Diffuse thalamic degeneration in fatal familial insomnia. A morphometric study.

A morphometric investigation disclosed most thalamic nuclei severely degenerated in two patients with fatal familial insomnia. Associative and motor nuclei lost 90% neurons, and limbic-paralimbic, intralaminar and reticular nuclei lost 60%. These findings point to the disorganization of most thalamic circuits as a condition necessary for the sleep-wake rhythm being affected.

Immunosuppressive activity of 13-cis-retinoic acid and prevention of experimental autoimmune encephalomyelitis in rats.

Some activities of retinoids on cellular and humoral immunity have been described, but the available data are conflicting or obtained at concentrations that are toxic in vivo. In this study, we demonstrate that 13-cis-retinoic acid (13-cRA), a retinoid well tolerated in human therapy, can suppress T cell-mediated immunity in rats. Treatment with pharmacological concentrations of 13-cRA prevented active as well as passive transfer experimental autoimmune encephalomyelitis (EAE) and suppressed lymphocyte responsiveness to T cell mitogens, suggesting that the drug activity included suppression of an effector T cell response. In addition, mitogen- and antigen-induced lymphocyte proliferation was inhibited in vitro in the presence of concentrations of 13-cRA equivalent to or less than those achieved in vivo, further suggesting that the prevention of EAE was due to a suppressive activity on T cell-mediated immunity. The immunosuppressive activity of 13-cRA included suppression of interleukin 2, whose production was inhibited in splenocytes. These data indicate that, in an in vivo mammalian system, 13-cRA exerts a suppressive activity on T cell-mediated immunity intensive enough to suppress an ongoing immune response, and that this effect can be achieved at nontoxic concentrations that may also be attained in human therapy.

[Development of the steady-state cortical visual evoked response in children]. / Le développement de la réponse stationnaire corticale évoquée visuelle chez l'enfant.

Steady-state VEPs responses (pattern reversal stimulation) have been studied by the application of frequency analysis with Fourier methods. Authors examined with this method a group of children aged from 4 to 12 years, without ophthalmological or neurological pathologies. Responses evaluation is based on the number of harmonic frequency components and also on the power spectra of the first two components. Frequency analysis shows a well proportioned responses development that can be considered as a good index of visual function growth.

Computed tomography, magnetic resonance imaging and pathological correlations in a case of Binswanger's disease.

The results of 3 computed tomography (CT) examinations carried out over a 7 year period and of a post-mortem magnetic resonance (MR) study showed aspects of a white matter disease in a hypertensive patient suffering from vascular dementia. Histopathology revealed the primary cause of dementia to be a white matter degeneration sparing the U fibers. Rarefaction of both the myelin sheaths and the axons was present together with severe thickening of the medullary arteries. These findings support the existence of Binswanger's disease (BD) as a distinct variety of arteriosclerotic dementia. CT and MR imaging are valuable aids for diagnosis. However, since there are many other causes of CT and MR demonstrated diffuse white matter degeneration in the elderly, a conclusive diagnosis of BD requires pathological confirmation.

Histopathological correlates of leuko-araiosis in patients with ischemic stroke.

A neuropathological study was carried out in 4 cases of ischemic stroke with leuko-araiosis (LA), 3 cases of clinically suspected Binswanger's subcortical arteriosclerotic encephalopathy (SAE) also showing LA, and 3 cases without LA. Unlike the SAE cases, in 3 of the cases in the first group the white matter changes corresponding to LA could not be explained by ischemic mechanisms related to small vessel changes.

Lysosomal enzymes in experimental allergic encephalomyelitis: time course and evidence of the source.

The lysosomal enzymes acid proteinase and beta-glucuronidase, were assayed in spinal cords of rats during the course of experimental allergic encephalomyelitis (EAE). Histological and histochemical examination was carried out versus controls, in selected areas of the same cords biochemically assayed, to look at the distribution of the lysosomal enzyme acid phosphatase. The biochemical assay showed a significant increase of the enzyme activities during the disease and the increase was significantly correlated with the intensity of the disease. The distribution in the nervous tissue of the increase in acid phosphatase activity observed in animals with EAE, suggests that endogenous nervous cells may contribute to the lysosomal enzyme increase in EAE.

Suppression of experimental allergic encephalomyelitis by retinoic acid.

