Autosomal dominant temporal lobe epilepsy in a Japanese family

We described autosomal dominant familial temporal lobe epilepsy in a Japanese family in which three individuals (one man and his two children) were affected. Their seizures commonly consisted of auditory symptoms and infrequent nocturnal generalized seizures. Repeated EEGs did not provide confirmative epileptiform discharges, but cranial MRI in one patient showed mild left hippocampal atrophy, and decreased glucose metabolism in the left temporal area was demonstrated by 18F-deoxyglucose positron emission tomography (FDG-PET). A confirmative diagnosis in one of the patients by FDG-PET was helpful for diagnosis in other patients in the same family. Seizure onset was adolescent commonly among the three patients, but better seizure control was achieved in the father as compared with the two children.     

Somatosensory rub evoked reflex epilepsy of a temporal lobe origin

Somatosensory rub reflex epilepsy, evoked by prolonged or repetitive cutaneous contact of a circumscribed body area, is an unusual form of reflex epilepsy. The peculiar complaints and the negative interictal electroencephalographic (EEG) recordings make it difficult to identify the epileptic origin. Here we report an unusual case whose seizures would be evoked by a touch or rub on a unilateral arm and shoulder, with a contralateral temporal lobe origin, demonstrated in immediate postictal single-photon emission computed tomography (SPECT).     

Hypergraphia in epilepsy: is there a specificity to temporal lobe epilepsy?

The purpose of this investigation was to determine the specificity of hypergraphia to temporal lobe epilepsy using the paradigm developed by Sachdev and Waxman (1981). One hundred and thirty-eight patients were sent a standard stimulus letter and the response rates were examined for the patient groups with temporal lobe epilepsy (N = 80), and without (N = 31), and mixed seizure types (N = 13). For those patients who responded, additional analyses involved the number of words per response and the presence/absence of any qualitative indices of the postulated interictal behavioural syndrome of temporal lobe epilepsy. The results were interpreted in the light of the contemporary definitions of hypergraphia and were related to the larger literature concerned with personality and behavioural change in temporal lobe epilepsy.     

Partial epilepsy syndrome in a Gypsy family linked to 5q31.3-q32

Purpose:   The restricted genetic diversity and homogeneous molecular basis of Mendelian disorders in isolated founder populations have rarely been explored in epilepsy research. Our long-term goal is to explore the genetic basis of epilepsies in one such population, the Gypsies. The aim of this report is the clinical and genetic characterization of a Gypsy family with a partial epilepsy syndrome.
Methods:   Clinical information was collected using semistructured interviews with affected subjects and informants. At least one interictal electroencephalography (EEG) recording was performed for each patient and previous data obtained from records. Neuroimaging included structural magnetic resonance imaging (MRI). Linkage and haplotype analysis was performed using the Illumina IVb Linkage Panel, supplemented with highly informative microsatellites in linked regions and Affymetrix SNP 5.0 array data.
Results:   We observed an early-onset partial epilepsy syndrome with seizure semiology strongly suggestive of temporal lobe epilepsy (TLE), with mild intellectual deficit co-occurring in a large proportion of the patients. Psychiatric morbidity was common in the extended pedigree but did not cosegregate with epilepsy. Linkage analysis definitively excluded previously reported loci, and identified a novel locus on 5q31.3-q32 with an logarithm of the odds (LOD) score of 3 corresponding to the expected maximum in this family.
Discussion:   The syndrome can be classified as familial temporal lobe epilepsy (FTLE) or possibly a new syndrome with mild intellectual deficit. The linked 5q region does not contain any ion channel–encoding genes and is thus likely to contribute new knowledge about epilepsy pathogenesis. Identification of the mutation in this family and in additional patients will define the full phenotypic spectrum.     

