Clinical manifestations

Presentation and course

Post-polio syndrome is manifested by neurologic, musculoskeletal, and systemic symptoms and signs. The most prominent neurologic manifestation is new progressive weakness, sometimes accompanied by muscle atrophy. When this occurs in an extremity, it has been referred to as post-polio progressive muscular atrophy. However, new weakness can also affect respiratory and bulbar muscles (51; 90). The diagnostic criteria for post-polio progressive muscular atrophy have been derived from the criteria first promulgated by Mulder and colleagues (120), which were updated by the Post-Polio Task Force (92). This includes four criteria: (1) A prior episode of paralytic poliomyelitis with residual motor neuron loss (which can be confirmed through a typical patient history, a neurologic examination, and, if needed, electromyography); (2) A period of neurologic recovery followed by an interval (usually 15 years or more) of neurologic and functional stability; (3) A gradual or abrupt onset of new weakness or abnormal muscle fatigue, decreased endurance, muscle atrophy, or generalized fatigue; and (4) Exclusion of medical, orthopedic, and neurologic conditions that may be causing the symptoms mentioned in number 3.

Neurologic manifestations. New, slowly progressive muscle weakness is the most important neurologic problem (Table 1), occurring in most post-polio syndrome patients (41; 77; 91). It appears to be related to a disintegration of the lower motor neuron unit (motor unit) (36; 50) and can occur in muscles previously affected and partially or fully recovered or in muscles previously unaffected (77; 91). Electromyography (EMG) (81) and animal studies (25; 145) indicate that some clinically unaffected muscles were involved subclinically during acute poliomyelitis. However, previously affected muscles are more likely than unaffected muscles to later become weak (77; 91). The distribution of the new weakness appears to correlate with the severity of paralysis at the time of the acute poliomyelitis and, thus, with the number of surviving motor neurons (24; 36). Studies by Wendebourg and colleagues, employing 3T axial 2D-rAMIRA MR-imaging, indicated that functional decline in post-polio syndrome is accompanied by progressive atrophy of spinal cord gray matter (174). These authors concluded that functional decline in post-polio syndrome was the result of a secondary neurodegenerative process, which was not explained by aging or residuals of the initial infection alone (174).

Table 1. Most Common New Late Manifestations of Poliomyelitis in Patients Referred to Post-polio Clinics*

New atrophy is not an isolated manifestation and is seen in fewer than half of the patients with new weakness (37; 77). In addition to the weakness and atrophy caused by the disintegration of the lower motor neuron unit, rarely upper motor neuron signs can occur (90). They include hyperreflexia, Babinski signs, and occasionally, spasticity. Of 180 post-polio syndrome patients, upper motor neuron signs were found in 15 (8.3%) (90), which is similar to the frequency of motor neuron signs found during acute poliomyelitis (90). Muscle pain (myalgias), which occurs in most patients (41; 77; 91), appears to be due to overuse of weak muscles. Similar symptoms occur in overused weakened muscles in other neuromuscular diseases (90). The pain is a soreness or aching feeling that occurs with minimal exercise. Some patients have muscle tenderness on palpation.

New muscle weakness may also involve specific muscle groups, causing bulbar muscle weakness, respiratory insufficiency, and sleep apnea. Bulbar muscle weakness is most frequently manifested by dysphagia, which has been reported in 10% to 36% of post-polio patients (32; 158). It is primarily due to pharyngeal and laryngeal muscle weakness; however, local pharyngeal or esophageal problems should also be excluded. Patients may complain of food sticking, making swallowing slow and difficult, often with coughing and choking (32). Videofluoroscopic studies may reveal impaired tongue movements, delayed pharyngeal constriction, pooling in the valleculae or pyriform sinuses, and rarely aspiration, which is usually mild (158). Less frequently, other bulbar muscles, such as the facial muscles and vocal cords, may become weaker in post-polio syndrome (34; 01); dysarthria has also been reported (90).

