Annals of Clinical and Translational Neurology最新文献

{"title":"Expanding molecular and clinical spectrum of CPT1C-associated hereditary spastic paraplegia (SPG73)—a case series","authors":"Alexandra K. Brooks,&nbsp;Vicente Quiroz,&nbsp;Luca Schierbaum,&nbsp;Amy Tam,&nbsp;Julian E. Alecu,&nbsp;Darius Ebrahimi-Fakhari","doi":"10.1002/acn3.52288","DOIUrl":"10.1002/acn3.52288","url":null,"abstract":"<p>Autosomal-dominant variants in the <i>CPT1C</i> gene have been associated with hereditary spastic paraplegia type 73 (SPG73), which typically presents with slowly progressive lower limb weakness and spasticity and is therefore considered a pure form of hereditary spastic paraplegia. However, we report two unrelated males with novel <i>CPT1C</i> variants (NM_001199753.2: patient 1: c.2057_2061del (p.Ile686SerfsTer8) and patient 2: c.2020-1G&gt;C (p.?)) who presented with lower limb spasticity at 4 and 3 years old, respectively. Both patients also experienced significant cognitive impairment, seizures, or neurobehavioral symptoms. These cases illustrate a broader and more complex clinical spectrum of SPG73, extending beyond the traditionally recognized pure motor symptoms.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 3","pages":"648-652"},"PeriodicalIF":4.4,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52288","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906454","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":"Cortical lesions impact cognitive decline in multiple sclerosis via volume loss of nonlesional cortex","authors":"Eva A. Krijnen,&nbsp;Maureen van Dam,&nbsp;Albulena Bajrami,&nbsp;Piet M. Bouman,&nbsp;Samantha Noteboom,&nbsp;Frederik Barkhof,&nbsp;Bernard M.J. Uitdehaag,&nbsp;Martijn D. Steenwijk,&nbsp;Eric C. Klawiter,&nbsp;Ismail Koubiyr,&nbsp;Menno M. Schoonheim","doi":"10.1002/acn3.52261","DOIUrl":"10.1002/acn3.52261","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess the interrelationship between cortical lesions and cortical thinning and volume loss in people with multiple sclerosis within cortical networks, and how this relates to future cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this longitudinal study, 230 people with multiple sclerosis and 60 healthy controls underwent 3 Tesla MRI at baseline and neuropsychological assessment at baseline and 5-year follow-up. Cortical regions (<i>N</i> = 212) were divided into seven functional networks. Regions were defined as either lesional or normal-appearing cortex based on presence of a cortical lesion on artificial intelligence-generated double inversion-recovery scans. Cortical volume and thickness were determined within lesional or normal-appearing cortex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Prevalence of at least one cortical lesion was highest in the limbic (73%) followed by the default mode network (70.9%). Multiple sclerosis-related cortical thinning was more pronounced in lesional (mean <i>Z</i>-score = 0.70 ± 0.84) compared to normal-appearing cortex (−0.45 ± 0.60; <i>P</i> &lt; 0.001) in all, except sensorimotor, networks. Cognitive dysfunction, particularly of verbal memory, visuospatial memory, and inhibition, at follow-up was best predicted by baseline network volume of normal-appearing cortex of the default mode network [<i>B</i> (95% CI) = 0.31 (0.18; 0.43), <i>P</i> &lt; 0.001]. Mediation analysis showed that the effect of cortical lesions on future cognition was mediated by volume loss of the normal-appearing instead of lesional cortex, independent of white matter lesion volume.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Multiple sclerosis-related cortical thinning was worse in lesional compared to normal-appearing cortex, while volume loss of normal-appearing cortex was most predictive of subsequent cognitive decline, particularly in the default mode network. Mediation analyses indicate that cortical lesions impact cognitive decline plausibly by inducing atrophy, rather than through a direct effect.