Title: Response of postpoliomyelitis patients to bisphosphonate treatment
Author: Alvarez A (1), Kremer R, Weiss DR, Benedetti A, Haziza M, Trojan DA
Affiliation: (1) Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University Health Centre, McGill University, Montreal, QC, Canada
Journal: PM&R: The Journal of Injury, Function, and Rehabilitation
Citation: PM R. 2010 Dec;2(12):1094-103. doi: 10.1016/j.pmrj.2010.08.009.
Publication Year and Month: 2010 12

Abstract: 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.

Outcome of Research: Effective

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Title: An Open Trial of Pyridostigmine in Post-poliomyelitis Syndrome
Author: Daria A. Trojan and Neil R. Cashman


Affiliation: From the Department of Neurology, Montreal Neurological Institute and Hospital, McGill University, Montreal.
Journal:
Citation: The Canadian Journal of Neurological Sciences Volume 22, No. 3 August 1995 223-227
Publication Year and Month: 1995 08

Abstract: Background: One of the major symptoms of postpoliomyelitis syndrome (PPS) is disabling generalized fatigue. Subjects with PPS also report muscle fatiguability and display electrophysiologic evidence of anticholinesterase-responsive neuromuscular junction transmission defects, suggesting that anticholinesterase therapy may be useful in the management of disabling fatigue. Methods: We initiated an open trial of the oral anticholinesterase pyridostigmine, up to 180 mg per day, in 27 PPS patients with generalized fatigue and muscle fatiguability. Response to Pyridostigmine was assessed with the Hare fatigue scale, the modified Barthel index for activities of daily living, and a modified Klingman mobility index. Results: Two patients could not tolerate the medication. After one month of therapy, 16 patients (64%) reported a reduction in fatigue on the Hare fatigue scale; three of 16 showed improvement on the modified Barthel index for activities of daily living, and two of 16 experienced improvement on a modified Klingman mobility index. Pyridostigmine responders were significantly more fatigued than non-responders on the pre-treatment Hare score, but were not significantly different with regard to age, sex, age at acute poliomyelitis, or severity of acute poliomyelitis. Conclusions: Pyridostigmine may be useful in the management of fatigue in selected patients with PPS. Response to pyridostigmine may be predicted by severity of pre-treatment fatigue.

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Outcome of Research: Not applicable

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Title: Anticholinesterases in Post-Poliomyelitis Syndrome
Author: Daria A. Trojan and Neil R. Cashman
Affiliation: Department of Neurology, Montreal Neurological Institute and Hospital, McGill University
Journal: Annals of the New York Academy of Sciences
Citation: Reprinted from The Post-Polio Syndrome: Advances in the Pathogenesis and Treatment, Volume 753 of the Annals of the New York Academy of Sciences, May 25, 1995
Publication Year and Month: 1995 05

Abstract: New weakness, fatigue, and pain after decades of functional stability in those who have recovered from acute paralytic poliomyelitis constitutes post-poliomyelitis syndrome (PPS).[1-7] The cause of PPS is unknown, but it is thought to be due to a distal degeneration of enlarged post-polio motor units produced by terminal axonal sprouting during the recovery process after acute polio.[8,9] The symptoms of weakness and fatigue may be a direct result of this distal motor unit degeneration;[2,7-13] however, it is presently unclear how pain relates to disease of the motor unit. PPS is a slowly progressive motor neuron disease for which there is currently no specific treatment.[4]

Conclusions: Our studies indicate that a proportion of fatigued post-poliomyelitis patients can experience an amelioration of defects in neuromuscular junction transmission and of clinical fatigue with anticholinesterases. Because S-SFEMG response was significantly associated with clinical response to anticholinesterases, fatigue in PPS may be caused by defects in neuromuscular junction transmission in a proportion of patients. Preliminary studies in a small group of patients indicate that anticholinesterases may produce their clinical neuromuscular response by producing an increase in isokinetic strength in a proportion of patients. Our studies provide a physiological rationale for the use of anticholinesterases in PPS for the symptom of fatigue. However, further randomized, placebo-controlled, double-blinded trials are needed to establish definitively the benefits and risks of these agents.

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Title: Anticholinesterase-responsive neuromuscular junction transmission defects in post-poliomyelitis fatigue
Author: Daria A. Trojan, Daniel Gendron and Neil R. Cashman
Affiliation: Department of Neurology, McGill University, Montreal Neurological Institute and Hospital
Journal: Journal of the Neurological Sciences
Citation: 114 (1993) 170-177
Publication Year and Month: 1992 08

Abstract: Disabling generalized fatigue and muscle fatiguability are common features of post-poliomyelitis syndrome (PPS). In 17 fatigued PPS patients, we measured jitter on stimulation single-fiber electromyography (S-SFEMG) for at least 3.5 min before and after i.v. injection of 10 mg edrophonium. We observed reduction in jitter (defined as a significant difference in jitter means before and after edrophonium, unpaired t-test P < 0.05) in 7 patients, no change in 8, and a significant increase in 2 patients. Blinded to their edrophonium results, the 17 patients were treated with pyridostigmine 180 mg/day for 1 month, with a subjective improvement of fatigue in 9 patients, and with a significant reduction in mean Hare fatigue scores in the entire group of 17 patients (pre = 2.71, and post = 1.71; Wilcoxan signed rank sum test, P < 0.05). Edrophonium-induced reduction of jitter on S-SFEMG was significantly associated with pyridostigmine-induced subjective improvement of fatigue (Fisher's exact test, P < 0.04). A significant reduction in fatigue with pyridostigmine was observed only in the 7 patients who experienced a significant reduction in jitter with edrophonium (Wilcoxan signed rank sum test, P = 0.03). In addition, the 9 pyridostigmine responders experienced a significant reduction in jitter means pre- and post-edrophonium (100% vs. 88%, Bonferroni corrected, P < 0.01). We conclude that neuromuscular transmission as measured by jitter on S-SFEMG can improve with edrophonium in a proportion of PPS patients, and that generalized fatigue and muscle fatiguability in some patients with PPS may be due to anticholinesterase-responsive NMJ transmission defects.

Conclusions:

Outcome of Research: Not applicable

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Title: Intravenous immunoglobulin treatment of the post-polio syndrome: sustained effects on quality of life variables and cytokine expression after one year follow up
Author: Gonzalez H (1), Khademi M (2), Borg K (1), Olsson T (2)
Affiliation: (1) Division of Rehabilitation Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, blg 39, fl 3, S-192 88, Stockholm, Sweden; (2) Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
Journal: Journal of Neuroinflammation
Citation: Journal of Neuroinflammation. 2012; 9: 167. doi: 10.1186/1742-2094-9-167
Publication Year and Month: 2012 07

Abstract: 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, TGFβ, 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.

Outcome of Research: More research required.

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Title: Prior poliomyelitis – IVIg treatment reduces proinflammatory cytokine production
Author: Gonzalez H, Khademi M, Andersson M, Piehl F, Wallström E, Borg K, Olsson T
Affiliation: Department of Neuroimmunology Unit, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden – [email protected]
Journal: Journal of Neuroimmunology
Citation: J Neuroimmunol. 2004 May; 150(1-2):139-44
Publication Year and Month: 2004 05

Abstract: 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.

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Title: Pyridostigmine in postpolio syndrome: no decline in fatigue and limited functional improvement
Author: Horemans H (1), Nollet F (1), Beelen A (1), Drost G (2), Stegeman D (2), Zwarts M (2), Bussmann J (3), de Visser M (4), Lankhorst G (1)
Affiliation: (1) Department of Rehabilitation Medicine, VU University Medical Centre, Amsterdam, Netherlands; (2) Department of Clinical Neurophysiology, University Medical Centre Nijmegen, Netherlands; (3) Department of Rehabilitation Medicine, Erasmus MC, University Medical Centre Rotterdam, Netherlands; (4) Department of Neurology, Academic Medical Centre, University of Amsterdam, Netherlands
Journal: Journal of Neurology, Neurosurgery and Psychiatry
Citation: J Neurol Neurosurg Psychiatry 2003;74:1655-1661 doi:10.1136/jnnp.74.12.1655
Publication Year and Month: 2003 12

Abstract: OBJECTIVES: To investigate the effect of pyridostigmine on fatigue, physical performance, and muscle function in subjects with postpoliomyelitis syndrome.

METHODS: 67 subjects with increased fatigue and new weakness in one quadriceps muscle showing neuromuscular transmission defects, were included in a randomised, double blind, placebo controlled trial of 60 mg pyridostigmine four times a day for 14 weeks. Primary outcome was fatigue (on the "energy" category of the Nottingham health profile). Secondary outcomes included two minute walking distance and quadriceps strength and jitter. Motor unit size of the quadriceps was studied as a potential effect modifier. The primary data analysis compared the changes from baseline in the outcomes in the last week of treatment between groups.

