Annals of Neurology最新文献

{"title":"The Utility of Long-Read Sequencing in Diagnosing Early Onset Parkinson's Disease.","authors":"Kensuke Daida, Hiroyo Yoshino, Laksh Malik, Breeana Baker, Mayu Ishiguro, Rylee Genner, Kimberly Paquette, Yuanzhe Li, Kenya Nishioka, Satoshi Masuzugawa, Makito Hirano, Kenta Takahashi, Mikhail Kolmogorov, Kimberley J Billingsley, Manabu Funayama, Cornelis Blauwendraat, Nobutaka Hattori","doi":"10.1002/ana.27155","DOIUrl":"https://doi.org/10.1002/ana.27155","url":null,"abstract":"<p><strong>Objective: </strong>Variants in PRKN and PINK1 are the leading cause of early-onset autosomal recessive Parkinson's disease, yet many cases remain genetically unresolved. We previously identified a 7 megabases complex structural variant in a pair of monozygotic twins using Oxford Nanopore Technologies (ONT) long-read sequencing. This study aims to determine if ONT long-read sequencing can detect a second variant in other unresolved early-onset Parkinson's disease (EOPD) cases with 1 heterozygous PRKN or PINK1 variant.</p><p><strong>Methods: </strong>ONT long-read sequencing was performed on EOPD patients with 1 reported PRKN/PINK1 pathogenic variant, with onset age under 50. Positive controls included EOPD patients with 2 known PRKN pathogenic variants. Initial testing involved short-read targeted panel sequencing for single nucleotide variants and multiplex ligation-dependent probe amplification for copy number variants.</p><p><strong>Results: </strong>A total of 47 patients were studied (PRKN \"one-variant,\" n = 23; PINK1 \"one-variant,\" n = 12; PRKN \"two-variants,\" n = 12). ONT long-read sequencing identified a second pathogenic variant in 26% of PRKN \"one-variant\" patients (6/23), but none in PINK1 \"one-variant\" patients (0/12). Detected variants included 1 complex inversion, 2 structural variant overlaps, and 3 duplications. In the PRKN \"two-variants\" group, both variants were identified in all patients (100%, 12/12).</p><p><strong>Interpretation: </strong>ONT long-read sequencing effectively identifies pathogenic structural variants in the PRKN locus missed by conventional methods. It should be considered for unresolved EOPD cases when a second variant is not detected through conventional approaches. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851696","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":"Identifying Individuals in the Prodromal Phase of Parkinson's Disease: A Prospective Cohort Study.","authors":"Mario H Flores-Torres, Katherine C Hughes, Marianna Cortese, Albert Y Hung, Brian C Healy, Michael A Schwarzschild, Kjetil Bjornevik, Alberto Ascherio","doi":"10.1002/ana.27166","DOIUrl":"https://doi.org/10.1002/ana.27166","url":null,"abstract":"<p><strong>Objective: </strong>We prospectively evaluated how well combinations of signs and symptoms can identify individuals in the prodromal phase of Parkinson's disease (PD).</p><p><strong>Methods: </strong>The study comprised 6,108 men who underwent repeated assessments of key prodromal features and were prospectively followed for the development of PD. Two composite measures of prodromal PD were evaluated: (i) the co-occurrence of constipation, probable rapid eye movement (REM) sleep behavior disorder (pRBD), and hyposmia, and (ii) the probability of prodromal PD based on the Movement Disorders Society (MDS) research criteria. We also examined the progression and heterogeneity of the prodromal PD phase.</p><p><strong>Results: </strong>One hundred three individuals were newly diagnosed with PD over an average follow-up of 3.4 years. Men with constipation, pRBD, and hyposmia had a 23-fold higher risk of receiving a PD diagnosis in the subsequent 3 years, compared with men without these features (risk ratio [RR] = 23.35, 95% confidence interval [CI] = 10.62-51.33). The risk of PD was 21-fold higher in men with a probability of prodromal PD ≥ 0.8 compared with those with a probability < 0.2 (RR = 21.96, 95% CI = 11.17-43.17). Both the co-occurrence of the 3 non-motor features and an MDS-based probability ≥ 0.8 had comparable predictive values, and both were stronger predictors of PD than any of the features individually. We identified 2 prodromal PD subtypes where RBD and visual color impairment were key discriminators.</p><p><strong>Interpretation: </strong>Our study demonstrates that combinations of key signs and symptoms strongly predict future clinically manifest PD. These measures may be integrated into screening strategies to identify individuals who could be targeted for enrollment into PD prevention trials. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862634","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":"In Memoriam: Barry GW Arnason, MD (8/2/1933-7/17/2023).","authors":"Anthony T Reder","doi":"10.1002/ana.27160","DOIUrl":"https://doi.org/10.1002/ana.27160","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833266","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":"Association that Neuroimaging and Clinical Measures Have with Change in Arm Impairment in a Phase 3 Stroke Recovery Trial.","authors":"Anne Schwarz, Marc Feldman, Vu Le, Jesse Dawson, Charles Y Liu, Gerard E Francisco, Steven L Wolf, Anand Dixit, Jen Alexander, Rushna Ali, Benjamin L Brown, Wuwei Feng, Louis DeMark, Leigh R Hochberg, Steven A Kautz, Arshad Majid, Michael W O'Dell, Jessica Redgrave, Duncan L Turner, Teresa J Kimberley, Steven C Cramer","doi":"10.1002/ana.27156","DOIUrl":"https://doi.org/10.1002/ana.27156","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Vagus nerve stimulation (VNS) paired with rehabilitation therapy improved motor status compared to rehabilitation alone in the phase III VNS-REHAB stroke trial, but treatment response was variable and not associated with any clinical measures acquired at baseline, such as age or side of paresis. We hypothesized that neuroimaging measures would be associated with treatment-related gains, examining performance of regional injury measures versus global brain health measures in parallel with clinical measures.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Baseline magnetic resonance imaging (MRI) scans in the VNS-REHAB trial were used to derive regional injury measures (extent of injury to corticospinal tract, the primary regional measure; plus extent of injury to precentral gyrus and postcentral gyrus; lesion volume; and lesion topography) and global brain health measures (degree of white matter hyperintensities, the primary global brain measure; plus volumes of cerebrospinal fluid, cortical gray matter, white matter, each thalamus, and total brain). Eight clinical measures assessed at baseline were also evaluated (treatment group, age, race, gender, paretic side, pre-stroke dominant hand, time since stroke, and baseline Fugl-Meyer upper extremity score). Bivariate analyses compared each measure with the primary trial end point (change in Fugl-Meyer upper extremity score from baseline to end of 6 weeks of treatment) across all subjects, with secondary analyses examining trial groups separately.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;MRIs were available from 80 patients (age = 59.8 ± 9.5 years, 29 women). Across all patients, less white matter hyperintensities (r = -0.25, p = 0.028) at baseline was associated with larger Fugl-Meyer score change. In the VNS group, less white matter hyperintensities (r = -0.37, p = 0.018) and larger ipsilesional thalamus volume (r = 0.33, p = 0.046) were each associated with larger Fugl-Meyer score change. Analysis of covariance (ANCOVA) analyses tested the interaction that each baseline measure had with treatment group and found that the model examining white matter hyperintensities had a significant interaction term, indicating 2.3 less change in Fugl-Meyer Upper Extremity (FM-UE) points in the VNS group relative to the control group for each point increase in modified Fazekas scale.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Neuroimaging measures are associated with extent of gains on the primary endpoint of a phase III stroke recovery trial. Among the neuroimaging measures examined, a measure of global brain health (extent of white matter hyperintensities) was better at explaining the change in arm impairment as compared with measures of regional injury; this was true when examining all study subjects as well as only those in the VNS group and is consistent with the global mechanism of action that VNS has throughout the cerebrum. Future studies can evaluate additional measures that further predict response to","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826865","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":"Cerebral Amyloid Angiopathy-Related Inflammation Spectrum Disorders: Introduction of a Novel Concept and Diagnostic Criteria.","authors":"Andreas Charidimou","doi":"10.1002/ana.27162","DOIUrl":"https://doi.org/10.1002/ana.27162","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823450","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":"Atlas of Cerebrospinal Fluid Immune Cells Across Neurological Diseases.","authors":"Michael Heming, Anna-Lena Börsch, Simone Melnik, Noemi Gmahl, Louisa Müller-Miny, Christine Dambietz, Lukas Fisch, Timm Kühnel, Tobias J Brix, Alice Janssen, Eva Schumann, Catharina C Gross, Julian Varghese, Tim Hahn, Heinz Wiendl, Gerd Meyer Zu Hörste","doi":"10.1002/ana.27157","DOIUrl":"https://doi.org/10.1002/ana.27157","url":null,"abstract":"<p><strong>Objective: </strong>Cerebrospinal fluid (CSF) provides unique insights into the brain and neurological diseases. However, the potential of CSF flow cytometry applied on a large scale remains unknown.</p><p><strong>Methods: </strong>We used data-driven approaches to analyze paired CSF and blood flow cytometry measurements from 8,790 patients (discovery cohort) and CSF only data from 3,201 patients (validation cohort) collected across neurological diseases in a real-world setting.</p><p><strong>Results: </strong>In somatoform controls (n = 788), activation of T cells increased with age in both CSF and blood, whereas double negative blood T cells (CD3⁺CD4^-CD8^-) decreased with age. A machine learning model of CSF and blood immune cells defined immune age, which correlated strongly with true biological age (r = 0.71). Classifying all diseases solely based on the CSF/blood parameters in 8,790 patients resulted in clusters of 4 disease categories: healthy, autoimmune, meningoencephalitis, and neurodegenerative. This clustering was validated in an analytically independent test dataset (8,790 patients) and in a temporally independent cohort (3,201 patients). Patients with multiple sclerosis were more likely to have progressive disease when assigned to the neurodegeneration cluster and to have lower disability in the autoimmune cluster. Patients with dementia in the neurodegeneration cluster showed more severe disease progression. Flow cytometry helped differentiate dementia from controls, thereby enhancing the diagnostic power of routine CSF diagnostics.</p><p><strong>Interpretation: </strong>Flow cytometry of CSF and blood thus identifies site-specific aging patterns and disease-overarching patterns of neurodegeneration. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811590","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":"Letter on Intramedullary Spinal Cord Abscess: Acupuncture Is the Real Infected Villain?","authors":"Hai Lu","doi":"10.1002/ana.27153","DOIUrl":"https://doi.org/10.1002/ana.27153","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798834","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":"Automated Neuroprognostication Via Machine Learning in Neonates with Hypoxic-Ischemic Encephalopathy.","authors":"John D Lewis, Atiyeh A Miran, Michelle Stoopler, Helen M Branson, Ashley Danguecan, Krishna Raghu, Linh G Ly, Mehmet N Cizmeci, Brian T Kalish","doi":"10.1002/ana.27154","DOIUrl":"https://doi.org/10.1002/ana.27154","url":null,"abstract":"<p><strong>Objectives: </strong>Neonatal hypoxic-ischemic encephalopathy is a serious neurologic condition associated with death or neurodevelopmental impairments. Magnetic resonance imaging (MRI) is routinely used for neuroprognostication, but there is substantial subjectivity and uncertainty about neurodevelopmental outcome prediction. We sought to develop an objective and automated approach for the analysis of newborn brain MRI to improve the accuracy of prognostication.</p><p><strong>Methods: </strong>We created an anatomic MRI template from a sample of 286 infants treated with therapeutic hypothermia, and labeled the deep gray-matter structures. We extracted quantitative information, including shape-related information, and information represented by complex patterns (radiomic measures), from each of these structures in all infants. We then trained an elastic net model to use either only these measures, only the infants' demographic and laboratory data, or both, to predict neurodevelopmental outcomes, as measured by the Bayley Scales of Infant and Toddler Development at 18 months of age.</p><p><strong>Results: </strong>Among those infants for whom Bayley scores were available for cognitive, language, and motor outcomes, we found sets of MRI-based measures that could predict their Bayley scores with correlations that were greater than the correlations based on only the demographic and laboratory data, explained more of the variance in the observed scores, and generated a smaller error; predictions based on the combination of the demographic-laboratory and MRI-based measures were similar or marginally better.</p><p><strong>Interpretation: </strong>Our findings show that machine learning models using MRI-based measures can predict neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy across all neurodevelopmental domains and across the full spectrum of outcomes. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798831","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":"Critical Care Decisions After Large Core Cerebral Infarctions: A Secondary Analysis From the SELECT2 Trial.","authors":"Scott E Kasner, Michael T Mullen, Michael DeGeorgia, Spiros Blackburn, Donna K George, Monisha Kumar, Steven Messe, Michael G Abraham, Michael Chen, Santiago Ortega-Gutierrez, Clark W Sitton, Jan-Karl Burkhardt, Muhammad Shazam Hussain, Leonid Churilov, Sophia Sundararajan, Yin C Hu, Nabeel A Herial, Pascal Jabbour, Daniel Gibson, Juan F Arenillas, Jenny P Tsai, Ronald F Budzik, William J Hicks, Osman Kozak, Bernard Yan, Dennis J Cordato, Nathan W Manning, Mark W Parsons, Ricardo A Hanel, Amin N Aghaebrahim, Teddy Y Wu, Pere Cardona Portela, Natalia Pérez de la Ossa, Joanna D Schaafsma, Jordi Blasco, Navdeep Sangha, Steven Warach, Chirag D Gandhi, Timothy J Kleinig, Daniel Sahlein, Edgar A Samaniego, Laith Maali, Mohammad A Abdulrazzak, Krishna Amuluru, Deep K Pujara, Faris Shaker, Hannah Johns, Rami Moussa, Faisal Al-Shaibi, Kelsey R Duncan, Stavropoula Tjoumakaris, Amanda Opaskar, Wei Xiong, Abhishek Ray, Sepideh Amin-Hanjani, Thanh N Nguyen, Johanna T Fifi, Stephen Davis, Lawrence Wechsler, Anthony Furlan, Cathy Sila, Nicholas Bambakidis, Michael D Hill, Vitor Mendes Pereira, Maarten G Lansberg, James C Grotta, Marc Ribo, Greg W Albers, Bruce C Campbell, Ameer E Hassan, Amrou Sarraj","doi":"10.1002/ana.27151","DOIUrl":"https://doi.org/10.1002/ana.27151","url":null,"abstract":"<p><strong>Objective: </strong>Among patients with large vessel occlusion (LVO) and large ischemic cores, critical decisions often need to be made about decompressive hemicraniectomy (DHC) or early withdrawal of life-sustaining therapy (WLST). In this study, we aimed to evaluate utilization of DHC and early WLST and factors associated with them in patients with large strokes from the SELECT2 trial.</p><p><strong>Methods: </strong>We analyzed the entire SELECT2 trial population, which randomized 352 patients with stroke due to LVO and large ischemic cores to endovascular thrombectomy (EVT) or medical management. We used the as-treated principle to compare the use of DHC and early WLST within 7 days after randomization. We further assessed functional outcomes (modified Rankin Score) after these decisions.</p><p><strong>Results: </strong>Of 352 patients enrolled in this study, 55 received DHC and 81 transitioned to early WLST. Patients treated with EVT were as likely to undergo DHC (16% vs 15%, adjusted relative risk [aRR] = 1.19, 95% CI:0.75-1.88, p = 0.46) or WLST (22% vs 24%, aRR = 0.94, 95% CI: 0.66-1.34, p = 0.72) as those given medical management. DHC was used more frequently in younger patients and WLST more in older patients. EVT efficacy was maintained after adjusting for DHC (adjusted generalized odds ratio [aGenOR] = 1.68, 95% CI: 1.24-2.11, p < 0.001), with no interaction between DHC and treatment (p-interaction = 0.93). At 1 year, 21% of DHC-treated patients were ambulatory; the outcomes were universally poor after early WLST.</p><p><strong>Interpretation: </strong>In the SELECT2 trial of patients with large ischemic core, DHC was performed in ~1 of 6 patients and early WLST in ~1 of 5 patients, without differences based on treatment with EVT or medical management, nor successful reperfusion. DHC or WLST did not detract from thrombectomy treatment benefit. Additionally, ~20% of patients achieved independent ambulation despite receiving DHC by the 1-year follow-up. The similar distribution of these critical care decisions provides reassurance that the overall trial outcomes were not biased by open-label treatment allocation. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794065","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":"Spontaneous Pneumocephalus Due to Skull Base Defect and Spinal Cerebrospinal Fluid-Venous Fistula.","authors":"Simon A Menaker, Gregory P Lekovic, Wouter I Schievink","doi":"10.1002/ana.27152","DOIUrl":"https://doi.org/10.1002/ana.27152","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794066","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}