Peripheral neuropathy (PN) is one of the most prevalent diseases in the United States. Six years ago, the 108th U.S. Congress estimated that at least 20 million U.S. citizens have this debilitating disorder. Although 27% of these cases result from diabetes (13), the largest subgroup, representing 33% of PN cases, is of unknown cause (33). Overall, PN affects more people than those with coronary heart diseases (13.7 million), various cancers combined (16.4 million), and diabetes (17.3 million) (26) and is prevalent especially in older adults, influencing more than 20% of individuals aged 60 to 74 yr (28).
NEUROMUSCULAR IMPAIRMENT AND CONTROL IN PN
Although PN affects both the motor and sensory systems, it commonly is considered a sensory neuropathy because of its profound effect on sensations through progressive deterioration of distal sensory nerves, especially at the early stage of the disease. This deterioration commonly leads to painful sensations and reduced sensitivity with time. Increases in detectable force at the hallux of up to 400 times that of age-matched controls exceed the increases in detectable forces at the mid-foot and heel to emphasize the distal to proximal deterioration of the disorder (9). Reductions in conduction velocities in sensory (sural) and motor (peroneal) nerves are common for PN (e.g., (2)). Strength loss, also observed in severe PN cases (e.g., (10)), can be blamed on a multitude of factors besides the disease, including disuse because of pain, discomfort, or fear of falling. Disuse also may explain an increase in body mass index. Increases in body mass index and disease severity significantly predict falls in this population (29).
PN Affects Physical Function
People with PN acquire balance and mobility problems, which may explain the altered movements during performance of certain tasks. They have greater sway during quiet stance (e.g., (27)). This point is emphasized in that type 2 diabetic patients with PN have greater standing sway and slower gait than type 2 diabetic patients without PN (27). Patients with PN and reduced lower limb sensations produce lower scores on the functional reach test (11), the 6-min walk test (6MW), and the Timed Up-and-Go (TUG) (21) compared with age-matched controls. People with PN also have exhibited greater endpoint errors than healthy young and older adults when performing a reaching task with a step (14). The significant link between poor postural stability and poor functional mobility for elderly patients with reduced foot sole sensations is unlike the significant link between reduced strength and poor functional mobility for elderly controls (Fig. 1). Together, these data show that abnormal sensory reductions for those with PN frequently affect mobility beyond the normal aging process. We further suggest that impaired postural control and gait mobility among people with PN is related directly to the reductions in foot sole sensation and likely not that of strength reductions associated with aging.
The Cycle of PN Deterioration
The reduction of foot sole sensation and slow conduction velocity are key clinical characteristics that accompany the pain and/or numbness complaints in patients with PN (28). Given time, possible neuroplastic changes in the central nervous system (i.e., reductions in interneuron excitability) and, in some cases, muscle weakness can lead to loss of coordination needed for balance and mobility. Consequently, placing limits on movement leads to decreases in physical activity, which also can lead to increases in pain/numbness. Therefore, the neurological impairments associated with PN could lead to behavior changes in a negative cycle that casts a shadow on this population’s independence and quality of life. Figure 2 summarizes the various aspects of this vicious cycle and its influences.
PN ADAPTATIONS WITH MEDICAL AND THERAPEUTIC TREATMENTS
Medical and Nontraining Therapeutic Interventions
Treatments for PN often consist of remedies and therapies to ameliorate the frequently debilitating symptoms of pain, burning sensations, numbness, and/or foot ulcers, which can lead to functional disability. In one study, low-level infrared therapy improved sensation in the feet, improved balance, and reduced pain for 27 people with PN (18). Unfortunately, such improvements are not observed consistently in this population (17). Medication also has been used to treat disorders blamed for causing neuropathy. For example, proper insulin used to treat diabetics may help limit the development or progression of PN (3). Four months of multipolar, static magnetic shoe insoles used by those with diabetic PN resulted in greater reductions in numbness, burning, and pain compared with those who wore unmagnetized shoe insoles (34). Electrical nerve stimulation (13) and isosorbide dinitrate spray, a numbing agent, have been shown to temporarily reduce pain for people with PN (37). Despite the widely believed and prescribed healing function of vitamin B-6, B-12, and folic acid supplementation for people with neuropathy by neurologists, the specific effects of these supplements are unknown (1a). Surgical decompression of the mechanical pressure of tissues surrounding peripheral nerves has been suggested for the treatment of diabetic neuropathy, but its effectiveness is unproven (6). Additional research is needed to clarify short- and long-term effects of such treatments.
Several experts have suggested that altering gait minimizes excessive plantar pressure loads to avoid foot ulcers. These alterations include using a shuffling gait with shorter steps (38), using a hip pull-off rather than foot push-off (24), and using a “step-to” gait pattern where the lag foot is brought beside the lead foot with or without a cane (4). Balance improvements for people with PN also can occur with cane use (see review by Richardson and coworkers (30)). Although medical and nontraining therapeutic interventions assist patients in dealing with some symptoms and/or functional deficits associated with having the disorder, they do not prevent disease progression or offer a cure for the disease, thus could, and possibly should, be used in conjunction with therapy and exercise that enhance functional performance.
With no available cure, combination therapies suggested for PN rehabilitation include modalities of nonpharmacologic nature, such as exercise (5). Clinicians treat the major problem of instability with strength training as one of the major foci (30). Although weakness is linked to falling in healthy older adults, there is no evidence to show that weakness is a key factor that leads to instability and falls in people with PN. In fact, our data show no significant correlation between reduction of knee extensor strength and functional mobility among PN participants, unlike the clear correlation that exists for healthy controls (Fig. 1) (21). These outcomes do not rule out the possibility that strength in other muscle groups, such as those surrounding the ankle joint, may contribute to PN deficits.
Training system stability has resulted in balance improvements in those with PN. For example, 3 wk of concentrated exercises involving balance and standing strength movements (i.e., toe raises, heel raises, eversion, and inversion) improved balance and functional reach performance in subjects with diabetic neuropathy but not the age-matched controls with whom they were compared (30). More recently, Morrison and coworkers reported positive outcomes from 6 wk of stretching, balance, and strengthening exercises primarily focused on the lower limbs of neuropathic patients with type 2 diabetes (23). Results indicated faster finger and foot reaction times to visual stimuli, less sway, greater leg strength, and reduced fall risk. People with PN produced similar results when training involved responding to platform oscillations or Frenkel exercises, which involve leg movements while laying down and stepping, turning, and writing movements when upright (25). The patients improved body sway and stability, balance, and gait scores after 10 1-h training sessions within a 2-wk time frame. For people with hereditary sensory and motor neuropathy, performance on the Berg Balance Scale, Up & Go test, and 10-m walk test also improved with balance training, which included different postural manipulations while maintaining upright stance (22). It was speculated that these functional improvements resulted from sensory substitution, in which the patients learned to rely more on accurate vestibular and visual inputs rather than their inadequate proprioceptive inputs from the lower limb (22). In fact, balance training using real-time visual feedback displays resulted in improvements in stability scores and medial-lateral sway (31) and fewer falls during platform perturbations (35) for individuals with PN to further support the use of sensory substitution in this population.
Clearly, different training protocols may result in improved balance and/or gait outcomes for those with PN. We reasoned that a move toward “sensation recovery” is needed for this population as neural plasticity may offer better rehabilitation opportunities for those with PN. It is well known that neural plasticity of the sensory system exists and that activity can alter synaptic strength, neural networks, and sensory perception. Improvements in sensation recovery are preferable to sensory substitution, which has been used successfully with different neurologic populations (e.g., those with vestibular deficits (8)). Although complete sensory restoration would alleviate movement deficits associated with PN, it is unclear whether adequate sensory restoration can occur in this population.
There is evidence to suggest that sensory improvements and rehabilitation efforts based on neural plasticity can occur with mind-body exercises, such as Tai Chi training, which emphasize control of movement. Long-term Tai Chi practitioners possess better ankle joint proprioception, even compared with long-term participation in other forms of exercise, such as running and swimming (36). Tai Chi practitioners also possess superior tactile spatial acuity in the fingers (16). Such enhancements in sensory perception provide evidence that Tai Chi may slow age-related declines in tactile sensation (16) and add to the reasons to use it for the PN population, as it has the potential to help people with PN regain reduced sensations associated with the disease. Results from our laboratory (Fig. 3) reveal improvements in foot sole cutaneous sensation and performances on TUG and 6MW tests after people with idiopathic PN completed a 24-wk program of Tai Chi exercises (19). In this case, improvements in functional mobility were accompanied with the improvements in foot sole sensation. Tai Chi (15) and yoga (20) practice can also result in improved peripheral nerve conduction velocities. Further, neuropathic people with type 2 diabetes experienced improved fasting blood glucose levels, balance, and functional mobility after training with Tai Chi (15). These initial findings indicate that mind-body exercises, such as Tai Chi and possibly yoga, can result in sensory improvements in those with PN, thus supporting the promising idea of sensory recovery in this population.
PN ADAPTATIONS: THE ROLE OF EXERCISE
It has been suggested that exercise may prevent early onset of neuropathy in patients with type 2 diabetes (1). The current evidence in the literature also suggests that it is possible to reverse the viscous cycle of PN deterioration through exercise (at least temporarily). Figure 4 depicts a model for rehabilitation efforts, in which increased physical activity of appropriately designed exercises could be used to decrease the pain and/or numbness resulting from PN and eventually lead to improvements in balance and mobility. Given time, neuroplastic changes in the central nervous system may occur. Compared with the undesirable effects of PN on movement dysfunction, as illustrated in Figure 2, exercise may break the vicious cycle and remove the metaphorical shadow cast over the patient’s independence and quality of life (Fig. 4).
The PN rehabilitation model in Figure 4 does not address the precise changes in neural plasticity that occur with increased physical activity. Neural plastic changes in Tai Chi practitioners include those resulting in improved cutaneous sensations for those with PN (19) as well as superior responses in ankle joint proprioception (36) and spatial acuity in the fingers (16) as compared with individuals trained in endurance exercises or without training. Whether such changes were induced by attentional mechanisms (7), like those observed with Tai Chi training (16) or reductions in pain that ensue from Tai Chi practice (32) or something else remains to be tested. However, we reasoned that despite the sensory declines, which occur with normal aging and PN, long-term participation in Tai Chi enhances the use of the active neural networks through an all-inclusive, mind-body approach (19). These neural changes involve motor control improvements and/or strategies, which lead to improved coordination needed for functional balance and mobility. Training that emphasizes reductions in sensory declines or improvements in sensations (16) should be more effective for people with PN because their decline in functional mobility links to sensory dysfunction (21). Low-impact options like Tai Chi also are of interest because such training may decrease the potential for developing joint injuries or foot ulcers, which occur in a large fraction of people with PN. This does not negate the fact that people with PN always should be wary of weight-bearing exercises because of plantar loading links to potential foot ulcer development.
There still is much to learn about the chronic neurological and behavior progress of PN. What amount of deterioration of cutaneous sensation, proprioception, and sensory nerve conduction velocity does it take to affect nervous system control over mobility, balance, and goal-directed actions? Does the risk associated with sensory reductions in this population differ from sensory reductions because of aging? Although a better understanding of this process will help address the problems at different stages of the disease and to design more effective interventions, it should not preclude researchers and clinicians from developing strategies to help curb or improve the neural and functional declines associated with PN. Results presented in this review indicate some hope for reversing the debilitating outcomes associated with having PN. Use of certain exercises reveals at least short-term reversal of plantar sensitivity and improvements in balance and functional mobility in this population. Whether exercise training can prevent neuropathic disease progression resulting in long-term improvements remains to be tested. However, the limited research on the use of exercise with this population reveals promise for potential long-term improvements with training.
There was no funding received by authors to support this work.
The authors have no conflict of interests to be declared.
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