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Autistic spectrum disorder: evaluating a possible contributing or causal role of epilepsy.

The onset of epilepsy in brain systems involved in social communication and/or recognition of emotions can occasionally be the cause of autistic symptoms or may aggravate preexisting autistic symptoms. Knowing that cognitive and/or behavioral abnormalities can be the presenting and sometimes the only symptom of an epileptic disorder or can even be caused by paroxysmal EEG abnormalities without recognized seizures, the possibility that this may apply to autism has given rise to much debate. Epilepsy and/or epileptic EEG abnormalities are frequently associated with autistic disorders in children but this does not necessarily imply that they are the cause; great caution needs to be exercised before drawing any such conclusions. So far, there is no evidence that typical autism can be attributed to an epileptic disorder, even in those children with a history of regression after normal early development. Nevertheless, there are several early epilepsies (late infantile spasms, partial complex epilepsies, epilepsies with CSWS, early forms of Landau-Kleffner syndrome) and with different etiologies (tuberous sclerosis is an important model of these situations) in which a direct relationship between epilepsy and some features of autism may be suspected. In young children who primarily have language regression (and who may have autistic features) without evident cause, and in whom paroxysmal focal EEG abnormalities are also found, the possible direct role of epilepsy can only be evaluated in longitudinal studies.

Adult↗

Six-year follow-up study on the efficacy and safety of vigabatrin in patients with epilepsy.

Twenty-five patients with epilepsy (mostly with partial seizures) who had responded favourably to a short-term trial of add-on vigabatrin entered maintenance treatment. After 52 to 78 months, 15 patients continue to take the drug with good therapeutic response. Median monthly seizure frequency during the last 2 months on vigabatrin in all patients, including drop-outs, was 3.5 (range 0-74) as compared with 10 (range 3-98) during an initial placebo period (p < 0.01). Drop-outs were caused by adverse events in 2 cases (ataxia and psychotic symptoms respectively), seizure breakthrough in 4 cases and reasons unrelated to treatment in 4 patients. In most patients, side effects were absent or mild, the most frequent complaint being weight gain. It is concluded that the antiepileptic efficacy and good clinical tolerability of vigabatrin are generally maintained during long-term treatment for up to 6 years.

Adolescent↗

[Magnetic resonance tomography in comprehensive examination in epilepsy in children].

The paper presents the results of examining 100 children suffering from various epilepsies by magnetic resonance tomography, which determined a morphological substrate of the disease in 26%. The findings were compared with the clinical picture and the results of routine study tools (skull X-ray, EEG, EchoEG, REG). The diagnostic value of the techniques applied was defined. It is concluded that a set of diagnostic tools rather than individual techniques should be applied to reveal etiological and pathogenetic factors of the disease.

Adolescent↗

[The duration of antiepileptic treatment].

110 patients at the age of 18 years and older with different forms of epilepsy and epileptic syndromes were observed during 2-15 years after the first fits. These patients did not follow medical advice. All of them were either treated for short time, irregularly or were not treated at all after their first hospitalisation after beginning of epileptic attacks. In spite of violation of the treatment regimen, 80 patients experienced improvement, 60 patients achieved long-term remissions. It is suggested that even short-term antiepileptic therapy may activate the patient's own antiepileptic system. Negative prognostic criteria were involvement of the temporal structures, multifocal disease.

Adolescent↗

Direct measurement of extracellular lactate in the human hippocampus during spontaneous seizures.

The effect of clinical, spontaneous-onset seizures on extracellular fluid lactate was investigated by the method of lactography, the in vivo on-line measurement of lactate levels using microdialysis. Studies of experimental animals have suggested that generation of extracellular lactate as measured by microdialysis is an index of local glucose utilization and is dependent on the activity of neurons under physiological conditions. Patients with medically refractory complex partial epilepsy underwent stereotactic implantation of combination depth electrode/microdialysis probes into both hippocampi for 7-16 days. During spontaneous complex partial seizures with secondary generalization, extracellular lactate levels rose by 91 +/- 32%. Moreover, this increase persisted for 60-90 min. During a unilateral hippocampal seizure that did not propagate to the contralateral hippocampus, the increase in lactate content was restricted to the side of seizure activity. Between seizures, extracellular lactate levels correlated with the frequency of interictal spikes. In summary, these data suggest that brief clinical seizures increase nonoxidative glucose metabolism significantly as measured by the generation of extracellular lactate. Furthermore, the increase in extracellular lactate levels is limited to the site of seizure activity. Lactate is transported extracellularly via a lactate/proton cotransporter, therefore, the rise in extracellular lactate level may mediate the drop in pH0 associated with seizure activity. As acidification of the extracellular compartment has an inhibitory effect on neuronal excitability, the rise in extracellular lactate content may be a mechanism of seizure arrest and postictal refractoriness. Moreover, extracellular lactate may also mediate the decreased seizure susceptibility associated with frequent interictal spikes.

Adolescent↗

[Psychosis in a case of temporal lobe epilepsy associated with a dysembryoplastic neuroepithelial tumour].

INTRODUCTION: Psychosis is an acknowledged, although infrequent, complication that occurs in 0.5 9% of all cases of epilepsy. In this work, we present a case of complex partial epilepsy due to a dysembryoplastic neuroectodermal tumour in the right hippocampus, which began as acute psychosis and was cured following its surgical removal. Both its aetiology and its pathogenesis are discussed. CASE REPORT: We describe the case of a 17 year old male with a family history of schizophrenia. While studying his last years of secondary education, and apparently well adapted, he was taken into custody and hospitalised urgently because of personality disorders. The patient suffered from somatic and auditory hallucinations, simple visual pseudohallucinations, formal alterations to his thinking, cosmovisions, delusions of influence, persecution, grandeur and of a mystic nature, with no other neurological focus. At the same time, the patient also had complex partial seizures. Magnetic resonance imaging revealed a cystic tumour in the right temporal lobe. Pathology laboratory findings showed a dysembryoplastic neuroepithelial tumour. For a period of two years following surgical removal, the schizophrenic symptoms and the complex partial seizures disappeared and the patient no longer required antipsychotic medication. CONCLUSIONS: Epileptic psychosis may be related to pathological conditions of the hippocampus. In this study we present what we believe to be the first case of a dysembryoplastic neuroepithelial tumour giving rise to such psychosis. Surgical removal of the tumour cured both entities.

Adolescent↗

Complex partial status epilepticus: a depth-electrode study.

Of 87 patients with complex partial epilepsy who were evaluated with depth electrodes, 8 developed complex partial status epilepticus (CPSE). Seizures originated extratemporally in all 8 patients. Frontal lobe onset was established in 4 patients and was probable in 1 more. Medial parietal onset was documented in 1 patient. Medial occipitoparietal onset occurred in another, and 1 patient had multifocal onsets. Even when seizures did not begin frontrally, the frontal lobes were prominently involved during CPSE. CPSE did not occur in 60 patients with seizures originating in the temporal lobe. Both recurrent clinical seizures and continuous altered behavior were observed. Some patients exhibited both clinical patterns at different times during the same episode. Depth recording consistently demonstrated recurrent isolated seizure discharges throughout episodes. The clinical patterns were related, in part, to electroencephalographic seizure frequency, duration, and intensity. Episodes of CPSE were not associated with intellectual deterioration.

Adult↗

Effects of propofol sedation on seizures and intracranially recorded epileptiform activity in patients with partial epilepsy.

BACKGROUND: Case reports suggesting both pro- and anticonvulsant effect(s) of propofol have been published in recent years. The effects of sedative doses of propofol on epileptiform activities in patients suffering from intractable partial epilepsy were systematically investigated. METHODS: Fourteen patients suffering from complex partial seizures were studied. Electroencephalogram (EEG) was recorded from intracranial electrodes implanted in the hippocampi and temporal neocortex. Propofol was given as a computer-controlled infusion in four steps to achieve target plasma propofol concentrations of 0.3, 0.6, 0.9, and 1.2 micrograms/ml. Each concentration was maintained for 30 min, and steady-state kinetics were confirmed by blood levels drawn at 10th and 30th min at each level. Between the 15th and 30th min of each concentration of propofol, EEG was analyzed for presence of electroencephalographic seizure activity and/or number of interictal spikes (IIS). Effects of propofol on IIS frequency at different electrode sites were compared using a two-way repeated measures analysis of variance. A value of P < 0.05 was considered significant. RESULTS: None of the patients developed a seizure during the 2 h of propofol infusion. No "false spikes" (spikes developing with propofol infusion in areas where no spikes were seen in baseline EEG) were seen. Although effects of propofol on IIS frequency were highly variable across patients and at different propofol doses in the same patient, there was no statistically significant effect of propofol on any electrode site with any of the doses studied. CONCLUSIONS: We were unable to demonstrate a significant change in epileptiform activity with sedative doses of propofol in patients suffering from complex partial epilepsy.

Adult↗

Classifications and epidemiologic considerations of epileptic seizures and epilepsy.

The manifestations of epileptic disorders are widely known to be extremely protean. Classifying the disorders is a way of achieving a common understanding of the terminology used in identifying seizure disorders in the clinical or research settings. Two International Classifications have been developed, namely the International Classification of Epileptic Seizures and the International Classification of Epilepsy and Epileptic Syndromes. The first divides epileptic seizures into two major categories: partial and generalized. Partial epileptic seizures are further classified according to the impairment or the preservation of consciousness into simple partial and complex partial seizures. Either condition may secondarily generalize into tonic-clonic seizures. Under the International Classification, epilepsy and epileptic syndromes are initially classified according to their corresponding types of seizures into localization-related and generalized disorders. Each disorder is further classified according to the relationship to etiologic or predisposing factors into symptomatic, cryptogenic, or idiopathic types. The classifications undoubtedly will be further revised as more is learned about epileptic disorders with advances in electrophysiology, neuroimaging techniques, and molecular genetics. An overview of the epidemiology of epileptic disorders shows that, contrary to the popular belief, they are primarily disorders of childhood; age-specific incidence rates of first unprovoked seizure and of epilepsy are highest in the elderly. An appreciation of the epidemiology of seizure disorders is essential in their clinical and laboratory evaluation.

Adolescent↗

Complex partial seizures. Clinical features and differential diagnosis.

Complex partial seizures are the most common seizure type in patients with partial epilepsy. Most complex partial seizures emanate from the temporal lobe; however, the seizures also may be extratemporal in origin. The clinical phenomenology may distinguish complex partial seizures from nonepileptic paroxysmal disorders and other seizure types. Physiologic and psychological disorders need to be considered in the differential diagnosis of seizure activity. Long-term EEG monitoring may be necessary for select patients to confirm the diagnosis of epilepsy and to classify appropriately seizure type. Carbamazepine and phenytoin are the antiepileptic drugs of choice in the management of complex partial seizures. Polypharmacy and use of cognitively impairing antiepileptic drugs may reduce patient compliance and further impair the quality of life of the patient with epilepsy. Finally, epilepsy surgery is an important alternative for the patient with intractable partial seizures.

Anticonvulsants↗

Electrophysiological effects of felbamate.

Felbamate is a broad spectrum antiepileptic drug recently introduced into clinical practice for controlling seizures in patients affected by Lennox-Gastaut epilepsy, complex partial seizures or otherwise intractable epilepsies. However, the cellular mechanisms by which the drug exerts its anticonvulsant actions are not fully understood. The aim of the present article is to outline the possible mechanisms of action of felbamate as suggested by findings obtained with electrophysiological approaches.

Animals↗

The association between seizure clustering and convulsive status epilepticus in patients with intractable complex partial seizures.

PURPOSE: We examined the association between seizure clustering and convulsive status epilepticus (SE) in patients with intractable complex partial seizures, to identify whether patients whose seizures typically cluster are at high risk for convulsive SE (CSE). METHODS: Seventy-six patients with intractable complex partial epilepsy who underwent presurgical evaluation in the Montefiore Epilepsy Management Unit from 1993 to 1997 were contacted and interviewed about typical seizure frequency and distribution and history of CSE. Seizure clustering was defined as three or more complex partial seizures within a 24-h period, with return to baseline between seizures. RESULTS: Of the 76 patients contacted, 21 (28%) had experienced at least one episode of CSE, and 36 (47%) typically experienced clustered seizures. SE occurred in 16 (44%) of 36 patients with clustered seizures, and in five (12.5%) of 40 patients with nonclustered seizures (p < 0.002). Of 53 patients with temporal lobe epilepsy, CSE occurred in 13 (50%) of 26 patients with clustered seizures, and four (14.8%) of 27 patients with nonclustered seizures (p < 0.006). CONCLUSIONS: Patients with intractable complex partial or localization-related epilepsy who typically experience seizure clustering are at a significantly higher risk for CSE than are patients with nonclustered seizures.

Adolescent↗

Cardiac rhythm during temporal lobe seizures.

We studied the neuroanatomic correlates of ictal tachycardia in 27 seizures from five patients with unilateral temporal lobe epilepsy being evaluated with bilateral temporal lobe depth electrodes and orbitofrontal subdural electrodes. There were 11 complex partial seizures, three simple partial seizures, and 13 subclinical seizures. For all seizures, heart rate (HR) increased in a graded fashion as new cortical regions anywhere in the brain were recruited into the seizure. HR plateaued at the new level despite EEG frequency changes until the next region became involved. Increases in HR did not correlate with increased duration of seizures but rather with volume of brain involved. Restricted amygdaloid seizure activity was generally insufficient to alter HR. We conclude that the amygdala has a limited role in modulating HR during seizures, and ictal tachycardia depends principally on the volume of cerebral structures recruited into a seizure.

Adult↗

Near infrared spectroscopy (NIRS) distinguishes seizure types.

Near infrared spectroscopy (NIRS) is a noninvasive method for bedside measurement of cerebral oxygenation (SaO(2)). The purpose of this study was to establish differences in SaO(2)for complex partial seizures (CPS) and rapidly secondarily generalized CPS (RCPS). We studied eight adults with medically refractory epilepsy undergoing evaluation for temporal lobectomy. We continually measured cerebral SaO(2)via a Somanetic Invos 3100a cerebral oximeter, pre-ictal (5 minutes), ictal, immediate (30 seconds) post-ictal, and late post-ictal (5 minutes after ictus). Seventeen seizures (12 CPS, four RCPS and one subclinical) were recorded in eight patients. The percentage change in cerebral SaO(2)from pre-ictal to ictal periods was derived. Cerebral SaO(2)increased (percentage change, mean: 16.6, SD: 13.9) for CPS and decreased (percentage change, mean: 51.1, SD: 18.1) for RCPS. No change in cerebral oximetry was recorded for the subclinical seizure. Post-ictal (immediate and late) increase in cerebral SaO(2)was seen for 11 of the 17 seizures (nine CPS and two RCPS). Peripheral SaO(2)rose greater than 93% for all CPS and the subclinical seizure, but decreased between 78 and 84% during RCPS. These results suggest NIRS distinguishes cerebral SaO(2)patterns between CPS and RCPS. The decrease in peripheral SaO(2), however, may account for the decrease in cerebral SaO(2)seen in generalized seizures.

Adult↗

Levetiracetam and partial seizure subtypes: pooled data from three randomized, placebo-controlled trials.

PURPOSE: To determine the effect of levetiracetam (LEV) on partial seizure subtypes (simple partial, complex partial, and secondarily generalized seizures) in patients with refractory epilepsy. METHODS: Pooled results from three placebo-controlled trials were analyzed. RESULTS: A statistically significant reduction in the frequency of all partial seizures and all seizure subtypes was observed in the LEV group (p < 0.001 vs. placebo). The proportion of patients in whom secondarily generalized seizures could be prevented over and above the reduction of partial seizures was significantly greater in the LEV group as compared with placebo, with an odds ratio of 1.83 [95% confidence interval (CI), 1.10-3.05]. CONCLUSIONS; LEV reduces frequency of simple and complex partial seizures. In addition, it demonstrates a specific, independent reduction of secondarily generalized seizures.

Adult↗

Familial temporal lobe epilepsy: a clinically heterogeneous syndrome.

We describe the clinical characteristics of a group of patients with familial temporal lobe epilepsy (TLE) in 11 kindreds with 36 affected individuals identified and investigated at the Montreal Neurological Hospital. Seizure types were simple partial (n = 20), complex partial (n = 29), and rare generalized tonic-clonic. Simple and complex partial seizures were infrequent or well controlled by anticonvulsant medication in 17 of 29 patients (59%) and without optimal response to medical therapy in 12 of 29 patients (41%). Pedigree analysis suggested autosomal dominant inheritance with incomplete penetrance. The syndrome of familial TLE has heterogeneous clinical manifestations and is not always benign.

Adolescent↗

Randomized, double-blind, placebo-controlled, clinical trial of D-alpha-tocopherol (vitamin E) as add-on therapy in uncontrolled epilepsy.

In a double-blind, cross-over trial, vitamin E, and placebo were compared as add-on therapy in 43 patients with uncontrolled epilepsy. The study consisted of a 3-month baseline period followed by two treatment phases of vitamin E or placebo with cross-over to the second phase after 3 months. No significant side effects were noted during the study. Mean seizure frequency in the baseline period was 15.9 +/- 10.5 as compared with 11.8 +/- 10.9 during the placebo phase and 13.7 +/- 11.1 during the vitamin E phase. No significant change in seizure frequency was observed with vitamin E as compared with placebo (p > 0.1). Similar observation was noted in subgroups with generalized seizures (n = 25), partial with secondarily generalized seizures (n = 11), or complex partial seizures (CPS) (n = 7). This study did not corroborate the earlier claims of therapeutic efficacy of vitamin E as add-on therapy in refractory epilepsy in adults.

Adolescent↗