Annals of Neurology最新文献_第9页

Cerebrovascular Function in Sporadic and Genetic Cerebral Small Vessel Disease 散发性和遗传性脑小血管病的脑血管功能

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology

Pub Date : 2024-11-18 DOI: 10.1002/ana.27136

Michael S. Stringer PhD, Gordon W. Blair PhD, Anna Kopczak MD, Danielle Kerkhofs PhD, Michael J. Thrippleton PhD, Francesca M. Chappell PhD, Susana Muñoz Maniega PhD, Rosalind Brown PhD, Kirsten Shuler PhD, Iona Hamilton BSc, Daniela Jaime Garcia MSc, Fergus N. Doubal PhD, Una Clancy PhD, Eleni Sakka MSc, Tetiana Poliakova MSc, Esther Janssen PhD, Marco Duering MD, Michael Ingrisch PhD, Julie Staals PhD, Walter H. Backes PhD, Robert van Oostenbrugge PhD, Geert Jan Biessels PhD, Martin Dichgans MD, Joanna M. Wardlaw MD, The SVDs@target consortium

Objective

Cerebral small vessel diseases (SVDs) are associated with cerebrovascular dysfunction, such as increased blood–brain barrier leakage (permeability surface area product), vascular pulsatility, and decreased cerebrovascular reactivity (CVR). No studies assessed all 3 functions concurrently. We assessed 3 key vascular functions in sporadic and genetic SVD to determine associations with SVD severity, subtype, and interrelations.

Methods

In this prospective, cross-sectional, multicenter INVESTIGATE-SVDs study, we acquired brain magnetic resonance imaging in patients with sporadic SVD/cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), including structural, quantitative microstructural, permeability surface area product, blood plasma volume fraction, vascular pulsatility, and CVR (in response to CO₂) scans. We determined vascular function and white matter hyperintensity (WMH) associations, using covariate-adjusted linear regression; normal-appearing white matter and WMH differences, interrelationships between vascular functions, using linear mixed models; and major sources of variance using principal component analyses.

Results

We recruited 77 patients (45 sporadic/32 CADASIL) at 3 sites. In adjusted analyses, patients with worse WMH had lower CVR (B = −1.78, 95% CI −3.30, −0.27) and blood plasma volume fraction (B = −0.594, 95% CI −0.987, −0.202). CVR was worse in WMH than normal-appearing white matter (eg, CVR: B = −0.048, 95% CI −0.079, −0.017). Adjusting for WMH severity, SVD subtype had minimal influence on vascular function (eg, CVR in CADASIL vs sporadic: B = 0.0169, 95% CI −0.0247, 0.0584). Different vascular function mechanisms were not generally interrelated (eg, permeability surface area product~CVR: B = −0.85, 95% CI −4.72, 3.02). Principal component analyses identified WMH volume/quantitative microstructural metrics explained most variance in CADASIL and arterial pulsatility in sporadic SVD, but similar main variance sources.

Interpretation

Vascular function was worse with higher WMH, and in WMH than normal-appearing white matter. Sporadic SVD-CADASIL differences largely reflect disease severity. Limited vascular function interrelations may suggest disease stage-specific differences. ANN NEUROL 2025;97:483–498

目的：脑小血管疾病（SVD）与脑血管功能障碍有关，如血脑屏障渗漏（通透性表面积乘积）增加、血管搏动性和脑血管反应性（CVR）降低。目前还没有研究同时评估这三种功能。我们评估了散发性和遗传性 SVD 的 3 种关键血管功能，以确定与 SVD 严重程度、亚型和相互关系的关联：在这项前瞻性、横断面、多中心 INVESTIGATE-SVDs 研究中，我们采集了散发性 SVD/大脑常染色体显性动脉病伴皮层下梗死和白质脑病（CADASIL）患者的脑磁共振成像，包括结构、定量微结构、通透性表面积乘积、血浆容量分数、血管搏动性和 CVR（对二氧化碳的反应）扫描。我们使用协变量调整线性回归法确定血管功能与白质高密度（WMH）的关联；使用线性混合模型确定正常外观白质与 WMH 的差异、血管功能之间的相互关系；使用主成分分析确定主要的变异来源：我们在 3 个地点招募了 77 名患者（45 名散发性患者/32 名 CADASIL 患者）。在调整分析中，WMH 较差的患者 CVR（B = -1.78, 95% CI -3.30, -0.27）和血浆容积分数（B = -0.594, 95% CI -0.987, -0.202）较低。WMH 中的 CVR 比正常外观白质中的 CVR 更差（例如，CVR：B = -0.048，95% CI -0.079，-0.017）。调整 WMH 严重程度后，SVD 亚型对血管功能的影响微乎其微（例如，CADASIL 与散发性的 CVR：B = 0.0169，95% CI -0.0247，0.0584）。不同的血管功能机制一般没有相互关联（例如，渗透性表面积乘积~CVR：B = -0.85，95% CI -4.72，3.02）。主成分分析发现，WMH体积/定量微结构指标解释了CADASIL和散发性SVD中动脉搏动性的大部分变异，但主要变异来源相似：WMH越高，血管功能越差，WMH高于正常白质。散发性SVD与CADASIL的差异在很大程度上反映了疾病的严重程度。有限的血管功能相互关系可能表明疾病的阶段性差异。ann neurol 2024.

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引用次数: 0

Micro-Doses of DNP Preserve Motor and Muscle Function with a Period of Functional Recovery in Amyotrophic Lateral Sclerosis Mice 微剂量 DNP 可保护肌萎缩侧索硬化症小鼠的运动和肌肉功能，并有一段时间的功能恢复期。

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology

Pub Date : 2024-11-18 DOI: 10.1002/ana.27140

Renjia Zhong MD, PhD, Demi L.A. Dionela BS, Nina Haeyeon Kim MS, Erin N. Harris BS, John G. Geisler PhD, Lan Wei-LaPierre PhD

Objective

Mitochondrial dysfunction is one of the earliest pathological events observed in amyotrophic lateral sclerosis (ALS). The aim of this study is to evaluate the therapeutic efficacy of 2,4-dinitrophenol (DNP), a mild mitochondrial uncoupler, in an ALS mouse model to provide preclinical proof-of-concept evidence of using DNP as a potential therapeutic drug for ALS.

Methods

hSOD1^G93A mice were treated with 0.5–1.0 mg/kg DNP through daily oral gavage from presymptomatic stage or disease onset until 18 weeks old. Longitudinal behavioral studies were performed weekly or biweekly from 6 to 18 weeks old. In situ muscle contraction measurements in extensor digitorum longus muscles were conducted to evaluate the preservation of contractile force and motor unit numbers in hSOD1^G93A mice following DNP treatment. Muscle innervation and inflammatory markers were assessed using immunostaining. Extent of protein oxidation and activation of Akt pathway were also examined.

Results

DNP delayed disease onset; improved motor coordination and muscle performance in vivo; preserved muscle contractile function, neuromuscular junction morphology, and muscle innervation; and reduced inflammation and protein oxidation at 18 weeks old in hSOD1^G93A mice. Strikingly, symptomatic hSOD1^G93A mice exhibited a period of recovery in running ability at 20 cm/s several weeks after 2,4-dinitrophenol treatment started at disease onset, offering the first observation in disease phenotype reversal using a small molecule.

Interpretation

Our results strongly support that micro-dose DNP may be used as a potential novel treatment for ALS patients, with a possibility for recovery, when used at optimal doses and time of intervention. ANN NEUROL 2025;97:542–557

目的：线粒体功能障碍是肌萎缩性脊髓侧索硬化症（ALS）最早出现的病理现象之一。本研究旨在评估 2,4-二硝基苯酚（DNP）（一种温和的线粒体解偶联剂）在 ALS 小鼠模型中的疗效，为使用 DNP 作为 ALS 的潜在治疗药物提供临床前概念证明。从 6 到 18 周龄期间，每周或每两周进行一次纵向行为研究。对拇长伸肌进行原位肌肉收缩测量，以评估 DNP 治疗后 hSOD1G93A 小鼠收缩力和运动单位数量的保存情况。使用免疫染色法评估了肌肉神经支配和炎症标记物。此外，还检测了蛋白质氧化程度和 Akt 通路的激活情况：结果：DNP能延缓发病；改善体内运动协调性和肌肉表现；保护肌肉收缩功能、神经肌肉接头形态和肌肉神经支配；并能减少 hSOD1G93A 小鼠 18 周龄时的炎症和蛋白质氧化。令人震惊的是，有症状的 hSOD1G93A 小鼠在发病时开始接受 2,4-二硝基酚治疗数周后，表现出 20 厘米/秒的跑步能力恢复期，这是首次观察到使用小分子药物逆转疾病表型的情况：我们的研究结果有力地证明，微剂量 DNP 可作为 ALS 患者的一种潜在新型治疗方法，在最佳剂量和干预时间内使用，患者有可能康复。ann neurol 2024.

