Biomedical subjects

C Marescaux

Publications and source records attributed to C Marescaux.

At least 37 records · Page 2Linked to original sources

PubMed2000

Neuroprotective effects of chronic estradiol benzoate treatment on hippocampal cell loss induced by status epilepticus in the female rat.

Neuroprotective properties of estrogen are supported by extensive experimental evidence. In this study, the effects of estrogen were examined on the neurodegeneration secondary to status epilepticus induced by kainic acid in the rat. Chronic supplementation of ovariectomized rats with estradiol benzoate (20 microg/day) did not modify the expression of seizures monitored by electroencephalography, but significantly reduced cellular loss in the hippocampus. This neuroprotection was in particular observed in the dentate hilus and CA3 pyramidal layer when treatment with estradiol benzoate was started five days before status epilepticus induction. These findings suggest that estrogen can exert neuroprotective effects in a model of status epilepticus, in the absence of anti-epileptic properties.

Animals↗

PubMed2000

GABA(B) receptor antagonists elevate both mRNA and protein levels of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) but not neurotrophin-3 (NT-3) in brain and spinal cord of rats.

In this study we show that single, physiologically-active and non-convulsive doses of the three GABA(B) receptor antagonists CGP 36742, CGP 56433A and CGP 56999A increase NGF and BDNF mRNA levels by 200-400% and protein levels by 200-250% in rat neocortex, hippocampus as well as spinal cord. In all areas examined the increase in NGF protein preceded that of BDNF. Peak levels of both neurotrophins are transient and occur between 24 and 72 h, depending on the region. In contrast, NT-3 protein concentrations in the neocortex and hippocampus were decreased significantly to 50% of control values within 48-96 h. The decrease in the spinal cord was less than 30% and did not reach significant levels. These data clearly demonstrate that GABA(B) receptor antagonists induce a specific neurotrophin expression in the central nervous system at physiologically relevant doses, as opposed to the extreme conditions of seizure paradigms. The results are in line with the concept that neuronal neurotrophin synthesis and release in brain are controlled by afferent nerve activity. GABA(B) receptor antagonists could therefore be a valuable new approach to selectively increase endogenous neurotrophin levels in the central nervous system.

Animals↗

PubMed2000

Mapping of the progressive metabolic changes occurring during the development of hippocampal sclerosis in a model of mesial temporal lobe epilepsy.

We have recently characterized the histopathological changes in an experimental model of mesial temporal lobe epilepsy (MTLE) induced by the intrahippocampal injection of low dose of kainate in mice. Although cerebral metabolism and blood flow are extensively studied and used in human MTLE to locate the regions involved in seizures before surgery, this exploration is only performed once the disease has fully developed. Therefore, in the present study, we followed the temporal evolution of intrahippocampal kainate-induced metabolic changes in mice from kainate injection to 120 days later by the quantitative autoradiographic [14C]2-deoxyglucose (2DG) technique. At day 0 (late phase of status epilepticus (SE)) and 15 days after kainate, i.e., during the period of ongoing neuropathological changes, glucose utilization was decreased bilaterally in all parts of the cerebral cortex, and ipsilaterally in the thalamus. In the hippocampus, CA1 metabolic activity was depressed at day 0 and increased at day 15 while CA3 glucose utilization was increased at both day 0 and 15. By day 30, there were almost no pyramidal cells left in the two hippocampal regions. At day 120, ipsilateral decreases persisted in the entorhinal cortex, anterior and ventromedian thalamus, and metabolic increases were recorded bilaterally in the central amygdala, anterior hypothalamus and mamillary body. At all times after kainate, a normo-, hypo- or hypermetabolic level was recorded in the dentate gyrus. The present study shows that the process of hippocampal sclerosis involves bilateral cortical reactivity and the participation of some limbic forebrain and motor structures. When hippocampal sclerosis has fully developed, hypometabolism is limited to regions directly connected to the damaged hippocampus and most likely involved in the new hyperexcitable circuit of limbic seizures.

