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Effects of conventional antiepileptic drugs in a model of spontaneous recurrent seizures in rats.

Pilocarpine (PILO) induces in rats limbic seizures that become secondarily generalized and evolve to status epilepticus (SE). Spontaneous recurrent seizures are registered during the long-term period following the systemic administration of PILO in rats. EEG, behavioral, and pathological features resemble those of complex partial seizures. The antiepileptic drugs (AEDs) diazepam, phenobarbital (PB), valproic acid (VPA) and trimethadione protect against PILO-induced SE while phenytoin (PHT) and carbamazepine (CBZ) are ineffective. Studies with AEDs on spontaneous seizures (chronic period) of this model have not yet been established. We now report the effects of different AEDs on spontaneous seizures. Male Wistar rats were subjected to PILO-induced SE. Following recovery from SE animals were daily observed in order to detect spontaneous seizures and to establish the baseline seizure frequency. PB 40 mg/kg, PHT 100 mg/kg, CBZ 120 mg/kg, VPA (450 mg/kg and 600 mg/kg) and ethosuximide (ETX) 400 mg/kg were given daily to epileptic rats for two weeks during the spontaneous recurrent seizures period. PB, CBZ and PHT were effective against spontaneous seizures. VPA was also effective against spontaneous seizures at the dose of 600 mg/kg and ETX was inactive against these seizures. Such pharmacological profiles correlate well with complex partial seizures. The results indicate that spontaneous recurrent seizures after PILO-induced SE may be a useful model for finding new AEDs with better efficacy against complex partial seizures. The use of animal models that share both pharmacological and phenomenological features with human epilepsy might improve their predictive value for specific types of human epilepsy.

Animals↗

MR spectroscopy in the evaluation of epilepsy.

MR spectroscopy may be a helpful, reliable, noninvasive test with which to lateralize the seizure focus in patients with partial complex seizures. MR spectroscopy is complementary to other studies, especially MR imaging, and both may be performed in a single integrated examination and result in improved surgical management and outcome.

Brain↗

Alumina gel injections into the temporal lobe of rhesus monkeys cause complex partial seizures and morphological changes found in human temporal lobe epilepsy.

The goal of the present study was to determine whether alumina gel injections into temporal lobe structures cause complex partial seizures (CPS) and pathological changes observed in human temporal lobe epilepsy. Rhesus monkeys with alumina gel injections in the amygdala, perirhinal and entorhinal cortices, or Ammon's horn and dentate gyrus all initially displayed focal pathological electroencephalographic (EEG) slowing limited to the site of injection. After clinical seizures developed, they also displayed widespread pathological EEG slowing over both hemispheres, interictal and ictal epileptiform EEG abnormalities limited to the mesial-inferior temporal lobe on the side of injection, and different degrees of spread to other ipsilateral and contralateral structures. Noninjected control and nonepileptic monkeys with injections into the middle and inferior temporal gyri displayed no hippocampal neuronal loss or mossy fiber sprouting. When alumina gel was injected into the amygdala, CPS began within 3-6 weeks and degeneration of neurons and gliosis occurred in the perirhinal cortex or the hippocampus, with consequent sprouting of mossy fibers in the dentate gyrus. Dispersion of the granule cell layer was also observed. Other monkeys with alumina gel in the perirhinal and entorhinal cortices developed CPS within 2-3 weeks after the injections and displayed mossy fiber sprouting only after 4 weeks after the injections. Alumina gel in Ammon's horn and the dentate gyrus also induced CPS, but mossy fiber sprouting was limited to sites immediately adjacent to the injection, probably because none survived more than 4 weeks after the injections. This nonhuman primate model of CPS displayed similar anatomical, behavioral, and EEG features as observed in human temporal lobe epilepsy and provides opportunities to analyze the chronological sequence of epileptogenesis and to test potential therapies.

Aluminum Oxide↗

Transient Kluver-Bucy syndrome following complex partial status epilepticus.

The characteristic features of Kluver-Bucy syndrome include hypersexuality, hyperorality, placidity, hypermetamorphosis, visual agnosia, changes in dietary habits, and memory impairment. Human cases have been reported with herpes simplex encephalitis, head injury, Pick's disease, transtentorial herniation, adrenoleukodystrophy, and Reye's syndrome, all involving bilateral temporal lobe pathology. We present the case of a patient with no evidence of a structural lesion in the temporal lobes and behavioral changes consistent with Kluver-Bucy syndrome following complex partial status epilepticus.

Adult↗

Acquired aetiological factors in Nigerian Epileptics (an investigation of 378 patients).

378 classifiable epileptics attending the neurology clinics at Lagos University Teaching Hospital were investigated for acquired aetiological factors. 34.9% had identifiable aetiology. The commonest aetiological factor was childhood febrile convulsion, a factor most commonly associated with partial epilepsy with complex symptomatology. Other factors were: head injury, birth injury, CNS infections, cerebrovascular accidents, intracranial space occupying lesions and sickle cell disease; 39% of patients with partial epilepsy had acquired aetiological factors. The 61% of them without identifiable aetiology reflect inherent low seizure threshold which makes it possible for a clinically undetectable minimal organic lesion to be epileptogenic. 22.9% of patients with generalised epilepsy had identified aetiology suggesting that idiopathic epilepsy is not synonymous with generalised epilepsy and symptomatic epilepsy not exclusive to partial epilepsy.

Birth Injuries↗

[Lamotrigine: monotherapy in refractory epilepsy].

CBZ (mean 1219 mg, DS +/- 94.6) + LTG (mean 55.8 mg, DS +/- 80) were administered in 31 subjects with refractory partial complex and/or partial secondary generalized seizures. The age ranged from 18 to 62 years (mean/yr 37.1, DS +/- 12.5). This first trial is concluded after a period of 8-12 months (mean 11.4, DS +/- 11.2). A follow trial with LTG at lower dose monotherapy ranged from 125-250 mg (mean 190.32, DS +/- 40.6) was conducted in same patients. There was a 82.2% (DS +/- 15.3) reduction in total seizure frequency with LTG monotherapy compared to LTG + CBZ = 53.5 (DS +/- 29.3). The difference remained highly significant (p < 0.0001) in favor of LTG monotherapy. The LTG leads major improvement if submitted like a single drug in therapy resistant epilepsy.

Adolescent↗

Neuropsychological and behavioral status of children with complex partial seizures.

Neuropsychological and behavioral status were examined in 57 children aged 7 to 16 years with complex partial seizures (CPS) and compared with 27 sibling control children of the same age. Epilepsy had a significant effect on both cognitive and behavioral adjustment measures. Children with CPS had significant impairment across all seven cognitive domains assessed, reflective of a profile of relatively diffuse and generalized cognitive dysfunction. Age at onset of recurrent seizures was the strongest and most consistent predictor of adequacy of cognitive functioning; earlier age at onset was associated with poorer cognitive status. Children with CPS also had more problems compared with sibling control children on measures of social and school competence and internalizing behavior problems, but not externalizing behaviors. Further, frequency of seizure activity in the past year, rather than age at seizure onset, emerged as the strongest predictor of these behavioral difficulties. These findings are discussed in the context of understanding the impact of CPS on cognition and behavioral adjustment, and identifying the contribution of various aspects of the neurodevelopmental course of CPS to these issues.

Achievement↗

Formal thought disorder in pediatric complex partial seizure disorder.

We compared the formal thought disorder ratings of 27 children with complex partial seizure disorder, 31 schizophrenic children and 58 normal children. The epileptic children with fullscale IQ scores below 100 had significantly more formal thought disorder than normal children with a similar IQ. The severity of their formal thought disorder was related to the age of seizure onset, seizure control and a diagnosis of schizophrenia spectrum disorder. The schizophrenic children had thought disorder irrespective of IQ scores. The cognitive correlates of their formal thought disorder scores differed from those of the epileptic children. Possible anatomical substrates of thought disorder in childhood complex partial seizure disorder and schizophrenia are discussed.

Attention↗

Neuroimaging in intractable complex partial seizures.

We retrospectively analyzed 19 patients with intractable complex partial seizures who underwent temporal lobectomy and compared the usefulness of various imaging techniques in diagnosis and localization. Pathologic findings consistent with mesial temporal sclerosis were found in 12 patients arteriovenous malformations in four, tumors in three, and coexistence of a tumor and mesial temporal sclerosis in one. Electroencephalography and single photon emission computed tomography detected lateralized functional abnormality in two patients when computed tomography (CT) and magnetic resonance imaging (MRI) showed equivocal results. Both CT and MRI showed all arteriovenous malformations and tumors. CT detected only four cases of mesial temporal sclerosis, while MRI showed nine cases. Detection, delineation and diagnosis of lesions responsible for complex partial seizures are essential for good surgical results. Thus, the importance of image studies, especially MRI, should be emphasized in patients with complex partial seizures.

Adolescent↗

Genital automatisms in complex partial seizures.

OBJECTIVE: To determine which brain region is responsible for the generation of sexual automatisms. METHODS: Ninety consecutive patients with medically refractory focal epilepsy (74 with temporal lobe and 16 with frontal lobe epilepsy) referred to an epilepsy monitoring unit were studied. The occurrence of the following sexual automatisms was assessed during prolonged video-EEG monitoring: 1) repeatedly grabbing or fondling the genitals and 2) pelvic or truncal thrusting or similar movements. RESULTS: Five patients repeatedly fondled or grabbed their genitals during or immediately after some of their seizures. All five had temporal lobe epilepsy, as evidenced from prolonged video-EEG monitoring, high-resolution MRI, and good to excellent outcome after epilepsy surgery. Sexual automatisms did not occur with frontal lobe epilepsy. CONCLUSION: Sexual automatisms cannot be related exclusively to frontal lobe seizures. As previously proposed, apparently sexual hypermotoric pelvic or truncal movements are common in frontal lobe seizures, but this study suggests that discrete genital automatisms, like fondling and grabbing the genitals, are more common in seizures evolving from the temporal lobe.

Adult↗

Clinical characteristics and predictive factors in 98 patients with complex partial seizures treated with temporal resection.

OBJECTIVE: To analyze the preoperative and operative factors predictive of outcome in patients undergoing surgery for temporal lobe epilepsy. DESIGN: From 1984 to 1992, 98 patients with medically refractory temporal lobe epilepsy underwent surgery. Evaluation included the following: video electroencephalography (13 patients had intracranial recordings), head magnetic resonance imaging, interictal and ictal single photon emission computed tomography, psychometric testing, and Wada testing. Seizure-free groups and non-seizure-free groups were analyzed. Follow-up of 1 year to 8 years was available for 89 patients (mean, 3.2 years). SETTING: Indiana University Epilepsy Surgery Program, Indianapolis. OUTCOME: Sixty percent (53/89) were seizure free, 16% (14/89) had rare seizures, 13% (12/89) had worthwhile improvement, and 11% (10/89) showed no improvement. Forty-two percent of seizure-free patients had a history of febrile seizures compared with 5% of non-seizure-free patients. Ictal single photon emission computed tomography showed increased flow on the side of seizure onset in 86% of seizure-free patients compared with 62% of non-seizure-free patients. Ninety-seven percent of seizure-free patients had a pathologic diagnosis; mesial temporal structures were identified in 61%. Only 64% of non-seizure-free patients had a pathologic diagnosis, and mesial temporal structures were identified in only 36% of non-seizure-free patients. CONCLUSIONS: Eighty-nine percent (79/89) of our patients benefited from surgery. The following factors were predictive of good outcome: a history of febrile seizures; ictal single photon emission computed tomography showing increased blood flow ipsilateral to the epileptogenic zone; a pathologic diagnosis; and the presence of mesial temporal structures in the resected tissue.

Adolescent↗

Role of foramen ovale electrodes in presurgical evaluation of intractable complex partial seizures.

BACKGROUND: The value of intracranial electrodes such as depth electrodes and subdural grids for intracranial electroencephalographic (EEG) recording in patients with intractable epilepsies has been well recognized. A new technique, foramen ovale electrode (FOE) implantation, was first introduced by Wieser in 1984 for the lateralization of bilateral mesiotemporal lobe (MTL) onset of seizures. METHODS: Since October 1993, a multipolar, three-contact FOE has been used in 12 intractable epileptic patients for presurgical evaluation. The reasons for FOE implantation included bilateral MTL onset of seizures recorded by extracranial EEGs in nine patients, and extracranial EEG abnormalities inconsistent with the results of magnetic resonance imaging (MRI), positron emission tomogram (PET) or Wada test in three patients. Under general anesthesia, the FOEs were implanted according to the technique introduced by Kirschner, using Barters landmarks. RESULTS: After long-term telemetry recording with FOE, seven patients revealed clear onset of seizures originating from one side of the MTL and underwent anterior temporal lobectomy (ATL). Two patients had seizures of bilateral MTL onset. However, they received ATL due to predominantly unilateral interictal epileptiform discharges (EDs) and/or MRI and PET abnormalities. Seven (78%) of the nine operated patients became seizure-free after ATL. Three patients were considered not operable because two had multifocal onset of seizures and one had seizures with independent bilateral MTL onset. No serious complication resulted from implantation of FOE in this series. CONCLUSIONS: The semi-invasive technique of FOE is reliable for lateralization of bilateral MTL onset of seizures which are often not clearly recorded by extracranial EEGs. This procedure is safe and can be an alternative to invasive implantation of depth electrodes and subdural grids.

Adult↗