Pathophysiology

Many years after acute paralytic poliomyelitis, new neuromuscular symptoms may develop in a condition termed postpoliomyelitis syndrome or postpolio syndrome (PPS). In 2000 the diagnostic criteria were revised as follows³⁹:

Population-based studies have demonstrated that the prevalence of new symptoms in prior polio patients is high. In these studies, new muscle weakness varied between 35% and 58% and new neuromuscular symptoms between 64% and 78%.^31,53,71 Risk indicators for the development of PPS are more severe initial polio paresis, better recovery from the acute polio, more severe residual impairments, contraction of acute polio at older age, number of years elapsed since acute polio, increasing age, and female gender.^{31,36,53,64,71}

Paralytic poliomyelitis develops in 0.1% to 2% of polio virus infections when the virus invades the central nervous system and destroys the motor neurons in the spinal cord, causing an acute, usually asymmetrically distributed, flaccid paresis. After the acute paralytic phase, muscle function usually recovers partially to fairly completely due to extensive reinnervation of denervated muscle fibers through collateral sprouting of axons from motor neurons that survived the acute phase and regained their function. Motor units may increase five to eight times in size.⁶⁰ Strength also improves because of muscle fiber hypertrophy, with fiber areas increasing up to twice their normal size.^21,25 It is assumed that muscle fiber hypertrophy develops in response to the relatively high loads on paretic muscles in performing activities of daily living.²⁵ After the recovery phase, the severity and extent of residual paresis, with large intraindividual and interindividual variation, remain stable for decades.

The origin of PPS is unknown. The leading hypothesis is that excessive metabolic stress on remaining motor neurons over many years eventually causes premature degeneration of the nerve terminals that were newly formed through reinnervation.⁶⁹ The role of aging seems limited, as most PPS patients develop new symptoms in their 40s, an age range in which a physiological loss of motor neurons normally does not occur.¹¹ A persistent poliovirus infection seems unlikely, but this theory has proponents.⁵⁶ An immune-mediated hypothesis is not commonly accepted, but a study has shown increased intrathecal cytokine production in PPS patients.²⁴ The validity of the different hypotheses on the pathophysiological mechanisms underlying PPS remains uncertain.

No diagnostic tests for PPS are available. Laboratory tests are used to show evidence of prior polio paralysis and to exclude other diseases. EMG displays signs of reinnervation and denervation in both symptomatic and nonsymptomatic muscles. Muscle biopsy findings include type grouping of muscle fibers as the result of reinnervation and hypertrophy of muscle fibers as compensation for loss of muscle fibers.^12,15,25 Size and number of motor units diminish over time.^41,60 However, even with these investigations PPS cannot be distinguished from stable neuromuscular functioning following polio.

The central issue in PPS is the gradual loss of muscle function, that is, new weakness. It is important to realize that the effect on neurons in the acute phase of polio often was more widespread than clinically apparent, and paralytic and nonparalytic polio are not two distinctly different forms of polio virus infection. In 1961, Beasley⁴ demonstrated in a large sample of polio patients that the degree of paresis showed a continuum from severe to normal, and that strength, especially in the larger lower extremity muscles, could be markedly reduced but remain undetected on clinical examination due to the upper limit in measurement range of manual muscle testing. (Note that manual strength testing can easily lead to overestimation of the individual’s capacity for activities such as walking.) Modern imaging techniques have confirmed that loss of muscle mass may be present while manual muscle strength is objectively normal.³² These observations are relevant to understanding that even patients without clinically detected weakness may retain residuals of their polio and can develop PPS later in life.⁵⁵

A major complaint of patient with PPS is fatigue.⁴⁴ Fatigue may be associated with exertion, but often patients have the perception of general fatigue. Several causes of fatigue have been considered, such as impaired calcium kinetics. Altered calcium levels may account for disturbances in excitation–contraction coupling of actin and myosin filaments,⁵⁷ decreased capillary density, reduced oxidative and glycolytic enzyme potentials,⁸ impaired voluntary muscle activation (possibly due to impaired reflex mechanism),^3,5 increased neuromuscular transmission defects in degenerating nerve terminals,⁶⁶ and degeneration of neurons of the reticular formation and basal ganglia.¹⁰

