Hot Topics and MS Research News for September 2014
This month's selections are studies which have not received much attention. Enjoy.
Melatonin supplementation may improve quality of life in MS patients.
A team of researchers in Poland evaluated the effects of 5 mg daily melatonin supplementation over 90 days in 102 patients with MS and 20 matched controls in regard to oxidative stress and the physical and psychological quality of life of MS patients. Melatonin is known to have antioxidative properties and helps to regulate circadian rhythms which in turn affect sleep. As an antioxidant, melatonin acts on superoxide dismutase (SOD) activity, in which enzymes battle antioxidants, and malondialdehyde (MDA) serum concentration level which is a marker of lipoprotein peroxidation, a process in which free radicals cause cell damage. The products of lipid peroxidation are neurotoxic, have proinflammatory properties, and could be involved in demyelination and axonal injury in MS.
Patients in this study were grouped together by which disease-modifying therapy they used or none. At the beginning of the study, a marked increase in serum MDA concentration was observed in all MS patients groups. A significant increase in SOD activity compared to controls was observed only in the glatiramer acetate-treated group. Only the mitoxantrone-treated group showed higher scores on the Multiple Sclerosis Impact Scale (MSIS-19) in both the physical and psychological subscales as compared to other groups.
After melatonin treatment, serum MDA concentration decreased significantly in interferon-beta and glatiramer acetate-treated groups, but not in the mitoxantrone-treated or untreated (no DMT) group. The SOD activity increased in interferons beta-treated groups compared to initial values. No significant differences in mean MSIS-29-PHYS scores were observed before and after melatonin therapy, although melatonin supplementation did cause a decrease in mean MSIS-29-PSYCH scores compared to initial values in interferons beta-treated groups.
Based on the findings from their study, authors suggest that melatonin can act as an antioxidant and improves reduced quality of life in MS patients. The results point to the importance of endogenous antioxidants, such as melatonin, in the development and course of MS. Its ability to regulate circadian rhythm, especially in a disease associated with sleep disturbances such as MS, could be beneficial. Melatonin exhibits a high level of safety, is well tolerated, and generates no side effects even in high doses. More research is needed to determine the exact role of melatonin in the treatment and pathophysiology of MS.
Adamczyk-Sowa M, Pierzchala K, Sowa P, et al. Influence of melatonin supplementation on serum antioxidative properties and impact of the quality of life in multiple sclerosis patients. J Physiol Pharmacol. 2014 Aug;65(4):543-50.
Actemra safely used in patient diagnosed with MS and RA.
Patients diagnosed with both multiple sclerosis and rheumatoid arthritis have limited treatment choices. Since anti-tumor necrosis factor (anti-TNF) therapies, such as Enbrel, Humira, Remicade, Cimzia, and Simponi, can cause complications of demyelinating diseases, such as an increase in MS relapses, the use of anti-TNF therapies are contraindicated in MS. Few reports have been published regarding the use of anti-interleukin-6 receptor therapy, such as Actemra, in patients with the RA/MS dual diagnosis. The current case study reports that anti-interleukin-6 therapy was safely used in a patient diagnosed with RA and MS.
A 53-year-old Japanese woman with MS and RA was admitted to a hospital because her RA was uncontrolled with oral methotrexate, tacrolimus (Prograf), and prednisolone. She had developed MS at age 25 and was treated with glucocorticoid therapy. Her MS has been in remission for more than 9 years. Doctors chose to treat her RA with the anti-interleukin-6 receptor antibody, tocilizumab, starting at 8 mg/kg every 4 weeks. She achieved complete remission with the second dose of tocilizumab and has remained in remission with tocilizumab without recurrence of multiple sclerosis for more than 5 years.
Sato H, Kobayashi D, Abe A, et al. Tocilizumab treatment safety in rheumatoid arthritis in a patient with multiple sclerosis: a case report. BMC Res Notes. 2014 Sep 12;7(1):641. doi: 10.1186/1756-0500-7-641.
Long-term disability may be predicted by evoked potentials in 20 year MS study.
Multiple sclerosis is an unpredictable disease which causes varying degrees of disability in individuals. The development of predictors of longterm disability is difficult due to clinical variability and a complex interplay of factors. Researchers in Switzerland conducted a 20-year study in 28 patients with clinically definite MS. Participants had prospective follow-up visits at 6 (T1), 12 (T2) and 24 (T3) months, at year 14 (T4) and at year 20 (T5). Examinations comprised Expanded Disability Status Scale (EDSS) scores and combined visual and motor evoked potentials to upper and lower extremities at entry (T0), T1, T2, T3, and T3, as well as brain MRI scan at T0 and T2. EDSS testing was repeated at T4 and T5. The EDSS of patients who could not be assessed in person at the clinic at year 20 (T5) were accessed by phone, as was the case in 13 out of 28 participants.
Researchers demonstrated for the first time at a numerical scores of combined visual and motor evoked potentials (EPs) at baseline allows prediction of the development of long-term clinical disability after 20 years in a group of patients with RRMS and SPMS. However, baseline EDSS and conventional MRI data (number of Gd-enhancing lesions and T2-lesions at baseline) did not improve prediction of long-term disability.
Authors acknowledge that their small sample size may not be entirely representative of the MS population at large since patients were chosen to be included who demonstrated high inflammatory disease activity at baseline. However a strength of the study is the nearly complete follow-up of 93% at year 20. One patient died at year 6 due to non-MS-related cause and one patient was lost to follow-up.
While none of the participants received approved disease-modifying therapies before month 24, a substantial number did between month 25 and year 20, and this potentially could influence the relationship between baseline EPs and later disability. Including ‘therapy’ as a variable revealed a statistically significant effect on the prediction of EDSS at year 20, lowering the predicted EDSS by about two points in favor of those who received one or more disease-modifying therapies between month 25 and year 20.
Evoked potentials assess the functional integrity of specific neural pathways by measuring conduction propagation. Though EPs are not entirely specific for the underlying pathophysiology in MS, authors point out, they seem especially sensitive for subclinical lesions, which later might become functionally relevant.
Schlaeger R, Schindler C, Grize L, et al. Combined visual and motor evoked potentials predict multiple sclerosis disability after 20 years. Mult Scler. 2014 Sep;20(10):1348-54. doi: 10.1177/1352458514525867. Epub 2014 Feb 26.
Other studies of interest:
Burschka JM, Keune PM, Oy U, Oschmann P, Kuhn P. Mindfulness-based interventions in multiple sclerosis: beneficial effects of Tai Chi on balance, coordination, fatigue and depression. BMC Neurol. 2014 Aug 23;14(1):165. [Epub ahead of print]
Blight AR, Henney HR 3rd, Cohen R. Development of dalfampridine, a novel pharmacologic approach for treating walking impairment in multiple sclerosis. Ann N Y Acad Sci. 2014 Aug 25. doi: 10.1111/nyas.12512. [Epub ahead of print].
Caporro M, Disanto G, Gobbi C, Zecca C. Two decades of subcutaneous glatiramer acetate injection: current role of the standard dose, and new high-dose low-frequency glatiramer acetate in relapsing-remitting multiple sclerosis treatment. Patient Prefer Adherence. 2014 Aug 21;8:1123-34. doi: 10.2147/PPA.S68698. eCollection 2014.
Iseri P, Başyiğit I, Ozerdem C, Başyiğit H, Efendi H, Yildiz F. The effect of pulse methylprednisolone plus theophylline treatment on clinical, pulmonary and inflammatory markers in relapses of multiple sclerosis. Balkan Med J. 2013 Mar;30(1):33-6. doi: 10.5152/balkanmedj.2013.004. Epub 2013 Mar 1.
Kalron A. The Relationship between Specific Cognitive Domains, Fear of Falling, and Falls in People with Multiple Sclerosis. Biomed Res Int. 2014;2014:281760. doi: 10.1155/2014/281760. Epub 2014 Jul 24.