Molecular imaging in the diagnosis of Alzheimer's disease and related disorders.

INTRODUCTION: The diagnosis of Alzheimer's disease (AD) and its related disorders rely on clinical criteria. There is, however, a large clinical overlap between the different neurodegenerative diseases affecting cognition and, frequently, there are diagnostic uncertainties with atypical clinical presentations. Current clinical practices can now regularly use positron emission tomography (PET) and single-photon emission computed tomography (SPECT) molecular imaging to help resolve such uncertainties. The Neurology Group of the French Society of Nuclear Medicine and Federations of Memory, Resources and Research Centers have collaborated to establish clinical guidelines to determine which molecular imaging techniques to use when seeking a differential diagnosis between AD and other neurodegenerative disorders affecting cognition. STATE OF KNOWLEDGE: According to the current medical literature, the potential usefulness of molecular imaging to address the typical clinical criteria in common forms of AD remains modest, as typical AD presentations rarely raise questions of differential diagnoses with other neurodegenerative disorders. However, molecular imaging could be of significant value in the diagnosis of atypical neurodegenerative disorders, including early onset, rapid cognitive decline, prominent non-amnestic presentations involving language, visuospatial, behavioral/executive and/or non-cognitive symptoms in AD, or prominent amnestic presentations in other non-AD dementias. CONCLUSION AND PERSPECTIVE: The clinical use of molecular imaging should be recommended for assessing cognitive disturbances particularly in patients with early clinical onset (before age 65) and atypical presentations. However, diagnostic tools should always be part of the global clinical approach, as an isolated positive result cannot adequately establish a diagnosis of any neurodegenerative disorder.

Brain metabolic abnormalities during gait with freezing in Parkinson's disease.

INTRODUCTION: Freezing of gait (FoG) is a debilitating gait disorder in Parkinson's disease (PD). In advanced PD patients with FoG, the supraspinal locomotor network may be dysregulated (relative to similar patients without FoG) during gait. Here, we sought to characterize the metabolism of locomotor networks involved in FoG. METHODS: Twenty-two PD patients (11 with off-drug FoG and 11 without) each underwent two [(18)F]-fluorodeoxyglucose PET brain scans in the off-drug state: one at rest and another during radiotracer uptake while performing a standardized gait trajectory that incorporated the usual triggers for FoG. RESULTS: For the 11 freezers, FoG was present for 39% (± 23%) of the time during the gait trajectory. The FoG-associated abnormalities were characterized by (i) hypometabolism in frontal regions (the associative premotor, temporopolar and orbitofrontal areas, i.e. Brodmann areas 6 and 8), (ii) hypermetabolism in the paracentral lobule (Brodmann area 5), and (iii) deregulation of the basal ganglia output (the globus pallidus and the mesencephalic locomotor region). CONCLUSION: FoG during a real gait task was associated with impaired frontoparietal cortical activation, as characterized by abnormally low metabolic activity of the premotor area (involved in the indirect locomotor pathway) and abnormally high metabolic activity of the parietal area (reflecting the harmful effect of external cueing).

Undetectable specific striatal [¹²³I]-ioflupane binding in patients with parkinsonism.

[(123)I]-Ioflupane single photon emission computed tomography (SPECT) is widely used to evaluate the impairment of the nigrostriatal pathway in patients with parkinsonism. We describe a patient with visually undetectable specific striatal [123I]-ioflupane binding in the striatum. Of the 950 [123I]-ioflupane SPECT scans of patients acquired in our department, only one did not show any visually detectable striatal binding. To investigate this issue, we described multimodality imaging in this patient, including a second [123I]-ioflupane SPECT with a higher dose of [123I]-ioflupane, a [18F]-fluoro-l-dopa positron emission tomography (PET), a new MRI and an FDG-PET. Clinical and imaging data (FDG-PET and MRI) led to a diagnosis of progressive supranuclear palsy (PSP). Visual analysis of the second [(123)I]-ioflupane SPECT performed with a higher dose of [(123)I]-ioflupane confirmed nearly undetectable specific striatal binding of the tracer. The [(18)F]-fluoro-l-dopa-PET striatal binding was decreased. After ruling out all technical issues, an undetectable specific [(123)I]-ioflupane striatal binding in a patient with parkinsonism can be a sign of severe DaT loss as we have observed in a case of probable PSP even with moderate motor signs.

[Neuropsychiatric systemic lupus erythematosus (1st part). Cases definitions and diagnosis and treatment of central nervous system and psychiatric manifestations of systemic lupus erythematosus]. / Neurolupus (1re partie). Description et démarche diagnostique et thérapeutique dans les manifestations neurologiques centrales et psychiatriques au cours du lupus érythémateux systémique.

Systemic lupus erythematosus (SLE) is an autoimmune disease, which primarily affects skin and joints. Peripheral neurologic syndrome and central nervous system (CNS) manifestations are common in lupus patients but are not always attributable to lupus itself. A classification, published in 1999 by the American College of Rheumatology (ACR) research committee, described 12 CNS syndromes and seven peripheral neurologic syndromes compatible with "neuropsychiatric systemic lupus erythematosus" (NPSLE). Despite this consensus, studies which have been published since 1999 have reported a prevalence of NPSLE varying from 20 to 97 %, which shows the diagnosis difficulty and the heterogeneity of neuropsychiatric manifestations in SLE. In order to understand the limits of this classification, we propose in this first part an exhaustive review of publications describing neuropsychiatric manifestations according to the ACR 1999 classification. We also detail case definitions, prevalence and risk factors, clinical characteristics and diagnosis of each lupus-related psychiatric and CNS manifestation.

[Neuropsychiatric systemic lupus erythematosus (2nd part). Diagnostic and treatment tools in psychiatric or central nervous system manifestations in systemic lupus erythematosus]. / Neurolupus (2e partie). Description des outils diagnostiques et thérapeutiques devant une manifestation psychiatrique ou neurologique centrale au cours du lupus érythémateux systémique.

Neurological and psychiatric manifestations of systemic lupus erythematosus are a heterogeneous set of clinical manifestations grouped under the term of "neuropsychiatric systemic lupus erythematosus". The classification of these manifestations published in 1999 has harmonized the definitions cases used in the studies but did not help the clinician to positively identify a specific manifestation of lupus or a neurological or psychiatric event occurred independently of the disease. Published cases series help us to identify neurological or psychiatric manifestations of lupus but modern diagnosis tools contribution have to be evaluated in order to optimize diagnosis management of such manifestations and to distinguish specific events related to lupus and independent manifestations. In this second part of our literature review about neuropsychiatric lupus, we propose to identify arguments, which could be in favor of lupus responsibility in front of a neurological or psychiatric event, and immunosuppressive treatments which are recommended.

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.

[Nuclear medicine imaging: new radiotracers and future techniques]. / L'imagerie de médecine nucléaire: nouveaux traceurs et techniques d'avenir.

Nuclear medicine imaging is based upon positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging. PET and SPECT are widely used in patients with medically refractory partial epilepsy. For clinical purposes, PET is performed using FDG and SPECT is performed using perfusion agents. PET is also used to better understand the pathophysiological mechanisms of epilepsies. New radiotracers are available for PET and SPECT imaging such as (18)F-fluoro-L-Dopa and (123)I-FP-CIT and others are under development. In addition, there are currently new methodological developments combining techniques such as SPECT associated with computed tomography and in the near future PET combined with MRI. This progress will improve the performance of nuclear medicine imaging techniques.

[Medicoeconomic assessment of epilepsy surgery in adults with medically intractable partial epilepsy. Three-year outcomes from a multicenter French cohort]. / Evaluation médicoéconomique de la chirurgie des épilepsies partielles pharmacorésistantes de l'adulte. Résultats à trois ans d'une étude prospective multicentrique française.

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.

Basal ganglia involvement in temporal lobe epilepsy: a functional and morphologic study.

OBJECTIVES: A decrease of [(18)F]fluoro-l-dopa uptake in basal ganglia was recently reported in medically refractory epilepsy. The purpose of this study was to assess the involvement of dopaminergic neurotransmission in refractory temporal lobe epilepsy (TLE) and its relationship to glucose metabolism and morphologic changes. METHODS: Twelve TLE patients were studied using [(18)F]fluorodeoxyglucose PET, [(18)F]fluoro-l-dopa PET, and MRI and compared with healthy control volunteers. Morphologic cerebral changes were assessed using voxel-based morphometry. Student t test statistical maps of functional and morphologic differences between patients and controls were obtained using a general linear model. RESULTS: In TLE patients, [(18)F]fluoro-l-dopa uptake was reduced to the same extent in caudate and putamen in both cerebral hemispheres as well as in the substantia nigra (SN). These dopaminergic functional alterations occurred without any glucose metabolism changes in these areas. The only mild morphologic abnormality was found in striatal regions without any changes in the SN. CONCLUSION: The present study provides support for dopaminergic neurotransmission involvement in temporal lobe epilepsy. The discrepancies between gray matter volume atrophy and the pattern of [(18)F]fluoro-l-dopa suggest that basal ganglia involvement is not related to structural subcortical abnormalities. A functional decrease can be ruled out because there was no change of the glycolytic pathway metabolism in these areas.

[Use of generic anti-epilepsy drugs in France: survey of neurologists and review of the literature]. / Utilisation des médicaments génériques des anti-épileptiques en France: résultats d'une enquête auprès des neurologues et revue de la littérature.

INTRODUCTION: The use of generic substitution for antiepileptic drugs is more and more frequent but remains controversial. PURPOSE AND METHODS: This survey aimed to assess physicians' feelings towards effectiveness, tolerability and clinical impact of generic substitution of antiepileptic drugs on their patients. A questionnaire was sent to all French private neurologists and hospital specialists in epilepsy. Their responses were recorded from December 2005 to March 2006. RESULTS: A total of 312 neurologists responded. A few prescribed generic antiepileptic drugs; but a few as well indicated not to switch their prescription. Most of them felt discomfort by generic substitution. One third reported breakthrough seizures or new adverse events after generic substitution and 70p.cent extra phone consultation. DISCUSSION: Neurologists' reluctance with prescribing generic AEDs may be explained by several different facts: no controlled study about the safety and efficacy of generic AEDs as compared with brand name drugs, substitutions by pharmacists without their agreement, lack of medical information about generic AEDs, symbolic dimension of the treatment, and, most of all, the fear of breakthrough seizures in patients good controlled. CONCLUSION: A prospective controlled evaluation of the safety and efficacy of generic substitution in epilepsy needs to be performed.

Uncinate fasciculus fiber tracking in mesial temporal lobe epilepsy. Initial findings.

In temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS), ictal discharge spread to the frontal and insulo-perisylvian cortex is commonly observed. The implication of white matter pathways in this propagation has not been investigated. We compared diffusion tensor imaging (DTI) measurements along the uncinate fasciculus (UF), a major tract connecting the frontal and temporal lobes, in patients and controls. Ten right-handed patients referred for intractable TLE due to a right HS were investigated on a 1.5-T MR scanner including a DTI sequence. All patients had interictal fluorodeoxyglucose PET showing an ipsilateral temporal hypometabolism associated with insular and frontal or perisylvian hypometabolism. The controls consisted of ten right-handed healthy subjects. UF fiber tracking was performed, and its fractional anisotropy (FA) values were compared between patients and controls, separately for the right and left UF. The left-minus-right FA UF asymmetry index was computed to test for intergroup differences. Asymmetries were found in the control group with right-greater-than-left FA. This asymmetrical pattern was lost in the patient group. Right FA values were lower in patients with right HS versus controls. Although preliminary, these findings may be related to the preferential pathway of seizure spread from the mesial temporal lobe to frontal and insulo-perisylvian areas.

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.

[Cost-effectiveness of epilepsy surgery in a cohort of patients with medically intractable partial epilepsy--preliminary results]. / Evaluation médico-économique de la chirurgie des épilepsies partielles pharmaco-résistantes de l'adulte. Etude coût-efficacité--résultats préliminaires.

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.

PET evidence for a role of the basal ganglia in patients with ring chromosome 20 epilepsy.

BACKGROUND: Studies in animal models and epileptic patients have suggested that circuits of the basal ganglia may control epileptic seizures and that striatal dopaminergic transmission plays a key role in seizure interruption. Ring chromosome 20 (r[20]) epilepsy is a very homogenous type of epilepsy and is clinically characterized by long-lasting seizures suggesting a dysfunction in the seizure control system. The hypothesis that these long-lasting seizures are associated with a reduction of striatal dopamine was addressed in the present study in drug-resistant patients with r(20) epilepsy using PET. METHOD: The authors performed [18F]fluoro-l-DOPA PET in 14 patients with r(20) epilepsy and compared uptake constants in the putamen and the caudate with those of 10 controls. In addition, the authors examined the correlation between these constants and the percentage of cells with r(20) mosaicism. RESULTS: [18F]fluoro-l-DOPA uptake was significantly decreased bilaterally in the putamen and in the caudate nucleus of patients. This reduction was equal for both nuclei and was not correlated to the percentage of cells with r(20). CONCLUSION: Striatal dopamine is modulated in r(20) epilepsy; dysfunction of this neurotransmission may impair the mechanisms that interrupt seizures.

