Influence of different spectra of NOTCH3 variants on the clinical phenotype of CADASIL - experience from Slovakia.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary vascular disorder causing ischaemic attacks and strokes in middle-aged adults. Though the clinical spectrum includes some typical symptoms, recognition of the disease, especially at an earlier stage, is very difficult because of the highly variable manifestation and incomplete clinical picture. Characteristic brain MRI findings and the presence of pathogenic variants in the NOTCH3 gene are fundamental for CADASIL diagnosis. In this paper, we provide the first comprehensive report on CADASIL patients from Slovakia. Altogether, we identified 23 different pathogenic variants in 35 unrelated families. In our cohort of patients with clinical suspicion of CADASIL, we found a causal genetic defect and confirmed the diagnosis in 10.2% of cases. We present the case reports with up-to-date unpublished NOTCH3 variants and describe their phenotype-genotype correlation: p.(Cys65Phe), p.(Pro86Leu/Ser502Phe), p.(Arg156*), p.(Cys408Arg), p.(Tyr423Cys), p.(Asp1720His), and p.(Asp1893Thrfs*13). The most frequently described location for pathogenic variants was in exon 4, whereas the most common single variant was p.Arg1076Cys in exon 20. Based on the results of our study, we propose a re-evaluation of the criteria for the selection of patients suitable for NOTCH3 gene analysis. We hereby state that the currently used protocol of a high score requirement is not ideal for assessing molecular analysis, and it will be desirable to be less strict in criteria for genetic testing.

Molecular diagnosis of spinal and bulbar muscular atrophy in Slovakia.

OBJECTIVES: Molecular-genetic analysis is a determining step in setting the diagnosis of spinal and bulbar muscular atrophy (SBMA). We present the first nation-wide study and experience with this disease and its diagnosis in Slovakia. The study is enriched by comparison of genetic findings from Slovak patients to patients from other countries. METHODS: Molecular-genetic analysis was performed for patients suspected of SBMA. Data of patients with confirmed diagnosis were statistically evaluated. In addition, the detection rate and the prevalence of the disease for Slovakia were estimated. RESULTS: In 40 patients with confirmed diagnosis of SBMA, average values were observed at 44.7 CAG repeats and 52.5 years at the time of molecular-genetic diagnosis. The detection rate represents approximately 23% and an estimated prevalence is of 1 : 41,700. CONCLUSION: Concerning the population of Slovakia with 5,420,000 inhabitants, we document a relatively large cohort of SBMA patients. This is obvious when comparing similar studies from other countries, while this is the only study representing the Central Europe. Our findings prove that molecular-genetic analyses for the detection of this neuromuscular disorder show high efficiency. This fact underlines the necessity of such testing and may serve as a guide for clinicians from other countries in setting the right diagnosis for these patients (Tab. 1, Fig. 2, Ref. 29).

[Analgesia for labour in the Czech Republic in the year 2011 from the perspective of OBAAMA-CZ study - prospective national survey]. / Analgezie u porodu v Ceské republice v roce 2011 z pohledu studie OBAAMA-CZ- prospektivní observacní studie.

GOAL OF THE STUDY: The aim of national survey was to describe current practice for analgesia during labour provided by anaesthesiologists in the Czech Republic (CZE). TYPE OF THE STUDY: National prospective observational. SETTING: 49 obstetric departments in CZE. METHODS: We aimed to enrol all 97 obstetric departments in CZE and to monitor every case of anaesthetic care in peripartum period during November 2011. Data were recorded to Case Report Form with two parts (Demography 2010 and Case Report) into TrialDB database (Yale University, USA; adapted IBA, MU, CZE). Demographic data for CZE were obtained on request by ÚZIS. The data were analysed using SPSS 22. RESULTS: We enrolled 1943 cases of anaesthesiological care and 579 (29.8%) of them was to relief labour pain. Population and center weighted estimate of incidence of epidural labour analgesia was 12.5% (95% CI: 10.6% - 14.4%). Epidural analgesia was the most frequently applied via Tuohy needle G18 (97.8%), with administration of an epidural catheter G20 (95.7%), via medial approach (98.8%), in lateral position (76.7%) by the loss of resistance method (94.3%). All administrations of epidural analgesia were started by initial bolus, only in 28.2% of cases were followed continously. Always has been applied mixture of local anaesthetic with sufentanil at a dose of 3-10 mcg. Bupivacaine was most frequently used local anaesthetic (80.7%), followed by levobupivacaine (12.6%). Median concentrations both bupivacaine and levobupivacaine were 0.125% (min. 0.1%, max. 0.3%).The most common complication of epidural analgesia was repeated puncture (21.2%), blood in the catheter (1.4%), blood in the needle (1.2%), unintended puncture of the dura mater (0.7%) and transient paresthesias (0.5%). CONCLUSION: In comparison to previously published data there was trend for lower incidence of epidural analgesia for labour in the CZE.

Establishment and evaluation of a post caesarean acute pain service in a perinatological center:retrospective observational study.

OBJECTIVE: The aim of this study was to determine the efficacy of establishing a Post Caesarean Acute Pain Service. DESIGN: Retrospective observational study. SETTING: University Hospital Brno. METHODS: We evaluated all patients undergoing delivery via Caesarean Section under anaesthesia in the periods 10/2009 - 9/2010 and 11/2010 - 10/2011. During the postoperative period at predefined times, we measured the Visual Analogue Scale, Additional Analgesic Requests, blood pressure, pulse rate and recorded any complications. We compared the Visual Analogue Scale Score and number of Additional Analgesic Requests in two groups of women, 212 patients before and 195 patients after the establishment of an Acute Pain Service in the first 72 hours after Caesarean Section. RESULTS: There was a statistically significant difference in Visual Analogue Scale Score between the groups (p<0.05). The number of Additional Analgesic Requests 24-72 hours after Caesarean Section decreased below one requirement per 24 hours. The most effective analgesic method after Caesarean Section during the first 24 hours postoperatively was epidural analgesia. There was no statistically significant difference 24-72 hours after Caesarean Section between the methods of analgesia used. CONCLUSION: In conclusion, implementation of a Post Caesarean Acute Pain Service led to decrease in Visual Analogue Scale Score postoperatively. KEYWORDS: Acute Pain Service, postoperative analgesia, Caesarean Section, non-opioid analgesia, opioid analgesia, epidural analgesia.

Peroxisomal D-bifunctional protein deficiency: First case reports from Slovakia.

D-bifunctional protein deficiency (#OMIM 261515) is a rare autosomal recessive hereditary metabolic disorder causing severe clinical and biochemical abnormalities that are usually fatal in the course of the first years of life. This disease is classified as single enzyme peroxisomal disorder affecting the ß-oxidation pathway in this compartment. In this paper we present a full overview of the clinical presentation, magnetic resonance imaging, biochemical and molecular data of two Slovak D-bifunctional protein deficient patients. In the clinical presentation of both patients severe generalized hypotonia, depression of neonatal reflexes, craniofacial dysmorphism and seizures dominated starting from the second day of life. In both patients, who died up to two years of life, we found elevated plasma levels of very long chain fatty acids and we identified the presence of causative mutations in the HSD17B4 gene. In the first case, we found the homozygous mutation c.46G>A, which is responsible for a defect in the dehydrogenase domain. In the second patient, the heterozygous mutations c.1369A>G and c.1516C>T were present and functionally they are related to the hydratase domain of the protein. This combination of mutations in the second patient is very rare and has not been reported until now. The presence of mutations was examined in all family members, and the resulting data were successfully utilized for prenatal diagnosis.