BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

OBJECTIVE: To explore the effects of acupuncture in comparison with sham acupuncture on cognitive functions in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: In this randomized controlled trial, 31 RRMS patients in the acupuncture group were treated with traditional Chinese acupuncture based on the treatment principle of calming the mind, reinforcing qi and blood, and 31 patients in the control group were treated with sham acupuncture (shallow needling at non-acupuncture points) twice a week for 12 weeks. The primary outcome was the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) score, which was evaluated by a psychologist at baseline and after 12 weeks of treatment. The secondary outcomes were the Symptom Checklist 90-Revised (SCL-90-R), Pittsburgh Sleep Quality Index (PSQI), and Fatigue Severity Scale (FSS) scores. The participants were provided with contact information from the researchers with constant access to report any adverse symptoms. RESULTS: In total, 62 participants were enrolled and allocated to the acupuncture group (31 cases) or control group (31 cases). After 12 weeks of acupuncture treatment, BICAMS including Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-2 (CVLT-2) and delayed CVLT-2 scores were significantly improved in comparison with the control group (P<0.01). However, the changes in the Brief Visuospatial Memory Test-Revised (BVMT-R) and delayed BVMT-R scores related to visual/spatial memory did not differ significantly between the two groups (both P>0.05). The FSS, PSQI, and SCL-90-R scores were significantly reduced after 12-week treatment in the acupuncture group compared to the control group (P<0.05 or P<0.01). No life-threatening adverse events occurred throughout the study. CONCLUSIONS Twelve weeks of acupuncture treatment was effective in improving immediate and short-term auditory/verbal memory, attention and processing speed; reducing fatigue and decreasing sleep latency and the use of sleeping medications; alleviating depression, somatization, obsessive-compulsive and paranoid disorders in patients with RRMS. (Iranian Registry of Clinical Trials, No. IRCT20220101053582N1).
Humans ; Multiple Sclerosis, Relapsing-Remitting/physiopathology* ; Acupuncture Therapy ; Female ; Male ; Cognition/physiology* ; Adult ; Treatment Outcome ; Middle Aged

Plasma homocysteine level and megaloblastic anemia status are two factors that can affect the quality of life of patients with multiple sclerosis (MS). We conducted this study to determine the effect of vitamin B12 and folic acid supplementation on serum homocysteine, megaloblastic anemia status and quality of life of patients with MS. A total of 50 patients with relapsing remitting multiple sclerosis (RRMS) included in this study which divided into 2 groups. The vitamin group received 5 mg folic acid tablet daily and 3 doses of vitamin B12 (1,000 mcg) injection and the other group received placebo and normal saline injection (same doses). The quality of life was measured by using Multiple Sclerosis Quality of Life-54 questionnaire (MSQOL-54). Fully automated fluorescence polarization immunoassay was used to measure serum homocysteine, vitamin B12 and folate. Complete blood count blood test was conducted to determine the anemia status. The mean homocysteine level reduced by 2.49 ± 0.39 µmol/L (p = 0.001), hemoglobin increased from 11.24 ± 1.54 to 13.12 ± 1.05 g/dL (p = 0.001), and mean corpuscular volume decreased from 95.50 ± 6.65 to 89.64 ± 4.24 in the vitamin group (p = 0.001). There was a significant improvement in the mental field of life quality in the placebo group (37.46 ± 19.01 to 50.98 ± 21.64; p = 0.001), whereas both physical and mental fields of quality of life were improved significantly in the vitamin group (40.38 ± 15.07 to 59.21 ± 12.32 and 29.58 ± 15.99 to 51.68 ± 18.22, respectively; p = 0.001). Serum homocysteine level decrease and anemia status improvement with vitamin B12 and folic acid supplementation reveal the potential role of these two vitamins in improving the life quality of MS patients. TRIAL REGISTRATION: Iranian Registry of Clinical Trials Identifier: IRCT2015100313678N7
Anemia* ; Anemia, Megaloblastic ; Blood Cell Count ; Erythrocyte Indices ; Fluorescence Polarization Immunoassay ; Folic Acid* ; Hematologic Tests ; Homocysteine* ; Humans ; Multiple Sclerosis* ; Multiple Sclerosis, Relapsing-Remitting ; Plasma ; Quality of Life* ; Vitamin B 12* ; Vitamins*

BACKGROUND AND PURPOSE: The objective of this study was to determine the frequencies of different clinical presentations and the phenotypic spectrum of multiple sclerosis (MS). METHODS: This cross-sectional study was performed in the Neurology Department of King Fahd Hospital of University Alkhobar in the Kingdom of Saudi Arabia (KSA). Data of 190 MS patients who fulfilled the McDonald criteria were retrieved from medical records and analyzed. RESULTS: The age at disease onset was 26.27±8.2 years (mean±SD) and disease duration was 6.38±5.10 years. The male-to-female ratio was 1:1.6. Optic neuritis and myelitis were the most-frequent first clinical presentations. Sensory (73.1%), motor (61%), and visual (58.4%) symptoms were the most-frequent established clinical symptoms. Relapsing-remitting multiple sclerosis (RRMS) was present in 75% of the cases. Supratentorial T2-weighted white-matter lesions and deep-gray-matter or juxtacortical lesions were the most-frequent magnetic resonance imaging (MRI) lesions, comprising 28% and 23.7% of all MRI lesions observed in 93.6% and 79.4% of the cases, respectively. The scores on the Expanded Disability Status Scale were within the range of 1.0–5.5 in 82.1% of the patients. There were 145 (76.3%) patients taking interferon β therapy. CONCLUSIONS: MS presenting in the hospital setting is more common in KSA than reported previously, and the number of diagnosed cases in increasing. It is therefore an emerging and disabling neurological illness in KSA with clinical characteristics not dissimilar to those in other middle eastern countries. A decrease in the frequency of patients with secondary progressive multiple sclerosis (SPMS) indicates either that more new cases of RRMS are being diagnosed or that adequate treatments of RRMS are preventing the evolution to SPMS. Further larger and population-wide epidemiological and clinical studies with the long-term follow-up of MS patients are required to better assess the clinical spectrum of MS in KSA.
Cross-Sectional Studies ; Epidemiology ; Follow-Up Studies ; Humans ; Interferons ; Magnetic Resonance Imaging ; Medical Records ; Multiple Sclerosis* ; Multiple Sclerosis, Chronic Progressive ; Multiple Sclerosis, Relapsing-Remitting ; Myelitis ; Neurology ; Optic Neuritis ; Phenotype ; Prevalence ; Saudi Arabia*

BACKGROUND AND PURPOSE: The number of disease-modifying drugs (DMDs) available for treating relapsing-remitting multiple sclerosis is increasing. Numerous drugs have been approved since 2010 in South America, which has increased the complexity of the treatment algorithm. The aim of this study was to determine the changes in multiple sclerosis treatments relative to the underlying causes and the availability of new DMDs in Argentina. METHODS: A descriptive retrospective study was carried out on a group of 59 patients diagnosed with RRMS who use more than one DMD. RESULTS: The first treatment switch occurred before 2010 in 27% of the patients and after 2010 in the other 73%. Efficacy was the main reason for switching during both periods. A second treatment switch was required in 25% of the patients, with this occurring after 2010 in 86.6% of them. Interferon was the most-used drug before 2010 and fingolimod was the most-used drug thereafter. CONCLUSIONS: We have identified that the tendency for treatment changes has increased following the arrival of new drugs. Efficacy has been the main cause of these changes.
Argentina ; Drug Therapy ; Fingolimod Hydrochloride ; Humans ; Interferons ; Multiple Sclerosis* ; Multiple Sclerosis, Relapsing-Remitting ; Retrospective Studies ; South America

No abstract available.
Humans ; Interferon-beta* ; Interferons* ; Multiple Sclerosis ; Multiple Sclerosis, Relapsing-Remitting*

No abstract available.
Humans ; Interferon-beta* ; Interferons* ; Multiple Sclerosis ; Multiple Sclerosis, Relapsing-Remitting*

BACKGROUND AND PURPOSE: It is exceedingly difficult to differentiate benign multiple sclerosis (BMS) from relapsing-remitting multiple sclerosis (RRMS) based on clinical characteristics, neuroimaging, and cerebrospinal fluid tests. Optical coherence tomography (OCT) allows quantification of retinal structures, such as the retinal nerve fiber layer (RNFL) thickness, at the optic disc and the ganglion cell layer (GCL) at the macula, on a micrometer scale. It can also be used to trace minor alterations and the progression of neurodegeneration, help predict BMS, and influence the choice of therapy. To utilize OCT to detect the extent of changes of the optic disk and macular microstructure in patients with BMS and RRMS compared to healthy controls (HCs), with special focus on changes related to the presence/absence of optic neuritis (ON). METHODS: Spectral-domain OCT was applied to examine eyes from 36 patients with multiple sclerosis (MS), comprising 11 with BMS and 25 with RRMS, and 34 HCs. RESULTS: The RNFL and GCL were significantly thinner in eyes previously affected by ON, irrespective of the type of MS (i.e., BMS or RRMS), than in HCs. Significant thinning of the GCL was also observed in non-ON RRMS (and not non-ON BMS) compared to HCs. Correspondingly, a significant association between disease duration and thinning rates of the RNFL and GCL was observed only in non-ON RRMS (-0.54+/-0.24 and -0.43+/-0.21 microm/year, mean+/-SE; p<0.05 for both), and not in non-ON BMS (-0.11+/-0.27 and -0.24+/-0.24 microm/year). CONCLUSIONS: The RNFL and GCL were thinner in both ON- and non-ON MS, but the change was more pronounced in ON MS, irrespective of the MS subtype studied herein. GCL thinning and the thinning rate of both the GCL and RNFL were less pronounced in non-ON BMS than in non-ON RRMS. These findings may help to predict the course of BMS.
Cerebrospinal Fluid ; Ganglion Cysts* ; Humans ; Multiple Sclerosis* ; Multiple Sclerosis, Relapsing-Remitting ; Nerve Fibers* ; Neuroimaging ; Optic Disk ; Optic Neuritis ; Retinaldehyde* ; Tomography, Optical Coherence

Glatiramer acetate (GA) is a synthetic amino acid polymer, used for relapsing-remitting multiple sclerosis. The most common adverse effect of GA is a skin reaction at the injection site with a probable IgE-mediated mechanism. We report a case of a 45-year-old woman with multiple sclerosis and urticaria to interferon-beta1a, who underwent a challenge test to GA. She presented itching wheals at the intradermal sites. A month later the patient repeated the test and presented the same reactions of the first test. The next day she continued the test with subcutaneous injections. One hour later she presented a flare up of the reactions appeared during the previous 2 tests. No reactions appeared at the subcutaneous injection sites. The patient also presented dyspnea. Flare-up reactions are characterized by the reactivation of previously positive reactions to intradermal or skin tests triggered by patch testing and after systemic provocation with an allergen. The phenomenon is not common to drugs. The mechanisms involved in this reaction seem to be heterogeneous and are not completely understood. To our knowledge this is the first case of allergic reaction to GA manifested as a flare-up reaction during challenge test.
Dyspnea ; Female ; Humans ; Hypersensitivity* ; Injections, Subcutaneous ; Interferons* ; Intradermal Tests ; Middle Aged ; Multiple Sclerosis ; Multiple Sclerosis, Relapsing-Remitting ; Patch Tests ; Polymers ; Pruritus ; Skin ; Skin Tests ; Urticaria

BACKGROUND AND PURPOSE: The relationship between contingent negative variation (CNV), which is an event-related potential, and cognition in multiple sclerosis (MS) has not been examined previously. The primary objective of the present study was thus to determine the association between CNV and cognition in a sample of MS patients. METHODS: The subjects of this study comprised 66 MS patients [50 with relapsing-remitting MS (RRMS) and 16 with secondary progressive MS (SPMS)] and 40 matched healthy volunteers. A neuropsychological battery was administered to all of the subjects; CNV recordings were made from the Cz, Fz, and Pz electrodes, and the amplitude and area under the curve (AUC) were measured at each electrode. RESULTS: RRMS patients exhibited CNVs with lower amplitudes and smaller AUCs than the controls at Pz. SPMS patients exhibited CNVs with lower amplitudes and smaller AUCs than the controls, and CNVs with a smaller amplitude than the RRMS patients at both Cz and Pz. After correcting for multiple comparisons, a lower CNV amplitude at Pz was significantly associated with worse performance on measures of speed of information processing, verbal fluency, verbal learning, and verbal recall. CONCLUSIONS: CNV may serve as a marker for disease progression and cognitive dysfunction in MS. Further studies with larger samples and wider electrode coverage are required to fully assess the value of CNV in these areas.
Area Under Curve ; Automatic Data Processing ; Cognition ; Contingent Negative Variation* ; Disease Progression ; Electrodes ; Evoked Potentials ; Healthy Volunteers ; Humans ; Multiple Sclerosis* ; Multiple Sclerosis, Chronic Progressive ; Multiple Sclerosis, Relapsing-Remitting ; Neuropsychological Tests ; Verbal Learning