Pierre Genton - Academia.edu (original) (raw)

Papers by Pierre Genton

Epilepsy & Behavior, 2015

The aim of this study was to investigate the potential role of an acute adverse stress as &am... more The aim of this study was to investigate the potential role of an acute adverse stress as &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;trigger&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; for the onset of epilepsy. Among 4618 consecutive patients, twenty-two reported a major life event within three months before the onset of epilepsy. All patients had focal epilepsy except one with idiopathic generalized epilepsy. The temporal lobe was involved in 90% of patients with focal epilepsy. More precisely, 13 patients (62% of patients with focal epilepsy) had medial temporal lobe epilepsy (MTLE), two had lateral temporal lobe epilepsy, four had temporoparietooccipital junction epilepsy, and two patients had central lobe epilepsy. The mean age and the median age at onset of epilepsy for patients with MTLE were both 38years (range: 9.5-65years). Ten patients had right and three had left MTLE. Among patients with focal epilepsy, MRI was abnormal in 7 (33%) with hippocampal sclerosis in four, periventricular nodular heterotopia in two, and complex cortical dysgenesis in one. The mean age at onset of epilepsy for patients with brain lesions was 26years (range: 9.5-49). Twelve patients (54%) reported a death as a triggering factor for the onset of their epilepsy. Seven patients (32%) reported that a relationship of trust had been broken. Three patients (14%) had been subjects of violence. No patient reported sexual abuse as a triggering factor. This study provides evidence that some patients (5/1000 patients) began their seizures in the wake of significant life events. The average age at onset of epilepsy is quite late, around age 30, even in the presence of brain lesions. These patients are emotionally and affectively more prone to have consequences of a stressful life event. The recognition and management of such situations may bring significant relief with improvement of the control of epilepsy.

Journal of Neurology Neurosurgery and Psychiatry, 2001

Juvenile myoclonic epilepsy is a comparatively benign form of idiopathic generalised epilepsy. Li... more 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);

Journal of Neurology Neurosurgery and Psychiatry, 1989

Thirteen patients with dyssynergia cerebellaris myoclonica (Ramsay Hunt syndrome) had full clinic... more Thirteen patients with dyssynergia cerebellaris myoclonica (Ramsay Hunt syndrome) had full clinical and neurophysiological study as well as muscle biopsy. The patients had action myoclonus, generalised epileptic seizures, and mild cerebellar syndrome. The disease was inherited in an autosomal recessive pattern in five patients, and occurred as isolated cases in the remaining eight patients. The age at onset of symptoms

PloS one, 2015

Carboxypeptidase A6 (CPA6) is a peptidase that removes C-terminal hydrophobic amino acids from pe... more Carboxypeptidase A6 (CPA6) is a peptidase that removes C-terminal hydrophobic amino acids from peptides and proteins. The CPA6 gene is expressed in the brains of humans and animals, with high levels of expression during development. It is translated with a prodomain (as proCPA6), which is removed before secretion. The active form of CPA6 binds tightly to the extracellular matrix (ECM) where it is thought to function in the processing of peptides and proteins. Mutations in the CPA6 gene have been identified in patients with temporal lobe epilepsy and febrile seizures. In the present study, we screened for CPA6 mutations in patients with juvenile myoclonic epilepsy and identified two novel missense mutations: Arg36His and Asn271Ser. Patients harboring these mutations also presented with generalized epilepsy. Neither of the novel mutations was found in a control population. Asn271 is highly conserved in CPA6 and other related metallocarboxypeptidases. Arg36 is present in the prodomain ...