Administration of retinoic acid (RA) prevented the development of experimental allergic encephalomyelitis (EAE) in Lewis rats. RA suspended in corn oil was given for 3 days before the expected onset of the disease to rats immunized with myelin and to controls. The drug suppressed the neurological symptoms as well as the perivascular infiltrates observed in vehicle-treated animals. The results indicate that under these experimental conditions, RA has immunosuppressive activity by interfering with the efferent phase of the immune response.

The control of experimental allergic encephalomyelitis with retinoic acid. Further studies.

Two form of retinoic acid (RA) prevented the development of experimental allergic encephalomyelitis (EAE) in Lewis rats. RA suspended in corn oil was given before the expected onset of the disease to rats immunized with myelin and to controls. The drug suppressed the neurological symptoms as well as the perivascular infiltrates observed in vehicle treated animals. The results indicate that, under these experimental conditions, RA has immunosuppressive activity by interfering with the efferent phase of the immune response.

Changes in cortical acetylcholine output induced by modulation of the nucleus basalis.

The modulatory inputs of the cholinergic neurons of the nucleus basalis have been investigated in midpontine transected and freely moving rats by measuring acetylcholine release from the cerebral cortex using the cortical cup technique. Acetylcholine release was found to be the same in both groups of rats indicating similar levels of activity of the cholinergic neurons ascending to the cortex. The electrical stimulation of the nucleus basalis was always followed by an increase in acetylcholine release. Conversely, in some experiments only the stimulation of the midbrain reticular formation enhanced acetylcholine output. The stimulation of the nucleus accumbens prevented the increase in acetylcholine release elicited by amphetamine. The dose-dependent increase in acetylcholine output following IP administration of amphetamine was also prevented by the 6-hydroxydopamine induced degeneration of the dopaminergic fibres. However injection of apomorphine in the nucleus basalis did not modify acetylcholine output. Direct injection of the GABAergic agonist muscimol resulted in a decrease in acetylcholine output which was prevented by picrotoxin. In conclusion, the cholinergic neurons ascending to the cortex can be inhibited by GABA receptors located in the nucleus basalis and stimulated indirectly by dopaminergic fibres.

On the white matter lesions of the Creutzfeldt-Jakob disease. Can a new subentity be recognized in man?

One case of CJD with severe involvement of the white matter is discussed. The patient was admitted after a 3-month clinical course with rapidly increasing mental deterioration, coma vigil-like state, myoclonic twitching of the limbs and of the facial muscles. The EEG showed the typical features of CJD. The first CT scan, performed 3 months after onset, revealed only a mild cortical and subcortical atrophy of the brain. The second CT scan, 12 months later, showed a considerable cortical and subcortical atrophy of the brain. The patient died 18 months after onset. Neuropathological examination showed a severe degeneration in the gray matter, with spongiosis, loss of neurones and hypertrophic glial reaction. The white matter was also involved with severe spongiosis, demyelination and hypertrophic glial proliferation. The case is discussed in relation to the data in the literature. It is argued that cases of CJD with severe involvement of the white matter should be classified as a new neuropathological subentity of CJD.

Light microscopy and ultrastructural studies of Sturge-Weber disease.

Different degrees of cerebral calcifications together with encephalofacial angiomatosis and seizure disorders characterize the Sturge-Weber syndrome. According to the observations reported in the literature, calcium deposits may be found in the wall of cerebral vessels, in the perivascular tissue and rarely within the neurons. Corresponding to the variety of localizations, the interpretation of the phenomenon remains obscure. Most theories postulate the role of a vascular factory and of a mesenchymal factor. Ultramicroscopic studies of the specimens obtained in 2 children with the Sturge-Weber Syndrome provided the following findings. A mucopolysaccharidic substance constitutes the substratum for the deposition of calcium. Small amounts of this substance and calcium deposits may be detected within the connective tissue of cerebral vessels precociously; later on, while increasing in size and calcium concentration, they obviously migrate to outside the vessels. Successively, the calcium deposits seem to localize around the blood vessels, In our opinion, these observations stress the role of a primitive vascular factor; consequently, anoxia, necrosis of cerebral tissues, and variation in the calcium ion concentration would act only as secondary factors.

Arachnoid cysts in children: ultrastructural findings.

Light and electron microscopic features of four arachnoid cysts in children are presented. The wall of the cyst appeared composed of a dense collagen tissue in which dark and clear cells were intermingled without any specific arrangement. Abutting onto this membrane, at the luminal surface, these cells were arranged in layers. Tight junctions between arachnoid cells were absent. It is suggested that the arachnoid cysts derive from a developmental aberration of the meninges.