European trends in epilepsy surgery.

OBJECTIVE: Resective surgery is effective in treating drug-resistant focal epilepsy, but it remains unclear whether improved diagnostics influence postsurgical outcomes. Here, we compared practice and outcomes over 2 periods 15 years apart. METHODS: Sixteen European centers retrospectively identified 2 cohorts of children and adults who underwent epilepsy surgery in the period of 1997 to 1998 (n = 562) or 2012 to 2013 (n = 736). Data collected included patient (sex, age) and disease (duration, localization and diagnosis) characteristics, type of surgery, histopathology, Engel postsurgical outcome, and complications, as well as imaging and electrophysiologic tests performed for each case. Postsurgical outcome predictors were included in a multivariate logistic regression to assess the strength of date of surgery as an independent predictor. RESULTS: Over time, the number of operated cases per center increased from a median of 31 to 50 per 2-year period (p = 0.02). Mean disease duration at surgery decreased by 5.2 years (p < 0.001). Overall seizure freedom (Engel class 1) increased from 66.7% to 70.9% (adjusted p = 0.04), despite an increase in complex surgeries (extratemporal and/or MRI negative). Surgeries performed during the later period were 1.34 times (adjusted odds ratio; 95% confidence interval 1.02-1.77) more likely to yield a favorable outcome (Engel class I) than earlier surgeries, and improvement was more marked in extratemporal and MRI-negative temporal epilepsy. The rate of persistent neurologic complications remained stable (4.6%-5.3%, p = 0.7). CONCLUSION: Improvements in European epilepsy surgery over time are modest but significant, including higher surgical volume, shorter disease duration, and improved postsurgical seizure outcomes. Early referral for evaluation is required to continue on this encouraging trend.

The relationship between morphological lesion, magnetic source imaging, and intracranial stereo-electroencephalography in focal cortical dysplasia.

Magnetoencephalography (MEG) is a useful non-invasive technique for presurgical evaluation of focal cortical dysplasia patients. We aimed at clarifying the precise spatial relationship between the spiking volume determined with MEG, the seizure onset zone and the lesional volume in patients with focal cortical dysplasia. We studied the spatial relationships between the MEG spiking volume determined with a recent analysis pipeline, the seizure-onset zone location determined with a quantitative index calculated from intracranial EEG signals ('Epileptogenicity Index') and the lesional volume delineated on brain MRI in 11 patients with Focal Cortical Dysplasia explored with Stereo-electroencephalography (SEEG). A significant correlation between the MEG spiking activity and the Epileptogenicity Index was found in 8/11 patients. 7/8 patients were operated upon and had good surgical outcome. For three patients, no correlation between Epileptogenicity Index and spiking activity was observed; only one of those three patients had good surgical outcome. The lesion was at least partially overlapping with the seizure-onset zone in 8/9 patients with a lesion clearly identifiable by MRI. However, 57% of the SEEG epileptogenic contacts were located outside of the lesional volume. Lastly 44% of the highly epileptogenic SEEG contacts were located within the spiking volume and 22% of them were located exclusively in the spiking volume and not in the lesion. For 7/9 patients with a lesion, < 50% of epileptogenic SEEG contacts were included within the lesion: for 5/7 patients MEG provided an added value for targeting the epileptogenic region through intracranial electrodes, while for two of seven patients MEG detected only a few extralesional epileptogenic contacts. Our study suggests that modeling of the spiking volume with MEG is a promising tool to localize non-invasively the seizure-onset zone in patients with focal cortical dysplasia. Combined with brain MRI, MEG modeling of the spiking volume contributes to delineate the spatial extent of the seizure-onset zone.

Stereotactic Electroencephalography Is a Safe Procedure, Including for Insular Implantations.

