In adults, partial epilepsy is more difficult to treat than idiopathic generalized epilepsy. In patients who have partial epilepsy, the location of the epileptogenic zone does not seem to be a determining factor. Brain abnormalities--especially HS, either alone or associated with another lesion--are a major prognostic factor.

Promoting myelin repair is one of the most promising therapeutic avenues in the field of myelin disorders. In future clinical trials, evaluation of remyelination will require a reliable and quantifiable myelin marker to be used as a surrogate marker. To date, MRI assessment lacks specificity for evaluating the level of remyelination within the brain. Here, we describe 1,4-bis(p-aminostyryl)-2-methoxy benzene (BMB), a synthesized fluorescent molecule, that binds selectively to myelin both ex vivo and in vivo. The binding of BMB to myelin allows the detection of demyelinating lesions in an experimental autoimmune encephalitis model of demyelination and allows a mean for quantifying myelin loss in dysmyelinating mutants. In multiple sclerosis brain, different levels of BMB binding differentiated remyelination in shadow plaques from either demyelinated lesions or normal-appearing white matter. After systemic injection, BMB crosses the blood-brain barrier and binds to myelin in a dose-dependent and reversible manner. Finally, we provide evidence that 11 C-radiolabeled BMB can be used in vivo to image CNS myelin by positron-emission tomography in baboon. Our results provide a perspective for developing a brain myelin imaging technique by positron-emission tomography.multiple sclerosis ͉ remyelination ͉ leukodystrophy M yelin is a unique structure in the nervous system that allows rapid, economic, and secure conduction of impulses along axons. The loss or lack of myelin resulting from an acquired or inherited disease may produce a delay or failure of conduction in affected fibers, with concomitant neurological dysfunction. In the human CNS, multiple sclerosis (MS) is the most common acquired demyelinating disease, affecting Ϸ2 million people worldwide (1). The leukodystrophies, induced by inherited enzyme deficiencies, also affect CNS white matter, resulting in abnormal formation, destruction, or turnover of myelin sheaths (2). Both acquired and inherited myelin disorders share a poor prognosis, leading to major disability in young people.Spontaneous remyelination can occur in the CNS and was first demonstrated by electron microscopy of lesions in the adult mammalian spinal cord (3). Remyelination results in the formation of short and thin myelinated internodes, but it enables the restoration of a sufficient conduction along axons and allows some functional recovery (4, 5). In demyelinating diseases such as MS, this regenerative process does occur and sometimes proceeds to completion (6), but it is less efficient than in experimental animal models (7). Improving repair processes can theoretically be achieved by either promoting endogenous repair mechanisms or providing an exogenous source of myelinating cells by transplantation (8-10). Clinical trials are expected to be carried out in the latter field soon.A major clinical issue of such trials is to assess and quantify myelin repair in vivo. To date, MRI is the reference test for diagnosing and monitoring the evolution of white-matter diseases (2, 11, 12). Unfortunatel...

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Developmental disorders of the hippocampal formation (HF) have been described in epileptic syndromes associated with lissencephaly, but HF malformations can be found without widespread cortical changes. We report 19 patients with partial epilepsy and abnormal HF patterns on magnetic resonance imaging (MRI). The changes consisted of incomplete folding with abnormal medial location along the choroid fissure, globular shape and/or verticalization, and were observed in the following three contexts: (1) diffuse disorder of neuronal migration (n=1); (2) temporal lobe malformation (n=5), including heterotopia, abnormal gyration, and, in 2 cases, reduced HF volume; and (3) apparently isolated HF changes (n=13, bilateral in 3 cases). The clinical features were heterogeneous in terms of severity of epilepsy and, when the focus could be determined, in localization (temporal or extratemporal). In 4 patients with apparently isolated HF changes, MRI was suggestive of both abnormal development and hippocampal sclerosis. In these patients, presurgical investigation and postoperative results suggested multiple epileptogenic foci, involving the frontal lobes in 2 cases. One HF specimen was large enough for the observation of developmental abnormalities corresponding to the changes seen on MRI. HF changes in shape and/or position should be included among the structural abnormalities associated with partial epilepsies. They may represent the visible part of a more extensive or more distant disorder of brain development.

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.

The mechanism of interictal glucose hypometabolism remains unclear, but this abnormality occurs more frequently in temporal lobe epilepsy (TLE) than in other types of partial epilepsy. Therefore temporal hypometabolism has been suggested to reflect mesial temporal sclerosis (MTS). To investigate this, we selected 22 patients with refractory partial epilepsy of mesial temporal lobe origin (MTLE) who had hippocampal atrophy based on magnetic resonance imaging (MRI) volumetric analysis. We then analyzed the metabolic correlates of unilateral hippocampal atrophy. Thirteen temporal regions of interest (ROI) were defined on MRI scans for each individual and then applied to high-resolution FDG-positron emission tomography (PET) images obtained parallel to the long axis of the hippocampus. The most hypometabolic regions were the temporal pole and the hippocampal region. When we analyzed ensembles of temporal regions grouped into related networks, the temporolimbic network, which included the hippocampal region and the temporal pole, was abnormal in 95% of the patients at a 3-SD threshold. PET hypometabolism was highly correlated with the degree of hippocampal atrophy in this network, but not in other parts of the temporal lobe, which were less frequently hypometabolic. These data indicate that hypometabolism is a consequence of MTS in the temporolimbic region but not necessarily in the other parts of the temporal lobe. Our results also suggest that the combination of PET and MRI may facilitate the noninvasive diagnosis of MTLE.

Somesthetic and emotional symptoms that are common in patients with mesial temporal lobe epilepsy are usually related to hippocampo-amygdalar complex involvement. Recent stereo-electroencephalographic studies have shown a relationship between such symptoms and epileptic insular discharges. To further investigate this problem, we carried out a positron emission tomography study using fluorodeoxyglucose (18F-FDG) and flumazenil (11C-FMZ) in mesial temporal lobe epilepsy patients. The aim of our study was to assess the existence of a cortical insular involvement in order to examine its clinical correlates and the relationship between the postoperative outcome and the insular involvement. Fluorodeoxyglucose and flumazenil-positron emission tomography studies were carried out in 18 patients with mesial temporal lobe epilepsy patients. A statistical parametric mapping (SPM96) was performed to analyze the data in comparison to 18 healthy volunteers. For each set of fluorodeoxyglucose and flumazenil images a group and an individual analysis were performed. In addition, a region of interest analysis was performed to validate the results. Focusing on the metabolic abnormalities, we also investigated the role of insular cortex in the symptoms experienced by the patients and the prognostic value of insular metabolic abnormalities. Highly significant hypometabolism and BZR binding decreases were detected in the insular cortex. Results were similar using the region of interest approach. Insular involvement (mainly ipsilateral to the seizure focus) was present in 60% of the patients. Emotional symptoms correlated with hypometabolism in the anterior part of the ipsilateral insular cortex, whereas somesthetic symptoms correlated with hypometabolism in the posterior part. No relationship between postoperative outcome and ipsilateral insular hypometabolism was found. Unilateral mesial temporal lobe epilepsy is associated with insular hypometabolism and benzodiazepine receptor loss. Our results also suggest that the anterior part of the insular cortex is involved in the emotional symptoms and the posterior insular cortex is involved in the somesthetic symptoms. Hypometabolism located in the insula did not influence postoperative outcome after anterior lobectomy.

Progressive facial hemiatrophy (PFH), a rare disorder characterized by progressive and self-limited atrophy of the skin and the subcutaneous tissues, is often associated with epilepsy but the link between these two conditions is poorly understood. The cause of PFH remains unclear. We report four patients with PFH associated with partial epilepsy in whom brain MRI showed cerebral dysgenesis. The four patients (two men, two women; age range: 24 to 73 years) developed parasagittal PFH in their second decade. Seizures started before the age of 20 years in three patients and were refractory simple, or complex partial seizures. All the patients had focal MRI showing cortical dysgenesis, ipsilateral to PFH, consisting of cortex thickening, gyral effacement, and blurring of the white-gray interface. The underlying white matter was hyperintense on T2-weighted sequences, with nodular areas in two patients. These areas were stable over time, without contrast enhancement, and were consistent with the MRI characteristics of cystic encephalomalacia. These neuroradiologic features suggest a localized cerebral hemispheric defect of congenital origin. Because cells participating in the formation of the fronto-nasal bud derive from common progenitors with the cells that give rise to the cerebral hemisphere, we suggest that an early malformative process affecting one side of the rostral neural tube could underlie both cerebral dysgenesis and facial hemiatrophy.