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

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

Hlboká mozgová stimulácia (deep brain stimulation; DBS) je súčasťou pokročilej liečby vybraných neurologických ochorení, pri ktorých nie je dostatočne efektívna konzervatívna terapia. Etablovanými indikáciami sú Parkinsonova choroba, rôzne formy dystónie a esenciálny tras. V posledných rokoch sa rozšírilo indikačné spektrum DBS v rámci neurológie o vybrané formy epilepsie a v experimentálnej rovine prebiehajú klinické štúdie s využitím DBS pri chronickej klastrovej bolesti hlavy a ďalších extrapyramídových ochoreniach (Tourettov syndróm, Huntingtonova choroba). Ďalším posunom sú technologické inovácie v oblasti hardvéru. Prakticky všetky neurostimulátory sú kompatibilné s MR a životnosť batérie sa výrazne predĺžila (výrobca garantuje 13 rokov, ale experimentálne dáta predikujú životnosť pri nabíjateľných neurostimulátoroch až do 25 rokov). V rutinnej praxi sa začali používať tzv. smerovateľné elektródy, ktoré umožňujú presnejšie zacielenie elektrického poľa a minimalizáciu stimuláciou indukovaných nežiaducich účinkov. DBS je teda bezpečnou a efektívnou liečbou medicínsky refraktérnych neurologických ochorení a rýchlosť pokroku na tomto poli predpokladá ešte ďalšie zdokonalenie (automatizácia programovania, zmenšovanie a ďalšie predlžovanie životnosti batérie, jednoduchšia obslužnosť).

Deep brain stimulation (DBS) is an established advanced treatment option for selected neurological disorders with failed conservative therapy. Present indications of DBS are Parkinson‘s disease, various types of dystonia and essential tremor. In recent years, the DBS indication spectrum of neurological disorders has broadened with epilepsy and other more experimental indications such as chronic cluster headache and other movement disorders (Tourette’s syndrome, Huntington’s disease). Technological hardware innovations are another important step. Almost all currently manufactured neurostimulators are MRI compatible and the longevity of batteries has significantly improved (manufacturer guarantees a longevity of 13 years and the experimental data predict up to 25 years). Directional leads became a standard practice enabling the shaping of the electrical fields and minimalization of stimulation-induced side effects. Deep brain stimulation is a safe and effective therapy option for medically refractory neurological disorders and we may predict further substantial advances in this field (time-saving automatic programming, minimalization and longevity of batteries, user-friendly patient programmers).

• MeSH
• hluboká mozková stimulace * metody   přístrojové vybavení   trendy   MeSH
• lidé MeSH
• nemoci nervového systému terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Orfenadrín sa používa na liečbu parkinsonizmu a muskuloskeletálnych bolestivých syndrómov už viac ako 50 rokov. Hlavným dôvodom vedľajších účinkov tohto lieku je jeho anticholínergický efekt. Uvádzame prípady dvoch pacientok s pokročilou Parkinsonovou chorobou, u ktorých kombinovaná analgetická medikácia diklofenak/orfenadrín viedla k zhoršeniu fluktuácií a nástupu ťažkých dyskinéz.

Orphenadrine has been used for treatment of both parkinsonism and musculoskeletal diseases for more than 50 years. Anticholinergic mechanism of action is the main reason for side effects. We report on two patients with advanced Parkinson's disease in whom combined analgetic medication diclofenac/orphenadrine led to worsening of fluctuations and onset of severe dyskinesia.

• MeSH
• bolesti zad farmakoterapie   komplikace   MeSH
• diklofenak škodlivé účinky   MeSH
• fixní kombinace léků MeSH
• lidé středního věku MeSH
• lidé MeSH
• nežádoucí účinky léčiv etiologie   patofyziologie   MeSH
• orfenadrin škodlivé účinky   MeSH
• Parkinsonova nemoc * farmakoterapie   komplikace   MeSH
• polékové dyskineze * etiologie   patofyziologie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• lidé MeSH
• LRRK2 genetika   MeSH
• mutace MeSH
• Parkinsonova nemoc genetika   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Maďarsko MeSH
• Polsko MeSH
• Rumunsko MeSH
• Slovenská republika MeSH

