AIM OF STUDY: To determine whether a high dose of levodopa-carbidopa intestinal gel (LCIG), expressed as levodopa equivalent daily dose (LE daily dose), is a risk factor for acute polyneuropathy in patients treated with LCIG. CLINICAL RATIONALE FOR STUDY: Treatment with LCIG is an effective device-assisted therapy in the advanced stages of Parkinson's Disease (PD). Polyneuropathy is a well-known complication of PD treatment. Patients treated with oral levodopa usually suffer from sub-clinical or mild chronic sensory polyneuropathy. However, severe acute polyneuropathy occurs in patients treated with LCIG, which is causally related to the treatment and leads to its immediate discontinuation. The etiology is not yet clear, but some patients with acute polyneuropathy have been given high doses of LCIG. MATERIAL AND METHODS: A retrospective multicentre study of patients treated with LCIG was performed. Patients with acute polyneuropathy were subjected to a detailed analysis including statistical processing. RESULTS: Of 183 patients treated with LCIG in seven centres, six patients (five females, median age 63 years) developed acute polyneuropathy with LCIG discontinuation. The median (interquartile range) initial and final LE daily dose in patients with and without acute polyneuropathy was 3,015 (2,695-3,184) and 1,898 (1,484-2,167) mg, respectively. The final LE daily dose of 2,605 mg cut-off had 83% sensitivity and 93% specificity for the prediction of acute polyneuropathy. CONCLUSIONS AND CLINICAL IMPLICATIONS: The risk of acute polyneuropathy in LCIG-treated patients was associated with a daily LE dose of greater than 2,605 mg or with more than a 62% increase in the daily LE dose during LCIG treatment.

• MeSH
• antiparkinsonika * škodlivé účinky   aplikace a dávkování   MeSH
• fixní kombinace léků * MeSH
• gely * MeSH
• karbidopa * aplikace a dávkování   škodlivé účinky   MeSH
• levodopa * aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• Parkinsonova nemoc * farmakoterapie   MeSH
• polyneuropatie * chemicky indukované   farmakoterapie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

INTRODUCTION: Bradykinesia is an essential diagnostic criterion for Parkinson's disease (PD) but is frequently observed in many non-parkinsonian movement disorders, complicating differential diagnosis, particularly in disorders featuring tremors. The presence of bradykinetic features in the subset of dystonic tremors (DT), either "pure" dystonic tremors or tremors associated with dystonia, remains currently unexplored. The aim of the current study was to evaluate upper limb bradykinesia in DT patients, comparing them with healthy controls (HC) and patients with PD by observing repetitive finger tapping (FT). METHODS: The protocol consisted of two main parts. Initially, the kinematic recording of repetitive FT was performed using optical hand tracking system (Leap Motion Controller). The values of amplitude, amplitude decrement, frequency, frequency decrement, speed, acceleration and number of halts of FT were calculated. Subsequently, three independent movement disorder specialists from different movement disorders centres, blinded to the diagnosis, rated the presence of FT bradykinesia based on video recordings. RESULTS: Thirty-six subjects participated in the study (12 DT, 12 HC and 12 early-stage PD). Kinematic analysis revealed no significant difference in the selected parameters of FT bradykinesia between DT patients and HC. In comparisons between DT and PD patients, PD patients exhibited bigger amplitude decrement and slower FT performance. In the blinded clinical assessment, bradykinesia was rated, on average, as being present in 41.6% of DT patients, 27.7% of HC, and 91.7% of PD patients. While overall inter-rater agreement was moderate, weak agreement was noted within the DT group. DISCUSSION: Clinical ratings indicated signs of bradykinesia in almost half of DT patients. The objective kinematic analysis confirmed comparable parameters between DT and HC individuals, with more pronounced abnormalities in PD across various kinematic parameters. Interpretation of bradykinesia signs in tremor patients with DT should be approached cautiously and objective motion analysis might complement the diagnostic process and serve as a decision support system in the choice of clinical entities.