BACKGROUND: In some cases of drug-resistant focal epilepsy, noninvasive presurgical investigation may be insufficient to identify the ictal onset zone and the eloquent cortical areas. In such situations, invasive investigations are proposed using either stereotactic electroencephalography (SEEG) or subdural grid electrodes. Meta-analysis suggests that SEEG is safer than subdural grid electrodes, but insular implantation of SEEG electrodes has been thought to carry an additional risk of intraparenchymal hemorrhagic complications. Our objectives were to determine whether an insular SEEG trajectory is a risk factor for intracranial hematoma and to report the global safety of the procedure and provide some guidelines to prevent and detect complications. METHODS: In a retrospective analysis of a surgical series of 525 consecutive procedures between 1995 and 2015, all electrodes were classified according to their insular or extrainsular trajectory. All complications were classified as major or minor according to their potential consequences regarding patient neurologic status. RESULTS: Four intraparenchymal hematomas, all related to extrainsular electrodes (4/4974; 0.08%) were reported; no hematoma was found along insular electrodes (0/1042; 0%). There were 8 major complications (1.52%): 7 intracranial hematomas (1.33%) and 1 case of meningitis. Two patients had long-term neurologic impairment (0.38%), and 1 death (not directly related to the procedure) occurred (0.19%). Eleven minor complications (2.09%) were encountered, including broken electrode (1.52%), acute pneumocephalus (0.38%), and local cutaneous infection (0.19%). CONCLUSIONS: SEEG is a safe procedure. Insular trajectories cannot be considered an additional risk of intracranial bleeding.

Stereo electroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) in drug-resistant focal epilepsy: Results from a 10-year experience.

OBJECTIVE: Stereo electroencephalography (SEEG)-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) has been proposed since 2004 as a possible treatment of some focal drug-resistant epilepsy. The aim of this study is to provide extensive data about efficacy and safety of SEEG-guided RF-TC. METHODS: Over a 10-year period, 162 patients with drug-resistant focal epilepsy were eligible for SEEG-guided RF-TG during phase II invasive investigation by SEEG. All follow-up and safety data were collected prospectively. The primary outcome was seizure freedom at 2 months and at 1 year after SEEG-guided RF-TC. Secondary outcomes were the responders' rate (patient with at least 50% decrease in seizure frequency) and their long-term follow-up. RESULTS: Twenty-five percent of patients were seizure-free at 2 months and 7% at 1 year. We reported 67% of responders at 2 months and 48% at 1 year; 58% of responders maintained their status during the long-term follow-up. The seizure outcome was significantly better when the SEEG-guided RF-TC involved the occipital region (p = 0.007). When surgery followed an SEEG-guided RF-TC, the positive predictive value of being a responder 2 months after an SEEG-guided RF-TC and to be Engel's class I or II after surgery was 93%. We reported 1.1% of permanent deficit and 2.4% of transient side effects. SIGNIFICANCE: Our results, gathered in a large population over a 10-year period, confirm that SEEG-guided RF-TC is a safe technique, being efficient in many cases. More than two thirds of patients showed a short-term improvement, and almost half of them were responders at 1-year follow-up. The technique appears to be especially interesting for limited epileptic zone inaccessible to surgery and when epilepsy is related to a large unilateral network (network disruption by multiple RF-TC). Furthermore, SEEG-guided RF-TC effect is a predictor of outcome after conventional cortectomy in patients eligible for surgery.

Stereo-electro-encephalography-Guided Radiofrequency Thermocoagulation: From In Vitro and In Vivo Data to Technical Guidelines.

BACKGROUND: Deep brain electrodes have been used for the past 10 years to produce bipolar stereo-electro-encephalography-guided radiofrequency thermocoagulation (SEEG RF-TC). However, this technique is based on empiric knowledge. The aim of this study is 3-fold: 1) provide in vivo animal data concerning the effect of bipolar RF-TC on brain and its safety; 2) assess the parameters of this procedure (current delivery and dipole selection) that produce the most efficient lesion; and 3) provide technical guidelines. METHODS: First we achieved in vivo RF-TC on rabbit brains with several conditions (power delivered and lesioning duration) and analyzed their influence on the lesion produced. Only a difference in terms of volume was found, and type of histologic lesions was similar whatever the settings were. We then performed multiple RF-TC in vitro on egg albumen, first with several parameters of radiofrequency and then with different dipole spatial selections. The end point was the size of the radiofrequency thermolesion produced. RESULTS: Using unfixed parameters of radiofrequency current delivery and increasing it until the power delivered by the generator collapsed produced significantly larger lesions (P = 0.008) than other conditions. Concerning the dipole selection, the use of contiguous contacts on electrodes led to lesions with a higher volume (P = 7.7 × 10-13) than those produced with noncontiguous ones. CONCLUSION: Besides the target selection in SEEG RF-TC, which is summarized on the basis of a literature review, we report the optimal parameters: Radiofrequency current must be increased until the power delivered collapses, and dipoles should be constituted by contiguous electrode contacts.

