Adults with cerebral palsy: a workshop to define the challenges of treating and preventing secondary musculoskeletal and neuromuscular complications in this rapidly growing population
CONFLICTS OF INTEREST
The authors declare no conflicts of interest.
Laura L Tosi at Division of Paediatric Orthopaedics and Sports Medicine, Children’s National Medical Center, 111 Michigan Ave, NW, Washington, DC 20010, USA. E-mail: email@example.com
Although the neurological injury associated with cerebral palsy (CP) is non-progressive, adults with the disorder often develop musculoskeletal and neurological symptoms, such as severe pain, chronic fatigue, and a premature decline in mobility and function, as they age. Little is known about how to manage, much less prevent, these symptoms. This paper summarizes the findings of a multi-disciplinary workshop, sponsored by the Cerebral Palsy International Research Foundation, the American Academy for Cerebral Palsy and Developmental Medicine, and Reaching for the Stars, convened to review current knowledge and begin to develop a blueprint for future research. The goals of the workshop were to (1) define the current incidence and prevalence of CP, (2) review the known complications for persons aging with CP, (3) review current understanding of physiological processes that may contribute to loss of function and premature aging in CP, (4) evaluate current treatment interventions in terms of long-term outcomes, (5) identify cutting-edge technologies in neurorehabilitation that may help prevent or treat the effects of accelerated aging for persons diagnosed with CP, and (6) identify strategies to ensure that individuals with CP receive evidence-based care as they transition from pediatric to adult-care services.
LIST OF ABBREVIATIONS
Bone mineral density
Body-weight-supported treadmill training
Complementary and alternative medicine
Spinal cord injury
Transcranial magnetic stimulation
Most individuals born with cerebral palsy (CP) are now surviving well into adulthood; their life span is approaching that of the general population. This advance, however heartening, poses new challenges to the medical community. Although the neurological injury associated with CP is non-progressive, adults with the disorder often develop musculoskeletal and neurological symptoms, such as severe pain, chronic fatigue, and a premature decline in mobility and function, as they age. Little is known about how to manage, much less prevent, these symptoms and thereby ensure that adults with CP lead healthy and productive lives.
To encourage research and multidisciplinary collaboration in addressing this issue, the Cerebral Palsy International Research Foundation, in partnership with the American Academy for Cerebral Palsy and Developmental Medicine, and Reaching for the Stars, a support group for families with a child with CP, hosted a workshop on 16th to 17th September 2008. The workshop brought together more than 140 scientists, health-care professionals, families, and individuals living with CP to review current knowledge and begin to develop a blueprint for future research.
Workshop goals were to define the current incidence and prevalence of CP, to review the known complications for persons aging with CP, to review current understanding of physiological processes that may contribute to loss of function and symptoms consistent with premature aging in CP, to evaluate current treatment interventions in terms of long-term outcomes, to identify cutting-edge technologies in neurorehabilitation that may help prevent or treat the effects of accelerated aging for persons diagnosed with CP, and to identify strategies to ensure that individuals with CP receive evidence-based care as they transition from pediatric to adult-care services. On the basis of their discussions, participants identified important gaps in our current knowledge base and developed a set of recommendations to guide future research.
Epidemiology and Life Expectancy
Cerebral palsy, the most common major disabling motor disorder of childhood, is ‘a group of permanent disorders of the development of movement and posture, causing activity limitations that are attributable to disturbances that occurred in the developing fetal or infant brain.’ A recent study by the Centers for Disease Control and Prevention found that the average prevalence of CP across three geographical areas in the United States was 3.6 cases per 1,000 among 8-year-old children. This figure is consistent with international data from Western countries: the Surveillance of Cerebral Palsy in Europe Network, which used a clear definition of CP to accurately and consistently identify cases of CP, reported that the prevalence of CP within the collaboration varies from 2 to 3 per 1,000 live births. The number of infants born with the disorder appears steady, notwithstanding the many improvements in the management of pregnancy and labor of recent decades; however, the number of individuals living with the disorder is increasing because of the increasing survival rates of low and very low birth weight infants and the increasing longevity of adults with the disorder. It is estimated that up to 1,000,000 children and adults in the United States are living with CP; of these, many are over the age of 45. Because of the lack of registries of individuals with CP, there are no firm data on the age-specific prevalence of the disorder
Deaths among children with CP, never common, have become very rare, unless the child has severe and multiple disabilities. This encouraging trend continues into adulthood. To cite just one example, among a cohort of individuals with CP born between 1940 and 1960 in the UK, 86% of those alive at age 20 survived to age 50. This compares to a survival rate of 96% among individuals in the UK population during the same period.
Proposed way forward: Improve the public health surveillance of persons of all ages with CP by exploring the following issues:
- • What is the age-specific prevalence of individuals with CP? How is that prevalence influenced by sex, level of motor function, and type of CP?
- • What is the life expectancy of an individual with CP?
- • What factors have influenced changes in prevalence and survival in individuals with CP?
Secondary Musculoskeletal Conditions Associated with CP in Adults
The aging process inevitably interacts with the motor disorder in the adult with CP, and increasing survival rates for adults with CP have led both patients and clinicians to draw attention to the increased incidence of secondary musculoskeletal and neurological conditions in this population. Secondary musculoskeletal and neurological conditions include pain and fatigue, decreased mobility, decreased fine motor control, and diminished independence. In addition, adults with CP frequently experience progressive orthopaedic problems. No large-scale studies have tracked children with CP into and through adulthood.
Pain and chronic fatigue
Pain management is the overarching musculoskeletal issue in the care of adults with CP. This incidence of pain is high across all Gross Motor Function Classification System (GMFCS) levels and appears to increase with age. Studies of adults with CP have reported pain in 67 to 82% of their cohorts. The back, hip, and lower extremities were the most common pain locations in many studies. Osteoarthritis was reported as a cause of pain in several studies; one study found clinical evidence of arthritis in 27% of young adult participants with CP compared with only 4% of the general population.
Despite the broad acknowledgment of pain in this population, the impact of pain on a given individual’s activity level and participation in the community is not well understood. Adults experience pain associated with contractures, spasticity, orthopaedic deformity, fractures, poor nutrition, pressure from sitting on bony prominences, weakness, and fatigue, as well as pain associated with gastrointestinal issues. Assessment of pain in some individuals with CP is difficult because of communication barriers or severe intellectual disability. The effects of pain have a ripple effect: pain may lead to sleep deprivation, which causes fatigue, which exacerbates pain.
Decline in mobility and function
Most studies report a decrease in functional status with aging among adults with CP. About a third of adult participants in one study, for example, reported modest-to-significant decreases in walking or self-care tasks, especially in dressing and walking. In addition, some individuals with CP start to lose motor function early in life. One author has reported that of 7550 children with CP who walked and climbed stairs without difficulty at age 10, 77% still did so 15 years later; and of 5721 adults with CP who walked and climbed stairs without difficulty at age 25, 76% still did so 15 years later.
Musculoskeletal conditions secondary to CP
Numerous musculoskeletal impairments, including patella alta, hip displacement, spondylolysis, cervical stenosis, scoliosis, foot deformities, and disuse osteoporosis, have a particular impact on the adult with CP. In addition, spasticity, which affects 70% of individuals with CP, is a major contributor to the development of contractures and bony deformities. Patella alta, most common in individuals with CP of the spastic diplegic type, can cause anterior knee pain and is complicated by stress fractures, tendonitis/bursitis, and subluxations/dislocations. Hip subluxation/dislocation occurs in approximately 1% of individuals with spastic hemiplegia, 5% of those with diplegia, and up to 59% of those with quadriplegia. Approximately 50% of these hips become painful, which decreases the person’s ability to walk or stand and, in the non-ambulatory patient, to sit comfortably or to stand for transfers. The more severely involved patients have a greater incidence of hip subluxation/dislocation. Spondylolysis is an acquired impairments related to stress fracture through the pars interarticularis from repetitive hyperextension. Its prevalence in weight-bearing adults with CP is reported to be up to 21 to 30%. Cervical stenosis, most likely an overuse injury, has been found to be more common in individuals with CP than in the general population. Neuromuscular scoliosis is found in 15 to 80% of people with CP. Acquired foot deformities probably contribute to reduced mobility.
In addition, increased rates of fracture and low bone mineral density (BMD) have been documented in both children and adults with CP. The fractures have been primarily found in persons who are non-ambulatory, who demonstrate poor nutrition and growth, and who take antiepileptic drugs, which have been noted to increase the risk of osteoporosis. Research into the relationship between pain and BMD is an especially critical need because many adults with CP who walked as children cease to do so in early adulthood, thereby increasing the risk for osteoporosis. Chronic immobilization also raises the risk for metabolic syndrome.
The wide range in the prevalence of these conditions described in the literature is due to variations in the populations being studied – variations that include age, nature, and severity of neurological dysfunction, as well as the extent of impairment of physical function. Similarly, while there are abundant anecdotal reports of adults with CP suffering from these conditions, scientific documentation of the true incidence and prevalence of these complications among large cohorts is sparse. Nonetheless, there is a consensus that early recognition of all these problems is essential because all of them may be lessened, or even prevented, with early intervention and diagnosis.
Proposed way forward: Improve understanding of the natural history of musculoskeletal and neurological impairments across the lifespan in persons with CP by researching the following areas:
- • How is the natural history of musculoskeletal impairments in individuals with CP affected by age, sex, GMFCS level, subtype, and impairments?
- • What is the age-specific and type-of-CP-specific prevalence of secondary musculoskeletal conditions in individuals with CP? Are any of these conditions preventable or treatable?
- • What is the etiology and prevalence of pain in adults with CP? How can pain and chronic fatigue be prevented and managed in these individuals?
- • Do persons with CP experience pain and chronic fatigue earlier or more frequently than their peers?
- • What is the relationship between pain and spasticity as persons with CP grow older?
- • What is the relationship between type of CP to location, severity, duration, and age at onset of pain?
The Aging Process in the Adult with CP
Several authors have established that adults with CP may experience age-related changes earlier in life than their non-disabled peers. CP frequently causes a cycle of deconditioning, in which physical function deteriorates, followed by a further decrease in physical activity, and a cascade of functional decline. It is unclear which specific elements of health status are most important for maintaining independent function in persons with physical disability. The reasons for these early changes have similarly not been fully worked out; it is known, however, that the natural history of mobility in CP is one of early decline. Several authors have noted that children and young adults with CP have deficits in muscle volume in their lower limbs, with individual muscle volume being as low as 50% of that of their age- and weight-matched, typically developing peers.
Individuals affected by CP may develop the neuromuscular performance needed to complete motor tasks much later than their healthy peers, and at their peak motor function, may have less reserve. Because of this, they may fall below the threshold in muscular performance needed to perform motor tasks much earlier than non-disabled individuals. Since muscle growth depends on intense levels of activation, the magnitude of the muscular reserve that each child with CP develops may depend on the extent to which he/she can activate his/her musculature given the severity of the neurological lesion.
Children with CP are less active than their non-disabled peers and have a lower maximum oxygen consumption, muscular endurance, and peak anaerobic power. Weakness often prohibits their participation in vigorous cardiovascular conditioning programs. Ensuring that persons with CP remain as active as possible is of critical importance; one study, for example, showed that physical activity and health among people with disabilities were highly correlated with greater longevity.
Sarcopenia is responsible for much of the loss of muscle mass in the typically developing adult. A decline in muscle mass begins in the mid-twenties and occurs rapidly in the 7th and 8th decades. In the non-disabled population, progressive strengthening has been shown to increase muscle volume and strength and to improve function and mobility. It is possible that the large muscle deficits of those with CP during childhood, coupled with the natural history of decline of muscle size and properties in adulthood, contribute to an early loss of mobility. The real value of strengthening programs in CP may be in the improvement of muscular reserve in the short term and the maintenance of muscle mass above critical thresholds in the longer term. Thus, function and mobility of adults with CP may be extended by progressive resistance training. However, the most effective method of extending mobility in adulthood may be to develop a significant muscular reserve in childhood and adolescence, when muscles may be more adaptable to mechanical stimulus.
This logic has also led some investigators to question the long-term risks of some treatment modalities, especially botulinum toxin type A (BoNT-A) injections, serial casting, and prolonged postoperative immobilization, as these treatments may further contribute to muscle deficits. Failure to develop normal muscle volumes, moreover, may have implications that extend beyond mobility. It may have an impact on cardiovascular disease, osteoporosis, and osteoarthritis.
It is increasing clear that, independent of body weight or body composition, cardiopulmonary fitness is of importance in determining the risk of cardiovascular disease. If the level of fitness falls with age, it would be expected that persons with CP would not be spared the adverse metabolic and cardiovascular consequences amply described in the general population. This has relevance for adults with CP, who may have ‘normal’ body mass index (BMI), body fat by skin-fold measurement, or dual-energy X-ray absorptiometry, and even normal levels of daily activity, but may still have reduced fitness. Although an increased risk of cardiovascular disease has not been reported in adults with CP, it has been reported extensively in persons with spinal cord injury (SCI), a group that also suffers from muscle loss and inactivity. Cardiovascular disease is the most frequently reported cause of death among persons with SCI more than 30 years after injury (46% of all deaths) and among those more than 60 years of age (35% of all deaths).
Adverse changes in body composition and inactivity predispose persons with disability to metabolic abnormalities. Because of pain, fatigue, and myriad other secondary consequences of their disability, adolescents with CP who were ambulatory and active may become less physically functional later in life. Reduced ability to ambulate may be associated with changes in body composition, muscle atrophy, and absolute and/or relative increases in body fat, which may be a progressive process of deterioration in persons aging with CP. Insulin resistance and hyperinsulinemia, especially if a genetic predisposition is present, may develop with associated disorders in carbohydrate and lipid metabolism. In an unfavorable metabolic milieu, the ability of the pancreas to compensate for these changes may diminish with advancing age.
The epidemiology of osteoporosis and fractures in children and adults with CP is not well characterized. An assumption of susceptibility to fractures in the CP population is based on anecdotes, clinical experience, and limited surveys in select groups, as well as on the fact that impact loading, a critical determinant of bone health, is sharply reduced when a patient loses mobility. Epidemiological studies in children with CP have found a fracture rate similar to that of normal children, but fracture incidence was higher in the most severely impaired individuals. The major risk factors for fractures are ambulatory status, nutritional state, extent of neurological injury, degree of physical disability, dietary intake of calcium and vitamin D, and periods of immobilization.
A few studies have looked at BMD as a risk factor in adults with CP. One group of researchers found that 51% of a population of 108 institutionalized males with developmental disabilities had a quantitative ultrasound index (a measure of BMD risk) more than 2SD below the mean. Another group of investigators performed peripheral BMD screening in a community-based study of 429 females with different disabilities, 25 of whom had CP. Among these women, 53.1% had evidence of low BMD, regardless of whether or not they had gone through menopause. Risk factors for low BMD were white race, lack of exercise, and medication use.
Early osteoarthritis is a significant issue in many adults with CP. The morphogenesis, remodeling, and degeneration of diarthroidial joints are directly under the control of the loading histories created by the musculoskeletal system during development and aging. The altered loading histories in individuals with CP lead to aberrations in joint morphogenesis and an acceleration of joint degeneration. Joint destruction is believed to occur disproportionately in persons with CP, particularly of the hip because (1) altered muscle activity and restricted range of motion result in abnormal joint morphology, subluxation, and poor joint coverage of the femoral head; (2) joint incongruities created in early development cause local stress concentrations that can mechanically damage the articular cartilage; (3) the reduced magnitudes of muscular forces reduce the contact pressures at the joints, creating thinner cartilage and osteopenia; and (4) the thinner cartilage degenerates early, and subchondral bone collapse further contributes to the mechanical destruction of the remaining cartilage.
Proposed way forward: Elucidate the biological mechanisms associated with musculoskeletal and neuromuscular disorders in the adult with CP by focusing on the following questions:
- • Is there evidence that the muscular deficits in childhood, coupled with the natural history of sarcopenia and atrophy in adulthood, contribute to early loss of strength and mobility in the adult with CP?
- • Do weight bearing and activity lead to early arthritis in the person with CP? If so, how can it be prevented?
- • Does decreased muscle mass lead to an increased incidence of metabolic syndrome and cardiovascular complications in adults with CP?
- • Are the factors that contribute to osteoporosis in adults with CP different from those that cause osteoporosis the general population? What impact would such differences have on screening and interventions?
- • What is the evidence for accelerated aging in persons with CP?
- • What is the physiology of this process?
- • What risk factors can cause the manifestation of aging to vary for persons with CP?
- • Should health maintenance services be different for persons who have prematurely aged than for those who have not?
- • What age-related changes are unaffected by CP?
- • What is the prevalence of early loss of mobility, early onset of osteoarthritis, osteoporosis/fragility fractures, and worsening spasticity and dystonia in adults with CP? How can these conditions be delayed, prevented, and managed?
- • How does physical activity contribute to the lives of adults with CP?
- • What types of physical activity (strengthening, aerobic, flexibility, aquatic), combinations of activity, and doses of exercise and activity are most effective for specific disabilities and secondary conditions?
- • What physiological parameters provide the most reliable information needed to discern fitness need and decline or improvement?
- • How effective are programs that train strength and aerobic capacity at the same time?
Musculoskeletal Care of Adults with CP: What Do We Know? What Do We Need to Know?
The long-term impact of interventions used to treat both children and adults with CP have not been well studied. A wide menu of treatments exists, but without longitudinal studies, there is little evidence directing clinicians toward best practices.
The overarching issue in the care of adult individuals with CP is pain management; however, solutions for chronic pain in CP are not well studied. More than 50% of adults with CP reportedly use non-steroid anti-inflammatory drugs, and about 33% use antispasticity medications or narcotics with limited success. Other interventions include intrathecal baclofen, BoNT-A injections, exercise, and orthopaedic surgery, as well as complementary and alternative therapies.
Management of spasticity
Spasticity affects 70% of individuals with CP and is a major contributor to the development of bony deformities and contractures. Antispasmodic medications are commonly used to address spasticity, but no study has demonstrated that they alleviate pain in adults with CP. BoNT-A is frequently used to manage spasticity interfering with motor control and function in children and adults with CP. It is injected directly into selected muscles and acts by preventing the release of acetylcholine at the neuromuscular junction. Studies evaluating BoNT-A as a pain intervention modality have been performed primarily on individuals with a history of stroke or chronic neuropathic pain. Reports of pain reduction using BoNT-A in CP are primarily anecdotal.
Intrathecal baclofen (ITB) reduces both dystonic and spastic tonal abnormalities and is often preferred to oral baclofen or other antispasmodics because its direct delivery to the spinal cord diminishes the sedating side effects observed with oral medication. Risks include mild to very serious infections, cerebrospinal fluid leakages, and hardware complications. Other adverse events related to drug dosage have been reported, including decreased cognitive function, listlessness, fatigue, constipation, incontinence, urinary retention, and impotence. Functional outcomes also depend on the amount of rehabilitation therapy that the patient receives after pump implantation. ITB has been reported to increase independence, mobility, and self-care; to improve sleep patterns and bladder function; and to decrease pain. Little has been published on ITB use and gait/mobility, but studies with small cohorts have reported increased stride length and walking speed. It remains to be seen whether early pump implantation will prevent the development of severe deformities.
Exercise approaches to pain
Correlations have been identified between inactivity and increased pain incidence. Exercise and activity are effective means of pain management. Exercise as a means of pain management has been widely studied in many conditions and has shown significant success. Exercise can also stave off conditions that increase the opportunities for pain development, such as obesity and cardiovascular disease. Obesity rates may be increasing among individuals with CP, particularly in the higher-functioning individuals. Obesity in adults with CP, as in the general population, increases the opportunities for pain development. However, many barriers exist to individuals with CP gaining access to exercise facilities, including cost, transportation, and availability of assistance.
Musculoskeletal pain and deformity
The long list of acquired progressive musculoskeletal disorders found in adults with CP belies the common assumption that CP is a static disease. Although no correlation between GMFCS level and pain location or intensity has been demonstrated, significant associations between severity of deformity and pain have been reported. A trend between inactivity and pain has also been noted. Increased rates of fracture and lower BMD have been documented in both children and adults with CP, primarily in less ambulatory populations and those who take antiepileptic drugs.
Surgical interventions primarily focus on improving function, preventing deformity and dislocation, and improving functional problems caused by progressive deformities such as crouched gait and patella alta.
Hip. Appropriate interventions during childhood provide stable hips for the adult with CP. Intervening surgically to correct painful bony deformities is less successful in adults. Acquired subluxation and dislocation, resulting from delayed weight bearing and muscle imbalance, is reported in up to 28% of all individuals with CP and in up to 59% of individuals with quadriplegia. Hip deformity is generally progressive, even with bracing, and results in pain, difficulty sitting, and challenges in hygiene.
The surgical options for an adult with CP are head-neck resection (removal of the femoral head and neck), valgus osteotomy (selective removal of bone), interposition arthroplasty (interposition of other tissue such as muscle or tendon to separate inflamed bone surfaces in arthritic joints), hip arthrodesis (use of bone grafts to fuse the joint), and total hip replacement. Successful surgical intervention in the hip can result in decreased pain and an increased sitting tolerance.
Another hip deformity is femoral anteversion, an inward twisting of the femur that presents with internal rotation of the lower extremity, increased difficulty walking, and hip pain. Because this deformity results in increased pain and decreased function, any surgical correction should be performed in the younger patient.
Upper and lower extremities. Many adults with CP note that pain in the lower extremities is one reason why they stop walking; in many cases, this occurs before the age of 25. In the lower extremities, foot deformities such as equinovarus and equinovalgus, as well as toe deformities, can make weight bearing and shoe wear painful. Other less common issues are contractures of the hip and knee.
Contractures in the upper extremity are often treated surgically. These deformities are most often treated with lengthenings as opposed to transfers, sometimes accompanied with joint fusions.
Spine. Progressive and large scoliosis deformities in persons with CP impair function and are troublesome. Surgery may be reasonable. The average size of the deformity at the time of surgery is much larger, and the curves are much more rigid, than those in patients with idiopathic scoliosis. When surgeons evaluate an adolescent with CP and a 50º scoliosis, they see an opportunity to intervene before inevitable (and debilitating) change occurs – a moment when the best possible outcome can be achieved from a surgery that they readily acknowledge will be difficult. Unfortunately, that moment usually comes well before parents and other providers believe the spine deformity is a significant problem. This underscores the value of stable and long-term relationships between physicians and their patients and families, which may facilitate more timely decisions for a difficult problem. Treatment for cervical stenosis and spondylolysis, likely to be overuse injuries attributable to spasticity and other movement disorders, remains controversial.
Complementary and alternative medicine
There is no published study specifically addressing complementary and alternative medicine (CAM) in adults with CP; however, national surveys of adults with chronic disabilities document that a majority of these individuals use such treatments. Studies have been published on CAM interventions such as hyperbaric oxygen, Adeli suit, patterning, electrical stimulation, functional neuromuscular stimulation, hippotherapy, craniosacral therapy, Feldenkrais, acupuncture, and conductive education in children with CP. These interventions may be carried over into adulthood.
Practitioners of both conventional and CAM therapies believe that exercise can be beneficial; accordingly, activities such as recreational sports, yoga, and hippotherapy may be continued from childhood into adulthood. General treatments for stress and anxiety, through such activities as yoga and meditation, though not directed at CP per se, may be more popular for adults than children.
Proposed way forward: Extend and refine research on the effectiveness of current treatments for CP by seeking answers to questions such as the following:
- • How can we define best practices and evidence-based medicine in the care of adults with CP?
- • Which interventions are most often and most successfully used to prevent secondary conditions and age-related problems?
- • What are the key points currently known regarding the long-term outcomes of early interventions, including BoNT-A, rhizotomy, intrathecal baclofen, tendon lengthenings and transfers, osteotomies, and spine surgeries?
- • What are the effects of childhood intervention on adult function?
Proposed way forward: Initiate research on how to best maintain musculoskeletal and neurological function and restore lost function in the individual with CP by systematically investigating the following questions:
- • How effective are prevention strategies such as exercise, nutrition, neurorehabilitative therapy, weight bearing, and other modalities in promoting wellness and preventing musculoskeletal impairments, pain, fatigue, and secondary medical conditions in individuals with CP?
- • How aggressively and how early should these prevention strategies be pursued?
- • What specific types (strengthening, aerobic, flexibility, combinations and doses of exercise and physical activity, intensive therapy, passive standing, robotic training) are best for specific disabilities and secondary conditions?
Proposed way forward: Design and initiate long-term studies of optimal methods to prevent and treat musculoskeletal and neuromuscular complications in adults with CP. These studies should take into account issues such as the following:
- • How can current studies conducted in CP be improved to include larger sample size, controls, and subgroups of CP (hemiplegia, diplegia, etc.) and reduce confounding influences from other treatments?
- • How can we encourage studies to optimize the intervention strategy (e.g. dose, duration, frequency of dosing)? For example, studies designed to investigate dose-concentration, dose-response, or concentration-response relationships may contribute to optimal dosage selection for definitive trials?
Can Cutting-Edge Technologies in Neurorehabilitation Improve Outcomes in Adults with CP?
Cerebral palsy is a brain injury, and a growing body of evidence demonstrates that the brain is capable of recovery after an injury because of the ability of neurons and other brain cells to alter their structure and function (plasticity) in response to external and internal pressures, including behavioral training. Neuroscientists have now determined many principles of experience-dependent plasticity that may be relevant to brain-damage recovery and rehabilitation outcomes. For instance, experiments have demonstrated that repetition drives plasticity and concomitant motor learning and thus may be critical for rehabilitation. Repetition is critical to this outcome; many studies have shown that rats trained on a skilled task do not show increases in synaptic strength, synaptic number, or map reorganization until they have undergone several days of training. The quality of the intervention is equally important, with task-specific, goal-directed interventions enhancing neural reorganization and recovery.
Most of the current research has been based on animal models of stroke. A critical question therefore, is how generalizable these findings are to other conditions. The brain injury resulting in CP occurs early in neurodevelopment, while stroke occurs in adulthood: there is a difference not only in the age of the injury but also in the timing of the injury relative to introduction of rehabilitation therapy. Should further research in animal models be conducted to provide a framework of neuroplastic principles for the child and adult with CP, or should scientists move ahead to clinical research?
A better understanding of the processes underlying neuroplasticity might make it possible to improve the effectiveness of therapies administered throughout the lifespan. These therapies might include physical therapy such as task-specific training; pharmacological treatments such as neuronal growth factors; transcranial magnetic stimulation; and neuromuscular stimulation, probably in combination.
Transcranial magnetic stimulation
Transcranial magnetic stimulation (TMS) is used to measure brain activity and the function of specific brain circuits. It offers information regarding prognosis for recovery and the pathophysiology underlying motor skill deficits. TMS can be used to evaluate brain recovery after rehabilitation treatments with motor mapping. Cells in the motor and sensory areas of the cerebral cortex are associated with different parts of the body and are arranged in such a way as to represent the anatomical correspondence of these parts. One research team used TMS to map the motor cortex before and after therapy in a cohort of stroke patients. They found that before treatment, the cortical representation area of the affected hand muscle was significantly smaller than that of the contralateral side. After treatment, the muscle-output area size in the affected hemisphere was significantly enlarged, corresponding to a greatly improved motor performance of the paretic limb.
It is possible that TMS could be used to correlate functional motor performance with patterns of motor control representation and reorganization and thus to assess the efficacy of treatment, both over the short and long term. In addition, repetitive TMS (rTMS) may be used to stimulate damaged areas of the brain in persons with CP. Preliminary data have indicated that rTMS may induce a beneficial effect in conditions of stroke, dystonia, Parkinson’s disease, depression, and epilepsy.
Innovations in robotic technology, together with an improved understanding of the neurological recovery process in individuals with chronic stroke, have led to new neurorehabilitation therapies to restore function in the upper and lower limbs and hands. Researchers have focused on whether task-specific, robot-assisted training can influence brain recovery, and several studies have shown neurological recovery is possible in mature and damaged nervous systems (persons with a history of stroke).
Task-oriented rehabilitative modalities include robot-assisted, body-weight-supported treadmill training (BWSTT) for the lower limbs and the MIT-MANUS (developed at the Massachusetts Institute of Technology) shoulder and elbow robot for upper-limb training. These devices enable severely affected individuals to perform a series of movements that therapists cannot emulate. The robots can detect the amount of force the patient has to complete the movement and adjust the assistance provided accordingly. Several studies have shown that BWSTT can improve walking ability in stroke patients, in adults who have sustained spinal cord injuries, and in children with CP. A recent meta-analysis of the effectiveness of robotic-assisted BWSTT in stroke patients indicated this treatment modality, combined with usual care, significantly increases walking capacity as compared with usual care alone.
One group of researchers adapted upper-extremity robots, work stations, video games, and outcome measures meant for adult stroke patients for use with pediatric patients who had lost motor function owing to brain injury. A second study demonstrated that children aged 4 to 12 with hemiplegia due to CP or acquired brain injury could improve upper motor function after 16 training sessions. A third research team demonstrated similar results in children with hemiplegic CP after 18 sessions of goal-directed robotic therapy. Preliminary data from a randomized, controlled study of robotic-assisted therapy in children with hemiplegic CP have demonstrated increased mobility and functional gains in both the active (goal-directed) and passive robot-assisted groups for almost all of the functional outcome measures; however, the active group showed a greater degree of improvement than the passive group in most measures.
High-intensity, task-specific therapies, while promising, require many hours of practice that engage and challenge the patient. Preliminary data have demonstrated how important it is that robot-assisted therapy be active rather than passive. Virtual reality technology can alleviate this problem. It not only provides feedback but also creates an environment in which the presentation of stimuli (e.g. a video game) can be modified as performance improves. Virtual reality has shown promise in improving upper- and lower-limb function in patients post stroke and/or with CP when used in conjunction with neurorehabilitation modalities such as those as discussed above. In addition, haptic technology has been recently employed in many virtual reality rehabilitation techniques. ‘Haptic’ refers to the science of touch and force feedback in human-computer interactions. These force-feedback devices not only sense a person’s movement but also apply forces during movement. Similar to robotic therapy devices, these devices can simulate the sense of touch and movement, and apply therapeutic patterns of forces to the hand and arm as the user attempts to move.
Electrical stimulation can be used to depolarize the axon membrane and trigger an action potential and, when applied to motor neurons that innervate skeletal muscle, to induce a muscle contraction. When applied repeatedly, electrical stimulation can strengthen muscles, reduce muscle spasticity and cocontraction, and increase range of motion in patients with neuromuscular disorders such as stroke, multiple sclerosis, and CP. It can also induce neuroplastic changes in the motor cortex.
A small number of studies have been conducted using neuromuscular electrical simulation (the application of an electrical current of sufficient intensity to elicit muscle contraction) in persons with CP to reduce spasticity in the upper extremities and improve hand function; many more such studies have been done in the lower extremities. While the majority of these studies have shown improvement in function and strength, they remain inconclusive because of the lack of sufficient control groups, statistical power, and standardization in dose and outcome measures
Some studies have shown that vibration therapy can improve balance and gait in Parkinson’s disease and chronic stroke. Vibration therapy has also been shown to prevent loss of muscle strength and bone density in a population of young immobilized volunteers. In a study of 20 children immobilized as a result of CP who underwent vibration therapy, bone mineral density in the tibia increased over a 6-month period.
The mechanism by which vibration therapy improves bone density and muscle strength is unclear; however, it is postulated that vibrations stimulate muscles spindles and alpha-motor neurons and induce muscle contraction. The literature supporting the use of vibration therapy to increase muscle strength and BMD in persons with neuromuscular disorders suffers from a lack of studies using similar dosages, treatment parameters, and outcome measures.
Extending neurorehabilitation therapies to individuals with CP may require special considerations. Most of the research results are based on studies with patients post stroke, a majority of whom probably had normal movement patterns before incurring their injury. Individuals with CP, who are much younger, may never have developed ‘typical’ movement patterns. In other words, individuals with CP do not relearn normal movement: they must learn normal movements for the first time. Initial studies are showing promise for the application of current and developing neurorehabilitation modalities to individuals with CP, but more work is needed to validate these early findings. If muscle strength and balance can be improved and if new motor skills and normal movement patterns can be learned, then many of the secondary conditions associated with CP may be prevented or mitigated.
Proposed way forward: Expand understanding of the role of new and developing technologies by exploring the following areas of inquiry:
- • What is the capacity for neural plasticity in the adult with CP?
- • Can we apply the principles established for experience-dependent neural plasticity in stroke rehabilitation to CP?
- • What is the role of neuroimaging and transcranial magnetic stimulation in assessing the efficacy of neurorehabilitation modalities, as well as rehabilitation outcomes, in the adult with CP?
- • What role can neurorehabilitative therapies such as robot-assisted mass practice, electrical stimulation, virtual reality environments, vibration therapy, transcranial magnetic stimulation, and combinations thereof, play in improving motor control and function in adults with CP?
The Adult with CP: Can the Medical System Keep Up?
The diagnosis of CP is often thought of as a pediatric condition; it must be understood as a life-long disorder. And, treating adults with complicated musculoskeletal and neuromuscular impairments is challenging. Few medical facilities are prepared to treat adults with developmental disabilities, and adults with CP needing surgery often find themselves in pediatric environments, where personnel have not been trained in adult care.
The result is a community that is badly underserved. Research suggests that adults with CP view their general health as good, but they use preventive care services less than do persons without disabilities. Adults with CP use specialty health-care and rehabilitation services less, and emergency room care more, than their non-CP peers. Less than half of women with CP receive Pap smears, and there have been no studies addressing the impact of menopause on bone health in adult women with CP. Adults with CP have poor access to dental care owing to lack of insurance coverage and of dental residents who are trained to treat these individuals’ needs.
These problems and the urgent need to improve access to care, exercise, and rehabilitation services came up repeatedly during the workshop. The phrase ‘Children are not just small adults,’ used frequently in the pediatric world, was reversed, and the fact that adults with CP ‘are not just big children’ was repeated often. It is not just that musculoskeletal problems grow worse with age but also that medical comorbidities in adults are different from those in children. Most pediatric facilities, even if they want to care for adults with CP, do not have access to the anesthesia, pulmonary, cardiology, and other specialists needed to provide safe, high-quality care. Moreover, few adult medicine practitioners have been trained in the care of the patient with CP, and they are therefore uncomfortable providing care. It is difficult for the typical adult medical facility to justify the investment of significant resources in enhancing care for this low-volume, but potentially high-risk, patient population.
Even our definitions of ‘best practices’ and ‘evidence-based care’ need attention, particularly in the pediatric facilities that are starting to extend their mandate to include adults. What patient-safety issues require special attention in the adult with CP? What equipment and supplies (lifts, adult code carts, etc.) represent the minimum standard? What new competencies should nurses and support staff develop? What linkages to other providers such as dentists, optometrists, obstetricians, internists, and/or gerontologists should be encouraged? What clinical pathways need to be developed to ensure optimum care? What additional protocols and procedures for problems such as end-of-life care and employment issues need to be developed by Family Services? Even case management/discharge planning, usually a straightforward matter, differs for the adult with CP.
The experience of the Gillette Lifetime Care Center in St. Paul, Minnesota, provides one approach to resolving these tensions. Gillette built an adult extension to its pediatric service, capitalizing on the knowledge of the pediatric team, especially in the equipment adjustments and support services that the young adult with CP requires. Perhaps most important, Gillette brought the principle of coordinated care from its pediatric setting to meet the challenges presented by the adult CP patient. Even Gillette, however, does not offer ‘till death do us part’ support. It does not address the needs of middle-aged and senior adults.
Coordinated care may be the right way forward, but it will succeed only if there is true collaboration among practitioner communities. The lack of such collaboration is one of the main barriers to producing evidence-based recommendations on treating the adult with CP. Put differently, our current ‘silo’ approach to service delivery and research is standing in the way of progress.
One of the lead collaborators must the patient who presents with CP and his or her family. The patient and family must be empowered to participate. A ‘navigator’ in the transition from pediatric to adult care is essential, and that navigator may need to stay with the patient and the family as they continue their journey.
Improving all participants’ access to information is critical to success, especially as research delivers fresh insights into the best-care practices for the adult CP patient. We cannot, however, assume that simply making the information available is sufficient. Proactive educational strategies will be required to bring information to the attention of collaborators, so that they can absorb that information and put it to use in servicing patients diagnosed with CP.
Proposed way forward: Undertake research in the following areas in order to improve the care of children with CP as they enter young adulthood by investigating the following:
- • What outcomes represent a successful transition from pediatric to adult care?
- • How medical professionals can best help ensure that adolescents and young adults with CP become independent consumers of health services?
- • What adolescents with CP need to know about the transition to adulthood? How will their transition be different from that of their peers without CP?
- • How the health-care community can prepare to support the increasing number of adults with CP?
- • What combination of services/facilities do young people need to maximize their musculoskeletal and neuromuscular health as adults?
- • How do we address problems with access to health care, therapies, and exercise facilities?
- • How the health-care community can work together to establish best practices and evidence-based standards of care for adults with CP?
- • How we can best deal with personnel shortages, such as the dearth of adult orthopaedic surgeons, neurologists, and other specialists trained in the care of adults with developmental disorders?
- • Can we improve the education of students and residents in the treatment of adults with CP? Which specialties should be targeted for improved education?
- • How do we best educate primary care physicians, specialists, and therapists on the health needs of adults with CP?
Recent increases in the survival rate and longevity of individuals with CP attest to the power of modern medicine. The same sense of responsibility and compassion that motivated the research that led to such advances as increasing the survival rates of very low birth weight infants must now be applied to developing the best means of caring for children with CP as they reach adulthood. Extending the life span of persons with CP, however encouraging, is only half the battle. The other half is to understand the unique neuromuscular and musculoskeletal challenges of this population and to develop the most effective treatments and therapies.
The medical and research communities have helped these individuals survive. It is now our responsibility to help them thrive and live productive lives, as uninhibited as possible by the chronic pain and secondary conditions associated with CP.