A systematic review of the course of functional status and muscle strength showed that muscle strength deteriorated slowly over years, and this effect was reported only in studies with follow-up of at least 4 years.⁶³ No prognostic factors could be identified, and the influence of comorbidity and aging is unknown. In another study of 38 subjects who were followed for 15 years, 31 reported progressive weakness during the study period.⁵⁸ All subjects showed a modest decline of strength and functioning of motor unit numbers. In this small group, no difference was found between symptomatic and asymptomatic subjects, and only the magnitude of neurological deficit at baseline was a prognostic factor for the development of new symptoms. In a study with 6-year follow-up of functional status, the severity of paresis at baseline was found to be the single prognostic factor for increasing problems with physical mobility over the study period.⁴⁷

Historical perspective

One of the first descriptions of late-onset muscle weakness following poliomyelitis was made by Raymond⁵⁴ in 1875. Several cases have been reported since then. These early papers often described patients with rapidly progressive paresis.⁴⁶ At that time, little was known about the cause and transmission of acute polio, and the diagnosis of infantile paralysis was not always certain. This explains why an association between PPS and amyotrophic lateral sclerosis has been suggested in the past,⁴² but the idea has been abandoned because of lack of supporting evidence.

PPS became generally recognized in the 1980s when large numbers of polio survivors of the polio epidemics in the 1940s and 1950s voiced new complaints as they grew older.²⁶ The diagnostic criteria of PPS have been adapted several times. Initially different forms of PPS were distinguished, such as postpoliomyelitis progressive muscle atrophy (PPMA).¹⁵ PPMA was intended to classify cases in which strength loss and new atrophy were objectified with serial examinations. However, the ability to detect individual changes in strength is limited^28,43 given that the rate of decline in muscle strength is slow and has been found only in studies with long-term follow-up.⁶³ The current conclusion is that there is insufficient basis to classify subtypes of PPS.³⁹

Between the end of the 19th century and the middle of the 20th century, when large polio epidemics swept across the western world, physicians were familiar with acute polio, the subsequent forms of recovery, and the treatment of residual impairments. Because of the disappearance of acute polio, much of that experience has been lost. Now the challenge is to treat large numbers of former polio patients who have new neuromuscular symptoms and functional deterioration many years after their acute polio infection.

Current issues

The nature and time course of PPS are still matters of debate. Although the symptoms and functional decline of PPS are recognized as common problems in many former polio patients, discussion continues on whether they signify a progressive loss of muscle function.³⁰ Some argue that degenerative disorders of the locomotory system are the main cause of the complaints reported by many patients with new neuromuscular complaints and therefore are not to be considered as signifying PPS. However, both joint degeneration and a decline in muscle function can occur simultaneously in the same individual and can negatively affect each other. Making the distinction between PPS and joint degeneration may be impossible in such cases. The ability to make such a distinction would be especially important if it were relevant to long-term prognosis or choice of treatment. The debate will continue as long as no diagnostic test for PPS is available. A better knowledge of the pathophysiological mechanisms of PPS is needed.

Another important issue is the lack of success of pharmacological treatment. A number of agents with different therapeutic actions have been investigated: human growth hormone and insulinlike growth factor-1, which promote protein synthesis in muscle cells and axonal sprouting; amantadine, bromocriptine, and selegiline, which are centrally acting dopaminergic agonists; high-dose prednisone, which has a strong antiinflammatory effect; and pyridostigmine, which improves neuromuscular transmission. No medication has been proven to increase strength or decrease fatigue in patients with PPS in a randomized controlled trial.^19,29,61,65 Reasons proposed to explain the failure of medications to show an effect include the slow progression of the disease, the heterogeneity of patients, and the variation in measurement.¹⁶ Given these factors, relatively large study samples and long follow-up periods are required to reveal clinical relevant effects of pharmacological interventions or exercise programs.

Current research

Current research issues include the long-term changes in PPS and its prognostic factors, the continued search for the pathophysiology of PPS, the search for pharmacological treatment, the design and evaluation of rehabilitation regimens, and the further development and evaluation of orthotic devices and assistive technology.

Long-term prospective studies underway include use of age-matched controls and specific attention to potential prognostic factors such as aging and comorbidity.

Treatment recommendations

No curative treatment exists for PPS. Pharmacological treatment is available only for relief of symptoms such as pain. Management of PPS aims to restore the balance between decreasing physical capacity and the persistent demands of conducting activities of daily living. The leading concept in treatment is that symptoms of PPS, such as muscle pain, increased fatigue after physical activity, and delayed recovery following physical activity, signify that muscles are overused in conducting ordinary activities of daily living.^6,50 Support for the theory of chronic overuse of muscles has been provided by studies showing elevated levels of serum creatine kinase related to the distance walked during the previous day⁶⁸ and by studies showing a predominance of type I fibers in lower leg muscles supposedly due to fiber type transformation from chronic overload.⁷ Also, PPS subjects have been found to recover more slowly from fatiguing exercise than do stable polio subjects.² Another factor said to contribute to symptoms is a poor cardiorespiratory condition,^18,49 but one study reported that the cardiorespiratory condition of polio subjects was not worse than that of healthy, comparably active subjects.⁴⁵ In this study, the reduced submaximal performance capacity of the polio subjects appeared to be strongly correlated with the limited available muscle capacity, and movement economy was diminished compared with the control subjects. Lower concentrations of some oxidative enzymes in the muscles of polio subjects have been reported, whereas other oxidative enzymes within normal ranges have been reported.⁸ The clinical significance of these findings has been debated.⁴⁸

PPS patients are best treated with a multidisciplinary, specialized rehabilitative approach.²³ Because individuals show considerable differences in polio residuals, treatment is adjusted on a case-by-case basis and should be preceded by a thorough customized medical and functional evaluation. PPS is a diagnosis by exclusion, and other possible causes for the symptoms should be ruled out first. The most commonly encountered neuromuscular problems that can be managed effectively and should not be confused with PPS include radiculopathies and compression neuropathies, such as carpal tunnel syndrome, ulnar neuropathies at the wrist or elbow, and plexopathies. Compression of nerves may result from long-term use of wheelchairs, crutches, or braces, or from poor posture. Orthopedic disorders are common, especially pain from joint degeneration and joint instability, and distinguishing these symptoms from PPS may be difficult. Patients with significant joint pain may limit their physical activity, which can lead to disuse weakness and atrophy. It is important to recognize orthopedic problems as a possible cause for declining muscle function in patients with PPS because appropriate treatment of orthopedic problems may slow down or arrest that decline.

To reduce overuse and rebalance the capacities and demands, conservative management consists of three essential components: exercise, assistive devices, and lifestyle changes. Exercise can optimize cardiorespiratory fitness and may add to the patient’s sense of well-being.^33,70 Exercise should be nonfatiguing and performed at submaximal levels to avoid overloading the limited muscle capacity. Exercise can improve muscle strength, especially when caused by disuse in muscle groups that are only moderately affected. Intensive strengthening exercises are not generally recommended, although they may occasionally be indicated. Functional training may be useful to improve the efficiency of ambulation.

Assistive devices (e.g., crutches, wheelchairs, and motorized scooters) and home adaptations (e.g., elevators and seating devices in the kitchen or shower) may be helpful. The need for these devices should be individually indicated and aim to reduce the physical strain of performing highly demanding activities of daily living.

Pacing of activities and taking rest intervals are of paramount importance to relieve symptoms. It has been shown that upper extremity complaints often result from overuse of shoulder and arm muscles.³⁵ Many PPS patients have successfully learned to deny their symptoms from childhood on in order to achieve a normal life.⁴⁰ Therefore, PPS patients may have great difficulty adapting their lifestyle to their decreasing abilities, and psychological support may be necessary.