Tremor je najčastejším abnormálnym pohybom a môže byť príznakom mnohých patologických stavov. Adekvátnu terapiu volíme podľa etiológie, preto je presná a včasná diagnostika nevyhnutná. Okrem podrobnej anamnézy a precízneho klinického vyšetrenia nám cenné informácie prinášajú aj neurofyziologické metódy - hlavne elektromyografia, ale aj elektroencefalografia či evokované potenciály. Vzhľadom na zameranie časopisu sa budeme venovať hlavne využitiu neurofyziológie v klinickej praxi.

Tremor is the most common movement disorder and it can be a symptom of many pathological conditions. According to its etiology, we choose adequate therapy, so accurate and early diagnosis is essential. In addition to a detailed medical history and precise clinical examination, neurophysiological methods - especially electromyography, but also electroencephalography or evoked potentials - provide valuable information. Considering the focus of the journal, we will deal mainly with the use of neurophysiology in daily clinical practice.

• MeSH
• diagnostické techniky neurologické MeSH
• diferenciální diagnóza MeSH
• lidé MeSH
• neurofyziologický monitoring * metody   MeSH
• neurofyziologie MeSH
• tremor diagnóza   MeSH
• Check Tag
• lidé MeSH

Cieľ: Alzheimerova demencia (AD) patrí medzi najviac invalidizujúce ochorenia prevažne staršej populácie. Dáta nasvedčujú, že pridružené komorbidity komplikujú diagnostiku aj liečbu a urýchľujú progresiu AD. Epidemiologické dáta zo strednej Európy chýbajú, preto cieľom projektu COSMOS bolo odhaliť prevalenciu psychiatrických a somatických komorbidít pacientov s AD v slovenskej populácii. Metódy: V tejto multicentrickej prierezovej observačnej štúdii boli údaje o pacientoch s AD z celého Slovenska získané z 89 pracovísk pomocou on-line dotazníka, ktorý obsahoval demografické a klinické údaje, informácie o všetkých komorbiditách a ich vplyve na adherenciu a účinnosť terapie. Výsledky: Zo všetkých 494 pacientov malo 94,53 % aspoň jednu somatickú komorbiditu, 80,16 % malo aspoň jednu psychiatrickú komorbiditu. So závažnosťou AD korelovali počet somatických (rs = 0,120; p = 0,008) aj psychiatrických (rs = 0,267; p < 0,001) komorbidít. Počet psychiatrických komorbidít (b = –0,021; p = 0,025) a závažnosť AD (b = –0,071; p < 0,001) predikovali horší efekt terapie. Adherentní pacienti mali väčšiu pravdepodobnosť účinnej terapie demencie (OR 5,270; 95% CI 3,061–9,073; p < 0,001). Záver: Komorbidity pri AD dokázane akcelerujú progresiu základného ochorenia a komplikujú diagnostiku a terapiu. Sú to ale najviac ovplyvniteľné faktory kognitívnej deteriorácie, preto ich aktívne vyhľadávanie, včasná diagnostika a adekvátna terapia môžu zlepšiť adherenciu pacientov a tak zefektívniť manažment AD.

Aim: Alzheimer‘s disease (AD) is one of the most disabling conditions predominantly affecting an elderly population. Data suggest that comorbidities complicate both diagnosis and treatment and accelerate AD progression. Epidemiological data from the Central Europe are missing, therefore, the aim of the COSMOS project was to reveal the prevalence of psychiatric and somatic comorbidities among AD patients in the Slovak population. Methods: In this multicenter, cross--sectional, observational study, data of AD patients from all Slovak regions (89 sites) were obtained using an online questionnaire. It contained demographic and clinical data, information about all comorbidities, and their impact on adherence and tratment efficacy. Results: Out of all 494 patients, 94.53% had at least one somatic comorbidity, 80.16% had at least one psychiatric comorbidity. The number of both somatic (rs = 0.120; P = 0.008) and psychiatric (rs = 0.267; P < 0.001) comorbidities correlated with the severity of AD. The number of psychiatric comorbidities (b = –0.021; P = 0.025) and the severity of AD (b = –0.071; P < 0.001) predicted a worse therapy effect. Adherent patients were more likely to have effective therapy of dementia (OR 5.270; 95% CI 3.061–9.073; P < 0.001). Conclusion: Comorbidities in AD have been shown to accelerate progression of underlying disease and complicate diagnosis and therapy. However, they represent the most modifiable factors of cognitive deterioration. Their active screening, early diagnosis and adequate therapy can improve patient’s adherence and, thus, make AD management more effective.

