Clinical and Health Affairs
New Approaches to Neurorehabilitation: The Increasing Evidence Base
By Karl J. Sandin, M.D., M.P.H.
■ Recent advances in neuroscience have led to newer, more scientific approaches to rehabilitation for patients who have had a stroke or sustained a brain or spinal cord injury. Specifically, the pendulum in rehabilitation has swung away from a focus on compensatory techniques and toward impairment-mitigating therapies. In addition, there is a new push to base therapies on scientific evidence. This article explores these changes and the developments that led to them, including discoveries in basic science that have enhanced our understanding of neuroplasticity. It also describes new research directions in neurorehabilitation.
The International Classification of Functioning, Disability, and Health (ICF) is the World Health Organization’s framework for measuring disability at both the individual and population levels The ICF has three domains: body structure and function, activity, and participation. Loss of body structure and function refers to an impairment such as paralysis; activity limitation refers to inability to perform daily tasks or activities such as walking; and participation restriction refers to the inability to work or take part in social activities. A person who has had a stroke may have disability in all three domains, for example, left-sided weakness, inability to walk or dress themselves without help, and inability to work full-time.
Traditionally, neurorehabilitation for stroke would have focused on preventing the impairment from becoming worse through passive range-of-motion, stretching, and positioning exercises to prevent contracture and maximizing activity through compensatory strategies (eg, using a wheelchair to get around rather than walking). Regaining neural structure and function was not the goal.
The approach to rehabilitation for patients who have had a stroke or sustained a brain or spinal cord injury was empiric; determining which therapies to use, how often to use them, and for what duration they should be used was based more on what was feasible rather than on what had been shown to be effective through scientific research. As a result, there has been a lack of specificity about what is required in terms of neurorehabilitation for optimal recovery.
In recent years, the field has begun to change. Advances in neuroscience that shed light on neuroplasticity have led to changes in thinking about the goals of and our approaches to neurorehabilitation. This knowledge has been the catalyst for scientific research into the efficacy of treatments. This article explores this shift in neurorehabilitation.
A New Look at Rehabilitation
Actor Christopher Reeve, who in 1995 sustained a C4 spinal cord injury after falling from a horse that resulted in tetraplegia, inspired many to begin to think differently about rehabilitation. Reeve insisted that the goal of his rehabilitation be recovery of ability. Although many individuals enter rehabilitation saying their goal is to “walk out of here,” Reeve had both the personal determination and economic resources to insist that his rehabilitation regimen include therapies that did more than help him accommodate his disabilities. Reeve received stem cell treatment and participated in robust locomotor training, both of which are not part of traditional rehabilitation. His findings on neurological examination did improve over time to an exceptional degree: He regained sensibility through C6 and some left index finger extension. Although Reeve did not achieve meaningful recovery of movement or enough sensibility to regain “normal” activity, his case prompted many to take a new look at rehabilitation following neurologic injuries. Since then, many rehabilitation clinicians have added improvement in body structure and function as a primary goal of rehabilitation.
During the same time that Reeve was challenging the traditional paradigm in rehabilitation, scientists were making tremendous strides in understanding the brain and nervous system. Especially relevant to rehabilitation medicine was new information about neuroplasticity. The concept of neuroplasticity is not a new one—American psychologist William James first introduced the idea in 1890—and a century of research has confirmed it is a fundamental, evolutionarily conserved property of all nervous tissue. However, we have not been able to truly understand what is occurring at the cellular level until recently.
Neuroplasticity refers to any change in neuron structure or function in response to input from the environment. For example, individual neurons might enlarge their dendritic or axonal arbors, or populations of neurons may become denser. Changes in behavior are not on their own measures of neuroplasticity.
Also relevant to rehabilitation has been new information about the brain itself. With imaging and other technologies, we observed that humans have structural redundancies, several areas of the brain that can do the same thing, that allow for both neural recovery (restoring the function of injured brain tissue) and compensation (residual neural tissue takes over a lost function).
As imaging and other technologies provided evidence of brain remodeling in response to changes in input, the rehabilitation community began reconsidering its focus on adaptation. If exercise and training could change neural structure and function, which in turn would abrogate the need for accommodation, wouldn’t such an approach be superior?
Rehabilitation Research
With that in mind, researchers began trying to better understand which therapies worked best and why. They also started better describing therapies to allow their replication in other settings. In 2006, the first article on neurorehabilitation for stroke patients that met standards used elsewhere in medical research was published. Here is a look at that and some other scientifically sound trials that have enlightened the medical community about new approaches to neurorehabilitation.
■ Forced-Use Therapy
The EXCITE trial conducted by Wolf and colleagues was the first clinical trial of its kind in rehabilitation therapy.1 It looked at the effect of two weeks of constraint-induced movement therapy (CIMT), a forced-used paradigm, on upper-extremity (UE) function. The researchers randomized stroke survivors who had some UE movement three months to nine months after stroke into two groups. One group wore a restraining mitt on the less-affected hand while they practiced doing various tasks with their weak hand; the other group received usual care. Patients were involved in training up to six hours a day. Efficacy was assessed using the Wolf Motor Function Test, which measures movement speed and facility, and the Motor Activity Log, which assesses ability to perform 30 common activities. The CIMT group experienced statistically significant improvement in paretic arm motor ability and use as compared with the group that received usual care. Pointing to their desire to improve their paretic limb, adherence to the program was high, according to the participants’ self-reports.
In process now is the Accelerated Skill Acquisition Program (ASAP) trial, which will compare the results of 30 hours of traditional rehabilitation with a combination of forced-use/constraint-induced therapy and skill-based/impairment-mitigating motor learning training for people with arm weakness after stroke.2 Additionally, the study aims to describe the frequency, duration, and content of traditional outpatient treatment, since “usual care” in neurorehabilitation has not been well-defined or described in the past.
Other studies of neurorehabilitation following stroke are using more clear definitions for the frequency, duration, and type of therapeutic exercise used. Questions, of course, remain: One is whether delay of forced-use therapies is harmful or helpful.
■ Medications
Several pharmacological approaches have been tried for improving outcomes after stroke. Some studies have looked at use of medications alone, and others at medicines in combination with rehabilitation. Most studied is treatment with amphetamines, typically dextroamphetamine, which stimulate the central and peripheral nervous systems. Walker-Batson used dextroamphetamine 10 mg in a promising double-blind placebo-controlled study of stroke survivors with aphasia.3 Using the Porch Index of Communicative Ability as the primary outcome measure, they concluded that administration of dextroamphetamine facilitated recovery from aphasia when paired with 10 one-hour sessions of speech/language therapy in a group of 21 patients during the subacute period after stroke. Small sample sizes have been a problem with research into the use of stimulants for neurorehabilitation; thus, a recent Cochrane review concluded there is not enough evidence to support the routine use of amphetamines to promote recovery after stroke.4
Determining the effect of selective serotonin reuptake inhibitors (SSRIs) in stroke patients has proved more complicated. Some studies have shown functional outcomes are worse for people who are taking SSRIs at the time of stroke;5 others point to potential benefits of SSRIs on functional outcomes because of increased levels of brain-derived neurotropic factors.6 Most studies support the efficacy of SSRIs in treating depression after stroke. Patients may be more motivated to participate in rehabilitation when their depression is under control and, as a result, see improvements in their mobility and ability to care for themselves.
In the recent FLAME study, a randomized placebo-controlled trial, 113 ischemic stroke survivors who had moderate to severe hemiplegia were treated with either fluoxetine 20 mg daily or placebo, beginning five to 10 days after stroke.7 Both groups received physical therapy. The main outcome measure was the Fugl-Mayer motor scale, which measures impairment on a scale of 0 to 100 points; secondary measures were the National Institutes of Health Stroke Scale, a measure of activity limitation, and a measure of mood. Although scores on the Fugl-Mayer scale showed a statistically significant difference between the groups, scores on the other outcome measures showed no difference. A Cochrane review is in process to address SSRI use in stroke patients.8
■ Physical Agents
Noninvasive brain stimulation (NIBS) methods such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) show promise for inducing neuroplasticity in patients with brain lesions.9 The general idea is that physical forces cause changes in cortical excitability leading to recovery or reorganization of the brain network. In preclinical work, both TMS and tDCS may facilitate motor, perceptual, and cognitive performance in patients with brain lesions. As with other aspects of neurorehabilitation, there is a lack of specificity with regard to the duration, location, and frequency of stimulation. There also is uncertainty about how NIBS should be combined with other therapy protocols, medications, and rehabilitation interventions. Research continues in this promising area.
Conclusion
We are on the cusp of more accurately identifying the type, duration, and frequency of physical, occupational, and speech therapies that lead to the best outcomes for patients who have experienced brain or neurologic injuries. Researchers are also exploring potential interactions of those therapies with medications as well as the efficacy of magnetic or electrical stimulation and other treatments. For now, it would appear that new approaches to neurorehabilitation such as trying to minimize impairment through forced used of the affected body part (Figure) should trump old approaches that focus on preventing contracture and compensating for disability. Although regaining neural structure and function is now a goal of neurorehabilitation, a truly effective rehabilitation program should ensure that the patient not only improves his or her physical body but also is able to fully engage in daily activities and participate in social functions. MM
Karl Sandin is physician-in-chief of Sister Kenny Rehabilitation Institute.
References
1. Wolf, SL, Winstein CJ, Miller JP et.al. JAMA 2006;296:2095-2104.
2. Dromerick A, Wolf SL, Winstein CJ. Arm rehabilitation study after stroke “ICARE.” The Internet Stroke Center. Available at: www.strokecenter.org/trials/clinicalstudies/arm-rehabilitation-study-after-stroke/description. Accessed December 17, 2011.
3. Walker-Batson D, Curtis S, Natarajan R, et al. A double-blind, placebo-controlled study of the use of amphetamine in the treatment of aphasia. Stroke. 2001;32(9):2093-8.
4. Martinsson L,HårdemarkHG, Eksborg S. Amphetamines for improving recovery after stroke. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD002090. DOI: 10.1002/14651858.CD002090.pub2.
5. Miedema I, Horvath KM, Uyttenboogaart M, et al. Effect of selective serotonin re-uptake inhibitors (SSRIs) on functional outcome in patients with acute ischemic stroke treated with tPA. J Neurol Sci. 2010;293(1-2):65-7.
6. Mostert JP, Koch MW, Heerings M, et.al. Therapeutic potential of fluoxetine in neurological disorders. JCNS Neurosci Ther. 2008;14(2):153-64
7. Chollet F, Tardy J, Albucher JF, et.al. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomized placebo-controlled trial. Lancet Neurology. 2011;10(2):123-30.
8. Mead GE, Hankey GJ, Kutlubaev MA, et.al. Selective serotonin reuptake inhibitors for stroke. Cochrane Database of Systematic Reviews 2011, Issue 11. Art. No.: CD009286. DOI 10.1002/14651858. CD009286.
9. Miniussi C, Vallar G. Non-invasive brain stimulation: new prospects in cognitive neurorehabilitation. Neuropsych Rehab. 2011;21(5):553-768.