Cerebellar atrophy is a characteristic sign of late-onset Tay-Sachs disease (LOTS). Other structural neuroimaging abnormalities are inconsistently reported. Our study aimed to perform a detailed whole-brain analysis and quantitatively characterize morphometric changes in LOTS patients. Fourteen patients (8 M/6F) with LOTS from three centers were included in this retrospective study. For morphometric brain analyses, we used deformation-based morphometry, voxel-based morphometry, surface-based morphometry, and spatially unbiased cerebellar atlas template. The quantitative whole-brain morphometric analysis confirmed the finding of profound pontocerebellar atrophy with most affected cerebellar lobules V and VI in LOTS patients. Additionally, the atrophy of structures mainly involved in motor control, including bilateral ventral and lateral thalamic nuclei, primary motor and sensory cortex, supplementary motor area, and white matter regions containing corticospinal tract, was present. The atrophy of the right amygdala, hippocampus, and regions of occipital, parietal and temporal white matter was also observed in LOTS patients in contrast with controls (p < 0.05, FWE corrected). Patients with dysarthria and those initially presenting with ataxia had more severe cerebellar atrophy. Our results show predominant impairment of cerebellar regions responsible for speech and hand motor function in LOTS patients. Widespread morphological changes of motor cortical and subcortical regions and tracts in white matter indicate abnormalities in central motor circuits likely coresponsible for impaired speech and motor function.

• MeSH
• atrofie patologie   MeSH
• bílá hmota * diagnostické zobrazování   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   MeSH
• retrospektivní studie MeSH
• Tay-Sachsova nemoc * patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Fabry disease (FD) can be undiagnosed in the context of multiple sclerosis (MS) due to similar clinical and paraclinical features. Our study aimed to determine the prevalence (and the necessity of screening) of FD among patients with possible or definite MS. METHODS: In this prospective monocentric observational study, we included consecutive patients enrolled between May 2017 and May 2019 after the first clinical event suggestive of MS. All patients underwent FD screening using dried blood spots in a stepwise manner combining genetic and enzyme testing. Patients were followed until May 2022. RESULTS: We included 160 patients (73.1% female, mean age 33.9 years). The 2017 revised McDonald's criteria for definite MS were fulfilled by 74 (46.3%) patients at the time of study recruitment and 89 (55.6%) patients after 3-5 years of follow-up. None of the patients had a pathogenic GLA variant, and four (2.5%) had a variant of unknown significance (p.A143T, p.S126G, 2 × p.D313Y). In two of these patients, the intrathecal synthesis of oligoclonal bands was absent, and none had hyperproteinorachia or pleocytosis in cerebrospinal fluid. Detailed examination of FD organ manifestations revealed only discrete ocular and kidney involvement in two patients. CONCLUSION: The prevalence of FD in the population of suspected or definite MS patients does not appear to be high. Our results do not support routine FD screening in all patients with a possible diagnosis of MS, but there is an urgent need to search for red flags and include FD in the differential diagnosis of MS.

• MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• Fabryho nemoc * diagnóza   epidemiologie   MeSH
• lidé MeSH
• nepoznaná diagnóza MeSH
• prospektivní studie MeSH
• roztroušená skleróza * diagnóza   epidemiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

Niemann-Pick typ C predstavuje veľmi vzácne a závažné lyzozómové ochorenie. Diagnostika tohto ochorenia je komplementárna a žiadny z testov sám o sebe nemusí stačiť pre jednoznačné stanovenie diagnózy. Tento príspevok opisuje, ako sa od pozorovania prvých príznakov krok za krokom prišlo k stanoveniu konečnej diagnózy, a ktoré vyšetrenia boli pre diagnostiku potrebné. Pozornosť bude venovaná aj dôrazu na potrebu genetického vyšetrenia v prípade potvrdenia tejto diagnózy u rodičov ako prevencia prepuknutia ochorenia u ďalších súrodencov.

The Niemann-Pick type C is a very rare and serious lysosomal storage disease. The diagnosis of this disease is complex, and none of the tests alone is sufficient to confirm the diagnosis. This thesis describes the diagnosis from initial observation of first symptoms to confirmation of the final diagnosis. We also list all the test required to establish the diagnosis. We also focus on importance of genetic testing of parents as a preventative approach to disease onset of other children.

