Type of preoperative aura may predict postsurgical outcome in patients with temporal lobe epilepsy and mesial temporal sclerosis

PurposeAs the initial symptoms of epileptic seizures, many types of auras have significant localizing or lateralizing value. In this study, we hypothesized that the type of aura may predict postsurgical outcome in patients with medically refractory temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS).MethodsIn this retrospective study, all patients with a clinical diagnosis of medically refractory TLE due to unilateral mesial temporal sclerosis who underwent epilepsy surgery at the Jefferson Comprehensive Epilepsy Center were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups: seizure freedom or relapse. Outcome was compared between seven groups of patients according to their preoperative auras.ResultsTwo hundred thirty-seven patients were studied. The chance of becoming free of seizures after surgery in patients with abdominal aura was 65.1%, while in other patients, this was 43.3% (P = 0.01). In two-by-two comparisons, no other significant differences were observed.ConclusionPatients with medically refractory TLE–MTS who reported abdominal auras preceding their seizures fared better postoperatively with regard to seizure control compared with those who did not report auras, which may indicate bitemporal dysfunction, and to patients with other auras, which may indicate a widespread epileptogenic zone in the latter group of patients.     

A new clinico-pathological classification system for mesial temporal sclerosis

We propose a histopathological classification system for hippocampal cell loss in patients suffering from mesial temporal lobe epilepsies (MTLE). One hundred and seventy-eight surgically resected specimens were microscopically examined with respect to neuronal cell loss in hippocampal subfields CA1–CA4 and dentate gyrus. Five distinct patterns were recognized within a consecutive cohort of anatomically well-preserved surgical specimens. The first group comprised hippocampi with neuronal cell densities not significantly different from age matched autopsy controls [no mesial temporal sclerosis (no MTS); n = 34, 19%]. A classical pattern with severe cell loss in CA1 and moderate neuronal loss in all other subfields excluding CA2 was observed in 33 cases (19%), whereas the vast majority of cases showed extensive neuronal cell loss in all hippocampal subfields (n = 94, 53%). Due to considerable similarities of neuronal cell loss patterns and clinical histories, we designated these two groups as MTS type 1a and 1b, respectively. We further distinguished two atypical variants characterized either by severe neuronal loss restricted to sector CA1 (MTS type 2; n = 10, 6%) or to the hilar region (MTS type 3, n = 7, 4%). Correlation with clinical data pointed to an early age of initial precipitating injury (IPI < 3 years) as important predictor of hippocampal pathology, i.e. MTS type 1a and 1b. In MTS type 2, IPIs were documented at a later age (mean 6 years), whereas in MTS type 3 and normal appearing hippocampus (no MTS) the first event appeared beyond the age of 13 and 16 years, respectively. In addition, postsurgical outcome was significantly worse in atypical MTS, especially MTS type 3 with only 28% of patients having seizure relief after 1-year follow-up period, compared to successful seizure control in MTS types 1a and 1b (72 and 73%). Our classification system appears suitable for stratifying the clinically heterogeneous group of MTLE patients also with respect to postsurgical outcome studies.     

Intracranial EEG Seizure-Offset Termination Patterns: Relation to Outcome of Epilepsy Surgery in Temporal Lobe Epilepsy

Summary: Purpose: Studies using stereo-EEG (SEEG) and electrocorticography (ECoG) should not only identify a patient's epileptogenic zone, but also should provide prognostic information for surgical outcome. In this respect, seizure-offset patterns have so far been the subject of only one study, in which they were shown to be associated with poor outcome when recorded over cortical areas outside the temporal lobe of seizure onset. To clarify whether seizure-offset patterns are reliable in predicting seizure outcome, we studied SEEG/ECoG in a similar group of patients with temporal lobe epilepsy (TLE). Methods: SEEGECoG records of 44 patients with refractory TLE were analyzed. The areas of seizure termination were classified as ipsilateral or contralateral (mesial and/or lateral) temporal, (temporal and) frontal, and diffusehilateral. Patients were classified with respect to seizure outcome as either seizure-free (UCLA class la) or not seizure free (UCLA class 2–4); both groups were correlated with specific seizure-offset categories using Fisher's exact probability test and analysis of variance (ANOVA). Results: Of the 44 patients, the majority (n = 36) had at least part of their seizure offsets in the ipsilateral temporal lobe, whereas 8 patients manifested no seizure offsets in this lobe. Only 9 patients (20%) showed exclusive offsets in the ipsilateral temporal lobe. No statistically significant difference was evident between patients with all seizure offsets in the ipsilateral temporal lobe and those with offsets elsewhere. Similarly, no statistically significant difference was evident between patients with a diffuse seizure offset and those with seizure offsets of a different category. Conclusions: Seizure-offset patterns in SEEGECoG are unreliable in predicting seizure outcome after resective activity surgery for TLE.     

Temporal lobe surgery in medically refractory epilepsy: A comparison between populations based on MRI findings

IntroductionHigh resolution MRI findings suggestive of mesial temporal sclerosis (MRI-MTS) correlate with good outcome after surgery. However, a large group of patients present with normal brain MRI (N-MRI) and temporal lobe epilepsy (TLE). We aim to compare pre-operative ictal EEG patterns in predicting surgical outcomes in the population with MRI-MTS vs. N-MRI after selective anterior-mesial temporal lobe (AMTL) resection.Methods241 patients with unilateral anterior ictal EEG findings underwent selective AMTL resection. 143 MRI-MTS and 98 N-MRI patients were identified. Outcome was based on the modified Engel classification, ictal EEG pattern at seizure onset, demographics and MRI findings.ResultsSeizure-free outcome was seen in the MRI-MTS in 79% of patients, compared to 59.1% (p < .005) of the N-MRI group. No significant difference was identified in ictal EEG patterns at presentation between groups. Class I outcome was achieved in 78.9% of patients that had theta rhythm and MRI-MTS compared to 57.9% of patients that had theta rhythm and N-MRI (p < 0.05).Discussion and conclusionSurgical treatment for mesial TLE is effective. Positive MRI suggestive of mesial temporal sclerosis (MTS) predicts better seizure control after surgery. Theta rhythm is the most common ictal pattern and seems to carry the best prognosis for TLE. However, a well-selected group of patients with N-MRI will benefit from surgical intervention, and similar outcome to MRI-MTS patients can be achieved if delta ictal EEG pattern is presented at initial onset. Early referral to an epilepsy center cannot be emphasized enough, even in situations when high-resolution brain MRI is normal.     

Correlation Between Interictal Regional Cerebral Blood Flow and Depth-Recorded Interictal Spiking in Temporal Lobe Epilepsy

Summary: Purpose: Single photon emission computed tomography (SPECT) is used as an adjunctive method in preoperative localization of epileptic foci. In temporal lobe epilepsy (TLE), interictal hypoperfusion is observed in 60–70% of cases. Correlation with ictal EEG changes is observed in ～50–60% of cases. Relationships with interictal EEG have been studied less. We compared interictal SPECT data obtained in 20 patients with their interictal intracerebral electrical activity recorded by depth electrodes to evaluate a potential relationship. Methods: We studied 20 sequential patients whose clinical, surface, and depth EEG data indicated seizure originating in the temporal lobe and who had interictal [^99mTc]hexamethyl-propylene amine oxime (HMPAO)-SPECT stereo-EEG (SEEG). Intracerebral electrodes were placed according to the patient's profile. The interictal extent of epileptiform activity allowed delineation of the irritative zone. Interictal spike frequency was also analyzed semiquantitatively. Visual and numerical SPECT analysis was performed blind to SEEG data. Results: Interictal hypoperfusion was observed in 16 patients, involving the epileptogenic temporal lobe in 14. Except for 1 patient who manifested lateral temporal hypoperfusion corresponding to a mass lesion, two distinctive patterns of hypoperfusion were noted: (a) mesial hypoperfusion (5 patients), and (b) global temporal hypoperfusion (8 patients). In 8 patients, hypoperfusion had also extended into the adjacent cortex. Temporal mesial hypoperfusion was associated with spiking limited to the mesial structures, whereas global temporal hypoperfusion or hypoperfusion extending beyond the temporal lobe was associated with a similar topographic pattern of spikes. Conclusions: Comparison between SPECT and SEEG data collected in the interictal phase indicated that the extent of the hypoperfused area correlated topographically with that of the underlying irritative zone.     

Relative preservation of GABAA receptor β-subunit immunoreactivity in the hippocampus in mesial temporal sclerosis

The pattern of cell loss and changes in the expression of inhibitory and excitatory receptors in the subzones of the hippocampus in patients with pharmacoresistant (drug-refractory) complex partial seizures was studied. Neuronal densities were measured in the mid-hippocampus in temporal lobectomy (n = 10) and total hemispherectomy (n = 2) specimens from 12 patients with mesial temporal sclerosis (MTS), in temporal lobectomy (n = 6) and hemispherectomy (n = 5) samples from 11 epileptic patients without MTS, and in six autopsy brains from patients without neurological disease. No differences in hippocampal cell densities were found between the autopsy and the non-MTS group. The MTS group, compared with the non-MTS or the autopsy group, showed a 95% decrease in neuronal density in CA1, a 70% decrease in cornu ammonis (CA)2, an 85% decrease in CA3, and an 80% decrease in CA4. The proportion of neurons staining positively with a polyclonal antibody for the α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) glutamate receptor subunits GluR2 and GluR3 was increased to 32% in the CA1 region in the MTS group, compared with 21% in the non-MTS hippocampi. This difference was, however, just at the level of statistical significance (P = 0.054). Elsewhere in the hippocampus no significant change was observed. By contrast, the proportion of cells staining positively with a monoclonal antibody to the β-subunit of the GABA_A benzodiazepine (BZ) receptor was markedly increased in the MTS hippocampi, from 13% in non-MTS CA1 to 50% in MTS CA1 region; and from 26% in non-MTS CA3 to 63% in MTS CA3. Although previous studies (in vivo and ex vivo) have emphasized a loss of BZ receptors in temporal lobe epilepsy, this study shows that the expression of the GABA_A receptor immunopositive population appears to be increased relative to the neuronal density.     

Effects of dual pathology on cognitive outcome following left anterior temporal lobectomy for treatment of epilepsy

The objective of this retrospective study was to determine if dual pathology [DUAL — focal cortical dysplasia (FCD) and mesial temporal sclerosis (MTS)] in patients with left temporal lobe epilepsy is associated with greater risk for cognitive decline following temporal lobectomy than single pathology (MTS only). Sixty-three adults (M_age = 36.5 years, female: 52.4%) who underwent left anterior temporal lobectomy for treatment of epilepsy (MTS = 28; DUAL = 35) completed preoperative and postoperative neuropsychological evaluations. The base rate of dual pathology was 55.5%. Repeated measures ANOVAs yielded significant 2-way interactions (group × time) on most measures of language and memory with generally moderate effect sizes. Specifically, patients with MTS only demonstrated postoperative declines, while those with dual pathology remained unchanged or improved. Results suggest that dual pathology may be associated with better cognitive outcome following epilepsy surgery than MTS alone, possibly reflecting limited functionality of the resected tissue or intrahemispheric reorganization of function in the context of a developmental lesion.     

Major depressive disorder as a predictor of a worse seizure outcome one year after surgery in patients with temporal lobe epilepsy and mesial temporal sclerosis

PurposeThe association between pre-surgical psychiatric disorders (PDs) and worse seizure outcome in patients with refractory epilepsy submitted to surgery has been increasingly recognized in the literature. The present study aimed to verify the impact of pre- and post-surgical PD on seizure outcome in a series of patients with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE–MTS).MethodData from 115 TLE–MTS patients (65 females; 56.5%) who underwent cortico-amygdalohippocampectomy (CAH) were analyzed. Pre- and post-surgical psychiatric evaluations were performed using DSM-IV and ILAE criteria. The outcome subcategory Engel IA was considered as corresponding to a favorable prognosis. A multivariate logistic regression model was applied to identify possible risk factors associated with a worse seizure outcome.ResultsPre-surgical PDs, particularly major depressive disorder (MDD), anxiety and psychotic disorders, were common, being found in 47 patients (40.8%). Fifty-six patients (48.7%) were classified as having achieved an Engel IA one year after CAH. According to the logistic regression model, the presence of pre-surgical MDD (OR = 5.23; p = 0.003) appeared as the most important risk factor associated with a non-favorable seizure outcome.ConclusionAlthough epilepsy surgery may be the best treatment option for patients with refractory TLE–MTS, our findings emphasize the importance of performing a detailed psychiatric examination as part of the pre-surgical evaluation protocol.     

Perisylvian vulnerability to postencephalitic epilepsy

ObjectivePostencephalitic epilepsy is often resistant to antiseizure medications, leading to evaluation for epilepsy surgery. Characterizing its localization carries implications for optimal surgical approach. We aimed to determine whether a prior history of encephalitis is associated with specific epileptogenic networks among patients with drug resistant epilepsy undergoing stereotactic EEG (SEEG).MethodsWe conducted a retrospective cohort study of drug resistant epilepsy, with and without a prior history of encephalitis. We analyzed SEEG recordings to identify patterns of seizure onset and organization. Seventeen patients with a history of encephalitis (of infectious etiology in two subjects) were identified from a database of patients undergoing SEEG and were compared to seventeen drug-resistant epilepsy controls without a history of encephalitis matched for confounding variables including pre-implantation hypotheses, epilepsy duration, age, and sex.ResultsIndependent bilateral seizures were noted in 65% of the postencephalitic epilepsy cohort. We identified four SEEG-ictal patterns in patients with a prior history of encephalitis: (1) anteromesial temporal onset (24%), (2) anteromesial temporal onset with early spread to the perisylvian region (29%), (3) perisylvian (59%) and (4) synchronized anteromesial temporal and perisylvian (29%) onsets. Patterns 3 and 4, with perisylvian involvement at onset, were unique to the encephalitis group (p = 0.0003 and 0.04 respectively) and exhibited a “patchwork” organization. None of the encephalitis patients vs 5/7 matched controls had Engel I outcome (p = 0.0048).ConclusionsPostencephalitic epilepsies involve anteromesial temporal and perisylvian networks, often in a bilateral independent manner. Unique ictal patterns involving the perisylvian regions was identified in the encephalitis group, but not in the matched control group. Significance: These findings may reflect a selective vulnerability of the perisylvian regions to epilepsy resulting from encephalitis, significantly mitigating the chances of success with SEEG-guided temporal resections.     

Epilepsy in neurofibromatosis type 1

ObjectivesTo describe the characteristics of epilepsy in patients with Neurofibromatosis type 1 (NF1).MethodsAnalysis of a cohort of consecutive NF1 patients seen in our NF1 clinic during a three-year period.ResultsOf the 184 NF1 patients seen during that period, 26 had epilepsy and three had febrile seizures. Of the 26, 17 (65%) had localization-related epilepsy, seven of whom (41%) were drug resistant. Six (23%) had apparently primary generalized epilepsy (0/6 drug resistant), two (8%) Lennox-Gastaut syndrome, and one (4%) West syndrome (all three were drug-resistant). As compared to the patients with no epilepsy, those with epilepsy were more likely to have MRI findings of mesial temporal sclerosis (MTS) (23% vs. 5%, p = 0.0064), and cerebral hemisphere tumors (31% vs. 10%, p = 0.0079), but not of the other MRI findings including neurofibromatosis bright objects, or optic gliomas. Three of the six patients with MTS underwent temporal lobectomy with subsequent control of their seizures with confirmation of MTS on pathology in 3/3 and presence of coexisting focal cortical dysplasia (FCD) in 2/3. We also have observed three additional patients outside the above study with the association of NF1, MTS, and intractable epilepsy.SignificanceEpilepsy is relatively common in NF1, often occurs in patients with brain tumors or with MTS which can coexist with FCD, can be associated with multiple types of epilepsy syndromes, and when localization-related is often drug-resistant. Patients with NF1 and MTS can respond to medial temporal lobectomy and may have coexisting medial temporal lobe cortical dysplasia.     

Granule cell dispersion is associated with memory impairment in right mesial temporal lobe epilepsy

PurposeWe analyzed the association of granule cell dispersion (GCD) with memory performance, clinical data and surgical outcome in a series of patients with mesial temporal lobe epilepsy (MTLE) and mesial temporal sclerosis (MTS).MethodHippocampal specimens from 54 patients with MTLE (27 patients with right MTLE and 27 with left MTLE) and unilateral MTS, who were separated into GCD and no-GCD groups and thirteen controls were studied. Quantitative neuropathological evaluation was performed using hippocampal sections stained with NeuN. Patients’ neuropsychological measures, clinical data, type of MTS and surgical outcome were reviewed.ResultsGCD occurred in 28 (51.9%) patients. No correlation between GCD and MTS pattern, clinical data or surgical outcome was found. The presence of GCD was correlated with worse visuospatial memory performance in right MTLE, but not with memory performance in left MTLE.ConclusionGCD may be related to memory impairment in right MTLE-MTS patients. However, the role of GCD in memory function is not precisely defined.     

Stimulation better targets fast-ripple generating networks in super responders to the responsive neurostimulator system

How responsive neurostimulation (RNS) decreases seizure frequency is unclear. Stimulation may alter epileptic networks during inter-ictal epochs. Definitions of the epileptic network vary but fast ripples (FRs) may be an important substrate. We, therefore, examined whether stimulation of FR-generating networks differed in RNS super responders and intermediate responders. In 10 patients, with subsequent RNS placement, we detected FRs from stereo-electroencephalography (SEEG) contacts during pre-surgical evaluation. The normalized coordinates of the SEEG contacts were compared with those of the eight RNS contacts, and RNS-stimulated SEEG contacts were defined as those within 1.5 cm³ of the RNS contacts. We compared the post-RNS placement seizure outcome to (1) the ratio of stimulated SEEG contacts in the seizure-onset zone (SOZ stimulation ratio [SR]); (2) the ratio of FR events on stimulated contacts (FR SR); and (3) the global efficiency of the FR temporal correlational network on stimulated contacts (FR SGe). We found that the SOZ SR (p = .18) and FR SR (p = .06) did not differ in the RNS super responders and intermediate responders, but the FR SGe did (p = .02). In super responders, highly active desynchronous sites of the FR network were stimulated. RNS that better targets FR networks, as compared to the SOZ, may reduce epileptogenicity more.     

Postsurgical outcome in patients with auditory auras and drug-resistant epilepsy

PurposeWe assessed whether patients with auditory auras have similar outcomes after epilepsy surgery as patients without auditory auras, and hypothesized that patients with non-dominant hemisphere foci might fare better after temporal lobe surgery than patients with dominant resections.MethodsIn this retrospective study, outcome after temporal resection was assessed for patients with drug-resistant epilepsy. Preoperative demographic data, clinical data, and surgical outcome were prospectively registered in a database from 1986 through 2016. Seizure outcome was classified as either seizure-free or relapsed.ResultsData were available in 1186 patients. Forty five patients (3.8%) reported auditory auras; 42 patients (93%) had temporal lobe epilepsy (TLE), and three patients (7%) had extratemporal epilepsy. Since most patients with auditory auras had TLE and in order to have comparable groups, we selected 41 patients with auditory auras and compared them with patients without auditory auras who had temporal lobe resections (767 patients). There were no significant demographic or clinical differences between TLE patients with auditory auras and those without. Patients who had auditory auras were more likely to relapse after temporal lobe surgery than those without (p = 0.03). Among patients who had auditory auras and temporal lobe surgery, side of surgery was not related to postoperative outcome (p = 0.3).ConclusionAuditory auras are rare among patients with drug-resistant TLE. The presence of an auditory aura in a patient with drug-resistant TLE carries a worse prognosis for a postoperative seizure free outcome and this is not related to the side of surgery.     

Clinical,semiological, electroencephalographic,and neuropsychological features of “pure” neocortical temporal lobe epilepsy

Aims: We examined the clinical, semiological, scalp EEG, and neuropsychological features of patients with “pure” neocortical temporal lobe epilepsy (NTLE) who were successfully treated by neocortical temporal resection sparing the mesial temporal structures. Methods: This retrospective study included 17 patients with lesional NTLE who satisfied the following criteria: presence of a discrete structural lesion in the lateral temporal lobe on preoperative MRI; lateral temporal resection sparing the mesial temporal structures; follow‐up for at least two years after surgery; and favourable postoperative seizure outcome (Engel Class I). The study included 10 females and seven males, and the age at surgery ranged from 15 to 48 years (mean: 30.7 years). Auras, video‐recorded seizure semiology, interictal and ictal EEG, and pre‐ and post‐operative neuropsychological data were reviewed. Twenty patients with mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis, who had a favourable postoperative seizure outcome (Engel Class I), were selected as a control group. Results: Age at seizure onset was significantly greater in patients with NTLE than in controls. A history of febrile convulsion was significantly less frequent in NTLE patients. Epigastric ascending sensation (6% versus 40%; p=0.017), oral automatisms (29% versus 80%; p=0.003), gestural automatisms (47% versus 80%; p=0.047), and dystonic posturing (0% versus 40%; p=0.003) were significantly less frequent in NTLE than controls. Ictal unitemporal rhythmic theta activity was also significantly less frequent in NTLE than controls (35.3% versus 75%; p=0.015). Preoperative IQ score (range: 68 to 114; mean: 88.9) and preoperative memory quotient score (range: 56–122; mean: 98.1) were significantly higher in NTLE (p=0.003 and p=0.048, respectively). Conclusion: There were notable differences in clinical, semiological, EEG, and neuropsychological features between “pure” NTLE and MTLE. These findings may be useful to identify the epileptogenic zone.     

Benign mesial temporal lobe epilepsy: A clinical cohort and literature review

ObjectiveWe present a single-center retrospective study of benign mesial temporal lobe epilepsy (bMTLE) between 1995 and 2014.MethodsHospital records and clinic charts were reviewed. The clinical, Eelectroencephalographic (EEG), imaging features, and response to treatment with antiepileptic drugs (AEDs) were documented. Patients were included in this study if they were seizure-free for a minimum of 24 months with or without an AED.ResultsTwenty-seven patients were identified. There were 19 (70%) females, mean age at first seizure was 32.2 (range: 15–80 years). In all patients, seizures were mild, and seizure freedom was readily achieved with the initiation of AED therapy. Sixteen patients (59%) had mesial temporal sclerosis (MTS). In three patients, we attempted to discontinue AED therapy after a prolonged period of remission (5–8 years), but all had seizure recurrence within 2 to 4 weeks.SignificanceNot all temporal lobe epilepsy is refractory to medication, despite the presence of MTS. Until clinical trials indicate otherwise, surgery is not indicated but life-long medical treatment is advocated.     

Is reoperation an option for patients with temporal lobe epilepsy after failure of surgery?

PurposeEpilepsy surgery is the most efficacious therapeutic modality for patients with medically refractory focal epilepsies, but surgical failures remain a challenge to the epilepsy treatment team. The aim of present study was to evaluate the postoperative outcome of patients who underwent reoperation after a failed epilepsy surgery on the temporal lobe.MethodsWe systematically analyzed the results of comprehensive preoperative evaluations before the first surgery, and before and after reoperation in 17 patients with drug resistant temporal lobe epilepsies.ResultsOverall, 13 of 17 patients (76.5%) improved after reoperation: five patients (29.4%) were completely seizure free after reoperation (median duration 60 months, range 12–72); six patients (35.3%) were seizure free at least 12 month before observation points (median duration 120.5 months, range 35–155) and two patients (11.8%) had a decrease in seizure frequency. Four patients (23.5%) remained unchanged with respect to seizure frequency and severity. There was no correlation between the improvement in seizure outcome after reoperation and other clinical data except of the history of traumatic brain injury (TBI). The patients who had no history of TBI improved after reoperation, compared to patients with TBI (p = 0.044). The postoperative seizure outcome of patients with incongruent Video-EEG results before the first surgery (p = 0.116) and before reoperation (p = 0.622) was not poorer compared to patients with congruent Video-EEG results.ConclusionsReoperation can considerably improve the operative outcome of the first failed epilepsy surgery in patients with drug resistant temporal lobe epilepsies. Epilepsy centres should be encouraged to report the results of failed epilepsy surgeries.     

Prognostic factors in patients with mesial temporal lobe epilepsy

Purpose:   To disclose clinical, electrophysiologic, and neuroradiologic factors correlated to prognosis in patients with mesial temporal lobe epilepsy (MTLE).
Methods:   One hundred thirty-six MTLE patients were studied for family history, clinical characteristics, instrumental data [electroencephalography (EEG), video-EEG, neuroimaging], and outcome. The population was divided into drug-resistant (DR: 108 patients, 79.4%) and non–drug-resistant (NDR: 28 patients, 20.6%) groups; all variables were analyzed in the two groups.
Results:   The comparison between the two groups shows a relation between resistance to therapy and febrile seizures (FS) (DR 43.5% vs. NDR 17.8%, p = 0.008), mesial temporal sclerosis (MTS) (DR 64.8% vs. NDR 32.1%, p = 0.0025), early age at seizure onset (DR 23.1% vs. NDR 3.6% p = 0.0160), and epileptiform interictal abnormalities (DR 89.7% vs. NDR 68%, p = 0.010). FS were more frequent in patients with MTS than in patients without (46.28% vs. 26.3%, p = 0.0199). Sixty-nine patients underwent surgery and 85.3% of them had a good outcome.
Conclusion:   MTLE is a heterogeneous syndrome. Establishing the factors responsible for and associated with drug resistance is important for therapeutic purposes, as prompt diagnosis of drug resistance must lead to early surgical management. This study shows that FS, MTS, early age at seizure onset, and epileptiform interictal abnormalities are negative prognostic factors and that FS are related to MTS.     

Surgical outcome in adolescents with mesial temporal sclerosis: Is it different?

There are extensive studies evaluating mesial temporal sclerosis (MTS) in adults and limited studies in children, with adolescents being included within both patient populations. Our aim was to evaluate predictors of surgical outcome solely in adolescent patients with MRI- and pathology -proven MTS.The Yale Epilepsy Surgery Database was reviewed from 1987 to 2012 for adolescent patients with confirmed MTS on MRI and pathology who underwent temporal lobectomy and had greater than two-year postsurgical follow-up. Clinical and electrographic data were reviewed. Eighteen patients were identified.Eleven patients (61%) were seizure-free. All seven patients (39%) who were not seizure-free free were found to have lateralized ictal onset within one hemisphere involving two or more lobes on scalp EEG (p < 0.001). Of the 7 patients who were not seizure-free, 4 had a history of status epilepticus (compared to 1/11 seizure-free patients; p = 0.047), and 4 had lateralized hypometabolism involving two or more lobes within a hemisphere seen on PET (compared to 0/8 seizure-free patients; p = 0.002).A novel finding in our study was that lateralized (rather than localized) ictal onset on scalp EEG, lateralized hypometabolism on PET, and history of status epilepticus were risk factors for not attaining seizure freedom in adolescents with MTS who underwent temporal lobectomy.     

Towards a clinico-pathological classification of granule cell dispersion in human mesial temporal lobe epilepsies

The dentate gyrus (DG) plays a pivotal role in the functional and anatomical organization of the hippocampus and is involved in learning and memory formation. However, the impact of structural DG abnormalities, i.e., granule cell dispersion (GCD), for hippocampal seizure susceptibility and its association with distinct lesion patterns in epileptic disorders, such as mesial temporal sclerosis (MTS) remains enigmatic and a large spectrum of pathological changes has been recognized. Here, we propose a clinico-pathological classification of DG pathology based on the examination of 96 surgically resected hippocampal specimens obtained from patients with chronic temporal lobe epilepsy (TLE). We observed three different histological patterns. (1) A normal granule cell layer was identified in 11 patients (no-GCP; 18.7%). (2) Substantial granule cell loss was evident in 36 patients (referred to as granule cell pathology (GCP) Type 1; 37.5%). (3) Architectural abnormalities were observed in 49 specimens, including one or more of the following features: granule cell dispersion, ectopic neurons or clusters of neurons in the molecular layer, or bi-lamination (GCP Type 2; 51%). Cell loss was always encountered in this latter cohort. Seventy-eight patients of our present series suffered from MTS (81.3%). Intriguingly, all MTS patients displayed a compromised DG, 31 (40%) with significant cell loss (Type 1) and 47 (60%) with GCD (Type 2). In 18 patients without MTS (18.7%), seven displayed focally restricted DG abnormalities, either cell loss (n = 5) or GCD (n = 2). Clinical histories revealed a significant association between DG pathology patterns and higher age at epilepsy surgery (p = 0.008), longer epilepsy duration (p = 0.004), but also with learning dysfunction (p < 0.05). There was no correlation with the extent of pyramidal cell loss in adjacent hippocampal segments nor with postsurgical seizure relief. The association with long-term seizure histories and cognitive dysfunction is remarkable and may point to a compromised regenerative capacity of the DG in this cohort of TLE patients.     

Outcome after cortico-amygdalo-hippocampectomy in patients with severe bilateral mesial temporal sclerosis submitted to invasive recording

IntroductionAlthough some degree of bilateral hippocampal involvement might be frequent in patients with temporal lobe epilepsy, severe bilateral mesial temporal sclerosis (MTS) is very rare. We present our experience while treating patients with severe bilateral MTS submitted to invasive recordings.MethodsNine adult patients were studied. All patients had simple and complex partial seizures. All patients had bilateral independent interictal temporal lobe spiking and non-lateralizing video-EEG findings. MRI showed severe bilateral MTS and no other brain lesion. All patients had severe verbal and non-verbal memory deficits. All patients were submitted to invasive recordings after bilateral subdural grids implantation. Cortico-amygdalo-hippocampectomy (CAH) was performed in all patients on the side suggested by invasive recording. Follow-up time ranged from 5 to 10 years.ResultsInvasive video-EEG showed exclusively unilateral seizure onset in seven patients; in two patients, seizures originating from both temporal lobes were found (80% of them originated from one side). Five patients were submitted to left and four to right CAH. Seven patients were rendered seizure-free after surgery (Engel I); the other two were rated as Engel II. There was no additional memory decline. There was no surgical morbidity or mortality. Pathological examination showed MTS in all patients.DiscussionGood surgical outcome (77% seizure-free patients) could be obtained even in this apparently unsuitable group of patients. All patients benefit from the procedure. We did not see any cognitive decline in our patients with severe bilateral MTS. Patients with severe bilateral MTS would need invasive recordings despite any findings during surface video-EEG.