Journal of Neurology最新文献

{"title":"Contactin proteins in cerebrospinal fluid show different alterations in dementias.","authors":"Besnik Muqaku, Sarah Anderl-Straub, Leonie Werner, Magdalena Nagl, Markus Otto, Charlotte E Teunissen, Patrick Oeckl","doi":"10.1007/s00415-024-12694-6","DOIUrl":"https://doi.org/10.1007/s00415-024-12694-6","url":null,"abstract":"<p><strong>Background: </strong>The proteins contactin (CNTN) 1-6 are synaptic proteins for which there is evidence that they are dysregulated in neurodegenerative dementias. Less is known about CNTN changes and differences in cerebrospinal fluid (CSF) of dementias, which can provide important information about alterations of the CNTN network and be of value for differential diagnosis.</p><p><strong>Methods: </strong>We developed a mass spectrometry-based multiple reaction monitoring (MRM) method to simultaneously determine all six CNTNs in CSF samples using stable isotope-labeled standard peptides. The analytical performance of the method was evaluated for peptide stability, dilution linearity and precision. CNTNs were measured in 82 CSF samples from patients with Alzheimer's disease (AD, n = 19), behavioural variant frontotemporal dementia (bvFTD, n = 18), Parkinson's disease dementia/dementia with Lewy bodies (PDD/DLB, n = 18) and non-neurodegenerative controls (n = 27) and compared with core AD biomarkers.</p><p><strong>Results: </strong>The MRM analysis revealed down-regulation of CNTN2 (fold change (FC) = 0.77), CNTN4 (FC = 0.75) and CNTN5 (FC = 0.67) in bvFTD and CNTN3 (FC = 0.72), CNTN4 (FC = 0.75) and CNTN5 (FC = 0.73) in PDD/DLB compared to AD. CNTN levels strongly correlated with each other in controls (r = 0.73), bvFTD (r = 0.86) and PDD/DLB (r = 0.70), but the correlation was significantly lower in AD (r = 0.41). CNTNs in AD did not show correlation even with core AD biomarkers. Combined use of CNTN1-6 levels increased diagnostic performance of AD core biomarkers.</p><p><strong>Conclusions: </strong>Our data show CNTNs differentially altered in dementias and indicate CNTN homeostasis being selectively dysregulated in AD. The combined use of CNTNs with AD core biomarkers might help to improve differential diagnosis.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Axial tics in Tourette syndrome and chronic tic disorders.","authors":"José Fidel Baizabal-Carvallo, Joseph Jankovic","doi":"10.1007/s00415-024-12707-4","DOIUrl":"https://doi.org/10.1007/s00415-024-12707-4","url":null,"abstract":"<p><strong>Background: </strong>Tics are the hallmark of Tourette syndrome (TS) and chronic tic disorders (CTD). Although typically involving the face, especially at onset, tics may involve any muscle under voluntary control, including axial muscles of the neck (causing head movements), shoulders and trunk (thorax and abdomen). We aimed to characterize these tics and provide a clinical frame for their associations and complications.</p><p><strong>Materials and methods: </strong>We reviewed video recordings and clinical history of 196 patients with TS or CTD according to DSM-5.</p><p><strong>Results: </strong>Any axial tic was identified in 75% of patients. Tic distribution were head (n = 113, 57.6%), shoulder (n = 91, 46.4%), and trunk (n = 63, 32.2%). There were no differences in sex, age at onset or at evaluation between patients with and without axial tics. The most common axial tics by anatomical distribution were head turning, bilateral synchronous shoulder elevation and trunk jerks; however, tic phenomenology was quite variable. A greater severity of tics (P = 0.018) was associated with axial tics in the multivariate regression analysis. Head/neck tics associated with simple phonic tics (P = 0.002); whereas shoulder and trunk tics associated with complex motor tics (P < 0.05) in a bivariate analysis. Neck pain, breathing interference, sleep limitation and radiculopathy, secondary to axial tics were complications observed in a proportion of these cases.</p><p><strong>Conclusions: </strong>Axial tics are commonly observed in patients with TS/CTD with variable phenomenology. They associate with greater tic severity, phonic tics and complex motor tics. They may result in neck pain, breathing interference, sleeping problems and cervical spine injuries.