0.0005) and increased intravenous drug users (IVDU) (8.3% vs 44.0%; p=0.02) in the IERS cohort. The remainder of the stroke population demonstrated a significant rise in hypertension, diabetes, atrial fibrillation, and peri-operative stroke. Infective endocarditis status significantly interacted with the trend in hypertension prevalence (p=0.001).

From 2005 to 2015, infective endocarditis-related stroke was increasingly associated with intravenous drug use and fewer risk factors, specifically hypertension. These trends likely reflect the demographics of the opioid epidemic, which has affected younger patients with fewer comorbidities.

Non-standard Abbreviations and Acronyms

infective endocarditis-related stroke; IVDU: intravenous drug users; GCNKSS: Greater Cincinnati Northern Kentucky Stroke Study; NIHSS: National Institute of Health Stroke Scale; tPA: tissue plasminogen activator

从六个真实世界/自然史数据源(UZ Leuven，由CureDuchenne、iMDEX、North Star UK、Cincinnati Children&rsquo ' s Hospital Medical Center和DMD意大利组共享的prod -DMD-01)中研究了超过1600例患者年的随访(>700例患者)，基因型分为可跳过外显子44、45、51或53，其他可跳过的，无意义的和其他突变。在每个数据源中研究基因型类别与1年内North Star动态评估总分(NSAA)和10米步行/跑步速度(10MWR)变化之间的关系，无论是否调整基线预后因素。

研究的基因型类别约占12个月后NSAA结果变化的2%，而在大型数据源中，其他预后因素解释了30%的变化。基于对所有数据源的荟萃分析，所研究的可忽略突变类别的综合效应估计值都很小(1年随访中NSAA总分为2个单位)，小于NSAA的临床重要差异，并且在调整非基因型预后因素后，以1个单位的标准误差精确估计。讨论:

这些发现表明，在长达12个月的运动功能结局中，纳入基因典型混合或不匹配对照的试验设计的可行性，这将缓解招募挑战并减少分配给安慰剂的患者数量。这些试验设计，包括多基因型平台试验和混合设计，应确保治疗组和对照组之间最重要的预后因素的基线平衡，同时考虑到本研究中量化的少量剩余基因型效应。

多种生殖因素与卒中相关。生殖生命过程中生殖因素对脑卒中及其亚型的累积影响尚不清楚，特别是在中国女性中。

评估中国绝经后女性因生殖因素导致的终生累计雌激素暴露与卒中及其病因亚型的关系。

来自中国嘉里生物库(CKB)研究，选择基线时无卒中史的绝经后女性(2004-2008)。使用三个复合指标评估生殖因素导致的终生累积雌激素暴露:生殖寿命(RLS)、内源性雌激素暴露(EEE)和总雌激素暴露(TEE)。卒中及其亚型，缺血性卒中(IS)，脑出血(ICH)和蛛网膜下腔出血(SAH)，在随访期间(2004-2015)通过与疾病登记系统和健康保险数据的联系确定。采用多变量校正Cox比例风险回归模型，分别以RLS、EEE和TEE的四分位数估计卒中风险的校正风险比(aHR)和95%置信区间(CI)。

共纳入122,939名绝经后受试者，年龄40至79岁，基线时无卒中史。在中位8.9年的随访期间，确定了15,139例新发卒中病例，包括12,853例IS, 2,580例ICH和269例SAH。与RLS的最低四分位数(Q1)相比，最高四分位数(Q4)的总卒中风险(aHR: 0.95, 95% CI: 0.92-0.98)、IS (aHR: 0.95, 95% CI: 0.92-0.98)和ICH (aHR: 0.87, 95% CI: 0.81-0.94)较低。EEE和TEE与随后的总卒中风险下降呈分级相关(Q4 vs Q1的aHR: EEE: 0.85, 95% CI: 0.82-0.89;TEE: 0.87, 95% CI: 0.84-0.90)， IS (Q4 vs Q1的aHR: EEE: 0.86, 95% CI: 0.83-0.90; TEE: 0.86, 95% CI: 0.83-0.89), and ICH (EEE: 0.73, 95% CI: 0.65-0.81; TEE: 0.83,95% CI: 0.76-0.91), with a P-trend<0.001 for all of these associations.

Patients’ cumulative estrogen exposure due to reproductive factors could potentially be a valuable indicator for risk stratification of stroke events following menopause.

