Diffuse brain connectivity changes in Charcot-Marie-Tooth type 1a patients: a resting-state functional magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Changes of brain structure and function have been described in peripheral neuropathies. The aim of our study was to systematically investigate possible modifications of major large-scale brain networks using resting-state functional magnetic resonance imaging (RS-fMRI) in Charcot-Marie-Tooth disease type 1A (CMT1A) patients. METHODS: In this cross-sectional study, 3-T MRI brain scans were acquired of right-handed genetically confirmed CMT1A patients and age- and sex-comparable healthy controls. Patients also underwent clinical and electrophysiological examinations assessing neurological impairment. RS-fMRI data were analysed using a seed-based approach, with 32 different seeds sampling the main hubs of default mode, sensorimotor, visual, salience (SN), dorsal attention, frontoparietal, language and cerebellar networks. Between-group differences in terms of functional connectivity (FC) with the explored seeds were tested voxelwise, correcting for local grey matter density to account for possible structural abnormalities, whilst the relationship between FC modifications and neurological impairment was investigated using robust correlation analyses. RESULTS: Eighteen CMT1A patients (34.0 ± 11.4 years; M/F 11/7) were enrolled, along with 20 healthy controls (30.1 ± 10.2 years; M/F 11/9). In the CMT group compared to controls, clusters of increased FC with the visual cortex (P = 0.001), SN (P < 6 × 10-4 ), dorsal attention network (P < 8 × 10-5 ) and language network (P < 7 × 10-4 ) were found, along with a single cluster of reduced FC with the visual cortex in the left lentiform nucleus (P = 10-6 ). A significant correlation emerged between neurophysiological impairment and increased FC with right temporal language areas (r = 0.655, P = 0.006), along with an association between walking ability and increased FC with the left supramarginal gyrus (SN) (r = 0.620, P = 0.006). CONCLUSIONS: Our data show evidence of diffuse functional reorganization involving multiple large-scale networks in the CMT1A brain, independent of structural modifications and partially correlating with peripheral nerve damage and functional impairment.

Possible role of pirenzepine on the release of pancreatic polypeptide in duodenal ulcer patients: preliminary results of a randomized cross-over study.

The effects of repeated oral doses of pirenzepine (100 mg daily for 7 days) and antacid (Maalox, 105 ml daily for 7 days) on the test-meal-stimulated release of pancreatic polypeptide (PP) were evaluated in 7 duodenal ulcer outpatients by means of a randomized cross-over study, with a wash-out period of one week between pirenzepine and antacid administration. The effects of pirenzepine (100 mg daily for 7 days) were also evaluated in 5 healthy adult volunteers. The stimulus test was performed on each fasting patient two days before the treatment started and after a 7-day treatment. Venous blood samples were obtained before the test meal (basal) and 3, 10 and 30 minutes after it. Plasma PP levels were estimated by means of a specific RIA. The results obtained showed that pirenzepine significantly inhibits the PP response to the test meal in the duodenal ulcer patients and in the healthy volunteers. The above-mentioned effects suggest that one of the mechanisms of action on the therapeutic activity of pirenzepine on peptic ulcer might be explained by the preservation of pancreatic secretion unimpaired by an increase in PP release after meal stimulus.