Treatment with L-Citrulline in patients with post-polio syndrome: A single center, randomized, double blind, placebo-controlled trial.

This single-centered, randomized, double-blind, placebo-controlled study reports the results of L-Citrulline treatment for 24 weeks in patients with post-polio syndrome (PPS). Twenty-nine patients were randomized and assigned into receiving a treatment of 15 g L-Citrulline or placebo. The primary endpoint was the change of the 6 min walking distance test. Secondary endpoints included motor function measure, quantitative muscle strength, quantitative MRI and self-reported impairment questionnaires. Patients receiving L-Citrulline walked 17.5 longer in the 6 min walking distance test when compared to placebo group, however not statistically significant (95% CI = -14.69; 49.68, p = 0.298). None of the secondary endpoints showed a statistically significant change in the L-Citrulline group when compared to placebo group. The motor function measure showed a change of -0.78 (95% CI= [-3.39; 1.83] p = 0.563). Muscle degeneration of leg muscles assessed with quantitative MRI indicated no significant change (estimate= -0.01, 95% CI =-0.13; 0.11, p = 0.869). L-Citrulline was safe and well tolerated. In conclusion, administration of 15 g L-Citrulline daily for 24 weeks to patients with PPS showed no beneficial treatment effect in timed muscle function.

Effectiveness of Intravenous Immunoglobulin for Management of Pain in Patients with Postpolio Syndrome.

Objective: Many patients with postpolio syndrome (PPS) experience pain. In this study, we aimed to review previous studies to investigate the effectiveness of intravenous immunoglobulin (IVIG) for managing pain in patients with PPS. We performed a narrative review. Methods: In PubMed, we searched for the keywords ((Immunoglobulin OR IVIG) AND (poliomyelitis OR poliomyelitis syndrome)). We included articles in which IVIG was infused in patients with PPS and pain severity was measured before and after treatment. Results: In the results, five articles (4 randomized controlled trials and 1 prospective observational study) were included in this review. Four of the studies reported that IVIG had a positive pain-reducing effect in patients with PPS. In addition, 4 studies evaluated the outcomes related to muscle strength and function. Of these studies, 3 showed some improvement in measurements for muscle strength and function. Conclusion: In conclusion, IVIG might be one of the beneficial options for managing pain in PPS. Pain reduction might be responsible for the improvement of muscle strength or function. To confirm the benefits of IVIG in reducing pain, more high-quality studies are required.

Relationship of depression and medications on incidence of falls among people with late effects of polio.

The purpose of this study was to determine if falls in polio survivors, with or without post-polio syndrome (PPS), are related to number of medications taken, use of anti-depressant or psychoactive medications, or self-report of depression. A survey was sent to 300 members of a regional polio support group, asking them to document their fall history, medications used, and the presence of depression. Depression was measured by self-report and with the Geriatric Depression Scale, short form (GDS-15). One hundred and seventy-two usable surveys were returned with 146 of those completing the medication list. Sixty-two percent reported at least one fall in the past year. The multiple logistic regression was significant (p = 0.023), and it indicated depression to be a significant predictor (p = 0.012) of falls in polio survivors with and without PPS. The number of total medications or anti-depressant or psychoactive medications used was not related to fall incidence. Routine screening and treatment for depression may be one aspect of fall prevention which can be implemented through primary care.

Treatment with L-citrulline in patients with post-polio syndrome: study protocol for a single-center, randomised, placebo-controlled, double-blind trial.

BACKGROUND: Post-polio syndrome (PPS) is a condition that affects polio survivors years after recovery from an initial acute infection by the Poliomyelitis virus. Most often, patients who suffered from polio start to experience gradual new weakening in muscles, a gradual decrease in the size of muscles (muscle atrophy) and fatigue years after the acute illness. L-citrulline is known to change muscular metabolism synthesis by raising nitric oxide (NO) levels and increasing protein synthesis. This investigator-initiated, randomised, placebo-controlled, double-blind, trial aims to demonstrate that L-citrulline positively influences muscle function and increases muscular energy production in patients with PPS. METHODS/DESIGN: Thirty ambulant PPS patients will be recruited in Switzerland. Patients will be randomly allocated to one of the two arms of the study (placebo:verum 1:1). After a 24-week run-in phase to observe natural disease history and progression, participants will be treated either with L-citrulline or placebo for 24 weeks. The primary endpoint is change in the 6-min Walking Distance Test. Secondary endpoints will include motor function measure, quantitative muscle force, quantitative muscle magnetic resonance imaging and magnetic resonance spectroscopy and serum biomarker laboratory analysis DISCUSSION: The aim of this phase IIa trial is to determine if treatment with L-citrulline shows a positive effect on clinical function and paraclinical biomarkers in PPS. If treatment with L-citrulline shows positive effects, this might represent a cost-efficient symptomatic therapy for PPS patients. TRIAL REGISTRATION: ClinicalTrial.gov, ID: NCT02801071 . Registered on 6 June 2016.

