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Biomedical subjects

Edouard Hirsch

Publications and source records attributed to Edouard Hirsch.

At least 19 recordsLinked to original sources
PubMed2006

Optimizing therapy of seizures in patients with renal or hepatic dysfunction.

Patients with epilepsy may suffer from renal or hepatic diseases that interfere with their antiepileptic drug (AED) treatment. Furthermore, such diseases may themselves cause seizures. Reduced renal function and hypoalbuminemia lead to accumulation of renally excreted AEDs, such as gabapentin, vigabatrin, topiramate, levetiracetam, and phenytoin. Valproate, lamotrigine, and benzodiazepines are less affected. Low protein-bound AEDs are extensively removed by hemodialysis and supplemental doses are required for dialysis patients. Uremia and related conditions, including intracranial hemorrhage, glucose and electrolyte imbalances, and concomitant drug use, can cause seizures, as can dialysis encephalopathy, primary cerebral lymphoma, fungal infections, and immunosuppressant toxicity in renal transplant recipients. Hepatic dysfunction reduces enzymatic metabolism of AEDs and causes hypoalbuminemia. Gabapentin, topiramate, and levetiracetam are preferred in these conditions, whereas conversely valproate and felbamate are potentially hepatotoxic and should be avoided. Seizures related to hepatic encephalopathy are controlled by oral lactulose or neomycin. Porphyria sufferers may benefit from gabapentin, oxcarbazepine, or levetiracetam. Seizures in Wilson's disease may derive from d-penicillamine-induced pyridoxine deficiency. Effective treatment of seizures in renal and hepatic diseases requires attention to changes in AED pharmacokinetics and adequate care of the underlying illnesses. Monitoring of free drug concentrations is a valuable aid to therapy.

Anticonvulsants↗
PubMed2006

Neural responses associated with positive and negative emotion processing in patients with left versus right temporal lobe epilepsy.

Studies on emotion processing in patients with temporal lobe epilepsy have dealt mainly with the processing of negative emotions. To further understand the neural basis of emotional disorders in temporal lobe epilepsy, we studied patterns of brain activation induced by implicit processing of negative and positive emotions perceived through facial expressions and emotionally salient stimuli in candidates for surgical treatment of intractable epilepsy. Using functional MRI, we compared, in patients with mesial temporal lobe epilepsy and healthy subjects, the patterns of brain activation elicited by the implicit processing of fearful, sad, and happy faces and pleasant and unpleasant scenes. The results revealed different patterns of activation in patients with left and right mesial temporal lobe epilepsy, compared with healthy subjects, suggesting that the left and right mesial temporal regions are involved differently in emotion processing, which could be related to different contributions in emotional arousal.

Adult↗
PubMed2006

Landau-Kleffner syndrome is not an eponymic badge of ignorance.

In a 1992 editorial article, Landau expressed the hope of collective agreement in the medical community about Landau-Kleffner syndrome (LKS) in terms of diagnosis criteria, etiology, pathophysiology and rational therapy. Since then, neurophysiological and neuroimaging studies have led to the view that LKS is an acquired aphasia, secondary to an epileptic disturbance affecting a cortical area involved in verbal processing. This fits with the hypothesis of a "functional ablation" caused by epileptic activity. Under these criteria, epileptic aphasia becomes a subgroup of the continuous spike-waves syndrome in which epileptic discharges originate from the temporal cortex. Genetic predisposition for KLS could be related to hyperexcitability and synchronization of interneurons within the perisylvian cortices, which generate the spike-waves. Activation of these waves during NREM sleep, following thalamo-cortical uncoupling, might then alter the blood brain barrier and provoke an autoimmune reaction. Interneuron hyperactivity might in turn have an antiepileptic protective effect, associated with the inhibition of a specific function, and spike-waves activity over the long term might eventuate in focal atrophy. This morphological defect might explain the poor verbal outcome in some cases of LKS. From this study we recommend a multicenter control study of good design and methodology be carried out to compare the efficacies of early versus delayed (3 months) corticosteroid treatment in patients with typical LKS that is being treated by clobazam (or diazepam) monotherapy.

Adrenal Cortex Hormones↗
PubMed2006

SRPX2 mutations in disorders of language cortex and cognition.

