Vigabatrin for tuberous sclerosis complex

ArticleinBrain and Development 23(7):649-53 · December 2001with4 Reads
DOI: 10.1016/S0387-7604(01)00290-X · Source: PubMed
Vigabatrin (VGB) was found to be an effective anti-epileptic drug to reduce infantile spasms in about 50% of patients and it has been found most effective in infantile spasms due to tuberous sclerosis (TSC) in which up to 95% of infants had complete cessation of their spasms. VGB was synthesized to enhance inhibitory gamma-aminobutyric acidergic (GABAergic) transmission by elevating GABA levels via irreversible inhibition of GABA transaminase. The mechanism underlying the particular efficacy of VGB in TSC is still unknown. However, its efficacy suggests that epileptogenesis in TSC may be related to an impairment of GABAergic transmission. VGB should be considered as the first line monotheraphy for the treatment of infantile spasms in infants with confirmed diagnosis of TSC. The efficacy of VGB treatment can be assessed in less than 10 days, but usually a few days treatment with a dose of about 100 mg/kg/day stops infantile spasms. The cessation of the spasms is associated with a marked improvement of behaviour and mental development. Unfortunately, it has become clear that the use of VGB is associated with a late appearance of visual-field defects in up to 50% of patients. Currently the minimum duration and doses of VGB treatment that can produce side effects are unknown. The feasibility of using short treatment periods (2-3 months) should be investigated.
    • "VGB has been reported to be effective in European studies of infantile spasms, where most studies used doses of 100–200 mg/kg/d [2]. Currently, the relevant effective period and doses of VGB to avoid serious side effects still need further investigation [3]. Here, we describe a clinical case of west syndrome with tuberous sclerosis, where VGB was efficacious at a markedly lower dose than previously reported. "
    Full-text · Article · Jul 2015
    • "Эпилептические приступы являются первым симптомом приблизительно в 60 % наблюдений, но во многих случаях диагноз устанавливается не сразу , даже при наличии и других клинических проявлений заболевания [21, 60]. Эпилепсия при ТС часто протекает тяжело, и достаточного контроля эпилептических приступов на фоне медикаментозной терапии удается достичь менее чем у половины пациентов [13, 18, 19]. Высокий риск умственной отсталости (50–80 %) [13, 21, 42, 53, 54] и тот факт, что у многих пациентов с ТС наблюдаются признаки аутизма [20, 24, 66], – дополнительные факторы, повышающие тяжесть заболевания. "
    [Show abstract] [Hide abstract] ABSTRACT: With a few exceptions patients with tuberous sclerosis (TS) suffering from drug-resistant epilepsies have potentially epileptogenic lesionswithin both hemispheres. Until one decade ago in general such a constellation was an xclusion criteria for considerations with respect to epilepsy surgery. However experience has shown that it is not so rare to find patients in whom over the ears seizures are generated from just one single focus and that these patients can be good candidates for epilepsy surgery. Almost revolutionary was the further evelopment: multi-step procedures in patients with bilateral epileptogenic lesions – with promising results in terms of postoperative seizure outcome. Also, with increasing experience, it becomes more and more possible to differentiate already non-invasively which lesions could be epileptogenic and which are rather not the source of the seizures. The most important achievement of epilepsy surgery in TS however is that in selected cases early surgical intervention is able to prevent severe mental retardations, which are often the main burden for families who have members with this peculiar disease.
    Full-text · Article · Apr 2015
    • "However, in contrast to most other antiseizure medications, VGB is particularly effective for seizures in TSC, especially infantile spasms, a typically devastating type of childhood seizure. VGB has been reported to eliminate spasms in about 95% of cases, which is much higher than all other treatments for spasms due to TSC or any other cause [8,9]. In fact, this special relationship between VGB and TSC is one of the few documented examples of a medication having individualized efficacy for a specific epilepsy syndrome or cause of epilepsy. "
    [Show abstract] [Hide abstract] ABSTRACT: Epilepsy is a common neurological disorder and cause of significant morbidity and mortality. Although antiseizure medication is the first-line treatment for epilepsy, currently available medications are ineffective in a significant percentage of patients and have not clearly been demonstrated to have disease-specific effects for epilepsy. While seizures are usually intractable to medication in tuberous sclerosis complex (TSC), a common genetic cause of epilepsy, vigabatrin appears to have unique efficacy for epilepsy in TSC. While vigabatrin increases gamma-aminobutyric acid (GABA) levels, the precise mechanism of action of vigabatrin in TSC is not known. In this study, we investigated the effects of vigabatrin on epilepsy in a knock-out mouse model of TSC and tested the novel hypothesis that vigabatrin inhibits the mammalian target of rapamycin (mTOR) pathway, a key signaling pathway that is dysregulated in TSC. We found that vigabatrin caused a modest increase in brain GABA levels and inhibited seizures in the mouse model of TSC. Furthermore, vigabatrin partially inhibited mTOR pathway activity and glial proliferation in the knock-out mice in vivo, as well as reduced mTOR pathway activation in cultured astrocytes from both knock-out and control mice. This study identifies a potential novel mechanism of action of an antiseizure medication involving the mTOR pathway, which may account for the unique efficacy of this drug for a genetic epilepsy.
    Full-text · Article · Feb 2013
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