A multimodal intervention for progressive multiple sclerosis

Multiple sclerosis (MS) is a complex, progressive disease of the central nervous system with potential multifactorial etiology. Subjects with MS experience varying symptoms such as fatigue, muscle weakness, gait and balance impairments, etc. With time, intensity of the symptoms progresses, especially if subjects are in the progressive phase of the disease. So far, there is no effective treatment available which can reverse or even stop progression of the symptoms and disability associated with MS. Given the multifactorial nature of MS, use of multiple interventions is recommended for its treatment. As use of multiple pharmacological agents is usually limited due to adverse side effects, non-pharmacological treatments such as diet, exercises and stress management may provide a safer and potentially effective treatment option. The main aim of this study was to investigate the effects of a combination of non-pharmacological treatments on subjects with progressive MS.

In this open-label, single arm cohort study, we investigated the effects of a multimodal intervention consisting of modified Paleolithic diet, nutritional supplements, stretching exercises, strengthening exercises with electrical stimulation of trunk and lower limb muscles, meditation and massage on multiple symptoms associated with progressive MS. We investigated the effects on fatigue, quality of life, clinical disability, walking performance and balance of the subjects over a period of 12 months. Twenty subjects (15 female) with progressive MS (18 secondary progressive and 2 primary progressive) and mean Expanded Disability Status scale (EDSS) score of 6.2 (range, 3.5 to 8) participated in the 12-month main phase of the study. In a subset of subjects (8 SPMS, 2 PPMS; EDSS 6.2 + 1.4), effects of the intervention on microstructure of whole brain, corpus callosum and corticospinal tracts using diffusion tensor imaging (DTI), and measures of clinical disability including ambulation, hand function and cognitive functions were also investigated. Adherence and dosage of individual components of the intervention were calculated from subjects' daily logs. All clinical assessments were completed at baseline, 3, 6, 9 and 12 months. MRI data were collected at 1 and 12 months post-intervention on a subset of 10 subjects. Safety analyses were completed based on monthly side effects questionnaires and blood analyses at 1, 3, 6, 9 and 12 months.

Overall subjects showed good adherence with this intervention and did not report any serious side effects. Subjects reported significant improvement in perceived fatigue, energy and general health within 3 months from baseline and sustained the improvement until 12 months. Fifty percent of the subjects showed significant and consistent increases in both comfortable (during timed up and go test) and fast (during timed 25 foot walk) walking speeds. Small but significant improvements in the measures of balance such as Berg Balance test and time to stand up from seated position were also observed. Interestingly, subjects with comparatively lower physical impairment at baseline showed higher improvements in fatigue, walking and balance tests compared to the subjects with severe physical impairments at baseline. We observed consistent improvements in the cognitive functions of the subjects and in the white matter integrity of left corticospinal tracts. Clinical disability assessed with EDSS, and DTI metrics of most white matter tracts did not change significantly during the study period.

These results show that a multimodal intervention can be safely implemented and sustained by subjects with progressive MS. This intervention decreases perception of fatigue and improves quality of life of these subjects. Furthermore, this intervention has beneficial effects on subject's walking ability, balance and cognitive functions and white matter integrity. Initiating this intervention during early stage of the disease when subjects have only mild to moderate disability seems to be more beneficial. Larger, randomized, controlled trials are needed to establish efficacy of this multimodal intervention on MS and elucidate mechanisms underlying its effects on MS.