Functional anatomy of the insula: new insights from imaging.

Little is known about the functional anatomy of the insula. Several experimental data suggest that the organization of the insular connections from the different insular cytoarchitectonic regions is related to different functional domains within the insula, and recent electrophysiological and neuroimaging studies have shown the existence of an anterior-posterior organization within the insular cortex. To further investigate this point, we carried out a positron emission tomography (PET) study using fluorodeoxyglucose ((18)F-FDG) in patients with medial temporal lobe epilepsy who experienced emotional or visceral symptoms that are supposed to be elicited in the insula. The aim of our study was to assess the existence of a functional insular somatotopic organization. FDG-PET studies were carried out in 18 epileptic patients. Data were analyzed using statistical parametric mapping (SPM96). The results showed that the emotional symptoms were correlated with hypometabolism in the anterior part of the ipsilateral insular cortex, while visceral symptoms were correlated with hypometabolism in the posterior part ( p=0.001). This neuroimaging study demonstrates that the anterior part of the insular cortex corresponding to the agranular cortex subserves emotional functions while the posterior part of the insular cortex corresponding to the granular cortex subserves ascending visceral symptoms.

Early and late seizures after cryptogenic ischemic stroke in young adults.

OBJECTIVES: To assess the incidence and predictive factors of early and late seizures after ischemic stroke in young adults. METHODS: A total of 581 patients (aged 18 to 55 years) with recent cryptogenic ischemic stroke were prospectively enrolled at 30 neurology departments and followed for 37.8 +/- 9.7 months. Early seizures (occurring within 7 days of stroke) were assessed by chart review and late seizures were prospectively recorded at each follow-up visit. Clinical and brain imaging findings were reviewed by two neurologists and two neuroradiologists who were blinded to the occurrence of seizures. RESULTS: Fourteen of the 581 patients (2.4%) developed early seizures, 71% of which occurred within the first 24 hours. Rankin scale >or=3 (odds ratio [OR] 3.9, 95% CI 1.2 to 12.7) and cortical involvement (OR 7.7, 95% CI 1.0 to 61.1) were independently associated with early seizures. Late seizures occurred only in patients with hemispheric stroke (n = 20). The risk of first late seizure was 3.1% (95% CI 1.4 to 4.8) within 1 year and 5.5% (95% CI 3.1 to 7.9) within 3 years. The mean delay between stroke and first late seizure was 12.9 months (0.3 to 33.9). Late seizures were associated with early seizure (hazard ratio [HR] 5.1, 95% CI 1.8 to 14.8), cortical signs (HR 4.5, 95% CI 1.6 to 13.1), and size of infarct superior to one-half hemisphere (HR 9.7, 95% CI 3.1 to 30.8). Eleven of the 20 patients with late seizure experienced recurrences (multiple in eight) on antiepileptic drug treatment. Most of them were seizure free at the end of the follow-up. CONCLUSION: Epilepsy is rarely a major problem in young cryptogenic ischemic stroke survivors. Early seizures are associated with stroke disability and cortical involvement. Early seizures, cortical signs, and large infarct are independent risk factors for late seizures.

Is amygdalohippocampectomy really selective in medial temporal lobe epilepsy? A study using positron emission tomography with (18)fluorodeoxyglucose.

PURPOSE: Selective amygdalohippocampectomy (SAH) is a surgical technique effective for the treatment of medial temporal lobe epilepsy, which selectively removes the epileptogenic hippocampus and amygdala but spares the temporal neocortex. However, the benefit of SAH in terms of functional outcome is debated. In this study, we aimed to assess the metabolic consequences of SAH. METHODS: Volumetric magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (PET) studies were performed in nine patients with medial temporal lobe epilepsy associated with hippocampal sclerosis before and after SAH. Regions of interest were delineated on MRIs and then replaced on PET images using an automatic 3D image registration. We calculated absolute metabolic rates of glucose and normalized metabolic values in each region of interest. RESULTS: The comparison between preoperative and postoperative metabolic values showed a statistically significant worsening of the hypometabolism on the ipsilateral temporal pole on the superior and the hippocampal levels (p < 0.05 and 0.0045, respectively). A postoperative increase of the metabolic activity also was noted in the contralateral anterior hippocampus (p < 0.05) and the orbitofrontal cortex bilaterally (p < 0.002 and 0.001, respectively) CONCLUSIONS: SAH functional benefit is controversial. SAH worsened significantly the hypometabolism of a temporal structure that was not surgically removed (i.e., the temporal pole), and it improved postoperatively the metabolic activity in the contralateral hippocampus and the orbitofrontal cortex. Whether this postoperative improvement is linked to the selectivity of the surgical procedure must be further clarified.

Accurate prediction of postoperative outcome in mesial temporal lobe epilepsy: a study using positron emission tomography with 18fluorodeoxyglucose.

BACKGROUND: Recent studies suggest that positron emission tomography may be a reliable predictive indicator of clinical outcome following surgical treatment for epilepsy. OBJECTIVE: We evaluated 30 patients with documented medial temporal lobe epilepsy to determine if prediction of postoperative outcome is improved with the use of positron emission tomography with (18)fluorodeoxyglucose. PATIENTS AND METHODS: We performed a discriminant analysis to determine the combination of metabolic asymmetry indexes in temporal and extratemporal regions defined by magnetic resonance imaging that best predicted the postoperative outcome. Seizure outcome was assessed at least 2 years after surgery: patients were classified as seizure free (n = 14, group A), mostly improved (n = 10, group B), or as having persistent seizures (n = 6, group C). RESULTS: Discriminant analysis was first performed in groups A and C. The temporal pole seemed to be the only temporal region for which metabolism was a significant predictor of the postoperative outcome (F(1,18) = 10.19; P =.005). The predictive value of positron emission tomography with (18)fluorodeoxyglucose was considerably improved by the multivariate analysis (F(4,15) = 7.21; P =.002), which correctly predicted the 2 -year prognosis in 100% of the patients using 4 regions: the temporal pole, the medial temporal region, the anterior part of the lateral temporal neocortex, and the basofrontal region. As a validation, we performed this 4-region analysis in the patients in group B. The difference among the 3 groups was highly significant (F = 15.5, P<.001). CONCLUSION: These findings suggest that the interictal metabolic pattern reliably predicts the 2-year prognosis after surgery in patients with medial temporal lobe epilepsy.

Gamma knife surgery for mesial temporal lobe epilepsy.

PURPOSE: Gamma knife radiosurgery (GK) allows precise and complete destruction of chosen target structures containing healthy and/or pathologic cells, without significant concomitant or late radiation damage to adjacent tissues. All the well-documented radiosurgery of epilepsy cases are epilepsies associated with tumors or arteriovenous malformations (AVMs). Results prompted the idea to test radiosurgery as a new way of treating epilepsy without space-occupying lesions. METHODS: To evaluate this new method, we selected seven patients with drug-resistant "mesial temporal lobe epilepsy" (MTLE). The preoperative evaluation program was the one we usually perform for patients selected for microsurgery of TLE [video-EEG analysis of seizures, foramen ovale electrode recording, magnetic resonance imaging (MRI) positron emission tomography (PET) scan, neuropsychological testing]. In lieu of microsurgery, the amygdalohippocampectomy was performed by using GK radiosurgery. RESULTS: Morphologic (MRI) signs of destruction of the target took place at 9 months after GK surgery. Since the treatment day, the first patient has been seizure free. Seizure improvement came more gradually for the following patients, and complete cessation of seizures occurred around the tenth month (range, 8-15 months). MRI shows that the amygdaloentorhinohippocampal target was selectively injured. No significant side effect (except one case of homologous quadrantanopia) or morbidity and no mortality was observed. The current follow-up is 24-61 months, and all (but one) patients are seizure free. CONCLUSIONS: This initial experience proves clearly the short-to middle-term efficiency and safety of GK for MTLE surgery. These results need further confirmation of long-term efficiency, but the introduction of GK surgery into epilepsy surgery can reduce dramatically its invasiveness and morbidity.