Biomedical subjects
Publications and source records attributed to J A Wada.
Significant susceptibility to photically induced seizures has in the past been observed only in Senegales baboons (Papio papio) and epileptic humans. However, we have unexpectedly observed a photomyoclonic response to intermittent photic stimulation in 5 of a sample of 6 yellow baboons (Papio cynocephalus).
A group of 7 baboon brains was examined for the presence of an asymmetry of the frontal poles. 6 of the 7 brains exhibited an asymmetry in which the right frontal pole was longer than the left by a mean of 1.4 mm. The seventh brain had frontal poles of equal length.
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.
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The bioavailability of two preparations of carbamazepine--the tablet and a new syrup-was studied in 9 adult male volunteers by measuring saliva and serum levels. Peak time was significantly earlier and peak level significantly higher in serum for syrup as compared to tablet. Levels remained higher for syrup for 12 hr. Saliva was contaminated for up to 2 hr by syrup ingestion, possibly for a half hour by the tablet. Beyond that, saliva/serum ratios remained stable. Saliva level variation was too large for pharmacokinetic studies but acceptable for clinical purposes if sampling was long enough after the last dose.
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The antiepileptic and prophylactic effects of delta9-tetrahydrocannabinol (delta9-THC) and delta8-THC were examined in rats that developed generalized seizures in response to intermittent electrical stimulation of the amygdala (kindling). Both isomers of the THC were able to acutely suppress kindled seizures, but consistent antiepileptic effects were obtained only with high, toxic dosages. Tolerance to the antiepileptic effects of THC developed very rapidly when the drugs were give repeatedly, and there was evidence that the repeated administration of a high dosage of delta9-THC resulted in a state of acute physical dependence. Administration of the isomers of THC during seizure development resulted in a suppression of kindling, suggestive of a prophylactic effect. The rate of rekindling after withdrawal of the drugs was not significantly different from that of vehicle-treated control rats, however, indicating that a genuine prophylactic effect was not obtained.
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.
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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.
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Morphological speech zone asymmetry in man cannot be due to environmental or developmental factors after birth. The functional implication of such a finding is not yet clear. Morphological asymmetry of the human brain is paralleled by electrophysiological evidence of cerebral hemispheric asymmetries. The results of our analysis of 50 infants suggest that clear occipital-temporal coherency asymmetry similar, but not identical to the adult pattern, also exists at or near birth. These asymmetries are generated by stimuli with no verbal content and in infants who presumably have no or an undeveloped capability for language. It is suggested that language is only a part of much more fundamental asymmetries which include the processing of auditory and visual information. Our results, and those of other, are consistent with the assumption that the left hemisphere is more able to relate stimuli to past experience, either short or long-term, while the right hemisphere is more able to process, stimuli which are not easily identifiable or referable. These capabilities would not be based on language, and hence would be expected to develop independently and possibly before speech. The demonstration that reversing electrophysiological asymmetries can be generated with non-speech stimuli in the visual and auditory modalities, and in neonates, supports such an assumption.
A computerised evoked potential test for the lateralisation of speech dominance was compared with the intracarotid sodium amylobarbitone test in 22 epileptic patients. Based on spectral analysis, the computer test correctly predicted the speech dominance of 15 of 16 left speech dominant and five of six right speech dominant patients. This non-invasive test is simple, quick, and innocuous and can be easily implemented on a small laboratory computer.
Examination of the effects of primary site kindling upon the development of secondary site amygdaloid kindling in cats showed that the former exerts powerful positive as well as negative after effects upon the latter. The positive after effect appears to be directed towards establishing a linkage between the secondary site and the Stage 6 generalized convulsive mechanism. The negative after effects were strikingly similar to those observed in animals with forebrain bisection subjected to amygdaloid kindling, suggesting that it is primarily directed towards functional accessibility of the cerebral structures interconnected by the forebrain commissure. The similarity of the findings in animals with anterior neocortical lesions supports such an assumption. The transient nature of the negative after effects was indicated by the development of a 'normal' clinical ictal pattern from the secondary site when it occurred spontaneously. Secondary site kindling exerted similar but less prominent negative after effects when the primary site was re-tested. Stage 6 seizure was elicited upon the first trial, however.