Teresa Kleinz, Leonard Scholz, Sophie Huckemann, Rachel Rohmann, Eva Kühn, Paulina Averdunk, Saskia Kools, Lovis Hilker, Antonia Bieber, Katharina Müller, Jeremias Motte, Anna-Lena Fisse, Christiane Schneider-Gold, Ralf Gold, Eun Hae Kwon, Lars Tönges, Kalliopi Pitarokoili
{"title":"The association of vagal atrophy with parameters of autonomic function in multiple system atrophy and progressive supranuclear palsy.","authors":"Teresa Kleinz, Leonard Scholz, Sophie Huckemann, Rachel Rohmann, Eva Kühn, Paulina Averdunk, Saskia Kools, Lovis Hilker, Antonia Bieber, Katharina Müller, Jeremias Motte, Anna-Lena Fisse, Christiane Schneider-Gold, Ralf Gold, Eun Hae Kwon, Lars Tönges, Kalliopi Pitarokoili","doi":"10.1177/17562864241267300","DOIUrl":"10.1177/17562864241267300","url":null,"abstract":"<p><strong>Background: </strong>Vagal atrophy is a hallmark of Parkinson's disease (PD) and has been found to be associated with autonomic dysfunction, while analyses of the vagus nerve (VN) in atypical Parkinsonian syndromes (APS) have not yet been performed. We here investigate the characteristics of the VN in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) and, in a second step, its potential as a possible biomarker for orthostatic dysregulation.</p><p><strong>Objectives: </strong>The aim was to compare the VN pathology in MSA and PSP with healthy individuals and patients with PD as a differentiating factor and to further analyse the correlation of the VN with clinical parameters and cardiovascular response.</p><p><strong>Design: </strong>We conducted a monocentric, cross-sectional cohort study in 41 APS patients and compared nerve ultrasound (NUS) parameters with 90 PD patients and 39 healthy controls.</p><p><strong>Methods: </strong>In addition to a detailed neurological history and examination, several clinical severity and motor scores were obtained. Autonomic symptoms were reported in the Scales for Outcomes in Parkinson's Disease - Autonomic questionnaire. Further scores were used to detect other non-motor symptoms, quality of life and cognition. Additionally, we performed a head up tilt test (HUTT) and NUS of the VN. We conducted correlation analyses of the VN cross-sectional area (CSA) with clinical scores and the heart rate and blood pressure variability parameters of the HUTT.</p><p><strong>Results: </strong>The examination demonstrated a high prevalence of abnormal autonomic response in both MSA (90%) and PSP (80%). The VN CSA correlated with spectral parameters of the HUTT, which are associated with sympatho-vagal imbalance. In addition, the CSA of the VN in patients with PD and PSP were significantly smaller than in healthy controls. In MSA, however, there was no marked vagal atrophy in comparison.</p><p><strong>Conclusion: </strong>The occurrence of autonomic dysfunction was high in MSA and PSP, which underlines its impact on these syndromes. Our findings indicate a connection between vagal pathology and autonomic dysfunction and might contribute to a better comprehension of APS. To further evaluate the clinical relevance and the VN as a possible marker of autonomic dysfunction in APS, prospective longitudinal observations are necessary.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241267300"},"PeriodicalIF":4.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037062","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}
Markus Kneihsl, Natalie Berger, Stefan Sumerauer, Susanne Asenbaum-Nan, Franz Stefan Höger, Thomas Gattringer, Christian Enzinger, Martin Aigner, Julia Ferrari, Wilfried Lang
{"title":"Management of delirium in acute stroke patients: a position paper by the Austrian Stroke Society on prevention, diagnosis, and treatment.","authors":"Markus Kneihsl, Natalie Berger, Stefan Sumerauer, Susanne Asenbaum-Nan, Franz Stefan Höger, Thomas Gattringer, Christian Enzinger, Martin Aigner, Julia Ferrari, Wilfried Lang","doi":"10.1177/17562864241258788","DOIUrl":"10.1177/17562864241258788","url":null,"abstract":"<p><p>Delirium is a common complication in acute stroke patients, occurring in 15-35% of all stroke unit admissions and is associated with prolonged hospital stay and a poor post-stroke prognosis. Managing delirium in acute stroke patients necessitates an intensive and multiprofessional therapeutic approach, placing a significant burden on healthcare staff. However, dedicated practical recommendations for delirium management developed for the population of acute stroke patients are lacking. For