R. Mutani

Free Amino Acids in Serum of Patients with Epilepsy: Significant Increase in Taurine

More than half the amino acids determined in serum were lower in patients with epilepsy than in control subjects. Taurine was the only amino acid to be increased in epilepsy. The changes could represent a compensatory metabolic reaction to limit the imbalance of amino acids in epileptic brain and to facilitate uptake of taurine, which has an anticonvulsant action.

Levels of Free Amino Acids in Serum and Cerebrospinal Fluid After Administration of Taurine to Epileptic and Normal Subjects

The modifications associated with taurine treatment of the free amino acid content of serum and cerebrospinal fluid were investigated in epileptic and control subjects. In patients with epilepsy the main findings were, in the serum, the correction toward normal of the amino acid levels that were low prior to therapy, and in the cerebrospinal fluid, the increase up to above‐normal levels of glutamic acid, greatly diminished before treatment. Thus taurine, which has an anticonvulsant action, appears to partially correct the amino acid imbalance in epileptics. The monitoring of taurine‐induced glutamate changes in the cerebrospinal fluid could help to establish the correct therapeutic dose.

Mechanisms of Interaction of Asymmetrical Bilateral Epileptogenic Foci in Neocortex

The mechanisms of interaction of bilateral asymmetrical foci on cat neocortex were studied with varying concentrations of the epileptogenic agent and with callosal splitting and cortical‐callosal isolation. When epilepsy was severe, a facilitatory interaction occurred. This was the result of two opposing mechanisms simultaneously operating, namely a transcallosal inhibitory mechanism and a predominant facilitatory subcortical mechanism: When epilepsy was less intense, subcortical structures were not involved and only the inhibitory transcallosal mechanism was at work, leading to an inhibitory interaction. The conclusion is put forward that two asymmetrical cortical foci do not necessarily interact in only one simple way. Their type of interaction (facilitatory or inhibitory) depends on the pathways involved in the interaction and this, in turn, depends on the severity of epilepsy.

Diphenylhydantoin and primidone in tears.

Summary: Diphenylhydantoin (PHT) and primidone (PRM) were determined by the EMIT® technique in the plasma, tears, saliva, and CSF of epileptic patients. Results indicate for PHT that tear values are more strictly correlated than are the saliva values to plasma and CSF concentrations. As for PRM, the data obtained show great interindividual variability of concentration in the different body fluids–in agreement with the wide range of both protein binding and half‐life of this drug.

Myotonia, potassium and taurine. A preliminary report.

The effect of taurine administration upon potassium-induced muscular hyperexcitability was studied in patients affected with dystrophic myotonia and in normal volunteers. Intra-arterial infusions of increasing concentrations of potassium chloride were given and venous potassium levels simultaneously monitored. Taurine prevented or remarkably reduced the electric signs of muscular hyperexcitability. Potassium chloride and taurine effects upon muscular excitability are discussed in terms of changes of membrane conductance, particularly for potassium ions.

The quantification of myotonia ☆: A problem in the evaluation of new antimyotonic drugs

The evaluation of an antimyotonic drug is often difficult since the severity of myotonia is itself hard to assess. The rise in arterial potassium level produced by the infusion of increasing concentrations of potassium chloride brought about reproducible changes in the excitability level of myotonic muscles proportional to the plasma potassium concentration. The excitability changes were assessed by three methods commonly used for evaluating antimyotonic drugs. The duration of the electromyographic relaxation time after maximal voluntary effort proved to be the only test which reliably assessed the variations of muscular excitability proportional to the increased plasma potassium. By contrast, the duration of percussion- or electrically-induced myotonic after-discharges was extremely variable and independent of plasma potassium.

The effects of the increase of arterial potassium upon the excitability of normal and dystrophic myotonic muscles in man

Progressively increasing concentrations of potassium chloride were administered intra-arterially to patients affected with dystrophia myotonica (Steinerts disease) and to healthy volunteers before and after parenteral taurine treatment. Changes in the excitability of thenar eminence muscles were related to plasma potassium concentrations. A rise in the plasma potassium brought about a parallel increase of muscular excitability in normal individuals whilst in dystrophic myotonic patients it was associated with a two-phase phenomenon: the severity of myotonia first decreased and then, at higher plasma potassium levels, greatly worsened with the occurrence of spontaneous myotonic discharges. The administration of taurine, a membrane-stabilizing drug, considerably lowered the excitability of both normal and dystrophic myotonic muscles. The effects of potassium and taurine on muscular membrane conductance may explain the observed changes in muscular excitability.

Brain Uptake of Carbamazepine in the Cat

Summary: Carbamazepine (CBZ) was determined by EMIT® assay in plasma, cerebrospinal fluid (CSF), and brain samples of cats after administration of the drug (40 mg/kg, i.p.). Plasma and CSF levels increase in a parallel manner from time 0 to 90 min after completion of injection, indicating a passive transport from one body fluid to the other. Brain levels reach a steady state at 15 min, with no significant difference being found between the concentrations at 15, 30, 60, and 90 min postinjection; this indicates that substantial early binding occurs in the brain. Since peak CSF concentrations occur at 90 min, concomitant with those for plasma, while brain levels are already high at 15 min, it is likely that CBZ enters the two compartments by independent mechanisms.

Psychotic onset of multiple sclerosis

A case is reported of a woman in whom acute manic attacks were followed later in life by neurological signs of multiple sclerosis, thus suggesting a possible correlation between the two clinical entities.SommarioÈ descritto il caso di una donna in cui la sclerosi multipla fu preceduta da attacchi acuti di tipo psicotico (maniacale).

Cerebellar Impairment Following Acute Nontoxic Administration of Phenytoin in Rat

Summary: In awake paralyzed Wistar rats, the following effects of an acute nontoxic dose of phenytoin (PHT) on different parameters of cerebellar electrical activity were evaluated: spontaneous discharge rate of single Purkinje cells (P‐cells), field potentials, and responses of P‐cells generated by electrical stimulation of a forelimb nerve. Variations of the response of single neurons located in the inferior olive were also studied, in order to assess the effects of PHT on this precerebellar relay station. The drug was administered orally and plasma and cerebellar levels regularly estimated. The results indicate that an acute, nontoxic dose of PHT is associated with an increase of P‐cell firing rate. This finding is supported by the analysis of the frequency distribution of in‐terspike intervals, and by the field potentials, P‐cell, and olivary responses induced by stimulation of a radial nerve. In addition, it was observed that the increase in P‐cell firing was mainly depending upon a higher activity of the climbing fibers. The increase in the response of P‐cells and olivary cells was correlated with plasma and cerebellar drug levels. The conclusion was reached that PHT increases the cerebellar cortical activity through two mechanisms: (a) by acting directly on the cerebellar P‐cell; and (b) indirectly by acting on the origin of climbing fibers at the inferior olive nucleus.