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
Syndróm GLUT1 deficiencie je zriedkavé neurometabolické ochorenie mozgu vznikajúce pri poruche transportu glukózy cez hematoencefalickú bariéru. Keďže mozog je takmer úplne závislý od dodávky glukózy ako hlavného zdroja energie a GLUT1 je hlavným transportérom glukózy cez hematoencefalickú bariéru, klasický typ ochorenia sa prejavuje závažnými dôsledkami neuroglykopénie: včasnou neurovývojovou encefalopatiou s epileptickými záchvatmi, získanou mikrocefáliou, kognitívnym deficitom a rozličnými perzistentnými alebo paroxyzmálnymi motorickými (často komplexnými) prejavmi, ako je ataxia, spasticita alebo dystónia. Najdôležitejším diagnostickým krokom je dôkaz hypoglykorachie (menej ako 2,2 mmol/l) v likvore a zníženého pomeru glukózy likvor/sérum (väčšinou menej než 0,4). Definitívnu diagnózu však prináša molekulárne genetické vyšetrenie SLC2A1 génu. Najúčinnejšou formou liečby je ketogénna diéta, pri ktorej sa utilizujú mastné kyseliny ako náhradný zdroj energie pre mozog. Z hľadiska prognózy je však kritickým včasné rozpoznanie ochorenia a tým včasné zavedenie ketogénnej diéty.
GLUT1-deficiency syndrome is a rare neurometabolic brain disorder caused by disruption of glucose transport across the blood-brain barrier. As brain almost completely depends on glucose supply as the main source of energy, and the GLUT-1 represents the main transporter of glucose across the blood-brain barrier, the classic form of the disease manifests by severe consequences of neuroglycopenia: early neurodevelopmental encephalopathy with seizures, acquired microcephaly, cognitive deficit and various persistent or paroxysmal motor (often complex in nature) features such as ataxia, spasticity or dystonia. The evidence of low glucose cerebrospinal fluid level (lower than 2.2 mmol/l) and the low CSF/serum glucose ratio (mostly lower than 0.4) are the most important diagnostic clues. Definite diagnosis, however, lies on the molecular-genetic testing of the SLC2A1 gene. The most efficacious treatment strategy is the ketogenic diet, in which the body utilizes fatty acids as an alternative source of energy for the brain. However, early recognition of the disease and early introduction of ketogenic diet is crucial for better prognosis.
Dystonia is a prevalent, heterogeneous movement disorder characterized by involuntarily abnormal postures. Biomarkers of dystonia are notoriously lacking. Here, a biomarker is reported for histone lysine methyltransferase (KMT2B)-deficient dystonia, a leading subtype among the individually rare monogenic dystonias. It was derived by applying a support vector machine to an episignature of 113 DNA CpG sites, which, in blood cells, showed significant epigenome-wide association with KMT2B deficiency and at least 1× log-fold change of methylation. This classifier was accurate both when tested on the general population and on samples with various other deficiencies of the epigenetic machinery, thus allowing for definitive evaluation of variants of uncertain significance and identifying patients who may profit from deep brain stimulation, a highly successful treatment in KMT2B-deficient dystonia. Methylation was increased in KMT2B deficiency at all 113 CpG sites. The coefficients of variation of the normalized methylation levels at these sites also perfectly classified the samples with KMT2B-deficient dystonia. Moreover, the mean of the normalized methylation levels correlated well with the age at onset of dystonia (P = 0.003)-being lower in samples with late or incomplete penetrance-thus serving as a predictor of disease onset and severity. Similarly, it may also function in monitoring the recently envisioned treatment of KMT2B deficiency by inhibition of DNA methylation.
Huntingtonova choroba je zriedkavé autozomálne dominantne dedičné neliečiteľné neurodegeneratívne ochorenie, ktoré sa prejavuje demenciou, behaviorálnymi poruchami, choreou a ďalšími motorickými príznakmi. Choroba nesie svoj názov po Georgeovi Huntingtonovi (1850-1916), v poradí treťom lekárovi z rodiny Huntingtonovcov, ktorí pracovali v East Hampton vo východnej časti Long Island (štát New York). Tu mal od svojho detstva možnosť vidieť niekoľko pacientov s dedičným ochorením, ktoré v roku 1872 opísal v článku s názvom "O chorei", publikovanom v časopise The Medical and Surgical Reporter. V ňom charakterizoval choreu po klinickej stránke a taktiež tri hlavné prejavy Huntingtonovej choroby: dedičnosť, sklon k šialenstvu a výskyt v dospelosti. Hoci sa už vie, že túto chorobu opísali pred Huntingtonom aj iní autori, článok mu priniesol slávu. Na počesť 150. výročia tejto udalosti sme sa v príspevku zamerali na Georga Huntingtona a na historické okolnosti, ktoré sa udiali v čase tohto dôležitého míľnika v histórii neurológie.
Huntington's disease is a rare autosomal dominant incurable neurodegenerative disease, manifested by dementia, behavioral symptoms, chorea and other motor features. The disease bears his name after George Huntington (1850-1916), representing the third generation physician of Huntington ́s family, working in East Hampton on the east part of Long Island, New York. Here, since his childhood, he could see several patients with a hereditary disease, described by him in a paper entitled "On chorea", published in The Medical and Surgical Reporter in 1872. In this article, he characterized chorea from the clinical point of view, and also the three main features of Huntington's disease: heredity, tendency to insanity and occurrence in adulthood. Although it has been known that the disease has been described by other authors before Huntington, this paper has brought him fame. In honor of the 150th anniversary of this story, in this review we have focused on George Huntington and historical circumstances that happened in the time around this important milestone in the history of neurology.
- MeSH
- dějiny 19. století MeSH
- Huntingtonova nemoc * dějiny genetika patofyziologie MeSH
- lidé MeSH
- Check Tag
- dějiny 19. století MeSH
- lidé MeSH
- Publikační typ
- biografie MeSH
- historické články MeSH
- O autorovi
- Huntington, George, 1851-1916 Autorita
