Effects of anterior thalamic nucleus DBS on interictal heart rate variability in patients with refractory epilepsy.

OBJECTIVE: Heart rate variability (HRV) changes were investigated by several studies after resective epilepsy surgery/vagus nerve stimulation. We examined anterior thalamic nucleus (ANT)-deep brain stimulation (DBS) effects on HRV parameters. METHODS: We retrospectively analyzed 30 drug-resistant epilepsy patients' medical record data and collected electrocardiographic epochs recorded during video- electroencephalography monitoring sessions while awake and during N1- or N2-stage sleep pre-DBS implantation surgery, post-surgery but pre-stimulation, and after stimulation began. RESULTS: The mean square root of the mean squared differences between successive RR intervals and RR interval standard deviation values differed significantly (p < 0.05) among time-points, showing increased HRV post-surgery. High (0.15-0.4 Hz) and very low frequency (<0.04 Hz) increased, while low frequency (0.04-0.15 Hz) and the LF/HF ratio while awake decreased, suggesting improved autonomic regulation post-surgery. Change of effect size was larger in patients where both activated contacts were located in the ANT than in those where only one or none of the contacts hit the ANT. CONCLUSIONS: In patients with drug-resistant epilepsy, ANT-DBS might positively influence autonomic regulation, as reflected by increased HRV. SIGNIFICANCE: To gain a more comprehensive outcome estimation after DBS implantation, we suggest including HRV measures with seizure count in the post-surgery follow-up protocol.

Investigation of synapses in the cortical white matter in human temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is one of the most common focal pharmacotherapy-resistant epilepsy in adults. Previous studies have shown significantly higher numbers of neurons in the neocortical white matter in TLE patients than in controls. The aim of this work was to investigate whether white matter neurons are part of the neuronal circuitry. Therefore, we studied the distribution and density of synapses in surgically resected neocortical tissue of pharmacotherapy-resistant TLE patients. Neocortical white matter of temporal lobe from non-epileptic patients were used as controls. Synapses and neurons were visualized with immunohistochemistry using antibodies against synaptophysin and NeuN, respectively. The presence of synaptophysin in presynaptic terminals was verified by electron microscopy. Quantification of immunostaining was performed and the data of the patients' cognitive tests as well as clinical records were compared to the density of neurons and synapses. Synaptophysin density in the white matter of TLE patients was significantly higher than in controls. In TLE, a significant correlation was found between synaptophysin immunodensity and density of white matter neurons. Neuronal as well as synaptophysin density significantly correlated with scores of verbal memory of TLE patients. Neurosurgical outcome of TLE patients did not significantly correlate with histological data, although, higher neuronal and synaptophysin densities were observed in patients with favorable post-surgical outcome. Our results suggest that white matter neurons in TLE patients receive substantial synaptic input and indicate that white matter neurons may be integrated in epileptic neuronal networks responsible for the development or maintenance of seizures.

The role of hybrid FDG-PET/MRI on decision-making in presurgical evaluation of drug-resistant epilepsy.

BACKGROUND: When MRI fails to detect a potentially epileptogenic lesion, the chance of a favorable outcome after epilepsy surgery becomes significantly lower (from 60 to 90% to 20-65%). Hybrid FDG-PET/MRI may provide additional information for identifying the epileptogenic zone. We aimed to investigate the possible effect of the introduction of hybrid FDG-PET/MRI into the algorithm of the decision-making in both lesional and non-lesional drug-resistant epileptic patients. METHODS: In a prospective study of patients suffering from drug-resistant focal epilepsy, 30 nonlesional and 30 lesional cases with discordant presurgical results were evaluated using hybrid FDG-PET/MRI. RESULTS: The hybrid imaging revealed morphological lesion in 18 patients and glucose hypometabolism in 29 patients within the nonlesional group. In the MRI positive group, 4 patients were found to be nonlesional, and in 9 patients at least one more epileptogenic lesion was discovered, while in another 17 cases the original lesion was confirmed by means of hybrid FDG-PET/MRI. As to the therapeutic decision-making, these results helped to indicate resective surgery instead of intracranial EEG (iEEG) monitoring in 2 cases, to avoid any further invasive diagnostic procedures in 7 patients, and to refer 21 patients for iEEG in the nonlesional group. Hybrid FDG-PET/MRI has also significantly changed the original therapeutic plans in the lesional group. Prior to the hybrid imaging, a resective surgery was considered in 3 patients, and iEEG was planned in 27 patients. However, 3 patients became eligible for resective surgery, 6 patients proved to be inoperable instead of iEEG, and 18 cases remained candidates for iEEG due to the hybrid FDG-PET/MRI. Two patients remained candidates for resective surgery and one patient became not eligible for any further invasive intervention. CONCLUSIONS: The results of hybrid FDG-PET/MRI significantly altered the original plans in 19 of 60 cases. The introduction of hybrid FDG-PET/MRI into the presurgical evaluation process had a potential modifying effect on clinical decision-making. TRIAL REGISTRATION: Trial registry: Scientific Research Ethics Committee of the Medical Research Council of Hungary. TRIAL REGISTRATION NUMBER: 008899/2016/OTIG . Date of registration: 08 February 2016.

