Multiple Sclerosis: van der Meché FG

Comi G, Kappos L, Clanet M, Ebers G, Fassas A, Fazekas F, Filippi M, Hartung HP, Hertenstein B, Karussis D, Martino G, Tyndall A, van der Meché FG. · Multiple Sclerosis Centre, San Raffaele Scientific Institute, Milan, Italy. · J Neurol. · Pubmed #10896270 No free full text.

Abstract: 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 for 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.

Janssens AC, Buljevac D, van Doorn PA, van der Meché FG, Polman CH, Passchier J, Hintzen RQ. · Department of Public Health, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands. · Mult Scler. · Pubmed #17263009 No free full text.

Abstract: OBJECTIVE: To investigate the course of anxiety, depression and disease-related distress of patients with multiple sclerosis (MS) and their partners in the first years after diagnosis. METHODS: The Hospital Anxiety and Depression Scale (HADS) and Impact of Event Scale (IES) were completed at baseline, six-month, one- and two-year follow-up in 101 recently diagnosed patients and 78 partners. The Expanded Disability Status Scale (EDSS) was assessed annually. RESULTS: Mean time since diagnosis at baseline was 7.8 (SD 6.5) months. Mean anxiety scores of patients and partners did not change during the two years of follow-up and remained higher than that observed in the general population at all assessments (P < 0.05). The high levels of disease-related distress at baseline were lower at follow-up. Of the patients and partners with high anxiety scores at baseline (HADS anxiety > or = 8), 69% also had high scores at any time during follow-up, compared to 26% in those with low baseline anxiety scores. For severe distress at follow-up, these percentages were 41 and 14%. The sensitivity and specificity of baseline anxiety screening for the prediction of high anxiety or distress scores at follow-up were 55 and 85%. CONCLUSION: MS patients and their partners continued to have high levels of anxiety and distress in the first years after diagnosis. Screening for anxiety after diagnosis can be used to predict levels of anxiety and distress during two-year follow-up.

Samijn JP, te Boekhorst PA, Mondria T, van Doorn PA, Flach HZ, van der Meché FG, Cornelissen J, Hop WC, Löwenberg B, Hintzen RQ. · Department of Neurology, MS Centre ErasErasmus MC, Postbox 2040, 3000 CA Rotterdam, The Netherlands. · J Neurol Neurosurg Psychiatry. · Pubmed #16361591 links to  free full text

Abstract: BACKGROUND: Certain stem cell transplantation procedures might slow down inflammatory pathology in multiple sclerosis (MS). AIMS: To halt disease progression in aggressive MS by a bone marrow transplantation (BMT) protocol aimed at maximum T cell suppression. METHODS: Autologous BMT was performed in 14 patients with rapid secondary progressive MS (median EDSS score at baseline, 6; median disease duration, five years). To accomplish rigorous T cell ablation, a strong conditioning protocol was chosen--cyclophosphamide, total body irradiation, and antithymocyte globulin. To minimise the possibility of reinfusing mature T cells in the graft, bone marrow, not peripheral blood, was used as the CD34+ stem cell source. RESULTS: Median follow up was 36 months (range, 7-36). Post-transplant haemopoietic recovery was successful in all patients. Early toxicity included Epstein-Barr virus related post-transplantation lymphoproliferative disorder. Longterm effects were development of antithyroid antibodies (three) and myelodysplastic syndrome (one). One patient died of progressive disease five years after transplantation. Treatment failure, defined by EDSS increase sustained for six months or more, was seen in nine patients and stabilisation or improvement in five. Other clinical parameters generally showed the same outcome. No gadolinium enhanced lesions were seen on post-treatment magnetic resonance imaging, in either cerebral or spinal cord scans. However, cerebrospinal fluid oligoclonal bands remained positive in most cases. CONCLUSIONS: This strong immunosuppressive regimen did not prevent clinical progression in patients with aggressive secondary MS. The lack of efficacy, together with some serious side effects, does not favour the use of similar rigorous T cell depleting protocols in the future.

Buljevac D, van Doornum GJ, Flach HZ, Groen J, Osterhaus AD, Hop W, van Doorn PA, van der Meché FG, Hintzen RQ. · Department of Neurology, Erasmus MC, Rotterdam, the Netherlands. · J Neurol Neurosurg Psychiatry. · Pubmed #16170080 links to  free full text

Abstract: OBJECTIVES: To study in relapsing-remitting (RR) multiple sclerosis (MS) whether exacerbations and brain activity as measured by magnetic resonance imaging (MRI) are associated with plasma levels of anti-Epstein Barr (EBV) antibodies and EBV DNA. METHODS: This was a prospective study with 73 RR MS patients followed for an average of 1.7 years with frequent neurological examination and blood sampling. Antibodies to various EBV proteins were measured by ELISA and plasma EBV DNA was measured by PCR. RESULTS: All MS patients had IgG antibodies to EBV (viral capsid antigen (VCA) and/or EBV nuclear antigen (EBNA)), irrespective whether samples were taken at stable disease or exacerbation. A significantly elevated percentage of the patients (48%) had antibodies against EBV antigens (early antigen, EA) that indicate active viral replication, compared with the age matched healthy controls (25%). Antibodies against a control herpesvirus, cytomegalovirus, were similar between the two groups. The percentage of EA positive individuals and EA titres did not differ between stable disease or exacerbation. Anti-VCA IgM was positive in three cases, unrelated to disease activity. Using a highly sensitive PCR on 51 samples taken at exacerbation visits, only three patients were found to have one timepoint with viraemia, and this viraemia was unrelated to disease activity. Of special note was the fact that anti-EA seropositive patients remained seropositive during follow up, with stable titres over time. We hypothesised that these patients may constitute a subgroup with higher disease activity, due to the triggering effect of a chronic attempt of the virus to reactivate. The EA positive group did not differ from the EA negative with respect to clinical disease activity or other characteristics. However, in the EA positive group, analysis with gadolinium enhanced MRI indicated more MRI disease activity. CONCLUSIONS: There was no evidence for increased clinical disease activity in the subgroup of MS patients with serological signs of EBV reactivation. However, the observation that chronic EBV reactivation may be associated with increased inflammatory activity as assessed by gadolinium enhanced MRI lesions should be reproduced in a larger and independent dataset.

