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P Genton

Publications and source records attributed to P Genton.

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

Tiagabine in clinical practice.

Among the newly introduced antiepileptic drugs (AEDs), tiagabine (TGB) stands out as a compound with a well-understood and documented mechanism of action. It is a lipophilic derivative of nipecotic acid that blocks gamma-aminobutyric acid (GABA) reuptake by inhibition of the GAT-1 transportation system, and that has no other significant pharmacodynamic effect. The relationship between intake and blood levels is linear. Usual daily maintenance doses range from 20 to 50 mg. It is completely absorbed by the gastrointestinal tract, and its half-life is approximately 7-9 h. TGB is sensitive to enzyme induction: when coprescribed with enzyme-inducing AEDs, its half-life is shortened to 2-3 h, whereas the daily dosage has to be increased into the upper range. It should be given 3 times per day. Placebo-controlled, double-blind, add-on studies conducted in patients with drug-resistant focal epilepsies have demonstrated its efficacy and overall safety. The clinical benefits appear to persist over time. Data on its use in monotherapy are scanty. The efficacy and tolerability of TGB in the pediatric age still remain to be investigated adequately. In daily practice, TGB appears to be a safe drug, but mild to moderate side effects are frequently seen, especially during titration: these include dizziness and fatigue, and are clearly abated when the drug is absorbed during meals. Titration should be especially slow, no faster than 5 mg weekly. Clinicians also should beware of the possible occurrence of confusion, which may be misdiagnosed as absence status, a short-lasting, quickly reversible central nervous system-related side effect that appears to be correlated with the peak plasma concentrations of TGB. Particularly beneficial indications for TGB and/or AED associations including TGB have not been pointed out, but there is a hint that it works best in temporal lobe epilepsies.

Anticonvulsants↗
PubMed2001

On the association between valproate and polycystic ovary syndrome.

Recent studies by Isojärvi et al. have raised the issue of an increased incidence of polycystic ovary syndrome (PCOS) in women with epilepsy treated with valproate (VPA) and have proposed replacement with lamotrigine (LTG). Polycystic ovaries (PCO) are a common finding, with a prevalence >20% in the general population, and are easily detected by pelvic or vaginal ultrasonography, whereas PCOS is comparatively rare: few women with PCO have fully developed PCOS, which includes hirsutism, acne, obesity, hypofertility. hyperandrogenemia, and menstrual disorders. From an extensive review of the current literature, it appears that there are no reliable data on the actual prevalence of PCOS in normal women and in women with epilepsy. The pathogenesis of PCO is multifactorial, including genetic predisposition and the intervention of environmental factors, among which weight gain and hyperinsulinism with insulin resistance may play a part. The roles of central (hypothalamic/pituitary), peripheral, and local ovarian factors are still debated. PCO and PCOS appear to be more frequent in women with epilepsy, but there are no reliable data showing a greater prevalence after VPA. The recent studies by Isojärvi et al. may have been biased by the retrospective selection of patients. To date, there is no reason to contraindicate the use of VPA in women with epilepsy. However, patients should be informed about the risk of weight gain and its consequences.

Adolescent↗
PubMed2001

Incidence of drug-induced aggravation in benign epilepsy with centrotemporal spikes.

PURPOSE: Benign epilepsy with centrotemporal spikes (BECTS) is characterized by an excellent prognosis. Drug therapy is necessary in only a minority of patients. Carbamazepine (CBZ) and phenobarbital (PB) have been reported to cause electroclinical aggravation in some cases. The incidence of drug-induced aggravation in BECTS has never been established. METHODS: We retrospectively studied 98 consecutive cases of BECTS, examined at the Centre Saint Paul between 1984 and 1999; 82 patients had received one or more treatments, often successively and in association. RESULTS: We found only one case of electroclinical aggravation with CBZ among 40 patients exposed to CBZ (35 in monotherapy, five in polytherapy). An additional case showed a marked EEG aggravation on CBZ + PB among 14 patients taking PB (nine with monotherapy and five with polytherapy), and PB was apparently responsible. No patient treated with valproate or benzodiazepines showed aggravation. CONCLUSIONS: Aggravation of BECTS caused by antiepileptic drugs happens only rarely. There is a minor risk of aggravation with CBZ and also probably with PB. Drug-induced aggravation may occur only during certain periods coinciding with spontaneous worsening of BECTS.

Acute Disease↗
PubMed2001

Clinical factors of drug resistance in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy is a comparatively benign form of idiopathic generalised epilepsy. Little is known about the prevalence of difficult to treat or drug resistant patients. Among 155 consecutive patients with newly diagnosed juvenile myoclonic epilepsy evaluated between 1981 and 1998 and followed up for at least 1 year (61 men, 94 women; aged 15-70 years, mean 33 (SD 10.3); onset of juvenile myoclonic epilepsy at the age of 14.5 (SD 3.7), range 6-26; follow up 1-52 years, mean 13.5 (SD 9.9)), there were 15 pseudoresistant patients (9.7%: lack of compliance (eight), insufficient treatment (three), abnormal lifestyle (four)) and 24 patients (15.5%) who had persisting seizures despite adequate therapy and lifestyle. Clinical features associated with drug resistance were (1) the presence of psychiatric problems (58.3% v 19%; chi(2) p<0.001) and (2) independently, the combination of seizure types (Fischer's exact 2 by 4, p=0.0026). Three types were present in 62.5% of resistant patients versus 23.3% in non-resistant patients (chi(2), p=0.0001). None of the resistant patients had myoclonic jerks as the only seizure type or a combination of absences and myoclonic jerks. Family history of epilepsy, age at onset of seizures, sex, presence of photoparoxysmal response, results of conventional neuroimagings (CT and MRI), and delayed diagnosis were not significantly associated with drug resistance. There is thus a significant subgroup of patients with juvenile myoclonic epilepsy who pose difficult therapeutic problems, and the prevalence of resistant cases may be increased in the experience of a referral epilepsy centre.

Adolescent↗
PubMed2001

[Psychiatric disorders in juvenile myoclonic epilepsy].

Mild personality problems have been described in patients with juvenile myoclonic epilepsy (JME), but clinical practice shows that JME can be diagnosed in patients with more or less severe psychiatric disorders (PD). The presence in JME patients of personality disorders has been described repeatedly, but never quantified. We thus decided to evaluate, using the DSM IV, the current prevalence and types of PD in a large series of consecutive, newly referred patients with JME. Among 170 consecutive JME cases referred to two departments of epileptology (Marseilles and Nice) between 1981 and 1998 (66 males, 104 females; aged 11.7-70; mean+/-SD 32.4+/-10.4 follow-up 12.7+/-10 [0.5-52]), we found 45 patients (26.5p.100) with PD. According to the DSM IV, they could be classified as severe mental retardation (main diagnosis) (one case); pervasive developmental disorders (2 cases); tic disorder (1 case); enuresis (1 case); psychotic disorders (5 cases, including schizophrenia paranoid type (1 case), disorganized type (1 case), delusional disorder (1 case), unspecified (2 cases)); depressive disorders (3 cases); generalized anxiety (6 cases); anorexia nervosa (2 cases); personality disorders (24 cases, including borderline personality (11 cases), dependent personality (5 cases), histrionic personality (2 cases), obsessive-compulsive personality (1 case), not specified (5 cases)). Sudden unexplained death occurred in 2 cases (borderline personality and pervasive developmental disorder not otherwise specified, respectively) and death due to pneumonia in 1 cases (anorexia). Although uncommonly severe cases of JME may have been selected in our referral centers, it appears that JME may be associated with PD. Comparatively mild personality disorders are the most common finding, and may be part of the clinical picture to some extent, while severe PD are less common, and probably coincidental. The presence of PD does not exclude the diagnosis of JME, and PD may represent a further challenge in the comprehensive care of these patients.

Adolescent↗
PubMed2000

Do carbamazepine and phenytoin aggravate juvenile myoclonic epilepsy?

BACKGROUND: Juvenile myoclonic epilepsy is a frequent form of idiopathic generalized epilepsy that is usually and easily controlled by valproate monotherapy. However, juvenile myoclonic epilepsy is often misdiagnosed, and some drugs, especially carbamazepine and phenytoin, may have an aggravating effect. OBJECTIVES: To determine the risk of aggravation of juvenile myoclonic epilepsy in patients treated with carbamazepine and phenytoin. METHODS: Among 170 consecutive patients with juvenile myoclonic epilepsy (104 female, 66 male) referred between 1981 and 1998, the authors retrospectively found 40 patients (23%) who had received carbamazepine or phenytoin (duration of epilepsy at referral, 1 to 34 years; mean +/- SD, 13.8 +/- 8.5 years; follow-up, 3 to 50 years; mean +/- SD, 16.4 +/- 11 years). RESULTS: Twenty-three patients (57.5%) experienced aggravation of seizures, whereas 6 (15%) apparently benefited from these drugs. There was no effect in the remaining 11 cases (27.5%). Carbamazepine was prescribed to 28 patients: 19 (68%) had aggravated symptoms, including myoclonic status in two; 4 (14%) were improved, one in association with valproate and one in association with valproate and phenobarbital. Phenytoin was prescribed in 16 cases: 6 (38%) had aggravation and 2 (12%) were improved, including one in association with phenobarbital. Vigabatrin was given in only one case, in association with carbamazepine, and provoked a mixed absence and myoclonic status. CONCLUSIONS: Among commonly prescribed anticonvulsants, carbamazepine appears to have the strongest aggravating potential in patients with juvenile myoclonic epilepsy, whereas the aggravating effect of phenytoin is less prominent. Aggravation was mostly in the form of increased myoclonic jerks.