Animals↗

PubMed2000

Bilateral focal polymicrogyria in Ehlers-Danlos syndrome.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a heterogeneous group of generalized connective tissue disorders that has been described in association with epilepsy and cerebral cortical dysplasia, mostly gray matter heterotopias, in 3 reports. However, to our knowledge, association of EDS with another type of cortical cerebral dysplasia, bilateral focal polymicrogyria, has never previously been described. SETTING: Two research-oriented hospitals. PATIENTS: We describe 2 patients with EDS and bilateral polymicrogyria. The first, a 29-year-old black man, presented with EDS of unspecified type, seizures, and bilateral frontocentral and frontoposterior polymicrogyria with hypoplasia of the inferior part of the cerebellar vermis. The second, a 20-year-old woman, had type III EDS, seizures and congenital bilateral perisylvian syndrome with polymicrogyria. CONCLUSIONS: The association of bilateral focal polymicrogyria and EDS in these 2 patients suggests that extracellular matrix proteins implicated in the pathogenesis of EDS, such as collagen and tenascin, may play an important role in cerebral cortical formation and organization. In a clinical setting, the association of EDS with these cortical structural lesions has implications for diagnosis and management.

Adult↗

PubMed2000

Early loss of interneurons and delayed subunit-specific changes in GABA(A)-receptor expression in a mouse model of mesial temporal lobe epilepsy.

Unilateral injection of kainic acid (KA) into the dorsal hippocampus of adult mice induces spontaneous recurrent partial seizures and replicates histopathological changes observed in human mesial temporal lobe epilepsy (MTLE) (Bouilleret V et al., Neuroscience 1999; 89:717-729). Alterations in pre- and postsynaptic components of GABAergic neurotransmission were investigated immunohistochemically at different time points (1-120 days) in this mouse model of MTLE. Markers of GABAergic interneurons (parvalbumin, calbindin-D28k, and calretinin), the type-1 GABA transporter (GAT1), and major GABA(A)-receptor subunits expressed in the hippocampal formation were analyzed. Acutely, KA injection produced a profound loss of hilar cells but only limited damage to CA1 and CA3 pyramidal cells. In addition, parvalbumin and calbindin-D28k staining of interneurons disappeared irreversibly in CA1 and dentate gyrus (DG), whereas calretinin staining was spared. The prominent GABA(A)-receptor alpha1 subunit staining of interneurons also disappeared after KA treatment, suggesting acute degeneration of these cells. Likewise, GAT1 immunoreactivity revealed degenerating terminals at 24 h post-KA in CA1 and DC and subsided almost completely thereafter. Loss of CA1 and, to a lesser extent, CA3 neurons became evident at 7-15 days post-KA. It was more accentuated after 1 month, accompanied by a corresponding reduction of GABA(A)-receptor staining. In contrast, DC granule cells were markedly enlarged and dispersed in the molecular layer and exhibited a prominent increase in GABA(A)-receptor subunit staining. After 4 months, the dorsal CA1 area was lost almost entirely, CA3 was reduced, and the DG represented most of the remaining dorsal hippocampal formation. No significant morphological alterations were detected contralaterally. These results suggest that loss of hilar cells and GABAergic neurons contributes to epileptogenesis in this model of MTLE. In contrast, long-term degeneration of pyramidal cells and granule cell dispersion may reflect distinct responses to recurrent seizures. Finally, GABA(A)-receptor upregulation in the DG may represent a compensatory response persisting for several months in epileptic mice.

Animals↗

PubMed2000

Pallido-Luysio-Nigral atrophy revealed by rapidly progressive hemidystonia: a clinical, radiologic, functional, and neuropathologic study.

Pallido-luysio-nigral atrophy (PLNA) is a rare neurodegenerative disease in which the clinical and radiologic correlates have not yet been clearly established. A 62-year-old man insidiously developed dystonic postures, choreoathetoid movements, slowness, and stiffness, which initially affected the right hand and foot and progressively spread to the entire right side. T2-weighted magnetic resonance imaging showed increased signal intensity in both left and right medial pallida and in the left substantia nigra. Tests using HMPAO-SPECT and FDG-PET demonstrated left cortical hyperperfusion and hypermetabolism, whereas the left lenticular nucleus was slightly hypometabolic. At age 65, abnormal movements and postures involved all four limbs and the axis causing major gait disturbances, and facial and bulbar muscles atrophied resulting in dysarthria, dysphagia, and impaired breathing. Diffuse amyotrophy and fasciculations also appeared. Death occurred at age 66, 4 years after onset. At autopsy, severe bilateral neuronal loss and gliosis restricted to the pallidum, the subthalamic nucleus, the substantia nigra, and the hypoglossal nucleus were noted, accounting for the diagnosis of PLNA with lower motor neuron involvement. Progressive hemidystonia with adult onset represents an unusual clinical presentation for this disorder. Moreover, this observation indicates that a diagnosis of PLNA should be considered for specific magnetic resonance imaging, SPECT, and/or PET data, and suggests that in PLNA, pallidal dysfunction might play a key role in the dystonic presentation.

