• MeSH
• endosonografie * metody   MeSH
• gastrointestinální nádory ultrasonografie   MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• gastroenterologie
• onkologie
• radiologie, nukleární medicína a zobrazovací metody
• NLK Publikační typ
• kolektivní monografie
• učebnice vysokých škol

Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive central nervous system tumor characterized by loss of SMARCB1/INI1 protein expression and comprises three distinct molecular groups, ATRT-TYR, ATRT-MYC and ATRT-SHH. ATRT-SHH represents the largest molecular group and is heterogeneous with regard to age, tumor location and epigenetic profile. We, therefore, aimed to investigate if heterogeneity within ATRT-SHH might also have biological and clinical importance. Consensus clustering of DNA methylation profiles and confirmatory t-SNE analysis of 65 ATRT-SHH yielded three robust molecular subgroups, i.e., SHH-1A, SHH-1B and SHH-2. These subgroups differed by median age of onset (SHH-1A: 18 months, SHH-1B: 107 months, SHH-2: 13 months) and tumor location (SHH-1A: 88% supratentorial; SHH-1B: 85% supratentorial; SHH-2: 93% infratentorial, often extending to the pineal region). Subgroups showed comparable SMARCB1 mutational profiles, but pathogenic/likely pathogenic SMARCB1 germline variants were over-represented in SHH-2 (63%) as compared to SHH-1A (20%) and SHH-1B (0%). Protein expression of proneural marker ASCL1 (enriched in SHH-1B) and glial markers OLIG2 and GFAP (absent in SHH-2) as well as global mRNA expression patterns differed, but all subgroups were characterized by overexpression of SHH as well as Notch pathway members. In a Drosophila model, knockdown of Snr1 (the fly homologue of SMARCB1) in hedgehog activated cells not only altered hedgehog signaling, but also caused aberrant Notch signaling and formation of tumor-like structures. Finally, on survival analysis, molecular subgroup and age of onset (but not ASCL1 staining status) were independently associated with overall survival, older patients (> 3 years) harboring SHH-1B experiencing relatively favorable outcome. In conclusion, ATRT-SHH comprises three subgroups characterized by SHH and Notch pathway activation, but divergent molecular and clinical features. Our data suggest that molecular subgrouping of ATRT-SHH has prognostic relevance and might aid to stratify patients within future clinical trials.

• MeSH
• gen SMARCB1 genetika   metabolismus   MeSH
• lidé MeSH
• metylace DNA MeSH
• nádory centrálního nervového systému * genetika   MeSH
• neuroepitelové nádory * genetika   MeSH
• prognóza MeSH
• proteiny hedgehog genetika   metabolismus   MeSH
• rhabdoidní nádor * genetika   MeSH
• teratom * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The present article describes two unrelated cases of progressive myoclonic epilepsy (PME) of the Lafora's disease and Unverricht-Lundborg types who were treated with topiramate (TPM) as add-on therapy for their myoclonus. After the initiation of topiramate therapy both cases responded with marked decrease in myoclonic seizure frequency and improvement of quality of life. Topiramate appears to be a useful alternative agent in cases of PME and could be consider for adjunctive therapy.

• MeSH
• antikonvulziva terapeutické užití   MeSH
• fruktosa analogy a deriváty   terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• mladý dospělý MeSH
• myoklonické epilepsie progresivní farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

BACKGROUND: The progressive myoclonic epilepsies (PME) are a heterogeneous group of disorders in which a specific diagnosis cannot be made in a subset of patients, despite exhaustive investigation. C9orf72 repeat expansions are emerging as an important causal factor in several adult-onset neurodegenerative disorders, in particular frontotemporal lobar degeneration and amyotrophic lateral sclerosis. An association with PME has not been reported previously. OBJECTIVE: To identify the causative mutation in a Belgian family where the proband had genetically unexplained PME. RESULTS: We report a 33-year old woman who had epilepsy since the age of 15 and then developed progressive cognitive deterioration and multifocal myoclonus at the age of 18. The family history suggested autosomal dominant inheritance of psychiatric disorders, epilepsy, and dementia. Thorough workup for PME including whole exome sequencing did not reveal an underlying cause, but a C9orf72 repeat expansion was found in our patient and affected relatives. Brain biopsy confirmed the presence of characteristic p62-positive neuronal cytoplasmic inclusions. CONCLUSION: C9orf72 mutation analysis should be considered in patients with PME and psychiatric disorders or dementia, even when the onset is in late childhood or adolescence.

• MeSH
• dospělí MeSH
• expanze repetic DNA * MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozek patologie   MeSH
• myoklonické epilepsie progresivní genetika   patologie   patofyziologie   psychologie   MeSH
• protein C9orf72 genetika   MeSH
• rodina MeSH
• rodokmen MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

• MeSH
• analgezie MeSH
• bolest diagnóza   farmakoterapie   MeSH
• výsledek terapie MeSH
• Publikační typ
• kongresy MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• anesteziologie a intenzivní lékařství

• Klíčová slova
• lékařství vnitřní - nemoci - klasifikace - učebnice, lékařství preventivní - diagnostika - učebnice, systémy terapeutické - lékařství vnitřní - učebnice,

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• vnitřní lékařství
• chemie, klinická chemie

• MeSH
• akutní intermitentní porfyrie komplikace   patologie   MeSH
• antikonvulziva terapeutické užití   MeSH
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mozek patologie   MeSH
• myoklonické epilepsie progresivní komplikace   patologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH

• MeSH
• lékařská informatika MeSH
• Publikační typ
• kongresy MeSH
• sborníky MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• lékařská informatika

• MeSH
• chirurgie trávicího traktu MeSH
• laparoskopie MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• gastroenterologie