MRI of the central nervous system in MS patients with and without pain.

BACKGROUND: Central pain (CP) is a common symptom in MS. Multiple theories are present about the mechanism of CP. Previous studies suggested that lesion of the spinothalamic tract is a necessary condition for development of CP. No previous study has in detail evaluated the association between the specific site of demyelinations and the presence of CP in MS. OBJECTIVE: The study aimed to evaluate the location of plaques in MS patients with CP including a group of MS patients without pain as a reference group. METHODS: All patients underwent a bedside sensory examination and MRI of the brain and spinal cord. MR imaging was acquired on an 1.5 Tesla MR equipment. A trained neuroradiologist, blinded to pain status, evaluated the MRI. RESULTS: Thirteen MS patients with CP and 10 MS patients without pain were included. Allodynia and/or dysesthesia were more frequent in pain patients (11/13 vs. 1/10, P<0.01). No difference was found in the number of patients with plaques in spinothalamic tract, dorsal column-medial lemniscus, dorsolateral funiculus, grey substance, thalamus or capsula interna. A non-significantly lower number of pain patients had lesions in thalamo-cortical pathways (8/13 vs. 10/10, P=0.027). CONCLUSIONS: No association between CP and site of demyelinations was found, although a trend toward a higher prevalence of intact thalamo-cortical pathways was seen in pain patients. CP was associated with allodynia, suggesting central hyperexcitability.

Activation of endogenous retrovirus reverse transcriptase in multiple sclerosis patient lymphocytes by inactivated HSV-1, HHV-6 and VZV.

Human endogenous retroviruses (HERVs) and herpesviruses have been associated with the development of multiple sclerosis (MS). These virus groups interact with each other and have been shown to induce synergistic immune responses. Here, we focus on the possible role of herpesviruses as contributing factors in HERV activation. We demonstrate the ability of HSV-1, HHV-6, and VZV antigens to induce higher RT activity in peripheral lymphocytes from MS patients vs. controls during the first 6 days post-antigen stimulation. On subsequent days, only VZV can sustain the increase in the RT expression in cells from MS patients. The RT induction does not depend on herpes replication.

Immunomodulatory treatment of multiple sclerosis in denmark: a prospective nationwide survey.

OBJECTIVE: The aim of the present study was to provide data on the use of immunomodulatory therapies in a population comprising all treated patients with relapsing-remitting multiple sclerosis (RRMS) in Denmark. PATIENTS AND METHODS: From the introduction of immunomodulatory therapy in Denmark in 1996 through 2003, all patients that started immunomodulatory therapy were followed prospectively with neurological examination and standard laboratory tests every six months, and clinical data were reported to the MS Treatment Register, including relapses, Expanded Disability Status Scale scores and side effects. RESULTS: From 1996 through 2003 in all 2393 patients had started immunomodulatory therapy for RRMS, of whom 1252 (52.3%) were still on therapy with the same product at follow-up on 1 January 2005, whereas 1141 patients had discontinued or changed immunomodulatory therapy. Multiple Cox regression analysis of the risk of suffering a relapse showed a hazard ratio of 1.48 in patients with three or more relapses in the 24 months prior to onset compared with patients with two relapses or less; the hazard ratio was 0.84 in patients with age 238 years at treatment start compared with patients of age <38, and 1.17 for females compared with males. For disease progression the hazard ratio was 1.24 for age =38 years compared with age 2 37 years. Significant differences were observed in the hazard ratios between the different preparations, probably due to selection bias. CONCLUSION: The response to immunomodulatory therapy can be predicted to some extent from demographic variables. Differences between preparations can mainly be ascribed to selection bias, and open studies are not suited for comparison of efficacy between different preparations.

Sensory function and quality of life in patients with multiple sclerosis and pain.

Central neuropathic pain is well known in multiple sclerosis (MS), but the underlying mechanisms are unclear. In the present study we studied sensory function in MS patients with pain, MS patients without pain and healthy subjects in order to clarify the role of sensory abnormalities in pain. Fifty MS patients with pain were randomly recruited from a previous epidemiological MS study in Aarhus County, Denmark. Age and gender stratified MS patients without pain (N=50) and healthy subjects (N=50) served as controls. Patients with pain underwent a structured pain interview. Sensory function was examined by bedside and quantitative sensory testing. Quality of life was assessed using the health-related quality of life questionnaire, SF-36. Patients with pain had lower pressure pain threshold than pain-free patients (260 kPa vs. 322 (median), P=0.02) otherwise quantitative sensory testing was similar. Pain patients more frequently had cold allodynia (9/50 vs. 0/50, P=0.003) and abnormal temporal summation (10/48 vs. 3/49, P=0.03). Fifty-eight percent had central pain. Central pain patients did not differ from musculoskeletal pain patients in quantitative sensory testing, but allodynia was more common in MS patients with central pain. Pain patients scored lower in all dimensions of SF-36 compared with pain-free patients and healthy subjects. The results suggest that pain in MS is central in more than half of the patients and is associated with mechanical or thermal hyperalgesia.

Simultaneous presence of endogenous retrovirus and herpes virus antigens has profound effect on cell-mediated immune responses: implications for multiple sclerosis.

Retroviruses have been suggested as possible pathogenic factors in multiple sclerosis (MS), supported by the observation that endogenous retroviruses are activated in MS patients. Different members of the herpes family of which several are neurotropic have also been suggested as factors in MS pathogenesis. Further, interactions between retroviruses and herpes viruses have been implied in the development of MS. The objective of the study was investigation of cell-mediated immune responses of MS patients to retrovirus and herpes virus antigens, particularly antigen combinations, with analyses of the influence of retrovirus antigens on cellular immunological reactivity toward other viral antigens. Cellular immunity as measured by blast transformation assays was analyzed using freshly isolated peripheral blood mononuclear cells from 47 MS patients and 36 healthy volunteers. Combinations of the endogenous retrovirus HERV-H and herpes virus antigens resulted in highly increased cellular immune responses among both the MS patients and healthy subjects. The increase was synergistic in character in most samples. Very pronounced effects were obtained using HHV-6A and HSV-1 antigens. Blast transformation assays combining antigens from two different herpes viruses or combinations of measles and herpes antigens showed no synergy. The obtained data indicate a pronounced synergistic effect on the cellular immune response when retrovirus and herpes antigens are present together. The cause of the synergy is unknown so far. The effect on the immune response may influence the disease progression.

Pain in patients with multiple sclerosis: a population-based study.

BACKGROUND: Pain is an important symptom in patients with multiple sclerosis (MS). The estimated pain prevalence varies between 30% and 90%. To our knowledge, previous studies do not include a whole population sample of patients with MS. OBJECTIVE: To assess pain prevalence and its clinical characteristics and impact on daily life in a population sample of MS patients and in a reference group. DESIGN: Postal survey. SETTING: Aarhus County, Denmark. PARTICIPANTS: The population of patients with definite MS in Aarhus County (n = 771) and a sex- and age-stratified reference group from the general population (n = 769). MAIN OUTCOME MEASURES: Pain prevalence, intensity, and treatment requirement; and the impact of pain on daily life. RESULTS: Response rates for MS patients and reference subjects were 81.3% and 63.3%, respectively. Pain in the month preceding assessment occurred in 79.4% of MS patients and in 74.7% of reference subjects (prevalence proportion ratio, 1.06; 95% confidence interval, 0.99-1.13). Patients with MS had a higher pain intensity ("when pain is at its least" median visual analog scale score, 20.0 vs 11.0 mm [P<.01];and "when pain is at its worst" median visual analog scale score, 68.0 vs 55.0 mm [P<.01]). Daily intake of analgesics occurred in 24.4% of MS patients and 9.0% of reference subjects (prevalence proportion ratio, 2.7; 95% confidence interval, 2.0-3.6). Patients with MS more often reported that pain interfered with daily life "most of the time" or "all the time." CONCLUSIONS: The frequency of reported pain in MS patients was not higher than in the background population. However, pain intensity, the need for analgesic treatment, and the impact of pain on daily life were higher in MS patients.

Evidence of tolerance to baclofen in treatment of severe spasticity with intrathecal baclofen.

In a retrospective study, changes in baclofen dose and complication frequency were recorded in 79 patients with intrathecal baclofen administration and the effect on nightly muscle spasms was measured over a mean observation period of 34 months, during which time an increase in the daily dose of baclofen during the first 1--1-1/2 years is notified. On subsequent pump fillings the daily dose of baclofen remained stable in the group of non-multiple sclerosis patients. In contrast, the group of multiple sclerosis patients showed a steady increase in their daily dose of baclofen. We found a frequency of complications of 0.014 monthly often due to catheter problems. There was a significant decrease in numbers of nightly muscle spasms in an 8 h recording period from 77+/-20 preoperatively and 9+/-3 (P=0.02) 3 months after surgery. The steady increase in the daily dose of baclofen in order to obtain adequate reduction in spasticity and nightly muscle spasms in the first 1--1-1/2 years cannot fully be explained by caution and difficulties in achieving the correct dose, but also indicates that tolerance to baclofen occurs. Complications are often due to infection or catheter problems.