The rolandic and sylvian fissures divide the human cerebral hemispheres and the adjacent areas participate in speech processing. The relationship of rolandic (sylvian) seizure disorders with speech and cognitive impairments is well known, albeit poorly understood. We have identified the Xq22 gene SRPX2 as being responsible for rolandic seizures (RSs) associated with oral and speech dyspraxia and mental retardation (MR). SRPX2 is a secreted sushi-repeat containing protein expressed in neurons of the human adult brain, including the rolandic area. The disease-causing mutation (N327S) resulted in gain-of-glycosylation of the secreted mutant protein. A second mutation (Y72S) was identified within the first sushi domain of SRPX2 in a male with RSs and bilateral perisylvian polymicrogyria and his female relatives with mild MR or unaffected carrier status. In cultured cells, both mutations were associated with altered patterns of intracellular processing, suggesting protein misfolding. In the murine brain, Srpx2 protein expression appeared in neurons at birth. The involvement of SRPX2 in these disorders suggests an important role for SRPX2 in the perisylvian region critical for language and cognitive development.

Adult↗
PubMed2006

Nocturnal hypermotor seizures, suggesting frontal lobe epilepsy, can originate in the insula.

PURPOSE: To report three patients with drug-resistant nocturnal hypermotor seizures (NHSs), no detectable brain lesion, and clinically defined nocturnal frontal lobe epilepsy (NFLE) or autosomal dominant NLFE (ADNFLE), whose intracerebral EEG ictal onset primarily involved the insula, rather than the mesial or orbital frontal cortex. METHODS: Fourteen to 15 intracerebral electrodes were implanted in each patient, primarily sampling the frontal lobes with 80 to 91 recording leads covering the most likely side of seizure onset, and two to six leads placed within the ipsilateral insula. Electrical stimulation was used to test the epileptic threshold of frontal and insular brain regions at the various recording sites. RESULTS: In all three patients, a low-voltage fast activity was recorded within the anterosuperior aspect of the insula at ictal onset, either in isolation, or extending to the nearby frontal operculum in the ADNFLE patient. The role of the insula was further supported in all three patients either by the presence of high-amplitude spikes that clearly predominated over that region (n = 2) or by triggering the patient's typical aura or seizure when applying an electrical stimulation at that site, selectively (n = 2). CONCLUSIONS: The anterosuperior portion of the insula might play a pivotal role in generating nocturnal hypermotor seizures in some patients with nonlesional drug-resistant epilepsy suggesting NFLE or ADNFLE. Whether these patients are amenable to successful surgery remain an open issue.

Adolescent↗
PubMed2006

Language-induced epilepsy, acquired stuttering, and idiopathic generalized epilepsy: phenotypic study of one family.

PURPOSE: Language-induced epilepsy involves seizure precipitation by speaking, reading, and writing. Seizures are similar to those of reading epilepsy (RE). The nosologic position of language-induced epilepsy is not clear. We performed a clinical and neurophysiological study in a multigenerational family with the association of idiopathic generalized epilepsy (IGE) with ictal stuttering as a manifestation of reflex language-induced epilepsy. METHODS: Nine members on three generations were studied. All patients underwent video-polygraphic EEG recordings (awake and during sleep). A standardized protocol was applied to test the effect of language and non-language-related tasks. RESULTS: Six patients presented language-induced jaw jerking that mimicked stuttering and corresponded to focal myoclonus involving facial muscles. This was associated with an IGE phenotype in four of these patients. Focal EEG spikes were found in all six patients by visual analysis and/or back-averaging techniques. The focal spikes were either asymptomatic (when followed by a slow wave) or symptomatic of facial myoclonia (when isolated). Levetiracetam, used as add-on or monotherapy in four patients, suppressed ictal stuttering. One additional case only had a phenotype of IGE without focal features. CONCLUSIONS: This family study demonstrates the phenotypic heterogeneity of the association of IGE phenotype with ictal stuttering (language-related reflex seizure). Our data suggest that this particular form of reflex epilepsy related to language has more similarities with generalized epilepsies than with focal ones. Neurophysiological investigations should be performed more systematically in patients with acquired stuttering, especially if there is family history of IGE.

Adolescent↗
PubMed2006

Isolated paroxysmal arousals as focal epilepsy.

