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Biomedical subjects

P Ryvlin

Publications and source records attributed to P Ryvlin.

At least 19 recordsLinked to original sources

Rating of olfactory judgements in migraine patients.

The aim of this study was to evaluate olfactory hypersensitivity (OHS) between attacks in migraine patients. Seventy-four migraine patients and 30 controls were enrolled. The presence of OHS was evaluated using an oral questionnaire and a chemical odour intolerance index. Subjects had to rate the intensity and hedonicity of 12 odourants using a linear rating scale. Twenty-six patients (35.2%) but no control subjects reported an interictal OHS (P<0.001). Logistic regression analysis showed that patients with OHS presented a greater attack frequency, a higher number of odour-induced migraines and visual hypersensitivity when compared with other patients. Disease duration, age, gender and auditory hypersensitivity were not associated with OHS. OHS patients judged odours less pleasant than did other patients and controls, whereas the intensity scores were identical in both groups. OHS between attacks was significantly associated with odour-triggered migraine and an alteration of hedonic judgement.

Adult↗

Opsoclonus-myoclonus as a manifestation of Lyme disease.

Opsoclonus-myoclonus syndrome (OMS) is a rare condition that includes chaotic multidirectional saccadic eye movements associated with myoclonus and ataxia. In adults, it is usually considered to be an autoimmune disease occurring either in a paraneoplastic context or after central nervous system infection. We report the case of a patient who presented with the classic features of OMS as a manifestation of acute Borrelia burgdorferi infection that was shown both on serum and cerebrospinal fluid examination. The outcome was favourable after prolonged antibiotic treatment. Lyme disease could be added to the list of aetiologies to be screened in OMS, as it would allow effective treatment and avoidance of unnecessary investigations.

Adult↗

Temporo-mesial epilepsy surgery: outcome and complications in 100 consecutive adult patients.

BACKGROUND: We studied the surgical outcome, and the complications in a group of 100 consecutive adult patients with medically refractory epilepsy arising from the temporo-mesial structures. METHODS: Hundred patients were treated surgically between 1994 and 2003 for drug-resistant epilepsy involving the temporo-mesial structures. All of them underwent a comprehensive noninvasive presurgical evaluation. Fourty-eight of them underwent depth electrodes recordings (according to the Talairach's StereoElectroEncephaloGraphic (SEEG) methodology) because the noninvasive investigations were not congruent enough to identify the epileptic zone. The patients presenting with any space-occupying lesion, or with a cavernoma, or with a strictly lateral neocortical epileptic focus, were excluded. The MRI-examination was abnormal in 87 cases, displaying a hippocampal atrophy in 69 cases. The extent of temporal resection was planned according to the results of the presurgical investigation in each particular patient. Consequently, this "tailored" resection varied from selective amygdalo-hippocampectomy (6 cases), to anterior temporal lobectomy (76 cases), or to total temporal lobectomy (18 cases). FINDINGS: The mean post-operative follow-up period was 53 months. 85 patients were found to be in Engel's class I post-operatively (free of disabling seizures), among them 74 were in class Ia (totally seizure free). Nine patients were in Engel's class II and six were in Engel's class III or IV (failures). There was no surgical mortality. Three patients had a postoperative hematoma; two patients required a shunt insertion; in three patients meningitis occurred; and two patients had postoperative ischaemia of the anterior choroidal artery territory, which resulted in a mild permanent hemiparesis. Neuropsychological complications are not addressed in detail in this article. CONCLUSIONS: These data indicate that "tailored" resective surgery for temporo-mesial epilepsy can be performed with a low rate of morbidity, and is highly efficacious. The use of invasive presurgical investigation (SEEG) may explain this high rate of success.

Adolescent↗

Hippocampal-orbitofrontal connectivity in human: an electrical stimulation study.

OBJECTIVE: The identification of the pathways involved in seizure propagation remains poorly understood in humans. For instance, the respective role of the orbitofrontal cortex (OFC) and of the commissural pathways in the interhemispheric propagation of mesial temporal lobe seizures (mTLS) is a matter of debate. In order to address this issue, we have directly tested the functional connectivity between the hippocampus and the OFC in 3 epileptic patients undergoing an intra-cranial stereotactic EEG investigation. METHODS: 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 the hippocampus. Evoked potentials (EPs) were analysed for each series, separately. Grand average of reproducible EPs was then used to calculate latency of the first peak of each individual potential. RESULTS: Hippocampal stimulations evoked reproducible responses in the OFC in all 3 patients, with a mean latency of the first peak of 222 ms (range: 185-258 ms). CONCLUSIONS: Our data confirm a functional connectivity between the hippocampus and the OFC in human. SIGNIFICANCE: This connectivity supports the potential role of the OFC in the propagation of mTLS.

Adolescent↗

Defining success in clinical trials--profiling pregabalin, the newest AED.

The efficacy and safety of pregabalin as adjunctive therapy for patients with partial epilepsy with or without secondary generalization has been established by four randomized, 12-week, double-blind, placebo-controlled trials (n = 1396) and four long-term open-label studies (n = 1480). Patients in the three fixed-dose trials were >/=12 years of age, had >/=6 partial seizures and no 4-week seizure-free period during the 8-week baseline period. Seventy-three per cent of patients were taking >/=2 concomitant antiepileptic drugs. Responder rates across the effective doses (150-600 mg/day) ranged from 14% to 51% and demonstrated a significant dose-response relationship. The most common adverse events were central nervous system related, generally mild or moderate, transient, and tended to be dose related. The fourth placebo-controlled trial compared a fixed dose of pregabalin 600 mg/day with a flexible-dose regimen (150-600 mg/day). Responder rates were greater for both the fixed dose (45.3%, P < 0.001) and flexible dose (31.3%, P < 0.001) when compared with placebo (11.0%). Compared with the fixed-dose group, the flexible-dose patients had a lower incidence of adverse events and study discontinuations. In long-term open-label trials, the efficacy of pregabalin was maintained with respect to 50% responder rates suggesting no obvious tolerance developing over 2 years. Seizure-free rates were 8.9% and 5.8% for the last 6 months and 1 year of pregabalin treatment, respectively. Long-term open-label pregabalin treatment was well tolerated.

Anticonvulsants↗

[11C]-Methionine PET: dysembryoplastic neuroepithelial tumours compared with other epileptogenic brain neoplasms.

BACKGROUND AND OBJECTIVES: Brain tumours responsible for longstanding partial epilepsy are characterised by a high prevalence of dysembryoplastic neuroepithelial tumour (DNT), whose natural evolution is much more benign than that of gliomas. The preoperative diagnosis of DNT, which is not yet feasible on the basis of available clinical and imaging data, would help optimise the therapeutic strategy for this type of tumour. This study tested whether [(11)C]-methionine positron emission tomography (MET-PET) could help to distinguish DNTs from other epileptogenic brain tumours. METHODS: Prospective study of 27 patients with partial epilepsy of at least six months duration related to a non-rapidly progressing brain tumour on magnetic resonance imaging (MRI). A structured visual analysis, which distinguished between normal, moderately abnormal, or markedly abnormal tumour methionine uptake, as well as various regions of interest and semiquantitative measurements were conducted. RESULTS: Pathological results showed 11 DNTs (41%), 5 gangliogliomas (18%), and 11 gliomas (41%). MET-PET visual findings significantly differed between the various tumour types (p<0.0002), regardless of gadolinium enhancement on MRI, and were confirmed by semiquantitative analysis (p<0.001 for all calculated ratios). All gliomas and gangliogliomas were associated with moderately or markedly increased tumour methionine uptake, whereas 7/11 DNTs had a normal methionine uptake, including all six located in the mesiotemporal structures. No DNT presented with a marked MET-PET abnormality. CONCLUSION: Normal MET-PET findings in patient with an epileptogenic and non-rapidly progressing brain tumour are suggestive of DNT, whereas a markedly increased tumour methionine uptake makes this diagnosis unlikely.

