Priorities in the discovery of the implications of water channels in epilepsy and duchenne muscular dystrophy.

In addition to the priority in the discovery of the first water channel protein in the red blood cell membrane the group of Gheorghe Benga in Cluj-Napoca, Romania, also has a world priority in the discovery of the implications of water channel proteins in epilepsy and Duchenne muscular dystrophy. This priority is briefly presented here. In 1977 Benga and Morariu reported a decreased water permeability of red blood cells in children with idiopathic epilepsy (cases selected by Ileana Benga). This investigation was performed as part of a program of research of hydroelectrolytic alterations in child epilepsy. On the other hand the group of Gheorghe Benga has reported a decreased water permeability of RBC in patients with Duchenne muscular dystrophy. These findings were interpreted as an expression of generalized membrane defects affecting water permeability in epilepsy and Duchenne muscular dystrophy. In recent years this idea was confirmed by reports indicating aquaporin abnormalities in the brain of epileptic patients and in the muscle of Duchenne muscular dystrophy patients.

Plasma and cerebrospinal fluid concentrations of magnesium in epileptic children.

In order to discriminate between conflicting reports in the literature, plasma and cerebrospinal fluid magnesium levels from epileptic children were compared with those of control children. To exclude the possibility of methodological artifacts, two methods for Mg determination were used: atomic absorption spectrophotometry and a colorimetric procedure. By both methods a significantly decreased concentration of Mg in plasma was found in epileptics. A positive correlation of the hypomagnesemia with the severity of epilepsy was found: the more severe the epilepsy, the lower was the plasma Mg. A significant increase of Mg concentration in CSF of epileptics was found. The most likely origin of Mg in CSF in epilepsy is the CNS tissue from which Mg is released. It is suggested that these alterations of Mg concentrations in plasma and CSF originate from a functional impairment of the cell membranes which might occur in epilepsy.

Amino acid composition of band 3 protein from red blood cells of normal and epileptic children.

Amino acid analyses of the band 3 protein purified from erythrocyte membranes of control and epileptic children showed that no major structural abnormalities of this protein could be linked with the red blood cell membrane alterations previously described in child epilepsy and, consequently, the molecular basis of these alterations should be looked for elsewhere.

A neuropsychological assessment, using computerized battery tests (CANTAB), in children with benign rolandic epilepsy before AED therapy.

RATIONALE: Benign rolandic epilepsy (BRE) is a form of partial idiopathic epilepsy according to the International League Against Epilepsy (ILAE) syndromes classification (1989). Recent studies have identified cases of BRE that do not meet the initial definition of 'benign'; these included reports of cases with specific cognitive deficits. It is still a matter of debate, whether these deficits are due to epilepsy per se, to treatment or other associated factors. OBJECTIVES: The aim of this study was to evaluate if BRE children have cognitive deficits at the onset of their seizures, prior to their participation in any anti-epileptic drug therapy (AED). METHODS AND RESULTS: We performed a neuropsychological assessment of 18 BRE children compared with a corresponding age-matched control group. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB). Subjects were at their first neurological evaluation, before any AED therapy. We assessed: visual memory, induction and executive functions. In our group, the BRE children performed comparably with the control children for the induction and executive functions. Substantial differences were identified for the visual memory subtests: PRM percent correct (t = -2.58, p = 0.01) and SRM percent correct (t = -2.73, p = 0.01). Age of seizure onset had a negative impact on the visual memory subtest performances (PRM mean correct latency). We found significant correlations between the different CANTAB subtests results and characteristics of the centrotemporal spikes (CTS). DISCUSSION: Our results are consistent with the findings of other similar studies. This form of epilepsy is associated with subtle neuropsychological deficits, present at seizure onset. Neuropsychological deficits identified, suggest a more diffuse brain involvement in the epileptiform process.

Decreased water permeability of erythrocyte membranes in patients with Duchenne muscular dystrophy.

The water proton relaxation times of erythrocytes (T'2a) from 15 Duchenne muscular dystrophy (DMD) patients and age-matched controls have been determined by a pulse nuclear magnetic resonance technique. Statistically significant higher values of T'2a were noted for the DMD erythrocytes, both in the presence or absence of p-chloromercuribenzene sulfonate, a potent inhibitor of water diffusion through erythrocyte membrane. As the values of T'2a are inversely related to the water permeability, the results indicate a decreased permeability of erythrocyte membrane in DMD. The findings are discussed in relation to the molecular mechanisms of water diffusion across erythrocyte membrane and in regard to the general problem of membrane abnormalities in DMD.

Studies of water permeability and proteins of erythrocyte membranes in patients with Duchenne muscular dystrophy.

The characteristics of water permeability of erythrocytes from 54 Duchenne muscular dystrophy (DMD) patients and age-matched controls have been determined by a pulse nuclear magnetic resonance (NMR) technique. A decreased permeability of erythrocyte membrane in DMD was definitely found at all temperatures between 15 and 42 degrees C, with normal values for the activation energy of water diffusion. No differences between DMD and control subjects in the pattern of erythrocyte membrane polypeptides separated by two-dimensional electrophoresis could be detected. The findings are discussed in relation to the molecular mechanisms of water diffusion across erythrocyte membrane and the problem of erythrocyte membrane abnormalities in DMD. A new interpretation of erythrocyte membrane alterations is proposed based on the recent findings regarding the molecular pathology of DMD.