Elisabeth Landré

FDG-PET improves surgical outcome in negative MRI Taylor-type focal cortical dysplasias

Objective: To determine the diagnostic accuracy and prognostic value of 18FDG-PET in a recent series of patients operated for intractable partial epilepsy associated with histologically proven Taylor-type focal cortical dysplasia (TTFCD) and negative MRI. Methods: Of 23 consecutive patients (12 male, 7–38 years old) with negative 1.5-Tesla MRI, 10 exhibited subtle nonspecific abnormalities (e.g., unusual sulcus depth or gyral pattern) and the 13 others had strictly normal MRI. FDG-PET was analyzed both visually after coregistration on MRI and using SPM5 software. Metabolic data were compared with the epileptogenic zone (EZ) determined by stereo-EEG (SEEG) and surgical outcome. Results: Visual PET analysis disclosed a focal or regional hypometabolism in 18 cases (78%) corresponding to a single gyrus (n = 9) or a larger cortical region (n = 9). PET/MRI coregistration detected a partially hypometabolic gyrus in 4 additional cases. SPM5 PET analysis (n = 18) was concordant with visual analysis in 13 cases. Location of PET abnormalities was extratemporal in all cases, involving eloquent cortex in 15 (65%). Correlations between SEEG, PET/MRI, and histologic findings (n = 20) demonstrated that single hypometabolic gyri (n = 11) corresponded to EZ and TTFCD, which was localized at the bottom of the sulcus. Larger hypometabolic areas (n = 9) also included the EZ and the dysplastic cortex but were more extensive. Following limited cortical resection (mean follow-up 4 years), seizure freedom without permanent motor deficit was obtained in 20/23 patients (87%). Conclusions: 18FDG-PET coregistered with MRI is highly sensitive to detect TTFCD and greatly improves diagnosis and surgical prognosis of patients with negative MRI.

Type II focal cortical dysplasia: electroclinical phenotype and surgical outcome related to imaging.

Purpose:  Type II focal cortical dysplasia (TTFCD), a highly epileptogenic lesion with severe epilepsy curable by surgery, is missed by magnetic resonance imaging (MRI) in about one third of cases. Little is known about the electroclinical presentation in these MRI‐negative patients and a poor surgical outcome is frequently reported. We compared the clinical and neurophysiologic features in MRI‐negative and MRI‐positive cases in order to better identify candidates for surgery.

Intralesional recordings and epileptogenic zone in focal polymicrogyria

Purpose: Polymicrogyria (PMG) is recognized as an epileptogenic lesion but few data concerning organization of the epileptogenic zone (EZ) are available.

Dystonic posturing in seizures of mesial temporal origin: Electroclinical and metabolic patterns

Objective: To test the hypothesis that extratemporal neuronal networks are involved in dystonic posturing (DP) observed in mesial temporal epilepsy (MTLE). Methods: The authors analyzed electroclinical findings in 36 patients with MTLE with or without DP. Three DP types were defined (types I, II, III) corresponding to a gradual increase in duration and complexity. Interictal [18F]fluorodeoxyglucose-PET in different groups and subgroups was compared with control subjects using statistical parametric mapping software (SPM99). Results: DP was found in 20 patients (55%), contralateral to the epileptogenic focus in 95%. Patients with DP had longer seizure duration, higher frequency of head deviation, salivation, motor manifestations, secondary generalization, severe clouding of consciousness, and prolonged postictal confusion when compared with patients without DP. Ictal discharge patterns during DP consisted of fast rhythmic activity spreading to frontal or suprasylvian areas, whereas slow rhythmic activity restricted to the temporal areas occurred in the absence of DP. In patients with DP, widespread temporal and extratemporal hypometabolism including the putamen was found. Hypometabolism was restricted to the anteromesial part of the temporal lobe and anterior insula in patients without DP. Putaminal hypometabolism was found in all DP types, but different extratemporal cortical involvements were found in DP subgroups: insula and inferior frontal gyrus in type I, inferior and superior frontal gyri and anterior cingulate gyrus in type II, and parietal areas in type III. Conclusion: Dystonic posturing may result from involvement of both putaminal and extratemporal cortical areas. Moreover, different frontal or parietal networks may be involved according to the duration or complexity of dystonic posturing.

