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

Figures & data

Table 1 Study diet developed by T Wahls

Food item	Instruction	Recommended daily intake
Green leafy vegetables	Recommended^*	Three cups cooked/six cups raw = three servings
Sulfur-rich vegetables	Recommended^*	Three cups, raw or cooked = three servings
Intensely colored fruits or vegetables	Recommended^*	Three cups, raw or cooked = three servings
Omega-3 oils	Encouraged	Two tablespoons
Animal protein	Encouraged	4 ounces or more
Plant protein	Encouraged	4 ounces or more
Nutritional yeast	Encouraged	One tablespoon
Milks of soy, almond, peanut, rice, and coconut	Encouraged	According to subject choice
Kelp	Encouraged	¼ teaspoon powder or two capsules
Spirulina/chlorella/klamath blue green algae	Encouraged	¼–1 teaspoon or 4–8 capsules
Gluten-free grains/starchy food	Allowed	Only two servings per week
Gluten-containing grain	Excluded
Dairy products	Excluded
Eggs	Excluded

Notes:*If not able to take total nine servings of the recommended food, subjects were asked to take equal proportions of each category. Copyright © 2014. Reprinted with permission from Mary Ann Liebert, Inc. Bisht B, Darling WG, Grossmann RE, et al. A multimodal intervention for patients with secondary progressive multiple sclerosis: feasibility and effect on fatigue. J Altern Complement Med. 2014;20(5):347–355.¹⁷

Table 2 Demographics and baseline characteristics of the subjects in the main study

Subject ID	Age (years)	Sex/race	MS duration (years)	MS type	Baseline EDSS	Walking aid	Education	DMDs^a	FSS-9 (scores)
S1	45.6	F/C	10	SPMS	6	–	High school	Interferon beta-1a	5.9
S2	53.8	F/C	14	SPMS	6	Cane	Some college		7.0
S3	54.2	F/C	20	SPMS	6.5	Walker	Masters		5.6
S5	57.3	F/C	11	SPMS	6.5	Walker	Masters	Interferon beta-1a	6.4
S6	52.5	F/C	3	SPMS	6	–	Some college		6.9
S8	55.2	F/C	35	SPMS	6.5	Walker	Masters		5.2
S9	52.2	F/C	25	SPMS	6	Cane	2-year associate	Glatiramer acetate	3.1
S11	54.8	F/C	11	SPMS	6	–	Bachelor		5.3
S14	45.9	M/H	13	SPMS	6.5	Poles	Doctorate (MD)	Interferon beta-1b	7.0
S15	54.8	F/C	10	SPMS	6.5	Walker	Bachelor		4.4
S16	39.6	F/C	4	SPMS	7	Walker	Bachelor		7.0
S17	66.0	F/C	4		6.5	Brace + cane	2-year associate		6.7
S18	57.7	M/C	6	PPMS	8	FES + walker	2-year associate		4.4
S19	55.4	M/C	27	SPMS	7	Walker	Masters		3.1
S20	47.3	F/C	19	SPMS	7	Walker	Masters		5.4
S21	53.7	F/C	10	SPMS	6.5	Cane	Masters	Natalizumab	6.6
S22	47.8	F/C	17	SPMS	6	Cane	Masters	Naltrexone hydrochloride	5.8
S26	37.6	M/C	8	SPMS	3.5	–	2-year associate		4.6
S27	52.9	M/C	21	SPMS	6.5	Cane	Masters	Glatiramer acetate	4.0
S28	50.3	F/C	25	SPMS	4	–	Bachelor	Interferon beta-1a	5.4
Mean	51.7		14.7		6.2				5.5
SD	6.4		8.7		1.0				1.2

Notes: aSubjects chose to take DMDs although they understood that DMDs are not considered effective therapy for SPMS. Copyright © 2014. Adapted with permission from Mary Ann Liebert, Inc. Bisht B, Darling WG, Grossmann RE, et al. A multimodal intervention for patients with secondary progressive multiple sclerosis: feasibility and effect on fatigue. J Altern Complement Med. 2014;20(5):347–355.17

Abbreviations: Brace, ankle brace; C, Caucasian; DMDs, disease-modifying drugs; EDSS, Expanded Disability Status Scale; F, female; FES, dorsiflexion assist functional electrical stimulation; FSS-9, nine-item Fatigue Severity Scale; H, Hispanic; M, male; MS, multiple sclerosis; PPMS, primary progressive MS; SD, standard deviation; SPMS, secondary progressive MS; MD, Doctor of Medicine.

Figure 1 Flowchart of the screening, enrollment, and follow-up of participants in the study.

Abbreviations: S, subject; NMES, neuromuscular electrical stimulation; MS, multiple sclerosis.

Figure 2 Subject’s nine-item Fatigue Severity Scale scores during the study.

Notes: Red dots represent individual subject scores and dotted lines represent mean scores. P<0.0005, statistical significant change from baseline to 3, 6, 9 and 12 months.
Abbreviations: B, baseline; 3M, 3 months; 6M, 6 months; 9M, 9 months; 12M, 12 months.

Figure 3 SF-36 energy, SF-36 general health and FSS-9 scores during the study, and correlation of mean SF-36 energy and mean SF-36 general health scores with mean FSS-9 scores at different time-points during the study.

Notes: Data is shown as mean ± SE. r= Pearson’s correlation coefficient. **P<0.005, *P<0.05 for significant difference from baseline.
Abbreviations: B, baseline; 3M, 3 months; 6M, 6 months; 9M, 9 months; 12M, 12 months; SF-36, Short Form-36; FSS-9, nine-item Fatigue Severity Scale; SE, standard error.

Figure 4 Comparison of good- and fair-responders’ dosage of (A) average massage duration, (B) average duration of stretch per muscle, (C) average duration of meditation per day and (D) average exercise-NMES adherence during 12 months.

Notes: Upper and lower borders of the boxes represent 25th and 75th percentiles respectively. The line within the boxes represents median and + sign represents mean. The whisker error bars represent minimum and maximum values. Red dots represent each subject’s score.
Abbreviation: NMES, neuromuscular electrical stimulation.

Figure 5 Correlations between changes in FSS-9 scores and (A) duration since MS diagnosis, (B) baseline PDDS scale scores, (C) baseline EDSS scores.

Notes: r, Pearson’s correlation coefficient; rs, Spearman’s correlation coefficient. After excluding data of two subjects (circled dots in C) with much lower baseline EDSS scores than other subjects, correlation stayed moderately positive (rs=0.482, P=0.022).
Abbreviations: EDSS, Expanded Disability Status Scale; MS, multiple sclerosis; PDDS, Patient Determined Disease Steps; FSS-9, nine-item Fatigue Severity Scale.

Table S1 List of exercises and the muscle group stimulated during the particular exercise

Exercises	Muscle group stimulated
Supine dorsiflexion	Dorsiflexors
Sitting dorsiflexion
Dorsiflexion with weight
Standing toe raise
Sit/prone plantar flex	No neuromuscular electrical stimulation
Plantar flex with weight
Standing heel raise
Hip flexion in sitting	Quadriceps
Supine hip flexion without/with weight
Isometric quadriceps
Terminal knee extension
Sitting knee extension without/with weight
Hamstrings sets	Hamstrings
Supine hip and knee flexion
Prone knee flexion without/with weight
Isometric gluteal contraction	Gluteus maximus
Hip abduction in supine position
Hip abduction without/with weight
Hip extension without/with weight
Bridging/single leg bridging	Erector spinae
Back extension with elbow support
Back extension
Pelvic tilt	Abdominals
Crunch
Side crunch
Right angle bridge
Wall slides/squatting	No neuromuscular electrical stimulation
Four-point kneeling with upper and/or lower limb lift	No neuromuscular electrical stimulation

Figure S1 Subject’s Performance Scales-fatigue scores during the study.

Notes: Upper and lower borders of the boxes represent 25th and 75th percentiles respectively. The line within the boxes represents median and + sign represents mean. The whisker error bars represent minimum and maximum values. **** represent median values overlapping with upper quartile values. ------ represent lower quartile values overlapping with minimum values. P= significant difference from baseline.
Abbreviations: B, baseline; 3M, 3 months; 6M, 6 months; 9M, 9 months; 12M, 12 months.

Figure S2 Health related quality of life scores: (A) SF-36 physical functioning, (B) role physical, (C) bodily pain and (D) social function scores during the study.

Notes: Upper and lower borders of the boxes represent 25th and 75th percentiles respectively. The line within the boxes represents median and + sign represents mean. The whisker error bars represent minimum and maximum values. **** represent median values overlapping with upper quartile values. ------ represent lower quartile values overlapping with minimum values.
Abbreviations: B, baseline; 3M, 3 months; 6M, 6 months; 9M, 9 months; 12M, 12 months, SF-36, Short Form-36.

Figure S3 Comparison of baseline characteristics of good- and fair-responders in terms of (A) EDSS scores, (B) PDDS scores, (C) Sf-36 physical functioning scores and (D) mean daily serving of Gl + D + E.

Notes: Red dots represent each subject’s score. In figures A–C, upper and lower borders of the boxes represent 25th and 75th percentiles respectively. The line within the boxes represents median. The whisker error bars represent minimum and maximum values. Overlapping values are indicated in the figure. In figure D, values are mean + SD.
Abbreviations: EDSS, Expanded Disability Status Scale; Gl + Dr + E, gluten-containing grains + dairy products + eggs; max, maximum; md, median; min, minimum; PDDS, Patient Determined Disease Steps; SD, standard deviation.

Bisht B, Darling WG, Grossmann RE, et al A multimodal intervention for patients with secondary progressive multiple sclerosis: feasibility and effect on fatigue. J Altern Complement Med. 2014;20(5):347–355.24476345

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