Annals of Clinical and Translational Neurology最新文献

{"title":"Early BMI Change, Cognitive Decline, and CSF AD Biomarkers Alterations in Parkinson's Disease.","authors":"Rui Zhong, Kezhong Zhang","doi":"10.1002/acn3.70018","DOIUrl":"https://doi.org/10.1002/acn3.70018","url":null,"abstract":"<p><strong>Objective: </strong>To examine the relationship of early BMI change with subsequent cognitive decline, CSF AD biomarkers alterations, and progression to dementia in patients with PD.</p><p><strong>Methods: </strong>Study data were prospectively collected from the PPMI cohort. Weight/height data at enrollment and second-year clinical visit were utilized to calculate BMI change. Cognitive tests and CSF AD biomarkers were measured at enrollment and each visit during the 5-year follow-up. Generalized linear mixed analyses were employed to identify the impact of BMI change on the deterioration of cognitive performance and CSF AD biomarkers alterations. Cox regression analyses were employed to assess the relationship of BMI change with dementia conversion.</p><p><strong>Results: </strong>BMI loss predicted a more rapid deterioration in global cognitive performance over time. Regarding specific cognitive domains, participants in the BMI loss group experienced a significantly more rapid decline in verbal episodic memory, language, and processing speed/attention compared with those in the stable BMI group. Additionally, patients in the BMI gain group showed a slower decline in verbal episodic memory than those in the stable BMI group. BMI loss predicted a more rapid longitudinal decrease of CSF Aβ42 over time. BMI change was not associated with the risk of progression to dementia.</p><p><strong>Conclusions: </strong>Early BMI loss is a risk factor for faster decline in cognition and longitudinal decrease of CSF Aβ42. These findings emphasize the need to monitor early BMI change in PD patients. Attention to early BMI change may help identify those at greater risk of cognitive decline.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-chain fatty acids in multiple sclerosis: Associated with disability, number of T2 lesions, and inflammatory profile","authors":"Maria Inmaculada Dominguez-Mozo,&nbsp;Daniel López-Mecández,&nbsp;Luisa María Villar,&nbsp;Lucienne Costa-Frossard,&nbsp;Noelia Villarrubia,&nbsp;Yolanda Aladro,&nbsp;Belén Pilo,&nbsp;Xavier Montalbán,&nbsp;Manuel Comabella,&nbsp;Ignacio Casanova-Peño,&nbsp;Inés González-Suárez,&nbsp;María Luisa Martínez-Ginés,&nbsp;Jose Manuel García-Domínguez,&nbsp;Estefanía García-Calvo,&nbsp;Andrés Machuca-Marcos,&nbsp;Jose Luis Luque-Garcia,&nbsp;María Angel Garcia-Martinez,&nbsp;Rafael Arroyo,&nbsp;Roberto Alvarez-Lafuente","doi":"10.1002/acn3.52259","DOIUrl":"10.1002/acn3.52259","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>An alteration in the composition of the intestinal microbiota has been observed in patients with multiple sclerosis (pwMS) with respect to healthy controls (HC). Microorganism-derived metabolites such as short-chain fatty acids (SCFA) have been suggested to play a role in the disease. Thus, to analyze the association of SCFA with clinical and radiological parameters of the disease and with those related to the inflammatory response of the immune system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Multicentric observational retrospective cross-sectional study. In addition 161 pwMS and 130 HC were included. The following plasma SCFA were analyzed using liquid chromatography coupled to mass spectrometry: acetate (AA), propionate (PA) and butyrate (BA). Blood cell subpopulations and cytokine expression were analyzed by flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Plasma PA and PA/AA ratio was lower in pwMS than in HC (<i>P</i> = 0.0001, and <i>P</i> = 0.00005, respectively). PA/AA and BA/AA ratios were lower in pwMS with higher disability (<i>P</i> = 0.001, and <i>P</i> = 0.001, respectively). T2 lesion load inversely correlated with PA/AA (<i>r</i> = −0.353; <i>P</i> = 0.002) and BA/AA (<i>r</i> = −0.322; <i>P</i> = 0.005) ratios. Plasma PA/AA and/or BA/AA ratios negatively correlated with the following pro-inflammatory cytokines producing cells: GM-CSF+CD4+T, GM-CSF+CD8+T, TNF-alpha+CD4+T, TNF-alpha+CD8+T, IFN-gamma+CD4+T, IFN-gamma+CD8+T, and