Neurology最新文献

{"title":"Better Communication With the Public: Understanding Science Phobia and Mistrust as Neurobiological Phenomena.","authors":"Nina F Schor","doi":"10.1212/WNL.0000000000213862","DOIUrl":"10.1212/WNL.0000000000213862","url":null,"abstract":"<p><p>Much has been written recently about science mistrust and illiteracy and consequent phobia of recommendations and interventions that have grown out of that science. Both reinforcing and reversing these phenomena depend on strategies aimed at brain networks that generate them. The neurogenesis of specific phobias involves a network that includes the amygdala and the hypothalamus and their connection through the stria terminalis. Decreased GABAergic inhibition of this circuit results in limbic activation and induction of fear pathways. The neurogenesis of mistrust involves suppression of a network that includes the central amygdala and the shell of the nucleus accumbens, both of which are rich in oxytocin receptors and yield dopaminergic output. Oxytocin signaling mediates trust, whereas, at least in men, dihydrotestosterone signaling mediates mistrust. The possibility of involvement of these limbic circuits in both science phobia and mistrust may underlie the high efficacy of emotionally focused communication in reinforcing them. Yet, recent efforts to reverse science phobia and mistrust have more often involved intellectually focused communication. Assuming limbic network origins of science phobia and mistrust, this commentary presents and discusses the use of emotionally focused communication and explicit, public identification of manipulative techniques and innuendo to influence the prevalence of these phenomena.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"105 2","pages":"e213862"},"PeriodicalIF":7.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time Course and Severity of Cognitive Changes as a Function of Aβ Positivity and <i>APOE</i> Genotype in Alzheimer Disease.","authors":"Casey R Vanderlip, Craig E L Stark","doi":"10.1212/WNL.0000000000213853","DOIUrl":"10.1212/WNL.0000000000213853","url":null,"abstract":"<p><strong>Background and objectives: </strong>APOE4 is the strongest genetic risk factor of sporadic Alzheimer disease (AD), associated with greater β-amyloid (Aβ) deposition and accelerated cognitive decline, especially in episodic memory. However, it remains unclear whether this decline is driven by increased Aβ burden in APOE4 carriers or by greater susceptibility to Aβ-related effects. In this study, we examined whether the accelerated decline in episodic memory among APOE4 carriers is due to increased Aβ deposition or heightened susceptibility to Aβ-related effects.</p><p><strong>Methods: </strong>We analyzed data from individuals in the Alzheimer's Disease Neuroimaging Initiative who underwent neuropsychological assessments, Aβ PET imaging, and APOE genotyping. Using sampled iterative local approximation, we estimated Aβ duration, defined as the number of years each individual was amyloid positive (Aβ+). Using these estimates, we examined its impact on cognitive trajectories across multiple domains, including episodic memory, executive function, processing speed, visuospatial abilities, semantic memory, and crystallized intelligence.</p><p><strong>Results: </strong>We analyzed data from 1,542 participants (mean age = 72.2 years, SD = 7.2; 50.8% female; mean education = 16.3 years, SD = 2.6) and found that APOE4 was associated with steeper declines in episodic memory as a function of Aβ duration. Homozygous APOE4 carriers (4/4) exhibited the most pronounced decline, followed by heterozygotes (3/4), with noncarriers (3/3) showing the slowest decline. This genotype-dependent pattern was specific to episodic memory; no consistent or meaningful differences were observed across other cognitive domains. In all genotype groups, episodic memory was the first domain to show impairment. However, the lag between memory decline and subsequent nonmemory decline was substantially longer in APOE homozygote individuals compared with the other groups, suggesting a more domain-specific vulnerability early in the disease process.