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Biomedical subjects

C Chiron

Publications and source records attributed to C Chiron.

At least 37 records · Page 2Linked to original sources
PubMed2000

Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. STICLO study group.

BACKGROUND: Stiripentol is an inhibitor of cytochrome P450 that showed antiepileptic efficacy in severe myoclonic epilepsy in infancy (SMEI) in association with clobazam and valproate in an open study. To confirm these results, 41 children with SMEI were included in a randomised, placebo-controlled, add-on trial. METHODS: After a baseline period of 1 month, placebo (n=20) or stiripentol (n=21) was added to valproate and clobazam during a double-blind period of 2 months. Patients then received stiripentol in an open fashion. Responders were defined as having more than 50% reduction in the frequency of clonic (or tonic-clonic) seizures during the second month of the double-blind period compared with baseline. FINDINGS: 15 (71%) patients were responders on stiripentol (including nine free of clonic or tonic-clonic seizures), whereas there was only one (5%) on placebo (none were seizure free; stiripentol 95% CI 52.1-90.7 vs placebo 0-14.6). The 95% CI of the difference was 42.2-85.7. Percentage of change from baseline was higher on stiripentol (-69%) than on placebo (+7%), p<0.0001. 21 patients on stiripentol had moderate side-effects (drowsiness, loss of appetite) compared with eight on placebo, but side-effects disappeared when the dose of comedication was decreased in 12 of the 21 cases. INTERPRETATION: This controlled trial shows the antiepileptic efficacy, of add-on stiripentol in children with SMEI. The results also provide good reason to focus studies on a specific epilepsy syndrome-a small sample of patients is sufficient to show the efficacy that might have been missed in a heterogeneous population.

Anti-Anxiety Agents↗
PubMed2000

Mental and behavioural outcome of infantile epilepsy treated by vigabatrin in tuberous sclerosis patients.

Vigabatrin (VGB) has demonstrated high efficacy in infantile spasms (IS) due to tuberous sclerosis. Our first objective was to evaluate the cognitive long term effect outcome of children whose refractory spasms definitely disappeared when VGB was given as an add on drug. Our second objective was to determine the response of generalized epilepsy (infantile spasms) compared to partial epilepsy on cognitive impairment. A non selected series of 13 children underwent psychometric and behavioural evaluation before VGB initiation at a mean of 3 years on VGB treatment. Eight of them could perform detailed neuropsychological tests at follow-up. Seven had infantile spasms (Group I), they all were spasm free before 2 years of age and five remained with rare partial seizures (mean age, 5.5 years). Six others had partial epilepsy without spasms (Group II) and five remained with rare seizures (mean age, 7.5 years). Patients of Group I experienced dramatic changes. Developmental quotient (DQ) significantly rose in six out of seven by ten to more than 45 points (P = 0.03) and autistic behaviour disappeared in five out of the six who presented with. The four tested children had normal verbal level after 5 years and could integrate at school but they remained with marked visuospatial disabilities. By contrast, patients of Group II remained with an unchanged DQ of about 60 so that both groups had similar DQ levels on follow-up. The cessation of spasms with VGB is therefore associated with significant improvement of cognition and behaviour in children with tuberous sclerosis. Controlling secondary generalization induced by infantile spasms seems to be a key factor for mental development.

Anticonvulsants↗
PubMed1999

Hemispheric specialization using SPECT and stimulation tasks in children with dysphasia and dystrophia.

Developmental dysphasia, a severe childhood learning disorder, is thought to result from problems in hemispheric specialization involving both left and right cerebral hemispheres. Regional cerebral blood flow (rCBF) was measured at rest and during stimulation of both hemispheres independently: dichotic listening for the left, dichaptic palpation for the right. Eight right-handed boys with expressive dysphasia, aged 8 to 12 years, were investigated using SPECT and compared with eight right-handed age-matched boys with Duchenne muscular dystrophy with reading disorders but normal speech. rCBF values at rest were also compared with those of five right-handed age-matched normal boys. In the dichotic task, children with dysphasia differed from children with dystrophia by failure to increase rCBF in the left hemisphere, in Broca's area, but rCBF increased in the right hemisphere, in the region homologous to Broca's area. In the dichaptic task, rCBF increased bilaterally for children with dysphasia whereas in children with dystrophia rCBF increased only in the right hemisphere. At rest the physiological asymmetry was reversed in favor of the right hemisphere in all areas except Broca's area. Surprisingly, the same applied at rest and for all areas in children with dystrophia. These results confirm that functional specialization of both hemispheres is impaired in developmental dysphasia. Moreover, they suggest that learning disabilities associated with Duchenne muscular dystrophy could also be related to abnormal hemispheric specialization.

