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
• imatinib mesylát škodlivé účinky   MeSH
• inhibitory tyrosinkinasy škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myasthenia gravis * chemicky indukované   diagnóza   terapie   MeSH
• nežádoucí účinky léčiv terapie   MeSH
• nivolumab škodlivé účinky   MeSH
• protinádorové látky škodlivé účinky   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• autoimunitní nemoci chemicky indukované   diagnóza   farmakoterapie   MeSH
• lidé MeSH
• nekróza * chemicky indukované   diagnóza   farmakoterapie   MeSH
• nemoci svalů * chemicky indukované   diagnóza   farmakoterapie   MeSH
• nežádoucí účinky léčiv MeSH
• rosuvastatin kalcium škodlivé účinky   MeSH
• senioři MeSH
• statiny škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Huntington ́s disease (HD) is a progressive neurodegenerative disease with onset in adulthood that leads to a complete disability and death in approximately 20 years after onset of symptoms. HD is caused by an expansion of a CAG triplet in the gene for huntingtin. Although the disease causes most damage to striatal neurons, other parts of the nervous system and many peripheral tissues are also markedly affected. Besides huntingtin malfunction, mitochondrial impairment has been previously described as an important player in HD. This study focuses on mitochondrial structure and function in cultivated skin fibroblasts from 10 HD patients to demonstrate mitochondrial impairment in extra-neuronal tissue. Mitochondrial structure, mitochondrial fission, and cristae organization were significantly disrupted and signs of elevated apoptosis were found. In accordance with structural changes, we also found indicators of functional alteration of mitochondria. Mitochondrial disturbances presented in fibroblasts from HD patients confirm that the energy metabolism damage in HD is not localized only to the central nervous system, but also may play role in the pathogenesis of HD in peripheral tissues. Skin fibroblasts can thus serve as a suitable cellular model to make insight into HD pathobiochemical processes and for the identification of possible targets for new therapies.

• MeSH
• dospělí MeSH
• fibroblasty metabolismus   MeSH
• Huntingtonova nemoc * genetika   metabolismus   patologie   MeSH
• lidé MeSH
• mitochondrie patologie   MeSH
• neurodegenerativní nemoci * metabolismus   patologie   MeSH
• neurony patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články 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.

• MeSH
• COVID-19 * terapie   MeSH
• koronavirové infekce * MeSH
• lidé MeSH
• myasthenia gravis * komplikace   farmakoterapie   epidemiologie   MeSH
• pasivní imunizace MeSH
• SARS-CoV-2 MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: From 2012 to 2013, there was a mass methanol poisoning outbreak in the Czech Republic. Methanol metabolites can cause specific lesions in the basal ganglia, subcortical white matter, and optic nerve. However, long-term sequelae of methanol poisoning on cognitive functioning have not yet been explored. The current study aimed to delineate the cognitive changes observed in methanol poisoning survivors in the seven years since 2012. METHODS: We conducted longitudinal research with repeated measurements in 2013, 2015, 2017 and 2019 to evaluate the development of cognitive changes after acute methanol poisoning. A complex neuropsychological battery consisted of tests of global cognitive performance, auditory and visual attention, executive functioning, learning and memory, working memory and language. Motor performance measures and depression scale were also included. RESULTS: Repeated measures ANOVA of four measurements with post-hoc tests showed a significant decline in the Mini-Mental State Examination (p = 0.007); however, other parameters were not significantly decreasing. In comparison to normative values, the z-scores for each test measure, in the memory domain, in particular, ranged from 43 to 60 % of participants below 1.5 SD. Mild to severe depression levels from the onset of poisoning improved during the seven years, returning to normal in up to 27 % of participants. CONCLUSION: In the longitudinal perspective, methanol poisoning survivors manifest progressive global cognitive decline and overall persistent below-average cognitive performance with some improvements in the frequency of depressive symptoms.

• MeSH
• časové faktory MeSH
• deprese chemicky indukované   diagnóza   epidemiologie   psychologie   MeSH
• dospělí MeSH
• epizodická paměť * MeSH
• kognice účinky léků   MeSH
• kognitivní dysfunkce chemicky indukované   diagnóza   epidemiologie   psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• methanol otrava   MeSH
• mladý dospělý MeSH
• neuropsychologické testy MeSH
• neurotoxické syndromy diagnóza   epidemiologie   psychologie   MeSH
• poruchy paměti chemicky indukované   diagnóza   epidemiologie   psychologie   MeSH
• prevalence MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Acute methanol poisoning leads to optic neuropathy and necrotic lesions of basal ganglia (BG) and subcortical white matter. Survivors of methanol poisoning exhibit long-term executive and memory deficits. Associations between brain volumetry parameters and cognitive sequelae of methanol poisoning are not known. The aim of our study was to identify long-term associations between the cognitive performance of survivors of methanol poisoning and the volume of the brain structures that are selectively vulnerable to methanol. METHODS: We conducted a cross-sectional follow-up study on a sample of patients (n = 33, age 50 ± 14 years, 82% males) who survived acute methanol poisoning during methanol mass poisoning outbreak from September 2012 till January 2013 in the Czech Republic. A battery of neuropsychological tests and brain magnetic resonance imaging were included in the clinical examination protocol. Specific brain structures (putamen, globus pallidus, nucleus caudatus, and frontal white matter) were selected as regions of interest, and their volumes were estimated using the MorphoBox prototype software. RESULTS: In robust multiple regression models, sustained visual attention performance (as assessed by Trail Making Test and Prague Stroop Test) was positively associated with BG structures and frontal white matter volumes (Wald = 9.03 to 85.50, p < 0.01), sensitivity to interference (as assessed by Frontal Battery Assessment) was negatively associated with frontal white matter volume (Wald = 35.44 to 42.25, p < 0.001), and motor performance (as assessed by Finger Tapping Test) was positively associated with globus pallidus and frontal white matter volumes (Wald = 9.66 to 13.29, p < 0.01). CONCLUSIONS: Our results demonstrate that smaller volumes of elements of BG-thalamocortical circuitry, namely the BG and frontal white matter, relate to attention and motor performance in methanol poisoning from a long-term perspective. Disruption of those functional circuits may underlie specific cognitive deficits observed in methanol poisoning.

• MeSH
• bazální ganglia diagnostické zobrazování   MeSH
• bílá hmota diagnostické zobrazování   MeSH
• dospělí MeSH
• exekutivní funkce účinky léků   MeSH
• kognice účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• methanol otrava   MeSH
• mozek diagnostické zobrazování   MeSH
• následné studie MeSH
• nervová síť diagnostické zobrazování   MeSH
• neuropsychologické testy MeSH
• paměť účinky léků   MeSH
• pozornost účinky léků   MeSH
• přežívající MeSH
• průřezové studie MeSH
• psychomotorický výkon účinky léků   MeSH
• senioři MeSH
• učení účinky léků   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
• přehledy MeSH

Neurological sequelae including gait impairment were reported in survivors after methanol intoxication; however, no systematic study has been published so far. We aimed to analyse gait and balance impairment in a group of Czech methanol poisoning survivors. We examined 43 patients (age 46 ± 13 years) 2-8 months after methanol poisoning and 43 healthy controls. Investigations contained a shortened version of Falls Efficacy Scale (FES), clinical tests of gait and balance including Timed Up and Go test (TUG) and gait analysis using GaitRite® system, neurological and neuropsychological examination, brain imaging, EMG and tests of alcohol consumption. Nineteen patients admitted balance and gait impairment according to FES. Mild to moderate parkinsonian signs showed seven patients. Patients were slower (8.8 versus 5.7 s, p < 0.001) and performed more steps (11.1 versus 7.9, p < 0.001) in TUG compared with the controls. Gait analysis revealed shorter step length (76.5 versus 88.7 cm, p < 0.001), increased double support phase (18.8 versus 15.5%, p < 0.001) and wider base of support (11.3 versus 9.6 cm, p = 0.006) in patients. Eleven patients had deficit of executive function and performed higher cadence compared to the patients with normal execution (122.7 versus 115.0 step/min., p = 0.025). Lower limb polyneuropathy was verified in nine patients, without relation with gait or balance parameters. Neuroimaging revealed lesions mainly in the basal ganglia. Methanol poisoning survivors presented slower wide-based gait with shortened steps corresponding with frontal gait disorder. Higher stepping cadence associated with executive deficit supported the evidence of frontal lobe dysfunction related to impairment of basal ganglia and connections in frontal cortico-basal ganglia loops.

• MeSH
• chůze (způsob) účinky léků   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• methanol otrava   MeSH
• mozek diagnostické zobrazování   účinky léků   MeSH
• nemoci nervového systému chemicky indukované   diagnóza   epidemiologie   MeSH
• neurozobrazování metody   MeSH
• posturální rovnováha účinky léků   MeSH
• přežívající statistika a číselné údaje   MeSH
• rozpouštědla otrava   MeSH
• senioři MeSH
• test chůzí MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

• Klíčová slova
• polština, čeština,

• Konspekt
• Lingvistika. Jazyky
• NLK Obory
• lingvistika
• NLK Publikační typ
• slovníky