this purpose, the Austrian Stroke Society, in cooperation with the Austrian Society of Neurology, the Austrian Society of Neurorehabilitation, and the Austrian Society of Psychiatry, Psychotherapy, and Psychosomatics has formulated an evidence-based position paper addressing the management of delirium in acute stroke patients. The paper outlines practical recommendations on the three pillars of care in stroke patients with delirium: (a) Key aspects of delirium <i>prevention</i> including stroke-specific delirium risk factors and delirium prediction scores are described. Moreover, a non-pharmacological delirium prevention bundle is presented. (b) The paper provides recommendations on timing and frequency of delirium screening to ensure early <i>diagnosis</i> of delirium in acute stroke patients. Moreover, it reports on the use of different delirium screening tools in stroke populations. (c) An overview of non-pharmacological and pharmacological <i>treatment</i> strategies in patients with delirium and acute stroke is presented and summarized as key recommendation statements.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241258788"},"PeriodicalIF":4.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005334","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}
Yasmin Alt, Monique Wochatz, Anne Schraplau, Tilman Engel, Hadar Sharon, Michael Gurevich, Shay Menascu, Frank Mayer, Alon Kalron
{"title":"No immediate change in systemic cytokines following an eccentric muscle training session in people with multiple sclerosis.","authors":"Yasmin Alt, Monique Wochatz, Anne Schraplau, Tilman Engel, Hadar Sharon, Michael Gurevich, Shay Menascu, Frank Mayer, Alon Kalron","doi":"10.1177/17562864241266113","DOIUrl":"10.1177/17562864241266113","url":null,"abstract":"<p><strong>Background: </strong>Eccentric muscle contractions elicit distinct physiological responses, including modulation of the cytokine profile. Although relevant for rehabilitation, the effect of eccentric muscle training on the immune system has never been investigated in multiple sclerosis (MS).</p><p><strong>Objectives: </strong>Examine the immediate cytokine response of interleukin-4 (IL-4), IL-6, IL-10, IL-17a, interferon-gamma, and tumor necrosis factor-alpha after a moderate eccentric training session in individuals with MS. Additionally, further investigate the association between systemic cytokine levels at rest and clinical measures of mobility and lower limb functional strength.</p><p><strong>Design: </strong>Observational study.</p><p><strong>Methods: </strong>The first session included blood sampling for baseline cytokine measures. Subsequently, the participant completed a battery of clinical assessments related to mobility and lower limb strength, that is, the Timed-Up-and-Go Test, Five-Repetition-Sit-to-Stand-Test (5STS), Four-Square-Step-Test, and Two-Minute-Walk-Test. The second session included the eccentric exercise training session, followed by a second blood sampling to assess the acute cytokine response to the eccentric training bout. This session comprised 10 exercises concentrating on the strength of the trunk and lower extremities.</p><p><strong>Results: </strong>Twenty-seven people with MS (pwMS), with a mean age of 40.1 years, participated in the study. No difference was demonstrated in the cytokine concentration values between baseline and immediately after the eccentric training session. The 5STS explained 30.3% of the variance associated with interferon-gamma, 14.8% with IL-4, and 13.8% with IL-10.</p><p><strong>Conclusion: </strong>An eccentric training bout does not impact cytokine concentration in the blood and, consequently, does not boost a pro-inflammatory response, thus, it can be performed on pwMS in a rehabilitation setting.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241266113"},"PeriodicalIF":4.7,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11292683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876041","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 rare adverse effect in inebilizumab therapy for neuromyelitis optica spectrum disorder: a case report.","authors":"Xuefen Chen, Ziyan Shi, Rui Wang, Hongyu Zhou","doi":"10.1177/17562864241258787","DOIUrl":"10.1177/17562864241258787","url":null,"abstract":"<p><p>Inebilizumab is one of the monoclonal antibodies approved as maintenance therapy for aquaporin-4 immunoglobulin G-seropositive neuromyelitis optica spectrum disorder (NMOSD). It is a humanized monoclonal antibody targeting cluster of differentiation 19 (CD19). Common adverse reactions include urinary tract infections, nasopharyngitis, arthralgia, infusion reactions, headaches and a decrease in immunoglobulin levels. Here, we present a case of an NMOSD patient who experienced transient hyperCKaemia after the use of inebilizumab. The adverse reactions of this very rare monoclonal antibody drug improved after discontinuation.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241258787"},"PeriodicalIF":4.7,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789110","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}
