BMJ Neurology Open最新文献

{"title":"Assessing insomnia after stroke: a diagnostic validation of the Sleep Condition Indicator in self-reported stroke survivors.","authors":"Declan M McLaren, Jonathan Evans, Satu Baylan, Monika Harvey, Megan C Montgomery, Maria Gardani","doi":"10.1136/bmjno-2024-000768","DOIUrl":"10.1136/bmjno-2024-000768","url":null,"abstract":"<p><strong>Background: </strong>Insomnia is common after stroke and is associated with poorer recovery and greater risk of subsequent strokes. Yet, no insomnia measures have been validated in English-speaking individuals affected by stroke.</p><p><strong>Aims: </strong>This prospective diagnostic validation study investigated the discriminatory validity and optimal diagnostic cut-off of the Sleep Condition Indicator when screening for Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) insomnia disorder post-stroke.</p><p><strong>Methods: </strong>A convenience sample of 180 (60.0% women, mean age=49.61 ± 12.41 years) community-based, adult (≥18 years) self-reported stroke survivors completed an online questionnaire. Diagnosis of DSM-5 insomnia disorder was based on analysis of a detailed sleep history questionnaire. Statistical analyses explored discriminant validity, convergent validity, relationships with demographic and mood variables, and internal consistency. Receiver operating characteristic curves were plotted to assess diagnostic accuracy.</p><p><strong>Results: </strong>Data from the sleep history questionnaire suggested that 75 participants (41.67%) met criteria for DSM-5 insomnia disorder, 33 (18.33%) exhibited symptoms of insomnia but did not meet diagnostic criteria, and 72 (40.0%) had no insomnia symptoms at the time of assessment. The Sleep Condition Indicator (SCI) demonstrated 'excellent' diagnostic accuracy in the detection of insomnia post-stroke, with an area under the curve of 0.86 (95% CI (0.81, 0.91)). The optimal cut-off was determined as being ≤13, yielding a sensitivity of 88.0% and a specificity of 71.43%.</p><p><strong>Conclusions: </strong>The findings of this study demonstrate the SCI to be a valid and reliable method with which to diagnose DSM-5 insomnia disorder and symptoms post-stroke. However, a lower threshold than is used in the general population may be necessary after stroke.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Major vascular events after first incident stroke: a population-based study.","authors":"Rayka Malek, Salha Alasiri, Charles D A Wolfe, Abdel Douiri","doi":"10.1136/bmjno-2024-000723","DOIUrl":"10.1136/bmjno-2024-000723","url":null,"abstract":"<p><strong>Background: </strong>Recent advances in stroke care have led to improvements in survival and rates of stroke recurrence. However, there is a lack of data on trends of major vascular events, and risk factors associated with non-fatal and fatal outcomes. We aim to identify demographical and clinical factors leading to incidence of subsequent major vascular events after the first-ever stroke.</p><p><strong>Methods: </strong>6051 patients' records with first-ever stroke between 1995 and 2018 in South London, UK were analysed. Semicompeting risks models were constructed to estimate factors affecting time to incidence of recurrent stroke, myocardial infarction (MI), mortality and transitions from poststroke recurrence/MI to mortality (indirect mortality). Cumulative incidence functions were plotted for each major vascular event, stratified by stroke subtypes. All models were adjusted for age, sex, socioeconomic status, comorbidities, stroke severity and stroke subtype.</p><p><strong>Results: </strong>Five years of cumulative incidences were 9.2% (95% CI (8.4% to 10.0%)) for recurrent stroke, 4.4% (95% CI 3.9% to 5.0%) for MI, and 45% (95% CI 44% to 47%) for mortality. Prior atrial fibrillation was associated with 47% increased risk of mortality (HR=1.47 (95% CI 1.23 to 1.75)) and a previous diagnosis of MI was the strongest risk factor for poststroke MI (HR=9.17 (95% CI 6.28 to 13.39)). Stroke unit was associated with a 40% lower hazard of mortality without having a recurrent stroke/MI (HR=0.60 (95% CI 0.50 to 0.72)) and a 39% lower hazard of indirect mortality (HR=0.57 (95% CI 0.37 to 0.87)).</p><p><strong>Conclusion: </strong>Major vascular events are prevalent after stroke, particularly among those with concurrent vascular conditions. The rate of stroke recurrence plateaued in the last decade, yet MI incidence increased. Targeted strategies to control risk factors are required to reduce the incidence of a second vascular event and prevent progression to mortality in these high-risk groups.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and internal validation of prehospital prediction models for identifying intracerebral haemorrhage in suspected stroke patients.","authors":"Mohammed Almubayyidh, Adrian R Parry-Jones, David A Jenkins","doi":"10.1136/bmjno-2024-000878","DOIUrl":"10.1136/bmjno-2024-000878","url":null,"abstract":"<p><strong>Introduction: </strong>Distinguishing patients with intracerebral haemorrhage (ICH) from other suspected stroke cases in the prehospital setting is crucial for determining the appropriate level of care and minimising the onset-to-treatment time, thereby potentially improving outcomes. Therefore, we developed prehospital prediction models to identify patients with ICH among suspected stroke cases.</p><p><strong>Methods: </strong>Data were obtained from the Field Administration of Stroke Therapy-Magnesium prehospital stroke trial, where paramedics evaluated multiple variables in suspected stroke cases within the first 2 hours from the last known well time. A total of 19 candidate predictors were included to minimise overfitting and were subsequently refined through the backward exclusion of non-significant predictors. We used logistic regression and eXtreme Gradient Boosting (XGBoost) models to evaluate the performance of the predictors. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), confusion matrix metrics and calibration measures. Additionally, models were internally validated and corrected for optimism through bootstrapping. Furthermore, a nomogram was built to facilitate paramedics in estimating the probability of ICH.</p><p><strong>Results: </strong>We analysed 1649 suspected stroke cases, of which 373 (23%) were finally diagnosed with ICH. From the 19 candidate predictors, 9 were identified as independently associated with ICH (p<0.05). Male sex, arm weakness, worsening neurological status and high systolic blood pressure were positively associated with ICH. Conversely, a history of hyperlipidaemia, atrial fibrillation, coronary artery disease, ischaemic stroke and improving neurological status were associated with other diagnoses. Both logistic regression and XGBoost demonstrated good calibration and predictive performance, with optimism-corrected sensitivities ranging from 47% to 49%, specificities from 89% to 90% and AUCs from 0.796 to 0.801.</p><p><strong>Conclusions: </strong>Our models demonstrate good predictive performance in distinguishing patients with ICH from other diagnoses, making them potentially useful tools for prehospital ICH management.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimising the rate of vascular complications in Deep Brain Stimulation surgery for the management of Parkinson's disease: a single-centre 600-patient case series.","authors":"Raymond Cook, Nyssa Chennell Dutton, Peter A Silburn, Linton J Meagher, George Fracchia, Nathan Anderson, Glen Cooper, Hoang-Mai Dinh, Stuart J Cook, Paul Silberstein","doi":"10.1136/bmjno-2024-000793","DOIUrl":"10.1136/bmjno-2024-000793","url":null,"abstract":"<p><strong>Objectives: </strong>Deep Brain Stimulation (DBS) is an effective, yet underused therapy for people living with Parkinson's disease (PD) in whom tremor, motor fluctuations and/or dyskinesia are not satisfactorily controlled by oral medical therapy. Fear of vascular complications related to the operative procedure remains a strong reason for both the referrer and patient reluctance. We review the incidence of vascular complications in the first 600 patients with Parkinson's disease treated at our centre by a single neurologist/neurosurgical team.</p><p><strong>Methods: </strong>Surgical data routinely collected for patients who underwent DBS implantation for the management of PD between the years 2001-2023 was retrospectively reviewed. Incidences of vascular complication were analysed in detail, examining causal factors.</p><p><strong>Results: </strong>Including reimplantations, 600 consecutive DBS patients underwent implantation with 1222 DBS electrodes. Three patients (0.50%) experienced vascular complications.</p><p><strong>Conclusion: </strong>This vascular complication rate is at the low end of that reported in the literature. Risk mitigation strategies discussed include a consistent neurosurgical team, dual methodology target and trajectory planning, control of cerebrospinal fluid egress during the procedure, use of a specialised microelectrode recording (MER)/macrostimulation electrode without an introducing brain cannula and low number of MER passes. A reduced vascular complication rate may improve the acceptability of DBS therapy for both patients and referrers.