Intrathecal Analgesic Drug Delivery is Effective for Analgesia in a Patient with Post-Poliomyelitis Syndrome: A Case Report.

BACKGROUND Post-poliomyelitis syndrome (PPS) is a progressive neuromuscular syndrome, with chronic pain being one of the most prevalent symptoms. We present a case report on intrathecal analgesic drug delivery to diminish chro-nic, refractory pain in a patient with PPS. CASE REPORT In a wheelchair-bound 45-year-old female patient (Caucasian, body mass index [BMI] 20.5) with severe chronic, refractory pain, a Synchromed® II pump (Medtronic, Minneapolis, Minnesota, USA) was implanted after multidisciplinary consultation and a successful trial period. After 8 months, relocation of the pump due to regional pressure problems with surrounding erythema had to occur. A second pump relocation due to pressure pro-blems and skin erosion was needed 18 months after the first relocation, moving from the abdominal wall to the sheath of the rectus abdominis muscle, resulting in resolution of the problems. CONCLUSIONS In patients with PPS, intrathecal analgesic drug delivery can be an option to treat chronic, refractory pain. Multidisciplinary consultation is necessary to deal with the wide variety of problems in these patients. Skin problems at the site of the pump reservoir can be challenging and time-consuming and, ultimately, can necessitate relocation (or removal) of the device.

Immunoglobulin treatment in post-polio syndrome: Identification of responders and non-responders.

OBJECTIVE: To define and characterize responders and non-responders in a group of 124 patients with post-polio syndrome who received a single treatment with intravenous immunoglobulin. DESIGN: Open trial, prospective follow-up study. METHODS: Clinical examination and data from medical records. Short Form 36 (SF-36), Physical Activity Scale for the Elderly (PASE) and visual analogue scale (VAS) measured quality of life, physical activity and intensity of pain, respectively. Data were obtained before treatment and at 6-month follow-up. RESULTS: Two responder groups were identified with the outcome SF-36 Vitality and 3 with Bodily pain, respectively. Forty-five percent were positive-responders, identified before treatment by reduced physical function, muscle atrophy in the lower extremities, higher levels of fatigue and pain, and a VAS pain score above 20. Negative-responders were identified by good physical function and mental health, lesser muscle atrophy in the lower extremities, and low levels of fatigue and pain. CONCLUSION: Intravenous immunoglobulin is a biological intervention, and therefore it is important to be able to identify responders and non-responders. In order to maximize a positive outcome it is suggested that patients with a high level of fatigue and/or pain and reduced physical function are selected.

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 postpolio syndrome: a systematic review and meta-analysis.

BACKGROUND: Postpolio syndrome (PPS) is characterized by progressive disabilities that develop decades after prior paralytic poliomyelitis. Because chronic inflammation may be the process underlying the development of PPS, immunomodulatory management, such as intravenous immunoglobulin (IVIg) administration, may be beneficial. METHODS: We performed a systematic review and meta-analysis of published randomized controlled trials (RCTs) and prospective studies that evaluated the efficacy of IVIg in managing PPS. Electronic databases, including PubMed, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials, were searched for articles on PPS published before December 2014. The primary outcomes were pain severity, fatigue scores, and muscle strength. The secondary outcomes were physical performance, quality of life (QoL), and cytokine expression levels. RESULTS: We identified 3 RCTs involving 241 patients and 5 prospective studies involving 267 patients. The meta-analysis of pain severity (weighted mean difference [WMD] = -1.02, 95% confidence interval [CI] = -2.51 to 0.47), fatigue scores (WMD = 0.28, 95% CI -0.56 to 1.12), and muscle strength revealed no significant differences between the IVIg and the placebo group. Regarding QoL, the RCTs yielded controversial outcomes, with improvement in only certain domains of the Short Form 36 (SF-36). Moreover, one prospective study reported significant improvement on SF-36, particularly in patients aged younger than 65 years, those with paresis of the lower limbs, and high pain intensity. CONCLUSION: The present review indicated that IVIg is unlikely to produce significant improvements in pain, fatigue, or muscle strength. Thus, routinely administering IVIg to patients with PPS is not recommended based on RCTs. However, a potential effect in younger patients with lower limbs weakness and intense pain requires confirmation from further well-structured trials.

[Polio, late effects and post-polio].

Approximately 7,000 Danes are still living with sequelae after surviving an acute polio infection. Late effects of polio include deformities, arthrosis and overloaded muscles. In the long run polio patients are at risk of having a further decrease of muscle function and a wide variety of other symptoms, a condition called post-polio syndrome (PPS). Treatment of PPS is in general symptomatic. Recently it has been shown that treatment with intravenous immunoglobulin may have an effect on pain, tiredness and walking distance. Patients with prior polio have an increase in morbidity and mortality, and may be more sensitive to a variety of medicine.

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

BACKGROUND: Expression 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. METHODS: From 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, TGFß, IFNγ, IL-23, IL-13 and IL-10 were measured in blood cells and CSF cells with RT-PCR. RESULTS: Scores 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). CONCLUSIONS: IVIG 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.

IVIG treatment in post-polio patients: evaluation of responders.

The aim of this work is to evaluate the outcome of IVIG treatment in patients with post-polio syndrome (PPS) and to identify responders. The study included 113 PPS patients who had received one IVIG treatment in an open trial, prospective follow-up study. Clinical examination was performed and clinical data were retrieved from medical records. The short form 36 (SF-36), physical activity scale for the elderly (PASE), and the visual analogue scale (VAS) were used as measurements of quality of life, physical activity, and the intensity of pain. Data before treatment and at 6-month follow-up were collected. Analysis was performed in subgroups based on demographic and medical parameters. A statistically significant increase of the SF-36 sub domains bodily pain, vitality, social function, role emotional, and the mental compound score (MCS) was found at the 6-month follow-up. A significant decrease of pain was found in patients who reported pain intensity over VAS of 20 mm, in patients younger than 65 years of age and in patients who had paresis in the lower extremities. A trend was found in patients with PPS as the only diagnosis. IVIG leads to increase of quality of life at 6-month follow-up for SF-36 regarding sub domains of bodily pain, vitality, social function, role emotional, as well as for pain. Age below 65 years, paresis in the lower extremities, and lack of concomitant disorders may be the main indicators for a future identification of responders.

Effect of intravenous immunoglobulin on pain in patients with post-polio syndrome.

OBJECTIVE: Pain is a common symptom that affects quality of life in patients with post-polio syndrome. An increase in cytokine in the cerebrospinal fluid suggests that inflammation is pathophysiologically important in post-polio syndrome. Intravenous immunoglobulin might therefore be a therapeutic option. The aim of this study was to analyse the effect of intravenous immunoglobulin treatment on pain in post-polio syndrome. METHODS: An uncontrolled clinical study. Patients with post-polio syndrome and pain (n = 45) underwent a neurological examination and were interviewed about pain before and 6 months after treatment with intravenous immunoglobulin. Pain intensity was measured on a visual analogue scale. The pain was classified according to the International Association for the Study of Pain criteria as neuropathic when it occurred in an area with decreased sensibility, or nociceptive when signs of inflammation and/or painful joints movements were present. RESULTS: After treatment 31/45 (69%) patients were improved, with a mean visual analogue scale decrease from 53 to 42 (p = 0.001). Eighteen patients (40%) had a decrease of 20 or more points on the visual analogue scale. The effect of treatment did not differ regarding age, gender and severity of disability. CONCLUSION: Two-thirds of 45 patients with post-polio syndrome and pain reported a decrease on the visual analogue scale for pain after treatment with intravenous immunoglobulin, and 40% reported a decrease of 20 or more points on the visual analogue scale.

Treatment for postpolio syndrome.