Diagnostic utility of somatosensory evoked potentials in chronic polyradiculopathy without electrodiagnostic signs of peripheral demyelination.

INTRODUCTION: Diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) remains uncertain when nerve conduction studies (NCS) fail to show demyelination. METHODS: We conducted a retrospective study of patients who presented with clinical criteria of CIDP in whom electrodiagnostic (EDx) criteria of definite or probable CIDP were missing [axonal sensorimotor neuropathy (n = 23), normal EDx with pure sensory presentation (n = 3)]. All patients received immunomodulatory treatment. Twenty-six patients were evaluated with somatosensory evoked potentials (SSEPs), MRI of spinal roots, cerebrospinal fluid analysis, and/or nerve biopsy. Diagnosis of CIDP was considered to be confirmed in patients who responded to immunotherapy. RESULTS: Twenty-two of 26 patients (85%) had SSEPs reflecting abnormal proximal conduction in sensory fibers, including 14 who had only clinical and SSEP data in favor of CIDP. SSEPs were abnormal in 16 of 20 responders (80%) to immunotherapy. CONCLUSION: SSEP recording contributes to the diagnosis of CIDP when nerve conduction studies fail to detect peripheral demyelination.

Seizures Outcome After Stereoelectroencephalography-Guided Thermocoagulations in Malformations of Cortical Development Poorly Accessible to Surgical Resection.

BACKGROUND: Radiofrequency thermocoagulation (RFTC) guided by stereoelectroencephalography (SEEG) has proved to be a safe palliative method to reduce seizure frequency in patients with drug-resistant partial epilepsy. In malformation of cortical development (MCD), increasing the number of implanted electrodes over that needed for mapping of the epileptogenic zone could help to maximize RFTC efficiency. OBJECTIVE: To evaluate the benefit of SEEG-guided RFTC in 14 patients suffering from drug-resistant epilepsy related to MCD located in functional cortical areas or in regions poorly accessible to surgery. METHODS: Ten men and 4 women were treated by RFTC. Thermolesions were produced by applying a 50-V, 120-mA current for 10 to 30 seconds within the epileptogenic zone as identified by the SEEG investigation. RESULTS: An average of 25.8 ± 17.5 thermolesions were made per procedure. The median follow-up after the procedure was 41.7 months. Sixty-four percent of the patients experienced a long-term decrease in seizure frequency of >50%, of whom 6 (43%) presented long-lasting freedom from seizure. When a focal low-voltage fast activity was present at seizure onset on SEEG recordings, 87.5% of patients were responders or seizure free. All of the patients in whom electric stimulation reproduced spontaneous seizures were responders. CONCLUSION: Our results show the good benefit-risk ratio of the SEEG-guided procedure for patients suffering from MCD in whom surgery is risky. This study identifies 2 factors, focal low-voltage, high-frequency activity at seizure onset and lowered epileptogenic threshold in the coagulated area, that could be predictive of a favorable seizure outcome after RFTC.

Periventricular [(11)C]flumazenil binding for predicting postoperative outcome in individual patients with temporal lobe epilepsy and hippocampal sclerosis.

