Self-injectable DMTs in relapsing MS: NEDA assessment at 10 years in a real-world cohort.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disorder of the central nervous system. DMTs effectively reduce the annual relapse rate-thus reducing disease activity-and, to a lesser extent, some DMTs prevent disease progression in some people with MS. Monitoring the efficacy of DMTs with no evidence disease activity (NEDA) provides an objective perspective for evaluating treatment success. OBJECTIVE: Our goal is to detect the prevalence of NEDA-3 in people with MS treated with self-injectable DMTs at two years and 10 years in a retrospective study. METHODS: The treatment continuation rates and NEDA-3 parameters in the 2nd and 10th years were evaluated. RESULTS: A total of 1032 patients diagnosed with RRMS were included in the study, and 613 patients (59.3%) continued with treatment after 10 years. In the first two years, NEDA-3 was detected in 321 patients (52.4%), and 112 of the 613 patients continued with self-injectable DMTs at the end of 10 years (18.3%). The rate of NEDA-3 in patients starting treatment over the age of 35 was 15.1% compared to that in the patient group starting treatment aged 34 or less at 20.2% (p = .004). CONCLUSION: Our study includes the most comprehensive NEDA-3 data from real world evidence and supports the idea that NEDA-3 can be an effective early predictor of progression-free status at treatment follow-up of up to 10 years.

Monthly Pulse Methylprednisolone Therapy is Effective in Preventing Permanent Disease Progression in Secondary Progressive Multiple Sclerosis.

INTRODUCTION: Secondary progressive multiple sclerosis (SPMS) is the phase in which disability continues to worsen with or without accompanying attacks. Monthly methylprednisolone pulse therapy can be used in the secondary progressive phase. The purpose of the present study was to evaluate the effects of methylprednisolone pulse therapy on the basis of clinical and MRI parameters in patients with SPMS. METHODS: This was a multi-center, examiner-blinded, prospective study. Patients with SPMS with EDSS scores of 3 or more, using one or none of azathioprine, interferon or glatiramer acetate, were evaluated. Patients were given IVMP (1 dose of 1 g IV) once a month for 24 months. EDSS scores, MRI findings, quality of life, and adverse events were evaluated. RESULTS: Ninety-seven SPMS patients were included in the study. Significant decreases in new/enlarging, Gd-enhanced, and spinal lesions were observed from baseline to year 2. EDSS scores remained stable at the end of the second year. Monthly high-dose IVMP resulted in a significant decrease in attacks. CONCLUSION: This study is important in terms of emphasizing that this therapeutic option should not be overlooked, since monthly pulse therapy can halt or even reverse progression, regarded as a natural course in SPMS, albeit to a small extent.

The Turkish validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery.

BACKGROUND: Cognitive impairment may be seen in as many as 43-70% of patients with multiple sclerosis (MS) and may be observed in all MS subtypes. The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS) battery may be used to evaluate cognition status. The purpose of the current study is to validate the BICAMS battery in Turkish. METHODS: Patients with MS attending our clinic between September 2014 and April 2015 were invited to participate. Healthy control participants were matched in terms of age, gender and years of education. RESULTS: One hundred seventy-three MS patients and 153 healthy control participants were enrolled in the study. MS patients performed significantly worse in all trials than the members of the healthy control group. In addition, cognitive dysfunction was identified in 78 of the 173 (45.1%) patients. In the MS with cognitive impairment group, 64 out of 151 (42.4%) subjects were RRMS patients, 12 out of 18 (66.7%) were secondary progressive MS patients, and 2 out of 4 (50%) were primer progressive MS patients. CONCLUSIONS: The BICAMS has been proposed for assessing cognitive impairment in MS patients. This study shows that the battery is suitable for use in Turkey.

Monthly methylprednisolone in combination with interferon beta or glatiramer acetate for relapsing-remitting multiple sclerosis: A multicentre, single-blind, prospective trial.

OBJECTIVES: Multiple sclerosis is usually clinically characterized by repeated subacute relapses followed by remissions. Corticosteroids are used for relapses, and this treatment has been shown to increase the speed of recovery from these. We aimed to evaluate the efficacy and safety of pulsed methylprednisolone given every month as an add-on therapy to interferon beta or glatiramer acetate in patients with relapsing-remitting multiple sclerosis. PATIENTS AND METHODS: This was a multi-center, examiner-blinded, prospective study. Absolute annualized relapse rates and Expanded Disability Status Scale scores were calculated. RESULTS: 103 patients were given intravenous methylprednisolone (1 dose of 1g IV) once a month for 12 months as add-on therapy and were assessed during this period. The decrease in the absolute annualized relapse rate was 0.69, and 72 patients were relapse-free at the end of the year. Sixty-nine of the 103 patients had the same Expanded Disability Status Scale scores at the end of one year, while 21 were less disabled, and 13 sustained disability progression. Health related quality of life measured using the MS Quality of Life scale improved significantly during the study period. CONCLUSION: The addition of monthly pulsed methylprednisolone to subcutaneous interferon beta or glatiramer acetate therapy significantly reduced the relapse rate and may also be beneficial in terms of disease progression. These combinations were also safe, and most patients tolerated methylprednisolone as an add-on to interferon beta or glatiramer acetate.

Intrathecal IgM index correlates with a severe disease course in multiple sclerosis: Clinical and MRI results.

OBJECTIVES: Intrathecally synthesized IgM can be seen not only in the cerebrospinal fluid (CSF) in infectious and inflammatory diseases of the central nervous system, but also in that of patients with multiple sclerosis (MS). Intrathecal IgM synthesis in MS seems to be correlated with an unfavorable disease course. In one cross-sectional study, intrathecal synthesis of IgM (IgM index) was found to be correlated with cranial magnetic resonance imaging (MRI) parameters. The purpose of this study was to determine the possible relationship between the IgM index and MRI and clinical parameters. PATIENTS AND METHODS: Eighty-one patients with MS (58 female) undergoing lumbar puncture were included in the study. Fifty-one patients had a relapsing-remitting (RR) disease course, while 30 cases were secondary progressive MS (SPMS). IgM was detected in paired CSF and serum specimens using ELISA. The IgM index was calculated using the formula CSF IgM/serum IgM: CSF albumin/serum albumin. IgM indexes higher than 0.1 were considered "increased". All patients underwent brain and whole spinal cord MRI. RESULTS: The IgM index was normal in 43 of the 81 patients (53.1%) and increased in 38 (46.9%). A significant correlation was determined between the IgM index and Expanded Disability Status Scale (EDSS) (r=0.638, p=0.001). Most of the subjects with increased IgM indexes were SPMS patients, 28 having a SPMS course and 10 a RRMS course. Only two patients with SPMS courses had normal IgM indexes. EDSS scores were significantly higher in patients with increased IgM indexes (EDSS 4.3 vs EDSS 2.8, p=0.000). All patients with EDSS >3 had increased IgM indexes. All patients with IgM index values higher than 0.2 IgM had SPMS courses and EDSS >6. Time to onset of the secondary progressive phase of the disease was correlated with IgM index values (p=0.004). IgM index values were also correlated with T1 hypointense lesions (r=0.0431, p=0.008) and Gd enhancing lesions (r=0.0396, p=0.006). Patients with increased IgM indexes also had more spinal lesions (p=0.000). No relation was determined between an increased IgM index and an increased IgG index. No relation was determined with IgG oligoclonal band positivity. No correlation was also observed between IgM index and IgG index values. CONCLUSION: According to our findings, intrathecal IgM synthesis is associated with a worse long-term prognosis. It also correlates with a higher relapse rate, greater disability, and worse MRI outcomes. Early observation of increased IgM index values will be a helpful tool for clinicians in selecting patients for early immunomodulatory or immunosuppressant treatments.

Cognitive dysfunction in patients with multiple sclerosis treated with first-line disease-modifying therapy: a multi-center, controlled study using the BICAMS battery.

Multiple sclerosis (MS) can impair cognitive functions even in the early stages. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery is very short and highly sensitive and can be used to evaluate cognitive status in the disease. Several clinical trials have shown beneficial effects of disease-modifying drugs (DMDs) on long-term cognitive measures which may even reduce cognitive deficits in MS patients. Relapsing remitting MS patients using DMDs were enrolled in the study and monitored for 12 months. BICAMS and the Expanded Disability Status Scale were applied to the study group. We evaluated and monitored 161 newly diagnosed cases of definite MS by the end of the trial. 110 patients (68.2%) were female. One hundred and two healthy subjects (female to male ratio 68:34) were enrolled into the study. MS patients were categorized into three DMT groups: IFNB1-a SC, IFNB1-b, and GA. Mean scores of all three cognitive tests (SDMT, BVMT-R, and CVLT-II) were significantly higher in the control group than in the MS patients. The number of cognitively impaired patients decreased from 31.7 to 21.7% on the basis of CVLT (p = 0.024), and 42 (26.1%) to 30 (18.6%) on the basis of BVMT-R at month 12. A significant difference was determined in terms of cognitive status between MS patients using both IFNB and GA and the healthy control group. Ours is the first study to compare IFNB and GA in terms of evaluating cognitive involvement and to use the BICAMS battery in monitoring treatment.

Tau protein levels in the cerebrospinal fluid of the patients with multiple sclerosis in an attack period: Low levels of tau protein may have significance, too.

OBJECTIVES: Axonal loss is the cause of permanent neurologic disability in patients with MS. There are a lot of candidates to be a surrogate biological marker of the axonal loss in MS including tau protein. In the present study, we aimed to assess the levels of the tau protein in patients with MS, and in neurologically healthy controls. PATIENTS AND METHODS: We included 41 patients with MS (32 RRMS, 9 SPMS) in this study. All the patients with MS were in an attack period. Control group was consist of 18 neurologically healty patients who underwent spinal anesthesia for orthopedic operations. The CSF tau protein level was measured by double antibody sandwich ELISA. RESULTS: The patients with RRMS had a higher tau protein level than the patients with SPMS and the control group. The patients with SPMS had a lower tau protein level than the control group. CONCLUSION: High levels of tau protein in the CSF of RRMS patients in an attack period may indicate ongoing axonal transection owing to inflammation. Due to the brain atrophy, the patients with SPMS have less neurons to produce tau protein. The low levels of tau protein in the CSF of SPMS patients may denote axonal degeneration.

Reassessment of Lhermitte's sign in multiple sclerosis.

The reliability and diagnostic value of Lhermitte's sign in multiple sclerosis (MS) has not been fully established. The purpose of this study was to determine the clinical, neurophysiological and neuroradiological correlations of Lhermitte's sign in a cohort of MS patients and reassess the relevance of this phenomenon in the clinical history of the disease. A prospective study of 694 patients with MS and 110 age-matched healthy adults was evaluated by a structured questionnaire that included basic demographic data, age of onset, clinical characteristics of the disease, and the inquiry of Lhermitte's sign. Cranial and spinal magnetic resonance imagings (MRI) and median and tibial somatosensory evoked potentials (SSEP) were performed at the same time. One hundred and twelve (16 %) patients were reported to have Lhermitte's sign; 582 (84 %) patients did not experience Lhermitte's sign during their disease duration (P < 0.026). No correlation was found between Lhermitte's sign and age, gender, EDSS, and disease duration; 88 % of patients with Lhermitte's sign had a demyelinating lesion on the cervical MRI. In negative Lhermitte's sign group, 64 % patients had a positive MRI. SSEP conductions were delayed in 92 % of patients with positive Lhermitte's sign and in 70 % of patients with negative Lhermitte's sign. Regarding the data, a significant correlation was found between MRI lesion and Lhermitte's sign (P < 0.001), and between SSEP abnormality and Lhermitte's sign as well (P < 0.001). This study underlines the relevance of this phenomenon with neuroradiological and neurophysiological abnormalities.

The significance of oligoclonal bands in multiple sclerosis: relevance of demographic and clinical features, and immunogenetic backgrounds.

There has been no data on oligoclonal IgG bands (OCBs) for Turkish MS population, who is believed to be placed between Western and Eastern world regarding the clinical and immunological features. In the present study, we examined the correlation between the frequency of OCB and clinical and demographical features of MS in Turkish MS population. Our objective was to determine whether, population with OCB-positive and OCB-negative MS constitutes distinct subpopulations in terms of clinical, demographic and genetic base. A total of 210 clinically definite MS patients were included in the study. Patients were assessed clinically at baseline, 1 month later, every 3 months, and at year 5. No CSF OCB could be detected in 30 (14.3%) cases. 141 of the 156 female patients (90.4%) and 39 of the 54 male patients (72.2%) were positive for OCB. The female to male ratio was higher in the OCB-positive than in the OCB-negative group (p=0.007). Clinical course and disability were similar in the two patient groups. But mean relapse severity was higher in patients without OCBs in CSF. EDSS values got worse in OCB-negative group in year 5 (p=0.008). EDSS was also significantly higher in OCB-negative group in year 5 (p=0.003). There was no statistically significant difference regarding the usage of disease modifying therapy between the two groups. HLA DR15 antigen frequency was statistically higher in the OCB-positive than in the OCB-negative patients (p=0.007) and control group (p=0.0002). In conclusion, our results suggested that, MS patients with CSF OCBs have a female predominance, better clinical course with less disability and better prognosis, are associated with HLA-DR15.