TNF-alpha+B cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>In MS, plasma PA/AA and BA/AA ratios are unbalanced, promoting an environment that could be boosting the mechanisms underlying the pathogenesis of the disease. Since we have found statistical significant associations with the EDSS and the number of T2 lesions, but not with the number of relapses or gadolinium enhancing lesions, PA/AA and BA/AA ratios could be more associated with those mechanisms of the disease related to the neurodegenerative processes than those related with the activity of the disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 3","pages":"478-490"},"PeriodicalIF":4.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-Phase C-11 PiB PET Images for Detecting Tau Pathology in Cerebral Amyloid Angiopathy.","authors":"Meng-Ting Chiang, Chia-Ju Liu, Bo-Ching Lee, Ruoh-Fang Yen, Hsin-Hsi Tsai","doi":"10.1002/acn3.70021","DOIUrl":"https://doi.org/10.1002/acn3.70021","url":null,"abstract":"<p><strong>Background: </strong>Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage and cognitive dysfunction in the elderly, and frequently coexists with Alzheimer's disease and tau pathology. Dual-phase ¹¹C-PiB PET detects amyloid deposition and cerebral perfusion changes and may have diagnostic value for identifying tau in CAA.</p><p><strong>Methods: </strong>We prospectively enrolled patients with probable CAA for dynamic PiB and AV1451 scans. We compared early-phase (0-6 min after tracer injection) and late-phase (40-70 min) PiB PET between the tau(+) and tau(-) groups (based on AV1451 PET) and investigated their diagnostic values for detecting tau.</p><p><strong>Results: </strong>CAA/tau(+) had lower early-phase temporal PiB uptake than CAA/tau(-) (p = 0.014) and higher late-phase uptake in the whole cortex and temporal and parietal lobes (all p < 0.05). Early-phase temporal PiB SUVR correlated with tau burden (r = -0.34, p = 0.038). Using Youden's cut-off, early-phase and late-phase PET had sensitivities of 55% and 80% and specificities of 85% and 65% for detecting tau, respectively. Combining early- and late-phase scans provided a rule-out sensitivity of 90% and rule-in specificity of 100% for tau pathology in CAA.</p><p><strong>Conclusions: </strong>Dual-phase ¹¹C-PiB PET represents a reliable approach for assessing tau and could potentially identify CAA patients for tau biomarker testing.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Long-Read Sequencing as a Single Assay Improves the Diagnosis of Spastic-Ataxia Disorders.","authors":"Laura Ivete Rudaks, Igor Stevanovski, Dennis Yeow, Andre L M Reis, Sanjog R Chintalaphani, Pak Leng Cheong, Hasindu Gamaarachchi, Lisa Worgan, Kate Ahmad, Michael Hayes, Andrew Hannaford, Samuel Kim, Victor S C Fung, Gabor M Halmagyi, Andrew Martin, David Manser, Michel Tchan, Karl Ng, Marina L Kennerson, Ira W Deveson, Kishore Raj Kumar","doi":"10.1002/acn3.70008","DOIUrl":"https://doi.org/10.1002/acn3.70008","url":null,"abstract":"<p><strong>Objective: </strong>The hereditary spastic-ataxia spectrum disorders are a group of disabling neurological diseases. The traditional genetic testing pathway is complex, multistep and leaves many cases unsolved. We aim to streamline and improve this process using long-read sequencing.</p><p><strong>Methods: </strong>We developed a targeted long-read sequencing strategy with the capacity to characterise the genetic variation of all types and sizes within 469 disease-associated genes, in a single assay. We applied this to a cohort of 34 individuals with unsolved spastic-ataxia. An additional five individuals with a known genetic diagnosis were included as positive controls.</p><p><strong>Results: </strong>We identified causative pathogenic variants that would be sufficient for genetic diagnosis in 14/34 (41%) unsolved participants. The success rate was 5/11 (45%) in those who were naïve to genetic testing and 9/23 (39%) in those who were undiagnosed after prior genetic testing, completed on a clinical basis. Short tandem repeat expansions in FGF14 were the most common (7/34, 21%). Two individuals (2/34, 6%) had biallelic pathogenic expansions in RFC1 and one individual had a monoallelic pathogenic expansion in ATXN8OS/ATXN8. Causative pathogenic sequence variants other than short tandem repeat expansions were found in four individuals, including in VCP, STUB1, ANO10 and SPG7. Furthermore, all five positive controls were identified.