RESULTS: 31 subjects treated with pyridostigmine and 31 subjects treated with placebo completed the trial. No significant effect of pyridostigmine was found on fatigue. The walking distance improved more in the pyridostigmine group than in the placebo group (by 7.2 m (6.0%); p<0.01). Subgroup analysis showed that a significant improvement in walking performance was only found in subjects with normal sized motor units. Quadriceps strength improved more in the pyridostigmine group than in the placebo group (by 6.7 Nm (7.2%); p = 0.15). No effect of pyridostigmine was found on jitter.

Conclusions: Pyridostigmine in the prescribed dose did not reduce fatigue in subjects with postpoliomyelitis syndrome. However, it may have a limited beneficial effect on physical performance, especially in subjects with neuromuscular transmission defects in normal sized motor units.

Outcome of Research: More research required.

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Title: Intravenous immunoglobulin for postpolio syndrome: a systematic review and meta-analysis
Author: Huang Y-H (1), Chen H-C (2,3), Huang K-W (4,5,6), Chen P-C (1,7), Hu C-J (1,8), Tsai C-P (5,9), Tam K-W (2,10,11,12,13,14), Kuan Y-C (1,5,8,14)
Affiliation: (1) Department of Neurology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; (2) Center for Evidence-Based Health Care, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; (3) Department of Physical Medicine and Rehabilitation, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; (4) Department of Gastroenterology, College of Medicine, Taipei Medical University, Taipei, Taiwan; (5) Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; (6) Department of Gastroenterology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; (7) College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; (8) Department of Neurology, School of Medicine, Taipei Medical University, Taipei, Taiwan; (9) Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; (10) Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; (11) Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; (12) Division of General Surgery, Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan; (13) Center for Evidence-Based Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; (14) Taipei Medical University-Shuang Ho Hospital, 291 Zhongzheng Road, Zhonghe District, New Taipei City 23561, Taiwan
Journal: BioMed Central Neurology
Citation: BMC Neurology 2015, 15:39 doi:10.1186/s12883-015-0301-9
Publication Year and Month: 2015 03

Abstract: 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.

Conclusions: 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.

Outcome of Research: More research required

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Title: Updated consensus statement: Intravenous immunoglobulin in the treatment of neuromuscular disorders report of the AANEM ad hoc committee
Author: Jinny Tavee MD (1), Thomas H. Brannagan III MD (2), Michael W. Lenihan MD (3), Sri Muppidi MD (4), Liz Kellermeyer BA, MLS (1), Peter D Donofrio MD, AANEM (5)
Affiliation: (1) National Jewish Health, Division of Neurology, Denver, Colorado, USA

(2) Vagelos College of Physicians and Surgeons, Neurological Institute, Columbia University, New York, New York, USA

(3) Adirondack Neurology Associates, PC, Glens Falls, New York, USA

(4) Stanford Neuroscience Health Center, Palo Alto, California, USA

(5) Neurology Clinic, Vanderbilt University, Nashville, Tennessee, USA
Journal: Muscle & Nerve
Citation: Tavee, J, Brannagan, TH, Lenihan, MW, et al. Updated consensus statement: Intravenous immunoglobulin in the treatment of neuromuscular disorders report of the AANEM ad hoc committee. Muscle & Nerve. 2023; 1-19. doi:10.1002/mus.27922
Publication Year and Month: 2023 07

Abstract: Intravenous immune globulin (IVIG) is an immune-modulating biologic therapy that is increasingly being used in neuromuscular disorders despite the paucity of high-quality evidence for various specific diseases. To address this, the AANEM created the 2009 consensus statement to provide guidance on the use of IVIG in neuromuscular disorders. Since then, there have been several randomized controlled trials for IVIG, a new FDA-approved indication for dermatomyositis and a revised classification system for myositis, prompting the AANEM to convene an ad hoc panel to update the existing guidelines.New recommendations based on an updated systemic review of the literature were categorized as Class I-IV. Based on Class I evidence, IVIG is recommended in the treatment of chronic inflammatory demyelinating polyneuropathy, Guillain-Barré Syndrome (GBS) in adults, multifocal motor neuropathy, dermatomyositis, stiff-person syndrome and myasthenia gravis exacerbations but not stable disease. Based on Class II evidence, IVIG is also recommended for Lambert-Eaton myasthenic syndrome and pediatric GBS. In contrast, based on Class I evidence, IVIG is not recommended for inclusion body myositis, post-polio syndrome, IgM paraproteinemic neuropathy and small fiber neuropathy that is idiopathic or associated with tri-sulfated heparin disaccharide or fibroblast growth factor receptor-3 autoantibodies. Although only Class IV evidence exists for IVIG use in necrotizing autoimmune myopathy, it should be considered for anti-hydroxy-3-methyl-glutaryl-coenzyme A reductase myositis given the risk of long-term disability. Insufficient evidence exists for the use of IVIG in Miller-Fisher syndrome, IgG and IgA paraproteinemic neuropathy, autonomic neuropathy, chronic autoimmune neuropathy, polymyositis, idiopathic brachial plexopathy and diabetic lumbosacral radiculoplexopathy.

Conclusions: IVIG is not recommended for Post-Polio Syndrome (PPS) as there is no long-term benefit.

Outcome of Research: More research required

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Title: Effect of intravenous immunoglobulin in patients with post-polio syndrome - an uncontrolled pilot study
Author: Kaponides G, Gonzalez H, Olsson T, Borg K
Affiliation: Department of Public Health Sciences, Division of Rehabilitation Medicine, Stockholm, Sweden - [email protected]

Journal: Journal of Rehabilitation Medicine
Citation: J Rehabil Med. 2006 Mar;38(2):138-40
Publication Year and Month: 2006 03

Abstract: 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.

Conclusions: 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.

Outcome of Research: More research required.

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Title: Beneficial Effect of Medical Cannabis in the Treatment of a Pharmacoresistant Nausea Associated with a Somatoform Disorder in a Patient with Post-Polio Syndrome
Author: Markus Bleckwenn, Klaus Weckbecker, Sebastian Voss
Affiliation: Markus Bleckwenn  Institut für Hausarztmedizin der Medizinischen Fakultät der Universität Bonn
Klaus Weckbecker  Institut für Hausarztmedizin der Medizinischen Fakultät der Universität Bonn
Sebastian Voss  Institut für Hausarztmedizin der Medizinischen Fakultät der Universität Bonn
Journal: Dtsch Med Wochenschr.
Citation: 2018 Mar;143(5):344-348
Publication Year and Month: 2018 03

Abstract: HISTORY AND CLINICAL FINDINGS:
We report a 79-year-old patient with post-polio syndrome (PPS). In the course of this disease, recurrent upper abdominal pain and a therapy-resistant nausea developed without vomiting. In addition, the patient was limited by the combination of muscular weakness, obesity, dietary-treated diabetes and a degenerative spinal cord injury significantly in its mobility and physical capacity.

INVESTIGATIONS AND DIAGNOSIS:
Despite extensive diagnostics, no somatic cause could be found neither for the nausea nor for the upper abdominal pain. Due to the psychological stress within the scope of the PPS, the development of a somatoform autonomic function disorder of the upper gastrointestinal tract may have occurred.

TREATMENT AND COURSE:
Even under combination therapy of antiemetic and pain-modulating drugs, no adequate symptom control could be achieved. In the absence of therapy alternatives and increasing psychological strain the patient was prescribed medical cannabis. Under the therapy there was a relief of the nausea symptoms and decreased pain.

Conclusions: CONCLUSION:
Cannabis is a treatment option for treatment-resistant symptoms as part of a PPS.

Outcome of Research: More research required

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Title: Immunoglobulin treatment in post-polio syndrome: Identification of responders and non-responders
Author: Östlund G (1), Broman L, Werhagen L, Borg K
Affiliation: (1) Department of Rehabilitation Medicine, Danderyd University Hospital, Building 39, 3rd floor, SE-182 88 Stockholm, Sweden
Journal: Journal of Rehabilitation Medicine
Citation: J Rehabil Med. 2015 Aug 18. doi: 10.2340/16501977-1985
Publication Year and Month: 2015 08

Abstract: 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.

Conclusions: 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.

Outcome of Research: Effective

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Title: IVIG treatment in post-polio patients: evaluation of responders
Author: Ostlund G (1), Broman L, Werhagen L, Borg K
Affiliation: (1) Division of Rehabilitation Medicine, Department of Clinical Sciences, Karolinska Institute, Danderyd Hospital, Building 39, 3rd floor, 182 88 Stockholm, Sweden
Journal: Journal of Neurology
Citation: J Neurol. 2012 Dec;259(12):2571-8. doi: 10.1007/s00415-012-6538-y. Epub 2012 May 17
Publication Year and Month: 2012 05

Abstract: 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.

