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Biomedical subjects

C Chiron

Publications and source records attributed to C Chiron.

At least 55 records · Page 3Linked to original sources
PubMed1997

Vigabatrin in partial seizures in children.

Patients with partial seizures aged 1 week to 19 years (n = 175) were included in several prospective vigabatrin studies at the hospital Saint Vincent de Paul. A decrease in seizure frequency of over 50% was achieved in 70% of patients, with 30% becoming seizure free, and only 6% experiencing an increase. Tuberous sclerosis gave the best response (85%), tumors the lowest (45%), the usual figure for other causes being 70%. Patients with malformations were the most likely to experience seizure increase. Regarding topography of focus, the lowest rate of seizure-free patients was in rolandic foci. Early treatment produced better results. Infants experienced the highest rate of response, but also of relapse, the latter occurring mainly between 6 months and 1 year. The incidence of loss of efficacy depended on etiology and topography of focus, tumors and frontal foci having the highest risk. Occurrence of new seizures was more frequent in young patients with tuberous sclerosis, the third experiencing status epilepticus. Vigabatrin monotherapy could only be achieved in 33% of seizure-free patients, reduction of comedication being a risk of relapse and of further intractability.

4-Aminobutyrate Transaminase↗
PubMed1997

Optimizing the indication of vigabatrin in children with refractory epilepsy.

This review was conducted to evaluate the long-term prognosis of children responding to vigabatrin by examining the incidence of increased seizure frequency, loss of efficacy, and appearance of new seizures in a cohort of 196 children (mean age, 68.2 months; range, 2 months to 19 years) with drug-resistant epilepsy, who had received vigabatrin as add-on treatment in clinical trials. The results indicate that an increase in seizure frequency was uncommon, occurring in only 10% of children with highly drug-resistant epilepsy and that it usually appears shortly after the initiation of treatment. It was clearly not dose-dependent and most often occurred in patients with nonprogressive myoclonic epilepsy. No specific seizure type was specially involved and usually the problem reversed on discontinuing vigabatrin. Loss of efficacy was also uncommon (12% of patients), and again no specific seizure type was found to be associated. Epilepsy syndrome does seem to be a better predictor of loss of efficacy because it occurred most often in symptomatic generalized epilepsies and cryptogenic infantile spasms. A total of 21 patients (11%) developed genuinely new types of seizures. Fifteen of these patients developed new partial seizures that had little impact on the patients' overall clinical improvement. The new partial seizures were better tolerated than the initial seizure type which in most cases had disappeared. Approximately 3% of patients experienced new generalized seizures that aggravated their initial condition. These occurred most often in patients with nonprogressive myoclonic epilepsy; therefore vigabatrin should be used with particular caution in such patients.

Adolescent↗
PubMed1997

[Role of physiopathological hypotheses in therapeutic choice in epilepsy in children].

Choosing an anti-epileptic treatment is different in adults and in children. In children, it depends upon epilepsy syndromes and pathophysiological hypotheses may be helpful. In childhood absence epilepsy, vigabatrin is contraindicated because it induces worsening of absences by increasing the gabaergic inhibition, in children as in animal models. In infantile epilepsies, cerebral development is to be taken into account since functional maturation is still incomplete during the first years of life. In immature brain, focal epileptic discharges tend to generalize. Thus, in infantile spasms, seizures and EEG abnormalities are generalized although there can be a focal lesion. Such a diffuse hyperexcitability is resistant to antiepileptic drugs except to steroids, which decrease the brain level activity. When hyperexcitability is not so marked (spasms without hypsarrhythmia), vigabatrin has the best efficiency, as in spasms due to tuberous sclerosis that are controlled in more than 80 p. 100 of the cases by this drug. Persisting spasms are deleterious for cortical maturation and further cognitive development. Seizures of the first year of life could therefore considered as an emergency to treat, eventually by surgery in cases of focal or hemispheric malformation, before the development become impossible due to the epileptic phenomenon.

Age Factors↗
PubMed1996

Accelerated myelination in early Sturge-Weber syndrome: MRI-SPECT correlations.

The prognosis of Sturge-Weber syndrome (SWS) is partly related to early occurrence of seizures but the diagnosis of this phakomatosis may be difficult during the 1st year of life. We have performed a retrospective study of seven patients with confirmed SWS (age 7 days to 3 months). None of the patients was asymptomatic at the time of the study. They all underwent MRI (T1 and T2 sequences) and single photon emission computed tomography (SPECT) at the same time. Regional cerebral blood flow was measured using xenon-133. In all cases, myelination appeared to be accelerated in the areas underlying the leptomeningeal angioma on both MRI sequences. In five cases, SPECT showed hyperperfusion in the damaged hemisphere. In one case, the SPECT was symmetrical and in another it showed hypoperfusion in the damaged hemisphere which was already atrophied. These data suggest that the accelerated myelination is not related to ischemia but to transient hyperperfusion. This MRI pattern can be helpful for the early diagnosis of SWS, which is of utmost importance for preventive antiepileptic treatment.

Anticonvulsants↗
PubMed1996

Effect of stiripentol on carbamazepine plasma concentration and metabolism in epileptic children.

OBJECTIVE: To study the relationship between the plasma concentration of stiripentol (STP), a new antiepileptic drug, and its inhibitory effect on the formation of carbamazepine epoxide (CBZE) in epileptic children treated with carbamazepine (CBZ) either alone or in combination with another antiepileptic drug. METHODS: Minimum plasma concentration of antiepileptic drugs was measured before initiation of STP therapy (day 0) and on days 28 (STP 60 mg.kg-1.day-1) and 84 (STP 90 mg.kg-1.day-1) by HPLC. RESULTS: The CBZE/CBZ plasma concentration ratio decreased exponentially with increasing minimum plasma STP concentration (r = 0.80). The asymptote of the curve allowed the calculation of the minimum plasma STP concentration required to obtain the maximum inhibitory effect, i.e. 6.7 mg.l-1. CONCLUSION: The inhibitory effect of STP on CBZ metabolism expressed as the CBZE/CBZ plasma concentration ratio is dependent on STP plasma concentration, with a maximum effect at an average of 7 mg.l-1. The present data suggest that in order to evaluate the anticonvulsant efficacy of STP as add-on therapy, the minimum plasma STP concentration should be maintained above 7 mg.l-1 and the dosage of CBZ should simultaneously be decreased in steps by more than 50% to minimize the change in CBZ plasma concentration.

Adolescent↗
PubMed1996

Brain functional imaging SPECT in agyria-pachygyria.

Agyria-pachygyria or lissencephaly type I, a diffuse cortical malformation, provides infantile spasms (IS) which are refractory and persisting after the first decade, an age at which IS have disappeared in the other causes. In order to study the functional postnatal development of the lissencephalic cortex, we measured regional cerebral blood flow (rCBF) using SPECT (Single photon emission computed tomography) and 133Xe in 14 children with lissencephaly, aged from 4 months to 12 years (mean = 40 months) compared to normal children of the same age range and to children with cryptogenic IS aged from 3 months to 3 years (mean = 13 months). rCBF was calculated in frontal (FR) and parieto-temporo-occipital (PTO) cortex as well as the ratio FR/PTO. FR/PTO was higher in lissencephalic patients than in controls (P < 0.001) due to higher FR rCBF (P < 0.001), particularly in patients aged less than 3 years. FR/PTO was also higher in lissencephalic patients than in patients with cryptogenic IS (P < 0.001) also due to higher FR rCBF (P < 0.001). The values of FR/PTO and FR rCBF remained stable during the first years of life and did not exhibit any age- or topography-related changes as they do in controls or in patients with cryptogenic IS. There results suggest that the normal process of postnatal development in the brain is lacking in agyria-pachygyria. That could play a role in determining the persistence of epileptic spasms, the specific seizure type of this malformation.

Aging↗
PubMed1996

[Problems related to neurosurgical treatment of epilepsy in children].

Neurosurgery of epilepsy in children has undergone rapid development during the past decade. This was justified by the high incidence of intractable epilepsy and its consequences on cognitive development. Any decision in the area of surgery must take in account specific etiology and the rapid maturation of the infant's brain. As in adulthood, both the epileptogenic and the functional zones must be identified, but this is a challenge when the brain is not mature and the functions not yet developed. In addition, the ability to recover must be determined. At the present time no precise methodology can be advised for presurgical work-up and surgical indications.

Age Factors↗
PubMed1996

Vigabatrin withdrawal randomized study in children.