Etiology-related Degree of Sprouting of Parvalbumin-immunoreactive Axons in the Human Dentate Gyrus in Temporal Lobe Epilepsy.

In the present study, we examined parvalbumin-immunoreactive cells and axons in the dentate gyrus of surgically resected tissues of therapy-resistant temporal lobe epilepsy (TLE) patients with different etiologies. Based on MRI results, five groups of patients were formed: (1) hippocampal sclerosis (HS), (2) malformation of cortical development, (3) malformation of cortical development + HS, (4) tumor-induced TLE, (5) patients with negative MRI result. Four control samples were also included in the study. Parvalbumin-immunoreactive cells were observed mostly in subgranular location in the dentate hilus in controls, in tumor-induced TLE, in malformation of cortical development and in MR-negative cases. In patients with HS, significant decrease in the number of hilar parvalbumin-immunoreactive cells and large numbers of ectopic parvalbumin-containing neurons were detected in the dentate gyrus' molecular layer. The ratio of ectopic/normally-located cells was significantly higher in HS than in other TLE groups. In patients with HS, robust sprouting of parvalbumin-immunoreactive axons were frequently visible in the molecular layer. The extent of sprouting was significantly higher in TLE patients with HS than in other groups. Strong sprouting of parvalbumin-immunoreactive axons were frequently observed in patients who had childhood febrile seizure. Significant correlation was found between the level of sprouting of axons and the ratio of ectopic/normally-located parvalbumin-containing cells. Electron microscopy demonstrated that sprouted parvalbumin-immunoreactive axons terminate on proximal and distal dendritic shafts as well as on dendritic spines of granule cells. Our results indicate alteration of target profile of parvalbumin-immunoreactive neurons in HS that contributes to the known synaptic remodeling in TLE.

Surgical outcomes related to invasive EEG monitoring with subdural grids or depth electrodes in adults: A systematic review and meta-analysis.

