Randomized control trial evaluation of a modified Paleolithic dietary intervention in the treatment of relapsing-remitting multiple sclerosis: a pilot study.

BACKGROUND/OBJECTIVE: A Paleolithic diet may improve fatigue and quality of life in progressive multiple sclerosis (MS) patients, but past research has evaluated the effects of this dietary intervention in combination with other treatments such as exercise. Thus, the purpose of this pilot study was to evaluate a modified Paleolithic dietary intervention (MPDI) in the treatment of fatigue and other symptoms in relapsing-remitting MS (RRMS). METHODS: We measured the effects of a MPDI in 17 individuals with RRMS. Of 34 subjects randomly assigned to control (maintain usual diet) and intervention (MPDI) groups, nine subjects (one man) completed the control group and eight subjects (one man) completed the MPDI. RESULTS: Significant improvements were seen in Fatigue Severity Scale score and also in Multiple Sclerosis Quality of Life-54 and time to complete (dominant hand) 9-Hole Peg Test from baseline in MPDI subjects compared to controls. Increased vitamin K serum levels were also observed in MPDI subjects postprotocol compared to controls. CONCLUSION: A Paleolithic diet may be useful in the treatment and management of MS, by reducing perceived fatigue, increasing mental and physical quality of life, increasing exercise capacity, and improving hand and leg function. By increasing vitamin K serum levels, the MPDI may also reduce inflammation.

Multimodal intervention improves fatigue and quality of life in subjects with progressive multiple sclerosis: a pilot study.

BACKGROUND: Fatigue is a disabling symptom of multiple sclerosis (MS) and reduces quality of life. The aim of this study was to investigate the effects of a multimodal intervention, including a modified Paleolithic diet, nutritional supplements, stretching, strengthening exercises with electrical stimulation of trunk and lower limb muscles, and stress management on perceived fatigue and quality of life of persons with progressive MS. METHODS: Twenty subjects with progressive MS and average Expanded Disability Status Scale (EDSS) score of 6.2 (range: 3.5-8.0) participated in the 12-month phase of the study. Assessments were completed at baseline and at 3 months, 6 months, 9 months, and 12 months. Safety analyses were based on monthly side effects questionnaires and blood analyses at 1 month, 3 months, 6 months, 9 months, and 12 months. RESULTS: Subjects showed good adherence (assessed from subjects' daily logs) with this intervention and did not report any serious side effects. Fatigue Severity Scale (FSS) and Performance Scales-fatigue subscale scores decreased in 12 months (P<0.0005). Average FSS scores of eleven subjects showed clinically significant reduction (more than two points, high response) at 3 months, and this improvement was sustained until 12 months. Remaining subjects (n=9, low responders) either showed inconsistent or less than one point decrease in average FSS scores in the 12 months. Energy and general health scores of RAND 36-item Health Survey (Short Form-36) increased during the study (P<0.05). Decrease in FSS scores during the 12 months was associated with shorter disease duration (r=0.511, P=0.011), and lower baseline Patient Determined Disease Steps score (r s=0.563, P=0.005) and EDSS scores (r s=0.501, P=0.012). Compared to low responders, high responders had lower level of physical disability (P< 0.05) and lower intake of gluten, dairy products, and eggs (P=0.036) at baseline. High responders undertook longer duration of massage and stretches per muscle (P<0.05) in 12 months. CONCLUSION: A multimodal intervention may reduce fatigue and improve quality of life of subjects with progressive MS. Larger randomized controlled trials with blinded raters are needed to prove efficacy of this intervention on MS-related fatigue.

A multimodal intervention for patients with secondary progressive multiple sclerosis: feasibility and effect on fatigue.

BACKGROUND: Multiple sclerosis is an autoimmune disease influenced by environmental factors. OBJECTIVES: The feasibility of a multimodal intervention and its effect on perceived fatigue in patients with secondary progressive multiple sclerosis were assessed. DESIGN/SETTING: This was a single-arm, open-label intervention study in an outpatient setting. INTERVENTIONS: A multimodal intervention including a modified paleolithic diet with supplements, stretching, strengthening exercises with electrical stimulation of trunk and lower limb muscles, meditation, and massage was used. OUTCOME MEASURES: Adherence to each component of the intervention was calculated using daily logs. Side-effects were assessed from a monthly questionnaire and blood analyses. Fatigue was assessed using the Fatigue Severity Scale (FSS). Data were collected at baseline and months 1, 2, 3, 6, 9, and 12. RESULTS: Ten (10) of 13 subjects who were enrolled in a 2-week run-in phase were eligible to continue in the 12-month main study. Of those 10 subjects, 8 completed the study and 6 subjects fully adhered to the study intervention for 12 months. Over a 12-month period, average adherence to diet exceeded 90% of days, and to exercise/muscle stimulation exceeded 75% of days. Nutritional supplements intake varied among and within subjects. Group daily average duration of meditation was 13.3 minutes and of massage was 7.2 minutes. No adverse side-effects were reported. Group average FSS scores decreased from 5.7 at baseline to 3.32 (p=0.0008) at 12 months. CONCLUSIONS: In this small, uncontrolled pilot study, there was a significant improvement in fatigue in those who completed the study. Given the small sample size and completer rate, further evaluation of this multimodal therapy is warranted.

Rehabilitation with neuromuscular electrical stimulation leads to functional gains in ambulation in patients with secondary progressive and primary progressive multiple sclerosis: a case series report.

BACKGROUND: Gait disability in patients with secondary progressive multiple sclerosis (SPMS) or primary progressive multiple sclerosis (PPMS) rarely improves. PRIMARY STUDY OBJECTIVE: This article reports on a case series of patients with SPMS and PPMS who were treated using neuromuscular electrical stimulation (NMES), a well-tolerated physical therapy (PT) treatment modality used to aid musculoskeletal recovery, coupled with a home-exercise program (HEP) to treat MS-related gait disability. SETTING: The setting for this trial was a PT private practice. PATIENTS: This trial was conducted with patients who had SPMS or PPMS with MS-related gait disability. CASE SERIES DESCRIPTION/INTERVENTION: Between June 2007 and June 2009, a licensed physical therapist (R.D.) used NMES coupled with a HEP to work with patients who had SPMS/PPMS and multiple sclerosis (MS)-related gait disability. All of the cases in which an NMES test session of NMES was conducted were included in the case series. Data regarding MS symptoms, treatment, gait, and function were abstracted from the PT clinic notes. Results of assessment with the expanded Kurtzke Disability Status Scale (EDSS) at presentation and at most recent visit were abstracted from the clinical record by the treating physical therapist (R.D.). CLINICAL OUTCOME/RESULTS: Nine (9) patients (7 with SPMS and 2 with PPMS) met inclusion criteria for review. Mean of years of diagnosis was 10.4 (range, 4-15), and mean EDSS score at presentation was 5.9 (range, 4.5-6.5). Mean of days of NMES was 140 (range, 22-495). Mean EDSS scores improved by 0.78 (range, 0-2.0). CONCLUSIONS: NMES, an approved Food and Drug Administration treatment modality for muscle spasm, muscle pain, and disuse atrophy-all of which are commonly present in patients with gait disability associated with SPMS and PPMS-was associated with measurable gains in ambulatory function. Additional studies are warranted.

Linear summation of cat motor cortex outputs.

Recruitment of movement-related muscle synergies involves the functional linking of motor cortical points. We asked how the outputs of two simultaneously stimulated motor cortical points would interact. To this end, experiments were done in ketamine-anesthetized cats. When prolonged (e.g., 500 ms) trains of intracortical microstimulation were applied in the primary motor cortex, stimulus currents as low as 10-20 microA evoked coordinated movements of the contralateral forelimb. Paw kinematics in three dimensions and the electromyographic (EMG) activity of eight muscles were simultaneously recorded. We show that the EMG outputs of two cortical points simultaneously stimulated are additive. The movements were represented as displacement vectors pointing from initial to final paw position. The displacement vectors resulting from simultaneous stimulation of two cortical points pointed in nearly the same direction as the algebraic resultant vector. Linear summation of outputs was also found when inhibition at one of the cortical points was reduced by GABAA receptor antagonists. A simple principle emerges from these results. Notwithstanding the underlying complex neuronal circuitry, motor cortex outputs combine nearly linearly in terms of movement direction and muscle activation patterns. Importantly, simultaneous activation does not change the nature of the output at each point. An additional implication is that not all possible movements need be explicitly represented in the motor cortex; a large number of different movements may be synthesized from a smaller repertoire.