BACKGROUND: Postpolio syndrome (PPS) may affect survivors of paralytic poliomyelitis and is characterised by a complex of neuromuscular symptoms leading to a decline in physical functioning. The effectiveness of pharmacological treatment and rehabilitation management in PPS is not yet established. OBJECTIVES: To review systematically the effects of any treatment for PPS compared to placebo, usual care or no treatment.   SEARCH STRATEGY: We searched the following databases on 1 October 2010: Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO and CINAHL Plus from inception to September 2010. SELECTION CRITERIA: Randomised and quasi-randomised trials of any form of pharmacological or non-pharmacological treatment for people with PPS. The primary outcome was self-perceived activity limitations and secondary outcomes were muscle strength, muscle endurance, fatigue, pain and adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently selected eligible studies, assessed risk of bias and extracted data. MAIN RESULTS: Nine pharmacological (modafinil, intravenous immunoglobulin, pyridostigmine, lamotrigine, amantadine, prednisone) and three non-pharmacological (muscle strengthening, rehabilitation in a warm climate (i.e. temperature ± 25°C, dry and sunny) and a cold climate (i.e. temperature ± 0°C, rainy or snowy), static magnetic fields) studies were included in this review. None of the included studies was completely free from any risk of bias and the most prevalent risk of bias was lack of blinding.There is moderate quality evidence that intravenous immunoglobulin has no beneficial effect on activity limitations and there is inconsistency in the evidence for effectiveness on muscle strength and pain. Results of one trial provide very low quality evidence that lamotrigine might be effective in reducing pain and fatigue, resulting in fewer activity limitations. Data from two single trials suggest that muscle strengthening of thumb muscles (very low quality evidence) and static magnetic fields (moderate quality evidence) are beneficial for improving muscle strength and pain, respectively, with unknown effects on activity limitations. Finally, there is evidence varying from very low quality to high quality that modafinil, pyridostigmine, amantadine, prednisone and rehabilitation in a warm or cold climate are not beneficial in PPS. AUTHORS' CONCLUSIONS: Due to insufficient good quality data and lack of randomised studies it is impossible to draw definite conclusions on the effectiveness of interventions for PPS. Results indicate that IVIG, lamotrigine, muscle strengthening exercises and static magnetic fields may be beneficial but need further investigation.

Response of postpoliomyelitis patients to bisphosphonate treatment.

OBJECTIVE: To evaluate (1) the rate of change of bone mineral density (BMD) at the hip in postpolio patients treated with bisphosphonates compared with the rate of change in BMD in (a) postpolio patients not treated with bisphosphonates and (b) non-postpolio patients treated with bisphosphonates; and (2) to compare the fracture rate in postpolio patients before and after treatment. DESIGN: Retrospective chart review. SETTING: University-affiliated hospital postpolio clinic and bone metabolism clinic. PARTICIPANTS: Patients with at least 2 BMD assessments. We included 144 postpolio patients and 112 non-postpolio patients. For the fracture analysis, 32 postpolio patients with a history of fractures and treatment with bisphosphonates were included. METHODS: The effect of treatment on BMD in postpolio patients was analyzed with use of a multiple linear regression model and a mixed effects model, with the rate of change in hip BMD and the change in BMD from baseline, respectively, as the dependent variables. The effect of treatment on occurrence of fractures in postpolio patients was analyzed with use of conditional logistic regression and Poisson regression. MAIN OUTCOME MEASURES: BMD measurements at the femoral neck (g/cm²) and occurrence of fractures before and after initiation of treatment. RESULTS: In an adjusted model, postpolio patients treated with bisphosphonates (54/144) had a greater rate of change in BMD (0.031 g/cm²/year; 95% confidence interval 0.010-0.052) compared with nontreated postpolio patients. The effect of treatment in postpolio patients was similar to that in non-postpolio patients. Evidence indicated that treated postpolio patients have a lower risk of fracture after treatment (odds ratio 0.3, P = .046; rate ratio 0.4, P = .183). CONCLUSIONS: In this retrospective study, it was found that treatment with oral bisphosphonates significantly increases BMD at the hip in postpolio patients. The effect of bisphosphonate treatment appears to be similar in postpolio patients compared with a control group without polio. Treatment with bisphosphonates may have a protective effect on fracture risk in this population.

Post-polio syndrome: Pathophysiological hypotheses, diagnosis criteria, drug therapy.

Post-polio syndrome (PPS) refers to a clinical disorder affecting polio survivors with sequelae years after the initial polio attack. These patients report new musculoskeletal symptoms, loss of muscular strength or endurance. PPS patients are tired, in pain and experience new and unusual muscular deficits, on healthy muscles as well as deficient muscles initially affected by the Poliovirus. Once a clinical diagnosis is established, the therapeutic options can be discussed. Some pathophysiological mechanisms have been validated by research studies on PPS (inflammatory process in cerebrospinal fluid [CSF] and cytokines of the immune system). Several studies have been conducted to validate medications (pyridostigmine, immunoglobulin, coenzyme Q10) or physical exercises protocols. This article focuses on the relevance and efficacy that can be expected from these therapeutics. Very few studies reported some improvements. Medications combined to individual and supervised exercise training programs are promising therapeutic strategies for PPS patients care management.

Post-polio syndrome patients treated with intravenous immunoglobulin: a double-blinded randomized controlled pilot study.

Post-polio syndrome (PPS) is characterized by new muscle weakness, atrophy, fatigue and pain developing several years after the acute polio. Some studies suggest an ongoing inflammation in the spinal cord in these patients. From this perspective, intravenous immunoglobulin (IvIg) could be a therapeutic option. We performed a double-blinded randomized controlled pilot study with 20 patients to investigate the possible clinical effects of IvIg in PPS. Twenty patients were randomized to either IvIg 2 g/kg body weight or placebo. Primary endpoints were changes in pain, fatigue and muscle strength 3 months after treatment. Surrogate endpoints were changes in cerebrospinal fluid (CSF) cytokine levels. Secondary endpoints were pain, fatigue and isometric muscle strength after 6 months. Patients receiving IvIg reported a significant improvement in pain during the first 3 months, but no change was noted for subjective fatigue and muscle strength. CSF levels of tumour necrosis factor-alpha (TNF-alpha) were increased compared with patients with non-inflammatory neurological disorders. In conclusion, in this small pilot study no effect was seen with IvIg treatment on muscle strength and fatigue, however IvIg treated PPS patients reported significantly less pain 3 months after treatment. TNF-alpha was increased in the CSF from PPS patients. The results are promising, but not conclusive because of the low number of patients studied.

Randomized controlled trial of modafinil for the treatment of fatigue in postpolio patients.

The purpose of this study was to test whether modafinil is effective in alleviating the symptoms of fatigue in postpolio patients, because it has been helpful for such symptoms in other neurologic disorders. Using a double-blind, randomized, placebo-controlled cross-over design, 14 postpolio patients with moderate to severe fatigue were assigned to receive modafinil or placebo first. Piper Fatigue Scale, Epworth Sleepiness Scale, digit span, and reaction time tests were done at baseline and then at weekly intervals. The Piper Fatigue Scale scores improved by 27 +/- 40% (mean +/- SD) following modafinil and by 43 +/- 36% following placebo. Scores for most of the other tests did not change during the study. Therefore, we conclude that modafinil was not effective in alleviating the symptoms of fatigue in postpolio patients.

Successful treatment of a postpolio tinnitus with type a botulinum toxin.

OBJECTIVES/HYPOTHESIS: Objective tinnitus is a symptom often observed in patients with chronic hyperactivity of masticatory muscles. METHODS: We report here the unusual case of a 63-year-old woman who developed a distressing tinnitus related to contractions of reinnervated masticatory muscles. This reinnervation process was caused by a postpolio syndrome that gave rise to an acoustic resonance phenomenon transmitted to the middle ear as an audible sound. RESULTS: The tinnitus was successfully treated with electromyography-guided intramuscular injections of type A botulinum toxin. CONCLUSION: The intramuscular injection of botulinum toxin was found to be effective in relieving severe and disabling postpolio tinnitus.

Effects of lamotrigine on the symptoms and life qualities of patients with post polio syndrome: a randomized, controlled study.

The aim of this study is to find out if lamotrigine gives symptomatic relief and enhances quality of life in patients with post-polio syndrome. Thirty patients were randomly assigned to receive or not to receive lamotrigine treatment. Lamotrigine at a daily dose of 50-100 mg was given to the fifteen patients, and fifteen patients were used as the control group. Interventional advice and home exercises were given to all of the patients. Clinical assessments were made at baseline and repeated at the second and fourth weeks by the physician who was unaware of medication. The severity of pain, fatigue and muscle cramps were rated on a visual analogue scale. Health-related quality of life was measured using the Nottingham Health Profile. The patient's perceived level of fatigue was assessed using Fatigue Severity Scale. Comparing to the baseline values, statistically significant improvements were obtained in the mean scores of VAS, NHP and FSS at two weeks and four weeks in the patients on lamotrigine. No significant improvements were reported in the control group. These preliminary results indicate that lamotrigine relieves the symptoms and improves the life qualities of patients with post polio syndrome.