Annals of Clinical and Translational Neurology最新文献

{"title":"Unleashing the Power of Multiomics: Unraveling the Molecular Landscape of Peripheral Neuropathy","authors":"Julie Choi,&nbsp;Zitian Tang,&nbsp;Wendy Dong,&nbsp;Jenna Ulibarri,&nbsp;Elvisa Mehinovic,&nbsp;Simone Thomas,&nbsp;Ahmet Höke,&nbsp;Sheng Chih Jin","doi":"10.1002/acn3.70019","DOIUrl":"10.1002/acn3.70019","url":null,"abstract":"<p>Peripheral neuropathies (PNs) affect over 20 million individuals in the United States, manifesting as a wide range of sensory, motor, and autonomic nerve symptoms. While various conditions such as diabetes, metabolic disorders, trauma, autoimmune disease, and chemotherapy-induced neurotoxicity have been linked to PN, approximately one-third of PN cases remain idiopathic, underscoring a critical gap in our understanding of these disorders. Over the years, considerable efforts have focused on unraveling the complex molecular pathways underlying PN to advance diagnosis and treatment. Traditional methods such as linkage analysis, fluorescence in situ hybridization, polymerase chain reaction, and Sanger sequencing identified initial genetic variants associated with PN. However, the establishment and application of next-generation sequencing (NGS) and, more recently, long-read/single-cell sequencing have revolutionized the field, accelerating the discovery of novel disease-causing variants and challenging previous assumptions about pathogenicity. This review traces the evolution of genomic technologies in PN research, emphasizing the pivotal role of NGS in uncovering genetic complexities. We provide a comprehensive analysis of established genomic approaches such as genome-wide association studies, targeted gene panel sequencing, and whole-exome/genome sequencing, alongside emerging multiomic technologies including RNA sequencing and proteomics. Integrating these approaches promises holistic insights into PN pathophysiology, potentially revealing new biomarkers and therapeutic targets. Furthermore, we discuss the clinical implications of genomic and multiomic integration, highlighting their potential to enhance diagnostic accuracy, prognostic assessment, and personalized treatment strategies for PN. Challenges and questions in standardizing these technologies for clinical use are raised, underscoring the need for robust guidelines to maximize their clinical utility.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 4","pages":"674-685"},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699188","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":"Home-Based Tele-tDCS in Amyotrophic Lateral Sclerosis: Feasibility, Safety, and Preliminary Efficacy.","authors":"Sangeetha Madhavan, Shravni Deshmukh, Mark Cummings, Aditi Doshi, Kourosh Rezania, Sally Freels, Gina Sawa","doi":"10.1002/acn3.70038","DOIUrl":"https://doi.org/10.1002/acn3.70038","url":null,"abstract":"<p><strong>Objective: </strong>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited treatment options. Transcranial direct current stimulation (tDCS) shows promise as a neuromodulatory intervention in various neurological disorders, but its application in ALS, particularly in a remote, home-based format, remains underexplored. This study investigates the feasibility, safety, and preliminary efficacy of remotely supervised tele-tDCS in ALS patients.</p><p><strong>Methods: </strong>This double-blinded pilot study included 14 spinal-onset ALS participants randomized into two groups: the intervention group received 72 tele-tDCS sessions over 24 weeks, and the delayed-start group received 36 sham sessions followed by 36 tele-tDCS sessions. Stimulation was delivered at 2 mA for 20 min 3 times a week. Primary outcomes included feasibility, safety, and disease progression measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). Adherence and adverse effects were monitored throughout.</p><p><strong>Results: </strong>Ten participants completed the study, with an overall compliance rate of 98.3%. No serious adverse events were reported, and mild side effects, like itching and tingling, were consistent with tDCS literature. The intervention group demonstrated a significantly slower decline in ALSFRS-R scores than the delayed-start group. At 24 weeks, the intervention group had a mean ALSFRS-R change of -1.7, compared to -13.6 in the delayed-start group (p = 0.0018). Additionally, the change in ALSFRS-R between pre- and mid-intervention significantly differed between groups (p = 0.0071).