Rana Karabudak

Survival and predictors of disability in Turkish MS patients

Objective: To examine the natural history, survival, and prognostic factors in a sample of Turkish MS patients. Method: This multicenter study included 1,259 definite MS patients diagnosed according to the criteria of Poser et al. Actuarial analysis of selected disability levels of 3, 6, 8, and 10 achieved with the Expanded Disability Status Scale (EDSS); a multivariate Cox regression analysis for prognostic factors related to time to reach EDSS ≥ 6; and Pearsons correlation coefficient for individual factors were performed. Results: The survival (±SE) at 15 years from onset was 94.6 ± 2.9%, and at 25 years was 89.0 ± 5.8%. The disability reached by 15 years was EDSS ≥ 3 in 66.4%, EDSS ≥ 6 in 41.2%, EDSS ≥ 8 in 10.5%, and EDSS = 10 in 5.4%. The most significant unfavorable prognostic factors were progressive course (relative risk [RR], 3.73; CI, 2.71 to 5.13) and sphincter symptoms at onset (RR, 1.86; CI, 1.23 to 2.82), followed by male sex, motor symptoms at onset, and a high attack frequency within the first 5 years. Primary progressive disease was correlated positively with male sex (r = 0.0895, p = 0.001), older age (r = 0.1807, p = 0.000), and motor (r = 0.1433, p = 0.000) or sphincter symptoms (r = 0.1001, p = 0.000) at onset, unlike relapsing-remitting and secondary progressive disease. Conclusions: Although a slightly better prognosis is observed in the Turkish MS population, early prognostic factors are similar to most of the previous Western series. Primary progressive disease, mostly seen in older men with motor and sphincter involvement at onset, has a worse prognosis and may represent a distinct behavioral variant of MS.

Six-minute walk distance as a measure of functional exercise capacity in multiple sclerosis.

Purpose. We hypothesised that six-minute walk (6MWT) distance of patients with ambulatory multiple sclerosis (MS) would differ from age-matched healthy control subjects. We also investigated the contribution of demographic, physical and physiological factors to impaired functional capacity in MS. Method. Thirty MS patients and 30 healthy subjects participated in this study. Respiratory muscle strength was measured. Pulmonary function test and 6MWT were performed. The Barthel Index (BI) was used to assess activities of daily living, and the Modified Ashworth Scale was used to determine spasticity. Symptomatic fatigue was measured using the Fatigue Severity Scale (FSS). Results. Pulmonary function and respiratory muscle strength of ambulatory MS patients were significantly lower, and baseline heart rate and fatigue perception were significantly higher than were healthy controls (p < 0.05). MS patients reached a significantly higher exercise heart rate, and walked significantly shorter distance than did healthy subjects (p < 0.05). The BI score, baseline heart rate and FSS score together accounted for 81 percent variance in 6MWT distance of MS patients (p < 0.05). Conclusion. The shorter distance covered during a 6MWT is determined by the limitations in activities of daily living, resting heart rate and subjective symptomatic fatigue in ambulatory patients with MS. Respiratory muscle weakness, lung function and level of neurological impairment do not contribute to impaired functional exercise capacity in these patients.

Physiotherapy Approaches in the Treatment of Ataxic Multiple Sclerosis: A Pilot Study

Objective: This study was planned to investigate the efficacy of neuromuscular rehabilitation and Johnstone Pressure Splints in the patients who had ataxic multiple sclerosis. Methods: Twenty-six outpatients with multiple sclerosis were the subjects of the study. The control group (n = 13) was given neuromuscular rehabilitation, whereas the study group (n = 13) was treated with Johnstone Pressure Splints in ad dition. Results: In pre- and posttreatment data, significant differences were found in sensation, anterior balance, gait parameters, and Expanded Disability Status Scale (p < 0.05). An important difference was observed in walking-on-two-lines data within the groups (p < 0.05). There also was a statistically significant difference in pendular movements and dysdiadakokinesia (p < 0.05). When the posttreatment values were compared, there was no significant difference between sensation, anterior balance, gait parameters, equilibrium and nonequilibrium coordination tests, Expanded Disability Status Scale, cortical onset latency, and central conduction time of somatosensory evoked potentials and motor evoked potentials (p > 0.05). Comparison of values re vealed an important difference in cortical onset-P37 peak amplitude of somatosen sory evoked potentials (right limbs) in favor of the study group (p < 0.05). Conclu sions : According to our study, it was determined that physiotherapy approaches were effective to decrease the ataxia. We conclude that the combination of suitable phys iotherapy techniques is effective multiple sclerosis rehabilitation. Key Words: Multi ple sclerosis—Ataxia—Physical therapy.

A recommended treatment algorithm in relapsing multiple sclerosis: report of an international consensus meeting

An International Working Group for Treatment Optimization in MS met to recommend evidence‐based therapeutic options for the management of suboptimal responses or intolerable side‐effects in patients treated with disease‐modifying drugs (DMDs) for multiple sclerosis (MS). Several DMDs are now available for the treatment of MS that have been shown to alter the clinical course of the disease by decreasing disease activity and delaying the progression of disability. Nevertheless, many patients continue to experience disease activity whilst on treatment, and recommendations have been made on how the success of therapy in an individual patient can be assessed. However, even after having identified criteria for a suboptimal response to current treatments, clinicians require guidance on how to improve the outcomes. This report summarizes the conclusions from a workshop at which this issue was addressed. We suggest treatment pathways for optimizing therapy for those patients with suboptimal responses to DMDs, and therapeutic options for patients with unacceptable side‐effects on their current therapy.

Peripheral Nervous System Involvement in Behçet’s Disease

Central nervous system complication of Behcet’s disease are well recognized. However, peripheral nervous system involvement has been rarely observed. A case of Behcet’s disease with prominent peripher

Effect of interferon β-1a on serum matrix metalloproteinase—9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in relapsing remitting multiple sclerosis patients

Abstract.There is emerging evidence that matrix metalloproteinases (MMPs) might be involved in blood brain barrier (BBB) breakdown in multiple sclerosis.A group of natural tissue inhibitors of metalloproteinases (TIMPS) regulates proteolytic activity to prevent tissue damage. TIMP-1 and MMP-9 are known to be secreted as heterodimers and TIMP-1 preferentially functions to inhibit MMP-9 activity. In this present study, the effects of IFNβ-1a on serum MMP-9 and TIMP-1 were evaluated longitudinally during a one-year period. The MMP-9 levels showed no significant changes while TIMP-1 levels gradually and significantly increased during 3rd and 6th months of therapy compared with pretreatment levels.

Characterization of neuromyelitis optica and neuromyelitis optica spectrum disorder patients with a late onset

Background: Few data are available for patients with a late onset (≥ 50 years) of neuromyelitis optica (LONMO) or neuromyelitis optica spectrum disease (LONMOSD), defined by an optic neuritis/longitudinally extensive transverse myelitis with aquaporin-4 antibodies (AQP4-Ab). Objective: To characterize LONMO and LONMOSD, and to analyze their predictive factors of disability and death. Methods: We identified 430 patients from four cohorts of NMO/NMOSD in France, Germany, Turkey and UK. We extracted the late onset patients and analyzed them for predictive factors of disability and death, using the Cox proportional model. Results: We followed up on 63 patients with LONMO and 45 with LONMOSD during a mean of 4.6 years. This LONMO/LONMOSD cohort was mainly of Caucasian origin (93%), women (80%), seropositive for AQP4-Ab (85%) and from 50 to 82.5 years of age at onset. No progressive course was noted. At last follow-up, the median Expanded Disability Status Scale (EDSS) scores were 5.5 and 6 in the LONMO and LONMOSD groups, respectively. Outcome was mainly characterized by motor disability and relatively good visual function. At last follow-up, 14 patients had died, including seven (50%) due to acute myelitis and six (43%) because of opportunistic infections. The EDSS 4 score was independently predicted by an older age at onset, as a continuous variable after 50 years of age. Death was predicted by two independent factors: an older age at onset and a high annualized relapse rate. Conclusion: LONMO/LONMOSD is particularly severe, with a high rate of motor impairment and death.

