Preliminary evaluation of the effect of GABA and phosphatidylserine in epileptic patients.

The effect of the combined administration of gamma-aminobutyric acid (GABA) and phosphatidylserine was evaluated in a pilot study of 42 patients with drug-resistant epilepsy. The group included patients with complex partial seizures, simple partial seizures and absence seizures. Patients with complex partial seizures and simple partial seizures showed no significant improvement; on the other hand, there was a remarkable decrease in absence seizures, linearly related to the dose of GABA and phosphatidylserine. Side effects occurred in 9 patients and were usually mild.

Preliminary observations on the activity of progabide, administered as monotherapy in complex partial seizures.

Progabide (PGB), a gamma-amino-butyric acid receptor agonist, was administered, according to an open-label long-term design, to 40 adult patients suffering from complex partial seizures, with or without secondary generalization, whose response to carbamazepine (CBZ) monotherapy was unsatisfactory. A reference-baseline period of two months with carbamazepine monotherapy was followed by a two-month "add-on" period where increasing doses of progabide were added without modifying the CBZ regimen; then CBZ was withdrawn over 15-60 days and patients were followed up to 12 months' progabide treatment. Twenty-seven patients completed the trial but 12 of them had to be returned to CBZ + PGB bitherapy due to an increase of seizures following CBZ withdrawal. A definite therapeutic effect could be observed in nine patients on PGB monotherapy and in six patients on CBZ + PGB bitherapy. Side-effects of clinical relevance occurred in three cases and were represented by remarkable anxiety in two patients and a rise in serum glutamic oxalo-acetic acid and pyruvic transaminases with clinical symptoms of liver dysfunction in one, with rapid recovery following progabide discontinuation. In conclusion, progabide was effective against complex partial seizures in about 40% of patients not responding satisfactorily to available antiepileptic drugs. Although the withdrawal of previous antiepileptic drugs was not possible in all patients, progabide monotherapy was sometimes more effective than CBZ monotherapy, and several patients in whom bitherapy had to be restored benefited from the association of progabide.

Parenteral penicillin model of epilepsy in the rat: a reappraisal.

A parenteral penicillin model of epilepsy in the rat was investigated with the aim of evaluating its reliability. Behavioral and EEG patterns were strongly variable in a group of 100 rats injected with 1,000,000 IU/kg of penicillin i.p. Gross counts of spikes were Fourier transformed and grouped into two time windows in 24 out of the 100 rats. Analysis of variance applied to compare the two time windows showed a sufficient suitability of the phenomenon for antiepileptic drug testing purposes. Five subsequent injections of penicillin performed in 8 rats showed that a spontaneous decrease of the response takes place, preventing a crossover design in pharmacological analyses. Evans Blue studies demonstrated that there was not a breakdown of the blood-brain barrier; this model can be used for testing anticonvulsants unable to penetrate the blood-brain barrier.

Aphasic status epilepticus.

We studied a case of focal status epilepticus with aphasia as the sole manifestation, lasting 21 days. A 77-year-old woman developed aphasic seizures followed by aphasic status epilepticus 10 months after a left temporo-occipital hemorrhage. The diagnosis was made only after EEG, and seizures were stopped by anticonvulsant medication. Aphasic status epilepticus may be only a reflection of cerebral irritability, suggesting the possibility of a functional etiology for prolonged language disorders also in adults.

[Retrospective study on side effects in 410 patients in antiepileptic therapy. Proposal for new biochemical screening]. / Studio retrospettivo sugli effetti collaterali di 410 pazienti in terapia antiepilettica. Proposta di un nuovo screening bioumorale.

The authors evaluated hematological side effects in 410 epileptic patients under chronic therapy. The aim of the study was to find out the most suitable parametres for preliminary screening. Values outside the normal range were seen in patients treated with multiple drug therapy and in patients receiving antiepileptic drugs from 3 years at least. The following tests were the most frequently influenced: GOT, GPT, alcaline phosphatase, protrombin time, fibrinogen.

[Tolosa-Hunt syndrome. Observations in 11 cases]. / La sindrome di Tolosa-Hunt. Osservazioni su undici casi.

The authors report 11 cases of Tolosa-Hunt syndrome, a painful ophthalmoplegia due to an aspecific, benign, steroid-responsive inflammation of the cavernous sinus. Other causes of painful ophthalmoplegia, diagnostic findings and etiological hypothesis are discussed.

Carbamazepine and cardiac conduction disturbances.

Carbamazepine-induced cardiac conduction disturbance is reported in 2 patients suffering from epilepsy. The cardiac defects disappeared in both patients after carbamazepine was discontinued, and reappeared in 1 patient after treatment was resumed.

[Late degeneration of spinal motor neurons in patients with previous poliomyelitis]. / Degenerazione tardiva del motoneurone spinale in pazienti con pregressa poliomielite.

The Authors describe 5 cases of "motor neuron disease" in patients who had suffered from an acute episode of poliomyelitis. The literature and the fundamental pathogenetic theories have been reviewed.

Liposome-entrapped gamma-aminobutyric acid inhibits isoniazid-induced epileptogenic activity in rats.

Sprague-Dawley rats with interictal and ictal spike activity induced by intraperitoneally injected isoniazid (INH) were treated, 5 min before or 30 min later, with liposome-entrapped gamma-aminobutyric acid (GABA) (LEG) or GABA or phosphatidylserine. Crossover injections were given in random sequence and INH alone ws also injected in every animal as a control. LEG inhibited either seizures or interictal spikes in both groups. No decrease of epileptogenic activity was seen after GABA or phosphatidylserine treatment alone. It is suggested that LEG could contribute to the reconstitution of the GABA pool decreased by INH.

Preliminary note on the effect of denzimol in partial epilepsy.

The antiepileptic activity of the imidazole derivative denzimol has been evaluated in 10 patients with poorly controlled partial epilepsy by adding on the drug to the current therapy, in an open preliminary trial. A sustained drop in seizure frequency greater than 50% occurred in 5 patients. Although denzimol increased blood concentrations of carbamazepine, correlation analysis indicated that the improvement was more likely due to intrinsic properties of denzimol. No severe side effects were reported, although several patients experienced nausea and vomiting, which caused 2 patients to drop out.

[Arterial hypertension caused by carbamazepine]. / Ipertensione arteriosa da carbamazepina.

A 20-year-old epileptic patient developed hypertension during CBZ treatment, without any demonstrable etiological factor. After CBZ discontinuation, a gradual normalization of blood pressure values was observed. The authors discuss the possible role of ADH in the production of this unfrequent side effect.

Parenteral penicillin epilepsy: tolerance to subsequent treatments.

We recorded spike activity induced by i.p. penicillin injections in eight rats, repeating the experiment five times per each rat, at 48-h intervals. Spike frequency was significantly reduced in all sessions subsequent to the first, without changes in penicillin blood concentrations. The penicillin model of epilepsy is therefore not advisable in studies on antiepileptic drugs with a crossover design.

GABA and phospholipids in penicillin-induced seizures.

The effect of a suspension of GABA and phosphatidylserine (PS), phosphatidylcholine, or phosphatidylethanolamine was studied on penicillin-induced epileptic activity in rats. GABA-PS significantly reduced the number of spikes, in comparison with either the other phospholipid compounds or normal saline. No effect was observed after GABA or PS administration alone. We suggest that the different effects probably depend on extracellular and intracellular factors.

Ischemic stroke and atrial fibrillation. A clinical study.

In view of the higher prevalence of severe ischemic stroke among patients with atrial fibrillation (AF) and of the recently reported higher frequency of stroke with AF in females, 516 consecutive patients with ischemic stroke, of whom 93 had AF, were retrospectively evaluated. The main anamnestic, clinical and laboratory features of the AF and non-AF groups were statistically compared and the features of the AF group were statistically evaluated according to gender and age. Our results confirm the greater severity of stroke in AF patients than in non-AF patients and the higher frequency of stroke with AF in female patients. Moreover, a significantly higher frequency of stroke with AF was found in the male 60-69 and the female 80-89 age groups than in the other age groups. Relevant risk factors in females aged 80-89 were hypertension and left ventricular hypertrophy (LVH), while diabetes, alcohol, smoking and LVH prevailed among 60-69 year old males.