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引用次数: 0

Elevated Cerebrospinal Fluid Ubiquitin Carboxyl-Terminal Hydrolase Isozyme L1 in Asymptomatic C9orf72 Hexanucleotide Repeat Expansion Carriers 无症状的 C9orf72 六核苷酸重复扩增携带者脑脊液泛素羧基末端水解酶同工酶 L1 升高

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology

Pub Date : 2024-11-16 DOI: 10.1002/ana.27133

Elizabeth R. Dellar DPhil, Iolanda Vendrell PhD, Benazir Amein MSc, David G. Lester MBBS, Evan C. Edmond DPhil, Katie Yoganathan MB, BCh, Thanuja Dharmadasa PhD, Aitana Sogorb-Esteve PhD, Roman Fischer PhD, Kevin Talbot DPhil, Jonathan D. Rohrer PhD, Martin R. Turner PhD, Alexander G. Thompson DPhil

Objective

To identify biochemical changes in individuals at higher risk of developing amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) via C9orf72 hexanucleotide repeat expansion (HRE) heterozygosity.

Methods

Cross-sectional observational study of 48 asymptomatic C9orf72 HRE carriers, 39 asymptomatic non-carrier controls, 19 people with sporadic ALS, 10 with C9orf72 ALS, 14 with sporadic FTD, and 10 with C9orf72 FTD. Relative abundance of 30 pre-defined cerebrospinal fluid biomarkers of ALS and FTD were compared in asymptomatic C9orf72 HRE carriers and age-matched non-carrier controls. Differential abundance of these proteins was quantified using data independent acquisition mass spectrometry or electro chemiluminescent assay for neurofilament light chain. Unbiased analysis of the entire cerebrospinal fluid proteome was then carried out.

Results

Ubiquitin carboxyl-hydrolase isozyme L1 levels were higher in asymptomatic C9orf72 HRE carriers compared with age-matched non-carriers (log₂fold change 0.20, FDR-adjusted p-value = 0.034), whereas neurofilament light chain levels did not significantly differ. Ubiquitin carboxyl-hydrolase isozyme L1 levels remained elevated after matching of groups by neurofilament levels (p = 0.011), and after adjusting for age, sex, and neurofilament levels. A significant difference was also observed when restricting analysis to younger participants (<37) matched by neurofilament level (p = 0.007).

Interpretation

Elevated cerebrospinal fluid ubiquitin carboxyl-hydrolase isozyme L1 levels in C9orf72 HRE carriers can occur in the absence of increased neurofilament levels, potentially reflecting either compensatory or pathogenic mechanisms preceding rapid neuronal loss. This brings forward the window on changes associated with the C9orf72 HRE carrier state, with potential to inform understanding of penetrance and approaches to prevention. ANN NEUROL 2025;97:449–459

目的通过C9orf72六核苷酸重复扩增（HRE）杂合子，确定肌萎缩侧索硬化症（ALS）或额颞叶痴呆症（FTD）高风险人群的生化变化：方法：对 48 名无症状的 C9orf72 HRE 携带者、39 名无症状的非携带者对照者、19 名散发性 ALS 患者、10 名 C9orf72 ALS 患者、14 名散发性 FTD 患者和 10 名 C9orf72 FTD 患者进行横断面观察研究。在无症状的 C9orf72 HRE 携带者和年龄匹配的非携带者对照组中，比较了 ALS 和 FTD 的 30 种预定义脑脊液生物标记物的相对丰度。采用数据独立采集质谱法或神经丝蛋白轻链电化学发光法对这些蛋白质的丰度差异进行量化。然后对整个脑脊液蛋白质组进行无偏分析：结果：无症状的 C9orf72 HRE 携带者与年龄匹配的非携带者相比，泛素羧基水解酶同工酶 L1 的水平更高（对数 2 倍变化 0.20，FDR 调整后的 p 值 = 0.034），而神经丝轻链的水平没有显著差异。根据神经丝水平对各组进行匹配（p = 0.011），并对年龄、性别和神经丝水平进行调整后，泛素羧基水解酶同工酶 L1 的水平仍然升高。将分析范围限制在较年轻的参与者时，也观察到了明显的差异（解释：脑脊液中脑蛋白酶 L1 水平升高可能与神经丝水平有关：C9orf72 HRE携带者脑脊液泛素羧基水解酶同工酶L1水平升高可能发生在神经丝水平未升高的情况下，这可能反映了神经元快速丧失之前的代偿或致病机制。这为了解与 C9orf72 HRE 携带者状态相关的变化提供了一个窗口，有可能为了解渗透性和预防方法提供信息。ann neurol 2024.

