BACKGROUND: Rituximab (RTX) and ocrelizumab (OCR), B cell-depleting therapy targeting CD20 molecules, affect the humoral immune response after vaccination. How these therapies influence T-cell-mediated immune response against SARS-CoV-2 after immunization remains unclear. We aimed to evaluate the humoral and cellular immune response to the COVID-19 vaccine in a cohort of patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myasthenia gravis (MG). METHODS: Patients with MS (83), NMOSD (19), or MG (7) undergoing RTX (n=47) or OCR (n=62) treatment were vaccinated twice with the mRNA BNT162b2 vaccine. Antibodies were quantified using the SARS-CoV-2 IgG chemiluminescence immunoassay, targeting the spike protein. SARS-CoV-2-specific T cell responses were quantified by interferon γ release assays (IGRA). The responses were evaluated at two different time points (4-8 weeks and 16-20 weeks following the 2nd dose of the vaccine). Immunocompetent vaccinated individuals (n=41) were included as controls. RESULTS: Almost all immunocompetent controls developed antibodies against the SARS-CoV-2 trimeric spike protein, but only 34.09% of the patients, without a COVID-19 history and undergoing anti-CD20 treatment (via RTX or OCR), seroconverted. This antibody response was higher in patients with intervals of longer than 3 weeks between vaccinations. The duration of therapy was significantly shorter in seroconverted patients (median 24 months), than in the non-seroconverted group. There was no correlation between circulating B cells and the levels of antibodies. Even patients with a low proportion of circulating CD19+ B cells (<1%, 71 patients) had detectable SARS-CoV-2 specific antibody responses. SARS-CoV-2 specific T cell response measured by released interferon γ was detected in 94.39% of the patients, independently of a humoral immune response. CONCLUSION: The majority of MS, MG, and NMOSD patients developed a SARS-CoV-2-specific T cell response. The data suggest that vaccination can induce SARS-CoV-2-specific antibodies in a portion of anti-CD20 treated patients. The seroconversion rate was higher in OCR-treated patients compared to those on RTX. The response represented by levels of antibodies was better in individuals, with intervals of longer than 3 weeks between vaccinations.
- MeSH
- autoimunitní nemoci nervového systému * MeSH
- COVID-19 * MeSH
- glykoprotein S, koronavirus MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- lidé MeSH
- myasthenia gravis * MeSH
- protilátky virové MeSH
- rituximab terapeutické užití MeSH
- roztroušená skleróza * farmakoterapie MeSH
- SARS-CoV-2 MeSH
- vakcína BNT162 MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- COVID-19 * MeSH
- lidé MeSH
- myasthenia gravis * komplikace MeSH
- SARS-CoV-2 MeSH
- thymektomie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- komentáře MeSH
BACKGROUND AND PURPOSE: Myasthenia gravis (MG) patients could be a vulnerable group in the pandemic era of coronavirus 2019 (COVID-19) mainly due to respiratory muscle weakness, older age and long-term immunosuppressive treatment. We aimed to define factors predicting the severity of COVID-19 in MG patients and risk of MG exacerbation during COVID-19. METHODS: We evaluated clinical features and outcomes after COVID-19 in 93 MG patients. RESULTS: Thirty-five patients (38%) had severe pneumonia and we recorded 10 deaths (11%) due to COVID-19. Higher forced vital capacity (FVC) values tested before COVID-19 were shown to be protective against severe infection (95% CI 0.934-0.98) as well as good control of MG measured by the quantified myasthenia gravis score (95% CI 1.047-1.232). Long-term chronic corticosteroid treatment worsened the course of COVID-19 in MG patients (95% CI 1.784-111.43) and this impact was positively associated with dosage (p = 0.005). Treatment using azathioprine (95% CI 0.448-2.935), mycophenolate mofetil (95% CI 0.91-12.515) and ciclosporin (95% CI 0.029-2.212) did not influence the course of COVID-19. MG patients treated with rituximab had a high risk of death caused by COVID-19 (95% CI 3.216-383.971). Exacerbation of MG during infection was relatively rare (15%) and was not caused by remdesivir, convalescent plasma or favipiravir (95% CI 0.885-10.87). CONCLUSIONS: As the most important predictors of severe COVID-19 in MG patients we identified unsatisfied condition of MG with lower FVC, previous long-term corticosteroid treatment especially in higher doses, older age, the presence of cancer, and recent rituximab treatment.
COVID-19 is a pandemic respiratory disease caused by the SARS-CoV-2 coronavirus. The worldwide epidemiologic data showed higher mortality in males compared to females, suggesting a hypothesis about the protective effect of estrogens against severe disease progression with the ultimate end being patient's death. This article summarizes the current knowledge regarding the potential effect of estrogens and other modulators of estrogen receptors on COVID-19. While estrogen receptor activation shows complex effects on the patient's organism, such as an influence on the cardiovascular/pulmonary/immune system which includes lower production of cytokines responsible for the cytokine storm, the receptor-independent effects directly inhibits viral replication. Furthermore, it inhibits the interaction of IL-6 with its receptor complex. Interestingly, in addition to natural hormones, phytestrogens and even synthetic molecules are able to interact with the estrogen receptor and exhibit some anti-COVID-19 activity. From this point of view, estrogen receptor modulators have the potential to be included in the anti-COVID-19 therapeutic arsenal.
- MeSH
- COVID-19 komplikace patologie virologie MeSH
- internalizace viru účinky léků MeSH
- lidé MeSH
- modulátory estrogenních receptorů metabolismus farmakologie terapeutické užití MeSH
- nádory prsu komplikace farmakoterapie patologie MeSH
- proteiny virové matrix antagonisté a inhibitory metabolismus MeSH
- receptory pro estrogeny chemie metabolismus MeSH
- replikace viru účinky léků MeSH
- SARS-CoV-2 účinky léků izolace a purifikace fyziologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Gerstmann-Sträussler-Scheinker syndrome (GSS) with the P102L mutation is a rare genetic prion disease caused by a pathogenic mutation at codon 102 in the prion protein gene. Cluster analysis encompassing data from 7 Czech patients and 87 published cases suggests the existence of 4 clinical phenotypes (typical GSS, GSS with areflexia and paresthesia, pure dementia GSS, and Creutzfeldt-Jakob disease-like GSS); GSS may be more common than previously estimated. In making a clinical diagnosis or progression estimates of GSS, magnetic resonance imaging and real-time quaking-induced conversion may be helpful, but the results should be evaluated with respect to the overall clinical context. ANN NEUROL 2019;86:643-652.
- MeSH
- dospělí MeSH
- fenotyp MeSH
- Gerstmannova-Strausslerova-Scheinkerova nemoc patologie patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cíl: Porucha chování v REM (rapid eye movement) spánku (REM sleep behavior disorder; RBD) je parasomnie charakterizovaná nepřítomností fyziologické atonie a chováním uskutečňování snu v REM spánku. Jako idiopatická RBD (iRBD) je RBD označena v nepřítomnosti jiné nemoci, která RBD obvykle vyvolává. Idiopatická RBD je známkou prodromální fáze synukleinopatie a má vysokou míru fenokonverze do neurodegenerativních nemocí ze skupiny synukleinopatií. Cílem této průřezové studie bylo zjistit stav čichové funkce u pacientů s iRBD a její vztah k jiným symptomům. Materiál a metody: Do studie bylo zahrnuto 54 pacientů s iRBD s mediánem věku 67 (IQR 63–72) let a 37 kontrolních subjektů s mediánem věku 67 (57,5–70,0) let, které byly spárovány podle věku a pohlaví. Všichni účastníci studie absolvovali komplexní vyšetření, které obsahovalo Identifikační čichový test Pensylvánské univerzity (University of Pennsylvania Identifaction Test; UPSIT). Výsledky: Úplnou ztrátu čichu anebo jeho těžkou dysfunkci mělo 62,9 % pacientů s iRBD, přitom u kontrolních subjektů to bylo pouze 8,1 %. Porucha atonie v REM spánku v polysomnografi i nepřímo korelovala se skóre UPSIT (p < 0,01). Závěr: Studie prokázala významně horší čich u pacientů s iRBD než u kontrolních osob.
Aim: Rapid eye movement (REM) sleep behaviour disorder (RBD) is a sleep abnormality heralded by the absence of physiological atonia in REM sleep and dream enactment behaviour. Idiopathic RBD (iRBD), diagnosed when no primary RBD cause can be identified, is a marker of prodromal synucleinopathy with a high conversion rate to overt neurodegenerative disorders from the synucleinopathy group. The aim of this cross-sectional study was to investigate olfactory function in iRBD patients and its relation to other symptoms. Patients and methods: This study included 54 iRBD patients with a median age of 67 (IQR 63–72) years; the 37 control subjects, matched by gender and age, had a median age of 67 (57.5–70.0) years. All subjects underwent a complex examination, which included olfactory testing using the University of Pennsylvania Smell Identification Test (UPSIT). Results: In total, 62.9% of iRBD patients had either total loss of olfactory function or severe hyposmia. In contrast, only 8.1% of controls showed such a degree of olfactory dysfunction. Furthermore, we found that the percentage of REM sleep without atonia on polysomnography negatively correlates with the UPSIT score (P < 0.01). Conclusion: This study demonstrated a significantly lower olfactory function in the iRBD group compared to controls.
- Klíčová slova
- fenokonverze,
- MeSH
- klinická studie jako téma MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc patofyziologie MeSH
- porucha chování v REM spánku * MeSH
- poruchy čichu MeSH
- senioři MeSH
- synukleinopatie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
Neuropathological diagnostic criteria of neurodegenerative disorders are based on the presence of specific inclusions in a specific area of brain tissue that correlate with clinical manifestations. Concomitant neurodegenerative disorders correspond to a combination of two (or more) different fully developed diseases in the same patient. Concomitant neurodegenerative pathology represents the presence of definite neurodegeneration and deposits of pathological proteins specific for another disease, which is not, however, fully developed. Very frequent overlaps include Alzheimer's disease and alpha-synuclein inclusions. Nevertheless, careful neuropathological investigations reveal an increasing frequency of different co-pathologies in examined brains. In Alzheimer's disease, protein TDP-43 may co-aggregate, but it is not clear whether this is atypical isolated Alzheimer's disease or overlap of Alzheimer's disease with early frontotemporal lobar degeneration. Comorbidities of Alzheimer's disease and tauopathies are relatively rare. A combination of vascular pathology with primary neurodegeneration (mostly Alzheimer's disease or dementia with Lewy bodies) is historically called mixed dementia. Overlap of different neuropathologically confirmed neurodegenerations could lead to atypical and unusual clinical presentations and may be responsible for faster disease progression. Several CSF biomarkers have been evaluated for their utility in diagnostic processes in different neurodegenerative dementias; however, evidence regarding their role in neurodegenerative overlaps is still limited.
- MeSH
- alfa-synuklein metabolismus MeSH
- Alzheimerova nemoc metabolismus patologie MeSH
- biologické markery metabolismus MeSH
- demence s Lewyho tělísky metabolismus patologie MeSH
- DNA vazebné proteiny metabolismus MeSH
- lidé MeSH
- patologická konformace proteinů metabolismus patologie MeSH
- proteiny tau metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: We aimed to produce a detailed neuropathological analysis of pyramidal motor system pathology and provide its clinical pathological correlation in cases with definite progressive supranuclear palsy (PSP). METHODS: Pyramidal motor system pathologies were analyzed in 18 cases with neuropathologically confirmed PSP. Based on a retrospective clinical analysis, cases were subtyped according to Movement Disorder Society criteria for clinical diagnosis of PSP as probable, possible or suggestive of PSP with Richardson's syndrome (n = 10), PSP with predominant corticobasal syndrome (n = 3), PSP with predominant parkinsonism (n = 3), PSP with predominant speech/language disorder (n = 1), and PSP with progressive gait freezing (n = 1). Clinical manifestations of motor neuron involvement (pseudobulbar or bulbar signs and spasticity) were retrospectively assessed semiquantitatively. Neuropathologically, hyperphosphorylated tau-related pyramidal motor system neuronal, neuritic, and glial pathology using anti-tau AT8 clone immunohistochemistry, was also evaluated. RESULTS: Clinical manifestations of pyramidal motor system involvement were found in patients with different PSP subtypes. A statistically significant higher load of tau pathology was found in the pyramidal system in PSP-Richardson's syndrome compared to other PSP subtypes (p = 0.016); however, there was no significant correlation between pyramidal system tau pathology and related motor clinical symptoms. CONCLUSIONS: Tau pathology in the spinal cord and pyramidal motor system structures is very common in progressive supranuclear palsy and may neuropathologically supplement the distinction between classic Richardson's syndrome from other progressive supranuclear palsy subtypes.
- MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozková kůra patologie MeSH
- parkinsonské poruchy diagnóza patologie MeSH
- pohybové poruchy diagnóza patologie MeSH
- progresivní supranukleární obrna diagnóza patologie MeSH
- proteiny tau metabolismus MeSH
- pyramidové dráhy patologie MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- dynamika vysychání, FTIR,
- MeSH
- antimikrobiální peptidy MeSH
- cirkulární dichroismus metody využití MeSH
- dehydratace MeSH
- kationické antimikrobiální peptidy * MeSH
- lidé MeSH
- liposomy aplikace a dávkování MeSH
- permeabilita buněčné membrány * fyziologie MeSH
- prospektivní studie MeSH
- spektroskopie infračervená s Fourierovou transformací metody využití MeSH
- struktury buněčné membrány klasifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- grafy a diagramy MeSH