• MeSH
• dítě MeSH
• lyzozomální střádavé nemoci v nervovém systému MeSH
• Niemannova-Pickova nemoc typu C diagnostické zobrazování   diagnóza   genetika   patofyziologie   terapie   MeSH
• splenomegalie MeSH
• Check Tag
• dítě MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• biologická terapie MeSH
• hypercholesterolemie * farmakoterapie   MeSH
• LDL-cholesterol účinky léků   MeSH
• lidé MeSH
• PCSK9 inhibitory farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH

Tirzepatid – duální agonista receptorů pro glukagon-like peptid-1 (GIP) a glukózo-dependentní inzulinotropní polypeptid (GIP) je účinným antidiabetikem s významným efektem na redukci hmotnosti, u kterého je předpokládaný potenciál ovlivnit i kardiovaskulární riziko pacientů. Tento přehled se věnuje jeho vlivu na lipidové spektrum, srovnává jej s účinky selektivních agonistů GLP-1 receptoru a poskytuje pohled na vývoj dalších inkretinových agonistů a jejich metabolické působení.

Tirzepatide - a dual agonist of receptors for glucagon-like peptide-1 (GIP) and glucose-dependent insulinotropic polypeptide (GIP) is an effective antidiabetic drug associated with significant weight loss, which is expected to have the potential to influence the cardiovascular risk of patients. This review focuses on its effects on the lipid spectrum, compares it to the effects of selective GLP-1 receptor agonists, and provides insight into the development of other incretin agonists and their metabolic actions.

• Klíčová slova
• tirzepatid,
• MeSH
• diabetes mellitus 2. typu * farmakoterapie   MeSH
• dyslipidemie farmakoterapie   MeSH
• hmotnostní úbytek účinky léků   MeSH
• hypoglykemika farmakologie   terapeutické užití   MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• obezita farmakoterapie   MeSH
• receptor pro glukagonu podobný peptid 2 terapeutické užití   MeSH
• žaludeční inhibiční polypeptid farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

• MeSH
• dyslipidemie farmakoterapie   MeSH
• fixní kombinace léků MeSH
• hypertenze diagnóza   farmakoterapie   MeSH
• kardiovaskulární nemoci prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• primární prevence metody   MeSH
• rizikové faktory kardiovaskulárních chorob * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: Large deletions and duplications within the low-density lipoprotein receptor (LDLR) gene make up approximately 10% of LDLR pathogenic variants found in Czech patients with familial hypercholesterolemia. The goal of this study was to test the hypothesis that all probands with each rearrangement share identical breakpoints inherited from a common ancestor and to determine the role of Alu repetitive elements in the generation of these rearrangements. METHODS: The breakpoint sequence was determined by PCR amplification and Sanger sequencing. To confirm the breakpoint position, an NGS analysis was performed. Haplotype analysis of common LDLR variants was performed using PCR and Sanger sequencing. RESULTS: The breakpoints of 8 rearrangements within the LDLR gene were analysed, including the four most common LDLR rearrangements in the Czech population (number of probands ranging from 8 to 28), and four less common rearrangements (1-4 probands). Probands with a specific rearrangement shared identical breakpoint positions and haplotypes associated with the rearrangement, suggesting a shared origin from a common ancestor. All breakpoints except for one were located inside an Alu element. In 6 out of 8 breakpoints, there was high homology (≥ 70%) between the two Alu repeats in which the break occurred. CONCLUSIONS: The most common rearrangements of the LDLR gene in the Czech population likely arose from one mutational event. Alu elements likely played a role in the generation of the majority of rearrangements inside the LDLR gene.