Paroxysmal motor phenomena and arousals during sleep are frequent. The differential diagnoses between benign hypnic transient events, epileptic and non-epileptic seizures represent a common clinical problem. Video-EEG monitoring during sleep, recording several episodes in the same patient, is essential in order to characterize these phenomena. It offers the possibility to compare electro-clinical data, to demonstrate the eventual stereotyped pattern of motor phenomena and their progression in time, and to study EEG-polygraphic correlates. The recently described double split-screen synchronized display (DSSSD) technique represents a useful tool for comparing particular clinical patterns of epileptic seizures when dealing with complex, hypermotor phenomena observed in frontal lobe epilepsy. We reviewed the data of 24 patients admitted during a two-year period (2002-2003) to our epilepsy sleep unit for isolated paroxysmal sleep motor events. Four patients presented with very brief paroxysmal arousals without daytime fits. Three of our patients presented isolated paroxysmal arousals, whereas in one, the events were associated with hypermotor seizures. We present a simplified variant of the DSSSD method (modified DSSSD) that can be used to study episodes of paroxysmal arousals in order to confirm their stereotyped motor pattern. The clinical aspects and the EEG-polygraphy patterns were informative, with the absence of asymmetrical tonic or dystonic posturing of the limbs. Scalp EEG alone does not usually provide much information in patients with isolated paroxysmal arousals. Coupled to the modified DSSSD technique, it may allow confirmation of the diagnosis of frontal epilepsy, as was the case in our four patients. [Published with video sequences].

Adult↗
PubMed2006

Towards a definition of the "practical" epileptogenic zone: a case of epilepsy with dual pathology.

Presurgical evaluation for patients with drug-resistant epilepsy requires the definition of various zones that have a variable spatial relationship with the epileptogenic zone. All the available methods to directly measure the actual seizure-onset zone and to define "the minimum amount of cortical tissue that must be resected to produce seizure-freedom" have significant limitations. We report on the case of a patient with dual pathology (hippocampal sclerosis and a post-traumatic scar) and discuss the contribution of the various presurgical investigations that led to surgery and seizure-freedom.

Adult↗
PubMed2005

Selective memory impairment for public events in a patient with left temporal lobe epilepsy.

Highly selective memory impairment for public events was demonstrated in a patient (JR), who suffered from temporal lobe epilepsy (TLE). We successfully trained JR's memory for a set of news events and discuss, on those bases, the characteristics of news events processing that may have contributed to its increased vulnerability relative to autobiographical memory (AbM).

Epilepsy, Temporal Lobe↗
PubMed2005

Antiglial cell autoantibodies and childhood epilepsy: a case report.

We report the case of a patient with severe partial epilepsy associated with a focal rolandic, pathologically proven, cortical dysplasia. By measuring intracellular calcium concentrations, functional antiglial non-glutamate receptor 3 (GluR3) autoantibodies were identified in the serum of this patient. Antineuronal autoantibodies, which interfere with GluR3-receptor function, also were detected. This observation provides new clues about the involvement of immunologic mechanisms in epileptic disorders.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2004

Genome-wide linkage scan of epilepsy-related photoparoxysmal electroencephalographic response: evidence for linkage on chromosomes 7q32 and 16p13.

Photoparoxysmal response (PPR) is an abnormal visual sensitivity of the brain in reaction to intermittent photic stimulation. It is an epilepsy-related electroencephalographic trait with high prevalence in idiopathic epilepsies, especially in common idiopathic generalized epilepsies (IGEs), such as childhood absence epilepsy and juvenile myoclonic epilepsy. This degree of co-morbidity suggests that PPR may be involved in the predisposition to IGE. The identification of genes for PPR would, therefore, aid the dissection of the genetic basis of IGE. Sixteen PPR-multiplex families were collected to conduct a genome-wide linkage scan using broad (all PPR types) and narrow (exclusion of PPR types I and II and the occipital epilepsy cases) models of affectedness for PPR. We found an empirical genome-wide significance for parametric (HLOD) and non-parametric (NPL) linkage (Pgw(HLOD)=0.004 and Pgw(NPL)=0.01) for two respective chromosomal regions, 7q32 at D7S1804 (HLOD=3.47 with alpha=1, P(NPL)=3.39x10(-5)) and 16p13 at D16S3395 (HLOD=2.44 with alpha=1, P(NPL)=7.91x10(-5)). These two genomic regions contain genes that are important for the neuromodulation of cortical dynamics and may represent good targets for candidate-gene studies. Our study identified two susceptibility loci for PPR, which may be related to the underlying myoclonic epilepsy phenotype present in the families studied.

