Complex partial and pseudoseizure disorders.

The differentiation of ictal and nonictal seizure disorders is difficult, particularly in patients suffering from partial seizures with complex symptomatology. The authors state that observation of a patient's habitual seizure during EEG recording is the ideal diagnostic tool and describe their method of seizure activation with sphenoidal electrodes and simultaneous audiovisual monitoring. They emphasize the necessity for early, aggressive treatment of both ictal and nonictal seizure disorders, point out risks to the patient if the incorrect diagnosis is made, and urge further cooperation between psychiatrists and neurologists in this borderland area.

Pharmacological prophylaxis in the kindling model of epilepsy.

Review of antiepileptic drug assessment to date by means of the kindling model of epilepsy suggests that it fills a gap that is evident in standard screening methods such as maximum electroshock or pentylenetetrazol screening tests. However, in order to obtain a comprehensive profile of antiepileptic drugs regarding prophylaxis of developing seizures and treatment of well-established seizures through the kindling preparation, it is desirable to have the following: (1) standardization of kindling techniques, (2) examination of drug effects on developing as opposed to developed seizures, (3) use of a variety of animal species, involving different functional brain sites, and (4) monitoring of plasma levels of the drug administered. It is envisaged that judicious use of the kindling preparation might also enable us to gain some insight into the mechanisms by which drugs produce their prophylactic or therapeutic effect.

Cerebral hemispheric asymmetry in humans. Cortical speech zones in 100 adults and 100 infant brains.

Morphological asymmetry of the frontal operculum and temporal planum becomes measurable at the 29th week of gestation. There is evidence of subsequent differential development of the planum in favor of the left, with the left planum larger than the right. While both the frontal operculum and left planum were always present, the right planum ranged in size from absent (10%)to larger than the left (about 10%). Females predominated (P less than .05) in the latter group. The findings suggest that (1) a higher percentage of persons may have right-sided cerebral representation for speech than has been assumed previously; (2) a predetermined morphological asymmetry contributes to establishing the ultimate pattern of cerebral speech representation following an early insult to a predisposed hemisphere; and (3) it is necessary to scrutinize clinical material for the differential organization of hemispheric development between sexes.

Amino acids in human epileptogenic foci.

Free amino compounds were measured in 16 rapidly frozen epileptogenic foci excised from temporal or frontal cortex of nine patients with focal epilepsy, and in single cortical biopsy specimens obtained from 16 nonepileptic patients. Unlike the findings of a previous study, glutamic and aspartic acids were not diminished in the foci, nor was there a decrease in gamma-aminobutyric acid (GABA) or taurine levels. Glycine content was markedly elevated in two of 16 epileptogenic foci. These results do not suggest that deficiencies of GABA or of taurine, amino acids that may act physiologically as inhibitory neurotransmitters or modulators of inhibition, are causes of focal epilepsy, nor do they provide a logical basis for clinical trials of taurine in treatment of human epilepsy.

Prophylactic effects of phenytoin, phenobarbital, and carbamazepine examined in kindling cat preparations.

Prophylactic effects of phenobarbital, phenytoin (diphenylhydantoin), and carbamazepine were examined in amygdaloid kindling preparations in cats. Daily electrical stimulation was delivered at the time of peak plasma levels. Comparative examination of the chronological pattern of the clinical seizure development, after discharge growth, and formation of distant independent spike foci was made between periods of kindling with chronic drug administration and of rekindling without drugs. Both phenobarbital and carbamazepine were effective, but phenytoin was totally ineffective. Prophylactic action of phenobarbital and carbamazepine was mainly through the suppression of the development of motor seizures manifestations in the former and the same with the development of sustained after discharge in the latter. The kindling preparation appears to possess many desirable features as an ideal model of human epilepsy for the purpose of assessment and recruitment of potential antiepileptic drugs and development of a rational pharmacotherapeutic approach for the management and prevention of seizure disorder.

Spontaneous recurrent seizure state induced by daily electric amygdaloid stimulation in Senegalese baboons (Papio papio).

Daily electrical stimulation of the amygdala in Senegalese baboons (Papio papio) resulted in the development of generalized convulsive seizures focal onset through five distinct clinical stages in an average of 72 days. The chronologic pattern of electroclinical features suggested that vertical intrahemispheric ictal dissemination was of primary importance in the progressive seizure development. Some animals developed spontaneous recurrence of both partial complex and primary generalized seizures. The kindling preparation in P. papio represents a unique model of human epilepsy with its secondary generalized convulsive seizure development, spontaneously recurrent partial and primary generalized seizures in the background of predisposed epileptogenic susceptibility.

Secondarily generalized convulsive seizures induced by daily amygdaloid stimulation in rhesus monkeys.

Amygdaloid kindling in rhesus monkeys resulted in development of secondarily generalized convulsive seizures in an average of 196 days. Prior pharmacologic (bemegride) kindling accelerated this seizure development in one animal. None of the animals reached the stage 5 primary generalized seizure of baboons (Papio papio), even after 400 daily amygdaloid stimulations. Seizure stage instability, with frequent regression to an earlier stage, and the difficulty of establishing a generalized seizure triggering threshold in most of the rhesus monkeys, contrasts with our experiences in Papio papio. Thus, differences in the speed of kindling and in the quality of kindled convulsion between rhesus monkeys and epileptic baboons probably reflect the presence or absence of an epileptogenic predisposition in these two species. The difficulty of developing convulsive seizure in rhesus monkeys suggests that this species is particularly suited for the study of partial complex seizure. These studies indicate that the abrupt onset of human epilepsy with a fully developed convulsive seizure must represent and overwhelming central pathophysiologic event resulting from an endogenous, exogenous or a combined insult interacting with a genetically predisposed seizure susceptibility.

An epileptic syndrome caused by mesial frontal lobe seizure foci.

We describe an epileptic syndrome of bilaterally coordinated limb movements, axial movements, vocalization, and nonmasticatory oral activity. EEG and physiologic evidence indicates the syndrome is caused by ictal discharge in the mesial frontal lobes. Two of 12 patients were not helped by anterior temporal lobectomy, and 3 others improved after section of the anterior two-thirds of the corpus callosum.

Cerebral organization of affect suggested by temporal lobe seizures.

A right-handed woman with independent left- and right-sided temporal lobe discharges was studied by continuous EEG and videotape monitoring for 3 weeks. Changes in affect were noted in the immediate and extended postictal periods and varied with the side of discharge. After a left-sided discharge, she became globally aphasic and depressed. Right-sided discharges evoked laughing and postictal hypomania. These manifestations were attributed to contralateral hemispheric disinhibition after ipsilateral seizure inactivation. This case provides evidence that the speech-dominant hemisphere subserves positive feelings and the nondominant hemisphere negative ones.

Results of anterior corpus callosum section in 24 patients with medically intractable seizures.

Twenty-four medically refractory seizure patients, who did not qualify for excisional surgery, had anterior two-thirds corpus callosum section. Three to 11 years' postoperative follow-up suggests that this procedure can (1) lateralize a frontal lobe focus, which may lead to subsequent localized excision and (2) significantly reduce seizure frequency and severity in 75% of the patients without giving any permanent neurologic deficits. Patients with an ictal focus confined to one frontal lobe did best (8/8 improved), followed by patients with secondarily generalized seizures and multifocal bilateral foci (5/6 improved). Patients with mental retardation benefited less frequently (5/10 improved), but 4/4 from this group with ictal falls associated with Lennox-Gastaut syndrome did benefit. In this series, the improvements following the anterior partial section were lasting if present at 1 year of follow-up. Anterior corpus callosum section should be considered as a diagnostic (lateralizing) and therapeutic option in appropriately defined medically refractory patients who do not qualify for excisional surgery.

Long-term follow-up after cerebral hemispherectomy: neurophysiologic, radiologic, and psychological findings.

Eight patients were studied 3 to 16 years (mean, 10 years) after cerebral hemispherectomy. Seven have infantile hemiplegia, and one had Sturge-Weber disease. Preoperative assessment included EEG responses to intracarotid drug injections. Postoperative complications occurred in seven patients. The operation was followed by a marked reduction in seizure frequency and improvement in behavior, with little change in intellect or hemiplegia. Neuropsychological assessment performed in four patients showed that they were not aphasic, but nonverbal spatial abilities were poor. CT showed marked shift of the remaining hemisphere in five of six patients scanned.

Dual task performance by patients with left or right speech dominance as determined by carotid amytal tests.

Patients who had their speech dominance determined by carotid Amytal testing were evaluated with a dual task procedure consisting of reading and finger tapping. As expected, the asymmetry of interference between tasks varied with speech dominance. Patients with left hemisphere speech tended to show greater interference in the right hand whereas patients with right hemisphere speech showed greater interference in the left hand. Since the right hemisphere dominant patients were also right-handed, the results suggest that interference effects are more closely linked to speech than to motor dominance.

Language dominance: correlation of radiological and functional data.

Morphological asymmetry of the posterior sylvian region was measured in carotid arteriograms of patients with medically refractory seizures. Anatomical asymmetry correlated with ear superiority on dichotic listening tests.

Suppression of amygdaloid kindled convulsion following unilateral injection of 2-amino-7-phosphonoheptanoic acid (2-APH) into the substantia innominata of rats.

The comparative effect of intracerebral injection of 2-APH, a selective antagonist for N-methyl-D-aspartate (NMDA) receptors, into the substantia innominata (SI) and the amygdala (AM) of AM-kindled rats was examined. The intra-SI injection (ipsilateral to the kindled AM) induced a transient incoordination followed by immobility with loss of the rightening reflex, beginning at about 5 min following the injection and lasting for about 3 h. When the animals were stimulated at the previously established generalized seizure triggering threshold (GST) 45 min after the injection, the kindled seizure regressed to earlier stages although the afterdischarge (AD) duration remained unchanged. At 24 h, kindled seizure was readily activated at the GST. When 2-APH was injected into the kindled AM, no behavioural change occurred but AM stimulation at the GST failed to produce AD 45 min after the injection. Kindled seizure could be elicited, however, when the stimulus intensity was increased. This elevation of the GST lasted for 1-18 days. The findings suggest that NMDA receptors in the AM and SI play a differential role in AM seizure initiation and propagation, respectively. They also provide further support to the role presumed to be played by the SI in transforming the limbic seizure into motor seizure.

Reversible suppression of amygdaloid kindled convulsion following unilateral gabaculine injection into the substantia innominata.

Amygdaloid kindled generalized convulsion was reversibly blocked despite continued afterdischarge generation by amygdaloid stimulation for about 60 h following intracerebral administration of gabaculine, a GABA-transaminase inhibitor, into the substantia innominata (SI) ipsilateral to the side of amygdaloid kindling. It is suggested that the SI plays an important role in convulsive seizure generalization of amygdaloid origin.

Kindling of the massa intermedia of the thalamus in rats.

The kindling response of the massa intermedia (MI) was assessed in rats. Clinical manifestation of the MI kindling was generally similar to that of limbic kindling, and positive transfer to the amygdala (AM) was obtained following MI kindling. However, MI kindling showed (1) a relatively high after discharge threshold which sometimes increased during the course of kindling, (2) a seizure stage instability with frequent regression to earlier stages, (3) a failure to establish a generalized seizure triggering threshold with an 'all-or-none' property, and (4) a generalized tonic-clonic seizure, which was quite different from a kindled limbic seizure, during early phase of kindling. Furthermore, the MI stimulation caused violent beating movement of the forelimbs, jumping, or running regardless of presence/absence of afterdischarge. The findings suggest that mechanisms other than a simple activation of limbic structures are involved in the process of MI kindling.

Convulsive seizures in rats induced by N-methyl-D-aspartate injection into the massa intermedia.

The behavioral and electroencephalographic effects of N-methyl-D-aspartate (NMDA, 25 nmol/1 microliter) injection into the massa intermedia (MI) was examined in rats. The injection caused violent running/jumping and shrill vocalization without evidence of EEG seizure in the hippocampus (HP) and amygdala (AM). Animals with the injection site located in the reuniens nucleus subsequently developed generalized tonic and then clonic seizure, leading to fatal status epilepticus in some animals. Intermittent or continuous EEG discharge in the limbic system was found during clonic seizures. These findings suggest that the NMDA receptor in the reuniens nucleus in the MI participates in the generation and expression of convulsive seizure in rats.

Facilitation of premotor cortical seizure development by intranigral muscimol.

The role of the substantia nigra in seizure development was investigated using a chronic model of partial onset generalized seizure induced by low frequency cortical stimulation. Unilateral intranigral micro-injection of muscimol, a GABA receptor agonist, was found to facilitate partial onset seizure development, but did not affect developed seizures. This finding suggested that a non-dopaminergic, presumably GABAergic, mechanism was involved since the facilitatory effect of intranigral muscimol was not modified by haloperidol pretreatment.

Bidirectional transfer between kindling induced by excitatory amino acids and electrical stimulation.

Chemical (C) kindling by means of repeated spaced injections into the amygdala (AM) of a subconvulsive dose of L-glutamate and L-aspartate combined in a molar ratio of 1:3. (Glu/Asp) produced progressive seizure development culminating in generalized convulsion strikingly similar to electrically kindled Stage 5 seizure in rats. These C-kindled AM sites responded readily to electrical stimulation with very rapid development of kindled seizure. When a separate group of rats electrically kindled at the AM were subjected to identical C-kindling at the kindled AM site, a similar positive transfer effect was observed. In addition, 30 days following the last injection, kindled Stage 5 seizure was triggered with a single injection of Glu/Asp, one-half of the dose used for C-kindling. These results suggest that the glutamate and/or aspartate systems participate in the development and persistence of increased seizure susceptibility induced by AM kindling.

Amygdala kindling in rats with brainstem bisection.

The effect of midsagittal bisection of the brainstem (the midbrain to the pons) on amygdala (AM) kindling at the primary and the secondary sites was examined in rats. It was found that the kindling rate was not affected at either primary or secondary sites regardless of the extent of bisection. However, seizure progression beyond stage 4 bilateral clonus did not occur with extensive dorsal bisection. The findings suggest that the dorsal midline brainstem structure bisected in this study participates in the mechanism of stage 5 seizure but is not involved in the transhemispheric positive transfer mechanism in rodent AM kindling.