A third of patients with intractable temporal lobe epilepsy and hippocampal sclerosis (HS) are not seizure free (NSF) after surgery. Increased periventricular [(11)C]flumazenil (FMZ) binding, reflecting heterotopic neuron concentration, has been described as one predictor of NSF outcome at the group level. We aimed to replicate this finding in an independent larger cohort and investigated whether NSF outcome can be predicted in individuals. Preoperative [(11)C]FMZ summed radioactivity images were available for 16 patients with HS and 41 controls. Images were analyzed using SPM8, explicitly including the white matter, and correction for global radioactivity via group-specific ANCOVA. Periventricular increases were assessed with a mask and different cutoffs for distinguishing NSF and seizure free (SF) patients. NSF patients had increased [(11)C]FMZ binding around the posterior horn of the ventricles ipsilaterally (z = 2.53) and contralaterally (z = 4.44) to the seizure focus compared with SF patients. Compared with controls, SF patients had fewer periventricular increases (two clusters, total volume 0.87 cm(3), zmax = 3.8) than NSF patients (two ipsilateral and three contralateral clusters, 6.15 cm(3), zmax = 4.8). In individuals and at optimized cutoffs, five (63%) of eight NSF patients and one (13%) of eight SF patients showed periventricular increases compared with controls (accuracy 75%). Only one (2%) of the 41 controls had increases at the same cutoff. The association between periventricular [(11)C]FMZ increases and NSF outcome after temporal lobe resection for HS has been confirmed in an independent cohort on simple summed activity images. [(11)C]FMZ-PET may be useful for individual preoperative counseling with clinically relevant accuracy.

The value of magnetoencephalography for seizure-onset zone localization in magnetic resonance imaging-negative partial epilepsy.

Surgical treatment of epilepsy is a challenge for patients with non-contributive brain magnetic resonance imaging. However, surgery is feasible if the seizure-onset zone is precisely delineated through intracranial electroencephalography recording. We recently described a method, volumetric imaging of epileptic spikes, to delineate the spiking volume of patients with focal epilepsy using magnetoencephalography. We postulated that the extent of the spiking volume delineated with volumetric imaging of epileptic spikes could predict the localizability of the seizure-onset zone by intracranial electroencephalography investigation and outcome of surgical treatment. Twenty-one patients with non-contributive magnetic resonance imaging findings were included. All patients underwent intracerebral electroencephalography investigation through stereotactically implanted depth electrodes (stereo-electroencephalography) and magnetoencephalography with delineation of the spiking volume using volumetric imaging of epileptic spikes. We evaluated the spatial congruence between the spiking volume determined by magnetoencephalography and the localization of the seizure-onset zone determined by stereo-electroencephalography. We also evaluated the outcome of stereo-electroencephalography and surgical treatment according to the extent of the spiking volume (focal, lateralized but non-focal or non-lateralized). For all patients, we found a spatial overlap between the seizure-onset zone and the spiking volume. For patients with a focal spiking volume, the seizure-onset zone defined by stereo-electroencephalography was clearly localized in all cases and most patients (6/7, 86%) had a good surgical outcome. Conversely, stereo-electroencephalography failed to delineate a seizure-onset zone in 57% of patients with a lateralized spiking volume, and in the two patients with bilateral spiking volume. Four of the 12 patients with non-focal spiking volumes were operated upon, none became seizure-free. As a whole, patients having focal magnetoencephalography results with volumetric imaging of epileptic spikes are good surgical candidates and the implantation strategy should incorporate volumetric imaging of epileptic spikes results. On the contrary, patients with non-focal magnetoencephalography results are less likely to have a localized seizure-onset zone and stereo electroencephalography is not advised unless clear localizing information is provided by other presurgical investigation methods.

Mesio-temporal ictal semiology as an indicator for surgical treatment of epilepsies with large multilobar cerebral lesions.