Therapeutic drug monitoring, 1992

We retrospectively collected plasma level assessments performed in 96 adult patients with epileps... more We retrospectively collected plasma level assessments performed in 96 adult patients with epilepsy on stable monotherapy, including 9 patients on clobazam (CLB), 34 on carbamazepine (CBZ), 24 on phenobarbital (PB), 9 on phenytoin (PHT), and 20 on valproate (VPA); these results were compared to those obtained in 54 adult patients on stable bitherapy with the association of CLB with either CBZ (n = 17), PB (n = 17), PHT (n = 5), or VPA (n = 15). Our results show that CLB has no significant effect on the level to dose ratio (LDR) of CBZ, PB, PHT, or VPA. Conversely, CBZ, PB, and PHT significantly decrease the LDR of CLB. CBZ and PHT significantly increase the LDR of N-desmethylclobazam (NCLB), the major metabolite of CLB. A significant increase in the NCLB/CLB ratio was found in CBZ + CLB, PB + CLB, and PHT + CLB bitherapies. These findings are of clinical significance: clobazam is useful as adjunctive treatment in human epilepsy and is often chosen as the benzodiazepine adjunctive dru...

Advances in neurology, 2005

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Seizure, 2008

Ictal paresis (IP) is a rare negative motor phenomenon presenting challenging differential diagno... more Ictal paresis (IP) is a rare negative motor phenomenon presenting challenging differential diagnostic problems with transient ischemic attacks, post-ictal paralysis, migraine and psychogenic paralysis. Video-EEG undoubtedly represents the essential mean for a proper diagnosis. Periodic lateralised epileptiform discharges (PLEDs) are a distinctive EEG pattern, consisting of periodic spike or sharp wave discharges, often associated with seizures. It is under debate if PLEDs should be considered only a peri-ictal or also an ictal EEG pattern. We describe two children with severe focal epilepsies, who presented IP recorded during video-EEG monitoring, associated to PLEDs. Clinical observation along with interictal and ictal scalp-EEG findings, suggested a fronto-temporal seizure onset in the first, and a temporo-insular onset in the second. We confirm that PLEDs may be an ictal pattern associated with negative motor phenomena.

European Neurology, 1999

Rationale: Cortical dysplasia (CD) designates a diverse group of malformations resulting from one... more Rationale: Cortical dysplasia (CD) designates a diverse group of malformations resulting from one or more abnormalities in the development of the cerebral cortex. The clinical manifestations of CD are varied, probably depending on the type, location and extent of CD. Epilepsy is a potential late manifestation of any cortical malformation. To our knowledge, however, no study has focused specifically on

Epilepsia, 2002

Recent studies by Isojärvi et al. have raised the issue of an increased incidence of polycystic o... more 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 mul-

Nature Genetics, 2009

We identified 15q13.3 microdeletions encompassing the CHRNA7 gene in 12 of 1,223 individuals with... more We identified 15q13.3 microdeletions encompassing the CHRNA7 gene in 12 of 1,223 individuals with idiopathic generalized epilepsy (IGE), which were not detected in 3,699 controls (joint P ¼ 5.32 Â 10 À8 ). Most deletion carriers showed common IGE syndromes without other features previously associated with 15q13.3 microdeletions, such as intellectual disability, autism or schizophrenia. Our results indicate that 15q13.3 microdeletions constitute the most prevalent risk factor for common epilepsies identified to date.

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Seizure, 2010

In Down syndrome (DS), epilepsy is frequent in all age classes and is recognized as a significant... more In Down syndrome (DS), epilepsy is frequent in all age classes and is recognized as a significant cause of additional handicap and morbidity. Longer life expectancy has led to the recognition of the high incidence of both Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease and seizures in elderly persons with DS. Neuropathological markers of AD are found in all DS brains and clinical symptoms of AD become apparent by the age of 60 years and above in over 50% of DS subjects. Following preliminary description of myoclonic seizures and/or myoclonic epilepsy in isolated cases or small series, we wish to report the diagnostic criteria, treatment and prognosis of a specific and recognizable form of epilepsy associated with AD in a larger group of middle-aged to elderly DS patients. This markedly under-recognized entity may indeed concern an already large and steadily increasing number of patients. We reviewed all medical records of patients with DS referred to our centers (Centre Saint Paul-Gastaut, Marseille; Epilepsy Unit, Montpellier University Hospital; Department of Neurology, Hospital General de Asturias, Oviedo) since 1995. DS had been diagnosed in all at birth, and all presented with the typical morphological changes associated with DS. We selected all cases (18) referred as adults with new onset of myoclonic jerks (MJ) and/or behavioral or cognitive deterioration (CD).