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引用次数: 0

Sex-Specific Vulnerabilities to Subclinical Vascular Brain Injury in Early Late-Life: The Framingham Heart Study 晚年早期亚临床血管性脑损伤的性别特异性易感性：弗雷明汉心脏研究

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology

Pub Date : 2024-11-14 DOI: 10.1002/ana.27135

Wai-Ying Wendy Yau MD, Matthew R. Scott BA, Rodica E. Petrea MD, Rachel F. Buckley PhD, Daniel Kojis BA, Reisa A. Sperling MD, Jasmeer P. Chhatwal MD, PhD, Pauline Maillard PhD, Hugo J. Aparicio MD, MPH, Jose Rafael Romero MD, Charles S. DeCarli MD, Alexa S. Beiser PhD, Sudha Seshadri MD

Objective

Subclinical vascular brain injury is an increasingly recognized risk factor for stroke and dementia. Despite well-established sex differences in vascular risk and disease prevalence, the impact of sex on drivers of subclinical vascular brain injury remains unclear, presenting a barrier to developing sex-specific prevention guidelines. We aimed to establish the extent to which sex moderates associations between vascular risk factors and magnetic resonance imaging (MRI) measures of subclinical brain injury in stroke-free older adults.

Methods

We leveraged cross-sectional data from 1,579 stroke- and dementia-free Framingham Heart Study Offspring participants at exam 8 (age 65.7 ± 8.8 years, 53% women). Vascular risks were assessed using components of the Framingham Stroke Risk Profile (FSRP) and diastolic blood pressure (DBP). White matter hyperintensity volume (WMH), total cerebral brain volume (TBV), and covert brain infarcts were quantified using MRI. We examined whether vascular risk factors were associated with MRI measures across the combined cohort, and then determined whether sex modified these associations.

Results

Higher FSRP and specifically systolic blood pressure (SBP) were associated with greater WMH. These associations were stronger in women and remained after adjusting for menopause age and hormone therapy use. By contrast, diabetes and lower DBP were associated with smaller TBV primarily in men. The DBP-atrophy relationship was only observed in men with declining DBP or prior hypertension.

Interpretation

Our findings highlight differential vulnerability to the impact of vascular risk factors on white matter health in women and global atrophy in men, supporting the development of sex-specific guidelines to better preserve vascular brain health in aging. ANN NEUROL 2025;97:460–469

目的：亚临床血管性脑损伤是导致中风和痴呆的一个日益公认的危险因素。尽管血管风险和疾病患病率的性别差异已得到证实，但性别对亚临床血管性脑损伤驱动因素的影响仍不清楚，这对制定针对不同性别的预防指南构成了障碍。我们旨在确定性别在多大程度上调节无中风老年人的血管风险因素与亚临床脑损伤的磁共振成像（MRI）测量之间的关联：我们利用了 1579 名无中风和痴呆的弗雷明汉心脏研究后代参与者在第 8 次检查时的横截面数据（年龄为 65.7 ± 8.8 岁，53% 为女性）。血管风险通过弗雷明汉卒中风险档案（Framingham Stroke Risk Profile，FSRP）和舒张压（DBP）进行评估。白质高密度体积（WMH）、大脑总体积（TBV）和隐蔽性脑梗死均通过核磁共振成像进行量化。我们研究了血管风险因素是否与合并队列中的核磁共振成像指标相关，然后确定性别是否会改变这些关联：结果：较高的FSRP，尤其是收缩压（SBP）与较高的WMH相关。女性的这些相关性更强，在调整绝经年龄和使用激素治疗后仍保持不变。相比之下，糖尿病和较低的 DBP 主要与男性较小的 TBV 相关。DBP与萎缩的关系仅在DBP下降或曾患高血压的男性中观察到：我们的研究结果凸显了血管风险因素对女性脑白质健康和男性脑白质整体萎缩影响的不同易感性，支持制定针对不同性别的指南，以更好地保护衰老过程中的脑血管健康。ann neurol 2024.

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引用次数: 0

Automated and Interpretable Detection of Hippocampal Sclerosis in Temporal Lobe Epilepsy: AID-HS 颞叶癫痫海马硬化的自动和可解释检测：AID-HS.