Age of Onset↗

PubMed2000

Selective susceptibility to inhibitors of GABA synthesis and antagonists of GABA(A) receptor in rats with genetic absence epilepsy.

Thalamocortical spike-and-wave discharges characterize the nonconvulsive absence seizures that occur spontaneously in genetic absence epilepsy rats from Strasbourg (GAERS), a selected strain of Wistar rats. GABA is crucial in the generation of absence seizures. The susceptibility to convulsions induced by threshold doses of various GABA receptor antagonists and inhibitors of GABA synthesis, kainic acid and strychnine, was compared in GAERS and in nonepileptic rats from a selected control strain (NE). The brain structures involved in the drug-elicited convulsive seizures were mapped by c-Fos immunohistochemistry. Injection of various antagonists of the GABA(A) receptor, bicuculline and picrotoxin, and inverse agonists of the benzodiazepine site (FG 7142 and DMCM) induced myoclonic spike-and-wave discharges followed by clonic or tonic-clonic seizures with high paroxysmal activity on the cortical EEG. The incidence of the convulsions was dose-dependent and was higher in GAERS than in NE rats. Mapping of c-Fos expression showed that the frontoparietal cortex was constantly involved in the convulsive seizures elicited by a threshold convulsant dose, whereas limbic participation was variable. In contrast, GAERS were less susceptible than NE rats to the tonic-clonic convulsions induced by the inhibitors of glutamate decarboxylase, isoniazide and 3-mercaptopropionic acid. The GABA(B) receptor antagonist CGP 56999 and kainic acid induced a similar incidence of seizures in GAERS and NE rats and predominantly activated the hippocampus. No difference in the tonic seizures elicited by strychnine could be evidenced between the strains. These results suggest that an abnormal cortical GABAergic activity may underlie absence seizures in GAERS.

3-Mercaptopropionic Acid↗

PubMed2000

Increased expression of mRNA encoding ferritin heavy chain in brain structures of a rat model of absence epilepsy.

Differential mRNA display was carried out to find genes that are differentially regulated in the brain of a rat strain with absence epilepsy, the genetic absence epilepsy rats from Strasbourg (GAERS). Among the 32 differentially displayed cDNA fragments actually cloned and sequenced, one shows 100% identity with the rat heavy chain ferritin (H-ferritin) mRNA. Northern blot analysis confirmed the up-regulation of the H-ferritin mRNA. Using dot blotting, a 40% increase in expression was reported in the subcortical forebrain of the adult GAERS, while cortex, brain stem, and cerebellum appeared unmodified. This change was not observed in the brain of 25-day-old rats, an age at which the epileptic phenotype is not present. By in situ hybridization, the enhanced expression was localized in the hippocampus. The increase in mRNA encoding H-ferritin was not immunodetected at the protein level by Western blotting. These results are not apparently related to the neural substrate of SWD or to the distribution of local increase in glucose metabolism previously described in the GAERS. It is hypothesized that the up-regulation of the H-ferritin mRNA is part of a mechanism protecting the hippocampus, a seizure-prone area, against a possible overactivation during absence seizures.

Age Factors↗

PubMed2000

Progressive metabolic changes underlying the chronic reorganization of brain circuits during the silent phase of the lithium-pilocarpine model of epilepsy in the immature and adult Rat.

The lithium-pilocarpine (Li-Pilo) model of epilepsy reproduces most of the features of human temporal lobe epilepsy. In the present study, we explored the correlation between metabolic changes, neuronal damage, and epileptogenesis during the silent phase following status epilepticus (SE) induced by Li-Pilo in 10- (P10) and 21-day-old (P21) and adult rats. Cerebral metabolic rates for glucose (CMR(glcs)) were measured at 14 and 60 days after SE by the 2-[(14)C]deoxyglucose method and neurodegeneration was assessed by the silver staining and cresyl violet techniques. In P10 rats, there was no damage and no metabolic consequences at any time after SE. In P21 rats, metabolic decreases were recorded at 14 days after SE, mainly in damaged forebrain regions. Conversely at 60 days after SE, P21 rats exhibited metabolic increases in both forebrain-damaged and brain-stem-intact areas. Finally, in adult rats studied at 14 days after SE, CMR(glcs) decreased in damaged forebrain areas involved in the circuitry of spontaneous seizures and increased in nondamaged brain-stem areas involved in the remote control of epilepsy. The increase in CMR(glcs) in damaged forebrain areas of P21 rats at 60 days after SE may reflect the genesis of a new circuitry underlying the occurrence of spontaneous seizures. The metabolic increase recorded in nondamaged brain-stem areas of P21 and adult rats occurs in regions involved in the remote control of seizures and might underlie a process of protection against the occurrence of seizures.

Age Factors↗

PubMed2000

The lesional and epileptogenic consequences of lithium-pilocarpine-induced status epilepticus are affected by previous exposure to isolated seizures: effects of amygdala kindling and maximal electroshocks.

In temporal lobe epilepsy, the occurrence of seizures seems to correlate with the presence of lesions underlying the establishment of a hyperexcitable circuit. However, in the lithium-pilocarpine model of epilepsy, neuronal damage occurs both in the structures belonging to the circuit of initiation and maintenance of the seizures (forebrain limbic system) as in the propagation areas (cortex and thalamus) and in the circuit of remote control of seizures (substantia nigra pars reticulata). To determine whether or not we could protect the brain from lesions and epileptogenesis induced by status epilepticus and identify cerebral structures involved in the genesis of epilepsy, we studied the effects of the chronic exposure to non-deleterious seizures, either focalized with secondary generalization (amygdala kindling, kindled-pilocarpine rats), or primary generalized (ear-clip electroshocks, electroshock-pilocarpine rats) on neuronal damage and epileptogenesis induced by lithium-pilocarpine status epilepticus. These animals were compared to rats subjected to status epilepticus but not pretreated with seizures (sham-kindled-pilocarpine or sham-electroshock-pilocarpine rats). Compared to sham-pilocarpine rats, neuronal damage was prevented in the limbic system of the kindled-pilocarpine rats, except in the hilus of the dentate gyrus and the entorhinal cortex, while it was enhanced in rats pretreated with electroshocks, mainly in the entorhinal and perirhinal cortices. Most sham-kindled- and sham-electroshock-pilocarpine rats (92-100%) developed recurrent seizures after a silent period of 40-54days. Likewise, all kindled-pilocarpine rats developed spontaneous seizures after the same latency as their sham controls, while only two of 10 electroshock-pilocarpine rats became epileptic after a delay of 106-151days. The present data show that the apparent antiepileptic properties of electroshocks correlate with extensive damage in midbrain cortical regions, which may prevent the propagation of seizures from the hippocampus and inhibit their motor expression. Conversely, the extensive neuroprotection of the limbic system but not the hilus and entorhinal cortex provided by amygdala kindling does not prevent epileptogenesis. Thus, the hilus, the entorhinal and/or perirhinal cortex may be key structure(s) for the establishment of epilepsy.

Amygdala↗

PubMed2000

Dopamine in the striatum modulates seizures in a genetic model of absence epilepsy in the rat.

Inhibition of the substantia nigra pars reticulata has been shown to suppress seizures in different animal models of epilepsy. The striatum is the main input of the substantia nigra pars reticulata. The aim of the present study was to examine the role of dopaminergic neurotransmission within the striatum in the control of absence seizures in a genetic model in the rat. Injections of mixed dopaminergic D1/D2 or of selective D1 or D2 agonists or antagonists in the dorsal parts of the striatum led to suppression of absence seizures associated with strong behavioral and electroencephalographic side-effects. When injected in the ventral part of the striatum (i.e. the nucleus accumbens core), all these agonists and antagonists respectively decreased and increased absence seizures without behavioral or electroencephalographic side-effects. Combined injections of low doses of a D1 and a D2 agonist in the core of the nucleus accumbens had an additive effect in absence seizures suppression. Furthermore, combined injections of low doses of a GABA(A) agonist and a N-methyl-D-aspartate antagonist in the substantia nigra also had cumulative effects in absence seizures suppression. These results show that dopamine neurotransmission in the core of the nucleus accumbens is critical in the control of absence seizures. The modulatory and additive effects on absence seizures of dopaminergic neurotransmission through both the D1 and D2 receptors in the core of the nucleus accumbens further suggest that ventral pathways of the basal ganglia system are involved in the modulation of absence seizures.