Jie Song, Xiao Huan, Yuanyi Chen, Yeting Luo, Huahua Zhong, Yuan Wang, Lei Yang, Caihua Xi, Yu Yang, Jianying Xi, Jianming Zheng, Zongtai Wu, Chongbo Zhao, Sushan Luo
{"title":"The safety and efficacy profile of eculizumab in myasthenic crisis: a prospective small case series.","authors":"Jie Song, Xiao Huan, Yuanyi Chen, Yeting Luo, Huahua Zhong, Yuan Wang, Lei Yang, Caihua Xi, Yu Yang, Jianying Xi, Jianming Zheng, Zongtai Wu, Chongbo Zhao, Sushan Luo","doi":"10.1177/17562864241261602","DOIUrl":"10.1177/17562864241261602","url":null,"abstract":"<p><p>Eculizumab has improved recovery from ventilatory support in myasthenic crisis (MC) cases. However, the safety and efficacy profiles from prospective studies are still lacking. This study aimed to explore eculizumab's safety and efficacy in a prospective case series of patients with refractory MC. We followed a series of anti-acetylcholine receptor (AChR) antibody-positive myasthenia gravis (MG) patients who received eculizumab as an add-on therapy for 12 weeks during MC to facilitate the weaning process and reduced disease activity. Serum anti-AChR antibodies and peripheral immune molecules associated with the complement pathway were evaluated before and after eculizumab administration. Compared to the baseline Myasthenia Gravis Foundation of America (MGFA)-quantitative MG test (QMG) scores (22.25 ± 4.92) and MG-activities of daily living (MG-ADL; 18.25 ± 2.5) scores at crisis, improvements were observed from 4 weeks (14.5 ± 10.47 and 7.5 ± 7.59, respectively) through 12 weeks (7.5 ± 5.74 and 2.25 ± 3.86, respectively) post-treatment. Muscle strength consistently improved across ocular, bulbar, respiratory, and limb/gross domain groups. One patient died of cardiac failure at 16 weeks. Three cases remained in remission at 24 weeks, with a mean QMG score of 2.67 ± 2.89 and ADL score of 0.33 ± 0.58. No significant side effects were reported. Serum CH50 and soluble C5b-9 levels significantly declined, while there were no significant changes in serum anti-AChR antibody levels, C1q, C5a levels, or peripheral lymphocyte proportions. Eculizumab was well tolerated and showed efficacy in this case series. Large prospective cohort studies with extended follow-up periods are needed to further explore the safety and efficacy profile in real-world practice.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241261602"},"PeriodicalIF":4.7,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789111","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}
Bernhard J Steinhoff, Elinor Ben-Menachem, Pavel Klein, Jukka Peltola, Bettina Schmitz, Rhys H Thomas, Vicente Villanueva
{"title":"Therapeutic strategies during cenobamate treatment initiation: Delphi panel recommendations.","authors":"Bernhard J Steinhoff, Elinor Ben-Menachem, Pavel Klein, Jukka Peltola, Bettina Schmitz, Rhys H Thomas, Vicente Villanueva","doi":"10.1177/17562864241256733","DOIUrl":"10.1177/17562864241256733","url":null,"abstract":"<p><p>The goal of epilepsy treatment is seizure freedom, typically with antiseizure medication (ASM). If patients fail to attain seizure control despite two trials of appropriately chosen ASMs at adequate doses, they are classified as having drug-resistant epilepsy (DRE). Adverse events (AEs) commonly occur in people with DRE because they are typically on ⩾2 ASMs, increasing the potential for drug-drug interactions. Early emerging AEs may impact adherence, decrease quality of life, and delay achieving optimal treatment dosages. Cenobamate is an oral ASM with a long half-life which has proven to be highly effective in clinical trials. An international Delphi panel of expert epileptologists experienced in the clinical use of cenobamate and other ASMs was convened to develop consensus best practices for managing patients during and after cenobamate