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Outcome of Research: Effective

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Title: Bromocriptine In The Treatment Of Post-Polio Fatigue: A pilot study with implications for the pathophysiology of fatigue
Author: Richard L. Bruno, Ph.D., Jerald R. Zimmerman, M.D., Susan Creange, M.A., Todd Lewis, Ph.D., Terry Molzen, M.A., and Nancy M. Frick, M.Div, Lh.D.
Affiliation: Post-Polio Rehabilitation and Research Service; Kessler Institute for Rehabilitation, Department of Physical Medicine and Rehabilitation; UMDNJ/New Jersey Medical School, Harvest Center; Hackensack, New Jersey
Journal: American Journal of Physical Medicine & Rehabilitation
Citation: American Journal of Physical Medicine and Rehabilitation, 1997 (in press)
Publication Year and Month: 1997

Abstract: Objective: Determine the effectiveness of bromocriptine in the treatment of severe and disabling post-polio fatigue.
Design: Placebo-controlled drug trial in a pilot series of patients.
Setting: Outpatient rehabilitation hospital.
Patients: Of 83 patients without comorbidities who completed treatment with the Post-Polio Service, 5 of 8 patients who had paralytic polio and continued to report moderate to severe daily fatigue after complying with conservative treatments for post-polio fatigue agreed to be studied.
Intervention: Placebo was given for four weeks followed by increasing doses of bromocriptine mesylate (Parlodel®) administered at noon for 28 days reaching a total dose of 12.5 mg/day.
Main Outcome Measures: Daily logs of subjective fatigue and cognitive difficulties.
Results: Three of the subjects reported symptom improvement on bromocriptine but not on placebo. However, all subjects experienced nausea on bromocriptine, likely eliminating blinding. Drug responders had clinically impaired performance on neuropsychological tests of attention and information processing speed. Logged daily difficulty with attention, cognition, word finding memory, staying awake and fatigue on awakening were significantly negatively correlated with days on bromocriptine, but not with days on placebo, in drug responders.
Conclusions: A double-blind, placebo-controlled multicenter study will be needed to confirm bromocriptine's effectiveness in treating attentionally-impaired polio survivors whose severe and disabling fatigue does not responded to conservative treatment.

Conclusions: This pilot study of severely fatigued polio survivors suggests that bromocriptine may be of use in the treatment of post-polio fatigue that has not responded to conservative therapies. However, the small sample size and methodological limitations make this suggestion merely tentative. Since nausea was universally experienced, all subjects may have realized that they were receiving active drug and were thereby biased toward reporting reductions in symptoms. The percentage of days on which side effects were experienced on bromocriptine was higher in the responders (48%) than non-responders (34%). Although the placebo phase was not compromised, the bromocriptine phase of the study may have been as unblinded as an open-label drug trial. Reductions in morning fatigue and fatigue-related cognitive symptoms as the dose of bromocriptine increased were not paralleled by drug-related improvements in neuropsychologic test scores, most likely since the same form of the tests was administered on placebo and on bromocriptine. Subjects repeatedly taking the same test would be expected to demonstrate a learning effect and have their test scores improve. This has been seen even in polio survivors with severe fatigue who were repeatedly administered the same neuropsychologic tests over the course of several hours [4] It was also surprising that drug responders noticed no reduction in fatigue during the afternoon, since bromocriptine was administered at noon so that a peak blood level would be reached at 3:00 PM when many polio survivors report hitting an afternoon "wall" of fatigue. Since the pharmacokinetics of bromocriptine could differ from the time course of its pharmacological effect, as is seen with D2 receptor antagonists, moving the dose of drug to before sleep or upon awakening may prolong any beneficial effect of the drug into the afternoon. [18]

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Title: Efficacy of Modafinil on fatigue and excessive daytime sleepiness associated with neurological disorders: a systematic review and meta-analysis
Author: Sheng P, Hou L, Wang X, Wang X, Huang C, Yu M, Han X, Dong Y.
Affiliation: Department of Neurosurgery, Shanghai Institute of Neurosurgery, Military Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China
Journal: Public Library of Science
Citation: PLoS One. 2013 Dec 3;8(12):e81802. doi: 10.1371/journal.pone.0081802
Publication Year and Month: 2013 03

Abstract: BACKGROUND: Modafinil is a novel wake-promoting agent approved by the FDA ameliorating excessive daytime sleepiness (EDS) in three disorders: narcolepsy, shift work sleep disorder and obstructive sleep apnea. Existing trials of modafinil for fatigue and EDS associated with neurological disorders provided inconsistent results. This meta-analysis was aimed to assess drug safety and effects of modafinil on fatigue and EDS associated with neurological disorders.

METHODS: A comprehensive literature review was conducted in order to identify published studies assessing the effects of modafinil on fatigue and EDS associated with neurological disorders. Primary outcomes included fatigue and EDS. Secondary outcomes included depression and adverse effects.

FINDINGS: Ten randomized controlled trials were identified including 4 studies of Parkinson's disease (PD), 3 of multiple sclerosis (MS), 2 of traumatic brain injury (TBI) and 1 of post-polio syndrome (PPS). A total of 535 patients were enrolled. Our results suggested a therapeutic effect of modafinil on fatigue in TBI (MD -0.82 95% CI -1.54 - -0.11 p=0.02, I(2)=0%), while a beneficial effect of modafinil on fatigue was not confirmed in the pooled studies of PD or MS. Treatment results demonstrated a clear beneficial effect of modafinil on EDS in patients with PD (MD -2.45 95% CI -4.00 - -0.91 p=0.002 I(2)=14%), but not with MS and TBI. No difference was seen between modafinil and placebo treatments in patients with PPS. Modafinil seemed to have no therapeutic effect on depression. Adverse events were similar between modafinil and placebo groups except that more patients were found with insomnia and nausea in modafinil group.

Conclusions: Existing trials of modafinil for fatigue and EDS associated with PD, MS, TBI and PPS provided inconsistent results. The majority of the studies had small sample sizes. Modafinil is not yet sufficient to be recommended for these medical conditions until solid data are available.

Outcome of Research: More research required.

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Title: Use of Medication in People with Post-Polio Syndrome
Author: Susan Perlman, MD
Affiliation: University of California Los Angeles (UCLA)
Journal: NEW - PUT DETAILS IN CITATION FIELD
Citation: Polio Network News (Now called Polio-Polio Health)

WINTER 1999, VOL. 15, No. 1
Publication Year and Month: 1999 12

Abstract: Until we better understand the causes of post -polio syndrome, we will have no curative medication. At best, we can use medication to treat the symptoms and to improve the quality of life, and we can avoid using medication that could make the symptoms worse. Certain other diseases (elevated blood cholesterol levels, high blood pressure, heart disease, and cancers) require use of medications with side effects that can exacerbate symptoms of post-polio syndrome. These should be used, but with careful monitoring of the polio survivor's functioning.

Conclusions: Polio survivors and their physicians should scrutinize all medications - current and newly added - used to treat various medical problems to be assured that related conditions, such as fibromyalgia, elevated cholesterol, high blood pressure, etc., are appropriately treated, but with minimal effect on polio-related symptoms.

Outcome of Research: Not applicable

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Title: Immunoglobulin g for the treatment of chronic pain: report of an expert workshop
Author: Tamburin S (1), Borg K, Caro XJ, Jann S, Clark AJ, Magrinelli F, Sobue G, Werhagen L, Zanette G, Koike H, Späth PJ, Vincent A, Goebel A
Affiliation: (1) Department of Neurological and Movement Sciences, University of Verona, Verona, Verona, Italy
Journal: Pain Medicine
Citation: Pain Med. 2014 Jul;15(7):1072-82. doi: 10.1111/pme.12319
Publication Year and Month: 2014 07

Abstract: BACKGROUND: The treatment of chronic pain is still unsatisfactory. Despite the availability of different drugs, most patients with chronic pain do not receive satisfactory pain relief or report side effects. Converging evidence implicates involvement of the immune system in the pathogenesis of different types of nociceptive and neuropathic chronic pain.

DESIGN: At a workshop in Liverpool, UK (October 2012), experts presented evidence suggesting immunological involvement in chronic pain and recent data supporting the concept that the established immune-modulating drug, polyvalent immunoglobulin G (IgG), either given intravenously (IVIg) or subcutaneously (SCIg), may reduce pain in some peripheral neuropathies and a range of other pain disorders. Workshop's attendees discussed the practicalities of using IVIg and SCIg in these disorders, including indications, cost-effectiveness, and side effects.

RESULTS: IgG may reduce pain in a range of nociceptive and neuropathic chronic pain conditions, including diabetes mellitus, Sjögren's syndrome, fibromyalgia, complex regional pain syndrome, post-polio syndrome, and pain secondary to pathological autoantibodies.

Conclusions: IgG is a promising treatment in several chronic pain conditions. IgG is a relatively safe therapeutic strategy, with uncommon and mild side effects but high costs. Randomized, controlled trials and predictive tests are needed to better support the use of IgG for refractory chronic pain.

