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1.
Epileptic Disord ; 26(1): 1-59, 2024 Feb.
Article En | MEDLINE | ID: mdl-38116690

Epilepsy surgery is the therapy of choice for many patients with drug-resistant focal epilepsy. Recognizing and describing ictal and interictal patterns with intracranial electroencephalography (EEG) recordings is important in order to most efficiently leverage advantages of this technique to accurately delineate the seizure-onset zone before undergoing surgery. In this seminar in epileptology, we address learning objective "1.4.11 Recognize and describe ictal and interictal patterns with intracranial recordings" of the International League against Epilepsy curriculum for epileptologists. We will review principal considerations of the implantation planning, summarize the literature for the most relevant ictal and interictal EEG patterns within and beyond the Berger frequency spectrum, review invasive stimulation for seizure and functional mapping, discuss caveats in the interpretation of intracranial EEG findings, provide an overview on special considerations in children and in subdural grids/strips, and review available quantitative/signal analysis approaches. To be as practically oriented as possible, we will provide a mini atlas of the most frequent EEG patterns, highlight pearls for its not infrequently challenging interpretation, and conclude with two illustrative case examples. This article shall serve as a useful learning resource for trainees in clinical neurophysiology/epileptology by providing a basic understanding on the concepts of invasive intracranial EEG.


Drug Resistant Epilepsy , Epilepsies, Partial , Epilepsy , Child , Humans , Electrocorticography/methods , Epilepsies, Partial/diagnosis , Epilepsies, Partial/surgery , Electroencephalography/methods , Seizures/diagnosis , Drug Resistant Epilepsy/diagnosis , Drug Resistant Epilepsy/surgery
2.
Eur J Neurol ; 28(1): 15-32, 2021 01.
Article En | MEDLINE | ID: mdl-32959446

BACKGROUND AND PURPOSE: Some epilepsy syndromes (sleep-related epilepsies, SREs) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life. Our purpose was to define the standard procedures for the diagnostic pathway of patients with possible SRE (scenario 1) and the general management of patients with SRE and comorbidity with sleep disorders (scenario 2). METHODS: The project was conducted under the auspices of the European Academy of Neurology, the European Sleep Research Society and the International League Against Epilepsy Europe. The framework entailed the following phases: conception of the clinical scenarios; literature review; statements regarding the standard procedures. For the literature search a stepwise approach starting from systematic reviews to primary studies was applied. Published studies were identified from the National Library of Medicine's MEDLINE database and Cochrane Library. RESULTS: Scenario 1: Despite a low quality of evidence, recommendations on anamnestic evaluation and tools for capturing the event at home or in the laboratory are provided for specific SREs. Scenario 2: Early diagnosis and treatment of sleep disorders (especially respiratory disorders) in patients with SRE are likely to be beneficial for seizure control. CONCLUSIONS: Definitive procedures for evaluating patients with SRE are lacking. Advice is provided that could be of help for standardizing and improving the diagnostic approach of specific SREs. The importance of identifying and treating specific sleep disorders for the management and outcome of patients with SRE is underlined.


Epilepsy, Reflex , Sleep Wake Disorders , Consensus , Humans , Quality of Life , Sleep , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/epidemiology
3.
Rev Neurol (Paris) ; 175(3): 163-182, 2019 Mar.
Article En | MEDLINE | ID: mdl-30686486

Medically treated patients suffering from tuberous sclerosis complex (TSC) have less than 30% chance of achieving a sustained remission. Both the international TSC consensus conference in 2012, and the panel of European experts in 2012 and 2018 have concluded that surgery should be considered for medically refractory TSC patients. However, surgery remains currently underutilized in TSC. Case series, meta-analyses and guidelines all agree that a 50 to 60% chance of long-term seizure freedom can be achieved after surgery in TSC patients and a presurgical work-up should be done as early as possible after failure of two appropriate AEDs. The presence of infantile spasms, the second most common seizure type in TSC, had initially been a barrier to surgical planning but is now no longer considered a contraindication for surgery in TSC patients. TSC patients undergoing presurgical evaluation range from those with few tubers and good anatomo-electro-clinical correlations to patients with a significant "tuber burden" in whom the limits of the epileptogenic zone is much more difficult to define. Direct surgery is often possible in patients with a good electro-clinical and MRI correlation. For more complex cases, invasive monitoring is often mandatory and bilateral investigations can be necessary. Multiple non-invasive tools have been shown to be helpful in determining the placement of these invasive electrodes and in planning the resection scheme. Additionally, at an individual level, multimodality imaging can assist in identifying the epileptogenic zone. Increased availability of investigations that can be performed without sedation in young and/or cognitively impaired children such as MEG and HR EEG would most probably be of great benefit in the TSC population. Of those selected for invasive EEG, rates of seizure freedom following surgery are close to cases where invasive monitoring is not required, strengthening the important and efficient role of intracranial investigations in drug-resistant TSC associated epilepsy.


