Annals of Clinical and Translational Neurology最新文献

{"title":"Interaction between riluzole treatment and dietary glycemic index in the disease progression of amyotrophic lateral sclerosis","authors":"Ikjae Lee,&nbsp;Hiroshi Mitsumoto,&nbsp;Seonjoo Lee,&nbsp;Edward Kasarskis,&nbsp;Michael Rosenbaum,&nbsp;Pam Factor-Litvak,&nbsp;Jeri W. Nieves","doi":"10.1002/acn3.52294","DOIUrl":"10.1002/acn3.52294","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We examined whether riluzole treatment modifies the associations between the dietary glycemic index (GI) and load (GL) and disease progression in amyotrophic lateral sclerosis (ALS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sporadic ALS patients in the Multicenter Cohort Study of Oxidative Stress who completed a baseline food frequency questionnaire were included (<i>n</i> = 304). Interactions between baseline riluzole treatment and GI/GL on functional decline and tracheostomy-free survival were examined using linear regression and Cox proportional hazard models adjusted for covariates. Age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised ALS functional rating scale (ALSFRS-r) total score, and forced vital capacity, from baseline were included as covariates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Baseline higher GI and GL were associated with less decline of ALSFRS-r total score at 3-month follow-up in the riluzole treatment group (RTG) but not in the no-riluzole group (NRG). When quartile groups were used, GI second [β = −1.9, 95% CI (−4.1, −0.2), <i>p</i> = 0.07], third [β = −3.0, 95% CI (−5.1, −0.8), <i>p</i> &lt; 0.01] and fourth [β = −2.2, 95% CI (−4.3, −0.01), <i>p</i> &lt; 0.05] quartile groups were associated with less ALSFRS-r decline at 3-months compared to the first quartile group (GI &lt; 47.2) among the RTG. Similarly, GL fourth quartile group (GL &gt; 109.5) was associated with less ALSFRS-r decline at 3 months compared to the first quartile group [β = −2.6, 95% CI (−4.7, −0.5), <i>p</i> &lt; 0.05] among the RTG. In NRG, no statistically significant differences in ALSFRS-r decline were found among GI/GL quartile groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>High dietary GI and GL are associated with a slower functional decline only among ALS patients taking riluzole.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 3","pages":"491-498"},"PeriodicalIF":4.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52294","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941799","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":"Tofersen treatment leads to sustained stabilization of disease in SOD1 ALS in a “real-world” setting","authors":"Sean E. Smith,&nbsp;Kelly McCoy-Gross,&nbsp;Amber Malcolm,&nbsp;Jeri Oranski,&nbsp;Jesse W. Markway,&nbsp;Timothy M. Miller,&nbsp;Robert C. Bucelli","doi":"10.1002/acn3.52264","DOIUrl":"10.1002/acn3.52264","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Patients with amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations (SOD1 ALS) treated with tofersen have shown slowing of disease progression, and disease stabilization with recovery of function in some patients. We report our clinical experience with treating patients with SOD1 ALS and the effects of tofersen on outcome measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a single-center observational study of patients with SOD1 ALS receiving treatment with tofersen. The effects of tofersen treatment on neurofilament levels, muscle strength, and clinical outcome measures were assessed. Several patients had outpatient neuromuscular rehabilitation in addition to tofersen treatment and we report changes in functional outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seven SOD1 ALS patients received treatment at our institution. All patients showed robust and sustained declines in serum NfL and CSF pNFH (mean change serum NfL: −57.9%; mean change CSF pNFH: −67.6%). There was apparent disease stabilization as assessed by the ALSFRS-R total score, mean change 1.1 (SD = 0.7). There was notable improvement in functional independence measured by the FIM motor score, mean change 5.13 points (SD = 3.85).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This study provides evidence that tofersen treatment in SOD1 ALS can lead to meaningful preservation of function and suggestions of sustained improvement in neurologic function in some patients, and strongly supports the role of neurofilaments as therapeutic biomarkers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 2","pages":"311-319"},"PeriodicalIF":4.