This paper reviews some recent developments concerning the “non-essential” amino acid Taurine. It is shown that taurine is important in metabolic regulations within the heart, muscle and brain. Particular attention is paid to the neuropharmacology of taurine, such as its possible role in epilepsy.

The specific behavioral manifestation associated with the different disorders producing the syndrome of dementia have remained poorly investigated. We examined the memory performance of three distinct groups of patients with dementia secondary to Alzheimer's disease (AD) multiple-infarctions (MID) and vertebrobasilar insufficiency (VBI) on the ten subtests of the Wechsler Memory Scale (WMS). Statistical methods of analysis were used to maximize the differences between the groups. Univariate statistical procedures revealed that the AD group performed significantly and consistently lower than the two cerebrovascular groups. There were no significant differences between the two cerebrovascular disease groups, even though the MID group tended to perform consistently more poorly than the VBI group. For heuristic and conceptual purposes as well as to determine which combination of the ten WMS variables produced the “best” statistical model differentiating the groups the data was analyzed by multivariate techniques. A discriminate function analysis obtained a 100% valid positive hit rate in discriminating among the three groups. One hundred percent diagnostic accuracy was also obtained in discriminating between MID and AD as well as AD and VBI. The two cerebrovascular groups tended to overlap in their probability distributions with an 81% hit rate. Different predicitive statistical models were identified to differentiate the various diagnostic groups. It was possible to discriminate the three diagnostic groups by different patterns of memory performance.

This is a report of the first recorded observation of displacement of temporal cortex into the central spinal canal in an infant with the Arnold Chiari malformation, platybasia, aqueductal atresia, hydrocephalus and meningomyelocele. The combination of an absent tentorium, absent right cerebellar hemisphere and malformed fourth ventricular roof provided the anatomical background for this unique event.

This is a review of the total care of those acute spinal cord injury patients in Ontario during the years 1969 and 1970, from extrication and transportation following the accident to death, or the completion of primary definitive rehabilitation.

Information was extracted from the available ambulance records, the patients and many of the responsible physicians were interviewed personally. The study was detailed and intensive and included a review of each patient's hospital records in each hospital up to discharge from the rehabilitation programme into the community, or to a chronic care unit. The data was compiled in accordance with a detailed and lengthy questionnaire developed for this study.

The incidence of acute cord injuries in Ontario in 1969 and 1970 amounted to 244; in 1969, 15.9 per million population and in 1970, 13.6 per million. As in other studies road accidents took first place, followed by falls from a height; sports injuries ranked third and 65.7% of these were caused by diving into shallow water. Age incidence, and incidence by month, day of week and time of day were identified. Fridays and Saturday afternoons in July and August are particularly hazardous.

The study continued to the end of 1974 by which time 34 deaths had been recorded. Peak incidence of death occurred within fourteen days of injury. The most common cause of death was respiratory in origin.

Geographical distribution was identified and the type of hospital treating the acutely injured patient.

Fourteen percent of persons with spinal column injury suffered progressive or sequential spinal cord damage both prior to and following medical contact. The incidence of pressure sores and genitourinary sepsis and calculosis was high in all types of hospitals. The effect of operative treatment was noted in the cases of complete quadriplegia and paraplegia.

Of the 133 survivors who undertook a rehabilitation program, 84% returned to their homes and 59% achieved gainful employment or ongoing education.

The cost was determined of general hospital services and rehabilitation programmes.

A new model for the care of the spinal cord injury patients in Ontario was proposed.

A method of internal fixation of adjacent vertebrae that have been dislocated or subluxed has been presented. In the author's hands and in the hands of associates this has proven to be a satisfactory method of fixation in this type of injury. It has the advantage over many other posterior techniques that only two vertebrae are fixed together.

The kindling effect is a relatively permanent alteration in brain function which results from repeated electrical or chemical stimulation and culminates in the appearance of electrographic and behavioral convulsions whenever the original stimulus is reapplied. The effect results from tetanic activation in the anterior cortex, limbic system or associated areas of the adult mammalian brain, and the lasting alterations are transynaptic and quite widespread. They are based in part on synaptic facilitation, and they are accompanied by specific alterations in normal behavior. In these and other respects, kindling is analogous to normal learning. It is possible that the stored component (engram) of kindling involves the same physiological mechanism as the engram of normal long term memory. Morphological study of identified synapses has not provided conclusive evidence for an anatomical substrate of kindling, but physiological experiments demonstrate a lasting potentiation of the excitatory postsynaptic potential.

Two approaches to the study of the kindling phenomenon were discussed: 1) an attempt to identify the pattern of neural activity required to produce the changes underlying kindling and 2) an investigation into the nature of those changes. Three experiments were reported that used the neocortical transcallosal system as a monosynaptic model system in which to study possible synaptic mechanisms of the kindling effect. Experiment I showed an increase in the transcallosal evoked potential following neocortical kindling. Experiment II showed an increase in the strength of the transcallosal evoked cell discharge following neocortical kindling. Experiment III reported the results of an histological examination of neocortical tissue in kindled and non-kindled animals using the Golgi-Cox technique. Spine density, spine dimension and branching were measured for pyramidal cell apical dendrites. No differences were found between primary and secondary (contralateral) foci or between kindled and non-kindled animals.

Secondary epileptogenesis was induced in the hippocampal cortex of the paralyzed bullfrog by means of localized, unilateral, intermittent electrical stimulation (kindling). Stimuli were designed to yield a brief but definite after-discharge. In control animals a progressive increase in after-discharge duration occurred at the 1° (stimulated) site and then at the 2° site (contralateral hippocampus). Spontaneous epileptiform potentials (SEP's) occurred between stimuli, eventually independently on both sides.

Cycloheximide (50 mg/kg) caused 88-99% reduction in protein synthesis, measured by 14C-leucine incorporation into brain protein. Cycloheximide-treated animals revealed no evidence of progressive prolongation of after-discharge duration when subjected to the kindling procedure (p = 0.1205xl0-7). SEP's were reduced in the cycloheximide-treated animals, and confined to 1° hemisphere (p=0.6xl0-10).

Since cycloheximide did not disturb normal electrogenesis or disrupt the after-discharges, this experiment distinguishes processes dependent upon electrical events from those requiring macromolecular synthesis. Protein synthesis seems critical to the emergence of spontaneous and autonomous epileptiform behavior of neural aggregates.

An investigation was made of both primary and “transfer” kindling as they occur in ipsilateral limbic sites. Primary kindling was found to involve progressive growth of afterdischarge (AD), propagation and convulsive behavior. It was noted that AD growth did not take place gradually but occurred in sudden, large increments. “Transfer” (a significant acceleration of secondary kindling) was found at every secondary limbic site. It was associated with the early appearance of full-blown AD's, super-normal propagation, and well-developed seizures. The post-transfer interference of primary site function previously reported by Goddard et al was also found, but it occurred in significant amounts only after transfer kindling of the amygdala. It is believed that the data offer some support for both of the hypothetical mechanisms of transfer which have been proposed.

Rats were subjected to varying degrees of commissurotomy, followed by implantation of a bipolar electrode into each amygdala. After the kindling of six convulsions at one electrode (primary site), the procedure was applied to the contralateral amygdala (secondary site). Convulsions were observed to develop more rapidly, independent of the degree or kind of transection. After 6 secondary site convulsions, the primary site was re-tested and convulsion-triggering was blocked, except in animals with transection of the rostral portion of the corpus callosum (CC).

Collectively, the data indicate: (i) amygdala kindling develops a lasting trace which operates through the midbrain or brainstem; (ii) kindling from a second site utilizes this trace; (iii) a series of 6 convulsions produces negative after-effect which manifests itself at the convulsion level via the anterior CC; (iv) the anterior CC is important in determining the laterality of the forelimb clonus; and (v) the inter-amygdala propagation of after-discharge is blocked by the combined sectioning of the anterior CC and the anterior commissure.

Seizure development and transference phenomenon were investigated in hippocampal and amygdaloid kindled cats. The behavioral and electrographic findings during the kindling procedures showed that motor seizure development in hippocampal seizures occurred with the emergence of independent discharging in the amygdala, globus pallidus and contralateral hippocampus. Furthermore, secondary site convulsions developed upon the first stimulation of these structures in the hippocampal group but only after over a month of hippocampal stimulation in the amygdaloid group. It was, therefore, concluded that role of the amygdala and globus pallidus in hippocampal seizure development was more essential than that of hippocampal stimulation in amygdaloid seizure development. The common findings between the hippocampal and amygdaloid kindled animals were the systematic progression to seizures, the all-or-nothing nature of the electrical response and the relative permanency of the seizure susceptibility. Seizure susceptibility increased during slow wave sleep and decreased during REM sleep. These latter findings were examined with preliminary data of brain bioassays of catecholamines.

A longitudinal study of the effects of sleep on amygdaloid kindling showed that kindling disrupted normal sleep patterns by reducing REM sleep and increasing awake time. Few interictal spike discharges were observed during the awake stage, while a marked increase in discharge was observed during the light and deep sleep stages. No discharges were observed during REM sleep. During the immediate post-stimulation period the nonstimulated amygdala showed a much higher rate of spike discharge. On the other hand, there was an increase in spike discharge in the stimulated amygdala during natural sleep without preceding amygdaloid stimulation. Amygdaloid stimulation at the generalized seizure threshold during each sleep stage resulted in a generalized convulsion.

The influence of subcortical electrical stimulation on kindled amygdaloid convulsions was investigated in a second experiment. Stimulation of the centre median and the caudate nucleus was without effect on kindled convulsions, while stimulation of the mesencephalic reticular formation at high frequency (300 Hz) reduced the latency of onset of kindled generalized convulsions. Stimulation of the nucleus ventralis lateralis of the thalamus at low frequency (10 Hz) prolonged the convulsion latency, and at high current levels blocked the induced convulsion. Stimulation in the central gray matter at low frequency (10 Hz) also blocked kindled amygdaloid convulsions.

This report presents studies which relate limbic epileptic excitability to behavioral measures of defensive suppression of predatory attack in cats. Correlated with heightened defensiveness to environmental stimuli among non-killer cats is a heightened amygdaloid epileptic excitability, as well as a heightened conduction of amygdaloid epileptic activity to thalamic and hypothalamic substrates of predatory response in the amygdala to the complex visual stimuli presented by rat prey. These neurosensory responses correlate well with measures of epileptic excitability. Brain and behavior measures appear related since enhancement of excitability in the amygdala and of projection of epileptic activity by repeated electrical stimulation of predatory attacks. Furthermore, the ventral hippocampus seems capable of antagonizing the behaviorally suppressive effects of heightened amygdaloid excitability perhaps at points of convergence of amygdaloid and hippocampal output.

The purpose of the present investigations was to explore the generality of the kindling phenomenon and its applicability to clinical situations. Whether local brain stimulation, electroconvulsive shock (ECS), or metrazol the consequence of periodic administration of convulsive agents was found to be the same; in each case repeated application of the agent resulted in the gradual development and intensification of convulsive symptoms (kindling). Moreover, in each case the resulting intensification was not specific to the agent being used and seemed to increase the responsiveness to convulsive agents in general. In the present studies this interaction was seen in the form of an intensified alcohol withdrawal syndrome observed 18 days after cessation of a series of metrazol injections, amygdaloid stimulations, or ECS. Thus, it appears that one of the hazards of the convulsive therapies is that they may induce enduring changes in brain function which leave the patient in a state of increased susceptibility to a variety of potentially convulsive agents.

In our earlier study of amygdaloid kindling in Papio papio (Pp), the development of partial complex seizure and of focal motor seizure was correlated with bifrontal theta discharge and increasing Rolandic spike discharge respectively and the final stage was characterized by primary generalized convulsive seizure. Since the latter seizure pattern is known to originate from the frontal focus in man, the frontal cortex became suspect in the development of the final stage seizure pattern. Daily prefrontal stimulation showed that Pp can be kindled from this site, culminating in a recurrent spontaneous seizure state identical to that induced by amygdaloid kindling in this species. However, our observation did not support our original assumption regarding the genesis of primary generalized convulsive seizure. Prefrontal and amygdaloid kindling are significantly different with respect to morphology, distribution and propagation of afterdischarge and interictal spike discharge, and speed and pattern of clinical seizure development. Most intriguingly, inter-ictal behavioral aberration associated with depth EEG changes was observed only in the prefrontal animals and not in the amygdaloid animals.

Our observation of amygdaloid seizure development in cats indicated early afterdischarge propagation into basal cortical areas prior to the development of bifrontal sharp theta discharge. In view of the implied participation of the frontal lobe in amygdaloid kindling, both fractional lesioning and kindling of selective areas were performed. This paper summarizes our stimulation study involving premotor, prefrontal, mesial frontal and orbital cortices. Except for the orbital series which showed a rather strikingly similar pattern of seizure development to that of amygdaloid kindling, all areas showed significantly different features in terms of the speed of seizure development, afterdischarge propagation, fragility of developing seizure, final stage 5 seizure and post-ictal behavior pattern, interictal discharge morphology and propagation, and generalized seizure triggering threshold intensity. All these findings suggest that the frontal lobe participates in, but is not essential for, the amygdaloid seizure development. The results of ongoing fractional lesion series support such a conclusion.

To test the hypothesis that the cortex participates in amygdaloid kindling in rats, bilateral aspiration lesions were made in various cortical areas in rats prior to kindling. Lesions in orbital cortex (on the dorsal lip of the rhinal sulcus) or prefrontal cortex (area 10) significantly retarded the rate of amygdaloid kindling; lesions in motor cortex, anterior cingulate cortex, or visual cortex were without effect. Detailed analysis indicated that the orbital lesioned and frontal-lesioned rats kindled relatively normally up to the second-last stage of amygdaloid kindling, in which stage they perseverated significantly longer than the controls and the other lesioned rats. These results suggest that areas of the frontal lobe participate in the elaboration and generalization of amygdaloid seizures in rats. Although retarded in rate, kindling nonetheless occurred in the lesioned rats, indicating that these cortical areas are not essential for the development of amygdaloid seizures.