</p><p><strong>Interpretation: </strong>Our results demonstrate the utility of targeted long-read sequencing in the genetic evaluation of patients with spastic-ataxia spectrum disorders, highlighting both the capacity to increase overall diagnostic yield and to streamline the testing pathway by capturing all known genetic causes in a single assay.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence of blood-brain barrier dysfunction and CSF immunoglobulin synthesis in Down Syndrome Regression Disorder.","authors":"Jonathan D Santoro, Neetha Paul Eduthan, Mellad M Khoshnood, Saba Jafarpour, Natalie K Boyd, Benjamin N Vogel, Lina Nguyen, Lilia Kazerooni, Eleanor Britton, Hannah R Lyford, Matthew D Galbraith, Angela L Rachubinski, Joaquin M Espinosa","doi":"10.1002/acn3.52299","DOIUrl":"https://doi.org/10.1002/acn3.52299","url":null,"abstract":"<p><strong>Objectives: </strong>This study sought to evaluate proteomic, metabolomic, and immune signatures in the cerebrospinal fluid of individuals with Down Syndrome Regression Disorder (DSRD).</p><p><strong>Methods: </strong>A prospective case-control study comparing proteomic, metabolomic, and immune profiles in individuals with DSRD was performed. Samples were obtained from a biorepository of affected individuals and compared to clinically available data and previously obtained neurodiagnostic studies. Individuals with DSRD were compared to individuals with established neuroinflammatory conditions (e.g., multiple sclerosis), and neurotypical controls undergoing a lumbar puncture for headaches. Samples underwent high-throughput proteomic, metabolomic, and immune marker profiling. Data was compared across groups and clinical phenotypes. Gene set enrichment analysis and pathway analyses were utilized to analyze the data.</p><p><strong>Results: </strong>In total, 34 individuals with DSRD, 22 neuroinflammatory controls, and 27 neurotypical controls were enrolled in the study. We observed a highly significant concordance in dysregulated proteomics signatures in DSRD and neuroinflammatory controls versus healthy controls, most prominently upregulation of many immunoglobulin sequences. In addition, individuals with DSRD displayed strong upregulation of liver-derived plasma proteins and erythrocyte proteins in the CSF, indicating poor blood-brain barrier integrity. The immune marker profile of DSRD is clearly similar to other neuroimmunological conditions, including strong elevation of MIP3-α, eotaxin, and IFN-γ.</p><p><strong>Interpretation: </strong>Individuals with DSRD have unique CSF proteomic and metabolomic signatures consistent with neuroinflammation and increased blood-brain barrier permeability. The CSF of individuals with DSRD was more comparable to individuals with neuroinflammatory disorders than neurotypical controls, indicating the potential for an immune etiology of disease.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Capturing what matters: Patient-reported LGI1-ANTibody encephalitis outcome RatiNg scale (LANTERN).","authors":"Mark J Kelly, Barbara Wagner, Bryan Ceronie, Christine Strippel, Ann Yee Lin, Adam Handel, John Soltys, Sophie Binks, Philip A Powell, Sarosh R Irani","doi":"10.1002/acn3.70006","DOIUrl":"https://doi.org/10.1002/acn3.70006","url":null,"abstract":"<p><strong>Background: </strong>LGI1-antibody encephalitis (LGI1-Ab-E) is a common form of autoimmune encephalitis where most patients demonstrate 'good' clinician-rated outcomes. However, more targeted questionnaires reveal numerous debilitating symptoms for many years. To better quantify these persistent features, we designed the LGI1-Antibody Encephalitis Rating (LANTERN) scale, a quantified, disease-specific patient-reported outcome measure (PROM), adhering to FDA guidelines.</p><p><strong>Methods: </strong>A participant-driven mixed-methods approach to develop a clinically valid questionnaire over three stages: (1) Item generation through semi-structured interviews; (2) Repeated cognitive debriefing rounds to advance comprehensibility, relevance and comprehensiveness; (3) Psychometric survey to condense the most sensitive and valid questions. Analyses incorporated sensitivity testing with multiple internal and external validations.</p><p><strong>Results: </strong>From 73 items across six domains (Stage 1; n = 18), a questionnaire assessing the frequency and severity of 43 symptoms (80 questions), plus nine activities of daily living (ADL), was developed through cognitive debriefing (Stage 2; n = 15). This 89-question survey was completed (Stage 3; n = 66 patients and 32 relatives) and distilled, using exploratory factor analyses, to a three-factor symptom-burden questionnaire comprising 41 questions (19 symptoms and 6 ADL), separated into physical, cognitive/behavioural and ADL domains. These factors demonstrated strong internal reliability (Cronbach alpha: 0.85-0.91), correlations with relative-completed questionnaires (R = 0.73-0.85; p < 0.001), good-to-excellent intraclass re-testing correlations (0.81-0.98; n = 19) and strong associations with numerous predefined external measures.</p><p><strong>Discussion: </strong>LANTERN represents a PROM for LGI1-Ab-E, with initial content, structural and construct validity and test-retest reliability. It can be used as a reliable, tailored, efficient and sensitive method to establish symptom burden in people with LGI1-Ab-E, both in clinical practice and trials.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Trajectories of Digital Cognitive Biomarkers for Multiple Sclerosis.","authors":"Yi Chao Foong, Daniel Merlo, Melissa Gresle, Chao Zhu, Katherine Buzzard, Jeannette Lechner-Scott, Michael Barnett, Chenyu Wang, Bruce V Taylor, Tomas Kalincik, Trevor Kilpatrick, David Darby, Pamela Dobay, Johan van Beek, Robert Hyde, Steve Simpson-Yap, Helmut Butzkueven, Anneke van der Walt","doi":"10.1002/acn3.70015","DOIUrl":"https://doi.org/10.1002/acn3.70015","url":null,"abstract":"<p><strong>Background: </strong>Cognitive impairment is one of the most common and debilitating symptoms of relapsing-remitting multiple sclerosis (RRMS). Digital cognitive biomarkers require less time and resources and are rapidly gaining popularity in clinical settings. We examined the longitudinal trajectory of the iPad-based Processing Speed Test (PST) and predictors of PST scores.</p><p><strong>Methods: </strong>We prospectively enrolled RRMS patients between 2017 and 2021 across six Australian MS centres. Longitudinal data was analysed with mixed effect modelling and latent class mixed models. We then examined whether latent class group membership predicted confirmed decrease in correct PST responses.</p><p><strong>Results: </strong>We recruited a total of 1093 participants, of which 724 had complete baseline data with a median follow up duration of 2 years. At a population level, PST trajectory was stable. A small practice effect was present up to the 4th visit. Age, baseline disability, T2 lesion volume, male sex and depression were associated with lower correct PST responses, whilst years of education and full/part-time employment were associated with more correct PST responses. We identified four latent class trajectories of PST. The worst latent class was typified by low baseline PST and lack of a practice effect. Being in the worst latent class was associated with a greater hazard of time to sustained 5% decrease in PST (HR 2.84, 95% CI 1.16-6.94, p = 0.02).</p><p><strong>Conclusion: </strong>Worse baseline cognitive performance and lack of a practice effect predicted future cognitive decline in RRMS.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Fat and Low-Carbohydrate Dietary Environments Are Linked to Reduced Idiopathic Epilepsy Incidence and Prevalence.","authors":"Duan Ni, Alistair Senior, David Raubenheimer, Stephen J Simpson, Ralph Nanan","doi":"10.1002/acn3.70017","DOIUrl":"https://doi.org/10.1002/acn3.70017","url":null,"abstract":"<p><p>Dietary manipulations like ketogenic diets are established interventions for recalcitrant epilepsy. However, it remains unknown whether specific macronutrient exposure through dietary environments could possibly extend to primary preventive qualities, associated with changes in epilepsy disease burden (prevalence and incidence). Here, macronutrient supply, GDP, and idiopathic epilepsy disease burden data were collated from more than 150 countries from 1990 to 2018. Nutritional geometry generalized additive mixed models (GAMMs) modeling unraveled that dietary environments with high-fat and low-carbohydrate supplies were linked to lower epilepsy incidence and prevalence. Our analyses suggested a plausible primary preventive role of dietary manipulations for epilepsy.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical impact and safety of brain biopsy in unexplained central nervous system disorders: a real-world cohort study.","authors":"Robin W van Steenhoven, Saan Salih, Juna M de Vries, Ide Smets, Rob M Verdijk, Mayke Gardeniers, Jeroen Kerstens, Juliette Brenner, Yvette S Crijnen, Marjolein Geurts, Jacoline E C Bromberg, Corine H GeurtsvanKessel, Peter A E Sillevis Smitt, Rutger K Balvers, Maarten J Titulaer","doi":"10.1002/acn3.70000","DOIUrl":"https://doi.org/10.1002/acn3.70000","url":null,"abstract":"<p><strong>Objective: </strong>A substantial part of central nervous system (CNS) disorders remains unexplained, despite various new and minimally invasive diagnostic techniques. Within this rapidly developing diagnostic field, the precise role of brain biopsy is unknown. We aimed to study the clinical impact and safety of brain biopsies in unexplained CNS disorders.</p><p><strong>Methods: </strong>In this retrospective cohort study, we included all adult patients who were referred for a diagnostic work-up to our academic center with neuro-inflammatory, neuro-oncological, and neuro-infectious expertise and underwent a brain biopsy between January 2010 and December 2023. Typical cases of CNS neoplasms and infections were not analyzed. Brain biopsies were evaluated with respect to diagnostic and therapeutic impact and complication risk.</p><p><strong>Results: </strong>Brain biopsy was performed in 587 patients. Ninety-four patients with a CNS disorder of unknown cause, with 107 biopsies, were analyzed (44% female, median age 58 years). Postoperative diagnoses included brain tumors/lymphomas (37/94, 39%), inflammatory disorders (11/94, 12%), infections (8/94, 9%), autoimmune encephalitis (8/94, 9%), and primary angiitis of the CNS (4/94, 4%). Diagnostic yield of brain biopsy was 62%, increasing up to 72% after repeat biopsies, as 10 additional patients were diagnosed with a brain tumor. In 77% of patients, brain biopsy changed the treatment strategy. Symptomatic intracranial hemorrhage occurred in 4 of 107 brain biopsies (4%).</p><p><strong>Interpretation: </strong>In a selected population of patients with unexplained CNS disorders, clinical impact of brain biopsies is high, while being relatively safe. A multidisciplinary team approach is fundamental in establishing optimal indication for brain biopsy and subsequent treatment decisions.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Throughput Immunoassays for Cavin-4 IgG: A Diagnostic Tool for Immune-Mediated Rippling Muscle Disease.","authors":"Reghann G LaFrance-Corey, Haidara Kherbek, Nimalan Harinesan, Margherita Milone, Naveen K Paramasivan, Pallab Sarker, Andrew M Knight, Carley Karsten, Surendra Dasari, Teerin Liewluck, William J Litchy, Sean J Pittock, John R Mills, Divyanshu Dubey","doi":"10.1002/acn3.70012","DOIUrl":"https://doi.org/10.1002/acn3.70012","url":null,"abstract":"<p><p>Cavin-4 was identified as a potential autoantigen for immune-mediated rippling muscle disease (iRMD). To validate this, we developed and tested various immunoassays, including a cell-based assay (CBA), cavin-4 recombinant protein ELISA, and multi-peptide ELISA. Among 19 iRMD patients, all exhibited muscle rippling, and 13 had percussion-induced mounding. All immunoassays demonstrated clinical and analytical specificities greater than 95%. The protein ELISA had the highest sensitivity (94.7%) and specificity (99.9%), outperforming CBA (sensitivity 89.5%, specificity 99.6%) and the multi-peptide ELISA (sensitivity 79.0%, specificity 97.2%). Our results suggest that the cavin-4 protein ELISA is a promising tool for high-throughput clinical testing in iRMD.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}