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Experimental limbic epilepsy: models, pathophysiologic concepts, and clinical relevance.

Complex partial seizures originating in the temporal lobe are one of the most common types of seizures in patients with epilepsy. They are frequently intractable to medical treatment and are increasingly considered for surgical therapy. These seizures are often associated with focal epileptogenicity in limbic structures (amygdala and hippocampus) or with rapid spread of seizure activity to these areas. Much research is being undertaken to better understand this disorder and to develop more effective approaches to diagnosis and treatment. Experimental work in animals has contributed to the understanding of epileptogenesis, the interictal state, and the homeostatic mechanisms that limit seizure activity.

Aluminum Oxide↗

Spectrum of epilepsy in neurocysticercosis: a long-term follow-up of 143 patients.

To characterize the clinical profile and the prognostic factors of the epilepsy due to parenchymal neurocysticercosis (NCC) 143 patients were analysed. Patients (62 men, 81 women) had a mean age at epilepsy onset of 29 years (range 2-71), mean epilepsy duration of 16 years (range 1-58) and mean follow-up of 5.2 years. Seizures were generalised tonic-clonic (GTC) in 50 patients (35%), simple partial (SP) in 66 (46%) and complex partial (CP) in 27 (19%). Epilepsy began as a single seizure in 73% and as a cluster of seizures or status epilepticus in 27%. Seizures were controlled in 64% of patients. Multivariate analysis revealed that significant prognostic factors associated with seizure control were type of seizures and age at epilepsy onset. Control is more likely in GTC and SP seizures and in patients with a higher age at seizures onset. Our analysis establishes that epilepsy due to NCC is a heterogeneous syndrome concerning age and mode of onset, seizure type, duration of epilepsy and pattern of evolution probably related with different pathogenic mechanisms.

Adolescent↗

Ceruloplasmin gene defect associated with epilepsy in EL mice.

Epilepsy is a dominant trait in EL mice, a model for human complex partial seizures. We recently mapped the major gene, El-1, to chromosome 9 near the predicted location for the ceruloplasmin (Cp) gene. We now present evidence for a partial duplication in the Cp gene in EL mice. This Cp duplication is coinherited with seizures in backcross generations and is associated with enhanced expression of Cp mRNA and increased Cp oxidase activity. Moreover, the duplication is associated with an enhanced frequency of double recombinants, simulating negative interference. The findings are relevant to the basic mechanisms of epilepsy and to theories of genetic recombination and gene mapping.

Animals↗

Observing of the asymmetry of hippocampal formation on patients with complex partial attacks.

Lobus limbicus is anatomical basis for explaining the temporal epilepsy because it not only includes the focus of infection of temporal lobe but also the frontal lobe, and with it we can explain many of the phenomenon's of the epilepsy (hallucinations, the change of the effects, and so on.). The goal of this assignment was to explore the asymmetry of hippocampal formation on the patients with complex partial attacks. The results show that the least number of patients with epilepsy have a symmetric (same) size of the hippocampal formation both from the left and the right side. The number is statistically significantly lower than the number of patients with epilepsy who has asymmetric (different size) hippocampal formation both from the left and the right side. By the direction of asymmetry the difference in the number of patients with epilepsy isn't statistically significant. Coefficient. of asymmetry shows that the asymmetry on the left side is more common to men, while it is distributed evenly on sides, left and right in women. Testing of significance in age differences depends on the sim./asim. of the hippocampal formation of both the right and the left side of coronal slice is a statistical significance. While with axial and sagittal slices, we have a statistical significance between a women and a man on the level of the course of asymmetry. So, the use of MRI technique in examining asymmetry of the hippocampal formation, that we used on this asymmetry, we suggest it as an template of future examinations in a sense of shedding light of the anatomical functions that is located on the basis of neuropsychiatrics dysfunctions.

Journal Article↗

Complex partial seizures presenting as a psychiatric illness.

A 36-year-old woman was treated for a wide variety of psychiatric illnesses over a span of two decades before a diagnosis of complex partial seizures was made. Her history included poor impulse control, rage attacks, multiple suicide attempts, rapid mood swings, depression, and psychotic episodes. Bulimia, panic attacks, severe obsessive-compulsive symptoms, and multiple somatic complaints were also present. In retrospect, these symptoms could be attributed to complex partial seizures with cognitive and affective symptomatology, automatisms, and psychosensory symptoms, and were controlled by anticonvulsant medications. Therefore, so-called "purely" psychiatric disorders should not be diagnosed before a diagnosis of limbic epilepsy (however, this might be labeled, e.g., complex partial seizure, psychomotor seizure, psychical seizure, or temporal lobe epilepsy) has been considered.

Adult↗

Carbamazepine-induced tics.

A variety of movement disorders are known to occur in association with carbamazepine (CBZ) therapy in adults and children, but development of tics has been described infrequently and only in patients with underlying Tourette's syndrome or other movement disorders. We report 3 children with epilepsy who developed facial motor tics after initiation of CBZ for complex partial seizures. All 3 had documented CBZ blood levels in the therapeutic range at the time, and none had other symptoms or signs of clinical intoxication. Neurologic examinations were normal in 2 and showed developmental delay of expressive language in the third. Brain imaging was normal in all. After development of the tics in 2, CBZ was continued at the same or higher dose, and the tics abated and then ceased spontaneously < or = 6 months. In the third child, the tics ceased after CBZ discontinuation. These cases demonstrate that CBZ can induce simple motor tics in children. These idiosyncratic reactions may be transient and do not always necessitate drug discontinuation.

Adolescent↗

[Longitudinal study of epilepsies occurring in adults (author's transl)].

In 24% of epileptic patients the first seizure occurred between 19 and 64 years. A longitudinal study was undertaken on data from 152 subjects, ranged according to the international classification. For each group the following parameters were considered: age at onset of the first seizure; familial and individual antecedents; existence and modification in time of epileptogenic factors and of clinical and electrical interictal semiology. It was noted in particular that the occurrence of illness decreased as subjects grew older; that partial epilepsies (about 2/3 of the cases) were more common than generalized ones; that individual antecedents indicating a lesional aetiology were very frequent; that primary generalized epilepsies had a relatively favourable course, contrary to the partial epilepsies (and particularly those with complex semiological seizures). The results are discussed with reference to statistical data in the literature.

Adult↗

Direct and indirect costs of refractory epilepsy in a tertiary epilepsy center in Germany.

PURPOSE: There are only few studies on the costs of epilepsy in Germany. Therefore, we performed a pilot study to estimate the direct and indirect costs of refractory epilepsy in a German epilepsy center. METHODS: A "prevalence-based," cross-sectional convenience sample of adults with active epilepsy attending the outpatient clinic of our tertiary epilepsy center was evaluated. Seizure-free patients and patients presenting with their first seizure were excluded. Direct and indirect costs were prospectively recorded over a three-month period using questionnaires and a patient diary. Cost driving factors were identified. RESULTS: One hundred one patients were included (40.7+/-15.2 years; disease duration: 18.1+/-15.3 years; 6 patients had focal epilepsy with simple partial seizures only, 28 with complex partial seizures, 43 with secondarily generalized tonic-clonic seizures; 20 had idiopathic generalized epilepsy with generalized tonic-clonic seizures). The total costs of epilepsy per patient were in average euro 2610+/-4200 over the three-month period. Direct cost contributed 39% to the total costs. Costs of anticonvulsant medication were the main contributor to the direct costs while indirect costs were caused mainly by losses due to early retirement. Cost driving factors included higher seizure frequency, longer disease duration, ictal falls, and situationally inappropriate complex behavior during or after the seizure. CONCLUSIONS: Indirect costs were higher than direct costs in adult patients with active epilepsy attending a German epilepsy center. Medication contributed the most to the direct costs and early retirement was the main factor for the indirect costs. The costs of poorly controlled epilepsy in this German study were above average of the European costs of epilepsy.

Adolescent↗

Dysembryoplastic neuroepithelial tumour as a potentially treatable cause of intractable epilepsy in children.

Dysembryoplastic neuroepithelial tumour (DNT) represents a morphologically unique and surgically treatable benign lesion typically associated with complex partial seizures (CPS). Although the radiological features are not pathognomonic the histology is quite distinct. They may account for a significant minority of children with intractable CPS. We present four histologically proven cases to demonstrate and discuss the range of radiological features. Recent recognition that CPS may be caused by a number of conditions including DNT emphasizes that all children with partial seizures should have radiological investigations early in their course.

Brain↗

[Vigabatrin in the treatment of intractable focal epilepsy in children and adolescents. Two-year study].

UNLABELLED: Vigabatrin VGB is the drug of III generation applied for a long time to patients in Poland. In Polish literature there were many reports published concerning the efficacy of VGB, however, most are short-term examinations. The AIM OF THE STUDY WAS: 1. the analysis of VGB efficacy in long term treatment of intractable focal epilepsies in children and adolescents; 2. stating if efficacy of VGB treatment depends on localization of epileptic focus; 3. answering if the effect of tolerance is developed in relation to VGB. MATERIALS AND METHODS: There were 50 patients between 4 to 20 years of age (average 12.7 +/- 4.8) with intractable focal epilepsy in the examined group. partial complex seizures were the dominant type of seizures at 74% of the examined patients. Time of observation amounted to 24 months. The patients were administered with VGB as add-on therapy. 37 patients (74%) were diagnosed with temporal lobe epilepsy, 11 (22%) with frontal lobe epilepsy, 1 patient (2%) with parietal lobe epilepsy and 1 (2%) with occipital lobe epilepsy. Patients who did not complain of seizures for a period of at least one year were classified as those with "seizure free". RESULTS: The examination was completed for 36 patients (76%). The treatment was discontinued in 12 patients (24%) as there was not a sufficient seizure control. One patient with temporal lobe epilepsy stopped the drug as three occurred the epileptic state of atypic generalised absence seizures induced by VGB. The final evaluation comprised all 50 examined patients. 9 patients (18%) achieved complete seizure control, 24 (48%) reduction to 50-99%. There was no change in 17 patients (34%). The examined patients with frontal localisation of epileptic focus presented significantly worse results of treatment, i.e. (reduction in the number of seizures over 35.3-36.5%) than the patients with temporal lobe epilepsy (reduction over 63.8 +/- 37.2%--p < 0.001). No significant difference in the average number of seizures in the 5th and 24th month of treatment was reported in the whole examined group. This contradicts the existence of the effect of tolerance in relation to VGB. CONCLUSIONS: 1. Vigabatrin is a very efficient drug in long-term treatment of patients with intractable focal epilepsies. 2. Patients with temporal lobe epilepsy present statistically better treatment results than patients with frontal lobe epilepsy. 3. No effect of tolerance to VGB was recorded during a 2-year observation.

Adolescent↗

Thalamic kindling: electrical stimulation of the lateral geniculate nucleus produces photosensitive grand mal seizures.

Kindling is traditionally viewed as a chronic, focal epilepsy model which consistently induces complex partial seizures from limbic structures in animals. This study revealed that primary or exceedingly rapid secondary generalized seizures could also be kindled when stimulation was applied to the lateral geniculate nucleus, a thalamic region involved in sleep regulation and possibly also photosensitive epilepsy. Two experiments were conducted in cats. Experiment 1 compared the development of generalized tonic-clonic convulsions and associated sleep disorders following electrical stimulation of the lateral geniculate nucleus (N = 4) and the amygdala (N = 4). Experiment 2 described the effects of intermittent light stimulation on seizure thresholds in both groups. Three primary findings distinguished the epileptogenic process in those two brain regions. First, generalized electroencephalographic and clinical seizures accompanied the first afterdischarge obtained with thalamic stimulation. In contrast, focal seizures with secondary generalization appeared during a 3- to 4-week period of afterdischarge elicitations from the amygdala. Second, amygdala-kindled cats showed fewer sleep spindles during slow-wave sleep whereas cats kindled in the lateral geniculate nucleus had abnormal sleep spindles approaching spike wave-like activity. Third, only the latter cats showed reduced seizure thresholds in response to photic stimulation. Based on the anatomic substrates involved, the clinical and electrographic profiles observed during kindling and the type of sleep disturbance shown, we concluded that lateral geniculate nucleus kindling may represent primary generalized epilepsy, possibly of a photosensitive nature; alternatively, the rapid propagation of abnormal discharge was also consistent with the important role of the thalamus in secondary seizure generalization.

Amygdala↗

Prevalence of epilepsy in Okayama Prefecture: a neuroepidemiologic study.

On the prevalence day, 2,378 epileptic children were identified. Therefore, the prevalence rate for epilepsy was 8.2 per 1,000. The lowest prevalence rate was 1.2 in children under one year of age, and the highest was 11.0 at five years of age. The rate was higher for males than females. The annual incidence rate for epilepsy was estimated at 145.0 per 100,000 for 1975. The onset of seizures was high in the first three years, totaling 1,795 cases (77.7%), and this decreased after four years of age. Primary generalized epilepsy was found in 577 cases (31.7%), secondary generalized epilepsy in 167 (9.2%), partial epilepsy with elementary symptomatology in 205 (11.3%), with complex symptomatology in 61 (3.3%) and partial seizures secondarily generalized in 801 (44.5%). The study on such a number of cases had hitherto never been reported in the world.

Age Factors↗

Quantifying interictal metabolic activity in human temporal lobe epilepsy.

The majority of patients with complex partial seizures of unilateral temporal lobe origin have interictal temporal hypometabolism on [18F]fluorodeoxyglucose positron emission tomography (FDG PET) studies. Often, this hypometabolism extends to ipsilateral extratemporal sites. The use of accurately quantified metabolic data has been limited by the absence of an equally reliable method of anatomical analysis of PET images. We developed a standardized method for visual placement of anatomically configured regions of interest on FDG PET studies, which is particularly adapted to the widespread, asymmetric, and often severe interictal metabolic alterations of temporal lobe epilepsy. This method was applied by a single investigator, who was blind to the identity of subjects, to 10 normal control and 25 interictal temporal lobe epilepsy studies. All subjects had normal brain anatomical volumes on structural neuroimaging studies. The results demonstrate ipsilateral thalamic and temporal lobe involvement in the interictal hypometabolism of unilateral temporal lobe epilepsy. Ipsilateral frontal, parietal, and basal ganglial metabolism is also reduced, although not as markedly as is temporal and thalamic metabolism.

Brain↗

Long-term study of gamma-vinyl GABA in the treatment of epilepsy.

The purpose of this study was to investigate the long-term efficacy and tolerability of gamma-vinyl GABA (GVG) in the treatment of epilepsy. 36 patients with severe therapy resistant epilepsies participated, the majority exhibiting complex partial seizures. The mean follow-up period was 9.3 months. GVG was administered as add-on therapy, to keep serum levels of concomitant treatment constant. The mean dose of GVG was 2.6 g's per day. Fifty-six per cent of the patients, including three patients with juvenile myoclonic epilepsy, experienced more than a 50% reduction in seizure frequency. No signs of tolerance development to the antiepileptic effect of GVG was demonstrated. Two patients were withdrawn from GVG treatment due to increased seizure frequency, and two due to side effects in the form of vomiting and nausea. Incidentally, the side effects observed were harmless and transient. Fifty per cent of the patients experienced no side effects at all. GVG seems to be a valuable antiepileptic compound. The results of this long-term study confirm observations from several short controlled trials.

Adolescent↗

Psychomotor epilepsy and psychosis. I. Physical aspects.

In a controlled investigation the clinical findings in 96 patients with paranoid/hallucinatory psychosis and partial epileptic seizures with complex symptoms, were compared with the findings in 96 control patients with the same type of epilepsy without psychosis of median 24 years' duration. The median age at onset of psychosis was 34 years, after epilepsy of median 21 years' duration. The seizure frequency of complex, partial seizures was significantly lower in the psychotic group, while the frequency of generalized seizures did not differ. A significant preponderance in the psychotic group of left-handed patients, etiological factors and neurological signs reflecting organic damage, and seizures of automatic behaviour indicates that epileptic psychoses are caused by structural lesions affecting the deep parts of the temporal lobe.

Adolescent↗

Complex partial status epilepticus: a recurrent problem.

Twenty patients with complex partial status epilepticus were identified retrospectively from a specialist neurology hospital. Seventeen patients experienced recurrent episodes of complex partial status epilepticus, often occurring at regular intervals, usually over many years, and while being treated with effective anti-epileptic drugs. No unifying cause for the recurrences, and no common epilepsy aetiologies, were identified. In spite of the frequency of recurrence and length of history, none of the patients showed any marked evidence of cognitive or neurological deterioration. Complex partial status epilepticus is more common than is generally recognised, should be differentiated from other forms of non-convulsive status, and is often difficult to treat.

Adult↗

Spinal muscular atrophy with oculomotor palsy, epilepsy, and cerebellar hypoperfusion.

We report a boy with spinal muscular atrophy (SMA) type 1, who developed novel clinical and neuroradiologic features, indicating the broad spectrum of this degenerative disease. Widespread lesions in the central nervous system were disclosed by magnetic resonance imaging and single photon emission computed tomography (SPECT) studies. In particular, scattered regions of hypoperfusion demonstrated by SPECT suggested multisystem involvement including the cerebellum. The novel features of this patient were complex partial seizures and oculomotor palsy.

Cerebellum↗

Neuron-glia relationships in human and experimental epilepsy: a biochemical point of view.

The generation of focal cortical epilepsy as observed in human partial complex seizures is presumably due to enhanced physiologic responses or paroxysmal depolarization shifts (PDSs). However, the molecular mechanism that underlies these phenomena remains unknown. It could be due to a genetically determined error in a structural or regulatory protein or to posttranslational events that modulate membrane excitability. Since neither neuronal PDSs or interictal EEG spikes are sufficient to produce clinical epilepsy, the clinical expression of epilepsy may need the breakdown of neuronal or glial mechanisms that limit the spread of seizures. Hence, biochemical membrane studies of neurons and glia are necessary to understand the expression of human and experimental epilepsy. This chapter will review the role of glia in controlling neuronal excitability and neuron-glia relationships in experimental and human epilepsy. Data exploring the hypothesis that glial control of extracellular K+ or (K+)o is deficient in focal epilepsy induced by cold lesions will be reviewed. The role of glial carbonic anhydrase (CA) and glial control of putative amino acid transmitters in audiogenic epilepsy will be discussed. In the cold lesion, (K+)o activation constants of synaptosomal (Na+,K+)-ATPase are significantly decreased in the actively firing chronic focus, suggesting that the apparent affinity of the synaptosomal enzyme for K+ was increased within epileptic tissue that was actively firing. Interestingly, while sustained focal paroxysms could raise synaptosomal (Na+,K+)-ATPase, glial (Na+,K+)-ATPase and its activation by (K+)o remained decreased during sustained paroxysms in both acute and chronic lesions. Moreover, while the decrease of the absolute level of glial enzyme activity was less evident 45 days after lesion production, the poor response of glial enzyme to (K+)o never reversed to "normal" values. Hence, these experiments provided new information that glial (Na+,K+)-ATPase responds to K+ in a different manner when compared to synaptic enzyme. Glial ATPase and its activation by (K+)o remain decreased in either actively discharging acute lesions or in the indolent chronic foci. This could mean a reduction in the ability of glial membranes to maintain (K+)o homeostasis. As already suggested by Dichter, the impairment in glial control of elevated (K+)o could be mainly responsible for the transition of interictal discharges to ictal episodes, within the primary and the secondary foci.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