BACKGROUND: The neurofilament light chain (NfL) in cerebrospinal fluid (CSF) and serum as a marker of neuronal damage may be a potential biomarker of neuropsychiatric involvement in SLE (NPSLE). METHODS: 80 patients with SLE were included.We obtained paired serum and CSF samples from 48 patients (NPSLE n=32, non-NPSLE n=16) and 31 controls. The serum and CSF levels of NfL were determined using ELISA. RESULTS: Patients with NPSLE demonstrated significantly higher levels of serum NfL compared with the non-NPSLE group (mean 31.68±36.63 pg/mL vs mean 16.75±12.48 pg/mL, respectively, p<0.05) and with controls (mean 10.74±4.36 pg/mL, p<0.01). Notably, CSF NfL concentrations in patients with NPSLE showed an upward trend (mean 1600±2852 pg/mL) in contrast to non-NPSLE patients (mean 393.4±191.9 pg/mL) and controls (mean 509.7±358.5 pg/mL). Furthermore, a positive correlation was observed between serum and CSF NfL levels in patients with NPSLE (R=0.8686, p<0.01). Elevated serum triacylglycerol concentrations, C reactive protein and organ damage were linked to increased serum (p=0.002; p<0.001; p=0.036) and CSF (p=0.008; p=0.007; p<0.001) NfL concentrations. In addition, we established a significant correlation between intrathecal NfL concentrations and interleukin-6 levels in the CSF of patients with NPSLE (R=0.5118, p<0.05). CONCLUSION: The serum NfL levels may be a readily available marker of neuropsychiatric involvement in SLE.

• Klíčová slova
• autoimmune diseases, cytokines, systemic lupus erythematosus,
• MeSH
• biologické markery * krev   mozkomíšní mok   MeSH
• dospělí MeSH
• ELISA MeSH
• interleukin-6 krev   mozkomíšní mok   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• neurofilamentové proteiny * krev   mozkomíšní mok   MeSH
• průřezové studie MeSH
• studie případů a kontrol MeSH
• vaskulitida centrálního nervového systému při lupus erythematodes * krev   mozkomíšní mok   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery * MeSH
• interleukin-6 MeSH
• neurofilament protein L MeSH Prohlížeč
• neurofilamentové proteiny * MeSH

OBJECTIVE: Refractory epilepsy may have an underlying autoimmune etiology. Our aim was to assess the prevalence of neural autoantibodies in a multicenter national prospective cohort of patients with drug-resistant epilepsy undergoing epilepsy surgery utilizing comprehensive clinical, serologic, and histopathological analyses. METHODS: We prospectively recruited patients undergoing epilepsy surgery for refractory focal epilepsy not caused by a brain tumor from epilepsy surgery centers in the Czech Republic. Perioperatively, we collected cerebrospinal fluid (CSF) and/or serum samples and performed comprehensive commercial and in-house assays for neural autoantibodies. Clinical data were obtained from the patients' medical records, and histopathological analysis of resected brain tissue was performed. RESULTS: Seventy-six patients were included, mostly magnetic resonance imaging (MRI)-lesional cases (74%). Mean time from diagnosis to surgery was 21 ± 13 years. Only one patient (1.3%) had antibodies in the CSF and serum (antibodies against glutamic acid decarboxylase 65) in relevant titers; histology revealed focal cortical dysplasia (FCD) III (FCD associated with hippocampal sclerosis [HS]). Five patients' samples displayed CSF-restricted oligoclonal bands (OCBs; 6.6%): three cases with FCD (one with FCD II and two with FCD I), one with HS, and one with negative histology. Importantly, eight patients (one of them with CSF-restricted OCBs) had findings on antibody testing in individual serum and/or CSF tests that could not be confirmed by complementary tests and were thus classified as nonspecific, yet could have been considered specific without confirmatory testing. Of these, two had FCD, two gliosis, and four HS. No inflammatory changes or lymphocyte cuffing was observed histopathologically in any of the 76 patients. SIGNIFICANCE: Neural autoantibodies are a rare finding in perioperatively collected serum and CSF of our cohort of mostly MRI-lesional epilepsy surgery patients. Confirmatory testing is essential to avoid overinterpretation of autoantibody-positive findings.

• Klíčová slova
• CSF, GAD65, epilepsy, epilepsy surgery, neural antibodies,
• MeSH
• autoprotilátky MeSH
• epilepsie * epidemiologie   chirurgie   komplikace   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• malformace mozkové kůry * komplikace   MeSH
• prevalence MeSH
• prospektivní studie MeSH
• refrakterní epilepsie * diagnostické zobrazování   chirurgie   komplikace   MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• autoprotilátky MeSH

BACKGROUND AND OBJECTIVES: Autoimmune encephalitis (AE) refers to a heterogenous group of inflammatory CNS diseases. Subgroups with specified neural autoantibodies are more homogeneous in presentation, trigger factors, outcome, and response to therapy. However, a considerable fraction of patients has AE features but does not harbor detectable autoantibodies and is referred to as antibody-negative AE. Our aim was to describe clinical features, trigger factors, treatments, and outcome of a cohort of comprehensively tested antibody-negative AE patients. METHODS: This retrospective monocentric study recruited adult patients whose serum and/or CSF was sent to our tertiary center for neural antibody testing between 2011 and 2020, who entered the diagnostic algorithm as possible antibody-negative AE and had the following: (1) probable antibody-negative AE, definite antibody-negative acute disseminated encephalomyelitis (ADEM), or definite autoimmune limbic encephalitis (LE) according to diagnostic criteria; (2) available data on MRI of the brain, CSF, and EEG; and (3) stored serum and/or CSF samples. These samples were reanalyzed using a comprehensive combination of cell-based and tissue-based assays. RESULTS: Of 2,250 patients tested, 33 (1.5%) were classified as possible antibody-negative AE. Of these, 5 were found to have antibodies by comprehensive testing, 5 fulfilled the criteria of probable AE (3F:2M, median age 67, range 42-67), 4 of definite autoimmune LE (2F:2M, median age 45.5, range 27-60 years), one of definite antibody-negative ADEM, 2 of Hashimoto encephalopathy, one had no samples available for additional testing, and 15 had no further categorization. Of 10 probable/definite AE/LE/ADEM, one had a malignancy and none of them received an alternative diagnosis until the end of follow-up (median 18 months). In total, 80% (8/10) of patients received immunotherapy including corticosteroids, and 6/10 (60%) patients received rituximab, azathioprine, cyclophosphamide, plasma exchange, or IV immunoglobulins. Five (50%) patients improved, one (10%) stabilized, one (10%) worsened, and 3 (30%) died. All deaths were considered to be related to encephalitis. We did not observe differences of immunotherapy-treated patients in likelihood of improvement with or without nonsteroidal immunotherapy (with 2/6, without 1/2). DISCUSSION: Antibody-negative AE should be diagnosed only after comprehensive testing. Diagnostic effort is important because many patients benefit from immunotherapy and some have malignancies.

• MeSH
• autoimunitní nemoci nervového systému * diagnóza   terapie   MeSH
• autoimunitní nemoci MeSH
• autoprotilátky MeSH
• dospělí MeSH
• encefalitida * diagnóza   terapie   MeSH
• Hashimotova nemoc MeSH
• lidé středního věku MeSH
• lidé MeSH
• limbická encefalitida MeSH
• nádory * MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• autoprotilátky MeSH

BACKGROUND AND PURPOSE: N-methyl-d-aspartate receptor (NMDAR) and leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis are important types of autoimmune encephalitis (AE) with significant morbidity. In this study, we used a proteomic approach in search of novel clinically relevant biomarkers in these types of encephalitides. METHODS: Swedish and Czech tertiary neuroimmunology centers collaborated in this retrospective exploratory study. Fifty-eight cerebrospinal fluid (CSF) samples of 28 patients with AE (14 definite NMDAR, 14 with definite LGI1 encephalitis) and 30 controls were included. CSF samples were analyzed using proximity extension assay technology (Olink Target 96 Inflammation panel). For each CSF sample, 92 proteins were measured. Clinical variables were retrospectively collected, and correlations with protein levels were statistically analyzed. RESULTS: Patients and controls differed significantly in the following 18 biomarkers: TNFRSF9, TNFRSF12, TNFRSF14, TNFβ, TNFα, IL7, IL10, IL12B, IFNγ, CD5, CD6, CASP8, MMP1, CXCL8, CXCL10, CXCL11, IL20RA, and sirtuin 2 (SIRT2). In LGI1 encephalitis, no clinically useful association was found between biomarkers and clinical variables. In the NMDAR encephalitis group, SIRT2, TNFβ, and CD5 were significantly associated with ovarian teratoma. For SIRT2, this was true even for the first patients' CSF sample (SIRT2 without vs. with tumor, mean ± SD = 2.2 ± 0.29 vs. 2.88 ± 0.48; p = 0.007, 95% confidence interval = -1.15 to -0.22; r statistic in point-biserial correlation (rpb) = 0.66, p = 0.011). SIRT2 was positively correlated with age (rpb = 0.39, p = 0.018) and total hospital days (r = 0.55, p = <0.001). CONCLUSIONS: SIRT2 should be investigated as a biomarker of paraneoplastic etiology in NMDAR encephalitis.

• Klíčová slova
• anti-N-methyl-d-aspartate receptor encephalitis, encephalitis, limbic encephalitis, paraneoplastic syndromes, sirtuin 2,
• MeSH
• autoprotilátky MeSH
• biologické markery mozkomíšní mok   MeSH
• encefalitida s protilátkami proti NMDA receptorům * mozkomíšní mok   MeSH
• encefalitida MeSH
• Hashimotova nemoc MeSH
• lidé MeSH
• novorozenec MeSH
• proteomika MeSH
• retrospektivní studie MeSH
• sirtuin 2 MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH
• biologické markery MeSH
• SIRT2 protein, human MeSH Prohlížeč
• sirtuin 2 MeSH

BACKGROUND: The possibility to better predict the severity of the disease in a patient newly diagnosed with multiple sclerosis would allow the treatment strategy to be personalized and lead to better clinical outcomes. Prognostic biomarkers are highly needed. OBJECTIVE: To assess the prognostic value of intrathecal IgM synthesis, cerebrospinal fluid and serum IL-2, IL-6, IL-10, chitinase 3-like 2 and neurofilament heavy chains obtained early after the onset of the disease. METHODS: 58 patients after the first manifestation of multiple sclerosis were included. After the initial diagnostic assessment including serum and cerebrospinal fluid biomarkers, all patients initiated therapy with either glatiramer acetate, teriflunomide, or interferon beta. To assess the evolution of the disease, we followed the patients clinically and with MRI for two years. RESULTS: The IL-2:IL-6 ratio (both in cerebrospinal fluid) <0.48 (p = 0.0028), IL-2 in cerebrospinal fluid ≥1.23pg/ml (p = 0.026), and chitinase 3-like 2 in cerebrospinal fluid ≥7900pg/ml (p = 0.033), as well as baseline EDSS ≥1.5 (p = 0.0481) and age <22 (p = 0.0312), proved to be independent markers associated with shorter relapse free intervals. CONCLUSION: The IL-2:IL-6 ratio, IL-2, and chitinase 3-like 2 (all in cerebrospinal fluid) might be of value as prognostic biomarkers in early phases of multiple sclerosis.

• MeSH
• biologické markery mozkomíšní mok   MeSH
• chitinasy metabolismus   MeSH
• chronická nemoc MeSH
• interleukin-2 metabolismus   MeSH
• interleukin-6 metabolismus   MeSH
• lidé MeSH
• recidiva MeSH
• roztroušená skleróza * mozkomíšní mok   diagnóza   farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• CHI3L2 protein, human MeSH Prohlížeč
• chitinasy MeSH
• IL2 protein, human MeSH Prohlížeč
• IL6 protein, human MeSH Prohlížeč
• interleukin-2 MeSH
• interleukin-6 MeSH

BACKGROUND AND OBJECTIVES: To investigate the genetic determinants of the most common type of antibody-mediated autoimmune encephalitis, anti-NMDA receptor (anti-NMDAR) encephalitis. METHODS: We performed a genome-wide association study in 178 patients with anti-NMDAR encephalitis and 590 healthy controls, followed by a colocalization analysis to identify putatively causal genes. RESULTS: We identified 2 independent risk loci harboring genome-wide significant variants (p < 5 × 10-8, OR ≥ 2.2), 1 on chromosome 15, harboring only the LRRK1 gene, and 1 on chromosome 11 centered on the ACP2 and NR1H3 genes in a larger region of high linkage disequilibrium. Colocalization signals with expression quantitative trait loci for different brain regions and immune cell types suggested ACP2, NR1H3, MADD, DDB2, and C11orf49 as putatively causal genes. The best candidate genes in each region are LRRK1, encoding leucine-rich repeat kinase 1, a protein involved in B-cell development, and NR1H3 liver X receptor alpha, a transcription factor whose activation inhibits inflammatory processes. DISCUSSION: This study provides evidence for relevant genetic determinants of antibody-mediated autoimmune encephalitides outside the human leukocyte antigen (HLA) region. The results suggest that future studies with larger sample sizes will successfully identify additional genetic determinants and contribute to the elucidation of the pathomechanism.

• MeSH
• celogenomová asociační studie * MeSH
• dospělí MeSH
• encefalitida s protilátkami proti NMDA receptorům genetika   MeSH
• genetické lokusy MeSH
• lidé MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

OBJECTIVE: Diagnosing autoimmune encephalitis (AIE) is difficult in patients with less fulminant diseases such as epilepsy. However, recognition is important, as patients require immunotherapy. This study aims to identify antibodies in patients with focal epilepsy of unknown etiology, and to create a score to preselect patients requiring testing. METHODS: In this prospective, multicenter cohort study, adults with focal epilepsy of unknown etiology, without recognized AIE, were included, between December 2014 and December 2017, and followed for 1 year. Serum, and if available cerebrospinal fluid, were analyzed using different laboratory techniques. The ACES score was created using factors favoring an autoimmune etiology of seizures (AES), as determined by multivariate logistic regression. The model was externally validated and evaluated using the Concordance (C) statistic. RESULTS: We included 582 patients, with median epilepsy duration of 8 years (interquartile range = 2-18). Twenty patients (3.4%) had AES, of whom 3 had anti-leucine-rich glioma inactivated 1, 3 had anti-contactin-associated protein-like 2, 1 had anti-N-methyl-D-aspartate receptor, and 13 had anti-glutamic acid decarboxylase 65 (enzyme-linked immunosorbent assay concentrations >10,000IU/ml). Risk factors for AES were temporal magnetic resonance imaging hyperintensities (odds ratio [OR] = 255.3, 95% confidence interval [CI] = 19.6-3332.2, p < 0.0001), autoimmune diseases (OR = 13.31, 95% CI = 3.1-56.6, p = 0.0005), behavioral changes (OR 12.3, 95% CI = 3.2-49.9, p = 0.0003), autonomic symptoms (OR = 13.3, 95% CI = 3.1-56.6, p = 0.0005), cognitive symptoms (OR = 30.6, 95% CI = 2.4-382.7, p = 0.009), and speech problems (OR = 9.6, 95% CI = 2.0-46.7, p = 0.005). The internally validated C statistic was 0.95, and 0.92 in the validation cohort (n = 128). Assigning each factor 1 point, an antibodies contributing to focal epilepsy signs and symptoms (ACES) score ≥ 2 had a sensitivity of 100% to detect AES, and a specificity of 84.9%. INTERPRETATION: Specific signs point toward AES in focal epilepsy of unknown etiology. The ACES score (cutoff ≥ 2) is useful to select patients requiring antibody testing. ANN NEUROL 2021;89:698-710.

• MeSH
• autoimunitní nemoci diagnostické zobrazování   imunologie   psychologie   MeSH
• autoprotilátky analýza   MeSH
• chování MeSH
• dospělí MeSH
• elektroencefalografie MeSH
• epilepsie parciální diagnostické zobrazování   imunologie   psychologie   MeSH
• glutamát dekarboxyláza genetika   imunologie   MeSH
• kognitivní poruchy etiologie   psychologie   MeSH
• kohortové studie MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• záchvaty diagnostické zobrazování   etiologie   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Nizozemsko MeSH
• Názvy látek
• autoprotilátky MeSH
• glutamát dekarboxyláza MeSH
• glutamate decarboxylase 2 MeSH Prohlížeč

Alemtuzumab as a treatment of highly active multiple sclerosis causes a rapid decrease in inflammatory activity due the lysis of immune cells. Subsequent cytokine release determines the infusion-associated reaction that is a frequent adverse event of alemtuzumab treatment. Recently, serious cardiovascular and thrombotic adverse reactions following alemtuzumab infusion have been described. In our study, the dynamics of coagulation parameters were analyzed in 13 multiple sclerosis patients treated with alemtuzumab. An immediate, significant increase in the level of D-dimer was observed after the first administration of alemtuzumab. This observation provides evidence of coagulation activation and the potential risk of thrombotic complications with this therapy. Prophylactic low molecular weight heparin pretreatment maybe considered in patients receiving alemtuzumab.

• Klíčová slova
• Alemtuzumab, D-dimer, coagulation, multiple sclerosis,
• MeSH
• alemtuzumab MeSH
• fibrin-fibrinogen - produkty degradace MeSH
• lidé MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   MeSH
• roztroušená skleróza * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alemtuzumab MeSH
• fibrin fragment D MeSH Prohlížeč
• fibrin-fibrinogen - produkty degradace MeSH