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In multiple sclerosis patients a single serum neurofilament light chain (sNFL) dosage is strongly associated with 12 months outcome: data from a real-life clinical setting.","authors":"Simona Malucchi, Cecilia Irene Bava, Paola Valentino, Serena Martire, Marianna Lo Re, Antonio Bertolotto, Alessia Di Sapio","doi":"10.1007/s00415-024-12701-w","DOIUrl":"https://doi.org/10.1007/s00415-024-12701-w","url":null,"abstract":"<p><strong>Background: </strong>Neurofilament light chain (NFL) is a neuroaxonal cytoskeletal protein released into cerebrospinal fluid (CSF) and eventually into blood upon neuronal injury. Its detection in serum (sNFL) makes it a promising marker in multiple sclerosis (MS).</p><p><strong>Objective: </strong>To evaluate the usefulness of a single dosage of sNFL in clinical practice.</p><p><strong>Methods: </strong>626 consecutive relapsing-remitting (RR) MS patients treated with disease modifying treatments (DMTs) for at least 12 months underwent a single sNFL dosage. 553 patients had NEDA-3 status (no relapses, no disability progression, no new/enlarging or contrast-enhancing lesions on brain magnetic resonance imaging) in the 12 months prior blood sampling. sNFL levels were measured by single molecule array (Simoa™). Association between sNFL levels and NEDA-3 status at 12, 24, and 36 months was evaluated with logistic regression models adjusted for sex, EDSS, disease duration, and type of DMTs.</p><p><strong>Results: </strong>469 out of the 553 NEDA-3 patients had normal sNFL level, whereas 42 had elevated level. The two groups did not differ regarding baseline characteristics. A very strong association between elevated sNFL levels and loss of NEDA-3 status within 12 months was found, with an odds ratio [OR] of 10.74 (95% CI 4.34-26.57); 15 and 10 patients with normal and elevated sNFL, respectively lost NEDA-3 (p < 0.001). The effect was not detected during the subsequent 13-24 and 25-36 months.</p><p><strong>Conclusions: </strong>A single elevated sNFL is strongly associated with NEDA-3 loss within 1 year. Elevated sNFL in apparently stable patients suggests an ongoing disease activity below the detection threshold of standard parameters.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frida Kahlo could have had cauda equina syndrome: a case report.","authors":"Oyku Arslantas, Sergiu Albu, Josep Valls-Sole, Hatice Kumru","doi":"10.1007/s00415-024-12695-5","DOIUrl":"https://doi.org/10.1007/s00415-024-12695-5","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Admission hyperglycemia effect on symptomatic intracranial hemorrhage in tenecteplase versus alteplase before large vessel occlusion stroke thrombectomy.","authors":"Philipp Hendrix, Prateeka Koul, Anthony Noto, Jiang Li, Clemens M Schirmer, Michael J Lang, Alhamza R Al-Bayati, Raul G Nogueira, Bradley A Gross","doi":"10.1007/s00415-024-12704-7","DOIUrl":"https://doi.org/10.1007/s00415-024-12704-7","url":null,"abstract":"<p><strong>Introduction: </strong>Intravenous thrombolysis (IVT) with alteplase (TPA) in hyperglycemic stroke patients is associated with an increased risk of symptomatic intracranial hemorrhage (sICH) and poor functional outcomes. We aimed to explore the association between admission hyperglycemia and sICH in large vessel occlusion stroke (LVOS) patients treated with TNK versus TPA before endovascular thrombectomy (EVT).</p><p><strong>Methods: </strong>We reviewed consecutive LVOS patients treated with TPA or TNK before EVT from 01/2020 to 06/2023. EVT was performed across five comprehensive stroke centers (CSCs) in Pennsylvania. Of 569 patients, 462 met inclusion criteria: LVOS, pre-stroke modified Rankin Scale (mRS) 0-2, and last-known-well to IVT (LKW-to-IVT) ≤ 4.5 h. The rates of sICH and parenchymal hematomas (PHs) between TPA and TNK cohorts were assessed.</p><p><strong>Results: </strong>Of 462 patients, 254 (55%) received TNK, and 208 (45%) received TPA. Admission hyperglycemia (≥ 140 mg/dl) was present in 153 (33.1%) patients. Hyperglycemic patients were more frequently diabetic (p < 0.001). Admission hyperglycemia was associated with a significantly increased rate of sICH (5.9% versus 1.6%, p = 0.019) and PH (20.3% versus 11.3%, p = 0.010). Hyperglycemic patients had a significantly higher degree of overall disability as compared to normoglycemic patients (90d-mRS shift aOR 0.611, p = 0.007). Comparable rates of sICH and PH were observed in the hyperglycemic and normoglycemic cohorts among both TNK and TPA groups.</p><p><strong>Conclusion: </strong>In LVOS patients receiving IVT before EVT, admission hyperglycemia significantly increased the risk of sICH and PH and was associated with worse outcomes at 90 days. No differences in sICH or PH were observed between TNK and TPA groups.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aquaporin4-IgG seropositivity significantly increases the risk of comorbid autoimmune diseases in NMOSD patients: population-based registry data.","authors":"Tatjana Pekmezovic, Vanja Jovicevic, Marko Andabaka, Nikola Momcilovic, Nikola Veselinovic, Olivera Tamas, Maja Budmkic, Stefan Todorovic, Marta Jeremic, Evica Dincic, Slobodan Vojinovic, Sladjana Andrejevic, Sarlota Mesaros, Jelena Drulovic","doi":"10.1007/s00415-024-12698-2","DOIUrl":"https://doi.org/10.1007/s00415-024-12698-2","url":null,"abstract":"<p><strong>Background: </strong>The aim of our study was to estimate the frequency of autoimmune comorbidities, in NMOSD patients from the national Serbian NMOSD Registry.</p><p><strong>Methods: </strong>Our study comprises 136 patients with NMOSD, diagnosed according to the NMOSD criteria 2015. At the time of the study, in the Registry were collected demographic and clinical data, including those related to the coexisting comorbidities and pathogenic autoantibodies. Not all patients were tested for all autoimmune antibodies. None of the seronegative aquaporin4-IgG (AQP4-IgG) NMOSD patients, included in the Registry, were positive for the myelin oligodendrocyte glycoprotein IgG.</p><p><strong>Results: </strong>Among 136 NMOSD patients, 50 (36.8%) had at least one associated autoimmune disorder. AQP4-IgG was present in the sera from 106 patients (77.9%), the proportion of NMOSD patients with autoimmune comorbidities being significantly higher in the AQP4-IgG positive subgroup in comparison to the AQP4-IgG negative (p = 0.002). AQP4-IgG seropositive NMOSD patients had 5.2-fold higher risk of comorbid autoimmune diseases (OR = 5.2, 95% CI 1.4-18.5, p = 0.012). The most frequently reported diseases were autoimmune thyroid disease (15.4%), Sjogren's syndrome (11.0%), systemic lupus erythematosus (5.1%), myasthenia gravis (4.4%), and primary antiphospholipid antibody syndrome (2.9%). Antinuclear antibodies (ANAs) were frequently detected in the subgroup of NMOSD patients tested for this antibody (50/92; 54.3%). The higher frequency of ANAs and anti-extractable nuclear antigen autoantibodies, in the subgroups of AQP4-IgG-positive patients compared to the AQP4-IgG negative, tested for these antibodies, was statistically significant (p = 0.009, and p = 0.015, respectively).</p><p><strong>Conclusion: </strong>In conclusion, based on our results, in a defined cohort with European ethnical background, a wide spectrum of autoimmune diseases is frequently associated with AQP4-IgG seropositive NMOSD patients.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive performance from childhood to old age and intergenerational correlations in the multigenerational Young Finns Study.","authors":"Marja A Heiskanen, Jaakko Nevalainen, Katja Pahkala, Markus Juonala, Nina Hutri, Mika Kähönen, Eero Jokinen, Tomi P Laitinen, Päivi Tossavainen, Leena Taittonen, Jorma S A Viikari, Olli T Raitakari, Suvi P Rovio","doi":"10.1007/s00415-024-12693-7","DOIUrl":"https://doi.org/10.1007/s00415-024-12693-7","url":null,"abstract":"<p><strong>Background: </strong>Cognitive performance changes during the lifespan, but the information is gathered from studies on separate age cohorts. Computerized neurocognitive testing enables efficient and similar assessments for all ages. We investigated (i) the effect of age at different stages of life and (ii) intergenerational correlations across cognitive domains in the multigenerational Young Finns Study.