PURPOSE: Resective epilepsy surgery based on an invasive EEG-monitors performed with subdural grids (SDG) or depth electrodes (stereo-electroencephalography, SEEG) is considered to be the best option towards achieving seizure-free state in drug-resistant epilepsy. The authors present a meta-analysis, due to the lack of such a study focusing on surgical outcomes originating from SDG- or SEEG-monitors. METHOD: English-language studies published until May 2018, highlighting surgical outcomes were reviewed. Outcome measures including total number of SDG- or SEEG-monitors and resective surgeries; consecutively followed surgical cases; surgical outcomes classified by Engel in overall, temporal/extratemporal and lesional/nonlesional subgroups were analyzed. RESULTS: 19 articles containing 1025 SDG-interventions and 16 publications comprising 974 SEEG-monitors were researched. The rate of resective surgery deriving from SDG-monitoring hovered at 88.8% (95%CI:83.3-92.6%) (I2 = 77.0%;p < 0.001); in SEEG-group, 79.0% (95%CI:70.4-85.7%) (I2 = 72.5%;p < 0.001) was measured. After SDG-interventions, percentage of post-resective follow-up escalated to 96.0% (95%CI:92.0-98.1%) (I2 = 49.1%;p = 0.010), and in SEEG-group, it reached 94.9% (95%CI:89.3-97.6%) (I2 = 80.2%;p < 0.001). In SDG-group, ratio of seizure-free outcomes reached 55.9% (95%CI:50.9-60.8%) (I2 = 54.47%;p = 0.002). Using SEEG-monitor, seizure-freedom occurred in 64.7% (95%CI:59.2-69.8%) (I2 = 11.9%;p = 0.32). Assessing lesional cases, likelihood of Engel I outcome was found in 57.3% (95%CI:48.7%-65.6%) (I2 = 69.9%;p < 0.001), using SDG; while in SEEG-group, it was 71.6% (95%CI:61.6%-79.9%) (I2 = 24.5%;p = 0.225). In temporal subgroup, ratio of seizure-freedom was found to be 56.7% (95%CI:51.5%-61.9%) (I2 = 3.2%;p = 0.412) in SDG-group; whereas, SEEG-group reached 73.9% (95%CI:64.4%-81.6%); (I2 = 0.00%;p = 0.45). Significant differences between seizure-free outcomes were found in overall (p = 0.02), lesional (p = 0.031), and also, temporal (p = 0.002) comparisons. CONCLUSIONS: SEEG-interventions were associated, at least, non-inferiorly, with seizure-freedom compared with SDG-monitors in temporal, lesional and overall subgroups.

[Postoperative outcome of surgical interventions for epilepsy between 2005 and 2016 at the Epilepsy Center of Pécs]. / Epilepsziasebészeti beavatkozások eredményei a Pécsi Epilepszia Centrumban 2005 és 2016 között.

INTRODUCTION: Epilepsy as a chronic, severe neurologic disease significantly influences the quality of life of the epileptic patients. In candidates well selected for surgery, the seizure freedom is realistically achievable, and the quality of life can be further improved with complex individual rehabilitation. AIM: We aimed to evaluate the postoperative outcome of patients who underwent epilepsy surgery between 2005 and 2016 at the Epilepsy Center at Pécs. METHOD: We evaluated seizure status at regular follow-up visits after surgery and the quality of life using questionnaires focusing on employment and social status. RESULTS: 76% of the 72 patients who underwent surgical resection for epilepsy were free from disabling seizures , and 10% had rare disabling seizures (almost seizure-free), 7% experienced worthwhile improvement and 7% had no worthwhile improvement. Comparing the employment status of patients free from disabling seizures to patients not free from disabling seizures, we found that the employment status is significantly influenced by seizure freedom (p<0.01, Fisher's exact test). While 67% of seizure-free patients were employed, only 19% of patients not free from disabling seizures were hired. CONCLUSION: Our results resemble the international tendencies and success rate, proving epilepsy surgery as an available, valid and effective treatment in well selected patients. Orv Hetil. 2019; 160(7): 270-278.

Ictal asystole: A systematic review.

OBJECTIVE: To comprehensively analyze ictal asystole (IA) on a large number of subjects. METHODS: We performed a systematic review of case report studies of patients diagnosed with IA (1983-2016). Each included case was characterized with respect to patient history, IA seizure characteristics, diagnostic workup, and therapy. In addition, comparative analyses were also carried out: two alignments were developed based on the delay between epilepsy onset and IA onset ("new-onset" if <1 year, "late-onset" if ≥1 year) and asystole duration (asystole was "very prolonged" if lasted >30 s). RESULTS: One hundred fifty-seven cases were included. All patients had focal epilepsy. In 7% of cases IA developed during a secondary generalized tonic-clonic seizure. Both the seizure-onset zone and the focal seizure activity at asystole beginning were usually temporal (p < 0.001 and p = 0.001, respectively) and were lateralized to the left hemisphere in 62% (p = 0.005 and p = 0.05, respectively). Asystole duration was 18 ± 14 s (mean±SD) (range 3-96 s); 73% of patients had late-onset, 27% had new-onset IA. Compared to late-onset IA, new-onset IA was associated with female gender (p = 0.023), preexisting heart condition (p = 0.014), focal seizure activity at asystole beginning (p = 0.012), normal neuroimaging (p = 0.013), normal interictal EEG (p < 0.001), auditory aura (p = 0.012), and drug-responsive epilepsy (p < 0.001). "Very prolonged" asystole was associated with secondary generalized tonic-clonic seizures (p = 0.003) and tended to occur in extratemporal lobe seizures (p = 0.074). No IA-related death was reported. SIGNIFICANCE: Characteristics considered to be typical of IA (focal, left temporal seizures appearing on grounds of a long-lasting, intractable epilepsy) seem only partially legitimate. We suggest that in new-onset IA, female gender and a preexisting heart condition could serve as predispositions in an otherwise benign epilepsy. We speculate that in late-onset IA, male-predominant changes in neuronal networks in chronic, intractable epilepsy and an accompanying autonomic dysregulation serve as facilitating factors.

