Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years

We present a comprehensive multi-omic analysis of the EPISTOP prospective clinical trial of early intervention with vigabatrin for pre-symptomatic epilepsy treatment in Tuberous Sclerosis Complex (TSC), in which 93 infants with TSC were followed from birth to age 2 years, seeking biomarkers of epilepsy development. Vigabatrin had profound effects on many metabolites, increasing serum deoxycytidine monophosphate (dCMP) levels 52-fold. Most serum proteins and metabolites, and blood RNA species showed significant change with age. Thirty-nine proteins, metabolites, and genes showed significant differences between age-matched control and TSC infants. Six also showed a progressive difference in expression between control, TSC without epilepsy, and TSC with epilepsy groups. A multivariate approach using enrollment samples identified multiple 3-variable predictors of epilepsy, with the best having a positive predictive value of 0.987. This rich dataset will enable further discovery and analysis of developmental effects, and associations with seizure development in TSC.</p

Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years

We present a comprehensive multi-omic analysis of the EPISTOP prospective clinical trial of early intervention with vigabatrin for pre-symptomatic epilepsy treatment in Tuberous Sclerosis Complex (TSC), in which 93 infants with TSC were followed from birth to age 2 years, seeking biomarkers of epilepsy development. Vigabatrin had profound effects on many metabolites, increasing serum deoxycytidine monophosphate (dCMP) levels 52-fold. Most serum proteins and metabolites, and blood RNA species showed significant change with age. Thirty-nine proteins, metabolites, and genes showed significant differences between age-matched control and TSC infants. Six also showed a progressive difference in expression between control, TSC without epilepsy, and TSC with epilepsy groups. A multivariate approach using enrollment samples identified multiple 3-variable predictors of epilepsy, with the best having a positive predictive value of 0.987. This rich dataset will enable further discovery and analysis of developmental effects, and associations with seizure development in TSC

Socio-demographic factors influencing disabled people’s professional activity

Podstawowym celem naszych poszukiwań badawczych było ustalenie, jakie są kompetencje psychospołeczne osób z ograniczoną sprawnością w zakresie podejmowania i utrzymania aktywności zawodowej oraz psychologiczne i społeczno-kulturowe (1) czynniki ryzyka, ograniczające korzystanie z posiadanych zasobów i (2) czynniki ochraniające bądź wzmacniające zasoby i wpływające pozytywnie na funkcjonowanie na rynku pracy. Celem czwartego etapu badań, którego wyniki prezentujemy tutaj, było ustalenie, jakie czynniki związane są z podejmowaniem aktywności zawodowej przez osoby niepełnosprawne oraz z odczuwanym przez nie zadowoleniem z życia. Czynniki te podzieliliśmy na kilka grup: (1) lokalizacyjne, demograficzne i związane z niepełnosprawnością – stanowiły one kryteria doboru grupy badanej, (2) związane z socjalizacją i wychowaniem w okresie dzieciństwa oraz z aktualnymi relacjami społecznymi w rodzinie i poza nią i (3) podmiotowe, związane z kompetencjami osobistymi. Tutaj prezentujemy wyniki dotyczące tylko pierwszego bloku zmiennych.The following article presents the goals and assumptions contained in the project entitled “Psychosocial influences concerning disabled people’s professional activity”. The study was conducted in four stages: (1) document analysis and literature review presenting research concerning how disabled people function on the job market; (2) expert opinions, including disabled people; (3) qualitative studies employing Maxqda2 to analyze information gathered from 311 interviews; and (4) quantitative research on a sample of 1498 participants with various types of disabilities (hearing, sight, physical, somatic, and psychological) conducted in 2007. The following article presents the first set of results obtained, referring to connections on a socio- demographic level (place of residence, gender, age, education, and marital status) as well as those isolating disability characteristics (type, level, and genesis) against degree of life satisfaction. Comparisons were executed for five groups with various employment statuses: employed, those looking for employment who had worked before, those looking for employment who had no previous employment experience, previously employed but had no intention of returning to the workforce and those who had never worked and had no intention of becoming employed. Lowest feelings of life satisfaction were among those not looking for employment whereas highest levels of life satisfaction occurred amongst employed participants. Important risk factors: gender (female), age (elderly), low education, marital status (single), place of residence (non-city dwellers), disability (innate and level).Wyniki, jakie prezentujemy, uzyskane zostały w ramach projektu badawczego pt. Psychospołeczne uwarunkowania aktywności zawodowej osób niepełnosprawnych. Projekt ten – nr WUE/0041/IV/05 realizowany był (w okresie: listopad 2005 – marzec 2008 r.) w ramach Sektorowego Programu Operacyjnego Rozwój Zasobów Ludzkich – priorytet 1 pt.: Aktywna polityka rynku pracy oraz integracji zawodowej i społecznej, działanie 1.4. pt.: Integracja zawodowa i społeczna osób niepełnosprawnych. Kierownikiem projektu była prof. dr hab. Anna Izabela Brzezińska. Projekt współfinansowany ze środków Unii Europejskiej w ramach Europejskiego Funduszu Społecznego realizowany był w Szkole Wyższej Psychologii Społecznej w Warszawie

Association of Early MRI Characteristics with Subsequent Epilepsy and Neurodevelopmental Outcomes in Children with Tuberous Sclerosis Complex

Background and Objectives:Multiple factors have been found to contribute to the high risk of epilepsy in infants with tuberous sclerosis complex (TSC), including evolution of EEG abnormalities, TSC gene variant, and MRI characteristics. The aim of this prospective multicenter study was to identify early MRI biomarkers of epilepsy in infants with TSC aged &lt;6 months and before seizure onset, and associate these MRI biomarkers with neurodevelopmental outcomes at 2 years of age. The study was part of the EPISTOP project.Methods:We evaluated brain MRIs performed in infants younger than 6 months with TSC. We used harmonized MRI protocols across centers and children were monitored closely with neuropsychological evaluation and serial video EEG. MRI characteristics, defined as tubers, radial migration lines, white matter abnormalities, cysts, calcifications, subependymal nodules (SEN), and subependymal giant cell astrocytoma (SEGA), were visually evaluated and lesions were detected semiautomatically. Lesion to brain volume ratios were calculated and associated with epilepsy and neurodevelopmental outcomes at 2 years.Results:Lesions were assessed on MRIs from 77 infants with TSC; 62 MRIs were sufficient for volume analysis. The presence of tubers and Fhigher tuber-brain ratios were associated with the development of clinical seizures, independently of TSC gene variation and preventive treatment. Furthermore, higher tuber-brain ratios were associated with lower cognitive and motor development quotients at 2 years, independently of TSC gene variation and presence of epilepsy.Discussion:In infants with TSC, there is a significant association between characteristic TSC lesions detected on early brain MRI and development of clinical seizures, as well as neurodevelopmental outcomes in the first 2 years of life. According to our results, early brain MRI findings may guide clinical care for young children with TSC.Classification of Evidence:This study provides Class I evidence that in infants with TSC, there is a significant association between characteristic TSC lesions on early brain MRI and the development of clinical seizures and neurodevelopmental outcomes in the first 2 years of life.</p

Prevention of Epilepsy in Infants with Tuberous Sclerosis Complex in the EPISTOP Trial

Objective Epilepsy develops in 70 to 90% of children with tuberous sclerosis complex (TSC) and is often resistant to medication. Recently, the concept of preventive antiepileptic treatment to modify the natural history of epilepsy has been proposed. EPISTOP was a clinical trial designed to compare preventive versus conventional antiepileptic treatment in TSC infants.Methods In this multicenter study, 94 infants with TSC without seizure history were followed with monthly video electroencephalography (EEG), and received vigabatrin either as conventional antiepileptic treatment, started after the first electrographic or clinical seizure, or preventively when epileptiform EEG activity before seizures was detected. At 6 sites, subjects were randomly allocated to treatment in a 1:1 ratio in a randomized controlled trial (RCT). At 4 sites, treatment allocation was fixed; this was denoted an open-label trial (OLT). Subjects were followed until 2 years of age. The primary endpoint was the time to first clinical seizure.Results In 54 subjects, epileptiform EEG abnormalities were identified before seizures. Twenty-seven were included in the RCT and 27 in the OLT. The time to the first clinical seizure was significantly longer with preventive than conventional treatment [RCT: 364 days (95% confidence interval [CI] = 223-535) vs 124 days (95% CI = 33-149); OLT: 426 days (95% CI = 258-628) vs 106 days (95% CI = 11-149)]. At 24 months, our pooled analysis showed preventive treatment reduced the risk of clinical seizures (odds ratio [OR] = 0.21, p = 0.032), drug-resistant epilepsy (OR = 0.23, p = 0.022), and infantile spasms (OR = 0, p &lt; 0.001). No adverse events related to preventive treatment were noted.Interpretation Preventive treatment with vigabatrin was safe and modified the natural history of seizures in TSC, reducing the risk and severity of epilepsy. ANN NEUROL 202

Association of Early MRI Characteristics with Subsequent Epilepsy and Neurodevelopmental Outcomes in Children with Tuberous Sclerosis Complex