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"121-136"},"PeriodicalIF":4.4,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890619","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":"Real-world efficacy of transfusion with liberal or restrictive strategy in traumatic brain injury","authors":"Liang-Wen Cui,&nbsp;Nian Liu,&nbsp;Chao Yu,&nbsp;Ming Fang,&nbsp;Rui Huang,&nbsp;Cheng Zhang,&nbsp;Min Shao","doi":"10.1002/acn3.52272","DOIUrl":"10.1002/acn3.52272","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The short-term efficacy of red blood cell (RBC) transfusion among general traumatic brain injury (TBI) patients is unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used the MIMIC database to compare the efficacy of liberal (10 g/dL) versus conservative (7 g/dL) transfusion strategy in TBI patients. The outcomes were neurological progression (decrease of Glasgow coma scale (GCS) of at least 2 points) and death within 28 days of ICU admission. Each eligible individual was cloned and assigned each of the replicates to one of the treatment arm. The imbalance induced by informative censoring was adjusted by inverse probability weighting. The standardized, weighted pooled logistic regression with 500 bootstrap resampling was used to estimate the cumulative risk difference and 95% confidence interval (CI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 1141 eligible individuals, 29.0% received RBC transfusion. Compared with the restrictive group, the liberal strategy reduced early death (3 days: 5%, 95% CI: 2%–7%; 7 days: 6%, 95% CI: 3%–11%); however, no significant difference of mortality risk at 28-day or neurological progression risk at any time points was observed. The risk of coagulopathy at 3 days was increased by 7% (95% CI: 1%–19%) in the liberal group. The subgroup analysis indicated a beneficial effect of liberal transfusion on mortality in hemodynamically unstable patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Compared with the restrictive strategy, the liberal strategy does not improve the short-term neurological prognosis and death among patients with TBI in a real-world situation. The liberal strategy may be beneficial to survival at very early stage or in hemodynamically unstable subgroup.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"203-212"},"PeriodicalIF":4.4,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890628","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":"Ofatumumab treatment in new-onset narcolepsy type 1 following SARS-CoV-2 infection","authors":"Xiaoli Wang,&nbsp;Xinbo Zhang,&nbsp;Na Yuan,&nbsp;Yonghong Liu","doi":"10.1002/acn3.52284","DOIUrl":"10.1002/acn3.52284","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To explore the efficacy of ofatumumab in new onset narcolepsy type 1 following SARS-CoV-2 infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We present a 9-year-old girl who experienced new onset narcolepsy type 1 following SARS-CoV-2 infection. Polysomnography (PSG) followed by a daytime multiple sleep latency test (MSLT) was under taken after admission. A lumbar puncture was performed to evaluate the CSF orexin-A level. We assessed the CSF hypocretin-1 concentration utilizing the RIA kit from Phoenix Pharmaceuticals Inc. HLA typing was performed. Furthermore, we treated the patient with subcutaneous injections of ofatumumab, and followed her for nearly six-month. The CSF orexin-A level, CD19+ and total B cell population were measured before and after treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The girl had experienced SARS-CoV-2 infection 4 months before presentation. After that, she started to experience excessive daytime sleepiness and cataplexy. She also began to experience nightmares and violent behaviors during her nocturnal sleep, which were not present before her SARS-CoV-2 infection. At the same time, she developed obesity and exhibited psychiatric symptoms such as agitation, anxiety, and aggression. MSLT showed a mean sleep latency of 2.7 min, and 5 times sleep onset REM periods. The CSF orexin-A level was pathologically low at 34.06 pg/mL, and she tested positive for HLA-DQB1*06:02. Consequently, a diagnosis of narcolepsy type 1 was confirmed. Before and after treatment with subcutaneous injections of ofatumumab, the CD19+ and total B cell population before treatment and after 1 months showed a significant reduction from 11% and 296 cells per microliter to 0.56% and 11 cells per microliter, respectively. Within a week following ofatumumab therapy, there was a marked improvement in both excessive daytime sleepiness and cataplexy. Notably, her cataplexy was almost entirely resolved following ofatumumab therapy. Her condition remained stable throughout the 9-month follow-up period. She could normally attend school.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The efficacy of ofatumumab in this case provides additional support for an autoimmune etiology in narcolepsy with cataplexy, highlighting the potential involvement of B-cells in its pathophysiology. This understanding will aid in the development of specific immunotherapeutic strategies for early implementation upon disease onset.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 3","pages":"666-669"},"PeriodicalIF":4.4,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890624","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":"Iatrogenic cerebral amyloid angiopathy and Alzheimer's disease co-pathology","authors":"Francisco Hernández-Fernández,&nbsp;Isabel Martínez-Fernández,&nbsp;Rosa Barbella-Aponte,&nbsp;Inmaculada Feria Vilar,&nbsp;Oscar Ayo-Martín,&nbsp;Jorge García-García,&nbsp;Rosa Collado,&nbsp;Alberto Andrés,&nbsp;Mar Hernández-Guillamón,&nbsp;Francisco José Pena Pardo,&nbsp;Cristina Barrena,&nbsp;Miguel de la Fuente,&nbsp;Gemma Serrano-Heras,&nbsp;María Melero,&nbsp;Elena Lozano Setién,&nbsp;Luis López,&nbsp;Tomás Segura","doi":"10.1002/acn3.52278","DOIUrl":"10.1002/acn3.52278","url":null,"abstract":"<p>Iatrogenic cerebral amyloid angiopathy, a disease caused by contact with neurosurgical material or human growth hormone contaminated by beta-amyloid peptide (Aβ), has a prion-like transmission mechanism. We present a series of three patients under 55 years of age who underwent cranial surgery. All of them developed multiple cerebral hemorrhages, transient focal neurological deficits, and/or cognitive impairment after 3–4 decades. MRI was compatible with CAA, and Aβ deposition was confirmed. The third patient, who had a ventriculoperitoneal valve, also showed Aβ deposition in the peritoneum and diagnostic biomarkers of Alzheimer's disease. Co-pathology with Alzheimer disease and its iatrogenic transmission should be considered.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"235-241"},"PeriodicalIF":4.4,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890622","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":"Alpha-synuclein RT-QuIC assay in gastroduodenal and skin biopsies of Parkinson disease patients","authors":"Aron Emmi,&nbsp;Angela Mammana,&nbsp;Michele Sandre,&nbsp;Simone Baiardi,&nbsp;Luca Weis,&nbsp;Marcello Rossi,&nbsp;Franco Magliocchetti,&nbsp;Edoardo Savarino,&nbsp;Francesco Paolo Russo,&nbsp;Andrea Porzionato,&nbsp;Miryam Carecchio,&nbsp;Marta Campagnolo,&nbsp;Angelo Antonini,&nbsp;Piero Parchi","doi":"10.1002/acn3.52282","DOIUrl":"10.1002/acn3.52282","url":null,"abstract":"<p>In this study, we compared the value of pathological alpha-synuclein (αSyn) seed amplification assay (SAA) in gastric and duodenal biopsies with skin biopsies in Parkinson disease (PD) patients with different disease duration. The accuracy of αSyn SAA was 87.7% in skin, 67.4% in duodenum, and 80.0% in gastric biopsies, with significantly higher sensitivity in advanced PD (skin: 81.8%; gastric: 88.9%; duodenal 58.8%). Misfolded αSyn was detected with higher sensitivity in advanced PD across all matrices, likely reflecting the progression of αSyn pathology. The seeding activity was lower in the duodenal than in the gastric wall, indicating differences in αSyn burden.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 3","pages":"637-642"},"PeriodicalIF":4.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870603","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":"Progressive brain atrophy and cortical reorganization related to surgery in temporal lobe epilepsy","authors":"Wei Li,&nbsp;Yingjie Qin,&nbsp;Xiuli Li,&nbsp;Heng Zhang,&nbsp;Qiyong Gong,&nbsp;Dong Zhou,&nbsp;Dongmei An","doi":"10.1002/acn3.52285","DOIUrl":"10.1002/acn3.52285","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Epilepsy is associated with progressive cortical atrophy exceeding normal aging. We aimed to explore longitudinal cortical alterations in patients with temporal lobe epilepsy (TLE) and distinct surgery outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We obtained longitudinal T1-weighted MRI data in a well-designed cohort, including 53 operative TLE patients, 23 nonoperative TLE patients, and 23 healthy controls. According to seizure outcomes at 24 months after surgery, operative patients were divided into seizure-free (SF) and nonseizure-free (NSF) group. Operative patients were scanned before and after surgery, while nonoperative patients and healthy controls were rescanned with similar interval times. We measured gray matter volume (GMV) in all participants and compared longitudinal cortical alterations among groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In nonoperative group, statistically significant GMV decrease was observed in ipsilateral median cingulate and paracingulate gyri and cerebellum crus I when compared with healthy controls. In operative group, postoperative GMV increase was discovered in many regions involving bilateral hemispheres, especially in the frontal lobe, without differences between SF and NSF group. Postoperative GMV decrease was found in ipsilateral inferior frontal gyrus, putamen, thalamus, and insula. GMV decrease in ipsilateral inferior frontal gyrus, putamen, and insula was more significant in SF group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Progressive cortical atrophy existed in nonoperative TLE patients. Cortical remodeling indicated by postoperative GMV increase may arise mostly from the surgery itself, rather than postsurgical seizure outcomes. More significant GMV decrease in ipsilateral inferior frontal gyrus, putamen, and insula may imply their closer connections with resected regions in seizure-free patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 2","pages":"383-392"},"PeriodicalIF":4.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52285","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870618","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":"Autoimmune brainstem encephalitis: Clinical associations, outcomes, and proposed diagnostic criteria","authors":"Michael Gilligan,&nbsp;Smathorn Thakolwiboon,&nbsp;Emma Orozco,&nbsp;Samantha Banks,&nbsp;Eoin P. Flanagan,&nbsp;Sebastian Lopez-Chiriboga,&nbsp;Jan-Mendelt Tillema,&nbsp;John R. Mills,&nbsp;Sean J. Pittock,&nbsp;Cristina Valencia Sanchez,&nbsp;Anastasia Zekeridou,&nbsp;Divyanshu Dubey,&nbsp;Andrew McKeon","doi":"10.1002/acn3.52273","DOIUrl":"10.1002/acn3.52273","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We describe neurologic phenotype, clinical associations, and outcomes in autoimmune brainstem encephalitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Medical records of neural-IgG positive autoimmune brainstem encephalitis patients diagnosed at Mayo Clinic (January 1, 2006–December 31, 2022) were reviewed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ninety-eight patients (57 male) were included. Median age of symptom onset was 51 years (range, 8 months-85 years). Frequent presenting features were ≥1: diplopia (80%), ataxia (78%), dysarthria (68%), vestibulocochlear symptoms (67%), dysphagia (61%), nausea/vomiting (42%), and facial weakness (32%). Altered mental status (11%) was uncommon. Neural antibodies detected were as follows: KLHL-11 (26 patients), GAD65 (high titer, 12), ANNA-1 (anti-Hu, 8), ANNA-2 (anti-Ri, 8), Ma2 (7), IgLON-5 (6), AQP4 (6), MOG (4), glycine receptor (4), GQ1B (4), PCA-1 (anti-Yo, 4), DPPX (2), neurochondrin (2), neurofilament (2), NMDA-R (2), AGNA-1 (SOX-1, 1), ANNA-3 (DACH1, 1), amphiphysin (1), CRMP-5 (1), ITPR-1 (1), PCA-Tr (DNER, 1), and PDE10A (1). Cancer was identified in 55 patients: germ cell (23 patients; 3 extra-testicular), ductal breast adenocarcinoma (8), small cell carcinoma (6, lung 4), adenocarcinomas (6), neuroendocrine carcinoma (3), hematologic (2), squamous cell (2), and other (7). Median modified Ranking score (mRS) at last follow-up was 3 (range, 0–6). Factors associated with poor outcome included abnormal brain MRI, bulbar symptoms, and elevated CSF IgG index. Kaplan–Meier analysis revealed faster progression to wheelchair in patients who were immunotherapy refractory and with elevated CSF IgG index. Diagnostic criteria for autoimmune brainstem encephalitis (definite and probable) are proposed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Autoimmune brainstem encephalitis is a distinct clinical subphenotype of autoimmune encephalitis. Abnormal brain MRI, bulbar symptoms, and elevated CSF-IgG index associate with poor outcome.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"213-225"},"PeriodicalIF":4.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870616","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":"The epidemiology and clinical presentation of seropositive neuromyelitis optica spectrum disorder in a US population","authors":"Aaron M. Carlson,&nbsp;Carlos E.V. Sollero,&nbsp;Andrew B. Wolf,&nbsp;Stefan Sillau,&nbsp;Barrie L. Schmitt,&nbsp;Kelli M. Money,&nbsp;Kavita V. Nair,&nbsp;Amanda L. Piquet,&nbsp;Jeffrey L. Bennett","doi":"10.1002/acn3.52268","DOIUrl":"10.1002/acn3.52268","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To define the epidemiology and clinical presentation of seropositive neuromyelitis optica spectrum disorder (NMOSD) in a large US health system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We completed a retrospective observational study of adult patients in the University of Colorado Health System from 1 January 2011 to 31 December 2020, using Health Data Compass (HDC), a data warehouse that combines electronic health information with claims and public health data in Colorado. We screened HDC for patients with either (1) an abnormal aquaporin-4 IgG test or (2) any G36 ICD-10 code. We extracted key clinical elements by chart review and confirmed diagnosis by the 2015 International Panel for NMO Diagnosis criteria. Annual incidence and prevalence rates were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our population consisted of 2,475,591 individuals contributing 11,103,522.72 person-years of observation. In total, 115 seropositive NMOSD patients were identified. The average yearly incidence was 0.22 per 100,000 person-years. Age and sex-adjusted prevalence (per 100,000) was 4.33, and highest among those identifying as Asian or Pacific Islander (17.72), and Black (14.74), as separately by Hispanic ethnicity (8.02). Prevalence was higher in women (6.20:1 female:male ratio). Transverse myelitis (45%) and optic neuritis (43%) were the most common presenting clinical syndromes. In total, 6% of initial presentations were characterized by short-segment transverse myelitis without other features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Seropositive NMOSD incidence is higher in our cohort than many contemporary studies. Women and those identifying as Asian or Pacific Islander, Black, and Hispanic shoulder the highest burden of disease. Clinical onset with short-segment myelitis underscores the need for serum aquaporin-4 IgG testing in acute myelitis presentations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"169-179"},"PeriodicalIF":4.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870620","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":"APOE genotype and brain amyloid are associated with changes in the plasma proteome in elderly subjects without dementia","authors":"Sarah M. Philippi,&nbsp;Kailash BP,&nbsp;Towfique Raj,&nbsp;Joseph M. Castellano","doi":"10.1002/acn3.52250","DOIUrl":"10.1002/acn3.52250","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Recent work has bolstered the possibility that peripheral changes may be relevant to Alzheimer's disease pathogenesis in the brain. While age-associated blood-borne proteins have been targeted to restore function to the aged brain, it remains unclear whether other dysfunctional systemic states can be exploited for similar benefits. Here, we investigate whether <i>APOE</i> allelic variation or presence of brain amyloid are associated with plasma proteomic changes and the molecular processes associated with these changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the SOMAscan assay, we measured 1305 plasma proteins from 53 homozygous, <i>APOE3</i> and <i>APOE4</i> subjects without dementia. We investigated the relationship of either the <i>APOE-ε4</i> allele or amyloid positivity with plasma proteome changes by linear mixed effects modeling and ontology-based pathway and module–trait correlation analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>APOE4</i> is associated with plasma protein differences linked to atherosclerosis, tyrosine kinase activity, cholesterol transport, extracellular matrix, and synaptogenesis pathways. Independent of <i>APOE4</i>, we found that subjects likely harboring brain amyloid exhibit plasma proteome signatures associated with AD-linked pathways, including neurovascular dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our results indicate that <i>APOE4</i> status or presence of brain amyloid are associated with plasma proteomic shifts prior to the onset of symptoms, suggesting that systemic pathways in certain risk contexts may be plausible targets for disease modification.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 2","pages":"366-382"},"PeriodicalIF":4.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845559","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}