Therapeutic drug monitoring of levetiracetam by high-performance liquid chromatography with photodiode array ultraviolet detection : Preliminary observations on correlation between plasma concentration and clinical response in patients with refractory epilepsy

Levetiracetam is a new antiepileptic drug prescribed for the treatment of patients with refractory partial seizures with or without secondary generalization as well as for the treatment of juvenile myoclonic epilepsy. A rapid and specific method by high-performance liquid chromatography diode array detection was developed to measure the concentration of levetiracetam in human plasma. The trough plasma concentrations measured in 69 epileptic patients treated with 500 to 3000 mg/d of levetiracetam ranged from 1.1 to 33.5 μg/mL. The mean (range) levetiracetam plasma concentrations in responders and nonresponders were 12.9 μg/mL (4.6-21 μg/mL) and 9.5 μg/mL (1.1-20.9 μg/mL), respectively. A wide variability in concentration-response relationships was observed in patients. Using a receiver operating characteristic curve, the threshold levetiracetam concentration for a therapeutic response was 11 μg/mL. The sensitivity and specificity for this threshold levetiracetam concentration were 73% and 71%, respectively. According to χ2 analysis, this finding was not significant probably because of the small number of patients and because of their refractory seizure type. Nevertheless, the levetiracetam plasma concentration could be used to help clinicians detect severe intoxication or to verify compliance by repeating the measurement in patients.

Dysembryoplastic neuroepithelial tumors An MRI-based scheme for epilepsy surgery

Objective: To determine optimal resections in the 3 dysembryoplastic neuroepithelial tumor (DNT) histologic subtypes (simple, complex, and nonspecific) based on MRI features. Methods: In 78 consecutive epilepsy patients operated for DNT, MRI features were classified as follows: type 1 (cystic/polycystic-like, well-delineated, strongly hypointense T1), type 2 (nodular-like, heterogeneous), or type 3 (dysplastic-like, iso/hyposignal T1, poor delineation, gray–white matter blurring). Correlations between histology, neurophysiologic findings, and surgical outcome were established for each MRI subtype. Results: Type 1 MRI (25 cases, in temporal and extratemporal areas) always corresponded to simple or complex DNTs. Type 2 MRI (25 cases, predominantly in neocortical areas) and type 3 MRI (28 cases, mainly in the mesial temporal lobe) corresponded to nonspecific forms. The epileptogenic zone (EZ) differed significantly according to the MRI subtype (p = 0.0029). It colocalized with the tumor in type 1 MRI, included perilesional cortex in type 2 MRI, and involved extensive areas in type 3 MRI. Cortical dysplasia was predominantly found in type 3 MRI (p < 0.0001). The main prognostic factors for seizure-free outcome (83%) were complete tumor (p < 0.0001) and EZ (p = 0.0115) removal. Other factors favorably influencing the outcome were a short epilepsy duration (p = 0.013) and absence of cortical–subcortical damage at the resection site (p = 0.053). Age at surgery was not related to outcome; however, cortical-subcortical damage was correlated with old age (p = 0.021). Treatment discontinuation was correlated with young age at surgery (p = 0.004) and short epilepsy duration (p = 0.001). Conclusion: We propose that resection might be restricted to the tumor in type 1 MRI and be more extensive in other MRI subtypes, especially in type 3 MRI. Early surgery and clean surgical margins are crucial for curing epilepsy.

Chronic Intractable Epilepsy Associated with a Tumor Located in the Central Region: Functional Mapping Data and Postoperative Outcome

Out of 57 patients operated for intractable epilepsy of the central region, 8 harbored an indolent glioma (7 dysembryoplastic neuroepithelial tumors, 1 ganglioglioma). Mapping of the sensorimotor area with depth electrodes implanted for stereoelectroencephalographic exploration demonstrated no or abnormal motor responses after low-frequency stimulation, and variable sensory responses to high-frequency stimulation, suggesting reorganization of the sensorimotor cortex representation around the tumor and absence of functional tissue within the neoplastic volume. After lesionectomy (3 cases) or corticectomy including the tumor (5 cases), 6 (75%) patients were seizure-free (class I of Engel) at the time to follow-up. No permanent motor or sensory deficit was observed in 6 cases. In 2, a mild facial (in 1) and arm (in 1) deficit persisted. It is concluded that the resection of intrinsic low-grade tumors associated with long-standing epilepsy and located in the central region can be associated with excellent seizure outcome and no or minimal postoperative deficit because of functional reorganization of the sensorimotor cortex.

Chirurgie des dysplasies corticales focales en région centrale

BACKGROUND AND PURPOSE Taylor-type focal cortical dysplasias (TTFCD) represent a particular pathological entity responsible for severe drug-resistant epilepsy of extratemporal location. Epilepsy can be surgically cured if complete removal of the lesion can be performed. However, identification on imaging may be difficult and negative standard MRIs are not rare. The frequent location of TTFCD in the central region restrains the possibilities of complete resection. We report a series of patients operated on for intractable epilepsy associated with TTFCD in the central area. PATIENTS AND METHODS Between 2000 and 2006, of 34 consecutive patients with TTFCD, 17 had a lesion located in the central area. MRI was considered normal in eight, although in five a subtle gyral abnormality was disclosed on further analysis. A (18)FDG PET scan performed in 16 cases demonstrated focal hypometabolism in 15 that correlated with abnormalities on MRI when visible. SEEG performed in 13 cases revealed typical abnormalities for TTFCD in 10 cases. At resection, cortical and subcortical stimulations of the dysplastic cortex did not elicit a motor response. RESULTS Postoperative motor or sensory deficit was observed in 13 patients--severe in four--which subsequently resolved completely in seven. Six patients had a minor permanent, motor or sensory deficit. Four patients were reoperated for seizure recurrence and residual dysplastic tissue was found at reoperation in three cases. Average postoperative follow-up was 3.7 years. Sixteen patients (94%) were in Engel Class I (65% in Class IA). CONCLUSION This study suggests that surgical resection of central region TTFCD may be associated with favorable seizure outcome and no or minor functional permanent disability. In cases of seizure relapse, reoperation can be performed without further permanent deficit and lead to seizure-free outcome. Future techniques for intraoperative detection of these lesions could optimize their complete resection in functional areas.

Résections en région fonctionnelle : étude d’une série de 89 cas

Surgical resections for intractable epilepsy are generally associated with a high risk of permanent neurological deficit and a poor rate of seizure control. We present a series of 89 patients operated on from 1992 through 2007 for drug-resistant partial epilepsy, in whom surgery was performed in a functional area of the brain: the central (sensorimotor and supplementary motor areas) region in 48 cases, posterior regions (parietal and occipital) in 27, the insula in eight, and the language areas in six. Epilepsy was cryptogenic in 12 patients, and lesion-related in 77: malformation of cortical development in 43, tumor in 17, perinatal cicatrix in 13, vascular lesion in three, and another prenatal lesion in one. Seventy patients underwent stereoelectroencephalographic (SEEG) exploration. The surgical procedure was resective (lesionectomy or SEEG-guided corticectomy) in 83 patients and multiple stereotactic thermocoagulations in six. Ten patients were reoperated because of early seizure recurrence. A postoperative complication was observed in 12 patients. Postoperative deficits were observed in 54 patients (61%) and resolved completely in 29. In 25, a permanent deficit persisted, minor in 19 and moderate to severe in six, which did not correlate with localization or etiology. With a one-year follow-up in 74 patients (mean, 3.6 years), 53 (72%) were in Engels class I, including 38 (51%) in class IA. Seizure outcome was significantly associated with etiology: 93% of Taylor-type focal cortical dysplasia, whereas only 40% of cryptogenic epilepsies were in class I (p<0.05). This suggests that resective or disconnective surgery for intractable partial epilepsy in functional areas of the brain may be followed by excellent results on seizures and a moderate risk of permanent neurological sequelae.

Determinants of brain metabolism changes in mesial temporal lobe epilepsy.

To determine the main factors influencing metabolic changes in mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS).