Long-Term Effectiveness of Fingolimod for Multiple Sclerosis in a Real-World Clinical Setting.

INTRODUCTION: The primary aim of the present study was to evaluate the long-term efficacy of fingolimod in patients with multiple sclerosis (MS); secondary aims were to describe the safety of fingolimod with the evaluation of treatment satisfaction and impact on the quality of life in real life. METHODS: We collected clinical, demographical, neuroradiological, and treatment data, including pre- and posttreatment status health-related quality of life from 286 MS patients consecutively treated with fingolimod. Clinical assessment was based on the Expanded Disability Status Scale (EDSS), and quality of life assessment was performed with MS-related quality of life inventory (MSQOLI). The data were recorded at baseline and every 6 months for 2 years. RESULTS: One hundred and fourteen males and 172 females were enrolled. The annualized relapse rate and EDSS showed a statistically significant reduction during the observation period (p < 0.001). The patients also demonstrated substantial improvements in magnetic resonance imaging (MRI) outcomes (p < 0.001). Health-related quality of life scores improved significantly between baseline and 24-month visit (p < 0.001). No serious adverse events occurred. CONCLUSION: In our cohort, fingolimod treatment was associated with reduced relapse, MRI activity, and improved EDSS and MSQOLI scores. Additionally, fingolimod has been able to maintain its effectiveness over a considerable long period of treatment.

Effectiveness, Safety, and Health-Related Quality of Life of Chronic Migraine Patients Treated with Onabotulinum Toxin A.

OBJECTIVE: The present study aims to describe the efficacy and safety of onabotulinum toxin A (BonT-A) with evaluation of treatment satisfaction and impact on quality of life in chronic migraine (CM) patients in real life. METHODS: This study was conducted in CM patients who were treated with BoNT-A with 12 months of follow-up. Data about outcome, adverse events, and patients' pre- and post-treatment status including health-related quality of life data were analyzed. Health-related quality of life scores were measured at baseline and months 6 and 12 after the beginning of BoNT-A administration. RESULTS: Of 42 enrolled patients, 30 were included in the analysis. At 12 months, all patients showed a reduction in number of headaches and analgesic use per month and none reported adverse events. After BoNT-A supplementation, health-related quality-of-life scores improved significantly. There was a direct association between health-related quality of life with reduction of headache days at the end of study. CONCLUSION: This study confirms that BoNT-A treatment is effective on CM and improves the functional well-being and quality of life of patients.

Vitamin D deficiency and its association with fatigue and quality of life in multiple sclerosis patients.

BACKGROUND: Vitamin D deficiency is associated with the incidence and prevalence of a variety of neurologic disorders, including multiple sclerosis. However, available studies to date have not provided convincing evidence that vitamin D treatment improves fatigue and life quality in patients with multiple sclerosis. AIM: To assess the relationship of vitamin D deficiency with health-related quality-of-life issues and fatigue in multiple sclerosis patients. METHODS: Vitamin D3 levels were measured in 149 multiple sclerosis patients. In patients with lower than 30 ng/mL levels, vitamin D was administered. Fatigue and health-related quality of life scores were measured at baseline and months 1, 3, 6, and 12 after the beginning of vitamin D3 administration. RESULTS: Among 149 patients, 90% were vitamin D deficient. After vitamin D supplementation, health-related quality of life and fatigue scores improved significantly. There was a direct association between health-related quality of life with absence of fatigue and vitamin D status at the end of study. CONCLUSION: The 90% frequency of multiple sclerosis patients with vitamin D deficiency, together with the significant association of vitamin D status with the absence of fatigue and improved physical and functional well-being, points to vitamin D supplementation as a potential therapy to enhance the patient's quality of life. RELEVANCE OF THE ARTICLE FOR PREDICTIVE PREVENTIVE AND PERSONALIZED MEDICINE: This article emphasizes that vitamin D supplementation can improve clinical outcome in multiple sclerosis patients providing immune modulation and neuroprotection. Identification and correction of vitamin D deficiency has the potential to treat the related quality of life in patients with multiple sclerosis.

Headache characteristics in multiple sclerosis.

OBJECTIVES: The aims of this study were to study the prevalence and characteristics of headache in patients with multiple sclerosis and to clarify the relationship between headache and multiple sclerosis therapies. METHOD: 782 MS patients were consecutively admitted. All patients filled out a detailed headache questionnaire and 754 patients were included. RESULTS: Of 754 patients, 515 (68%) reported having headache. According to the International Headache Society criteria, we detected 202 (39%) suffering from migraine, 103 (20%) suffering from tension-type headache and 198 (38%) with medication overuse headache. Twelve patients (2%) had unclassified headache. Three hundred and seventy seven patients (73%) were treated with interferon beta, 81 (16%) with fingolimod, 35 (7%) with teriflunamide and 22 (4%) with natalizumab, respectively. One hundred and one (20%) reported that onset of headache occured prior to onset of multiple sclerosis therapies, while 414 (80%) had headaches occured after therapy. A higher incidence of headache was found in patients treated with interferon beta. We found a significant association between migraine and the age of onset of multiple sclerosis therapies. The age of onset of headache was the earliest in the patients with migraine. In migraine patients, the duration of medication use until the headache onset was the shortest when compared to other headache groups. Four hundred and fifty nine patients (89%) have sought help from a physician because of the severity and frequency of headache. CONCLUSION: In our study, the prevalence of headache among all multiple sclerosis patients was 68%. The results of this study indicate a possible relationship may exist between headache and multiple sclerosis therapies since 80% of patients described headaches after the onset of treatments. The younger start and the shorter duration of interferon beta use caused the higher incidence of headache, but this correlation was not observed in other drugs. Interestingly, medication overuse headache was far more prevalent in multiple sclerosis patients than in previously reported community populations.

Effects of low-frequency repetitive transcranial magnetic stimulation and neuromuscular electrical stimulation on upper extremity motor recovery in the early period after stroke: a preliminary study.

OBJECTIVE: To assess the efficacy of inhibitory repetitive transcranial magnetic stimulation (rTMS) and neuromuscular electrical stimulation (NMES) on upper extremity motor function in patients with acute/subacute ischemic stroke. METHODS: Twenty-five ischemic acute/subacute stroke subjects were enrolled in this randomized controlled trial. Experimental group 1 received low frequency (LF) rTMS to the primary motor cortex of the unaffected side + physical therapy (PT) including activities to improve strength, flexibility, transfers, posture, balance, coordination, and activities of daily living, mainly focusing on upper limb movements; experimental group 2 received the same protocol combined with NMES to hand extensor muscles; and the control group received only PT. Functional magnetic resonance imaging (fMRI) scan was used to evaluate the activation or inhibition of the affected and unaffected primary motor cortex. RESULTS: No adverse effect was reported. Most of the clinical outcome scores improved significantly in all groups, however no statistically significant difference was found between groups due to the small sample sizes. The highest percent improvement scores were observed in TMS + NMES group (varying between 48 and 99.3%) and the lowest scores in control group (varying between 13.1 and 28.1%). Hand motor recovery was significant in both experimental groups while it did not change in control group. Some motor cortex excitability changes were also observed in fMRI. CONCLUSION: LF-rTMS with or without NMES seems to facilitate the motor recovery in the paretic hand of patients with acute/subacute ischemic stroke. TMS or the combination of TMS + NMES may be a promising additional therapy in upper limb motor training. Further studies with larger numbers of patients are needed to establish their effectiveness in upper limb motor rehabilitation of stroke.

GNE Myopathy in Turkish Sisters with a Novel Homozygous Mutation.

Background. Hereditary inclusion body myopathy is caused by biallelic defects in the GNE gene located on chromosome 9p13. It generally affects adults older than 20 years of age. Methods and Results. In this study, we present two Turkish sisters with progressive myopathy and describe a novel mutation in the GNE gene. Both sisters had slightly higher levels of creatine kinase (CK) and muscle weakness. The older sister presented at 38 years of age with an inability to climb steps, weakness, and a steppage gait. Her younger sister was 36 years old and had similar symptoms. The first symptoms of the disorder were seen when the sisters were 30 and 34 years old, respectively. The muscle biopsy showed primary myopathic features and presence of rimmed vacuoles. DNA analysis demonstrated the presence of previously unknown homozygous mutations [c.2152 G>A (p.A718T)] in the GNE genes. Conclusion. Based on our literature survey, we believe that ours is the first confirmed case of primary GNE myopathy with a novel missense mutation in Turkey. These patients illustrate that the muscle biopsy is still an important method for the differential diagnosis of vacuolar myopathies in that the detection of inclusions is required for the definitive diagnosis.

Histopathological and genetic features of patients with limb girdle muscular dystrophy type 2C.

OBJECTIVE: In this study, it was aimed to describe the clinical, histopathological and genetic features of 20 patients with gamma sarcoglycanopathy confirmed by muscle biopsies and genetic analysis. MATERIAL AND METHOD: We retrospectively reviewed 20 patients from whom muscle biopsy specimens were obtained between 2007 and 2012. All patients were clinically diagnosed as muscular dystrophy and biopsy materials were collected from five different centers of neurological disorders. All DNAs were extracted from muscle tissues or blood samples of patients and genetic tests (mutation analyses for gamma sarcoglycan gene and deletion-duplication analyses for all 4 sarcoglycan genes) were performed. RESULTS: The mean age of the patients was 7.6 years (2 -21 years). Only one case (5%) was older than 14 years. The mean CPK level was 10311 U/L (1311 - 35000 U∕L). There were 4 siblings in these series. Expression defects of gamma sarcoglycan staining were determined in (15 males, and 5 females) all patients with muscle biopsy specimens. But only in 9 of them, disease-causing defects could be determined with genetic analyses. CONCLUSION: The present study has demonstrated that both examination of muscle biopsy specimens and DNA analysis remain important methods in the differential diagnosis of muscular dystrophies. Because dystrophinopathies and sarcoglycanopathies have similar clinical manifestation.

Comparison of neurophysiological and MRI findings of patients with multiple sclerosis using oligoclonal band technique.

BACKGROUND: The correlation of oligoclonal bands (OCBs) and intrathecal IgG synthesis are not yet clear in multiple sclerosis (MS). PURPOSE: In this study, we investigated the OCB situation and IgG index, cranial and cervical magnetic resonance imaging (MRI) findings and also compared visual evoked potentials (VEP) and somatosensorial evoked potentials (SEP) in order to better understand the OCB pattern and pathogenesis. METHODS: Retrospective study included 40 patients (19 male, 21 female, mean age 29 ± 4,24) with precise MS diagnosis according to McDonald criteria. RESULT: Sixteen of the patients were OCB negative, and 24 patients were positive. The different between the OCB situation and number of plaques in cranial and cervical MRI, atrophy, oedema and contrast material retention were insignificant. The different between the OCB situation and VEP and SEP were insignificant. CONCLUSION: These laboratory findings are all specific, all developing via independent mechanisms and are not related to each other during the silence periods of patients.

A regional panorama of dysferlinopathies.

OBJECTIVE: We describe the characteristic features of 11 patients (6 men and 5 women) with dysferlinopathies confirmed by muscle biopsies. In addition, we aimed to provide a realistic comprehensive picture of the severe muscle diseases in the Aegean Region of Turkey. MATERIAL AND METHOD: We retrospectively reviewed 90 patients who underwent muscle biopsy examinations between 2008 and 2011 in the pathology laboratory of Izmir Dr.Behcet Uz Children's Hospital. Biopsy specimens of all patients clinically diagnosed as muscular dystrophy referred from 4 different centers of neurological disorders were collected. RESULTS: Dystrophinopathy was the most (n=45) and gammasarcoglycanopathy was the second common (n=13) muscular dystrophy in this series. The mean age of all 90 patients was 8.8 years (3 months- 64 years). Only 14 cases (15.5%) were older than 14, and 23 cases were younger than two years. Dysferlinopathy was the most common dystrophy in the older age group. There were statistical significant differences between the types of dystrophy and inflammation (0.021), creatine kinase levels (p= 0.001), age (p=0.001), and gender (p < 0.001) of the patients. CONCLUSION: The present study revealed that dysferlinopathies is not an uncommon form of muscular dystrophies in western Turkey. We have concluded that if avoidance from unnecessary therapeutic interventions is desired, we must be aware of the relative frequencies of dysferlinopathies.