PURPOSE: Mesio-temporal ictal semiology is sometimes observed in patients with large multilobar lesion. In this situation, surgery is often discarded because of the lesion size and/or suspicion of extended or multifocal epileptogenic areas. In this retrospective study we evaluated the surgical outcome of such patients in order to assess whether the electro-clinical presentation of seizures could be a prognostic marker of surgical outcome. METHODS: Among the temporal lobe epilepsy population explored in our department between 2000 and 2011 (240 patients), we identified 7 patients who presented an extensive lesion on brain Magnetic Resonance Imaging (MRI) (multilobar in four, hemispheric in two, and bilateral in one). All patients underwent (18)Fluorodeoxyglucose Positron Emission Tomography, which showed large, hemispheric or multilobar, areas of glucose hypometabolism. Because of the large lesion size, all patients were explored by stereoelectroencephalography (SEEG) before taking a decision regarding surgical indication. RESULTS: SEEG confirmed the temporal origin of the seizures and discarded the possibility of multiple epileptogenic zones. A temporal lobectomy, tailored on the basis of SEEG data, was proposed to the seven patients. The seven patients are classified Engel class I after the surgery (mean follow-up: 37.4±22.1 months). CONCLUSION: Our data thus suggest that, even in the absence of hippocampal MRI abnormality, ictal symptoms compatible with a temporal origin of seizures should be considered as a reliable indicator for surgery eligibility regardless of MRI lesion size. On the basis of our findings, the mesio-temporal semiology of seizures appears as one of the most reliable markers of operability in patients with large MRI lesions. These patients should not be excluded a priori from invasive exploration and surgical treatment, even if a large portion of their lesion is likely to be left in place after surgery.

Stimulation of the human cortex and the experience of pain: Wilder Penfield's observations revisited.

Thanks to the seminal work of Wilder Graves Penfield (1891-1976) at the Montreal Neurological Institute, electrical stimulation is used worldwide to localize the epileptogenic cortex and to map the functionally eloquent areas in the context of epilepsy surgery or lesion resections. In the functional map of elementary and experiential responses he described through >20 years of careful exploration of the human cortex via stimulation of the cortical surface, Penfield did not identify any 'pain cortical area'. We reinvestigated this issue by analysing subjective and videotaped behavioural responses to 4160 cortical stimulations using intracerebral electrodes implanted in all cortical lobes that were carried out over 12 years during the presurgical evaluation of epilepsy in 164 consecutive patients. Pain responses were scarce (1.4%) and concentrated in the medial part of the parietal operculum and neighbouring posterior insula where pain thresholds showed a rostrocaudal decrement. This deep cortical region remained largely inaccessible to the intraoperative stimulation of the cortical surface carried out by Penfield after resection of the parietal operculum. It differs also from primary sensory areas described by Penfield et al. in the sense that, with our stimulation paradigm, pain represented only 10% of responses. Like Penfield et al., we obtained no pain response anywhere else in the cortex, including in regions consistently activated by pain in most functional imaging studies, i.e. the first somatosensory area, the lateral part of the secondary somatosensory area, anterior and mid-cingulate gyri (mid-cingulate cortex), anterior frontal, posterior parietal and supplementary motor areas. The medial parietal operculum and posterior insula are thus the only areas where electrical stimulation is able to trigger activation of the pain cortical network and thus the experience of somatic pain.

Does the insula tell our brain that we are in pain?

Current knowledge on pain-related cerebral networks has relied so far on stimulus-induced brain responses, but not on the analysis of brain activity during spontaneous pain attacks. In this case report, correlation between intracerebral field potentials and online sensations during spontaneously painful epileptic seizures suggests a crucial role of the insula in the development of subjective pain. Attacks originated from a very limited dysplasia located in the posterior third of the right insula and propagated to other areas of the pain matrix, including the parietal operculum and the midcingulate gyrus. Concomitant painful symptoms started on the left hand or the left foot and extended in a few seconds to the whole left side of the body, sparing the head. Continuous during the first seconds of the attack, the painful feeling evolved to throbbing and remained so until it progressively vanished, together with the spike discharge. Stimulation of the insula, but not of other pain matrix regions, induced pain identical to that of seizures. After thermocoagulation of the insular epileptic focus, a short, transient exacerbation of seizures with same painful features but different location was observed before a long-lasting and complete remission of the attacks. Although these preliminary data need to be confirmed, they strongly suggest that if the full pain experience involves the pain matrix network, the posterior insula seems to play a leading role in the triggering of this network and the resulting emergence of subjective pain experience.

Voxel-based analysis of asymmetry index maps increases the specificity of 18F-MPPF PET abnormalities for localizing the epileptogenic zone in temporal lobe epilepsies.

UNLABELLED: (18)F-4-(2'-methoxyphenyl)-1-[2'-(N-2-pyridinyl)-p-fluorobenzamido]-ethyl-piperazine ((18)F-MPPF) PET has proved to be a sensitive technique in the presurgical evaluation of patients with drug-resistant temporal lobe epilepsy (TLE), but a significant proportion of visually detected abnormalities failed to be detected by standard statistical parametric mapping (SPM) analysis. This study aimed at describing a voxel-based method for computing interhemispheric asymmetric index (AI) using statistical software and applying and validating the clinical relevance of this method for analyzing asymmetries of (18)F-MPPF PET images in patients with drug-resistant TLE. METHODS: (18)F-MPPF PET scans of 24 TLE patients who achieved an Engel class I outcome after epilepsy surgery and of 41 controls were analyzed visually, with standard SPM, and by computing voxel-based AIs. Both SPM methods were assessed using 2 different statistical thresholds (P < 0.05, corrected at the cluster level, and P < 0.05, familywise error (FWE) corrected at the voxel level). Sensitivity and specificity of each method were estimated and compared using McNemar tests. RESULTS: The sensitivity of AI analysis to detect decreases of (18)F-MPPF binding potential ipsilateral to the epileptogenic lobe was 92% (P < 0.05, corrected at the cluster level) and 96% (P < 0.05, familywise error corrected at the voxel level), whereas specificity (defined as the congruence between the localization of the voxel associated with the greatest z score and that of the epileptogenic zone) was 88% at both thresholds. AI analysis was significantly more sensitive (P < 0.05) and specific (P < 0.005) than standard SPM analysis, regardless of the applied threshold. AI analysis also proved to be more sensitive than visual analysis. CONCLUSION: AI analysis of (18)F-MPPF PET was more sensitive and specific than previous methods of analysis. This noninvasive imaging procedure was especially informative for the presurgical assessment of patients presenting with clinical histories atypical of mesial TLE or with normal brain MRI results.

Facial pain as first manifestation of anti-Hu paraneoplastic syndrome.

The diagnosis of anti-Hu-associated encephalomyelitis/sensory neuropathy may be particularly difficult when cranial nerve involvement represents the first clinical manifestation of the disease. We report a case of a patient who presented with facial pain as the first manifestation of an anti-Hu paraneoplastic syndrome, which needs a rapid detection and treatment of the underlying tumour. We suggest that paraneoplastic neuropathy should be considered during the management of trigeminal neuropathic pain, especially when brain imagery is normal.

Initial neuro-ophthalmological manifestations in Churg-Strauss syndrome.

Churg-Strauss syndrome (CSS) is a systemic vasculitis with frequent respiratory tract involvement. It can also affect the nervous system, notably the optic tract. The present work reports the case of a 65-year-old man diagnosed as having CSS in the context of several acute onset neurological symptoms including muscle weakness and signs of temporal arteritis, including bilateral anterior ischaemic optic neuropathy (ON). Electroretinograms (ERGs) and visual evoked potentials (VEPs) were performed. Flash ERGs were normal whereas VEPs were highly abnormal, showing a dramatic voltage reduction, thus confirming the ON. The vision outcome was poor. Ophthalmological presentations of CSS have rarely been reported, but no previous case of sudden blindness documented by combined ERG and VEP investigations were found in the literature. The present case strongly suggests that the occurrence of visual loss in the context of systemic inflammation with hypereosinophilia should lead to considering the diagnosis of CSS.

Natural history of adult-onset eIF2B-related disorders: a multi-centric survey of 16 cases.

Mutations in one of the five eukaryotic initiation factor 2B genes (EIF2B1-5) were first described in childhood ataxia with cerebral hypomyelination--vanishing white matter syndrome. The syndrome is characterized by (i) cerebellar and pyramidal signs in children aged 2-5 years; (ii) extensive cavitating leucoencephalopathy; and (iii) episodes of rapid deterioration following stress. Since then a broad clinical spectrum from congenital to adult-onset forms has been reported, leading to the concept of eIF2B-related disorders. Our aim was to describe clinical and brain magnetic resonance imaging characteristics, genetic findings and natural history of patients with adult-onset eIF2B-related disorders (after age 16). The inclusion criteria were based on the presence of eIF2B mutations and a disease onset after the age of 16 years. One patient with an asymptomatic diagnosis (age 16 years) was also included. Clinical and magnetic resonance findings were retrospectively recorded in all patients. All patients were examined to assess clinical evolution, using functional, pyramidal, cerebellar and cognitive scales. This multi-centric study included 16 patients from 14 families. A sex ratio imbalance was noted (male/female = 3/13). The mean age of onset was 31.1 years (range 16-62). Initial symptoms were neurologic (n = 11), psychiatric (n = 2) and ovarian failure (n = 2). Onset of the symptoms was linked to a precipitating factor in 13% of cases that included minor head trauma and delivery. During follow-up (mean: 11.2 years, range 2-22 years) 12.5% of the patients died. Of the 14 survivors, 62% showed a decline in their cognitive functions, and 79% were severely handicapped or bedridden. One case remained asymptomatic. Stress worsened clinical symptoms in 38% of the patients. Magnetic resonance imaging findings consist of constant cerebral atrophy, extensive cystic leucoencephalopathy (81%), corpus callosum (69%) and cerebellar (38%) T2-weighted hyperintensities. All families except one showed mutations in the EIF2B5 gene. The recurrent p.Arg113His-eIF2Bepsilon mutation was found in 79% of the 14 eIF2B-mutated families, mainly at a homozygous state. The family with a mutation in EIF2B2 had the relatively prevalent p.Glu213Gly mutation. eIF2B-related disorder is probably underestimated as an adult-onset inherited leucoencephalopathy. In this late-onset form, presentation ranges from neurologic symptoms to psychiatric manifestations or primary ovarian failure. Cerebral atrophy is constant, whereas the typical vanishing of the white matter can be absent. Functional and/or cognitive prognosis remains severe. Molecular diagnosis is facilitated for these forms by the screening of the two recurrent p.Arg113His-eIF2Bepsilon and p.Glu213Gly-eIF2Bbeta mutations, positive in 86% of cases.

PET imaging of brain 5-HT1A receptors in the preoperative evaluation of temporal lobe epilepsy.

[(18)F]MPPF PET has previously been used to identify the epileptic lobe in temporal lobe epilepsy (TLE) patients at the group level. This study aims to validate the visual analysis of [(18)F]MPPF PET in the assessment of individual TLE patients for their suitability to undergo temporal lobe resection. Forty-two patients suffering from TLE and 18 control subjects matched for age and gender were prospectively enrolled for [(18)F]MPPF PET. Four subtypes were defined according to the presurgical evaluation: mesio-TLE (MTLE, 32 patients), temporal neocortical epilepsy (NC, five patients), temporo-perisylvian epilepsy (T+, three patients) and temporal epilepsy without further information (t, two patients). Parametric binding potential (BP(ND)) images were obtained using a simplified reference tissue model. Three examiners, who were blinded to other data, visually interpreted each scan and delineated areas of decreased [(18)F]MPPF BP(ND). Statistical parametric mapping (SPM) analysis of MPPF BP(ND) images was also performed. Visual analysis showed a low rate of disagreement between the three examiners (7%). PET scans were considered normal in four patients (9.5%). In the remaining 38 patients (90.5%), areas of focal BP(ND) decrease were identified. A specific pattern was encountered in the MTLE subgroup, consisting of a BP(ND) decrease involving hippocampus, amygdala and temporal pole altogether. Combining the results from the presurgical investigations and the surgical outcome, we estimated that the area of BP(ND) decrease coincided with the epileptogenic zone in 40% of patients in the MTLE subgroup and 33% in the other TLE subtypes. This relatively low precision was due to 47% of patients who showed BP(ND) decreases in the insula ipsilateral to the epileptogenic lobe. The SPM analysis had much lower sensitivity (67%) to detect BP(ND) decreases in the epileptogenic temporal lobe, but revealed areas of increased BP(ND) outside the epileptogenic zone and bitemporal BP(ND) decreases of undetermined clinical significance, which were undetectable by visual analysis, in 29% of patients. In conclusion, visual analysis of [(18)F]MPPF BP(ND) images helps in the correct identification of the epileptogenic temporal lobe in all patients showing BP(ND) decreases, with a false negative rate inferior to 10% and no false positives in control subjects. All TLE patients with [(18)F]MPPF BP(ND) decreases involving hippocampus, amygdala and temporal pole together, with or without extension to the ipsilateral insula, were good candidates for anterior temporal lobectomy. All these patients became seizure free after surgery, even when the clinical presentation was not that of a typical MTLE, or when MRI failed to detect hippocampal atrophy.

