Annals of Clinical and Translational Neurology最新文献

{"title":"Epigenome-wide association study, meta-analysis, and multiscore profiling of whole blood in Parkinson's disease.","authors":"Ingeborg Haugesag Lie, Manuela M X Tan, Maren Stolp Andersen, Mathias Toft, Lasse Pihlstrøm","doi":"10.1002/acn3.52292","DOIUrl":"https://doi.org/10.1002/acn3.52292","url":null,"abstract":"<p><strong>Objectives: </strong>An increasing body of evidence indicates altered DNA methylation in Parkinson's disease, yet the reproducibility and utility of such methylation changes are largely unexplored. We aimed to further elucidate the role of dysregulated DNA methylation in Parkinson's disease and to evaluate the biomarker potential of methylation-based profiling.</p><p><strong>Methods: </strong>We conducted an epigenome-wide association study (EWAS) in whole blood, including 280 Parkinson's disease and 279 control participants from Oslo, Norway. Next, we took advantage of data from the Parkinson's Progression Markers Initiative (PPMI) and a previously published EWAS to conduct a whole blood EWAS meta-analysis in Parkinson's disease, incorporating results from a total of 3068 participants. Finally, we generated multiple methylation-based scores for each Oslo and PPMI participant and tested their association with disease status, individually and in a joint multiscore model.</p><p><strong>Results: </strong>In EWAS meta-analysis, we confirm SLC7A11 hypermethylation and nominate a novel differentially methylated CpG near LPIN1. A joint multiscore model incorporating polygenic risk and methylation-based estimates of epigenetic Parkinson's disease risk, smoking, and leukocyte proportions differentiated patients from control participants with an area under the receiver-operator curve of 0.82 in the Oslo cohort and 0.65 in PPMI.</p><p><strong>Interpretation: </strong>Our results highlight the power of DNA methylation profiling to capture multiple aspects of disease risk, indicating a biomarker potential for precision medicine in neurodegenerative disorders. The reproducibility of specific differentially methylated CpGs across data sets was limited but may improve if future studies are designed to account for disease stage and incorporate environmental exposure data.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187724","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":"Comparison of offspring outcomes in women with and without epilepsy.","authors":"Huali Luo, Xiaomin Mao, Shuli Zhu, Qiong Luo, Jiajia Fang, Qiwei Li","doi":"10.1002/acn3.52316","DOIUrl":"https://doi.org/10.1002/acn3.52316","url":null,"abstract":"<p><strong>Objective: </strong>The potential impact of antiseizure medications (ASMs) on abortion rate and bone metabolism in the offspring of pregnant women with epilepsy (WWE) is currently unknown. This research aimed to assess the potential risk by conducting a comparative analysis of bone metabolism-related indicators in the offspring of WWE.</p><p><strong>Methods: </strong>We retrospectively analyzed data from 83 epileptic parturients receiving antenatal care at our hospital and a co-operative hospital from January 1, 2012, to December 31, 2021, comparing them to a control group of 249 parturients. The study analyzed and compared the two groups' growth parameters, including delivery mode, femoral length, biparietal diameter, and birth weight. Differences in femoral length, biparietal diameter, and birth weight among different ASM groups were also examined.</p><p><strong>Results: </strong>WWE were more likely to undergo a cesarean section with a lower abortion rate (55.4% vs. 37.3%, P = 0.004). After adjusting for potential confounding variables, offspring femoral length in WWE was significantly reduced compared to the control group (6.812 cm vs. 6.923 cm, P < 0.0001). Moreover, those born to WWE using multiple ASMs had significantly reduced femoral and biparietal lengths compared to those whose mothers used a single ASM or none (P < 0.0001). Additionally, birth weight was significantly lower in offspring of WWE using multiple ASMs than those not using ASM (P < 0.05).</p><p><strong>Interpretation: </strong>WWE experienced fewer abortions but worse negative offspring outcomes. The bone metabolism of the offspring of WWE was decreased and exhibited shortened femoral length, particularly in those on multiple ASMs.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121765","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":"Radiomics in glioma: emerging trends and challenges.","authors":"Zihan Wang, Lei Wang, Yinyan Wang","doi":"10.1002/acn3.52306","DOIUrl":"https://doi.org/10.1002/acn3.52306","url":null,"abstract":"<p><p>Radiomics is a promising neuroimaging technique for extracting and analyzing quantitative glioma features. This review discusses the application, emerging trends, and challenges associated with using radiomics in glioma. Integrating deep learning algorithms enhances various radiomics components, including image normalization, region of interest segmentation, feature extraction, feature selection, and model construction and can potentially improve model accuracy and performance. Moreover, investigating specific tumor habitats of glioblastomas aids in a better understanding of glioblastoma aggressiveness and the development of effective treatment strategies. Additionally, advanced imaging techniques, such as diffusion-weighted imaging, perfusion-weighted imaging, magnetic resonance spectroscopy, magnetic resonance fingerprinting, functional MRI, and positron emission tomography, can provide supplementary information for tumor characterization and classification. Furthermore, radiomics analysis helps understand the glioma immune microenvironment by predicting immune-related biomarkers and characterizing immune responses within tumors. Integrating multi-omics data, such as genomics, transcriptomics, proteomics, and pathomics, with radiomics, aids the understanding of the biological significance of the underlying radiomics features and improves the prediction of genetic mutations, prognosis, and treatment response in patients with glioma. Addressing challenges, such as model reproducibility, model generalizability, model interpretability, and multi-omics data integration, is crucial for the clinical translation of radiomics in glioma.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121767","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":"Real-world clinical experience with serum MOG and AQP4 antibody testing by live versus fixed cell-based assay.","authors":"Yana Said, Angeliki Filippatou, Conlan Tran, LuAnn Rezavi, Kai Guo, Matthew D Smith, Yasmin Resto, John J Chen, Peter A Calabresi, Patrizio Caturegli, Sean J Pittock, Eoin P Flanagan, Elias S Sotirchos","doi":"10.1002/acn3.52310","DOIUrl":"https://doi.org/10.1002/acn3.52310","url":null,"abstract":"<p><strong>Objective: </strong>To assess the real-world performance of a live (LCBA) versus a fixed (FCBA) cell-based assay for the detection of serum antibodies directed against myelin oligodendrocyte glycoprotein (MOG-IgG) and aquaporin-4 (AQP4-IgG).</p><p><strong>Methods: </strong>This was a retrospective study of patients evaluated at a single tertiary academic referral center, with serum testing performed clinically for AQP4-IgG and/or MOG-IgG by FCBA and LCBA on the same day. Additionally, frozen banked sera from the same day for patients tested only by one assay were retrieved and tested by the other assay. FCBA was performed by the Johns Hopkins Immunology Laboratory using Euroimmun kits with detection by indirect immunofluorescence (FCBA-IF), whereas LCBA was performed by the Mayo Clinic Neuroimmunology Laboratory with detection by flow cytometry (LCBA-FACS).</p><p><strong>Results: </strong>Of 594 specimens with paired MOG-IgG testing, 500 were negative by both assays, 33 were positive by both assays, 56 were positive exclusively by LCBA-FACS, and 5 were only positive by FCBA-IF. Overall, MOG-IgG LCBA-FACS exhibited 95.1% sensitivity and 97.7% specificity, whereas MOG-IgG FCBA-IF had 45.7% sensitivity and 99.8% specificity. Of 577 specimens with paired AQP4-IgG testing, 503 were negative by both assays, 51 were positive by both assays, 21 were positive exclusively by LCBA-FACS, and 2 were only positive by FCBA-IF. Overall, AQP4-IgG LCBA-FACS exhibited 97.3% sensitivity and 100% specificity, whereas AQP4-IgG FCBA-IF had 71.6% sensitivity and 100% specificity.</p><p><strong>Interpretation: </strong>LCBA-FACS for both MOG-IgG and AQP4-IgG had markedly better sensitivity than FCBA-IF, with similar specificity. The use of FCBA-IF may result in underrecognition of both MOG antibody-associated disease (MOGAD) and AQP4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD).</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121770","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":"Blood exosome connexins and small RNAs related to demyelinating disease activity.","authors":"Guzailiayi Maimaitijiang, Jun-Ichi Kira, Yuri Nakamura, Mitsuru Watanabe, Ezgi Ozdemir Takase, Satoshi Nagata, Ayako Sakoda, Xu Zhang, Katsuhisa Masaki, Ryo Yamasaki, Noriko Isobe, Hiroo Yamaguchi, Tomohiro Imamura","doi":"10.1002/acn3.52307","DOIUrl":"https://doi.org/10.1002/acn3.52307","url":null,"abstract":"<p><strong>Objectives: </strong>To assess blood exosome (Ex)-connexin (Cx)43 (encoded by GJA1) and its truncated isoforms in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), which show distinct alterations in astroglial Cx43.</p><p><strong>Methods: </strong>Serum Exs from 48 patients with MS (34 relapsing-remitting, 14 secondary-progressive), 35 with NMOSD, 20 with other inflammatory neurologic diseases (OIND), and 17 healthy controls (HC) were subjected to quantitative Western blotting for Cx43, single-molecule array for neurofilament-L, and quantitative polymerase chain reaction for non-coding RNAs detected by RNA sequencing. Sera from control and astroglia-specific Cx43 inducible conditional knockout (Cx43-icKO) mice with experimental autoimmune encephalomyelitis (EAE) were also tested.</p><p><strong>Results: </strong>Ex-GJA1-29k was markedly higher in MS than in NMOSD, OIND, and HC; it successively increased at relapse, remission, and secondary progression, and positively correlated with disability scores. Ex-hsa-miR-133b and other hsa-miRs that bind to full-length Cx43 were significantly lower in secondary-progressive MS than in HC, and Ex-hsa-miR-133b was negatively correlated with disability scores. Ex-GJA1-11k expression was lower in NMOSD at relapse than in HC and OIND, and was negatively correlated with disability score worsening and Ex-neurofilament-L levels. NMOSD at relapse had significantly higher expression of small nucleolar RNA (SNORD37, SNORD95, and SNORD97) than HC, and SNORD37 and SNORD95 showed strong negative correlations with disability scores. Control mice showed increased Ex-GJA1-43k and -29k during EAE; this effect was markedly reduced in Cx43-icKO mice with attenuated EAE.</p><p><strong>Interpretation: </strong>Blood Ex-Cx43-truncated isoforms and small non-coding RNAs, which partially come from brain astroglia, are distinctly dysregulated in MS and NMSOD.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121763","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":"Right-sided vagus nerve stimulation: Worldwide collection and perspectives.","authors":"Marc Zanello, Berthold Voges, Ramesh Chelvarajah, Arjune Sen, Željka Petelin Gadže, Guillaume Penchet, Alessandro De Benedictis, Riccardo Fornaro, Masaki Iwasaki, Keiya Iijima, Elena Jiltsova, Goran Mrak, Sami Barrit, Alessandro Moiraghi, Andrea Landi, Marcus Neale, Shailendra Magdum, François Caire, Bertrand Godet, Philippe Domenech, Raphael Gaillard, Marc Guenot, Jason Labuschagne, Alexandre Rainha Campos, Herbert Rooijakkers, Riëm El Tahry, Tatiana Von Hertwig Fernandes De Oliveira, Amelia Alvarez-Sala, Cristina V Torres, Fernando Vale, Johan Pallud, Romain Carron","doi":"10.1002/acn3.52312","DOIUrl":"https://doi.org/10.1002/acn3.52312","url":null,"abstract":"<p><strong>Objective: </strong>Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy (DRE) and is indicated for implantation on the left vagus nerve-only. In rare cases right-sided VNS may be the only option. With only seven published cases in the literature, data on safety and effectiveness of right-sided VNS is very limited.</p><p><strong>Methods: </strong>An anonymous 38-item questionnaire was sent to expert surgeons implanting VNS for DRE. The questions covered demographics and clinical characteristics, the reason for right-sided implantation and both neurological and surgical outcomes of right-sided VNS.</p><p><strong>Results: </strong>The survey captured 38 cases of right-sided VNS (18 females, mean age at surgery of 28.0 ± 16.3 years). Right-sided VNS was performed because of VNS lead deficiency (n = 20), anatomical constraints (n = 8), infection of a left-sided VNS site (n = 9), and presence of a left ventricular shunt (n = 1). Thirty-two patients (84%) had a preoperative cardiac assessment. Three patients presented postoperative cardiac side-effects. Right-sided VNS was stopped at last follow-up in three patients: due to deep infection (n = 1), due to dyspnea (n = 1), and due to sleep apnea syndrome (n = 1). Twenty-one patients (55%) were responders to right-sided VNS and the mean reduction of seizure frequency under right-sided VNS was 56.2 ± 18.8%. Focusing on seizure frequency reduction between right-sided VNS and left-sided VNS: 20 patients experienced similar effectiveness, 1 experienced lesser effectiveness, and 2 patients experienced greater effectiveness with right-sided VNS.</p><p><strong>Interpretation: </strong>This multicenter case series significantly augments the available literature on right-sided VNS. This suggests comparable effectiveness to left-sided VNS but potentially lower tolerability. Further studies are warranted to better evaluate safety and efficacy of right-sided VNS.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121774","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":"Healthcare use is elevated two decades before a first demyelinating event and differs by age and sex","authors":"Helen Tremlett,&nbsp;Feng Zhu,&nbsp;Karl Everett,&nbsp;Ayesha Asaf,&nbsp;Ali Manouchehrinia,&nbsp;Ping Li,&nbsp;Kyla A. McKay,&nbsp;Jan Hillert,&nbsp;Yinshan Zhao,&nbsp;Colleen Maxwell,&nbsp;Ruth Ann Marrie","doi":"10.1002/acn3.52267","DOIUrl":"10.1002/acn3.52267","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Elevated healthcare use before multiple sclerosis (MS) onset suggests earlier opportunity to identify MS. Yet their timing and sociodemographic effects are unclear. We examined rates of healthcare use (and by age/sex) for &gt;two decades pre-MS onset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We identified people with MS (PwMS) using administrative data from Canada (Ontario) and Sweden (1991–2020) (“administrative” cohort), and the Swedish MS Registry (“clinical” cohort). The first MS/demyelinating diagnostic code (administrative) or symptom onset (clinical) defined MS onset. We compared annual rates of healthcare use (hospital, physician, and emergency-room [ED]) pre-onset between PwMS and up to five matched population controls using negative binomial regression, and by age/sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The administrative cohort = 35,018/136,007 PwMS/controls (Ontario), and 10,269/51,297 (Sweden). Rates of healthcare use were higher for PwMS than controls up to 28 (of 29) years (Ontario) and up to 15 (of 19) years (Sweden) pre-onset. Annual healthcare use rose steadily as onset approached, particularly escalating 7 years pre-onset in Ontario (e.g., hospital visit rate ratios [RRs] exceeded 1.30), and 6 years in Sweden (physician visit RRs &gt; 1.10). RRs peaked the year pre-onset (ED visits [Ontario] = 3.04; 95% CI: 2.94–3.13, physician visits [Sweden] = 2.51; 95% CI: 2.44–2.59). In the year pre-onset, RRs were disproportionately higher for males (ED RRs [Ontario] = 3.30; 95% CI: 3.13–3.48 vs. females = 2.90; 95% CI: 2.79–3.02), and dropped steadily by age (physician visit RRs [Sweden] = 2.61/2.27/1.97/1.72 for 50/40/30/20-year-olds). The smaller clinical cohort (7604/37,974 PwMS/controls) exhibited similar patterns, albeit more modest, with RRs elevated up to 5 years pre-onset (physician visit RR [year-5] = 1.08; 95% CI: 1.02–1.14; RR [year-1] = 1.39;1.33–1.46).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Higher healthcare use was evident decades before MS onset, escalating 6–7 years pre-onset, peaking the year before, being disproportionately higher for males and older PwMS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 2","pages":"415-432"},"PeriodicalIF":4.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062147","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":"An MRI assessment of mechanisms underlying lesion growth and shrinkage in multiple sclerosis.","authors":"Ermelinda De Meo, Ferran Prados Carrasco, J William L Brown, Alasdair J Coles, Nick G Cunniffe, Amy E Jolly, Baris Kanber, Rebecca Samson, Frederik Barkhof, Declan Chard","doi":"10.1002/acn3.52308","DOIUrl":"https://doi.org/10.1002/acn3.52308","url":null,"abstract":"<p><strong>Objective: </strong>To assess the pathological mechanisms contributing to white matter (WM) lesion expansion or contraction and remyelination in multiple sclerosis (MS).</p><p><strong>Methods: </strong>We assessed 1,613 lesions in 49 people with relapsing-remitting MS in the CCMR-One bexarotene trial (EudraCT 2014-003145-99). We measured lesion orientation relative to WM tracts, surface-in gradients and veins. Jacobian deformation was used to assess lesion expansion over 6 months, while magnetization transfer ratio (MTR) imaging was used to assess remyelination.</p><p><strong>Results: </strong>At baseline, 33% of lesions were aligned with veins, 2% along WM tracts, 0% with surface-in gradients, and 4% orthogonal to veins. No significant differences were observed in lesion shape, while lesions aligned with surface-in gradients and with veins had lower volume compared to all remaining orientations. At follow-up, 13% of lesions expanded and 7% contracted. The directions for both expansion and contraction were 18% and 8%, respectively, along WM tracts, 20% and 15% parallel to veins, 22% and 23% orthogonal to veins and 0% and 1% along surface-in gradients. Bexarotene had no effect on lesion expansion or contraction, but MTR significantly increased in lesions aligned with surface-in gradients and veins.</p><p><strong>Interpretation: </strong>Lesion expansion and shrinkage are affected by venous and WM tract factors, but these do not influence bexarotene's capacity to promote remyelination. This, instead, appears to be affected by surface-in factors. To limit lesion expansion and maximize tissue repair, multiple processes may need to be targeted.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050973","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":"Heterozygous variants in AP4S1 are not associated with a neurological phenotype.","authors":"Vicente Quiroz, Umar Zubair, Luca Schierbaum, Amy Tam, Nicole Battaglia, Joshua Rong, Habibah A P Agianda, Julian E Alecu, Kathryn Yang, Darius Ebrahimi-Fakhari","doi":"10.1002/acn3.52302","DOIUrl":"https://doi.org/10.1002/acn3.52302","url":null,"abstract":"<p><p>Biallelic loss-of-function variants in AP4S1 cause childhood-onset hereditary spastic paraplegia. A recent report suggested that heterozygous AP4S1 variants lead to a syndrome of lower limb spasticity and dysregulation of sphincter function. We critically evaluate this claim against clinical observations in 28 heterozygous carriers of the same AP4S1 variant (NM_007077.3: c.289C>T, p.Arg97Ter). In these 14 males and 14 females (mean age: 37.6 ± 4.9 years [SD], range: 30-50 years), we ascertain no increased prevalence of neurological manifestations. Alternative causes should be considered when evaluating patients with heterozygous AP4S1 variants and neurological symptoms, as misattribution of pathogenicity can impact clinical care and genetic counseling.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045086","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":"CSF cytokine, chemokine and injury biomarker profile of glial fibrillary acidic protein (GFAP) autoimmunity.","authors":"Yahel Segal, Georgios Mangioris, Vanda Lennon, Binxia Yang, Divyanshu Dubey, Eoin P Flanagan, Andrew McKeon, John R Mills, Michel Toledano, Ivana Vodopivec, Sean J Pittock, Anastasia Zekeridou","doi":"10.1002/acn3.52305","DOIUrl":"https://doi.org/10.1002/acn3.52305","url":null,"abstract":"<p><p>Defining the CSF cytokine/chemokine and injury biomarker signature of glial fibrillary acidic protein (GFAP) autoimmunity can inform immunopathogenesis. CSF GFAP-IgG-positive samples (N = 98) were tested for 17 cytokines/chemokines, neurofilament light chain (NfL), and GFAP (ELLA, Bio-Techne). Controls included non-inflammatory (N = 42), AQP4-IgG-positive (N = 83), CNS infections (N = 13), and neurosarcoidosis (N = 32). IL5, IL6, IL10, IL8/CXCL8, CXCL9, CXCL10, CXCL13, BAFF, GM-CSF, IFN-gamma, and TNF-alpha concentrations were higher compared to non-inflammatory controls (P < 0.01). GFAP concentrations were similar to those of AQP4-IgG-positive patients; NfL was higher (P < 0.001) and correlated with MRI changes and outcomes. CSF cytokine/chemokine findings in GFAP autoimmunity correlate with histopathology; GFAP and NfL hold promise as disease biomarkers.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051109","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}