• MeSH
• adherence a compliance při léčbě MeSH
• Alzheimerova nemoc * komplikace   MeSH
• komorbidita * MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• pozorovací studie jako téma MeSH
• průřezové studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• Geografické názvy
• Slovenská republika MeSH

BACKGROUND: Dystonia is a clinically and genetically heterogeneous condition that occurs in isolation (isolated dystonia), in combination with other movement disorders (combined dystonia), or in the context of multisymptomatic phenotypes (isolated or combined dystonia with other neurological involvement). However, our understanding of its aetiology is still incomplete. We aimed to elucidate the monogenic causes for the major clinical categories of dystonia. METHODS: For this exome-wide sequencing study, study participants were identified at 33 movement-disorder and neuropaediatric specialty centres in Austria, Czech Republic, France, Germany, Poland, Slovakia, and Switzerland. Each individual with dystonia was diagnosed in accordance with the dystonia consensus definition. Index cases were eligible for this study if they had no previous genetic diagnosis and no indication of an acquired cause of their illness. The second criterion was not applied to a subset of participants with a working clinical diagnosis of dystonic cerebral palsy. Genomic DNA was extracted from blood of participants and whole-exome sequenced. To find causative variants in known disorder-associated genes, all variants were filtered, and unreported variants were classified according to American College of Medical Genetics and Genomics guidelines. All considered variants were reviewed in expert round-table sessions to validate their clinical significance. Variants that survived filtering and interpretation procedures were defined as diagnostic variants. In the cases that went undiagnosed, candidate dystonia-causing genes were prioritised in a stepwise workflow. FINDINGS: We sequenced the exomes of 764 individuals with dystonia and 346 healthy parents who were recruited between June 1, 2015, and July 31, 2019. We identified causative or probable causative variants in 135 (19%) of 728 families, involving 78 distinct monogenic disorders. We observed a larger proportion of individuals with diagnostic variants in those with dystonia (either isolated or combined) with coexisting non-movement disorder-related neurological symptoms (100 [45%] of 222; excepting cases with evidence of perinatal brain injury) than in those with combined (19 [19%] of 98) or isolated (16 [4%] of 388) dystonia. Across all categories of dystonia, 104 (65%) of the 160 detected variants affected genes which are associated with neurodevelopmental disorders. We found diagnostic variants in 11 genes not previously linked to dystonia, and propose a predictive clinical score that could guide the implementation of exome sequencing in routine diagnostics. In cases without perinatal sentinel events, genomic alterations contributed substantively to the diagnosis of dystonic cerebral palsy. In 15 families, we delineated 12 candidate genes. These include IMPDH2, encoding a key purine biosynthetic enzyme, for which robust evidence existed for its involvement in a neurodevelopmental disorder with dystonia. We identified six variants in IMPDH2, collected from four independent cohorts, that were predicted to be deleterious de-novo variants and expected to result in deregulation of purine metabolism. INTERPRETATION: In this study, we have determined the role of monogenic variants across the range of dystonic disorders, providing guidance for the introduction of personalised care strategies and fostering follow-up pathophysiological explorations. FUNDING: Else Kröner-Fresenius-Stiftung, Technische Universität München, Helmholtz Zentrum München, Medizinische Universität Innsbruck, Charles University in Prague, Czech Ministry of Education, the Slovak Grant and Development Agency, the Slovak Research and Grant Agency.

• MeSH
• dítě MeSH
• dystonie diagnóza   epidemiologie   genetika   MeSH
• exom genetika   MeSH
• genetická variace genetika   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• rodokmen MeSH
• sekvenování exomu metody   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH