Brain : a journal of neurology最新文献

{"title":"The kappa free light chain index and oligoclonal bands have a similar role in the McDonald criteria.","authors":"Georgina Arrambide, Carmen Espejo, Pere Carbonell-Mirabent, Romina Dieli-Crimi, Marta Rodríguez-Barranco, Mireia Castillo, Cristina Auger, Simón Cárdenas-Robledo, Joaquín Castilló, Álvaro Cobo-Calvo, Ingrid Galán, Luciana Midaglia, Carlos Nos, Susana Otero-Romero, Jordi Río, Breogán Rodríguez-Acevedo, Mariano Ruiz-Ortiz, Annalaura Salerno, Paula Tagliani, Carmen Tur, Angela Vidal-Jordana, Ana Zabalza, Jaume Sastre-Garriga, Alex Rovira, Manuel Comabella, Manuel Hernández-González, Xavier Montalban, Mar Tintore","doi":"10.1093/brain/awac220","DOIUrl":"https://doi.org/10.1093/brain/awac220","url":null,"abstract":"<p><p>Intrathecal production of kappa free light chains occurs in multiple sclerosis and can be measured using the kappa free light chain index. Kappa free light chain index values can be determined more easily than oligoclonal bands detection and seem more sensitive than the immunoglobulin (Ig)G index to diagnose multiple sclerosis. We assessed the value of oligoclonal bands, kappa free light chain index cut-offs 5.9, 6.6 and 10.61, and IgG index to diagnose multiple sclerosis with prospectively acquired data from a clinically isolated syndrome inception cohort. We selected patients with sufficient data to determine oligoclonal bands positivity, MRI dissemination in space and time, IgG index and sufficient quantities of paired CSF and blood samples to determine kappa free light chain indexes (n = 214). We used Kendall's Tau coefficient to estimate concordance, calculated the number of additional diagnoses when adding each positive index to dissemination in space and positive oligoclonal bands, performed survival analyses for oligoclonal bands and each index with the outcomes second attack and 2017 MRI dissemination in space and time and estimated the diagnostic properties of oligoclonal bands and the different indexes for the previously mentioned outcomes at 5 years. Oligoclonal bands were positive in 138 patients (64.5%), kappa free light chain-5.9 in 136 (63.6%), kappa free light chain-6.6 in 135 (63.1%), kappa free light chain-10.61 in 126 (58.9%) and IgG index in 101 (47.2%). The highest concordance was between oligoclonal bands and kappa free light chain-6.6 (τ = 0.727) followed by oligoclonal bands and kappa free light chain-5.9 (τ = 0.716). Combining dissemination in space plus oligoclonal bands or kappa free light chain-5.9 increased the number of diagnosed patients by 11 (5.1%), with kappa free light chain-6.6 by 10 (4.7%), with kappa free light chain-10.61 by 9 (4.2%) and with IgG index by 3 (1.4%). Patients with positive oligoclonal bands or indexes reached second attack and MRI dissemination in space and time faster than patients with negative results (P < 0.0001 except IgG index in second attack: P = 0.016). In multivariable Cox models [adjusted hazard ratio (95% confidence interval)], the risk for second attack was very similar between kappa free light chain-5.9 [2.0 (0.9-4.3), P = 0.068] and kappa free light chain-6.6 [2.1 (1.1-4.2), P = 0.035]. The highest risk for MRI dissemination in space and time was demonstrated with kappa free light chain-5.9 [4.9 (2.5-9.6), P < 0.0001], followed by kappa free light chain-6.6 [3.4 (1.9-6.3), P < 0.0001]. Kappa free light chains-5.9 and -6.6 had a slightly higher diagnostic accuracy than oligoclonal bands for second attack (70.5, 71.1 and 67.8) and MRI dissemination in space and time (85.7, 85.1 and 81.0). Kappa free light chain indexes 5.9 and 6.6 performed slightly better than oligoclonal bands to assess multiple sclerosis risk and in terms of diagnostic accuracy. Given the concordance bet","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"3931-3942"},"PeriodicalIF":14.5,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40141245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is postural tachycardia syndrome a psychogenic disorder?","authors":"David S Goldstein","doi":"10.1093/brain/awac345","DOIUrl":"https://doi.org/10.1093/brain/awac345","url":null,"abstract":"","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"e105-e106"},"PeriodicalIF":14.5,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33480333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patients with POTS fear that data on abnormal haemodynamic physiology have been ignored.","authors":"Kate M Bourne, Vidya Raj, Robert S Sheldon, Satish R Raj","doi":"10.1093/brain/awac347","DOIUrl":"https://doi.org/10.1093/brain/awac347","url":null,"abstract":"","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"e109-e110"},"PeriodicalIF":14.5,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33480334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vestibular