</p><p><strong>Discussion: </strong>These findings suggest that APOE4 carriers, particularly homozygotes, exhibit reduced cognitive resilience to Aβ accumulation, but that this effect is largely specific to episodic memory. These findings indicate that cognitive trajectories in AD differ by APOE genotype, highlighting the importance of examining clinical symptoms in the context of APOE status. Future research should investigate whether these differences are driven by distinct pathologic mechanisms in APOE4 carriers.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"105 2","pages":"e213853"},"PeriodicalIF":7.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An FDG-PET-Based Machine Learning Framework to Support Neurologic Decision-Making in Alzheimer Disease and Related Disorders.","authors":"Leland Barnard, Hugo Botha, Nick Corriveau-Lecavalier, Jonathan Graff-Radford, Ellen Dicks, Venkatsampath Gogineni, Gemeng Zhang, Brian J Burkett, Derek R Johnson, Sean J Huls, Aditya Khurana, John L Stricker, Hoon-Ki Paul Min, Matthew L Senjem, Winnie Z Fan, Heather Wiste, Mary M Machulda, Melissa E Murray, Dennis W Dickson, Aivi T Nguyen, R Ross Reichard, Jeffrey L Gunter, Christopher G Schwarz, Kejal Kantarci, Jennifer L Whitwell, Keith Anthony Josephs, David S Knopman, Bradley F Boeve, Ronald C Petersen, Clifford R Jack, Val J Lowe, David T Jones","doi":"10.1212/WNL.0000000000213831","DOIUrl":"10.1212/WNL.0000000000213831","url":null,"abstract":"<p><strong>Background and objectives: </strong>Distinguishing neurodegenerative diseases is a challenging task requiring neurologic expertise. Clinical decision support systems (CDSSs) powered by machine learning (ML) and artificial intelligence can assist with complex diagnostic tasks by augmenting user capabilities, but workflow integration poses many challenges. We propose that a modeling framework based on fluorodeoxyglucose PET (FDG-PET) imaging can address these challenges and form the basis of an effective CDSS for neurodegenerative disease.</p><p><strong>Methods: </strong>This retrospective study focused on FDG-PET images in a discovery cohort drawn from 3 research studies plus routine clinical patients. When selecting research study participants, the inclusion criterion was the availability of an FDG-PET image from within 2.5 years of diagnosis with 1 of 9 specific neurodegenerative syndromes or designation as unimpaired. Participants from disease groups were recruited from the clinical patient population while unimpaired participants came primarily from a population study. The discovery cohort was used to develop a clinical decision support framework we call StateViewer, which applies a neighbor matching algorithm to detect the presence of 9 different neurodegenerative phenotypes. The ML performance of this framework was evaluated in the discovery cohort by nested cross-validation and externally validated in the Alzheimer's Disease Neuroimaging Initiative. Potential for clinical integration was demonstrated in a radiologic reader study focused on differentiating posterior cortical atrophy from Lewy body dementia.</p><p><strong>Results: </strong>The discovery cohort contained 3,671 individuals with a mean age of 68 years and consisted of 49% reported female. Our model framework was able to detect the presence of 9 different neurodegenerative phenotypes with a sensitivity of 0.89 ± 0.03 and an area under the receiver operating characteristic curve of 0.93 ± 0.02. In the radiologic reader study, readers using our model were found to have 3.3 ± 1.1 times greater odds of making a correct diagnosis than readers using a current standard-of-care workflow.</p><p><strong>Discussion: </strong>Our proposed framework provides strong classification performance with high interpretability, and it addresses many of the challenges that face clinical integration of ML-based decision support tools. One limitation of this study is a uniform discovery cohort that is not representative of other patient populations in some regards.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"105 2","pages":"e213831"},"PeriodicalIF":7.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Ischemic Stroke Risk After Cardiac Interventions: An Increasing Threat.","authors":"Katrina Hannah D Ignacio, Umberto Pensato","doi":"10.1212/WNL.0000000000213858","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213858","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"105 1","pages":"e213858"},"PeriodicalIF":7.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266909","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}