A novel GEFS+ locus on 12p13.33 in a large Roma family

We report a clinical and genetic follow-up study of a large consanguineous family from an endogamous Roma/Gypsy sub-isolate, where previous analyses have been inconclusive. Detailed clinical information was collected through extensive field work, repeat interviews and electrophysiological and neuroimaging investigations on 18 affected subjects. The phenotype is compatible with GEFS+, with some unusual features, e.g. GTCS persisting into late adult life and high frequency of focal epilepsy. Updated genealogical information, a dense SNP genome scan and linkage analysis identified a novel GEFS+ locus on 12p13.33, where 13 affected individuals from two branches of the kindred shared an identical haplotype. This haplotype was not found in the 3rd branch or in the remaining 21 Roma epilepsy families in our collection. Genetic heterogeneity and evidence of bilineality were found despite the inbreeding and endogamous nature of the family and population of origin. These data add to the growing evidence of lack of founder effect and significant genetic heterogeneity in epilepsy in the Roma/Gypsy population. Sequencing of the coding regions of three genes linked to neurotransmitter transport and release, SLC6A12, SLC6A13 and ERC1, on 12p did not identify a causative mutation.     

Resistance to phenobarbital extends to phenytoin in a rat model of temporal lobe epilepsy

PURPOSE: Most patients who are resistant to the first antiepileptic drug (AED) treatment are also resistant to a treatment with a second or third AED, indicating that patients who have an inadequate response to initial treatment with AEDs are likely to have refractory epilepsy. Animal models of refractory epilepsy are important tools to study mechanisms of AED resistance and develop new treatment strategies for counteracting resistance. We have recently described a rat model of temporal lobe epilepsy (TLE), in which spontaneous recurrent seizures (SRS) develop after a status epilepticus induced by sustained electrical stimulation of the basolateral amygdala. Prolonged treatment of epileptic rats with phenobarbital (PB) resulted in two subgroups, PB responders and PB nonresponders. METHODS: In the present study we examined if rats with PB-resistant seizures are also resistant to phenytoin (PHT), using continuous EEG/video recording of spontaneous seizures. RESULTS: First, a new group of 15 epileptic rats was produced and selected by treatment with PB into responders (8 rats) and nonresponders (6 rats), respectively. During subsequent treatment with PHT, the doses of PHT had to be individually adjusted for each rat to avoid toxicity. Treatment with PHT led to complete seizure control in two animals and a >50% reduction of seizure frequency in three other rats, which were considered PHT responders. In nine of the remaining rats, PHT did not exert any clear anticonvulsant effect, so that these rats were considered nonresponders. Plasma levels of PHT did not differ significantly between responders and nonresponders. When comparing the PB and PHT nonresponder groups, five of the six PB-resistant rats (83%) were also resistant to PHT, demonstrating that rats that have an inadequate response to initial treatment with PB are likely to be also resistant to treatment with a second AED. CONCLUSIONS: The AED-resistant rats of our model meet the definition of pharmacoresistance in animal models, that is, persistent seizure activity not responding to at least two AEDs at maximum tolerated doses. This new model of pharmacoresistant TLE may be useful in the targeted development of new therapies for refractory epilepsy.     

Focal cortical dysplasias in temporal lobe epilepsy surgery: Challenge in defining unusual variants according to the last ILAE classification

ObjectiveFocal cortical dysplasias (FCDs) represent a common architectural cortical disorder underlying pharmacoresistant focal epilepsy. The recent ILAE classification defines different types of FCDs based on their histopathological features, MRI imaging, and presumed pathogenesis; however, their clinical features and their prognostic significance are still incompletely defined. In addition, the combination of different histopathological abnormalities can represent “unusual” subtypes that can be difficult to classify. The aim of our study was to analyze the incidence and the significance of these “unusual” subtypes of FCDs in drug-resistant mesial temporal lobe epilepsy (MTLE).MethodsWe retrospectively analyzed 133 patients consecutively submitted to tailored anteromesial temporal lobe resection for pharmacoresistant MTLE. Seizure onset, seizure duration, age at surgery, and postoperative seizure outcome were evaluated in relation to the different neuropathological groups defined according to the new ILAE classification.ResultsFocal cortical dysplasias were found in 80 out of 133 patients. Six patients were affected by isolated FCD type I, 12 patients by FCD type II, and 44 patients by FCD type III. Furthermore, we found 18 “atypical” cases (20.5% of all FCD cases and 26.6% of FCDs associated with a principal lesion): 10 cases of associated FCD type II–hippocampal sclerosis (HS) and 8 cases associated with FCD II–epilepsy-associated tumors (EATs).ConclusionOur results indicate that “unusual” subtypes of FCDs, in particular associated FCD type II, are not uncommon findings, suggesting that they deserve a classification recognition. Similarities in seizure outcome and immunohistochemical and molecular evidences, shared by FCD type II + EATs and EATs, suggest a common pathogenic link. The choice to create a specific unifying class or, on the contrary, to also include “associated FCD type II” in the definition of the new unifying class FCD type III should be further discussed.     

Versive seizures of probable occipital origin in a case of posttraumatic epilepsy

Oculoclonic versive elemental partial seizures developed in a 38-year-old male, who has suffered from a grave traumatism by impaling. Posttraumatic epileptic symptoms could be related to anatomical lesions at the exit orifice in the right occipitoparietal region.     

Relation of sorting impairment to hippocampal damage in temporal lobe epilepsy

One hundred and twelve patients with left (n=65) or right (n=47) temporal lobe epilepsy (TLE), associated with mesial or lateral temporal lobe lesion, were compared to 53 patients with left (n=30) or right (n=23) frontal lobe epilepsy (FLE), in order to explore the contributions of hippocampal lesions and of memory deficits to sorting impairment. Thirty-six healthy subjects of similar age and education were controls. The Modified Wisconsin Card Sorting Test (MWCST) was used to explore sorting ability. The two-syllable word span and consistent long-term retrieval from the selective reminding procedure for word-list learning were used to evaluate memory. Raven's Coloured Progressive Matrices and Attentive Matrices served to control for abstract reasoning and attention. Left FLE patients and TLE patients with left hippocampal sclerosis were significantly impaired on MWCST, short-term memory, and word learning. TLE patients with other left hippocampal lesions were also impaired on MWCST, although not significantly so. Analysis of individual scores showed that 42% of TLE patients with left hippocampal sclerosis, 14% of TLE patients with other hippocampal lesions, 63% of left FLE patients, and 30% of right FLE patients were impaired on the MWCST. In patients with left hippocampal sclerosis, MWCST score was associated with the learning score provided by the selective reminding procedure and Raven's Coloured Progressive Matrices score, whereas in FLE patients, MWCST score was associated with Attentive Matrices score. These results suggest that only some TLE patients, i.e. those with hippocampal damage, may be expected to be impaired on card sorting. The impaired sorting ability of these TLE patients may be due to involvement of the hippocampal function in forming associations or in registering new information.     

Influence of anxiety on memory performance in temporal lobe epilepsy

This study examined the degree to which anxiety contributed to inconsistent material-specific memory difficulties among 243 patients with temporal lobe epilepsy from the Multisite Epilepsy Study. Visual memory performance on the Rey Complex Figure Test (RCFT) was poorer for those with high versus low levels of anxiety but was not found to be related to the TLE side. The verbal memory score on the California Verbal Learning Test (CVLT) was significantly lower for patients with left-sided TLE than for patients with right-sided TLE with low anxiety levels but equally impaired for those with high anxiety levels. These results suggest that we can place more confidence in the ability of verbal memory tests like the CVLT to lateralize to left-sided TLE for those with low anxiety levels, but that verbal memory will be less likely to produce lateralizing information for those with high anxiety levels. This suggests that more caution is needed when interpreting verbal memory tests for those with high anxiety levels. These results indicated that RCFT performance was significantly affected by anxiety and did not lateralize to either side, regardless of anxiety levels. This study adds to the existing literature which suggests that drawing-based visual memory tests do not lateralize among patients with TLE, regardless of anxiety levels.     

颞叶癫(癎)患者前颞叶切除对认知功能影响的短期观察

目的评价难治性颞叶癫患者一侧标准前颞叶切除术后短期内对认知功能的影响。方法23例左前颞叶切除和42例右前颞叶切除患者在术前及术后3个月分别行韦氏智力及韦氏记忆量表测定,观察相应指标的变化。结果65例标准前颞叶切除患者术前言语智商(VIQ)、操作智商(PIQ)及全量表智商(FIQ)各值分别为80.5±15.6、89.9±16.2和83.3±15.2;术后3个月为74.3±16.1、81.8±15.9和76.1±15.2,术后各值虽较术前下降,但经配对t检验,差异无统计学意义(P>0.05)。记忆商数(MQ)值术前为70.7±20.5,术后3个月为57.5±22.3,较术前下降明显(P<0.05)。左前颞叶切除患者术前VIQ、PIQ、FIQ及MQ各值分别为78.6±15.6、87.5±17.8、81.1±16.2和69.1±22.4,术后3个月分别为66.5±11.9、77.9±18.6、69.7±14.2和49.9±18.8,术后各项指标下降明显,与术前比较差异均有统计学意义(P<0.05);右前颞叶切除患者术前VIQ、PIQ、FIQ及MQ各值分别为81.9±15.7、91.9±14.9、84.9±14.4和71.8±19.3,术后3个月分别为80.2±16.6、84.7±13.1、81.0±14.3和63.3±23.3,术后所有指标下降均无统计学意义(P>0.05)。结论一侧标准右前颞叶切除患者短期内对认知功能的影响较左前颞叶切除者小。     

Endogenous neurosteroids modulate epileptogenesis in a model of temporal lobe epilepsy

Neurosteroids modulate seizure susceptibility, but their role in the regulation of epileptogenesis is unknown. Status epilepticus (SE) induces temporal lobe epileptogenesis following a latent period in which glial cells are activated. Here, we found that P450scc, the rate-limiting enzyme in steroid synthesis, is upregulated in hippocampal glia during the latent period after pilocarpine-induced SE in rats. More prolonged SE was associated with greater P450scc expression and longer latencies to the development of seizures, suggesting that enhanced steroid synthesis retards epileptogenesis. The 5alpha-reductase inhibitor finasteride, which blocks neurosteroid synthesis, reduced the latent period, indicating that glia-derived neurosteroids may be antiepileptogenic.     

Ictal apnea linked to contralateral spread of temporal lobe seizures: Intracranial EEG recordings in refractory temporal lobe epilepsy

Purpose: Respiratory mechanisms are implicated in sudden unexpected death in epilepsy (SUDEP). We previously demonstrated a high incidence of ictal hypoxemia in temporal lobe seizures. We now report on the temporal relationship between ictal apnea and seizure onset and spread in patients undergoing video‐EEG (electroencephalography) telemetry (VET) with intracranial electrodes. Methods: Ten patients with medically refractory temporal lobe epilepsy (TLE) undergoing VET were studied. Data from synchronously recorded digital pulse oximetry (SaO₂), end‐tidal CO₂ (ETCO₂), nasal airflow, abdominal excursions, and electrocardiography were obtained. Results: Sixty‐one seizures were captured. SaO₂ in the ictal/postictal period was available for 52 seizures, apnea onset times for 27 seizures, and ETCO₂ for 16 seizures. Apneas occurred only when seizures spread to the contralateral temporal lobe. The mean delay to apnea onset was significantly shorter after contralateral seizure spread (2.87 s) than after seizure onset (58.4 s); p < 0.001. The mean SaO₂ nadir with partial seizures or partial seizures prior to secondary generalization was 89.4 ± 8.6% (91.5, 69–100). Following generalized convulsions the mean oxygen saturation nadir was 75.8 ± 10.6% (78.5, 58–90). ETCO₂ elevations occurred with each ictal desaturation below 85%. Conclusions: There is a close temporal relationship between spread of seizures to the contralateral hemisphere and the onset of seizure‐associated apnea. Apnea onsets are more tightly linked to time of contralateral spread than to time of seizure onset. Patients with TLE in whom there is evidence of contralateral seizure spread may be at higher risk for ictal‐related respiratory dysfunction than those in whom seizures remain unilateral.     

颞叶癫痫患者颞叶切除术前后的记忆评估

目的探讨颞叶切除术对颞叶癫痫患者术后记忆功能的影响。方法回顾性分析2012年7月至2013年12月收治的17例颞叶癫痫患者的临床资料,采用成人韦氏量表测量患者颞叶切除术前及术后6个月记忆商（MQ）值。结果术前MQ平均值为（89.94±4.45）,术后6个月为（104.76±4.96）,差异显著（P〈0.05）。术前长时MQ值为（37.53±1.95）,术后为（40.53±1.70）,术后长时记忆改善不明显（P〉0.05）。术前短时记忆MQ值为（46.29±2.43）,术后为（54.94±3.18）;术前瞬时MQ均值为（6.12±1.37）,术后为（9.29±1.00）;术后短时及瞬时MQ均较术前有显著差异（P〈0.05）。EngleⅠ～Ⅱ级15例病人中,术后MQ较术前改善11例,无明显变化4例;EngleⅢ～Ⅳ级2例病人中,MQ值较术前下降1例,无改变1例。结论颞叶切除术可明显改善颞叶癫痫患者术后MQ。     

Structural and functional asymmetry of medial temporal subregions in unilateral temporal lobe epilepsy: A 7T MRI study

Mesial temporal lobe epilepsy (TLE) is a common neurological disorder affecting the hippocampus and surrounding medial temporal lobe (MTL). Although prior studies have analyzed whole‐brain network distortions in TLE patients, the functional network architecture of the MTL at the subregion level has not been examined. In this study, we utilized high‐resolution 7T T2‐weighted magnetic resonance imaging (MRI) and resting‐state BOLD‐fMRI to characterize volumetric asymmetry and functional network asymmetry of MTL subregions in unilateral medically refractory TLE patients and healthy controls. We subdivided the TLE group into mesial temporal sclerosis patients (TLE‐MTS) and MRI‐negative nonlesional patients (TLE‐NL). Using an automated multi‐atlas segmentation pipeline, we delineated 10 MTL subregions per hemisphere for each subject. We found significantly different patterns of volumetric asymmetry between the two groups, with TLE‐MTS exhibiting volumetric asymmetry corresponding to decreased volumes ipsilaterally in all hippocampal subfields, and TLE‐NL exhibiting no significant volumetric asymmetries other than a mild decrease in whole‐hippocampal volume ipsilaterally. We also found significantly different patterns of functional network asymmetry in the CA1 subfield and whole hippocampus, with TLE‐NL patients exhibiting asymmetry corresponding to increased connectivity ipsilaterally and TLE‐MTS patients exhibiting asymmetry corresponding to decreased connectivity ipsilaterally. Our findings provide initial evidence that functional neuroimaging‐based network properties within the MTL can distinguish between TLE subtypes. High‐resolution MRI has potential to improve localization of underlying brain network disruptions in TLE patients who are candidates for surgical resection.     

Absence of gender effect on amygdala volume in temporal lobe epilepsy

Sexual dimorphism has already been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). This study evaluated the effect of gender on amygdala volume in patients with TLE-MTS. One hundred twenty-four patients with refractory unilateral or bilateral TLE-MTS who were being considered for epilepsy surgery underwent a comprehensive presurgical evaluation and MRI. Amygdalas of 67 women (27 with right; 32 with left, and 8 with bilateral TLE) and 57 men (22 with right, 30 with left, and 5 with bilateral TLE) were manually segmented. Significant ipsilateral amygdala volume reduction was observed for patients with right and left TLE. No gender effect on amygdala volume was observed. Contralateral amygdalar asymmetry was observed for patients with right and left TLE. Although no gender effect was observed on amygdala volume, ipsilateral amygdala volume reductions in patients with TLE might be related to differential rates of cerebral maturation between hemispheres.