migraine treatment: a comprehensive practical review.","authors":"Duncan Smyth,&nbsp;Zelie Britton,&nbsp;Louisa Murdin,&nbsp;Qadeer Arshad,&nbsp;Diego Kaski","doi":"10.1093/brain/awac264","DOIUrl":"https://doi.org/10.1093/brain/awac264","url":null,"abstract":"<p><p>Vestibular migraine is an underdiagnosed but increasingly recognized neurological condition that causes episodic vertigo associated with other features of migraine. It is now thought to be the most common cause of spontaneous (non-positional) episodic vertigo, affecting up to 1% of the population. A meta-analysis of preventative treatments for vestibular migraine was published in 2021, but the authors were unable to establish a preferred treatment strategy due to low quality of evidence and heterogeneity of study design and outcome reporting. Therefore, there remains a clinical need for pragmatic management guidelines specific to vestibular migraine using the available evidence. Here, we provide a practical review utilizing a systematic qualitative assessment of the evidence for abortive and preventative interventions in adults. The overall evidence base for vestibular migraine treatment is of low quality. Nevertheless, we provide practical treatment recommendations based on the available evidence and our experience to help guide clinicians treating patients with vestibular migraine. We also discuss how future clinical trials could be designed to improve the quality of evidence in this condition.</p>","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"3741-3754"},"PeriodicalIF":14.5,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d3/b5/awac264.PMC9679161.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40609015","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":"Amyloid-β levels and cognitive trajectories in non-demented pTau181-positive subjects without amyloidopathy.","authors":"Timo Jan Oberstein,&nbsp;Manuel Alexander Schmidt,&nbsp;Anna Florvaag,&nbsp;Anna-Lena Haas,&nbsp;Eva-Maria Siegmann,&nbsp;Pauline Olm,&nbsp;Janine Utz,&nbsp;Philipp Spitzer,&nbsp;Arnd Doerfler,&nbsp;Piotr Lewczuk,&nbsp;Johannes Kornhuber,&nbsp;Juan Manuel Maler","doi":"10.1093/brain/awac297","DOIUrl":"https://doi.org/10.1093/brain/awac297","url":null,"abstract":"<p><p>Phosphorylated Tau181 (pTau181) in CSF and recently in plasma has been associated with Alzheimer's disease. In the absence of amyloidopathy, individuals with increased total Tau levels and/or temporal lobe atrophy experience no or only mild cognitive decline compared with biomarker-negative controls, leading to the proposal to categorize this constellation as suspected non-Alzheimer's disease pathophysiology (SNAP). We investigated whether the characteristics of SNAP also applied to individuals with increased CSF-pTau181 without amyloidopathy. In this long-term observational study, 285 non-demented individuals, including 76 individuals with subjective cognitive impairment and 209 individuals with mild cognitive impairment, were classified based on their CSF levels of pTau181 (T), total Tau (N), amyloid-β42 (Aβ42) and Aβ42/Aβ40 ratio (A) into A+T+N±, A+T-N±, A-T+N±, and A-T-N-. The longitudinal analysis included 154 subjects with a follow-up of more than 12 months who were followed to a median of 4.6 years (interquartile range = 4.3 years). We employed linear mixed models on psychometric tests and region of interest analysis of structural MRI data. Cognitive decline and hippocampal atrophy rate were significantly higher in A+T+N± compared to A-T+N±, whereas there was no difference between A-T+N± and A-T-N-. Furthermore, there was no significant difference between A-T+N± and controls in dementia risk [hazard ratio 0.3, 95% confidence interval (0.1, 1.9)]. However, A-T+N± and A-T-N- could be distinguished based on their Aβ42 and Aβ40 levels. Both Aβ40 and Aβ42 levels were significantly increased in A-T+N± compared to controls. Long term follow-up of A-T+N± individuals revealed no evidence that this biomarker constellation was associated with dementia or more severe hippocampal atrophy rates compared to controls. However, because of the positive association of pTau181 with Aβ in the A-T+N± group, a link to the pathophysiology of Alzheimer's disease cannot be excluded in this case. We propose to refer to these individuals in the SNAP group as 'pTau and Aβ surge with subtle deterioration' (PASSED). The investigation of the circumstances of simultaneous elevation of pTau and Aβ might provide a deeper insight into the process under which Aβ becomes pathological.</p>","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"4032-4041"},"PeriodicalIF":14.5,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/78/46/awac297.PMC9679169.