BACKGROUND: Immune-mediated mechanisms substantially contribute to the Rasmussen encephalitis (RE) pathology, but for unknown reasons, immunotherapy is generally ineffective in patients who have already developed intractable epilepsy; overall laboratory data regarding the effect of immunotherapy on patients with RE are limited. We analyzed multiple samples from seven differently treated children with RE and evaluated the effects of immunotherapies on neuroinflammation. Immunotherapy was introduced to all patients at the time of intractable epilepsy and they all had to undergo hemispherothomy. METHODS: Immunohistochemistry, flow cytometry, Luminex multiplex bead and enzyme-linked immunosorbent assay techniques were combined to determine: 1) inflammatory changes and lymphocyte subpopulations in 45 brain tissues; 2) lymphocyte subpopulations and the levels of 12 chemokines/cytokines in 24 cerebrospinal fluid (CSF) samples and 30 blood samples; and 3) the dynamics of these parameters in four RE patients from whom multiple samples were collected. RESULTS: Sustained T cell-targeted therapy with cyclophosphamide, natalizumab, alemtuzumab, and intrathecal methotrexate (ITMTX), but not with azathioprine, substantially reduced inflammation in brain tissues. Despite the therapy, the distributions of CD8+ T cells and the levels of C-X-C motif ligand (CXCL) 10, CXCL13, and B cell activating factor (BAFF) in patients' CSF remained increased compared to controls. A therapeutic approach combining alemtuzumab and ITMTX was the most effective in producing simultaneous reductions in histopathological inflammatory findings and in the numbers of activated CD8+ T cells in the brain tissue, as well as in the overall CD8+ T cell population and chemokine/cytokine production in the CSF. CONCLUSIONS: We provide evidence that various T cell-targeted immunotherapies reduced inflammation in the brains of RE patients. The observation that intractable epilepsy persisted in all of the patients suggests a relative independence of seizure activity on the presence of T cells in the brain later in the disease course. Thus, new therapeutic targets must be identified. CXCL10, CXCL13 and BAFF levels were substantially increased in CSF from all patients and their significance in RE pathology remains to be addressed.

• MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• cytokiny imunologie   MeSH
• dítě MeSH
• ELISA MeSH
• encefalitida patologie   terapie   MeSH
• imunoterapie metody   MeSH
• lidé MeSH
• mozek patologie   MeSH
• předškolní dítě MeSH
• zánět terapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The recognition of active inflammation in the central nervous system (CNS) in the absence of infectious agents is challenging. The present study aimed to determine the diagnostic relevance of five selected chemo/cytokines in the recognition of CNS inflammation and in the context of traditional cerebrospinal fluid (CSF) biomarkers (white blood cell [WBC] counts, oligoclonal bands, protein levels, CSF/serum albumin ratios) and clinical diagnoses. METHODS: C-C and C-X-C motif ligands (CCL2, CXCL8, 10 and 13) and interleukin (IL) 6 levels in the CSF and serum from 37 control and 87 symptomatic children with ten different (mostly noninfectious) inflammatory CNS disorders (16 of which had follow-up samples after recovery) were determined using Luminex multiple bead technology and software. Nonparametric tests were used; p < 0.05 was considered statistically significant. Receiver operating characteristic curves were constructed to analyze controls and 1) all symptomatic samples or 2) symptomatic samples without CSF pleocytosis. RESULTS: Compared with the control CSF samples, levels of all investigated chemo/cytokines were increased in symptomatic CSF samples, and only IL-6 remained elevated in recovery samples (p ≤ 0.001). CSF CXCL-13 levels (> 10.9 pg/mL) were the best individual discriminatory criterion to differentiate neuroinflammation (specificity/sensitivity: 97/72% and 97/61% for samples without pleocytosis), followed by CSF WBC counts (specificity/sensitivity: 97/62%). The clinical utility of the remaining CSF chemo/cytokine levels was determined in descending order of sensitivities corresponding to thresholds that ensured 97% specificity for neuroinflammation in samples without pleocytosis (pg/mL; sensitivity %): IL-6 (3.8; 34), CXCL8 (32; 26), CXCL10 (317; 24) and CCL2 (387; 10). Different diagnosis-related patterns of CSF chemo/cytokines were observed. CONCLUSIONS: The increased CSF level of CXCL13 was the marker with the greatest predictive utility for the general recognition of neuroinflammation among all of the individually investigated biomarkers. The potential clinical utility of chemo/cytokines in the differential diagnosis of neuroinflammatory diseases was identified.

• MeSH
• biologické markery krev   mozkomíšní mok   MeSH
• chemokin CCL2 krev   mozkomíšní mok   MeSH
• chemokin CXCL10 krev   mozkomíšní mok   MeSH
• chemokin CXCL13 krev   mozkomíšní mok   MeSH
• chemokiny krev   mozkomíšní mok   MeSH
• dítě MeSH
• interleukin-6 krev   mozkomíšní mok   MeSH
• interleukin-8 krev   mozkomíšní mok   MeSH
• krevní obraz MeSH
• lidé MeSH
• mladiství MeSH
• nemoci centrálního nervového systému mozkomíšní mok   diagnóza   imunologie   MeSH
• předškolní dítě MeSH
• ROC křivka MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cíl: Naše práce upozorňuje na současnou problematiku akutní myelitidy u dětí a sdílí naše klinické zkušenosti. Soubor a metodika: 20 pacientů (10 chlapců a 10 dívek; věk 4–17 let, medián 14 let; doba sledování 1–73 měsíců, medián 15 měsíců) s akutním míšním syndromem, bez encefalopatie a po vyloučení míšní komprese, u kterých byla zvažována zánětlivá etiologie. Analýza klinických dat a paraklinických vyšetření (MR mozku a míchy, likvor, mikrobiologický a imunologický skríning, protilátky proti akvaporinu 4 v séru). Hodnotili jsme: klinický průběh, odpověď na akutní terapii a výslednou diagnózu; zda byla naplněna diagnostická kritéria pro klinicky izolovaný syndrom (clinically isolated syndrome; CIS), RS nebo onemocnění ze spektra neuromyelitis optica (neuromyelitis optica spectrum disorders; NMOSD). Výsledky: Jeden pacient měl myelitidu boreliové etiologie. Akutní myelitida byla projevem/součástí CIS/RS u osmi a NMOSD u tří pacientů. Idiopatická myelitida byla u osmi dětí. Pacienti s CIS/RS měli oproti pacientům s NMOSD rozdílné klinické i laboratorní projevy a odpověď na akutní terapii. Nejzávažnější byli pacienti s idiopatickou myelitidou, u kterých došlo k rychlému rozvoji neurologických příznaků s rozsáhlým nálezem na MR míchy. Odpověď na kortikoterapii byla u této skupiny nedostatečná, někteří profitovali z kombinované imunosuprese. Závěr: Akutní myelitida je komplikovaná diagnóza vyžadující komplexní přístup a klinické zkušenosti.

Aim: In this study, we focused on the current issue of pediatric myelitis and shared our clinical experience. Patients and methods: 20 patients (10 girls, 10 boys; age 4–17 years, median 14 years; follow-up period 1–73 months, median 15 months) with acute spinal syndrome and without encephalopathy; acute spinal compression was excluded and inflammatory etiology was considered. Analysis of clinical and para-clinical data (magnetic resonance imaging [MRI] of the brain and spinal cord, cerebrospinal fluid examination, microbiological and immunological testing, serum aquaporin 4 antibodies). We evaluated the clinical course, response to acute therapy and the final diagnosis; whether the current international diagnostic criteria were fulfilled for clinically isolated syndrome (CIS), pediatric multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD). Results: One patient had infectious Borrelia-related myelitis. Acute myelitis as a symptom of CIS/MS was in eight cases and as a symptom of NMOSD in three cases. Idiopathic myelitis was diagnosed in eight children. CIS/MS patients in comparison to NMOSD patients had different clinical courses, laboratory findings and responses to acute therapy. The most serious were patients with idiopathic myelitis – with rapid progression of spinal symptoms and extensive spinal lesions detected using MRI of spinal cord. They had poor response to corticotherapy. Some of these patients were successfully treated with combined immunosuppression. Conclusions: Acute myelitis is a complicated diagnosis, which requires a comprehensive approach and clinical experience.

• MeSH
• akutní nemoc MeSH
• algoritmy MeSH
• antibakteriální látky terapeutické užití   MeSH
• Borrelia burgdorferi izolace a purifikace   MeSH
• demyelinizační autoimunitní nemoci CNS * diagnóza   etiologie   farmakoterapie   MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• imunologické testy MeSH
• infekce bakteriemi rodu Borrelia * diagnóza   farmakoterapie   MeSH
• intravenózní imunoglobuliny terapeutické užití   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mícha diagnostické zobrazování   imunologie   patologie   MeSH
• mikrobiologické techniky MeSH
• mladiství MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• myelitida * diagnóza   etiologie   farmakoterapie   MeSH
• neuromyelitis optica diagnóza   farmakoterapie   MeSH
• plazmaferéza MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• roztroušená skleróza diagnostické zobrazování   diagnóza   farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system (CNS). Its immunopathogenesis has been proposed to include early cerebrospinal fluid (CSF) lymphocytosis, subsequent CNS disease restriction and B cell mechanism predominance. There are limited data regarding T cell involvement in the disease. To contribute to the current knowledge, we investigated the complex system of chemokines and cytokines related to B and T cell functions in CSF and sera samples from anti-NMDAR encephalitis patients at different time-points of the disease. One patient in our study group had a long-persisting coma and underwent extraordinary immunosuppressive therapy. METHODS: Twenty-seven paired CSF/serum samples were collected from nine patients during the follow-up period (median 12 months, range 1-26 months). The patient samples were stratified into three periods after the onset of the first disease symptom and compared with the controls. Modified Rankin score (mRS) defined the clinical status. The concentrations of the chemokines (C-X-C motif ligand (CXCL)10, CXCL8 and C-C motif ligand 2 (CCL2)) and the cytokines (interferon (IFN)γ, interleukin (IL)4, IL7, IL15, IL17A and tumour necrosis factor (TNF)α) were measured with Luminex multiple bead technology. The B cell-activating factor (BAFF) and CXCL13 concentrations were determined via enzyme-linked immunosorbent assay. We correlated the disease period with the mRS, pleocytosis and the levels of all of the investigated chemokines and cytokines. Non-parametric tests were used, a P value <0.05 was considered to be significant. RESULTS: The increased CXCL10 and CXCL13 CSF levels accompanied early-stage disease progression and pleocytosis. The CSF CXCL10 and CXCL13 levels were the highest in the most complicated patient. The CSF BAFF levels remained unchanged through the periods. In contrast, the CSF levels of T cell-related cytokines (INFγ, TNFα and IL17A) and IL15 were slightly increased at all of the periods examined. No dynamic changes in chemokine and cytokine levels were observed in the peripheral blood. CONCLUSIONS: Our data support the hypothesis that anti-NMDAR encephalitis is restricted to the CNS and that chemoattraction of immune cells dominates at its early stage. Furthermore, our findings raise the question of whether T cells are involved in this disease.

• MeSH
• B-lymfocyty metabolismus   MeSH
• chemokin CXCL10 MeSH
• chemokin CXCL13 MeSH
• chemokiny MeSH
• cytokiny MeSH
• dítě MeSH
• dospělí MeSH
• encefalitida s protilátkami proti NMDA receptorům terapie   MeSH
• faktor aktivující B-buňky MeSH
• imunoterapie MeSH
• kóma etiologie   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• progrese nemoci MeSH
• steroidy terapeutické užití   MeSH
• T-lymfocyty metabolismus   MeSH
• výměna plazmy MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH