Towards a better identification of ictal semiology patterns in insular epilepsies: A stereo-EEG study.

OBJECTIVE: To describe pure insular ictal semiology and patterns of extra-insular spread demonstrated by stereoelectroencephalography (SEEG) according to a classification based on the insular cytoarchitecture. METHODS: We investigated the ictal semiology in 17 patients undergoing SEEG for insular epilepsy. The insular cortex was divided into three regions roughly overlapping with the agranular, dysgranular and granular regions. Ictal semiology was described accordingly: anterior insula (AI, short anterior and middle gyri), middle insula (MI, short posterior and long anterior gyri) and posterior insula (PI, long posterior gyrus). RESULTS: Awareness impairment occurred secondarily to extra-insular ictal spread. Subjective manifestations were constant. AI seizures (n = 3) presented with autonomic (increased heart rate [HR], respiratory changes), oropharyngeal (mainly throat sensations), emotional (fear, anguish) semiology and the "hand-to-throat" sign followed by frontal-like semiology. MI seizures (n = 8) presented with mainly non-painful paresthesia, some autonomic (respiratory, increased HR), oropharyngeal or thermic symptoms and early motor features with spread to the opercular cortex. PI seizures (n = 6) were characterized by somatosensory semiology, mainly paresthesia potentially painful, and cephalic sensations. CONCLUSIONS: Cytoarchitectonic-based classification and the corresponding ictal features support the antero-posterior grading of insular seizures and highlight specific ictal symptoms. SIGNIFICANCE: This refinement of insular semiology can help optimize the planning of SEEG for presumed insular epilepsy.

Spinal cord stimulation and return to work of patients with failed back surgery syndrome.

OBJECTIVES: Chronic pain has a substantial negative impact on work-related outcomes, which underlines the importance of interventions to reduce the burden. Spinal cord stimulation (SCS) efficiently relieves pain in specific chronic pain syndromes and is recommended for treating failed back surgery syndrome (FBSS) or post-surgical chronic back pain that is refractory to other treatments. To examine the impact of SCS in patients with FBSS on the return to work (RTW), we determined the RTW rate and the factors positively associated with the RTW. MATERIALS AND METHODS: Among 106 patients with FBSS who benefitted from SCS at a single institution in France between September 1999 and March 2010, we retrospectively included 59 who had stopped work at the time of SCS because of disability or sick leave and evaluated the RTW (rate and predictors, estimating odds ratios [ORs] and 95% confidence intervals [CIs]). RESULTS: The mean (SD) post-surgery follow-up for the 59 patients (34 men; mean [SD] age 46.9 [7.4] years) was 7.5 (3.6) years (range 5-15). The RTW rate was 30.5%, with a median [IQR] recovery time of 5.5 months [3-8.5]. RTW was improved with functional improvement evolution (OR 1.1, 95% CI [1.01-1.1], p = 0.02) and was reduced with unemployment > 3 years (OR 0.1, 95% CI [0.01-0.7], p = 0.02). CONCLUSIONS: Our protocol for SCS for patients with FBSS, including a strict selection of patients and a multidisciplinary approach, led to good results, especially for the RTW. RTW should be a therapeutic goal, directly affecting indirect costs related to FBSS.

Benefits and Risks of Epilepsy Surgery in Patients With Focal Cortical Dysplasia Type 2 in the Central Region.

BACKGROUND AND OBJECTIVES: Focal cortical dysplasia type 2 (FCD2) in the central region can cause drug-resistant epilepsy for which surgery remains challenging because of subsequent functional deficits. Advances in imaging and surgical techniques have progressively improved outcome. We aimed to assess the benefits on epilepsy and the functional risks after FCD2 resections in these highly eloquent areas. METHODS: We retrospectively studied all consecutive patients with histologically confirmed FCD2 located in the central region operated on between 2000 and 2019 at a single center. We analyzed electroclinical and imaging features (including fMRI), seizure outcome, and early and late postoperative neurologic status correlating to anatomo-functional areas (primary motor cortex [PMC], paracentral lobule [PCL], supplementary motor area [SMA], precentral gyrus [PrCG], postcentral gyrus [PoCG], central operculum [COp]). RESULTS: Sixty patients (35 female, age 7-65 years) were included in the study. Epilepsy was characterized by early onset, high seizure frequency with clusters (30-90/d), drop attacks, and status epilepticus. Ictal semiology included sensory-motor auras, motor and postural manifestations, and postictal motor deficits. EEG and stereo-EEG patterns were like those typically recorded in FCD2. MRI was positive in 63% and 18F-fluorodeoxyglucose-PET was positive in 86% of the patients. fMRI demonstrated activations close to the FCD2 (59%) or minor reorganization (41%) but none within the lesion. Seizure-free outcome (2- to 20-year follow-up) was obtained in 53 patients (88%), including 37 achieving Engel class IA (62%), correlating with complete FCD2 removal. Early transitory postoperative deficits occurred in 52 patients (87%), which were severe in 19, mostly after PMC, PCL, and SMA resections, while PrCG, PoCG, and COp resections were associated with minor/moderate deficits. Total recovery was observed in 21 of 52 patients (40%), while a permanent deficit (>2 years) persisted in 31 (minor 19, moderate 9, major 3). The best outcome (seizure freedom without deficit [48%] or with minor deficit (28%]) was significantly more frequent in children (p = 0.025). Antiseizure medications were discontinued in 28 patients (47%). Quality of life correlated with seizure-free outcome and absence of postoperative deficit; 43 patients (72%) reported a schooling or socio-professional improvement. DISCUSSION: Excellent seizure outcome and low rates of major permanent disability can be achieved after central FCD2 resections despite functional risks. CLASSIFICATION OF EVIDENCE: Due to its retrospective nature, this study provides Class IV evidence that good seizure outcomes with minor additional deficits can be achieved after epilepsy surgery in the central region.

The Effectiveness of Vagus Nerve Stimulation in Drug-Resistant Epilepsy Correlates with Vagus Nerve Stimulation-Induced Electroencephalography Desynchronization.

Introduction: VNS is an adjunctive neuromodulation therapy for patients with drug-refractory epilepsy. The antiseizure effect of VNS is thought to be related to a diffuse modulation of functional connectivity but remains to be confirmed. Aim: To investigate electroencephalographic (EEG) metrics of functional connectivity in patients with drug-refractory epilepsy treated by vagus nerve stimulation (VNS), between VNS-stimulated "ON" and nonstimulated "OFF" periods and between responder (R) and nonresponder (NR) patients. Methods: Scalp-EEG was performed for 35 patients treated by VNS, using 21 channels and 2 additional electrodes on the neck to detect the VNS stimulation. Patients were defined as VNS responders if a reduction of seizure frequency of ∼50% was documented. We analyzed the synchronization in EEG time series during "ON" and "OFF" periods of stimulation, using average phase lag index (PLI) in signal space and phase-locking value (PLV) between 10 sources. Based on graph theory, we computed brain network models and analyzed minimum spanning tree (MST) for responder and nonresponder patients. Results: Among 35 patients treated by VNS for a median time of 7 years (range 4 months to 22 years), 20 were R and 15 were NR. For responder patients, PLI during ON periods was significantly lower than that during OFF periods in delta (p = 0.009), theta (p = 0.02), and beta (p = 0.04) frequency bands. For nonresponder patients, there were no significant differences between ON and OFF periods. Moreover, variations of seizure frequency with VNS correlated with the PLI OFF/ON ratio in delta (p = 0.02), theta (p = 0.04), and beta (p = 0.03) frequency bands. Our results were confirmed using PLV in theta band (p < 0.05). No significant differences in MST were observed between R and NR patients. Conclusion: The correlation between VNS-induced interictal EEG time-series desynchronization and decrease in seizure frequency suggested that VNS therapeutic impact might be related to changes in interictal functional connectivity. Impact statement Electroencephalography (EEG) desynchronization has been proposed to be a mechanism for antiepileptic effect of vagus nerve stimulation (VNS). We measured interictal EEG time-series synchronization during stimulated (ON) and nonstimulated (OFF) periods in epileptic patients treated by VNS. Phase lag index differences between ON and OFF periods were measured in delta, theta, and beta bands only in responder patients. To our knowledge, our study is the first to statistically correlate interictal cortical desynchronization during ON periods with reduction in seizure frequency. Our result supports the hypothesis that the antiseizure effect of VNS is mediated by cortical desynchronization.

Stereotactic thermocoagulation for insular epilepsy: Lessons from successes and failures.

OBJECTIVE: To assess factors associated with favorable outcome in refractory insular epilepsy treated by volume-based stereotactic radiofrequency thermocoagulation (RFTC). METHODS: We performed volume-based RFTC in 19 patients (11 males, 7-44 years old). The volume for thermocoagulation was identified by multimodal data including electroencephalography (EEG)-video, magnetic resonance imaging (MRI), and fluorodeoxyglucose-positron emission tomography (PET) in all patients, and epileptogenic zone (EZ) was assessed by stereo-electroencephalography (SEEG) in 16. MRI showed insular lesions in four patients (benign tumors, n = 2; focal cortical dysplasia [FCD], n = 1; polymicrogyria, n = 1). MRI was negative in 15 cases; however, PET was positive in 18, and FCD pattern was detected by SEEG in nine cases. The dominant hemisphere was involved in 12 cases. RFTC was performed as a separate procedure after SEEG, or as a single MRI-guided procedure. The insular volume to be coagulated was determined by a tridimensional identification of the epileptogenic cortex using MRI, PET, and SEEG, and was destroyed with coalescent thermal lesions. RESULTS: Seizure-free outcome was achieved in 10 patients (53%), including Engel class IA in three (follow-up = 1-12 years, mean = 5.4). The responder rate (including Engel classes I-III) was 89%. Transient postoperative deficits (mild hemiparesia, dysarthria, hypoesthesia, dysgeusia) were observed in eight patients (42%), with rapid and total recovery in all but one with persistent mild dysarthria. Neurological deficits were related to higher number of RFTC procedures (P = .036) and greater volume of RFTC (P = .028). Neuropsychological status was unchanged or improved in all; however, psychiatric status transitorily worsened in three patients. Factors contributing to seizure-free outcome were the detection of FCD pattern (P = .009), localized EZ (P = .038), low RFTC volume (P = .002), low number of RFTC procedures (P = .001), and low RFTC volume/number ratio (P = .012). Optimal volume of RFTC around 2 cm3 offered the best compromise between efficacy and safety. SIGNIFICANCE: RFTC may be curative in insular epilepsy after accurate localization of EZ with SEEG. Best outcome was associated with low volume of thermolesions.

Real-time Brain Tumor imaging with endogenous fluorophores: a diagnosis proof-of-concept study on fresh human samples.

The primary line of therapy for high-grade brain tumor is surgical resection, however, identifying tumor margins in vivo remains a major challenge. Despite the progress in computer-assisted imaging techniques, biopsy analysis remains the standard diagnostic tool when it comes to delineating tumor margins. Our group aims to answer this challenge by exploiting optical imaging of endogenous fluorescence in order to provide a reliable and reproducible diagnosis close to neuropathology. In this study, we first establish the ability of two-photon microscopy (TPM) to discriminate normal brain tissue from glioblastomas and brain metastasis using the endogenous fluorescence response of fresh human brain sample. Two-photon fluorescence images were compared to gold standard neuropathology. "Blind" diagnosis realized by a neuropathologist on a group of TPM images show a good sensitivity, 100%, and specificity, 50% to discriminate non tumoral brain tissue versus glioblastoma or brain metastasis. Quantitative analysis on spectral and fluorescence lifetime measurements resulted in building a scoring system to discriminate brain tissue samples.

History of psychosurgery at Sainte-Anne Hospital, Paris, France, through translational interactions between psychiatrists and neurosurgeons.

Sainte-Anne Hospital is the largest psychiatric hospital in Paris. Its long and fascinating history began in the 18th century. In 1952, it was at Sainte-Anne Hospital that Jean Delay and Pierre Deniker used the first neuroleptic, chlorpromazine, to cure psychiatric patients, putting an end to the expansion of psychosurgery. The Department of Neuro-psychosurgery was created in 1941. The works of successive heads of the Neurosurgery Department at Sainte-Anne Hospital summarized the history of psychosurgery in France. Pierre Puech defined psychosurgery as the necessary cooperation between neurosurgeons and psychiatrists to treat the conditions causing psychiatric symptoms, from brain tumors to mental health disorders. He reported the results of his series of 369 cases and underlined the necessity for proper follow-up and postoperative re-education, illustrating the relative caution of French neurosurgeons concerning psychosurgery. Marcel David and his assistants tried to follow their patients closely postoperatively; this resulted in numerous publications with significant follow-up and conclusions. As early as 1955, David reported intellectual degradation 2 years after prefrontal leucotomies. Jean Talairach, a psychiatrist who eventually trained as a neurosurgeon, was the first to describe anterior capsulotomy in 1949. He operated in several hospitals outside of Paris, including the Sarthe Psychiatric Hospital and the Public Institution of Mental Health in the Lille region. He developed stereotactic surgery, notably stereo-electroencephalography, for epilepsy surgery but also to treat psychiatric patients using stereotactic lesioning with radiofrequency ablation or radioactive seeds of yttrium-90. The evolution of functional neurosurgery has been marked by the development of deep brain stimulation, in particular for obsessive-compulsive disorder, replacing the former lesional stereotactic procedures. The history of Sainte-Anne Hospital's Neurosurgery Department sheds light on the initiation-yet fast reconsideration-of psychosurgery in France. This relatively more prudent attitude toward the practice of psychosurgery compared with other countries was probably due to the historically strong collaboration between psychiatrists and neurosurgeons in France.

Evoked potentials in final epoch of self-initiated hand movement: A study in patients with depth electrodes.

Comparison between the intended and performed motor action can be expected to occur in the final epoch of a voluntary movement. In search for electrophysiological correlates of this mental process the purpose of the current study was to identify intracerebral sites activated in final epoch of self-paced voluntary movement. Intracerebral EEG was recorded from 235 brain regions of 42 epileptic patients who performed self-paced voluntary movement task. Evoked potentials starting at 0 to 243ms after the peak of averaged, rectified electromyogram were identified in 21 regions of 13 subjects. The mean amplitude value of these late movement potentials (LMP) was 56.4±27.5µV. LMPs were observed in remote regions of mesiotemporal structures, cingulate, frontal, temporal, parietal, and occipital cortices. Closely before the LMP onset, a significant increase of phase synchronization was observed in all EEG record pairs in 9 of 10 examined subjects; p<0.001, Mann-Whitney U test. In conclusion, mesiotemporal structures, cingulate, frontal, temporal, parietal, and occipital cortices seem to represent integral functionally linked parts of network activated in final epoch of self-paced voluntary movement. Activation of this large-scale neuronal network was suggested to reflect a comparison process between the intended and actually performed motor action. Our results contribute to better understanding of neural mechanisms underlying goal-directed behavior crucial for creation of agentive experience.

Multimodal optical analysis discriminates freshly extracted human sample of gliomas, metastases and meningiomas from their appropriate controls.

Delineating tumor margins as accurately as possible is of primordial importance in surgical oncology: extent of resection is associated with survival but respect of healthy surrounding tissue is necessary for preserved quality of life. The real-time analysis of the endogeneous fluorescence signal of brain tissues is a promising tool for defining margins of brain tumors. The present study aims to demonstrate the feasibility of multimodal optical analysis to discriminate fresh samples of gliomas, metastases and meningiomas from their appropriate controls. Tumor samples were studied on an optical fibered endoscope using spectral and fluorescence lifetime analysis and then on a multimodal set-up for acquiring spectral, one and two-photon fluorescence images, second harmonic generation signals and two-photon fluorescence lifetime datasets. The obtained data allowed us to differentiate healthy samples from tumor samples. These results confirmed the possible clinical relevance of this real-time multimodal optical analysis. This technique can be easily applied to neurosurgical procedures for a better delineation of surgical margins.

18F-FDG-PET patterns of surgical success and failure in mesial temporal lobe epilepsy.

OBJECTIVE: To search for [18F]-fluorodeoxyglucose (FDG)-PET patterns predictive of long-term prognosis in surgery for drug-resistant mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS). METHODS: We analyzed metabolic data with [18F]-FDG-PET in 97 patients with MTLE (53 female participants; age range 15-56 years) with unilateral HS (50 left) and compared the metabolic patterns, electroclinical features, and structural atrophy on MRI in patients with the best outcome after anteromesial temporal resection (Engel class IA, completely seizure-free) to those with a non-IA outcome, including suboptimal outcome and failure. Imaging processing was performed with statistical parametric mapping (SPM5). RESULTS: With a mean follow-up of >6 years (range 2-14 years), 85% of patients achieved a class I outcome, including 45% in class IA. Class IA outcome was associated with a focal anteromesial temporal hypometabolism, whereas non-IA outcome correlated with extratemporal metabolic changes that differed according to the lateralization: ipsilateral mesial frontal and perisylvian hypometabolism in right HS and contralateral fronto-insular hypometabolism and posterior white matter hypermetabolism in left HS. Suboptimal outcome presented a metabolic pattern similar to the best outcome but with a larger involvement of extratemporal areas, including the contralateral side in left HS. Failure was characterized by a mild temporal involvement sparing the hippocampus and relatively high extratemporal hypometabolism on both sides. These findings were concordant with electroclinical features reflecting the organization of the epileptogenic zone but were independent of the structural abnormalities detected on MRI. CONCLUSIONS: [18F]-FDG-PET patterns help refine the prognostic factors in MTLE and should be implemented in predictive models for epilepsy surgery.

Multimodal optical analysis of meningioma and comparison with histopathology.

Meningioma is the most frequent primary central nervous system tumor. The risk of recurrence and the prognosis are correlated with the extent of the resection that ideally encompasses the infiltrated dura mater and, if required, the infiltrated bone. No device can deliver real-time intraoperative histopathological information on the tumor environment to help the neurosurgeon to achieve a gross total removal. This study assessed the abilities of nonlinear microscopy to provide relevant and real-time data to help resection of meningiomas. Nine human meningioma samples (four World Health Organization Grade I, five Grade II) were analyzed using different optical modalities: spectral analysis and imaging, lifetime measurements, fluorescence lifetime imaging microscopy, fluorescence emitted under one- and two-photon excitation and the second-harmonic generation signal imaging using a multimodal setup. Nonlinear microscopy produced images close to histopathology as a gold standard. The second-harmonic generation signal delineated the collagen background and two-photon fluorescence underlined cell cytoplasm. The matching between fluorescence images and Hematoxylin and Eosin staining was possible in all cases. Grade I meningioma emitted less autofluorescence than Grade II meningioma and Grade II meningioma exhibited a distinct lifetime value. Autofluorescence was correlated with the proliferation rates and seemed to explain the observed differences between Grade I and II meningiomas. This preliminary multimodal study focused on human meningioma samples confirms the potential of tissue autofluorescence analysis and nonlinear microscopy in helping intraoperatively neurosurgeons to reach the actual boundaries of the tumor infiltration. Correspondence between H&E staining (top pictures) and the two-photon fluorescence imaging (bottom pictures).

Vagus Nerve Stimulation Removal or Replacement Involving the Lead and the Electrode: Surgical Technique, Institutional Experience and Outcome.

OBJECTIVE: To analyze the outcome of epileptic patients who had redo surgery involving the vagus nerve stimulation's lead. METHODS: We reviewed the clinical and surgical records of all patients who had a complete vagus nerve stimulation (VNS) removal or replacement or any redo surgical procedure involving the system lead at Sainte-Anne Hospital in Paris, France. RESULTS: Between the years 1999 and 2016, 41 redo surgical procedures involving the lead or electrode were achieved, of which 23 were complete VNS explantations, 12 were complete system replacements, 5 were lead changes only, and 1 was isolated lead removal. 41% of the surgical procedures were achieved in female patients. This population has a median age at VNS implantation of 33.6 years (interquartile range [IQR], [21.4-38.6]. Median time between the VNS implantation and the redo surgery involving the lead was 4.9 years (IQR, 2.9-8). The reason for VNS removal was mainly a lack of clinical effectiveness. No preoperative or postoperative complications occurred after complete VNS system removal or lead replacement. The effectiveness of the VNS therapy remained unchanged after lead replacement. No vagus nerve injury was reported, nor did symptoms suggest that it was disabled. CONCLUSIONS: Complete removal or replacement of the VNS system including the lead and the electrode is feasible and safe. These procedures should be offered to patients who would no longer benefit from the VNS or when only a lead change is needed.

Combining intraoperative carmustine wafers and Stupp regimen in multimodal first-line treatment of primary glioblastomas.

BACKGROUND: The study investigated if intraoperative use of carmustine wafers, particularly in combination with Stupp regimen, is a viable and safe first-line treatment option of glioblastomas. METHODS: Eighty-three consecutive adult patients (50 men; mean age 60 years) with newly diagnosed supratentorial primary glioblastomas that underwent surgical resection with intraoperative carmustine wafers implantation (n = 7.1 ± 1.7) were retrospectively studied. RESULTS: The median overall survival (OS) was 15.8 months with 56 patients dying over the course of the study. There was no significant association between the number of implanted carmustine wafers and complication rates (four surgical site infections, one death). The OS was significantly longer in Stupp regimen patients (19.5 months) as compared with patients with other postoperative treatments (13 months; p = 0.002). In addition patients with eight or more implanted carmustine wafers survived longer (24.5 months) than patients with seven or less implanted wafers (13 months; p = 0.021). Finally, regardless of the number of carmustine wafers, median OS was significantly longer in patients with a subtotal or total resection (21.5 months) than in patients with a partial resection (13 months; p = 0.011). CONCLUSIONS: The intraoperative use of carmustine wafers in combination with Stupp regimen is a viable first-line treatment option of glioblastomas. The prognostic value of this treatment association should be evaluated in a multicenter trial, ideally in a randomized and placebo-controlled one.

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.

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. METHODS: Among 62 consecutive TTFCD patients (38 male, 24 female; 7-52 years old; 22 children) operated for intractable epilepsy, 25 (40%) presented negative MRI findings. We compared the history of epilepsy; the type, frequency, and distribution of seizures; neurologic examination cognitive and psychiatric impairment; interictal-ictal electroencephalography (EEG) and stereo-EEG (SEEG) data, fluorodeoxyglucose positron emission tomography (FDG-PET) data, neuropathologic findings; and surgical outcome in the MRI-negative and the MRI-positive groups. KEY FINDINGS: Severe partial epilepsy beginning in childhood, high seizure frequency including status epilepticus, stereotyped seizures suggestive of precise brain localization, extratemporal location and functional area involvement were characteristic and similarly found in both groups. On EEG, pseudorhythmic activity was found in about 40% of patients in each group. SEEG recordings demonstrated the typical pattern characterizing TTFCD in both groups. FDG-PET had a localization value in 84% of the MRI-negative cases and helped to delineate the dysplastic cortex in 65% of the MRI-positive cases. The combination of imaging and neurophysiologic data allowed us to perform safe and restricted resections, limited to a single gyrus in more than half of all cases. In addition, we were able to avoid invasive monitoring in most MRI-positive cases and even in some selected MRI-negative cases. The proportion of patients with a favorable surgical outcome was comparable in both groups (88% in MRI-negative and 94% in MRI-positive cases). The main difference between the groups was a significantly higher frequency of sleep-related epilepsy in the MRI-negative group (p = 0.028). This phenotypic characteristic provides a new argument for TTFCD in MRI-negative extratemporal epilepsy. SIGNIFICANCE: These results lead us to consider that children or adult patients in whom electroclinical data suggest TTFCD, are highly suitable for surgery, especially for cryptogenic sleep-related epilepsy.

Intracerebral recordings of the Bereitschaftspotential demonstrate the heterogeneity of its components.

Though consisting of early and late components, the evoked potential preceding a voluntary movement (Bereitschaftspotential - BP) is often considered as a unitary phenomenon. By analyzing intracerebrally recorded BP we attempted to demonstrate that the components are electrophysiological correlates of separate operations. The BPs recorded in 42 epilepsy surgery candidates (28 men, 14 women; aged from 18 to 49 years) during self-paced clenching movements of the hand opposite to the explored hemisphere were investigated in the study. Microdeep intracerebral 5 to 15-contact electrodes were used. The averaged curves were calculated from approximately 30 trials in each case. All the records were taken with a binaural reference. The total number of explored brain regions was 235; the event-related premovement potentials were observed in 121 of them. Three types of premovement responses were observed: (i) the BP with both components; (ii) the BP with the early component only; and (iii) the BP with the late component only. The generators of the early one-component BP were demonstrated in two frontal cortical areas (precentral and middle frontal gyri) and in the parietal area known to be involved in action planning and decision making (precuneus). Some structures generating the early one-component BP were activated during movement; the others were without motor responsiveness. The results suggest a separate elaboration of functional task items in some and their integration in other brain structures, and the existence of volitional mechanisms of different hierarchical character.

Lability of GABAA receptor function in human partial epilepsy: possible relationship to hypometabolism.

The function of the gamma-aminobutyric acid type A receptor (GABA(A)R) is maintained by endogenous phosphorylation. We have shown that the corresponding kinase is the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), using the locally produced glycolytic ATP. In addition, using cerebral tissue obtained during curative surgery for epilepsy, we showed that both the endogenous phosphorylation and the GABA(A)R function are significantly reduced in the "epileptogenic" cerebral cortex when compared to "control" tissue. This dysfunction likely contributes to seizure generation and/or transition from the interictal to the ictal state. Glucose utilization is decreased in the epileptogenic cortex of patients with partial epilepsy in the interictal state, but the relationship to the disorder remains unclear. We propose that this hypometabolism is related to the deficiency in the endogenous phosphorylation of GABA(A)R and the resulting greater lability of GABAergic inhibition. Several lines of evidences indeed suggest that GABAergic inhibition is costly in terms of metabolic consumption. The deficiency of this glycolysis-dependent mechanism may thus link epileptogenicity to glucose hypometabolism. The antiepileptic effect of ketogenic diets may be mediated by the subsequent rise in the NADH/NAD(+) index, which favors GABA(A)R endogenous phosphorylation and should contribute to restoration of GABAergic inhibition in the epileptogenic zone.

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. METHODS: We analyzed the distribution of the EZ according to Stereo-EEG (SEEG) with intralesional recordings in four patients evaluated for intractable partial epilepsy associated with focal unilateral PMG, involving the posterior temporal region in two, the perisylvian area in one and the temporoparietal junction in the other. All had ictal scalp EEG, high-resolution structural and functional MRI, fluorodeoxyglucose positron emission tomography (FDG-PET), and SEEG. For each patient, several depth electrodes were implanted both within the PMG and in extralesional areas. RESULTS: In three patients, the PMG displayed high-frequency spiking activity. However, interictal and ictal recordings demonstrated a large epileptogenic network, which was more widespread than the PMG, including the mesial temporal structures in two. In another patient, interictal spiking and seizure onset site were located within the hippocampus and outside of the PMG, although it was rapidly involved during seizure spread. Overall, EZ was considered to be larger than the PMG in all patients although hypometabolic areas detected by PET were concordant with EZ. Three patients underwent extensive surgery including the PMG and are seizure free with a follow-up >2 years. DISCUSSION: Although intralesional recordings demonstrated intrinsic epileptogenicity in PMG, our data provide evidence that unilateral focal PMG belongs to a large epileptogenic network extending beyond the MRI lesion. SEEG may be helpful for planning surgery with favorable outcome, providing large resections are feasible, even in apparently focal PMG.

Dysfunction of GABAA receptor glycolysis-dependent modulation in human partial epilepsy.

A reduction in GABAergic neurotransmission has been put forward as a pathophysiological mechanism for human epilepsy. However, in slices of human epileptogenic neocortex, GABAergic inhibition can be clearly demonstrated. In this article we present data showing an increase in the functional lability of GABAergic inhibition in epileptogenic tissue compared with nonepileptogenic human tissue. We have previously shown that the glycolytic enzyme GAPDH is the kinase involved in the glycolysis-dependent endogenous phosphorylation of the alpha1-subunit of GABA(A) receptor, a mechanism necessary for maintaining GABA(A) function. In human epileptogenic cortex obtained during curative surgery of patients with partial seizures, we demonstrate an intrinsic deficiency of GABA(A) receptor endogenous phosphorylation resulting in an increased lability of GABAergic currents in neurons isolated from this tissue when compared with neurons from nonepileptogenic human tissue. This feature was not related to a reduction in the number of GABA(A) receptor alpha1-subunits in the epileptogenic tissue as measured by [(3)H]flunitrazepam photoaffinity labeling. Maintaining the receptor in a phosphorylated state either by favoring the endogenous phosphorylation or by inhibiting a membrane-associated phosphatase is needed to sustain GABA(A) receptor responses in epileptogenic cortex. The increased functional lability induced by the deficiency in phosphorylation can account for transient GABAergic disinhibition favoring seizure initiation and propagation. These findings imply new therapeutic approaches and suggest a functional link to the regional cerebral glucose hypometabolism observed in patients with partial epilepsy, because the dysfunctional GABAergic mechanism depends on the locally produced glycolytic ATP.

Laser-assisted endoscopic third ventriculostomy for obstructive hydrocephalus: technique and results in a series of 40 consecutive cases.

BACKGROUND AND OBJECTIVES: To report a case series of endoscopic third ventriculostomy (ETV) using laser in 40 consecutive patients with obstructive hydrocephalus. STUDY DESIGN/MATERIALS AND METHODS: Under stereotactic and endoscopic guidance, multiple perforations in the ventricular floor using a 1.32 microm neodymium-yttrium/aluminum/garnet (Nd-YAG) or a 0.805 microm diode laser unit and removal of intervening coagulated tissue ensued with a 4-6 mm opening between third ventricle and basilar cisterns. RESULTS: The procedure could be completed in all cases. A transient complication occurred in five cases. In 39 patients (mean follow-up 28 months), 31 (79%) had a favorable outcome. Failure occurred in six patients, requiring permanent shunting leading to complete recovery, and two patients remained in a poor clinical status despite ETV. CONCLUSIONS: Laser-assisted ETV is a safe and efficient procedure for the treatment of obstructive hydrocephalus. Laser is advantageous in cases of distorted anatomy and may reduce technical failures.