Variability of fMRI-response patterns at different spatial observation scales.

Functional organization units of the cerebral cortex exist over a wide range of spatial scales, from local circuits to entire cortical areas. In the last decades, scale-space representations of neuroimaging data suited to probe the multi-scale nature of cortical functional organization have been introduced and methodologically elaborated. For this purpose, responses are statistically detected over a range of spatial scales using a family of Gaussian filters, with small filters being related to fine and large filters-to coarse spatial scales. The goal of the present study was to investigate the degree of variability of fMRI-response patterns over a broad range of observation scales. To this aim, the same fMRI data set obtained from 18 subjects during a visuomotor task was analyzed with a range of filters from 4- to 16-mm full width at half-maximum (FWHM). We found substantial observation-scale-related variability. For example, using filter widths of 6- to 8-mm FWHM, in the group-level results, significant responses in the right secondary visual but not in the primary visual cortex were detected. However, when larger filters were used, the responses in the right primary visual cortex reached significance. Often, responses in probabilistically defined areas were significant when both small and large filters, but not intermediate filter widths were applied. This suggests that brain responses can be organized in local clusters of multiple distinct activation foci. Our findings illustrate the potential of multi-scale fMRI analysis to reveal novel features in the spatial organization of human brain responses.

Microvasculitic paraproteinaemic polyneuropathy and B-cell lymphoma.

Microvasculitis may play a greater part in the pathogenesis of paraproteinaemic neuropathies than is generally recognised, producing tissue destruction by convergent immune and physical mechanisms. We present a patient with a clinical syndrome of mononeuritis multiplex and a circulating IgM lambda paraprotein, in whom bone marrow aspiration revealed a lymphoplasmacytoid lymphoma. Microvasculitic changes were present in the first nerve biopsy, and the second showed extensive destruction of neural architecture and deposition of IgM-related material. A 2-stage pathogenic cascade is postulated and explored with a review of the relevant literature.

Vitamin E deficiency and its clinical significance in adults with primary biliary cirrhosis and other forms of chronic liver disease.

The vitamin E status of 146 adults with chronic liver disease was assessed by estimating both their serum vitamin E concentration and the ratio of serum vitamin E to serum cholesterol concentration. Low levels of vitamin E occurred most frequently in patients with primary biliary cirrhosis and other forms of chronic cholestatic liver disease. When a serum vitamin E concentration of 12.3 mumol/l (mean-2 SD of a control population) was taken as the lower limit of normal, 44% of patients with primary biliary cirrhosis and 32% with other chronic cholestatic liver disease had a reduced concentration, indicating a biochemical deficiency of vitamin E. If a vitamin E/total cholesterol ratio of 2.35 mumol/mmol was taken as the lower limit of normal, then 64% and 43% of patients with primary biliary cirrhosis and other chronic cholestatic liver disease, respectively, had a biochemical deficiency of vitamin E. Of the patients with chronic cholestasis and a serum bilirubin concentration greater than 100 mumol/l, 91% had a reduced vitamin E/cholesterol ratio. Twelve patients with primary biliary cirrhosis and severe vitamin E deficiency (serum vitamin E less than 5.0 mumol/l and a vitamin E/cholesterol ratio less than 1.0 mumol/mmol) underwent extensive neurological investigation. Five had a mild mixed sensorimotor peripheral neuropathy, which was not, however, typical of the neurological syndrome associated with vitamin E deficiency. In patients with severe biochemical deficiency of vitamin E (less than 5 mumol/l and less than 1 mumol/mmol total cholesterol), administration of large oral doses of vitamin E only increased serum concentrations to within the normal range in one patient; in the others even weekly parenteral administration over a 3-month period did not correct deficiency. In patients with less severe biochemical deficiency, the serum vitamin E concentration and vitamin E/total cholesterol ratio were restored to normal by oral or intramuscular supplements of the vitamin.

The effect of suppression of macrophage activity on the development of experimental allergic neuritis.

The selective toxicity of silica dust for macrophages has been used to assess the role of these cells in experimental allergic neuritis (EAN). Inbred Lewis rats were inoculated with bovine dorsal roots in Freund's complete adjuvant (day 0). In two experiments, animals received 200 mg of silica dust in 1 cm3 of saline intraperitoneally (IP) at days 8 and 16. In another two experiments, animals received IP silica at days 3, 7, and 11. Control animals received 1 cm3 saline IP at corresponding times. Regular clinical assessment showed that in animals treated on days 8 and 16 there was a significant delay in the time taken to reach their maximum degree of illness. This delay was not seen in the animals treated on days 3, 7, and 11. Neither of the injection regimes reduced the final maximum severity of the disease. In three experiments recovery of the treated and control animals occurred concurrently, hence the duration of the disease was reduced in the animals treated at days 8 and 16. However, in one group of animals given silica at days 3, 7 and 11, there was a delay in the time taken to recover from the most severe phase of the disease but thereafter the treated animals improved more quickly to reach their best grade at the same time as the controls. If the silica blockade of macrophages is to be effective in delaying the onset of EAN, the timing of injections is critical.

Nerve conduction velocity in experimental diabetes in the rat and rabbit.

Tibial motor nerve conduction velocity was measured in rats, before and two months after the induction of diabetes with streptozotocin. A second group of diabetic animals was also administered 1% dietary myoinositol supplements. An analysis of variance was performed on these data. Myoinositol supplements had no effect whatsoever. The period of diabetes had a statistically significant and quantitatively marginal effect (a decrease of 2.2 m s-1) on conduction velocity. This is considerably less than in previous reports. The reasons for this are discussed. Tibial motor nerve conduction velocity was also measured in a group of alloxan-diabetic rabbits two months after the induction of diabetes and in an age-matched control group. Conduction velocity was again slightly but significantly less in the diabetic animals.

Influence of dietary myoinositol on nerve conduction and inositol phospholipids in normal and diabetic rats.

Observations have been made on motor conduction velocity in the tibial nerve of rats given 35% myoinositol in the diet. Comparison between the values before and with up to nine weeks of dosing revealed no alteration in conduction velocity. In such animals, the free myoinositol content in the sciatic nerve was increased; there was no detectable alteration in the lipid inositol concentration. In a second series of experiments, tibial motor nerve conduction velocity in rats with streptozotocin-induced diabetes was compared with conduction velocity in diabetic animals given 1% supplementary dietary myoinositol, and with a control group of nondiabetic rats. Conduction velocity was reduced in the diabetic animals, but no influence from the added dietary myoinositol was detected. No statistically significantly difference in sciatic nerve myoinositol was demonstrated, but the sorbitol and fructose concentrations were increased. Those animals fed the myoinositol supplement had a significantly lower lipid inositol content. The significance of these findings is discussed.