Outcome of Research: More research required

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Title: Effect of intravenous immunoglobulin on pain in patients with post-polio syndrome
Author: Werhagen L, Borg K
Affiliation: Department of Clinical Sciences, Division of Rehabilitation Medicine, Karolinska Institutet Danderyds Hospital, Stockholm, Sweden
Journal: Journal of Rehabilitation Medicine
Citation: J Rehabil Med. 2011 Nov;43(11):1038-40. doi: 10.2340/16501977-0884.
Publication Year and Month: 2011 11

Abstract: 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.

Conclusions: 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.

Outcome of Research: Not applicable.

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There are currently 18 papers in this category.

Title: An Open Trial of Pyridostigmine in Post-poliomyelitis Syndrome
Author: Daria A. Trojan and Neil R. Cashman


Affiliation: From the Department of Neurology, Montreal Neurological Institute and Hospital, McGill University, Montreal.
Journal:
Citation: The Canadian Journal of Neurological Sciences Volume 22, No. 3 August 1995 223-227
Publication Year and Month: 1995 08

Abstract: Background: One of the major symptoms of postpoliomyelitis syndrome (PPS) is disabling generalized fatigue. Subjects with PPS also report muscle fatiguability and display electrophysiologic evidence of anticholinesterase-responsive neuromuscular junction transmission defects, suggesting that anticholinesterase therapy may be useful in the management of disabling fatigue. Methods: We initiated an open trial of the oral anticholinesterase pyridostigmine, up to 180 mg per day, in 27 PPS patients with generalized fatigue and muscle fatiguability. Response to Pyridostigmine was assessed with the Hare fatigue scale, the modified Barthel index for activities of daily living, and a modified Klingman mobility index. Results: Two patients could not tolerate the medication. After one month of therapy, 16 patients (64%) reported a reduction in fatigue on the Hare fatigue scale; three of 16 showed improvement on the modified Barthel index for activities of daily living, and two of 16 experienced improvement on a modified Klingman mobility index. Pyridostigmine responders were significantly more fatigued than non-responders on the pre-treatment Hare score, but were not significantly different with regard to age, sex, age at acute poliomyelitis, or severity of acute poliomyelitis. Conclusions: Pyridostigmine may be useful in the management of fatigue in selected patients with PPS. Response to pyridostigmine may be predicted by severity of pre-treatment fatigue.

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Outcome of Research: Not applicable

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Title: Bromocriptine In The Treatment Of Post-Polio Fatigue: A pilot study with implications for the pathophysiology of fatigue
Author: Richard L. Bruno, Ph.D., Jerald R. Zimmerman, M.D., Susan Creange, M.A., Todd Lewis, Ph.D., Terry Molzen, M.A., and Nancy M. Frick, M.Div, Lh.D.
Affiliation: Post-Polio Rehabilitation and Research Service; Kessler Institute for Rehabilitation, Department of Physical Medicine and Rehabilitation; UMDNJ/New Jersey Medical School, Harvest Center; Hackensack, New Jersey
Journal: American Journal of Physical Medicine & Rehabilitation
Citation: American Journal of Physical Medicine and Rehabilitation, 1997 (in press)
Publication Year and Month: 1997

Abstract: Objective: Determine the effectiveness of bromocriptine in the treatment of severe and disabling post-polio fatigue.
Design: Placebo-controlled drug trial in a pilot series of patients.
Setting: Outpatient rehabilitation hospital.
Patients: Of 83 patients without comorbidities who completed treatment with the Post-Polio Service, 5 of 8 patients who had paralytic polio and continued to report moderate to severe daily fatigue after complying with conservative treatments for post-polio fatigue agreed to be studied.
Intervention: Placebo was given for four weeks followed by increasing doses of bromocriptine mesylate (Parlodel®) administered at noon for 28 days reaching a total dose of 12.5 mg/day.
Main Outcome Measures: Daily logs of subjective fatigue and cognitive difficulties.
Results: Three of the subjects reported symptom improvement on bromocriptine but not on placebo. However, all subjects experienced nausea on bromocriptine, likely eliminating blinding. Drug responders had clinically impaired performance on neuropsychological tests of attention and information processing speed. Logged daily difficulty with attention, cognition, word finding memory, staying awake and fatigue on awakening were significantly negatively correlated with days on bromocriptine, but not with days on placebo, in drug responders.
Conclusions: A double-blind, placebo-controlled multicenter study will be needed to confirm bromocriptine's effectiveness in treating attentionally-impaired polio survivors whose severe and disabling fatigue does not responded to conservative treatment.

Conclusions: This pilot study of severely fatigued polio survivors suggests that bromocriptine may be of use in the treatment of post-polio fatigue that has not responded to conservative therapies. However, the small sample size and methodological limitations make this suggestion merely tentative. Since nausea was universally experienced, all subjects may have realized that they were receiving active drug and were thereby biased toward reporting reductions in symptoms. The percentage of days on which side effects were experienced on bromocriptine was higher in the responders (48%) than non-responders (34%). Although the placebo phase was not compromised, the bromocriptine phase of the study may have been as unblinded as an open-label drug trial. Reductions in morning fatigue and fatigue-related cognitive symptoms as the dose of bromocriptine increased were not paralleled by drug-related improvements in neuropsychologic test scores, most likely since the same form of the tests was administered on placebo and on bromocriptine. Subjects repeatedly taking the same test would be expected to demonstrate a learning effect and have their test scores improve. This has been seen even in polio survivors with severe fatigue who were repeatedly administered the same neuropsychologic tests over the course of several hours [4] It was also surprising that drug responders noticed no reduction in fatigue during the afternoon, since bromocriptine was administered at noon so that a peak blood level would be reached at 3:00 PM when many polio survivors report hitting an afternoon "wall" of fatigue. Since the pharmacokinetics of bromocriptine could differ from the time course of its pharmacological effect, as is seen with D2 receptor antagonists, moving the dose of drug to before sleep or upon awakening may prolong any beneficial effect of the drug into the afternoon. [18]

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Title: Anticholinesterases in Post-Poliomyelitis Syndrome
Author: Daria A. Trojan and Neil R. Cashman
Affiliation: Department of Neurology, Montreal Neurological Institute and Hospital, McGill University
Journal: Annals of the New York Academy of Sciences
Citation: Reprinted from The Post-Polio Syndrome: Advances in the Pathogenesis and Treatment, Volume 753 of the Annals of the New York Academy of Sciences, May 25, 1995
Publication Year and Month: 1995 05

Abstract: New weakness, fatigue, and pain after decades of functional stability in those who have recovered from acute paralytic poliomyelitis constitutes post-poliomyelitis syndrome (PPS).[1-7] The cause of PPS is unknown, but it is thought to be due to a distal degeneration of enlarged post-polio motor units produced by terminal axonal sprouting during the recovery process after acute polio.[8,9] The symptoms of weakness and fatigue may be a direct result of this distal motor unit degeneration;[2,7-13] however, it is presently unclear how pain relates to disease of the motor unit. PPS is a slowly progressive motor neuron disease for which there is currently no specific treatment.[4]

Conclusions: Our studies indicate that a proportion of fatigued post-poliomyelitis patients can experience an amelioration of defects in neuromuscular junction transmission and of clinical fatigue with anticholinesterases. Because S-SFEMG response was significantly associated with clinical response to anticholinesterases, fatigue in PPS may be caused by defects in neuromuscular junction transmission in a proportion of patients. Preliminary studies in a small group of patients indicate that anticholinesterases may produce their clinical neuromuscular response by producing an increase in isokinetic strength in a proportion of patients. Our studies provide a physiological rationale for the use of anticholinesterases in PPS for the symptom of fatigue. However, further randomized, placebo-controlled, double-blinded trials are needed to establish definitively the benefits and risks of these agents.

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Title: Intravenous immunoglobulin for postpolio syndrome: a systematic review and meta-analysis
Author: Huang Y-H (1), Chen H-C (2,3), Huang K-W (4,5,6), Chen P-C (1,7), Hu C-J (1,8), Tsai C-P (5,9), Tam K-W (2,10,11,12,13,14), Kuan Y-C (1,5,8,14)
Affiliation: (1) Department of Neurology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; (2) Center for Evidence-Based Health Care, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; (3) Department of Physical Medicine and Rehabilitation, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; (4) Department of Gastroenterology, College of Medicine, Taipei Medical University, Taipei, Taiwan; (5) Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; (6) Department of Gastroenterology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; (7) College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; (8) Department of Neurology, School of Medicine, Taipei Medical University, Taipei, Taiwan; (9) Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; (10) Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; (11) Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; (12) Division of General Surgery, Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan; (13) Center for Evidence-Based Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; (14) Taipei Medical University-Shuang Ho Hospital, 291 Zhongzheng Road, Zhonghe District, New Taipei City 23561, Taiwan
Journal: BioMed Central Neurology
Citation: BMC Neurology 2015, 15:39 doi:10.1186/s12883-015-0301-9
Publication Year and Month: 2015 03

Abstract: 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.