titration, with consideration for its known pharmacokinetic and pharmacodynamic interactions, to allow patients to reach the most appropriate cenobamate dose while limiting tolerability issues. The modified Delphi process included one open-ended questionnaire and one virtual face-to-face meeting. Participants agreed that cenobamate can be prescribed for most patients experiencing focal-onset seizures. Patients initiating cenobamate therapy should have access to healthcare professionals as needed and their treatment response should be evaluated at the 100-mg dose. Patients with intellectual disabilities may need additional support to navigate the titration period. Proactive down-titration or withdrawal of sodium channel blockers (SCBs) is recommended when concomitant ASM regimens include ⩾2 SCBs. When applicable, maintaining a concomitant clobazam dose at ~5-10 mg may be beneficial. Patients taking oral contraceptives, newer oral anticoagulants, or HIV antiretroviral medications should be monitored for potential interactions. Because clinical evidence informing treatment decisions is limited, guidance regarding dose adjustments of non-ASM drugs was not developed beyond specific recommendations presented in the Summary of Product Characteristics.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241256733"},"PeriodicalIF":5.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331739","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}
Damemarie Paul, Elyse Swallow, Oscar Patterson-Lomba, Tychell Branchcomb, Laetitia N'Dri, Andres Gomez-Lievano, Jingyi Liu, Akanksha Dua, Marisa McGinley
{"title":"Comparative effectiveness and safety of ozanimod <i>versus</i> other oral DMTs in relapsing-remitting multiple sclerosis: a synthesis of matching-adjusted indirect comparisons.","authors":"Damemarie Paul, Elyse Swallow, Oscar Patterson-Lomba, Tychell Branchcomb, Laetitia N'Dri, Andres Gomez-Lievano, Jingyi Liu, Akanksha Dua, Marisa McGinley","doi":"10.1177/17562864241237856","DOIUrl":"10.1177/17562864241237856","url":null,"abstract":"<p><strong>Background: </strong>Several oral disease-modifying therapies (DMTs) have been approved by the Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis (RRMS). In the absence of head-to-head randomized data, matching-adjusted indirect comparisons (MAICs) can evaluate the comparative effectiveness and safety of ozanimod <i>versus</i> other oral DMTs in RRMS.</p><p><strong>Objectives: </strong>To synthesize results from the published MAICs of ozanimod and other oral DMTs for 2-year outcomes in RRMS.</p><p><strong>Methods: </strong>Published MAICs involving ozanimod for the treatment of RRMS were identified. Extracted data elements included efficacy [annualized relapse rate (ARR), confirmed disability progression (CDP), and brain volume loss] and safety [adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, and infection] outcomes.</p><p><strong>Results: </strong>The four MAIC studies identified compared ozanimod with fingolimod, teriflunomide, dimethyl fumarate (DMF), and ponesimod. All comparisons were adjusted for differences in age, sex, relapses within the previous year, Expanded Disability Status Scale score, and percentage of patients with prior DMTs. Outcomes at 2 years were analyzed based on comparisons that lacked a common comparator arm. Ozanimod was associated with significantly lower ARR <i>versus</i> teriflunomide [ARR ratio (95% CI) 0.73 (0.62, 0.84) and DMF 0.80 (0.67, 0.97)], with no significant difference <i>versus</i> fingolimod or ponesimod. The proportions of patients treated with ozanimod or fingolimod had similar 3- and 6-month CDP. Compared with teriflunomide and DMF, ozanimod was associated with a significantly lower risk of 3-month CDP; 6-month CDP was comparable. Ozanimod was associated with significantly lower rates of any AE and AEs leading to discontinuation compared with the other oral DMTs evaluated. Ozanimod also had significantly lower rates of SAEs <i>versus</i> teriflunomide and DMF and lower rates of reported infection outcomes <i>versus</i> fingolimod and ponesimod.</p><p><strong>Conclusion: </strong>Compared with the other oral DMTs evaluated in MAICs, ozanimod was associated with a favorable safety profile and improved or comparable efficacy outcomes.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241237856"},"PeriodicalIF":5.9,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11162124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296738","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":"Comment on: Cytokines (IL1β, IL6, TNFα) and serum cortisol levels may not constitute reliable biomarkers to identify individuals with post-acute sequelae of COVID-19.","authors":"Matthias Kohl","doi":"10.1177/17562864241254268","DOIUrl":"10.1177/17562864241254268","url":null,"abstract":"","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241254268"},"PeriodicalIF":5.9,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200613","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}