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology

Pub Date : 2024-11-14 DOI: 10.1002/ana.27089

Mathilde Ripart, Jordan DeKraker, Maria H. Eriksson, Rory J. Piper, Siby Gopinath, Harilal Parasuram, Jiajie Mo, Marcus Likeman, Georgian Ciobotaru, Philip Sequeiros-Peggs, Khalid Hamandi, Hua Xie, Nathan T. Cohen, Ting-Yu Su, Ryuzaburo Kochi, Irene Wang, Gonzalo M. Rojas-Costa, Marcelo Gálvez, Costanza Parodi, Antonella Riva, Felice D'Arco, Kshitij Mankad, Chris A. Clark, Adrián Valls Carbó, Rafael Toledano, Peter Taylor, Antonio Napolitano, Maria Camilla Rossi-Espagnet, Anna Willard, Benjamin Sinclair, Joshua Pepper, Stefano Seri, Orrin Devinsky, Heath R. Pardoe, Gavin P. Winston, John S. Duncan, Clarissa L. Yasuda, Lucas Scárdua-Silva, Lennart Walger, Theodor Rüber, Ali R. Khan, Torsten Baldeweg, Sophie Adler, Konrad Wagstyl, MELD HS study group

Objective

Hippocampal sclerosis (HS), the most common pathology associated with temporal lobe epilepsy (TLE), is not always visible on magnetic resonance imaging (MRI), causing surgical delays and reduced postsurgical seizure-freedom. We developed an open-source software to characterize and localize HS to aid the presurgical evaluation of children and adults with suspected TLE.

Methods

We included a multicenter cohort of 365 participants (154 HS; 90 disease controls; 121 healthy controls). HippUnfold was used to extract morphological surface-based features and volumes of the hippocampus from T1-weighted MRI scans. We characterized pathological hippocampi in patients by comparing them to normative growth charts and analyzing within-subject feature asymmetries. Feature asymmetry scores were used to train a logistic regression classifier to detect and lateralize HS. The classifier was validated on an independent multicenter cohort of 275 patients with HS and 161 healthy and disease controls.

Results

HS was characterized by decreased volume, thickness, and gyrification alongside increased mean and intrinsic curvature. The classifier detected 90.1% of unilateral HS patients and lateralized lesions in 97.4%. In patients with MRI-negative histopathologically-confirmed HS, the classifier detected 79.2% (19/24) and lateralized 91.7% (22/24). The model achieved similar performances on the independent cohort, demonstrating its ability to generalize to new data. Individual patient reports contextualize a patient's hippocampal features in relation to normative growth trajectories, visualise feature asymmetries, and report classifier predictions.

Interpretation

Automated and Interpretable Detection of Hippocampal Sclerosis (AID-HS) is an open-source pipeline for detecting and lateralizing HS and outputting clinically-relevant reports. ANN NEUROL 2025;97:62–75

目的：海马硬化症（HS）是颞叶癫痫（TLE）最常见的相关病理，但在磁共振成像（MRI）上并不总能看懂，导致手术延迟和术后癫痫发作自由度降低。我们开发了一款开源软件来描述和定位HS，以帮助对疑似TLE的儿童和成人进行术前评估：我们纳入了一个由 365 名参与者（154 名 HS；90 名疾病对照；121 名健康对照）组成的多中心队列。HippUnfold用于从T1加权磁共振成像扫描中提取海马的形态表面特征和体积。我们将患者的病理海马与常模生长图进行比较，并分析受试者内部的特征不对称性，从而确定病理海马的特征。特征不对称性得分被用于训练逻辑回归分类器，以检测和侧定HS。该分类器在由 275 名 HS 患者和 161 名健康及疾病对照者组成的独立多中心队列中进行了验证：HS的特征是体积、厚度和回旋减少，同时平均曲率和固有曲率增加。分类器检测出90.1%的单侧HS患者和97.4%的侧位病变。在核磁共振成像阴性、组织病理学确诊的 HS 患者中，分类器检测出 79.2%（19/24）的病变，并对 91.7%（22/24）的病变进行了侧位分类。该模型在独立队列中也取得了类似的表现，证明了其对新数据的归纳能力。患者个人报告将患者的海马特征与正常生长轨迹联系起来，直观显示特征的不对称性，并报告分类器的预测结果：海马硬化症的自动可解读检测（AID-HS）是一个开源管道，用于检测海马硬化症并将其侧向化，同时输出临床相关报告。ann neurol 2024.

