OSTEOPATHIC CARE IN WOMEN WITH MULTIPLE SCLEROSIS

OMT and MULTIPLE SCLEROSIS

PROLONGED EFFECTS OF EXERCISE AND OSTEOPATHIC CARE IN WOMEN WITH MULTIPLE SCLEROSIS
Herbert A. Yates,(1)* Terence C. Vardy,(2) Michael L. Kuchera,(3) Brett Ripley,(1) Jane C. Johnson,(1) Bruce Stouch(3)

(1)Kirksville College of Osteopathic Medicine in Kirksville, MO (2)Neuromuscular Clinic, Tweed Heads. Australia; (3)Philadelphia College of Osteopathic Medicine in Philadelphia, PA; *Deceased
ABSTRACT


This study documents the effects of a physical intervention protocol combining maximal effort exercise (MEE) and osteopathic manipulative treatment (OMT) on strength, endurance, fatigue, coordination and ambulation in female Multiple Sclerosis (MS) subjects.

Twelve weeks of twice weekly MEE/OMT supplemented existing care of seven female MS subjects (aged 42-68 years; mild-moderate disease severity; EDSS=2-6). Isometric and eccentric vertical leg presses and isometric semi-erect whole body exercise (lunge) were conducted on specialized equipment. Each session, exercises (with Valsalva) were repeated 3-5 times lasting 4-8 seconds each. OMT reduced somatic dysfunction each session.

Every 0.25 seconds during exercise an IsoPump® load-cell measured MEE strength and endurance. Subjects completed a Subjective Perception of Fatigue Scale (SPFS) before and after every session. Coordination and ambulation were measured by Block & Box (BB) and Timed 25-foot Walk (TW-25) tests respectively. Subjects were tested throughout the 12-week protocol and every three months thereafter for nine months. There was no further MEE/OMT after the 12-week training/treatment period.

Immediate effects previously published documented post-intervention positive changes (p<0.05) in TW-25 and BB tests, improved strength and endurance with no session fatigue, and a 45% baseline SPFS decrease overall.

This study documented prolonged effects of the protocol. MEE/OMT increases in isometric lunge strength (170%) and TW-25 reductions were maintained for nine months. Leg press strength gains (87% isometric; 36% eccentric) began to decline after six months, but retained significance from baseline for nine months.

CONCLUSION: Without creating fatigue during exercise, an MEE/OMT protocol increases strength, ambulatory ability, coordination and endurance while decreasing overall fatigue in women with mild-moderate MS impairment. Measurable benefits in walking and strength still existed nine months after discontinuing the protocol.

KEYWORDS: Eccentric exercise, Clinical trial; Fatigue; Manipulation
INTRODUCTION


Paragraph Number 1 The purpose of this study was to investigate the benefits of an intervention for de-conditioned patients with multiple sclerosis using progressive maximal effort isometric and eccentric exercises. The pilot study conducted was a single blind, within subject repeated measures and report design. It was used to test the hypothesis that progressive anaerobic maximal effort exercise (MEE) together with osteopathic manipulative treatment (OMT) would produce prolonged positive benefits including increases in strength, physical performance, and dexterity in a cohort of women with mild-to-moderate MS, while simultaneously showing a reduction in fatigue.

PREVALENCE OF MULTIPLE SCLEROSIS

Paragraph Number 2 Multiple Sclerosis (MS) is a disease of the central nervous system (CNS), accompanied by secondary de-conditioning of the muscular system; particularly the muscles of the lower extremities. Currently unknown causes lead to an autoimmune dysfunction characterized by the eventual formation of plaques on the myelin sheath.(15,22,25) Better understood is the de-conditioning process that is often the result of prolonged bed-rest and/or restriction of normal physical activities.

Paragraph Number 3 MS appears between the ages of 10 and 60 with the peak onset at age 22 years. 28. Due to the relatively long life expectancy of most patients with the disease, the average age of an MS patient is 45 years. The tremendous impact of MS on the financial and biopsychosocial structure of families is aggravated by this disorder’s propensity to affect those who may otherwise be most active and productive in business and family life.