Adolescent↗
PubMed2000

When antiepileptic drugs aggravate epilepsy.

Paradoxically, an antiepileptic drug (AED) may aggravate epilepsy. The number of AEDs is steadily increasing, and the occurrence of paradoxical aggravation will probably become a frequent problem. The overall status of the patient treated for epilepsy can be altered due to maladjustment to the diagnosis of epilepsy, to unwanted side-effects, to overdosage and to the occurrence of tolerance. However, the main mechanism of aggravation is the occurrence of an inverse pharmacodynamic effect. The specific effect of the AED is such that it controls epilepsy in most cases and increases seizures in other cases. Idiopathic generalised epilepsies (IGE) are particularly prone to pharmacodynamic aggravation: typical absences are constantly increased by carbamazepine (CBZ), vigabatrin, tiagabine, gabapentin, while phenytoin (PHT) is less aggravating. Juvenile myoclonic epilepsy is often aggravated by CBZ, less constantly by PHT and other AEDs. Generalised tonic-clonic seizures found in IGEs may respond to AEDs that aggravate the other seizure types. In symptomatic generalised epilepsies, patients have often several seizure types that respond differently to AEDs: myoclonias are generally aggravated by the same drugs that aggravated IGEs; tonic seizures in the Lennox-Gastaut syndrome respond to CBZ, which may however aggravate atypical absences. In severe myoclonic epilepsy of infancy, there is a nearly constant aggravating effect of lamotrigine. In some patients with benign rolandic epilepsy, a clear aggravation may be produced by CBZ, with occurrence of negative myoclonias, atypical absences, drop attacks, and at the maximum evolution into a state of electrical status epilepticus during sleep. It is much more difficult to pinpoint specific pharmacological sensitivity in other focal epilepsies, but aggravation clearly occurs. When treating epilepsy, the clinician should act according to seizure type, or, better, to epilepsy type. Patients are usually aware of aggravation before their doctors: we should listen carefully whenever they express a 'dislike' for an AED.

Anticonvulsants↗
PubMed2000

Structural brain lesions do not influence the prognosis of juvenile myoclonic epilepsy.

OBJECTIVES: In juvenile myoclonic epilepsy (JME) neuroimaging procedures are usually unnecessary but are often performed following the first generalized tonic-clonic seizure before a specific diagnosis has been reached. Our aim was to evaluate the influence of abnormal findings on the clinical presentation and prognosis of JME. MATERIAL AND METHODS: We retrospectively analyzed all medical records of JME patients first referred in two epilepsy centers (Marseilles, Nice) between 1981 and 1998. RESULTS: Among 170 consecutive unselected newly diagnosed JME patients, neuroimaging was performed in 82 cases (MRI: 22, CT: 75, including MRI+CT: 15). In 4 subjects, specific neurological abnormalities had justified neuroimaging: severe head trauma after the onset of JME (2, both with lesions related to the trauma), multiple sclerosis with onset after JME (1, with normal MRI before the onset of multiple sclerosis and abnormal, specific findings later), severe mental retardation (1, with diffuse MRI changes but a typical electro-clinical presentation and evolution). In the other 78 cases, 9 had abnormal findings: common arachnoid cyst (3), mild diffuse cerebral atrophy and ventricular enlargement (1), mild ventricular enlargement only (3), septum lucidum cavum (1), mildly increased T2 signal in the left temporal lobe (1). Abnormal neuroimaging did not influence therapeutic decisions or prognosis. CONCLUSIONS: These data confirm that neuroimaging procedures should not be routinely performed in patients with typical JME, unless additional neurological problems, that are unrelated to the diagnosis of epilepsy, occur.

Adolescent↗
PubMed2000

Dominant partial epilepsies. A clinical, electrophysiological and genetic study of 19 European families.