</p><p><strong>Interpretation: </strong>Tele-tDCS was feasible, safe, and well-tolerated in individuals with ALS. Preliminary efficacy results suggest that tele-tDCS may slow disease progression, underscoring the potential of tele-tDCS as a promising home-based neuromodulatory intervention in ALS management.</p><p><strong>Trial registration: </strong>Clinical trial registration: NCT04866771.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690608","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":"Combination Therapy With Vigabatrin and Prednisolone Versus Vigabatrin Alone for Infantile Spasms.","authors":"Rachata Boonkrongsak, Kantapon Trongkamolchai, Sirorat Suwannachote, Somjit Sri-Udomkajorn, Raviwan Wittawassamrankul, Ravindra Arya, Kullasate Sakpichaisakul","doi":"10.1002/acn3.70034","DOIUrl":"https://doi.org/10.1002/acn3.70034","url":null,"abstract":"<p><strong>Objective: </strong>The study evaluated the effectiveness of combination therapy with vigabatrin and prednisolone versus vigabatrin alone for treating infantile epileptic spasms syndrome (IESS).</p><p><strong>Methods: </strong>This single-center, single-blind, randomized trial enrolled infants aged 2-14 months with new-onset IESS, randomly assigned them (1:1) to receive either combination therapy with vigabatrin (100-150 mg/kg/day) and prednisolone (40-60 mg/day) or vigabatrin alone. The primary outcome was sustained spasm remission between days 14 and 42. The trial (ClinicalTrials.gov identifier) was terminated early due to an interim analysis revealing a significant difference between treatment groups.</p><p><strong>Results: </strong>In all, 17 infants were assigned to combination therapy and 24 to vigabatrin alone. The median lead time to treatment for combination therapy was 30 days, compared to 60 days for the vigabatrin group (p = 0.442). Sustained spasm remission between days 14 and 42 occurred in 13 (77%) of 17 infants on combination therapy and in 8 (33%) of 24 infants on vigabatrin alone (OR 6.5, 95% CI 1.7, 29.6, p = 0.009). Combination therapy was more effective in achieving an electroclinical response by day 14 (OR 9.3, 95% CI 2.0, 54.3, p = 0.006) but not by day 42 (OR 1.9, 95% CI 0.5, 7.1, p = 0.351). Hospitalization occurred in six (35%) infants in the combination therapy group and two (8%) in the vigabatrin alone group (p = 0.05). One death was reported in the vigabatrin group.</p><p><strong>Interpretation: </strong>Despite early termination, this study showed that combination therapy is significantly more effective in achieving clinical remission of spasms and an electroclinical response by day 14.</p><p><strong>Trial registration: </strong>NCT04302116.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672979","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":"Universal Proteomic Signature After Exercise-Induced Muscle Injury in Muscular Dystrophies.","authors":"Mads G Stemmerik, Benjamin Barthel, Nanna R Andersen, Sofie V Skriver, Alan J Russell, John Vissing","doi":"10.1002/acn3.70035","DOIUrl":"https://doi.org/10.1002/acn3.70035","url":null,"abstract":"<p><strong>Objective: </strong>Several neuromuscular disorders (NMDs) are characterized by progressive muscle damage and are marked by the elevation of circulating muscle proteins from activity-related injury. Despite a diverse array of genetic drivers, many NMDs share similar patterns of exercise intolerance and higher concentrations of muscle injury proteins relative to unaffected individuals. While the interplay between the nature of the muscle injury and the specific genetic driver is poorly understood, the similarities exhibited by various NMDs suggest that a common proteomic signature of muscle injury may exist.</p><p><strong>Methods: </strong>We used an established exercise challenge and the SOMAscan proteomics platform to study the baseline and post-exercise proteomic profiles in a cross-sectional study of three different muscular dystrophies: Becker muscular dystrophy (BMD) and limb girdle muscular dystrophy types R9 and R12.</p><p><strong>Results: </strong>Our Results Uncover a Common Signature of Circulating Proteins That Are Elevated in all Three Myopathies, Some of Which Are Further Elevated by Exercise in Becker Muscular Dystrophy and Limb Girdle Muscular Dystrophy Type R9, and Others That Are Not Responsive to Exercise.</p><p><strong>Interpretation: </strong>Interestingly, these two signatures exhibit opposing trajectories with age in a larger cross-sectional cohort of BMD individuals. This research represents a first step toward defining an annotated protein signature coupled with activity-injury, a defining pathophysiological feature of many myopathies.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661783","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":"Abnormal Synchronization Between Cortical Delta Power and Ripples in Hippocampal Sclerosis.","authors":"Takamitsu Iwata, Takufumi Yanagisawa, Ryohei Fukuma, Yuji Ikegaya, Satoru Oshino, Naoki Tani, Hui Ming Khoo, Hidenori Sugano, Yasushi Iimura, Hiroharu Suzuki, Haruhiko Kishima","doi":"10.1002/acn3.70032","DOIUrl":"https://doi.org/10.1002/acn3.70032","url":null,"abstract":"<p><strong>Objective: </strong>Discriminating between epileptogenic and physiological ripples in the hippocampus is important for identifying epileptogenic (EP) zones; however, distinguishing these ripples on the basis of their waveforms is difficult. We hypothesized that the nocturnal synchronization of hippocampal ripples and cortical delta power could be used to classify epileptogenic and physiological ripples in the hippocampus.</p><p><strong>Methods: </strong>We enrolled 38 patients with electrodes implanted in the hippocampus or parahippocampal gyrus between April 2014 and March 2023 at our institution. We divided 11 patients (11 hippocampi) who were pathologically diagnosed with hippocampal sclerosis into the EP group and five patients (six hippocampi) with no epileptogenicity in the hippocampus into the nonepileptogenic (NE) group. Hippocampal ripples were detected using intracranial electroencephalography with hippocampal or parahippocampal electrodes. Cortical delta power (0.5-4 Hz) was assessed using cortical electrodes. The Pearson correlation coefficient between the ripple rates and cortical delta power (Corr-RD) was calculated on the basis of the intracranial electroencephalographic signals recorded each night.</p><p><strong>Results: </strong>Although hippocampal ripples were similar among the EP and NE groups based on their waveforms and frequency properties, the Corr-RDs in the EP group (mean [standard deviation]: 0.20 [0.049]) were significantly lower than those in the NE group (0.67 [0.070]). On the basis of the minimum Corr-RDs, the two groups were classified with 94.1% accuracy.</p><p><strong>Interpretation: </strong>Our results demonstrate that the Corr-RD is a biomarker of hippocampal epileptogenicity.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661782","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":"Development of a Disease Model for Predicting Postoperative Delirium Using Combined Blood Biomarkers.","authors":"Hengjun Wan, Huaju Tian, Cheng Wu, Yue Zhao, Daiying Zhang, Yujie Zheng, Yuan Li, Xiaoxia Duan","doi":"10.1002/acn3.70029","DOIUrl":"https://doi.org/10.1002/acn3.70029","url":null,"abstract":"<p><strong>Objective: </strong>Postoperative delirium, a common neurocognitive complication after surgery and anesthesia, requires early detection for potential intervention. Herein, we constructed a multidimensional postoperative delirium risk-prediction model incorporating multiple demographic parameters and blood biomarkers to enhance prediction accuracy.</p><p><strong>Methods: </strong>We included 555 patients undergoing radical surgery for colorectal cancer. Demographic characteristics and lipid profiles were collected preoperatively, and perioperative anesthesia and surgical conditions were recorded; blood biomarkers were measured before and after surgery. The 3D-CAM scale was used to assess postoperative delirium occurrence within 3 days after surgery. Patients were divided into the postoperative delirium (N = 100) and non-postoperative delirium (N = 455) groups. Based on machine learning, linear and nine non-linear models were developed and compared to select the optimal model. Shapley value-interpretation methods and mediation analysis were used to assess feature importance and interaction.</p><p><strong>Results: </strong>The median age of the participants was 65 years (interquartile range: 56-71 years; 57.8% male). Among the 10 machine-learning models, the random forest model performed the best (validation cohort, area under the receiver operating characteristic curve of 0.795 [0.704-0.885]). Lipid profile (total cholesterol, triglycerides, and trimethylamine-N-oxide) levels were identified as key postoperative delirium predictors. Mediation analysis further confirmed mediating effects among total cholesterol, trimethylamine-N-oxide, and postoperative delirium; a nomogram model was developed as a web-based tool for external validation and use by other clinicians.