VALIDATION OF THE BRIEF INTERNATIONAL COGNITIVE ASSESSMENT FOR MULTIPLE SCLEROSIS (BICAMS) IN A LARGE COHORT OF RELAPSING-REMITTING MS PATIENTS.

Cognitive impairment is one of the most frequently reported symptoms in persons with multiple sclerosis (MS). The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been recommended as a standardized international screening and monitoring tool for brief cognitive assessment. The aim of our study was to assess the reliability and validity of the Serbian version of the BICAMS. A total of 500 relapsing-remitting MS (RRMS) patients and 69 age-, gender- and education-matched healthy control (HC) subjects were examined. All participants performed the BICAMS test battery, which includes the oral version of the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test second edition (CVLT-II), and Brief Visuospatial Memory Test Revised (BVMTR). A randomly selected subset of patients were retested one to three weeks after baseline. Statistically significant differences between patients and HCs were evident on the SDMT and BVMTR (p<0.001). HCs had higher CVLT-II scores but this difference did not reach statistical significance (p=0.063). Cognitive impairment, defined as an abnormal test score on ≥1 subtest, was found in 62.9% of MS patients. There were statistically significant correlations between BICAMS scores and age, education, EDSS and disease duration in patient sample. Test-retest reliability was confirmed with Pearson correlation coefficient of 0.70 in all measures. This study supported the reliability and validity of the Serbian BICAMS, although the CVLT-II version tested here lacked sensitivity to detect MS compared to healthy volunteers.

Immune thrombocytopenia in alemtuzumab-treated MS patients: Incidence, detection, and management.

BACKGROUND: Alemtuzumab is a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS), and immune thrombocytopenia (ITP) has been identified as a risk. OBJECTIVE: To examine ITP incidence, treatment, and outcomes during the clinical development of alemtuzumab for RRMS and discuss postmarketing experience outside clinical trials. METHODS: CAMMS223 and Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) I and II investigated two annual courses of alemtuzumab 12 mg (or 24 mg in CAMMS223/CARE-MS II) versus subcutaneous interferon beta-1a three times per week. Patients completing core studies could enroll in an extension. Monthly monitoring for ITP continued until 48 months after the last alemtuzumab infusion. RESULTS: Of 1485 alemtuzumab-treated MS patients in the clinical development program, 33 (2.2%) developed ITP (alemtuzumab 12 mg, 24 [2.0%]; alemtuzumab 24 mg, 9 [3.3%]) over median 6.1 years of follow-up after the first infusion; most had a sustained response to first-line ITP therapy with corticosteroids, platelets, and/or intravenous immunoglobulin. All cases occurred within 48 months of the last alemtuzumab infusion. Postmarketing surveillance data suggest that the ITP incidence is not higher in clinical practice than in clinical trials. CONCLUSION: Alemtuzumab-associated ITP occurs in approximately 2% of patients and is responsive to therapy. Careful monitoring is key for detection and favorable outcomes.

Influence of Cognitive and Motor Abilities on the Level of Current Functioning in People with Multiple Sclerosis.

INTRODUCTION: Multiple sclerosis (MS) results in a wide range of disabilities. The effects of cognitive and motor dysfunctions are significant and affect level of functioning in people with MS. OBJECTIVE: The aim of the research was to determine the common contribution of neurological, motor and cognitive status to the overall functioning of MS patients. METHOD: The sample consisted of 108 subjects with RRMS. The instruments used in the research included: The General Questionnaire, the World Health Organization Disability Assessment Schedule, the Audio Recorded Cognitive Screen, Paced Auditory Serial Addition Test, the Nine Hole Peg Test, the 25 Foot Walk Test, and the Expanded Disability Status Scale. RESULTS: Subjects with a mild neurological deficit had a higher level of current functioning in all domains (a lower WHODAS 2.0 score) than subjects with a moderate neurological deficit (r=0.43, p<0.001). We found a positive correlation between the level of cognitive impairment and motor deficits of both upper and lower extremities and the level of neurological deficit (p<0.001). Subjects with lower neurological deficits had significantly lower WHODAS 2.0. scores, i.e. better motor abilities of both upper and lower extremities than subjects with moderate neurological deficits (p<0.001). The greatest contribution to explaining the overall level of current functioning of people with MS had subjects' age, cognitive abilities and motor abilities of the upper extremities. CONCLUSION: Inverse relationship of neurological, motor and cognitive status affects the overall daily functioning of people with MS, requiring planning of comprehensive programs in the rehabilitation of people with MS.

The impact of betaplus program on patient treatment satisfaction with interferon beta-1b in multiple sclerosis: Multicentric cross-sectional survey in the western Balkan countries.

BACKGROUND: Long-term treatment adherence to disease-modifying drugs (DMDs) may have significant impact on clinical outcomes in multiple sclerosis (MS). It has been recently emphasized that low treatment satisfaction (TS) may be an important factor for achieving high rates of treatment adherence. Interferon (IFN) beta-1b was the first DMD approved for the treatment of MS. The aims of our study were to assess TS in subjects with relapsing-remitting (RR) MS treated with IFN beta-1b in Serbia, Montenegro and the Republika Srpska, Bosnia and Herzegovina (B&H), and additionally, to evaluate the impact of patient support program on TS and adherence. METHODS: This is a cross-sectional survey performed in order to examine TS and adherence with IFN beta-1b in seven MS centers across three countries (Serbia, Montenegro and B&H). Included in the study were 296 adult patients with RRMS treated with IFN beta-1b for at least 6 months. They were invited to complete the Treatment Satisfaction Questionnaire for Medication (TSQM). Additional two treatment adherence questions were also asked. Patient support program (Betaplus®) was available exclusively for patients in Serbia and not for those in Montenegro and the Republika Srpska, B&H. In order to assess the potential impact of this program on TSQM, we combined two groups of patients from Montenegro and B&H and compared their results with those from patients in Serbia. Statistical analysis includes multivariable linear regression analysis in order to assess the differences between three MS patients groups in terms of the TSQM scores, adjusted for potential confounders. For the evaluation of the effects of Betaplus® program, multivariable logistic regression was used, controlling for the same confounding factors. RESULTS: Each of the TSQM summary scores in all three countries implicated high level of patients' satisfaction. There was statistically significant group difference on the Effectiveness summary score (p=0.001) and the Side effects summary score (p=0.006) between the group of subjects from Serbia and the combined group of subjects from Montenegro and B&H, in favor of the former cohort. There was statistically significant group difference neither on the Convenience summary score nor on the Overall satisfaction summary score. Results of adjusted logistic regression analysis based on the availability of patient support program (dependent variable) implicate that it had the most significant impact on the Effectiveness summary score (p=0.008). According to the correlation coefficients in the total patient cohort, all TSMQ summary scores except Effectiveness significantly correlated with the decreased adherence (Side effects: p=0.037; Convenience: p=0.016; Overall satisfaction: p=0.046). CONCLUSION: TS with IFN beta-1b was high in our MS patients. Additionally, these results have demonstrated that patient support program have significant impact on TS with IFN beta-1b in the Balkan cohort of RRMS patients.

Comparison between auditory steady-state responses and pure-tone audiometry.

BACKGROUND/AIM: A more recent method, the auditory steady-state response (ASSR), has become more and more important test method due to difference that was found in previous investigations between hearing thresholds determined by the ASSR and the pure-tone audiometry (PTA). The aim of this study was to evaluate the reliability of the ASSR in determining the frequency specific hearing thresholds by establishing a correlation between the thresholds determined by PTA, as well as to evaluate the reliability of ASSR in determining the hearing threshold with respect to the level of hearing loss and the configuration of the PTA findings. METHODS: The prospective study included 46 subjects (92 ears) which were assigned to groups based on their level of hearing loss and audiometric configuration. All the subjects underwent determination of hearing thresholds by PTA and ASSR without insight into their previously obtained PTA results. RESULTS: The overall sample differences between the ASSR and PTA thresholds were 4.1, 2.5, 4.4, and 4.2 dB at 0.5, 1, 2, and 4 kHz, respectively. A high level of correlation was achieved in groups with different configurations of PTA findings. The correlation coefficients between the hearing thresholds determined by ASSR and PTA were significant in subjects with all levels of hearing loss. The differences between hearing thresholds determined by ASSR and PTA were less than 10 dB in 85% of subjects (ranging from 4 dB for moderately severe hearing loss to 7.2 dB for normal hearing). CONCLUSION: The ASSR is an excellent complementary method for the determination of hearing thresholds at the 4 carrier frequencies, as well as determination of the level of hearing loss and the audiometric configuration.

The management of multiple sclerosis in children: a European view.

About 3-5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity in the paediatric multiple sclerosis population has triggered the use of disease-modifying therapies that have been shown to reduce relapse rate, disease progression and cognitive decline in adult patients with multiple sclerosis. Hard evidence for the right treatment and its appropriate timing is scarce in paediatric multiple sclerosis. Nevertheless, expertise in this field has grown thanks to recent open-label trials and experience generated in specialized centres. In spring 2009, a first meeting was held in Rotterdam with clinicians from 11 European countries (one from Canada) that are all active in the management of paediatric multiple sclerosis. One of the aims was to generate a common view on the management of paediatric multiple sclerosis patients. The result of this meeting is presented here to help standardize treatment and to support clinicians with less experience in this field.

Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis.

OBJECTIVE: To evaluate the efficacy and safety of BHT-3009 in relapsing-remitting multiple sclerosis (MS) and to confirm that BHT-3009 causes immune tolerance. METHODS: BHT-3009 is a tolerizing DNA vaccine for MS, encoding full-length human myelin basic protein. Relapsing-remitting MS patients were randomized 1:1:1 into three groups: placebo, 0.5 mg BHT-3009, or 1.5 mg BHT-3009, given intramuscularly at weeks 0, 2, 4, and every 4 weeks thereafter until week 44. The primary end point was the 4-week rate of occurrence of new gadolinium-enhancing lesions on brain magnetic resonance images from weeks 28 to 48. Protein microarrays were used to measure levels of anti-myelin autoantibodies. RESULTS: Compared with placebo, in the 267 patient analysis population the median 4-week rate of new enhancing lesions during weeks 28 to 48 was 50% lower with 0.5 mg BHT-3009 (p = 0.07) and during weeks 8 to 48 was 61% lower with 0.5 mg BHT-3009 (p = 0.05). The mean volume of enhancing lesions at week 48 was 51% lower on 0.5 mg BHT-3009 compared with placebo (p = 0.02). No significant improvement in magnetic resonance imaging lesion parameters was observed with 1.5 mg BHT-3009. Dramatic reductions in 23 myelin-specific autoantibodies in the 0.5 mg BHT-3009 arm were observed, but not with placebo or 1.5 mg BHT-3009. CONCLUSIONS: In relapsing-remitting MS patients, treatment with the lower dose (0.5 mg) of BHT-3009 for 44 weeks nearly attained the primary end point for reduction of the rate of new enhancing magnetic resonance imaging lesions (p = 0.07) and achieved several secondary end points including a reduction of the rate of enhancing magnetic resonance imaging lesions from weeks 8 to 48 (p = 0.05). Immunological data in a preselected subgroup of patients also indicated that treatment with 0.5 mg induced antigen-specific immune tolerance. The greater dose was ineffective.