Animals↗

PubMed2000

Brain-derived neurotrophic factor delays hippocampal kindling in the rat.

Epileptic seizures increase the expression of brain-derived neurotrophic factor in the hippocampus. Since this neurotrophin exerts modulatory effects on neuronal excitability in this structure, it may play an important role in hippocampal epileptogenesis. This question was addressed by studying the effects of chronic infusions of recombinant brain-derived neurotrophic factor and brain-derived neurotrophic factor antisense in the hippocampus during the first seven days of hippocampal kindling. Infusion with brain-derived neurotrophic factor (6-24 microg/day) significantly delayed the progression of standard hippocampal kindling and strongly suppressed seizures induced by rapid hippocampal kindling. These suppressive effects were dose dependent, long lasting, not secondary to neuronal toxicity and specific to this neurotrophin, as nerve growth factor accelerated hippocampal kindling progression. They also appeared to be specific to the hippocampus, as infusion of brain-derived neurotrophic factor (48 microg/day) in the amygdala only resulted in a slight and transient delay of amygdala kindling. Conversely to the protective effects of exogenous brain-derived neurotrophic factor, chronic hippocampal infusion of antisense oligodeoxynucleotides (12 nmol/day), resulting in reduced expression of endogenous brain-derived neurotrophic factor in the hippocampus, aggravated seizures during hippocampal kindling. Taken together, our results lead us to suggest that the seizure-induced increase in brain-derived neurotrophic factor expression in the hippocampus may constitute an endogenous regulatory mechanism able to restrain hippocampal epileptogenesis.

Amygdala↗

PubMed2000

Electroshocks delay seizures and subsequent epileptogenesis but do not prevent neuronal damage in the lithium-pilocarpine model of epilepsy.

Electroconvulsive therapy, which is used to treat refractory major depression in humans increases seizure threshold and decreases seizure duration. Moreover, the expression of brain derived neurotrophic factor induced by electroshocks (ECS) might protect hippocampal cells from death in patients suffering from depression. As temporal lobe epilepsy is linked to neuronal damage in the hippocampus, we tested the effect of repeated ECS on subsequent status epilepticus (SE) induced by lithium-pilocarpine and leading to cell death and temporal epilepsy in the rat. Eleven maximal ECS were applied via ear-clips to adult rats. The last one was applied 2 days before the induction of SE by lithium-pilocarpine. The rats were electroencephalographically recorded to study the SE characteristics. The rats treated with ECS before pilocarpine (ECS-pilo) developed partial limbic (score 2) and propagated seizures (score 5) with a longer latency than the rats that underwent SE alone (sham-pilo). Despite this delay in the initiation and propagation of the seizures, the same number of ECS- and sham-pilo rats developed SE with a similar characteristic pattern. The expression of c-Fos protein was down-regulated by repeated ECS in the amygdala and the cortex. In ECS-pilo rats, c-Fos expression was decreased in the piriform and entorhinal cortex and increased in the hilus of the dentate gyrus. Neuronal damage was identical in the forebrain areas of both groups, while it was worsened by ECS treatment in the substantia nigra pars reticulata, entorhinal and perirhinal cortices compared to sham-pilo rats. Finally, while 11 out of the 12 sham-pilo rats developed spontaneous recurrent seizures after a silent period of 40+/-27 days, only two out of the 10 ECS-pilo rats became epileptic, but after a prolonged latency of 106 and 151 days. One ECS-pilo rat developed electrographic infraclinical seizures and seven did not exhibit any seizures. Thus, the extensive neuronal damage occurring in the entorhinal and perirhinal cortices of the ECS-pilo rats seems to prevent the establishment of the hyperexcitable epileptic circuit.

Animals↗

PubMed2000

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Journal Article↗

PubMed2000

Landau-Kleffner syndrome: sleep EEG characteristics at onset.

