Electroencephalographic coherence analysis in multiple sclerosis: correlation with clinical, neuropsychological, and MRI findings

OBJECTIVE: To explore functional corticocortical connections in multiple sclerosis by means of coherence of the EEG, and to evaluate their correlations with the degree of cognitive impairment and with brain lesion load assessed by MRI. METHODS: EEG coherence was studied from 28 patients with clinically definite multiple sclerosis. Ten minutes of resting EEG were recorded with 20 scalp electrodes, with binaural reference. FFT power and coherence were calculated in artifact free epochs of 1 second and compared with values from 22 control subjects of comparable age and sex distribution. Patients also underwent MRI (n=27) and neuropsychological examination (n=21). RESULTS: Compared with controls, patients with multiple sclerosis showed increased theta power in the frontotemporal-central regions (p<0.005). theta Band coherence was decreased between homologous areas (p<0.02). alpha Band coherence was decreased both in the local and long distance connections (p<0.0005). These findings were most striking both in patients with high MRI subcortical lesion load and in patients with cognitive involvement. A significant correlation was found between interhemispheric theta (p=0.02) and alpha (p=0. 017) and anteroposterior alpha (p=0.013) coherence and subcortical MRI lesion load, but not with exclusively periventricular lesion load. CONCLUSIONS: These findings support the hypothesis that cognitive impairment in multiple sclerosis is mostly dependent on involvement of corticocortical connections related to demyelination and/or axonal loss within the white matter immediately underlying the cortex.     

A quality network model for the daily care of multiple sclerosis

The urgent need to optimise treatment strategies for patients with Multiple Sclerosis (MS) was recognised by the participants at the 1998 European Charcot Foundation (ECF) symposium in Nice. The 'Nice Declaration' led to the formation of a Task Force Essentials Group charged with developing measures of the quality of MS care in Europe. Algorithms for nine critical domains (disability, spasticity, ataxia, pain, cognition, mood, fatigue, bladder function and sexual activity) and 'educated guesses' have been developed to measure interventions and outcomes which reflect the quality of clinical decision-making processes. A generic model called a 'quality network', consisting of a group of clinics connected to a central server, has been successfully applied to the care of diabetes across Europe. This model will now be developed and applied to MS management, to provide clinicians with longitudinal epidemiological data and, to evolve treatment algorithms and further quality measures. The ECF will next validate the system in a 1-year pilot study using a net of 10 clinics. Finally, an extended European network working in a learning environment will continuously assess, update and improve the quality of care of MS patients. Multiple Sclerosis (2000) 6 231 - 236     

Functional adenosine receptors in human corpora cavernosa

We have demonstrated that adenosine has potent relaxant activity on the rabbit corpus cavernosum, acting through the A2a subtype receptor for adenosine. We now report studies on the identification and functional characterization of adenosine receptors in human penile vessels. To identify A2 receptors in human corpora cavernosa (HCC) we performed binding studies using the selective radioligand [125I]PAPA-APEC in membranes from HCC. We found the presence of a single class of high affinity (Kd= 0.23 +/- 0.06 nM), low capacity (Bmax=134 +/- 37 fmoles/mg protein) binding sites. Adenosine and CGS 21680 completely displaced [125I]PAPA-APEC binding (Kd= 146.7 +/- 64 microM and 51.52 +/- 27 nM, respectively). Accordingly, in functional studies adenosine relaxed phenylephrine precontracted HCC with an IC50=2.28 +/- 0.17 mM. The effect of adenosine was independent from nitric oxide (NO), and was counteracted by the A2 antagonist CGS 15943. In order to evaluate the in vivo effect of adenosine, increasing concentrations (6, 60, 600 microg) of adenosine or prostaglandin E1 (PGE1) (10 microg) were injected into the corpora cavernosa of four healthy volunteers. Blood flow and erectile response were evaluated at different times by duplex sonography and visual inspection, respectively. It was found that adenosine increased cavernosal peak blood flow velocity in a time- and dose-dependent manner. The highest concentrations of injected adenosine elicited a response that was not statistically different from that of PGE1 (10 microg). However, in contrast to PGE1, a full or partial erection was never obtained. To further investigate the lack of effect of adenosine on penile tumescence (despite the substantial increase in cavernosal blood flow), in vitro experiments were performed on human deep dorsal penile veins (DDPV) obtained from surgical ligation for impotence. Adenosine did not affect basal tone, but it induced almost complete relaxation in noradrenaline-precontracted vein strips with an IC50=1.6 +/- 0.22 mM. Conversely, PGE1 stimulated a sustained increase in basal tone. Therefore, the lack of effect of adenosine on penile tumescence could be due to a simultaneous relaxing activity on penile corpora cavernosa and veins. In conclusion, our study indicates that adenosine relaxes HCC as well as penile veins without affecting erection, at least at the concentrations we have used. Conversely, PGE1 relaxes corpora cavernosa as well as adenosine but strongly stimulates vein contraction, allowing penile tumescence.     

The use of magnetic resonance imaging in multiple sclerosis treatment trials: power calculations for annual lesion load measurement

Phase III definitive treatment trials of new multiple sclerosis (MS) therapies now routinely incorporate an annual magnetic resonance imaging protocol, with change in T2-weighted brain lesion load providing an important outcome measure. To date the accepted strategy has been to perform a core imaging protocol on all patients in such studies. The aim of this study was to provide power calculations based on this MRI endpoint. Serial MRI data from 128 patients with either relapsing remitting (RR) or secondary progressive (SP) MS were used to calculate sample size requirements using a repeated measures analysis of variance design. We provide sample size calculations based on various follow-up intervals and effect sizes. Sample sizes for the SPMS cohort were substantially larger than for the RRMS group, reflecting the greater variance in lesion load changes between patients in the SPMS group. With a follow-up of 3 years, we estimate that only 12 and 33 patients per arm are needed to show stabilisation of MRI lesion load in the RRMS and SPMS groups, respectively. Our results suggest that ongoing phase III treatment trials are more than adequately powered to detect even subtle treatment effects, and indicate that incorporating measurements from longer follow-up durations increases power substantially. We conclude that an annual imaging protocol provides a robust and powerful tool for assessing effects on the radiological appearance of the disease process. Received: 11 February 1999/Received in revised form: 28 July 1999/Accepted: 10 October 1999     

Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation

Recent reports suggest the possible beneficial effects of haemopoietic stem cell transplantation (HSCT) in autoimmune diseases such as multiple sclerosis (MS). The definition of the risk/benefit ratio for such a treatment is perceived as a major issue for the neurological community worldwide. The First Consensus Conference on Bone Marrow Transplantation in Patients with Multiple Sclerosis was held in Milan, Italy on 21 February 1998. Participants from 16 European, North American, and South American countries discussed the guidelines form performing HSCT in MS. This conference was organized in order to : (a) define criteria for patient selection; (b) define transplantation procedures to maximize efficacy of the treatment and minimize its toxicity; (c) standardize patient outcome evaluation; and (d) establish an international working group to evaluate the efficacy and safety of HSCT in MS and to study the immunological changes related to HSCT in MS patients. During the meeting in Milan agreement was reached on: (a) the preparation and distribution of a consensus report on HSCT in MS and (b) the design of an open trial for an initial assessment of the safety and efficacy of HSCT in MS. The consensus reached during the meeting and the design of the clinical trial are summarized in this contribution. Received: 14 May 1999, Received in revised form: 4 January 2000, Accepted: 19 January 2000     

The role of CE-MRA of the supraortic vessels in the detection of associated intracranial pathology

Neurological Sciences - Contrast-enhanced magnetic resonance angiography (CE-MRA) has become a very popular imaging technique in the evaluation of the extracranial vessels pathology, while it is...