The possible role of the insula in the epilepsy and the gambling disorder of Fyodor Dostoyevsky.

Background The retrospective diagnosis of Fyodor Mikhailovich Dostoyevsky's (1821-1881) neurological and psychiatric disease proves to be particularly interesting. Recent neurobiological data suggest a solution to the questions regarding the writer's retrospective diagnosis, claiming the insular cortex to be the origin of the rare ecstatic seizures. Regarding Dostoyevsky's pathological gambling, this hypothesis is consistent with another finding from recent neuroscience, namely that the malfunction of the insula could be an important underlying pathology in gambling disorder. Case study Literary and scientific overview (1928-2015) on the subjects of Dostoyevsky's epilepsy and gambling disorder. Discussion and conclusion Taking Dostoyevsky's neurological (ecstatic seizures) and psychiatric (pathological gambling) disease and the crossroads into consideration, these two disciplines make regarding the underlying pathology, we would like to suggest a speculative theory that these two disorders have a common insular pathomechanism, namely, the malfunctioning of the risk prediction-risk prediction error coding system. Furthermore, based on Dostoyevsky's case, regarding gambling disorder in general, we would like to hypothesize that the three common gambling-related cognitive distortions (near-miss effect, gambler's fallacy, and the illusion of control) can be all attributed to the impairment of the anterior insular risk prediction-risk prediction error coding system.

Concussive convulsions: A YouTube video analysis.

OBJECTIVE: To analyze seizure-like motor phenomena immediately occurring after concussion (concussive convulsions). METHODS: Twenty-five videos of concussive convulsions were obtained from YouTube as a result of numerous sports-related search terms. The videos were analyzed by four independent observers, documenting observations of the casualty, the head injury, motor symptoms of the concussive convulsions, the postictal period, and the outcome. RESULTS: Immediate responses included the fencing response, bear hug position, and bilateral leg extension. Fencing response was the most common. The side of the hit (p = 0.039) and the head turning (p = 0.0002) was ipsilateral to the extended arm. There was a tendency that if the blow had only a vertical component, the bear hug position appeared more frequently (p = 0.12). The motor symptom that appeared with latency of 6 ± 3 s was clonus, sometimes superimposed with tonic motor phenomena. Clonus was focal, focally evolving bilateral or bilateral, with a duration of 27 ± 19 s (5-72 s). Where lateralization of clonus could be determined, the side of clonus and the side of hit were contralateral (p = 0.039). SIGNIFICANCE: Concussive convulsions consist of two phases. The short-latency first phase encompasses motor phenomena resembling neonatal reflexes and may be of brainstem origin. The long-latency second phase consists of clonus. We hypothesize that the motor symptoms of the long-latency phase are attributed to cortical structures; however, they are probably not epileptic in origin but rather a result of a transient cortical neuronal disturbance induced by mechanical forces.

Age at onset and seizure frequency affect white matter diffusion coefficient in patients with mesial temporal lobe epilepsy.

In mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), structural abnormalities are present not only in the hippocampus but also in the white matter with ipsilateral predominance. Although the timing of epilepsy onset is commonly associated with clinical and semiological dissimilarities, limited data exist regarding white matter diffusion changes with respect to age at epilepsy onset. The aim of this study was to investigate diffusion changes in the white matter of patients with unilateral MTLE-HS with respect to clinical parameters and to compare them with an age- and sex-matched healthy control group. Apparent diffusion coefficients (ADCs) were derived using monoexponential approaches from 22 (11 early and 11 late age at onset) patients with unilateral MTLE-HS and 22 age- and sex-matched control subjects after acquiring diffusion-weighted images on a 3T MRI system. Data were analyzed using two-tailed t-tests and multiple linear regression models. In the group with early onset MTLE-HS, ADC was significantly elevated in the ipsilateral hemispheric (p=0.04) and temporal lobe white matter (p=0.01) compared with that in controls. These differences were not detectable in late onset MTLE-HS patients. Apparent diffusion coefficient of the group with early onset MTLE-HS was negatively related to age at epilepsy onset in the ipsilateral hemispheric white matter (p=0.03) and the uncinate fasciculus (p=0.03), while in patients with late onset MTLE-HS, ADC was no longer dependent on age at epilepsy onset itself but rather on the seizure frequency in the ipsilateral uncinate fasciculus (p=0.03). Such diffusivity pattern has been associated with chronic white matter degeneration, reflecting myelin loss and higher extracellular volume which are more pronounced in the frontotemporal regions and also depend on clinical features. In the group with early onset MTLE-HS, the timing of epilepsy seems to be the major cause of white matter abnormalities while in late onset disease, it has a secondary role in provoking diffusion changes.

[Dostoyevsky's epilepsy in the light of recent neurobiological data]. / Dosztojevszkij epilepsziájáról az újabb neurobiológiai adatok tükrében.

BACKGROUND AND PURPOSE: Since the 1960s several theories have developed on the epilepsy of Fyodor Mikhailovich Dostoyevsky. Probably the most exciting and still actual question might be the subject of the "ecstatic aura", he described in his novels based on his own experiences. During this extremely rare seizure onset the patients experience a strong sense of happiness, harmony and wholeness. The symptomatogenic zone of ecstatic seizures were considered to be of temporal lobe origin for a long time. Lately though this theory seems to be questioned based on the results of SPECT and deep brain EEG monitoring techniques in addition to the enrichment of our knowledge concerning the function of the insular cortex. METHODS: Literary and scientific overview on the subject of Dostoyevsky's epilepsy, with special concern to his ecstatic seizures. RESULTS AND CONCLUSION: According to new electrophysiology and imaging techniques ecstatic seizures--including the seizure onset of Dostoyevsky--could rather be connected to the insular cortex.

[Antiepileptic drugs in treatment of epilepsy and follow up of their efficacy]. / Antiepileptikumok alkalmazása az epilepszia kezelésében és hatásosságuk követése.

Epilepsy is one of the most common neurological diseases usually demanding long term treatment. The prime goal of therapy is to achieve seizure freedom with avoidance of side effects. Precise diagnosis is fundamental selecting the proper antiepileptic drug(s). In addition of wide-spectrum antiepileptics, selective syndrome-specific antiepileptic drugs are available. Pharmacological features of the new antiepileptics allow more personalized clinical use. Aim of this paper is to provide a comprehensive pragmatic review of therapeutic possibilities and recommendations currently accessible in Hungary.

Sturge-Weber syndrome: clinical and radiological correlates in 86 patients.

BACKGROUNDS AND PURPOSE: To correlate the extent of the leptomeningeal angiomatosis with clinical features in Sturge-Weber syndrome (SWS). METHODS: The study group consisted of 86 consecutive patients aged two months to 56 (mean 7.9 +/- 10.3) years with SWS and epilepsy. Clinical and MRI data were analyzed. RESULTS: Based on the extent of leptomeningeal angiomatosis, patients were divided into two subgroups: 43 patients had hemispheric angiomatosis and atrophy, whereas, another 43 had focal involvement. Nine of the 43 hemispherial patients (10%) showed bilateral involvement: all of these bilateral cases demonstrated dominance in a single side with hemispheric leptomeningeal angiomatosis and contralateral focal extension. Hemispheric and focal subgroups were clinically different. Patients with hemispheric SWS were younger at the age of epilepsy onset (p < 0.001) and age at MRI examination (p < 0.05). Neither gender, lateralization, duration of epilepsy, appearance of secondarily generalized seizures, nor seizure frequency revealed a significant difference between subgroups. CONCLUSION: Bilateral involvement is frequent and occurs in cases with a hemisperic involvement on one side. The age of epilepsy onset is related to the extent of leptomeningeal angiomatosis. Patients with hemispheric form of SWS presented with earlier age of seizure onset. Focal pial angiomatoses do not tend to progress (a longer duration is not associated with more frequent hemispheric involvement). Other variables including seizure frequency and secondary generalized tonic-clonic seizures are not associated with the extent of angiomatosis.