Conclusions: 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.

Outcome of Research: More research required

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Title: Beneficial Effect of Medical Cannabis in the Treatment of a Pharmacoresistant Nausea Associated with a Somatoform Disorder in a Patient with Post-Polio Syndrome
Author: Markus Bleckwenn, Klaus Weckbecker, Sebastian Voss
Affiliation: Markus Bleckwenn  Institut für Hausarztmedizin der Medizinischen Fakultät der Universität Bonn
Klaus Weckbecker  Institut für Hausarztmedizin der Medizinischen Fakultät der Universität Bonn
Sebastian Voss  Institut für Hausarztmedizin der Medizinischen Fakultät der Universität Bonn
Journal: Dtsch Med Wochenschr.
Citation: 2018 Mar;143(5):344-348
Publication Year and Month: 2018 03

Abstract: HISTORY AND CLINICAL FINDINGS:
We report a 79-year-old patient with post-polio syndrome (PPS). In the course of this disease, recurrent upper abdominal pain and a therapy-resistant nausea developed without vomiting. In addition, the patient was limited by the combination of muscular weakness, obesity, dietary-treated diabetes and a degenerative spinal cord injury significantly in its mobility and physical capacity.

INVESTIGATIONS AND DIAGNOSIS:
Despite extensive diagnostics, no somatic cause could be found neither for the nausea nor for the upper abdominal pain. Due to the psychological stress within the scope of the PPS, the development of a somatoform autonomic function disorder of the upper gastrointestinal tract may have occurred.

TREATMENT AND COURSE:
Even under combination therapy of antiemetic and pain-modulating drugs, no adequate symptom control could be achieved. In the absence of therapy alternatives and increasing psychological strain the patient was prescribed medical cannabis. Under the therapy there was a relief of the nausea symptoms and decreased pain.

Conclusions: CONCLUSION:
Cannabis is a treatment option for treatment-resistant symptoms as part of a PPS.

Outcome of Research: More research required

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Title: Prior poliomyelitis – IVIg treatment reduces proinflammatory cytokine production
Author: Gonzalez H, Khademi M, Andersson M, Piehl F, Wallström E, Borg K, Olsson T
Affiliation: Department of Neuroimmunology Unit, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden – [email protected]
Journal: Journal of Neuroimmunology
Citation: J Neuroimmunol. 2004 May; 150(1-2):139-44
Publication Year and Month: 2004 05

Abstract: 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.

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Title: Intravenous immunoglobulin treatment of the post-polio syndrome: sustained effects on quality of life variables and cytokine expression after one year follow up
Author: Gonzalez H (1), Khademi M (2), Borg K (1), Olsson T (2)
Affiliation: (1) Division of Rehabilitation Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, blg 39, fl 3, S-192 88, Stockholm, Sweden; (2) Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
Journal: Journal of Neuroinflammation
Citation: Journal of Neuroinflammation. 2012; 9: 167. doi: 10.1186/1742-2094-9-167
Publication Year and Month: 2012 07

Abstract: 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, TGFβ, 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.

Outcome of Research: More research required.

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Title: IVIG treatment in post-polio patients: evaluation of responders
Author: Ostlund G (1), Broman L, Werhagen L, Borg K
Affiliation: (1) Division of Rehabilitation Medicine, Department of Clinical Sciences, Karolinska Institute, Danderyd Hospital, Building 39, 3rd floor, 182 88 Stockholm, Sweden
Journal: Journal of Neurology
Citation: J Neurol. 2012 Dec;259(12):2571-8. doi: 10.1007/s00415-012-6538-y. Epub 2012 May 17
Publication Year and Month: 2012 05

Abstract: 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.

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Outcome of Research: Effective

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Title: Pyridostigmine in postpolio syndrome: no decline in fatigue and limited functional improvement
Author: Horemans H (1), Nollet F (1), Beelen A (1), Drost G (2), Stegeman D (2), Zwarts M (2), Bussmann J (3), de Visser M (4), Lankhorst G (1)
Affiliation: (1) Department of Rehabilitation Medicine, VU University Medical Centre, Amsterdam, Netherlands; (2) Department of Clinical Neurophysiology, University Medical Centre Nijmegen, Netherlands; (3) Department of Rehabilitation Medicine, Erasmus MC, University Medical Centre Rotterdam, Netherlands; (4) Department of Neurology, Academic Medical Centre, University of Amsterdam, Netherlands
Journal: Journal of Neurology, Neurosurgery and Psychiatry
Citation: J Neurol Neurosurg Psychiatry 2003;74:1655-1661 doi:10.1136/jnnp.74.12.1655
Publication Year and Month: 2003 12

Abstract: OBJECTIVES: To investigate the effect of pyridostigmine on fatigue, physical performance, and muscle function in subjects with postpoliomyelitis syndrome.

METHODS: 67 subjects with increased fatigue and new weakness in one quadriceps muscle showing neuromuscular transmission defects, were included in a randomised, double blind, placebo controlled trial of 60 mg pyridostigmine four times a day for 14 weeks. Primary outcome was fatigue (on the "energy" category of the Nottingham health profile). Secondary outcomes included two minute walking distance and quadriceps strength and jitter. Motor unit size of the quadriceps was studied as a potential effect modifier. The primary data analysis compared the changes from baseline in the outcomes in the last week of treatment between groups.

RESULTS: 31 subjects treated with pyridostigmine and 31 subjects treated with placebo completed the trial. No significant effect of pyridostigmine was found on fatigue. The walking distance improved more in the pyridostigmine group than in the placebo group (by 7.2 m (6.0%); p<0.01). Subgroup analysis showed that a significant improvement in walking performance was only found in subjects with normal sized motor units. Quadriceps strength improved more in the pyridostigmine group than in the placebo group (by 6.7 Nm (7.2%); p = 0.15). No effect of pyridostigmine was found on jitter.

Conclusions: Pyridostigmine in the prescribed dose did not reduce fatigue in subjects with postpoliomyelitis syndrome. However, it may have a limited beneficial effect on physical performance, especially in subjects with neuromuscular transmission defects in normal sized motor units.

Outcome of Research: More research required.

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Title: Effect of intravenous immunoglobulin on pain in patients with post-polio syndrome
Author: Werhagen L, Borg K
Affiliation: Department of Clinical Sciences, Division of Rehabilitation Medicine, Karolinska Institutet Danderyds Hospital, Stockholm, Sweden
Journal: Journal of Rehabilitation Medicine
Citation: J Rehabil Med. 2011 Nov;43(11):1038-40. doi: 10.2340/16501977-0884.
Publication Year and Month: 2011 11

Abstract: 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.

Conclusions: 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.

Outcome of Research: Not applicable.

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Title: Effect of intravenous immunoglobulin in patients with post-polio syndrome - an uncontrolled pilot study
Author: Kaponides G, Gonzalez H, Olsson T, Borg K
Affiliation: Department of Public Health Sciences, Division of Rehabilitation Medicine, Stockholm, Sweden - [email protected]

Journal: Journal of Rehabilitation Medicine
Citation: J Rehabil Med. 2006 Mar;38(2):138-40
Publication Year and Month: 2006 03

Abstract: 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.

Conclusions: 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.

Outcome of Research: More research required.

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Title: Immunoglobulin treatment in post-polio syndrome: Identification of responders and non-responders
Author: Östlund G (1), Broman L, Werhagen L, Borg K
Affiliation: (1) Department of Rehabilitation Medicine, Danderyd University Hospital, Building 39, 3rd floor, SE-182 88 Stockholm, Sweden
Journal: Journal of Rehabilitation Medicine
Citation: J Rehabil Med. 2015 Aug 18. doi: 10.2340/16501977-1985
Publication Year and Month: 2015 08

Abstract: 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.

Conclusions: 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.

Outcome of Research: Effective

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Title: Anticholinesterase-responsive neuromuscular junction transmission defects in post-poliomyelitis fatigue
Author: Daria A. Trojan, Daniel Gendron and Neil R. Cashman
Affiliation: Department of Neurology, McGill University, Montreal Neurological Institute and Hospital
Journal: Journal of the Neurological Sciences
Citation: 114 (1993) 170-177
Publication Year and Month: 1992 08

Abstract: Disabling generalized fatigue and muscle fatiguability are common features of post-poliomyelitis syndrome (PPS). In 17 fatigued PPS patients, we measured jitter on stimulation single-fiber electromyography (S-SFEMG) for at least 3.5 min before and after i.v. injection of 10 mg edrophonium. We observed reduction in jitter (defined as a significant difference in jitter means before and after edrophonium, unpaired t-test P < 0.05) in 7 patients, no change in 8, and a significant increase in 2 patients. Blinded to their edrophonium results, the 17 patients were treated with pyridostigmine 180 mg/day for 1 month, with a subjective improvement of fatigue in 9 patients, and with a significant reduction in mean Hare fatigue scores in the entire group of 17 patients (pre = 2.71, and post = 1.71; Wilcoxan signed rank sum test, P < 0.05). Edrophonium-induced reduction of jitter on S-SFEMG was significantly associated with pyridostigmine-induced subjective improvement of fatigue (Fisher's exact test, P < 0.04). A significant reduction in fatigue with pyridostigmine was observed only in the 7 patients who experienced a significant reduction in jitter with edrophonium (Wilcoxan signed rank sum test, P = 0.03). In addition, the 9 pyridostigmine responders experienced a significant reduction in jitter means pre- and post-edrophonium (100% vs. 88%, Bonferroni corrected, P < 0.01). We conclude that neuromuscular transmission as measured by jitter on S-SFEMG can improve with edrophonium in a proportion of PPS patients, and that generalized fatigue and muscle fatiguability in some patients with PPS may be due to anticholinesterase-responsive NMJ transmission defects.

Conclusions:

Outcome of Research: Not applicable

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Title: Updated consensus statement: Intravenous immunoglobulin in the treatment of neuromuscular disorders report of the AANEM ad hoc committee
Author: Jinny Tavee MD (1), Thomas H. Brannagan III MD (2), Michael W. Lenihan MD (3), Sri Muppidi MD (4), Liz Kellermeyer BA, MLS (1), Peter D Donofrio MD, AANEM (5)
Affiliation: (1) National Jewish Health, Division of Neurology, Denver, Colorado, USA

(2) Vagelos College of Physicians and Surgeons, Neurological Institute, Columbia University, New York, New York, USA

(3) Adirondack Neurology Associates, PC, Glens Falls, New York, USA

(4) Stanford Neuroscience Health Center, Palo Alto, California, USA

(5) Neurology Clinic, Vanderbilt University, Nashville, Tennessee, USA
Journal: Muscle & Nerve
Citation: Tavee, J, Brannagan, TH, Lenihan, MW, et al. Updated consensus statement: Intravenous immunoglobulin in the treatment of neuromuscular disorders report of the AANEM ad hoc committee. Muscle & Nerve. 2023; 1-19. doi:10.1002/mus.27922
Publication Year and Month: 2023 07

Abstract: Intravenous immune globulin (IVIG) is an immune-modulating biologic therapy that is increasingly being used in neuromuscular disorders despite the paucity of high-quality evidence for various specific diseases. To address this, the AANEM created the 2009 consensus statement to provide guidance on the use of IVIG in neuromuscular disorders. Since then, there have been several randomized controlled trials for IVIG, a new FDA-approved indication for dermatomyositis and a revised classification system for myositis, prompting the AANEM to convene an ad hoc panel to update the existing guidelines.New recommendations based on an updated systemic review of the literature were categorized as Class I-IV. Based on Class I evidence, IVIG is recommended in the treatment of chronic inflammatory demyelinating polyneuropathy, Guillain-Barré Syndrome (GBS) in adults, multifocal motor neuropathy, dermatomyositis, stiff-person syndrome and myasthenia gravis exacerbations but not stable disease. Based on Class II evidence, IVIG is also recommended for Lambert-Eaton myasthenic syndrome and pediatric GBS. In contrast, based on Class I evidence, IVIG is not recommended for inclusion body myositis, post-polio syndrome, IgM paraproteinemic neuropathy and small fiber neuropathy that is idiopathic or associated with tri-sulfated heparin disaccharide or fibroblast growth factor receptor-3 autoantibodies. Although only Class IV evidence exists for IVIG use in necrotizing autoimmune myopathy, it should be considered for anti-hydroxy-3-methyl-glutaryl-coenzyme A reductase myositis given the risk of long-term disability. Insufficient evidence exists for the use of IVIG in Miller-Fisher syndrome, IgG and IgA paraproteinemic neuropathy, autonomic neuropathy, chronic autoimmune neuropathy, polymyositis, idiopathic brachial plexopathy and diabetic lumbosacral radiculoplexopathy.

Conclusions: IVIG is not recommended for Post-Polio Syndrome (PPS) as there is no long-term benefit.

Outcome of Research: More research required

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Title: Use of Medication in People with Post-Polio Syndrome
Author: Susan Perlman, MD
Affiliation: University of California Los Angeles (UCLA)
Journal: NEW - PUT DETAILS IN CITATION FIELD
Citation: Polio Network News (Now called Polio-Polio Health)

WINTER 1999, VOL. 15, No. 1
Publication Year and Month: 1999 12

Abstract: Until we better understand the causes of post -polio syndrome, we will have no curative medication. At best, we can use medication to treat the symptoms and to improve the quality of life, and we can avoid using medication that could make the symptoms worse. Certain other diseases (elevated blood cholesterol levels, high blood pressure, heart disease, and cancers) require use of medications with side effects that can exacerbate symptoms of post-polio syndrome. These should be used, but with careful monitoring of the polio survivor's functioning.

Conclusions: Polio survivors and their physicians should scrutinize all medications - current and newly added - used to treat various medical problems to be assured that related conditions, such as fibromyalgia, elevated cholesterol, high blood pressure, etc., are appropriately treated, but with minimal effect on polio-related symptoms.

Outcome of Research: Not applicable

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Title: Immunoglobulin g for the treatment of chronic pain: report of an expert workshop
Author: Tamburin S (1), Borg K, Caro XJ, Jann S, Clark AJ, Magrinelli F, Sobue G, Werhagen L, Zanette G, Koike H, Späth PJ, Vincent A, Goebel A
Affiliation: (1) Department of Neurological and Movement Sciences, University of Verona, Verona, Verona, Italy
Journal: Pain Medicine
Citation: Pain Med. 2014 Jul;15(7):1072-82. doi: 10.1111/pme.12319
Publication Year and Month: 2014 07

Abstract: BACKGROUND: The treatment of chronic pain is still unsatisfactory. Despite the availability of different drugs, most patients with chronic pain do not receive satisfactory pain relief or report side effects. Converging evidence implicates involvement of the immune system in the pathogenesis of different types of nociceptive and neuropathic chronic pain.

DESIGN: At a workshop in Liverpool, UK (October 2012), experts presented evidence suggesting immunological involvement in chronic pain and recent data supporting the concept that the established immune-modulating drug, polyvalent immunoglobulin G (IgG), either given intravenously (IVIg) or subcutaneously (SCIg), may reduce pain in some peripheral neuropathies and a range of other pain disorders. Workshop's attendees discussed the practicalities of using IVIg and SCIg in these disorders, including indications, cost-effectiveness, and side effects.

RESULTS: IgG may reduce pain in a range of nociceptive and neuropathic chronic pain conditions, including diabetes mellitus, Sjögren's syndrome, fibromyalgia, complex regional pain syndrome, post-polio syndrome, and pain secondary to pathological autoantibodies.

Conclusions: IgG is a promising treatment in several chronic pain conditions. IgG is a relatively safe therapeutic strategy, with uncommon and mild side effects but high costs. Randomized, controlled trials and predictive tests are needed to better support the use of IgG for refractory chronic pain.

Outcome of Research: More research required

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Title: Response of postpoliomyelitis patients to bisphosphonate treatment
Author: Alvarez A (1), Kremer R, Weiss DR, Benedetti A, Haziza M, Trojan DA
Affiliation: (1) Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University Health Centre, McGill University, Montreal, QC, Canada
Journal: PM&R: The Journal of Injury, Function, and Rehabilitation
Citation: PM R. 2010 Dec;2(12):1094-103. doi: 10.1016/j.pmrj.2010.08.009.
Publication Year and Month: 2010 12

Abstract: 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.

Outcome of Research: Effective

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Title: Efficacy of Modafinil on fatigue and excessive daytime sleepiness associated with neurological disorders: a systematic review and meta-analysis
Author: Sheng P, Hou L, Wang X, Wang X, Huang C, Yu M, Han X, Dong Y.
Affiliation: Department of Neurosurgery, Shanghai Institute of Neurosurgery, Military Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China
Journal: Public Library of Science
Citation: PLoS One. 2013 Dec 3;8(12):e81802. doi: 10.1371/journal.pone.0081802
Publication Year and Month: 2013 03

Abstract: BACKGROUND: Modafinil is a novel wake-promoting agent approved by the FDA ameliorating excessive daytime sleepiness (EDS) in three disorders: narcolepsy, shift work sleep disorder and obstructive sleep apnea. Existing trials of modafinil for fatigue and EDS associated with neurological disorders provided inconsistent results. This meta-analysis was aimed to assess drug safety and effects of modafinil on fatigue and EDS associated with neurological disorders.

METHODS: A comprehensive literature review was conducted in order to identify published studies assessing the effects of modafinil on fatigue and EDS associated with neurological disorders. Primary outcomes included fatigue and EDS. Secondary outcomes included depression and adverse effects.