</p><p><strong>Interpretation: </strong>Blood biomarkers are crucial in predicting postoperative delirium and aid anesthesiologists in identifying its risks in a timely manner. This model facilitates personalized perioperative management and reduces the occurrence of postoperative delirium.</p><p><strong>Trial registration: </strong>ChiCTR2300075723.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646611","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":"If it does not help, it might hurt: Pharmacodynamics of a second IVIg course in Guillain-Barré syndrome.","authors":"Sander J van Tilburg, Ruth Huizinga, Krista Kuitwaard, Sebastiaan D T Sassen, Christa Walgaard, Pieter A van Doorn, Bart C Jacobs, Birgit C P Koch","doi":"10.1002/acn3.52313","DOIUrl":"https://doi.org/10.1002/acn3.52313","url":null,"abstract":"<p><strong>Objectives: </strong>Intravenous immunoglobulin (IVIg) is an effective treatment for Guillain-Barré syndrome (GBS), but recovery varies between patients. This study aims to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of a single and a second IVIg dose (SID) in patients with GBS.</p><p><strong>Methods: </strong>Data were analyzed from the SID-GBS trial, a double-blind, randomized, placebo-controlled study. Patients with poor prognosis (modified Erasmus GBS Outcome Score, mEGOS ≥6) after a standard course of IVIg (0.4 g/kg for 5 days) were randomized to receive either SID or placebo. Serum IgG levels were measured at standard serial time points and clinical outcomes were assessed using the GBS disability score and Medical Research Council sum score. PK modeling was performed to predict IVIg exposure and its association with clinical outcomes.</p><p><strong>Results: </strong>Serum IgG concentration after a single and double course of IVIg was variable, but accurately described by the current PK model. Lower ΔIgG and IVIg exposure were associated with poorer clinical outcomes. SID increased the IgG concentration, but did not result in an improvement in clinical outcome. Serious adverse events, including thromboembolic events, occurred more frequently in the SID group and were associated with lower IVIg exposure.</p><p><strong>Interpretation: </strong>SID increases serum IgG levels in GBS patients as predicted by the current PK model, but does not improve clinical outcomes and increases the risk of serious adverse events. Model-informed precision dosing may guide individualization of treatment.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622865","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":"Claustrum Volume Is Reduced in Multiple Sclerosis and Predicts Disability.","authors":"Nicole Shelley, Bradley Judge, Dmitriy A Yablonskiy, Robert T Naismith, Matthew R Brier, Anne H Cross","doi":"10.1002/acn3.70020","DOIUrl":"10.1002/acn3.70020","url":null,"abstract":"<p><strong>Objective: </strong>The claustrum is a small, thin structure of predominantly gray matter with broad connectivity and enigmatic function. Little is known regarding the impact of claustrum pathology in multiple sclerosis (MS).</p><p><strong>Methods: </strong>This study assessed whether claustrum volume was reduced in MS and whether reductions were associated with specific disability domains. We compared the impact of claustrum volume reductions on neurological disability versus the well-studied thalamus. Data from the 15,793 participants in the MS PATHS study were used for primary analyses. A second cohort of 71 people with MS and healthy controls from our center was used for validation.</p><p><strong>Results: </strong>Claustrum and thalamic volumes were reduced to a similar degree across MS types. Claustrum volume, like thalamic volume, was associated with disability measures of walking speed, upper extremity dexterity, and cognition. Partial correlation analyses supported that both claustrum and thalamic volumes independently contribute to disability. Interestingly, claustrum volume outperformed thalamic volume as a predictor of future disability progression.</p><p><strong>Interpretation: </strong>This study suggests that damage and resulting atrophy to the claustrum may be an important component of MS-related disability.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622864","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":"The Impact of In-Hospital Disease Modifying Treatments on Mental and Physical Burden in Caregiver of Patients With MS.","authors":"Giuseppe Schirò, Salvatore Iacono, Michele Andolina, Gabriele Sorbello, Andrea Calì, Erika Gentile, Marco D'Amelio, Paolo Aridon, Giuseppe Salemi, Paolo Ragonese","doi":"10.1002/acn3.70026","DOIUrl":"https://doi.org/10.1002/acn3.70026","url":null,"abstract":"<p><strong>Objective: </strong>People with multiple sclerosis (pwMS) may require a high level of daily assistance both for indoor and outdoor activities. Usually, relatives or friends provide daily support to MS patients who have lost personal autonomy. Several factors such as disability level and disease duration may affect the burden of care in caregivers of pwMS; however, the relationship between disease-modifying therapies (DMTs) and caregiver burden has never been explored so far. The aim of this study is to explore the impact of hospital-based therapies on anxiety, depression, and burden of care in caregivers of pwMS.</p><p><strong>Methods: </strong>Hospital Anxiety and the Depression Scale (HADS) and Caregiver Burden Inventory (CBI) questionnaires were administered to caregivers of pwMS who performed planned visits in the outpatient setting. Multivariable regression models were built to evaluate the association between hospital-based therapies and depression (HADS-D > 7), anxiety (HADS-A > 7) and need to rest (CBI > 24).</p><p><strong>Results: </strong>Caregivers of pwMS receiving in-hospital therapies achieved higher scores in HADS and CBI questionnaires, resulting in a higher proportion of anxiety, depression, and need to rest among these. The multivariable models also showed that hospital-based therapies were positively associated with caregivers' depression (aOR = 2.38 [1.04-5.5; p = 0.04]), anxiety (aOR = 2.36 [1.03-5.4; p = 0.043]) and need to rest (aOR = 2.06 [0.8-5.29]; p = 0.13).</p><p><strong>Interpretation: </strong>Hospital-based therapies in pwMS negatively affect the burden of care and mental health of their own caregivers. The availability of home-based highly effective DMTs may contribute to reducing the outdoor caregiver burden without renouncing highly effective treatments.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595933","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 and Imaging Features of Sporadic and Genetic Frontotemporal Lobar Degeneration TDP-43 A and B.","authors":"Sean Coulborn, Rhiana Schafer, Ashlin R K Roy, Andrzej Sokolowski, Noah G Cryns, Dana Leichter, Argentina Lario Lago, Eliana Marisa Ramos, Yann Cobigo, Salvatore Spina, Lea T Grinberg, Daniel H Geschwind, Maria L Gorno-Tempini, Joel H Kramer, Howard J Rosen, Bruce L Miller, William W Seeley, David C Perry","doi":"10.1002/acn3.70014","DOIUrl":"https://doi.org/10.1002/acn3.70014","url":null,"abstract":"<p><strong>Objective: </strong>Certain frontotemporal lobar degeneration subtypes, including TDP-A and B, can either occur sporadically or in association with specific genetic mutations. It is uncertain whether syndromic or imaging features previously associated with these patient groups are subtype or genotype specific. Our study sought to discern the similarities and differences between sporadic and genetic TDP-A and TDP-B.</p><p><strong>Methods: </strong>We generated individual atrophy maps and extracted mean atrophy scores for regions of interest-frontotemporal, occipitoparietal, thalamus, and cerebellum-in 54 patients with FTLD-TDP types A or B. We calculated asymmetry as the absolute difference in atrophy between right and left frontotemporal regions, and dorsality as the difference in atrophy between dorsal and ventral frontotemporal regions. We used ANCOVAs adjusted for disease severity to compare atrophy extent or imbalance, neuropsychological tests, and behavioral measures.</p><p><strong>Results: </strong>For some regions, volumetric differences were found either between TDP subtypes (e.g., worse occipitoparietal and cerebellum atrophy in TDP-A than B), or within subtypes depending on genetic status (e.g., worse thalamic and occipitoparietal atrophy in C9orf72-associated TDP-B than sporadic TDP-B). While progranulin mutation-associated TDP-A and sporadic TDP-A cases can be strongly asymmetric, TDP-A and TDP-B associated with C9orf72 tended to be symmetric. TDP-A was more dorsal in atrophy than TDP-B, regardless of genetic status.</p><p><strong>Interpretation: </strong>While some neuroimaging features are FTLD-TDP subtype-specific and do not significantly differ based on genotype, other features differ between sporadic and genetic forms within the same subtype and could decrease accuracy of classification algorithms that group genetic and sporadic cases.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595862","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}