Chromosome Mapping↗
PubMed2004

Epilepsy and videogames.

Since the first case of videogame (VG) epilepsy was reported in 1981, many cases of seizures triggered by VGs were reported, not only in photosensitive, but also in non-photosensitive children and adolescents with epilepsy. We provide an overview of the literature with overall conclusions and recommendations regarding VG playing. Specific preventive measures concerning the physical characteristics of images included in commercially available VGs (flash rate, choice of colors, patterns, and contrast) can lead in the future to a clear decrease of this problem. In addition to the positive effect of such measures, the collaborative studies performed in France and in the rest of Europe have stressed the importance of a safe distance to the screen of > or = 2 m, and the less provocative role of 100-Hz screens.

Adolescent↗
PubMed2004

Ictal and interictal perfusion variations measured by SISCOM analysis in typical childhood absence seizures.

Single photon emission computed tomography (SPECT) is currently used in the presurgical evaluation of medically intractable partial epilepsies, but not very often, in generalized epilepsy. In the present study, we used the SISCOM procedure, which represents the fusion of MRI and ictal-interictal difference SPECT images using (99m)Tc-ECD, to study cerebral blood flow changes during the ictal and postictal phases of typical childhood absence seizures. The study was performed on four children with typical, difficult to treat absence seizures, aged 10-13 years at the time of scan. The delay between the onset of absence seizures and the injection of (99m)Tc-ECD was carefully noted. One scan was performed during the ictal phase and showed diffuse blood flow decreases, while the three other scans performed during the postictal phase, showed generalized blood flow increase. These data are consistent with most previous data reporting generalized changes in functional activity, not limited to the thalamo-cortical circuit in which absence seizures originate, and a decrease in cerebral blood flow during the ictal phase. Our data are concordant with the hypothesis that neuronal activity underlying the occurrence of spike-and-wave discharges does not seem to require an increase in metabolic demand and blood flow rates. [Published with videosequences].

Adolescent↗
PubMed2003

Antiepileptic drug-induced pharmacodynamic aggravation of seizures: does valproate have a lower potential?

Thirty-five years since its introduction into clinical use, valproate (valproic acid) has established itself as one of the most widely used antiepileptic drugs (AEDs). In recent years, there has been a growing awareness of the potential aggravation of seizure disorders by AEDs. Such aggravation may be due to a variety of factors that include a paradoxical pharmacodynamic effect. In order to address this important safety aspect of AED treatment, we reviewed all available published evidence in search of factors related to seizure aggravation during valproate therapy. We analysed the 20 available publications, which outline about 99 case reports (in some papers, the exact number was not specified) of aggravation of seizures associated with valproate. Almost all of these cases occurred in a specific clinical context known to be linked to seizure aggravation, such as overdose, encephalopathy, hepatopathy or metabolic disorders. However, we found no consistent evidence of pure pharmacodynamic aggravation in the absence of any of the above quoted factors. In view of the large number of patients treated worldwide with valproate, the number of reported cases of seizure aggravation in patients taking the drug in the literature is low. Conditions in which worsening of seizures as a result of valproate use may occur are well known and often avoidable. Thus, unlike most AEDs, including the newer ones, valproate appears to have a very low potential for pharmacodynamic paradoxical seizure aggravation. This knowledge is in accordance with long-standing clinical experience and practice.

Anticonvulsants↗
PubMed2003

Levetiracetam: preliminary efficacy in generalized seizures.

Levetiracetam is a novel antiepileptic drug (AED) with proven efficacy against partial seizures, but there is limited information about its effectiveness against generalized seizures. In animal models, levetiracetam protects against seizures in audiogenic susceptible rodents, and it is effective in the Genetic Absence Epilepsy Rat from Strasbourg, a model of absence seizures. In these models, levetiracetam has a therapeutic index that is higher than those of other AEDs. A number of small open-label studies suggest that levetiracetam reduces seizure frequency in patients with generalized seizures, including primarily generalized seizures and myoclonic seizures. Case reports provide additional information regarding the potential efficacy of levetiracetam in postanoxic, post-encephalitic and progressive myoclonus. Although random-ized controlled studies of patients with generalized seizures have not yet been conducted, on the basis of available information, levetiracetam may be prom-ising in the treatment of generalized seizures.

Animals↗