Neurosurgical Procedures/history , Neurosurgical Procedures/methods , Neurosurgical Procedures/trends , Tuberous Sclerosis/surgery , Child , Electroencephalography/methods , History, 19th Century , History, 20th Century , History, 21st Century , Humans , Magnetic Resonance Imaging/methods , Neurosurgeons/history , Neurosurgical Procedures/statistics & numerical data , Treatment Outcome , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis/epidemiology
4.
Acta Neurol Scand ; 135(1): 92-99, 2017 Jan.
Article En | MEDLINE | ID: mdl-27080243

OBJECTIVE: While status epilepticus (SE) persisting after two antiseizure agents is called refractory (RSE), super-refractory status epilepticus (SRSE) defines SE continuing after general anaesthesia. Its prevalence and related clinical profiles have received limited attention, and most studies were restricted to intensive care facilities. We therefore aimed at describing RSE and SRSE frequencies and identifying associated clinical variables. METHODS: Between 2006 and 2015, consecutive adult SE episodes were prospectively recorded in a registry. Occurrence of RSE and SRSE and their relationship to clinical variables of interest, including outcome, were analysed. RESULTS: Of 804 SE episodes, 268 (33.3%) were RSE and 33 (4%) SRSE. Coma induction for SE treatment occurred in 79 (9.8%) episodes. Severe consciousness impairment (OR 1.67; 95% CI 1.24-2.46; P = 0.001), increasing age (OR 1.01, 95% CI 1.01-1.02), and lack of remote symptomatic SE aetiology (OR 0.48; 95% CI 0.32-0.72) were independently associated with RSE, while severe consciousness impairment (OR 4.26; 95% CI 1.44-12.60) and younger age (OR 0.96; 95% CI 0.95-0.99) correlated with SRSE; however, most SRSE episodes were not predicted by these variables. Mortality was 15.5% overall, higher in RSE (24.5%) and SRSE (37.9%) than in non-refractory SE (9.8%) (P < 0.001). SIGNIFICANCE: Super-refractory status epilepticus appears clearly less prevalent in this cohort than previously reported, probably as it is not restricted to intensive care unit. SRSE emerges in younger patients with marked consciousness impairment, pointing to the underlying severe clinical background, but these variables do not predict most SRSE developments. There is currently a knowledge gap for prediction of SRSE occurrence that needs to be filled.


Status Epilepticus/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Anticonvulsants/therapeutic use , Female , Humans , Male , Middle Aged , Prevalence , Registries , Status Epilepticus/diagnosis , Status Epilepticus/drug therapy , Switzerland
5.
Rev Neurol (Paris) ; 172(3): 174-81, 2016 Mar.
Article En | MEDLINE | ID: mdl-26993563

Invasive EEG recordings are frequently required during the presurgical exploration of patients with drug-resistant focal epilepsy in order to clarify the epileptic zone location. Intracranial direct electrical stimulations (DES) induce EEG and/or clinical responses that participate in this evaluation. Clinical DES protocols (1Hz and/or 50Hz) trigger massive cortical activation that can elicit seizures, after-discharges or complex clinical signs. In contrast, low-energy (<1Hz) protocols activate more localized cortical regions using single-pulse electrical stimulations (SPES). SPES can elicit two main types of responses. Cortico-cortical evoked potentials (CCEPs) correspond to highly consistent early responses, appearing before 100ms after stimulation, with fixed latency; they are considered physiological and assess the effective connectivity between the recorded regions. Late responses appear after 100ms; they are rare, inconsistent with variable latency and are suggestive of an underlying epileptogenic cortex. Paired-pulse stimulation paradigm associates a conditioning and a test stimulation to induce intracortical inhibition or facilitation by modifying the response amplitude. Largely used in transcranial magnetic stimulation, it has rarely been applied to CCEP although the mechanisms put in place seem highly similar. Low frequency intracerebral stimulations allow analysing brain connectivity and cortical excitability with a high temporal and spatial resolution. The development of new stimulation protocols and the combination with imaging or statistical techniques recently offered promising results.


Electric Stimulation/methods , Electroencephalography/instrumentation , Electroencephalography/methods , Epilepsy/diagnosis , Epilepsy/surgery , Humans , Neurosurgical Procedures
6.
Rev Neurol (Paris) ; 172(1): 27-36, 2016 Jan.
Article En | MEDLINE | ID: mdl-26754036

Epilepsy is a burden affecting no fewer than 50 million patients worldwide. It is a heterogeneous group of disorders comprising both common and very rare forms, thus rendering its epidemiological investigations rather difficult. Moreover, making an epilepsy diagnosis per se can be challenging due to an evolving system of classification, and its dependency on local habits and culture. Any attempt at meta-analyses must consider such biases when pooling data from different centers and countries. Differentiating a contextual seizure from chronic epilepsy is every epileptologist's daily mission, yet it is also crucial for achieving a proper estimation of the epidemiology of epilepsy. Our present objective was to provide an overview of the epidemiology of both syndromic and non-syndromic epilepsy. Most epileptic syndromes tend to be rare and, thus, the feasibility of epidemiological quantification in populations is also addressed. Regarding its prevalence and cost, epilepsy deserves greater attention than it generally receives, as it appears to continue to be a condition under persistent taboos.


Epilepsy/epidemiology , Humans , Prevalence
7.
Rev Neurol (Paris) ; 171(3): 267-72, 2015 Mar.
Article En | MEDLINE | ID: mdl-25748333

The concept of temporal 'plus' epilepsy (T+E) is not new, and a number of observations made by means of intracerebral electrodes have illustrated the complexity of neuronal circuits that involve the temporal lobe. The term T+E was used to unify and better individualize these specific forms of multilobar epilepsies, which are characterized by electroclinical features primarily suggestive of temporal lobe epilepsy, MRI findings that are either unremarkable or show signs of hippocampal sclerosis, and intracranial recordings which demonstrate that seizures arise from a complex epileptogenic network including a combination of brain regions located within the temporal lobe and over closed neighbouring structures such as the orbitofrontal cortex, the insulo-opercular region, and the temporo-parieto-occipital junction. We will review here how the term of T+E has emerged, what it means, and which practical consideration it raises.


Epilepsy, Temporal Lobe/pathology , Epilepsy, Temporal Lobe/physiopathology , Hippocampus/pathology , Electroencephalography , Hippocampus/physiopathology , Humans , Sclerosis
8.
Neuroimage Clin ; 7: 122-31, 2015.
Article En | MEDLINE | ID: mdl-25610774

PURPOSE: We have previously shown that an imaging marker, increased periventricular [(11)C]flumazenil ([(11)C]FMZ) binding, is associated with failure to become seizure free (SF) after surgery for temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). Here, we investigated whether increased preoperative periventricular white matter (WM) signal can be detected on clinical [(18)F]FDG-PET images. We then explored the potential of periventricular FDG WM increases, as well as whole-brain [(11)C]FMZ and [(18)F]FDG images analysed with random forest classifiers, for predicting surgery outcome. METHODS: Sixteen patients with MRI-defined HS had preoperative [(18)F]FDG and [(11)C]FMZ-PET. Fifty controls had [(18)F]FDG-PET (30), [(11)C]FMZ-PET (41), or both (21). Periventricular WM signal was analysed using Statistical Parametric Mapping (SPM8), and whole-brain image classification was performed using random forests implemented in R (http://www.r-project.org). Surgery outcome was predicted at the group and individual levels. RESULTS: At the group level, non-seizure free (NSF) versus SF patients had periventricular increases with both tracers. Against controls, NSF patients showed more prominent periventricular [(11)C]FMZ and [(18)F]FDG signal increases than SF patients. All differences were more marked for [(11)C]FMZ. For individuals, periventricular WM signal increases were seen at optimized thresholds in 5/8 NSF patients for both tracers. For SF patients, 1/8 showed periventricular signal increases for [(11)C]FMZ, and 4/8 for [(18)F]FDG. Hence, [(18)F]FDG had relatively poor sensitivity and specificity. Random forest classification accurately identified 7/8 SF and 7/8 NSF patients using [(11)C]FMZ images, but only 4/8 SF and 6/8 NSF patients with [(18)F]FDG. CONCLUSION: This study extends the association between periventricular WM increases and NSF outcome to clinical [(18)F]FDG-PET, but only at the group level. Whole-brain random forest classification increases [(11)C]FMZ-PET's performance for predicting surgery outcome.


Epilepsy, Temporal Lobe/diagnostic imaging , Epilepsy, Temporal Lobe/surgery , Positron-Emission Tomography/methods , Radiopharmaceuticals , Adult , Carbon Radioisotopes , Female , Flumazenil , Fluorodeoxyglucose F18 , Hippocampus/diagnostic imaging , Hippocampus/pathology , Hippocampus/surgery , Humans , Image Interpretation, Computer-Assisted , Male , Middle Aged , Neurosurgical Procedures , Sclerosis/pathology , Treatment Outcome , Young Adult
9.
Clin Neurophysiol ; 122(12): 2488-97, 2011 Dec.
Article En | MEDLINE | ID: mdl-21669549

OBJECTIVE: To explore in human potential hippocampal projections within and outside the temporal lobe. METHODS: We performed intra-cerebral electrical stimulations in seven patients investigated by depth electrodes for refractory epilepsy and analyzed the presence of evoked potentials (EPs) in all brain regions explored. Bipolar electrical stimulations, consisting of two series of 25 pulses of 1 ms duration, 0.2 Hz frequency, and 3 mA intensity, were delivered in a total of 36 hippocampal stimulations sites. RESULTS: Reproducible EPs were recorded in several brain regions with variable latencies, amplitudes and morphologies. Within the temporal lobe, EPs were present in the amygdala, entorhinal cortex, temporal pole and temporal neocortex. EPs were also observed in the frontal lobe, anterior cingulate gyrus and orbito-frontal cortex, midcingulate and posterior cingulate gyrus, insula and thalamic pulvinar nucleus. CONCLUSION: Our results demonstrate a large distribution of direct or indirect hippocampal projections. SIGNIFICANCE: This widespread connectivity supports the previous definition of different networks involved mainly in memory and behavioral processes, implicating the temporal lobe, the cingulate gyrus or the prefrontal region. Our data provide some clues to further evaluate potential pathways of propagation of mesial temporal lobe seizure, via the insula or the pulvinar nucleus.


Brain/physiopathology , Epilepsy/physiopathology , Evoked Potentials/physiology , Hippocampus/physiopathology , Adolescent , Adult , Brain/surgery , Electric Stimulation , Electrodes , Epilepsy/surgery , Female , Hippocampus/surgery , Humans , Male , Middle Aged , Neurosurgical Procedures/instrumentation , Neurosurgical Procedures/methods , Reproducibility of Results , Young Adult
10.
Cephalalgia ; 31(1): 84-94, 2011 Jan.
Article En | MEDLINE | ID: mdl-21036859

BACKGROUND: Among serotonin receptors, 5-HT(1A) receptors are implicated in the regulation of central serotoninergic tone and could be involved in the abnormal brain 5-HT turnover suspected in migraineurs. The aim of this study was to investigate 5-HT(1A) receptors' availability during migraine attacks. METHODS: Ten patients suffering from odor-triggered migraine attacks and 10 control subjects were investigated using positron emission tomography (PET) and [(18)F]MPPF PET tracer, a selective 5-HT(1A) antagonist. All subjects underwent calibrated olfactory stimulations prior to the PET study. RESULTS: Four patients developed a migraine attack during the PET study. In these patients, statistical parametrical mapping and region of interest analyses showed an increased [(18)F]MPPF binding potential (BP(ND)) in the pontine raphe when compared to headache-free migraineurs and control subjects. This ictal change was confirmed at the individual level in each of the four affected patients. In comparison with the headache-free migraineurs, patients with a migraine attack also showed significantly increased [(18)F]MPPF BP(ND) in the left orbitofrontal cortex, precentral gyrus and temporal pole. No significant change in [(18)F]MPPF BP(ND) was observed between headache-free migraineurs and controls. CONCLUSIONS: Our results emphasize the role of 5HT(1A) receptors in the pontine raphe nuclei during the early stage of migraine attacks.


Brain Stem/diagnostic imaging , Brain Stem/metabolism , Migraine Disorders/diagnostic imaging , Migraine Disorders/metabolism , Receptor, Serotonin, 5-HT1A/biosynthesis , Adult , Humans , Image Processing, Computer-Assisted , Migraine Disorders/drug therapy , Piperazines , Positron-Emission Tomography , Radiopharmaceuticals , Serotonin 5-HT1 Receptor Antagonists/therapeutic use
11.
Eur J Neurol ; 17(5): 726-32, 2010 May.
Article En | MEDLINE | ID: mdl-20113339

BACKGROUND AND PURPOSE: Pregabalin has demonstrated efficacy in controlled trials as adjunctive treatment in patients with refractory seizures. METHODS: This open-label, 21-week study in adults with at least two partial seizures in the last 2 months, who were inadequately controlled with one to three antiepileptic drugs, evaluated pregabalin 150-600 mg/day (dosed twice daily). The study comprised a prospective or retrospective 8-week baseline phase, and 9-week dose optimization and 12-week maintenance periods. The primary assessment was the mean percentage change in 28-day seizure frequency between baseline and end-point (last 12 weeks of treatment, last observation carried forward, modified intention-to-treat population). RESULTS: Four hundred and seventy-six patients from Europe were included in this study (51% men; mean age/epilepsy duration 40.1/24.1 years). The median baseline seizure frequency was 5.5/28 days. Amongst the patient population, 78% completed the 21-week treatment period; 7% discontinued for lack of efficacy and 12% because of adverse events (AEs). The mean last pregabalin dose was 359 mg/day. The mean (95% CI) reduction in seizure frequency was 36% (31%; 41%). The median reduction was 33%, and 39% of patients had a >or=50% reduction in seizure frequency. There were 19% and 8% of patients free of seizures during their last 4 and 12 weeks of treatment, respectively. The three most common AEs were dizziness (17%), somnolence (13%) and weight increase (13%). CONCLUSIONS: This open-label study of pregabalin demonstrated efficacy that was consistent with that observed in previous controlled epilepsy trials. Pregabalin was well tolerated. The AE profile was also consistent with that reported in previous trials.


Anticonvulsants/administration & dosage , Epilepsies, Partial/drug therapy , gamma-Aminobutyric Acid/analogs & derivatives , Adult , Anticonvulsants/adverse effects , Dose-Response Relationship, Drug , Drug Administration Schedule , Europe , Female , Humans , Male , Pregabalin , Prospective Studies , Retrospective Studies , Time Factors , Treatment Outcome , gamma-Aminobutyric Acid/administration & dosage , gamma-Aminobutyric Acid/adverse effects
12.
Apoptosis ; 14(11): 1308-16, 2009 Nov.
Article En | MEDLINE | ID: mdl-19728097

This study was designed to determine the role of tumor necrosis factor-alpha (TNFalpha) in apoptosis observed in the myocardium and limbic system after myocardial ischemia. PEG sTNFRI, a recombinant, human, soluble p55 Type 1 TNF receptor (3 mg/kg) or vehicle (saline) was administered s.c. to male Sprague-Dawley rats on days 5, 3 and 1 before myocardial ischemia. The animals were then subjected, under anesthesia, to left anterior descending coronary artery occlusion for 40 min, followed by 15-min or 72-h reperfusion. Caspase-3 and -8 activities as well as terminal dUTP nick-end labelling-positive cells were examined in the myocardium (subendocardial and subepicardial regions), lateral (LA) and medial amygdala (MA) and hippocampus (CA1, CA3, dentate gyrus (DG)). After 15 min of reperfusion, the subendocardial and CA1 regions presented an increase in caspase-3 activity, whereas caspase-8 activity appeared to be augmented in the DG. PEG sTNFRI inhibited caspase-8 activation in the DG. After 72 h of reperfusion, plasma TNFalpha levels were reduced in the treated groups. The DG, CA1, CA3 and MA showed an increment of caspase-8 activity, which was reversed by PEG sTNFRI, except in the MA. Furthermore, caspase-3 activity was increased in the CA1, DG, LA and MA. These results indicate that TNFalpha contributes to apoptosis via activation of the extrinsic pathway in the limbic system after myocardial infarction, which is not the case in the myocardium.


Apoptosis/physiology , Limbic System/pathology , Myocardial Infarction/pathology , Tumor Necrosis Factor-alpha/metabolism , Animals , Apoptosis/drug effects , Caspase 3/metabolism , Caspase 8/metabolism , Humans , In Situ Nick-End Labeling , Male , Myocardium/enzymology , Rats , Rats, Sprague-Dawley , Receptors, Tumor Necrosis Factor/physiology , Tumor Necrosis Factor-alpha/blood
13.
Neurology ; 71(21): 1719-26, 2008 Nov 18.
Article En | MEDLINE | ID: mdl-19015488

OBJECTIVE: Intracranial stereotactic EEG recordings (SEEG) in presurgical epilepsy assessment are currently carried out in our department. The SEEG method generally used for exploration can also be used to perform radiofrequency thermocoagulations (RFTC) of the epileptic foci. To assess the indications of the RFTC procedure in the therapeutic arsenal of drug-resistant epilepsies, we report the results obtained in 41 patients to whom RFTC was proposed as a first therapeutic step before surgery or as a palliative treatment when surgery was not possible. METHODS: RFTC were produced by applying a 50-volt, 110 mA current, during 10-30 seconds within the epileptogenic zone, as identified by the SEEG investigation. Two to 31 RFTC (mean, 12) were performed per patient. The median follow-up was 19 months (range: 4 to 72). RESULTS: Twenty patients (48.7%) experienced a seizure frequency decrease of at least 50%, which was over 80% in eight of them. One patient was seizure-free. The tolerance was excellent. A total of 67% of the 21 patients presenting a cortical development malformation benefited from RFTC (p = 0.052). In the group of noneligible patients for resective surgery (n = 13), six were responders to SEEG-guided RFTC and one of them was seizure-free. CONCLUSIONS: This study suggests that stereotactic EEG-guided radiofrequency thermocoagulations can be proposed only as a palliative procedure, able to bring a substantial improvement of seizure frequency, to drug-resistant patients with epilepsy for whom conventional resection surgery is risky or contraindicated on the basis of invasive presurgical evaluation.


Electroencephalography/methods , Epilepsies, Partial/therapy , Palliative Care/methods , Radiosurgery/methods , Adolescent , Adult , Anticonvulsants/therapeutic use , Child , Combined Modality Therapy , Epilepsies, Partial/pathology , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Positron-Emission Tomography/methods , Statistics, Nonparametric , Stereotaxic Techniques , Tomography, Emission-Computed, Single-Photon/methods , Treatment Outcome , Young Adult
14.
Brain ; 131(Pt 10): 2765-82, 2008 Oct.
Article En | MEDLINE | ID: mdl-18765418

Brain and brainstem changes of serotoninergic 5-hydroxytryptophan (5-HT)(1A) receptor density have been reported in patients with major depressive disorder as well as in patients with temporal lobe epilepsy (TLE), using PET and the selective antagonist radiotracers [(11)C]WAY-100635 or [(18)F]FC-WAY. We used a distinct 5-HT(1A) antagonist, [(18)F]MPPF, whose binding potential depends on both receptor density and extracellular serotonin concentration, in 24 patients with drug-resistant TLE and MRI evidence of hippocampal sclerosis but without prior antidepressant exposure. Their Beck Depression Inventory (BDI-2) score ranged from 0 to 34, with nine patients having a score >11. We used a simplified reference tissue model, statistical parametric mapping and anatomical regions of interest (ROIs) to correlate parametric images of [(18)F]MPPF BP with the total BDI score and its four subclasses. The total BDI score, as well as symptoms of psychomotor anhedonia and negative cognition, correlated positively with [(18)F]MPPF BP in the raphe nuclei and in the insula contralateral to seizure onset, whereas somatic symptoms correlated positively with [(18)F]MPPF binding potential in the hippocampal/parahippocampal region ipsilateral to seizure onset, the left mid-cingulate gyrus and the inferior dorsolateral frontal cortex, bilaterally. We confirm an association of depressive symptoms in TLE patients with changes of the central serotoninergic pathways, in particular within the raphe nuclei, insula, cingulate gyrus and epileptogenic hippocampus. These changes are likely to reflect lower extracellular serotonin concentration in more depressed patients, with an upregulation of receptors a less likely alternative.


Brain/diagnostic imaging , Depression/complications , Epilepsy, Temporal Lobe/psychology , Image Interpretation, Computer-Assisted , Positron-Emission Tomography/methods , Adult , Aminopyridines/metabolism , Brain/metabolism , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/metabolism , Depression/diagnostic imaging , Depression/metabolism , Epilepsy, Temporal Lobe/diagnostic imaging , Epilepsy, Temporal Lobe/metabolism , Female , Fluorodeoxyglucose F18 , Hippocampus/diagnostic imaging , Hippocampus/metabolism , Humans , Male , Middle Aged , Piperazines/metabolism , Prospective Studies , Radiopharmaceuticals , Raphe Nuclei/diagnostic imaging , Raphe Nuclei/metabolism , Receptor, Serotonin, 5-HT1A/metabolism , Serotonin/metabolism , Serotonin 5-HT1 Receptor Antagonists
15.
Cephalalgia ; 28(12): 1282-91, 2008 Dec.
Article En | MEDLINE | ID: mdl-18727636

In this study we aimed to assess the brain distribution of 5-HT(1A) receptors in migraine patients without aura. Ten female migraine patients and 24 female healthy volunteers underwent magnetic resonance imaging and positron emission tomography using a radioligand antagonist of 5-HT(1A) receptors [4-(2'-methoxyphenyl)-1-[2'-(N-2-pirydynyl)-p-fluorobenzamido]-ethylpiperazine ((18)F-MPPF)]. A simplified reference tissue model was used to generate parametric images of 5-HT(1A) receptor binding potential (BP) values. Statistical Parametrical Mapping (SPM) analysis showed increased MPPF BP in posterior cortical areas and hippocampi bilaterally in patients compared with controls. Region of interest (ROI) analysis showed a non-significant trend in favour of a BP increase patients in cortical regions identified by the SPM analysis except in hippocampi, left parietal areas and raphe nuclei. During the interictal period of migraine patients without aura, the increase of MPPF BP in posterior cortical and limbic areas could reflect an increase in receptor density or a decrease of endogenous serotonin, which could explain their altered cortical excitability.


Brain/metabolism , Migraine without Aura/metabolism , Positron-Emission Tomography/methods , Receptor, Serotonin, 5-HT1A/metabolism , Adult , Aged , Brain/diagnostic imaging , Case-Control Studies , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging/methods , Middle Aged , Migraine without Aura/diagnostic imaging , Piperazines/metabolism , Pyridines/metabolism , Radiopharmaceuticals/metabolism , Surveys and Questionnaires , Tomography, Emission-Computed/methods , Young Adult
16.
Cephalalgia ; 28(10): 1069-80, 2008 Oct.
Article En | MEDLINE | ID: mdl-18727640

Olfactory hypersensitivity (OHS) may occur during migraine attacks and seems to be very specific to this form of headache. OHS is also observed during migraine-free periods and is associated with the presence of odour-triggered attacks. Yet the pathophysiology of OHS remains unknown. The aim of our study was to evaluate olfactory processing in migraineurs with OHS and to investigate whether regional cerebral blood flow (rCBF) associated with olfactory stimulation is modified in these patients compared with controls. Eleven migraineurs with OHS and 12 controls participated in a H(2)(15)O-positron emission tomography study, including three scans in which odours were delivered and three scans where only odourless air was delivered. rCBF during olfactory condition was compared with that for the odourless baseline condition. Between-group analyses were performed using voxel-based and region-of-interest analyses. During both olfactory and non-olfactory conditions, we observed higher rCBF in the left piriform cortex and antero-superior temporal gyrus in migraineurs compared with controls. During odour stimulation, migraineurs also showed significantly higher activation than controls in the left temporal pole and significantly lower activation in the frontal (left inferior as well as left and right middle frontal gyri) and temporo-parietal (left and right angular, and right posterior superior temporal gyri) regions, posterior cingulate gyrus and right locus coeruleus. These results could reflect a particular role of both the piriform cortex and antero-superior temporal gyrus in OHS and odour-triggered migraine. Whether these rCBF changes are the cause or a consequence of odour-triggered migraines and interictal OHS remains unknown. Further comparisons between migraineurs with and without OHS are warranted to address this issue. The abnormal cerebral activation patterns during olfactory stimulation might reflect altered cerebrovascular response to olfactory stimulation due to the migraine disease, or an abnormal top-down regulation process related to OHS.


Migraine Disorders/complications , Migraine Disorders/diagnostic imaging , Olfaction Disorders/diagnostic imaging , Olfaction Disorders/etiology , Positron-Emission Tomography , Adult , Female , Humans , Middle Aged , Odorants , Olfactory Pathways/diagnostic imaging , Oxygen Radioisotopes , Young Adult
17.
Brain Res ; 1216: 87-91, 2008 Jun 24.
Article En | MEDLINE | ID: mdl-18495089

Apoptosis is known to occur in the limbic system after myocardial infarction (MI) in the rat. Our study was designed to evaluate the time course dynamics of this phenomenon in limbic areas. Apoptosis, i.e., caspase-3 activity and the number of terminal dUTP nick-end labelling-positive cells, as well as brain-derived neurotrophic factor (BDNF) were quantitated in sham-operated controls and MI rats 1, 2 and 7 days after surgery. Both apoptosis parameters were increased throughout, although in different structures: the CA1 region of the hippocampus and the medial amygdala at day 1, the CA1 region of the hippocampus and the lateral amygdala at day 2, and the frontal cortex at day 7. At day 2, BDNF was decreased in the prefrontal cortex and medial amygdala, whereas it was elevated in the dentate gyrus of the hippocampus; at day 7, BDNF was reduced in the frontal cortex and posterior hypothalamus but was augmented in the medial amygdala. These data indicate that post-MI apoptosis in the limbic system is a dynamic process occurring mainly in the hippocampus and amygdala during the first days after MI. The fact that BDNF was increased as early as 2 days after MI suggests that neurogenesis can occur rapidly in selected limbic regions after MI.


Amygdala/pathology , Apoptosis/physiology , Hippocampus/pathology , Myocardial Infarction/pathology , Amygdala/metabolism , Animals , Brain-Derived Neurotrophic Factor/metabolism , Caspase 3/metabolism , Hippocampus/metabolism , Limbic System/metabolism , Limbic System/pathology , Male , Neurons/metabolism , Neurons/pathology , Rats , Rats, Sprague-Dawley , Time Factors , Tissue Distribution
18.
Neurochirurgie ; 54(3): 484-98, 2008 May.
Article Fr | MEDLINE | ID: mdl-18440571

PURPOSE: To compare resective surgery and medical therapy in a cost-effectiveness analysis in a multicenter cohort of adult patients with partial intractable epilepsy. POPULATION AND METHODS: Adult patients with partial, medically intractable, potentially operable epilepsy were eligible and followed every year over five years. Effectiveness was defined as one year without seizure. The long-term costs and effectiveness were extrapolated over the patients' lifetime with a Markov model. Productivity (indirect costs) and quality of life (QOLIE-31, SEALS) were also assessed. Changes before and after surgery were compared between the two groups. RESULTS: Two hundred and eighty-nine patients were included (119 with surgery, 161 medically treated, six not eligible, three lost to follow-up). One year after surgery, 81% of the patients were seizure-free; at two and three years, this rate was 78%. In the medical group, these rates were 10, 18, and 15%, respectively. The cost of the explorations was euro 8464; including surgery, it was euro 19,700. In the medical group, the average annual direct costs were between 3500 and euro 6000. At two years after surgery, the annual direct cost decreased to euro 2768, at three years, it was euro 1233, predominately antiepileptic drug costs. Surgery became cost-effective between seven and eight years. In the surgical group, all the quality-of-life scores improved at one year after surgery and were stable during the second and third years. CONCLUSION: Surgical therapy was cost-effective at the middle term even though indirect costs were not considered.


Epilepsies, Partial/economics , Epilepsies, Partial/surgery , Neurosurgical Procedures/economics , Adolescent , Adult , Anticonvulsants/therapeutic use , Cohort Studies , Cost-Benefit Analysis , Drug Resistance , Efficiency , Epilepsies, Partial/psychology , Female , Follow-Up Studies , France , Humans , Male , Markov Chains , Middle Aged , Models, Economic , Postoperative Complications/epidemiology , Postoperative Complications/psychology , Quality of Life , Treatment Outcome
19.
Neurochirurgie ; 54(3): 282-6, 2008 May.
Article Fr | MEDLINE | ID: mdl-18420228

Patients with epilepsy suffer from a two to three fold increased death rate as compared to age and sex matched control population. This increased risk culminate to five fold in patients with drug resistant partial epilepsy eligible for epilepsy surgery, with the majority of deaths classified as sudden unexpected death in epilepsy (SUDEP). The pathophysiology of SUDEP remains uncertain, but all witnessed cases occurred during or immediately after a seizure. Several studies have evaluated the impact of epilepsy surgery on the risk of seizure related death and SUDEP. Four series have concentrated on operated patients, and have compared the death rates in those seizure free and non seizure free post-operatively. Three of these studies reported a significantly lower risk of SUDEP in patients cured by surgery as compared to those still seizing. Four other series have compared the mortality in surgically versus medically treated patients with refractory partial epilepsy. Three of these studies failed to show any significant difference in death or SUDEP rates between operated and and non operated patients. All the above series suffer various types of methological limitations, hampering any definite conclusion regarding the impact of epilepsy surgery on mortality. The launching of novel and large multicentric studies, which address the pitfalls of prior series, should allow to provide conclusive results within the next three years.


Epilepsy/mortality , Epilepsy/surgery , Neurosurgical Procedures , Anticonvulsants/therapeutic use , Drug Resistance , Epilepsy/drug therapy , Humans , Temporal Lobe/pathology , Temporal Lobe/surgery , Treatment Outcome
20.
Neurochirurgie ; 54(3): 479-83, 2008 May.
Article Fr | MEDLINE | ID: mdl-18417159

We report on the experience of a network created in 1994 to evaluate children with drug-resistant epilepsies who are candidates for surgical treatment. The network includes epilepsy units from several university hospitals in France that decided to share not only their clinical expertise to better respond to the need for a multidisciplinary approach of epilepsy surgery in children, but also all the technical and human resources available in the various teams. This mode of operation has certainly provided concrete proof of its efficacy since it undoubtedly facilitated, and even accelerated, access to optimal presurgical evaluation and epilepsy surgery for hundreds of children. However, after 10 years of this very enriching practice it became evident that our approach was certainly necessary but not sufficient. It is estimated that every year in France nearly 500 children are candidates for surgical treatment, and following a presurgical evaluation, 50% of them could be operated on. Today, only 150-200 children have access to a presurgical evaluation every year. This is a highly paradoxical situation since, even if the human suffering component that such a situation generates is set aside, the direct and indirect life-time costs for every 100 nonoperated patients is estimated at 40 million euros. As a result of our cumulated experience, in 2004 we proposed a different operating model with the creation of an expertise center that will combine not only medical care services provided by a fully equipped multidisciplinary team, but also a pole of applied clinical and fundamental research, a medicosocial center managed by a lay association and an industrial development pole. The project has been recently validated by the Ministry of Health and is supported by a number of national and regional institutions. The Institute for Children and Adolescents with Epilepsy--IDEE--is designed to accelerate diagnostic procedures and, when indicated, access to optimal presurgical evaluation, while also serving as a model for a medical and economic evaluation of epilepsy care in children.


Academic Medical Centers/organization & administration , Community Networks/organization & administration , Epilepsy/surgery , Neurosurgical Procedures , Adolescent , Adult , Child , Child, Preschool , Clinical Competence , Epilepsy/economics , Female , France , Humans , Male , Models, Organizational , Neurosurgical Procedures/economics , Neurosurgical Procedures/statistics & numerical data , Research
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