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引用次数: 0

Distinct Constructs Underlie Patient-Reported and Performance-Rated Outcomes after Stroke 中风后患者自述结果和表现评定结果的不同结构特征

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology

Pub Date : 2024-11-14 DOI: 10.1002/ana.27129

Julie A. DiCarlo MS, Abhishek Jaywant PhD, Perman Gochyyev PhD, Anna K. Bonkhoff MD, Richard Hardstone PhD, Kimberly S. Erler PhD, Jessica Ranford MS, OT, Alison Cloutier MS, Nathan Ward PhD, Kelly L. Sloane MD, Lee H. Schwamm MD, Steven C. Cramer MD, David J. Lin MD

Objective

Patient-reported outcome measures (PROMs), which capture patients' perspectives on the consequences of health and disease, are widely used in neurological care and research. However, it is unclear how PROMs relate to performance-rated impairments. Sociodemographic factors are known to affect PROMs. Direct damage to brain regions critical for self-awareness (i.e., parietal regions and the salience/ventral-attention network) may also impair self-report outcomes. This study examined the relationship between PROMs and performance-based measures in stroke survivors with arm motor impairments. We hypothesized that PROMs would be distinct from performance-based outcomes, influenced by sociodemographic factors, and linked to damage in brain circuits involved in self-perception.

Methods

We longitudinally assessed 54 stroke survivors using patient-reported and performance-rated measures at 4 timepoints. We used factor analysis to reveal the outcome battery's factorial structure. Linear regression examined the association between classes of measures and sociodemographics. Voxel-lesion-symptom-mapping, region-of-interest-based analysis, and voxel-lesion-network-mapping investigated the relationship between classes of outcomes and stroke-related injury.

Results

Performance-based and patient-reported measures formed distinct factors, consistent across recovery phases. Higher education (β1 = 0.36, p = 0.02) and income adequacy (β2 = 0.48, p = 0.05) were associated with patient-reported, but not performance-rated outcomes. Greater parietal lobe injury, irrespective of hemisphere, was associated with worse patient-reported outcomes; greater corticospinal tract injury related to worse performance-rated outcomes. Lesions with greater functional connectivity to the salience/ventral-attention network were associated with worse patient-reported outcomes (r = −0.35, p = 0.009).

Interpretation

Our findings reveal important differences between performance-rated and patient-reported outcomes, each with specific associated factors and anatomy post-stroke. Incorporating sociodemographic and neuroanatomic characteristics into neurorehabilitation strategies may inform and optimize patient outcomes. ANN NEUROL 2025;97:242–253

目的：患者报告结果测量法（PROMs）能反映患者对健康和疾病后果的看法，在神经病学护理和研究中得到广泛应用。然而，目前还不清楚 PROMs 与表现评定损伤之间的关系。已知社会人口因素会影响 PROMs。对自我意识至关重要的脑区（即顶叶区和显著性/内侧注意网络）的直接损伤也可能会损害自我报告结果。本研究考察了有手臂运动障碍的中风幸存者的 PROMs 与基于表现的测量之间的关系。我们假设 PROMs 与基于表现的结果不同，受社会人口因素的影响，并与涉及自我感知的大脑回路的损伤有关：方法：我们在 4 个时间点使用患者报告和表现评分方法对 54 名中风幸存者进行了纵向评估。我们使用因子分析揭示了结果电池的因子结构。线性回归检验了测量类别与社会人口统计学之间的关联。体素-病灶-症状图谱、基于兴趣区域的分析和体素-病灶-网络图谱研究了结果类别与中风相关损伤之间的关系：结果：基于表现的测量和患者报告的测量形成了不同的因素，这些因素在不同的恢复阶段是一致的。教育程度较高（β1 = 0.36，p = 0.02）和收入充足（β2 = 0.48，p = 0.05）与患者报告的结果相关，但与表现评分结果无关。顶叶损伤程度越严重，无论其在哪个半球，患者报告的结果越差；皮质脊髓束损伤程度越严重，表现评分结果越差。与显著性/内省注意网络功能连接性更强的病变与患者报告的结果更差有关（r = -0.35，p = 0.009）：我们的研究结果揭示了脑卒中后表现评定结果与患者报告结果之间的重要差异，每种结果都与特定的相关因素和解剖结构有关。将社会人口学和神经解剖学特征纳入神经康复策略可为患者提供信息并优化其康复效果。ann neurol 2024.

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引用次数: 0

Annals of Neurology: Volume 96, Number 6, December 2024 神经病学年鉴》：第 96 卷第 6 号，2024 年 12 月

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology

Pub Date : 2024-11-14 DOI: 10.1002/ana.26708

引用次数: 0

Cinematic Rendering of Pure Arterial Malformations 纯动脉畸形的电影渲染。

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology

Pub Date : 2024-11-09 DOI: 10.1002/ana.27134

Linggen Dong MD, Ming Lv MD

引用次数: 0

Goal-Directed Rehabilitation Versus Standard Care for Individuals with Hereditary Cerebellar Ataxia: A Multicenter, Single-Blind, Randomized Controlled Superiority Trial 针对遗传性小脑共济失调患者的目标导向康复治疗与标准护理：多中心、单盲、随机对照优越性试验。

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology

Pub Date : 2024-11-09 DOI: 10.1002/ana.27130

Sarah C Milne PhD, Melissa Roberts GCertG&RStud, Shannon Williams MNR, Jillian Chua BAppSc(Physio), Alison C Grootendorst MPH, Genevieve Agostinelli BPhysio, Anneke C Grobler PhD, Hannah L Ross BPhysio, Amy Robinson BAppSc(Physio), Kristen Grove BSc(Physio), Gabrielle Modderman BPhysio, Annabel Price BPhysio, Megan Thomson MPhysio, Libby Massey MPH, Christina Liang PhD, Kishore R Kumar PhD, Kim Dalziel PhD, Joshua Burns PhD, Carolyn M Sue PhD, Pubudu N Pathirana PhD, Malcolm Horne PhD, Nikki Gelfand PostGradDipGenCounss, Helen Curd MGenCoun, David Szmulewicz PhD, Louise A Corben PhD, Martin B Delatycki PhD

Objective

Rehabilitation is thought to reduce ataxia severity in individuals with hereditary cerebellar ataxia (HCA). This multicenter, randomized controlled superiority trial aimed to examine the efficacy of a 30-week goal-directed rehabilitation program compared with 30 weeks of standard care on function, ataxia, health-related quality of life, and balance in individuals with an HCA.

Methods

Individuals with an autosomal dominant or recessive ataxia (aged ≥15 years) were enrolled at 5 sites in Australia. Participants were randomized (1:1) to receive rehabilitation (6 weeks of outpatient physiotherapy followed by a 24-week home exercise program) (n = 39) or continued their usual activity (n = 37). The primary outcome measure was the motor domain of the Functional Independence Measure (mFIM) at 7 weeks. Secondary outcomes included the Scale for the Assessment and Rating of Ataxia (SARA) and the SF-36v2, assessed at 7, 18, and 30 weeks. Outcome assessors were blinded to treatment allocation.

Results

Seventy-one participants (rehabilitation, 37; standard-care, 34) were included in the intention-to-treat analysis. At 7 weeks, mFIM (mean difference 2.26, 95% confidence interval [CI]: 0.26 to 4.26, p = 0.028) and SARA (−1.21, 95% CI: −2.32 to −0.11, p = 0.032) scores improved after rehabilitation compared with standard care. Compared with standard care, rehabilitation improved SARA scores at 30 weeks (mean difference −1.51, 95% CI: −2.76 to −0.27, p = 0.017), but not mFIM scores (1.74, 95% CI: −0.32 to 3.81, p = 0.098). Frequent adverse events in both groups were fatigue, pain, and falls.

Interpretation

Goal-directed rehabilitation improved function at 7 weeks, with improvement in ataxia and health-related quality of life maintained at 30 weeks in individuals with HCA, beyond that of standard care. ANN NEUROL 2025;97:409–424

目的：康复治疗被认为可以减轻遗传性小脑共济失调（HCA）患者共济失调的严重程度。这项多中心随机对照优越性试验旨在研究为期 30 周的目标导向康复计划与为期 30 周的标准护理相比，对遗传性小脑共济失调患者的功能、共济失调、与健康相关的生活质量和平衡能力的疗效：澳大利亚的 5 个研究机构招募了常染色体显性或隐性共济失调患者（年龄≥15 岁）。参与者被随机分配（1:1）接受康复治疗（6 周门诊物理治疗，然后进行为期 24 周的家庭锻炼计划）（39 人）或继续其日常活动（37 人）。主要研究结果为7周时的功能独立性测量（mFIM）运动领域。次要结果包括共济失调评估和评级量表 (SARA) 和 SF-36v2 (分别在 7 周、18 周和 30 周进行评估)。结果评估者对治疗分配双盲：71名参与者（康复治疗37名；标准治疗34名）被纳入意向治疗分析。7周时，与标准护理相比，康复治疗后的mFIM（平均差异为2.26，95%置信区间[CI]：0.26至4.26，p = 0.028）和SARA（-1.21，95% CI：-2.32至-0.11，p = 0.032）评分有所改善。与标准护理相比，康复治疗提高了患者30周时的SARA评分（平均差-1.51，95% CI：-2.76至-0.27，p = 0.017），但未提高mFIM评分（1.74，95% CI：-0.32至3.81，p = 0.098）。两组患者经常出现的不良反应是疲劳、疼痛和跌倒：目标导向康复治疗在7周时改善了HCA患者的功能，30周时共济失调和健康相关生活质量的改善得以维持，超出了标准治疗的效果。ann neurol 2024.

{"title":"Goal-Directed Rehabilitation Versus Standard Care for Individuals with Hereditary Cerebellar Ataxia: A Multicenter, Single-Blind, Randomized Controlled Superiority Trial","authors":"Sarah C Milne PhD, Melissa Roberts GCertG&RStud, Shannon Williams MNR, Jillian Chua BAppSc(Physio), Alison C Grootendorst MPH, Genevieve Agostinelli BPhysio, Anneke C Grobler PhD, Hannah L Ross BPhysio, Amy Robinson BAppSc(Physio), Kristen Grove BSc(Physio), Gabrielle Modderman BPhysio, Annabel Price BPhysio, Megan Thomson MPhysio, Libby Massey MPH, Christina Liang PhD, Kishore R Kumar PhD, Kim Dalziel PhD, Joshua Burns PhD, Carolyn M Sue PhD, Pubudu N Pathirana PhD, Malcolm Horne PhD, Nikki Gelfand PostGradDipGenCounss, Helen Curd MGenCoun, David Szmulewicz PhD, Louise A Corben PhD, Martin B Delatycki PhD","doi":"10.1002/ana.27130","DOIUrl":"10.1002/ana.27130","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Rehabilitation is thought to reduce ataxia severity in individuals with hereditary cerebellar ataxia (HCA). This multicenter, randomized controlled superiority trial aimed to examine the efficacy of a 30-week goal-directed rehabilitation program compared with 30 weeks of standard care on function, ataxia, health-related quality of life, and balance in individuals with an HCA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Individuals with an autosomal dominant or recessive ataxia (aged ≥15 years) were enrolled at 5 sites in Australia. Participants were randomized (1:1) to receive rehabilitation (6 weeks of outpatient physiotherapy followed by a 24-week home exercise program) (n = 39) or continued their usual activity (n = 37). The primary outcome measure was the motor domain of the Functional Independence Measure (mFIM) at 7 weeks. Secondary outcomes included the Scale for the Assessment and Rating of Ataxia (SARA) and the SF-36v2, assessed at 7, 18, and 30 weeks. Outcome assessors were blinded to treatment allocation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy-one participants (rehabilitation, 37; standard-care, 34) were included in the intention-to-treat analysis. At 7 weeks, mFIM (mean difference 2.26, 95% confidence interval [CI]: 0.26 to 4.26, <i>p</i> = 0.028) and SARA (−1.21, 95% CI: −2.32 to −0.11, <i>p</i> = 0.032) scores improved after rehabilitation compared with standard care. Compared with standard care, rehabilitation improved SARA scores at 30 weeks (mean difference −1.51, 95% CI: −2.76 to −0.27, <i>p</i> = 0.017), but not mFIM scores (1.74, 95% CI: −0.32 to 3.81, <i>p</i> = 0.098). Frequent adverse events in both groups were fatigue, pain, and falls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Goal-directed rehabilitation improved function at 7 weeks, with improvement in ataxia and health-related quality of life maintained at 30 weeks in individuals with HCA, beyond that of standard care. ANN NEUROL 2025;97:409–424</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 3","pages":"409-424"},"PeriodicalIF":8.1,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Annals of Neurology: Volume 96, Number S33, November 2024 神经病学年鉴》：第 96 卷，第 S33 号，2024 年 11 月

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology

Pub Date : 2024-11-08 DOI: 10.1002/ana.27085

引用次数: 0