Nineteen families with autosomal dominant partial epilepsy were analysed clinically and electrophysiologically in detail. Seventy-one patients were studied as well as 33 non-epileptic at-risk family members. We subdivided the families into those with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) (n = 8), familial temporal lobe epilepsy (n = 7) and autosomal dominant partial epilepsy with variable foci (n = 4). However, the application of this nosology to certain families was difficult in cases of non-specific or conflicting clinical and electrophysiological evidence. This was underscored by the observation by depth electrode recordings in one patient that a so-called ADNFLE may originate in an extrafrontal area. The evolution of familial partial epilepsies, which exhibit great intrafamilial variability, is not always benign. The level of pharmacoresistance may reach 30%, close to that seen in classical cryptogenic partial epilepsies. The familial character of a partial epilepsy may be unrecognized in small families as some affected members may have only EEG abnormalities and are clinically asymptomatic, which reflects incomplete clinical penetrance. In view of the recent discoveries of mutations in the alpha4 nicotinic acetylcholine receptor subunit in a few families with ADNFLE, this genetic study focused on genes encoding nicotinic receptor subunits and a candidate region on chromosome 10q. No mutation was detected in the alpha4 and 012 nicotinic acetylcholine receptor subunits. Positive but not significant lod scores were obtained in four families with markers from the candidate region on chromosome 10q.

Adolescent↗
PubMed2000

[Ring chromosome 20: an identifiable epileptic syndrome].

Ring chromosome 20 (RC20) is a rare chromosomopathy characterized by slight mental deficiency, behavioral disorders and epilepsy. We report two cases of ring chromosome 20, who exhibited non convulsive status epilepticus lasting minutes to hours, often triggered by emotional events, with associated typical electroencephalographic features. Our report highlights the features of the electroclinical epilepsy syndrome associated with RC20, which represents a distinct and recognizable entity. The genetic basis of this disorder is discussed.

Adult↗
PubMed2000

Is it juvenile myoclonic epilepsy?

A 21-year old man with marked developmental delay was referred for the diagnosis of myoclonic jerks (MJ), which were sometimes responsible for sudden falls without loss of consciousness, that had begun 2 years before, and for a recent generalized tonic-clonic seizure preceded by a cluster of MJ. Physical examination revealed a small stature, bilateral pyramidal signs, severe mental retardation, and retinis pigmentosa. Etiological factors for this encephalopathy were not found (muscle and skin biopsies, karyotype and extensive blood chemistry). Waking interictal EEG showed a normal background activity and generalized poly-spike-and wave (PSW) discharges. Photic stimulation disclosed a marked photoparoxysmal response, sometimes associated with myoclonic jerks. Three spontaneous jerks accompanied by a burst of generalized PSW were recorded on awakening from a nap. The MRI disclosed wide ventricles, a thin corpus callosum, brainstem atrophy and a so-called "redundant gyration"; these changes were evocative of acquired perinatal damage. Juvenile myoclonic epilepsy (JME) was diagnosed and valproate was started resulting in complete control of seizures. During a 5-year follow-up, the patient has remained seizure-free and the EEG consistently normal. In our opinion, JME can be diagnosed in very uncommon settings, including patients with significant brain damage, as long as all the other criteria for the diagnosis are present.

Adult↗
PubMed2000

Piracetam and levetiracetam: close structural similarities but different pharmacological and clinical profiles.

Piracetam (PIR) and levetiracetam (LEV), an S-enantiomer, are pyrrolidone derivatives that share similar chemical structures but have distinct pharmacological profiles and consequently different clinical uses. Although the mode of action of neither drug has been fully elucidated, they do not interact with inhibitory or excitatory neurotransmission or alter membrane excitability. A brain-specific stereoselective binding site has been identified for which LEV and other S-enantiomers, but not PIR, have high affinity. In preclinical studies, PIR significantly improves learning and memory; in contrast, LEV has less effect but is much more active in preventing seizures. Both drugs have a high therapeutic index and are well tolerated. PIR, a nootropic drug, is used in the therapy of age-related cognitive disturbances and poststroke aphasia. Clinical experience has also shown that at high doses it is effective against cortical myoclonus. LEV is an antiepileptic drug. Clinical trials have confirmed its efficacy in partial seizures and preliminary findings suggest that it is also effective in generalized seizures and myoclonus.

Animals↗
PubMed2000

[Topiramate in clinical practice (part 1). Multicentric retrospective analysis of the efficacy of topiramate as add-on therapy according to the topographic form of focal epilepsy].

