Early clinical features of new-onset refractory status epilepticus (NORSE) in adults

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Ectopic germinal centers in the thymus accurately predict prognosis of myasthenia gravis after thymectomy

The ability of thymic histopathology to predict the long-term impact of thymectomy in non-thymomatous myasthenia gravis (NTMG) is mainly uncharted. We applied digital pathology to quantitatively characterize differences of thymic histology between early-onset (EOMG) and late-onset MG (LOMG) and to investigate the role of thymic changes for thymectomy outcomes in MG. We analyzed 83 thymic H&E slides from thymectomized NTMG patients, of which 69 had EOMG and 14 LOMG, using digital pathology open-access software QuPath. We compared the results to the retrospectively assessed clinical outcome at two years after thymectomy and at the last follow-up visit where complete stable remission and minimal use of medication were primary outcomes. The automated annotation pipeline was an effective and reliable way to analyze thymic H&E samples compared to manual annotation with mean intraclass correlation of 0.80. The ratio of thymic tissue to stroma and fat was increased in EOMG compared to LOMG (p = 8.7e-07), whereas no difference was observed in the ratio of medulla to cortex between these subtypes. AChRAb seropositivity correlated with the number of ectopic germinal centers (eGC; p = 0.00067) but not with other histological areas. Patients with an increased number of eGCs had better post-thymectomy outcomes at two years after thymectomy (p = 0.0035) and at the last follow-up (p = 0.0267). ROC analysis showed that eGC area predicts thymectomy outcome in EOMG with an AUC of 0.79. Digital pathology can thus help in providing a predictive tool to the clinician, the eGC number, to guide the post-thymectomy treatment decisions in EOMG patients.Peer reviewe

Multiple sclerosis in Finland 2018-Data from the national register

Objectives Finland is a high-risk multiple sclerosis (MS) region, but a national MS register has not existed until 2014. In this paper, we present the Finnish MS register variables and data collected by 31 December 2018. Materials and Methods Numbers and data counts of MS patients in the register (ICD-10 code G35) are presented. The disease types and proportion of patients receiving disease-modifying treatments (DMTs) were analysed in five hospital districts with most complete data sets. MS prevalence in Finland was estimated using administrative hospital discharge data as an additional resource. Results There were a total of 8722 MS patients in the Finnish MS register by 31 December 2018 (71.5% females). Mean age at MS diagnosis was 38.7 years and peak prevalence was at age 50-54 years. Disease course was relapsing remitting (RRMS) in 66.7%, secondary progressive (SPMS) in 13.5%, and primary progressive (PPMS) in 7.9% of the 5365 MS patients in the selected districts with most complete data. A total of 66.0% of RRMS patients, 19.6% of SPMS patients and 9.9% of PPMS patients were receiving DMTs. By combining MS register data with databases of those hospitals that had not joined the register, the nationwide prevalence estimate was between 10 and 11 thousand patients (corresponding to crude prevalence 180-200/100 000). Conclusions The Finnish MS register is currently used in 15/21 Finnish hospital districts. By register integration into the electronic patient files, the coverage of the register has increased to approximately 80% of the estimated Finnish MS population.Peer reviewe

Clinically relevant increases in serum neurofilament light chain and glial fibrillary acidic protein in patients with Susac syndrome

Background and purpose: Serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising neuro-axonal damage and astrocytic activation biomarkers. Susac syndrome (SS) is an increasingly recognized neurological condition and biomarkers that can help assess and monitor disease evolution are highly needed for the adequate management of these patients. sNfL and sGFAP levels were evaluated in patients with SS and their clinical relevance in the relapse and remission phase of the disease was assessed. Methods: As part of a multicentre study that enrolled patients diagnosed with SS from six international centres, sNfL and sGFAP levels were assessed in 22 SS patients (nine during a relapse and 13 in remission) and 59 age- and sex-matched healthy controls using SimoaTM assay Neurology 2-Plex B Kit. Results: Serum NfL levels were higher than those of healthy controls (p < 0.001) in SS patients and in both subgroups of patients in relapse and in remission (p < 0.001 for both), with significantly higher levels in relapse than in remission (p = 0.008). sNfL levels showed a negative correlation with time from the last relapse (r = -0.663; p = 0.001). sGFAP levels were slightly higher in the whole group of patients than in healthy controls (p = 0.046) and were more pronounced in relapse than in remission (p = 0.013). Conclusion: In SS patients, both sNFL and sGFAP levels increased compared with healthy controls. Both biomarkers had higher levels during clinical relapse and much lower levels in remission. sNFL was shown to be time sensitive to clinical changes and can be useful to monitor neuro-axonal damage in SS

Näyttää MS:ltä, kuulostaa MS:ltä, tuntuu MS:ltä — muttei ole MS

Tiivistelmä MS-taudin diagnoosi pyritään varmentamaan jo ensioireiden jälkeen, jotta hoito päästään aloittamaan aikaisin. Diagnoosin on oltava täsmällinen, koska virhediagnoosi kuormittaa potilasta ja terveydenhuoltoa, ja sen perusteella aloitettu hoito voi huonontaa tilannetta. Keskeistä MS-taudin tunnistamisessa on luottaa anamneesin ja kliinisen tutkimuksen merkitykseen ja peilata näitä magneettikuvauksen ja aivo-selkäydinnestenäytteen tulehduksellisiin löydöksiin. Tyypillinen aaltomaisen MS-taudin oirejakso on toispuolinen näköhermotulehdus, aivorunko-oireisto tai osittainen selkäydinoireyhtymä. Oirejakso tulee tunneissa tai päivissä voimistuen, esiintyy jatkuvana ja lievittyy muutamissa viikoissa. Aaltomaisen MS-taudin erotusdiagnostiikassa tärkeitä ovat muut autoimmuunisairaudet, tulehdukset, syöpäsairaudet sekä geneettiset sairaudet. Suoraan etenevän MS-taudin tyyppioire puolestaan on etenevä kävelyvaikeus, jonka tutkimuksissa etsitään tulehduksellisen demyelinoivan sairauden piirteitä ja suljetaan pois erityisesti selkäydinsairauksia

Trigeminal neuralgia in multiple sclerosis: prevalence and association with demyelination

Objectives The association of trigeminal neuralgia (TN) with multiple sclerosis (MS) is still widely unaddressed in larger, systematical clinical series. In this study, a cohort of Finnish MS patients was assessed regarding the incidence and prevalence of TN, as well as the presence of demyelinating lesions near the trigeminal ganglion, thus searching for a causative role of MS plaques in TN onset. Materials & Methods All consecutive patients treated and followed up for MS (ICD-code G35) in Helsinki University Hospital during 2004-2017 were identified from the Finnish MS register. A hospital administrative database search was used to identify all patients treated and followed up for TN during the same period. Among the MS patients, head MRI scans available from the diagnostic phase of TN or thereafter were analysed. Results We identified a total of 2575 patients with MS and 2008 patients with TN. Both diagnoses could be verified for 55 patients, giving a prevalence of 2.1% for TN in MS. The incidence of TN in MS patients was 149/100 000 person-years (95% CI 108-190). In the general outpatient population of our neurological department, the incidence of TN was 9.9/100 000 person-years (95% CI 9.5-10.3). A demyelinating lesion in the proximity of the trigeminal ganglia was seen for 63% of the 41 patients with relevant MRI data available. Conclusions Incidence of TN among MS patients was 15-fold higher than in the general neurological outpatient population, thus in favour of a strong association between MS and TN.Peer reviewe

Expanded CD4(+) Effector/Memory T Cell Subset in APECED Produces Predominantly Interferon Gamma

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Incidental demyelination in magnetic resonance imaging and 10-year risk of multiple sclerosis : A data lake cohort study

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Complete remission of central nervous system manifestations of IgG4-related disease with rituximab - a case report

IgG4-related disease (IgG4-RD) is an emerging immune-mediated chronic fibrotic disease characterized by tumour-like mass formation. Reports of brain parenchymal involvement in IgG4-RD are rare and complete treatment-related remission of lesions has never been reported. Here, we present a woman in her mid-50s who developed headache and seizures. Brain magnetic resonance imaging revealed frontal bilateral pachymeningitis and a left frontal lobe parenchymal lesion, and pathologic findings were consistent with an IgG4-RD central nervous system manifestation. She had a history of tumour-like growth around the right optic nerve, orbital and maxillary cavities treated successfully with corticosteroids 28 years ago, and was receiving infliximab as a maintenance therapy for uveitis for the last 14 years. After initial high-dose corticosteroid treatment, the patient was treated with rituximab, and after 3 months, the patient presented with complete remission of IgG4-RD lesions and associated symptoms. This case illustrates the chronic, decades-spanning nature of IgG4-RD, and a complete response to rituximab even with intracerebral mass lesions that had emerged despite the use of infliximab, a therapy previously reported successful in IgG4-RD.Peer reviewe

High Epstein-Barr virus capsid antigen IgG level associates with the carriership of CD8+ T cell somatic mutations in the STAT3 SH2 domain

Publisher Copyright: © 2023High carrier prevalence of STAT3 SH2 domain somatic mutations was recently discovered in CD8+ T cells. We found these low-allele-fraction clones in 26% of donors, without difference between multiple sclerosis (MS) patients and controls. Here we tested whether anti-viral antibodies associate with the carriership of these mutant clones. We compared antibody responses against common viruses in mutation carriers vs. non-carriers. Plasma samples of 152 donors (92 MS patients, 60 controls) were analyzed for antibodies against cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6A and parvovirus B19. The mutation carrier status associated with EBV VCA IgG level (p = 0.005) and remained significant after logistic regression (p = 0.036). This association was contributed similarly by MS patients and controls. These results suggest that EBV contributes to the generation or growth of these clones. The pathogenic role of the STAT3 mutant clones in MS is presently unclear, but their detailed characterization warrants further study.Peer reviewe