Adolescent↗
PubMed1999

Callosotomy for epilepsy after West syndrome.

PURPOSE: To analyze the results of callosotomy in 17 children with symptomatic generalized epilepsy after West syndrome, according to the different seizure types and surgical procedures, to define selection criteria for candidates to callosotomy. METHODS: Callosotomy was performed in two successive stages. Partial callosotomy, anterior in 13 and posterior in three, was followed by completion in 14 cases in all but four patients (complete callosotomy in one stage in one, no completion in three). All patients had clinical, video-EEG, and neuropsychological evaluation before and after each stage of callosotomy, with a mean final follow-up of 4 years. RESULTS: Seizure frequency improved in only two of 13 patients after anterior callosotomy, in none of three after posterior callosotomy, but in nine of 14 after complete callosotomy. After complete callosotomy, spasms disappeared in 80% of the cases, and drop attacks, the most severe ictal event, completely stopped or were dramatically reduced in 90% of the children. One patient no longer had episodes of status epilepticus, and another one acquired the ability to walk after complete callosotomy. From the cognitive viewpoint, nine patients with improved seizure frequency after complete callosotomy also had improved behavior and cognitive functions, but two others experienced speech deterioration after posterior callosotomy at age 11 years and completion of callosotomy at age 16 years. CONCLUSIONS: As in other severe generalized epilepsies in childhood, drop attacks provide the best indication for complete callosotomy in patients with previous West syndrome. Because drop attacks can be identifiable by falls only, the previous acquisition of walking should be considered as a key feature for any benefit to be obtained.

Child↗
PubMed1999

Stiripentol: efficacy and tolerability in children with epilepsy.

PURPOSE: Stiripentol (STP) is a new antiepileptic drug (AED) that inhibits cytochrome P450, resulting in increased plasma concentrations of concomitant AEDs. The efficacy and tolerability of STP as an add-on therapy in children were assessed. METHODS: Two hundred twelve patients with refractory epilepsy, aged from 1 month to 20.5 years, received STP either in a single-blind, placebo-controlled trial (108 patients) or in a further open trial (104 other patients selected by epilepsy syndrome for possible efficacy based on the results of the previous trial). RESULTS: Among the 97 patients who could be analyzed for efficacy in the placebo-controlled study, the median seizure frequency was lower at 3 months with STP than with the placebo (p<0.0001); 49% responded to the drug, including 10% who became seizure free. Patients with partial epilepsy had the highest response rate (57%). Results were confirmed in the open study where 68% of the 91 patients receiving STP responded at 3 months. These patients were mainly those with partial epilepsy (73%) who were receiving carbamazepine (CBZ) (75%) as comedication (p<0.001). Ten of the 20 children with severe myoclonic epilepsy in infancy also responded with clobazam (CLB) as comedication. Efficacy was sustained long term in 74% of the 94 patients still receiving STP at a mean 30-month follow-up. Adverse events were reported in 48% of the 212 patients, mainly anorexia and loss of weight, but these events required STP discontinuation in only nine cases. Side effects were minimized in the open trial by optimizing the dose of comedication. CONCLUSIONS: STP seems to be a promising add-on drug, particularly when combined with CBZ in patients with partial childhood epilepsy refractory to vigabatrin (VGB) and with CLB in patients with severe myoclonic epilepsy in infancy.

Adolescent↗
PubMed1999

Early diagnosis of subependymal giant cell astrocytoma in children with tuberous sclerosis.

