Lithium: clinical study by brain electrical activity mapping. A case report.

One of the axes of research in our department is oriented on the study of the action of psychotropic drugs on the Central Nervous System by the means of the non invasive and direct techniques of cerebral imagery. First approach: EEG mapping In depressive states, the modification of nocturnal wakefulness states observed under lithium therapy begins to be well known. However, under lithium monotherapy, few diurnal studies have been performed. EEG mapping, based on a protocol and a strict methodology, could represent an interesting technique to approach the mechanisms of lithium action in psychopathological states concerned by this type of therapy. Second approach: Nuclear Magnetic Resonance (NMR) We studied the manic-depressive states in man before and after chronic administration of lithium salts. This research is performed in fundamental molecular studies, in vitro, and from modification of certain parameters in protonic NMR imagery that can be observed in these pathological states. We are participating in a research program and we preliminarily present: 1. the study by protonic NMR of the in vitro interaction between the lithium ion and water which is free or bound to the total cerebral tissue of rats (acute intravenous treatment by Li+ in different doses and at different times of tissular penetration). 2. the study by lithium NMR of the in vitro kinetics of the erythrocyte's lithium penetration in man, for the plasmatic concentrations (acute intravenous dose) considered as therapeutic in manic-depressive states. These measures performed by spectroscopic NMR are coupled with a classical dosage of lithium made with a flame spectrophotometer.(ABSTRACT TRUNCATED AT 250 WORDS)

New type of electrode for clinical EEG.

The author describes a new type of small electrode for clinical electroencephalography. This practical electrode, constructed on the same principles as a felt tip pen, assures a good contact without conducting paste and gives excellent results.

Clinical and experimental neurotoxicity of 2-t-butylazo-2-hydroxy-5-methylhexane.

Seven workers developed weight loss, sensorimotor neuropathy, visual dysfunction, impaired mentation, and emotional lability shortly after the introduction of a new synthetic catalyst in a plant manufacturing reinforced bathtubs. The newly introduced catalyst, 2-t-butylazo-2-hydroxy-5-methylhexane, is shown to produce a similar syndrome in rats. Axonal degeneration of optic nerves, ascending and descending spinal tracts, and peripheral nerves appears to underlie this syndrome.

Effect of the oral administration of branched chain amino acids on hepatic encephalopathy in the rat.

The aim of this study was to investigate the effect of oral administration of branched-chain amino acid (BCAA)-enriched diets after portacaval shunt (PCS) in rats. Fifty-one Sprague-Dawley male rats (200 gm) underwent PCS and 55 a sham operation. Half of the animals received BCAA 142 mg per day through a gastric tube; the other half underwent a sham procedure. Sleep disturbances were evaluated at 7, 14, and 28 days postoperatively by measurement of the excitability of the reticular brain-stem formation during the slow-wave sleep and paradoxical sleep. Animals were killed at the same intervals and liver/body weight ratio, plasma, and brain amino acids, brain norepinephrine, brain serotonin, 5-hydroxyindolacetic acid and histamine were measured. Each group of animals was matched with a similar group of sham-operated rats, i.e., receiving or not receiving BCAA. After PCS (as compared to sham-operated animals) a significant hyperexcitability of the reticular brain-stem formation was found during the slow-wave sleep. The liver/body weight ratio was significantly lower. Tryptophan (free tryptophan in the plasma), phenylalanine, tyrosine, and histidine increased in the plasma and the brain. Leucine and isoleucine were decreased in the plasma. After PCS, an initial decrease at 7 days postoperatively of brain norepinephrine and blockade of the intracerebral metabolism of tryptophan were observed. These changes were transient and progressively disappeared at 14 and 28 days postoperatively. Brain histamine remained at a very high level through the experiment. A good correlation was demonstrated between modification of the sleep disturbance and tryptophan (or 5- hydroxyindolacetic acid) and histamine brain levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of postshunt encephalopathy with secondary arterialization: an experimental study in the rat.

Secondary arterialization of the hepatic stump of the portal vein has been performed in rats 7 days after portacaval anastomosis (PCA) at a date when the electrocorticographic changes of postshunt encephalopathy were evident. A complete regression of encephalopathy ensued. This correlated with an increase in the weight of the liver and estimated hepatic blood flow. These results confirm the efficiency of liver arterialization, primary or secondary, in the treatment of postshunt encephalopathy. In the groups of rats studied in this experiment a significant correlation was always found among encephalopathy, liver weight: body weight ratio, and hepatic blood flow. This reinforces the hypothesis that a decrease in hepatic blood flow is the main factor in the generation of liver atrophy, decrease of hepatic function, and encephalopathy following portacaval shunt. Primary arterialization of the liver in humans has not gained much favor because of technical difficulties, a high mortality rate, and the absence of clear-cut evidence of its efficiency. Our results suggest that arterialization of the liver might better be kept as a secondary procedure for those cases in which encephalopathy develops after PCA.

Liver atrophy and encephalopathy after portacaval shunt in the rat.

The effect of various types of portal diversion (portacaval, mesocaval and pancreatico-splenocaval anastomoses, portacaval transposition and arterialization) on liver atrophy and post-shunt encephalopathy was studied in the rat. Among all diversions, only portacaval anastomosis produced dramatic liver atrophy and encephalopathy. Moreover, portacaval anastomosis was also the only portal diversion which induced low body weight gain. There was no correlation between blood ammonia levels and encephalopathy. Liver atrophy was always correlated to a decrease of hepatic blood flow. Diminution of liver blood flow was only slight following partial (either mesenteric or pancreatico-splenic) diversion of portal blood and nil after portacaval transposition or anastomosis. These results suggest that: (1) pancreatic (insulin-rich) blood is not essential for maintenance of liver trophicity. Hemodynamic factors seem to be predominant in the pathogenesis of post-shunt liver atrophy. (2) Post-shunt encephalopathy arises only when total diversion of the portal blood and liver atrophy are associated.

[Experimental hepatic encephalopathy. Study of the organization of a diurnal sleep pattern in rats with portocaval anastomosis]. / Encéphalopathie hépatique expérimentale. Etude de lorganisation d'un échantillon du sommeil diurne chez le rat avec anastomose porto-cave.

The organization of the diurnal sleep pattern was studied in control rats and in rats with end-to-side portocaval shunt before operation and during five weeks after operation. In control rats, no modification of the states of sleep was observed during the experimentation. In shunted rats, the total duration of waking increased, the total duration of slow wave sleep and paradoxical sleep decreased. The number of phases of waking and slow wave sleep increased and the number of phases of paradoxical sleep decreased. The mean duration of the phases of slow wave sleep decreased. These results show that the electrophysiological expression of experimental hepatic encephalopathy is similar to the electroclinical expression of hepatic encephalopathy in man and the polygraphic study of sleep disturbances permits the description of the encephalopathies.

[Measurement of the excitability of reticulo-cortical and reticulo-thalamo-cortical system during different states of wakefulness and sleep in the rat: technique, results and application (author's transl)]. / Réactivité du système nerveux central chez le rat. Mesure de l'excitabilité du système réticulo-cortical et réticulo-thalamo-cortical pendant différents états de veille et de sommeil chez le rat: technique, résultats et application.

The measurement of excitability of reticulo-cortical and reticulo-thalamo-cortical system (RtCS) is realized in rats during the careless waking state, during slow-wave sleep and during paradoxical sleep and the ratio existing between these different levels of excitability is calculated. During the inattentive waking state, the excitability of RtCS is slightly higher than during the slow-wave sleep. During the slow-wave sleep, the excitability of RtCS is higher than during the paradoxical sleep. The calculation of the ratio and the relation existing between the three principal levels of excitability of RtCS allows to define the "constant of excitability" which can be utilized in the experimental investigations of the central nervous system. In discussion, the principal interpretations of the results are given.

[Experimental hepatic encephalopathy. Central nervous system excitability in rats following portacaval anastomosis]. / Encéphalopathie hépatique expérimentale. Etude de l'excitabilité du système nerveux central chez le rat après anastomose porto-cave.

The excitability of reticulo-thalamo-cortical and reticulo-cortical system (RtCS) was studied by electrical stimulation of reticular formation during waking, slow wave sleep and paradoxical sleep during five weeks in control rats and in rats with portocaval shunt. In control rats, no modification of the excitability of RtCS was observed during the experimentation. In rats with portocaval shunt and from the fourteenth post-operative day, the excitability of RtCS was decreased during waking. All along the post-operative period, the excitability of RtCS was increased during slow wave sleep. No modification of the excitability of RtCS was observed postoperatively during paradoxical sleep. These modifications of the excitability of RtCS during waking and slow wave sleep could be related to quantitative variation of the waking-sleep cycle that have been described in rat with portocaval shunt. Their responsability in the disorganization of the waking-sleep states during the experimental hepatic encephalopathy may be hypothetized.

[Experimental hepatic encephalopathy. The effect of portocaval shunt on the evolution of the anterior hypothalamic neurosecretion in the rat (author's transl)]. / Encéphalopathie hépatique expérimentale : effet de l'anastomose porto-cave sur l'évolution de la neurosécrétion hypothalamique antérieure du rat.

The evolution of the anterior hypothalamic neurosecretion is studied in control, sham-operated and portocaval shunt rats. In sham-operated related to control rats, no modification of the anterior hypothalamic neurosecretion is observed. In portocaval shunt rats, the hypothalamic neurosecretion increases. This increase is mainly observed into the median eminence in all the portocaval shunt rats. The hypothesis according to which the modification of neurosecretory acitivity of the hypothalamic structures may be related to a discrepancy between the central monoamines is discussed.

Experimental hepatic encephalopathy. Changes of the level of wakefulness in the rat with portacaval shunt.

The level of wakefulness in rats with portacaval shunt has been evaluated by measurement of the reactivity of the reticulocortical system by electric stimulation of the brain stem reticular formation during slow wave sleep. The voltage level of stimulus necessary to provoke cortical awakening is significantly decreased after portacaval shunt. This modification of the level of wakefulness is in accordance with the diminution of total sleep and the decrease in threshold of reaction to painful stimuli observed in rats after portacaval shunt. The measurement of the reactivity of the reticulocortical system is a simple procedure which permits quantification of post-shunt encephalopathy in the rat.