GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Wiley  (5)
  • Curatolo, Paolo  (5)
  • 1
    Online Resource
    Online Resource
    Prevention of Epilepsy in Infants with Tuberous Sclerosis Complex in the EPISTOP Trial
    Wiley ; 2021
    In:  Annals of Neurology Vol. 89, No. 2 ( 2021-02), p. 304-314
    Details
    In: Annals of Neurology, Wiley, Vol. 89, No. 2 ( 2021-02), p. 304-314
    Abstract: 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   〈  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 2021;89:304–314
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v89.2
    DOI: 10.1002/ana.25956
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2037912-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    MicroRNA‐34a activation in tuberous sclerosis complex during early brain development may lead to impaired corticogenesis
    Wiley ; 2021
    In:  Neuropathology and Applied Neurobiology Vol. 47, No. 6 ( 2021-10), p. 796-811
    Details
    In: Neuropathology and Applied Neurobiology, Wiley, Vol. 47, No. 6 ( 2021-10), p. 796-811
    Abstract: Tuberous sclerosis complex (TSC) is a genetic disorder associated with dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1) signalling pathway. Neurodevelopmental disorders, frequently present in TSC, are linked to cortical tubers in the brain. We previously reported microRNA‐34a (miR‐34a) among the most upregulated miRs in tubers. Here, we characterised miR‐34a expression in tubers with the focus on the early brain development and assessed the regulation of mTORC1 pathway and corticogenesis by miR‐34a. Methods We analysed the expression of miR‐34a in resected cortical tubers ( n  = 37) compared with autopsy‐derived control tissue ( n  = 27). The effect of miR‐34a overexpression on corticogenesis was assessed in mice at E18. The regulation of the mTORC1 pathway and the expression of the bioinformatically predicted target genes were assessed in primary astrocyte cultures from three patients with TSC and in SH‐SY5Y cells following miR‐34a transfection. Results The peak of miR‐34a overexpression in tubers was observed during infancy, concomitant with the presence of pathological markers, particularly in giant cells and dysmorphic neurons. miR‐34a was also strongly expressed in foetal TSC cortex. Overexpression of miR‐34a in mouse embryos decreased the percentage of cells migrated to the cortical plate. The transfection of miR‐34a mimic in TSC astrocytes negatively regulated mTORC1 and decreased the expression of the target genes RAS related ( RRAS ) and NOTCH1 . Conclusions MicroRNA‐34a is most highly overexpressed in tubers during foetal and early postnatal brain development. miR‐34a can negatively regulate mTORC1; however, it may also contribute to abnormal corticogenesis in TSC.
    Type of Medium: Online Resource
    ISSN: 0305-1846 , 1365-2990
    URL: Issue
    URL: Article
    DOI: 10.1111/nan.v47.6
    DOI: 10.1111/nan.12717
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2008293-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Early epileptiform EEG activity in infants with tuberous sclerosis complex predicts epilepsy and neurodevelopmental outcomes
    Wiley ; 2021
    In:  Epilepsia Vol. 62, No. 5 ( 2021-05), p. 1208-1219
    Details
    In: Epilepsia, Wiley, Vol. 62, No. 5 ( 2021-05), p. 1208-1219
    Abstract: To study the association between timing and characteristics of the first electroencephalography (EEG) with epileptiform discharges (ED‐EEG) and epilepsy and neurodevelopment at 24 months in infants with tuberous sclerosis complex (TSC). Methods Patients enrolled in the prospective Epileptogenesis in a genetic model of epilepsy – Tuberous sclerosis complex (EPISTOP) trial, had serial EEG monitoring until the age of 24 months. The timing and characteristics of the first ED‐EEG were studied in relation to clinical outcome. Epilepsy‐related outcomes were analyzed separately in a conventionally followed group (initiation of vigabatrin after seizure onset) and a preventive group (initiation of vigabatrin before seizures, but after appearance of interictal epileptiform discharges [IEDs]). Results Eighty‐three infants with TSC were enrolled at a median age of 28 days (interquartile range [IQR] 14–54). Seventy‐nine of 83 patients (95%) developed epileptiform discharges at a median age of 77 days (IQR 23–111). Patients with a pathogenic TSC2 variant were significantly younger ( P ‐value .009) at first ED‐EEG and more frequently had multifocal IED ( P ‐value .042) than patients with a pathogenic TSC1 variant. A younger age at first ED‐EEG was significantly associated with lower cognitive ( P ‐value .010), language ( P ‐value .001), and motor ( P ‐value .013) developmental quotients at 24 months. In the conventional group, 48 of 60 developed seizures. In this group, the presence of focal slowing on the first ED‐EEG was predictive of earlier seizure onset ( P ‐value .030). Earlier recording of epileptiform discharges ( P ‐value .019), especially when multifocal ( P ‐value .026) was associated with higher risk of drug‐resistant epilepsy. In the preventive group, timing, distribution of IED, or focal slowing, was not associated with the epilepsy outcomes. However, when multifocal IEDs were present on the first ED‐EEG, preventive treatment delayed the onset of seizures significantly ( P ‐value 〈 .001). Significance Early EEG findings help to identify TSC infants at risk of severe epilepsy and neurodevelopmental delay and those who may benefit from preventive treatment with vigabatrin.
    Type of Medium: Online Resource
    ISSN: 0013-9580 , 1528-1167
    URL: Issue
    URL: Article
    DOI: 10.1111/epi.v62.5
    DOI: 10.1111/epi.16892
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2002194-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Evolution of electroencephalogram in infants with tuberous sclerosis complex and neurodevelopmental outcome: a prospective cohort study
    Wiley ; 2022
    In:  Developmental Medicine & Child Neurology Vol. 64, No. 4 ( 2022-04), p. 495-501
    Details
    In: Developmental Medicine & Child Neurology, Wiley, Vol. 64, No. 4 ( 2022-04), p. 495-501
    Abstract: To describe the evolution of electroencephalogram (EEG) characteristics in infants with tuberous sclerosis complex (TSC) and the relationship with neurodevelopmental outcome at 24 months. Method Eighty‐three infants were enrolled in the EPISTOP trial and underwent serial EEG follow‐up until the age of 24 months (males n =45, females n =37, median age at enrolment 28d, interquartile range 14–54d). Maturation of the EEG background and epileptiform discharges were compared between the TSC1 and TSC2 variants and between preventive and conventional groups respectively. Results Children with TSC2 more frequently had a slower posterior dominant rhythm (PDR) at 24 months (51% vs 11%, p =0.002), a higher number of epileptiform foci (median=8 vs 4, p =0.003), and a lower fraction of EEGs without epileptiform discharges (18% vs 61%, p =0.001) at follow‐up. A slower PDR at 24 months was significantly associated with lower cognitive (median=70 vs 80, p =0.028) and motor developmental quotients (median=70 vs 79, p =0.008). A higher fraction of EEGs without epileptiform discharges was associated with a lower probability of autism spectrum disorder symptoms (odds ratio=0.092, 95% confidence interval=0.009–0.912, p =0.042) and higher cognitive ( p =0.004), language ( p =0.002), and motor ( p =0.001) developmental quotients at 24 months. Interpretation TSC2 is associated with more abnormal EEG characteristics compared to TSC1 , which are predictive for neurodevelopmental outcome.
    Type of Medium: Online Resource
    ISSN: 0012-1622 , 1469-8749
    URL: Issue
    URL: Article
    DOI: 10.1111/dmcn.v64.4
    DOI: 10.1111/dmcn.15073
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2001992-0
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex?
    Wiley ; 2020
    In:  Annals of Clinical and Translational Neurology Vol. 7, No. 8 ( 2020-08), p. 1371-1381
    Details
    In: Annals of Clinical and Translational Neurology, Wiley, Vol. 7, No. 8 ( 2020-08), p. 1371-1381
    Abstract: To evaluate the relationship between age at seizure onset and neurodevelopmental outcome at age 24 months in infants with TSC, as well as the effect on neurodevelopmental outcome of early versus conventional treatment of epileptic seizures with vigabatrin (80–150 mg/kg/day). Methods Infants with TSC, aged ≤4 months and without previous seizures were enrolled in a prospective study and closely followed with monthly video EEG and serial standardized neurodevelopmental testing (Bayley Scales of Infant Development and Autism Diagnostic Observation Schedule). Results Eighty infants were enrolled. At the age of 24 months testing identified risk of Autism Spectrum Disorder (ASD) in 24/80 children (30.0%), and developmental delay (DD) in 26/80 (32.5%). Children with epilepsy (51/80; 63.8%) had a higher risk of ASD ( P  = 0.02) and DD ( P  = 0.001). Overall, no child presented with moderate or severe DD at 24 months (developmental quotient  〈  55). In 20% of children abnormal developmental trajectories were detected before the onset of seizures. Furthermore, 21% of all children with risk of ASD at 24 months had not developed seizures at that timepoint. There was no significant difference between early and conventional treatment with respect to rate of risk of ASD ( P  = 0.8) or DD ( P  = 0.9) at 24 months. Interpretation This study confirms a relationship between epilepsy and risk of ASD/DD. However, in this combined randomized/open label study, early treatment with vigabatrin did not alter the risk of ASD or DD at age 2 years.
    Type of Medium: Online Resource
    ISSN: 2328-9503 , 2328-9503
    URL: Issue
    URL: Article
    DOI: 10.1002/acn3.v7.8
    DOI: 10.1002/acn3.51128
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2740696-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...