Analysis of clinical patterns and underlying epileptogenic zones of hypermotor seizures.

BACKGROUND: Hypermotor seizures (HMS) are characterized by complex movements involving the proximal segment of the limbs and trunk. Although they are primarily reported in mesial frontal or orbitofrontal epilepsies, they have also been described in patients with temporal or insular epilepsies, questioning the localizing value of HMS in patients contemplating epilepsy surgery. Furthermore, HMS can include different forms of HM behaviors. Whether these clinical variations may be systematized and may reflect different locations of the epileptogenic zone (EZ) has not been evaluated yet. METHODS: We have retrospectively analyzed ictal signs and intracerebral EEG data in 11 patients presenting with HMS who became seizure free following epilepsy surgery with a minimum follow-up of 24 months. Clinical phenomena were reviewed blinded to seizure onset zone. RESULTS: Two types of HMS could be distinguished in this population: HMS1, observed in six patients, mainly consisted of marked agitation that either included body rocking, kicking, or boxing, associated with a facial expression of fear. HMS2, observed in the five other patients, mainly consisted of mild agitation that included either horizontal movements or rotation of trunk and pelvis while lying on the bed, usually associated with tonic/dystonic posturing. SEEG findings showed that the EZ associated with HMS1 was mainly centered on the ventromesial frontal cortex. Conversely, HMS2 was primarily associated with an EZ localized within the mesial premotor cortex. CONCLUSIONS: Although these findings remain to be confirmed by larger studies, they may help optimize the placement of intracerebral electrodes in patients contemplating epilepsy surgery.

Long-term outcome of gamma-knife surgery in temporal lobe epilepsy.

PURPOSE: Indication of gamma-knife surgery (GKS) in temporal lobe epilepsy (TLE) remains a matter of debate. Either positive or negative results have been reported in studies with a maximum follow-up of 24 months. No long-term data have been published yet. METHODS: We collected data from 15 TLE patients who underwent GKS and whose follow-up was longer than 24 months. Localisation and extension of the epileptogenic zone (EZ) were assessed by SEEG in eight patients. Ten patients were presenting with mesial TLE (mTLE) while in the other five SEEG showed that the EZ was extending beyond mesio-temporal structures. GKS procedure was targeted to the EZ at a dose of 21.1+/-2.6Gy at the margin. RESULTS: The mean duration of the follow-up was 60+/-22.3 months. At last follow-up, seven patients (46.7%) were free of disabling seizure. The last seizure following GKS occurred on average after a delay of 19.75+/-20.62 months. No patient suffered recurrent seizures after a long period free of disabling seizures. No significant prognostic predictor could be individualized in this population. However, 6 of the 10 patients with mTLE (60%) were seizure free whereas only 1 of the 5 (20%) whose EZ was more extended exhibited the same seizure outcome. CONCLUSION: When a positive outcome is achieved, the risk of seizure recurrence remains low at long term. In patients with typical mTLE, long-term GKS results may be closed to those observed after conventional surgery. Conversely, this procedure should not be proposed to patients in whom SEEG results suggest that the EZ is not restricted to mesial temporal structures.