Elevated plasma inflammatory mediators in post-polio syndrome: No association with long-term functional decline.

A key feature of post-polio syndrome (PPS) is progressive loss of muscle strength. In other chronic diseases systemic inflammation has been linked to muscle wasting. In this study plasma TNF-α, IL-6, IL-8, and leptin levels were significantly increased in PPS-patients compared to healthy controls. There was however no association between these raised systemic levels of inflammatory mediators and long-term decline in quadriceps strength or other clinical parameters. In conclusion, there is evidence for systemic inflammation in PPS, yet the relationship with clinical deterioration remains tenuous.

Post-poliomyelitis syndrome as a possible viral disease.

This review summarizes current concepts on post-polio syndrome (PPS), a condition that may arise in polio survivors after partial or complete functional recovery followed by a prolonged interval of stable neurological function. PPS affects 15-20 million people worldwide. Epidemiological data are reported, together with the pathogenic pathways that possibly lead to the progressive degeneration and loss of neuromuscular motor units. As a consequence of PPS, polio survivors experience new weakness, generalized fatigue, atrophy of previously unaffected muscles, and a physical decline that may culminate in the loss of independent life. Emphasis is given to the possible pathogenic role of persistent poliovirus infection and chronic inflammation. These factors could contribute to the neurological and physical decline in polio survivors. A perspective is then given on novel anti-poliovirus compounds and monoclonal antibodies that have been developed to contribute to the final phases of polio eradication. These agents could also be useful for the treatment or prevention of PPS. Some of these compounds/antibodies are in early clinical development. Finally, current clinical trials for PPS are reported. In this area, the intravenous infusion of normal human immunoglobulins appears both feasible and promising.

Intravenous immunoglobulin for post-polio syndrome: a randomised controlled trial.

BACKGROUND: Survivors of poliomyelitis often develop increased or new symptoms decades after the acute infection, known as post-polio syndrome. Production of proinflammatory cytokines within the CNS indicates an underlying inflammatory process, accessible for immunomodulatory treatment. We did a multicentre, randomised, double-blind, placebo-controlled study of intravenous immunoglobulin in post-polio syndrome. METHODS: 142 patients at four university clinics were randomly assigned infusion of either 90 g in total of intravenous immunoglobulin (n=73) or placebo (n=69) during 3 consecutive days, repeated after 3 months. Seven patients were withdrawn from the study. Thus, 135 patients were assessed per protocol. Primary endpoints were muscle strength in a selected study muscle and quality of life as measured with the SF-36 questionnaire (SF-36 PCS). Secondary endpoints were 6-minute walk test (6MWT), timed up and go (TUG), muscle strength in muscles not chosen as the study muscle, physical activity scale of the elderly (PASE), visual analogue scale (VAS) for pain, multidimensional fatigue inventory (MFI-20), balance, and sleep quality. Outcome tests were done immediately before the first infusion and 3 months after the second infusion. This study is registered with , number NCT00160082. FINDINGS: Compared with baseline, median muscle strength differed by 8.3% between patients receiving intravenous immunoglobulin and placebo, in favour of the treatment group (p=0.029). SF-36 PCS did not differ significantly between the groups after treatment (p=0.321). Differences in the subscale vitality score (p=0.042) and PASE (p=0.018) favoured the active treatment group. MFI-20, TUG, muscle strength in the muscles not chosen as the study muscle, 6MWT, balance, and sleep quality did not differ between groups. For the whole study population there was no significant change in pain, as determined by VAS. Nevertheless, patients who reported pain at the study start improved in the intervention group but not in the placebo group (p=0.037). Intravenous immunoglobulin was well tolerated. INTERPRETATION: Intravenous immunoglobulin could be a supportive treatment option for subgroups of patients with post-polio syndrome. Further studies on responding subgroups, long-term effects, and dosing schedules are needed.

Effect of intravenous immunoglobulin in patients with post-polio syndrome -- an uncontrolled pilot study.

OBJECTIVE: To analyse changes in muscle strength, physical performance and quality of life during intravenous immunoglobulin (IVIg) treatment in patients with post-polio syndrome. DESIGN: Open clinical trial. PATIENTS: A total of 14 patients (6 women, 8 men; mean age 57 years, range 43-67 years) were included in the study. INTERVENTION: Treatment with 90 g IVIg (30 g daily for 3 days). MAIN OUTCOME: Muscle strength, measured with dynamic dynamometry, muscle function, by means of performing the 6-minute walk test, and quality of life, analysed by means of the SF-36 questionnaire, were performed before and after treatment. RESULTS: For quality of life there was a statistically significant improvement for all but one of the 8 multi-item scales of SF-36 when comparing data before and after treatment with IVIg. The multi-item scale most improved was Vitality. There was no significant increase in muscle strength and physical performance. CONCLUSION: Data indicate that IVIg may have a clinically relevant effect, with an improvement in quality of life. The effect may be due to a decrease in an inflammatory process in the central nervous system, which earlier has been reported in patients with past-polio syndrome after IVIg treatment. Since a possible placebo effect cannot be ruled out, a randomized controlled study is needed.

Aging in polio.

For a disease that was "conquered" some 40 years ago with the onset of effective vaccination, the issues of long-term survivors of paralytic polio as they age continue to present challenges to rehabilitation specialists. Aging with polio is a definition of PPS. There are over a million patients with PPS in the United States. Management has to include the appropriate use of exercises, appropriate bracing and support, and, in the case of bulbar and respiratory symptoms, the appropriate use of speech therapy services and ventilatory support. There are no prospective randomized trials studying the treatment of weakness and fatigue in PPS. Pharmacologic interventions are limited at this time but include anticholinergics for muscle weakness and dopaminergic agents or amantadine to control central fatigue. The pathophysiology of aging with polio is consistent with neuronal loss and denervation lying at the heart of the developing disorder, whereas the central nervous system components of the fatigue syndrome may be related to central changes with neuronal loss in the basal ganglia and reticular-activating system. Many of the survivors of the polio epidemics are in their later retirement years, and their needs will increase as they have other disabilities due to natural aging. Sensitivity to some of the special issues in PPS may help to avoid complications. Polio is an active infection in the third world. Although great strides have been made, the disease is endemic in eight nations and is threatening to spread. The lessons learned in treating PPS now will be useful in years to come as these individuals age and manifest PPS in the future.

[Intravenous immunoglobulin in postpolio syndrome]. / Intravenøst immunglobulin ved postpoliosyndrom.

BACKGROUND: Postpolio syndrome is characterised by new muscular weakness, pain, and fatigue several decades after the acute polio, and affects approximately 1/4 of patients with previous paralytic polio. MATERIAL AND METHODS: A 47-year-old woman with a previous history of acute poliomyelitis developed progressive muscular weakness in her left arm and right leg with muscular pain and fatigue. Clinical examination, MRI, and electromyography gave no other explanation to her progressive muscular weakness and fatigue than postpolio syndrome. She was treated with 400 mg/kg immunoglobulin intravenously for five consecutive days. RESULTS: At follow-up two and three months later, she had a considerable increase in isokinetic muscle strength in knee extension and flexion on the right side, and experienced less fatigue. INTERPRETATION: This case suggests that stabilisation of an autoimmune dysfunction may be a therapeutic option in postpolio syndrome.

Prior poliomyelitis-IVIg treatment reduces proinflammatory cytokine production.

The postpolio syndrome (PPS) is characterized by progressive disabilities decades after recovery from the acute paralytic disease. There are reports on intrathecal inflammatory reactions in PPS, including increased expression of cytokines by cerebrospinal fluid (CSF) mononuclear cells (CSF-MC). This is potentially of relevance for the clinical condition. We here explored if cytokine expression in the CSF of PPS patients could be modulated by high-dose intravenous immunoglobulins (IvIg). The expression of TNF-alpha, IFN-gamma, IL-10 and IL-4 mRNAs was measured by real-time RT-PCR in CSF and peripheral blood mononuclear cells (PBMC) of 16 PPS patients before, and 6-8 weeks after IvIg treatment, and in 26 patients with noninflammatory other neurological diseases (OND). TNF-alpha, IFN-gamma and IL-10 CSF mRNA levels were elevated in samples from untreated persons with PPS compared to OND. Upon IvIg treatment, IFN-gamma and TNF-alpha mRNA levels were dramatically reduced, while IL-10 remained unchanged. Placebo-controlled studies are now warranted to evaluate if IvIg treatment also has any effects on the clinical manifestations of PPS.

GM1 antibodies in post-polio syndrome and previous paralytic polio.

We studied the relationship between post-polio syndrome (PPS) and GM1 antibodies, since such antibodies have been associated with PPS and motor neuron disorders. Sera from 144 patients with previous poliomyelitis (105 paralytic, 22 nonparalytic and 17 PPS), 60 with previous Guillain-Barré syndrome, 44 with amyotrophic lateral sclerosis (ALS) and 22 healthy blood donors were analyzed with ELISA for GM1 IgM, IgG and IgA antibodies. GM1 antibodies were present in 14% of the PPS patients, but the prevalence did not differ significantly from that of the other groups. Our study does not support the hypothesis that GM1 antibodies are involved in the pathogenesis of PPS.

Antineurofilament antibodies in postpolio syndrome.

We determined the levels of antineurofilament antibodies in 29 patients with postpolio syndrome (PPS), 26 stable postpolio (PP) patients, 22 patients with ALS, and 20 normal controls (NCs). Patients with PPS had higher antibody levels to cholinergic neurofilaments than did all other groups. PP patients and those with ALS had antibody levels similar to those of NCs. The antibody binding level showed no relation to the age of the patients, duration of disease, or motor score.

Detection of poliovirus antibodies and poliovirus genome in patients with the post-polio syndrome.

To investigate the role of poliovirus (PV) infection in the development of the post-polio syndrome (PPS), we studied the serum, spinal fluid, peripheral blood lymphocytes, and muscle from 47 patients with PPS. We found high titers of IgM PV antibodies (up to 1:250) in the serum of 6 patients, compared to very low titers (less than 1:50) in normal subjects or disease controls. By polymerase chain reaction, using primers of the replicase PV gene, we amplified PV sequences in the peripheral blood lymphocytes in 7 of 37 patients and in the CSF in 4 of 40 patients, but in none of the controls. Sequencing of the amplified product confirmed that it belonged to PV type 1 with a 99.3% homology. We conclude that some patients with PPS have in the serum high titers of IgM anti-PV antibodies, implying an ongoing antibody response to a viral antigen. The presence of PV-RNA in the CSF or lymphocytes suggests possible persistence of mutated virus or defective PV particles. The significance of these findings in the pathogenesis of PPS remains to be determined.