The post-polio syndrome : studies of immunology and immunomodulatory intervention

Abstract

Late effects in patients with prior poliomyelitis were first reported in the nineteenth century and have been referred to as the post-polio syndrome (PPS). PPS is characterized by new muscular deterioration, fatigue and pain after a stable period of at least 15 years.

In order to study the pathophysiological role of a possible inflammatory reaction in PPS, four key cytokines were determined with mRNA expression in mononuclear cells from cerebrospinal fluid (CSF) and peripheral blood (PB) of 13 patients. The PPS patients displayed greater numbers of CSF cells expressing mRNA for TNF-alpha (p<0.02), IFN-gamma (p< 0.02), IL-4 (p<0.001) and IL-10 (p<0.05), compared to eight controls with other neurological disorders (OND). The level of increase was in the same range as found in seven control patients with multiple sclerosis (MS). There was no cytokine increase in PB. The increase of cytokines in the CSF indicates an inflammatory process in the CNS of PPS patients.

To explore whether the inflammatory process could be down-modulated, 16 patients were treated with high-dose (90g) intravenous immunoglobulins (IVIG). The increase of TNF-alpha, IFN-gamma, IL-10 and IL-4 mRNAs in CSF was reproduced with TaqMan RT-PCR. In PB TNF-alpha was significantly increased. Six–8 weeks after treatment TNF-alpha and IFN-gamma mRNA levels were significantly reduced, while IL-10 remained unchanged.

To analyze whether down-modulation of the inflammatory process was accompanied by changes of muscle strength, walking performance and Quality of Life, an open clinical trial including 14 PPS patients was performed. Regarding Quality of Life there was a statistically significant improvement for seven of eight subscales of the SF-36, most obvious in vitality. A trend towards an increase in muscle strength and function was found in the PPS patients when comparing data before and after IVIG treatment.

To further study the clinical effect of IVIG, a randomized double-blinded placebo-controlled study was performed. One hundred forty-two patients were randomly chosen to receive infusion of either 90 g IVIG or placebo, over three consecutive days, which was repeated after three months.

Average muscle strength was increased by 4.3% over baseline in patients receiving IVIG, while the placebo group displayed a 5.8 % decrease ( p=0.029). Five of eight subscales of the SF 36 improved significantly over baseline in the IVIG group, but none in the placebo group. Two subscales, vitality and general health, revealed a significantly better outcome in favor of IVIG (p=0.042 and p=0.048, respectively). The Physical Activity Scale of the Elderly ( PASE) was improved in the IVIG group compared to the placebo group (p=0.018). Patients reporting pain on the VAS scale improved in the IVIG group, but not in the placebo group (p=0.037).

It is concluded that there is an increase of cells expressing cytokines in the CSF of PPS patients corresponding to that in MS, a well-known neuroinflammatory disease. This indicates an inflammatory process in the CNS. IVIG treatment leads to a decrease of the inflammatory process which is then followed by an increase of muscle strength and physical activity as well as improved Quality of Life and decrease of pain over six months. This finding may open the way for new therapeutic strategies in the post-polio syndrome.