Randomized, controlled studies of new antiepileptic drugs do not always highlight their best utilization in clinical practice. The authors gathered 361 cases of focal epilepsies treated with topiramate (TPM) as an add-on to other anti epileptic drugs prior to marketing. Among these, only 237 were treated for at least 3 months and analyzed here. These patients were treated by neurologists in a clinical setting, with free choice of associated drugs, titration and final daily doses. Compared with controlled studies, TPM was titrated slowly (mean rate: 43 mg/week, vs 100 to 200), and was given at a lower final dose (346 mg/d, vs 200 to 1000). This analysis confirmed the efficacy of TPM as add-on therapy in focal epilepsies (9.3p.100 totally controlled, 19 p.100 with reduction of seizures=90 p. 100, 52.7 p.100 responders at=50 p.100). It showed that there was a striking response in epilepsies originating from the central areas, which are often drug-resistant (19 p.100 totally controlled, 33.33 p. 100 with reduction of seizures=90 p.100). There were responders in all topographic groups. There was however no specific response according to etiology.

Adolescent↗
PubMed2000

Gamma knife surgery for epilepsy related to hypothalamic hamartomas.

OBJECTIVE: Drug-resistant epilepsy associated with hypothalamic hamartomas (HHs) can be cured by microsurgical resection of the lesions. Morbidity and mortality rates for microsurgery in this area are significant. Gamma knife surgery (GKS) is less invasive and seems to be well adapted for this indication. METHODS: To evaluate the safety and efficacy of GKS to treat this uncommon pathological condition, we organized a multicenter retrospective study. Ten patients were treated in seven different centers. The follow-up periods were more than 12 months for eight patients, with a median follow-up period of 28 months (mean, 35 mo; range, 12-71 mo). All patients had severe drug-resistant epilepsy, including frequent gelastic and generalized tonic or tonicoclonic attacks. The median age was 13.5 years (range, 1-32 yr; mean, 14 yr) at the time of GKS. Three patients experienced precocious puberty. All patients had sessile HHs. The median marginal dose was 15.25 Gy (range, 12-20 Gy). Two patients were treated two times (at 19 and 49 mo) because of insufficient efficacy. RESULTS: All patients exhibited improvement. Four patients were seizure-free, one experienced rare nocturnal seizures, one experienced some rare partial seizures but no more generalized attacks, and two exhibited only improvement, with reductions in the frequency of seizures but persistence of some rare generalized seizures. Two patients, now seizure-free, were considered to exhibit insufficient improvement after the first GKS procedure and were treated a second time. A clear correlation between efficacy and dose was observed in this series. The marginal dose was more than 17 Gy for all patients in the successful group and less than 13 Gy for all patients in the "improved" group. No side effects were reported, except for poikilothermia in one patient. Behavior was clearly improved for two patients (with only slight improvements in their epilepsy). Complete coverage of the HHs did not seem to be mandatory, because the dosimetry spared a significant part of the lesions for two patients in the successful group. CONCLUSION: We report the first series demonstrating that GKS can be a safe and effective treatment for epilepsy related to HHs. We advocate marginal doses greater than or equal to 17 Gy and partial dose-planning when necessary, for avoidance of critical surrounding structures.

Adolescent↗
PubMed2000

[Use of topiramate in clinical practice (part 2). Multicentric retrospective evaluation of its safety].

Randomized, controlled studies of new antiepileptic drugs are carried out following strict rules and do not always predict the drug's tolerability in clinical practice. The authors gathered 361 cases of focal epilepsies treated with topiramate (TPM) as an add-on to other antiepileptic drugs prior to marketing, in order to retrospectively analyze the incidence of adverse effects (AE). These patients had been treated by neurologists in a clinical setting, with free choice of associated drugs, titration and final daily dose. Compared with controlled studies, TPM was titrated slowly (mean rate: 43 mg/week, vs 100-200), and was given at a lower final dose (296 mg/d, vs 200 to 1000). This analysis shows that AE were less frequent and that TPM had an original tolerability profile, with CNS-related AE, often combined in the same patient (somnolence: 16. 1p.100, fatigue: 11.9p.100, mental slowing: 9.1p.100, slurred speech: 2,2p.100), and weight loss (14.7p.100 of patients, mean 4.5 kg or 6.6p.100 of body weight). Severe AE were uncommon (psychosis, 1; skin rash, 2; urinary lithiasis, 2). Withdrawal of TPM was caused by AE (13.6p.100), lack of efficacy (8.3p.100), aggravation of epilepsy (6.1p.100) or by a combination of these (5p.100). It is useful to use slow titration, in order to allow the greatest possible number of patients to benefit from its efficacy as an add-on drug in the treatment of resistant focal epilepsies.

Adolescent↗