</p><p><strong>Methods: </strong>Participants in three familiarly related generations (n = 6486, aged 7-92 years) performed the Cambridge Neuropsychological Test Automated Battery (CANTAB). Overall cognitive performance and domains representing learning and memory, working memory, information processing, and reaction time were extracted by common principal component analysis from the cognitive data with several age groups. Linear models were used to study the association of age, sex, and education with overall cognitive performance and in the cognitive domains. Age-adjusted intergenerational correlations were calculated.</p><p><strong>Results: </strong>Learning and memory peaked earlier during the lifespan compared to working memory and information processing, and the rate of decline toward old age differed by domain. Weak intergenerational correlations existed between two consecutive generations but were nonsignificant between grandparents and grandchildren. There was no systematic sex-specific transmission in any cognitive domain.</p><p><strong>Conclusion: </strong>This study describes the natural course of cognitive performance across the lifespan and proves that cognitive performance changes differently across cognitive domains with weak intergenerational transmission.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why is vestibular migraine associated with many comorbidities?","authors":"Yan-Min Ma, Dao-Pei Zhang, Huai-Liang Zhang, Fang-Zheng Cao, Yu Zhou, Bin Wu, Ling-Zhe Wang, Bin Xu","doi":"10.1007/s00415-024-12692-8","DOIUrl":"https://doi.org/10.1007/s00415-024-12692-8","url":null,"abstract":"<p><p>Vestibular migraine (VM) is a usual trigger of episodic vertigo. Patients with VM often experience spinning, shaking, or unsteady sensations, which are usually also accompanied by photophobia, phonophobia, motor intolerance, and more. VM is often associated with a number of comorbidities. Recurrent episodes of VM can affect the patient's emotions, sleep, and cognitive functioning to varying degrees. Patients with VM may be accompanied by adverse moods such as anxiety, fear, and depression, which can gradually develop into anxiety disorders or depressive disorders. Sleep disorders are also a common concomitant symptom of VM, which significantly lower patients' quality of life. The influence of anxiety disorders and sleep disorders may reduce cognitive functions of VM, such as visuospatial ability, attention, and memory decline. Clinically, it is also common to see VM comorbid with other vestibular disorders, making the diagnosis more difficult. VM episodes are relieved but lingering, in which case VM may coexist with persistent postural-perceptual dizziness (PPPD). Anxiety may be an important bridge between recurrent VM and PPPD. The clinical manifestations of VM and Meniere's disease (MD) overlap considerably, and those who meet the diagnostic criteria for both can be said to have VM/MD comorbidity. VM can also present with positional vertigo, and some patients with VM present with typical benign paroxysmal positional vertigo (BPPV) nystagmus on positional testing. In this paper, we synthesize and analyze the pathomechanisms of VM comorbidity by reviewing the literature. The results show that it may be related to the extensive connectivity of the vestibular system with different brain regions and the close connection of the trigeminovascular system with the periphery of the vestibule. Therefore, it is necessary to pay attention to the diagnosis of comorbidities in VM, synthesize its pathogenesis, and give comprehensive treatment to patients.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Definition and diagnosis of Parkinson’s disease: guideline “Parkinson’s disease” of the German Society of Neurology","authors":"Franziska Hopfner, Günter Höglinger, Claudia Trenkwalder","doi":"10.1007/s00415-024-12687-5","DOIUrl":"https://doi.org/10.1007/s00415-024-12687-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Accurate definition and operational criteria for diagnosing Parkinson’s disease (PD) are crucial for evidence-based, patient-centered care.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>To offer evidence-based recommendations for defining and diagnosing PD, incorporating contemporary clinical, imaging, biomarker, and genetic insights.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The guideline development began with the steering committee establishing key PICO (patient, intervention, comparison, outcome) questions, which were refined by the coauthors. Systematic literature searches identified relevant studies, reviews, and meta-analyses. Recommendations were drafted, evaluated, optimized, and voted upon by the German Parkinson’s Guideline Group.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Parkinson’s disease (PD) is now understood to encompass a broader spectrum of etiologies than previously recognized. Advances in molecular pathogenesis, neuroimaging, and early clinical phenotypes suggest that PD is not a uniform disease entity and is often not idiopathic. This necessitates an updated framework for PD definition and diagnosis. The German Society for Neurology now endorses a broader concept of PD, incorporating both idiopathic and hereditary forms, as opposed to the previously narrower concept of “idiopathic Parkinson syndrome.” The revised guidelines recommend using the 2015 Movement Disorders Society diagnostic criteria, emphasize the importance of long-term clinical follow-up for improved diagnostic accuracy, and highlight the significance of non-motor symptoms in clinical diagnosis. Specific recommendations are provided for the use of imaging and fluid biomarkers and genetic testing to support the clinical diagnosis.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The updated guidelines from the German Society for Neurology enhance diagnostic accuracy for PD, promoting optimized clinical care.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoaminergic network abnormalities are associated with fatigue in pediatric multiple sclerosis","authors":"Monica Margoni, Paola Valsasina, Lucia Moiola, Damiano Mistri, Massimo Filippi, Maria A. Rocca","doi":"10.1007/s00415-024-12689-3","DOIUrl":"https://doi.org/10.1007/s00415-024-12689-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Fatigue is commonly observed in pediatric multiple sclerosis (pedMS) patients, but its underlying mechanisms remain largely unexplored. We evaluated whether resting-state (RS) functional connectivity (FC) abnormalities in monoaminergic networks contributed to explain fatigue in pedMS.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Fifty-five pedMS and twenty-three matched healthy controls (HC) underwent clinical and RS functional MRI assessment. Patients with Fatigue Severity Scale (FSS) score ≥ 4 were classified as fatigued (F). Patterns of dopamine-, noradrenaline- and serotonin-related RS FC were derived by constrained independent component analysis, using PET atlases for dopamine, noradrenaline, and serotonin transporters obtained in HCs’ brain.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Compared to non-fatigued (NF)-pedMS patients and HC, F-pedMS patients (15/55, 27.3%) showed decreased dopamine-related RS FC in the right postcentral gyrus. They also showed decreased dopamine-related RS FC in the left insula vs. HC and increased dopamine-related RS FC in the left middle temporal gyrus and cerebellum (lobule VI) vs. NF patients. In the noradrenaline-related network, F-pedMS patients showed decreased RS FC in the left superior parietal lobule and increased RS FC in the right thalamus vs. HC and NF-pedMS. Compared to HC, F-pedMS patients also showed decreased RS FC in the right calcarine cortex and increased RS FC in the right middle frontal gyrus. In the serotonin-related network, F-pedMS patients showed decreased RS FC in the right angular gyrus and increased RS FC in the right postcentral gyrus vs. NF-pedMS patients.</p><h3 data-test=\"abstract-sub-heading\">Discussion</h3><p>In pedMS, fatigue is associated with specific monoaminergic network abnormalities, providing pathological markers for this bothersome symptom and putative targets for its treatment.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}