FINDINGS: Ten randomized controlled trials were identified including 4 studies of Parkinson's disease (PD), 3 of multiple sclerosis (MS), 2 of traumatic brain injury (TBI) and 1 of post-polio syndrome (PPS). A total of 535 patients were enrolled. Our results suggested a therapeutic effect of modafinil on fatigue in TBI (MD -0.82 95% CI -1.54 - -0.11 p=0.02, I(2)=0%), while a beneficial effect of modafinil on fatigue was not confirmed in the pooled studies of PD or MS. Treatment results demonstrated a clear beneficial effect of modafinil on EDS in patients with PD (MD -2.45 95% CI -4.00 - -0.91 p=0.002 I(2)=14%), but not with MS and TBI. No difference was seen between modafinil and placebo treatments in patients with PPS. Modafinil seemed to have no therapeutic effect on depression. Adverse events were similar between modafinil and placebo groups except that more patients were found with insomnia and nausea in modafinil group.

Conclusions: Existing trials of modafinil for fatigue and EDS associated with PD, MS, TBI and PPS provided inconsistent results. The majority of the studies had small sample sizes. Modafinil is not yet sufficient to be recommended for these medical conditions until solid data are available.

Outcome of Research: More research required.

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There are currently 18 papers in this category.

Title: Updated consensus statement: Intravenous immunoglobulin in the treatment of neuromuscular disorders report of the AANEM ad hoc committee
Author: Jinny Tavee MD (1), Thomas H. Brannagan III MD (2), Michael W. Lenihan MD (3), Sri Muppidi MD (4), Liz Kellermeyer BA, MLS (1), Peter D Donofrio MD, AANEM (5)
Affiliation: (1) National Jewish Health, Division of Neurology, Denver, Colorado, USA

(2) Vagelos College of Physicians and Surgeons, Neurological Institute, Columbia University, New York, New York, USA

(3) Adirondack Neurology Associates, PC, Glens Falls, New York, USA

(4) Stanford Neuroscience Health Center, Palo Alto, California, USA

(5) Neurology Clinic, Vanderbilt University, Nashville, Tennessee, USA
Journal: Muscle & Nerve
Citation: Tavee, J, Brannagan, TH, Lenihan, MW, et al. Updated consensus statement: Intravenous immunoglobulin in the treatment of neuromuscular disorders report of the AANEM ad hoc committee. Muscle & Nerve. 2023; 1-19. doi:10.1002/mus.27922
Publication Year and Month: 2023 07

Abstract: Intravenous immune globulin (IVIG) is an immune-modulating biologic therapy that is increasingly being used in neuromuscular disorders despite the paucity of high-quality evidence for various specific diseases. To address this, the AANEM created the 2009 consensus statement to provide guidance on the use of IVIG in neuromuscular disorders. Since then, there have been several randomized controlled trials for IVIG, a new FDA-approved indication for dermatomyositis and a revised classification system for myositis, prompting the AANEM to convene an ad hoc panel to update the existing guidelines.New recommendations based on an updated systemic review of the literature were categorized as Class I-IV. Based on Class I evidence, IVIG is recommended in the treatment of chronic inflammatory demyelinating polyneuropathy, Guillain-Barré Syndrome (GBS) in adults, multifocal motor neuropathy, dermatomyositis, stiff-person syndrome and myasthenia gravis exacerbations but not stable disease. Based on Class II evidence, IVIG is also recommended for Lambert-Eaton myasthenic syndrome and pediatric GBS. In contrast, based on Class I evidence, IVIG is not recommended for inclusion body myositis, post-polio syndrome, IgM paraproteinemic neuropathy and small fiber neuropathy that is idiopathic or associated with tri-sulfated heparin disaccharide or fibroblast growth factor receptor-3 autoantibodies. Although only Class IV evidence exists for IVIG use in necrotizing autoimmune myopathy, it should be considered for anti-hydroxy-3-methyl-glutaryl-coenzyme A reductase myositis given the risk of long-term disability. Insufficient evidence exists for the use of IVIG in Miller-Fisher syndrome, IgG and IgA paraproteinemic neuropathy, autonomic neuropathy, chronic autoimmune neuropathy, polymyositis, idiopathic brachial plexopathy and diabetic lumbosacral radiculoplexopathy.

Conclusions: IVIG is not recommended for Post-Polio Syndrome (PPS) as there is no long-term benefit.

Outcome of Research: More research required

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Title: Beneficial Effect of Medical Cannabis in the Treatment of a Pharmacoresistant Nausea Associated with a Somatoform Disorder in a Patient with Post-Polio Syndrome
Author: Markus Bleckwenn, Klaus Weckbecker, Sebastian Voss
Affiliation: Markus Bleckwenn  Institut für Hausarztmedizin der Medizinischen Fakultät der Universität Bonn
Klaus Weckbecker  Institut für Hausarztmedizin der Medizinischen Fakultät der Universität Bonn
Sebastian Voss  Institut für Hausarztmedizin der Medizinischen Fakultät der Universität Bonn
Journal: Dtsch Med Wochenschr.
Citation: 2018 Mar;143(5):344-348
Publication Year and Month: 2018 03

Abstract: HISTORY AND CLINICAL FINDINGS:
We report a 79-year-old patient with post-polio syndrome (PPS). In the course of this disease, recurrent upper abdominal pain and a therapy-resistant nausea developed without vomiting. In addition, the patient was limited by the combination of muscular weakness, obesity, dietary-treated diabetes and a degenerative spinal cord injury significantly in its mobility and physical capacity.

INVESTIGATIONS AND DIAGNOSIS:
Despite extensive diagnostics, no somatic cause could be found neither for the nausea nor for the upper abdominal pain. Due to the psychological stress within the scope of the PPS, the development of a somatoform autonomic function disorder of the upper gastrointestinal tract may have occurred.

TREATMENT AND COURSE:
Even under combination therapy of antiemetic and pain-modulating drugs, no adequate symptom control could be achieved. In the absence of therapy alternatives and increasing psychological strain the patient was prescribed medical cannabis. Under the therapy there was a relief of the nausea symptoms and decreased pain.

Conclusions: CONCLUSION:
Cannabis is a treatment option for treatment-resistant symptoms as part of a PPS.

Outcome of Research: More research required

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Title: Immunoglobulin treatment in post-polio syndrome: Identification of responders and non-responders
Author: Östlund G (1), Broman L, Werhagen L, Borg K
Affiliation: (1) Department of Rehabilitation Medicine, Danderyd University Hospital, Building 39, 3rd floor, SE-182 88 Stockholm, Sweden
Journal: Journal of Rehabilitation Medicine
Citation: J Rehabil Med. 2015 Aug 18. doi: 10.2340/16501977-1985
Publication Year and Month: 2015 08

Abstract: 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.

Conclusions: 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.

Outcome of Research: Effective

Availability of Paper: Other - see Comments.

Comments (if any): The full text will become open access 6 months after publication.

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Title: Intravenous immunoglobulin for postpolio syndrome: a systematic review and meta-analysis
Author: Huang Y-H (1), Chen H-C (2,3), Huang K-W (4,5,6), Chen P-C (1,7), Hu C-J (1,8), Tsai C-P (5,9), Tam K-W (2,10,11,12,13,14), Kuan Y-C (1,5,8,14)
Affiliation: (1) Department of Neurology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; (2) Center for Evidence-Based Health Care, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; (3) Department of Physical Medicine and Rehabilitation, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; (4) Department of Gastroenterology, College of Medicine, Taipei Medical University, Taipei, Taiwan; (5) Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; (6) Department of Gastroenterology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; (7) College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; (8) Department of Neurology, School of Medicine, Taipei Medical University, Taipei, Taiwan; (9) Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; (10) Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; (11) Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; (12) Division of General Surgery, Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan; (13) Center for Evidence-Based Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; (14) Taipei Medical University-Shuang Ho Hospital, 291 Zhongzheng Road, Zhonghe District, New Taipei City 23561, Taiwan
Journal: BioMed Central Neurology
Citation: BMC Neurology 2015, 15:39 doi:10.1186/s12883-015-0301-9
Publication Year and Month: 2015 03

Abstract: 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.

Conclusions: 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.

Outcome of Research: More research required

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Title: Immunoglobulin g for the treatment of chronic pain: report of an expert workshop
Author: Tamburin S (1), Borg K, Caro XJ, Jann S, Clark AJ, Magrinelli F, Sobue G, Werhagen L, Zanette G, Koike H, Späth PJ, Vincent A, Goebel A
Affiliation: (1) Department of Neurological and Movement Sciences, University of Verona, Verona, Verona, Italy
Journal: Pain Medicine
Citation: Pain Med. 2014 Jul;15(7):1072-82. doi: 10.1111/pme.12319
Publication Year and Month: 2014 07

Abstract: BACKGROUND: The treatment of chronic pain is still unsatisfactory. Despite the availability of different drugs, most patients with chronic pain do not receive satisfactory pain relief or report side effects. Converging evidence implicates involvement of the immune system in the pathogenesis of different types of nociceptive and neuropathic chronic pain.