OBJECTIVES: Intraventricular astrocytomas (subependymal giant cell astrocytomas) of tuberous sclerosis have a poor prognosis due to the obstruction of CSF flow. The aim of this study was to determine whether they could be differentiated during childhood and at an early preclinical stage, from subependymal nodules without any growing potential. METHODS: The first two MRIs of all children referred to this neuropaediatric centre between 1987 and 1996 were retrospectively blindly reviewed. RESULTS: Out of 60 patients, 24 disclosed subependymal nodules localised near the foramen of Monro, and eight of the 24 developed astrocytomas. Subependymal nodules were first detectable on MRI from 1 year of age in all cases and the first MRI evidence of growth occurred between 1 and 9 years (mean 4 years). At an early stage, subependymal nodules had different characteristics in patients who developed subependymal giant cell astrocytomas from those who did not. The nodules over 5 mm in diameter that were incompletely calcified and enhanced by gadolinium were at higher risk of growing, particularly in children with a familial history of tuberous sclerosis. To detect the subependymal giant cell astrocytomas earlier in tuberous sclerosis, it is advisible to systematically perform an MRI examination before 2 years of age and to repeat it every year if the patient has risk factors for developing astrocytomas.

Brain Neoplasms↗
PubMed1999

Use of subtraction ictal SPECT co-registered to MRI for optimizing the localization of seizure foci in children.

UNLABELLED: Ictal SPECT studies are increasingly used to localize seizure foci in children with refractory epilepsy, but few studies have reported on ictal-interictal subtraction images co-registered to MRI at this age. METHODS: Twenty-seven children with partial epilepsy (aged 3 mo-18 y) underwent ictal ethyl cysteinate dimer (ECD) SPECT (20 mCi/1.73 m2) combined with video-electroencephalography (EEG) and interictal ECD SPECT followed 2 d later by three-dimensional MRI. Ictal-interictal and interictal-ictal subtraction images were computed by registering and normalizing the ictal to the interictal SPECT scans for each child. The ictal, interictal SPECT and subtraction images were registered to each child's MRI. Difference images (ictal-interictal) were then superimposed on MRI for anatomic localization of the perfusion changes. Intra- and interobserver reproducibility and "facility of interpretation" of overlay images were compared with standard analysis of the non-coregistered ictal and interictal scans. RESULTS: Overlay images allowed the detection of at least one hyperperfused focus in 93% of the children, compared with 74% using ictal and interictal scans separately. Seizure onset was suspected clinically, on EEG or on MRI in 20 children. Overlay images were concordant (n = 11) or larger (n = 7) than the suspected focus in 18 of 20 (90%), whereas these images failed to show any abnormality in 1 child and were discordant with MRI in another patient. In the remaining 7, images showed cortical localization in 6 patients. Among the 5 patients who underwent electrocorticography, overlay images were concordant in 3, larger in 1 and absent in 1. The intra- and interobserver reproducibility and facility of interpretation were significantly higher using overlay images than standard analysis, even when ictal and interictal SPECT were co-registered. CONCLUSION: The co-registration of ictal-interictal subtraction SPECT images to MRI seems to be a helpful technique in localizing the onset of seizure and guiding the intracranial recording in childhood epilepsy. Moreover, this method improves sensitivity, enhances intra- and interobserver reproducibility and makes interpretation easier.

Adolescent↗
PubMed1999

[Ictal SPECT in the epileptic child. Contribution of subtraction interictal images and superposition of with MRI].

Ictal SPECT is a highly sensitive method to localize the epileptogenic focus in refractory temporal lobe epilepsy in adults. In extratemporal epilepsy, sensitivity can be improved by subtracting interictal from ictal images and superimposing subtraction images on MRI. In children, such a procedure is potentially interesting because most epilepsies are extratemporal and ictal SPECT not yet routinely developed. The aim of this study was to test the feasibility of ictal SPECT with subtraction image processing in a pediatric population. Twenty-six children with refractory partial epilepsy and aged from 3 months to 18 years underwent ictal ECD-SPECT (20 mCi/1.73 m2) combined with video-EEG and interictal ECD-SPECT plus 3D-MRI two days later. Ictal-interictal subtraction images were computed by registering and normalizing the ictal to the interictal SPECT scans for each child. The ictal, interictal SPECT and subtraction images were registered to the children's MRI. Difference images were then superimposed to MRI for anatomical localization of the perfusion changes (overlay images). Looking for perfusion changes, overlay images allowed to detect at least one hyperperfused focus in 92 p. 100 of the 26 children compared to 73 p. 100 visually comparing ictal and interictal scans separately. Seizure onset was suspected on clinical and/or EEG and/or MRI in 19 children. Positive overlay images were concordant (n = 11) or larger (n = 7) than the suspected focus in 17/19 (90 p. 100), whereas they failed to show any abnormality in 1 child and were discordant with MRI in another one. In the 7 remaining patients, images showed cortical localization in 6 cases. Ictal SPECT is therefore faisable in very young children. Ictal-interictal subtraction SPECT images co-registered to MRI improves sensitivity compared to classical visual analysis. It seems therefore to be a helpful technique to localize the onset of seizure and to guide the intracranial recording in childhood epilepsy.

Adolescent↗
PubMed1998

[Treatment of infantile spasms with vigabatrin as first-line therapy and in monotherapy: apropos of 70 infants].

BACKGROUND: Steroids (hydrocortisone or ACTH) still remain the usual treatment for infantile spasms (IS). However, since 1990, some authors have reported the efficacy of vigabatrin (VGB), especially in cases related to tuberous sclerosis. POPULATION AND METHODS: Seventy children with infantile spasms were treated by VGB first line monotherapy. Modalities of treatment and monitoring were the same for all children. VGB was given at the daily dose of 100 mg/kg during 1 week. If spasms persisted, the daily VGB dose was increased to 150 mg/kg during a 2nd week. In case of persistence of IS, on the 15th day, hydrocortisone was then added to VGB. Of the 70 infants, 39 were symptomatic and 31 cryptogenic. RESULTS: On VGB, 37 children (54%) stopped having IS within a mean 3.5 days. Response to VGB was different according to etiology. Among cryptogenic cases, 22 infants (71%) definitively stopped having spasms and only one relapsed. Among symptomatic cases, only 15 infants (38%) stopped having IS, and half (8/15) relapsed. VGB mean daily dose at cessation of spasms was 114 mg/kg. Side effects were transient drowsiness (27%) and agitation (12%). Mean follow-up was 10 months (1-24 months). Seventy-five percent of the infants presenting with a focus of spike after the 1st month of treatment relapsed. CONCLUSION: Infants with cryptogenic spasms have a good response to VGB monotherapy. When mental retardation is noticed before IS, and MRI is normal, there is no efficacy. In these cases, the best treatment seems to be prolonged corticotherapy associated with VGB.

Anti-Inflammatory Agents↗
PubMed1998

Autism and visual agnosia in a child with right occipital lobectomy.

OBJECTIVES: Autistic disorder is a developmental handicap with an unknown neurological basis. Current neuropsychological models for autism suggest an abnormal construction of visual perceptual representation or a deficit in executive functions. These models predict cerebral lesions in the temporo-occipital or frontal regions of autistic patients. The present study aimed at studying the presence of symptoms of autism and visual agnosia in a 13 year old girl who had a right temporo-occipital cortical dysplasia that was surgically removed at the age of 7. METHODS: Neuropsychological evaluation included Wechsler and Kaufman intelligence scales, a test of word fluency, digit span, Corsi block, California verbal learning, Trail making, Benton facial recognition, Snoodgrass object recognition tests, Rivermead face learning subtest, and developmental test of visual perception. The ADI-R was used to show current and retrospective diagnosis of autistic disorder. Neuroimagery included brain MRI, single photon emission computed tomography (SPECT), and PET. RESULTS: Brain MRI showed a right occipital defect and an abnormal hyperintensity of the right temporal cortex. PET and SPECT disclosed a left frontal hypometabolism together with the right occipital defect. Neuropsychological testing showed a visual apperceptive agnosia and executive function deficits. Psychiatric study confirmed the diagnosis of autistic disorder. CONCLUSIONS: Although the possibility that autism and visual agnosia were dissociable factors in this patient cannot be excluded, the finding of both deficits supports the possibility that occipito-temporal lesions can predispose to the development of autism.

Adolescent↗
PubMed1997

Randomized trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis.

Vigabatrin has been shown to be efficient in infants with infantile spasms and tuberous sclerosis, in open studies. In order to compare vigabatrin to oral steroids, a prospective randomized multicenter study was implemented using both drugs as monotherapy in newly diagnosed patients with infantile spasms and tuberous sclerosis. Eleven infants received vigabatrin (150 mg/kg per day) and 11 hydrocortisone (15 mg/kg per day) for 1 month. Spasm free patients continued vigabatrin or progressively stopped hydrocortisone in 1 month, non-responders were crossed to the other drug for a new 2 month-period. All vigabatrin patients (11/11) were spasm-free versus 5/11 hydrocortisone infants (P < 0.01). Seven patients were crossed to vigabatrin (six for inefficacy, one for adverse events) and became also totally controlled. Mean time to disappearance of infantile spasms was 3.5 days on vigabatrin versus 13 days on hydrocortisone (P < 0.01). Five patients exhibited side effects on vigabatrin but nine on hydrocortisone (P = 0.006). Vigabatrin should therefore be considered as the first choice treatment for infantile spasms due to tuberous sclerosis.

Anticonvulsants↗
PubMed1997

Pharmacokinetics of the S(+) and R(-) enantiomers of vigabatrin during chronic dosing in a patient with renal failure.

AIMS: To study the pharmacokinetics of vigabatrin in a patient affected with tuberous sclerosis who developed major agitation and aggression, while receiving vigabatrin orally (1.5 g every 12 h) and in whom impaired renal function was diagnosed. METHODS: The patient received vigabatrin (0.5 g day(-1)). A pharmacokinetic study of the S(+) and R(-) enantiomers of vigabatrin was performed before and during dialysis. Plasma concentrations were measured at 0, 1, 2, 3, 4, 6, 12, 18 and 24 h by a specific GCMS assay. RESULTS: Before dialysis, the maximum and minimun plasma concentrations of vigabatrin at steady-state were lower for the S(+) than for the R(-) enantiomer, while the apparent oral clearance was higher for the S(+) than for the R(-) enantiomer (2.97 vs 0.48 l h(-1)). In addition, the haemodialysis clearance was similar for the two enantiomers (4.96 vs 5.15 l h(-1)). CONCLUSIONS: Vigabatrin is an irreversible inhibitor of GABA-transaminase, effective in the treatment of drug-resistant epilepsy and reported to be eliminated unchanged by renal excretion. Although vigabatrin is known to have stereoselective kinetics, the difference in plasma dry concentrations and pharmacokinetics of the S(+) and R(-) enantiomers that we observed during long term administration at high doses in a patient with impaired renal function, has not been reported before. The question remains of the potential toxicity of the high levels of the R(-) enantiomer.

Adult↗
PubMed1997

The right brain hemisphere is dominant in human infants.

The development of functional brain asymmetry during childhood is confirmed by changes in cerebral blood flow measured at rest using dynamic single photon emission computed tomography. Between 1 and 3 years of age, the blood flow shows a right hemispheric predominance, mainly due to the activity in the posterior associative area. Asymmetry shifts to the left after 3 years. The subsequent time course of changes appear to follow the emergence of functions localized initially on the right, but later on the left hemisphere (i.e. visuospatial and later language abilities). These findings support the hypothesis that, in man, the right hemisphere develops its functions earlier than the left.

Adolescent↗
PubMed1997

Early single photon emission computed tomography in Sturge-Weber syndrome.

OBJECTIVES: Functional cerebral imaging PET and SPECT have shown hypometabolism and hypoperfusion in the area of vascular malformation in children with epilepsy due to Sturge-Weber syndrome. However, data are scarce in infants and do not exist in patients with Sturge-Weber disease without epilepsy. The pattern of perfusion during the first two years of life was studied including patients before the onset of seizures. METHODS: Twenty two infants with later confirmed Sturge-Weber disease underwent SPECT examination using TOMOMATIC 564 (Medimatic) and xenon-133 at ages ranging from 8 days to 25 months. Twelve had never had seizures before SPECT and seven underwent a second SPECT a mean seven months later. Cerebral blood flow (CBF) was measured in the whole hemisphere and in the part of the cortex involved in the vascular malformation on both sides as well as a "pathological to normal" index for the hemisphere and vascular malformation. These values were compared with normal age paired values. RESULTS: Compared with controls, CBF and the indices in the hemisphere and vascular malformation were significantly decreased in patients who already had had seizures before SPECT, whereas they were significantly increased in 75% of the patients who had never had any seizures. On second SPECT, the indices were decreased in all patients, including the four who still remained non-epileptic. CONCLUSIONS: SPECT therefore detects CBF asymmetry in infants with Sturge-Weber disease, which tends to shift with age. The cortex involved in the vascular malformation is hyperperfused during the first year of life before first seizures. The classic hypoperfusion appears after one year of age, even in non-epileptic patients.

Brain↗