Michael Fleischer, Fabian Szepanowski, Anne K Mausberg, Livia Asan, Ellen Uslar, Denise Zwanziger, Mark Stettner, Lothar Volbracht, Christoph Kleinschnitz
{"title":"Author response to Comment on: Cytokines (IL1β, IL6, TNFα) and serum cortisol levels may not constitute reliable biomarkers to identify individuals with post-acute sequelae of COVID-19.","authors":"Michael Fleischer, Fabian Szepanowski, Anne K Mausberg, Livia Asan, Ellen Uslar, Denise Zwanziger, Mark Stettner, Lothar Volbracht, Christoph Kleinschnitz","doi":"10.1177/17562864241255819","DOIUrl":"10.1177/17562864241255819","url":null,"abstract":"","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241255819"},"PeriodicalIF":5.9,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200610","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}
Pablo Hervella, Maria Luz Alonso-Alonso, Ana Sampedro-Viana, Manuel Rodríguez-Yáñez, Iria López-Dequidt, José M Pumar, Alberto Ouro, Daniel Romaus-Sanjurjo, Francisco Campos, Tomás Sobrino, José Castillo, Yago Leira, Ramón Iglesias-Rey
{"title":"Differential blood-based biomarkers of subcortical and deep brain small vessel disease.","authors":"Pablo Hervella, Maria Luz Alonso-Alonso, Ana Sampedro-Viana, Manuel Rodríguez-Yáñez, Iria López-Dequidt, José M Pumar, Alberto Ouro, Daniel Romaus-Sanjurjo, Francisco Campos, Tomás Sobrino, José Castillo, Yago Leira, Ramón Iglesias-Rey","doi":"10.1177/17562864241243274","DOIUrl":"10.1177/17562864241243274","url":null,"abstract":"<p><strong>Background: </strong>Cerebral small vessel disease is the most common cause of lacunar strokes (LS). Understanding LS pathogenesis is vital for predicting disease severity, prognosis, and developing therapies.</p><p><strong>Objectives: </strong>To research molecular profiles that differentiate LS in deep brain structures from those in subcortical white matter.</p><p><strong>Design: </strong>Prospective case-control study involving 120 patients with imaging-confirmed LS and a 120 control group.</p><p><strong>Methods: </strong>We examined the relationship between Alzheimer's disease biomarkers [amyloid beta (Aβ<sub>1-40</sub>, Aβ<sub>1-42</sub>)], serum inflammatory marker (interleukin-6, IL-6), and endothelial dysfunction markers [soluble tumor necrosis factor-like weak inducer of apoptosis, and pentraxin-3 (sTWEAK, PTX3)] with respect to LS occurring in deep brain structures and subcortical white matter. In addition, we investigated links between LS, leukoaraiosis presence (white matter hyperintensities, WMHs), and functional outcomes at 3 months. Poor outcome was defined as a modified Rankin scale >2 at 3 months.</p><p><strong>Results: </strong>Significant differences were observed in levels of IL-6, PTX3, and sTWEAK between patients with deep lacunar infarcts and those with recent small subcortical infarcts (20.8 <i>versus</i> 15.6 pg/mL, <i>p</i> < 0.001; 7221.3 <i>versus</i> 4624.4 pg/mL, <i>p</i> < 0.0001; 2528.5 <i>versus</i> 1660.5 pg/mL, <i>p</i> = 0.001). Patients with poor outcomes at 3 months displayed notably higher concentrations of these biomarkers compared to those with good outcomes. By contrast, Aβ<sub>1-40</sub> and Aβ<sub>1-42</sub> were significantly lower in patients with deep LS (<i>p</i> < 0.0001). Aβ<sub>1-42</sub> levels were significantly higher in patients with LS in subcortical white matter who had poor outcomes. WMH severity only showed a significant association with deep LS and correlated with sTWEAK (<i>p</i> < 0.0001).</p><p><strong>Conclusion: </strong>The pathophysiological mechanisms of lacunar infarcts in deep brain structures seem different from those in the subcortical white matter. As a result, specific therapeutic and preventive strategies should be explored.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241243274"},"PeriodicalIF":5.9,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200615","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}