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PubMed2002

Pilocarpine-induced status epilepticus results in mossy fiber sprouting and spontaneous seizures in C57BL/6 and CD-1 mice.

Several rodent models are available to study the cellular mechanisms associated with the development of temporal lobe epilepsy (TLE), but few have been successfully transferred to inbred mouse strains commonly used in genetic mutation studies. We examined spontaneous seizure development and correlative axon sprouting in the dentate gyrus of CD-1 and C57BL/6 mice after systemic injection of pilocarpine. Pilocarpine induced seizures and status epilepticus (SE) after systemic injection in both strains, although SE onset latency was greater for C57BL/6 mice. There were also animals of both strains which did not experience SE after pilocarpine treatment. After a period of normal behavior for several days after the pilocarpine treatment, spontaneous tonic-clonic seizures were observed in most CD-1 mice and all C57BL/6 that survived pilocarpine-induced SE. Robust mossy fiber sprouting into the inner molecular layer was observed after 4-8 weeks in mice from both strains which had experienced SE, and cell loss was apparent in the hippocampus. Mossy fiber sprouting and spontaneous seizures were not observed in mice that did not experience a period of SE. These results indicate that pilocarpine induces spontaneous seizures and mossy fiber sprouting in both CD-1 and C57BL/6 mouse strains. Unlike systemic kainic acid treatment, the pilocarpine model offers a potentially useful tool for studying TLE development in genetically modified mice raised on the C57BL/6 background.

Animals↗

PubMed2002

Death in epilepsy with special attention to suicide cases.

To examine clinical features of cases of death among epilepsy patients as a case-control study, with special attention to suicide, we analyzed the records of 43 deceased patients with well-classified epilepsy. The subjects were compared with 1,722 control patients who showed definite subtypes of epilepsy. As a result, among the major causes of death, 13 of the subjects suffered accidents (mostly drowning), ten experienced sudden unexpected death, seven had status epilepticus, and six committed suicide. There were no significant differences with regard to clinical variables except for psychotic episodes, which were more frequently encountered in subjects than in controls (chi(2)=6.771, P=0.009, Yates' modification). Statistically significant differences were found by epilepsy type as well (chi(2)=14.72, P=0.002), with temporal lobe epilepsy (TLE) proving to be most closely associated with death among the epilepsy patients. Further, suicide was only encountered in patients with TLE and the association was statistically significant (chi(2)=5.119, P=0.024). Half of those who committed suicide (n=3), did so by jumping in front of an oncoming train while in the midst of an episode of postictal psychosis. In conclusion, most cases of suicide in patients with epilepsy were found to be the result of an immediate causal relationship with ictal or interictal epileptic manifestations, rather than a result of augmentation of psychosocial stressors generated by a long-standing handicap derived from the severe illness.

Adult↗

PubMed2003

Intelligence in childhood epilepsy syndromes.

UNLABELLED: Intellectual deficits play a significant role in the psychosocial comorbidity of children with epilepsy. Early educational intervention is critical. OBJECTIVE: This study aims to determine the intellectual ability of children with common childhood epilepsy syndromes-generalised idiopathic epilepsy (GIE), generalised symptomatic epilepsy (GSE), temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), central epilepsy (CE) and non-localised partial epilepsy (PE). METHODS: A prospective consecutive series of 169 children were recruited. Epilepsy syndrome was identified by clinical data, seizure semiology, interictal and ictal EEG in each child, using International League Against Epilepsy criteria. Each child had neuropsychology assessment using age-normed and validated instruments. After adjusting for important epilepsy variables, 95% confidence intervals were generated for mean full-scale intelligence quotient (FSIQ) using ANCOVA. RESULTS: Significant differences between epilepsy syndrome groups were found for age of onset (P<0.001), duration of active epilepsy (P=0.027), seizure frequency (P=0.037) and polytherapy (P=0.024). Analysing FSIQ, children with GIE, CE and TLE performed best, and did not differ statistically. Children with GSE had a statistically lower FSIQ than other syndrome groups except PE. FLE functioned significantly better than GSE, but did not differ statistically from other groups. CONCLUSIONS: In childhood epilepsy, delineation of the syndrome has important implications when considering intellectual potential. This information is invaluable in planning educational interventions and supporting the family.

