Gorkem Kosehasanogullari

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.

Difference between generic and multiple sclerosis-specific quality of life instruments regarding the assessment of treatment efficacy

Multiple sclerosis (MS) is a chronic and stressful disease, which significantly affects the quality of life (QoL) of patients. QoL instruments provide information which traditional outcome measures of MS do not. It is unclear if the longer disease-specific instruments provide more useful information than the shorter. We aimed to investigate whether there was any difference between general QoL instrument and MS-specific one on the basis of detecting the efficacy of pulse therapy. 112 clinically definite MS patients were included in the study. Patients enrolled in the study were in relapse period treated by 1 g/day methyl-prednisolone for 5 days. World Health Organization Quality of Life Brief Form, Turkish Version (WHOQoL-BREF-TR) was given as a generic measure and Multiple Sclerosis Quality of Life-54 (MSQoL-54) as an MS-specific measure to assess the QoL. The same scales were administered 1 month after the therapy. MSQoL-54 was correlated with the EDSS in the pre-treatment period but WHOQoL-BREF was not. On day 30, there was a significant increase in both WHOQoL-BREF and MSQoL-54 scores. Increase was more prominent in MSQoL-54. There was a weak correlation between WHOQoL-BREF and MSQoL-54 (r=0.17). Correlation between changes in WHOQoL-BREF and MSQoL-54 scores was even weaker (r=0.11). Correlation between WHOQoL-BREF and EDSS was weaker (r=0.13), and correlation between MSQoL-54 and EDSS was still moderate (r=0.46) when compared with day 0. We concluded that although it takes a longer time to administer, MSQoL-54, as a MS-specific QoL instrument, is favorable and reliable for detecting the QoL not only in the remission but also in the relapse period of MS. Our results also indicated that MS-specific measure of QoL might be used for detecting the treatment effects in relapse period of patients with MS.

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

BackgroundCognitive 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.MethodsPatients 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.ResultsOne 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.ConclusionsThe BICAMS has been proposed for assessing cognitive impairment in MS patients. This study shows that the battery is suitable for use in Turkey.

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

OBJECTIVESnAxonal 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.nnnPATIENTS AND METHODSnWe 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 ELİSA.nnnRESULTSnThe 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.nnnCONCLUSIONnHigh 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.

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 12xa0months. 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 (pxa0=xa00.024), 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.

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

OBJECTIVESnIntrathecally 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.nnnPATIENTS AND METHODSnEighty-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.nnnRESULTSnThe 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.nnnCONCLUSIONnAccording 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.

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 (16xa0%) patients were reported to have Lhermitte’s sign; 582 (84xa0%) patients did not experience Lhermitte’s sign during their disease duration (Pxa0<xa00.026). No correlation was found between Lhermitte’s sign and age, gender, EDSS, and disease duration; 88xa0% of patients with Lhermitte’s sign had a demyelinating lesion on the cervical MRI. In negative Lhermitte’s sign group, 64xa0% patients had a positive MRI. SSEP conductions were delayed in 92xa0% of patients with positive Lhermitte’s sign and in 70xa0% of patients with negative Lhermitte’s sign. Regarding the data, a significant correlation was found between MRI lesion and Lhermitte’s sign (Pxa0<xa00.001), and between SSEP abnormality and Lhermitte’s sign as well (Pxa0<xa00.001). This study underlines the relevance of this phenomenon with neuroradiological and neurophysiological abnormalities.

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

OBJECTIVESnMultiple 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.nnnPATIENTS AND METHODSnThis was a multi-center, examiner-blinded, prospective study. Absolute annualized relapse rates and Expanded Disability Status Scale scores were calculated.nnnRESULTSn103 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.nnnCONCLUSIONnThe 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.