Respiratory insufficiency primarily occurs in patients with severe residual respiratory impairment and minimal reserve from their acute polio illness (53; 23; 157). Similar to limb weakness, respiratory failure is more likely to occur in patients who required respiratory support during the acute disease and, hence, had more severe disease and in those who contracted polio at an age of 10 years or older (53; 157). Patients with post-polio syndrome chronic respiratory failure lose an average of 1.9% of their vital capacity per year (16). It is usually due to respiratory muscle weakness but can also be due to central hypoventilation because of the residual damage from acute bulbar poliomyelitis (137). Other factors, such as cardiac or pulmonary disease or scoliosis, may contribute to the problem. Initially, respiratory failure begins with nocturnal hypoventilation, and patients may require only nighttime respiratory support (82). If already on nighttime respiratory support, patients may eventually require total ventilator support (16).

Sleep apnea is not an uncommon problem in post-polio patients. It may be central, obstructive, or mixed (73; 163). Most patients with central sleep apnea had bulbar polio, and some required ventilatory support (73; 154). Probably residual damage to the brainstem reticular formation predisposes to central sleep apnea. Obstructive sleep apnea appears to be related to pharyngeal muscle weakness, obesity, and musculoskeletal deformities (163). Respiratory muscle weakness may also contribute to sleep apnea (15). Fasciculation and cramps without weakness, muscle pseudohypertrophy, and tingling paresthesia are other neuromuscular problems that occur infrequently in post-polio patients, with or without new weakness (90).

Musculoskeletal manifestations. Pain from joint instability is the major musculoskeletal problem and can occur without new weakness. The long-term overstress of joints because of residual weakness eventually results in joint deterioration and pain (98; 169). Progressive scoliosis, poor posture, unusual mechanics because of weak muscles, uneven limb size, bone deformities, overstressed tendons, failing tendon transfers, and failing joint fusions can all contribute to joint instability, increased fracture risk, and pain. These joint problems frequently lead to loss of mobility and a return to using old assistive devices (12). Progressive scoliosis may also contribute to pulmonary failure (112). Compressive radiculopathies and mononeuropathies may occur as secondary musculoskeletal complications (90; 175).

Systemic manifestations. Fatigue is the most prominent systemic manifestation, occurring in up to 80% of patients (51; 77; 90; 09). It is generally described as a disabling generalized exhaustion that follows even minimal physical activity (79). Patients frequently refer to hitting the “polio wall.” Their fatigue has also been described as “increasing physical weakness,” “tiredness,” “lack of energy,” and “increasing loss of strength during exercise” (20); thus, it can either be perceived as generalized or muscular in origin (79; 05). Fatigue can also affect mental as well as physical functioning. It may be improved by decreasing physical activity, pacing daily activities, and taking frequent rest periods and naps (05; 129). Post-polio syndrome fatigue appears to respond better to sleep than that of chronic fatigue syndrome, although frequent rest periods are also helpful. Apathy and decreased verbal fluency are also seen in a high proportion of patients. However, extensive cerebral neuroimaging studies of 36 post-polio patients with cognitive symptoms only demonstrated minimal cortical, subcortical, and white matter degeneration (153). In their study of fatigued and non-fatigued patients with post-polio syndrome, Östlund and colleagues report that fatigued post-polio patients can be considered a distinct subgroup across the fatigue continuum (128).

Other systemic manifestations less frequently reported include increased sleep requirements, cold intolerance, and psychological stresses (77; 90). Increased sleep requirements probably relate to severe fatigue. Many post-polio syndrome patients complain of cold intolerance (77). They report worsening symptoms, including increasing generalized fatigue and weakness when exposed to cold temperatures (31). Patients may also develop coolness and color changes, such as cyanosis and blanching of the affected extremity that probably relate to sympathetic intermediolateral column damage from the acute poliomyelitis (156). Psychological symptoms appear to relate to the re-emergence of a supposedly old resolved problem and to the stresses of new disabilities and the accompanying major lifestyle changes (101; 29; 33).

De Grandis and colleagues report a patient who developed restless legs syndrome concurrent with the development of classic post-polio syndrome 40 years after recovery from an episode of paralytic poliomyelitis (54). Marin and colleagues report a high prevalence of restless legs syndrome (36%) amongst 119 post-polio patients seen consecutively in their outpatient neuromuscular clinic (113).

Prognosis and complications

It has been difficult to determine the natural course of post-polio syndrome because of its slow progression with plateaus. However, weakness does lend itself to objective analysis. Mulder and colleagues (120) reported continuous progression of weakness over 12 years of follow-up. Dalakas and colleagues (49) used Medical Research Council grading and noted both steady and stepwise progression of weakness at an average rate of only 1% per year over a mean follow-up period of 12.2 years. Some studies with shorter follow-up periods of two years (86), two and a half years (10), and five years (183) did not demonstrate progression of the weakness. However, the latter group did demonstrate progression when patients were followed for a much longer period of 15 years (159). Two mechanically quantitated studies, with four-year follow-up periods, found rates of progression of 2% per year (03; 161). A quantitative study of only nine months duration found that the annual percentage decrease in strength varied from 11.2% for polio survivors in their early 40s to 17.5% for those in their late 60s and early 70s (99). Significant objective clinical weakening has been noted by others (121), including weakness of bulbar musculature (158). The prognosis is good when diaphragmatic paralysis is unilateral. It often goes unrecognized and, in the absence of any underlying lung disease, usually needs no treatment. Bilateral diaphragmatic paralysis can cause dyspnea, cor pulmonale, and ventilatory failure. Pulmonary function tests show a restrictive process, with symptoms worse on supine posture. In addition to chest x-ray, chest fluoroscopy, phrenic nerve conduction studies, and diaphragmatic electromyography help to confirm the diagnosis. Diaphragmatic pacing, placation of the diaphragm, tracheostomy, and mechanical ventilation might be needed alone or in combination (139).

Additional complications of post-polio syndrome most often relate to spine disease. Arthritis (spondylosis) of the spine and herniated discs may result in radiculopathies. These complications respond somewhat to conservative treatment and more often to surgical intervention, although this may be short-lived. Kyphoscoliosis may occur, which may result in respiratory and cardiac failure (112). At this stage, treatment is primarily supportive. Bulbar muscle weakness may predispose to aspiration and pneumonia.

Biological basis

Etiology and pathogenesis

It is now recognized that normal aging alone cannot explain the development of post-polio syndrome because the normal loss of anterior horn cells and motor units does not become prominent until after age 60 (90). More important than a patient’s chronological age is the interval from their acute polio to the onset of post-polio syndrome, an interval that averages between 30 and 40 years (90). The presently accepted most likely etiologic possibility is degeneration of enlarged motor units; however, alternative considerations include a chronic persistent poliovirus infection or an immune-mediated disease (18).

Degeneration of enlarged motor units. After acute poliomyelitis, remaining motor neurons send out sprouts to take over degenerated muscle fibers (collateral sprouting). This results in enlarged motor units, five to 10 times larger than normal. These new synapses never seem to stabilize fully (177). On average, 30 to 40 years after acute poliomyelitis, there is disintegration of the new terminal sprouts that formed after the acute infection (47; 71). Findings from single fiber electromyographic (SFEMG) studies reveal that the largest motor units are more likely to become unstable later in life (36; 59), and with increasing time from the acute polio, neuromuscular transmission becomes more unstable, as increased jitter and blocking occur (178). Spontaneous denervation activity, jitter, and blocking occur more frequently in symptomatic muscles (144; 114). These findings are supported by muscle biopsy studies that describe an increasing number of angulated fibers accumulating over time (50). This is followed by degeneration of axonal branches as demonstrated by the appearance of small group atrophy (57; 36). This can be followed by large group atrophy, suggesting neuronal degeneration (50). It has been frequently hypothesized that the increased metabolic demand of an increased motor unit territory results in premature exhaustion and death of the motor neuron (90). Although no definitive studies have examined the cell soma to prove this theory, electrophysiologic and muscle biopsy data appear to be supportive. The overuse of weakened muscles results in excessive muscular fatigue (152; 72; 08; 164; 165), which appears to contribute to the excessive metabolic demand on motor neurons and the premature exhaustion.

Chronic persistent poliovirus infection. Poliovirus and other picornaviruses can persist in the CNS of animals and cause delayed or chronic disease (90; 55; 18). Poliovirus and other enteroviruses can also persist in the CNS and systemically in immunodeficient children (90). Studies in tissue culture have found that poliovirus mutants can persist without killing the host cell (43; 26) and can also persist in neurons (132). Support for the persistent poliovirus hypothesis was enhanced by the findings of Sharief and colleagues (151), who demonstrated poliovirus antibodies and poliovirus-sensitized cells in the CSF of post-polio patients. Leon-Monzon and Dalakas (109) found elevated IgG poliovirus antibodies in the sera of post-polio syndrome patients as compared to controls; however, patients with amyotrophic lateral sclerosis had similar elevated levels. Other investigators have been unable to find poliovirus antibodies in the CSF of post-polio patients (106; 49; 146; 115; 93). CSF specimens have also been examined for the presence of poliovirus RNA by polymerase chain reaction, and the majority of studies have been negative or inconclusive (115; 109; 111; 119). The most positive study was that of Julien and colleagues (94) who detected poliovirus genome sequences in the CSF of 11 of 20 post-polio syndrome patients but in none of the 20 control patients. These same authors had reported similar findings: post-polio syndrome 5 of 10 positive, controls 0 of 23 positive, in an earlier study (111). Conclusive viral isolation and histochemical or hybridization studies have not as yet been reported using spinal cord tissues and will be required to resolve this possibility.

An immune-mediated disease. The strongest support for an inflammatory or immune-mediated mechanism for post-polio syndrome stems from the study of Pezeshkpour and Dalakas (Pezeshkpour and 47) in which inflammation in the spinal cords of seven post-polio patients was found. It consisted of both perivascular and parenchymal lymphocytic infiltrates, neuronal degeneration, and active gliosis. All changes were more prominent in three patients with new weakness. Other findings that support this hypothesis are the finding oligoclonal bands in the CSF (49) and activated T-cells in the peripheral blood (65). Others have not found oligoclonal bands in post-polio syndrome patients (36; 146); however, other histologic studies suggest an immune-mediated or viral-induced pathogenesis or at least an inflammatory mechanism. Miller (116) examined the spinal cord from one post-polio patient and found perivascular intraparenchymal chronic inflammatory infiltrates primarily composed of B lymphocytes with rare macrophages and no T-cells. Kaminski and colleagues (95) found inflammation in the spinal cords of eight of nine post-polio syndrome patients. Studies support an immune-mediated process with the finding of inflammatory cytokines (TNF-alpha, IFN-gamma, IL-4, IL-10) in the CSF of post-polio syndrome patients (67; 68).

In a study of patients with post-polio syndrome, Bickerstaffe and colleagues measured plasma TNF-α, IL-6, IL-8, and leptin levels and found them to be significantly increased compared to healthy controls (22). However, they found no association between these raised systemic levels of inflammatory mediators and long-term decline in quadriceps strength or other clinical parameters. In conclusion, this study suggests that there is evidence for systemic inflammation in post-polio syndrome, yet the relationship with clinical deterioration remains uncertain.

Epidemiology

Prevalence. Data regarding the incidence and prevalence of post-polio syndrome are variable. In survivors of acute polio, Codd and colleagues found a prevalence of post-polio syndrome of 22.4% (41), but a repeat study from the same institution found a prevalence of 64% (184). The 1987 National Health Interview Survey estimated that about half of the 1.63 million people in the United States who survived acute poliomyelitis had new late effects (29). Another study from 1987 found a prevalence of 42% (160); Ramlow and colleagues (140) found a prevalence of 28.5%. Other self-reporting surveys have found an even higher prevalence of new weakness: 53%, 58%, 85%, respectively (173; 87; 105). The large number of cases now being seen relate to the large epidemics of poliomyelitis that occurred in the United States in the 1940s and 1950s (90). Bertolasi and colleagues report that female gender, the presence of respiratory disturbance during the acute phase of polio, and the use of orthoses and aids during the recovery and stabilization are independent risk factors for post-polio syndrome in their studied population (21).

Delay in onset of post-polio syndrome. The delay in onset from acute poliomyelitis to post-polio syndrome ranges from eight to 71 years in various series (90). The more severe the acute polio, the earlier new symptoms are likely to occur (79). In various series the average interval is about 35 years (79; 90; 140; 97).

Prevention

Several risk factors have been identified that predispose to the development of post-polio syndrome. One is the severity of the polio and resulting paralysis (79; 04; 184; 166). The more severe the disease the more likely a patient will develop post-polio syndrome. Presumably, this is due to fewer motor neurons, which will result in earlier weakness when these few remaining motor neurons with enlarged motor units degenerate. The age at onset of the poliomyelitis is also a risk factor. Acute poliomyelitis in adolescents and adults is more severe than in infants and small children (90), and the former patients are more likely to develop post-polio syndrome (79; 100). Thus, older age at the time of the acute poliomyelitis as a risk factor probably relates to the greater severity of the disease. In one study, another risk factor is the amount of recovery; the greater the recovery, the more likely post-polio syndrome will occur (100), suggesting that reinnervation is unable to be maintained 30 to 40 years later. In these patients who do recover totally or partially, excessive exercise or overuse appears to predispose them to post-polio syndrome (100; 166). The only one of these risk factors that can be addressed preventively is the overuse of muscles (excessive exercise). Patients need to be educated not to excessively exercise and to pace their activities. Post-polio syndrome patients should not allow themselves to have muscle fatigue (increased weakness, loss of muscle tone, muscle numbness, muscle soreness) or even excessive generalized fatigue after exercise. Their exercise must be paced and be non-fatiguing.

In their descriptive study, Winberg and colleagues found that despite a progressive physical disability, people with late effects of polio are physically active, but much of it is performed as part of their household activities and not as traditional exercise (181). The relationship between physical activity, life satisfaction, and age further supports the general contention that an active lifestyle is an important factor for perceived well-being among older people. In ambulatory persons with late effects of polio, knee muscle strength and gait performance explain only a small portion of physical activity, necessitating further studies to understand how other impairments, activity limitations, environmental factors, and personal factors influence physical activity in persons with late effects of polio (182).

Differential diagnosis

Confusing conditions

Because the neurologic manifestations of post-polio syndrome are primarily those of a lower motor neuron or motor axonopathy, the differential diagnosis primarily encompasses diseases manifesting lower motor neuron or peripheral nerve involvement. These diseases are adult-onset spinal muscular atrophy (80; 123), multifocal motor neuropathy (168), chronic inflammatory polyradiculopathy (27), plasma cell dyscrasias (107), motor neuropathy and monoclonal gammopathy (28), hexosaminidase deficiency (88), thyrotoxicosis (142), parathyroid disorders (130), and heavy metal toxicity (44). Other entities in the differential might include lumbar spinal stenosis (75; 126), chronic disc degeneration and lumbar spondylosis (58), cauda equina syndromes (150), and lumbar-sacral cord tumors (149). Occasionally, involvement of a single extremity or nerve may be included in the differential, eg, monomelic atrophy (56), diabetic amyotrophy (19), radiculopathies, and entrapment neuropathies (52).

For the rare post-polio patient with upper motor neuron signs, amyotrophic lateral sclerosis (143), cervical spondylosis (162), foramen magnum tumors (60), and tumors of the cervical and thoracic cord (149) are part of the differential diagnosis.

Because fatigue is such a prominent feature of the post-polio syndrome, diseases that frequently cause this complaint such as myasthenia gravis (61), myasthenic syndrome (61), and some myopathies (124) and medical diseases (cardiac, hematologic, endocrine, cancer, chronic systemic infections) must be excluded. A number of unusual entities, manifested primarily by muscle pain, cramps, and fasciculations (85; 42; 13) also should be excluded. A syndrome of acute asymmetric flaccid paralysis has been described in numerous patients with West Nile virus infection (108). This resembles the paralysis of the anterior horn cell poliomyelitis seen in polio victims and is often associated with disabling fatigue and frequently hinders rehabilitation efforts.

Associated or underlying disorders

Sleep apnea--either central, obstructive, or mixed--is associated (73; 163).

Osteopenia and osteoporosis are also associated, predisposing to increased fracture risk (118).

Diagnostic workup

Because generalized fatigue is one of the most frequent manifestations of post-polio syndrome, many systemic diseases must be excluded. Most of these diseases can usually be excluded with blood tests and include hypo- and hyperthyroidism, anemia, leukemia, and cancer, which cause an elevated erythrocyte sedimentation rate and other blood test abnormalities, liver failure, and kidney failure. Cardiac failure and sleep disorders also need to be excluded as causes of fatigue. In post-polio syndrome patients, the creatinine kinase is often mildly elevated (90; 122; 184; 172). In one study, elevated creatinine kinase levels were more likely to occur in those with progressive weakness (184), and markedly increased levels indicated muscle overuse (134). Electrodiagnostic studies cannot differentiate patients with post-polio syndrome from asymptomatic post-polio patients (36; 92). However, these studies are important to exclude other neuromuscular diseases (amyotrophic lateral sclerosis, radiculopathy, polyneuropathy, myasthenia gravis, and myopathies). In a comparative EMG analysis of muscle activity and assessment of muscle strength and fatigue after maximal isometric contraction during knee extension in post-polio patients, Correa and colleagues were able to show a decreased endurance on initial muscle contraction and during contraction 15 minutes after the initial maximal voluntary contraction, along with muscle fatigue that was assessed through linear regression (46). Imaging studies (eg, CT, MRI) are needed to exclude spine problems such as spondylosis and stenosis.

Hachisuka and colleagues studied 43 polio survivors and 20 healthy controls with motor nerve conduction studies of the median and tibial nerves bilaterally, including sampling of F-waves elicited by 100 stimuli and the determination of motor unit number estimation (MUNE), with the intent to determine whether F-waves reveal electrophysiological features of anterior horn cells in polio survivors (74). They found a significant increase in abnormally stereotyped ("repeater") F-waves and a reduction of F-wave persistence in both nerves in the polio group compared to the control group. Repeater F-waves had a negative correlation with MUNE. It is well known that repeater F-waves are signs of motor unit pathology. The authors conclude that the trends in F-wave persistence and repeater F-waves following motor unit loss are characteristic findings in polio survivors.

Gonzalez and colleagues report that the CSF of persons with post-polio syndrome displayed a disease-specific and highly predictive (p=0.0017) differential expression of five distinct proteins: gelsolin, hemopexin, peptidylglycine alpha-amidating monooxygenase, glutathione synthetase, and kallikrein 6 in comparison with the control groups (70). An independent ELISA confirmed the increase of kallikrein 6, suggesting that these five proteins should be further evaluated as candidate biomarkers for the diagnosis and development of new therapies for post-polio syndrome patients.

Management

Generalized fatigue is best treated with lifestyle changes consisting of energy conservation measures (frequent rest periods and daytime naps, pacing of physical activities), weight-loss programs, avoidance of sedating medications, treatment of sleep or respiratory disorders, and the use of assistive devices (orthoses, canes, intermittent use of wheelchairs) (171; 133). Sleep disorder screening should also be considered as even an unrelated sleep disorder could exacerbate post-polio symptoms (110). Pharmacological agents (amantadine, pyridostigmine, fluoxetine, methylphenidate, modafinil, and coenzyme Q10) may be postulated to have a role in the amelioration of generalized fatigue. However, agents, including amantadine, pyridostigmine, modafinil, and coenzyme Q10, have been studied in a controlled fashion in post-polio fatigue, and all four were found to lack benefit (48; 167; 40; 135).

The most important advance in the treatment of new post-polio syndrome weakness is the finding in at least nine studies that mild-to-moderate weakness can be improved with a non-fatiguing exercise program (62; 07; 92; 39). All of these studies demonstrated increased muscle strength, and none showed laboratory evidence of muscle overuse (eg, an increase in creatinine kinase or electromyographic or biopsy evidence of muscle damage). These non-fatiguing exercise programs avoid overuse by using both submaximal and maximal strength combined with short-duration repetitions. Exercise should be performed on alternate days to allow for full recovery and to avoid overuse. A physical therapist is often needed to instruct patients on appropriate exercise techniques and to monitor the patients so they do not overexert. Patients with post-polio syndrome who could exercise at a level that avoided overuse (excessive muscle fatigue or increasing muscle or joint pain) have experienced positive results (06). Muscle fatigue can also be improved by interspersing bouts of activity with rest periods (pacing) to avoid excessive fatigue (05). This simple procedure significantly improved strength recovery after activity (05). Patients with post-polio syndrome who exert their weak muscles to the point of exhaustion (overuse) may require two to three days to recover from the resulting muscle fatigue. Furthermore, high intensity exercise regiments were not well tolerated and did not result in improved muscle strength or cardiovascular fitness (170). Pharmacological intervention with pyridostigmine and prednisone did not improve long-term muscle strength (48; 167). A clinical trial to understand the potential role of treatment with L-citrulline has been completed, but results are unpublished (148).

Koopman and colleagues conducted a multicenter, single-blinded, randomized controlled trial to study the efficacy of exercise therapy and cognitive therapy on reducing fatigue and improving activities and health-related quality of life in patients with post-polio syndrome (103). Over four months, severely fatigued patients with post-polio syndrome received exercise therapy, cognitive therapy, or usual care. Of 68 randomized patients, no differences were observed between the intervention and usual care groups for fatigue, suggesting that neither exercise therapy nor cognitive therapy was superior to usual care in reducing fatigue in severely fatigued post-polio syndrome patients.

In their report of an EFNS task force on post-polio syndrome, Farbu and colleagues recommend Halstead's definition of post-polio syndrome from 1991 as diagnostic criteria (63). They feel supervised, aerobic muscular training, both isokinetic and isometric, is a safe and effective way to prevent further decline for patients with moderate weakness (Level B). Muscular training can also improve muscular fatigue, muscle weakness, and pain. Farbu and colleagues note that training in a warm climate and non-swimming water exercises are particularly useful (Level B). They further add that recognition of respiratory impairment and early introduction of noninvasive ventilatory aids prevent or delay further respiratory decline and the need for invasive respiratory aid (Level C).

Bulbar muscle weakness may also lead to dysphagia, respiratory failure, and sleep disorders. Dysphagia can be improved by instruction on swallowing techniques (155). Chronic respiratory failure can often be managed with nighttime noninvasive positive-pressure ventilation (14). Mouth and nasal intermittent positive pressure ventilation, manually and mechanically assisted coughing, and noninvasive blood gas monitoring in the home were the main techniques used for optimizing quality of life and for avoiding complications (17). With the use of these measures, acute respiratory failure and tracheal intubation can usually be avoided (14). Only a small percentage of patients eventually require tracheotomy and permanent ventilation. Although not evidenced-based, influenza and pneumococcal vaccines are probably indicated. Smoking should be eliminated and obstructive disease treated. Sleep disorders occur frequently in post-polio syndrome patients and are treated similarly to sleep apnea seen in patients without post-polio syndrome (92). In patients with post-polio syndrome, Hsu and Staats identified three patterns of sleep disturbances: (1) obstructive sleep apnea, (2) hypoventilation, and (3) a combination of both (83). They further proposed that sleep-related disordered breathing (SRDB) is a late sequela of poliomyelitis, and clinical evaluation should include information about sleep. Another study found that transcranial direct current stimulation (tDCS) over the premotor areas for 15 days improved sleep and fatigue symptoms in patients with post-polio syndrome (02). Acler and colleagues further added that tDCS could be a noninvasive and valuable new tool for managing post-polio patients.

Musculoskeletal pain (muscle and joint pain) and joint instability can be treated with braces and wheelchairs (171), pacing activities (180) and lifestyle changes (133). Anti-inflammatory medications, anti-depressant pain medications (eg, amitriptyline, duloxetine), heat, and massage appear to be somewhat beneficial but have not been studied objectively. In a small, randomized controlled trial, lamotrigine significantly improved pain, muscle cramps, and fatigue at two and four weeks (125).

Osteopenia and osteoporosis are increasingly associated with post-polio syndrome, predisposing to increased fracture risk (118). Thus, bone density assessment, review of fall risk, and preventative intervention should be considered for all patients. Additionally, these patients are at high risk for intraoperative skeletal complications, and additional surgical planning for bone fracture repair is important (117).

Cardiac conditioning is important for all patients, and three trials using aerobic or general conditioning exercise with lower-limb cycle or arm ergometers have shown significant improvement in cardiorespiratory fitness in post-polio syndrome patients (104; 62; 06). Two aquatic exercise studies have demonstrated that flexibility, strength, and cardiorespiratory fitness can be improved in post-polio syndrome patients (138; 179). Finally, it is important to note that psychological symptoms related to the re-emergence of a supposedly resolved disease and the stresses of the needed major lifestyle changes can sometimes be overwhelming (92; 96).

The inflammatory or immune-mediated hypotheses, best supported by the increased expression of inflammatory cytokines in cerebrospinal fluid (CSF), has resulted in many clinical trials in post-polio syndrome, including prednisone and intravenous immunoglobulin (IVIG). Prednisone did not improve long-term muscle strength or fatigue (167). There have been many studies with IVIG. Randomized control studies have shown that IVIG is effective in reducing pain in complex regional pain syndrome (low-dose IVIG) and post-polio syndrome (high-dose IVIG) (66). Open trials have also shown efficacy in additional pain conditions. Farbu and colleagues, in their small pilot study on post-polio syndrome patients, concluded that no effect was seen with IVIG treatment on muscle strength and fatigue; however, IVIG-treated post-polio syndrome patients reported significantly less pain three months after treatment (64). TNF-alpha was increased in the CSF of post-polio syndrome patients. Ostlund and associates reported that IVIG leads to an increase of quality of life at 6-month follow-up by improving vitality, social function, and role-emotional, with significant decrease in bodily pain (127). Gonzalez and colleagues have also reported that IVIG therapy has sustained positive effects on relevant QoL variables and reduction of inflammatory cytokines for up to 1 year in patients with post-polio syndrome (69). However, systematic reviews and meta-analysis highlight the inconsistencies with IVIG treatment in post-polio syndrome, and the clinical use of IVIG cannot yet be recommended (84; 102).

Table 2. Evidence-Based Treatment for Patients with Post-polio Syndrome*†

Special considerations

Anesthesia

Post-polio syndrome patients with compromised respiratory status may need more respiratory supportive care than patients with normal pulmonary function.