In previous studies, the incorporation of 3H(G)L-leucine into muscles of patients with Charcot-Marie-Tooth (CMT) disease was shown to he increased in comparison with that observed in motor neuron disease (MND). To determine the cause of the increased uptake in CMT, studies of single fiber leucine incorporation have been undertaken. The results of this study indicate that the increased incorporation is into those muscle fibers which are undergoing regeneration following reinnervation. These results do not support the thesis that there is an associated myopathic process in CMT.

The effect of general anesthesia on 42 multiple sclerosis (MS) patients who underwent 88 episodes of general anesthesia was analyzed. One patient experienced a relapse after a procedure under general anesthesia, which is compatible with the natural history of the disease. A literature review revealed little information on this subject or on the use of particular anesthetic agents in MS. Our experience with spinal and local anesthesia is reported. In the evaluation of the former our limited data suggested that spinal anesthesia is less preferable than other alternatives in MS. Local anesthetics had a benign effect on the course of MS.

Transit (conduction) times from the wrist to the seventh cervical spinous process (C7) were measured by using the F-wave response (TA) and the cervical somatosensory response (SEPC). The mean values obtained in 25 controls were 10.1 ± 0.9 s-3 and 10.9 ± 1.0 s-3 respectively. The 0.8 ± 1.0 s-3 difference between the two methods represents central delay of SEPC, possibly at the level of the dorsal root ganglion. The mean onset latency of the cortical somatosensory response (SEPA) evoked by median nerve stimulation in the same subjects was 15.5 ± 1.0 s-3. Transit time from C7 to the cortex (TB) given by either SEPA - TA or SEPA - SEPC - 0.8, where 0.8 is the necessary corrective factor for central delay of SEPC, was 5.3 ± 1.0 s-3. These techniques were applied to 10 patients suspected of having multiple sclerosis, but without clinical evidence of involvement above C7. Six of the 10 cases showed prolongation of TB. In 4 of these, this could only be calculated by the F-wave method since SEPC was absent. It is concluded that transit times derived from either the F-wave or SEPC are equally valid and interchangeable. The absence of one response allows for its replacement by the other.

We have studied the brain regional distribution of methyl mercury following intravenous administration of CH3203HgCl in rat. Early peak levels were obtained in cerebellum, medulla oblongata and midbrain. The efficacy of removal of 203Hg by different chelators is also region dependent. The most efficient chelator for brain mercury proved to be mesodimercaptosuccinic acid.

The microvascular architecture of the subependymal matrix in premature infants was studied with microangiography and benzidine stains. This revealed that the subependymal matrix is the end zone or the border zone between cerebral arteries and the collection zone of the deep cerebral veins. Focal hypoxic changes of this subependymal matrix may occur in hypoxemia and ischemia because of the characteristic architecture.

The vascular permeability of these vessels was studied in rabbits using three different molecular weights of FITC-dextran. Vascular permeability was increased in the subependymal matrix by hypoxia and especially by hypoxia associated with an increased venous pressure. These findings may be related to the pathogenesis of subependymal hemorrhage in prematurity.

An adaptation of cellulose acetate electrophoresis for studying concentrated cerebrospinal fluid is described. Two hundred and twenty-one patients have been studied, and the specificity for multiple sclerosis and sub-acute sclerosing panencephalitis is discussed. This has been positive for oligoclonal banding (OB) in 79% of patients with clinically definite multiple sclerosis.

Stereotyped behavior was inclined in rats with ouabain administered intraventricularly in doses of 2, 3 and 4 μg in 50 μl saline. Haloperiodol reduced the stereotyped behaviour. Monoamine turnover studies showed a reduction in concentration of norepinephrine in hippocampus and midbrain, an increase in norepinephrine turnover in the medulla oblongata and a reduction in dopamine turnover in the striatum. The interpretation of these finds is discussed. It is suggested that this model could be significant clinically as it demonstrates that impairment of Na+-K+-ATP'ase may result in behavioral abnormalities characterised by stereotypy.

Two cases of systemic carnitine deficiency are described. In both patients, carnitine concentration was lower than normal in serum and muscle tissue. In the first case, the illness began at age 35; the clinical manifestations were only muscular. In the second case, the illness began in childhood; there were intermittent episodes of hepatic enlargement and coma. An excessive lipid content was present in muscle tissue, especially in type I fibers, of both cases, and in the liver of the second patient. Ultrastructural studies of muscle tissue revealed important changes of mitochondria.

During muscular exercise, aerobic and anaerobic metabolism were in vestigated. For a given relative work intensity, these patients showed abnormally high blood lactic acid concentration and lactic acid/pyruvic acid ratios. These data, together with the morphological alterations observed in mitochondria, suggest an impaired function of the respiratory chain, leading to a shift of the red/ox potential of the tissue towards a non reduced state.

A prolonged anticonvulsant action of taurine has been shown in a strain of seizure susceptible rats. The audiogenic rat (AS) has lower intracerebral electroshock thresholds in three auditory nuclei; the ventral cochlear, the inferior colliculi and the medial geniculate, and in one nonauditory structure; the reticular formation, than a strain of nonaudiogenic rats (NAS). Furthermore, the AS animals routinely display maximal (tonic-clonic) convulsion, regardless of brain structure stimulated, whereas NAS subjects respond with minimal (clonic) convulsions. Within three minutes of intraventricular injection of 8 μ moles, taurine reduces the susceptibility of AS rats to intracerebral electroshock seizures along with attenuation of the severity of the convulsion. The initial elevation in intracerebral electroshock threshold returns to pretreatment value at 24 hours, only to rise again at 48 hours and to remain elevated through day six after injection. In contrast, the severity of convulsions remains attenuated through 24 hours, after which it returns to pre-injection level. By comparison, NAS animals injected intracerebroventricularly in an identical fashion to the AS rats showed no changes in either seizure threshold or severity of convulsion. The direct injection of 200n-moles of taurine in the inferior colliculi of AS rats produced a slow developing, but prolonged, elevation of intracerebral electroshock threshold of this auditory nuclei. However, at no time after the intracerebral injection of taurine was convulsive severity changed. Injection of taurine into the inferior colliculi of NAS subjects did not change either susceptibility or severity of intracerebral electroshock seizures. The data indicate that taurine produces an anticonvulsant effect which is slow in onset, potent, selective and prolonged.

Seventy six regional cerebral blood flow (rCBF) studies were conducted on 32 patients who had a total of 39 aneurysms. Twenty three of these patients were studied pre- and post-operatively. Normal values were obtained from a control group of 33 subjects, each of whom underwent one rCBF study. Flow was reduced following subarachnoid hemorrhage (SAH); it increased significantly postoperatively. Lower flows were associated with poorer clinical grades. There was a greater variation in regional distribution of flow immediately following SAH than in normals or in patients who had recovered from the acute phase. rCBF studies correlated with CT scans demonstrated that a progressive increase in ventricular size was accompanied by a progressive reduction in flow. In addition, intraventricular hemorrhage (IVH) was associated with a significant reduction in cerebral blood flow (CBF). No significant correlation between CBF and spasm was demonstrable.

Ouabain, an inhibitor of Na+-K+-ATP'ase, has been administered intraventricularly to rats to study the effect of impairment of membrane transport mechanisms on the genesis of seizures. Running and leaping seizures occur rapidly after injection oj ouabain in a low volume (10μl) when the maximal uptake of ouabain (39.8%) is in the hippocampus. Generalized clonic-lonic seizures are induced by higher volume injections (50μl) associated with wider distribution of ouabain, including the cerebellum and brainstem.

Ouabain was injected into cerebral cortex, caudate nucleus, dorsal hippocampus, fastigeal nucleus, ventrolateral mesencephalic reticular formation and cerebellar cortex. The cerebellar injections produced both running and leaping and generalized clonic-lonic seizures. It is suggested that this results from decreased inhibitory effect of vermal and paravermal Purkinje cells on intra-cerebellar nuclei, which alters cerebellar influence on the reticular formation and the limbic system.

Diphenylhydantoin, phenobarbitone, phenacemide, carbamezepine and clonazepam but not ethosuximide are effective against generalized clonic-lonic seizures, suggesting that this is a model for “grand mat” but not “petit mal” seizure mechanisms. It is furthermore suggested that running and leaping are subcortical, probably limbic, seizures that are most relevant as a model for temporal lobe seizures.

Studies were made of visually and nonrvisitally guided movements by patients with Parkinson's disease. The subjects moved a light, horizontal handle using rotation primarily about the elbow. During visually guided trials both handle and target positions were displayed to the subject; during non-visually guided trials only the handle position was displayed. During non-visually guided trials all patients showed a tendency for an overall flexion drift, although there was no change in average movement amplitude. The overall error in position by the end of the non-visually guided trials was greatly in excess of the reported values for passive displacement thresholds in normal subjects. It is suggested that the data indicate an increased dependence on visual information for control of motor activity in Parkinson's patients.

Memory deficits in demented patients were studied by applying a computerized system to titrate individual memory performance. Two delayed matching to sample tasks were used. ABA1 involved random visual shapes used as a measure of visual memory. ABA 2 involved nonsense syllable trigrams used as a measure of verbal memory. A Human Test System panel with a display screen was utilized. This screen was a rear view projection window divided into four independent 3 x 2 sections arranged in a 2 x 2 matrix. The sample stimulus appeared on the upper left window for one second. The delay interval between stimulus sample and choices varied by 7 seconds dependent upon patient performance per trial. A Iso utilized was a color distractor task. Task parameters, data acquisition, retrieval, and graphic print-outs were all computerized. Individual titration levels reflected the severity of neurological impairment. Computerized assessment enabled subtle changes in memory performance to be readily identified. Implications for use of the system as a screening device in the assessment of mental changes in the elderly are apparent.

Previous research indicated that sequential alternation of stimulation of certain homologous brain areas via chronically implanted electrodes resulted in oscillation of high and low latencies for convulsions. This phenomenon suggested the establishment of interhemispheric facilitatory-inhibitory effects as a result of repeated stimulation of the two brain sites. In the present study, the latency oscillation pattern was observed in split-brain rats as well as in bilaterally stimulated controls, but not in rats stimulated on one side only. Significant differences were observed between split-brain and control rats in terms of initial kindling rates, duration of convulsions and type of oscillation. Results are discussed in the context of possible interhemispheric mechanisms involved in long term kindling.

The morphological, chemical, and physiological changes in the brain accompanying old age are reviewed. The deterioration of the striatal and hypothalamic dopaminergic systems were implicated in the onset of age related Parkinsonian-like slowing of performance and altered affect. Cholinergic hippocampal and neocortical systems were chemically and physiologically abnormal in the aged. The implications for slowed cognitive processing and persistance of the memory trace are presented.

Visual evoked responses (VER) to four geometric shapes (a square, circle, el and omega) were recorded from multiple scalp locations in twelve subjects. Significant differences were found between the occipital VERs to the square and el and between the VERs to the circle and omega. Consistent differences could not be demonstrated between the responses to the square and circle or to the el and omega.

The differences between the responses were quantified by three different methods, including measurement of peak latencies and amplitudes, computation of a ratio index called λ, and the performance of discriminant functions derived by Stepwise Discriminant Analysis Program (SWDA) in classifying other single trial responses. The amplitudes (but not the latencies) of a negative peak at approximately 150 msec, and a positive one at 220 msec, latency were found to be different in the pairs of shapes described. SWDA was able to separate these same pairs and classify from 63 to 68% of new trials correctly. The latency points chosen to make up the discriminant functions correlated partly with the and components that were found to be significantly different in amplitude.

It is suggested that the VER differences in the earlier part of the wave-form are related to the physical properties of the stimuli, including the contrast densities in the central 1.5° of the visual field and/'or the spatial frequencies contained in the stimuli. Differences demonstrated in later parts of the VERs may reflect differences in symbolic meaning of the stimuli.

A number of excellent and comprehensive reviews on various aspects of pyruvate dehydrogenase multienzyme complex have been written recently. The purpose of the present review is to summarize briefly the reaction mechanism and the regulation of this enzyme. Emphasis is put on the most recent literature not covered by previous reviews. Particular attention is also paid to the regulation of brain pyruvate dehydrogenase multienzyme complex, since a number of patients with neuromuscular diseases, such as Friedreich's ataxia, show a decreased rate of pyruvate oxidation.