Serkan Ozakbas

Motor assessment of upper extremity function and its relation with fatigue, cognitive function and quality of life in multiple sclerosis patients

OBJECTIVES The aim of this study was to assess the motor function of upper extremity and its relation with fatigue, cognitive function and quality of life in Multiple Sclerosis (MS) patients. DESIGN Cross-sectional and controlled study. SETTING Outpatient clinic in a university hospital. SUBJECTS Thirty-one patients with MS (25 women, 6 men; mean age 39.74 +/- 10.10 years; mean EDSS, 2.56 +/- 1.91) and 30 healthy subjects (20 women, 10 men; mean age 33.56 +/- 8.85 years) were enrolled into the study. MAIN MEASURES Nine-hole peg test (9-HPT) and Valpar Component Work Sample Test (VCWS-4), Upper Extremity Index (UEI), Paced Auditory Serial Addition Test (PASAT), Fatigue Severity Scale (FSS), and the Multiple Sclerosis Quality of Life-54 (MSQOL-54). RESULTS MS patients showed significant impairment in upper extremity motor functions, cognitive function and excessive fatigue compared to controls (p < 0.05). 9-HPT in MS group correlated with EDSS, UEI and MSQOL-54 physical health and cognitive function, whereas VCWS-4 scores (assembly right, assembly left and disassembly) correlated only with EDSS and UEI. No correlation was found between the VCWS-4 and cognitive function and fatigue in both of the groups. Compared to control group, a strong correlation existed between the 9-HPT and VCWS-4 in MS patients (p < 0.05). CONCLUSION The results indicate that disability level (EDSS), UEI and cognitive function in MS patients are related with impairment in upper extremity motor function. This again contributes to an impairment in physical domain of quality of life. A strong correlation of the 9-HPT with VCWS-4 supports the use of the 9-HPT as a measure of manual dexterity and gross motor functions.

Correlations between multiple sclerosis functional composite, expanded disability status scale and health-related quality of life during and after treatment of relapses in patients with multiple sclerosis.

The measurement of the clinical manifestations of multiple sclerosis (MS) is difficult. In the present study, we examined the changes in measurement of functions during and after pulse methylprednisolon (MP) treatment of MS exacerbations using the MSFC and EDSS. Correlation between multiple sclerosis quality of life (MSQoL)-54, EDSS and MSFC were studied. Thirty-six clinically definite MS patients were included in this study. Because of MSFCs repeating feature, we administered the tests to a control group to exclude practise effects. All patients received 1000-mg intravenous MP for 5 days, followed by tappering dose of 100-mg oral prednisolone. All three scales were assessed on day 0. EDSS and two components of MSFC (nine HPT and T25WT) were administered on the other days of pulse MP treatment. PASAT was not applied before the day 5 to exclude the practise effect. MSQoL-54 was assessed again on day 30. Mean EDSS values significantly decreased after the day 2. MSFC score improved from 0.03 +/- 1.71 on day 0 to 0.79 +/- 1.51 on day 5. Improvement continued on day 30. The mean physical health composite score increased from 66.50 +/- 9.3 on day 0 to 74.34 +/- 8.9 on day 30. Mental health composite had also a significant improvement on day 30. Correlation between the baseline overall MSFC and the EDSS was moderately strong. T25WT correlated most strongly with EDSS. Significant positive correlation was found between MSFC and both components of MSQoL-54. It is more prominent for the MSFC and physical health composite correlation. The same correlation was found for the EDSS and MSQoL-54 composites. Changes in EDSS and MSFC scores and MSQoL-54 were found significantly correlated for the overall score on day 30 compared with day 0. In conclusion, MSFC seems to be more sensitive in detecting changes in function than the EDSS. Hence, EDSS is still useful for daily routine practise. When these results combined with the significant correlation between MSFC and MSQoL-54 measures, which indicated the MSFC reflects the severity of MS as perceived by patients, MSFC seems to be the most useful scale for clinical trials.