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40701048","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":"Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis.","authors":"Macarena Cabrera-Serrano, Laure Caccavelli, Marco Savarese, Anna Vihola, Manu Jokela, Mridul Johari, Thierry Capiod, Marine Madrange, Enrico Bugiardini, Stefen Brady, Rosaline Quinlivan, Ashirwad Merve, Renata Scalco, David Hilton-Jones, Henry Houlden, Halil Ibrahim Aydin, Serdar Ceylaner, Sarah Drewes, Jerry Vockley, Rhonda L Taylor, Chiara Folland, Aasta Kelly, Hayley Goullee, Emil Ylikallio, Mari Auranen, Henna Tyynismaa, Bjarne Udd, Alistair R R Forrest, Mark R Davis, Drago Bratkovic, Nicholas Manton, Thomas Robertson, Cullen O'Gorman, Pamela McCombe, Nigel G Laing, Liza Phillips, Pascale de Lonlay, Gianina Ravenscroft","doi":"10.1093/brain/awab484","DOIUrl":"10.1093/brain/awab484","url":null,"abstract":"<p><p>Rhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety of genetic disorders predispose to rhabdomyolysis through different pathogenic mechanisms, particularly in patients with recurrent episodes. However, most cases remain without a genetic diagnosis. Here we present six patients who presented with severe and recurrent rhabdomyolysis, usually with onset in the teenage years; other features included a history of myalgia and muscle cramps. We identified 10 bi-allelic loss-of-function variants in the gene encoding obscurin (OBSCN) predisposing individuals to recurrent rhabdomyolysis. We show reduced expression of OBSCN and loss of obscurin protein in patient muscle. Obscurin is proposed to be involved in sarcoplasmic reticulum function and Ca2+ handling. Patient cultured myoblasts appear more susceptible to starvation as evidenced by a greater decreased in sarcoplasmic reticulum Ca2+ content compared to control myoblasts. This likely reflects a lower efficiency when pumping Ca2+ back into the sarcoplasmic reticulum and/or a decrease in Ca2+ sarcoplasmic reticulum storage ability when metabolism is diminished. OSBCN variants have previously been associated with cardiomyopathies. None of the patients presented with a cardiomyopathy and cardiac examinations were normal in all cases in which cardiac function was assessed. There was also no history of cardiomyopathy in first degree relatives, in particular in any of the carrier parents. This cohort is relatively young, thus follow-up studies and the identification of additional cases with bi-allelic null OBSCN variants will further delineate OBSCN-related disease and the clinical course of disease.</p>","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"3985-3998"},"PeriodicalIF":0.0,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39764566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"'Psychogenic' POTS: the NYU team misinterprets association as causation.","authors":"David Tuller,&nbsp;Svetlana Blitshteyn,&nbsp;David Davies-Payne,&nbsp;Brendan Delaney,&nbsp;Jonathan Edwards,&nbsp;Mady Hornig,&nbsp;Brian Hughes,&nbsp;David Putrino,&nbsp;John Swartzberg","doi":"10.1093/brain/awac348","DOIUrl":"https://doi.org/10.1093/brain/awac348","url":null,"abstract":"","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"e111-e112"},"PeriodicalIF":14.5,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33480332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management-induced distress syndrome.","authors":"Peter J Nestor","doi":"10.1093/brain/awac287","DOIUrl":"https://doi.org/10.1093/brain/awac287","url":null,"abstract":"","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"e104"},"PeriodicalIF":14.5,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40668728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineers drive new directions in translational epilepsy research.","authors":"Brian Litt","doi":"10.1093/brain/awac375","DOIUrl":"https://doi.org/10.1093/brain/awac375","url":null,"abstract":"","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"3725-3726"},"PeriodicalIF":14.5,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40505726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Is postural tachycardia syndrome a psychogenic disorder?; Notes on establishing fear conditioning as causal in the postural orthostatic tachycardia syndrome; Patients with POTS fear that data on abnormal haemodynamic physiology have been ignored; and 'Psychogenic' POTS: the NYU team misinterprets association as causation.","authors":"Lucy Norcliffe-Kaufmann,&nbsp;Jose-Alberto Palma,&nbsp;Horacio Kaufmann","doi":"10.1093/brain/awac349","DOIUrl":"https://doi.org/10.1093/brain/awac349","url":null,"abstract":"","PeriodicalId":121505,"journal":{"name":"Brain : a journal of neurology","volume":" ","pages":"e113-e114"},"PeriodicalIF":14.5,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33480335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}