• Publikační typ
• časopisecké články MeSH

• MeSH
• dospělí MeSH
• dystonie * genetika   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitochondriální nemoci * genetika   diagnóza   MeSH
• mladiství MeSH
• mutace MeSH
• pohybové poruchy genetika   diagnóza   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH

BACKGROUND: Spinocerebellar ataxia 21 (SCA21) is a rare neurological disorder caused by heterozygous variants in TMEM240. A growing, yet still limited number of reports suggested that hyperkinetic movements should be considered a defining component of the disease. CASE SERIES: We describe two newly identified families harboring the recurrent pathogenic TMEM240 p.Pro170Leu variant. Both index patients and the mother of the first proband developed movement disorders, manifesting as myoclonic dystonia and action-induced dystonia without co-occurring ataxia in one case, and pancerebellar syndrome complicated by action-induced dystonia in the other. We reviewed the literature on TMEM240 variants linked to hyperkinetic disorders, comparing our cases to described phenotypes. DISCUSSION: Adding to prior preliminary observations, our series highlights the relevance of hyperkinetic movements as clinically meaningful features of SCA21. TMEM240 mutation should be included in the differential diagnosis of myoclonic dystonia and ataxia-dystonia syndromes.

• MeSH
• ataxie MeSH
• dystonické poruchy * MeSH
• dystonie * diagnóza   genetika   MeSH
• hyperkineze MeSH
• lidé MeSH
• membránové proteiny MeSH
• myoklonus * diagnóza   genetika   MeSH
• spinocerebelární degenerace * MeSH
• syndrom MeSH
• vzácné nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• kazuistiky MeSH
• přehledy MeSH

Dysphagia is a common symptom of neurological disease, including multiple sclerosis (MS). The DYsphagia in MUltiple Sclerosis (DYMUS) questionnaire was developed as a screening tool for swallowing problems. The purpose of the present study was to validate the Czech version of the DYMUS questionnaire. We validated the questionnaire on a sample of 435 patients with MS and 135 healthy controls (HC) chosen by accidental sampling from larger, long-term studies conducted by the Prague MS Center. For the purposes of this study, we used both electronic (primary method of distribution) and paper-based (backup) versions of the questionnaire. The internal consistency of the whole scale was satisfactory (Cronbach's α =0.833). The DYMUS mean score in HC was 0.215 (standard deviation [SD] = 0.776). Normative data suggested a cut-off value for dysphagia between 1 and 2 points. Principal component analysis (PCA) showed a two-factor structure of the adapted scale. However, the structure did not completely correspond to the originally proposed dimensions of dysphagia for solids and liquids; our data supported dropout of item Q10. Criterion validity was proved by the difference in dysphagia between HC and patients MS (U = 25,546, p < 0.001) and by a positive correlation with the EDSS (Kendall's tau-b = 0.169, p < 0.001) and other patient-reported outcomes. The Czech version of the DYMUS questionnaire is a valid and reliable tool for evaluating swallowing impairment in Czech-speaking patients with MS. Moreover, the questionnaire can be administered electronically, with a paper-based backup.

• MeSH
• hodnocení výsledků péče pacientem MeSH
• lidé MeSH
• poruchy polykání * diagnóza   etiologie   MeSH
• průzkumy a dotazníky MeSH
• reprodukovatelnost výsledků MeSH
• roztroušená skleróza * komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

PURPOSE: ATP2B2 encodes the variant-constrained plasma-membrane calcium-transporting ATPase-2, expressed in sensory ear cells and specialized neurons. ATP2B2/Atp2b2 variants were previously linked to isolated hearing loss in patients and neurodevelopmental deficits with ataxia in mice. We aimed to establish the association between ATP2B2 and human neurological disorders. METHODS: Multinational case recruitment, scrutiny of trio-based genomics data, in silico analyses, and functional variant characterization were performed. RESULTS: We assembled 7 individuals harboring rare, predicted deleterious heterozygous ATP2B2 variants. The alleles comprised 5 missense substitutions that affected evolutionarily conserved sites and 2 frameshift variants in the penultimate exon. For 6 variants, a de novo status was confirmed. Unlike described patients with hearing loss, the individuals displayed a spectrum of neurological abnormalities, ranging from ataxia with dystonic features to complex neurodevelopmental manifestations with intellectual disability, autism, and seizures. Two cases with recurrent amino-acid variation showed distinctive overlap with cerebellar atrophy-associated ataxia and epilepsy. In cell-based studies, all variants caused significant alterations in cytosolic calcium handling with both loss- and gain-of-function effects. CONCLUSION: Presentations in our series recapitulate key phenotypic aspects of Atp2b2-mouse models and underline the importance of precise calcium regulation for neurodevelopment and cerebellar function. Our study documents a role for ATP2B2 variants in causing heterogeneous neurodevelopmental and movement-disorder syndromes.