Adolescent↗

Intracranial EEG study of seizure-associated nose wiping.

The authors studied the relation between seizure-associated nose wiping (NW) and intracerebral EEG data in 32 patients. NW was more frequent in mesial temporal lobe seizures (TLSs; 65%) than in other TLSs (36%; p < 0.05) and in frontal lobe seizures (3%; p < 0.0001). It was associated with the presence of an amygdala discharge at seizure onset (p < 0.05) and with the recording of an ictal low-voltage fast activity within that structure (p < 0.05), supporting the role of an amygdala dysfunction in the pathophysiology of NW.

Adolescent↗

[Polymorphism of epilepsy associated with the A3243G mutation of mitochondrial DNA (MELAS): reasons for delayed diagnosis].

INTRODUCTION: Mitochondrial disease is a potential diagnosis in patients with epilepsy beginning in childhood or adolescence with a typical polymorphic presentation and preponderant occipital lobe seizures. Diagnosis may however be delayed in some patients with long-standing disease, particularly when cardinal mitochondrial symptoms are missing; clinical manifestations may be dissociated over time leading to genetic diagnostic tests being prescribed long after disease onset. OBSERVATION: We report the case of a 17 year old woman in whom the diagnosis of lipothymic episodes, migraine, idiopathic photo-sensitive generalized epilepsy, and partial occipital epilepsy complicated by occipital epileptic status were successively proposed because of the initial clinical presentation and the slow disease course. Eleven years after disease onset the diagnosis of progressive myoclonic epilepsy was made due to the occurrence of myoclonic jerks with giant SEPs associated with a cerebellar syndrome, deterioration of psychomotor performances and diffuse slowing of EEG activity with pseudo-periodic bursts of delta waves. Genetic analysis showed an A3243G mutation of mitochondrial DNA, usually correlated with the MELAS phenotype, while the clinical presentation of progressive myoclonic epilepsy was more suggestive of MERRF. CONCLUSION: Although each of the symptoms successively observed in this patient has been reported in MELAS, the slow course of the disease, which is unusual in this mutation, the absence of stroke-like episodes, and the polymorphism of the epilepsy all contributed to delayed final diagnosis.

Adolescent↗

[Functional neuroimaging in adults].

A consensus has not been reached on the proper role of the different functional neuroimaging techniques available for the exploration of drug-resistant partial epilepsy, particularly in preparation for surgery. Several studies have suggested the potential contribution of positron emission tomography (PET) with [18F]-fluoro-deoxyglucose (FDG), [11C]-flumazenil (FMZ), or [11C]-alpha-methyl-tryptophane (AMT), single-photon emission computed tomography (SPECT) to measure ictal cerebral blood flow, magnetic resonance spectroscopy (MRS), and functional magnetic resonance imaging (fMRI) of language and memory functions, but to date there has been no impact study validating the clinical contribution of these different exploration techniques. The most robust data in the literature indicate that [18F]-FDG PET can help to predict surgical failures in patients with temporal lobe epilepsy. Studies with lesser power have suggested that SPECT measurement of ictal hyperperfusion blood flow, and [11C]-FMZ and [11C]-AMT PET can be useful in symptomatic neocortical epilepsy, particularly in patients with tuberous sclerosis explored with [11C]-AMT PET. Use of these different exploration techniques in epileptic patients with a normal MRI is warranted when complementary information could help in deciding on when and how to perform an invasive EEG, but there are significant risks of erroneous identification of the epileptogenic zone. Functional MRI assessment of language regions can be proposed as an alternative to the Wada test to determine hemispheric dominance in patients with temporal lobe epilepsy. Multicentric impact studies will be needed before evidence-based guidelines can be developed for the use of functional neuroimaging techniques in drug-resistant partial epilepsy.

Adult↗

[Cost-effectiveness of epilepsy surgery in a cohort of patients with medically intractable partial epilepsy--preliminary results].

OBJECTIVE: Patients with medically intractable epilepsy are potential candidates for surgery if the epileptogenic tissue is localized and resectable. Surgical therapy can eliminate seizures but is very expensive. We followed a prospective adult cohort of intractable epileptic patients in order to perform a cost-effectiveness analysis. POPULATION AND METHODS: Adult patients with a suspected partial medically intractable and operable epilepsy were eligible for evaluation, explorations and/or surgery. Clinical and economical data were collected at the inclusion and every 6 months over at least two years. Two patient groups were analyzed: some underwent a surgery, others did not. Clinical data were compared between both groups. As the data collection was not yet complete, we compared the surgery to a continuation of the preoperative medical management in a cost-effectiveness analysis. Direct medical and nonmedical costs were evaluated according to a societal perspective. The effectiveness was defined as one year without seizure. We assessed the incremental cost-effectiveness ratio (ICER) for the first two years after the surgery. We also modeled long-term costs and effectiveness and extrapolated the results over the patients' lifetime with a Markov model. We computed the ICER and performed a sensitivity analysis. Indirect costs were measured in physical units and intangible costs were assessed with quality-of-life measures (QOLIE-31, SEALS). Data were compared before and after surgery. RESULTS: Among the 286 patients included, 119 did not enter in the analysis: 7 were not eligible, 44 not operable, 31 did not present a follow-up, 37 still underwent exams. Finally, 89 underwent a surgical treatment, and 78 were medically treated. Disease was more severe in surgical patients than in medical patients: seizures frequency, depressive disorders and cognitive impairment were greater. One year after the surgery, 83% patients were seizure free. During the year before inclusion and the year after surgery, direct costs were mainly due to hospitalization. During the second year after surgery, the cost of antiepileptic drugs predominated. One additional year without seizure costs 23 531 euro one year after surgery and 9533 euro two years after surgery. In a long-term perspective, the surgery became cost-effective between 7 and 8 years after the surgery. CONCLUSION: Surgical therapy is a cost-effective treatment in a middle-term even without indirect costs consideration.

Adolescent↗

Does epilepsy surgery lower the mortality of drug-resistant epilepsy?

Drug-resistant epilepsy has proved to be associated with an increased standardized mortality ratio (SMR), primarily due to seizure-related fatalities including sudden unexpected death (SUDEP). Recent studies have suggested that the surgical cure of temporal lobe epilepsy (TLE) was likely to normalize the SMR of patients suffering from refractory TLE. However, these studies raise a number of methodological issues, which have not always been fully addressed. Some conclusions have relied on previously reported data, indicating a SMR of approximately 5, and a SUDEP incidence of 9/1000 patient-years in drug-resistant epilepsy. In fact, as shown in this review, SMR varied considerably, from 2 to 16, in the various series of patients with refractory epilepsy, whereas the average SUDEP incidence in the same populations was calculated at 3.7/1000 patient-years. Other conclusions were based on the comparison of either surgically and medically treated patients, or cured and non-cured operated patients. In both situations, the two groups included a different proportion of excellent and poor surgical candidates. The biological differences that distinguish these two populations might explain part of the differences observed in their mortality rate, regardless of the effect of surgery. In particular, temporal-plus epilepsies involving the insula, the frontal orbital, or the frontal operculum region, might favour ictal arrhythmias, central apnoea and secondary generalization, which in turn would increase the risk of SUDEP. Future studies are thus warranted to specifically address these issues.

Age Factors↗

The impact of temporal lobe surgery on cure and mortality of drug-resistant epilepsy: summary of a workshop.

The Third International Spring Epilepsy Research Conference took place in Georgetown, Cayman Islands from April 26 to May 3, 2003. One workshop discussed the impact of epilepsy surgery on seizure outcome and mortality of antiepileptic drug (AED)-resistant temporal lobe epilepsy. This article summarizes the information presented at this workshop. Although two-thirds of adult patients undergoing epilepsy surgery become seizure-free with continued AED treatment, current clinical experience shows that seizure recurrence occurs in one-third of patients when AEDs are withdrawn under medical supervision. Additional seizure recurrence occurring after AED taper, poor drug compliance and even while patients continue on AEDs after surgery leave only approximately one-third of patients cured after temporal lobe resection. Mostly because so many patients prefer to stay on AEDs although they are free of disabling seizures after surgery, a randomised controlled trial of AED discontinuation is needed to determine if in fact only one-third of patients are cured after surgery. Based on the functional anatomy of temporal lobe surgery two hypotheses are presented why only a minority of patients are cured after surgery. The type and the prognostic significance of seizures after surgery is discussed. Recent studies have suggested that successful temporal lobe surgery may be able to normalize the increased standard mortality ratio (SMR) of drug-resistant temporal lobe epilepsy. However, pre-existing differences in SMR between those cured and those not cured by temporal lobe surgery and other unresolved methodological issues make it difficult at present to fully evaluate the impact of surgery on mortality. Future studies are thus warranted to specifically address the impact of temporal lobe surgery on cure and mortality.

Drug Resistance↗

Extraction of epileptogenic foci from PET and SPECT images by fuzzy modeling and data fusion.

During the presurgical evaluation of medically intractable epilepsy, isotopic functional imagery provides an increasing amount of data concerning the potential location of the focus. The aim of this study is to facilitate the surgical decision by presenting an image fusion method able to extract epileptogenic foci from periictal single photon emission computed tomography (SPECT), interictal SPECT, fluoro-desoxy-glucose (FDG) position emission tomography (PET), and flumazenil PET. After spatial coregistration, the images are converted into fuzzy maps whose membership functions indicate the pathological degree of each voxel, according to each modality. These maps are then fused together thanks to a combination operator managing uncertainty (due to the sensitivity) and imprecision (due to poor resolution and partial volume effect) of the images. In the framework of possibilistic theory, this operator mimics the way the physicians evaluate and compare the various exams. The technique was successfully tested on simulated images with well-defined abnormalities, in terms of size and intensity. A preliminary clinical study was also performed and gave results in accordance with the "gold standard" investigation (deep electrodes or postsurgical outcome) in 11 patients out of 12.

Adult↗

Temporopolar changes in temporal lobe epilepsy: a quantitative MRI-based study.

OBJECTIVES: To quantify the morphologic changes of temporopolar structures to better understand the pathophysiology of anterior temporal white matter increased T2 signal observed in temporal lobe epilepsy (TLE). METHODS: MRI was performed in 30 patients with TLE and in 30 normal control subjects and independently assessed by visual analysis and quantitative measurements. Specifically, the temporal pole (TP) volume, as well as its gray and white matter components, was measured using three-dimensional T1 MR images and a semiautomatic protocol. The authors tested whether the presence of an increased T2-weighted signal in the anterior temporal white matter was associated with significant TP atrophy. The associations between the TP volume and MRI signs of hippocampal sclerosis, age at onset, seizure frequency, duration of illness, and a history of febrile convulsions were also studied. RESULTS: Both right and left TLE populations demonstrated a reduction of the temporopolar white and gray matter volumes ipsilateral to seizure onset (p < 0.02 in right TLE; p < 0.0001 in left TLE). Twenty-two patients (72%) exhibited significantly abnormal TP volume measurements, which correctly lateralized the epileptogenic zone in all cases. The presence of an increased T2-weighted signal in the anterior temporal white matter (ISWM), but not that of hippocampal sclerosis, was associated with a greater TP volume asymmetry index (p < 0.05). CONCLUSIONS: The temporal pole is frequently atrophic ipsilateral to seizure onset in refractory TLE. The association between TP atrophy and ISWM suggests that both abnormalities might derive from a common pathologic process.

Adolescent↗

Evidence of peripheral auditory activity modulation by the auditory cortex in humans.

At the auditory periphery, the medial olivocochlear system is assumed to be involved in complex sound processing and may be influenced by feedback from higher auditory nuclei. Indeed, the descending auditory pathway includes fibers coming from the auditory cortex that are anatomically well positioned to influence the superior olivary complex, and thus the medial efferent system. The aim of the present study was to verify the hypothesis of an implied influence of the auditory cortex on the peripheral auditory system. In three rare cases of patients presenting with intractable temporal lobe epilepsy, Heschl's gyrus (i.e. the temporal superior gyrus) was surgically removed in the right hemisphere in two patients and in the left hemisphere in a third patient, in order to minimize epilepsy attacks, as preoperative stereoencephalography had shown the epileptic focus or tumor to be situated in those locations. In all three cases, several weeks after the operation the medial olivocochlear system was clearly less functional on both sides, but especially on the side contralateral to the resection. In healthy controls, no such pattern was obtained. In four other epileptic patients, who were operated unilaterally at the anterior temporal pole, amygdala and hippocampus with the temporal gyrus partially spared, efferent suppression grew stronger in the ear ipsilateral to surgery. These results revealed that, in humans, the primary and secondary auditory cortex play a role in modulating auditory periphery activity through direct or indirect efferent fibers. In accordance with previous findings, this descending influence may improve the auditory afferent message by adapting the hearing function according to cortical analysis of the ascending input.

Adult↗

[Neurofunctional tests in presurgical strategies for partial epilepsies].

The presurgical evaluation of drug-resistant partial epilepsies primarily relies on two major investigations, including a long term video-EEG monitoring which aimed at recording the patient's typical seizures, and a specifically designed high quality magnetic resonance imaging (MRI). The latter demonstrates an abnormality within the epileptogenic lobe in the majority of cases, which might not, however, necessarily match the epileptogenic zone. Numerous functional neuro-imaging techniques have been progressively added to the pre-surgical evaluation of refractory partial epilepsies, such as the study of cerebral glucose metabolism, benzodiazepine receptor availability, and methionine incorporation using positron emission tomography (PET), the evaluation of ictal cerebral blood flow changes using single photon emission computerized tomography (SPECT), the measurement of N-acetyl-aspartate concentration with magnetic resonance spectroscopy, and the mapping of eloquent areas using functional MRI. These investigations can help to confirm the origin of seizure onset previously suggested by MRI and electro-clinical data, and provide independent prognostic information regarding the chance of a successful surgical treatment. Moreover, functional neuro-imaging data can have a critical diagnostic value when MRI is strictly normal or shows multifocal abnormalities. However, the variety and rapid evolution of functional neuro-imaging techniques makes it difficult to propose a standard protocol. Finally, it remains mandatory to proceed to an intracranial EEG investigation in a substantial number of patients, including the majority of those suffering from an extra-temporal epilepsy.

Electroencephalography↗

Asymmetrical localization of benzodiazepine receptors in the human auditory cortex.

In humans, administration of benzodiazepines (BZD) has been shown to have an asymmetrical effect on the medial olivocochlear system. Indeed, a decrease of evoked otoacoustic emission suppression by contralateral acoustic stimulation, which explores the medial olivocochlear efferent system, was observed in the right ear, with no left ear effect. This result suggests a possible left-right auditory pathway BZD receptor asymmetry. Given the anatomical link between auditory centers and the medial olivocochlear system, the existence of a larger volume of cortical connecting fibers in the left hemisphere, and the possible link between BZD receptor density and neuronal density, we tested the hypothesis of an asymmetrical localization of BZD receptors in the auditory system in 10 right-handed subjects using [11C]flumazenil positron emission tomography. Semi-quantitative measurements of flumazenil binding were evaluated in Heschl's gyrus showing a left-right asymmetry in favor of left auditory cortex. This result indicates a higher density of neurons in left auditory cortex. The possible link between neurochemical asymmetry and functional asymmetry, and the perceptual outcome of BZD administration, will be discussed.

Adult↗