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Biomedical subjects

O Dulac

Publications and source records attributed to O Dulac.

At least 37 records · Page 2Linked to original sources
PubMed2001

What is West syndrome?

The combination of axial spasms in clusters, hypsarrhythmia, and psychomotor delay beginning in the first year of life defines West syndrome. Variants of this classical triad comprise variations of age of onset ranging from the first month to 4 years, spasms that may be asymmetrical or combined with focal seizures, asymmetrical, synchronous or fragmented hypsarrhythmia, and psychomotor function which may be delayed, deteriorated or normal. These variations mainly seem to depend on etiology, and specific patterns have been identified for the various causes. Most causes relate to non-progressive uni- or multifocal cortical lesions, although some are due to inborn errors of metabolism. Ten to 20% exhibit no evidence of brain lesion and are considered idiopathic. This condition is intermediary between epilepsy in which the disorder is limited to paroxysmal events during which time the patient returns to his prior condition, and status epilepticus in which the paroxysmal activity is not interrupted. Here, there are both paroxysmal events and a continuous non-convulsive paroxysmal activity that contributes to the deterioration. In the present understanding of pathophysiology, spasms seem to involve subcortical structures, whereas hypsarrhythmia affects cortical areas, also causing psychomotor deterioration. Deafferentation of subcortical structures by the continuous spiking and slow wave activity could account for release of autonomic activity in the basal ganglia. Cortical paroxysmal activity could be caused by age-related hyperexcitability linked to the development of cortical neuronal networks throughout infancy. The mode of action of steroid and vigabatrin therapies, the two therapies with demonstrated efficacy, can be explained on this basis.

Brain↗
PubMed2001

Seizure types and syndromes: lumping or splitting.

The efficacy of antiepileptic drugs (AEDs) is partly determined by the type of seizure being treated. Some seizure syndromes may be improved by certain drugs, whereas others may be worsened. Therefore, drug trials, which recruit patients with different types of epilepsy syndrome may fail to show a global therapeutic effect. In order to demonstrate an effect, it is necessary to use a design of trial, which gives optimum power, and this may involve identifying as homogeneous a group of patients as possible. This 'splitting' approach permits a reduction in the number of patients included in a trial. It also allows identification of syndromes, which may be paradoxically worsened by a drug. It is necessary to review from time to time the diagnostic criteria for particular syndromes, otherwise they may prove to be too restrictive. At some point of drug development a 'lumping' approach is necessary in order to include patients whose clinical characteristics challenge any classification.

Animals↗
PubMed2001

Trials in children.

Over 20% of epilepsies in children are intractable, and are frequently associated with deterioration of motor and cognitive functions. Some are similar to those seen in adults, but many age-related epilepsies occur only in children. Therefore, a sizeable proportion of intractable epilepsies of childhood are different from those encountered in adults, and there is an urgent need for antiepileptic drug trials to be undertaken in children at an early stage of development. An ethical framework within which these trials can be conducted has been defined.

Anticonvulsants↗
PubMed2001

Recommendations on the clinical use of oxcarbazepine in the treatment of epilepsy: a consensus view.

Extensive clinical use and a series of clinical trials have shown that oxcarbazepine is a valuable antiepileptic drug for the treatment of adults and children with partial onset seizures both in initial monotherapy, for conversion to monotherapy and as adjunctive therapy. The clinically recommended titration scheme for all forms of therapy in adults is to start with 150 mg/day at night and to increase by 150 mg/day every second day until a target dose of 900-1200 mg/day is reached. If necessary, one can go faster and start with up to 600 mg/day and titrate with weekly increments of up to 600 mg/day. In children, treatment can be initiated with 8-10 mg/kg/day body weight in two to three divided doses. Dosage can be increased by 8-10 mg/kg/day in weekly increments if necessary for seizure control. Hyponatremia (serum sodium <125 mmol/l) can develop gradually during the first months of oxcarbazepine therapy in approximately 3% of patients with a previously normal serum sodium. However, there is no need to measure baseline serum sodium concentrations unless the patient has renal disease, is taking medication which may lower serum sodium levels (such as diuretics, oral contraceptives or nonsteroidal anti-inflammatory drugs) or--in rare cases--has clinical symptoms of hyponatremia. During oxcarbazepine maintenance therapy measurement of serum sodium levels should also be considered if medications known to decrease sodium levels are added or symptoms of hyponatremia develop. Oxcarbazepine does not appear to have any clinically notable effects on other safety parameters such as renal and liver function or haematological test results. In summary, oxcarbazepine is a safe and well tolerated antiepileptic drug for partial epilepsy.

Anticonvulsants↗
PubMed2001

Epileptic encephalopathy.

Epileptic encephalopathies are conditions in which neurologic deterioration results mainly from epileptic activity. It can be due to very frequent or severe seizures, or to subcontinuous paroxysmal interictal activity. The former consists mainly of severe myoclonic epilepsy in infancy (SMEN), in which patients exhibit seizures from the middle of the first year of life with repeated episodes of status epilepticus, and migrating partial epilepsy in infancy, in which, from the first trimester of life, partial seizures affect various areas of the cortex randomly and in a subcontinuous fashion. Cases with subcontinuous paroxysmal interictal activity affect newborns with suppression bursts, thus consisting of either Ohtahara syndrome or neonatal myoclonic encephalopathy, and infants with infantile spasms (IS), although rare cases do not start until age 4 years. In childhood, it consists of various types of generalized seizures combined with either slow spike-waves of the Lennox-Gastaut syndrome (LGS) or with myoclonus and 3-Hz spike-waves of myoclonic-astatic epilepsy, and continuous spike-waves in slow sleep (CSWS) combined with various neuropsychological patterns including Landau-Kleffner syndrome, frontal lobe syndrome, orofacial dyspraxia, or negative myoclonus. Management differs for all these syndromes, with the combination of clobazam (CLB) and stiripentol (STP) being promising for SMEN, vigabatrin (VGB) for IS, lamotrigine (LTG) for LGS, and steroids for CSWS. It is important to avoid potential drug-induced worsening by phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), tiagabine (TGB), and VGB; in children and especially in infants, treatment with valproate is preferred each time the proper diagnosis is not reached.

Adolescent↗
PubMed2001

Ictal perfusion changes during occipital lobe seizures in infancy: report of two serial ictal observations.

Serial-ictal single-photon-emission computed tomography (SPECT) examinations are presented in two infants (ages 1 and 2 years), with early ictal and ictal in one, and ictal and late ictal images in the other. Both had pharmacoresistant occipital epilepsy, due to focal cortical dysplasia. In the first case, size of ictal hyperperfusion increased in the course of the seizure from early ictal to ictal state. A concomitant ictal hypoperfusion was observed around the hyperperfused area. In the second patient, there was a dramatic difference between ictal and late ictal images. In the late ictal state, the previous occipital ictal hyperperfusion and extraoccipital ictal hypoperfusion disappeared, together with homolateral posterotemporal and contralateral occipital hyperperfusion, corresponding to seizure propagation. Ictal extratemporal blood-flow changes are therefore highly dynamic, particularly in very young children.

Age Factors↗
PubMed2001

Infantile spasms in Down syndrome: good response to a short course of vigabatrin.

PURPOSE: To evaluate the efficacy of vigabatrin (VGB) in the treatment of infantile spasms (ISs) associated with Down syndrome (DS) and to assess the feasibility of early discontinuation to reduce the possible retinal toxicity. METHODS: Five children with ISs with DS were treated with vigabatrin as first-line monotherapy in an open prospective study. The short-term response was evaluated, and VGB was continued in responders. The treatment was stopped after 6 months in children who were still spasm free. RESULTS: Four children of five became spasm free with VGB, three of them responding within 1 week. This response was maintained during the 6 months of VGB treatment. After VGB discontinuation, and with a follow-up ranging from 2 to 4 years, none of the responders experienced spasm recurrence or other types of seizures. CONCLUSIONS: This study confirms the efficacy of VGB in ISs associated with DS. Moreover, it shows that the duration of VGB treatment can be reduced to 6 months without relapse of ISs. This short treatment might reduce the risk of developing visual field constriction.

Adolescent↗
PubMed2001

Harnessing the clinical potential of antiepileptic drug therapy: dosage optimisation.