Paragraph Number 4 More women than men suffer from MS – a ratio of 1.8:1. (28) This gender difference, coupled with de-conditioning and reduced time weight-bearing, means that osteoporosis is another common secondary condition frequently seen in 60% of this patient group. Independent of gender, other common symptoms of MS patients (see Table I) include extreme fatigue, loss of balance, blurred or double-vision, speech difficulties and slurring, weakness and loss of lower and/or upper extremity control, continence problems, bowel dysfunction, hand tremors, tendency to drag one foot, numbness or pins and needles sensations, as well as problems with or changes in memory functioning.

Paragraph Number 5 The above diversity of symptoms indicates individual specific physical weaknesses that are highlighted and exacerbated by a general systemic dysfunction. Disease progress is therefore most typically assessed by a number of evaluations assessing different physical, mental, and emotional domains. Physical evaluation components most frequently include timed walking tests, tests of dexterity, and self-assessment of fatigue.

Paragraph Number 6 The Multiple Sclerosis Functional Composite (MSFC) is a multidimensional clinical outcome measure that includes quantitative tests of leg function/ambulation (Timed 25-Foot Walk), dexterity (9-Hole Peg Test), and cognitive function (Paced Auditory Serial Addition Test). Correlations among the three MSFC components were weak, suggesting they assess distinct aspects of neurological function in patients with MS. Among the MSFC components, the Timed 25-Foot Walk correlated most closely.
PHYSICAL EVALUATION OF MS PATIENTS


Paragraph Number 7 Currently the most widely used functional standard for classifying MS subjects is the Expanded Disability Status Scale (EDSS). (10) The EDSS is a global rating of neurological impairment. It summarizes the score of the eight functional systems (pyramidal, cerebellum, brainstem, cerebral cortex, sensory responses, bowel and bladder, visual and spasticity) and correlates well with the MSFC. An EDSS score can range from 0 (representing a positive diagnosis with no apparent neurological impairment) to 10 (complete disability due to MS) with minimal to moderate levels warranting an EDSS score below 6.

Paragraph Number 8 Accurate EDSS scores may guide clinicians in the choice of safe and effective exercise recommendations for MS patients. In persons with a minimal to moderate level of neurological impairment (EDSS scores of 2-6), abnormalities in heart rate (HR) and blood pressure are not often present and cardiovascular responses during exercise are not affected. (21) Furthermore, findings indicative of the exercise response of persons with MS appear to be influenced by the level of physical impairment of the experimental cohort. (21)

Paragraph Number 9 EDSS scores are heavily influenced by lower extremity function and the ability to ambulate effectively. As such, it is not surprising that EDSS scores and the Timed 25-foot Walk (TW-25) correlate well. The TW-25 (7) is included in most studies of MS. Furthermore, after adjustment for age, race/ethnicity, weight, and height, increasing knee extensor strength was associated with significant increases in feet walked per second.

Paragraph Number 10 Another physical test used in evaluating subjects with MS is specific to the upper extremity. The prevalence of upper extremity dysfunction in multiple sclerosis, as measured by the Block & Box (BB) test, is higher than previously appreciated. The BB test, along with the Nine-Holed Pegboard Test is more sensitive in detecting upper extremity functional status change (dexterity) than the EDSS. (4)

Paragraph Number 11 General fatigue is another common symptom monitored among many MS patients even though it is considered to have primary, secondary, and tertiary origins. Fatigue was common to both MS subjects and controls who participated in the Ponichtera study. (21) The maximal effort exercises used by Yates and by Vardy were all anaerobic and did not increase fatigue on the Subjective Perception of Fatigue Scale (SPFS) during the course of the exercise session. (26,27) This also supports the conclusion of Ponichtera-Mulcare’s study. (21)
EXERCISE IN MS PATIENTS


Paragraph Number 12 Most MS research is focused on establishing the pathology which is of little assistance to those patients suffering with this disorder currently. Despite 58 percent of all and 69 percent of female MS sufferers manifesting limitation of activity (12), there are few reports of MS patient rehabilitation strategy outcomes, particularly those focusing on specific exercise design. (1,3,8,17-20,23,27)

Paragraph Number 13 Current treatments for MS are directed at maintaining current abilities or reducing the number and intensity of exacerbations. From this perspective, exercise may offer an efficient and economical adjunct, or even alternative, to current treatments. In a stratified survey of over 300 MS subjects in the U.K., advice about exercise was the single most requested area. (24) Exercise in MS patient populations also intrigues many leading researchers. Our present understanding of the exercise response in individuals with MS comes primarily from studies by physical therapists, neurologists and occupational therapists. In addition to the effects of thermal stress, research here has focused on cardio-respiratory responses to exercise (autonomic cardiovascular regulation) and muscle function (strength and endurance). (1,3,8,18,19,21,23,25,27)

Paragraph Number 14 Petajan (16) clearly demonstrated that those MS patients who participated in an aerobic exercise program had better cardiovascular fitness, improved strength, better bladder and bowel function, less fatigue and depression, a more positive attitude, and increased participation in social activities. Furthermore, Moseley (15)studied exercise stress and the body’s “Immune Conversation” and concluded “exercise is an attractive model for the study of the change in immune function”.

Paragraph Number 15 While exercise activity is regarded as being universally beneficial for people from a mental, metabolic and musculoskeletal viewpoint, it is not uniformly applied in the treatment of physically de-conditioned persons such as those with MS. Inactivity in people with or without MS can result in numerous risk factors associated with coronary heart disease. In addition, it can lead to muscle weakness, decreased bone density with an increased risk of fracture, and shallow, inefficient breathing.

Paragraph Number 16 While regular exercise is believed to influence the course of an MS patient’s life by minimizing the de-conditioning process and maintaining an optimal level of physical function (3) the type, intensity, and frequency of exercise for optimum results have not been standardized. For example, few researchers outside Kraft/Alquist (8), Ponichtera-Mulcare et al (17,21), Yates et al (30) and Vardy (27) have exercised their MS subjects to a maximum level. Alternatively, a sub-maximal effort endpoint, such as that selected by Schipiro (23) has been used in many studies for safety reasons to minimize the risk of exacerbating MS symptoms, even though the use of high intensity and maximal levels of exercise per se has not been shown to provoke immediate and/or latent MS related symptoms. (10,20,21) Gehlsen (3) used one-hour sessions of aquatic exercise and Svenssen (25) had subjects doing 50 repetitions of knee extensions. Ponichtera-Mulcare(17,20,21)used prolonged aerobic exercise (averaging 40 minutes) and suggested that a combined arm and leg exercise could be more effective in utilizing full maximal effort. (17)The IsoPump® Lunge exercise phase is a combined, leg and torso or whole body exercise.
OMT IN CONJUNCTION WITH EXERCISE FOR PATIENTS WITH MS


Paragraph Number 17 Somatic dysfunction is defined as “impaired or altered function of related components of the somatic system: skeletal, arthrodial, and myofascial structures and related vascular, lymphatic, and neural elements. (29) Exercise, especially eccentric exercise, commonly results in delayed-onset somatic dysfunction, reduced range of motion, muscle swelling, and tender myofascial points capable of creating local and referred pain. (6) Maximal effort during exercise has also been implicated in the initiation of a variety of overuse phenomena, including somatic dysfunction and myofascial trigger points (MTrPs).

Paragraph Number 18 Osteopathic manipulative treatment (OMT) is most commonly used to reduce or remove somatic dysfunction (29) including MTrPs. OMT and many other hands-on approaches, including massage, physical therapy, chiropractic, and manual medicine treatments, are frequently used in conjunction with more traditional pharmacological approaches to multiple sclerosis. (9) While numerous other reasons involving postulated vascular, autonomic, and nociceptive mechanisms might justify exploring the role of OMT in the treatment of MS subjects, (9) this study is not designed to consider them.

Paragraph Number 19 OMT was paired with MEE in this study for a variety of specific reasons. The palpation of skeletal, arthrodial, and myofascial structures for somatic dysfunction prior to instituting OMT serves to provide secondary data with potential importance should injury or persistent dysfunction arise during the exercise portion of the study. Furthermore, treatment of pain is important in maintaining compliance in exercise studies. The OMT techniques employed in this study were selected to diminish any discomfort associated with somatic dysfunction or MTrPs that might arise from the exercise protocol.

Paragraph Number 20 Regardless of whether an exercise program would introduce somatic dysfunction in this population or not, approximately 55% of the people in this study reported what is called “clinically significant pain” at some time during the course of a lifetime with MS; almost half (48%) were troubled by chronic pain. Another rationale for the MEE/OMT combination to serve as the somatic adjunct in this protocol considers recent studies that suggest a combination back of exercise and manipulation may be superior to exercise alone in back pain. (26)
METHODS


Paragraph Number 21 Seven (7) female subjects between the ages of 42 and 68 years, diagnosed with chronic progressive MS and having an EDSS rating of between 2 and 6, were recruited to participate in this study. All were permitted complete written and oral informed consent according to national standards and those imposed by the Institutional Review Board of the Kirksville College of Osteopathic Medicine. All subjects in this study continued their existing pharmacological care regimen as prescribed by their attending physicians. All subjects participated in an adjunctive specialized somatic care protocol consisting of maximal effort exercise (MEE) program using a three-phase MS IsoPump® exercise protocol in combination with osteopathic manipulative treatment (OMT).

Paragraph Number 22 The IsoPump® is an electrically driven exercise device with which a subject can exert maximum forces through major muscle groups. The proposed effect of these forces is threefold:

1. Increase muscle strength without adding muscle bulk
2. Challenge the muscle component of the arterial system
3. Establish a changed proprioceptive feedback loop by pressure overload

OMT is a form of manual medicine delivered to remove somatic dysfunction and to enhance homeostatic mechanisms.
RESEARCH DESIGN


Paragraph Number 23 The study employed a single blind within subject repeated measures and report design to evaluate the effects of the Isopump® MEE program and OMT over a 12 week period. All seven subjects had the following inclusion and exclusion criteria:

1. were remitted from MS exacerbation for at least six months
2. had been diagnosed with MS for at least two years
3. gave informed consent to participate in this study
4. had no significant spasticity or ataxia
5. had no changes in prescription medicine within previous three months
6. had no clinically diagnosed depression
7. had no pulmonary or bladder infections, or were febrile (>100 deg. F.) at the time of the exercise session.

Paragraph Number 24 The short duration (12 weeks) of the program was intended to minimize maturation while the inclusion and exclusion factors maintain homogeneity of the sample and allowed externalization to the female MS population of a mild (2) to moderate (6) EDSS rating. An independent neurologist conducted the initial neurological evaluation and EDSS rating to insure that the inclusion and exclusion criteria were fully enforced.
MAXIMAL EFFORT EXERCISE INTERVENTION


Paragraph Number 25 The specialized Isopump® exercise program used in this study was a three-phase protocol combining isometric and eccentric vertical leg presses with an isometric semi-erect lunge exercise. In the first two exercise phases the major leg muscles are used while the whole body (leg:torso:arm) is used in the third exercise phase. The exercise protocol was performed twice weekly for twelve weeks. At each session, each individual exercise was performed for 4-6 seconds concomitant with a Valsalva maneuver. Initially, three repetitions were performed in each phase with a minimum rest period of less than 30 seconds between repetitions.

Paragraph Number 26 Frequency of the tests increased as planned from three repetitions of each exercise during the first four weeks, to four repetitions for weeks 5-8, to five repetitions during the last four weeks of the protocol. On the other hand, voluntary duration of exercise effort for all three types of exercise did not change significantly from the start to the end of the exercise intervention period. Exercisers were only capable of exerting maximal forces with Valsalva for an average of 4-8 seconds throughout any of the exercises.

Paragraph Number 27 The Isopump® isometric and eccentric leg exercise phases incorporated a supine anti-orthostatic body position of minus six degrees from horizontal to maximize elevation of torso segment volume. The Isopump® features a visual read-out screen displaying load-cell measurements of the forces applied during all exercises. Strength measured by the load cell was directly recorded every 0.25 seconds by a linked computer for subsequent analysis.
OSTEOPATHIC MANIPULATIVE INTERVENTION


Paragraph Number 28 Twice weekly, after each of the seven subjects exercised, each subject received OMT from an osteopathic physician with special expertise in delivering this somatic intervention. Throughout, the osteopathic physicians involved in the study applied OMT to each subject as determined most individually appropriate. Each OMT session consisted of a variety of techniques as needed to remove somatic dysfunction. This was to maximize axial and appendicular functions, and/or to enhance venous-lymphatic drainage and autonomic functions.
OBJECTIVE MEASUREMENTS


Paragraph Number 29 During interventions, weekly measurements were taken utilizing the Block and Box (BB) test and a Timed 25-foot Walk (TW-25). The Subjective Perception of Fatigue Scale (SPFS) was self-recorded twice weekly before and after each session. Summative evaluations, including the SPFS, TW-25, and BB tests, were conducted at the commencement and completion of the 12-week intervention program as well as at 3, 6 and 9 months after the cessation of the intervention period.

Paragraph Number 30 The SPFS is a seven-item questionnaire assessing features of fatigue on a 7-point Likert Scale; a standard for neurodegenerative disorders. It has demonstrated high test-rated reliability and interval consistency reliability. The BB test counts the number of blocks put into the box in 60 seconds and is a measurement of upper extremity dexterity. The TW-25 simply measures the number of seconds required to walk 25 feet, correlates highly with the EDSS, and also reflects lower extremity strength and endurance.

Paragraph Number 31 Measures of strength (PEAK), endurance (AREA), and duration of maximal effort (TIME) were collected twice weekly by the IsoPump® load-cell during each of the three isometric and eccentric maximal effort exercises. (See Figures 1 for Lunge PEAK. Figure 2 for Isometric Leg Press PEAK. Figure 3 for Eccentric Leg Press AREA). Maximum effort (PEAK) was measured in pounds. Duration of maximal effort (TIME) was measured in seconds. Endurance, indicated by the area under the load-cell generated peak-duration period (AREA), was measured in pound-seconds.
RESULTS


Paragraph Number 32 As reported in the May 2002 JAOA article (30), all individual strength, endurance, ambulation, coordination, and fatigue measures were analyzed to ascertain whether any significant gains were made from Baseline to the end of the 12-week MEE/OMT adjunctive intervention period. Consistent with this study’s additional hypothesis, the statisticians at KCOM and Philadelphia College of Osteopathic Medicine (PCOM) were also asked to evaluate the significance and duration of prolonged effects during a follow-up period without the benefit of further exercise or OMT. The relevant statistics were provided at 3, 6 and 9 months post intervention.

Paragraph Number 33 As previously reported in the (30) univariate analysis by parameter and observation time was conducted calculating arithmetic averages, medians, standard deviations and the associated 95% confidence intervals associated where relevant (see graphs 1-2 and tables 2-3). For each task, a two-factor analysis of variance with repeated measures on both factors test number (see graphs 1-2 and tables 2-3) was used to determine whether there were changes within a session and over the intervention period. Multiple comparisons were performed, when appropriate, using Duncan’s Multiple (DM) Range Test. For the purpose of this study, all participants’ results were assessed from the DM Range Test on five (5) separate occasions: Baseline, Post-Intervention, and at three Follow-Up points timed 3-, 6-, and 9-months after cessation of MEE/OMT.

Paragraph Number 34 Compared to baseline, measures of both strength (PEAK) and endurance (AREA) showed significant improvement (p<0.05) at the end of the 12-week long intervention period as did indicators of quicker ambulation (TW-25) (see graph 1, table 2), improved coordination (BB test) (see graph 2, table 3), and reduction of fatigue (SPFS) as reported in the 2002 JAOA article by Yates, et.al..

Paragraph Number 35 Beyond the original report, this study showed substantial prolonged effects after discontinuing the intervention. Total body strength, as demonstrated by PEAK Lunge (PEAKL) measurements had increased 70% over baseline (p=0.03) and was retained without diminution at all sample points over the nine months following MEE/OMT cessation.

Paragraph Number 36 Although both isometric and eccentric PEAK Leg Press (PEAKLP) measures increased throughout the intervention as previously reported and showed varying degrees of continuing without adjunctive care, the Post-intervention isometric PEAKLP had increased by 36%, Post-intervention eccentric PEAKLP had increased 87%, and, compared to baseline, these eccentric PEAKLP values were significant 3- and 6-months post-intervention. Isometric PEAKLP remained significantly improved for the full 9-month follow-up period.

Paragraph Number 37 As measured by the initial pilot study (30), by the end of the MEE/OMT period, endurance (AREA) increased for both total body lunge (AREAL) and leg presses (AREALP). Endurance measures by the end of the intervention period varied significantly (p<0.05) with isometric AREAL increasing by 93%, isometric AREALP by 113%, and eccentric AREALP by 44%.

Paragraph Number 38 In addition to these substantial strength and endurance improvements, MEE/OMT created a 30.5% reduction (p=0.03) in the Timed 25-foot Walk test. This improvement was fully retained from the end of the intervention throughout the 9-month follow-up period. Dexterity, as measured by the Block & Box test, demonstrated a 13% improvement at six months follow-up for seven subjects.
DISCUSSION


Paragraph Number 39 Overall, research (20,21)suggests that exercise would not be expected to exacerbate MS symptoms except when the physical activity is aerobic and/or performed in hot and humid conditions. (27) Outside these concerns then, MS patients should expect to gain many, if not all of the health-related benefits of an optimally designed exercise protocol. (13)

Paragraph Number 40 Concerning the type of exercise for de-conditioned subjects, a combination of exercise types similar to those selected for this study is recommended over a single isometric or concentric type. Research indicates that a resistance exercise protocol that includes eccentric as well as concentric exercise, particularly when the eccentric exercise is emphasized, results in greater strength gains than concentric exercise alone. (5) Lastayo further demonstrated that significant gains in isometric leg strength were seen in the eccentrically trained subjects only without muscle injury and with minimal increase in metabolic demand for oxygen. 11 (11)

Paragraph Number 41 Brockett demonstrated that continued eccentric exercise of the hamstrings was capable of shifting the optimal angle of human muscle “as a protective strategy” against injury from eccentric exercise. (2) In his study of normal subjects, initial discomfort, swelling, and internal distress caused upon initiation of eccentric exercise disappeared with repeated eccentric training. He and others have postulated that the well-known training effect involves increasing the number of sarcomeres in muscle fibers. (2,14)

Paragraph Number 42 To date most, if not all, studies have failed to conduct substantive follow-up programs to evaluate the prolonged effects of exercise in individuals with MS. There remains a need to conduct follow-up exercise and OMT research to establish what effect each intervention has on the course of Multiple Sclerosis. With the wide variance of symptoms experienced by the subjects, what systemic changes are initiated by these interventions to effect the beneficial changes noted in this pilot study? If MS is an immune dysfunctional response, does exercise and/or OMT provoke the pituitary or endocrine system to facilitate compensatory responses in MS individuals? Further, study is needed to determine whether the whole body (ie. Lunge exercise) is more effective than combined lower extremity exercise (ie. Leg Press). Other questions requiring investigation include whether eccentric exercise has a more lasting effect than isometric type exercise, what interval is most effective between each exercise session, and whether further strength gains are possible with the application of follow-up exercise sessions.

Paragraph 43 The design of the IsoPump® equipment allows the speed of the eccentric exercise to be varied thus altering the resistance applied by the exerciser. This may have important effects for MS sufferers who have bone density loss and who require a longer application of eccentric forces at a slower speed. The current view is that over 60% of MS sufferers may have bone density loss greater than 1.5%. It was observed that the average non-MS exerciser exerts maximal pressure for eight seconds in both isometric and eccentric exercise phases. What fluid and cellular effects does the Valsalva Maneuver maintained for this period of time have on the human mechanism and is this different in individuals with MS?

Paragraph 44 The beneficial effects and strength gains maintained over such a prolonged period of time as found in this study may have applications in a wide range of medical rehabilitation and exercise areas. That strength gains of such a magnitude can be maintained for over six months provoke thought as to the possibility of sustained changes without chemical intervention. Eccentric exercise would appear to be the key to safely and progressively overloading the muscular system and provoking such change. The maintenance of increased strength gains without further exercise sessions offer potential applications for zero gravity situations and increased technique training pre-competition for athletes.


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