Henrik Gonzalez

Management of postpolio syndrome.

Postpolio syndrome is characterised by the exacerbation of existing or new health problems, most often muscle weakness and fatigability, general fatigue, and pain, after a period of stability subsequent to acute polio infection. Diagnosis is based on the presence of a lower motor neuron disorder that is supported by neurophysiological findings, with exclusion of other disorders as causes of the new symptoms. The muscle-related effects of postpolio syndrome are possibly associated with an ongoing process of denervation and reinnervation, reaching a point at which denervation is no longer compensated for by reinnervation. The cause of this denervation is unknown, but an inflammatory process is possible. Rehabilitation in patients with postpolio syndrome should take a multiprofessional and multidisciplinary approach, with an emphasis on physiotherapy, including enhanced or individually modified physical activity, and muscle training. Patients with postpolio syndrome should be advised to avoid both inactivity and overuse of weak muscles. Evaluation of the need for orthoses and assistive devices is often required.

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 Seven patients were withdrawn from the study.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.

Prior poliomyelitis-evidence of cytokine production in the central nervous system

In order to study the role of a possible inflammatory reaction in the post-polio syndrome (PPS) four key cytokines were determined by means of mRNA expression in mononuclear cells from cerebrospinal fluid (CSF) and peripheral blood of 13 patients. Data were compared with those of samples from eight non-inflammatory control persons. The PPS-patients displayed increased 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), in comparison to the non-inflammatory controls. As positive controls, samples from patients with Multiple Sclerosis (MS) were examined. We conclude that there is a chronic intra CNS expression of inflammatory cytokines in PPS, in the range of that in MS, a well known neuroinflammatory disease. However, the pathogenic significance of this is unclear.

Identification of novel candidate protein biomarkers for the post-polio syndrome - implications for diagnosis, neurodegeneration and neuroinflammation.

Survivors of poliomyelitis often develop increased or new symptoms decades after the acute infection, a condition known as post-polio syndrome (PPS). The condition affects 20-60% of previous polio patients, making it one of the most common causes of neurological deficits worldwide. The underlying pathogenesis is not fully understood and accurate diagnosis is not feasible. Herein we investigated whether it was possible to identify proteomic profile aberrations in the cerebrospinal fluid (CSF) of PPS patients. CSF from 15 patients with well-defined PPS were analyzed for protein expression profiles. The results were compared to data obtained from nine healthy controls and 34 patients with other non-inflammatory diseases which served as negative controls. In addition, 17 samples from persons with secondary progressive multiple sclerosis (SPMS) were added as relevant age-matched references for the PPS samples. The CSF of persons with PPS 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, respectively, in comparison with the control groups. An independent ELISA confirmed the increase of kallikrein 6. We suggest that these five proteins should be further evaluated as candidate biomarkers for the diagnosis and development of new therapies for PPS patients.

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.

Intravenous immunoglobulin treatment of the post-polio syndrome: sustained effects on quality of life variables and cytokine expression after one year follow up.

BackgroundExpression of inflammatory cytokines in cerebrospinal fluid (CSF) has led to the hypothesis of intrathecal chronic inflammation to explain the denervation observed in post-polio syndrome (PPS). It has been shown that therapy with intravenous immunoglobulin (IVIG) improves physical performance and dampens down the inflammatory process at 6 months in PPS patients. We here examined the effects of IVIG on cytokine expression and clinical outcome one year after IVIG treatment.MethodsFrom a previous study with 135 PPS patients included, 41 patients were further evaluated before un-blinding for one year (21 placebo and 20 treated with IVIG, Xepol® 50 mg/ml), and were assessed for clinical variables by performing the Short Form-36 survey (SF-36) questionnaire assessment, the 6 minute walk distance test (6MWT) and registering pain level by Visual Analogue Scale (VAS) after IVIG treatment. A separate cohort of 37 PPS patients went through lumbar puncture (LP) at baseline and 20 patients, treated with IVIG, repeated the LP one year later. Thirty patients affected with other neurological diseases (OND) were used as control group. Inflammatory cytokines TNF, TGFβ, IFNγ, IL-23, IL-13 and IL-10 were measured in blood cells and CSF cells with RT-PCR.ResultsScores of the physical components of SF-36 were significantly higher at the one year follow up time-point in the IVIG-treated patients when compared to baseline as well as to the control subjects. Pain VAS score and 6MWT improved significantly in the IVIG-treated patients when compared with baseline Relative expression of TNF and IFN-γ in both PBMCs and CSF from PPS patients were increased compared to OND subjects at baseline (p < 0.05). One year after IVIG-treatment a decreased expression of IFN-γ and IL23 was found in CSF of PPS patients, while anti-inflammatory IL-13 was increased (p < 0.05).ConclusionsIVIG has effects on relevant QoL variables and inflammatory cytokines up to one year in patients with PPS. This gives a basis for scheduling IVIG in upcoming trials with this therapy.

Quality of life in Swedish patients with post-polio syndrome with a focus on age and sex.

To investigate the health-related quality of life (QOL) in Swedish patients with post-polio syndrome (PPS), with a focus on sex and age. A total of 364 patients were recruited from five Swedish post-polio clinics. Analysis was carried out using SF-36 and data were compared with those of a normal population. QOL was significantly lower in PPS patients for all eight subdomains and the two main scores (physical compound score and mental compound score) when compared with the controls. Male patients had a significantly higher QOL than female patients for all subdomains and also for mental compound score and physical compound score, a phenomenon also observed in the normal population. There was a decrease in QOL in the physical domains and an increase in vitality with age. PPS decreases health-related QOL in both sexes, more in female patients. QOL for physical domains decreases whereas vitality increases with age in both sexes.