• MeSH
• genová přestavba MeSH
• hyperlipoproteinemie typ II * genetika   epidemiologie   MeSH
• lidé MeSH
• mutace MeSH
• receptory LDL genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Niemann-Pick disease type C is a rare lysosomal storage disorder. We evaluated the safety and efficacy of N-acetyl-l-leucine (NALL), an agent that potentially ameliorates lysosomal and metabolic dysfunction, for the treatment of Niemann-Pick disease type C. METHODS: In this double-blind, placebo-controlled, crossover trial, we randomly assigned patients 4 years of age or older with genetically confirmed Niemann-Pick disease type C in a 1:1 ratio to receive NALL for 12 weeks, followed by placebo for 12 weeks, or to receive placebo for 12 weeks, followed by NALL for 12 weeks. NALL or matching placebo was administered orally two to three times per day, with patients 4 to 12 years of age receiving weight-based doses (2 to 4 g per day) and those 13 years of age or older receiving a dose of 4 g per day. The primary end point was the total score on the Scale for the Assessment and Rating of Ataxia (SARA; range, 0 to 40, with lower scores indicating better neurologic status). Secondary end points included scores on the Clinical Global Impression of Improvement, the Spinocerebellar Ataxia Functional Index, and the Modified Disability Rating Scale. Crossover data from the two 12-week periods in each group were included in the comparisons of NALL with placebo. RESULTS: A total of 60 patients 5 to 67 years of age were enrolled. The mean baseline SARA total scores used in the primary analysis were 15.88 before receipt of the first dose of NALL (60 patients) and 15.68 before receipt of the first dose of placebo (59 patients; 1 patient never received placebo). The mean (±SD) change from baseline in the SARA total score was -1.97±2.43 points after 12 weeks of receiving NALL and -0.60±2.39 points after 12 weeks of receiving placebo (least-squares mean difference, -1.28 points; 95% confidence interval, -1.91 to -0.65; P<0.001). The results for the secondary end points were generally supportive of the findings in the primary analysis, but these were not adjusted for multiple comparisons. The incidence of adverse events was similar with NALL and placebo, and no treatment-related serious adverse events occurred. CONCLUSIONS: Among patients with Niemann-Pick disease type C, treatment with NALL for 12 weeks led to better neurologic status than placebo. A longer period is needed to determine the long-term effects of this agent in patients with Niemann-Pick disease type C. (Funded by IntraBio; ClinicalTrials.gov number, NCT05163288; EudraCT number, 2021-005356-10.).

• MeSH
• dítě MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• klinické křížové studie MeSH
• látky ovlivňující centrální nervový systém * aplikace a dávkování   terapeutické užití   MeSH
• leucin analogy a deriváty   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Niemannova-Pickova nemoc typu C * komplikace   diagnóza   farmakoterapie   genetika   MeSH
• předškolní dítě MeSH
• sběr dat MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

• MeSH
• adherence k farmakoterapii MeSH
• amlodipin terapeutické užití   MeSH
• atorvastatin terapeutické užití   MeSH
• dyslipidemie farmakoterapie   MeSH
• fixní kombinace léků * MeSH
• hypertenze farmakoterapie   MeSH
• kardiovaskulární nemoci * farmakoterapie   komplikace   MeSH
• klinická studie jako téma MeSH
• kongresy jako téma MeSH
• lidé MeSH
• perindopril terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• novinové články MeSH

Kardiovaskulární choroby i přes pokles v poslední době zůstávají hlavní příčinou úmrtnosti a nemocnosti a jejich výskyt s věkem stoupá. Dyslipidemie představují základní rizikový faktor těchto chorob. Zahájení léčby dyslipidemií závisí na stanovení míry rizika. U starších pacientů s dokumentovanou kardiovaskulární chorobou je doporučen stejný postup jako u pacientů mladších. U starších nemocných bez dokumentované kardiovaskulární nemoci by mělo být zahájení léčby dyslipidemií zváženo v případě velmi vysokého rizika s ohledem k předpokládané délce života, adherenci k léčbě, lékovým interakcím, geriatrické křehkosti a preferenci nemocných.

Despite recent decline, cardiovascular diseases remain the main cause of mortality and morbidity and their occurrence is increasing with age. Dyslipidaemia represents a basic risk factor for cardiovascular disease. Dyslipidaemia treatment initiation depends on patient risk stratification. In older patients with documented cardiovascular disease, treatment is recommended in the same way as in younger patients. In older patients without documented cardiovascular disease, treatment should be considered in very-high-risk patients about estimated life expectancy, patient adherence, drug interactions, geriatric frailty and patient preference.

• MeSH
• dyslipidemie * farmakoterapie   MeSH
• hodnocení rizik MeSH
• kardiovaskulární nemoci prevence a kontrola   MeSH
• lidé MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• statiny terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• přehledy MeSH