For patients with epilepsy, effective seizure control is the most important determinant of good quality of life. To achieve this, antiepileptic drug (AED) dosages should be individualised to maximise therapeutic benefit and to avoid most--if not all--adverse effects. Several studies suggest that, in routine clinical practice, dosage individualisation is often suboptimal. This may lead to patients receiving unnecessarily large dosages. Conversely, it may lead to patients switching to an alternative therapy (when clinical response is deemed insufficient), without exploration of the full dosage range. Indeed, dosage optimisation--which should involve consideration of the treatment setting and individual patient characteristics--can be a complicated process requiring skill and patience. In general neurological practice, most AEDs should be started at a low dosage and gradually titrated upwards. Starting dosages are similar in most types of epilepsy; however, if a rapid onset of therapeutic action is required, phenytoin, phenobarbital (phenobarbitone), levetiracetam and gabapentin are probably the best tolerated AEDs for starting at full dosage. The initial target maintenance dosage of an AED should be based on the dose-response profile of the drug, and on specific patient characteristics. Usually, the lowest effective daily dose expected to provide seizure control should be used, although various factors (e.g. stage and severity of epilepsy, pharmacokinetic and pharmacodynamic considerations, attitude of the patient) will markedly influence dosage selection. If seizures are not controlled on the initial target dose, the dosage should be increased gradually until complete seizure control is achieved or intolerable adverse effects occur. In most patients who fail to respond to the initially prescribed drug, switching to another AED (monotherapy) is the best option. Combination therapy may be appropriate for patients unresponsive to 2 or more sequential monotherapies. Therapeutic drug monitoring (measurement of serum drug concentrations) is useful in various settings, such as when drug interactions are expected, toxicity is suspected, or when AEDs with nonlinear pharmacokinetics (e.g. phenytoin, carbamazepine) are used. No indications currently exist for routine therapeutic drug monitoring of the newer AEDs. In summary, dosage regimens of AEDs should be assessed regularly, and adjusted if necessary, so that patients can derive optimal therapeutic benefit. For patients considered 'difficult to treat' (i.e. those in whom seizures remain incompletely controlled after several attempts at treatment), referral to a specialist is recommended.

Anticonvulsants↗
PubMed2001

Genetic predisposition to severe myoclonic epilepsy in infancy.

PURPOSE: To address genetic predisposition to febrile convulsions (FCs) and epilepsy as an etiologic background of severe myoclonic epilepsy in infancy (SMEI). METHODS: Familial antecedents of epilepsy and FCs were analyzed in four groups of patients with SMEI (65 cases), FCs (57 cases), childhood absences (67 cases), and a control group of patients with no neurologic problems (64 cases). RESULTS: Patients with SMEI and those with FCs had significantly increased incidence of FCs in their relatives compared with those with absence epilepsy and with the control group. The incidence of epilepsy in relatives of patients with SMEI and absence epilepsy was increased compared with that in the control group and reached statistical significance. Epilepsy in relatives with SMEI had the characteristics of idiopathic generalized epilepsy. CONCLUSIONS: A genetic predisposition could determine three types of epileptic syndromes: FCs, idiopathic generalized epilepsy, and SMEI.

Adolescent↗
PubMed2001

[Andermann syndrome in an Algerian family: suggestion of phenotype and genetic homogeneity].

Andermann syndrome or Agenesis of the Corpus Callosum with Polyneuropathy (MIM 218000) is an autosomal recessive disease almost exclusively found in Québec. Only few cases have been reported in other populations. The locus for Andermann syndrome was assigned to chromosome 15q13-q15 in French Canadian families. We performed a haplotype analysis with two markers of this chromosomal region in an Algerian consanguineous family with two affected sibs. The children were homozygous for both markers, suggesting genetic homogeneity in Andermann syndrome.

Adolescent↗
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

A gene for pyridoxine-dependent epilepsy maps to chromosome 5q31.

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder characterized by generalized seizures in the first hours of life and responding only to pyridoxine hydrochloride. The pathogenesis of PDE is unknown, but an alteration in the binding of pyridoxal 5-phosphate to glutamic acid decarboxylase (GAD) has been postulated in patients with PDE. Results are reported for genetic linkage analyses in four families with consanguineous parents and in one family with nonconsanguineous parents. The GAD1 (2q31) and GAD2 genes (10p23) were tested and excluded. A genomewide search was subsequently performed, using microsatellite markers at an average distance of 10 cM, and the search revealed linkage of the disease-causing gene to markers on chromosome 5q31.2-q31.3 (maximum LOD score [Z(max)] 8.43 at recombination fraction [theta] 0 and Zmax=7.58 at straight theta=0 at loci D5S2017 and D5S1972, respectively). A recombination event, between loci D5S638 and D5S463, in one family defined the distal boundary, and a second recombination event between loci D5S2011 and D5S2017 in another family defined the proximal boundary of the genetic interval encompassing the PDE gene (5.1 cM). Ongoing studies may lead to the identification of the disease-causing gene.

Chromosome Mapping↗
PubMed2000

Phenytoin administration in the newborn and infant.

To evaluate the efficacy and safety of phenytoin (PHT) in the treatment of situation-related seizures and epilepsies in the newborn and infant; the clinical histories of 82 patients were retrospectively reviewed. Sixty patients received for status epilepticus (SE), intravenous PHT followed by long-term oral administration for 27 of them. The other 22 patients had oral treatment only. Intravenous administration made 55% of these patients seizure-free, whereas oral administration produced lasting seizure control in only 9.1%. During chronic oral treatment, it was most difficult to obtain adequate plasma concentrations in 69.1% of the patients, and 43.6% had side effects, most of which were related to very high plasma concentrations. In conclusion, in the first 2 years of life, intravenous administration of PHT is useful for SE, but oral treatment is poorly effective with difficulty to achieve appropriate and stable therapeutic plasma concentrations, and with frequent side effects.

Anticonvulsants↗
PubMed2000

Assessing risk to benefit ratio in antiepileptic drug therapy.

Assessment of risk to benefit ratio in patients with epilepsy is crucial in determining the need for treatment, the choice of drugs and the use of monitoring tools such as laboratory tests and other investigations. Active epilepsy per se carries significant risks in terms of increased mortality, susceptibility to psychopathology and physical injury, and reduced quality of life as a result of restricted lifestyle, stigma and prejudice. By preventing the occurrence of seizures, antiepileptic drugs (AEDs) attenuate or eliminate altogether seizure-related risks, but other risks may arise due to the side effects of the drugs, all of which have a relatively narrow therapeutic index. While there are no major differences in the degree of efficacy between AEDs which are effective in any given seizure type, side effect profiles differ considerably from one agent to another and represent a major factor in determining choice of treatment. Assessment of risk to benefit ratio should also take into consideration patient-specific factors such as type and severity of the epilepsy, age, sex, childbearing potential, medical and drug history, associated disease, use of concomitant medication (including the contraceptive pill) and the prospected patient's compliance. In some benign epilepsy syndromes, such as idiopathic partial epilepsy with centro-temporal spikes, the risk of side effects from AEDs may outweigh potential benefits in terms of seizure control, and treatment is generally not indicated. At the opposite end of the spectrum, the serious morbidity and mortality associated with severe epileptic encephalopathies, such as the Lennox-Gastaut syndrome, justifies aggressive treatment even with drugs associated with a relatively high risk of life threatening side effects such as felbamate. The present article will provide an overview of specific risks associated with epilepsy and with the various drugs used for its treatment, and will attempt to evaluate the complex balance between these risks and therapeutic benefits in different categories of patients.

Anticonvulsants↗
PubMed2000

Tiagabine adjunctive therapy in children with refractory epilepsy: a single-blind dose escalating study.

Tiagabine, a specific gamma-aminobutyric acid-uptake inhibitor, has been shown to be reasonably well tolerated and efficacious as adjunctive treatment for partial seizures in adults and is now being investigated in children. This 4-month, single-blind study evaluated the tolerability, safety and preliminary efficacy of ascending doses (0.25-1.5 mg/kg/day) of tiagabine add-on therapy in 52 children over the age of 2 years with different syndromes of refractory epilepsy. Adverse events, mostly mild to moderate, were reported by 39% of children during the single-blind placebo period and by 83% of children during tiagabine treatment. The events predominantly affected the nervous system with asthenia (19%), nervousness (19%), dizziness (17%) and somnolence (17%) being the most common. Only three children (6%) withdrew because of adverse events. Tiagabine appeared to reduce seizures more in localisation-related epilepsy syndromes than in generalised epilepsy syndromes. Twenty-three patients with localisation-related epilepsy syndromes were included and 17 of these patients entered the fourth dosing period. The 17 patients had a median reduction of seizure rate in the fourth month of treatment of 33% compared with baseline. In comparison, 13 of 22 children with seven different generalised epilepsy syndromes entered the fourth dosing period with a median change of seizure rate of 0%. Two patients experienced single episodes of status epilepticus during treatment; both cases resolved. Tiagabine showed efficacy mainly in localisation-related syndromes and was well tolerated by most children in a group of very refractory patients and warrants further study in children with epilepsy.

Adolescent↗
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↗
PubMed2000

Epileptic syndromes, cognitive assessment and school placement: a study of 251 children.

Two-hundred and fifty-one children (98 girls and 153 boys, aged from 3 to 17 years) with documented diagnosis of epileptic syndrome, IQ measurement, and information on school placement were included in this retrospective study. The relations between these three parameters as well as effects of age at onset and duration of epilepsy, seizure frequency, and number of antiepileptic drugs (AEDs) were analysed. Both IQ and schooling were univariately related to epileptic syndrome, age at onset and duration of epilepsy, and number of AEDs; seizure frequency was related to IQ but not to school placement. Multiple regression showed that IQ was independently related to epileptic syndrome and AED; multiple logistic regression showed that type of school (mainstream versus adapted or special) was independently related to IQ and AED. Children with idiopathic generalised or with localisation-related epilepsy had higher IQ scores and higher probability of mainstream schooling than those with symptomatic or cryptogenic generalised epilepsies or epileptic syndromes which were undetermined. Subtests profile of intelligence scale in localisation-related epilepsies showed different specific cognitive deficits, according to the location of the epileptic focus.

Adolescent↗