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Biomedical subjects

O Dulac

Publications and source records attributed to O Dulac.

At least 19 recordsLinked to original sources
PubMed2003

Ictal SPECT in children with epilepsy: comparison with intracranial EEG and relation to postsurgical outcome.

In order to validate the ability of ictal single photon emission computed tomography (SPECT) to localize the epileptogenic zone (EZ) in children, we compared in 20 patients aged from 10 months to 17 years (mean 6.5 years) the topography of the area of increased ictal perfusion (IPA), determined on the basis of ictal minus interictal scan values, with that of the EZ determined by intracranial EEG recordings and assessed its relationship with the postsurgical outcome. Eighteen patients had symptomatic epilepsy and 10 had extratemporal epilepsy. All patients except one had an ictal injection (mean time lag from clinical seizure onset was 18 s). Ictal and interictal SPECT images were successively co-registered, normalized, subtracted, smoothed and superimposed on MRI. All patients with ictal injection exhibited one or several IPAs. The topography of the 'highest' IPA, i.e. the maximal cerebral blood flow (CBF) change between ictal and interictal SPECT, significantly colocalized with the site of onset of the discharge, and that of the lower IPAs with that of the area of propagation (P < 0.0001). At a threshold of 30% of the maximal CBF change, the IPAs detected the onset of the discharge with a sensitivity of 0.80 and a specificity of 0.70. The highest IPA localized the EZ in 12 out of 15 patients. In the three others it missed the EZ and showed the area of propagation because of rapid seizure propagation or of infraclinical seizure onset. Among the patients with favourable surgery outcome, the highest IPA colocalized with the resected area in 70% of cases. Ictal SPECT could therefore plays an important role as a non-invasive presurgical method of investigation by optimizing the placement of intracranial electrodes, thus improving the postsurgery outcome of paediatric partial epilepsy.

Adolescent↗
PubMed2002

No evidence for a susceptibility locus for idiopathic generalized epilepsy on chromosome 5 in families with typical absence seizures.

A recent genome-wide scan revealed suggestive evidence for two susceptibility loci for idiopathic generalized epilepsy (IGE) in the chromosomal regions 5p15 and 5q14-q22 in families with typical absence seizures. The present replication study tested the validity of the tentative IGE loci on chromosome 5. Our study included 99 multiplex families in which at least one family member had typical absence seizures. Parametric and non-parametric multipoint linkage analyses were carried out between the IGE trait and 23 microsatellite polymorphisms covering the entire region of chromosome 5. Multipoint parametric heterogeneity lod scores < -2 were obtained along chromosome 5 when a proportion of linked families greater than 50% was assumed under recessive inheritance and > 60% under dominant inheritance. Furthermore, non-parametric multipoint linkage analyses revealed no hint of linkage throughout the candidate region (P > 0.05). Accordingly, we failed to support previous evidence for common IGE loci on chromosome 5. If there is a susceptibility locus for IGE on chromosome 5 then the size of the effect or the proportion of linked families is too small to detect linkage in the investigated family sample.

Chromosome Mapping↗
PubMed2002

[Long-term efficacy and tolerance of stiripentaol in severe myoclonic epilepsy of infancy (Dravet's syndrome)].

OBJECTIVE: To describe the long term efficacy and tolerance of stiripentol associated with valproate and clobazam in an exhaustive cohort of patients with severe myoclonic epilepsy of infancy (Dravet's syndrome), in which short term efficacy of such a treatment has recently been demonstrated in a placebo-controlled trial. RESULTS: In 46 patients the frequency and the duration of seizures was significantly reduced (p < 0.001) as well as the number of convulsive status at a median of three-year follow-up. Ten patients were dramatically improved (seizures significantly decreased in number [p = 0.002] and duration [p = 0.002] and status epilepticus disappeared), 20 were moderately improved (seizures significantly decreased in duration [p = 0.001] and status were less numerous), four had no response and efficacy was non evaluable in 12 mainly because of adverse events. Efficacy was better in the youngest patients. The most frequent adverse events were loss of appetite and loss of weight. They could be so severe in patients over 12 years of age that the stiripentol dosage could not be increased to 50 mg kg-1 j-1. CONCLUSION: This follow-up study shows that stiripentol added to valproate and clobazam maintains its efficacy at long term in children with severe myoclonic epilepsy of infancy and suggests that the tritherapy should be introduced as early as possible in these patients in order to suppress the convulsive status epilepticus.

Anti-Anxiety Agents↗
PubMed2002

Prophylactic antiepileptic treatment in Sturge-Weber disease.

PURPOSE: In Sturge-Weber disease, motor and cognitive defects are supposed to result mostly from severe epilepsy. They might, therefore be partly prevented by prophylactic antiepileptic drug treatment. This condition constitutes a possible model for the study of prophylactic drug treatment in severe epilepsy. In the present study, we compared the outcome of patients treated prospectively with phenobarbitone before the first seizure, with those referred following the first seizure, in order to identify the issues related to the evaluation of prophylactic treatment of severe epilepsy. METHODS: Motor and cognitive outcome were compared in patients treated prophylactically with phenobarbitone (16 cases) and in those treated following the first seizures (21 cases). RESULTS: Whereas the incidence of motor deficit was similar in both groups (44 vs. 52%), that of mental retardation was lower in the group treated prophylactically (76.2 vs. 43.7%, P< 0.05). The major methodological issues encountered included the small number of patients identified at birth that could be included in the study, the need for randomization taking into account the size of the angioma, and the choice of the prophylactic medication, including the occurrence of epilepsy together with the course of motor and cognitive functions among the endpoints. CONCLUSION: Prophylactic anti-epileptic drug treatment is worth considering for Sturge-Weber disease, but a randomized prospective study is necessary to determine this. It should be multicentric, take in account the size of the angioma, and decide what the most appropriate medication should be.

Adolescent↗
PubMed2001

Functional imaging in the work-up of childhood epilepsy.

In children with medically intractable lesional epilepsy, surgery is deemed successful if the epileptogenic focus can be removed while major neurological functions are spared. Current techniques rely on invasive intracranial recordings. The new developments in functional imaging offer the possibility of localizing the epileptogenic focus noninvasively (PET/SPECT) and mapping cognitive functions (fMRI). Ictal SPECT shows hyperperfusion in the focus and has proved to have better localizing value than interictal PET or SPECT, which show focal hypometabolism or hypoperfusion. Ictal SPECT is useful for deciding on the placement of intracranial electrodes in extratemporal epilepsies, particularly in young children. Functional MRI has proved highly accurate for localizing motor and language networks, thus offering the possibilities of replacing the Wada test (language hemispheric lateralization) and studying postlesional brain plasticity. Despite the difficulties of functional imaging in children owing to the limited cooperation that can be expected, ethical constraints, and poor normative data, SPECT/PET and fMRI provide clinically useful information for presurgical work-up of childhood epilepsies.

Adolescent↗
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↗