Seizure, 2011

To report three cases of juvenile absence epilepsy (JAE) with temporal intermittent, asynchronous... more To report three cases of juvenile absence epilepsy (JAE) with temporal intermittent, asynchronous delta activity over the temporal regions. Long term video-EEG using the international 10/20 system and supplementary anterior-inferior temporal electrodes. Cohort of 1123 patients included in our active file seen at least one time over one year. Among 23 patients with JAE (2% of our active file), temporal intermittent rhythmic delta activity (TIRDA) was observed in 3 (13%). Moreover, this activity was never observed in 80 patients with juvenile myoclonic epilepsy. None of the three patients had inadequate antiepileptic drug for idiopathic generalized epilepsy. Case 1 had no antiepileptic drug. Case 2 was treated with valproate (1000 mg/day) and case 3 with levetiracetam (1500 mg/day). These delta activities were activated by hyperventilation and drowsiness. They decreased in NREM sleep and reappeared in REM sleep. The frequency was around 3 Hz. These changes were not frequently recorded in any given patient. The presence of TIRDA in the clinical and EEG context is very suggestive of JAE as posterior delta waves are of childhood absence epilepsy but with a more anterior location over the temporal lobe. This pattern was not described before probably because in this easily diagnosed and treated type of IGE, few patients have long-term video-EEG and also because a wrong diagnosis of focal epilepsy can be made. This pattern must be known to avoid the risk of treating this epilepsy by inappropriate antiepileptic drugs.

PLoS Genetics, 2010

Epilepsy is one of the most common neurological disorders in humans with a prevalence of 1% and a... more Epilepsy is one of the most common neurological disorders in humans with a prevalence of 1% and a lifetime incidence of 3%. Several genes have been identified in rare autosomal dominant and severe sporadic forms of epilepsy, but the genetic cause is unknown in the vast majority of cases. Copy number variants (CNVs) are known to play an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID), autism, and schizophrenia. Genome-wide studies of copy number variation in epilepsy have not been performed. We have applied whole-genome oligonucleotide array comparative genomic hybridization to a cohort of 517 individuals with various idiopathic, non-lesional epilepsies. We detected one or more rare genic CNVs in 8.9% of affected individuals that are not present in 2,493 controls; five individuals had two rare CNVs. We identified CNVs in genes previously implicated in other neurodevelopmental disorders, including two deletions in AUTS2 and one deletion in CNTNAP2. Therefore, our findings indicate that rare CNVs are likely to contribute to a broad range of generalized and focal epilepsies. In addition, we find that 2.9% of patients carry deletions at 15q11.2, 15q13.3, or 16p13.11, genomic hotspots previously associated with ID, autism, or schizophrenia. In summary, our findings suggest common etiological factors for seemingly diverse diseases such as ID, autism, schizophrenia, and epilepsy.

