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Sudden unexpected death in epilepsy: a series from an epilepsy surgery program and speculation on the relationship to sudden cardiac death.

Sudden unexpected death represents a significant cause of mortality in people with epilepsy. It derives this significance not because it is the most frequent cause of death but because it is apparently a direct consequence of a seizure. The implication is that epilepsy is an inherently lethal disorder. Seven patients who were studied in an epilepsy surgery program died a sudden unexpected death. This incidence of sudden unexpected death was five times higher than the 1-2/1,000 per year reported in the general epilepsy population. Sudden unexpected death shares some of the characteristics associated with sudden cardiac death, which kills 300,000 people in the United States each year. A cardiac arrhythmia, usually ventricular fibrillation, is the most common terminal event for sudden cardiac death and is the leading candidate as the mechanism for sudden unexpected death. Despite this knowledge, little is known on how to identify a high-risk group of patients for sudden death or how these deaths might be prevented.

Coronary Disease↗

[Two cases of post-encephalitic epilepsy characterized by auditory cognitive dysfunction; comparison with "a peculiar type of post-encephalitic/encephalopathic epilepsy"].

Two cases of post-encephalitic epilepsy mainly characterized by auditory cognitive dysfunction were reported. In acute phase they only showed slight pleocytosis of CSF, and serum antiviral antibodies were all negative. Although their seizures were partial seizures with secondary generalization, their EEG and radiographic imaging did not show any lesions. Their waking state EEG continuously showed slowing with decrease of alpha activities. After clusters of convulsions, they showed delirium and aggressiveness. Both of them were thought to have post-encephalitic epilepsy with pathogen unknown and they were compatible with "a peculiar type of post-encephalitic/encephalopathic epilepsy" reported by Fukuyama and Awaya. The presented two cases were characterized by auditory cognitive dysfunction and intractable epilepsy with secondary generalization.

Acute Disease↗

Autosomal dominant cortical myoclonus and epilepsy (ADCME) with complex partial and generalized seizures: A newly recognized epilepsy syndrome with linkage to chromosome 2p11.1-q12.2.

We describe a pedigree in which eight individuals presented with a non-progressive disorder with onset between the ages of 12 and 50 years. It was characterized by predominantly distal, semi-continuous rhythmic myoclonus (all patients), generalized tonic-clonic seizures (all patients) and complex partial seizures (three patients). Most individuals had rarely suffered seizures and had a normal cognitive level, but three individuals with intractable seizures had mild mental retardation. The pattern of inheritance was autosomal dominant with high penetrance. We defined this disorder as autosomal dominant cortical myoclonus and epilepsy (ADCME). All patients had frontotemporal as well as generalized interictal EEG abnormalities. A neurophysiological study of the myoclonus suggested a cortical origin. Back-averaging of the data generated a series of waves with a frequency that mirrored the frequency of EMG bursts. Frequency analysis identified significant peaks with coherence between EMG and EEG, which were recorded over the contralateral rolandic area in five patients. The frequency of coherence was 8-25 Hz and phase spectra confirmed that EEG activity preceded EMG activity by 8-15 ms. In two individuals there was also significant coherence between the ipsilateral EEG and EMG, consistent with the transcallosal spread of myoclonic activity. The C-reflex at rest was enhanced and somatosensory and visual evoked potentials were of high amplitude. The resting motor threshold intensity to transcranial magnetic stimulation was significantly reduced (38%; SD +/- 7; P = 0.01) and the post-motor evoked potential silent period (101 ms; SEM +/- 10) was significantly shortened compared with the controls (137 ms; SEM +/- 18). These clinical and neuro- physiological characteristics suggest diffuse cortical hyperexcitability and high propensity for intra-hemispheric and inter-hemispheric cortical spread, as well as rhythmic myoclonic activity. Genome-wide linkage analysis identified a critical region spanning 12.4 cM between markers D2S2161 and D2S1897 in 2p11.1-q12.2, with a maximum two-point LOD score of 3.46 at Theta 0.0 for marker D2S2175. Multipoint LOD score values, reaching 3.74 around D2S2175, localize the ADCME gene to the centromeric region of chromosome 2. The exclusion of the locus for familial adult myoclonic epilepsy on chromosome 8q23.3-q24 from linkage to our family and the new localization of the responsible gene to chromosome 2cen, together with the different phenotype, define a new epilepsy syndrome. We hypothesize that the responsible gene causes cortical hyperexcitability that is widespread but particularly involves the frontotemporal circuits.

Adult↗

Differences between two feline epilepsy models in sleep and waking state disorders, state dependency of seizures and seizure susceptibility: amygdala kindling interferes with systemic penicillin epilepsy.

The objective of the study was to determine whether contemporary feline models of petit mal (systemic penicillin epilepsy) or temporal lobe epilepsy (amygdala kindling) resemble human seizure disorders with respect to disturbances of sleep and waking states, the state dependency of seizures, and transference of seizure susceptibility. These variables were examined in 6-h polygraphic recordings before and during exposure to both seizure models in 24 cats; 12 cats had intramuscular (i.m.) injections of 300,000 or 400,000 IU/kg of penicillin prior to kindling, and 12 were kindled before penicillin challenge. Results were as follows. First, penicillin increased light slow wave sleep (SWS) and drowsiness, during which spike-wave (SW) activity was maximal. Generalized tonic-clonic convulsions (GTCs) occurred predominantly in drowsiness after awakening from SWS. Second, kindling produced more deep SWS than did penicillin; susceptibility to kindled GTCs peaked during deep SWS, especially in transition to rapid eye movement sleep (REM). Third, penicillin did not influence subsequent sleep disorders or seizure susceptibility during kindling; kindling interfered with penicillin-induced GTCs, SW activity, and sleep disorders. Collectively, the findings suggest distinct state disorders and state-dependent seizure profiles in the two models. These differences parallel human analogues and may have contributed to the transference results. Kindling is a chronic model with persistent sleep and seizure abnormalities that differ from and may have discouraged penicillin epilepsy. Penicillin is an acute model with transient state and seizure disorders, a fact that may account for the absence of penicillin transference to kindling.

Amygdala↗

Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy [RETIRED]: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome. CONCLUSIONS: The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Acetates↗

[Clinico-electroencephalographic analysis of wakeful epilepsy and sleep epilepsy].

Some results of a clinico-physiological analysis of epileptic patients with a different diurnal distribution of generalized convulsive seizures in the sleep-vigilance cycle are reported. It is demonstrated that in vigilant epilepsy there is an intensification of L-rhythms in the EEG recordings in the different functional states of vigilance, combined with a prevalence of delta-sleep in the sleep structure. In sleep epilepsy there is a predominance of the 2nd sleep stage in the sleep structure, besides an EEG desynchronization in the state of vigilance. These results indicate some differences in the activity of nonspecific (synchronizing and desynchronizing) structures in epilepsy with a different diurnal distribution of generilized convulsive seizures.

Adolescent↗

Memory Complaints in Medically Refractory Epilepsy: Relationship to Epilepsy-Related Factors.

This study reports the results of a multicenter study on memory complaints in 252 patients with epilepsy who presented with subjective complaints about memory problems in daily life. Memory complaints were measured with a standardized memory questionnaire (GKLE). The main purpose was to analyze the type of memory complaints and to examine the relationship between subjective complaints and several epilepsy-related factors. These include seizure type, lateralization and location of the focus, etiology, duration, age at onset, and antiepileptic medication. As expected patients experienced significantly more memory complaints. In particular, patients of older age and higher intelligence level complained more about their memory functioning. Although the clinical significance is marginal, neuroticism showed a significant relationship to the total complaint score. The total amount of subjective complaints is not related to the localization or lateralization of the epileptic disturbances. Patients with a longer duration of epilepsy complained significantly more about memory problems, especially about retrieving information from memory. All other epilepsy-related factors showed no relationship to memory complaints.

Journal Article↗

When does childhood epilepsy become intractable? Indications and contraindications for epilepsy surgery in children

Surgery for intractable childhood epilepsy may be of great benefit; however, there is a natural tendency for many children with intractable epilepsy to gradually achieve seizure control over years of follow-up. This evolution is much more likely if intelligence is normal. Progressive deterioration in intelligence, school performance, or behavior may be more important in the decision for early surgery than are the seizures themselves. Indications for epilepsy surgery in infancy are most uncertain. Arguments for and against epilepsy surgery in children are presented.

Journal Article↗

Sequential occurrence of benign partial epilepsy and childhood absence epilepsy in three patients.

We first report 3 patients who experienced absence epilepsy (mean age at onset: 6.3 years; range: 4-9) 1-4 years after recovering from an electroclinical picture characteristic of benign childhood partial epilepsy (BCPE). All patients were put on monotherapy with sodium valproate, and their long-term course was excellent with remission of absences and normalization of EEG recordings. The exceptionality of our observation favors the hypothesis that BCPE and absence epilepsy are distinct entities.

Adolescent↗

MRI in the presurgical evaluation of patients with frontal lobe epilepsy and children with temporal lobe epilepsy: pathologic correlation and prognostic importance.

We performed magnetic resonance imaging (MRI) using a high-field strength magnet (1.5 T) in two series of 53 patients with intractable partial epilepsy of frontal lobe or temporal lobe origin who subsequently received ablative surgery for their seizure disorder. In the first series of patients the pathologic correlation and prognostic importance of an MRI-identified lesion in the frontal lobe were assessed. Twenty-five percent of the patients with negative MRI studies and 67% of patients with neuroimaging abnormalities restricted to the frontal lobe, were seizure-free at a minimum duration of follow-up of 1 year. None of the patients with a multilobar MRI-detected abnormality was seizure-free postoperatively. In the second study the sensitivity and specificity of MRI-based hippocampal volumetry was determined in pediatric patients with partial epilepsy of temporal lobe origin unrelated to foreign-tissue pathology. Hippocampal formation atrophy in the epileptic temporal lobe was identified in 63% of patients. The sensitivity and specificity of hippocampal volumetry was 100% in patients with mesial temporal sclerosis. The presence of an MRI-detected epileptogenic lesion in the frontal lobe and hippocampal formation atrophy in the temporal lobe may correlate with the underlying pathology and affect the identification of potential candidates for epilepsy surgery.

Adolescent↗

Response inhibition and set shifting in patients with frontal lobe epilepsy or temporal lobe epilepsy.

Patients with frontal lobe epilepsy (FLE), patients with temporal lobe epilepsy (TLE), and matched controls were administered a test of response inhibition and set shifting (switching) (Color Word Interference Test, CWIT). Patients with FLE were impaired relative to the controls across all conditions of the CWIT, with the FLE patients showing disproportionate impairment in the Inhibition and Inhibition/Switching conditions. In contrast, the TLE patients did not differ from controls. Further analysis of the patient groups revealed that patients with left FLE were impaired relative to those with right FLE, left TLE, and right TLE in the Inhibition condition. In the Inhibition/Switching condition, patients with left FLE and left TLE were impaired relative to their right-sided counterparts. Finally, performance by the TLE group in the Inhibition/Switching condition was correlated with seizure frequency. These data suggest that patients with FLE, but not TLE, show impaired inhibition and set shifting relative to controls. In addition, side of the seizure focus and seizure frequency may contribute to executive dysfunction in patients with epilepsy.

Adult↗

A study of the relationship between the seizure focus and 1H-MRS in temporal lobe epilepsy and frontal lobe epilepsy.

Several studies of temporal lobe epilepsy (TLE) patients have investigated the relationship between the seizure focus and 1H magnetic resonance spectroscopy (1H-MRS). There have also been a few reports in other types of partial epilepsy. We examined the relationship between the seizure focus and the reduction in N-acetylaspartate: creatine (NAA : Cr) ratio using 1H-MRS in both TLE and frontal lobe epilepsy (FLE) patients. We studied 21 patients with unilateral TLE and seven patients with unilateral FLE. We used a 1.5 Tesla magnetic resonance unit (Signa Horizon; General Electric). Approximately 15 x 15 x 20 mm3 voxel of interest (VOI) was placed over the anterior portion of the bilateral hippocampus in the TLE patients, and the anterodorsal position of bilateral frontal lobe in the FLE patients. The seizure focus was identified by interictal scalp electro-encephalogram (EEG). In the TLE patients the NAA : Cr ratios were reduced in the seizure focus, while in the FLE patients they were not always reduced in the seizure focus. In the TLE patients the coincidence rate between the seizure focus and the reduction in the NAA:Cr ratio was 90% (19 of 21 patients), while in the FLE patients the coincidence rate was only 57% (four of seven patients).

Adult↗

Inter-ictal and post-ictal psychoses in frontal lobe epilepsy: a retrospective comparison with psychoses in temporal lobe epilepsy.

There have been few studies of the psychopathology of patients with frontal lobe epilepsy (FLE). The majority of studies of both inter-ictal and post-ictal psychoses have strongly suggested the influence of temporal lobe disturbance on psychoses. Patients with organic brain damage or schizophrenia, however, sometimes show frontal lobe dysfunction. The purpose of this study was to better understand the effect, if any, of frontal lobe disturbance and seizure on psychopathology. Patients were divided into four groups based on epilepsy type and preceding seizures; 8 with FLE/inter-ictal psychosis, 3 with FLE/post-ictal psychosis, 29 with temporal lobe epilepsy (TLE)/inter-ictal psychosis, and 8 with TLE/post-ictal psychosis. Psychopathologic symptoms were retrospectively reviewed based on case notes, using a modified brief psychiatric rating scale (BPRS). Psychomotor excitement, hostility, suspiciousness, and hallucinatory behaviour were prominent features in all four groups. Six orthogonal factors were derived by factor analysis from the original data based on the 18 BPRS items. FLE patients with inter-ictal psychosis showed marked hebephrenic characteristics (i.e. emotional withdrawal and blunted effect). Our findings suggest that patients with FLE can exhibit various psychiatric symptoms. However, their psychotic symptoms, hebephrenic symptoms in particular, may often be overlooked.

Adult↗

Orbito-frontal epilepsy masquerading as temporal lobe epilepsy-a case report.

Temporal lobectomy fails to control seizures in a considerable percentage of patients who do not have hippocampal sclerosis. One theoretical reason for failure of surgery is that some of these patients may in fact have extratemporal epilepsy. We present a 28-year-old woman with clinical and scalp electroencephalogram (EEG) evidence of right temporal lobe epilepsy (TLE) supported by functional imaging with interictal positron emission tomography (PET) and ictal single-photon emission computerized tomography (SPECT). An invasive EEG monitoring was prompted by the discovery of a small right orbito-frontal lesion on MRI. Monitoring documented seizure onset at the lesion, with rapid right temporal involvement. The patient was almost seizure-free after a lesionectomy. The index of suspicion of orbito-frontal epilepsy should be high in patients with apparent TLE when the scalp EEG and neuroimaging data are not congruent, or if temporal lobe pathology cannot be identified on structural imaging.

Adult↗

Linkage analysis of idiopathic generalised epilepsy in families of probands with Juvenile Myoclonic Epilepsy and marker loci in the region of EPM 1 on chromosome 21 q: Unverricht-Lundborg disease and JME are not allelic variants.

The locus for Unverricht-Lundborg disease, EPM 1, has recently been mapped to chromosome 21q22.3. A locus, EJM 1, predisposing to idiopathic generalised epilepsy in families of probands with juvenile myoclonic epilepsy has been localised to chromosome 6p by evidence of linkage to the HLA region. However, segregation analysis suggests a two-locus model for JME and evidence has been obtained for genetic heterogeneity within the JME/IGE phenotype. EPM 1 was therefore investigated as a candidate locus in the set of families segregating for IGE and JME which do not show linkage to markers on chromosome 6p. Linkage analysis was carried out in 25 families using three microsatellite DNA markers around the EPM 1 gene region using different models of inheritance. Multipoint linkage analysis provided definite exclusion for 20cM around PFKL, the closet linked marker to EPM 1, under three out of four models tested. These results strongly suggest that the EPM 1 gene is not linked to the phenotype expressed in these families, and therefore that Unverricht-Lundborg disease and juvenile myoclonic epilepsy are not allelic variants.

Adolescent↗

Clinico-electroencephalographical study of focal epilepsy with special reference to "benign epilepsy of children with centro-temporal EEG foci" and its age dependency.

Childhood epilepsy with nocturnal seizure and rolandic (centro-temporal) discharge on EEG, had recently been noted by some French and other European authors. These types of epilepsy usually appeared in middle childhood and showed a favorable effect ot anticonvulsant therapy. The present investigation deals with analysis of seizures and of some characteristics of rolandic discharge, particularly with respect to the cerebral maturational process involved in the appearance of seizure discharge. The patients were selected out by the symptoms of epilepsy and features of EEG's, consisting of 20 children in total. Fifteen patients showed somatomotor attacks and five showed somatosensory as well as somatomotor attacks. As for the duration of seizure, those who had seizures before three and 10 years of age, had attacks for relatively short periods, whereas those who had attacks from four to nine years of age, usually had longer duration. The amplitude of "RD" remained lower than 50 muv up to three years of age, whereas it reached as high as 200 muv up to nine years, particularly during sleep, which became lower after the age of 10. It was concluded that there is an age dependency between the ages of four and nine.

Adolescent↗

The relationship between sleep and epilepsy in frontal and temporal lobe epilepsies: practical and physiopathologic considerations.

PURPOSE: The influence of sleep on the incidence of seizures and the reciprocal effects of epilepsy on sleep were analyzed in 30 patients with intractable partial seizures, all candidates for surgery. METHODS: The patients were classified into two groups of 15 patients according to the documented site of the epileptogenic zone: frontal lobe epilepsy (FLE) and medial temporal lobe epilepsy (TLE). Frequency and waking-sleep distribution of seizures were evaluated by continuous video-EEG monitoring for 5 days, under defined antiepileptic drug (AED), sleep, and sleep deprivation regimens. Sleep organization was analyzed by polysomnography prior to the presurgical protocol. RESULTS: Significant differences were found between the two groups in sleeping-waking distribution of seizures under varied conditions, and in the quality of sleep organization. In FLE patients, seizures most often occurred during sleep, although sleep organization was normal. In TLE patients, most seizures occurred while patients were awake, and sleep organization was characterized by a low efficiency index. The difference in seizure distribution between FLE and TLE persisted under all conditions investigated, i.e., after AED discontinuation and sleep deprivation. CONCLUSIONS: Sleep recording may be useful for diagnosis of FLE, and monitoring after sleep deprivation for that of TLE. We speculate that sleep-related seizures in FLE may depend on interaction between frontal lobe areas with the thalamus cortical synchronization system and the acetylcholine regulatory system of waking.

Adult↗

Regional cerebral blood flow during interictal state: differences between temporal lobe epilepsy and primary generalized epilepsy.

Regional cerebral blood flow (rCBF) was investigated during interictal state by 133Xenon intravenous clearance technique in two groups of epileptic patients: group I (n = 28) having partial complex seizures (temporal lobe epilepsy); group II (n = 14) having generalized seizures (primary generalized epilepsy). Mean hemispheric CBF was decreased in group I and unchanged in group II compared to normal controls. Modifications in rCBF pattern were observed in group I but not in group II. A marked hypoperfusion of one temporal region was found in patients from group I showing a unilateral and fixed epileptic focus. Hypoperfusion of other cerebral areas at a distance from the epileptic focus was greater for patients with a left epileptic focus than for those with a right epileptic focus. Patients with the same severity of disease and bilateral and variable foci had no significant modification of mean hemispheric CBF and rCBF distribution. These observations indicate that interictal investigations of rCBF may be of interest for a differential classification of epilepsy.

Adolescent↗