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
- 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
Psychóza pri Parkinsonovej chorobe je závažnou neuropsychiatrickou komplikáciou Parkinsonovej choroby. Zlatým štandardom v liečbe podľa úrovne dôkazov je klozapín, atypické antipsychotikum s multireceptorovým pôsobením, ktoré má nízke riziko výskytu extrapyramídových nežiaducich účinkov. Hoci je klozapín v tejto indikácii vysoko účinný, stále sa používa pomerne málo, a to hlavne zo strachu pred vznikom agranulocytózy, ktorý medzi lekármi často vedie k všeobecnej klozapínofóbii. Článok prináša základné fakty o klozapíne a praktický manažment v liečbe psychózy pri Parkinsonovej chorobe.
Parkinson ́s disease related psychosis is a serious neuropsychiatric complication of Parkinson ́s disease. According to evidence-based medicine, the gold standard in the treatment is treatment with clozapine, an atypical antipsychotic drug with multireceptor properties and low risk of extrapyramidal side effects. Although clozapine seems to be very effective, it is quite underused, mainly due to the fear of developing agranulocytosis. This fear leads commonly to clozaphobia among physicians. The review brings basic facts about clozapine and management of Parkinson ́s disease related psychosis.
Epizodické ataxie tvoria skupinu geneticky podmienených alebo získaných ochorení prejavujúcich sa epizodickými atakmi cerebelárnej dysfunkcie, ktoré tiež môžu byť sprevádzané rozličnými ďalšími príznakmi. Primárne epizodické ataxie, ktoré tvoria väčšinu prípadov, vznikajú v mladšom veku a sú charakterizované rozličnou frekvenciou a trvaním atakov, variabilnými interiktálnymi prejavmi a odpoveďou na acetazolamid (epizodické ataxie typ 1-9). Získané epizodické ataxie sa manifestujú väčšinou v neskoršom veku, a to krátko trvajúcimi atakmi ataxie a ďalšími prejavmi samotného ochorenia (roztrúsená skleróza a iné). V tomto prehľadovom článku prinášame didaktický prehľad a stručný diagnostický algoritmus epizodických ataxií pre potreby klinickej praxe.
Episodic ataxias encompass a group of genetic or acquired conditions with episodic attacks of the cerebellar dysfunction, which may be associated with another various symptoms. Primary episodic ataxias are mainly young-onset. They are characterized by various frequency and duration of the attacks, and variable interictal features and response to acetazolamide (episodic ataxias type 1-9). Acquired episodic ataxias are usually late-onset and manifested by short lasting attacks and other features of underlying condition (multiple sclerosis and others). In this article, we provide a didactive overview and a brief diagnostic algorithm of episodic ataxias suitable for clinical praxis.
- Klíčová slova
- epizodické ataxie,
- MeSH
- ataxie * diagnóza etiologie genetika klasifikace MeSH
- cerebelární ataxie * diagnóza etiologie genetika klasifikace MeSH
- diferenciální diagnóza MeSH
- geny MeSH
- lidé MeSH
- mutace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy 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
- 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
INTRODUCTION: Although shared genetic factors have been previously reported between dystonia and other neurologic conditions, no sequencing study exploring such links is available. In a large dystonic cohort, we aimed at analyzing the proportions of causative variants in genes associated with disease categories other than dystonia. METHODS: Gene findings related to whole-exome sequencing-derived diagnoses in 1100 dystonia index cases were compared with expert-curated molecular testing panels for ataxia, parkinsonism, spastic paraplegia, neuropathy, epilepsy, and intellectual disability. RESULTS: Among 220 diagnosed patients, 21% had variants in ataxia-linked genes; 15% in parkinsonism-linked genes; 15% in spastic-paraplegia-linked genes; 12% in neuropathy-linked genes; 32% in epilepsy-linked genes; and 65% in intellectual-disability-linked genes. Most diagnosed presentations (80%) were related to genes listed in ≥1 studied panel; 71% of the involved loci were found in the non-dystonia panels but not in an expert-curated gene list for dystonia. CONCLUSIONS: Our study indicates a convergence in the genetics of dystonia and other neurologic phenotypes, informing diagnostic evaluation strategies and pathophysiological considerations.
- MeSH
- časná diagnóza MeSH
- genetické testování MeSH
- lidé MeSH
- nemoci bazálních ganglií * diagnóza genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodní články MeSH