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of theories into the pathogenesis of normal pressure hydrocephalus.","authors":"Racheed Mani, Jade Basem, Liu Yang, Susan Fiore, Petar Djuric, Michael Egnor","doi":"10.1136/bmjno-2024-000804","DOIUrl":"10.1136/bmjno-2024-000804","url":null,"abstract":"<p><p>Normal pressure hydrocephalus (NPH) represents a unique form of hydrocephalus characterised by the paradox of ventriculomegaly without significant elevations in intracranial pressure, with the clinical triad of gait instability, cognitive impairment, and urinary incontinence. A myriad of neurobiological correlates have been implicated in its pathophysiology. We review the literature to provide an up-to-date, narrative review of the proposed mechanisms underlying the pathophysiology of NPH, proposing a holistic framework through which to understand the condition. We conducted a narrative review of the literature on NPH, assessing the various mechanisms underlying its pathophysiology and clinical presentation. NPH represents a unique form of hydrocephalus manifesting as a disorder of the cerebral vasculature, characterised by arteriosclerosis and reduced intracranial elastance. There are multiple mechanisms underlying its pathophysiology, which include windkessel impairment causing redistribution of intracranial pulsatility from the subarachnoid space to the ventricles, reductions in cerebral blood flow, impaired glymphatic clearance, reduced blood-brain barrier integrity and alterations in venous haemodynamics. Moreover, NPH shares similar clinical features and pathological mechanisms as other neurodegenerative conditions such as Alzheimer's disease and vascular dementia. The severity of each respective mechanism of pathophysiology can lead a patient to develop one condition versus another. Analysing NPH as a disorder of the cerebral vasculature, glymphatics, and most of all, the distribution of intracranial pulsatility, provides a novel framework through which to understand and manage this condition, one which requires further investigation.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and characteristics of headache among medical students in Egypt: a multicentric cross-sectional study.","authors":"Rashad G Mohamed, Khalid Sarhan, Basma Kamel, Rahma M Almetwaly, Eslam E Fouda, Mostafa Meshref, Sara Bioumy, Doaa Alemam, Hebatalla A Ahmed","doi":"10.1136/bmjno-2024-000851","DOIUrl":"https://doi.org/10.1136/bmjno-2024-000851","url":null,"abstract":"<p><strong>Background: </strong>Headaches are one of the most common neurological disorders, ranging in severity from mild discomfort to a severe, debilitating condition. Headaches are particularly prevalent among medical students, which can be attributed to various factors such as psychological stressors, extensive studying, long hours of clinical rotations and high-pressure examination. This study aims to ascertain the prevalence of different types of headaches, along with analysing their associated clinical characteristics among medical students in Egypt.</p><p><strong>Methods: </strong>A multicentric, descriptive questionnaire-based cross-sectional study was conducted across five governmental faculties of medicine in Egypt from November 2022 to March 2023. Using a multistage random sampling method, 600 undergraduate students were selected to participate. Headache was diagnosed based on the International Classification of Headache Disorders.</p><p><strong>Results: </strong>A total of 493 responses were included in the analysis; the prevalence of headache disorder was 264 (53.5%), with tension-type headaches (TTH) frequent episodic being the highest 89 (33.7%), while TTH chronic and migraine with aura were the least prevalent, accounting for 10 (3.8%) and 31 (11.7%), respectively. Women exhibited a higher overall headache prevalence (69.4%) compared with men (44.4%). A positive family history was found in 120 (45.5%) of students with headache. Lack of sleep and stress were the most frequently reported potential triggers for headaches. Out of 264 medical students, 171 (65%) took analgesics. Only 42 (24.6%) had a medical consultation, while most students 129 (75.4%) took over-the-counter medications.</p><p><strong>Conclusion: </strong>Notably, headaches were prevalent in 264 (53.5%) of the respondents. TTH frequent and infrequent emerged as the most common headaches among medical students, followed by migraine without aura then migraine with aura. Participants were statistically different according to sex, faculty, academic year and living conditions. Alarmingly, despite the substantial prevalence, only 42 (24.6%) students sought medical consultation.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paroxysmal sympathetic hyperactivity caused by neurosyphilis.","authors":"Shuko Fujiki, Masaki Fujino, Akira Machida","doi":"10.1136/bmjno-2024-000814","DOIUrl":"https://doi.org/10.1136/bmjno-2024-000814","url":null,"abstract":"<p><strong>Background: </strong>Paroxysmal sympathetic hyperactivity (PSH) is a condition characterised by dysregulation of the autonomic nervous system commonly associated with severe traumatic brain injury. Recently, non-traumatic causes, such as infections and autoimmune conditions, have also been reported as potential triggers.</p><p><strong>Case presentation: </strong>A 30-year-old man presented with convulsions following 5 days of soliloquy, insomnia and agitation. Neurosyphilis was diagnosed based on elevated non-treponemal and treponemal test findings in the serum and cerebrospinal fluid. Intravenous penicillin administration improved his alertness; however, by day 9, he experienced recurrent episodes of tachycardia, tachypnoea, hyperthermia, hypertension, limb stiffness and diaphoresis. The exclusion of sepsis, pulmonary embolism and malignant syndrome, combined with unremarkable interictal electroencephalogram findings and a high PSH Assessment Measure Score, led to a PSH diagnosis on day 40. Treatment with propranolol, gabapentin and clonidine resolved the episodes, and the patient regained independent ambulation.</p><p><strong>Conclusions: </strong>This is the first reported case of neurosyphilis accompanied by PSH. Although PSH is rare in central nervous system infections compared with traumatic brain injury, early recognition is crucial, as untreated cases can persist and result in severe complications.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pilot feasibility randomised controlled trial of cognitive-behavioural therapy for functional cognitive disorder after concussion.","authors":"Mathilde Rioux, Rinni Mamman, Miles T Byworth, William J Panenka, Andrew K Howard, David L Perez, Julia Schmidt, Caitlin Courchesne, Joelle LeMoult, Manraj Ks Heran, Noah D Silverberg","doi":"10.1136/bmjno-2024-000666","DOIUrl":"https://doi.org/10.1136/bmjno-2024-000666","url":null,"abstract":"<p><strong>Background: </strong>Functional cognitive disorder (FCD) may be common after a concussion, and no evidence-based treatment options are available. The current study evaluated the feasibility of a novel cognitive-behavioural therapy (CBT) protocol tailored to FCD after concussion.</p><p><strong>Methods: </strong>Participants were randomised to CBT (n=11) or the current standard of care, cognitive rehabilitation (n=13). Both interventions consisted of eleven 50 min manualised videoconference sessions. CBT involved cognitive reappraisal and exposure-based strategies. Cognitive rehabilitation involved traditional memory compensation strategy training. Prespecified feasibility criteria were set for recruitment, perceived credibility, patient adherence, therapist protocol compliance and retention. The primary efficacy outcome was the Multifactorial Memory Questionnaire-Satisfaction (MMQ-S). The first five CBT completers completed a semistructured interview about their experience with the intervention.</p><p><strong>Results: </strong>Most feasibility benchmarks were met, as 86% of invited patients consented, 96% of participants rated their intervention as credible, participants attended 96% of sessions, therapists covered all essential content in 94% of sessions and 100% of participants completed the post-treatment evaluation. Both groups improved on the MMQ-S. Post-treatment MMQ-S scores were similar between groups (Cohen's d=-0.05 (95% CI [-0.86, 0.75])). Two themes resulted from the qualitative data analysis, which highlighted aspects of the CBT interventions that participants valued.</p><p><strong>Implications: </strong>This pilot trial supports the feasibility of CBT tailored to FCD after concussion and suggests that patients with FCD may benefit from either CBT or standard cognitive rehabilitation. A larger trial is needed to evaluate the efficacy of these interventions for FCD after concussion and potentially FCD in other clinical contexts.</p><p><strong>Trial registration number: </strong>NCT05581810.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11474702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the concordance between International Classification of Diseases, Tenth Revision Code and stroke severity as measured by the National Institutes of Health Stroke Scale.","authors":"Mohamed Taha, Mamoon Habib, Victor Lomachinsky, Peter Hadar, Joseph P Newhouse, Lee H Schwamm, Deborah Blacker, Lidia M V R Moura","doi":"10.1136/bmjno-2024-000831","DOIUrl":"10.1136/bmjno-2024-000831","url":null,"abstract":"<p><strong>Background: </strong>The National Institutes of Health Stroke Scale (NIHSS) scores have been used to evaluate acute ischaemic stroke (AIS) severity in clinical settings. Through the International Classification of Diseases, Tenth Revision Code (ICD-10), documentation of NIHSS scores has been made possible for administrative purposes and has since been increasingly adopted in insurance claims. Per Centres for Medicare & Medicaid Services guidelines, the stroke ICD-10 diagnosis code must be documented by the treating physician. Accuracy of the administratively collected NIHSS compared with expert clinical evaluation as documented in the Paul Coverdell registry is however still uncertain.</p><p><strong>Methods: </strong>Leveraging a linked dataset comprised of the Paul Coverdell National Acute Stroke Program (PCNASP) clinical registry and matched individuals on Medicare Claims data, we sampled patients aged 65 and above admitted for AIS across nine states, from January 2017 to December 2020. We excluded those lacking documentation for either clinical or ICD-10-based NIHSS scores. We then examined score concordance from both databases and measured discordance as the absolute difference between the PCNASP and ICD-10-based NIHSS scores.</p><p><strong>Results: </strong>Among 87 996 matched patients, mean NIHSS scores for PCNASP and Medicare ICD-10 were 7.19 (95% CI 7.14 to 7.24) and 7.32 (95% CI 7.27 to 7.37), respectively. Concordance between the two scores was high as indicated by an intraclass correlation coefficient of 0.93.</p><p><strong>Conclusion: </strong>The high concordance between clinical and ICD-10 NIHSS scores highlights the latter's potential as measure of stroke severity derived from structured claims data.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurological manifestations in adult patients with the m.3243A>G variant in mitochondrial DNA.","authors":"Kari Majamaa, Mikko Kärppä, Jukka S Moilanen","doi":"10.1136/bmjno-2024-000825","DOIUrl":"https://doi.org/10.1136/bmjno-2024-000825","url":null,"abstract":"<p><strong>Abstract: </strong></p><p><strong>Background: </strong>The m.3243A>G variant in mitochondrial DNA (mtDNA) is the most common cause of the MELAS (Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes) syndrome usually commencing in childhood or adolescence. In adults, the variant presents with versatile and mostly neurological phenotypes, but MELAS may not be common.</p><p><strong>Objective: </strong>To examine the frequency of phenotypes in adults with m.3243A>G in a population-based cohort and in a meta-analysis of reported case series.</p><p><strong>Methods: </strong>We clinically examined 51 adult patients with m.3243A>G to determine the frequency of phenotypes and to analyse the contribution of variant heteroplasmy, age, sex and mtDNA haplogroup to the phenotypes. The frequencies of neurological features were also assessed in a meta-analysis on 25 published case series reporting 1314 patients.</p><p><strong>Results: </strong>Sensorineural hearing impairment (HI), cognitive impairment and myopathy were the most common manifestations, whereas stroke-like episodes were infrequent. Variant heteroplasmy and age were only modest predictors of the phenotypes, although heteroplasmy correlated significantly with disability and Kaplan-Meier analysis showed progression of phenotypes with age. Male sex predicted more severe disability, whereas haplogroup UK was associated with no significant disability. Meta-analysis revealed substantial heterogeneity of phenotype frequencies and preferential inclusion of the MELAS phenotype.</p><p><strong>Discussion: </strong>In adult patients with m.3243A>G sensorineural HI, cognitive impairment and myopathy are common manifestations with lifetime prevalences approaching unity. Stroke-like episodes are rare. Variant heteroplasmy, age, sex and mtDNA haplogroup contribute to the severity of the disease. Meta-analysis provided a solid estimate of the various neurological symptoms in adults with m.3243A>G.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}