Neurosurgery, 2000

Numerous neurosurgical approaches are available for children presenting with hypothalamic hamarto... more Numerous neurosurgical approaches are available for children presenting with hypothalamic hamartomas (HHs) associated with severe epilepsy. A concern regarding the impairment of short-term memory after resective surgery is promoting the exploration of less invasive alternatives like radiosurgery. Gamma knife radiosurgery (GKS) can lead to a real reversal of the epileptic encephalopathy. Three years after radiosurgery, 60% of the children have an excellent result with complete seizure cessation in 40% and rare nondisabling seizures in 20%, often in association with dramatic behavioral and cognitive improvement. No permanent neurologic complications have thus far been reported. Rare transient cases of poikilothermia have been observed. GKS is clearly the safer approach for these difficult patients. Young patients with severe epilepsy and neurocognitive comorbidity must be treated by using a curative approach as early as possible. Topological type (according to our original classification) is the major feature for selection of the best treatment strategy. Type I HH deeply embedded in the hypothalamus is treated safely and efficiently by GKS. Type II HH can be resected by either endoscopic or transcallosal approaches or treated by GKS depending on the parent's choice and severity of epilepsy. In small type III HH, GKS is the safer procedure because of the very close relationship to the fornix and mammillary bodies. Types V (rarely epileptic) and IV are frequently operable by disconnection. Very large type VI (or mixed type) with a large component above the floor of the third ventricle must be disconnected, and then the upper remnant is best treated by GKS using a staged technique. Overall, when the lesion is sufficiently small, GKS offers a rate of seizure control comparable to microsurgery but with much lower risk. The disadvantage of radiosurgery is its delayed action. Longer follow-up is mandatory for a reliable evaluation of the role of GKS. Semin Pediatr Neurol 14:73-79

Neurology, 2007

To assess the activity of brivaracetam, a novel SV2A ligand, in the photosensitivity model as a p... more To assess the activity of brivaracetam, a novel SV2A ligand, in the photosensitivity model as a proof-of-principle of efficacy in patients with epilepsy. A subject-blind placebo-controlled study in patients with photosensitive epilepsy was performed to investigate the effect of single-dose brivaracetam (10, 20, 40, or 80 mg) on photosensitive responses. Each patient was exposed to intermittent photic stimulation that evoked a generalized photoparoxysmal EEG response. Individual standard photosensitivity ranges (SPRs) were recorded post-placebo (day -1) and post-brivaracetam until return to baseline (day 1 to 3). Plasma concentrations of brivaracetam and any concomitant antiepileptic drugs were determined. Of the 18 evaluable patients, none achieved SPR abolishment post-placebo, whereas 14 (78%) achieved complete abolishment post-brivaracetam. Decrease in SPR was seen in 8 patients (44%) post-placebo compared to 17 (94%) post-brivaracetam. Duration of response was twice as long post-brivaracetam 80 mg (59.5 hours) compared with lower doses, although the overall effect was not dose-dependent. Time to maximal photosensitive response was dose-related with the shortest time interval observed at the highest dose (0.5 hours post-brivaracetam 80 mg). The area under the effect curve (SPR change from pre-dose vs time) appeared linearly correlated with the area under the plasma concentration curve. Brivaracetam was well tolerated. The most common adverse events were dizziness and somnolence. Our findings show that brivaracetam clearly suppresses generalized photoparoxysmal EEG response. As such, investigations of the antiepileptic properties and tolerability of brivaracetam are warranted in further clinical studies of patients with epilepsy.

Neurological Sciences, 2010

Hypomelanosis of Ito (HI) is a rare neuroectodermal disorder often associated with mental retarda... more Hypomelanosis of Ito (HI) is a rare neuroectodermal disorder often associated with mental retardation and epilepsy. We report on four new HI patients presenting with heterogeneous seizure manifestations and we review the literature concerning epileptic seizures in HI. At one extreme, there are patients with generalized seizures well controlled by drug treatment, whereas at the opposite there are patients with severe, often pharmacoresistant, focal seizures. The genetic substrate for HI syndrome is not homogenous and only partially understood. Further researches are required to shed light on the pathogenesis of HI phenotypes.

Neurological Sciences, 2009

Movement Disorders, 2009

We report a family of Algerian origin presenting an unusual, severe form of progressive myoclonus... more We report a family of Algerian origin presenting an unusual, severe form of progressive myoclonus epilepsy characterized by myoclonus, generalized tonic-clonic seizures and moderate to severe cognitive impairment, with probable autosomal recessive inheritance. Disease onset was between 6 and 16 years of age. The diagnosis of Unverricht-Lundborg disease and all other known causes of progressive myoclonus epilepsies were excluded by specific laboratory tests and molecular analysis.