• MeSH
• ATPasy přenášející vápník přes plazmatickou membránu MeSH
• behaviorální symptomy MeSH
• cerebelární ataxie * genetika   MeSH
• dystonie * genetika   MeSH
• fenotyp MeSH
• lidé MeSH
• mentální retardace * genetika   MeSH
• myši MeSH
• nedoslýchavost * MeSH
• neurovývojové poruchy * genetika   MeSH
• vápník MeSH
• záchvaty genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

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
• epilepsie * genetika   MeSH
• hyperkinetická porucha * MeSH
• hyperkineze genetika   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH

Parkinson's disease (PD) affects the language processes, with a significant impact on the patients' daily communication. We aimed to describe specific alterations in the comprehension of syntactically complex sentences in patients with PD (PwPD) as compared to healthy controls (HC) and to identify the neural underpinnings of these deficits using a functional connectivity analysis of the striatum. A total of 20 patients PwPD and 15 HC participated in the fMRI study. We analyzed their performance of a Test of sentence comprehension (ToSC) adjusted for fMRI. A task-dependent functional connectivity analysis of the striatum was conducted using the psychophysiological interaction method (PPI). On the behavioral level, the PwPD scored significantly lower (mean ± sd: 77.3 ± 12.6) in the total ToSC score than the HC did (mean ± sd: 86.6 ± 8.0), p = 0.02, and the difference was also significant specifically for sentences with a non-canonical word order (PD-mean ± sd: 69.9 ± 14.1, HC-mean ± sd: 80.2 ± 11.5, p = 0.04). Using PPI, we found a statistically significant difference between the PwPD and the HC in connectivity from the right striatum to the supplementary motor area [SMA, (4 8 53)] for non-canonical sentences. This PPI connectivity was negatively correlated with the ToSC accuracy of non-canonical sentences in the PwPD. Our results showed disturbed sentence reading comprehension in the PwPD with altered task-dependent functional connectivity from the right striatum to the SMA, which supports the synchronization of the temporal and sequential aspects of language processing. The study revealed that subcortical-cortical networks (striatal-frontal loop) in PwPD are compromised, leading to impaired comprehension of syntactically complex sentences.

• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Cerebral palsy (CP) is a group of permanent disorders attributed to non-progressive disturbances that occurred in the developing fetal or infant brain. Cerebral palsy-like (CP-like) disorders may clinically resemble CP but do not fulfill CP criteria and have often a progressive course and/or neurodevelopmental regression. To assess which patients with dystonic CP and dystonic CP-like disorder should undergo Whole Exome Sequencing (WES), we compared the rate of likely causative variants in individuals regarding their clinical picture, co-morbidities, and environmental risk factors. METHOD: Individuals with early onset neurodevelopmental disorder (ND) manifesting with dystonia as a core feature were divided into CP or CP-like cohorts based on their clinical picture and disease course. Detailed clinical picture, co-morbidities, and environmental risk factors including prematurity, asphyxia, SIRS, IRDS, and cerebral bleeding were evaluated. RESULTS: A total of 122 patients were included and divided into the CP group with 70 subjects (30 males; mean age 18y5m±16y6m, mean GMFCS score 3.3 ± 1.4), and the CP-like group with 52 subjects (29 males; mean age 17y7m±1y,6 m, mean GMFCS score 2,6 ± 1,5). The WES-based diagnosis was present in 19 (27.1%) CP patients and 30 CP-like patients (57.7%) with genetic conditions overlap in both groups. We found significant differences in diagnostic rate in CP individuals with vs. without risk factors (13.9% vs. 43.3%); Fisher's exact p = 0.0065. We did not observe the same tendency in CP-like (45.5% vs 58.5%); Fisher's exact p = 0.5. CONCLUSION: WES is a useful diagnostic method for patients with dystonic ND, regardless of their presentation as a CP or CP-like phenotype.

• MeSH
• dystonické poruchy * genetika   komplikace   MeSH
• dystonie * genetika   komplikace   MeSH
• lidé MeSH
• mozek MeSH
• mozková obrna * genetika   MeSH
• sekvenování exomu MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH