Etiology and Risk Factors

Evidence supports the view that GBS is an immune-mediated disorder. Bacterial (Campylobacter jejuni) and viral (Haemophilus influenza, Epstein-Barr virus, and cytomegalovirus [CMV]) infections, surgery, and vaccinations have been associated with the development of GBS. Of the two-thirds of persons reporting an acute infection within 2 months preceding onset of GBS, 90% had illnesses (e.g., respiratory or gastrointestinal) during the preceding 30 days.¹¹⁹

Pathogenesis

Lesions occur throughout the PNS from the spinal nerve roots to the distal termination of both motor and sensory fibers. Originally, GBS was classified as a single entity characterized by PNS demyelination. Now, however, it is defined as several heterogenous forms (Table 39-8). C. jejuni is associated more commonly with the axonal form, whereas greater sensory involvement is seen following CMV.⁶⁹ The axonal pattern of involvement can involve motor fibers only or in the more severely involved form, motor and sensory fiber degeneration. Finally, Miller Fisher syndrome is characterized by an acute onset of extraocular muscle paralysis with sluggish pupillary light reflexes, a peripheral sensory ataxia, and loss of deep tendon reflexes with relative sparing of strength in the extremities and trunk. Facial weakness and sensory loss in the limbs may also occur.

Molecular mimicry, an autoimmune theory, is the primary theory for the cause of GBS because evidence exists for antibody-mediated demyelination. Myelin of the Schwann cell is the primary target of attack. Researchers theorize that circulating antibodies to gangliosides penetrate and bind to an antigen on the surface of the myelin and activate either complement or an antibody-dependent macrophage.⁷⁰ The earliest pathologic changes in the PNS take the form of a generalized inflammatory response. Lymphocytes (T cells) and macrophages are the inflammatory cells present. Demyelination, initiated at the node of Ranvier, occurs because macrophages, responding to inflammatory signals, strip myelin from the nerves. After the initial demyelination, the body initi- ates a repair process. Schwann cells divide and remyelinate nerves, resulting in shorter internodal distances than were present initially.

In addition to the demyelination, there is another process that has longer-lasting effects. Although there is an axonal subtype, axonal degeneration to some degree occurs in most cases of demyelinating GBS. In the latter, many believe that the axons are damaged during the inflammatory process, according to what has been called a “bystander effect.” Products that are liberated by the macrophages as they strip myelin (e.g., free oxygen radicals and proteases) also damage axons.

Axonal patterns of involvement display a diminished or absent inflammatory response seen in demyelination. Researchers have reported the presence of macrophages that invade periaxonal spaces, causing the axon to degenerate within the ventral roots. Recovery for this wallerian-like degeneration would require an extremely long period. For those individuals with acute motor axonal neuropathy (AMAN), another mechanism may promote rapid recovery for what appears to be axonal involvement. Binding of antibodies to the nodes of Ranvier may cause blocking of nerve conduction by altering sodium channel conductance has been established in rabbits.

Although the autoimmune theory is the main one advanced for this disorder, it may not be the only reason for the development of GBS. Cases of GBS have been reported in immunosuppressed individuals after renal transplant.

Clinical Manifestations

Various subtypes of GBS exist; however, the “classic” picture is an acute form in which the time from onset to peak impairment is 4 weeks or less. A recurrent form of GBS is reported in up to 10% of cases. Acute relapses may occur in GBS and this characteristic may make it difficult to differentiate the acute from the chronic form, called chronic demyelinating polyradiculoneuropathy (CIDP). Most cases of CIDP progress over a period of months instead of weeks.

In GBS, symptoms are characterized by a rapidly ascending symmetric motor weakness and distal sensory impairments. The first neurologic symptom is often paresthesia in the toes. This is followed within hours or days by weakness distally in the legs. Weakness spreads to involve arms, trunk, and facial muscles. Flaccid paralysis is accompanied by absence of DTRs. Occasionally, sensory and motor symptoms begin in the hands and arms instead of the feet and legs. Palatal and facial muscles become involved in about half of all cases; even the muscles of mastication may be affected, but nerves to extraocular muscles typically are not involved. Up to 30% of all cases require mechanical ventilation.

Because the preganglionic fibers of the ANS are myelinated, they, too, may be subject to demyelination. If this occurs, tachycardia, abnormalities in cardiac rhythm, blood pressure changes, and vasomotor symptoms occur.

In 50% of the cases, progression of symptoms generally ceases within 2 weeks and in 90% of the cases, progression ends by 4 weeks. After the progression stops, a static phase begins, lasting 2 to 4 weeks before recovery occurs in a proximal to distal progression. This recovery may take months or even years.

DIAGNOSIS.

Careful clinical and neurophysiologic examinations and laboratory tests are needed to diagnosis GBS. Criteria have been developed by the National Institute of Neurologic and Communicative Disorders and Stroke (NINCDS) (Box 39-6); however, these criteria omit the variants that have been identified.¹⁵

After symptoms have existed for 1 week, a lumbar puncture can be performed to withdraw cerebrospinal fluid (CSF). Albumin (a protein) is elevated in the CSF with 10 or fewer mononuclear leukocytes present. Electrophysiologic tests will reveal slowed NCVs the entire length of the nerve when demyelination is present, as well as fibrillation potentials when axonal degeneration occurs. When both axonal involvement and demyelination occur, the amplitude of the evoked (NCV) potential will be reduced and the velocity is slowed, respectively.

These abnormalities may not be apparent during the first few weeks of the illness. In addition, to determine the extent of demyelination of the more proximal nerve roots, an F wave electrophysiologic test may be performed; it is often prolonged or absent. As recovery occurs, slowed NCVs persist, even though the person has made a full clinical recovery. Although electrophysiologic studies are used for diagnosis, the distal compound motor action potential (CMAP) is a predictor of prognosis. If the CMAP amplitude is less than 20% of normal limits at 3 to 5 weeks, it predicts a prolonged or poor outcome.¹²⁴

DIFFERENTIAL DIAGNOSIS.

Hysteria is the most common misdiagnosis. Because of the speed of onset, a stroke involving the brainstem will also be considered. Less common causes of acute neuropathies must also be considered, including tick paralysis, and metabolic disorders such as porphyria.

TREATMENT.

Because GBS is believed to be an autoimmune disease, treatment has been aimed at controlling the response. In two major trials, plasmapheresis, a technique (also called plasma exchange [PE]) that removes plasma from circulation and filters it to remove or dilute circulating antibodies, has been shown to significantly improve the impairments in GBS. Typically, the client will have 4 to 6 exchanges of 500 ml per treatment over the period of a week. Time on a respirator and time to independent ambulation (53 days) were both shorter than in the control group (85 days). Plasmapheresis is instituted when respiratory function drops precipitously (to 1.0 to 1.5 L), and the person is placed on a respirator.

High-dose intravenous (IV) administration of immunoglobulin (Ig; a protein the immune system normally uses to attack foreign organisms) has been found safe and effective in the treatment of GBS.¹⁶³ The therapeutic dose is 0.4 g/kg/day for 5 days.⁷¹ Practice parameter recommendations made after a review of PE and IVIg studies are that PE should be administered in nonambulatory adults seeking treatment within 4 weeks of GBS onset or ambulatory adults within 2 weeks of onset. IVIg was recommended in nonambulatory adults within 2 weeks of onset. Outcomes for either approach were equivalent. For children with severe GBS, either treatment approach is an option.⁷¹

PROGNOSIS.

The primary methods of managing GBS have helped to improve mortality rates, which can exceed 5%. Factors that predict a poor outcome include onset at an older age, a protracted time before recovery begins, and the need for artificial respiration. An important objective evaluation finding that predicts a poor outcome is significantly reduced evoked motor potential amplitude, which correlates with the presence of axonal degeneration. Although most persons recover, up to 20% can have remaining neurologic deficits. After 1 year, 67% of clients have complete recovery, but 20% remain with significant disability.⁴² Even after 2 years, 8% have not recovered.

Post-Polio Syndrome/Post-Polio Muscular Atrophy

DIAGNOSIS.

PPS is a clinical diagnosis requiring the exclusion of other medical, neurologic, orthopedic, or psychiatric disorders that could explain the new symptoms. Routine EMG can be used to confirm any new denervation, as can muscle biopsies. Single-fiber EMG and spinal fluid studies are rarely needed to establish a diagnosis.²²

TREATMENT.

Medical management is aimed at symptomatic treatment and modification of lifestyle. Surgery for residual calcaneovalgus deformities at the ankle include triple arthrodesis.⁴⁰ Perimalleolar tendon transfers have been performed to compensate for triceps surae insufficiency.³¹

PROGNOSIS.

PPS is a slowly progressive disorder with stable periods that last 3 to 10 years. A decline in functional status is reported to correlate with a poorer quality of life in individuals affected by PPS.⁸¹

Herpes Zoster/Post-Herpetic Neuralgia

Varicella-zoster virus (VZV) is a common herpes virus that affects the nervous system. VZV is the virus that causes chickenpox in children. After recovery from that childhood disease, the virus is not eliminated from the body; it lies dormant within sensory ganglia of cranial and spinal nerves and can become activated later in life to cause herpes zoster (HZ), or shingles.

DIAGNOSIS AND TREATMENT.

The diagnosis is made by clinical presentation. The disorder is treated symptomatically unless there is widespread involvement. Oral antiviral medications, such as Acyclovir, are used to control the response and accelerate the resolution of the pain, hypoesthesia, burning, and itching associated with the neuralgia. Although analgesic drugs may be prescribed to relieve pain, a randomized controlled trial using topical lidocaine patches, gabapentin, and controlled-released oxycodone shows better pain relief. Nortriptyline, a tricyclic antidepressant, also provides analgesia and may be tolerated better than other medications.⁷⁵

PROGNOSIS.

For immunosuppressed clients, there is a greater risk of developing postherpetic neuralgia and painful dysesthesias as a complication of HZ. Postherpetic pain is very resistant to treatment. Signs of the disorder in immunocompetent persons resolve within a month, but the area that was affected may be partly insensitive. Up to 20% of people who experience HZ will experience a second attack. See further discussion in Special Implications for Therapists boxes in Chapters 8 and 10.

Trigeminal Neuralgia/Tic Douloureux

Trigeminal neuralgia (TN), or tic douloureux, is a disorder of the trigeminal (fifth cranial) nerve in which there are intense paroxysms of lancinating pain within the nerve’s distribution.

DIAGNOSIS.

Subjective reports of pain in the typical pattern are the basis for the diagnosis. No impairment or loss of sensation or motor control is obvious on evaluation, The person can identify the trigger site. Skull radiographs, CT scans, and MRI are used to rule out tumors and vascular causes.

TREATMENT.

The preferred treatment of TN is oral carbamazepine (Tegretol, an anticonvulsant). Pain can be controlled with appropriate dosage in about 75% of clients with TN. Side effects of this medication include blurred vision, dizziness, drowsiness, as well as hematologic changes (anemia) and altered liver function. In addition, because carbamazepine has teratogenic effects, it should not be used in the first trimester of pregnancy nor should it be used by nursing mothers.⁵² Other medications, such as phenytoin (Dilantin), are less effective but should be tried in those who cannot tolerate carbamazepine. Promising new medications to manage TN include pimozide, tizanidine hydroxychloride, and topical capsaicin.²⁸

In persons whose pain is refractory to medications, neurosurgical procedures are advised. Radiofrequency rhizotomy is preferred over trigeminal nerve section or alcohol ablation. Microvascular surgery has also been used when small blood vessels have been found to constrict the trigeminal nerve near its root. This procedure provides immediate pain relief; however, it is a major and difficult surgery.

PROGNOSIS.

The efficacy of evaluating treatments for TN is complicated by the fact that the disorder may remit spontaneously. Remissions that occur soon after onset of TN may last for years. For those who do not remit, TN can be managed medically in most cases. The Trigeminal Neuralgia Association provides information and support for persons with this diagnosis.

Human Immunodeficiency Virus Advanced Disease (Acquired Immunodeficiency Syndrome)

Peripheral neuropathy, disease-or drug-induced myopathy, and musculoskeletal pain syndromes occur most often in advanced stages of human immunodeficiency virus (HIV) disease but can occur at any stage of HIV infection and may be the presenting manifestation. During the early phases of HIV when the immune system has altered responsiveness, GBS tends to develop. When immunoincompetence is severe, distal symmetric peripheral neuropathies occur; however, other parts of the body may be affected such as the face or trunk. The polyneuropathies are predominantly sensory. Painful dysesthesias characterized by burning, tingling, contact sensitivity and proprioceptive losses begin in the soles and ascend. Upper extremity involvement rarely occurs.³⁶ In severe cases, secondary motor deficits. In the individual with HIV and newly acquired neuropathy with a strong major motor component, vasculitis may be the underlying etiology (see the section on Vasculitis in Chapter 12). Involvement of the upper extremities can occur, but this is less common and usually later in the disease progression.

Vasculitis

Vasculitis can occur as a primary inflammation and necrosis of blood vessel walls (polyarteritis nodosa) or as a secondary process associated with autoimmune responses (rheumatoid vasculitis or systemic lupus erythematosus vasculitis), infections (hepatitis C with vasculitis), toxins, or drug exposure. Vasculitis can involve blood vessels of any size, type, or location and can affect any organ system, including blood vessels that supply the PNS, as well as the CNS. However, because the watershed zones between major vascular supplies exist in the PNS, peripheral nerves are apt to sustain ischemia.¹⁰⁹ Vasculitis may range from acute to chronic. Distribution of lesions may be irregular and segmental rather than continuous.

Paraneoplastic Neuropathies

A little over 50 years ago the symptoms of two individuals were reported whose autopsy revealed bronchial carcinoma. Both had developed a sensory neuropathy. Although subsequent reports of similar sensory neuropathies associated with other carcinomas have been reported, paraneoplastic syndromes can affect any portion of the nervous system (Table 39-9).

DIAGNOSIS.

The differential diagnosis of paraneoplastic neuropathy is extensive and includes many disorders identified in this chapter that affect sensory nerve fibers or neurons. In addition to electrophysiology findings of severely reduced amplitude or absence of sensory nerve potentials, with normal to slightly slowed sensory nerve conduction velocities, nerve biopsies show nonspecific axonal degeneration and a reduction in myelinated fibers. Lumbar puncture and serum assays for antibodies may be included in the diagnostic workup. High serum titers for antibodies are suggestive of an occult tumor, but the sensitivity and specificity of these tests yields false positives and negatives. CT and MRI scanning are used to locate the tumor.³⁴

TREATMENT.

Typical treatments for autoimmune disorders, such as immunosuppression using prednisone, cyclophosphamide, IVIg, or plasmapheresis, generally do not work with antinuclear antibodies because receptors are located within the nucleus of the neuron.

PROGNOSIS.

The course is fairly stereotypical. Individuals deteriorate over weeks or months and then stabilize at a level of severe disability; for example, sensory polyneuropathies progress proximally, then ataxias develop and become progressively greater. Neurologic improvement is rare.

Lead Neuropathy

DIAGNOSIS, TREATMENT, AND PROGNOSIS.

Diagnosis is based on the history, clinical examination, and motor NCVs, which will be slowed. If axonal degeneration has occurred, EMG will reveal fibrillation potentials, demonstrating loss of axonal innervation. Other tests to check for concentration of lead in the body are urine evaluation and radiographs to reveal a lead line at the metaphysis in the iliac creases, long bones, and tips of the scapula.

Treatment consists of the removal of the source of the lead toxin along with the introduction of the chelating agent, edetate calcium disodium (EDTA), administered twice daily, to rid the body of lead. Symptomatic management consists of cock-up splints for the wristdrop. Recovery depends on the length of exposure and removal of the toxin.

Pesticides and Organophosphates

DIAGNOSIS.

Overexposure to organophosphates will reduce cholinesterase activity of erythrocytes to less than 25% of normal. History and clinical evaluation may be accompanied by electrophysiologic studies to indicate the severity of the neuropathy (e.g., segmental demyelination or axonal degeneration or both).

TREATMENT.

Insecticides should be washed from the skin and hair; if toxins have been ingested, emesis or lavage should be carried out. Acutely, atropine is given in doses every 10 minutes until the pupils are dilated, the skin flushed and dry, and the pulse rate rises. Neuromuscular paralysis can be reversed by injection of pralidoxime, a cholinesterase reactivator. Endotracheal intubation and ventilation may be required in the presence of respiratory paralysis. Strictly neuropathic management is aimed at symptomatic management.

PROGNOSIS.

Recovery is based on removal from the toxin and the degree of involvement. If only segmental demyelination occurs, recovery will occur in weeks to months, but if axonal degeneration is present, recovery will take months to years.

Myasthenia Gravis

DIAGNOSIS.

History and clinical observation of symptoms of weakness with continued use and improvement with rest are important in diagnosing MG. Several conditions that cause weakness of cranial, or somatic, muscles must also be considered. These include drug-induced myasthenia, hyperthyroidism, botulism, intracranial mass lesions, and progressive disorders of the eye. Lambert-Eaton syndrome is a presynaptic disorder of the neuromuscular junction that can cause symptoms similar to those of MG. Lambert-Eaton syndrome is an autoimmune disorder associated with neoplasm, most commonly small cell (oat cell) carcinoma of the lung, which is believed to trigger the autoimmune response.

The three methods used to diagnose MG are (1) immunologic, (2) pharmacologic, and (3) electrophysiologic testing.¹⁰⁵ Immunologic testing detects anti-ACh receptor antibodies in the serum. The presence of anti-ACh receptor antibodies is virtually diagnostic of MG, but a negative test does not exclude diagnosis of the disease. There is no correlation between the amount of anti-ACh receptor antibodies and the severity of the disease. However, in a person with MG a treatment-induced fall in the antibody level often correlates with clinical improvement.

The drug edrophonium (Tensilon) is used to demonstrate improvement in the myasthenic muscles by inhibiting acetylcholinesterase (AChE), an enzyme required for ACh uptake. Muscle strength and endurance are measured before and after administration of the drug. This test confirms that ACh uptake is part of the pathologic status; however, a control test of saline should also be used for comparison.

Electrophysiologic testing of myasthenic disorders demonstrates a normal EMG at rest. Specialized testing must be employed using repetitive stimulation to demonstrate a rapid decrement in the motor action potential’s amplitude. Absence of sensory deficits and retention of tendon reflexes throughout the course of the disease also tend to confirm the diagnosis of MG. Because respiratory impairment is a serious complication of MG, measurements of ventilatory function should be performed.¹⁵⁸

TREATMENT.

AChE inhibitor medication provides for improvement of weakness but does not treat the underlying disease. Administration of this medication is tailored to the individual’s requirements throughout the day. For example, a person with difficulty chewing and swallowing would take the medication before meals. Side effects of AChE inhibitors include gastrointestinal effects such as nausea and vomiting, abdominal cramping, and increased bronchial and oral secretions.

Surgical removal of the thymus is successful in 85% of persons with MG. Up to 35% of those undergoing thymectomy achieve a drug-free remission, although this may take years.

Immunosuppression using drugs, such as corticosteroids (prednisone) and azathioprine, are effective in nearly all persons with MG. Initially, high daily doses are begun and then followed by alternate-day high doses that are tapered slowly over a period of months. Unfortunately, adverse side effects are associated with high-dose steroids. These include cushingoid appearance, weight gains, hypertension, and osteoporosis (see Chapter 7).

Plasmapheresis is performed to remove substances that affect ACh receptors. However, plasmapheresis produces only short-term reduction in anti-AChE antibodies and is not effective for long-term symptom control.

PROGNOSIS.

The course of MG is variable, typified by remissions and exacerbations, especially within the first year after onset. Symptoms often fluctuate in intensity during the day. This daily variability is superimposed on longer-term spontaneous relapses that may last for weeks. Remissions are rarely complete or permanent. This disorder follows a slowly progressive course. Onset of other systemic disorders and infections may precipitate an exacerbation of the disease and are the most common cause of a crisis. A myasthenic crisis is a medical emergency requiring attention to life-endangering weakening of the respiratory muscles. A myasthenic crisis requires ventilatory assistance. Treatment of a crisis occurs in the ICU because the client requires careful, immediate control of medications for survival.¹⁷⁸

When MG begins in children, it is important to establish the form it takes. Because AChE antibodies cross the placenta, 10% of newborns of mothers with MG develop a myasthenic reaction. Newborns with neonatal MG have a weak suck and cry and are hypotonic. Fortunately, this resolves in a few weeks.

Definition and Incidence

Botulism is a rare, often fatal condition (20% mortality) caused by ingestion of a potent neurotoxin produced by Clostridium botulinum, which is found in improperly preserved or canned foods, as well as in contaminated wounds. The Centers for Disease Control and Prevention (CDC) recognizes four categories of botulism: (1) foodborne, (2) wound, (3) infant, and (4) unclassified.²⁹ Approximately 10 adult cases and 100 cases of infant botulism are reported each year in the United States.

Etiology and Pathogenesis

The anaerobic bacillus releases a protein neurotoxin that is heat-labile; it is destroyed by boiling food for 10 minutes. Therefore inadequate food preparation allows the neurotoxin to be ingested.

Infant botulism affects babies aged from 3 weeks to 9 months; the most common source of infant botulism arises from the ingestion of honey, which is why children of less than 1 year are not allowed to have honey.

Botulism is not always ingested orally. Some cases occur after wounds are contaminated with soil, in chronic drug abusers, after cesarean delivery, and may even occur when antibiotics are administered to prevent wound infection.

When the neurotoxin is ingested, digestive acids and proteolytic enzymes cannot destroy the molecules of the toxin and it is absorbed into the blood from the small intestine. Minute amounts of circulating toxin reach the cholinergic nerve endings at the motor endplate and bind to gangliosides of the presynaptic nerve terminals. Flaccid paralysis is caused by inhibition of ACh released from cholinergic terminals at the motor endplate. Inhibition of ACh release causes a symmetric paralysis with normal sensory and mental status.

Clinical Manifestations

Onset of symptoms develops 12 to 36 hours after ingestion of food containing the toxin. Signs and symptoms include malaise, weakness, blurred and double vision (diplopia), dry mouth, and nausea and vomiting. Progression is variable, but respiratory failure can occur in 6 to 8 hours. People may also report difficulty swallowing (dysphagia), dysarthria (slurred speech), and photophobia. Because the motor endplate is involved, there are no sensory changes. Motor weakness of the face and neck muscles progresses to involve the diaphragm, accessory muscles of respiration, and muscles controlling the extremities. Secondary effects from the flaccid paralysis, such as severe muscle wasting, pressure sores, and aspiration pneumonia, occur.

DIAGNOSIS, TREATMENT, AND PROGNOSIS.

A history suggesting a food source and toxin identification made by serum or stool analysis aids in the diagnosis. EMG testing demonstrates a decreasing amplitude and facilitation of muscle action potential after tetanic stimulation. Differential diagnosis includes disorders that also display a rapidly evolving flaccid paralysis, such as GBS, MG, and tick paralysis.

Immediate treatment is directed toward neutralizing the toxin using injectable trivalent ABE serum, an antitoxin. Antitoxin prevents further binding of free botulism toxin to the presynaptic endings. If paralysis occurs because of wound botulism, care should include debridement and antibiotics.

Removal of unabsorbed toxin from the gastrointestinal tract is accomplished by gastric lavage and induced emesis. Finally, supportive measures should be instituted in the hospital; intubation and mechanical ventilation are needed when the individual’s vital capacity is compromised.

If untreated, this disorder can be fatal within 24 hours of ingestion. Respiratory failure leads to death. In mild-to-moderate cases, a gradual recovery of muscle strength can take as long as 12 months after onset. After hospitalization, graded rehabilitation is instituted to treat muscle wasting, deconditioning, and orthostatic hypotension.

Complex Regional Pain Syndrome/Reflex Sympathetic Dystrophy/Causalgia

Reflex sympathetic dystrophy (RSD) is a syndrome, first described in 1864, that changes over time and varies by etiology. Now, the preferred terminology for the syndrome that develops after trauma is complex regional pain syndrome, type I (CRPS I). Early on, pain is greater than expected for the degree of tissue trauma that has been sustained. The pain spreads from localized to a regional distribution, characterized by a burning sensation that occurs spontaneously and at an intensity that does not correspond with the stimulus that elicited it. If the trauma that was sustained involves a major nerve and the clinical syndrome develops, it is causalgia, or CRPS type II (CRPS II).⁹⁹

DIAGNOSIS.

Diagnosis of CRPS is based primarily on the clinical examination and history. A combination of diagnostic tests aimed at assessing secondary changes (radiographic examinations, thermographic studies, and laser Doppler flowmetry) may aid in establishing a diagnosis. Because of the evolutionary nature of CRPS, a correct diagnosis may be delayed, especially in children.³⁵

TREATMENT.

Treatment for CRPS tends to be multifactorial and prolonged. Successful treatment depends on early diagnosis, treatment of the underlying cause, and aggressive and sustained physical therapy.⁶⁷ Although stellate ganglion blocks or sympathectomy are used to alleviate pain and early symptoms, this approach is based on weak evidence.⁹⁸ All of the following treatments have limited evidence for their effectiveness.⁴⁷ Acupuncture, corticosteroids, and NSAIDs have been used early in stage I. They provide pain relief in up to 20%. Amitriptyline has been used to facilitate sleep and relieve depression. Calcium channel blockers help to improve peripheral circulation through their effect on the SNS.

Long-term intrathecal baclofen is used to control symptoms of motor dystonia. Its use is supported by the fact that γ-aminobutyric acid (GABA)-ergic inhibition is involved in motor function.

Although external TENS units have been minimally effective, implanted dorsal column stimulation has been shown to decrease pain intensity and perception of pain in randomized trials. Health-related quality of life improved only in individuals receiving spinal cord stimulation. It is best for intractable pain in one extremity.⁹⁹

PROGNOSIS.

CRPS is a complex syndrome with varying severity and disability. In many cases, the pain continues for years, or less frequently, it may remit, then recur after another injury. In some cases, malingering for secondary gain has been documented.¹⁸¹ Outcome measures for CRPS I typically concentrate on impairments, leaving measurement of disability, which is the most relevant to function, with few assessments.¹³⁸ Physical therapy is indicated, particularly as part of a program of pain control. Although the goal is to maintain function so that the individual can perform normal activities, a vigorous approach is not indicated. Current research is aimed at understanding physiologic processes and finding the most effective interventions.

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