Neuropathies associated with cytomegalovirus infection
Nov. 15, 2022
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Physical and occupational therapies can improve functional capacity in patients with peripheral nerve disorder. Therapeutic exercises, orthoses, devices, and other therapies are discussed in this article as the basis for rehabilitation in peripheral neuropathy. Patients should refer to physical and occupational therapists for evaluation and treatment. New orthoses and devices may be available with time to provide more comfort and mobility for patients with peripheral nerve disease.
• Refer to physical and occupational therapies for peripheral nerve disorders.
• Order orthoses and devices to adapt functional impairment and disability.
• Neuromuscular electrical stimulation may be beneficial in pain control or prevention of muscle atrophy.
The beneficial effects of various physical agents and exercise can be traced back to ancient human history. Electrical stimulation, heat, massage, and exercise were used therapeutically during and after World War I (10). Physical and occupational therapies play an important role in the improvement of function in acute or chronic nerve disease.
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 1 to 2 times a day. Strength exercise should be performed 2 to 3 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 on the 6-minute walk distance and average daily step counts in patients with diabetic neuropathy (39). Strength training 3 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 (32). 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 (15). A focused exercise regimen to increase ankle strength can improve balance in patients with peripheral neuropathy (41). 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 (51). A 14-week exercise program led to improved neck flexor endurance; this persisted at the 1-year follow-up (19). The carpal tunnel decompression exercise seems to improve symptoms of this entrapment neuropathy (44). Resistance training for the patients with diabetic neuropathy has the potential to improve muscle strength, endurance, and flexibility. Resistance training also decreases risk factors for cardiovascular disease as well as improves glucose tolerance and insulin sensitivity (03). Improvement in muscle strength after resistance exercises accelerated strength generation during stair ascent and descent in patients with diabetic polyneuropathy (20). Progressive-resisted exercise improved health-related quality of life in patients with HIV/AIDS-related distal symmetrical polyneuropathy (36; 52), as well as in individuals with type 2 diabetic polyneuropathy (24). Moderate-intensity aerobic exercise and progressive resisted exercise are also effective in reducing neuropathic pain in HIV-associated distal symmetrical polyneuropathy (33). Resistance exercise and aerobic exercise training improved fitness and strength measured by maximal O2 consumption velocity in chronic inflammatory demyelinating polyneuropathy (34). In a study of diabetic sensory polyneuropathy, an exercise program resulted in increased aerobic exercise capacity and improved motor and sensory conduction (16). 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 (27). 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 (54). In patients with type 2 diabetes and peripheral neuropathy, exercise programs led to improved fatigue, oxygen uptake, body fat, peripheral blood flow (28), and reduced HbA1C and neuropathy symptoms (53). In addition, long-term aerobic exercise may prevent diabetic neuropathy (06). 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 (18). 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 (14). A foot-ankle exercise program in people with diabetic neuropathy improved toe strength and gait, lasting for a year (38; 37). Lower body positive pressure treadmill training with 75% weight-bearing for 12 weeks in patients of diabetic polyneuropathy resulted in short- and long-term improvements of gait and balance (01). Exercise training improved balance, quality of life, and neuropathic pain associated with chemotherapy-induced peripheral neuropathy (43; 35; 11). Visual computer-feedback balance training improved balance in cancer patients with chemotherapy-induced peripheral neuropathy (09). Preservation of vibration and heat pain thresholds was found after physical therapy in taxane-induced peripheral neuropathy (04). Quality of life was higher for immediate versus delayed exercise in women receiving taxane for breast cancer, but not in sensorimotor symptoms or signs (08). Static balance improved more in the 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 (25).
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 (26). 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 (46). 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 (49).
Transcutaneous electrical stimulation for the relief of pain applies electrical stimulation to the skin to block pain perception. In a randomized controlled trial of 20 patients with carpal tunnel syndrome, transcutaneous electrical stimulation significantly decreased pain-related cortical activations measured by fMRI (23). Kumar and Marshall used transcutaneous electrical stimulation 30 minutes daily on each lower extremity for 4 weeks for painful diabetic neuropathy (31). Thirty-one patients were randomized to electrotherapy or sham treatment. Transcutaneous electrical stimulation unit generated a 4 ms electrical pulse, less or equal to 35 volts, and 35 milliamps at a frequency of 2 to 70 Hz. Of the 18 patients, 83% recorded reduced pain scores. No local or systemic side effects were noticed. Individual responses to electrotherapy varied significantly. Kumar and colleagues further studied the combined effect of amitriptyline and transcutaneous electrical stimulation unit (30). Amitriptyline 50 mg at bedtime alone reduced pain in 60% of 26 patients, but combined therapy improved symptoms in 85% of 14 patients. A metaanalysis by the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology showed modestly improved pain with transcutaneous electrical stimulation in diabetic neuropathy (13). Transcutaneous electrical nerve stimulation significantly reduced pain in medication-refractory postherpetic neuralgia (21). Transcutaneous electrical nerve stimulation to plantar area improved balance and gait to enhance motor performance and plantar sensation in people with diabetic neuropathy (40). In a small study, low-frequency, 8-week, plantar vibration training of patients with diabetic neuropathy was associated with improved sural and peroneal conductive velocity of nerves, postural stability, and pain and tingling (45).
Low-frequency pulsed electromagnetic field treatment was investigated for painful diabetic neuropathy in a multicenter, randomized, double-blind, placebo-controlled study (50). 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.
Whole body vibration is gaining attention as a novel somatosensory stimulation. When used in 20 patients with diabetic neuropathy for 6 weeks, tibialis anterior and quadriceps strength and balance improved (29).
Orthoses are devices that support, align, and prevent deformities or improve impaired function. Ankle-foot orthoses are commonly prescribed to patients with weakness of foot 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 brace (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 hereditary motor and sensory neuropathy (07). Disadvantages include a considerable weight burden placed on a weakened limb and more rigid position of the foot. Use of high-top boots incorporating a dorsiflexion-assisting device was reported to improve gait and comfort in a patient with Charcot-Marie-Tooth disease (48). The ankle orthoses placed on each ankle improved gait regularity in patients with peripheral neuropathy while walking on an irregular surface (42). Knee braces limit extension to neutral and flexion to 30° and prevent knee buckling and genu recurvatum due to weak extensors. Knee immobilizers have showed reduction in fall and increase in ambulatory distance in patients with femoral neuropathy (22). Wrist splints immobilize the wrist, but allow full metacarpophalangeal flexion and thumb opposition. They are frequently prescribed for median nerve entrapment at the wrist. Although both were effective, the wrist splint with a metacarpophalangeal unit was more effective at improving pain function compared to a classical wrist splint (17).
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 (05). 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 1 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 advance 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 in the series of articles on Charcot-Marie-Tooth disease (Charcot-Marie-Tooth disease type 1A, Charcot-Marie-Tooth disease type 1B, Charcot-Marie-Tooth disease type X, and Charcot-Marie-Tooth disease: CMT2, CMT4, and others).
Physical therapy and occupational therapy are indicated for patients with peripheral nerve disease with impaired strength, sensation, balance, ambulation, or activity of daily living.
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.
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.
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.
During pregnancy, physical exercises and devices may require modifications due to weight change and edema.
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.
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 (12). 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 (47). 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 use 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.
Yi Pan MD PhD
Dr. Pan of VA St. Louis Health Care System has no relevant financial relationships to disclose.See Profile
Florian P Thomas MD MA PhD MS
Dr. Thomas of Hackensack University Medical Center, Hackensack Meridian School of Medicine, received an honorarium from Pharnext for consulting work.See Profile
Louis H Weimer MD
Dr. Weimer of Columbia University has received consulting fees from Roche.See Profile
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