0510 Mitoxantrone induced cardiotoxicity in patients with multiple sclerosis

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Tuesday, November 8, 2005

0505 Mycophenolate Mofetil plus Interferon beta in Multiple Sclerosis Gogovska, L 1, Ljapcev, R 1. 1Clinic of Neurology, Skopje, Macedonia Objective: To investigate the efficacy and safety of a combination of Mycophenolate mofetil (MMF) and Interferon beta in patients with Multiple Sclerosis (MS). Method: In an open-label study, 17 patients with secondary progressive MS, with deterioration of _>1 point in Expanded Disability Status Scale (EDSS) score during 6 months preceding enrolment in the study, and patients with relapsing-remitting MS (RRMS) with >2 relapses in the previous 6 months, received M M F (CellCept) lg/day for 12 months in addition to Rebif or Betaferon. The primary outcome measures were the change in EDSS and the proportion of parients who improved, remained stable or worsened in disability, defined as a change of at least 1 point in EDSS for patients with baseline EDSS 4.5 or less, and change of 0.5 point if baseline EDSS > 5.0. Results: Benefit from treatment was observed in 88.2% o f patients; 76.4% improved and 11.7% remained stable. Only two patients deteriorated. This study also showed a significant beneficial effect on relapse rate and on proportion of relapse-free patients. No major side effects were observed. Conclusion: Combination of M M F and Interferon beta has influence on disability progression in MS. Its potential to stabilize the disease course and safe side effect profile would make this combination a promising treatment option for patients with MS who do not seem to benefit from one of the established therapies. 0506 Benign Multiple Sclerosis: The need Ior a new definition Gray, O M l, McDonnell, GV ~, Hawkins, SA ~. 1Department of

Neurology, Royal I,Tetoria Hospital, Grosvenor Road, Belfast ObjectiveS: To investigate the long term outcome of patients with berdgn onset multiple sclerosis and to establish the value of the Kurtzke Expanded Disability Status Scale (EDSS) as a prognostic indicator in benign onset multiple sclerosis. Methods: The Northern Ireland MS Registry contains 705 patients attending neurology clinics. This includes 137 patients with benign onset MS, as defined by a Kurtzke EDSS of less than or equal to 3.0 at 10 years from onset of symptoms. Of these, 72 patients had MS for more than 15 years, with 49 having MS for more than twenty years. We investigated the level o f disability as measured by a Kurtzke EDSS at 15 and 20 years respectively. Results: 72 patients had MS for more than 15 years. The Kurtzke EDSS score remained unchanged in 58%, increased by < 1.0 in 21% and increased by > 1.0 in 19.4%. 12.9 % of cases were walking with the assistance of an aid at 15 years, with 32.7% walking with an aid by 20 years. Of the patients whose EDSS was less than or equal to 2.0 at ten years, 76.6% remained so at 15 years, 10.6% progressed by < 1.0, with 12.8% progressing by > 1.0. Conclusions: Two tlffrds of patients with EDSS between 2.5 and 3.0 progressed between 10 and 15 years, but only 23.4% of cases with EDSS less than or equal to 2.0. We suggest that berdgn MS should be defined as an EDSS less than or equal to 2.0 at 10 years. 0507 Tile Ulini mental state examination and the paced auditory serial addition test in patients with Early Relapsing-Remitting Multiple Sclerosis Petravic, D 1, Habek, M 1, Brinar, W 1. 2Department of Neurology,

School of Medicine, University Hospital Zagreb, Croatia Background: Patients with multiple sclerosis (MS) have been found to be impaired on the Paced Auditory Serial Addition Test (PASAT). The Mird Mental State Exanffnation (MMSE) was found to be a useful predictor of focal cogrdtive impairment in patients with relatively minor physical disabilities. The aim o f tiffs study was to compare the

Poster Abstracts PASAT and the MMSE in patients with early relapsing-remitting multiple sclerosis. Method: Tile participants were 8 females and 5 males with median age of 32 years (20-49), duration of tire disease of 3 years (12-5), EDSS score of 1 (10-3) and MMSE of 27 (24-30). Eight patients had lffgh school, one had elementary school and 3 had university education. Data were analyzed by the Spaerman's rho test. Results: Statistical analysis revealed positive, significant correlation between MMSE score and total correct responses on the PASAT (p < 0.05), and negative, sigtfffiCallt correlation between MMSE score and missed responses on the PASAT (p < 0.05). However, even higher correlation was revealed when comparing results with the part of the MMSE, the serial subtraction test score, and total correct responses on the PASAT (p < 0.01) and missed responses on the PASAT (i~ < 0.05). There were no correlation between MMSE or serial subtraction test nor tire PASAT and duration of the disease or EDSS score. Conclusion: The MMSE could be used as a bed-side test for cognitive functions in patients with early, relapsing-remitting MS. If this test shows focal cognitive impairment, the patient's cognitive functions should be tested with more precise instruments like PASAT. 0508 Sulfatide is shedded into the CSF in Multiple Sclerosis patients Haghighi, S ~, Lekman, A ~, Tarkowski, E 1, Tarkowski, A ~, Fredman, p1, Andersen, 01 . 1Institute of Clinical Neuroscience,

The Sahlgrenska Academy at Gdteborg University, Gdteborg, Sweden; 2Institute of Internal Mediein, Department of Reurnatology and Inflammations research, The Sahlgrenska Academy at Go'teborg University, Gdteborg, Sweden Background: MS is associated with breakdown of myelin membrane llpids, two of which are sulfatide and galactosylceranffde (GalCer). A network of adhesion molecules, proinflanmmtory cytokines, and chemokines amplifies the local inflammation in MS. We here search for analogous inflammatory activity in the MS patients. The present study correlates CSF cytokine and glycosphingolipid levels in MS patients and their healthy siblings. Method: We investigated 47 sibling pairs, each with a patient with clirdcally definite MS and one healthy sibling including 9 healthy siblings with _>2 oligoclonal bands in the CSF (MS immunopathic trait), and 50 unrelated healthy controls. Results: Increased CSF levels of sulfaride were found not only in MS patients but also in the siblings. The CSF GalCer levels did not differ between these 3 groups. Serum IgM antibody levels were increased in the MS group as well as in the sibling group. We found increased level of TNF-alpha in CSF in the MS patients and the siblings group. There was a positive correlation between GalCer and IL-6 in the subgroup of siblings with MS immunopathic trait. Conclusion: The results of the present study reveal that shedding of glycosphingolipids to the CSF and an inflanmratory response against glycosphingolipids occurs in MS patients. Glycosplffngolipids may have immunomodulatory consequences and primarily antigen in MS pathogenesis and also may provide valuable tools for tracking disease activity. The relative importance of glycosphingolipids compared with myelin protein epitopes as early antigens needs to be evaluated in further studies. 0509 A limkage study in two families with MS and healthy meulbers with oligodonal CSF inununopathy Haghighi, S l, Andersen, 01, Nilsson, S2, Rydberg, L ~, Wahlstrtm, j4.

1Institute of Clinical Neuroseienee, The Sahlgrenska Academy at Gdteborg University, Gdteborg, Sweden; 2Institute of Mathematical Statistics, The Sahlgrenska Academy at GO'teborg University, Gdteborg, Sweden; 3Department of Clinical Chemistry and Tran,fusion Medicine, The Sahlgrenska Academy at Gdteborg University, Gdteborg, Sweden;

Poster Abstracts 4Department of Clinical Genetics, The Sahlgrenska Academy at Ggteborg University, Gdteborg, Sweden Background: We have studied two extended families (family A and P) in which not only MS segregates but also approximately 18% of the CSF investigated blood relatives have "MS ililmuliopattfic trait", all oligoclonal CSF immuno13athy similar to that seen in MS, but with no neurological symptoms. Both families fit a genetic model for autosomal dominant inheritance for MS immuno13athic trait. Methods: We performed a geliolile scan using the CHLC/Weber Screening Set ver 6A, with 285 successful markers, to test the hypothesis that a single gelie is causing the MS ilimmliopathic trait in these falifflies. Results: Using a parametric method, we identified regions with suggestive linkage at chromosome 6q12 with a LOD-score of 2.4, putative linkage with LOD-score 1.5 at chromosome 61321 (HLA region), putative linkage at chromosome 12@4 with a LOD-score of 1.7 and suggestive linkage at chromosome 19q13.2 with a LODscore of 1.8. The LOD-score at chromosome 19q13.2 increased to 2.2 when only family P was analysed. In family P, all MS patients and 2 of 5 individuals with MS immunopahtic trait had HLA DRBI*(15). In family B, all MS patients and blood relatives had the rare HLA type DRB 1*0103, which is associated with other autoilimmlie diseases. Conclusions: Tiffs analysis did IIot reveal any single gelie for the MS ilimmliopathic trait. Conceivably, the majority of the blood relatives with the MS immuno13athic trait will never reach threshold of clinically manifest MS. The occurrence of the rare H L A DRB 1*0103 in family B is suggestive of a dominantly heritable subgroup of MS. 0510 Mitoxanlrone induced cardiotoxicity in patients with Multiple Sclerosis Hamzehloo, A ~, Etemadifar, M a. 1Alzahra Hospital, Department of

Neurology, Iran Background: Treatment options for patients with secondary progressive and worsening relapsing remitting multiple sclerosis are few. Mitoxalitrolie is an atttilieoplastic drug recently approved for patients with multiple sclerosis. Mitoxantrone is associated with dose-related c.ordiotoxicity, and cardiac side effects limited mitoxantrone use in multiple sclerosis. Objective: the aim of tiffs study was to show cardiotoxicity o f mitoxalitrolie in multiple sclerosis patients. Methods: we studied 96 patients with worsening relapsili~remittilig or secondary progressive multiple sclerosis to evaluate cardiotoxicity during a one-year follow-up of mitoxantrone therapy. This study was performed to the clinic for multiple sclerosis of Isfahan University of Medical Sciences in October 2003 to October 2004. Analysis of mitoxalitrolie 12mg/m2 cardiac toxicity was based on patients who received at least four doses. Cardiac assessment were made every 6 months with Electrocardiogram and a spectral and color flow Doppler Echocardiography examination at enrollment and 6 and 12 months later. Results: of 104 patients included, 96 were assessed at 12 month. There was no evidence of clinically significant cardiac dysfunction. Three patients had left velitricular ejection fiactioli 10% below baseline and three others below 50%. Conclusion: Mitoxantrone 12 mg/m a as administered in this study was effective and generally well tolerated by patients with worsening relapsing remitting and secondary progressive multiple sclerosis. Our evidence suggested that the risk of cordiotoxicity low in patients with multiple steroids after one year mitoxalitrolie therapy. However, we emphasize that physician must be careful of mitoxalitrolie cardiac side effects.

Tuesday, November 8, 2005

Introduction: Oligoclonal bands (OCB) are present in the cerebrospinal fluid (CSF) in 90-95% patients with multiple sclerosis (MS). The most sensitive IIlethod for detection of OCB is isoelectric focusing. Occasionally patients with clinically definite MS can have lack OCB. Aims: To study the clinical characteristics, IIeurophysiologic and IIlagnetic resolialice findings ill patients with IIlultiple sclerosis diagnosed with criteria de MacDonald and without OCB Patients and Methods: In our database we have found between 20012004 six patients (12 female and 4 male) with MS clinically definite and lack OCB. Results: Mean age was 32.4 year (115-54 years), IIleali duration of the first symptoms was 22 months. In all cases were remitting-relapsing forms. The clinical more frequently was sensitive and brainstem. Mean attack was 2.:1 and mean EEDS score was 2.0. Mean Link Index was 0.52 (0.46-0.62) and total protein was 0.51. Basic protein o f myelin was negative in all patients except one. In all the patients the evoked potential findings were abnormal in some modalities. The Resonance Magnetic was abnormal in all patients and carried out MacDonald criteria. In two cases had been started treatment with inmunomodulator. Conclusions: The lack OCB in MS is infrequent and IIlore prevalent ill male. Out results did not reveal significant difference in clinical and IIeurophysiological findings. In some cases seems to have a relatively beliign prognosis. 0512 Getting the measure of spasticity in MS: The Multiple Sclerosis Spasticity Scale (MSSS-88) Hobart, J C ~;z'3, Riazi, A 2, Thompson, A J 2, Styles, I M ~, Ingrain, W 1, Vickery, P j1 Warner, M :, Fox, P j1, Zajicek, J P:.

ZPeninsula Medical School, Plymouth, UR\" 2Institute of Neurology, Queen Square, London, UK; 3School of Education, Murdoch University, Perth, WA Background: Spastidty can be measured through electrophysiological, biomechanical, and clinical evaluation, the latter most commonly using the Ashworth scale. None of these techniques incorporate the patient experience o f spasticity, nor how it affects people's daily lives. Our ailir was to construct a rating scale quantifying the impact of spasticity on people with multiple sclerosis (MS). Methods: Qualitative methods (in-de13th patient interviews, focus groups, expert opinion, literature review) were used to develop a conceptual framework of s13asticity impact, and to generate a pool of items with the potential to convert tiffs framework into a rating scale with multiple dimensions. Tiffs item pool was adliffliistered, in the folall of a questionnaire, to a salilple of people with MS and spasticity. Guided by Rasch analysis, we constructed and validated a rating scale for each component of the conceptual framework. Results: The qualitative phase (117 patient interviews, 3 focus groups) generated 144 potential scale itelilS and a coliceptual IIlodel with eight cOlilpolielits addressing symptolilS (iilUSCle stiffness, pain and discomfort, muscle spasms), physical impact (activities of daily living, walking, body movements), and psychosocial impact (emotional health, social functioning). Two postal surveys (n -- 272; n -- 259; mean response rate 80%) were used to construct and validate an 88-item ilistrulilelit. Conclusions; The 88-item MS Spasticity Scale (MSSS-88) is a reliable and valid patient-based measure of the impact of spasticity in people with MS. It has the potential to advance outcomes measurement in clinical trials and clinical practice, and provides a new perspective in the clinical evaluation of s13asticity.

0511 Oligoelonal bands negative and Multiple Selerosisz M.A. Hernfimlez, M.C. Sauz, M. Golizfilez-Plata, L.M. Prrez, J, Ode. A de Aiidres. Servicio de Neurolog[a," Servicio de Andlisis Clinico.

Hospital Universitario Ntra. Sra. de la Candelaria. Tenerife

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0513 Developing rating scales for neurological diseases: Lessons t~oIII Rasch analysis