RESUMEN
Three monozygotic twin pairs with the Creutzfeldt-Jakob diseases-specific mutation E200K are described. All three have been concordant for genetic CJDE200K and discordant for the age at death and the duration of the disease. Twin pairs have been compared with genetically non - identical sibling pairs also concordant for genetic CJDE200K and discordant for the age at death. The difference of the mean age at death in compared subgroups was not significant. Detailed analysis of twin pairs revealed considerable differences in the duration and quality of chronic stress, induced by the analysed exogenous factors. The stress was evidently of higher intensity in two of the three earlier affected twins. Clear correlation between the age at death and medical history of twins was not observed. The discordance of twins with genetic CJDE200K in the age at death and the striking correlation with the discordant intensity of analysed exogenous influence, draw attention to described potential risk factors (mainly to chronic social, economic and emotional stress) and support their role in accelerating the clinical onset of genetic CJDE200K.
Asunto(s)
Síndrome de Creutzfeldt-Jakob/genética , Síndrome de Creutzfeldt-Jakob/mortalidad , Gemelos Monocigóticos/genética , Adulto , Factores de Edad , Anciano , Síndrome de Creutzfeldt-Jakob/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Mutación/genética , Linaje , Factores de Riesgo , Tasa de Supervivencia/tendenciasRESUMEN
The aim of the presented study was to reveal the frequency of insomnia spells in E200K genetic Creutzfeldt-Jakob disease (gCJD) patients. Clinical records of 22 subjects diagnosed with E200K gCJD were retrospectively reviewed. The patients w/wo insomnia (n = 4, 18%/n = 18, 82%) did not differ in age, sex and the duration of the symptomatic phase. Analysis of the clinical features in the groups yielded differences in the clinical signs in the early phase of the disorder, proportion of homozygotes (Met/Met) at codon 129, MRI changes in the thalamus and the typical EEG abnormality. The study suggests that apart from traditional clinical features, the insomnia is not a rare early symptom in phenotype of E200K gCJD based on early thalamic involvement.
Asunto(s)
Síndrome de Creutzfeldt-Jakob/complicaciones , Síndrome de Creutzfeldt-Jakob/genética , Mutación Puntual , Proteínas Priónicas/genética , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Trastornos del Inicio y del Mantenimiento del Sueño/genética , Anciano , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Estudios RetrospectivosRESUMEN
OBJECTIVES: An extraordinary incidence of genetic Creutzfeldt-Jakob disease (gCJD) appearing in clusters in the Slovak Republic was described in the 1990's. The aim of the study was to analyse data of CJD cases obtained from surveillance in Eastern Slovakia (ES) (2004-2016), the region outside the described geographical clusters. METHODS: The database set in the project was the source for epidemiological and clinical analysis of CJD cases. RESULTS: The incidence of CJD in ES (2004-2016) was 1.7/million person-years (95% CI 1-2.4); the incidence increase in the last five years (2012-2016) was comparable to the whole country. Twenty seven of 29 reported CJD cases were available for analysis (mean age 59 years, F/M 15/12). The proportion of gCJD (E200K mutation) cases remained dominant (78%), with 9 familiar cases originating in 4 families. Analysis of the clinical features revealed shorter duration of the symptomatic phase in sporadic CJD (sCJD) (3.4 months) versus gCJD (5.15 months). Cognitive/behavioural changes, insomnia, and sensory disturbance were more pronounced in the early symptoms of gCJD. Periodic EEG discharges were more frequent in sCJD (83%) than gCJD (56%), all 19 available MR findings were CJD specific and localisation of abnormalities varied amongst the CJD forms. CONCLUSIONS: The surveillance of CJD in ES (2004-2016) showed an increased incidence of CJD in ES, reaching the incidence rate of the whole country, with a permanent proportion of 70% gCJD cases based on the E200K mutation. Clinical, electrophysiological and MR features of sCJD and gCJD cases were in conformity with already published data. Epidemiological analysis of CJD in ES shows increasing detection of CJD but also suggests that current routine surveillance systems for CJD may underestimate the true burden of disease, especially sporadic cases in Slovakia.
Asunto(s)
Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/genética , Encefalopatía Espongiforme Bovina , Priones/genética , Adolescente , Adulto , Anciano , Animales , Bovinos , Síndrome de Creutzfeldt-Jakob/epidemiología , Femenino , Genotipo , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Mutación , Linaje , Vigilancia de la Población , Eslovaquia/epidemiologíaRESUMEN
Creutzfeldt-Jakob disease is a rare, but rapidly progressive, up to now untreatable and fatal neurodegenerative disorder. Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is difficult; however, it can be facilitated by suitable biomarkers. Aim of the present study is to compare levels of cerebrospinal fluid biomarkers (total tau protein, phosphorylated-tau protein, protein 14-3-3 and amyloid beta) in Slovak population of CJD suspect cases, retrospectively in over a 10-year period. One thousand three hundred sixty-four CSF samples from patients with suspect CJD, forming a homogenous group in terms of geographical as well as of equal transport conditions, storage and laboratory processing, were analysed. Definite diagnosis of Creutzfeldt-Jakob disease was confirmed in 101 patients with genetic form, and 60 patients with its sporadic form of the disease. Specificity of protein 14-3-3 and total tau in both forms CJD was similar (87 % for P14-3-3/85 % for total tau), sensitivity to P 14-3-3 and total tau was higher in sporadic Creutzfeldt-Jakob disease (sCJD) (90/95 %) than in genetic Creutzfeldt-Jakob disease (gCJD) (89/74 %). As expected, the total tau levels were significantly higher in CJD patients than in controls, but there was also significant difference between gCJD and sCJD (levels in gCJD were lower; p = 0.003). There was no significant difference in p-tau and Aß 1-42 levels neither between both CJD forms nor between CJD patients and control group.