Controlled studies with new antiepileptic drugs are problematic and limited in children. Withdrawal randomization versus placebo in responders previously recognized in an open phase is a new design reported in adults which allows comparison to placebo without delaying the administration of the active compound. We applied such a design in refractory epileptic children in order to study vigabatrin (VGB) in children. Twenty-eight patients aged 1.5-18.5 years and having partially responded to VGB, prescribed in an open study for refractory epilepsy, were included. Patients were randomized to VGB (continued) or placebo (VGB blindy stopped in 3 weeks) for 2 months and seizure frequency was compared to the prerandomization period. More than 50% increase in seizure frequency induced drop-out. Fifteen patients received VGB, 13 others placebo, with the same clinical characteristics in both groups. The patients remaining in the study (primary efficacy endpoint) were more numerous on VGB (93%) than on placebo (46%) (P < 0.01) and seizure frequency (secondary endpoint) was lower on VGB than placebo (P < 0.05). The same results were observed in a subgroup of partial epilepsies. No status epilepticus was observed when withdrawing VGB and all patients returned to baseline status by reintroducing VGB. Such a randomized withdrawal design is therefore feasible in epileptic children. It provides the first VGB controlled study in this age range and demonstrates efficacy. It could be useful for future designs of drug trials in childhood epilepsy.

Adolescent↗
PubMed1996

Pharmacokinetics of the individual enantiomers of vigabatrin in neonates with uncontrolled seizures.

The antiepileptic drug vigabatrin (VGB) is a selective irreversible inhibitor of GABA-transaminase. It is administered as a racemic R(-), S(+) mixture, but the pharmacological activity of vigabatrin resides in the S(+) enantiomer and the R(-) enantiomer is inactive. The pharmacokinetic parameters of the two enantiomers have been studied after administration of a single oral 125 mg dose of the racemate to six neonates. The mean values of Cmax and AUC of the S(+) enantiomer were significantly lower (Cmax: 14.0 +/- 4.3 mg l-1; AUC: 143 +/- 44 mg l-1 h) than those of the R(-) enantiomer (Cmax: 34.1 +/- 9.5 mg l-1; AUC: 231 +/- 88 mg l-1 h), whereas no significant difference in the time to reach Cmax (S(+): 2.1 +/- 1.1 h; R(-): 2.2 +/- 1 h) was observed between the two enantiomers. During chronic administration (125 mg twice daily over 4 days), there was no evidence of accumulation of either enantiomer.

Anticonvulsants↗
PubMed1996

Malignant epileptic encephalopathies in children.

Malignant epileptic encephalopathies in children comprise a series of age-related generalized epilepsy syndromes: neonatal myoclonic encephalopathy and early epileptic encephalopathy in the neonatal period, migrating focal seizures in early infancy, infantile spasms and West syndrome, severe myoclonic epilepsy and non-progressive myoclonic encephalopathies in infancy, and Lennox-Gastaut syndrome, myoclonic astatic epilepsy, continuous spike waves in slow sleep and Rasmussen disease in childhood. Clinical and EEG characteristics are the major diagnostic clues. Aetiology remains unknown but for the majority of the cases, a combination of different factors, particularly lesions, genetic predisposition and age-related features seem to be variously combined to produce an intractable condition.

Child↗
PubMed1995

SPECT of the brain in childhood autism: evidence for a lack of normal hemispheric asymmetry.

Autism is thought to be associated with abnormal hemispheric specialization and left-hemispheric dysfunction. Brain functional imaging using 133Xe-SPECT (single photon emission computed tomography) was used to measure left/right asymmetry and absolute values of regional cerebral blood flow (rCBF) in 18 children with autism aged from four to 17 years and 10 age-matched controls. All controls but only 10 children with autism were right-handed. The left-to-right indices, both hemispheric and regional, were positive in controls, indicating higher left than right rCBF values, but were negative in patients with autism. This inversion was statically significant for total hemispheres, sensorimotor and language-related cortex and was explained by a significant decrease of the left absolute rCBF values in these regions in the patients with autism. The inversion was independent of handedness, sex and age. These results confirm the existence of left-hemispheric dysfunction in childhood autism, especially in the cortical areas devoted to language and handedness, leading to anomalous hemispheric specialization.

Adolescent↗
PubMed1995

Migrating partial seizures in infancy: a malignant disorder with developmental arrest.

Fourteen infants of both sexes had a previously unreported epileptic condition characterized by nearly continuous multifocal seizures. The first seizures occurred at a mean age of 3 months, without antecedent risk factors. At 1 to 10 months, the seizures became very frequent. They were partial with variable clinical expression, and the EEG showed that the discharges randomly involved multiple independent sites, moving from one cortical area to another in consecutive seizures. Although their topography varied, the EEG ictal pattern of each seizure was very similar. It consisted of rhythmic alpha or theta activity which spread to involve an increasing area of the cortical surface. Patients regressed developmentally and became quadriplegic with severe axial hypotonia. Three patients died at age 7 months and at age 7 and 8 years, respectively. Seizures were controlled in only 2 patients, and only 3 children resumed psychomotor development. Extensive investigation failed to determine an etiology, and there was no familial recurrence. Neuropathological examination of the brain in two cases showed only severe hippocampal neuronal loss and accompanying gliosis.

Anticonvulsants↗
PubMed1995

An unusual presentation of focal cortical dysplasia.

In a case of histologically proved focal cortical dysplasia, there was an absence of cortex-white matter delineation in the right parietooccipital area only on the T2-weighted images. This pattern correlated with the gross and histologic findings obtained on the resected cerebral tissue.

Cerebral Cortex↗
PubMed1995

Functional brain imaging in HIV-1-infected children born to seropositive mothers.

UNLABELLED: The aim of this work was to study cerebral function in vertically infected children with human immunodeficiency virus 1 (HIV-1). METHODS: PET with 18F-labeled fluorodeoxyglucose (FDG) was performed in eight children (2.5-5.5 yr): three with severe neurological symptoms and five without. Quantitative analysis was based on gray matter cortical and subcortical regions of interest for which glucose utilization was measured. RESULTS: Diffuse hypometabolism and subcortical hypermetabolism were found in the three children with severe neurological signs; the five other children had temporo-occipital cortical hypometabolism, mainly on the right side. CONCLUSION: Functional cerebral abnormalities seem to precede clinical symptoms in HIV-1infection of the brain in children.

AIDS Dementia Complex↗
PubMed1994

Is Rett syndrome a chromosome breakage syndrome?

Lymphocytes from venous blood from 15 girls with Rett syndrome (RTS), 7 girls with RTS "forme fruste," and 46 unrelated control females were examined. All subjects had a normal karyotype using RHG and RTBG technique. The frequency of gaps and breaks was determined for each group. A significantly higher (P < 0.01) frequency of chromosome breakage was observed in RTS subjects compared to controls. This work suggests that an increased tendency to chromosome breakage may be part of a genetically determined disorder in RTS patients.

Case-Control Studies↗
PubMed1994

Subcortical laminar heterotopia and lissencephaly in two families: a single X linked dominant gene.

Neuronal migration disorders can now be recognised by MRI. This paper reports two families in which the mothers had subcortical laminar heterotopia and four of their children had either similar heterotopia (two girls) or severe pachygyria or lissencephaly (two boys). Laminar heterotopia was more evident on MRI T2 weighted images. The patients had mild to severe epilepsy and mental retardation depending on the extent of cortical abnormalities. In these families, subcortical laminar heterotopia, pachygyria, and lissencephaly seem to share the same X linked or autosomal dominant gene. No chromosomal abnormalities, especially of chromosome 17, could be identified. For appropriate genetic counselling of the family of a child with lissencephaly or subcortical laminar heterotopia, MRI should be performed in parents or siblings with mental retardation or epilepsy.

Adolescent↗
PubMed1994

Infantile spasms: a pathophysiological hypothesis

Clinical and electroencephalogram (EEG) observations permit a hypothesis for the pathophysiology of infantile spasms. The triggering area(s) for spasms is probably cortical. Diffuse hyperexcitability of the immature cortex and/or diffusion of the epileptic process from a focal abnormality would allow development of hypsarrhythmia. Cortical maturation from posterior to anterior might account for the location of causative focal abnormalities. In cryptogenic West syndrome, the predominant pathophysiologic process may be diffuse cortical hyperexcitability, explaining the severe developmental deterioration at the onset of spasms. In symptomatic West syndrome with focal pathology, the initial deterioration is often less striking, suggesting that the predominant effect is diffusion of the epileptic process. The pattern of eventual cognitive deficits follows a similar pattern.

Journal Article↗