OBJECTIVES: Landau-Kleffner syndrome (LKS) and benign epilepsy with centro-temporal spikes (BECTS) are two forms of non-lesional age-related focal epilepsies. LKS is a severe disease, affecting language abilities, attention and behavior, and evolving to acquired global aphasia. As LKS is usually readily responsive to an adequate pharmacological management, an early diagnosis of children at risk for this syndrome is essential. BECTS is characterized by the absence of neurological or neuropsychological deficits throughout the course of epilepsy. However, children initially presenting some clinical and EEG features suggesting BECTS may develop severe cognitive impairments during the course of epilepsy. These cases raise the question of whether LKS and BECTS delineate fundamentally different conditions, or represent subclasses of a broad continuum. METHODS: We compared sleep EEG characteristics of 7 children with typical LKS to those of 6 children with classical BECTS. RESULTS: Morphology, topography, organization, and abundance of interictal abnormalities during sleep differentiated these two syndromes from epilepsy onset, before the occurrence of aphasic deficits in LKS. The specific sleep EEG patterns possibly predictive of LKS were (1) unilateral slow wave foci, (2) bilateral independent spike-and-wave discharges, and (3) major activation of spike-and-wave discharges during sleep, exceeding 40% (40-90%) of the first sleep cycle and 30% (30-80%) of the following cycles. CONCLUSIONS: These data support the hypothesis that during LKS evolution, language networks involved in the spread of abundant idiopathic interictal abnormalities (and mainly slow waves) may be progressively inhibited and become unable to carry out their normal physiological role.

Age of Onset↗

PubMed2000

Overexpression of neuropeptide Y induced by brain-derived neurotrophic factor in the rat hippocampus is long lasting.

Brain-derived neurotrophic factor (BDNF) plays an important role in hippocampal neuroplasticity. In particular, BDNF upregulation in the hippocampus by epileptic seizures suggests its involvement in the neuronal rearrangements accompanying epileptogenesis. We have shown previously that chronic infusion of BDNF in the hippocampus induces a long-term delay in hippocampal kindling progression. Although BDNF has been shown to enhance the excitability of this structure upon acute application, long-term transcriptional regulations leading to increased inhibition within the hippocampus may account for its suppressive effects on epileptogenesis. Therefore, the long-term consequences of a 7-day chronic intrahippocampal infusion of BDNF (12 microg/day) were investigated up to 2 weeks after the end of the infusion, on the expression of neurotransmitters contained in inhibitory hippocampal interneurons and which display anti-epileptic properties. Our results show that BDNF does not modify levels of immunostaining for glutamic acid decarboxylase, the rate-limiting enzyme for gamma-aminobutyric acid (GABA) synthesis, and somatostatin. Conversely, BDNF induces a long-lasting increase of neuropeptide Y (NPY) in the hippocampus, measured by immunohistochemistry and radioimmunoassay, outlasting the end of the infusion by at least 7 days. The distribution of BDNF-induced neuropeptide Y immunoreactivity is similar to the pattern observed in animals submitted to hippocampal kindling, with the exception of mossy fibres which only become immunoreactive following seizure activity. The enduring increase of neuropeptide Y expression induced by BDNF in the hippocampus suggests that this neurotrophin can trigger long-term genomic effects, which may contribute to the neuroplasticity of this structure, in particular during epileptogenesis.

Animals↗

PubMed2000

Future prospects of brain stimulation.

Chronic high frequency (130 Hz) stimulation (HFS) of the thalamic target Vim has replaced thalamotomy as a treatment of tremor of various origins and was extended to two other targets (Subthalamic nucleus (STN) and the medial pallidus (GPi)), since 1993 based on recent experimental data in rats and monkeys. STN appears to be a target of major interest, able to control the three cardinal symptoms and to allow the decrease or suppression of levodopa treatment, which then suppresses also levodopa induced dyskinesias. The mechanisms of action of HFS are not fully understood, but are definitely related to high frequency and are probably different depending on the target. Inhibition of cellular activity or of network functions could be induced, by jamming of a retroactive loop for tremor, or by shutdown of neurotransmitter release in STN. All cardinal symptoms are alleviated from tremor to akinesia and rigidity. The effects remain stable over more than five years chronic HFS of STN, as the method of choice when a surgical procedure is indicated for the treatment of Parkinson's disease and even more when a bilateral procedure is necessary. Recent data show that STN stimulation could be useful in the treatment of dystonia as well as some forms of epilepsies. It is therefore possible that DAS in STN as well as in other targets could become a potent therapeutic tool in the future for neurological disorders. The future of brain stimulation will depend on new technologies (new circuits, electrodes, web based programmers), waveforms (alternatives to square waves, random distribution), targets (hypothalamic nuclei, locus coeruleus) and indications (dystonia, epilepsy, eating disorders.

Animals↗

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↗