PubMed Health⌕ Search

Biomedical subjects

P Genton

Publications and source records attributed to P Genton.

At least 19 recordsLinked to original sources
PubMed2006

[Unverricht-Lundborg disease (PME1)].

Unverricht-Lundborg disease (ULD) is the purest and least severe type of progressive myoclonus epilepsy (PME), and is not associated with progressive cognitive deficit. Symptoms stabilize in adulthood, with a varying degree of permanent, often severe handicap that is mostly due to myoclonus. The disorder follows an autosomal recessive transmission pattern, with onset between 8 and 15 years years of age of generalized tonic-clonic or clonic-tonic-clonic seizures, action myoclonus (massive or segmental), photosensitivity, and often ataxia. Prevalence varies, it is highest in certain isolates (Finland, La Réunion Island) and in region with higher levels of inbreeding (Maghreb). ULD is due to a deficit in cystatin B (stefin B), but the mechanisms leading to the clinical symptoms are not well understood. The causative gene, PME1, was identified in 1991 and localized to chromosome 21q22.3. The mutations are mainly expansions of the CCCCGCCCCGCG dodecamer, but less common point mutations were also found. A variant has been recently reported in a Palestinian family, with localization on chromosome 12. The diagnosis of ULD is made on the basis of family history, age at onset, geographical and ethnic context, and on the typical features of myoclonus and epilepsy, in the absence of cognitive and sensory deficits. Neurophysiological evaluation yields interesting, but unspecific results. There are no biological or pathological markers for ULD. Molecular analysis confirms the diagnosis in most patients. Genetic testing for heterozygotes and even prenatal diagnosis are possible, although seldom performed, if the mutation has been identified. In spite of intensive research, ULD has yet to reveal all of its secrets. It remains a quasi "idiopathic" type of PME, with limited progression. Clinicians and patients are still waiting for an etiologically oriented treatment, which should, ideally, be admnistered early in the course of the disease, if possible before the onset of invalidating symptoms.

Adolescent↗
PubMed2006

Levetiracetam in a broad population of patients with refractory epilepsy: interim results of the international SKATE trial.

OBJECTIVE: To prospectively assess the safety and efficacy of levetiracetam in patients with uncontrolled focal epilepsy, in a common practice-based setting. PATIENTS AND METHODS: In this phase IV, open-label, 16-week community-based study, adult patients with focal seizures initially received levetiracetam 1,000 mg/day. Throughout the study, the dose was adjusted in increments of 1,000 mg (maximum 3,000 mg/day) to achieve seizure control and maintain tolerability. The outcome parameters were the percentage reduction in partial and total seizure frequency per week from historical baseline, global evaluation scale (GES), and adverse events (AE). RESULTS: Seven hundred and thirty-one patients were included in this analysis and 84.4% completed the study. The median percent reduction in all seizures was 47.8%, and 49.3% for all partial seizures. The 50% responder rate was 49%, and the seizure-free rate was 17.2% for all partial seizures. Approximately 60% of patients showed moderate to marked improvement on the GES. The majority of AE were of mild to moderate severity; the most commonly reported being asthenia, somnolence, headache, and dizziness. CONCLUSION: Levetiracetam is both efficacious and safe as an add-on therapy in patients with refractory epilepsy treated by clinicians in their daily practice.

Adult↗
PubMed2005

Lamotrigine associated with exacerbation or de novo myoclonus in idiopathic generalized epilepsies.

Five patients with idiopathic generalized epilepsies (IGE) treated with lamotrigine (LTG) experienced exacerbation or de novo appearance of myoclonic jerks (MJ). In three patients, LTG exacerbated MJ in a dose-dependent manner with early aggravation during titration. MJ disappeared when LTG dose was decreased by 25 to 50%. In two patients, LTG exacerbated MJ in a delayed but more severe manner, with myoclonic status that only ceased after LTG withdrawal.

Adult↗
PubMed2005

Progress in pharmaceutical development presentation with improved pharmacokinetics: a new formulation for valproate.

Successful long-term treatment of patients with epilepsy requires selection of an appropriate antiepileptic regimen, optimal dosing and patient compliance. Recent advances in our understanding of the biological basis of epilepsy and in the choice of treatment options are transforming the global management of these patients. If the achievement of seizure freedom remains the primary goal of any antiepileptic treatment, issues associated with drug acceptability and tolerability, and with quality of life of patients, have gained increasing attention as major determinants of ultimate therapeutic success. Sustained-release formulations of antiepileptic drugs can be very helpful in achieving treatment objectives. Stable serum levels without marked peak-to-trough fluctuations, reduced frequency of dosing and the possibility of dosing flexibility may all improve compliance, patient satisfaction and ultimately quality of life. The efficacy of sodium valproate for the treatment of most types of epilepsy has been demonstrated extensively and this drug remains the mainstay of treatment for many clinical situations. Among the various valproate formulations, extended-release tablets have shown improved patient compliance and satisfaction. However, the tablet size and the limited dosing flexibility could be unsuitable for individualized treatment in special populations such as children, the elderly and patients with swallowing difficulties. A new sustained-release formulation of sodium valproate consisting of tasteless microspheres that can be sprinkled on semi-solid food such as yoghurt or jam has been developed. A stick pack presentation allows individualized dosing and greater convenience.

Administration, Oral↗
PubMed2004

[The definition of drug resistance: an epileptologist's perspective].

Defining drug resistance is apparently simple: persisting seizures in spite of adequate treatment. Clinical reality is slightly different. The clinician should first be concerned with the possibility of pseudo-resistance, with multiple pitfalls that include non-epileptic seizures, external factors (associated illnesses, e. g. unstable diabetes mellitus or hyperthyroidism, or co-treatment with aggravating drugs, e. g. neuroleptics), lack of compliance, grossly abnormal lifestyle with irregular sleep schedule or abuse of toxics, but also the frequently overlooked but ever so frequent psychological factors. One should also keep in mind the possibility of a paradoxical, aggravating effect of antiepileptic drugs, and the fact that in some patients the primarily indicated drugs cannot be used because of side-effects or because of a particular background. One should also consider the fact that drug resistance is often a relative fact: are the persisting seizures really disabling? Are these seizures really the patient's major problem? Seizures may persist in an intermittent way, which opens new therapeutic possibilities. The most reliable factors of drug resistance are related to the etiology of epilepsy. From a clinical point of view, the following definition of drug resistance in focal epilepsy may be proposed: a focal epilepsy may be considered as drug-resistant if invalidating seizures persist after two years of adequate drug management (or after a shorter period, depending on the etiology), having tried at least three major drugs either in monotherapy or in combination, and if at least two neurologists agree after a detailed assessment of the patient's case.

Anticonvulsants↗
PubMed2003

Mosaic mutations of the LIS1 gene cause subcortical band heterotopia.

BACKGROUND: Subcortical band heterotopia (SBH) is a neuronal migration disorder. DCX mutations are responsible for almost all familial cases, 80% of sporadic female cases, and 25% of sporadic male cases of SBH, and are associated with more severe gyral and migration abnormality over the anterior brain regions. Somatic mosaicism has previously been hypothesized in a patient with posteriorly predominant SBH and a mutation of the LIS1 gene, which is usually mutated in patients with severe lissencephaly. The authors identified mosaic mutations of LIS1 in two patients (Patients 1 and 2) with predominantly posterior SBH. METHODS: After ruling out DCX mutations, the authors performed sequencing of the LIS1 gene in lymphocyte DNA. Because sequence peaks in both patients were suggestive of mosaic mutations, they followed up with denaturing high-pressure liquid chromatography analysis on blood and hair root DNA and compared the areas of heteroduplex and homoduplex peaks. A third patient showing the same mutation as Patient 2 but with no evidence of mosaicism was used for comparing the phenotype of mosaic vs full mutation. RESULTS: The two patients with posterior SBH harbored a missense (Arg241Pro) and a nonsense (R8X) mosaic mutation of LIS1. The rate of mosaicism in Patient 1 was 18% in the blood and 21% in the hair roots, whereas in Patient 2 it was 24% and 31% in the same tissues. The patient with a full R8X mutation of LIS1 had severe lissencephaly. CONCLUSIONS: Subcortical band heterotopia can occur with mosaic mutations of the LIS1 gene. Mutation analysis of LIS1, using highly sensitive techniques such as denaturing high-pressure liquid chromatography, should be considered for patients with posteriorly predominant subcortical band heterotopia and pachygyria.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2003

Current limitations of antiepileptic drug therapy: a conference review.

The current limitations of antiepileptic drug (AED) therapy were the topic of a discussion group meeting at the 5th European Congress on Epileptology, Madrid, 6-10 October 2002. This review contains four short papers covering the topics discussed by the speakers at this meeting and an account of the ensuing discussion with all participants. The meeting focused on four issues. (i) Are mechanisms of action of AEDs useful to predict treatment outcome? The short answer to this question was no, for several reasons. These include the fact that clinically relevant mechanisms in individual patients remain unclear, the treatment of epilepsy targets the symptoms rather than the cause of the disease, and that current seizure classification defines heterogeneous patient populations. (ii) The benefits of the often recommended titration of the dose to the maximum tolerated level when seizures persist at average AED doses. A re-evaluation of this practice showed that dose escalation achieves seizure freedom in only 1 of 4 patients with newly diagnosed epilepsy and only 1 of 10 patients with refractory epilepsy are likely to experience a greater than 50% reduction in seizure frequency. Being aware of the limited utility of maximum dose titration and subsequent dose reduction if no significant individual benefit is achieved avoids medical over-treatment with a worsening risk-benefit balance. (iii) When single drug therapy is not sufficiently effective, adding a second drug or alternative monotherapy are common options. Based on published data, there is no conclusive evidence in favour of either alternative monotherapy or second-line polytherapy. A pragmatic choice may be to evaluate the combination and then attempt to withdraw the first drug in the case of success. This may prevent the substitution of a partially efficacious drug by a non-efficacious drug. The choice of the second drug should, in theory, be based on which first drug has failed but again compelling evidence to support specific recommendations is lacking. (iv) Unexpected worsening of seizures may occur in many circumstances and has many causes, including tolerance and adverse pharmacodynamic effects of individual AEDs on seizure generating mechanisms. Patients are usually aware of aggravation and may express a "dislike" for a particular AED as a warning sign for physicians to modify the medication. The availability of numerous AEDs, particularly with single mechanisms of action, has increased the risk of paradoxical effects that may go undetected in clinical trials and only surface during astute clinical observations.

Anticonvulsants↗
PubMed2003

Dramatic effect of levetiracetam on epileptic negative myoclonus.

OBJECTIVE: To investigate the properties of levetiracetam in a patient with severe epileptic negative myoclonus. Treatment of epileptic negative myoclonus relies on the drugs that are effective in focal epilepsies, but it is usually pharmacoresistant. Levetiracetam is a new antiepileptic drug with a broad-spectrum activity that includes efficacy against positive myoclonus. CASE REPORT: This woman had had epileptic falls since the age of 2 years. In 2000, she was on phenobarbital (100 mg/day) and valproate (2000 mg/day) and had two drop attacks per month. Clinical examination showed negative myoclonus of the arms clearly predominating on the left side, which was confirmed by a polygraphic EEG. Levetiracetam (1000 mg/day in the first week, increased to 2000 mg/day thereafter) was added. During the first 2 months, the patient experienced four minor seizures without fall. A polygraphic EEG confirmed that the patient's epileptic negative myoclonus disappeared during levetiracetam treatment. At 1-year follow-up, this patient had had only one seizure. CONCLUSIONS: The result of levetiracetam treatment in this patient is encouraging, but efficacy should be confirmed in larger series. A long-term follow-up is also necessary to establish that this antimyoclonic effect of levetiracetam is maintained over a period of years.

Anticonvulsants↗
PubMed2003

[GEFS + syndrome: phenotypic variations from the newborn to the adult in a large French pedigree].

The GEFS + (generalized epilepsy with febrile seizures +) syndrome was described in 1997 in a large Australian pedigree and is characterized by the familial occurrence, following an autosomal dominant transmission, of febrile convulsive seizures in infants and young children that may last beyond the age of 6, and that are associated in some with afebrile convulsive seizures and a variety of other seizures types, including typical absences, myoclo-astatic seizures, myoclonias, and focal seizures. The genetic anomalies detected to date imply either Na channels or GABA receptors. In a large French pedigree, we identified 15 patients with the GEFS + syndrome. The index patient was a 15 month-old girl with repeated convulsive febrile, afebrile and atonic seizures, who was fully controlled on valproate. Her neurologic status and development were fully normal, and the interictal EEG did not show any specific abnormality. In this pedigree, all patients had febrile seizures except two who had only afebrile seizures, two had atonic drop attacks, and tonic seizures during sleep and a single secondarily generalized focal hemifacial motor seizure were seen once each. No patient had temporal lobe seizures; they did not have myoclonias nor typical absences. The seizure profile in this family appears to be original, and the existence of yet another type of underlying genetic defect can be suspected.

Adolescent↗
PubMed2002

Reproductive dysfunction in women with epilepsy: recommendations for evaluation and management.

BACKGROUND: Epilepsy is commonly associated with reproductive endocrine disorders. These include polycystic ovary syndrome (PCOS), isolated components of this syndrome such as polycystic ovaries, hyperandrogenaemia, hypothalamic amenorrhoea, and functional hyperprolactinaemia. OBJECTIVE: To summarise the currently known relations between epilepsy and reproductive endocrine disorders. METHODS: A review of clinical experience and published reports. RESULTS: The most likely explanations for endocrine disorders related to epilepsy or antiepileptic drugs are: (1) a direct influence of the epileptogenic lesion, epilepsy, or antiepileptic drugs on the endocrine control centres in the brain; (2) the effects of antiepileptic drugs on peripheral endocrine glands; (3) the effects of antiepileptic drugs on the metabolism of hormones and binding proteins; and (4) secondary endocrine complications of antiepileptic drug related weight changes or changes of insulin sensitivity. Regular monitoring of reproductive function at visits is recommended, including questioning about menstrual disorders, fertility, weight, hirsutism, and galactorrhoea. Particular attention should be paid to patients on valproate and obese patients or those experiencing significant weight gain. Single abnormal laboratory or imaging findings without symptoms may not constitute a clinically relevant endocrine disorder. However, patients with these kinds of abnormalities should be monitored to detect the possible development of a symptomatic disorder associated with, for example, menstrual disorders or fertility problems. CONCLUSIONS: If a reproductive endocrine disorder is found, antiepileptic drug treatment should be reviewed to ensure that it is correct for the particular seizure type and that it is not contributing to the endocrine problem. The possible benefits of a change in treatment must be balanced against seizure control and the cumulative side effect of alternative agents.

Anticonvulsants↗
PubMed2002

[Epileptic psychosis].

A relationship between serious psychiatric disorders and epilepsy has been observed since antiquity. An association between schizophrenia and epilepsy has been noted since the turn of century, but this relationship appeared to be uncertain. From the 1950s on, a number of studies were devoted to this subject. Epileptic patients are more risk for psychosis than the general population. Others psychiatric syndromes, some of which have been individualized recently, can occur in patients with epilepsy: alternative psychosis, affective states, postictal psychoses, postoperative psychoses. In this article we present the different aspects of the psychoses of epilepsy. Their knowledge allows in most cases a precise diagnosis and an appropriate treatment.

Affective Disorders, Psychotic↗
PubMed2001

Linkage of benign familial infantile convulsions to chromosome 16p12-q12 suggests allelism to the infantile convulsions and choreoathetosis syndrome.

The syndrome of benign familial infantile convulsions (BFIC) is an autosomal dominant epileptic disorder that is characterized by convulsions, with onset at age 3-12 mo and a favorable outcome. BFIC had been linked to chromosome 19q, whereas the infantile convulsions and choreoathetosis (ICCA) syndrome, in which BFIC is associated with paroxysmal dyskinesias, had been linked to chromosome 16p12-q12. BFIC appears to be frequently associated with paroxysmal dyskinesias, because many additional families from diverse ethnic backgrounds have similar syndromes that have been linked to the chromosome 16 ICCA region. Moreover, one large pedigree with paroxysmal kinesigenic dyskinesias only, has also been linked to the same genomic area. This raised the possibility that families with pure BFIC may be linked to chromosome 16 as well. We identified and studied seven families with BFIC inherited as an autosomal dominant trait. Genotyping was performed with markers at chromosome 19q and 16p12-q12. Although chromosome 19q could be excluded, evidence for linkage in the ICCA region was found, with a maximum two-point LOD score of 3.32 for markers D16S3131 and SPN. This result proves that human chromosome 16p12-q12 is a major genetic locus underlying both BFIC and paroxysmal dyskinesias. The unusual phenotype displayed by one homozygous patient suggests that variability of the ICCA syndrome could be sustained by genetic modifiers.

Age of Onset↗
PubMed2001

Premature death in juvenile myoclonic epilepsy.

OBJECTIVES: To report three cases of premature death in juvenile myoclonic epilepsy (JME), a benign form of idiopathic generalized epilepsy (IGE) in which no case of epilepsy-related death has been reported. MATERIAL AND METHODS: We retrospectively analyzed all medical records of JME patients first referred to two epilepsy centers (Marseilles, Nice) between 1981 and 1998. RESULTS: Among 170 consecutive JME cases, 3 female patients died prematurely. No autopsy was performed. The first had a history of severe anorexia nervosa (DSM IV: 307.1). She died at age 34 and 2 days, from severe inhalation pneumonia. The second is a woman with a history of infantile psychosis (DSM IV: 299.80) and with a case of IGE in her family. Her epilepsy was never controlled. At age 16, she was found cyanotic and unconscious one morning in the toilets. She died before resuscitation was undertaken. The third had a borderline personality (DSM IV: 301.83) and a history of alcoholism and low compliance. Her epilepsy was never well controlled. She also received neuroleptics. At age 42, she was found dead in her home. CONCLUSION: In the first case, death was apparently unrelated to epilepsy. In the second, an awakening seizure seems to be responsible. In the third, death is also possibly seizure-related. Cases two and three had persistent seizures and severe psychiatric disorders. Serious mental disorders seem to be risk factors for unexpected death. In JME, the overall death ratio was 1.4/1000 patient-years (or 0.9 if we exclude case 1).

Adolescent↗