{"title":"Screening and Care for Emotional and Cognitive Problems After Ischemic Stroke: Results of a Multicenter, Cluster-Randomized Controlled Trial.","authors":"Jos P L Slenders, Renske M Van Den Berg-Vos, Caroline M Van Heugten, Johanna Visser-Meily, Ruben P A van Eijk, Marthè A A Moonen, Sarah Godefrooij, Vincent I H Kwa","doi":"10.1212/WNL.0000000000213774","DOIUrl":"10.1212/WNL.0000000000213774","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Evidence regarding effectiveness of screening for emotional and cognitive problems after stroke is lacking. The primary aim of this study was to test the hypothesis that an intervention focusing on screening and care for emotional and cognitive problems after stroke would improve societal participation at 1 year. Second, we tested the hypotheses that this intervention would improve emotional and cognitive concerns, symptoms of anxiety, symptoms of depression, quality of life (QoL), self-efficacy, and disability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This multicenter, patient-masked, cluster-randomized controlled trial assigned clusters (1:1) to intervention or usual care. Clusters were Dutch nonuniversity hospitals with a stroke unit. Ischemic stroke patients aged 18 years and older discharged home without inpatient or outpatient rehabilitation were included. The intervention was a consultation conducted by a specialized stroke nurse at the outpatient neurology clinics at 6 weeks after stroke and included screening for emotional and cognitive problems, screening for participation restrictions, self-management support, and, if needed, referral to rehabilitation services. The primary outcome was societal participation (Restrictions subscale of the Utrecht Scale for Evaluation of Rehabilitation-Participation [USER-P-R]) 1 year after stroke. Secondary outcomes were cognitive and emotional concerns (Checklist for Cognitive and Emotional Consequences following Stroke), symptoms of anxiety (Hospital Anxiety and Depression Scale-Anxiety subscale [HADS-A]), symptoms of depression (HADS-Depression subscale), QoL (5-level version of the EuroQoL 5-dimensional questionnaire [EQ-5D-5L], EuroQoL Visual Analog Scale [EQ-VAS], and Patient-Reported Outcome Measurement Information System [PROMIS-10]), self-efficacy (General Self-Efficacy Scale), and disability (modified Rankin Scale) at 3 and 12 months. Continuous outcome data were analyzed using a mixed model for repeated measures, and ordinal data were analyzed with an ordinal mixed-effects model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Between August 14, 2019, and May 11, 2022, a total of 531 patients were included in 12 clusters. The mean age was 70.6 ± 9.7 years, 40.0% were female, and the median NIH Stroke Scale score was 2 (2). Two hundred sixty-four patients were included in 6 hospitals providing the intervention and 267 patients in 6 hospitals providing usual care. Primary analysis demonstrated no difference in USER-P-R score at 1 year after stroke (mean difference [MD] 0.77; 95% CI -2.46 to 4.06; &lt;i&gt;p&lt;/i&gt; = 0.652). Secondary outcome analyses at 3 months showed a MD between the intervention group and usual care group in HADS-A scores of -0.86 (95% CI -1.33 to -0.39), a MD in EQ-5D-5L index scores of 0.044 (95% CI 0.022-0.065), and a MD in EQ-VAS score of 2.90 (95% CI 0.69-5.10). Secondary outcome analyses at 1 year demonstrated a MD in EQ-5D-5L index scores of 0.043 (95% CI","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"105 1","pages":"e213774"},"PeriodicalIF":7.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remote Monitoring of Amyotrophic Lateral Sclerosis Using Digital Health Technologies: Shifting Toward Digitalized Care and Research?","authors":"Jordi W J van Unnik, Leslie Ing, Miguel Oliveira Santos, Christopher J McDermott, Mamede de Carvalho, Ruben P A van Eijk","doi":"10.1212/WNL.0000000000213738","DOIUrl":"10.1212/WNL.0000000000213738","url":null,"abstract":"<p><p>Current care and research pathways for amyotrophic lateral sclerosis (ALS) primarily rely on regularly scheduled visits to specialized centers. These visits provide intermittent clinical information to health care professionals and require patients to travel to the clinic. Digital health technologies enable continuous data collection directly from the patient's home, bringing new opportunities for personalized, timely care and a refined assessment of disease severity in clinical trials. In this review, we summarize the state of the art in digital health technologies for remote monitoring of patients with ALS, ranging from televisits through videoconferencing to sensor-based wearable devices. We explore how these technologies can benefit clinical care and advance treatment development. Despite significant progress, real-world adoption of these technologies remains limited. An overview is provided of the key barriers hindering their widespread implementation and the opportunities to advance the field. Significantly, there is an urgent need for harmonization across stakeholders through consensus guidelines and consortia. These efforts are essential to accelerate progress and harness the full potential of digital health technologies to better meet the needs of patients.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"105 1","pages":"e213738"},"PeriodicalIF":7.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Leucocyte Telomere Length With Stroke, Dementia, and Late-Life Depression: The Role of Modifiable Risk Factors.","authors":"Tamara N Kimball, Savvina Prapiadou, Reinier W P Tack, Benjamin Yong-Qiang Tan, Jasper R Senff, Christina Kourkoulis, Sanjula Singh, Jonathan Rosand, Christopher D Anderson","doi":"10.1212/WNL.0000000000213794","DOIUrl":"10.1212/WNL.0000000000213794","url":null,"abstract":"<p><strong>Background and objectives: </strong>Stroke, dementia, and late-life depression (LLD) are age-related brain diseases that pose significant public health challenges and costs. Leucocyte telomere length (LTL) is a biological aging marker influenced by both genetic and lifestyle factors. The aim of our study was to determine the association between LTL and these diseases. We further investigated whether modifying risk factors of age-related brain disease, as measured using the Brain Care Score (BCS), mitigates LTL associations.</p><p><strong>Methods: </strong>We analyzed participants from the UK Biobank with available LTL and risk factor information. We examined LTL's associations with stroke, dementia, and LLD, individually and as a composite outcome, using continuous measures and tertile stratification. Disease risks were evaluated through cumulative incidence curves, incidence rates per 1,000 person-years, and adjusted Cox models. Risk comparisons across LTL tertiles were stratified by risk factor profiles, with high BCS (≥15) indicating healthier lifestyle choices and low BCS (≤10) reflecting less optimal lifestyle choices. Mendelian randomization (MR) was used to test causal associations.</p><p><strong>Results: </strong>The study included 356,173 participants (median age 56 years; 53.69% female). Shorter LTL was consistently associated with higher incidence rates across all outcomes. Participants in the shortest LTL tertile had elevated risks of the composite outcome (hazard ratio [HR] 1.11; 95% CI 1.08-1.15), stroke (HR 1.08; 95% CI 1.02-1.15), dementia (HR 1.19; 95% CI 1.12-1.26), and LLD (HR 1.14; 95% CI 1.09-1.18). Individuals with both shorter LTL and lower BCS faced significantly increased risks of age-related brain diseases (HR 1.11; 95% CI 1.07-1.16) and individually for stroke (HR 1.10; 95% CI 1.02-1.19), dementia (HR 1.17; 95% CI 1.08-1.28), and LLD (HR 1.13; 95% CI 1.07-1.19). Conversely, individuals with higher BCS within the shortest LTL group did not show a significant increase in risk of any age-related brain diseases. MR analyses did not identify causal relationships between LTL and these outcomes.</p><p><strong>Discussion: </strong>Individuals with shorter LTL are at increased risk of stroke, dementia, and LLD. Improved modifiable risk factor profiles seem to mitigate the impact of LTL on these diseases. Future research should explore the effectiveness of lifestyle interventions in mitigating adverse biological aging effects on brain health.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"105 1","pages":"e213794"},"PeriodicalIF":7.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advance Care Planning and Decision Regret Among Stroke Surrogate Decision Makers: A Longitudinal Cohort Study.","authors":"Darin B Zahuranec, Christopher J Becker, Lourdes Carhuapoma, Carmen Ortiz, Rebecca J Lank, Guanghao Zhang, Kevin He, Erin Case, Lewis B Morgenstern","doi":"10.1212/WNL.0000000000213787","DOIUrl":"10.1212/WNL.0000000000213787","url":null,"abstract":"<p><strong>Objectives: </strong>Investigate the association between advance care planning and decision regret among stroke surrogate decision makers.</p><p><strong>Methods: </strong>People hospitalized with ischemic or hemorrhagic stroke and their surrogate decision makers were enrolled. Surrogates completed the validated decision regret scale (range 0-100, higher worse, analyzed as \"any\" vs \"none\") in the year after stroke (postdischarge, 3, 6, and 12 months). The association of advance care planning and regret was assessed with multilevel mixed effects logistic regression models, adjusted for prespecified covariates.</p><p><strong>Results: </strong>Participants were 317 surrogates for 255 patients with stroke (enrolled April 2016 to October 2020). Patients had a mean age of 74.6 years and mean NIH Stroke Scale of 14.7, with 53% deceased at 3 months. Surrogate characteristics were mean age: 55.8 years, child of patient: 62%, and decision considered (do-not-resuscitate 36%, comfort care 16%, feeding tube 14%, mechanical ventilation 14%, brain surgery 10%, and other 10%). Overall, 132/317 (42%) surrogates reported formal advance care plans. Decision regret scores overall were low (postdischarge mean: 11.2). Formal written advance care plans were associated with lower odds of any decision regret (odds ratio 0.46, 95% CI 0.24-0.89, <i>p</i> = 0.02) after full adjustment.</p><p><strong>Discussion: </strong>Formal written advance care plans were associated with lower odds of any decision regret among surrogate decision makers in the year after stroke.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"105 1","pages":"e213787"},"PeriodicalIF":7.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment Patterns and Disease Burden of Juvenile Myasthenia Gravis in the United States: A Cohort Study Using Health Care Claims Databases.","authors":"Jiachen Zhou, Sigrid Nilius, Olga Pilipczuk, Anna Scowcroft, Thaïs Tarancón, Frank Tennigkeit, Piotr Zaremba, Nishtha Chandra, Nancy Kuntz, Jonathan Strober, John Brandsema","doi":"10.1212/WNL.0000000000213736","DOIUrl":"10.1212/WNL.0000000000213736","url":null,"abstract":"<p><strong>Background and objectives: </strong>Juvenile myasthenia gravis (JMG) is a rare disorder defined as MG in patients younger than 18 years. Generalized JMG is more common in postpubertal than prepubertal patients. There are no formal international JMG treatment guidelines, and knowledge on treatment patterns and disease burden is limited. The aim of this study was to describe treatment patterns and health care resource utilization (HCRU) for patients with JMG and explore differences in disease presentation between prepubertal-onset (younger than 12 years) and postpubertal-onset (12-17 years) patients.</p><p><strong>Methods: </strong>Patients with JMG, newly diagnosed from 2008 to 2021, were identified from the US Merative MarketScan® Research Databases. Patients were followed from the first JMG claim (diagnosis/treatment with acetylcholinesterase inhibitors, immunoglobulin [Ig], or plasma exchange [PLEX]). The primary outcome was JMG-related treatment changes during follow-up, assessed descriptively. Rates of MG exacerbation, thymectomy, and acute intravenous immunoglobulin/PLEX treatment were assessed. HCRU was evaluated.</p><p><strong>Results: </strong>A total of 630 patients (64.1% female; mean [SD] age 9.07 [5.73] years; 57.6% prepubertal onset) were followed for a median (range) of 2.4 (0-13) years. Corticosteroids were started at a median (range) of 1.28 (0-37.02) and 3.19 (0-87.68) months from diagnosis for postpubertal-onset and prepubertal-onset patients, respectively. The rate of thymectomy was highest during treatment with maintenance Ig/PLEX (incidence rate [IR]; [95% CI] per 100 patient-years: 34.62 [14.41-83.17] for postpubertal-onset and 24.24 [9.10-64.60] for prepubertal-onset patients). MG exacerbations were most frequent during the first year of follow-up in both subgroups (34.1% and 30.3%). In postpubertal-onset patients, exacerbation was highest during treatment with maintenance Ig/PLEX and nonsteroid immunosuppressant therapy ([NSIST], mostly polytherapy) (IR [95% CI] 105.81 [68.99-162.29] and 91.22 [65.80-126.47]). For prepubertal-onset patients, exacerbation was most frequent during NSIST (polytherapy) and biologic treatment (IR [95% CI] 140.44 [115.45-170.85] and 142.95 [46.10-443.23]). JMG-related hospitalizations occurred in 36.0% and 30.0% of postpubertal-onset and prepubertal-onset patients, in the first year of follow-up.</p><p><strong>Discussion: </strong>Patients with JMG escalated rapidly through the treatment hierarchy. Postpubertal-onset patients escalated more quickly to later-line treatments than prepubertal-onset patients. However, some patients continued to experience high HCRU, highlighting the need for new JMG treatments to provide rapid disease control. A limitation is that treatment escalation reasons were not evaluated.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"105 1","pages":"e213736"},"PeriodicalIF":7.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimated Theoretical Benefit of Aggressive LDL Lowering in Patients With Symptomatic Intracranial Atherosclerosis.","authors":"James Ernest Siegler, Elena Badillo Goicoechea, Shadi Yaghi, Rami Z Morsi, Andrea Arevalo, Matthew M Smith, Sachin Kothari, Harsh Desai, Neha Sehgal, Rohini Rana, Caroline Alice Kellogg, Aditya Jhaveri, Adam de Havenon, Therese Dunne, Kamil Cameron, Seemant Chaturvedi, Malik Ghannam, Shyam Prabhakaran, Elisheva Coleman, James R Brorson, Rachel Mehendale, Tareq Kass-Hout","doi":"10.1212/WNL.0000000000213768","DOIUrl":"10.1212/WNL.0000000000213768","url":null,"abstract":"<p><strong>Objectives: </strong>Given the high risk of recurrent atherosclerotic vascular events in patients with stroke due to intracranial atherosclerotic disease (ICAD), we estimated the potential benefit of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in this population.</p><p><strong>Methods: </strong>In this secondary analysis of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, we estimated the association between 30-day low-density lipoprotein (LDL) reduction and recurrent stroke or myocardial infarction (MI) beyond 30 days (primary outcome). Estimates were assessed using adjusted Cox proportional hazards regression. We applied relative LDL reduction estimates from PCSK9i trials to project adjusted incidence rate differences of the primary outcome with an equivalent LDL reduction.</p><p><strong>Results: </strong>Of the 451 patients from SAMMPRIS, 378 met inclusion criteria. In adjusted Cox regression, every 10 mg/dL LDL improvement was associated with a 9% lower rate of the primary outcome (adjusted hazard ratio 0.91, 95% CI 0.83-0.997). Assuming an average projected effect of PCSK9i, estimating if half of SAMMPRIS patients were treated, PCSK9i use could reduce the annualized risk of the primary outcome by 33.2% in this trial population.</p><p><strong>Discussion: </strong>Every 10 mg/dL reduction in LDL for patients with stroke due to ICAD is associated with lower rates of recurrent stroke or MI, and this theoretical framework suggests that PCSK9i can help achieve this goal.</p><p><strong>Trial registration information: </strong>Secondary analysis of NCT00576693 prospectively registered interventional clinical trial. First registered December 7, 2007. Actual study start date: October 2008. https://clinicaltrials.gov/show/NCT00576693.</p><p><strong>Classification of evidence: </strong>This study provides Class IV evidence that a higher absolute reduction in LDL was associated with a lower risk of recurrent cerebral infarction or MI in patients with recent stroke due to intracranial stenosis.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"105 1","pages":"e213768"},"PeriodicalIF":7.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187450","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}