Postpolio Syndrome

One possible cause of postpolio syndrome (PPS) is decompensation of a chronic denervation and reinnervation process to the extent that the remaining healthy motor neurons can no longer maintain new sprouts; thus, denervation exceeds reinnervation.[10]

A second possible mechanism for PPS is motor neuronal loss due to reactivation of a persistent latent virus. In addition to muscle atrophy and denervation, foci of perivascular and interstitial inflammatory cells have been found on 50% of biopsies of patients with PPS. Activated T cells and immunoglobulin M and immunoglobulin G antibodies specific for gangliosides also have been found.

Another possibility is an infection of the polio survivor's motor neurons by an enterovirus that is different from the one responsible for the patient's polio. Others sources hypothesize that PPS is merely the loss of strength due to the usual stresses of aging and weight gain. In patients with PPS, these processes occur in muscles that already are weak, so the consequences are more noticeable compared with those of patients who have not had polio.[11]

A study by Wendebourg et al indicated that in patients with PPS, atrophy of spinal cord gray matter (SCGM) is a factor in muscle weakness. The investigators reported that “SCGM atrophy is significantly and segment‐wise associated with muscle strength in corresponding myotomes” in individuals with PPS and that the atrophy is especially pronounced at levels near the cervical and lumbar enlargements. Evidence pointed to SCGM atrophy being the result of a second disease phase rather than existing solely as a consequence of the initial infection or aging.[12]

A study by Li Hi Shing et al suggested that non-structural issues, including polypharmacy and poor sleep, play a role in the extramotor manifestations of PPS, such as apathy, verbal fluency deficits, and fatigue. The investigators’ proposal was related to a neural analysis of individuals with PPS, which found only limited degeneration of the brain’s cortical and subcortical regions and white matter.[13]

Frequency

United States

The incidence of postpolio syndrome (PPS) in previous acute polio patients ranges from approximately 22-68%. The prevalence of the PPS was estimated at 28.5% of all paralytic polio cases.[14] The current prevalence is approximately 1.6 million cases. Suggestions have been made that 100% of polio survivors, if tracked for a long period, can develop some symptoms of PPS. The risk of PPS was significantly higher among patients who sustained substantial permanent impairment after polio and among females. The incidence did not vary with age at acute onset, acute severity, or level of physical activity after recovery.

International

In a Brazilian tertiary care center, study the frequency of PPS was 77.2% of the studied population. Among them, 62.8% were women and 37.2% were men.[15] Prevalence rates were reported to be 31% and 41% in Italian population in 2 different studies.[16, 17] Again, it was more common in women.

Sex

PPS is more common in women. In a survey of persons with long-term, disabling conditions—specifically, neuromuscular disease, multiple sclerosis, postpolio syndrome, or spinal cord injury—Thakral et al found that fatigue and pain were reportedly greater in women than in men. Moreover, while younger women scored higher than younger men with regard to physical functioning, the opposite was true for older individuals.[18]

Age

The strongest determinant of PPS onset was the length of the interval following the acute illness, with incidence peaking at 30-34 years after acute polio.

Symptoms of postpolio syndrome (PPS) usually appear earlier in patients who have very severe residual weakness, individuals who had early bulbar respiratory difficulty in the acute illness, and persons who were older when they contracted acute polio. PPS symptoms tend to occur first in the weaker muscles.

Fatigue

In individuals without polio or PPS, the functional consequences of aging and loss of motor units may be unnoticeable until a very advanced age. In the individual with PPS, any further loss of strength may be more readily apparent. In contrast to patients with chronic fatigue syndrome, postpolio fatigue is prominent in the early hours of the afternoon and decreases after brief periods of rest and is exacerbated by minimal physical exercise. PPS-related fatigue usually does not prevent patients from working. Fatigue in PPS usually occurs on a daily basis, increases in severity as the day progresses, and is usually associated with physical weakness.[19, 20]

Fatigue in PPS is multidimensional. Different types of fatigue, such as general fatigue, physical fatigue, and mental fatigue, are determined by different variables. Potentially modifiable factors such as stress, depression, pain, and physical activity account for a portion of fatigue in PPS.[21]

Central pain pathogenesis can include chronic pain, type A personality, depression, dysfunctional reticular-activated system, sleep disorders, and respiratory dysfunction. PPS produces somnolence and difficulty in concentrating and remembering.

Peripheral pain pathogenesis may be metabolic exhaustion of the enlarged motor units, neuromuscular junction transmission defects, scarring within the motor neurons, or loss of motor units due to aging. PPS produces decreased muscular endurance and increased muscular fatigability.

A study by Romigi et al found a high prevalence of restless legs syndrome (RLS) in patients with PPS, with RLS possibly being a significant factor in fatigue. The investigators suggested that a link exists between neuroanatomic and inflammatory mechanisms in RLS and PPS.[22]

Muscle weakness

In PPS, muscle weakness and atrophy can be permanent, because of loss of motor units, or transient, because of muscle fatigue.[23, 24]

A number of functional etiologies for weakness have been hypothesized, including disuse, overuse, and chronic weakness, as well as weight gain.

Asymmetrical and scattered weakness may be present. Progression of muscle weakness is faster than in normal ageing.[25]

Some authors have found evidence that previously unaffected muscles later become weak; in these cases, they discovered that the patient was unaware of or had not been told that the particular muscle had been affected during the acute episode.

A systematic review conducted by Stolwijk-Swüste et al[26] concluded that the rate of decline in muscle strength in PPS is slow, and prognostic factors have not yet been identified. They suggested that long-term follow-up studies with unselected study populations and age-matched control individuals are needed to shed further light on this question.

Muscle pain

Deep aching pain may be a component of a myofascial pain syndrome or fibromyalgia.[10, 27]

This feature is extremely prevalent in PPS. Using a retrospective, cross-sectional survey, Stoelb et al investigated the frequency and most common sites of pain in patients with postpolio syndrome.[28] Pain symptoms were reported by 57 (90.5%) of the 63 study participants; pain was reported most often in the shoulders, legs, hips, and lower back, with the most intense pain occurring in the legs, knees, wrists, head, and lower back.

In a Swedish study, 68% of patients with PPS experienced pain at the examination. Pain was found to have a significant impact on their quality of life.[29]

Gait disturbance

Difficulty with gait is caused by progressive weakness, pain, osteoarthritis, or joint instability; it is common in patients who previously used assistive devices but later discarded them. The gait pattern of PPS patients is related to numerous intrinsic and extrinsic factors.[30] . Using 6-minute walk test, it was shown that walking speed was negatively correlated with the increased hip flexion, but not with the ankle plantar-flexion at foot-off in the patients with PPS.[31]

Respiratory problems

Respiratory disorders are most prevalent in patients with residual respiratory muscle weakness.

These changes cause chronic microatelectasis, diminished pulmonary compliance, increased chest wall tightness, chronic alveolar hypoventilation, decreased cough and expiratory flow, and decreased clearing of secretions.

The new respiratory difficulties are not only related to new respiratory muscle weakness but also to scoliosis, pulmonary emphysema, cardiovascular insufficiency, or poor posture.

A central component also may occur because acute bulbar polio often affects the medullary structures, including the reticular formation and sleep regulatory system.

Nonetheless, a study by Lira et al found that on spirometric evaluation, the only significant difference in lung function between patients with PPS and controls was an approximately 27% lower value in mean maximal voluntary ventilation.[32]

Swallowing problems (dysphagia)

Dysphagia can occur in patients with bulbar and nonbulbar postpolio.

Subclinical asymmetrical weakness in the pharyngeal constrictor muscles is almost always present in all postpolio muscular atrophy patients, including those who do not complain of new swallowing difficulties.

In one Finnish study of 51 people with PPS who were admitted to a rehabilitation center, 15 people reported daily problems with swallowing or voice production. The most commonly observed deficits in swallowing included decreased pharyngeal transit and food catching in the throat.[33]

Autonomic dysfunction

The cause is unclear; the peripheral component could include muscular atrophy and, therefore, diminished heat production.

Sleep apnea

This disorder is not uncommon in patients left with residual bulbar dysfunction or severe respiratory compromise. Patients with bulbar involvement had more frequent sleep apnea than patients without. They also had significantly more central apnea.[34]

Sleep apnea appears to be due to a combination of the following:

• Central apnea, due to a residual dysfunction of the surviving bulbar reticular neurons

• Obstructive apnea, due to pharyngeal weakness and increased musculoskeletal deformities from scoliosis or emphysema

• Postpolio muscular atrophy, resulting in diminished muscle strength of the respiratory, intercostal, and abdominal muscle groups

Restless legs syndrome

As previously mentioned, RLS is fairly common in people with postpolio syndrome. A study by Marin et al reported the prevalence of RLS to be 36% in the postpolio syndrome population, with the median severity, as measured using the Brazilian version of the International Restless Legs Syndrome Study Group (IRLSSG) severity score to be 23. In many patients, the onset of RLS and postpolio syndrome was concomitant.[35]

Flat-back syndrome

Another possible symptom in some patients with postpolio syndrome is the flat-back syndrome, which consists of the inability to stand erect because of forward flexion of the trunk and pain in the low back and legs.[36]

The flat-back syndrome typically occurs in patients with diminished lumbar lordosis as a result of instrumentation of the spine for scoliosis, vertebral fracture, or degenerative joint disease.

The trunk extensor musculature plays an essential role in maintaining upright posture, and it may be that PPS-related weakness in this musculature represents a major contributing factor to the flat-back syndrome in these patients.

In persons with postpolio syndrome, progressive weakness and atrophy may be observed in muscles that were affected initially by the poliovirus or in muscles that were spared clinically, which tends to happen in an asymmetrical distribution. Fasciculations sometimes can be observed in atrophic muscles, as a result of the lower motor neuron injury.

Obesity is widespread in postpolio survivors. A study by Chang indicates that the current body mass index (BMI) underestimates the total body fat mass percentage for those with poliomyelitis, leading the authors to suggest that a population-specific BMI should be used instead.[37]

Obtain a complete blood count (CBC) and cerebrospinal fluid analysis to exclude conditions other than postpolio syndrome. Also obtain swallowing studies.

Computed tomography (CT) scanning and magnetic resonance imaging (MRI) can be ordered to rule out other possible diagnoses or structural neurologic processes (eg, stroke, multiple sclerosis, tumor).

Electrodiagnostic studies[6] are used to rule out other neurologic or neuromuscular disorders in the differential diagnosis. The following 5 phases of electrodiagnostic study findings of anterior horn cell disease have been recognized:

• Acute myelitis (first month)

• Early recovery (2-12 mo)

• Late recovery

• Functional stability

• Late changes during functional stability (eg, fasciculations, positive waves, fibrillations, increased amplitude and duration of motor unit potentials)

In postpolio syndrome (PPS), sensory conductions should be normal; motor conductions usually are normal but may be slow. In late stages, amplitude decreases significantly.

Single-fiber electromyography reveals increased jitter and blocking. This observation is related to the fact that in PPS, variable degrees and different types of neuromuscular transmission failure have been found in affected patients who had associated histologic signs of reinnervation in their muscle biopsies.

Functional and structural abnormalities of neuromuscular junctions are common, but not necessary, conditions for the diagnosis of PPS. These neuromuscular junction transmission defects typically are observed in the early stage of the neuronal degeneration that produces PPS. Whether neuromuscular junction transmission defects increase with the passage of time is unclear.

In the chronically denervated muscles of patients with postpolio syndrome, there are secondary myopathic features, including endomysial inflammation and rare vacuolated fibers.

Physical Therapy

In a pilot study of postpolio syndrome (PPS) patients, a multidisciplinary rehabilitation approach involving tailored physiotherapy exercises has shown to have significant benefit on muscle endurance, exertion, and depression levels for up to 6 months.[38]

A retrospective study by Curtis et al of 214 patients with clinically confirmed PPS found improvement in multiple characteristics, but not in quality of life, after completion of a residential self-management program. Following the program, which was headed by a multi-disciplinary clinical team, the investigators determined that symptoms, knowledge concerning PPS, and walking speed had improved among the patients. However, no significant changes were seen in anxiety and depression scores, which remained low, or in self-reported quality of life. Although this was a group-based program, it also featured individually tailored support with regard to physical exercise and fatigue management.[39]

The basic management principles for individuals with PPS include energy conservation and pacing one's activities. Although basic, these activity modifications may be difficult for some patients to accept.

Psychological interventions, such as cognitive behavior therapy, may also be initiated to help reduce fatigue.[7, 8] (Although in a multicenter, single-blinded, randomized, controlled study of 68 patients with PPS, Koopman et al reported that neither exercise therapy nor cognitive behavioral therapy were better at reducing severe fatigue than was treatment with usual care.[40] )

Certain psychological issues have been studied in relation to postpolio syndrome. Most studies reveal that depression is not related to postpolio syndrome symptomatology or to the level of residual physical disability. Type A behavior is significantly higher in the polio population than in a control population.[41] Overall, normal psychological and emotional functioning has been found in patients with postpolio syndrome compared with controls.

Reports on exercises are conflicting, but the key factor seems to be exercise intensity. Strengthening exercises should be nonfatiguing. A specific suggestion is to exercise every other day, and the perceived rate of exertion should be less than "very hard." Loads should be held for only 4-5 seconds, and there should be a 10-second rest between bouts and a 5-minute rest between sets. The patient should perform about 3 sets of 5-10 repetitions.[42, 43]

A study by Voorn et al indicated that individuals suffering from severe PPS-associated fatigue tend to lack the ability to follow a high-intensity aerobic exercise program using a cycle ergometer, thus making it difficult for them to improve their lower extremity muscle function and cardiorespiratory fitness. Participants in the study were able most of the time to maintain exercise intensities at about the anaerobic threshold, but over more than 75% of the time, they did not exercise intensely enough to stay within their target heart range. The investigators stated that a more individualized approach to exercise in PPS, with patients using large muscle groups other than those of the lower extremities, may prove beneficial.[44]

In addition to specifying exercises for those body areas experiencing the deleterious effects of disuse, the exercise prescription also should consider how to protect (1) muscles and joints that are experiencing the adverse effects of overuse and (2) body areas with very significant chronic weakness (generally, areas where the muscles have less than antigravity strength on manual muscle testing).

Results of these exercises vary. Strengthening programs performed as described show a 60% increase on isokinetic strength, improved cardiorespiratory status, no decline in strength in 6-12 months, and 5% increase in isometric strength.

In one randomized controlled study, progressive resistance training program consisted of 3 sets of 8 isometric contractions, 3 times weekly for 12 weeks. Postpolio patients showed a significant improvement in their strength.[45] The training did not adversely affect motor unit survival, and the improvement was largely attributable to an increase in voluntary motor drive.

Electrical stimulation has been used to strengthen weakened muscles or to reeducate muscles weakened through disuse, as well as to decrease pain.

For myofascial pain, consider heat, electrical stimulation, trigger point injections, stretching exercises, biofeedback, muscle relaxation exercises, or static magnetic fields for trigger points.

For gait disturbances, assistive devices can be used, but sometimes patients refuse them because of the philosophy of "not giving in."[9] Treatment also can involve limitation of ambulation to shorter distances and the use of orthotics for joint protection.

A study by Da Silva et al of 15 polio survivors with/without postpolio syndrome indicated that whole-body vibration can safely be administered to these patients and, if first delivered at higher intensity, can improve walking speed.[46]

Exercise therapy and training programs in PPS patients should be carefully customized and planned by physiotherapists to avoid both overuse and disuse, and the level of physical activity should be modified to decrease pain.[47]

Occupational Therapy

Patients with postpolio syndrome usually benefit from different adaptive techniques and equipment to perform any activities of daily living, as well as education and energy conservation techniques.

Speech Therapy

Speech evaluation in persons with postpolio syndrome usually is recommended with any suggestion of swallowing problems. The therapist teaches the patient about different techniques to improve his/her swallowing function.

Pulmonologists

When the patient with postpolio syndrome reports respiratory problems, a full pulmonary evaluation may be required. Sometimes, the patient may even need mechanical respiratory support. A sleep evaluation may be necessary for suspected sleep apnea.

Orthopedists

The patient may present with various joint deformities that may require orthoses and sometimes even surgery.

Medications, most of which address fatigue, have been used with only partial success in patients with postpolio syndrome (PPS). Contradictory information is reported on the use of antivirals.

Some authors have found no significant improvement with antivirals as compared with placebo. Amantadine may act to release dopamine from dopaminergic terminals and other central sites, but it has been studied in the treatment of fatigue in PPS patients and has not been shown to be beneficial.[48] Corticosteroids, such as high-dose prednisone, have been studied, but with no good results.[49] Modafinil has been studied for fatigue in PPS patients and has not shown to be beneficial.[50, 51]

A Cochrane review of the different treatments for PPS concluded that intravenous immunoglobulin, lamotrigine, muscle strengthening exercises, and static magnetic fields may be beneficial but need further investigation.[52]

Neither controlled studies nor meta-analyses have shown that, when compared with placebo, pyridostigmine improves fatigue, muscle strength or function, or pain in patients with postpolio syndrome. However, a small noncontrolled trial did report that the drug improved fatigue in some patients.[53]

A prospective study by Östlund et al indicated that patients with PPS who respond to intravenous immunoglobulin therapy tend prior to treatment to have reduced physical function, muscle atrophy in the lower extremities, and greater fatigue and pain levels, as well as a visual analogue scale score above 20. The study, which included 124 patients, found that those who did not respond to the treatment tended to have good physical function, less muscle atrophy in the lower extremities, low pain and fatigue levels, and good mental health.[54]

A study by Bertolasi et al found that a single 5-day course of intravenous immunoglobulin did not cause significant changes in fatigue, muscle strength, or pain in patients with PPS. However, health-related quality of life associated with mental activity was improved.[55]

Class Summary

Some authors have reported that one of the mechanisms for production of fatigue may be related to neuromuscular junction transmission deficits; however, treatment with anticholinesterases has been successful in only half of the cases. This low success rate has been attributed to the variety of neuromuscular junction defects believed to be present in postpolio syndrome. The mechanism of response to anticholinesterases also is unclear because some patients experience improvement in muscular strength, rather than improvement in fatigability.

A multicenter, randomized, double-blinded, placebo-controlled trial of a 6-month course of pyridostigmine 60 mg 3 times per day in 126 postpolio syndrome patients showed no significant differences between pyridostigmine and placebo-treated postpolio syndrome patients on measures of quality of life, isometric strength, fatigue, and serum insulinlike growth factor levels.[56]

Pyridostigmine (Mestinon)

Acts in smooth muscle, the CNS, and secretory glands where it blocks action of acetylcholine at parasympathetic sites and facilitates transmission of impulses across the myoneural junction.

Class Summary

Modulate activity of immune system.[57, 55]

Immunoglobulin intravenous (Gammagard, Sandoglobulin)

Intravenous immunoglobulin has been recently studied in the treatment of symptoms related to postpolio syndrome. Results show that it could be a supportive treatment option for subgroups of patients with postpolio syndrome. Further studies are needed to investigate this in more detail.

Features that may be relevant to its efficacy include neutralization of circulating myelin antibodies through anti-idiotypic antibodies; down-regulation of proinflammatory cytokines, including IFN-gamma; blockade of Fc receptors on macrophages; suppression of inducer T and B cells and augmentation of suppressor T cells; blockade of the complement cascade; promotion of remyelination; 10% increase in CSF IgG.

Class Summary

Lamotrigine may reduce morbidity of the disease.[58]

Lamotrigine (Lamictal)

Some preliminary studies suggest the efficacy of lamotrigine in enhancing the quality of life and symptoms of patients with postpolio syndrome. Further studies are needed.

Inhibits release of glutamate and inhibits voltage-sensitive sodium channels, leading to stabilization of neuronal membrane.

The symptoms of postpolio syndrome are slowly progressive, with periods of stability from 3-10 years.