Correlation between calbindin expression in granule cells of the resected hippocampal dentate gyrus and verbal memory in temporal lobe epilepsy.

Calbindin expression of granule cells of the dentate gyrus is decreased in temporal lobe epilepsy (TLE) regardless of its etiology. In this study, we examined the relation between reduction of calbindin immunoreactivity and the verbal and visuo-spatial memory function of patients with TLE of different etiologies. Significant linear correlation was shown between calbindin expression and short-term and long-term percent retention and retroactive interference in auditory verbal learning test (AVLT) of patients including those with hippocampal sclerosis. In addition, we found significant linear regression between calbindin expression and short-term and long-term percent retention of AVLT in patients whose epilepsy was caused by malformation of cortical development or tumor and when no hippocampal sclerosis and substantial neuronal loss were detected. Together with the role of calbindin in memory established in previous studies on calbindin knock-out mice, our results suggest that reduction of calbindin expression may contribute to memory impairments of patients with TLE, particularly, when neuronal loss is not significant.

Secondarily generalized seizures in temporal lobe epilepsy.

PURPOSE: Secondarily generalized tonic-clonic seizure (SGTCS) may occur rarely in temporal lobe epilepsy (TLE), but SGTCS is the major risk factor for sudden death and for seizure-related fatal injuries. Our aim was to investigate clinical factors associated with the occurrence of SGTCS in TLE by addressing two questions: (1) What clinical features differentiate patients with TLE who regularly had SGTCS from those who did not? (2) Is there an association of secondarily generalized seizures with preceding seizure elements and clinical data? METHODS: We included 171 patients with TLE (mean age 34.4 ± 10) who participated in our presurgical evaluation program, which included continuous video-electroencephalography (EEG) and magnetic resonance imaging (MRI). Patients had a temporal lobectomy as a result of mesial or neocortical TLE. To reevaluate the archived seizures, we selected the consecutively recorded seizures of each patient. If the patient had more than three recorded seizures, then we reevaluated only the first three. Altogether video-recorded seizures of 402 patients were reanalyzed. KEY FINDINGS: A positive association between the presence of hippocampal sclerosis on the MRI and SGTCS in the patient history was found, whereas ictal speech and pedal automatism showed a negative association with a SGTCS history. The age of patients showed a positive association, whereas patient's reactivity before and during the seizure, oral/pedal automatisms, and vocalizations showed a negative association with secondary generalization of a focal-onset seizure during video-EEG monitoring. SIGNIFICANCE: Clinical features associated with SGTCS may help clinicians during presurgical monitoring identify high-risk patients for SGTCS. Our study may help in understanding the pathophysiology of secondary generalization.

Degree and pattern of calbindin immunoreactivity in granule cells of the dentate gyrus differ in mesial temporal sclerosis, cortical malformation- and tumor-related epilepsies.