Janssens AC, van Doorn PA, de Boer JB, van der Meché FG, Passchier J, Hintzen RQ. · Erasmus MC, Department of Neurology, PO Box 2040, 3000 CA Rotterdam, The Netherlands. · J Clin Epidemiol. · Pubmed #15125628 No free full text.

Abstract: OBJECTIVE: The aim of the study was to investigate the impact of perception of prognostic risk on anxiety, depression, and disease-related distress in patients with multiple sclerosis (MS). STUDY DESIGN AND SETTING: Perceived risk and perceived seriousness of the 2-year, 10-year, and lifetime prognosis of wheelchair dependence, disability status, anxiety, depression, and disease-related distress were assessed in 101 patients. Distress was measured as the intrusion and avoidance of MS-related thoughts and feelings. RESULTS: Patients with higher perceptions of 2-year, 10-year, or lifetime risk were bothered by more intrusion of MS-related thoughts and feelings. Only higher perception of the 2-year risk of wheelchair dependence was significantly related with higher levels of anxiety, depression, and avoidance. Similarly, higher perception of the seriousness of wheelchair dependence was consistently associated with more intrusion and avoidance, but only perceived seriousness of the 2-year prospect of wheelchair dependence was significantly correlated with anxiety and depression. All relations were independent of clinically assessed disability status. CONCLUSION: Perceptions of the short-term risk and seriousness of wheelchair dependence were significantly related to anxiety, depression, and disease-related distress in patients with MS. These findings underscore the importance of informing patients with chronic disorders about the short-term prognosis of important long-term consequences of disease.

Janssens AC, van Doorn PA, de Boer JB, van der Meché FG, Passchier J, Hintzen RQ. · Department of Neurology, Erasmus MC, Rotterdam, The Netherlands. · Acta Neurol Scand. · Pubmed #14616290 No free full text.

Abstract: OBJECTIVES: Studies demonstrating reduced quality of life and psychological well-being in multiple sclerosis (MS) have typically investigated patients within more advanced stages of disease. The aim of the present paper was to evaluate the emotional burden and quality of life of recently diagnosed MS patients and their partners. METHODS: Data on health-related quality of life (SF-36), anxiety and depression (Hospital Anxiety and Depression Scale) and disease-related distress (Impact of Event Scale) were obtained in 101 patients and their partners (n=78). RESULTS: On average 8 months after diagnosis (range 0-24 months), 34% of the patients and 40% of the partners had clinically high levels of anxiety, and 36% of the patients and 24% of the partners had levels of severe distress. Scores of anxiety, depression and distress were higher in patients with more functional limitations (Expanded Disability Status Scale=3.0). Quality of life was significantly poorer in patients compared with controls, particularly among those with higher disability. CONCLUSIONS: Both patients and their partners demonstrated high levels of anxiety and distress in the early period after the diagnosis. These findings indicate careful attention by health care professionals to identify those who may benefit from further psychological support.

Buljevac D, Hop WC, Reedeker W, Janssens AC, van der Meché FG, van Doorn PA, Hintzen RQ. · Department of Neurology, Erasmus MC, Postbox 2040, 3000 CA Rotterdam, Netherlands. · BMJ. · Pubmed #14500435 links to  free full text

Abstract: OBJECTIVE: To study the relation between self reported stressful life events not related to multiple sclerosis and the occurrence of exacerbations in relapsing-remitting multiple sclerosis. DESIGN: Longitudinal, prospective cohort study. SETTING: Outpatient clinic of department of neurology in the Netherlands. PARTICIPANTS: Patients aged 18-55 with relapsing-remitting multiple sclerosis, who could walk with a cane or better (score of 0-6.0 on the expanded disability status scale), and had had at least two exacerbations in 24 months before inclusion in the study. Patients with other serious conditions were excluded. MAIN OUTCOME MEASURE: The risk of increased disease activity as measured by the occurrence of exacerbations after weeks with stressful events. RESULTS: Seventy out of 73 included patients (96%) reported at least one stressful event. In total, 457 stressful life events were reported that were not related to multiple sclerosis. Average follow up time was 1.4 years. Throughout the study, 134 exacerbations occurred in 56 patients and 136 infections occurred in 57 patients. Cox regression analysis with time dependent variables showed that stress was associated with a doubling of the exacerbation rate (relative risk 2.2, 95% confidence interval 1.2 to 4.0, P = 0.014) during the subsequent four weeks. Infections were associated with a threefold increase in the risk of exacerbation, but this effect was found to be independent of experienced stress. CONCLUSION: Stressful events were associated with increased exacerbations in relapsing-remitting multiple sclerosis. This association was independent of the triggering effect of infections on exacerbations of multiple sclerosis.