BACKGROUND AND AIMS: Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by disease-associated variants in the alpha-galactosidase A gene (GLA). FD is a known cause of stroke in younger patients. There are limited data on prevalence of FD and stroke risk in unselected stroke patients. METHODS: A prospective nationwide study including 35 (78%) of all 45 stroke centers and all consecutive stroke patients admitted during three months. Clinical data were collected in the RES-Q database. FD was diagnosed using dried blood spots in a stepwise manner: in males-enzymatic activity, globotriaosylsphingosine (lyso-Gb3) quantification, if positive followed by GLA gene sequencing; and in females GLA sequencing followed by lyso-Gb3. RESULTS: 986 consecutive patients (54% men, mean age 70 years) were included. Observed stroke type was ischemic 79%, transient ischemic attack (TIA) 14%, intracerebral hemorrhage (ICH) 7%, subarachnoid hemorrhage 1% and cerebral venous thrombosis 0.1%. Two (0.2%, 95% CI 0.02-0.7) patients had a pathogenic variant associated with the classical FD phenotype (c.1235_1236delCT and p.G325S). Another fourteen (1.4%, 95% CI 0.08-2.4) patients had a variant of GLA gene considered benign (9 with p.D313Y, one p.A143T, one p.R118C, one p.V199A, one p.R30K and one p.R38G). The index stroke in two carriers of disease-associated variant was ischemic lacunar. In 14 carriers of GLA gene variants 11 strokes were ischemic, two TIA, and one ICH. Patients with positive as compared to negative GLA gene screening were younger (mean 60±SD, min, max, vs 70±SD, min, max, P = 0.02), otherwise there were no differences in other baseline variables. CONCLUSIONS: The prevalence of FD in unselected adult patients with acute stroke is 0.2%. Both patients who had a pathogenic GLA gene variant were younger than 50 years. Our results support FD screening in patients that had a stroke event before 50 years of age.

• MeSH
• alfa-galaktosidasa krev   genetika   MeSH
• cévní mozková příhoda krev   komplikace   epidemiologie   genetika   MeSH
• exprese genu MeSH
• Fabryho nemoc krev   komplikace   epidemiologie   genetika   MeSH
• genetické testování MeSH
• glykolipidy krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• prevalence MeSH
• prospektivní studie MeSH
• senioři MeSH
• sfingolipidy krev   MeSH
• test suché kapky krve 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
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications. OBJECTIVES: We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity). METHODS: We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses. RESULTS: Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81. CONCLUSIONS: The algorithm is a useful predictive tool and could be integrated into dystonia routine diagnostic protocols. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

• MeSH
• algoritmy MeSH
• dystonické poruchy * genetika   MeSH
• dystonie * diagnóza   genetika   MeSH
• genetické testování MeSH
• lidé MeSH
• Parkinsonova nemoc * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Next-generation sequencing is now used on a routine basis for molecular testing but studies on copy-number variant (CNV) detection from next-generation sequencing data are underrepresented. Utilizing an existing whole-exome sequencing (WES) dataset, we sought to investigate the contribution of rare CNVs to the genetic causality of dystonia. METHODS: The CNV read-depth analysis tool ExomeDepth was applied to the exome sequences of 953 unrelated patients with dystonia (600 with isolated dystonia and 353 with combined dystonia; 33% with additional neurological involvement). We prioritized rare CNVs that affected known disease genes and/or were known to be associated with defined microdeletion/microduplication syndromes. Pathogenicity assessment of CNVs was based on recently published standards of the American College of Medical Genetics and Genomics and the Clinical Genome Resource. RESULTS: We identified pathogenic or likely pathogenic CNVs in 14 of 953 patients (1.5%). Of the 14 different CNVs, 12 were deletions and 2 were duplications, ranging in predicted size from 124bp to 17 Mb. Within the deletion intervals, BRPF1, CHD8, DJ1, EFTUD2, FGF14, GCH1, PANK2, SGCE, UBE3A, VPS16, WARS2, and WDR45 were determined as the most clinically relevant genes. The duplications involved chromosomal regions 6q21-q22 and 15q11-q13. CNV analysis increased the diagnostic yield in the total cohort from 18.4% to 19.8%, as compared to the assessment of single-nucleotide variants and small insertions and deletions alone. CONCLUSIONS: WES-based CNV analysis in dystonia is feasible, increases the diagnostic yield, and should be combined with the assessment of single-nucleotide variants and small insertions and deletions.

• MeSH
• dospělí MeSH
• dystonické poruchy diagnóza   genetika   MeSH
• dystonie diagnóza   genetika   MeSH
• kohortové studie MeSH
• lidé MeSH
• sekvenování exomu * MeSH
• variabilita počtu kopií segmentů DNA * genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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

Diseases of the central nervous system (CNS) mean for the human organism a potentially dangerous situation. An investigation of cerebrospinal fluid (CSF) provides important information about a character of CNS impairment in the decision-making diagnostic and therapeutic algorithm. The authors present a brief overview of available cerebrospinal fluid assays, shortened indication criteria, a recommended algorithm of CSF assessment in different suspected diseases, and a view of the external quality system. The whole portfolio of obtainable CSF methodology is further subdivided according to the adequate choice into the first and inevitable basic routine panel, and following complicated analyses of highly specialized character. The basic panel is considered for standard laboratories, the complete specialized assessment should be provided by a super-consulting laboratory.

• MeSH
• algoritmy MeSH
• cytologické techniky MeSH
• klinické laboratorní techniky MeSH
• lidé MeSH
• makrofágy MeSH
• mozkomíšní mok chemie   cytologie   MeSH
• proteiny v mozkomíšním moku analýza   MeSH
• směrnice pro lékařskou praxi jako téma * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Karcinom prsu je jeden z nejčastějších typů nádoru, jenž postihuje mozek metastázami, a mezi solidními tumory se řadí na první místo ve frekvenci výskytu leptomeningeální karcinomatózy. Autoři popisují kazuistiku 61leté ženy s generalizovaným lobulárním karcinomem prsu, u níž se objevily posturální synkopy a rychle postupující hluchota a slepota. U pacientky byla pomocí vyšetření magnetickou rezonancí a likvorologickým rozborem zjištěna leptomeningeální karcinomatóza. Tento klinický soubor ve vztahu k leptomeningeální karcinomatóze je velice raritní.

Breast cancer is frequently associated with brain metastases and is the most common solid tumor to exhibit leptomeningeal carcinomatosis. The authors describe a case of a 61-years--old woman with generalized breast cancer who suffered from postural syncopes and suddenly developed deafness and blindness. Magnetic resonance imaging and cerebrospinal fluid analysis confirmed leptomeningeal infiltration. This type of clinical presentation of leptomeningeal carcinomatosis is considered to be very rare. Key words: breast neoplasms – meningeal carcinomatosis – postural syncope – blindness –deafness The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manu­script met the ICMJE “uniform requirements” for biomedical papers.

• MeSH
• diferenciální diagnóza MeSH
• fatální výsledek MeSH
• hluchota etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• meningeální karcinomatóza * diagnóza   komplikace   sekundární   MeSH
• metastázy nádorů MeSH
• mozkomíšní mok cytologie   MeSH
• nádory prsu * komplikace   MeSH
• nervový systém patofyziologie   MeSH
• slepota etiologie   MeSH
• synkopa etiologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Paraneoplastický syndrom s neurologickou manifestací je způsoben imunitní odpovědí proti tumoru, který ektopicky exprimuje neuronální antigen. Klinická manifestace paraneoplastického neurologického syndromu často předchází diagnostice vlastní malignity. V řadě případů se při něm také prokazují onkoneurální autoreaktivní protilátky. Tyto protilátky v jisté míře dokážou pomoci s lokalizací primárního tumoru. V posledních desetiletích rychle narůstají nové poznatky o patofyziologii vzniku poškození nervového systému, rozrůstá se skupina onkoneurálních protilátek a definují se jednotlivé klinické jednotky. Onkoneurální protilátka anti-Yo se nejčastěji spojuje s paraneoplastickou cerebelární degenerací, jen malé procento případů je v asociaci s postižením periferního nervového systému. Přinášíme popis pacientky s endometriálním karcinomem a progredující chabou paraparézou dolních končetin. U pacientky byla prokázána subakutní motorická axonální polyneuropatie a přítomnost onkoneurální protilátky anti-Yo. Případ jsme hodnotili jako projev atypického paraneoplastického neurologického syndromu.

Paraneoplastic syndrome with neurological manifestation results from an immune response to a tumor ectopically expressing a neuronal antigen. A clinical manifestation of neurological paraneoplastic syndrome often precedes the diagnosis of malignancy. Frequently, onconeural antibodies are measured in patients with paraneoplastic syndromes. To some extent, onconeural antibodies may assist in localizing the primary tumor. Over the recent decades, our understanding of pathophysiology of nervous system damage continues to grow, further onconeural antibodies are being identified and new clinical syndromes established. The anti- -Yo onconeural antibody has most commonly been associated with paraneoplastic cerebellar degeneration; only a small proportion of patients presents with an involvement of peripheral nervous system. We are describing a case of progressive flaccid paraparesis of lower extremities and endometrial carcinoma. The patient was diagnosed with subacute motor axonal polyneuropathy with the presence of onconeural anti-Yo antibody. We concluded that this was an atypical paraneoplastic neurological syndrome.

• MeSH
• diferenciální diagnóza MeSH
• lidé MeSH
• nádory endometria MeSH
• paraneoplastická polyneuropatie MeSH
• paraneoplastické neurologické syndromy diagnóza   MeSH
• protilátky nádorové MeSH
• protilátky MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

Amygdala a další struktury limbického systémujsou odpovědnéza analýzu signálůs emo­cionálním nábojem. Postižení limbického systému neurodegenerativním procesem může vést ke změně emocionálního vnímání nebo až k emoční agnozii. Předkládaná práce hodnotí vztah mezi in vivo naměřenými objemy amygdaly, hippocampu, předního cingulárního kortexu, pólu temporálního laloku a emocionální agnozií u pacientů s Alzheimerovou nemocí v porovnání s kontrolní populací. Materiál a metodika: 26 pacientů s Alzheimerovou nemocí a 17 členů kontrolní skupiny absolvovalo vyšetření magnetickou rezonancí a neuropsychologické vyšetření včetně testu rozpoznávání emocí podle výrazu obličeje. Metodou MR volumetrie byly změřeny objemy amygdaly, hippocampu, předního cingulárního kortexu a pólu temporálního laloku. Výsledky: všechny naměřené regionální objemy a výsledky neuropsychologických testů byly u pacientů s AN signifikantně horší oproti kontrolní skupině. Při srovnání regionálních objemů a výsledku testu rozeznávání emocí signifikantně korelovaly: objem levé amygdaly a schopnost rozpoznávat radost (r = 0,54, p < 0,01) a smutek (r = 0,49, p < 0,05), objem pravé amygdaly se schopností rozpoznávat strach (r = 0,34, p < 0,05) a smutek (r = 0,56, p < 0,01), objem obou hippocampů se schopností rozpoznávat hněv (r = 0,55 pravý a r = 0,58 levý, p < 0,01). Závěr: Zjištěný vztah mezi sníženým objemem amygdaly a sníženou schopností rozeznávat některé emoce u pacientů s AN podporuje hypotézu, že emocionální agnozie u AN je podmíněna atrofií amygdaly a dalších struktur limbického systému.

The amygdala and other structures of the limbic system are responsible for the analysis of signals carrying an emotional charge. The affection of the limbic system by a neurodegenerative process may cause a change in emotional perception or even emotional agnosia. The article evaluates the relation between in vivo measured volumes of the amygdala, hippocampus, anterior cingular cortex, temporal lobe pole and emotional agnosia in patients with Alzheimer's disease as compared with the control population. Material and method: 26 patients with Alzheimer's disease and 17 members of the control group were subject to a magnetic resonance exam and a neuropsychological exam including an emotion recognition test using facial expression. Magnetic resonance volumetry was used to measure the amy­gdala, hippocampus, anterior cingular cortex and temporal pole volumes. Results: All regional volume values obtained by the measurement and the results of neuropsychological tests were significantly worse in patients with AD as compared with the control group. Comparison of regional volumes with the results of the emotion recognition test showed significant corre­lation between: left amygdala volume and the capacity to recognise joy (r = 0.54, p < 0.01) and sadness (r = 0.49, p < 0.05), right amygdala volume and the capacity to recognise fear (r = 0.34, p < 0.05) and sadness (r = 0.56, p < 0.01), the volume of both hippocampi and the capacity to recognise anger (r = 0.55 / right, and r = 0.58 / left, p < 0.01). Conclusion: The relation observed between a lower amygdala volume and a reduced capacity to recognise some emotions in patients with AD corroborates the hypothesis that emotional agnosia in AD patients is linked with atrophy of the amygdala and other limbic system structures.

• MeSH
• afektivní symptomy etiologie   MeSH
• agnozie etiologie   MeSH
• Alzheimerova nemoc diagnóza   etiologie   patofyziologie   MeSH
• amygdala patofyziologie   patologie   MeSH
• financování organizované MeSH
• lidé MeSH
• limbický systém patofyziologie   patologie   MeSH
• magnetická rezonanční tomografie metody   využití   MeSH
• neuropsychologické testy statistika a číselné údaje   MeSH
• statistika jako téma metody   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH