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Managing Your Practice: What is your practice worth?
At least once during your career, you probably will have to put a value on your practice. The need arises more often than you might think – if you sell it, of course (more on that next month); but also for estate planning, preparation of financial statements, or divorce negotiations; or when an associate joins or leaves your office; or if you have occasion to combine or partner your practice with one or more others, as I will discuss in detail in a future issue.
As you might guess, a medical practice is trickier to value than an ordinary business, and usually requires the services of an experienced professional appraiser. Entire books have been written about the process, so I can’t hope to cover it completely in a few hundred words, but three basic yardsticks are essential for a practice appraisal:
Tangible assets: equipment, cash, accounts receivable, and other property owned by the practice.
Liabilities: accounts payable, outstanding loans, and anything else owed to others.
Intangible assets: sometimes called “good will” – the reputation of the physicians, the location and name recognition of the practice, the loyalty and volume of patients, and other, well, intangibles.
Armed with those numbers, an appraiser can then determine the “equity,” or book value, of the practice.
Valuing tangible assets is comparatively straightforward, but there are several ways to do it, and when reviewing a practice appraisal you should ask which of them was used. Depreciated value is the book value of equipment and supplies as determined by their purchase price, less the amount their value has decreased since purchase. Remaining useful life value estimates how long the equipment can be expected to last. Market (or replacement) value is the amount it would cost on the open market to replace all equipment and supplies.
Intangible assets are more difficult to value. Many components are analyzed, including location, interior and exterior decor, accessibility to patients, age and functional status of equipment, systems in place to promote efficiency, reasons patients come back (if they do), and the overall reputation of the practice in the community. Other important factors include the “payer mix” (what percentage pays cash, how many third-party contracts are in place and how well they pay, etc.), the extent and strength of the referral base, and the presence of clinical studies or other supplemental income streams.
It is also important to determine to what extent intangible assets are transferrable. For example, unique skills with a laser, neurotoxins, or filler substances (or extraordinary personal charisma) may increase your practice’s value to you, but they are worthless to the next owner, and he or she will be unwilling to pay for them unless your services become part of the deal.
Once again, there are many ways to estimate intangible asset value, and once again you should ask which were used. Cash flow analysis works on the assumption that cash flow is a measure of intangible value. Capitalization of earnings puts a value, or capitalization, on the practice’s income streams using a variety of assumptions. Guideline comparison uses various databases to compare your practice with other, similar ones that have changed hands in the past.
Two newer techniques, which some consider to provide a better estimate of intangible assets, are the replacement method, which estimates the costs of starting the practice over again in the current market; and the excess earnings method, which measures how far above average your practice’s earnings are (and thus its overall value).
Asset-based valuation is the most popular, but by no means the only, method available. Income-based valuation looks at the source and strength of a practice’s income stream as a creator of value, as well as whether or not the income stream under a different owner would mirror its present one. This in turn becomes the basis for an understanding of the fair market value of both tangible and intangible assets. Market valuation combines the asset-based and income-based approaches, along with an analysis of sales and mergers of comparable practices in the community, to determine the value of a practice in its local market.
Whatever methods are used, it is important that the appraisal be done by an experienced financial consultant, that all techniques used in the valuation be divulged and explained, and that documentation is supplied to support the conclusions reached. This is especially important if the appraisal will be relied upon in the sale or merger of the practice. I’ll talk about sales and mergers over the next several columns.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Skin & Allergy News.
At least once during your career, you probably will have to put a value on your practice. The need arises more often than you might think – if you sell it, of course (more on that next month); but also for estate planning, preparation of financial statements, or divorce negotiations; or when an associate joins or leaves your office; or if you have occasion to combine or partner your practice with one or more others, as I will discuss in detail in a future issue.
As you might guess, a medical practice is trickier to value than an ordinary business, and usually requires the services of an experienced professional appraiser. Entire books have been written about the process, so I can’t hope to cover it completely in a few hundred words, but three basic yardsticks are essential for a practice appraisal:
Tangible assets: equipment, cash, accounts receivable, and other property owned by the practice.
Liabilities: accounts payable, outstanding loans, and anything else owed to others.
Intangible assets: sometimes called “good will” – the reputation of the physicians, the location and name recognition of the practice, the loyalty and volume of patients, and other, well, intangibles.
Armed with those numbers, an appraiser can then determine the “equity,” or book value, of the practice.
Valuing tangible assets is comparatively straightforward, but there are several ways to do it, and when reviewing a practice appraisal you should ask which of them was used. Depreciated value is the book value of equipment and supplies as determined by their purchase price, less the amount their value has decreased since purchase. Remaining useful life value estimates how long the equipment can be expected to last. Market (or replacement) value is the amount it would cost on the open market to replace all equipment and supplies.
Intangible assets are more difficult to value. Many components are analyzed, including location, interior and exterior decor, accessibility to patients, age and functional status of equipment, systems in place to promote efficiency, reasons patients come back (if they do), and the overall reputation of the practice in the community. Other important factors include the “payer mix” (what percentage pays cash, how many third-party contracts are in place and how well they pay, etc.), the extent and strength of the referral base, and the presence of clinical studies or other supplemental income streams.
It is also important to determine to what extent intangible assets are transferrable. For example, unique skills with a laser, neurotoxins, or filler substances (or extraordinary personal charisma) may increase your practice’s value to you, but they are worthless to the next owner, and he or she will be unwilling to pay for them unless your services become part of the deal.
Once again, there are many ways to estimate intangible asset value, and once again you should ask which were used. Cash flow analysis works on the assumption that cash flow is a measure of intangible value. Capitalization of earnings puts a value, or capitalization, on the practice’s income streams using a variety of assumptions. Guideline comparison uses various databases to compare your practice with other, similar ones that have changed hands in the past.
Two newer techniques, which some consider to provide a better estimate of intangible assets, are the replacement method, which estimates the costs of starting the practice over again in the current market; and the excess earnings method, which measures how far above average your practice’s earnings are (and thus its overall value).
Asset-based valuation is the most popular, but by no means the only, method available. Income-based valuation looks at the source and strength of a practice’s income stream as a creator of value, as well as whether or not the income stream under a different owner would mirror its present one. This in turn becomes the basis for an understanding of the fair market value of both tangible and intangible assets. Market valuation combines the asset-based and income-based approaches, along with an analysis of sales and mergers of comparable practices in the community, to determine the value of a practice in its local market.
Whatever methods are used, it is important that the appraisal be done by an experienced financial consultant, that all techniques used in the valuation be divulged and explained, and that documentation is supplied to support the conclusions reached. This is especially important if the appraisal will be relied upon in the sale or merger of the practice. I’ll talk about sales and mergers over the next several columns.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Skin & Allergy News.
At least once during your career, you probably will have to put a value on your practice. The need arises more often than you might think – if you sell it, of course (more on that next month); but also for estate planning, preparation of financial statements, or divorce negotiations; or when an associate joins or leaves your office; or if you have occasion to combine or partner your practice with one or more others, as I will discuss in detail in a future issue.
As you might guess, a medical practice is trickier to value than an ordinary business, and usually requires the services of an experienced professional appraiser. Entire books have been written about the process, so I can’t hope to cover it completely in a few hundred words, but three basic yardsticks are essential for a practice appraisal:
Tangible assets: equipment, cash, accounts receivable, and other property owned by the practice.
Liabilities: accounts payable, outstanding loans, and anything else owed to others.
Intangible assets: sometimes called “good will” – the reputation of the physicians, the location and name recognition of the practice, the loyalty and volume of patients, and other, well, intangibles.
Armed with those numbers, an appraiser can then determine the “equity,” or book value, of the practice.
Valuing tangible assets is comparatively straightforward, but there are several ways to do it, and when reviewing a practice appraisal you should ask which of them was used. Depreciated value is the book value of equipment and supplies as determined by their purchase price, less the amount their value has decreased since purchase. Remaining useful life value estimates how long the equipment can be expected to last. Market (or replacement) value is the amount it would cost on the open market to replace all equipment and supplies.
Intangible assets are more difficult to value. Many components are analyzed, including location, interior and exterior decor, accessibility to patients, age and functional status of equipment, systems in place to promote efficiency, reasons patients come back (if they do), and the overall reputation of the practice in the community. Other important factors include the “payer mix” (what percentage pays cash, how many third-party contracts are in place and how well they pay, etc.), the extent and strength of the referral base, and the presence of clinical studies or other supplemental income streams.
It is also important to determine to what extent intangible assets are transferrable. For example, unique skills with a laser, neurotoxins, or filler substances (or extraordinary personal charisma) may increase your practice’s value to you, but they are worthless to the next owner, and he or she will be unwilling to pay for them unless your services become part of the deal.
Once again, there are many ways to estimate intangible asset value, and once again you should ask which were used. Cash flow analysis works on the assumption that cash flow is a measure of intangible value. Capitalization of earnings puts a value, or capitalization, on the practice’s income streams using a variety of assumptions. Guideline comparison uses various databases to compare your practice with other, similar ones that have changed hands in the past.
Two newer techniques, which some consider to provide a better estimate of intangible assets, are the replacement method, which estimates the costs of starting the practice over again in the current market; and the excess earnings method, which measures how far above average your practice’s earnings are (and thus its overall value).
Asset-based valuation is the most popular, but by no means the only, method available. Income-based valuation looks at the source and strength of a practice’s income stream as a creator of value, as well as whether or not the income stream under a different owner would mirror its present one. This in turn becomes the basis for an understanding of the fair market value of both tangible and intangible assets. Market valuation combines the asset-based and income-based approaches, along with an analysis of sales and mergers of comparable practices in the community, to determine the value of a practice in its local market.
Whatever methods are used, it is important that the appraisal be done by an experienced financial consultant, that all techniques used in the valuation be divulged and explained, and that documentation is supplied to support the conclusions reached. This is especially important if the appraisal will be relied upon in the sale or merger of the practice. I’ll talk about sales and mergers over the next several columns.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Skin & Allergy News.
A new form to fill out
I got my Medicare card 2 years ago (guess how old I am?). At this year’s physical exam (my first exam under new rules that let Medicare pay for routine annual physicals), the clerk asked me to fill out the “Health-Risk Assessment” form my PCP would need for billing.
This form had two pages. Page 1 listed 26 questions, each to be answered by checking off one of the following six choices: Never, Sometimes, Seldom, Often, Always, and Not Applicable.
Right away you see a problem. If this were an SAT test, say, where I actually cared whether or not I passed, I would summon a proctor and demand to know the difference between “Sometimes” and “Seldom,” or whether “Always” includes when I’m asleep, intoxicated, or filling out forms.
I will not burden you with all 26 questions. Instead, I’ll present several (these are the actual questions, folks, word for word), along with the answers I would have given had I not been hamstrung by the Six Categories. Each question is headed, “In the past 4 weeks.”
Q: How much have you felt little interest or pleasure?
A: I have very much felt little interest, and very little felt much interest. On the other hand, I have much interest in the little pleasure I have felt, and much pleasure in the little interest I have had.
Q: Has your physical and emotional health limited your social activities with family, friends, neighbors or groups?
A: No, but lack of money has.
Q: Have you needed help preparing your own meals?
A: Yes, ever since I got married, but that was more than 4 weeks ago. I can still make omelets, though.
Q: Are you having difficulties driving your car?
A: Do you know Boston drivers?
Q: Have you needed help managing your finances?
A: Not since 2008, and then it was my broker who needed the help.
Q: Have you needed help with household chores?
A: Never do ‘em.
Q: Do you have concerns about your memory?
A: What?
Q: DO YOU HAVE CONCERNS ABOUT YOUR MEMORY?
A: Not so much about what I can’t remember, mostly about what I can.
Q: Do any of your friends/family have concerns about your memory?
A: No, other than whether I’ll remember them in my will.
Q: Have you had sexual problems?
A: Too much. Too little. I forget. But that’s just the last 4 weeks. Six weeks ago was amazing.
Q: Have problems using a telephone?
A: Damn right. Cellular connectivity around here stinks.
Q: Do you exercise for about 20 minutes, 3 or more days a week?
A: I always exercise sometimes. I sometimes exercise always. Could you repeat the question?
Q: Does your home have throw rugs?
A: It has rugs, but nobody throws them.
Q: Does your home have poor lighting?
A: Ever since they outlawed incandescents. When I flip the switch, they’re fully lit by the time I finish breakfast, but by then it’s time to turn them off and go to work.
Q: During the past 4 weeks, how have things been going for you?
A: The Red Sox are doing lousy. Did you have to ask?
The form ends with thanks for taking the time to fill out the form and concludes with this cheery note: “Your responses will help you receive the best health and health care possible.”
When my physical was done, my doctor found the form in my paper pile. “I see you filled it out,” she said.
“By the way,” I asked her. ‘”What do you do with these forms?”
“Absolutely nothing,” she said.
“You don’t have to submit them for tabulation or something?”
“No,” she said.
If you’re not on Medicare yet, this is what you have to look forward to. Always.
Sometimes.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Skin & Allergy News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years.
I got my Medicare card 2 years ago (guess how old I am?). At this year’s physical exam (my first exam under new rules that let Medicare pay for routine annual physicals), the clerk asked me to fill out the “Health-Risk Assessment” form my PCP would need for billing.
This form had two pages. Page 1 listed 26 questions, each to be answered by checking off one of the following six choices: Never, Sometimes, Seldom, Often, Always, and Not Applicable.
Right away you see a problem. If this were an SAT test, say, where I actually cared whether or not I passed, I would summon a proctor and demand to know the difference between “Sometimes” and “Seldom,” or whether “Always” includes when I’m asleep, intoxicated, or filling out forms.
I will not burden you with all 26 questions. Instead, I’ll present several (these are the actual questions, folks, word for word), along with the answers I would have given had I not been hamstrung by the Six Categories. Each question is headed, “In the past 4 weeks.”
Q: How much have you felt little interest or pleasure?
A: I have very much felt little interest, and very little felt much interest. On the other hand, I have much interest in the little pleasure I have felt, and much pleasure in the little interest I have had.
Q: Has your physical and emotional health limited your social activities with family, friends, neighbors or groups?
A: No, but lack of money has.
Q: Have you needed help preparing your own meals?
A: Yes, ever since I got married, but that was more than 4 weeks ago. I can still make omelets, though.
Q: Are you having difficulties driving your car?
A: Do you know Boston drivers?
Q: Have you needed help managing your finances?
A: Not since 2008, and then it was my broker who needed the help.
Q: Have you needed help with household chores?
A: Never do ‘em.
Q: Do you have concerns about your memory?
A: What?
Q: DO YOU HAVE CONCERNS ABOUT YOUR MEMORY?
A: Not so much about what I can’t remember, mostly about what I can.
Q: Do any of your friends/family have concerns about your memory?
A: No, other than whether I’ll remember them in my will.
Q: Have you had sexual problems?
A: Too much. Too little. I forget. But that’s just the last 4 weeks. Six weeks ago was amazing.
Q: Have problems using a telephone?
A: Damn right. Cellular connectivity around here stinks.
Q: Do you exercise for about 20 minutes, 3 or more days a week?
A: I always exercise sometimes. I sometimes exercise always. Could you repeat the question?
Q: Does your home have throw rugs?
A: It has rugs, but nobody throws them.
Q: Does your home have poor lighting?
A: Ever since they outlawed incandescents. When I flip the switch, they’re fully lit by the time I finish breakfast, but by then it’s time to turn them off and go to work.
Q: During the past 4 weeks, how have things been going for you?
A: The Red Sox are doing lousy. Did you have to ask?
The form ends with thanks for taking the time to fill out the form and concludes with this cheery note: “Your responses will help you receive the best health and health care possible.”
When my physical was done, my doctor found the form in my paper pile. “I see you filled it out,” she said.
“By the way,” I asked her. ‘”What do you do with these forms?”
“Absolutely nothing,” she said.
“You don’t have to submit them for tabulation or something?”
“No,” she said.
If you’re not on Medicare yet, this is what you have to look forward to. Always.
Sometimes.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Skin & Allergy News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years.
I got my Medicare card 2 years ago (guess how old I am?). At this year’s physical exam (my first exam under new rules that let Medicare pay for routine annual physicals), the clerk asked me to fill out the “Health-Risk Assessment” form my PCP would need for billing.
This form had two pages. Page 1 listed 26 questions, each to be answered by checking off one of the following six choices: Never, Sometimes, Seldom, Often, Always, and Not Applicable.
Right away you see a problem. If this were an SAT test, say, where I actually cared whether or not I passed, I would summon a proctor and demand to know the difference between “Sometimes” and “Seldom,” or whether “Always” includes when I’m asleep, intoxicated, or filling out forms.
I will not burden you with all 26 questions. Instead, I’ll present several (these are the actual questions, folks, word for word), along with the answers I would have given had I not been hamstrung by the Six Categories. Each question is headed, “In the past 4 weeks.”
Q: How much have you felt little interest or pleasure?
A: I have very much felt little interest, and very little felt much interest. On the other hand, I have much interest in the little pleasure I have felt, and much pleasure in the little interest I have had.
Q: Has your physical and emotional health limited your social activities with family, friends, neighbors or groups?
A: No, but lack of money has.
Q: Have you needed help preparing your own meals?
A: Yes, ever since I got married, but that was more than 4 weeks ago. I can still make omelets, though.
Q: Are you having difficulties driving your car?
A: Do you know Boston drivers?
Q: Have you needed help managing your finances?
A: Not since 2008, and then it was my broker who needed the help.
Q: Have you needed help with household chores?
A: Never do ‘em.
Q: Do you have concerns about your memory?
A: What?
Q: DO YOU HAVE CONCERNS ABOUT YOUR MEMORY?
A: Not so much about what I can’t remember, mostly about what I can.
Q: Do any of your friends/family have concerns about your memory?
A: No, other than whether I’ll remember them in my will.
Q: Have you had sexual problems?
A: Too much. Too little. I forget. But that’s just the last 4 weeks. Six weeks ago was amazing.
Q: Have problems using a telephone?
A: Damn right. Cellular connectivity around here stinks.
Q: Do you exercise for about 20 minutes, 3 or more days a week?
A: I always exercise sometimes. I sometimes exercise always. Could you repeat the question?
Q: Does your home have throw rugs?
A: It has rugs, but nobody throws them.
Q: Does your home have poor lighting?
A: Ever since they outlawed incandescents. When I flip the switch, they’re fully lit by the time I finish breakfast, but by then it’s time to turn them off and go to work.
Q: During the past 4 weeks, how have things been going for you?
A: The Red Sox are doing lousy. Did you have to ask?
The form ends with thanks for taking the time to fill out the form and concludes with this cheery note: “Your responses will help you receive the best health and health care possible.”
When my physical was done, my doctor found the form in my paper pile. “I see you filled it out,” she said.
“By the way,” I asked her. ‘”What do you do with these forms?”
“Absolutely nothing,” she said.
“You don’t have to submit them for tabulation or something?”
“No,” she said.
If you’re not on Medicare yet, this is what you have to look forward to. Always.
Sometimes.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Skin & Allergy News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years.
Most VTE therapies produce comparable results, analysis suggests
Credit: CDC
A newly published meta-analysis suggests most anticoagulant therapies produce similar results in patients with venous thromboembolism (VTE).
Using data from 45 randomized trials, investigators compared 8 anticoagulation options and found that most were associated with similar rates of VTE recurrence and bleeding.
They did find that unfractionated heparin (UFH) plus a vitamin K antagonist (VKA) conferred the greatest risk of VTE recurrence.
And rivaroxaban and apixaban were associated with the lowest rates of bleeding.
Two treatments—apixaban and low-molecular-weight heparin (LMWH) plus edoxaban—had the highest probability of being the best therapy. And apixaban had the greatest probability of being the least harmful therapy.
Lana A. Castellucci, MD, of the Ottawa Hospital Research Institute in Ontario, Canada, and her colleagues reported these results in JAMA.
The team conducted this meta-analysis to compare the efficacy and safety of 8 anticoagulation options: rivaroxaban, apixaban, LMWH, LMWH plus dabigatran, LMWH plus edoxaban, LMWH plus a VKA, UFH plus a VKA, and fondaparinux plus a VKA.
A search of the medical literature revealed 45 randomized trials comparing treatment options for VTE. They included a total of 44,989 patients.
VTE recurrence
The investigators first compared the risk of VTE recurrence with LMWH-VKA to all other treatment strategies. They found that 6 of the other options were associated with a lower rate of VTE recurrence than LMWH-VKA.
The only exception was UFH-VKA. During 3 months of treatment, 1.84% of patients who received UFH-VKA had a VTE recurrence, compared to 1.30% of patients treated with LMWH-VKA.
When the investigators used UFH-VKA as the comparator, they found that LMWH-VKA and LMWH alone were the only treatments associated with a reduction in recurrent VTE.
Stepwise comparisons of the remaining treatment strategies did not reveal significant differences in VTE recurrence.
However, the investigators found that LMWH-edoxaban and apixaban had the greatest probability of being the best therapy—at 33.1% and 31.6%, respectively.
Bleeding risk
Compared with LMWH-VKA, rivaroxaban and apixaban were associated with the lowest bleeding risk. The incidence of major bleeding during 3 months of anticoagulation was 0.49% for rivaroxaban, 0.28% for apixaban, and 0.89% for LMWH-VKA.
For all other treatments, the risk of bleeding did not differ significantly from the risk associated with LMWH-VKA.
Additional pairwise comparisons showed that rivaroxaban, apixaban, or both were associated with the lowest bleeding rates compared with UFH-VKA, fondaparinux-VKA, LMWH-dabigatran, and LMWH-edoxaban.
Apixaban was associated with the greatest probability of being the least harmful therapy (88.9%).
Considering these results together, Dr Castellucci and her colleagues concluded that most of the VTE treatments studied elicited comparable safety and efficacy outcomes.
However, UFH-VKA may be the least effective strategy for managing VTE, and rivaroxaban and apixaban may be associated with the lowest risk of bleeding. 
Credit: CDC
A newly published meta-analysis suggests most anticoagulant therapies produce similar results in patients with venous thromboembolism (VTE).
Using data from 45 randomized trials, investigators compared 8 anticoagulation options and found that most were associated with similar rates of VTE recurrence and bleeding.
They did find that unfractionated heparin (UFH) plus a vitamin K antagonist (VKA) conferred the greatest risk of VTE recurrence.
And rivaroxaban and apixaban were associated with the lowest rates of bleeding.
Two treatments—apixaban and low-molecular-weight heparin (LMWH) plus edoxaban—had the highest probability of being the best therapy. And apixaban had the greatest probability of being the least harmful therapy.
Lana A. Castellucci, MD, of the Ottawa Hospital Research Institute in Ontario, Canada, and her colleagues reported these results in JAMA.
The team conducted this meta-analysis to compare the efficacy and safety of 8 anticoagulation options: rivaroxaban, apixaban, LMWH, LMWH plus dabigatran, LMWH plus edoxaban, LMWH plus a VKA, UFH plus a VKA, and fondaparinux plus a VKA.
A search of the medical literature revealed 45 randomized trials comparing treatment options for VTE. They included a total of 44,989 patients.
VTE recurrence
The investigators first compared the risk of VTE recurrence with LMWH-VKA to all other treatment strategies. They found that 6 of the other options were associated with a lower rate of VTE recurrence than LMWH-VKA.
The only exception was UFH-VKA. During 3 months of treatment, 1.84% of patients who received UFH-VKA had a VTE recurrence, compared to 1.30% of patients treated with LMWH-VKA.
When the investigators used UFH-VKA as the comparator, they found that LMWH-VKA and LMWH alone were the only treatments associated with a reduction in recurrent VTE.
Stepwise comparisons of the remaining treatment strategies did not reveal significant differences in VTE recurrence.
However, the investigators found that LMWH-edoxaban and apixaban had the greatest probability of being the best therapy—at 33.1% and 31.6%, respectively.
Bleeding risk
Compared with LMWH-VKA, rivaroxaban and apixaban were associated with the lowest bleeding risk. The incidence of major bleeding during 3 months of anticoagulation was 0.49% for rivaroxaban, 0.28% for apixaban, and 0.89% for LMWH-VKA.
For all other treatments, the risk of bleeding did not differ significantly from the risk associated with LMWH-VKA.
Additional pairwise comparisons showed that rivaroxaban, apixaban, or both were associated with the lowest bleeding rates compared with UFH-VKA, fondaparinux-VKA, LMWH-dabigatran, and LMWH-edoxaban.
Apixaban was associated with the greatest probability of being the least harmful therapy (88.9%).
Considering these results together, Dr Castellucci and her colleagues concluded that most of the VTE treatments studied elicited comparable safety and efficacy outcomes.
However, UFH-VKA may be the least effective strategy for managing VTE, and rivaroxaban and apixaban may be associated with the lowest risk of bleeding.
Credit: CDC
A newly published meta-analysis suggests most anticoagulant therapies produce similar results in patients with venous thromboembolism (VTE).
Using data from 45 randomized trials, investigators compared 8 anticoagulation options and found that most were associated with similar rates of VTE recurrence and bleeding.
They did find that unfractionated heparin (UFH) plus a vitamin K antagonist (VKA) conferred the greatest risk of VTE recurrence.
And rivaroxaban and apixaban were associated with the lowest rates of bleeding.
Two treatments—apixaban and low-molecular-weight heparin (LMWH) plus edoxaban—had the highest probability of being the best therapy. And apixaban had the greatest probability of being the least harmful therapy.
Lana A. Castellucci, MD, of the Ottawa Hospital Research Institute in Ontario, Canada, and her colleagues reported these results in JAMA.
The team conducted this meta-analysis to compare the efficacy and safety of 8 anticoagulation options: rivaroxaban, apixaban, LMWH, LMWH plus dabigatran, LMWH plus edoxaban, LMWH plus a VKA, UFH plus a VKA, and fondaparinux plus a VKA.
A search of the medical literature revealed 45 randomized trials comparing treatment options for VTE. They included a total of 44,989 patients.
VTE recurrence
The investigators first compared the risk of VTE recurrence with LMWH-VKA to all other treatment strategies. They found that 6 of the other options were associated with a lower rate of VTE recurrence than LMWH-VKA.
The only exception was UFH-VKA. During 3 months of treatment, 1.84% of patients who received UFH-VKA had a VTE recurrence, compared to 1.30% of patients treated with LMWH-VKA.
When the investigators used UFH-VKA as the comparator, they found that LMWH-VKA and LMWH alone were the only treatments associated with a reduction in recurrent VTE.
Stepwise comparisons of the remaining treatment strategies did not reveal significant differences in VTE recurrence.
However, the investigators found that LMWH-edoxaban and apixaban had the greatest probability of being the best therapy—at 33.1% and 31.6%, respectively.
Bleeding risk
Compared with LMWH-VKA, rivaroxaban and apixaban were associated with the lowest bleeding risk. The incidence of major bleeding during 3 months of anticoagulation was 0.49% for rivaroxaban, 0.28% for apixaban, and 0.89% for LMWH-VKA.
For all other treatments, the risk of bleeding did not differ significantly from the risk associated with LMWH-VKA.
Additional pairwise comparisons showed that rivaroxaban, apixaban, or both were associated with the lowest bleeding rates compared with UFH-VKA, fondaparinux-VKA, LMWH-dabigatran, and LMWH-edoxaban.
Apixaban was associated with the greatest probability of being the least harmful therapy (88.9%).
Considering these results together, Dr Castellucci and her colleagues concluded that most of the VTE treatments studied elicited comparable safety and efficacy outcomes.
However, UFH-VKA may be the least effective strategy for managing VTE, and rivaroxaban and apixaban may be associated with the lowest risk of bleeding.
FDA approves treatment for kids with hemophilia B
The US Food and Drug Administration (FDA) has approved a recombinant factor IX product (Rixubis) for use in children with hemophilia B.
Rixubis is indicated for routine prophylactic treatment, control and prevention of bleeding episodes, and perioperative management in these patients.
Rixubis was the first recombinant factor IX product to gain FDA approval for routine prophylaxis and control of bleeding episodes in adults with hemophilia B.
The latest FDA approval is based on results of a trial investigating the efficacy and safety of Rixubis in 23 previously treated male patients younger than 12 years of age who had severe or moderately severe hemophilia B.
The patients received a twice-weekly Rixubis prophylaxis regimen (mean dose 56 IU/kg) for a mean treatment duration of 6 months and a mean of 54 exposure days.
The median annualized bleeding rate was 2.0 (0.0 for spontaneous bleeds and joint bleeds). Nine patients (39.1%) experienced no bleeds, and 23 bleeding episodes (88.5%) were treated with 1 to 2 infusions.
There were no reports of inhibitor development, severe allergic reactions, thrombotic events, or treatment-related adverse events.
These data were presented at the 2013 ASH Annual Meeting (abstract 1118).
Common adverse reactions observed in more than 1% of subjects in clinical studies of Rixubis were dysgeusia, pain in an extremity, and a positive test for furin antibody. Rixubis may pose a risk of hypersensitivity reactions, inhibitor development, nephrotic syndrome, and thromboembolic complications.
Rixubis is contraindicated in patients who have known hypersensitivity to the product or its excipients (including hamster protein), patients with disseminated intravascular coagulation, and those with signs of fibrinolysis.
For more details on Rixubis, see the full prescribing information. Rixubis is under development by Baxter International Inc.
The US Food and Drug Administration (FDA) has approved a recombinant factor IX product (Rixubis) for use in children with hemophilia B.
Rixubis is indicated for routine prophylactic treatment, control and prevention of bleeding episodes, and perioperative management in these patients.
Rixubis was the first recombinant factor IX product to gain FDA approval for routine prophylaxis and control of bleeding episodes in adults with hemophilia B.
The latest FDA approval is based on results of a trial investigating the efficacy and safety of Rixubis in 23 previously treated male patients younger than 12 years of age who had severe or moderately severe hemophilia B.
The patients received a twice-weekly Rixubis prophylaxis regimen (mean dose 56 IU/kg) for a mean treatment duration of 6 months and a mean of 54 exposure days.
The median annualized bleeding rate was 2.0 (0.0 for spontaneous bleeds and joint bleeds). Nine patients (39.1%) experienced no bleeds, and 23 bleeding episodes (88.5%) were treated with 1 to 2 infusions.
There were no reports of inhibitor development, severe allergic reactions, thrombotic events, or treatment-related adverse events.
These data were presented at the 2013 ASH Annual Meeting (abstract 1118).
Common adverse reactions observed in more than 1% of subjects in clinical studies of Rixubis were dysgeusia, pain in an extremity, and a positive test for furin antibody. Rixubis may pose a risk of hypersensitivity reactions, inhibitor development, nephrotic syndrome, and thromboembolic complications.
Rixubis is contraindicated in patients who have known hypersensitivity to the product or its excipients (including hamster protein), patients with disseminated intravascular coagulation, and those with signs of fibrinolysis.
For more details on Rixubis, see the full prescribing information. Rixubis is under development by Baxter International Inc.
The US Food and Drug Administration (FDA) has approved a recombinant factor IX product (Rixubis) for use in children with hemophilia B.
Rixubis is indicated for routine prophylactic treatment, control and prevention of bleeding episodes, and perioperative management in these patients.
Rixubis was the first recombinant factor IX product to gain FDA approval for routine prophylaxis and control of bleeding episodes in adults with hemophilia B.
The latest FDA approval is based on results of a trial investigating the efficacy and safety of Rixubis in 23 previously treated male patients younger than 12 years of age who had severe or moderately severe hemophilia B.
The patients received a twice-weekly Rixubis prophylaxis regimen (mean dose 56 IU/kg) for a mean treatment duration of 6 months and a mean of 54 exposure days.
The median annualized bleeding rate was 2.0 (0.0 for spontaneous bleeds and joint bleeds). Nine patients (39.1%) experienced no bleeds, and 23 bleeding episodes (88.5%) were treated with 1 to 2 infusions.
There were no reports of inhibitor development, severe allergic reactions, thrombotic events, or treatment-related adverse events.
These data were presented at the 2013 ASH Annual Meeting (abstract 1118).
Common adverse reactions observed in more than 1% of subjects in clinical studies of Rixubis were dysgeusia, pain in an extremity, and a positive test for furin antibody. Rixubis may pose a risk of hypersensitivity reactions, inhibitor development, nephrotic syndrome, and thromboembolic complications.
Rixubis is contraindicated in patients who have known hypersensitivity to the product or its excipients (including hamster protein), patients with disseminated intravascular coagulation, and those with signs of fibrinolysis.
For more details on Rixubis, see the full prescribing information. Rixubis is under development by Baxter International Inc.
Protein discovery points the way to sepsis treatment
Credit: Eric Smith
A protein that helps the innate immune system target bacteria and viruses can fight sepsis by interacting with histones, according to research
published in Science Signaling.
The pattern recognition protein pentraxin 3 (PTX3) is known to activate the body’s immune system in response to sepsis conditions.
But researchers thought the protein might have an additional role in sepsis pathogenesis, in the form of host protection against extracellular histones.
They knew that, during sepsis, histones escape from dead cells and kill nearby healthy cells, causing inflammation.
And the team’s experiments showed that PTX3 forms strong bonds with histones and disrupts their cellular toxicity, specifically by bundling the histones into aggregates that no longer kill healthy cells.
“We observed extraordinarily rapid and tight interaction with histone, which we recognized as coaggregation after a variety of experiments,” said study author Takao Hamakubo, MD, PhD, of the University of Tokyo in Japan.
The researchers also found that mice pretreated with PTX3 and infused with histones showed reduced inflammation.
So the team decided to investigate the effects of PTX3 in 2 mouse models of sepsis. In both models, the protein substantially reduced mortality.
PTX3 worked even when administered hours after a sepsis-inducing procedure called cecal ligation and puncture, in which fecal material is released into the abdomen to generate a strong immune response.
The researchers said these results suggest the host-protective effects of PTX3 in sepsis are a result of its coaggregation with histones rather than its ability to mediate pattern recognition. And this effect provides a potential basis for treating sepsis by protecting cells from the toxic effects of extracellular histones.
“To our knowledge, this is the first report of coaggregation between different proteins that is protective to the host,” Dr Hamakubo said. “We expect our findings lead to a novel understanding of protein interaction and that they will benefit people who are suffering from severe illness.”
Credit: Eric Smith
A protein that helps the innate immune system target bacteria and viruses can fight sepsis by interacting with histones, according to research
published in Science Signaling.
The pattern recognition protein pentraxin 3 (PTX3) is known to activate the body’s immune system in response to sepsis conditions.
But researchers thought the protein might have an additional role in sepsis pathogenesis, in the form of host protection against extracellular histones.
They knew that, during sepsis, histones escape from dead cells and kill nearby healthy cells, causing inflammation.
And the team’s experiments showed that PTX3 forms strong bonds with histones and disrupts their cellular toxicity, specifically by bundling the histones into aggregates that no longer kill healthy cells.
“We observed extraordinarily rapid and tight interaction with histone, which we recognized as coaggregation after a variety of experiments,” said study author Takao Hamakubo, MD, PhD, of the University of Tokyo in Japan.
The researchers also found that mice pretreated with PTX3 and infused with histones showed reduced inflammation.
So the team decided to investigate the effects of PTX3 in 2 mouse models of sepsis. In both models, the protein substantially reduced mortality.
PTX3 worked even when administered hours after a sepsis-inducing procedure called cecal ligation and puncture, in which fecal material is released into the abdomen to generate a strong immune response.
The researchers said these results suggest the host-protective effects of PTX3 in sepsis are a result of its coaggregation with histones rather than its ability to mediate pattern recognition. And this effect provides a potential basis for treating sepsis by protecting cells from the toxic effects of extracellular histones.
“To our knowledge, this is the first report of coaggregation between different proteins that is protective to the host,” Dr Hamakubo said. “We expect our findings lead to a novel understanding of protein interaction and that they will benefit people who are suffering from severe illness.”
Credit: Eric Smith
A protein that helps the innate immune system target bacteria and viruses can fight sepsis by interacting with histones, according to research
published in Science Signaling.
The pattern recognition protein pentraxin 3 (PTX3) is known to activate the body’s immune system in response to sepsis conditions.
But researchers thought the protein might have an additional role in sepsis pathogenesis, in the form of host protection against extracellular histones.
They knew that, during sepsis, histones escape from dead cells and kill nearby healthy cells, causing inflammation.
And the team’s experiments showed that PTX3 forms strong bonds with histones and disrupts their cellular toxicity, specifically by bundling the histones into aggregates that no longer kill healthy cells.
“We observed extraordinarily rapid and tight interaction with histone, which we recognized as coaggregation after a variety of experiments,” said study author Takao Hamakubo, MD, PhD, of the University of Tokyo in Japan.
The researchers also found that mice pretreated with PTX3 and infused with histones showed reduced inflammation.
So the team decided to investigate the effects of PTX3 in 2 mouse models of sepsis. In both models, the protein substantially reduced mortality.
PTX3 worked even when administered hours after a sepsis-inducing procedure called cecal ligation and puncture, in which fecal material is released into the abdomen to generate a strong immune response.
The researchers said these results suggest the host-protective effects of PTX3 in sepsis are a result of its coaggregation with histones rather than its ability to mediate pattern recognition. And this effect provides a potential basis for treating sepsis by protecting cells from the toxic effects of extracellular histones.
“To our knowledge, this is the first report of coaggregation between different proteins that is protective to the host,” Dr Hamakubo said. “We expect our findings lead to a novel understanding of protein interaction and that they will benefit people who are suffering from severe illness.”
New assay could prove useful in HSCT
Credit: Chad McNeeley
Researchers say they’ve developed an assay that allows for ultrasensitive DNA detection.
This haplotype-based assay could be used to detect relapse in patients who have undergone hematopoietic stem cell transplant (HSCT).
In fact, the researchers believe it would enable relapse detection earlier than existing microsatellite-based assays.
The new assay could also be used to detect microchimerism in solid organ transplants, in forensics, and for patient identification.
James Eshleman, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues described this assay in The Journal of Molecular Diagnostics.
The team noted that most bone marrow engraftment testing currently uses microsatellites or short tandem repeats that are resolved by capillary electrophoresis.
“Repeat testing will only detect DNA that makes up at least 1% of a DNA sample, so it’s not great for situations in which results depend on small amounts of material within a larger sample,” Dr Eshleman said.
In these situations, evaluating single-nucleotide polymorphisms (SNPs) might seem like a better choice, but this method has a high error rate. Dr Eshleman and his colleagues found they could circumvent this problem by analyzing blocks of closely spaced SNPs, or haplotypes.
To test their method, the researchers chose the HLA-A locus. They aligned common HLA-A alleles and identified a region containing 18 closely spaced SNPs. The team then tested a series of primers surrounding this region and selected the best pair on the basis of amplification efficiency and specificity.
They found it easy to differentiate some combinations of HLA-A alleles but not others. For instance, they discovered that 11 SNPs differentiate allele A*01 from A*02. But A*02 and HLA-A* 68:01:01:01 have a single SNP difference.
To test the possible cross talk between molecules that vary by 11 SNPs, the researchers sequenced 2 samples—one homozygous for A*01 and another homozygous for A*02—and analyzed each for the other allele. They found that, when there are enough discriminating SNPs between 2 individuals’ alleles, the haplotype assay is highly specific.
To evaluate the assay’s accuracy and limit of detection, the researchers generated various dilutions of 2 cell lines with known HLA-A genotypes. They made dilutions with cell mixes varying from 1 in 1 million (0.0001%) to 1 in 100 (1%), using 10 million cells for each dilution.
The team isolated DNA and performed PCR using 600 ng of DNA. And they sequenced each sample at least twice.
The assay proved highly precise at the 0.1% cell mix but less precise at the 0.01% cell mix.
“[Nevertheless,] we could detect cells when they made up just 0.01% of the mixture, which is a big improvement over the current method, which can only detect DNA that makes up 1% to 5% of a sample,” Dr Eshleman said.
The researchers also used their assay to test samples from 18 HSCT patients whose donor-patient HLA genotypes varied by at least 4 SNPs. All but 1 sample tested positive for some level of patient DNA, and the positives ranged from 0.001% to 1.47% patient DNA.
Finally, the team analyzed the human genome using the 1000 Genomes database and identified many additional loci that could be used with their assay.
Credit: Chad McNeeley
Researchers say they’ve developed an assay that allows for ultrasensitive DNA detection.
This haplotype-based assay could be used to detect relapse in patients who have undergone hematopoietic stem cell transplant (HSCT).
In fact, the researchers believe it would enable relapse detection earlier than existing microsatellite-based assays.
The new assay could also be used to detect microchimerism in solid organ transplants, in forensics, and for patient identification.
James Eshleman, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues described this assay in The Journal of Molecular Diagnostics.
The team noted that most bone marrow engraftment testing currently uses microsatellites or short tandem repeats that are resolved by capillary electrophoresis.
“Repeat testing will only detect DNA that makes up at least 1% of a DNA sample, so it’s not great for situations in which results depend on small amounts of material within a larger sample,” Dr Eshleman said.
In these situations, evaluating single-nucleotide polymorphisms (SNPs) might seem like a better choice, but this method has a high error rate. Dr Eshleman and his colleagues found they could circumvent this problem by analyzing blocks of closely spaced SNPs, or haplotypes.
To test their method, the researchers chose the HLA-A locus. They aligned common HLA-A alleles and identified a region containing 18 closely spaced SNPs. The team then tested a series of primers surrounding this region and selected the best pair on the basis of amplification efficiency and specificity.
They found it easy to differentiate some combinations of HLA-A alleles but not others. For instance, they discovered that 11 SNPs differentiate allele A*01 from A*02. But A*02 and HLA-A* 68:01:01:01 have a single SNP difference.
To test the possible cross talk between molecules that vary by 11 SNPs, the researchers sequenced 2 samples—one homozygous for A*01 and another homozygous for A*02—and analyzed each for the other allele. They found that, when there are enough discriminating SNPs between 2 individuals’ alleles, the haplotype assay is highly specific.
To evaluate the assay’s accuracy and limit of detection, the researchers generated various dilutions of 2 cell lines with known HLA-A genotypes. They made dilutions with cell mixes varying from 1 in 1 million (0.0001%) to 1 in 100 (1%), using 10 million cells for each dilution.
The team isolated DNA and performed PCR using 600 ng of DNA. And they sequenced each sample at least twice.
The assay proved highly precise at the 0.1% cell mix but less precise at the 0.01% cell mix.
“[Nevertheless,] we could detect cells when they made up just 0.01% of the mixture, which is a big improvement over the current method, which can only detect DNA that makes up 1% to 5% of a sample,” Dr Eshleman said.
The researchers also used their assay to test samples from 18 HSCT patients whose donor-patient HLA genotypes varied by at least 4 SNPs. All but 1 sample tested positive for some level of patient DNA, and the positives ranged from 0.001% to 1.47% patient DNA.
Finally, the team analyzed the human genome using the 1000 Genomes database and identified many additional loci that could be used with their assay.
Credit: Chad McNeeley
Researchers say they’ve developed an assay that allows for ultrasensitive DNA detection.
This haplotype-based assay could be used to detect relapse in patients who have undergone hematopoietic stem cell transplant (HSCT).
In fact, the researchers believe it would enable relapse detection earlier than existing microsatellite-based assays.
The new assay could also be used to detect microchimerism in solid organ transplants, in forensics, and for patient identification.
James Eshleman, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues described this assay in The Journal of Molecular Diagnostics.
The team noted that most bone marrow engraftment testing currently uses microsatellites or short tandem repeats that are resolved by capillary electrophoresis.
“Repeat testing will only detect DNA that makes up at least 1% of a DNA sample, so it’s not great for situations in which results depend on small amounts of material within a larger sample,” Dr Eshleman said.
In these situations, evaluating single-nucleotide polymorphisms (SNPs) might seem like a better choice, but this method has a high error rate. Dr Eshleman and his colleagues found they could circumvent this problem by analyzing blocks of closely spaced SNPs, or haplotypes.
To test their method, the researchers chose the HLA-A locus. They aligned common HLA-A alleles and identified a region containing 18 closely spaced SNPs. The team then tested a series of primers surrounding this region and selected the best pair on the basis of amplification efficiency and specificity.
They found it easy to differentiate some combinations of HLA-A alleles but not others. For instance, they discovered that 11 SNPs differentiate allele A*01 from A*02. But A*02 and HLA-A* 68:01:01:01 have a single SNP difference.
To test the possible cross talk between molecules that vary by 11 SNPs, the researchers sequenced 2 samples—one homozygous for A*01 and another homozygous for A*02—and analyzed each for the other allele. They found that, when there are enough discriminating SNPs between 2 individuals’ alleles, the haplotype assay is highly specific.
To evaluate the assay’s accuracy and limit of detection, the researchers generated various dilutions of 2 cell lines with known HLA-A genotypes. They made dilutions with cell mixes varying from 1 in 1 million (0.0001%) to 1 in 100 (1%), using 10 million cells for each dilution.
The team isolated DNA and performed PCR using 600 ng of DNA. And they sequenced each sample at least twice.
The assay proved highly precise at the 0.1% cell mix but less precise at the 0.01% cell mix.
“[Nevertheless,] we could detect cells when they made up just 0.01% of the mixture, which is a big improvement over the current method, which can only detect DNA that makes up 1% to 5% of a sample,” Dr Eshleman said.
The researchers also used their assay to test samples from 18 HSCT patients whose donor-patient HLA genotypes varied by at least 4 SNPs. All but 1 sample tested positive for some level of patient DNA, and the positives ranged from 0.001% to 1.47% patient DNA.
Finally, the team analyzed the human genome using the 1000 Genomes database and identified many additional loci that could be used with their assay.
Most acute VTE therapies yield similar outcomes
For patients with acute venous thromboembolism, both clinical and safety outcomes were similar among seven of eight possible treatment strategies assessed in a network meta-analysis published online Sept. 16 in JAMA.
Clinicians have several treatment options but little guidance for choosing among them when managing acute VTE. Many strategies have shown promising results when assessed in single studies, but there have been few direct comparison studies. So investigators performed a network meta-analysis of 45 articles involving 44,989 patients, which enabled them to compare the safety and efficacy of eight possible approaches. The sample sizes of these studies ranged from 60 to 8,240 participants, with a median of 298. The median follow-up period was 3 months, with a range of 3-8 months.
The currently accepted standard treatment for acute VTE is the use of parenteral low-molecular-weight heparin (LMWH) for a minimum of 5 days, followed by transition to a vitamin K antagonist. This approach was compared against parenteral unfractionated heparin followed by a vitamin K antagonist; parenteral fondaparinux followed by a vitamin K antagonist; parenteral LMWH combined with dabigatran; parenteral LMWH combined with edoxaban; oral rivaroxaban; oral apixaban; and parenteral LMWH alone, said Dr. Lana A. Castellucci of the Ottawa Hospital Research Institute, University of Ottawa, and her associates.
Compared with standard parenteral LMWH plus a vitamin K antagonist, six of these approaches yielded comparable reductions in recurrent VTE and induced comparable rates of major bleeding, the investigators said (JAMA 2014 September 16 [doi:10.1001/jama.2014.10538]).
The only strategy that was less effective at reducing the rate of recurrent VTE was parenteral unfractionated heparin plus a vitamin K antagonist. However, “there are clinical circumstances that necessitate the use of unfractionated heparin, including for patients with severe renal insufficiency and those with massive or submassive pulmonary embolism who are potential candidates for thrombolysis or thrombectomy,” Dr. Castellucci and her associates noted.
Oral rivaroxaban and oral apixaban appeared to be associated with the lowest risk of major bleeding. “Future direct comparison trials, patient-level network meta-analyses, or high-quality nonrandomized studies are required to confirm our findings,” they added.
This study was supported by the Heart and Stroke Foundation of Canada, the University of Ottawa, the Canadian Institutes of Health Research, the Canadian Network and Centre for Trials Internationally, and the Heart and Stroke Foundation of Ontario. Dr. Castellucci reported no financial conflicts of interest; some of her associates reported ties to Bayer, Biomerieux, Boehringer Ingelheim, Bristol-Myers Squibb, Leo Pharma, Pfizer, and Sanofi.
*Correction, 9/17/2014: An earlier version of this article misstated the Key Clinical Point in the Vitals section.
For patients with acute venous thromboembolism, both clinical and safety outcomes were similar among seven of eight possible treatment strategies assessed in a network meta-analysis published online Sept. 16 in JAMA.
Clinicians have several treatment options but little guidance for choosing among them when managing acute VTE. Many strategies have shown promising results when assessed in single studies, but there have been few direct comparison studies. So investigators performed a network meta-analysis of 45 articles involving 44,989 patients, which enabled them to compare the safety and efficacy of eight possible approaches. The sample sizes of these studies ranged from 60 to 8,240 participants, with a median of 298. The median follow-up period was 3 months, with a range of 3-8 months.
The currently accepted standard treatment for acute VTE is the use of parenteral low-molecular-weight heparin (LMWH) for a minimum of 5 days, followed by transition to a vitamin K antagonist. This approach was compared against parenteral unfractionated heparin followed by a vitamin K antagonist; parenteral fondaparinux followed by a vitamin K antagonist; parenteral LMWH combined with dabigatran; parenteral LMWH combined with edoxaban; oral rivaroxaban; oral apixaban; and parenteral LMWH alone, said Dr. Lana A. Castellucci of the Ottawa Hospital Research Institute, University of Ottawa, and her associates.
Compared with standard parenteral LMWH plus a vitamin K antagonist, six of these approaches yielded comparable reductions in recurrent VTE and induced comparable rates of major bleeding, the investigators said (JAMA 2014 September 16 [doi:10.1001/jama.2014.10538]).
The only strategy that was less effective at reducing the rate of recurrent VTE was parenteral unfractionated heparin plus a vitamin K antagonist. However, “there are clinical circumstances that necessitate the use of unfractionated heparin, including for patients with severe renal insufficiency and those with massive or submassive pulmonary embolism who are potential candidates for thrombolysis or thrombectomy,” Dr. Castellucci and her associates noted.
Oral rivaroxaban and oral apixaban appeared to be associated with the lowest risk of major bleeding. “Future direct comparison trials, patient-level network meta-analyses, or high-quality nonrandomized studies are required to confirm our findings,” they added.
This study was supported by the Heart and Stroke Foundation of Canada, the University of Ottawa, the Canadian Institutes of Health Research, the Canadian Network and Centre for Trials Internationally, and the Heart and Stroke Foundation of Ontario. Dr. Castellucci reported no financial conflicts of interest; some of her associates reported ties to Bayer, Biomerieux, Boehringer Ingelheim, Bristol-Myers Squibb, Leo Pharma, Pfizer, and Sanofi.
*Correction, 9/17/2014: An earlier version of this article misstated the Key Clinical Point in the Vitals section.
For patients with acute venous thromboembolism, both clinical and safety outcomes were similar among seven of eight possible treatment strategies assessed in a network meta-analysis published online Sept. 16 in JAMA.
Clinicians have several treatment options but little guidance for choosing among them when managing acute VTE. Many strategies have shown promising results when assessed in single studies, but there have been few direct comparison studies. So investigators performed a network meta-analysis of 45 articles involving 44,989 patients, which enabled them to compare the safety and efficacy of eight possible approaches. The sample sizes of these studies ranged from 60 to 8,240 participants, with a median of 298. The median follow-up period was 3 months, with a range of 3-8 months.
The currently accepted standard treatment for acute VTE is the use of parenteral low-molecular-weight heparin (LMWH) for a minimum of 5 days, followed by transition to a vitamin K antagonist. This approach was compared against parenteral unfractionated heparin followed by a vitamin K antagonist; parenteral fondaparinux followed by a vitamin K antagonist; parenteral LMWH combined with dabigatran; parenteral LMWH combined with edoxaban; oral rivaroxaban; oral apixaban; and parenteral LMWH alone, said Dr. Lana A. Castellucci of the Ottawa Hospital Research Institute, University of Ottawa, and her associates.
Compared with standard parenteral LMWH plus a vitamin K antagonist, six of these approaches yielded comparable reductions in recurrent VTE and induced comparable rates of major bleeding, the investigators said (JAMA 2014 September 16 [doi:10.1001/jama.2014.10538]).
The only strategy that was less effective at reducing the rate of recurrent VTE was parenteral unfractionated heparin plus a vitamin K antagonist. However, “there are clinical circumstances that necessitate the use of unfractionated heparin, including for patients with severe renal insufficiency and those with massive or submassive pulmonary embolism who are potential candidates for thrombolysis or thrombectomy,” Dr. Castellucci and her associates noted.
Oral rivaroxaban and oral apixaban appeared to be associated with the lowest risk of major bleeding. “Future direct comparison trials, patient-level network meta-analyses, or high-quality nonrandomized studies are required to confirm our findings,” they added.
This study was supported by the Heart and Stroke Foundation of Canada, the University of Ottawa, the Canadian Institutes of Health Research, the Canadian Network and Centre for Trials Internationally, and the Heart and Stroke Foundation of Ontario. Dr. Castellucci reported no financial conflicts of interest; some of her associates reported ties to Bayer, Biomerieux, Boehringer Ingelheim, Bristol-Myers Squibb, Leo Pharma, Pfizer, and Sanofi.
*Correction, 9/17/2014: An earlier version of this article misstated the Key Clinical Point in the Vitals section.
FROM JAMA
Key clinical point: Seven of the eight available VTE therapies are equally safe and effective.*
Major finding: Compared with standard parenteral LMWH plus a vitamin K antagonist, six treatment approaches yielded comparable reductions in recurrent VTE and induced comparable rates of major bleeding; the only approach that was less effective at reducing the rate of recurrent VTE was parenteral unfractionated heparin plus a vitamin K antagonist.
Data source: A network meta-analysis of 45 articles on studies involving 44,989 patients with acute VTE who were treated using any of eight strategies and followed for a median of 3 months.
Disclosures: This study was supported by the Heart and Stroke Foundation of Canada, the University of Ottawa, the Canadian Institutes of Health Research, the Canadian Network and Centre for Trials Internationally, and the Heart and Stroke Foundation of Ontario. Dr. Castellucci reported no financial conflicts of interest; some of her associates reported ties to Bayer, Biomerieux, Boehringer Ingelheim, Bristol-Myers Squibb, Leo Pharma, Pfizer, and Sanofi.
Probiotics for IBS
Irritable bowel syndrome affects up to 15% of the U.S. adult population, which may be an underestimate. When patients are managing themselves well, their clinical course can be routine. When their self-management is poor, IBS can make life exceedingly challenging for both patients and their clinicians. Many of us may be stepping up our game in patients with known IBS experiencing symptoms, first by recommending a diet low in FODMAPs (fermentable oligo-, di-, and monosaccharides and polyols), which have been shown to reduce IBS symptoms.
My experience is that patients who have been struggling for years with IBS have a high degree of health literacy. And they are usually receptive to trying new things that might make their lives better. The exceptions are the occasional patients who are convinced that they do not have IBS and that their clinicians are just too poorly informed to figure out what the real cause is.
Anything else we can recommend?
Jun Sik Yoon and colleagues have published a clinical trial evaluating the effectiveness of multispecies probiotics on IBS symptoms and changes in the gut microbiota. In this randomized, placebo-controlled trial, 49 subjects (25 probiotics, 24 placebo) with clinically-diagnosed IBS received tablets twice a day for 4 weeks. The primary outcome was the proportion of individuals whose IBS symptoms were substantially relieved at 4 weeks.
Probiotics were associated with a significantly higher proportion of patients with reductions in IBS symptoms (68% vs. 37.5%; P < .05). Probiotics also improved abdominal pain/discomfort and bloating. Fecal analysis revealed increases in the microbiota obtained with the probiotics (J. Gastroenterol. Hepatol. 2014;29:52-9).
So probiotics may help our patients with IBS if a low FODMAP diet does not. But what probiotic (i.e., containing which species) should we select? Species may have different effects on gut motility. Importantly, taking probiotics with certain species does not mean that those species will set up permanent residence in the colon. In the current study, only three of the six species contained in the probiotics were still in the stool after 4 weeks. The author concluded that the alleviation in bowel symptoms was attributable to Bifidobacterium lactis, Lactobacillus rhamnosus, and Streptococcus thermophiles. So let’s tell patients to look for probiotics with these species.
Probiotics are generally safe with the only possible contraindication being their use in patients with a severely immunocompromised state, but this is debatable. But now we have another evidence-based tool for our patients struggling with symptom recrudescence.
Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician.
Irritable bowel syndrome affects up to 15% of the U.S. adult population, which may be an underestimate. When patients are managing themselves well, their clinical course can be routine. When their self-management is poor, IBS can make life exceedingly challenging for both patients and their clinicians. Many of us may be stepping up our game in patients with known IBS experiencing symptoms, first by recommending a diet low in FODMAPs (fermentable oligo-, di-, and monosaccharides and polyols), which have been shown to reduce IBS symptoms.
My experience is that patients who have been struggling for years with IBS have a high degree of health literacy. And they are usually receptive to trying new things that might make their lives better. The exceptions are the occasional patients who are convinced that they do not have IBS and that their clinicians are just too poorly informed to figure out what the real cause is.
Anything else we can recommend?
Jun Sik Yoon and colleagues have published a clinical trial evaluating the effectiveness of multispecies probiotics on IBS symptoms and changes in the gut microbiota. In this randomized, placebo-controlled trial, 49 subjects (25 probiotics, 24 placebo) with clinically-diagnosed IBS received tablets twice a day for 4 weeks. The primary outcome was the proportion of individuals whose IBS symptoms were substantially relieved at 4 weeks.
Probiotics were associated with a significantly higher proportion of patients with reductions in IBS symptoms (68% vs. 37.5%; P < .05). Probiotics also improved abdominal pain/discomfort and bloating. Fecal analysis revealed increases in the microbiota obtained with the probiotics (J. Gastroenterol. Hepatol. 2014;29:52-9).
So probiotics may help our patients with IBS if a low FODMAP diet does not. But what probiotic (i.e., containing which species) should we select? Species may have different effects on gut motility. Importantly, taking probiotics with certain species does not mean that those species will set up permanent residence in the colon. In the current study, only three of the six species contained in the probiotics were still in the stool after 4 weeks. The author concluded that the alleviation in bowel symptoms was attributable to Bifidobacterium lactis, Lactobacillus rhamnosus, and Streptococcus thermophiles. So let’s tell patients to look for probiotics with these species.
Probiotics are generally safe with the only possible contraindication being their use in patients with a severely immunocompromised state, but this is debatable. But now we have another evidence-based tool for our patients struggling with symptom recrudescence.
Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician.
Irritable bowel syndrome affects up to 15% of the U.S. adult population, which may be an underestimate. When patients are managing themselves well, their clinical course can be routine. When their self-management is poor, IBS can make life exceedingly challenging for both patients and their clinicians. Many of us may be stepping up our game in patients with known IBS experiencing symptoms, first by recommending a diet low in FODMAPs (fermentable oligo-, di-, and monosaccharides and polyols), which have been shown to reduce IBS symptoms.
My experience is that patients who have been struggling for years with IBS have a high degree of health literacy. And they are usually receptive to trying new things that might make their lives better. The exceptions are the occasional patients who are convinced that they do not have IBS and that their clinicians are just too poorly informed to figure out what the real cause is.
Anything else we can recommend?
Jun Sik Yoon and colleagues have published a clinical trial evaluating the effectiveness of multispecies probiotics on IBS symptoms and changes in the gut microbiota. In this randomized, placebo-controlled trial, 49 subjects (25 probiotics, 24 placebo) with clinically-diagnosed IBS received tablets twice a day for 4 weeks. The primary outcome was the proportion of individuals whose IBS symptoms were substantially relieved at 4 weeks.
Probiotics were associated with a significantly higher proportion of patients with reductions in IBS symptoms (68% vs. 37.5%; P < .05). Probiotics also improved abdominal pain/discomfort and bloating. Fecal analysis revealed increases in the microbiota obtained with the probiotics (J. Gastroenterol. Hepatol. 2014;29:52-9).
So probiotics may help our patients with IBS if a low FODMAP diet does not. But what probiotic (i.e., containing which species) should we select? Species may have different effects on gut motility. Importantly, taking probiotics with certain species does not mean that those species will set up permanent residence in the colon. In the current study, only three of the six species contained in the probiotics were still in the stool after 4 weeks. The author concluded that the alleviation in bowel symptoms was attributable to Bifidobacterium lactis, Lactobacillus rhamnosus, and Streptococcus thermophiles. So let’s tell patients to look for probiotics with these species.
Probiotics are generally safe with the only possible contraindication being their use in patients with a severely immunocompromised state, but this is debatable. But now we have another evidence-based tool for our patients struggling with symptom recrudescence.
Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician.
VIDEO: A fib screening finds 5% of elderly undiagnosed
BARCELONA – Roughly 5% of people aged 75 years or older have undiagnosed atrial fibrillation, based on a population-based screening study in Sweden that has assessed nearly 7,000 people, Dr. Mårten Rosenqvist said during an interview at the annual congress of the European Society of Cardiology.
Once diagnosed with atrial fibrillation, all these people immediately qualified for anticoagulant treatment because of their age-related stroke risk. The StrokeStop study will follow all the screened people for 5 years, as well as a concurrently assembled cohort of unscreened controls, to determine the benefit from screening for preventing strokes. “If we can reduce the rate of stroke, it would be a reason to implement a national atrial fibrillation screening program” for all people aged 75 years and older, said Dr. Rosenqvist, professor of cardiology at the Karolinska Institute in Stockholm.
Dr. Rosenqvist said that he is a consultant to Zenicor, a company that markets an ECG-based device for diagnosing atrial fibrillation being used in the StrokeStop study. He also is a consultant to several drug companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter@mitchelzoler
BARCELONA – Roughly 5% of people aged 75 years or older have undiagnosed atrial fibrillation, based on a population-based screening study in Sweden that has assessed nearly 7,000 people, Dr. Mårten Rosenqvist said during an interview at the annual congress of the European Society of Cardiology.
Once diagnosed with atrial fibrillation, all these people immediately qualified for anticoagulant treatment because of their age-related stroke risk. The StrokeStop study will follow all the screened people for 5 years, as well as a concurrently assembled cohort of unscreened controls, to determine the benefit from screening for preventing strokes. “If we can reduce the rate of stroke, it would be a reason to implement a national atrial fibrillation screening program” for all people aged 75 years and older, said Dr. Rosenqvist, professor of cardiology at the Karolinska Institute in Stockholm.
Dr. Rosenqvist said that he is a consultant to Zenicor, a company that markets an ECG-based device for diagnosing atrial fibrillation being used in the StrokeStop study. He also is a consultant to several drug companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter@mitchelzoler
BARCELONA – Roughly 5% of people aged 75 years or older have undiagnosed atrial fibrillation, based on a population-based screening study in Sweden that has assessed nearly 7,000 people, Dr. Mårten Rosenqvist said during an interview at the annual congress of the European Society of Cardiology.
Once diagnosed with atrial fibrillation, all these people immediately qualified for anticoagulant treatment because of their age-related stroke risk. The StrokeStop study will follow all the screened people for 5 years, as well as a concurrently assembled cohort of unscreened controls, to determine the benefit from screening for preventing strokes. “If we can reduce the rate of stroke, it would be a reason to implement a national atrial fibrillation screening program” for all people aged 75 years and older, said Dr. Rosenqvist, professor of cardiology at the Karolinska Institute in Stockholm.
Dr. Rosenqvist said that he is a consultant to Zenicor, a company that markets an ECG-based device for diagnosing atrial fibrillation being used in the StrokeStop study. He also is a consultant to several drug companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter@mitchelzoler
AT THE ESC CONGRESS 2014
Understanding and Treating Balance Impairment in Multiple Sclerosis
From the Department of Rehabilitation and Movement Science, University of Vermont, Burlington, VT.
Abstract
- Objective: To provide insight into the mechanisms and treatment options associated with balance impairments in individuals with multiple sclerosis (MS).
- Methods: Systematic reviews, randomized controlled trials, and noncontrolled studies were examined to collect current data regarding treatment options aimed at improving balance in MS.
- Results: Balance deficits are common in individuals with MS and result from a diverse set of constraints across multiple systems of postural control. Poor balance often leads to increased fall risk, reduced physical activity, added comorbidities, and decreased quality of life. A variety of exercise options are available for individuals with MS who experience balance and mobility problems. Physical interventions include targeted therapies, such as vestibular rehabilitation and weighted torso training, as well as more general exercise and balance training prescriptions.
- Conclusion: The evidence, albeit preliminary, suggests that therapeutic intervention aimed at ameliorating balance deficits associated with MS be multimodal. Exercise prescriptions should include sensory and motor strategy training, strength development, as well as functional gait activities. Further evidence-based research is needed to improve the management of balance deficits in those with MS and to identify the impact of improved balance on activity participation and quality of life.
Multiple sclerosis (MS) is one of the most common nontraumatic neurologic causes of disability among young adults. With greater awareness and improved diagnostics, more people are being diagnosed with the disease today than in the past. Prevalence estimates in the United States range from 90 to 135 per 100,000 individuals [1], with approximately 400,000 people currently diagnosed [2,3].
MS is a chronic inflammatory disease of the central nervous system typically characterized by increasing muscle weakness, spasticity, fatigue, pain, depression, visual and sensory disturbances, and cognitive difficulties. The clinical course of MS is highly variable and often unpredictable with increasing disability and physical decline spanning a 30- to 40-year period post diagnosis [4]. During this time, advancing symptoms can lead to a number of comorbidities and negatively impact daily functioning, mobility, and community participation [5–7]. From a public health standpoint, the early and disabling impact of symptoms and prolonged physical decline create a significant economic burden. The projected national heath care costs of MS are greater than $7 billion annually [8], with the average total annual cost per patient estimated at over $47,000 [9]. Of this annual cost, indirect costs associated with lost productivity represent the single highest component cost [9,10].
Of the wide range of disease-related challenges, mobility difficulties are most significant. Over 90% of people with MS report mobility difficulties [11], and maintaining mobility is consistently ranked as one of the highest priorities for this group, independent of disease duration or disability level [10,12]. Several studies have demonstrated that loss of balance and mobility contributes to substantial patient burden [13] and lower perceived quality of life [10]. Moreover, poor balance and increased fall risk have been associated with reduced physical activity and other health-related behaviors [14,15].
Because balance and mobility limitations are so prevalent and impacting, targeted treatments aimed at maintaining ambulation and function are critical goals in the management of MS. It is important for physicians and rehabilitation professionals to understand and recognize the underlying sensorimotor mechanisms related to postural instability and initiate appropriate evidenced-based treatments that can improve balance, reduce fall risk, and enhance quality of life for individuals with MS. This review seeks to analyze the evidence on the physical interventions aimed at ameliorating balance and mobility impairments associated with MS in the context of a case example.
Case Study
Initital Presentation and History
Ms. D is a 41-year-old woman with relapse-remitting MS. She was diagnosed 6 years ago after experiencing initial symptoms of optic neuritis and some numbness in her right hand. Since then, she has developed greater weakness in both her legs and reports that her MS significantly impacts her ability to walk, both in terms of distance and the effort needed to ambulate.
Ms. D is independently ambulatory without the use of any assistive device. She reports that her balance is worse when walking on uneven surfaces, moving about in dimly lit environments, turning, or when walking in crowded spaces. Ms. D also shares that she has difficulty standing on one leg while pulling on socks. She states that she must concentrate and focus on her balance when in these challenging situations and that she has to consistently look where she is stepping.
Ms. D does not have any spasticity in muscles of the lower extremities, but on occasion does experience some numbness and tingling in her left foot. She experiences moderate fatigue that requires her to pace herself throughout her daily activities. She reports that her fatigue impacts her ability to concentrate or pay attention for long periods of time and impacts her motivation to engage in social activities. She states that she sleeps restlessly and is consequently tired when she wakes in the morning. Although she is sedentary, she has no history of cardiopulmonary issues or orthopedic problems.
Physical Examination
Ms. D is 5’7” and weighs 175 pounds, with a BMI of 27.4. She presents with observable gait and balance impairment. On physical examination, she exhibits reduced bilateral strength of knee flexors and extensors as well as hip adductors, although the weakness is more evident on the left. On neurologic exam, she exhibits moderate disability in both sensory and cerebellar functioning (resulting in an Expanded Disability Status Scale score of 3.5) [16].
What is postural control?
What balance impairments are associated with MS?
Postural Equilibrium and Balance
For all individuals, postural orientation and equilibrium underlie the effective performance of life’s daily tasks. Postural orientation refers to the alignment of body segments to a reference (such as gravity, the support surface, or an object in the visual field), while postural equilibrium—often equated with balance—refers to maintaining or re-acquiring the body’s center of gravity (CoG) within the base of support (BoS) [17,18]. This paper will focus on postural equilibrium with MS across multiple contexts of balance tasks.
Horak [18] described contexts of balance tasks that affect the mechanisms of maintaining postural equilibrium. Some of these contextual variables include
- Biomechanical constraints (eg, strength)
- Limits of stability (functional reach, maximum lean)
- Anticipatory postural adjustments (voluntary postural transitions)
- Automatic postural responses (balance recovery from external perturbations)
- Sensory orientation (ability to reweight sensory information [somatosensory, visual, vestibular] depending on context
- Dynamic control during gait
- Cognitive-motor interaction (balance impairments when also performing a cognitive task)
Emotion represents another contextual variable of interest, because mood and fear can significantly modify postural control [19–23]. Knowing the contextual factors that modify balance control provides insight into underlying neuropathology associated with impairments of these postural control variables [24,25] as well as insight into what should be included during the examination of patients with MS based on patient descriptions of their symptoms and functional challenges.
Balance Assessment
Balance assessment indicates that Ms. D cannot abduct and hold either leg to her side for any noticeable length of time, cannot reach forward adequately without lifting her heels off the ground or falling forward, and cannot stand on one leg for more than 10 seconds without losing balance. She also needs to take multiple steps to recover balance with any slight perturbation and is unable to maintain stability while standing on foam with her eyes closed. She shows significant imbalance when rising from a chair, walking forward, and turning to come back to sit.
For Ms. D, the clinical balance exam suggests pervasive impairment of hip strength, limits of stability, anticipatory postural adjustments, postural responses, sensory integration, and gait. Furthermore, her reported need to focus vision on her gait is in accordance with compensation for existing sensory impairments. Lastly, fatigue and attention demand likely enhance the presentation of balance impairment.
What are the consequences of balance impairments associated with MS?
Balance impairments present considerable health problems for adults with MS. Greater than 50% of individuals with MS report falling in any 6-month period [81–85], with the incidence of recurrent falls reported to be as high as 9 falls per year [86]. In addition, fall-related injuries, including fractures, are more common with MS, although this increased risk is considerably greater for women with MS than men [86–90].
Common risk factors for falling in people with MS include variable or deteriorating MS status [90–96], problems with balance or mobility [88,92–94,96–99], use of walking aids [88,93,97], lower balance confidence [86,98], reduced executive functioning [99] and greater fatigue [85]. Increased postural sway [52,99,100], slower walking speed [99], greater gait asymmetry and variability [92,101], slower choice stepping reaction time [99], impaired forward limits of stability [92,99], impaired visually dependent sway [92,99], and leg weakness [88,92] have also been found predictive of future falls in MS. A link has also emerged between cognitive impairment and fall risk [86,95,99,102].
Fear of falling and fall-induced injuries are also the most common causes of restricted activity and disability for individuals with MS [14]. Research has shown that future physical activity associates with fear of falling, and fear of falling subsequently associated with lower-limb strength asymmetry and decreased limits of stability rather than past experience of falling [103]. Similarly, the perceived benefits of physical activity and an individual’s self-efficacy to engage in physical activity predict reported levels of physical activity independent of disability level for individuals with MS [104]. Thus, psychological perception represents an important, and potentially modifiable, correlate of physical activity.
Moreover, individuals with MS experience a high risk of cardiovascular disease and other chronic health conditions associated with deconditioning, as unfavorable blood lipid levels, poor glucose profiles, and obesity have been observed in this population [105]. Comorbid conditions, secondary conditions, and health behaviors are increasingly recognized to be important factors influencing a range of outcomes in MS [107].
Further History
Consistent with the consequences of balance and mobility impairment, Ms. D reports that she loses her balance and nearly falls at least 1 time per week while engaged in daily activities. She also shares that she fell 2 months ago while walking outside and across the lawn to get the mail. Her confidence is low for many daily tasks such as climbing stairs, picking up objects from the floor, reaching when on tiptoes, or walking on ramps or on slippery surfaces. While Ms. D is independent in all activities of daily living, she currently does not work due to her fatigue and poor balance. She indicates that she is not very physically active and feels somewhat isolated and depressed because her balance and mobility challenges keep her from going out with friends and socializing.
What exercise approaches are available to ameliorate the balance deficits associated with MS?
There are a variety of therapeutic approaches for the treatment of poor balance in MS. While pharmacologic treatment typically encompasses disease-modifying therapies, specific medications can also help in the management of symptoms (ie, fatigue, spasticity, gait variability) that can negatively impact balance and mobility. Other rehabilitative strategies for balance impairment include gait training, assistive devices for mobility, and environmental modifications for fall prevention. Although all of these avenues offer viable treatment options for improving balance, exercise is increasingly appreciated as an important adjunct to the rehabilitation management of MS [107], especially in terms of improving balance deficits, optimizing daily functioning, and increasing participation across various life contexts.
The diversity of exercise options available for individuals with MS who experience balance and mobility problems is expanding. Moreover, mounting evidence suggests that exercise is well tolerated by participants with the disease[108–110] and that individuals with MS can exercise sufficiently to improve their fitness, function, and quality of life [109,110]. Given the inherent variability of MS and the heterogeneity of symptoms and disease course across individuals, however, no one exercise prescription is optimal for all those diagnosed. Instead, treatment goals must be individualized and functionally based [107] with ongoing evaluation and modification of treatment plans due to disease progression, symptom fluctuations, and functional decline [107,111]. Regardless of specific approach, the aim of any exercise intervention is to reduce activity limitations, encourage participation, and facilitate independence and life satisfaction in those with the disease [112].
Resistance Training
There have been several structured reviews of exercise research in MS [108,110,113,114]. The existing evidence supports resistance exercise as compared with no exercise for improving general balance [115] or performing tasks such as a chair transfer [116] or sit-to-stand [117]. Two randomized controlled trials (RCTs) also revealed significant increases in functional reach (ie, limits of stability) as a result of progressive resistance exercise [118,119]. Resistance exercise has not, however, facilitated greater benefit over traditional rehabilitation in other postural control contexts such as those involving postural transitions, sensory integration, or postural sway [120–122].
The effects of resistance training on mobility have also been inconsistent. While several studies showed no significant improvement in functional mobility [118,122,123], a positive improvement was observed in other research [119,124,125]. Likewise, stair climbing was shown to improve in 2 noncontrolled studies [125,126] and one RCT [117] but not in another [127].
In a recent RCT to evaluate the comparative effectiveness of different methods of resistance training, Hayes et al [123] determined that the addition of high-intensity, eccentric resistance training offered no additional benefit over standard concentric resistance exercise in improving static standing balance and stair climbing. In addition, compared with no exercise or a home-based program to improve strength and balance, progressive resistance cycling showed significantly greater effect on functional reach and timed up-and-go in individuals with moderate MS [128]. Nonetheless, evidence for the efficacy of home-based training remains equivocal given issues of motivation, adherence, and training intensity [115,118,128].
Taken together, the systematic reviews to date conclude that there is insufficient evidence for the effects of resistance exercise on balance in MS, thus making solid evidenced-based conclusions difficult [108,110,113,129]. Moreover, it is difficult to ascertain a definitive and most efficacious exercise prescription for improving balance in MS given the inconsistency in protocols and findings across studies. There is some support, albeit preliminary, for progressive resistance training as a modality to improve balance, especially those functional tasks demanding greater strength [113]. Nonetheless, resistance training may contribute to improved posture and gait given it directly addresses one context of postural control, but it may not be fully effective due to lack of training to modify central neural control of posture in other contexts.
Aerobic Exercise
Many of the studies examining aerobic exercise in MS more often target walking capacity, exercise tolerance, fatigue, and quality of life than balance [130]. The limited research that has focused on aerobic exercise for balance improvement has shown equal benefit to that achieved from resistance exercise in those contexts involving limits of stability and dynamic balance while stepping or walking [119]. This finding was reasonable given that the aerobic exercise included step-up and treadmill walking. Still, it has been recommended that, for most people with MS, aerobic exercise also incorporate a degree of balance training [109].
Combined Exercise
The more recent exercise research involving people with MS often combines some aspect of aerobic, strengthening, and/or balance exercise. While only a few RCTs have examined the effects of combined training in this population, preliminary evidence suggests it is well tolerated and may have some benefit for improving function [110]. While one study found no differences in static balance after a combined strength and aerobic training program [131], review of the exercise protocol revealed that the training regime had only incorporated 2 standing exercises. Other studies more intentionally combining strength and balance exercise have demonstrated benefits in balance confidence [132], standing static balance or postural sway [132–134], step climbing [133], and functional mobility [135]. Combining aerobic exercise and strengthening has also been effective in reducing falls in those with MS [85].
Balance-Specific Exercise
Only one balance-specific RCT has been published to date. In this study, outcomes from balance training involving both motor and sensory strategies were compared to training of only motor strategies and to standard therapy [136]. Both the balance training groups significantly reduced the number of falls post intervention as compared to the conventional treatment group. There were no observed differences in self-reported balance confidence across the groups, although both the balance training groups significantly improved in static and dynamic standing balance over that achieved by the standard treatment group. The fact that only the group engaged in sensory training differed significantly on dynamic gait highlights the importance of sensory integration for dynamic balance and gait.
Video Game–Assisted Exercises
Novel rehabilitative approaches have taken advantage of advances in virtual reality and visual feedback training to improve balance and mobility deficits in people with MS. Exercise using the general physical activity games on the Nintendo Wii Fit provided short-term improvement in standing balance, strength, gait and physical activity in people with MS [137]. This general exercise offered no significant gains in self-efficacy, fatigue impact or quality of life, and physical activity levels returned to baseline levels 14 weeks after exercising. Subsequent review has, however, highlighted concerns that current commercially available video options for general exercise may not be sufficiently adaptive for people with moderate disability, leading to intimidation and low adherence [138].
Beyond general physical activity, the Wii Balance Board System has also been used to specifically target balance and mobility deficits in MS. Although one study found no significant benefit from Wii Fit balance exercise in balance performance and walking ability [139], other studies have shown positive effects in standing sway, static balance, dynamic stepping, walking speed, and MS impact [140–142].
The evidence, albeit preliminary, thus suggests that the Wii Fit may offer a feasible adjunct to traditional rehabilitation approaches, especially because the exercise can be done at home without the need for continuous support from a practitioner and because the technology aids in overcoming access barriers often associated with community-based physical activity programs [138]. Nonetheless, research shows that Wii Balance Board System training is more specific for static standing balance than for dynamic balance or mobility, the technology is not positively viewed by those with more advanced symptoms, and there exists a risk of adverse affects and training-related injuries associated with home-based use of the Wii [137,140].
Vestibular Rehabilitation Exercise
Vestibular rehabilitation is a specialized treatment approach that strengthens the vestibular sensory system by retraining the brain to recognize and process signals from the vestibular system and coordinate these with visual and proprioceptive inputs. To date, there has only been one RCT investigating the effects of vestibular rehabilitation on balance in adults with MS [143]. In this study, the outcomes of a standard vestibular rehabilitation program to those of an exercise regime as well as to no intervention were compared. The vestibular rehabilitation program consisted of static and dynamic tasks performed with changing bases of support, on various surfaces, with eyes open or closed, and different head movements. The 6-week vestibular rehabilitation program resulted in both statistically significant and clinically relevant change in standing balance under various sensory conditions compared with either of the other two groups, although no significant difference was found in walking capacity across groups.
Weighted Torso Training
Balance-based torso weighting (BBTW) involves strategically placing small weights on the trunk of an individual to decrease balance deviations observed during quiet stance, perturbed standing, walking, and transitioning [144]. While the specific mechanism underlying the therapeutic effect of rehabilitative weighting has been debated [145], various suggestions include joint compression to encourage co-contraction, enhanced conscious awareness of body segments, and biomechanical changes via shifting of the center of mass [146].
The one RCT examining the effectiveness of BBTW in people with MS found immediate and significant effects of BBTW on postural control and upright mobility [146]. The research confirmed preliminary investigations of BBTW in MS [144,147], demonstrating that BBTW can improve walking speed as well as functional tasks involving standing, walking, turning, and sitting down.
Whole Body Vibration
Whole body vibration (WBV) has been employed across a variety of neurological populations as a means of improving muscle tone, sensation, strength, stability, and functional performance. In WBV, multidimensional vibrations are transferred to an individual performing static or dynamic movements on an oscillating platform. The vibrations are believed to facilitate both neuroendocrine responses as well as motor unit recruitment [148–150].
Results have been inconsistent regarding the effectiveness of WBV as a way of improving postural control and functional mobility in individuals with MS. A few studies have shown significant positive effects of WBV lasting from 1 to 4 weeks on functional mobility [151–153], strength [151,153,154], walking speed [152,155], and standing balance [152]. Walking endurance has also been affected by vibration training designed to improve muscular endurance [156]. Although there have been noted benefits of WBV, these benefits were not significantly more advantageous than those offered by a vibration program in conjunction with lower-limb stretching and strengthening exercises [157] or in addition to a traditional rehabilitation program [154].
There has also been some evidence to show that prolonged WBV does not improve postural stability or functional mobility in individuals with MS after training [155,156,158]. Likewise, there is contradictory evidence supporting the use of WBV in improving walking speed [157], functional reaching [152,153] or overall quality of life [152].
While WBV does not appear to have a detrimental effect on symptoms of MS, there is insufficient evidence regarding its beneficial effects on balance, gait, muscle strength and quality of life compared to other interventions. Future research is necessary to examine various protocols in terms of vibratory parameters and length of intervention before specific prescriptions can be offered [159].
Aquatics
Although aquatic exercise has often been recommended for individuals with MS, much of the research employing this therapeutic modality has focused on outcomes of pain, fatigue, cardiorespiratory fitness, gait, and quality of life [160–164]. Research focused on aquatic exercise for improved balance is limited. Nonetheless, significant improvements in standing balance and functional mobility have been shown for individuals with MS following aquatic exercise [165,166]. Similar results on standing balance and functional mobility have also been shown from Ai Chi, a program in which Tai Chi is combined with other techniques and performed standing in shoulder-depth water using a combination of deep breathing and slow, broad movements of the arms, legs, and torso [167]. These methods of intervention, however, still lack evidence from rigorous designs involving control groups and randomization.
Yoga
Yoga has also been explored as a means to improve physical and mental health outcomes in MS. While an initial study showed no significant changes in one-leg stance from an Iyengar yoga program [168], more recent research found Ananda yoga practice effective in improving standing balance [169]. Likewise, other research has shown that static and dynamic standing balance improved after yoga practice, although not significantly better than that from treadmill exercise training [170].
Kickboxing
There has been only one study to date, albeit not an RCT, that has examined kickboxing as a training modality to improve balance in MS. Although kickboxing was found to be a feasible exercise activity, not all participants demonstrated improved balance and mobility outcomes [171]. As such, further investigation of this novel treatment approach is warranted.
Hippotherapy
Hippotherapy has also been employed as a means of balance training because the multidimensional and random nature of the horse’s movement requires the rider to process increased sensory information and make the necessary anticipatory and reactive adjustments for postural control. While one study reported no improvement in postural sway after hippotherapy [172], other research has shown some benefit in balance and gait after riding [173,174]. Although preliminary, findings from 2 of the studies reveal that hippotherapy may be most beneficial for those with primary progressive MS compared to other subtypes of MS [175]. While hippotherapy may have a positive effect on balance in individuals with MS, the data is limited and lacks rigorous examination through randomized controlled study of large samples in order to allow for its advocacy as a primary rehabilitation modality at this time.
What exercise prescription is indicated for Ms. D?
Because Ms. D’s balance deficits have begun to limit her daily functioning and increase her risk of falling, a formal and targeted balance intervention is warranted. Research confirms that exercise would be well tolerated by Ms. D and supports the feasibility of her engaging in various exercise modalities. Although a number of exercise inter-vention studies involving people with MS have been described in the literature, their clinical utility and results in improving balance and mobility are varied. Nonetheless, there is preliminary evidence suggesting that exercise training may have positive effects on balance and functional mobility and could offer Ms. D benefit. This is especially true given that much of the exercise research included individuals with mild or minimal disability and at same stage of disease progression as Ms. D.
Since Ms. D’s balance problems stem from a range of postural impairments across multiple contexts of balance control, her treatment approach must incorporate exercises that include and integrate these underlying control systems. A targeted and multimodal balance exercise program, rather than general physical activity, may be most efficacious toward this end.
Intervention Prescription
Ms. D has poor ability to utilize somatosensory and vestibular inputs in order to dynamically weight the influence of multiple sensory modalities for the control of standing sway under varying sensory conditions. This visual dependence contributes to her poor balance and increases her fall risk when visual inputs are absent (ie, walking in dimly lit rooms) or when optic flow is incongruent or when visual distractions are present (ie, walking in dynamic contexts such as crowded spaces). Ms. D would benefit from exercises requiring greater use of proprioceptive and vestibular inputs, thereby facilitating improved sensory integration. Exercises performed with eyes closed as well as those completed on mats, foam, or other compliant surfaces would be beneficial. She might also benefit from specific vestibular rehabilitation exercises as this approach has resulted in improved sensory integration [143]. Given that Ms. D must regularly concentrate and focus on her balance and consistently look where she is stepping, her balance exercise program should also address her central processing and attentional deficits by including dual-task training [26].
Ms. D also noted that her MS significantly impacts her ability to walk both in terms of effort and distance and adversely affects her participation in social events. Supplemental to her balance exercise program, aerobic exercise, particularly treadmill walking, may offer some benefit both in terms of her endurance as well as gait. While some of the more targeted modalities such as hippotherapy, yoga, and kickboxing have not been extensively studied, they do offer promise and could be used as adjuncts in order to facilitate Ms. D’s motivation and adherence through more diverse programming. Lastly, and although requiring further study, cognitive-behavioral interventions and patient education may be warranted to help Ms. D overcome her fear of falling, low exercise self-efficacy, and any negative beliefs regarding the potential benefits of exercise.
What additional research is needed?
Although valuable insight has been gained from studies of balance and gait impairment with MS, many contexts remain understudied, particularly with regard to understanding both the neuroanatomical and neurophysiologic pathologies that underlie the behavioral impairments of balance and gait in MS. Further, the value of applying this knowledge of balance impairment to clinical diagnostics and prognostics requires further study in order to develop the most cost- and time-effective exams and evidence-based treatment approaches.
Based on the research to date, it remains difficult to draw definitive evidenced-based conclusions regarding what specific exercise mode or training dose would be most beneficial for Ms. D and others with MS. Moreover, while there exists some evidence of efficacious balance outcomes from exercise training, many of the studies involved individuals with mild MS. Only a few studies to date have included those with more advanced disability, thus making prescription generalizations to those more moderately affected by MS tenuous. Irrespective of specific approach, all modalities of balance-oriented interventions require larger controlled studies, inclusion of those with advancing disability status, long-term follow-up, an evaluation of optimal dose or duration, and outcomes on the neural mechanisms of effect.
Summary
Challenges to balance and mobility present serious consequences for those with MS, as falls and fear of falling lead to poor health outcomes and low quality of life. Given that postural impairments result from a diverse set of deficits in different underlying control systems, therapeutic intervention should be multimodal. Exercise prescription should address all affected contexts of postural control, including sensory and motor strategy training during postural transitions as well as induced postural perturbations, strength development, and gait activity. Evidence from clinical trials suggests that targeted balance oriented exercise in people with MS has the potential to improve balance and functional mobility, although more rigorous study on the topic is needed.
Corresponding author: Susan L. Kasser, PhD, Dept. of Rehabilitation and Movement Science, Univ. of Vermont, 306 Rowell Bldg, 106 Carrigan Dr, Burlington, VT 05405, [email protected]
Financial disclosures: None.
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174. Silkwood-Sherer D, Warmbier H. Effects of hippotherapy on postural stability in persons with multiple sclerosis: a pilot study. J Neurol Phys Ther 2007;31:77–84.
175. Bronson C, Brewerton K, Ong J, et al. Does hippotherapy improve balance in persons with multiple sclerosis: a systematic review. Eur J Phys Rehabil Med 2010;46:347–53.
From the Department of Rehabilitation and Movement Science, University of Vermont, Burlington, VT.
Abstract
- Objective: To provide insight into the mechanisms and treatment options associated with balance impairments in individuals with multiple sclerosis (MS).
- Methods: Systematic reviews, randomized controlled trials, and noncontrolled studies were examined to collect current data regarding treatment options aimed at improving balance in MS.
- Results: Balance deficits are common in individuals with MS and result from a diverse set of constraints across multiple systems of postural control. Poor balance often leads to increased fall risk, reduced physical activity, added comorbidities, and decreased quality of life. A variety of exercise options are available for individuals with MS who experience balance and mobility problems. Physical interventions include targeted therapies, such as vestibular rehabilitation and weighted torso training, as well as more general exercise and balance training prescriptions.
- Conclusion: The evidence, albeit preliminary, suggests that therapeutic intervention aimed at ameliorating balance deficits associated with MS be multimodal. Exercise prescriptions should include sensory and motor strategy training, strength development, as well as functional gait activities. Further evidence-based research is needed to improve the management of balance deficits in those with MS and to identify the impact of improved balance on activity participation and quality of life.
Multiple sclerosis (MS) is one of the most common nontraumatic neurologic causes of disability among young adults. With greater awareness and improved diagnostics, more people are being diagnosed with the disease today than in the past. Prevalence estimates in the United States range from 90 to 135 per 100,000 individuals [1], with approximately 400,000 people currently diagnosed [2,3].
MS is a chronic inflammatory disease of the central nervous system typically characterized by increasing muscle weakness, spasticity, fatigue, pain, depression, visual and sensory disturbances, and cognitive difficulties. The clinical course of MS is highly variable and often unpredictable with increasing disability and physical decline spanning a 30- to 40-year period post diagnosis [4]. During this time, advancing symptoms can lead to a number of comorbidities and negatively impact daily functioning, mobility, and community participation [5–7]. From a public health standpoint, the early and disabling impact of symptoms and prolonged physical decline create a significant economic burden. The projected national heath care costs of MS are greater than $7 billion annually [8], with the average total annual cost per patient estimated at over $47,000 [9]. Of this annual cost, indirect costs associated with lost productivity represent the single highest component cost [9,10].
Of the wide range of disease-related challenges, mobility difficulties are most significant. Over 90% of people with MS report mobility difficulties [11], and maintaining mobility is consistently ranked as one of the highest priorities for this group, independent of disease duration or disability level [10,12]. Several studies have demonstrated that loss of balance and mobility contributes to substantial patient burden [13] and lower perceived quality of life [10]. Moreover, poor balance and increased fall risk have been associated with reduced physical activity and other health-related behaviors [14,15].
Because balance and mobility limitations are so prevalent and impacting, targeted treatments aimed at maintaining ambulation and function are critical goals in the management of MS. It is important for physicians and rehabilitation professionals to understand and recognize the underlying sensorimotor mechanisms related to postural instability and initiate appropriate evidenced-based treatments that can improve balance, reduce fall risk, and enhance quality of life for individuals with MS. This review seeks to analyze the evidence on the physical interventions aimed at ameliorating balance and mobility impairments associated with MS in the context of a case example.
Case Study
Initital Presentation and History
Ms. D is a 41-year-old woman with relapse-remitting MS. She was diagnosed 6 years ago after experiencing initial symptoms of optic neuritis and some numbness in her right hand. Since then, she has developed greater weakness in both her legs and reports that her MS significantly impacts her ability to walk, both in terms of distance and the effort needed to ambulate.
Ms. D is independently ambulatory without the use of any assistive device. She reports that her balance is worse when walking on uneven surfaces, moving about in dimly lit environments, turning, or when walking in crowded spaces. Ms. D also shares that she has difficulty standing on one leg while pulling on socks. She states that she must concentrate and focus on her balance when in these challenging situations and that she has to consistently look where she is stepping.
Ms. D does not have any spasticity in muscles of the lower extremities, but on occasion does experience some numbness and tingling in her left foot. She experiences moderate fatigue that requires her to pace herself throughout her daily activities. She reports that her fatigue impacts her ability to concentrate or pay attention for long periods of time and impacts her motivation to engage in social activities. She states that she sleeps restlessly and is consequently tired when she wakes in the morning. Although she is sedentary, she has no history of cardiopulmonary issues or orthopedic problems.
Physical Examination
Ms. D is 5’7” and weighs 175 pounds, with a BMI of 27.4. She presents with observable gait and balance impairment. On physical examination, she exhibits reduced bilateral strength of knee flexors and extensors as well as hip adductors, although the weakness is more evident on the left. On neurologic exam, she exhibits moderate disability in both sensory and cerebellar functioning (resulting in an Expanded Disability Status Scale score of 3.5) [16].
What is postural control?
What balance impairments are associated with MS?
Postural Equilibrium and Balance
For all individuals, postural orientation and equilibrium underlie the effective performance of life’s daily tasks. Postural orientation refers to the alignment of body segments to a reference (such as gravity, the support surface, or an object in the visual field), while postural equilibrium—often equated with balance—refers to maintaining or re-acquiring the body’s center of gravity (CoG) within the base of support (BoS) [17,18]. This paper will focus on postural equilibrium with MS across multiple contexts of balance tasks.
Horak [18] described contexts of balance tasks that affect the mechanisms of maintaining postural equilibrium. Some of these contextual variables include
- Biomechanical constraints (eg, strength)
- Limits of stability (functional reach, maximum lean)
- Anticipatory postural adjustments (voluntary postural transitions)
- Automatic postural responses (balance recovery from external perturbations)
- Sensory orientation (ability to reweight sensory information [somatosensory, visual, vestibular] depending on context
- Dynamic control during gait
- Cognitive-motor interaction (balance impairments when also performing a cognitive task)
Emotion represents another contextual variable of interest, because mood and fear can significantly modify postural control [19–23]. Knowing the contextual factors that modify balance control provides insight into underlying neuropathology associated with impairments of these postural control variables [24,25] as well as insight into what should be included during the examination of patients with MS based on patient descriptions of their symptoms and functional challenges.
Balance Assessment
Balance assessment indicates that Ms. D cannot abduct and hold either leg to her side for any noticeable length of time, cannot reach forward adequately without lifting her heels off the ground or falling forward, and cannot stand on one leg for more than 10 seconds without losing balance. She also needs to take multiple steps to recover balance with any slight perturbation and is unable to maintain stability while standing on foam with her eyes closed. She shows significant imbalance when rising from a chair, walking forward, and turning to come back to sit.
For Ms. D, the clinical balance exam suggests pervasive impairment of hip strength, limits of stability, anticipatory postural adjustments, postural responses, sensory integration, and gait. Furthermore, her reported need to focus vision on her gait is in accordance with compensation for existing sensory impairments. Lastly, fatigue and attention demand likely enhance the presentation of balance impairment.
What are the consequences of balance impairments associated with MS?
Balance impairments present considerable health problems for adults with MS. Greater than 50% of individuals with MS report falling in any 6-month period [81–85], with the incidence of recurrent falls reported to be as high as 9 falls per year [86]. In addition, fall-related injuries, including fractures, are more common with MS, although this increased risk is considerably greater for women with MS than men [86–90].
Common risk factors for falling in people with MS include variable or deteriorating MS status [90–96], problems with balance or mobility [88,92–94,96–99], use of walking aids [88,93,97], lower balance confidence [86,98], reduced executive functioning [99] and greater fatigue [85]. Increased postural sway [52,99,100], slower walking speed [99], greater gait asymmetry and variability [92,101], slower choice stepping reaction time [99], impaired forward limits of stability [92,99], impaired visually dependent sway [92,99], and leg weakness [88,92] have also been found predictive of future falls in MS. A link has also emerged between cognitive impairment and fall risk [86,95,99,102].
Fear of falling and fall-induced injuries are also the most common causes of restricted activity and disability for individuals with MS [14]. Research has shown that future physical activity associates with fear of falling, and fear of falling subsequently associated with lower-limb strength asymmetry and decreased limits of stability rather than past experience of falling [103]. Similarly, the perceived benefits of physical activity and an individual’s self-efficacy to engage in physical activity predict reported levels of physical activity independent of disability level for individuals with MS [104]. Thus, psychological perception represents an important, and potentially modifiable, correlate of physical activity.
Moreover, individuals with MS experience a high risk of cardiovascular disease and other chronic health conditions associated with deconditioning, as unfavorable blood lipid levels, poor glucose profiles, and obesity have been observed in this population [105]. Comorbid conditions, secondary conditions, and health behaviors are increasingly recognized to be important factors influencing a range of outcomes in MS [107].
Further History
Consistent with the consequences of balance and mobility impairment, Ms. D reports that she loses her balance and nearly falls at least 1 time per week while engaged in daily activities. She also shares that she fell 2 months ago while walking outside and across the lawn to get the mail. Her confidence is low for many daily tasks such as climbing stairs, picking up objects from the floor, reaching when on tiptoes, or walking on ramps or on slippery surfaces. While Ms. D is independent in all activities of daily living, she currently does not work due to her fatigue and poor balance. She indicates that she is not very physically active and feels somewhat isolated and depressed because her balance and mobility challenges keep her from going out with friends and socializing.
What exercise approaches are available to ameliorate the balance deficits associated with MS?
There are a variety of therapeutic approaches for the treatment of poor balance in MS. While pharmacologic treatment typically encompasses disease-modifying therapies, specific medications can also help in the management of symptoms (ie, fatigue, spasticity, gait variability) that can negatively impact balance and mobility. Other rehabilitative strategies for balance impairment include gait training, assistive devices for mobility, and environmental modifications for fall prevention. Although all of these avenues offer viable treatment options for improving balance, exercise is increasingly appreciated as an important adjunct to the rehabilitation management of MS [107], especially in terms of improving balance deficits, optimizing daily functioning, and increasing participation across various life contexts.
The diversity of exercise options available for individuals with MS who experience balance and mobility problems is expanding. Moreover, mounting evidence suggests that exercise is well tolerated by participants with the disease[108–110] and that individuals with MS can exercise sufficiently to improve their fitness, function, and quality of life [109,110]. Given the inherent variability of MS and the heterogeneity of symptoms and disease course across individuals, however, no one exercise prescription is optimal for all those diagnosed. Instead, treatment goals must be individualized and functionally based [107] with ongoing evaluation and modification of treatment plans due to disease progression, symptom fluctuations, and functional decline [107,111]. Regardless of specific approach, the aim of any exercise intervention is to reduce activity limitations, encourage participation, and facilitate independence and life satisfaction in those with the disease [112].
Resistance Training
There have been several structured reviews of exercise research in MS [108,110,113,114]. The existing evidence supports resistance exercise as compared with no exercise for improving general balance [115] or performing tasks such as a chair transfer [116] or sit-to-stand [117]. Two randomized controlled trials (RCTs) also revealed significant increases in functional reach (ie, limits of stability) as a result of progressive resistance exercise [118,119]. Resistance exercise has not, however, facilitated greater benefit over traditional rehabilitation in other postural control contexts such as those involving postural transitions, sensory integration, or postural sway [120–122].
The effects of resistance training on mobility have also been inconsistent. While several studies showed no significant improvement in functional mobility [118,122,123], a positive improvement was observed in other research [119,124,125]. Likewise, stair climbing was shown to improve in 2 noncontrolled studies [125,126] and one RCT [117] but not in another [127].
In a recent RCT to evaluate the comparative effectiveness of different methods of resistance training, Hayes et al [123] determined that the addition of high-intensity, eccentric resistance training offered no additional benefit over standard concentric resistance exercise in improving static standing balance and stair climbing. In addition, compared with no exercise or a home-based program to improve strength and balance, progressive resistance cycling showed significantly greater effect on functional reach and timed up-and-go in individuals with moderate MS [128]. Nonetheless, evidence for the efficacy of home-based training remains equivocal given issues of motivation, adherence, and training intensity [115,118,128].
Taken together, the systematic reviews to date conclude that there is insufficient evidence for the effects of resistance exercise on balance in MS, thus making solid evidenced-based conclusions difficult [108,110,113,129]. Moreover, it is difficult to ascertain a definitive and most efficacious exercise prescription for improving balance in MS given the inconsistency in protocols and findings across studies. There is some support, albeit preliminary, for progressive resistance training as a modality to improve balance, especially those functional tasks demanding greater strength [113]. Nonetheless, resistance training may contribute to improved posture and gait given it directly addresses one context of postural control, but it may not be fully effective due to lack of training to modify central neural control of posture in other contexts.
Aerobic Exercise
Many of the studies examining aerobic exercise in MS more often target walking capacity, exercise tolerance, fatigue, and quality of life than balance [130]. The limited research that has focused on aerobic exercise for balance improvement has shown equal benefit to that achieved from resistance exercise in those contexts involving limits of stability and dynamic balance while stepping or walking [119]. This finding was reasonable given that the aerobic exercise included step-up and treadmill walking. Still, it has been recommended that, for most people with MS, aerobic exercise also incorporate a degree of balance training [109].
Combined Exercise
The more recent exercise research involving people with MS often combines some aspect of aerobic, strengthening, and/or balance exercise. While only a few RCTs have examined the effects of combined training in this population, preliminary evidence suggests it is well tolerated and may have some benefit for improving function [110]. While one study found no differences in static balance after a combined strength and aerobic training program [131], review of the exercise protocol revealed that the training regime had only incorporated 2 standing exercises. Other studies more intentionally combining strength and balance exercise have demonstrated benefits in balance confidence [132], standing static balance or postural sway [132–134], step climbing [133], and functional mobility [135]. Combining aerobic exercise and strengthening has also been effective in reducing falls in those with MS [85].
Balance-Specific Exercise
Only one balance-specific RCT has been published to date. In this study, outcomes from balance training involving both motor and sensory strategies were compared to training of only motor strategies and to standard therapy [136]. Both the balance training groups significantly reduced the number of falls post intervention as compared to the conventional treatment group. There were no observed differences in self-reported balance confidence across the groups, although both the balance training groups significantly improved in static and dynamic standing balance over that achieved by the standard treatment group. The fact that only the group engaged in sensory training differed significantly on dynamic gait highlights the importance of sensory integration for dynamic balance and gait.
Video Game–Assisted Exercises
Novel rehabilitative approaches have taken advantage of advances in virtual reality and visual feedback training to improve balance and mobility deficits in people with MS. Exercise using the general physical activity games on the Nintendo Wii Fit provided short-term improvement in standing balance, strength, gait and physical activity in people with MS [137]. This general exercise offered no significant gains in self-efficacy, fatigue impact or quality of life, and physical activity levels returned to baseline levels 14 weeks after exercising. Subsequent review has, however, highlighted concerns that current commercially available video options for general exercise may not be sufficiently adaptive for people with moderate disability, leading to intimidation and low adherence [138].
Beyond general physical activity, the Wii Balance Board System has also been used to specifically target balance and mobility deficits in MS. Although one study found no significant benefit from Wii Fit balance exercise in balance performance and walking ability [139], other studies have shown positive effects in standing sway, static balance, dynamic stepping, walking speed, and MS impact [140–142].
The evidence, albeit preliminary, thus suggests that the Wii Fit may offer a feasible adjunct to traditional rehabilitation approaches, especially because the exercise can be done at home without the need for continuous support from a practitioner and because the technology aids in overcoming access barriers often associated with community-based physical activity programs [138]. Nonetheless, research shows that Wii Balance Board System training is more specific for static standing balance than for dynamic balance or mobility, the technology is not positively viewed by those with more advanced symptoms, and there exists a risk of adverse affects and training-related injuries associated with home-based use of the Wii [137,140].
Vestibular Rehabilitation Exercise
Vestibular rehabilitation is a specialized treatment approach that strengthens the vestibular sensory system by retraining the brain to recognize and process signals from the vestibular system and coordinate these with visual and proprioceptive inputs. To date, there has only been one RCT investigating the effects of vestibular rehabilitation on balance in adults with MS [143]. In this study, the outcomes of a standard vestibular rehabilitation program to those of an exercise regime as well as to no intervention were compared. The vestibular rehabilitation program consisted of static and dynamic tasks performed with changing bases of support, on various surfaces, with eyes open or closed, and different head movements. The 6-week vestibular rehabilitation program resulted in both statistically significant and clinically relevant change in standing balance under various sensory conditions compared with either of the other two groups, although no significant difference was found in walking capacity across groups.
Weighted Torso Training
Balance-based torso weighting (BBTW) involves strategically placing small weights on the trunk of an individual to decrease balance deviations observed during quiet stance, perturbed standing, walking, and transitioning [144]. While the specific mechanism underlying the therapeutic effect of rehabilitative weighting has been debated [145], various suggestions include joint compression to encourage co-contraction, enhanced conscious awareness of body segments, and biomechanical changes via shifting of the center of mass [146].
The one RCT examining the effectiveness of BBTW in people with MS found immediate and significant effects of BBTW on postural control and upright mobility [146]. The research confirmed preliminary investigations of BBTW in MS [144,147], demonstrating that BBTW can improve walking speed as well as functional tasks involving standing, walking, turning, and sitting down.
Whole Body Vibration
Whole body vibration (WBV) has been employed across a variety of neurological populations as a means of improving muscle tone, sensation, strength, stability, and functional performance. In WBV, multidimensional vibrations are transferred to an individual performing static or dynamic movements on an oscillating platform. The vibrations are believed to facilitate both neuroendocrine responses as well as motor unit recruitment [148–150].
Results have been inconsistent regarding the effectiveness of WBV as a way of improving postural control and functional mobility in individuals with MS. A few studies have shown significant positive effects of WBV lasting from 1 to 4 weeks on functional mobility [151–153], strength [151,153,154], walking speed [152,155], and standing balance [152]. Walking endurance has also been affected by vibration training designed to improve muscular endurance [156]. Although there have been noted benefits of WBV, these benefits were not significantly more advantageous than those offered by a vibration program in conjunction with lower-limb stretching and strengthening exercises [157] or in addition to a traditional rehabilitation program [154].
There has also been some evidence to show that prolonged WBV does not improve postural stability or functional mobility in individuals with MS after training [155,156,158]. Likewise, there is contradictory evidence supporting the use of WBV in improving walking speed [157], functional reaching [152,153] or overall quality of life [152].
While WBV does not appear to have a detrimental effect on symptoms of MS, there is insufficient evidence regarding its beneficial effects on balance, gait, muscle strength and quality of life compared to other interventions. Future research is necessary to examine various protocols in terms of vibratory parameters and length of intervention before specific prescriptions can be offered [159].
Aquatics
Although aquatic exercise has often been recommended for individuals with MS, much of the research employing this therapeutic modality has focused on outcomes of pain, fatigue, cardiorespiratory fitness, gait, and quality of life [160–164]. Research focused on aquatic exercise for improved balance is limited. Nonetheless, significant improvements in standing balance and functional mobility have been shown for individuals with MS following aquatic exercise [165,166]. Similar results on standing balance and functional mobility have also been shown from Ai Chi, a program in which Tai Chi is combined with other techniques and performed standing in shoulder-depth water using a combination of deep breathing and slow, broad movements of the arms, legs, and torso [167]. These methods of intervention, however, still lack evidence from rigorous designs involving control groups and randomization.
Yoga
Yoga has also been explored as a means to improve physical and mental health outcomes in MS. While an initial study showed no significant changes in one-leg stance from an Iyengar yoga program [168], more recent research found Ananda yoga practice effective in improving standing balance [169]. Likewise, other research has shown that static and dynamic standing balance improved after yoga practice, although not significantly better than that from treadmill exercise training [170].
Kickboxing
There has been only one study to date, albeit not an RCT, that has examined kickboxing as a training modality to improve balance in MS. Although kickboxing was found to be a feasible exercise activity, not all participants demonstrated improved balance and mobility outcomes [171]. As such, further investigation of this novel treatment approach is warranted.
Hippotherapy
Hippotherapy has also been employed as a means of balance training because the multidimensional and random nature of the horse’s movement requires the rider to process increased sensory information and make the necessary anticipatory and reactive adjustments for postural control. While one study reported no improvement in postural sway after hippotherapy [172], other research has shown some benefit in balance and gait after riding [173,174]. Although preliminary, findings from 2 of the studies reveal that hippotherapy may be most beneficial for those with primary progressive MS compared to other subtypes of MS [175]. While hippotherapy may have a positive effect on balance in individuals with MS, the data is limited and lacks rigorous examination through randomized controlled study of large samples in order to allow for its advocacy as a primary rehabilitation modality at this time.
What exercise prescription is indicated for Ms. D?
Because Ms. D’s balance deficits have begun to limit her daily functioning and increase her risk of falling, a formal and targeted balance intervention is warranted. Research confirms that exercise would be well tolerated by Ms. D and supports the feasibility of her engaging in various exercise modalities. Although a number of exercise inter-vention studies involving people with MS have been described in the literature, their clinical utility and results in improving balance and mobility are varied. Nonetheless, there is preliminary evidence suggesting that exercise training may have positive effects on balance and functional mobility and could offer Ms. D benefit. This is especially true given that much of the exercise research included individuals with mild or minimal disability and at same stage of disease progression as Ms. D.
Since Ms. D’s balance problems stem from a range of postural impairments across multiple contexts of balance control, her treatment approach must incorporate exercises that include and integrate these underlying control systems. A targeted and multimodal balance exercise program, rather than general physical activity, may be most efficacious toward this end.
Intervention Prescription
Ms. D has poor ability to utilize somatosensory and vestibular inputs in order to dynamically weight the influence of multiple sensory modalities for the control of standing sway under varying sensory conditions. This visual dependence contributes to her poor balance and increases her fall risk when visual inputs are absent (ie, walking in dimly lit rooms) or when optic flow is incongruent or when visual distractions are present (ie, walking in dynamic contexts such as crowded spaces). Ms. D would benefit from exercises requiring greater use of proprioceptive and vestibular inputs, thereby facilitating improved sensory integration. Exercises performed with eyes closed as well as those completed on mats, foam, or other compliant surfaces would be beneficial. She might also benefit from specific vestibular rehabilitation exercises as this approach has resulted in improved sensory integration [143]. Given that Ms. D must regularly concentrate and focus on her balance and consistently look where she is stepping, her balance exercise program should also address her central processing and attentional deficits by including dual-task training [26].
Ms. D also noted that her MS significantly impacts her ability to walk both in terms of effort and distance and adversely affects her participation in social events. Supplemental to her balance exercise program, aerobic exercise, particularly treadmill walking, may offer some benefit both in terms of her endurance as well as gait. While some of the more targeted modalities such as hippotherapy, yoga, and kickboxing have not been extensively studied, they do offer promise and could be used as adjuncts in order to facilitate Ms. D’s motivation and adherence through more diverse programming. Lastly, and although requiring further study, cognitive-behavioral interventions and patient education may be warranted to help Ms. D overcome her fear of falling, low exercise self-efficacy, and any negative beliefs regarding the potential benefits of exercise.
What additional research is needed?
Although valuable insight has been gained from studies of balance and gait impairment with MS, many contexts remain understudied, particularly with regard to understanding both the neuroanatomical and neurophysiologic pathologies that underlie the behavioral impairments of balance and gait in MS. Further, the value of applying this knowledge of balance impairment to clinical diagnostics and prognostics requires further study in order to develop the most cost- and time-effective exams and evidence-based treatment approaches.
Based on the research to date, it remains difficult to draw definitive evidenced-based conclusions regarding what specific exercise mode or training dose would be most beneficial for Ms. D and others with MS. Moreover, while there exists some evidence of efficacious balance outcomes from exercise training, many of the studies involved individuals with mild MS. Only a few studies to date have included those with more advanced disability, thus making prescription generalizations to those more moderately affected by MS tenuous. Irrespective of specific approach, all modalities of balance-oriented interventions require larger controlled studies, inclusion of those with advancing disability status, long-term follow-up, an evaluation of optimal dose or duration, and outcomes on the neural mechanisms of effect.
Summary
Challenges to balance and mobility present serious consequences for those with MS, as falls and fear of falling lead to poor health outcomes and low quality of life. Given that postural impairments result from a diverse set of deficits in different underlying control systems, therapeutic intervention should be multimodal. Exercise prescription should address all affected contexts of postural control, including sensory and motor strategy training during postural transitions as well as induced postural perturbations, strength development, and gait activity. Evidence from clinical trials suggests that targeted balance oriented exercise in people with MS has the potential to improve balance and functional mobility, although more rigorous study on the topic is needed.
Corresponding author: Susan L. Kasser, PhD, Dept. of Rehabilitation and Movement Science, Univ. of Vermont, 306 Rowell Bldg, 106 Carrigan Dr, Burlington, VT 05405, [email protected]
Financial disclosures: None.
From the Department of Rehabilitation and Movement Science, University of Vermont, Burlington, VT.
Abstract
- Objective: To provide insight into the mechanisms and treatment options associated with balance impairments in individuals with multiple sclerosis (MS).
- Methods: Systematic reviews, randomized controlled trials, and noncontrolled studies were examined to collect current data regarding treatment options aimed at improving balance in MS.
- Results: Balance deficits are common in individuals with MS and result from a diverse set of constraints across multiple systems of postural control. Poor balance often leads to increased fall risk, reduced physical activity, added comorbidities, and decreased quality of life. A variety of exercise options are available for individuals with MS who experience balance and mobility problems. Physical interventions include targeted therapies, such as vestibular rehabilitation and weighted torso training, as well as more general exercise and balance training prescriptions.
- Conclusion: The evidence, albeit preliminary, suggests that therapeutic intervention aimed at ameliorating balance deficits associated with MS be multimodal. Exercise prescriptions should include sensory and motor strategy training, strength development, as well as functional gait activities. Further evidence-based research is needed to improve the management of balance deficits in those with MS and to identify the impact of improved balance on activity participation and quality of life.
Multiple sclerosis (MS) is one of the most common nontraumatic neurologic causes of disability among young adults. With greater awareness and improved diagnostics, more people are being diagnosed with the disease today than in the past. Prevalence estimates in the United States range from 90 to 135 per 100,000 individuals [1], with approximately 400,000 people currently diagnosed [2,3].
MS is a chronic inflammatory disease of the central nervous system typically characterized by increasing muscle weakness, spasticity, fatigue, pain, depression, visual and sensory disturbances, and cognitive difficulties. The clinical course of MS is highly variable and often unpredictable with increasing disability and physical decline spanning a 30- to 40-year period post diagnosis [4]. During this time, advancing symptoms can lead to a number of comorbidities and negatively impact daily functioning, mobility, and community participation [5–7]. From a public health standpoint, the early and disabling impact of symptoms and prolonged physical decline create a significant economic burden. The projected national heath care costs of MS are greater than $7 billion annually [8], with the average total annual cost per patient estimated at over $47,000 [9]. Of this annual cost, indirect costs associated with lost productivity represent the single highest component cost [9,10].
Of the wide range of disease-related challenges, mobility difficulties are most significant. Over 90% of people with MS report mobility difficulties [11], and maintaining mobility is consistently ranked as one of the highest priorities for this group, independent of disease duration or disability level [10,12]. Several studies have demonstrated that loss of balance and mobility contributes to substantial patient burden [13] and lower perceived quality of life [10]. Moreover, poor balance and increased fall risk have been associated with reduced physical activity and other health-related behaviors [14,15].
Because balance and mobility limitations are so prevalent and impacting, targeted treatments aimed at maintaining ambulation and function are critical goals in the management of MS. It is important for physicians and rehabilitation professionals to understand and recognize the underlying sensorimotor mechanisms related to postural instability and initiate appropriate evidenced-based treatments that can improve balance, reduce fall risk, and enhance quality of life for individuals with MS. This review seeks to analyze the evidence on the physical interventions aimed at ameliorating balance and mobility impairments associated with MS in the context of a case example.
Case Study
Initital Presentation and History
Ms. D is a 41-year-old woman with relapse-remitting MS. She was diagnosed 6 years ago after experiencing initial symptoms of optic neuritis and some numbness in her right hand. Since then, she has developed greater weakness in both her legs and reports that her MS significantly impacts her ability to walk, both in terms of distance and the effort needed to ambulate.
Ms. D is independently ambulatory without the use of any assistive device. She reports that her balance is worse when walking on uneven surfaces, moving about in dimly lit environments, turning, or when walking in crowded spaces. Ms. D also shares that she has difficulty standing on one leg while pulling on socks. She states that she must concentrate and focus on her balance when in these challenging situations and that she has to consistently look where she is stepping.
Ms. D does not have any spasticity in muscles of the lower extremities, but on occasion does experience some numbness and tingling in her left foot. She experiences moderate fatigue that requires her to pace herself throughout her daily activities. She reports that her fatigue impacts her ability to concentrate or pay attention for long periods of time and impacts her motivation to engage in social activities. She states that she sleeps restlessly and is consequently tired when she wakes in the morning. Although she is sedentary, she has no history of cardiopulmonary issues or orthopedic problems.
Physical Examination
Ms. D is 5’7” and weighs 175 pounds, with a BMI of 27.4. She presents with observable gait and balance impairment. On physical examination, she exhibits reduced bilateral strength of knee flexors and extensors as well as hip adductors, although the weakness is more evident on the left. On neurologic exam, she exhibits moderate disability in both sensory and cerebellar functioning (resulting in an Expanded Disability Status Scale score of 3.5) [16].
What is postural control?
What balance impairments are associated with MS?
Postural Equilibrium and Balance
For all individuals, postural orientation and equilibrium underlie the effective performance of life’s daily tasks. Postural orientation refers to the alignment of body segments to a reference (such as gravity, the support surface, or an object in the visual field), while postural equilibrium—often equated with balance—refers to maintaining or re-acquiring the body’s center of gravity (CoG) within the base of support (BoS) [17,18]. This paper will focus on postural equilibrium with MS across multiple contexts of balance tasks.
Horak [18] described contexts of balance tasks that affect the mechanisms of maintaining postural equilibrium. Some of these contextual variables include
- Biomechanical constraints (eg, strength)
- Limits of stability (functional reach, maximum lean)
- Anticipatory postural adjustments (voluntary postural transitions)
- Automatic postural responses (balance recovery from external perturbations)
- Sensory orientation (ability to reweight sensory information [somatosensory, visual, vestibular] depending on context
- Dynamic control during gait
- Cognitive-motor interaction (balance impairments when also performing a cognitive task)
Emotion represents another contextual variable of interest, because mood and fear can significantly modify postural control [19–23]. Knowing the contextual factors that modify balance control provides insight into underlying neuropathology associated with impairments of these postural control variables [24,25] as well as insight into what should be included during the examination of patients with MS based on patient descriptions of their symptoms and functional challenges.
Balance Assessment
Balance assessment indicates that Ms. D cannot abduct and hold either leg to her side for any noticeable length of time, cannot reach forward adequately without lifting her heels off the ground or falling forward, and cannot stand on one leg for more than 10 seconds without losing balance. She also needs to take multiple steps to recover balance with any slight perturbation and is unable to maintain stability while standing on foam with her eyes closed. She shows significant imbalance when rising from a chair, walking forward, and turning to come back to sit.
For Ms. D, the clinical balance exam suggests pervasive impairment of hip strength, limits of stability, anticipatory postural adjustments, postural responses, sensory integration, and gait. Furthermore, her reported need to focus vision on her gait is in accordance with compensation for existing sensory impairments. Lastly, fatigue and attention demand likely enhance the presentation of balance impairment.
What are the consequences of balance impairments associated with MS?
Balance impairments present considerable health problems for adults with MS. Greater than 50% of individuals with MS report falling in any 6-month period [81–85], with the incidence of recurrent falls reported to be as high as 9 falls per year [86]. In addition, fall-related injuries, including fractures, are more common with MS, although this increased risk is considerably greater for women with MS than men [86–90].
Common risk factors for falling in people with MS include variable or deteriorating MS status [90–96], problems with balance or mobility [88,92–94,96–99], use of walking aids [88,93,97], lower balance confidence [86,98], reduced executive functioning [99] and greater fatigue [85]. Increased postural sway [52,99,100], slower walking speed [99], greater gait asymmetry and variability [92,101], slower choice stepping reaction time [99], impaired forward limits of stability [92,99], impaired visually dependent sway [92,99], and leg weakness [88,92] have also been found predictive of future falls in MS. A link has also emerged between cognitive impairment and fall risk [86,95,99,102].
Fear of falling and fall-induced injuries are also the most common causes of restricted activity and disability for individuals with MS [14]. Research has shown that future physical activity associates with fear of falling, and fear of falling subsequently associated with lower-limb strength asymmetry and decreased limits of stability rather than past experience of falling [103]. Similarly, the perceived benefits of physical activity and an individual’s self-efficacy to engage in physical activity predict reported levels of physical activity independent of disability level for individuals with MS [104]. Thus, psychological perception represents an important, and potentially modifiable, correlate of physical activity.
Moreover, individuals with MS experience a high risk of cardiovascular disease and other chronic health conditions associated with deconditioning, as unfavorable blood lipid levels, poor glucose profiles, and obesity have been observed in this population [105]. Comorbid conditions, secondary conditions, and health behaviors are increasingly recognized to be important factors influencing a range of outcomes in MS [107].
Further History
Consistent with the consequences of balance and mobility impairment, Ms. D reports that she loses her balance and nearly falls at least 1 time per week while engaged in daily activities. She also shares that she fell 2 months ago while walking outside and across the lawn to get the mail. Her confidence is low for many daily tasks such as climbing stairs, picking up objects from the floor, reaching when on tiptoes, or walking on ramps or on slippery surfaces. While Ms. D is independent in all activities of daily living, she currently does not work due to her fatigue and poor balance. She indicates that she is not very physically active and feels somewhat isolated and depressed because her balance and mobility challenges keep her from going out with friends and socializing.
What exercise approaches are available to ameliorate the balance deficits associated with MS?
There are a variety of therapeutic approaches for the treatment of poor balance in MS. While pharmacologic treatment typically encompasses disease-modifying therapies, specific medications can also help in the management of symptoms (ie, fatigue, spasticity, gait variability) that can negatively impact balance and mobility. Other rehabilitative strategies for balance impairment include gait training, assistive devices for mobility, and environmental modifications for fall prevention. Although all of these avenues offer viable treatment options for improving balance, exercise is increasingly appreciated as an important adjunct to the rehabilitation management of MS [107], especially in terms of improving balance deficits, optimizing daily functioning, and increasing participation across various life contexts.
The diversity of exercise options available for individuals with MS who experience balance and mobility problems is expanding. Moreover, mounting evidence suggests that exercise is well tolerated by participants with the disease[108–110] and that individuals with MS can exercise sufficiently to improve their fitness, function, and quality of life [109,110]. Given the inherent variability of MS and the heterogeneity of symptoms and disease course across individuals, however, no one exercise prescription is optimal for all those diagnosed. Instead, treatment goals must be individualized and functionally based [107] with ongoing evaluation and modification of treatment plans due to disease progression, symptom fluctuations, and functional decline [107,111]. Regardless of specific approach, the aim of any exercise intervention is to reduce activity limitations, encourage participation, and facilitate independence and life satisfaction in those with the disease [112].
Resistance Training
There have been several structured reviews of exercise research in MS [108,110,113,114]. The existing evidence supports resistance exercise as compared with no exercise for improving general balance [115] or performing tasks such as a chair transfer [116] or sit-to-stand [117]. Two randomized controlled trials (RCTs) also revealed significant increases in functional reach (ie, limits of stability) as a result of progressive resistance exercise [118,119]. Resistance exercise has not, however, facilitated greater benefit over traditional rehabilitation in other postural control contexts such as those involving postural transitions, sensory integration, or postural sway [120–122].
The effects of resistance training on mobility have also been inconsistent. While several studies showed no significant improvement in functional mobility [118,122,123], a positive improvement was observed in other research [119,124,125]. Likewise, stair climbing was shown to improve in 2 noncontrolled studies [125,126] and one RCT [117] but not in another [127].
In a recent RCT to evaluate the comparative effectiveness of different methods of resistance training, Hayes et al [123] determined that the addition of high-intensity, eccentric resistance training offered no additional benefit over standard concentric resistance exercise in improving static standing balance and stair climbing. In addition, compared with no exercise or a home-based program to improve strength and balance, progressive resistance cycling showed significantly greater effect on functional reach and timed up-and-go in individuals with moderate MS [128]. Nonetheless, evidence for the efficacy of home-based training remains equivocal given issues of motivation, adherence, and training intensity [115,118,128].
Taken together, the systematic reviews to date conclude that there is insufficient evidence for the effects of resistance exercise on balance in MS, thus making solid evidenced-based conclusions difficult [108,110,113,129]. Moreover, it is difficult to ascertain a definitive and most efficacious exercise prescription for improving balance in MS given the inconsistency in protocols and findings across studies. There is some support, albeit preliminary, for progressive resistance training as a modality to improve balance, especially those functional tasks demanding greater strength [113]. Nonetheless, resistance training may contribute to improved posture and gait given it directly addresses one context of postural control, but it may not be fully effective due to lack of training to modify central neural control of posture in other contexts.
Aerobic Exercise
Many of the studies examining aerobic exercise in MS more often target walking capacity, exercise tolerance, fatigue, and quality of life than balance [130]. The limited research that has focused on aerobic exercise for balance improvement has shown equal benefit to that achieved from resistance exercise in those contexts involving limits of stability and dynamic balance while stepping or walking [119]. This finding was reasonable given that the aerobic exercise included step-up and treadmill walking. Still, it has been recommended that, for most people with MS, aerobic exercise also incorporate a degree of balance training [109].
Combined Exercise
The more recent exercise research involving people with MS often combines some aspect of aerobic, strengthening, and/or balance exercise. While only a few RCTs have examined the effects of combined training in this population, preliminary evidence suggests it is well tolerated and may have some benefit for improving function [110]. While one study found no differences in static balance after a combined strength and aerobic training program [131], review of the exercise protocol revealed that the training regime had only incorporated 2 standing exercises. Other studies more intentionally combining strength and balance exercise have demonstrated benefits in balance confidence [132], standing static balance or postural sway [132–134], step climbing [133], and functional mobility [135]. Combining aerobic exercise and strengthening has also been effective in reducing falls in those with MS [85].
Balance-Specific Exercise
Only one balance-specific RCT has been published to date. In this study, outcomes from balance training involving both motor and sensory strategies were compared to training of only motor strategies and to standard therapy [136]. Both the balance training groups significantly reduced the number of falls post intervention as compared to the conventional treatment group. There were no observed differences in self-reported balance confidence across the groups, although both the balance training groups significantly improved in static and dynamic standing balance over that achieved by the standard treatment group. The fact that only the group engaged in sensory training differed significantly on dynamic gait highlights the importance of sensory integration for dynamic balance and gait.
Video Game–Assisted Exercises
Novel rehabilitative approaches have taken advantage of advances in virtual reality and visual feedback training to improve balance and mobility deficits in people with MS. Exercise using the general physical activity games on the Nintendo Wii Fit provided short-term improvement in standing balance, strength, gait and physical activity in people with MS [137]. This general exercise offered no significant gains in self-efficacy, fatigue impact or quality of life, and physical activity levels returned to baseline levels 14 weeks after exercising. Subsequent review has, however, highlighted concerns that current commercially available video options for general exercise may not be sufficiently adaptive for people with moderate disability, leading to intimidation and low adherence [138].
Beyond general physical activity, the Wii Balance Board System has also been used to specifically target balance and mobility deficits in MS. Although one study found no significant benefit from Wii Fit balance exercise in balance performance and walking ability [139], other studies have shown positive effects in standing sway, static balance, dynamic stepping, walking speed, and MS impact [140–142].
The evidence, albeit preliminary, thus suggests that the Wii Fit may offer a feasible adjunct to traditional rehabilitation approaches, especially because the exercise can be done at home without the need for continuous support from a practitioner and because the technology aids in overcoming access barriers often associated with community-based physical activity programs [138]. Nonetheless, research shows that Wii Balance Board System training is more specific for static standing balance than for dynamic balance or mobility, the technology is not positively viewed by those with more advanced symptoms, and there exists a risk of adverse affects and training-related injuries associated with home-based use of the Wii [137,140].
Vestibular Rehabilitation Exercise
Vestibular rehabilitation is a specialized treatment approach that strengthens the vestibular sensory system by retraining the brain to recognize and process signals from the vestibular system and coordinate these with visual and proprioceptive inputs. To date, there has only been one RCT investigating the effects of vestibular rehabilitation on balance in adults with MS [143]. In this study, the outcomes of a standard vestibular rehabilitation program to those of an exercise regime as well as to no intervention were compared. The vestibular rehabilitation program consisted of static and dynamic tasks performed with changing bases of support, on various surfaces, with eyes open or closed, and different head movements. The 6-week vestibular rehabilitation program resulted in both statistically significant and clinically relevant change in standing balance under various sensory conditions compared with either of the other two groups, although no significant difference was found in walking capacity across groups.
Weighted Torso Training
Balance-based torso weighting (BBTW) involves strategically placing small weights on the trunk of an individual to decrease balance deviations observed during quiet stance, perturbed standing, walking, and transitioning [144]. While the specific mechanism underlying the therapeutic effect of rehabilitative weighting has been debated [145], various suggestions include joint compression to encourage co-contraction, enhanced conscious awareness of body segments, and biomechanical changes via shifting of the center of mass [146].
The one RCT examining the effectiveness of BBTW in people with MS found immediate and significant effects of BBTW on postural control and upright mobility [146]. The research confirmed preliminary investigations of BBTW in MS [144,147], demonstrating that BBTW can improve walking speed as well as functional tasks involving standing, walking, turning, and sitting down.
Whole Body Vibration
Whole body vibration (WBV) has been employed across a variety of neurological populations as a means of improving muscle tone, sensation, strength, stability, and functional performance. In WBV, multidimensional vibrations are transferred to an individual performing static or dynamic movements on an oscillating platform. The vibrations are believed to facilitate both neuroendocrine responses as well as motor unit recruitment [148–150].
Results have been inconsistent regarding the effectiveness of WBV as a way of improving postural control and functional mobility in individuals with MS. A few studies have shown significant positive effects of WBV lasting from 1 to 4 weeks on functional mobility [151–153], strength [151,153,154], walking speed [152,155], and standing balance [152]. Walking endurance has also been affected by vibration training designed to improve muscular endurance [156]. Although there have been noted benefits of WBV, these benefits were not significantly more advantageous than those offered by a vibration program in conjunction with lower-limb stretching and strengthening exercises [157] or in addition to a traditional rehabilitation program [154].
There has also been some evidence to show that prolonged WBV does not improve postural stability or functional mobility in individuals with MS after training [155,156,158]. Likewise, there is contradictory evidence supporting the use of WBV in improving walking speed [157], functional reaching [152,153] or overall quality of life [152].
While WBV does not appear to have a detrimental effect on symptoms of MS, there is insufficient evidence regarding its beneficial effects on balance, gait, muscle strength and quality of life compared to other interventions. Future research is necessary to examine various protocols in terms of vibratory parameters and length of intervention before specific prescriptions can be offered [159].
Aquatics
Although aquatic exercise has often been recommended for individuals with MS, much of the research employing this therapeutic modality has focused on outcomes of pain, fatigue, cardiorespiratory fitness, gait, and quality of life [160–164]. Research focused on aquatic exercise for improved balance is limited. Nonetheless, significant improvements in standing balance and functional mobility have been shown for individuals with MS following aquatic exercise [165,166]. Similar results on standing balance and functional mobility have also been shown from Ai Chi, a program in which Tai Chi is combined with other techniques and performed standing in shoulder-depth water using a combination of deep breathing and slow, broad movements of the arms, legs, and torso [167]. These methods of intervention, however, still lack evidence from rigorous designs involving control groups and randomization.
Yoga
Yoga has also been explored as a means to improve physical and mental health outcomes in MS. While an initial study showed no significant changes in one-leg stance from an Iyengar yoga program [168], more recent research found Ananda yoga practice effective in improving standing balance [169]. Likewise, other research has shown that static and dynamic standing balance improved after yoga practice, although not significantly better than that from treadmill exercise training [170].
Kickboxing
There has been only one study to date, albeit not an RCT, that has examined kickboxing as a training modality to improve balance in MS. Although kickboxing was found to be a feasible exercise activity, not all participants demonstrated improved balance and mobility outcomes [171]. As such, further investigation of this novel treatment approach is warranted.
Hippotherapy
Hippotherapy has also been employed as a means of balance training because the multidimensional and random nature of the horse’s movement requires the rider to process increased sensory information and make the necessary anticipatory and reactive adjustments for postural control. While one study reported no improvement in postural sway after hippotherapy [172], other research has shown some benefit in balance and gait after riding [173,174]. Although preliminary, findings from 2 of the studies reveal that hippotherapy may be most beneficial for those with primary progressive MS compared to other subtypes of MS [175]. While hippotherapy may have a positive effect on balance in individuals with MS, the data is limited and lacks rigorous examination through randomized controlled study of large samples in order to allow for its advocacy as a primary rehabilitation modality at this time.
What exercise prescription is indicated for Ms. D?
Because Ms. D’s balance deficits have begun to limit her daily functioning and increase her risk of falling, a formal and targeted balance intervention is warranted. Research confirms that exercise would be well tolerated by Ms. D and supports the feasibility of her engaging in various exercise modalities. Although a number of exercise inter-vention studies involving people with MS have been described in the literature, their clinical utility and results in improving balance and mobility are varied. Nonetheless, there is preliminary evidence suggesting that exercise training may have positive effects on balance and functional mobility and could offer Ms. D benefit. This is especially true given that much of the exercise research included individuals with mild or minimal disability and at same stage of disease progression as Ms. D.
Since Ms. D’s balance problems stem from a range of postural impairments across multiple contexts of balance control, her treatment approach must incorporate exercises that include and integrate these underlying control systems. A targeted and multimodal balance exercise program, rather than general physical activity, may be most efficacious toward this end.
Intervention Prescription
Ms. D has poor ability to utilize somatosensory and vestibular inputs in order to dynamically weight the influence of multiple sensory modalities for the control of standing sway under varying sensory conditions. This visual dependence contributes to her poor balance and increases her fall risk when visual inputs are absent (ie, walking in dimly lit rooms) or when optic flow is incongruent or when visual distractions are present (ie, walking in dynamic contexts such as crowded spaces). Ms. D would benefit from exercises requiring greater use of proprioceptive and vestibular inputs, thereby facilitating improved sensory integration. Exercises performed with eyes closed as well as those completed on mats, foam, or other compliant surfaces would be beneficial. She might also benefit from specific vestibular rehabilitation exercises as this approach has resulted in improved sensory integration [143]. Given that Ms. D must regularly concentrate and focus on her balance and consistently look where she is stepping, her balance exercise program should also address her central processing and attentional deficits by including dual-task training [26].
Ms. D also noted that her MS significantly impacts her ability to walk both in terms of effort and distance and adversely affects her participation in social events. Supplemental to her balance exercise program, aerobic exercise, particularly treadmill walking, may offer some benefit both in terms of her endurance as well as gait. While some of the more targeted modalities such as hippotherapy, yoga, and kickboxing have not been extensively studied, they do offer promise and could be used as adjuncts in order to facilitate Ms. D’s motivation and adherence through more diverse programming. Lastly, and although requiring further study, cognitive-behavioral interventions and patient education may be warranted to help Ms. D overcome her fear of falling, low exercise self-efficacy, and any negative beliefs regarding the potential benefits of exercise.
What additional research is needed?
Although valuable insight has been gained from studies of balance and gait impairment with MS, many contexts remain understudied, particularly with regard to understanding both the neuroanatomical and neurophysiologic pathologies that underlie the behavioral impairments of balance and gait in MS. Further, the value of applying this knowledge of balance impairment to clinical diagnostics and prognostics requires further study in order to develop the most cost- and time-effective exams and evidence-based treatment approaches.
Based on the research to date, it remains difficult to draw definitive evidenced-based conclusions regarding what specific exercise mode or training dose would be most beneficial for Ms. D and others with MS. Moreover, while there exists some evidence of efficacious balance outcomes from exercise training, many of the studies involved individuals with mild MS. Only a few studies to date have included those with more advanced disability, thus making prescription generalizations to those more moderately affected by MS tenuous. Irrespective of specific approach, all modalities of balance-oriented interventions require larger controlled studies, inclusion of those with advancing disability status, long-term follow-up, an evaluation of optimal dose or duration, and outcomes on the neural mechanisms of effect.
Summary
Challenges to balance and mobility present serious consequences for those with MS, as falls and fear of falling lead to poor health outcomes and low quality of life. Given that postural impairments result from a diverse set of deficits in different underlying control systems, therapeutic intervention should be multimodal. Exercise prescription should address all affected contexts of postural control, including sensory and motor strategy training during postural transitions as well as induced postural perturbations, strength development, and gait activity. Evidence from clinical trials suggests that targeted balance oriented exercise in people with MS has the potential to improve balance and functional mobility, although more rigorous study on the topic is needed.
Corresponding author: Susan L. Kasser, PhD, Dept. of Rehabilitation and Movement Science, Univ. of Vermont, 306 Rowell Bldg, 106 Carrigan Dr, Burlington, VT 05405, [email protected]
Financial disclosures: None.
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