Clinical aspects

Description

Therapeutic exercises include range-of-motion, strength exercises, balance, and gait training. Range-of-motion exercise focuses on limbs and joints affected by impaired nerve function. In patients with severe generalized paralysis, as can occur in Guillain-Barré syndrome, all joints should undergo passive range-of-motion one to two times a day. Strength exercises should be performed two to three times a week for the identified weak muscles. In neuropathy patients, the intensity should not reach muscle fatigue to avoid overwork-induced damage. Compared to non-weight-bearing exercise, weight-bearing exercise showed greater gains in the 6-minute walk distance and average daily step counts in patients with diabetic neuropathy (41). Strength training three times a week for 8 weeks has shown significant improvement of knee torque and actual functional abilities (ascending and descending stairs, rising from sitting, putting on socks, and getting into and out of a car) in patients with hereditary motor and sensory neuropathy (34). Interval training exercise 3 days per week for 24 weeks showed significant improvements in cardiorespiratory capacities, isokinetic concentric strength, and functional ability as well as reduction of fatigue and pain in patients with Charcot-Marie-Tooth disease (16). A focused exercise regimen to increase ankle strength can improve balance in patients with peripheral neuropathy (43). Focused simple hand, finger, and foot exercises in patients with diabetic peripheral neuropathy showed significant improvements in motor function in daily living, such as climbing stairs and performing work or chores (54). A 14-week exercise program led to improved neck flexor endurance; this persisted at the 1-year follow-up (20). For mononeuropathy, such as carpal tunnel syndrome, decompression or neuromobilization exercise improved symptoms of entrapment neuropathy (46; 22). Resistance training also decreases risk factors for cardiovascular disease as well as improves glucose tolerance and insulin sensitivity (04). Improvement in muscle strength after resistance exercises accelerated strength generation during stair ascent and descent in patients with diabetic polyneuropathy (21). Progressive-resisted exercise improved health-related quality of life in patients with HIV/AIDS-related distal symmetrical polyneuropathy (38; 55) as well as in individuals with type 2 diabetic polyneuropathy (27). Moderate-intensity aerobic exercise and progressive resisted exercise are also effective in reducing neuropathic pain in HIV-associated distal symmetrical polyneuropathy (35). Resistance exercise and aerobic exercise training improved fitness and strength measured by maximal O2 consumption velocity in chronic inflammatory demyelinating polyneuropathy (36). In a study of diabetic sensory polyneuropathy, an exercise program resulted in increased aerobic exercise capacity and improved motor and sensory conduction (17). Improved neuropathic symptoms, reduced pain, and increased intraepidermal nerve fibers were found in 17 patients with diabetic neuropathy after a 10-week aerobic and strengthening exercise program (30). Aerobic exercise reduced interference of pain with walking, work, interpersonal relationships, and sleep in patients with painful diabetic peripheral neuropathy; however, there was no change in pain intensity (57). In patients with type 2 diabetes and peripheral neuropathy, exercise programs led to improved fatigue, oxygen uptake, body fat, peripheral blood flow (31), and reduced HbA1C and neuropathy symptoms (56). In addition, long-term aerobic exercise may prevent diabetic neuropathy (07). Based on a systematic review of clinical trials, Gravesande and Richardson found the most common risk factors for falling were impaired balance, reduced walking velocity, peripheral neuropathy, and comorbid conditions (19). Varieties of balance training programs have been developed for peripheral neuropathy patients. In patients with diabetic neuropathy, postural stability training with the Biodex Balance System improved postural stability and balance (15). A foot-ankle exercise program in people with diabetic neuropathy improved toe strength and gait, lasting for a year (39; 40). Lower body positive pressure treadmill training with 75% weight-bearing for 12 weeks in patients with diabetic polyneuropathy resulted in short- and long-term improvements in gait and balance (01). Exercise training improved balance, quality of life, and neuropathic pain associated with chemotherapy-induced peripheral neuropathy (45; 37; 12). Visual computer-feedback balance training improved balance in cancer patients with chemotherapy-induced peripheral neuropathy (10). Preservation of vibration and heat pain thresholds was found after physical therapy in taxane-induced peripheral neuropathy (05). Quality of life was higher for immediate versus delayed exercise in women receiving taxane for breast cancer, but not in sensorimotor symptoms or signs (09). Upper limb exercise also improved their function and reduced pain in patients with chemotherapy-induced peripheral neuropathy (23). Static balance improved more in middle-aged versus older adults with diabetic peripheral neuropathy after an 8-week outpatient exercise program (02). Older adults experience greater functional gains from inpatient rehabilitation than younger adults (28).

Neuromuscular electrical stimulation applies electrical current to the skin surface or intramuscularly to induce a muscle contraction and improve muscular control during stance and ambulation. It may retard muscle atrophy during gradual reinnervation. In a prospective, nonrandomized trial of high-tone external muscle stimulation, 73% of subjects with diabetic and uremic neuropathy had improved tingling, burning, pain, and numbness, and reduction in sleep disturbances (29). After 12 weeks of 1-hour external muscle stimulation, general well-being, physical capacity, and ulnar motor conduction velocity were improved in uremic neuropathy patients (48). Electrical stimulation of innervated muscle produces increased strength similar to that of voluntary contraction; however, the efficacy of electrical stimulation of denervated muscle is controversial. Muscle is significantly less excitable than nerve tissue; as a result, the stimulation intensity is much higher and, thus, poorly tolerated. To retard muscle atrophy, stimuli of sufficient intensity, pulse duration, and frequency must be given several times a day. This often makes electrical stimulation of denervated muscle impractical (52).

Transcutaneous electrical nerve stimulation (TENS) for pain relief applies stimulation to the skin to block pain perception. In a trial for carpal tunnel syndrome, TENS decreased pain-related cortical activations measured by fMRI (26). Kumar and Marshall used TENS for 30 minutes daily on each lower limb over 4 weeks for painful diabetic neuropathy (33). Patients were randomized to electrotherapy or sham treatment. No local or systemic side effects were noted. Although 83% of the patients recorded reduced pain scores, individual responses varied significantly. The authors also studied the combination of amitriptyline 50 mg at bedtime and TENS (32). Amitriptyline alone reduced pain in 60% versus 85% for the combination. TENS reduced neuropathic pain and increased quality of life in painful cisplatin-induced neuropathy (51). A metaanalysis by the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology showed modestly improved pain with TENS in diabetic neuropathy (14). TENS reduced pain in medication-refractory postherpetic neuralgia (24). TENS to the plantar area improved balance and gait to enhance motor performance and plantar sensation in people with diabetic neuropathy (42). Low-frequency, 8-week, plantar vibration training of patients with diabetic neuropathy was associated with improved sural and peroneal conduction velocity, postural stability, pain, and tingling (47).

Low-frequency pulsed electromagnetic field treatment was investigated for painful diabetic neuropathy in a multicenter, randomized, double-blind, placebo-controlled study (53). Two hundred twenty-five subjects applied a device or placebo device to the feet for 2 hours a day for 3 months. There were no significant differences in pain intensity between electromagnetic treatment and control groups on the Neuropathy Pain Scale or visual analog scale. Twenty-seven subjects completed serial punch skin biopsies. Interestingly, 29% of the subjects in the electromagnetic treatment group had an increased epidermal nerve fiber density of at least 0.5 standard deviation, versus none in the control group (P = .04). Increases in distal thigh epidermal nerve fiber density correlated with decreased pain.

Orthoses are devices that support, align, and prevent deformities or improve impaired function. Ankle-foot orthoses are commonly prescribed to patients with weak dorsiflexors and impaired foot eversion and inversion control. Models include ready-made plastic ankle-foot orthosis, custom-made leaf-spring ankle-foot orthosis, spring wire foot drop support, and double-upright braces (Kienzak ankle-foot orthosis). They facilitate plantar flexion and transfer the location of the ground reactive force forward at heel strike to prevent knee buckling. Optimizing the ankle-foot orthoses enhanced physiologic performance and improved efficiency of total body energy expenditure during ambulation in a patient with Charcot-Marie-Tooth neuropathy (08). Disadvantages include a considerable weight burden placed on a weakened limb and more rigid foot position. Use of high-top boots incorporating a dorsiflexion-assisting device improved gait and comfort in a patient with Charcot-Marie-Tooth disease (50). The ankle-foot orthoses improved gait regularity in patients with peripheral neuropathy while walking on an irregular surface (44). Knee braces limit extension to neutral and flexion to 30° and prevent knee buckling and genu recurvatum due to weak extensors. Knee immobilizers reduce falls and increase ambulatory distance in patients with femoral neuropathy (25). Wrist splints immobilize the wrist, but allow full metacarpophalangeal flexion and thumb opposition. They are often prescribed for median nerve entrapment at the wrist. Although both were effective, wrist splints with a metacarpophalangeal unit were more effective at improving pain function than a classical wrist splint (18).

Canes can increase stability and decrease forces at the weak limb. They are effective and inexpensive aids for reducing imbalance. Use of a standard cane has reduced the loss of balance 4-fold in patients with peripheral neuropathy (06). Unilateral upper extremity strength needs to support about 20% of body weight through the cane for it to be beneficial. Crutches are used in patients with good arm strength and impaired weight bearing in one leg. Crutch types include axillary, triceps (Canadian elbow extensor crutch), and forearm models. Walkers provide a wider base of support and are prescribed for patients requiring maximum balance assistance. Patients must have good grasp and arm strength bilaterally. Wheelchairs improve mobility and facilitate transfer for neuropathy patients with profound weakness.

Occupational therapy may also be necessary for neuropathy patients. A therapist may provide upper extremity exercises, splints, and self-care training including feeding, dressing, grooming, and assistive devices to adapt the neurologic deficits. Pistol grip reachers are useful to grab things from hard-to-reach places. Thickly gloved utensils, such as pens, screwdrivers, and cutlery, can greatly facilitate activities of daily living (ie, in patients with advanced hereditary neuropathies and hand weakness). Bathtub rails and bedside commodes will reduce the risk of a fall.

Goals include the compensation of, and adaptation for, functional impairment and disability, and specifically the enhancement and recovery of motor control and fine coordinated movement of the upper and lower extremities. Education, exercises, positioning, and use of corrective devices can reduce the impact of neuromuscular lesions, restore mobility, and facilitate daily activities. Clearly, both placebo effects of therapy and psychological effects derived from the attention of a caregiver occur as well as from the recognition that the patient has some control over the outcome of his condition.

Management of neuropathic pain is also discussed in the following articles: Neuropathic pain: treatment, Central neuropathic pain, Small fiber neuropathies, and Complex regional pain syndrome. Other supportive measures are discussed in the series of articles on Charcot-Marie-Tooth disease (Charcot-Marie-Tooth disease type 1A, Charcot-Marie-Tooth disease type 1B and other CMT neuropathies associated with MPZ mutations, Charcot-Marie-Tooth disease type X, and Charcot-Marie-Tooth disease: CMT2, CMT4, and others).

Indications

Physical therapy and occupational therapy are indicated for patients with peripheral nerve disease with impaired strength, sensation, balance, ambulation, or activity of daily living.

Contraindications

Modification in the type and intensity of exercise is needed for patients with different types and stages of peripheral nerve diseases. For example, patients with acute nerve injury should perform non-weight-bearing activities. Given the aerobic demands that can be associated with rehabilitation and exercise, prior medical clearance should be considered, especially in patients with comorbidities.

Outcomes

The majority of patients improve mobility and functional levels after physical therapy. The improvement will plateau after a certain amount of physical therapy. Physical therapy is frequently prescribed for 1 to 2 months; however, chronic therapy may be required to maintain this plateau.

Adverse effects

No major adverse effects take place with skilled physical therapy. Orthostatic hypotension during exercise in patients with autonomic neuropathy must be avoided.

The prognosis of peripheral nerve diseases depends on disease duration before specific treatment as well as the underlying etiology. Entrapment neuropathies may have a complete recovery of function after surgery. Nerve injuries might have residual weakness and sensory disturbances. Chronic progressive neuropathies may continue to diminish a patient's function levels and require increased dependence on devices.

Special considerations

During pregnancy, physical exercises and devices may require modifications due to weight change and edema.

Clinical vignette

A previously healthy, independently living 73-year-old woman developed gait problems 3 days before admission. Power was 4+/5 in the arms and 3/5 in the legs. She had sensory deficits in a glove and stocking distribution and areflexia. Nerve conduction studies showed demyelination. Cerebrospinal fluid revealed elevated protein with normal cell count. She was diagnosed with Guillain-Barré syndrome. Despite treatment with intravenous immunoglobulin 0.4 g/kg for 5 days, she developed respiratory failure and dysphagia on day 4 of admission. She was on mechanical ventilation for 2 weeks with gastric tube feeding.

Physical therapy started when she was in the intensive care unit with a passive 4-limb range-of-motion. Three weeks after admission, she was transferred to a rehabilitation unit. Her feet were splinted in dorsiflexion when she was in bed. She wore custom-made leaf-spring ankle-foot orthoses when standing and walking with maximal assistance. Dysphagia resolved and she tolerated soft food. Exercises for strength and endurance as well as gait training and occupational therapy for activities of daily living were scheduled twice daily. After 6 weeks, she was able to walk with a front-wheel-walker and minimal assistance. Her feeding, grooming, and upper body dressing activities were with standby assistance only; she needed moderate assistance with lower body dressing. She had a bedside commode. Her motor strength improved significantly, but ataxia due to sensory deficits persisted. She continued 3 months physical therapy, once a day, in a skilled nursing home. She used a wheelchair and walker to move around in the nursing home. She was discharged home for independent living 6 months after the diagnosis of Guillain-Barré syndrome.

Scientific basis

The potential to enhance recovery of nerve function by manipulating the biological adaptability is the mechanism of physical and occupational therapy. Neuronal plasticity of peripheral nerves involves improved efficacy of synaptic activity, synaptic sprouting, axonal regeneration, remyelination, actions of neurotransmitters, and modification of ion channels for impulse conduction (13). In the rat sciatic nerve transection and repairing model, moderate exercise 1 hour per day, either active treadmill walking or passive cycling, improved muscle reinnervation, increased the number of regenerated axons in the distal nerve, and reduced the increased excitability of spinal reflexes 2 months after nerve lesioning (49). During physical therapy, tonic and phasic stimuli are used to modify the excitability of spinal motor neuron pools via postural reflexes and co-contractions. Physical and occupational therapy uses muscle stimulation, tendon vibration, joint compression, and skin stroking to elicit reflex movement and to retrain voluntary movement. Skeletal muscles change their properties not only due to alterations in their connectivity to motor neurons, but also as a result of functional demands. Many of the properties of skeletal muscle can be modulated by the pattern and level of both active and passive mechanical activity. The regulation of acetylcholine receptors in muscle also depends on activity, innervation, and probably specific trophic influence. Physical and occupational therapy prevents disuse atrophy, increases endurance, and allows for adaptation after neurologic deficits. TENS also accelerates functional and motor recovery and increases axon density and diameter in animal models (03).