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Titolo:
Prolonged vigabatrin treatment modifies developmental changes of GABA(A)-receptor binding in young children with epilepsy
Autore:
Juhasz, C; Muzik, O; Chugani, DC; Shen, CG; Janisse, J; Chugani, HT;
Indirizzi:
Childrens Hosp Michigan, Detroit Med Ctr, Dept Pediat, Detroit, MI 48201 USA Childrens Hosp Michigan Detroit MI USA 48201 ediat, Detroit, MI 48201 USA Childrens Hosp Michigan, Detroit Med Ctr, Dept Radiol, Detroit, MI 48201 USA Childrens Hosp Michigan Detroit MI USA 48201 adiol, Detroit, MI 48201 USA Childrens Hosp Michigan, Detroit Med Ctr, Dept Neurol, Detroit, MI 48201 USA Childrens Hosp Michigan Detroit MI USA 48201 eurol, Detroit, MI 48201 USA Wayne State Univ, Sch Med, Ctr Hlth Effectiveness Res, Detroit, MI USA Wayne State Univ Detroit MI USA Hlth Effectiveness Res, Detroit, MI USA
Titolo Testata:
EPILEPSIA
fascicolo: 10, volume: 42, anno: 2001,
pagine: 1320 - 1326
SICI:
0013-9580(200110)42:10<1320:PVTMDC>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
GAMMA-AMINOBUTYRIC-ACID; POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE SPECTROSCOPY; BRAIN GABA LEVELS; BENZODIAZEPINE-RECEPTOR; INFANTILE SPASMS; ANTIEPILEPTIC DRUGS; HIPPOCAMPAL-NEURONS; SEIZURE CONTROL; IN-VITRO;
Keywords:
vigabatrin; PET; GABA(A) receptors; epilepsy; development;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Chugani, HT Childrens Hosp Michigan, PET Ctr, 3901 Beaubien Blvd, Detroit,MI 48201 USA Childrens Hosp Michigan 3901 Beaubien Blvd Detroit MI USA 48201
Citazione:
C. Juhasz et al., "Prolonged vigabatrin treatment modifies developmental changes of GABA(A)-receptor binding in young children with epilepsy", EPILEPSIA, 42(10), 2001, pp. 1320-1326

Abstract

Purpose: To determine whether prolonged treatment with vigabatrin (VGB), an antiepileptic drug (AED) that acts by elevating brain gamma -aminobutyricacid (GABA) levels, interferes with age-related changes of in vivo GABAA-receptor binding in children with epilepsy. Methods: Using [C-11]flumazenil (FMZ)-positron emission tomography (PET) imaging, 15 children (aged 1-8 years) with medically intractable epilepsy were studied. Seven of these children were treated with VGB (1,000-2,500 mg/day) for greater than or equal to3 months before the FMZ-PET study. The remaining eight patients were medicated with other drugs that are known not to act directly on the GABAergic system. Absolute quantification of PET data was performed by using the volume of distribution (VD) of FMZ in brain tissue representing FMZ ligand binding. Results: After controlling for age, hemispheric FMZ VD values were significantly lower in children treated with VGB as compared with the non-VGB group (p = 0.012). Regional FMZ VD values of the VGB-treated patients were significantly lower in all cortical regions and the cerebellum, whereas the difference was not significant in the thalamus and basal ganglia. No significant drug effect or drug-by-region interaction could be determined when the patients were separated according to treatment with carbamazepine (p = 0.97)or valproate (p = 0.55). Conclusions: VGB induces a decrease in GABA(A)-receptor binding in the cortex and cerebellum of the developing epileptic brain. A similar effect of other drugs and substances of abuse targeting the GABAergic system may be hypothesized. Because of the important role of the GABAergic system in developmental plasticity, the reversibility and functional consequences of this age-specific drug effect should be further studied.

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Documento generato il 02/04/20 alle ore 12:42:47