Nitric oxide as an activity marker in multiple sclerosis

Abstract. Nitric oxide (NO) molecules have one of the most important roles in the pathogenesis of multiple sclerosis (MS). It has been stated that a continuous and high concentration of NO metabolites in CSF and in the serum of MS patients in relapse may cause toxic damage to myelin and oligodendroglia. The aim of this study was to investigate whether NO is a marker of disease activity and is correlated with other disease activity markers such as active lesions on brain magnetic resonance imaging (MRI) and increased immunoglobulin G (IgG) index.Cerebrospinal fluid (CSF) and peripheral serum (PS) samples were taken from patients with definite MS (n = 24) during relapse and remission and from control subjects (n = 18). The Griess reaction was used to measure the NO metabolites, nitrite and nitrate in CSF and PS. Cranial MRI was carried out with triple dose (0,3 mmol/kg) gadolinium and the IgG index was determined.Nitrite and nitrate concentrations (NNCs) of CSF were 11.16 ± 8.60 μmol/ml in relapse and 6.72 ± 3.50 μmol/ml in remission, whereas in PS they were 12.89 ± 7.62 μmol/ml during relapse and 12.35 ± 6.62 μmol/ml during remission. In control subjects NNCs in CSF and PS were 7.42 ± 2.81 μmol/ml and 4.37 ± 1.63 μmol/ml respectively. NNCs in CSF during relapse period were significantly higher than those of both remission phase and control subjects (p = 0.000). Although serum NNCs did not differ in relapse and remission, they were still higher than normal controls. Validity analysis revealed that NNC measurement in CSF was 71 % specific and 66 % sensitive to disease activity. The most important result was the significant correlation of increased NNCs with the existence of active lesion in cranial MRI and an increase in IgG index (p < 0.05).In conclusion, these results add background data to assist in further outlining the possible role of NO in the pathogenesis of MS. Together with the other markers it may be used as an activity marker in relapses of MS.

Childhood and juvenile onset multiple sclerosis: clinical and paraclinical features

It is well known that multiple sclerosis (MS) is a demyelinating disease of the central nervous system that mostly starts in the second to third decade. In the present study, we reviewed our own observations of the clinical and paraclinical features in the 36 of 890 (4.04%) MS patients whose symptoms started before 16 years of age. The average age at onset of the disease in these 36 patients was 12.9 years. In 18 patients, the disease onset was monosymptomatic. Diplopia and sensory disturbances were the most common initial manifestations and occurred in 27.7% of cases. Twenty-one patients (59%) had a relapsing and 11 patients (30.5%) had a secondary progressive course. On the last evaluation, the EDSS score was above 5 in 11 patients and it was below 5 in 21 patients. As a result of this study, we concluded that childhood onset MS does not significantly differ from that it has been typically seen in adults in terms of major clinical manifestations and course of disease.

Sexual dysfunction ın multiple sclerosis: gender differences.

PURPOSE To assess the frequency and nature of sexual dysfunction in multiple sclerosis (MS) patients and to investigate the relationships of SD with clinical, demographic and psychosocial factors by comparing MS patients with and without SD. METHODS Eighty-nine patients were included, 45 males and 44 females, aging an average of 37.4 ± 8.6 years (range:21-56). We applied Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) and Arizona Sexual Experiences Scale (ASEX) to all patients. Disability was evaluated with the expanded disability status scale (EDSS). RESULTS 60.7% (n=54) of patients reported SD according to MSISQ scores. Women exhibited significantly higher MSISQ scores than men (42.6 ± 12.9 and 36.6 ± 13.3, respectively; P=0.034). Women (7.9%) also reported to experience sexual arousal difficulties significantly more than men (1.1%) (P=0.024) according to ASEX. The patients were classified into three MSISQ-19 subscales, Primary, Secondary and Tertiary SD. The most common reported dimension of SD was secondary (32.5%, n=41). In this dimension of SD, patients mostly complained of pain-burning, memory-concentration problems and bowel symptoms. A significant relationship was found between Secondary SD and both EDSS score and disease duration (r=0.34 p=0.001 and r=0.21 p=0.042, respectively). Tertiary SD was also associated with EDSS score (r=0.23 p=0.03). CONCLUSION Sexual Dysfunction, a frequent problem for MS patients, is associated with gender. Women reported more SD than men. Secondary SD symptoms were the most common complaints for both men and women. Nonetheless women had more secondary SD symptoms than men. The emotional dimension of SD is related with disability.

Cross-cultural adaptation and validation of multiple sclerosis quality of life questionnaire (MSQOL-54) in a Turkish multiple sclerosis sample

OBJECTIVE Multiple sclerosis (MS) is a chronic progressive disease with multiple neurological impairments. The disease can also dramatically affect the health-related quality of life of patients. The objective of this study was to investigate the validation of the translated and cross-culturally adapted MSQOL-54 in 183 Turkish MS patients. METHODS 183 adults classified as having definite MS patients were enrolled into the study. Patients were classified into four severity groups according to the expanded disability status scale (EDSS); group I (EDSS 0-4), group II (EDSS 4.5-5.5), group III (EDSS 6-6.5) and group IV (EDSS 7-8). MSQOL-54 questionnaire were translated and culturally adapted into Turkish. Associations between age, gender, disease duration, EDSS score, marital status, education and health insurance and the MSQOL-54 physical and mental health composite scores were determined. RESULTS The mean age of the 183 patients (138 female and 45 male) was 39+/-10 years. The questionnaire was well accepted but small cultural adaptations were required. EDSS scores showed significant associations with the MSQOL-54 physical and mental health composite scores. From the different EDSS groups only, the group I (EDSS 0-4) score was significantly associated with the physical health composite as well as the disease duration showed significant correlation with the physical and mental composite scores. None of the other EDSS groups and the other parameters showed correlation with physical health composite or mental health composite. CONCLUSION Assessment of quality of life of MS patients in addition to disease severity and disability level is important, because it provides unique information that is important to patients and to clinicians. A translation of an existing MS-targeted HRQOL measure from US English into Turkish was easily administered and well accepted in a Turkish MS sample.

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.

Utilization of the multiple sclerosis functional composite in follow-up: relationship to disease phenotype, disability and treatment strategies

As multiple sclerosis (MS) has a dynamic process, monitoring of the disability is important in the remission period. The main aim of the present study was to investigate the usefulness of MSFC instead of EDSS in the follow-up period of MS. In addition, evaluation of the effect of immunomodulatory therapy, and the difference among the type of MS in follow-up was purposed. One hundred and eighty-three patients with definite MS were enrolled in the present study. Patients were diagnosed as having relapsing-remitting (RR) MS (n=149) or secondary progressive (SP) MS (n=34). Fifty-eight out of 149 RRMS patients who had at least two relapses in the last 2 years have received any of the immunomodulator agents. The Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) were performed at baseline and after 2 years to assess disability. Patients who were under disease modifying therapy were assessed before the treatment and 2 years after starting the treatment. Cross-sectional correlations between MSFC and EDSS score at baseline and follow-up were studied. Patients were divided into three subgroups: (1) RRMS patients who did not receive disease modifying therapy (DMT)--non-DMT group, (2) RRMS patients who received DMT--DMT group, (3) SPMS patients who did not receive DMT--SPMS group. EDSS and MSFC scores got worsened significantly at the end of the second year. Decreases in either EDSS or MSFC scores were more prominent in SPMS group. The most significant worsening was found in T25WT. The most prominent and significant decrease was in PASAT of SPMS group. Moderately strong cross-sectional correlations were found between MSFC and EDSS scores at baseline and follow-up. The most prominent correlation was between EDSS and T25WT scores with an excellent correlation. We concluded that the MSFC assesses aspects of neurological function not measured by the EDSS, suggesting that it is more sensitive to detect change over time and better able to demonstrate a therapeutic effect. The pattern of correlations among the MSFC, its components, and the EDSS supported the validity of MSFC.

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.

Intrathecal sICAM-1 production in multiple sclerosis Correlation with triple dose Gd-DTPA MRI enhancement and IgG index

In this study the aim was to evaluate the intrathecal sICAM-1 production in multiple sclerosis (MS) patients during relapse and remission. In addition to this, we assessed whether there is a correlation between intrathecal sICAM-1 production and other disease activity markers such as IgG index and gadolinium enhancement in magnetic resonance imaging (MRI). Twenty four relapsing- remitting MS patients were included in the study. Serum and cerebrospinal fluid (CSF) samples were obtained both during relapse and remission. The soluble form of ICAM (sICAM) was measured by the ELISA method in serum and CSF. Cranial MRI with triple dose gadolinium injection was performed for each patient both during relapse and remission. Serum levels of sICAM-1 (245.23±92.88 ng/ml) were higher during relapse than those in remission (219.90±110.94 ng/ml), but the difference was not statistically significant. In relapse periods CSF levels of sICAM-1 (1.304±0.92 ng/ml) were higher than those in remission (1.06±0.86 ng/ml), but this was not significant. However, during relapse periods patients had significantly higher sICAM-1 index values (1.76±0.60) than those found during remission periods (1.01±0.44) (p<0.05). The IgG index values were higher in relapse periods than in remission (0.88±0.37 vs. 0.67±0.28) (p<0.005). On T1 weighted images following triple dose Gd injection, at least two or more enhancing lesions were present in 22/24 of the patients (91 %) in relapse and 4/24 of the patients (19 %) in remission. There was strong correlation both between the sICAM-1 index and Gd enhancement (r=0.72 p<0.05) and sICAM-1 index and IgG index in relapse (r=0.69 p<0.05). In conclusion, there is association between high sICAM-1 and IgG indices, as well as between high sICAM-1 index and Gd enhancing MRI lesions in relapsing MS patients.