在2143例符合条件的患者中，340例有责任ICAS, 1803例没有。替格瑞洛-阿司匹林降低了所有SSSI患者的卒中复发(HR: 0.54; 95% CI: 0.38-0.79; P=0.001) compared to clopidogrel-aspirin. Stroke recurrence occurred in 35/901 (3.9%) patients with SSSI-ICAS on ticagrelor-aspirin and in 72/902 (8.0%) on clopidogrel-aspirin (HR: 0.45; 95% CI: 0.29-0.68; P<0.001). In patients with SSSI+ICAS, the corresponding event rates were 14/176 (8.2%) and 13/164 (7.9%), respectively (HR: 1.20; 95% CI: 0.45-3.23; P=0.71; P for interaction=0.08). The risk of moderate to severe bleeding only occurred in SSSI-ICAS patients (5/901 [0.6%] vs. 5/902 [0.6%]).

In this prespecified substudy, ticagrelor-aspirin was superior to clopidogrel-aspirin in reducing the risk of stroke at 90 days among SSSI patients who carried CYP2C19 LOF allele(s). Although there was no treatment-by-heterogeneous etiology interaction, a greater absolute risk reduction of stroke was observed in patients with SSSI-ICAS than in those with SSSI+ICAS.

我们在英国生物银行进行了一项研究，评估欧洲血统的缺血性或出血性中风幸存者。为了模拟PSH，我们使用732个遗传变异创建了收缩压和舒张压的多基因评分(PRS)。我们将PRSs分为五分之一，并使用线性/逻辑回归来检验PSH升高是否会导致观察到的血压升高、未控制的血压升高(收缩压140 mmHg或舒张压90 mmHg)和耐药血压升高(尽管服用了3种降压药，但未控制的血压)。我们使用维生素干预预防中风(VISP)试验的数据进行了独立的重复研究。

我们分析了5,940名中风幸存者。当比较PSH非常低和非常高的中风幸存者时，平均收缩压为137 (SD 18)对143 (SD 20, p<0.001)，平均舒张压为81 (SD 10)对84 (SD 11, p<0001)，血压不受控制的患病率为42.8%对57.2% (p<0.001)，难治性高血压患病率为3.9%对11% (p<0.001)。使用多变量模型(p<0.001)，结果仍然显著，并在VISP研究中得到重复(所有试验均采用p<0.05)。

高PSH与卒中幸存者较差的血压控制相关。这些发现表明遗传易感性是该人群血压控制不良的重要决定因素 阿科斯塔，J.， Both, C. P.， Demarais, Z. S.， Conlon, C. J.， leure, A.， Torres-Lopez, V. M.， de Havenon, A.， Petersen, n.h.， Gill, t.m.， Sansing, L. H.， Sheth, k.n.， Falcone, G. J。 2023 - 01 - 23 - t12:45:25喂饲 信息:doi 10.1212 / / WNL.0000000000206763 hwp: master-id半岛投注体育官网:神经病学;WNL.0000000000206763 美国神经病学学会半岛投注体育官网 所有脑血管疾病/中风，队列研究，脑出血，蛛网膜下腔出血，所有遗传学 卒中幸存者高血压多基因易感性和血压控制 2023-01-23 半岛体育app苹果下载 hw_mjid:半岛投注体育官网神经病学;WNL.0000000000206763v1 http://n.半岛投注体育官网neurology.org/cgi/content/short/WNL.0000000000206899v1?rss=1 乔治吉斯，m.k.，安德森，c.d.。 2023 - 01 - 23 - t12:45:25喂饲 信息:doi 10.1212 / / WNL.0000000000206899 hwp: master-id半岛投注体育官网:神经病学;WNL.0000000000206899 美国神经病学学会半岛投注体育官网 丛集性头痛 多基因风险评分在临床:一个中风幸存者的案例 2023-01-23 社论 hw_mjid:半岛投注体育官网神经病学;WNL.0000000000206899v1 http://n.半岛投注体育官网neurology.org/cgi/content/short/WNL.0000000000206824v1?rss=1 虽然脱髓鞘是纵向广泛性脊髓病最常见的病因，但认识其他原因也很重要。在这里，我们提出一个病例纵向宫颈病变与一个非常罕见的原因。我们讨论了纵向脊髓病的鉴别诊断和检查方法。本临床推理病例也说明了症状性脊髓病变与非症状性颅内病因的解剖关系 陆，H，马，y -j。，刘，H，李，H - f。 2023 - 01 - 23 - t12:45:25喂饲 信息:doi 10.1212 / / WNL.0000000000206824 hwp: master-id半岛投注体育官网:神经病学;WNL.0000000000206824 美国神经病学学会半岛投注体育官网 MRI，全脊髓，动静脉畸形，脑静脉血栓形成 临床理由:一个49岁的女性孤立窦性颅内硬脑膜动静脉瘘伴髓周引流 2023-01-23 居民,amp;音箱;的部分 hw_mjid:半岛投注体育官网神经病学;WNL.0000000000206824v1 http://n.半岛投注体育官网neurology.org/cgi/content/short/WNL.0000000000206826v1?rss=1 背景/目的:

疾病修饰剂(DMAs)治疗脊髓性肌萎缩症(SMA)已进化成SMA表型并提高了生存率。持续口咽吞咽困难和呼吸并发症的报道。在这个人群中，吞咽困难和呼吸道疾病的程度，自从dma引入以来，还没有很好的描述。

一项全人群研究涉及我们医院治疗的所有1-3型SMA儿童。收集了影像透视吞咽研究([VFSS] 1型)、胸部计算机断层扫描(CT胸部)扫描和临床资料。

纳入36例患儿(1型9例，2型14例，3型13例;年龄范围0.3-15.4岁)。所有1型患儿均表现出异常吞咽特征(n=8;100%)。胸部CT显示支气管扩张:1、2、3型9例中3例(33.3%)，14例中2例(14.3%)，13例中2例(15.4%)。肺不张、粘液堵塞、支气管壁增厚和实质改变是常见的。

Swallow impairments were universal in children with type 1. Bronchiectasis was common in all paediatric SMA types, with a prevalence of 1 in 5. Routine monitoring and management of dysphagia/ recurrent respiratory infection should be implemented for improvement in lung health.

我们研究了31例MSA患者和54例根据目前临床共识标准诊断的PD患者。我们还纳入了24个匹配的对照。所有参与者都在三个部位进行了神经系统检查、自主神经测试和皮肤活检。测定表皮内神经纤维、支配运动神经纤维和支配运动神经纤维密度。定量测定α -突触核蛋白磷酸化的沉积。结果与临床评分评估和自主神经功能测试结果进行比较。

PD患者与MSA患者相比神经纤维密度降低(P<0.05，所有纤维类型)。 All patients with MSA and 51/54 with PD had evidence of phosphorylated alpha-synuclein in at least one skin biopsy. No phosphorylated alpha-synuclein was detected in controls. Patients with MSA had greater phosphorylated alpha-synuclein deposition (P<0.0001) and more widespread peripheral distribution (P<0.0001) than patients with PD. These results provided >90% sensitivity and specificity in distinguishing between the two disorders.

Alpha-synuclein is present in peripheral autonomic nerves of MSA patients, and when combined with synuclein distribution, accurately distinguishes MSA from PD.

This study provides Class II evidence that measurement of phosphorylated alpha-synuclein in skin biopsies can differentiate patients with MSA from those with PD.

本前瞻性分析包括来自18家机构的30名接受亚专科临床神经生理学培训的专家。专家独立地对不同数量的10秒脑电图片段进行评分:“癫痫发作(SZ)”、“侧化周期性放电(LPD)”、“广义周期性放电(GPD)”、“侧化节律性三角洲活动(LRDA)”、“广义节律性三角洲活动(GRDA)”或“其他”。2006年至2020年在马萨诸塞州总医院为临床适应症进行脑电图检查。主要结果测量指标为每个类别的两两IRR(专家对之间的平均百分比同意(PA))和多数IRR(小组共识的平均PA);并且偶然达成一致()。次要结果是专家评分与群体共识的校准，以及潜在特质分析，以调查偏差和噪音对评分变异性的贡献。

在2,711例脑电图中，49%来自女性，中位(IQR)年龄为55岁(41岁)。专家共评分50697个EEG片段; the median [range] number scored by each expert was 6,287.5 [1,002, 45,267]. Overall pairwise IRR was moderate (PA 52%, 42%), and majority IRR was substantial (PA 65%, 61%). Noise-bias analysis demonstrated that a single underlying receiver operating curve can account for most variation in experts' false positive vs true positive characteristics (median [range] of variance explained (R²): 95 [93, 98]%), and for most variation in experts’ precision vs sensitivity characteristics (R²: 75 [59, 89]%). Thus, variation between experts is mostly attributable not to differences in expertise, but rather to variation in decision thresholds.

Our results provide precise estimates of expert reliability from a large and diverse sample, and a parsimonious theory to explain the origin of disagreements between experts. The results also establish a standard for how well an automated IIIC classifier must perform to match experts.

This study provides Class II evidence that independent expert review reliably identifies ictal-interictal injury continuum patterns on EEG compared to expert consensus.