Quantitative electroencephalography reveals different physiological profiles between benign and remitting-relapsing multiple sclerosis patients

<p>Abstract</p> <p>Background</p> <p>A possible method of finding physiological markers of multiple sclerosis (MS) is the application of EEG quantification (QEEG) of brain activity when the subject is stressed by the demands of a cognitive task. In particular, modulations of the spectral content that take place in the EEG of patients with multiple sclerosis remitting-relapsing (RRMS) and benign multiple sclerosis (BMS) during a visuo-spatial task need to be observed.</p> <p>Methods</p> <p>The sample consisted of 19 patients with RRMS, 10 with BMS, and 21 control subjects. All patients were free of medication and had not relapsed within the last month. The power spectral density (PSD) of different EEG bands was calculated by Fast-Fourier-Transformation (FFT), those analysed being delta, theta, alpha, beta and gamma. Z-transformation was performed to observe individual profiles in each experimental group for spectral modulations. Lastly, correlation analyses was performed between QEEG values and other variables from participants in the study (age, EDSS, years of evolution and cognitive performance).</p> <p>Results</p> <p>Nearly half (42%) the RRMS patients showed a statistically significant increase of two or more standard deviations (SD) compared to the control mean value for the beta-2 and gamma bands (F = 2.074, p = 0.004). These alterations were localized to the anterior regions of the right hemisphere, and bilaterally to the posterior areas of the scalp. None of the BMS patients or control subjects had values outside the range of ± 2 SD. There were no significant correlations between these values and the other variables analysed (age, EDSS, years of evolution or behavioural performance).</p> <p>Conclusion</p> <p>During the attentional processing, changes in the high EEG spectrum (beta-2 and gamma) in MS patients exhibit physiological alterations that are not normally detected by spontaneous EEG analysis. The different spectral pattern between pathological and controls groups could represent specific changes for the RRMS patients, indicative of compensatory mechanisms or cortical excitatory states representative of some phases during the RRMS course that are not present in the BMS group.</p

Cluster analysis of behavioural and event-related potentials during a contingent negative variation paradigm in remitting-relapsing and benign forms of multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>Event-related potentials (ERPs) may be used as a highly sensitive way of detecting subtle degrees of cognitive dysfunction. On the other hand, impairment of cognitive skills is increasingly recognised as a hallmark of patients suffering from multiple sclerosis (MS). We sought to determine the psychophysiological pattern of information processing among MS patients with the relapsing-remitting form of the disease and low physical disability considered as two subtypes: 'typical relapsing-remitting' (RRMS) and 'benign MS' (BMS). Furthermore, we subjected our data to a cluster analysis to determine whether MS patients and healthy controls could be differentiated in terms of their psychophysiological profile.</p> <p>Methods</p> <p>We investigated MS patients with RRMS and BMS subtypes using event-related potentials (ERPs) acquired in the context of a Posner visual-spatial cueing paradigm. Specifically, our study aimed to assess ERP brain activity in response preparation (contingent negative variation -CNV) and stimuli processing in MS patients. Latency and amplitude of different ERP components (P1, eN1, N1, P2, N2, P3 and late negativity -LN) as well as behavioural responses (reaction time -RT; correct responses -CRs; and number of errors) were analyzed and then subjected to cluster analysis.</p> <p>Results</p> <p>Both MS groups showed delayed behavioural responses and enhanced latency for long-latency ERP components (P2, N2, P3) as well as relatively preserved ERP amplitude, but BMS patients obtained more important performance deficits (lower CRs and higher RTs) and abnormalities related to the latency (N1, P3) and amplitude of ERPs (eCNV, eN1, LN). However, RRMS patients also demonstrated abnormally high amplitudes related to the preparation performance period of CNV (cCNV) and post-processing phase (LN). Cluster analyses revealed that RRMS patients appear to make up a relatively homogeneous group with moderate deficits mainly related to ERP latencies, whereas BMS patients appear to make up a rather more heterogeneous group with more severe information processing and attentional deficits.</p> <p>Conclusions</p> <p>Our findings are suggestive of a slowing of information processing for MS patients that may be a consequence of demyelination and axonal degeneration, which also seems to occur in MS patients that show little or no progression in the physical severity of the disease over time.</p

Benign course in multiple sclerosis:a review

Since the 1950s, it has been recognized that a subgroup of multiple sclerosis (MS) patients exists that shows little or no progression in the severity of the disease over time. This group is referred to as 'benign' MS. Although a substantial amount of research in MS indicates a multifactorial background in disease severity, to date it is still difficult to predict whether the course will be benign at onset and it is difficult to find factors that influence the course of the disease over time. Maintaining or restoring neural conduction inside a central nervous system lesion seems to be the essence of staying 'benign

Serum uric acid, dehydroepiandrosterone sulphate, and apolipoprotein E genotype in benign vs. progressive multiple sclerosis

The majority of patients with multiple sclerosis (MS) experience gradual progression of disability, either as secondary progressive MS (SPMS) or primary progressive MS (PPMS). A subgroup with relapsing-remitting MS shows a benign course with little or no disease progression and minimal disability decades after the first manifestations, so called benign MS (BMS). In our search to identify factors that are associated with progression of MS, we investigated serum levels of uric acid and dehydroepiandrostenedione sulphate (DHEAS), and apolipoprotein (apo)E genotype in 28 patients with BMS, 33 with SPMS, 21 with PPMS, and 29 healthy individuals. We found no significant changes in uric acid levels and apoE genotype between the four groups. Mean DHEAS levels were lower in MS patients compared with healthy controls (P = 0.049), but there were no significant differences between the clinical subgroups of MS. In patients with SPMS and PPMS there was no correlation between progression rate and serum levels of either uric acid or DHEAS. Our results suggest that serum levels of uric acid and DHEAS, and apoE genotype do not differ between patients with a benign and progressive course of MS

Erythrocyte membrane fatty acids in benign and progressive forms of multiple sclerosis

BACKGROUND: There is no good explanation why a proportion of patients with multiple sclerosis (MS) have a relatively benign form of the disease. An imbalance between saturated and unsaturated fatty acids (FA) might influence the disease course of MS. AIM: To assess whether the erythrocyte membrane fatty acid composition, which is a biological marker of long term dietary FA consumption, is different between patients with benign and progressive MS. METHODS: The erythrocyte membrane FA composition was measured by gas chromatography in 23 healthy controls, 27 patients with benign MS, 32 patients with secondary progressive MS and 23 patients with primary progressive MS. None of the patients was following a special diet. RESULTS: No significant differences in levels of saturated and unsaturated FA or in omega-3- and omega-6-polyunsaturated FA were found between controls and patients with the different subtypes of MS. CONCLUSION: Our data suggest that factors other than dietary fatty acid consumption are responsible for the different disease courses of MS

Serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in relapsing and primary progressive multiple sclerosis

Using radioimmunoassay we measured serum levels of insulin- like growth factor ( IGF)- 1 and IGF binding protein ( IGFBP)- 3 in patients with relapsing multiple sclerosis ( MS) and a benign course ( Expanded Disability Status Scale ( EDSS) less than or equal to 3 despite > 10 years disease duration), relapsing MS with cumulative disability leading to an EDSS score > 4 within 10 years of disease duration, primary progressive MS and healthy controls. We found no differences in IGF- 1 and IGFBP- 3 serum levels, and the IGF- 1/ IGFBP- 3 ratio between the four groups. However, there was a significant correlation ( P = 0.005) between IGFBP- 3 serum levels and both the progression index of disability and the Multiple Sclerosis Severity Score in patients with primary progressive MS

Erythrocyte membrane fatty acids in benign and progressive forms of multiple sclerosis

BACKGROUND: There is no good explanation why a proportion of patients with multiple sclerosis (MS) have a relatively benign form of the disease. An imbalance between saturated and unsaturated fatty acids (FA) might influence the disease course of MS. AIM: To assess whether the erythrocyte membrane fatty acid composition, which is a biological marker of long term dietary FA consumption, is different between patients with benign and progressive MS. METHODS: The erythrocyte membrane FA composition was measured by gas chromatography in 23 healthy controls, 27 patients with benign MS, 32 patients with secondary progressive MS and 23 patients with primary progressive MS. None of the patients was following a special diet. RESULTS: No significant differences in levels of saturated and unsaturated FA or in omega-3- and omega-6-polyunsaturated FA were found between controls and patients with the different subtypes of MS. CONCLUSION: Our data suggest that factors other than dietary fatty acid consumption are responsible for the different disease courses of MS

Serum uric acid levels and leukocyte nitric oxide production in multiple sclerosis patients outside relapses

Background: A number of studies found that patients with multiple sclerosis (MS) have low serum levels of uric acid. It is unclear whether this represents a primary deficit or secondary effect. Uric acid is a scavenger of peroxynitrite, which is the product of nitric oxide (NO) and superoxide. Because peripheral blood leukocyte NO production and NO metabolites in serum are raised in MS patients, associations might be expected between serum uric acid levels and peripheral NO production. Methods: Serum levels of uric acid and NO production by peripheral blood leukocytes were measured in 60 patients with MS without a relapse in the past 3 months, and 30 age- and sex-matched healthy controls. Uric acid was determined with the uricase PAP method, and NO production was assayed by measuring nitrite concentration in supernatants of lysed leukocytes. Results: Serum uric acid levels were not different between MS patients and controls. Compared to controls, patients with MS had significantly higher peripheral blood leukocytes nitrite concentrations (p <0.001). There was no correlation between leukocyte nitrite concentration and serum uric acid levels. Conclusions: Our findings suggest that in MS patients there is no primary deficit in serum uric acid. NO production by peripheral blood leukocytes is increased, but there is no association with serum uric acid levels. (c) 2005 Elsevier B.V. All rights reserved

Oxidative stress in serum and peripheral blood leukocytes in patients with different disease courses of multiple sclerosis

Background The role of oxidative stress in patients with multiple sclerosis (MS) is poorly understood. Objective To investigate oxidative stress in serum and peripheral blood leukocytes in patients with different disease courses of MS. Methods Diene conjugate (DC) levels (a measure of lipid peroxidation), total antioxidative activity (AOA) and total anti-radical activity (ARA) were measured in serum and peripheral blood leukocytes from 30 patients with benign relapsing remitting MS (BMS), 27 with secondary progressive MS (SPMS), 29 with primary progressive MS (PPMS), and 30 healthy controls. All MS patients were in a clinically stable phase. Results Serum DC levels were elevated in patients with BMS (p <0.05), SPMS (p <0.01) and PPMS (p <0.001). Serum total AOA and ARA were not different between MS patients and controls. Compared to controls, leukocyte DC levels were not different in each MS subgroup, but total ARA was elevated. There was a strong correlation, both in controls and MS patients, between leukocyte D C levels and leukocyte total ARA (p <0.0001) and leukocyte total AOA (p <0.0001). Conclusion Oxidative stress occurs in progressive as well as benign MS. The finding that cells withstand oxidative stress, due to upregulated cellular antioxidant defence mechanisms, suggests that reactive oxygen species (ROS) formation in MS is not necessarily deleterious