Epilepsy and pregnancy: lamotrigine as main drug used.

OBJECTIVES: To study the risk of teratogenicity in infants of women with epilepsy. MATERIAL AND METHODS: Prospective data from 1996 to 2000 comprised 147 pregnancies. The most frequent antiepileptic drugs (AEDs) used were lamotrigine (LTG) 35% (n = 51), oxcarbazepine (OXC) 25% (n = 37) and valproate (VPA) 20% (n = 30). Seventy-four per cent (n = 109) received monotherapy. Folic acid supplementation was taken during first trimester by 118 patients (80%). RESULTS: The overall risk of malformations among newborns in the AED-exposed group was 3.1% (n = 4). Two children were born with multiple malformations (VPA monotherapy), two children had ventricular septal defects (one OXC monotherapy, and one OXC and LTG). The risk of malformations was 2.0% in women treated with LTG and 6.7% in women treated with VPA (NS). CONCLUSION: Despite the small number of cases in the study these data indicate that treatment with LTG during pregnancy might be relatively safe. Larger prospective studies are needed to obtain adequate power for statistical analysis.

No loss in total neuron number in the thalamic reticular nucleus and neocortex in the genetic absence epilepsy rats from Strasbourg.

The thalamic reticular nucleus (nRt) as well as the neocortex are involved in the bilateral spike- and wave-discharge loop in genetic absence epilepsy rats from Strasbourg (GAERS). Neuron loss in different brain areas has been described in relation to epilepsy with convulsive seizures. We have previously investigated the ventrolateral/posterior nucleus of thalamus in GAERS and found no neuron loss. We applied the same efficient and unbiased stereological methods to nRt and to neocortex and again found no loss of neurons. The oscillatory properties of nRt are not related to neurons loss.

The absolute number of nerve cells in substantia nigra in normal subjects and in patients with Parkinson's disease estimated with an unbiased stereological method.

Using an unbiased stereological technique, the total numbers of pigmented and non-pigmented neurons were estimated in the substantia nigra of seven patients with Parkinson's disease and seven control patients. Compared with the controls, in which the average total number of pigmented neurons was 550,000, the number of neurons was reduced by 66% in the patients. The average total number of non-pigmented neurons was 260,000 in controls and reduced by 24% in the patients. A significant correlation (r = 0.81) existed between the total numbers of pigmented and non-pigmented neurons in the controls, whereas a similar correlation (r = 0.72) in the patients fell just short of statistical significance. The stereological estimates made in this study are unbiased, in that they are independent of nerve cell size, section thickness and of dimensional changes in brain tissue induced by histological procedures. The stereological method is considerably more efficient than previous conventional methods.

Hippocampal neuron density and seizures in the Mongolian gerbil.

Mongolian gerbils of the seizure-sensitive strain exhibit epileptic seizures in relation to changes in the environment, a characteristic which has been increased to about 100% by inbreeding. The seizures vary from animal to animal but are rather stable in the individual animal, which makes it possible to study the neuron densities in the hippocampus of the gerbil in relation to seizure type and seizure intensity. Five groups of gerbils with seizures ranging from minor movements and motor arrest to intense generalized convulsions were investigated with a quantitative method including cell counting by light microscope and estimation of possible brain shrinkage, as well as determination of nucleoli and nuclei diameters. The cell densities were determined in different areas of the pyramidal cells of the hippocampus (H-fields). The study discloses a reduction of cell densities in fields H2 and H3 in relation to intense generalized convulsions. It is suggested that the reduction in cell density in field H2 is a result of seizure activity, whereas the field H3 cell loss can be the result of both the hypoxia and the seizure activity.

The density of neurons in the human hippocampus.

The aim of this study was to determine the density and pattern of distribution of the neurons in the human hippocampus, and twenty-nine brains of healthy individuals were examined. The cells counted in each unit area were the pyramidal cells in the H-fields and the granule cells. Difference in density was found between all H-fields. The neuronal density was highest in the H2-fields. The density decreased through the transitional area H1-2 and H1, with the lowest density in H3. The neuronal density increased in all H-fields in the antero-posterior direction, while the granule cells decreased in density. In the individual brain there was a positive correlation found respectively between high and low cell density in the different H-fields. The pyramidal cell density decreased in persons more than 68 years old. No difference was found between neruonal cell density in the two sides of the brain. Sex did not influence the neuronal cell density.

Shrinkage of the brain during histological procedures with fixation in formaldehyde solutions of different concentrations.

The purpose of this study was to measure the shrinkage of the brain during fixation and the subsequent histological procedures. In neuropathology formaldehyde solutions are the most common fixative, but different concentrations are used. This may lead to uncertainty in connection with quantitative comparative studies, because of the possibility of different degrees of shrinkage. Three groups of five brains each were fixed in three different formaldehyde solutions containing 4% buffered solution, 10% and 12% solutions without additives, respectively. The further procedure to the final histological preparation was the same in all groups. The total shrinkage in volume was 48%, with no significant difference between the three groups. A significant difference appears in relation to the duration of fixation in the most concentrated formaldehyde solution. In all three groups the shrinkage due to the fixation was more than half of the total shrinkage. Finally, it is concluded that comparative quantitative studies on brains can be performed without regard to the technique after fixation in any of the concentrations of formaldehyde investigated.

Detrusor hyperreflexia. A survey on its etiology and treatment.

Detrusor hyperreflexia (DH) is a frequently occurring condition. The symptomatology is characterized by frequency, urgency and urge incontinence. DH is defined as involuntary, uninhibited detrusor contractions. The physiology and pathophysiology of the micturition reflex is reviewed. The balance between cerebral stimulation and supraspinal inhibition is discussed. DH is caused by disturbances in this balance. Whereas increased afferent impulses to the central nervous system due to local disorders in bladder and/or urethra may produce DH, a neurological disorder affecting the inhibitory nervous pathways from cortical and subcortical centres always result in uninhibited detrusor contractions. DH was found in 25% of 2000 patients. In the majority of the patients the DH was caused by a neurological disorder. The incidence of DH in patients with enuresis, gynecological patients with urinary incontinence and/or genital prolapse and patients with benign prostatic hyperplasia (BPH) is reported. In 62% of the patients with BPH the DH was eliminated after adequate surgical treatment of the infravesical obstruction. By contrast, DH in women with genital prolapse and/or incontinence persisted despite operative treatment. In a retrospective investigation of 152 patients with DH, the cause of the DH was unknown in 32 patients (21%). A clinical neurological examination revealed no evidence of neurological disease in 45% of the 22 patients examined. Voiding symptoms were the only complaint in these patients as well as in 30-40% of the patients in the other groups mentioned. This calls for improved investigatory methods in the evaluation of the balance between stimulation and inhibition of the micturition reflex. The presence of uninhibited detrusor contractions in apparently healthy patients should indicate a neurological examination since DH may be the first sign of a neurological disorder. The micturition reflex is conducted through long, uninterrupted neurons with a marked central integration. Therefore cystometry may be used as a supplement to the clinical neurological examination in the early diagnosis of pyramidal or extrapyramidal central nervous system disorders.