Familial Mediterranean fever and multiple sclerosis

Abstract Central nervous system (CNS) manifestations of familial Mediterranean fever (FMF) are extremely rare. These include pseudotumor cerebri, optic neuritis, CNS complications of polyarteritis nodosa type vasculitis, or hypercoagulable states secondary to renal amyloidosis, recurrent aseptic meningitis, and amyloid ophthalmoplegia. We present three patients with FMF whose neurological findings and magnetic resonance imaging (MRI) abnormalities resembled multiple sclerosis (MS). These two conditions in the same patient could arise from either coincidence or an unknown pathophysiological relationship. Both explanations are equally speculative and this matter needs further study, especially to investigate MRI features in FMF patients without CNS symptoms.

Familial Mediterranean fever and central nervous system involvement: a case series.

We conducted this study to determine familial Mediterranean fever (FMF)-associated central nervous system involvement including demyelinating lesions, stroke, and posterior reversible leukoencephalopathy syndrome (PRES). Patients with MEFV mutations were systematically reviewed through the Medical Biology Unit database. All samples sent for mutation analysis were screened for 10 common MEFV mutations. Patients with FMF and neurologic disorders according to the clinical records were invited for reevaluation. Lumbar puncture, electroencephalography, and evoked potentials were used to determine the type of neurologic involvement in selected cases. Electrocardiography, transthoracic and/or transesophageal echocardiography, and magnetic resonance imaging and/or angiography were performed to clarify the etiology of cerebrovascular disease. Of 8864 patients in the genetic testing database, 18 with neurologic signs were assessed. The mean age of patients was 31.0 ± 11.8 years, mean age at first FMF symptom was 12.6 ± 5.6 years, and mean age at neurologic involvement was 25.8 ± 12.2 years. Fifty-five percent of patients were women. A homozygote MEFV mutation was detected in 16 of 18 patients (88.8%), and a homozygote M694V mutation was found in 72.2% of patients. We found 7 FMF patients with demyelinating lesions, 7 with cerebrovascular disease, and 4 with PRES. The mean interval between first FMF sign and neurologic involvement was 13.7 ± 8.9 years in the demyelinating group, and 23.4 ± 10.3 years in the group with cerebrovascular disease. Mean stroke age was 28.5 ± 16.4 years. All patients in the PRES group had hypertension. Three different neurologic conditions in FMF patients were noticeable. Demyelinating lesions and cerebrovascular disease were the most common clinical presentations. Approximately 70% of patients had the homozygote M694V mutation. Neurologic involvement is rare but serious in FMF. Abbreviations: BAEP = brainstem auditory evoked potentials, CNS= central nervous system, CSF = cerebrospinal fluid, EEG = electroencephalography, ESR = erythrocyte sedimentation rate, FMF= familial Mediterranean fever, HSP = Henoch-Schönlein purpura, IL = interleukin, MEFV = the FMF gene, MRI = magnetic resonance imaging, PAN= polyarteritis nodosa, PRES = posterior reversible leukoencephalopathy syndrome, SEP = somatosensorial evoked potential, VEP= visual evoked potential.

Psychometric study of Turkish version of Fatigue Impact Scale in multiple sclerosis patients

BACKGROUND The aims of this study were to test the validity, test-retest reliability, and internal consistency of Turkish version of FIS; the variables affecting FIS score. MATERIALS AND METHODS 71 MS patients and 68 healthy subjects were included to the study. RESULTS Total FIS score and subscale scores were different statistically between MS patients and healthy volunteers in both first and second FIS applications (p<0.001). These results showed that FIS is validated in divergent direction. BDI score was higher in MS patients than healthy volunteers (p<0.001). There was no statistically significant difference between two study groups for cognitive subscale scores, after the effect of depression was eliminated (p>0.05). To assess the test-retest reliability, the scores of two FIS applications did not differ statistically (cognitive t=1.948 p>0.05, physical t=1.420 p=0.160, social t=1.470 p=0.146, total t=1.990 p=0.05). Intraclass correlation coefficients were 0.89 (99% confidence interval: 0.79-0.94) for cognitive, 0.95 (0.91-0.97) for physical, 0.91 (0.83-0.95) for social, and 0.93 (0.86-0.96) for total FIS scores (p<0.001). EDSS correlated with physical subscores in both applications of FIS. CONCLUSION Turkish version of FIS, which is valid and reliable, seems an appropriate tool for the assessment of the effects of fatigue in Turkish MS population.