Adolescent↗

PubMed1998

Heart rate variability in patients with epilepsy.

Autonomic function was studied by the use of spectral analysis of heart-rate variability in patients with epilepsy in relation to type of epilepsy and anti-epileptic drug therapy. A total of 21 patients with juvenile myoclonic epilepsy (JME) and 21 with temporal lobe epilepsy (TLE) were included; 18 patients were treated with carbamazepine (CBZ), 16 with valproate (VPA) and seven with phenytoin (PHT). One healthy drug free control, matched for age and sex, was selected for each patient. Patients and controls underwent an ambulatory 24 h EKG. Heart-rate variability was analyzed in time and frequency domains. Patients with TLE had significantly lower S.D. of the RR-intervals, lower low frequency power and a lower low frequency/high frequency power ratio than their controls. A lower low frequency/high frequency power ratio was the only significant difference between the JME patient group and their controls. Treatment, however, may have had a considerable influence on the heart rate variability in the epilepsy patients. Patients on CBZ had significantly lower S.D. of RR-intervals, low frequency power and a low frequency/ high frequency power ratio than did their matched healthy drug free controls. The ratio of low frequency/high frequency power was also lower in patients on VPA compared with their controls, but apart from that no differences could be demonstrated between this treatment group and the controls. In conclusion, patients with epilepsy appear to have an altered autonomic control of the heart, with a reduction in some heart-rate variability measures, suggesting a decreased sympathetic tone, which may be related to the drug therapy or the epilepsy as such. Further studies are warranted to explore these changes and their possible relevance for sudden death in epilepsy.

Adult↗

PubMed1998

Supragranular mossy fiber sprouting is not necessary for spontaneous seizures in the intrahippocampal kainate model of epilepsy in the rat.

In a previous study, we suggested a dissociation between spontaneous recurrent epileptic seizures (SRS) and hippocampal supragranular mossy fiber sprouting (MFS) in the pilocarpine model of epilepsy (PILO). One possible explanation, would be that SRS in the PILO model do not originate in the hippocampus and thus would not depend on MFS. In the present study, we investigated whether MFS is necessary for the SRS that develop after a small intrahippocampal dose of kainic acid (KA), a model where seizures are more likely to start in the hippocampus. Intrahippocampal injections of KA were performed in rats, with and without the concomitant administration of cycloheximide (CHX) (0.5 microg of KA and 6 microg of CHX). After injection, recording electrodes were positioned in the same stereotaxic location. Here again, CHX was able to completely block (5/8 animals) MFS, visualized by neo-Timm staining, without altering the frequency and intensity of spontaneous ictal and interictal EEG events. From these data, we can conclude that, in the intra-hippocampal KA model, MFS is not necessary for the occurrence of ictal events. We suggest that CHX can be used together with classic epileptogenic agents, as a means to study temporal lobe epilepsy (TLE) without the contributing effect of MFS--as seen in TLE patients with mass lesions in the lateral temporal lobe.

Animals↗

PubMed1998

Amygdala damage in experimental and human temporal lobe epilepsy.

The amygdala complex is one component of the temporal lobe that may be damaged unilaterally or bilaterally in children and adults with temporal lobe epilepsy (TLE) or following status epilepticus. Most MR (magnetic resonance) imaging studies of epileptic patients have shown that volume reduction of the amygdala ranges from 10-30%. In the human amygdala, neuronal loss and gliosis have been reported in the lateral and basal nuclei. Studies in rats have more specifically identified the amygdaloid regions that are sensitive to status epilepticus-induced neuronal damage. These areas include the medial division of the lateral nucleus, the parvicellular division of the basal nucleus, the accessory basal nucleus, the posterior cortical nucleus, and portions of the anterior cortical and medial nuclei. Otherwise, other amygdala nuclei, such as the magnocellular and intermediate divisions of the basal nucleus and the central nucleus, remain relatively well preserved. Amygdala kindling studies in rats have shown that the density of a subpopulation of GABAergic inhibitory neurons that also contain somatostatin may be reduced even after a low number of generalized seizures. While analyses of histological sections and MR images indicate that in approximately 10% of TLE patients, seizure-induced damage is isolated to the amygdala, more often amygdala damage is combined with damage to the hippocampus and/or other brain areas. Moreover, recent data from rodents and nonhuman primates suggest that structural and functional alterations caused by seizure activity originating in the amygdala are not limited to the amygdala itself, but may also affect other temporal lobe structures. The information gathered so far on damage to the amygdala in epilepsy or after status epilepticus suggests that local alterations in inhibitory circuitries may contribute to a lowered seizure threshold and greater excitability within the amygdala. Furthermore, damage to select nuclei in the amygdala may predict impairment of performance in behavioral tasks that depend on the integrity of the amygdaloid circuits.

Amygdala↗

PubMed2001

Structural brain abnormalities in patients with schizophrenia, epilepsy, and epilepsy with chronic interictal psychosis.

Chronic interictal psychotic syndromes, often resembling schizophrenia, develop in some patients with epilepsy. Although widespread brain abnormalities are recognized as characteristic of schizophrenia, prevailing but controversial hypotheses on the co-occurrence of epilepsy and psychosis implicate left temporal lobe pathology. In this study, quantitative MRI methods were used to address the regional specificity of structural brain abnormalities in patients with epilepsy plus chronic interictal psychosis (E+PSY, n=9) relative to three comparison groups: unilateral temporal lobe epilepsy without chronic psychosis (TLE, n=18), schizophrenia (SCZ, n=46), and healthy control subjects (HC, n=57). Brain measures, derived from a coronal spin-echo MRI sequence, were adjusted for age and cerebral volume. Relative to HC, all patient groups had ventricular enlargement and smaller temporal lobe, frontoparietal, and superior temporal gyrus gray matter volumes, with the extent of these abnormalities greatest in E+PSY. Only TLE had temporal lobe white matter deficits, as well as smaller hippocampi, which were ipsilateral to the seizure focus. Structural brain abnormalities in E+PSY are not restricted to the left temporal lobe. The confluence of cortical gray matter deficits in E+PSY and SCZ suggests salience to chronic psychosis.

Adult↗

PubMed2003

Language lateralization in patients with temporal lobe epilepsy: a comparison of functional transcranial Doppler sonography and the Wada test.

This study prospectively investigates whether noninvasive functional transcranial Doppler sonography (fTCD) is a useful tool to determine hemispheric language lateralization in the presurgical evaluation of patients with medically intractable temporal lobe epilepsy (TLE). fTCD results were compared with the Wada test as the gold standard. Wada test and fTCD were performed in 13 patients suffering from TLE. fTCD continuously measured blood flow velocities in both middle cerebral arteries, while the patient was performing a cued word generation task. During the Wada test, spontaneous speech, comprehension, reading, naming, and repetition were investigated. A laterality index (LI) was obtained by both procedures. Due to a lack of an acoustic temporal bone window, fTCD could not be performed in two patients (15%). In 9 of the remaining 11 patients hemispheric language dominance was found on the left side, in 1 patient on the right side, and 1 patient showed bihemispheric language representation. In all patients fTCD and the Wada test were in good agreement regarding hemispheric language lateralization, and the LI of both techniques were highly correlated (r = 0.776, P = 0.005). fTCD gives predictions of hemispheric language dominance consistent with the Wada test results even in children, patients with low IQ, and nonnative speakers. It is an alternative to the Wada test in determining language lateralization in patients with temporal lobe epilepsy.

Adolescent↗

PubMed2003

Clinical differences in patients with unilateral hippocampal sclerosis and unitemporal or bitemporal epileptiform discharges.

PURPOSE: To investigate factors determining the presence of bilateral interictal epileptiform discharges (IEDs) in temporal lobe epilepsy (TLE) with unilateral hippocampal sclerosis (HS). METHODS: We analysed data of 243 TLE patients with unilateral HS who had long-term video-EEG. Eighty-one patients (33%) had bitemporal IEDs. RESULTS: We categorised patients into a unilateral group (UG), a bilateral group (BG) according to presence of bitemporal IEDs. We found no difference between UG and BG regarding epilepsy duration, secondarily generalised seizures, and history of febrile seizures. Mean seizure frequency was significantly higher in the BG (UG: 7.7+/-14.7 seizures/month; BG: 13+/-35 seizures/month, P=0.01). We found a significant correlation between late epilepsy onset and the presence of bitemporal IEDs. The mean age at epilepsy onset in UG was 10.1+/-7.9 years, while in BG it was 13+/-9.2 years (P=0.02). CONCLUSIONS: The traditional concept of the evolution of mirror focus cannot apply for humans because the duration of epilepsy does not influence the evolution of bitemporal IEDs. Other factors, i.e. age at onset and seizure frequency may play a role in this process. The association between the higher seizure frequency and mirror foci indicates that the development of mirror focus depends on seizures and not on a progressive 'interictal' epileptogenesis.

Adolescent↗

PubMed2001

Interpretation of interdependencies in epileptic signals using a macroscopic physiological model of the EEG.

This paper presents a neurophysiologically relevant model in which vectorial epileptiform electroencephalographic (EEG) signals are produced from multiple coupled neural populations. This model is used to evaluate the performances of non-linear regression analysis as a method to characterize couplings between neural populations from EEG signals they produce. Two quantities, estimated on generated signals, namely the non-linear correlation coefficient and the direction index, are related to the degree and direction of coupling parameters of the model. Their statistical behavior is first studied on a set of signals simulated for relevant configurations of the model. They are then measured on real stereoelectroencephalographic (SEEG) signals. Results obtained in three patients suffering from temporal lobe epilepsy (TLE) show that abnormal functional couplings between cerebral structures, that establish during seizures, can be interpreted in terms of causality. Perspectives are oriented to the identification of epileptogenic networks in TLE.

Algorithms↗

PubMed2001

Cortical current density reconstruction of interictal epileptiform activity in temporal lobe epilepsy.

OBJECTIVE: To investigate the value of cortical current density (CCD) reconstruction in localizing intracranial generators of interictal epileptiform activity in mesial and lateral temporal lobe epilepsy (TLE). METHODS: Non-linear minimum L(1)-norm CCD reconstruction (with current sources restricted to the individual cortical surface and a realistic boundary element method (BEM) head model) was used to localize and to study the propagation of interictal epileptiform EEG activity in 13 pre-surgical patients with TLE. RESULTS: In all but one patient with mesial temporal lesions, an initial activation maximum corresponding to the ascending part of averaged sharp waves was found in the ipsilateral anterior basolateral temporal lobe, mostly extending up to the affected mesial structures whose resection rendered the patients seizure-free. In all 3 patients with lateral temporal lesions, the activation was initially confined to temporal neocortex immediately adjacent to the epileptogenic lesion. Towards the peak of sharp waves, two patients showed a propagation of interictal activity to anterior and posterior and partly contralateral temporal regions. A conventional EEG analysis based on amplitude maxima or phase reversal would have missed the initial onset zone. CONCLUSIONS: The findings demonstrate that CCD reconstruction can be a valuable additional non-invasive component in the multimodal pre-surgical evaluation of epilepsy patients.

Adolescent↗

PubMed2002

Relative utility of sphenoidal and temporal surface electrodes for localization of ictal onset in temporal lobe epilepsy.

OBJECTIVES: To compare localization of ictal onsets in patients with possible temporal lobe epilepsy (TLE) using true temporal electrodes (TE), at positions T1 and T2, and sphenoidal electrodes (SpE). METHODS: A total of 101 ictal tracings in 31 patients with possible TLE were independently reviewed by two readers and graded as meeting (TE+, SpE+) or not meeting (TE-, SpE-) strictly-defined mesial temporal onset criteria. TE and SpE were reviewed in separate montages, with ad lib adjustment of filters and sensitivity. Discrepancies between TE and SpE were noted, with inter-reader disagreements resolved by a third reviewer. RESULTS: All seizures scored as SpE+ were also scored as TE+, with one exception. The sole SpE+/TE- seizure did not add incremental useful information in that patient, who had other, similar seizures which were TE+. Five seizures in 4 patients were scored as TE+ and SpE-, most due malfunction of SpE prior to seizure onset. One of these seizures was scored TE+/SpE- in a patient believed to have neocortical epilepsy. CONCLUSIONS: In this series, SpE were unnecessary to detect seizures which meet strict mesial temporal onset criteria and did not yield useful information for surgical evaluation beyond that provided by TE. It remains unclear if SpE are more helpful than TE in distinguishing lateral from mesial ictal onset. Digital review of ictal tracings may resolve discrepancies between TE and SpE.

Adolescent↗

PubMed2004

Fever, genes, and epilepsy.

About 13% of patients with epilepsy have a history of febrile seizures (FS). Studies of familial forms suggest a genetic component to the epidemiological link. Indeed, in certain monogenic forms of FS, for which several loci have been reported, some patients develop epilepsy with a higher risk than in the general population. Patients with generalised epilepsy with febrile seizures plus (GEFS+) can have typical and isolated FS, FS lasting more beyond age 6 years, and subsequent afebrile (typically generalised) seizures. Mutations associated with GEFS+ were identified in genes for subunits of the voltage-gated sodium channel and the gamma2 subunit of the ligand-gated GABAA receptor. Screening for these genes in patients with severe myoclonic epilepsy in infancy showed de novo mutations of the alpha1 subunit of the voltage-gated sodium channel. Antecedent FS are commonly observed in temporal-lobe epilepsy (TLE). In sporadic mesial TLE-characterised by the sequence of complex FS in childhood, hippocampal sclerosis, and refractory temporal-lobe seizures-association studies suggested the role of several susceptibility genes. Work on some large pedigrees also suggests that FS and temporal-lobe seizures may have a common genetic basis, whether hippocampus sclerosis is present or not. The molecular defects identified in the genetic associations of FS and epileptic seizures are very attractive models to aid our understanding of epileptogenesis and susceptibility to seizure-provoking factors, especially fever.

Epilepsy↗

PubMed2003

Psychopathological profile in patients with severe bilateral hippocampal atrophy and temporal lobe epilepsy: evidence in support of the Geschwind syndrome?

Bilateral symmetrical hippocampal atrophy (BHA) has been implicated as a possible causal element in various neuropsychiatric disorders, in particular depressive disorder and schizophrenia. To test the hypothesis that bilateral symmetrical severe volume loss of the hippocampi is of causal relevance to these psychiatric syndromes rather than an epiphenomenon we assessed the psychopathology in a group of patients with temporal lobe epilepsy (TLE) and very severe bilateral symmetrical hippocampal atrophy and compared it with that of a patient control group. Patients with TLE and hippocampal volumes smaller than three standard deviations below the mean of a control population were identified and compared with a matched patient population with normal hippocampal volumes. Psychopathology was assessed by blinded trained psychiatrists using the Present State Examination and Neurobehavioral Inventory. The prevalence of psychiatric syndromes was high in both patient groups; however, there was no significant difference between the two groups. With use of the more specific Neurobehavioral Inventory a psychopathological pattern reminiscent of the Geschwind syndrome emerged when patients with BHA were characterized by caregivers. While BHA does not result in an increased prevalence of specific psychiatric syndromes, specific symptoms that characterize the Geschwind syndrome like hypergraphia and hyposexuality might be pathogenically related to hippocampal atrophy.

Adult↗

PubMed2002

Positron emission tomography and epilepsy.

PURPOSE: This review examines the current role of positron emission tomography (PET) in the investigation and management of patients with epilepsy. PROCEDURES: A literature review utilizing MEDLINE(R) and other sources was undertaken. For the comparison of the accuracy of PET with magnetic resonance imaging (MRI) for seizure focus localization, only publications since 1994 were examined. Individual patient data was tabulated to provide figures for seizure focus localization rates for different types of focal epilepsy and the prognostic value of PET findings for epilepsy surgery outcome. RESULTS: The majority of PET studies used 2-deoxy-2-[18F]fluoro-D-glucose (FDG). The epileptogenic sites typically show reduced FDG uptake (hypometabolism). In patients with intractable temporal lobe epilepsy (TLE), unilateral temporal lobe hypometabolism (UTH) corresponding to the seizure focus was seen in 86% of patients. In the same population, MRI demonstrated relevant abnormalities in 76%. UTH contralateral to the seizure focus was rarely seen (3%). Following temporal lobectomy, 86% of patients with ipsilateral UTH had a good outcome. When MRI was normal, UTH predicted a good outcome in 82%. Fifty percent with bitemporal hypometabolism had independent bilateral foci, and in those who proceeded to surgery only 50% had a good result. In extratemporal epilepsy, hypometabolism relevant to the focus was seen in 67% but, as in TLE, it was often more extensive than pathological abnormality. Recently evidence of a role for 11C-Flumazenil has emerged with reduced binding in the primary epileptogenic site. 11C-Flumazenil abnormalities appear more restricted to abnormal cortex and may be a better guide to the extent of resection required for surgical success. CONCLUSIONS: FDG-PET has a key role in the evaluation of patients with intractable partial epilepsy, particularly when surgery is a treatment option. Development and application of more specific biochemical probes may further improve the clinical value of PET for the understanding and treatment of epilepsy.

Journal Article↗

PubMed2000

Intraoperative electrocorticography in temporal lobe epilepsy surgery.

Although in clinical use for many years, the validity of intraoperative electrocorticography (ECoG) in guiding resective temporal lobe epilepsy (TLE) surgery is uncertain. Advances in neuroimaging and extraoperative intracranial recordings have contributed greatly to the identification of epileptogenic lesions and cortex, clarifying the limitations of a brief intraoperative interictal recording. Studies of undifferentiated ECoG findings (which classify all interictal cortical spike discharges as equal) tend to not support this method. This article reviews ECoG and presents data from 86 TLE surgeries at the University of British Columbia suggesting that differentiation of ECoG features may enhance the contribution of this time honored method. Specifically, independent foci may be more important for epileptogenesis than synchronous foci, and postexcision activation appears to be a benign phenomenon, while residual spikes unaltered by the resection correlate with a greater proportion of seizure recurrence.

Anesthesia↗

PubMed2003

Auditory and visual naming tests: normative and patient data for accuracy, response time, and tip-of-the-tongue.

Naming is typically assessed with visual naming tasks, yet, some patients with genuine word-finding difficulty (evident in auditorily based discourse) show minimal difficulty on such measures. Evidence from cortical mapping, brain imaging and neuropsychological studies suggests that auditory naming measures might provide more relevant or at least, complementary information. We developed comparable auditory and visual naming tests and present normative data for accuracy, response time, and tip-of-the-tongue responses based on 100 controls. Test validity was supported by findings that left temporal lobe epilepsy (TLE) patients (i.e., a population with expected naming difficulty) performed more poorly on auditory but not visual naming compared to right TLE patients (i.e., a population without expected naming difficulty). Internal and test-retest reliability coefficients were reasonable. Finally, test utility was assessed on an individual basis, and auditory but not visual naming performance predicted impairment.

Adult↗

PubMed2006

Global/local scoring modifications for the Rey-Osterrieth Complex Figure: relation to unilateral temporal lobe epilepsy patients.

Observation of figural reproductions of right temporal lobe epilepsy (RTLE) patients have revealed overall configuration errors, whereas in left temporal lobe epilepsy (LTLE) patients, the global aspect of performance is generally preserved. This study compared performance of individuals with temporal lobe epilepsy (LTLE, n=83; RTLE, n=63) on a global/local modification of the Rey-Osterrieth Complex Figure Test (RCFT). In Phase I, neuropsychologists (n=6) and neuropsychology fellows (n=3) completed a survey identifying the global and local aspects of the RCFT. Questionnaire responses were used to categorize a list of global and local items (five global, five local) for re-scoring the protocols of TLE patients during study Phase II. Results showed that the RTLE and LTLE groups were not differentiated according to the global or local indices F(1,141) = .385; p = not significant. There were lower local scores for both groups in the copy F(1,142) = 5.23; p = .024, immediate F(1,142) = 445.26; p < .001, and delay trials F(1,142) = 427.82; p < .001, indicating less retention of local information over time. Results suggest general declines in figural memory for local stimulus properties in both unilateral TLE groups. However, this relationship was weakened after controlling for global and local item verbalizability.

Adult↗