A loss of calbindin immunoreactivity in granule cells of the hippocampal dentate gyrus is a characteristic feature of temporal lobe epilepsy with hippocampal sclerosis. Whether decreased calbindin expression is unique to the hippocampal sclerosis associated with cryptogenic temporal lobe epilepsy, or also occurs in tumor- or malformation-related epilepsy, is unknown. We show that calbindin immunoreactivity in granule cells has been decreased in epilepsy regardless of its etiology. In cases of cortical malformations or hippocampal sclerosis, calbindin immunoreactivity was undetectable in most granule cells. In tumor-related resections, in patients who had a long history of epileptic seizures, calbindin was detected only in one-third of granule cells. Regardless of etiology, calbindin expression correlated with age of onset and with duration of the epilepsy. In contrast to tumor-induced epilepsy, where calbindin-immunoreactive granule cells were equally distributed in the granule cell layer, in hippocampal sclerosis and malformation-related epilepsy, two-thirds of calbindin-immunoreactive granule cells were located in the outer half and only one-third in the inner half of the layer. Developmentally, granule cells at the border of the molecular layer are ontogenetically the oldest, and those at the border of the hilus are the youngest. The reduction of calbindin immunoreactivity in ontogenetically younger granule cells highlights the deleterious effect of early occurring epilepsy and initial early precipitating injury, including febrile seizures that may substantially affect developing immature granule cells, but less the earlier born matured ones.

Analysis of reoperation in mesial temporal lobe epilepsy with hippocampal sclerosis.

BACKGROUND: Most patients do well after epilepsy surgery for mesial temporal lobe sclerosis, and in only 8 to 12% of all operations, the outcome is classified as not improved. OBJECTIVE: To analyze the outcome of reoperation in cases of incomplete resection of mesial temporal lobe structures in patients with mesial temporal lobe sclerosis in temporal lobe epilepsy. METHODS: We analyzed 22 consecutive patients who underwent reoperation for mesial temporal lobe sclerosis (follow-up, 23-112 months; mean, 43.18 months) by evaluating noninvasive electroencephalographic/video monitoring before the first and second surgeries (semiology, interictal epileptiform discharges, ictal electroencephalography with special attention to the secondary contralateral evolution of the electroencephalographic seizure pattern after the initial regionalization), and magnetic resonance imaging (resection indices after the first and second surgeries on the amygdala, hippocampus, lateral temporal lobe). In 18 of 22 patients T2 relaxometry of the contralateral hippocampus was performed. RESULTS: Nine of 22 patients became seizure free; another 4 patients had a decrease in seizures and eventually became seizure free (range, 16-51 months; mean, 30.3). Recurrence of seizures is associated with (1) ictal electroencephalography with later evolution of an independent pattern over the contralateral temporal lobe (0 of 5 patients seizure free vs 5 of 7 patients non-seizure free; P = .046) and (2) a smaller amount of lateral temporal lobe resection in the second surgery (1.06 ± 0.59 cm vs 2.18 ± 1.37 cm; P = .019). No significant correlation with outcome was found for lateralization of interictal epileptiform discharges, change in semiology, other resection indices, T2 relaxometry, onset and duration of epilepsy, duration of follow-up, and side of surgery. CONCLUSION: Patients have a less favorable outcome with a reoperation if they show ictal scalp electroencephalography with secondary contralateral propagation and if only a small second resection of the lateral temporal lobe is performed.

Apical temporal lobe resection; "tailored" hippocampus-sparing resection based on presurgical evaluation data.

BACKGROUND: It is the aim of epilepsy surgery in patients with lesional epilepsy for the surgeon to not only remove the lesion itself, but also the epileptogenic zone. Here, we report our experience with a modified temporal resection technique confined to the apical temporal lobe, i.e., sparing the hippocampal formation in patients with epileptogenic lesions in the anterior part of the temporal lobe. This apical temporal lobe resection (aTLR) includes tailored lesionectomy, amygdalectomy, and resection of the mesial structures only in the apex of the temporal lobe. This paper presents our surgical technical details and the outcome of aTLR. METHODS: Between 2001 and 2008, aTLR was performed in 61 patients. All patients underwent comprehensive presurgical evaluation including video-EEG monitoring, magnetic resonance imaging (MRI), and neuropsychological testing. All patients had a lesion in the apex of the temporal lobe and a normal hippocampus as seen in MRI, as well as intact memory functions in neuropsychological examination. There were 33 males (54.1%) and 28 females (45.9%). The mean age in years at epilepsy onset was 20.2 ± 13.4, the mean age at epilepsy surgery was 32.1 ± 11.9, the mean preoperative epilepsy duration was 11.8 ± 8.8 years and the mean duration of follow-up was 2.1 ± 1.3 years (range 0.5-6 years). RESULTS: Fifty-four (88.5%) of 61 patients were in Engel Class 1 at 6 months, 38 (80.9%) of 47 at 2 years and nine (81.8%) of 11 at the 5 year follow-up. Histopathological examination showed tumors in 31 patients, FCD in ten patients, amygdala sclerosis in seven patients, cavernomas in six patients, unspecific reactions in eight patients, and gliosis in one patient. Surgical complications occurred in four patients: one had a permanent and three had transient complications which could be successfully treated. Fifty (82%) resections were considered to be complete resections as evaluated by serial postoperative MRI, seven patients (11.5%) had incomplete resection of the preoperative MRI lesion and in four patients (6.6%) it remained unclear. Fifteen patients (29.4%) were withdrawn from antiepileptic drugs for more than 2 years without relapse. Postoperative neuropsychological examination revealed worsening of memory performance in two patients (3.2%) and improved or no changes in the rest of the patients. CONCLUSIONS: Apical temporal resection sparing the mesial temporal structures is an effective procedure with good long-term seizure outcome in patients with refractory epilepsy due to lesions confined to the apex of the temporal lobe.

Absolute spike frequency and etiology predict the surgical outcome in epilepsy due to amygdala lesions.

PURPOSE: To identify surgical prognostic factors for temporal lobe epilepsy (TLE) due to amygdala lesions. METHODS: We included 42 patients (mean age: 31.4 ± 11) who underwent presurgical evaluation including long-term video-EEG and in whom the high-resolution MRI showed amygdala lesions without hippocampal abnormalities. All patients had apical temporal lobe resection without hippocampectomy. We distinguished patients with frequent spikes (spike frequency ≥ 60/h) and with non-frequent spikes (< 60 spikes/h). RESULTS: At the 2-year postoperative evaluation, 30 patients (71%) were seizure-free. The presence of infrequent spikes (p = 0.013), tumor on the MRI (p = 0.027), and no epilepsy history in the family (p = 0.027) were independently associated with 2-year seizure-free outcome. Of 33 patients with infrequent spikes, 79% became seizure-free, while of 9 patients with frequent spikes only 4 had a favorable surgical outcome (44%). CONCLUSION: In TLE patients due to amygdala lesions, high spike frequency and family history of epilepsy predicted an unfavorable, while tumoral etiology a favorable outcome after apical temporal lobe resection without hippocampectomy. Seventy-one percent of patients with amygdalar epilepsy who underwent this novel type of epilepsy surgery became seizure-free. This is comparable with results of "classical" anterior temporal lobe resections where hippocampus is NOT spared. Moreover, the surgical outcome may be predictable.

Epilepsy surgery, antiepileptic drug trials, and the role of evidence.

OBJECTIVE: We assessed whether recent randomized controlled trials (RCTs) of antiepileptic drugs (AEDs) are informed by evidence about surgical effectiveness. We explored whether RCTs of AEDs consider the patients' candidacy for surgery in their eligibility criteria, and whether the necessary investigations are requested in participating patients to determine their potential eligibility for surgery. METHODS: We systematically analyzed RCTs published in the last 2 years investigating the efficacy of new AEDs in localization-related epilepsy. Results from a surgical RCT and recommendations from an epilepsy surgery practice parameter were used to assess the degree to which surgical evidence informed the drug study design. RESULTS: Eleven RCTs were analyzed. All were conducted in countries with access to epilepsy surgery. None of the studies required magnetic resonance imaging (MRI) with an epilepsy protocol or explicit statement of the epilepsy syndrome, which could lead to the identification of surgical candidates. Having temporal lobe epilepsy or being a potential surgical candidate were not exclusion criteria in any of the trials. The primary efficacy end point was the reduction in seizure frequency or responder rate. Seizure freedom was never the primary outcome, and it was reported in only seven studies. The pooled data analysis of these trials revealed that 1.9% of patients became seizure-free on placebo and 4.4% on the study drug (p < 0.01). CONCLUSIONS: Important aspects of patient selection for new AED trials are not informed by the evidence about surgical effectiveness. Investigations that could lead to identification of patients for presurgical evaluation were not required in any of the studies.