Background and Objectives:Multiple factors have been found to contribute to the high risk of epilepsy in infants with tuberous sclerosis complex (TSC), including evolution of EEG abnormalities, TSC gene variant, and MRI characteristics. The aim of this prospective multicenter study was to identify early MRI biomarkers of epilepsy in infants with TSC aged &lt;6 months and before seizure onset, and associate these MRI biomarkers with neurodevelopmental outcomes at 2 years of age. The study was part of the EPISTOP project.Methods:We evaluated brain MRIs performed in infants younger than 6 months with TSC. We used harmonized MRI protocols across centers and children were monitored closely with neuropsychological evaluation and serial video EEG. MRI characteristics, defined as tubers, radial migration lines, white matter abnormalities, cysts, calcifications, subependymal nodules (SEN), and subependymal giant cell astrocytoma (SEGA), were visually evaluated and lesions were detected semiautomatically. Lesion to brain volume ratios were calculated and associated with epilepsy and neurodevelopmental outcomes at 2 years.Results:Lesions were assessed on MRIs from 77 infants with TSC; 62 MRIs were sufficient for volume analysis. The presence of tubers and Fhigher tuber-brain ratios were associated with the development of clinical seizures, independently of TSC gene variation and preventive treatment. Furthermore, higher tuber-brain ratios were associated with lower cognitive and motor development quotients at 2 years, independently of TSC gene variation and presence of epilepsy.Discussion:In infants with TSC, there is a significant association between characteristic TSC lesions detected on early brain MRI and development of clinical seizures, as well as neurodevelopmental outcomes in the first 2 years of life. According to our results, early brain MRI findings may guide clinical care for young children with TSC.Classification of Evidence:This study provides Class I evidence that in infants with TSC, there is a significant association between characteristic TSC lesions on early brain MRI and the development of clinical seizures and neurodevelopmental outcomes in the first 2 years of life.</p

Association of early MRI characteristics with subsequent epilepsy and neurodevelopmental outcomes in children with tuberous sclerosis complex

Background and objectives: Multiple factors have been found to contribute to the high risk of epilepsy in infants with tuberous sclerosis complex (TSC), including evolution of EEG abnormalities, TSC gene variant, and MRI characteristics. The aim of this prospective multicenter study was to identify early MRI biomarkers of epilepsy in infants with TSC aged &lt;6 months and before seizure onset, and associate these MRI biomarkers with neurodevelopmental outcomes at 2 years of age. The study was part of the EPISTOP project. Methods: We evaluated brain MRIs performed in infants younger than 6 months with TSC. We used harmonized MRI protocols across centers and children were monitored closely with neuropsychological evaluation and serial video EEG. MRI characteristics, defined as tubers, radial migration lines, white matter abnormalities, cysts, calcifications, subependymal nodules (SEN), and subependymal giant cell astrocytoma (SEGA), were visually evaluated and lesions were detected semiautomatically. Lesion to brain volume ratios were calculated and associated with epilepsy and neurodevelopmental outcomes at 2 years. Results: Lesions were assessed on MRIs from 77 infants with TSC; 62 MRIs were sufficient for volume analysis. The presence of tubers and higher tuber-brain ratios were associated with the development of clinical seizures, independently of TSC gene variation and preventive treatment. Furthermore, higher tuber-brain ratios were associated with lower cognitive and motor development quotients at 2 years, independently of TSC gene variation and presence of epilepsy. Discussion: In infants with TSC, there is a significant association between characteristic TSC lesions detected on early brain MRI and development of clinical seizures, as well as neurodevelopmental outcomes in the first 2 years of life. According to our results, early brain MRI findings may guide clinical care for young children with TSC. Classification of evidence: This study provides Class I evidence that in infants with TSC, there is a significant association between characteristic TSC lesions on early brain MRI and the development of clinical seizures and neurodevelopmental outcomes in the first 2 years of life

Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years

Abstract We present a comprehensive multi-omic analysis of the EPISTOP prospective clinical trial of early intervention with vigabatrin for pre-symptomatic epilepsy treatment in Tuberous Sclerosis Complex (TSC), in which 93 infants with TSC were followed from birth to age 2 years, seeking biomarkers of epilepsy development. Vigabatrin had profound effects on many metabolites, increasing serum deoxycytidine monophosphate (dCMP) levels 52-fold. Most serum proteins and metabolites, and blood RNA species showed significant change with age. Thirty-nine proteins, metabolites, and genes showed significant differences between age-matched control and TSC infants. Six also showed a progressive difference in expression between control, TSC without epilepsy, and TSC with epilepsy groups. A multivariate approach using enrollment samples identified multiple 3-variable predictors of epilepsy, with the best having a positive predictive value of 0.987. This rich dataset will enable further discovery and analysis of developmental effects, and associations with seizure development in TSC