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941805","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":"Correction to “Infantile Krabbe disease (0–12 months), progression, and recommended endpoints for clinical trials”","authors":"","doi":"10.1002/acn3.52275","DOIUrl":"10.1002/acn3.52275","url":null,"abstract":"<p>Article AID: ACN352114</p><p>\u0000 <b>Table 1</b>\u0000 </p><p>On Page 4, age at first evaluation for HSCT asymptomatic group should have a maximum of 40.7 not 40.1.</p><p>For initial psychosine levels, please update natural history median to 22.3 and range to 0.99–82.3, symptomatic HSCT median to 28.1 and range to 4.09–54.0, and asymptomatic HSCT range to 1.03–29.1.</p><p>For initial GALC levels, please update symptomatic HSCT median to 0.01 and asymptomatic HSCT range to 0.02–0.23.</p><p>\u0000 <b>Table 2</b>\u0000 </p><p>On Page 5, please update heading to say, “Summary of the growth percentiles in Natural History, Symptomatic HSCT, and Asymptomatic HSCT patients, indicating percentages below the third percentile for head circumference and below the fifth percentile for height, weight, and body mass index.”</p><p>\u0000 <b>Sitting</b>\u0000 </p><p>On Page 8, please update the last sentence from “52%” to “53%,” and replace “Table S6” with “Table S7” in the last sentence.</p><p>\u0000 <b>Neurodevelopmental Function</b>\u0000 </p><p>On Pages 10–11, the last sentence in the first paragraph of Page 11 (“<i>The Asympt HSCT group showed higher scores and greater gains over time than both the NH and Sympt HSCT groups for all domains (all p &lt; 0.001) (Table</i> <i>S9</i><i>)</i>.”) needs to be moved to Page 10 just after “<i>(Figs</i>. <i>S2</i> <i>and</i> <i>S3</i>, <i>Table</i> <i>S8</i><i>)</i>.” and before “<i>The group performed slightly better…</i>.”</p><p>\u0000 <b>Supporting Information</b>\u0000 </p><p><span>Table</span> <span>S4</span></p><p>Table S4 is incorrectly listed as Table S5.</p><p><span>Tables</span> <span>S7</span>, <span>S8</span>, <span>and</span> <span>S9</span></p><p>Table S7 is incorrectly listed as Table S9. Table S8 is incorrectly listed as Table S7. Table S9 is incorrectly listed as Table S8.</p><p>Additionally, the tables and figures under Supporting Information do not have numbers or legends when downloaded. To address all issues, we have prepared new, reformatted PDFs with correct figure numbers and legends to be included in Supporting Information. Please just replace those files with the new ones provided. Thank you!</p><p>We apologize for these errors.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 2","pages":"455"},"PeriodicalIF":4.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941798","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":"Psychiatric manifestations of encephalitis","authors":"Paris Bean,&nbsp;Ashley Heck,&nbsp;Ralph Habis,&nbsp;Swathi Sowmitran,&nbsp;Zoe Cartaina,&nbsp;Rajesh Gupta,&nbsp;John Probasco,&nbsp;Rodrigo Hasbun,&nbsp;Arun Venkatesan","doi":"10.1002/acn3.52260","DOIUrl":"10.1002/acn3.52260","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Encephalitis is a serious and potentially life-threatening condition of infectious or autoimmune cause. We aim to characterize the frequency and clinical spectrum of presenting psychiatric symptoms in encephalitis in order to inform earlier recognition and initiation of treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a retrospective study of adult patients who met the 2013 International Encephalitis Consortium (IEC) and/or 2016 Graus criteria between February 2005 and February 2023. The study included two hospital systems in Houston, Texas, and Baltimore, Maryland and included a total of 642 patients. Psychiatric manifestations were grouped into five high-level categories: behavior, psychosis, mood, sleep disturbances, and catatonia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In our cohort of 642 patients, 318 (49.6%) had psychiatric symptoms at the time of initial presentation, including 78.2% with autoimmune etiologies and 35.2% with viral etiologies (<i>P</i> &lt; 0.001). Those with psychiatric symptoms were younger (median age 47.5 vs. 51.5; <i>P</i> &lt; 0.001), and more likely to have a history of documented psychiatric disorders, as well as longer lengths of hospital stay, and poorer discharge outcomes. Of patients initially admitted to a psychiatric service (<i>n</i> = 28), most had autoimmune causes, although 3 out of 28 (10.7%) had herpes viral infections; admission to a psychiatric service was associated with substantially longer interval to initiation of antivirals and immunotherapy. Autoimmune and infectious etiologies differed in the spectrum and frequency of psychiatric manifestations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Psychiatric symptoms are common across etiologies of encephalitis and are associated with longer lengths of hospital stay and worse clinical outcomes. Specific patterns and dimensionality of psychiatric symptoms distinguish autoimmune from infectious causes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 2","pages":"405-414"},"PeriodicalIF":4.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941801","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":"Reactivation and consolidation of memory traces during post-encoding rest across the adult lifespan","authors":"Destaw B. Mekbib,&nbsp;Ian M. McDonough","doi":"10.1002/acn3.52290","DOIUrl":"10.1002/acn3.52290","url":null,"abstract":"<p>Episodic memory is a critical cognitive function that enables the encoding, storage, and retrieval of new information. Memory consolidation, a key stage of episodic memory, stabilizes this newly encoded information into long-lasting brain “storage.” Studies using fMRI to investigate post-encoding awake rest holds promise to shed light on early, immediate consolidation mechanisms. Here, we review fMRI studies during episodic memory to document common methods to investigate post-encoding consolidation, such as multivoxel pattern analysis (MVPA) and functional connectivity, and the current state of the science in both healthy younger and older adults. In young adults, post-encoding reactivation of stimuli-specific neural patterns in the hippocampus and its connectivity with cortical and subcortical areas (e.g., visual-temporal cortex, medial prefrontal, and medial parietal cortex) correlate with subsequent memory performance. Conversely, studies in older adults highlight the importance of large-scale brain networks during post-encoding rest, particularly the default mode network (DMN). Alterations in connectivity between the DMN and task-positive networks may help older adults maintain episodic memory. Furthermore, non-invasive brain stimulation techniques can enhance these post-encoding consolidation processes and improve memory performance in both younger and older adults. Notably, a lack of studies has investigated post-encoding memory consolidation in neurodegenerative disorders. This review underscores the importance of understanding how post-encoding neural reactivation and connectivity evolve with age to partially explain age-related declines in episodic memory performance and how such declines can be restored.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 2","pages":"246-254"},"PeriodicalIF":4.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941803","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":"Case of a 57-year-old woman with acute confusion and inability to recognize her husband","authors":"Elizabeth Anderson","doi":"10.1002/acn3.52289","DOIUrl":"10.1002/acn3.52289","url":null,"abstract":"<p>Patient is a 57-year-old Hispanic female with a past medical history of hypertension, asthma, and type II diabetes mellitus who presented to the emergency room (ER) for evaluation of 7 days of altered mental status. Upon initial presentation, the patient had difficulty following one step commands and was not fully oriented. Additionally, she appeared to be responding to external auditory and visual stimuli. Magnetic resonance imaging (MRI) completed in the ER was without acute intracranial abnormality (Figure 1), and electroencephalogram (EEG) was significant for diffuse slowing but no epileptiform activity was noted. She was admitted to the neurology service for further workup and treatment for possible autoimmune encephalitis, plasma exchange (PLEX), high-dose steroids, as well as intravenous immunoglobulin (IVIG) treatments. However, despite treatments, the patient continued to remain altered. Therefore, psychiatry was consulted as well as a cognitive specialist. Per patient's husband, he was able to recall that she had in fact had several years of cognitive decline, periods of altered mental status, hallucinations, and slowed gait. During her admission she had periods of not recognizing her husband, and identified him as an imposter, consistent with Capgras syndrome.<span>¹</span> Given clinical findings, our cognitive team determined the patient's most likely diagnosis and started her on rivastigmine 1.5 mg bid with improvement.<span>²</span></p><p>Lewy body dementia.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 2","pages":"452-453"},"PeriodicalIF":4.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941797","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":"Psoriasis and dementia: A population-based matched cohort study of adults in England","authors":"Julian Matthewman,&nbsp;Kathryn E. Mansfield,&nbsp;Sharon L. Cadogan,&nbsp;Katrina Abuabara,&nbsp;Catherine Smith,&nbsp;Krishnan Bhaskaran,&nbsp;Sinéad M. Langan,&nbsp;Charlotte Warren-Gash","doi":"10.1002/acn3.52283","DOIUrl":"10.1002/acn3.52283","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Evidence for an association between psoriasis and dementia is limited and conflicting. We aimed to investigate the association using large and representative population-based data and describe risk by dementia subtype and over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We compared dementia risk between people with and without psoriasis using an age-, sex- and primary care practice-matched cohort of adults aged ≥40 years from the Clinical Practice Research Datalink Aurum in England (1997–2021) linked to hospital admissions data, analysed with stratified Cox regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 360,014 individuals with psoriasis and 1,799,617 without, psoriasis was associated with a small increased risk of all-cause dementia (adjusted hazard ratio [aHR] 1.06, 95% CI 1.04–1.08; absolute rate difference 24 per 100,000 person-years). Strength of association increased with time since psoriasis diagnosis (e.g. aHR 0.99, 0.96–1.03 within 0 to 5 years; 1.20, 1.05–1.37 within 20 to 25 years). The association was stronger for vascular dementia (aHR 1.10, 1.06–1.14) than Alzheimer's dementia (aHR 1.03, 1.00–1.06). Hazard ratios were larger for severe psoriasis (all-cause aHR 1.32, 1.25–1.39; vascular aHR 1.58, 1.44–1.74; Alzheimer's aHR 1.11, 1.02–1.21).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Long-term risk of all-cause dementia and vascular dementia, but not Alzheimer's dementia, was slightly higher in people with psoriasis, but absolute risk differences were small. Risks were more substantially raised with time since psoriasis diagnosis and in severe psoriasis compared to mild to moderate psoriasis, suggesting a potential dose–response relationship.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 2","pages":"393-404"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913153","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":"Inflammatory disease in people with multiple sclerosis treated with immune checkpoint inhibitors","authors":"Saira Afzal,&nbsp;Yadi Li,&nbsp;Brittany Lapin,&nbsp;Le H. Hua,&nbsp;Lucy Boyce Kennedy,&nbsp;Wen Wee Ma,&nbsp;Marisa McGinley,&nbsp;Jeffrey A. Cohen,&nbsp;Amy Kunchok","doi":"10.1002/acn3.52287","DOIUrl":"10.1002/acn3.52287","url":null,"abstract":"<p>This study evaluated disease activity in people with Multiple Sclerosis (PwMS) who received immune checkpoint inhibitors (ICIs) compared to PwMS not treated with ICIs. There were 108 PwMS included (27 PwMS+ICIs and 81 PwMS controls), matched on age, sex, disease duration, DMTs, and MS disease course. Of 27 PwMS+ICIs, one (4%) had a relapse and four (15%) developed new MRI lesions without clinical symptoms. Time to relapse and MRI activity were compared using Kaplan–Meier curves and Cox regression models. There was no significant difference for either time to relapse (<i>p</i> = 0.34) or MRI activity (<i>p</i> = 0.15) in PwMS+ICIs compared to controls.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 3","pages":"643-647"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906456","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":"Refractory myasthenia gravis treated with autologous hematopoietic stem cell transplantation","authors":"Benjamin Beland,&nbsp;Jan Storek,&nbsp;Liam Quartermain,&nbsp;Christopher Hahn,&nbsp;C. Elizabeth Pringle,&nbsp;Pierre R. Bourque,&nbsp;Michael Kennah,&nbsp;Natasha Kekre,&nbsp;Christopher Bredeson,&nbsp;David Allan,&nbsp;Kareem Jamani,&nbsp;Christopher White,&nbsp;Harold Atkins","doi":"10.1002/acn3.52246","DOIUrl":"10.1002/acn3.52246","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Patients with refractory myasthenia gravis (MG) have few treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has been used to treat immune diseases; however, its use in the treatment of MG is not broadly considered. Our objective is to report on the efficacy and safety of HSCT in refractory MG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-one patients who underwent HSCT for MG were retrospectively reviewed. All patients had severe MG refractory to multiple therapies. Stem cells were mobilized with cyclophosphamide and granulocyte colony-stimulating factor. The grafts were depleted of immune cells by selecting CD34+ cells. HSCT conditioning consisted of high-dose cytoreductive therapy and anti-thymocyte globulin. The primary efficacy outcome was achieving clinically stable remission or minimal manifestations without treatment and remaining as such until most recent follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median time from MG diagnosis to HSCT was 4.0 years. The primary outcome was reached in 16 of 18 evaluable patients (89%) at a median of 1.7 years and maintained with a median follow-up of 6.7 years (range 1.0–21.9 years). Three patients were not evaluable for the primary outcome: one due to confounding illness and two died within 12 months of transplant. The transplant-related mortality at 100 days was 9.5%. Two late deaths occurred, with uncertain relation to the HSCT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>After HSCT for refractory MG, most patients achieved sustained disease remission. However, HSCT-related mortality in medically complex MG patients may be high. Prospective studies investigating the efficacy and safety of HSCT in the treatment of refractory MG are warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"56-68"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906458","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":"A novel de novo GABRA2 gene missense variant causing developmental epileptic encephalopathy in a Chinese patient","authors":"Li Yang,&nbsp;Xingyu Wan,&nbsp;Ran Hua,&nbsp;Junhong Jiang,&nbsp;Baotian Wang,&nbsp;Rui Tao,&nbsp;De Wu","doi":"10.1002/acn3.52262","DOIUrl":"10.1002/acn3.52262","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Variants in the <i>GABRA2</i> gene, which encodes the α2 subunit of the γ-aminobutyric acid A receptor, have been linked to a rare form of developmental and epileptic encephalopathy (DEE) referred to as DEE78. Only eight patients have been reported globally. This study presents the clinical presentation and genetic analysis of a Chinese family with a child diagnosed with DEE78, due to a novel <i>GABRA2</i> variant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genetic diagnosis was performed using trio-whole exome sequencing, followed by bioinformatics predictions of pathogenicity. Structural modeling assessed the potential impact of the variant. A mutant plasmid was constructed and transfected into 293 T cells. Western blotting (WB) was used to evaluate mutant protein expression, while co-immunoprecipitation (Co-IP) analyzed interactions with GABRB3 and GABRG2 proteins. Immunofluorescence (IF) assessed the subcellular localization of the mutant protein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The 6-year-old male proband presented with seizures starting at age two, along with global developmental delay and hypotonia. Genetic testing revealed a heterozygous de novo variant in <i>GABRA2</i> gene (NM_000807: c.923C&gt;T, p.Ala308Val). Structural modeling suggested that this variant is located within the extracellular domain, which may disrupt hydrogen bonding interactions with GABRB3 and GABRG2. WB and Co-IP showed reduced protein expression and impaired interactions, potentially destabilizing the pentamer receptor complex. If analysis revealed that the variant did not affect subcellular localization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identified a novel likely pathogenic <i>GABRA2</i> extracellular domain variant in a Chinese family causing the DEE phenotype. The results expand the genotypic and phenotypic spectrum of <i>GABRA2</i>-related DEE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"137-148"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906453","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}