DESIGN: At a workshop in Liverpool, UK (October 2012), experts presented evidence suggesting immunological involvement in chronic pain and recent data supporting the concept that the established immune-modulating drug, polyvalent immunoglobulin G (IgG), either given intravenously (IVIg) or subcutaneously (SCIg), may reduce pain in some peripheral neuropathies and a range of other pain disorders. Workshop's attendees discussed the practicalities of using IVIg and SCIg in these disorders, including indications, cost-effectiveness, and side effects.

RESULTS: IgG may reduce pain in a range of nociceptive and neuropathic chronic pain conditions, including diabetes mellitus, Sjögren's syndrome, fibromyalgia, complex regional pain syndrome, post-polio syndrome, and pain secondary to pathological autoantibodies.

Conclusions: IgG is a promising treatment in several chronic pain conditions. IgG is a relatively safe therapeutic strategy, with uncommon and mild side effects but high costs. Randomized, controlled trials and predictive tests are needed to better support the use of IgG for refractory chronic pain.

Outcome of Research: More research required

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Title: Efficacy of Modafinil on fatigue and excessive daytime sleepiness associated with neurological disorders: a systematic review and meta-analysis
Author: Sheng P, Hou L, Wang X, Wang X, Huang C, Yu M, Han X, Dong Y.
Affiliation: Department of Neurosurgery, Shanghai Institute of Neurosurgery, Military Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China
Journal: Public Library of Science
Citation: PLoS One. 2013 Dec 3;8(12):e81802. doi: 10.1371/journal.pone.0081802
Publication Year and Month: 2013 03

Abstract: BACKGROUND: Modafinil is a novel wake-promoting agent approved by the FDA ameliorating excessive daytime sleepiness (EDS) in three disorders: narcolepsy, shift work sleep disorder and obstructive sleep apnea. Existing trials of modafinil for fatigue and EDS associated with neurological disorders provided inconsistent results. This meta-analysis was aimed to assess drug safety and effects of modafinil on fatigue and EDS associated with neurological disorders.

METHODS: A comprehensive literature review was conducted in order to identify published studies assessing the effects of modafinil on fatigue and EDS associated with neurological disorders. Primary outcomes included fatigue and EDS. Secondary outcomes included depression and adverse effects.

FINDINGS: Ten randomized controlled trials were identified including 4 studies of Parkinson's disease (PD), 3 of multiple sclerosis (MS), 2 of traumatic brain injury (TBI) and 1 of post-polio syndrome (PPS). A total of 535 patients were enrolled. Our results suggested a therapeutic effect of modafinil on fatigue in TBI (MD -0.82 95% CI -1.54 - -0.11 p=0.02, I(2)=0%), while a beneficial effect of modafinil on fatigue was not confirmed in the pooled studies of PD or MS. Treatment results demonstrated a clear beneficial effect of modafinil on EDS in patients with PD (MD -2.45 95% CI -4.00 - -0.91 p=0.002 I(2)=14%), but not with MS and TBI. No difference was seen between modafinil and placebo treatments in patients with PPS. Modafinil seemed to have no therapeutic effect on depression. Adverse events were similar between modafinil and placebo groups except that more patients were found with insomnia and nausea in modafinil group.

Conclusions: Existing trials of modafinil for fatigue and EDS associated with PD, MS, TBI and PPS provided inconsistent results. The majority of the studies had small sample sizes. Modafinil is not yet sufficient to be recommended for these medical conditions until solid data are available.

Outcome of Research: More research required.

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Title: Intravenous immunoglobulin treatment of the post-polio syndrome: sustained effects on quality of life variables and cytokine expression after one year follow up
Author: Gonzalez H (1), Khademi M (2), Borg K (1), Olsson T (2)
Affiliation: (1) Division of Rehabilitation Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, blg 39, fl 3, S-192 88, Stockholm, Sweden; (2) Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
Journal: Journal of Neuroinflammation
Citation: Journal of Neuroinflammation. 2012; 9: 167. doi: 10.1186/1742-2094-9-167
Publication Year and Month: 2012 07

Abstract: 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, TGFβ, 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.

Outcome of Research: More research required.

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Title: IVIG treatment in post-polio patients: evaluation of responders
Author: Ostlund G (1), Broman L, Werhagen L, Borg K
Affiliation: (1) Division of Rehabilitation Medicine, Department of Clinical Sciences, Karolinska Institute, Danderyd Hospital, Building 39, 3rd floor, 182 88 Stockholm, Sweden
Journal: Journal of Neurology
Citation: J Neurol. 2012 Dec;259(12):2571-8. doi: 10.1007/s00415-012-6538-y. Epub 2012 May 17
Publication Year and Month: 2012 05

Abstract: 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.

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Outcome of Research: Effective

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Title: Effect of intravenous immunoglobulin on pain in patients with post-polio syndrome
Author: Werhagen L, Borg K
Affiliation: Department of Clinical Sciences, Division of Rehabilitation Medicine, Karolinska Institutet Danderyds Hospital, Stockholm, Sweden
Journal: Journal of Rehabilitation Medicine
Citation: J Rehabil Med. 2011 Nov;43(11):1038-40. doi: 10.2340/16501977-0884.
Publication Year and Month: 2011 11

Abstract: 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.

Conclusions: 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.

Outcome of Research: Not applicable.

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Title: Response of postpoliomyelitis patients to bisphosphonate treatment
Author: Alvarez A (1), Kremer R, Weiss DR, Benedetti A, Haziza M, Trojan DA
Affiliation: (1) Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University Health Centre, McGill University, Montreal, QC, Canada
Journal: PM&R: The Journal of Injury, Function, and Rehabilitation
Citation: PM R. 2010 Dec;2(12):1094-103. doi: 10.1016/j.pmrj.2010.08.009.
Publication Year and Month: 2010 12

Abstract: 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.

Outcome of Research: Effective

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Title: Effect of intravenous immunoglobulin in patients with post-polio syndrome - an uncontrolled pilot study
Author: Kaponides G, Gonzalez H, Olsson T, Borg K
Affiliation: Department of Public Health Sciences, Division of Rehabilitation Medicine, Stockholm, Sweden - [email protected]

Journal: Journal of Rehabilitation Medicine
Citation: J Rehabil Med. 2006 Mar;38(2):138-40
Publication Year and Month: 2006 03

Abstract: 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.

Conclusions: 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.

Outcome of Research: More research required.

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Title: Prior poliomyelitis – IVIg treatment reduces proinflammatory cytokine production
Author: Gonzalez H, Khademi M, Andersson M, Piehl F, Wallström E, Borg K, Olsson T
Affiliation: Department of Neuroimmunology Unit, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden – [email protected]
Journal: Journal of Neuroimmunology
Citation: J Neuroimmunol. 2004 May; 150(1-2):139-44
Publication Year and Month: 2004 05

Abstract: 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.

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Title: Pyridostigmine in postpolio syndrome: no decline in fatigue and limited functional improvement
Author: Horemans H (1), Nollet F (1), Beelen A (1), Drost G (2), Stegeman D (2), Zwarts M (2), Bussmann J (3), de Visser M (4), Lankhorst G (1)
Affiliation: (1) Department of Rehabilitation Medicine, VU University Medical Centre, Amsterdam, Netherlands; (2) Department of Clinical Neurophysiology, University Medical Centre Nijmegen, Netherlands; (3) Department of Rehabilitation Medicine, Erasmus MC, University Medical Centre Rotterdam, Netherlands; (4) Department of Neurology, Academic Medical Centre, University of Amsterdam, Netherlands
Journal: Journal of Neurology, Neurosurgery and Psychiatry
Citation: J Neurol Neurosurg Psychiatry 2003;74:1655-1661 doi:10.1136/jnnp.74.12.1655
Publication Year and Month: 2003 12

Abstract: OBJECTIVES: To investigate the effect of pyridostigmine on fatigue, physical performance, and muscle function in subjects with postpoliomyelitis syndrome.

METHODS: 67 subjects with increased fatigue and new weakness in one quadriceps muscle showing neuromuscular transmission defects, were included in a randomised, double blind, placebo controlled trial of 60 mg pyridostigmine four times a day for 14 weeks. Primary outcome was fatigue (on the "energy" category of the Nottingham health profile). Secondary outcomes included two minute walking distance and quadriceps strength and jitter. Motor unit size of the quadriceps was studied as a potential effect modifier. The primary data analysis compared the changes from baseline in the outcomes in the last week of treatment between groups.

RESULTS: 31 subjects treated with pyridostigmine and 31 subjects treated with placebo completed the trial. No significant effect of pyridostigmine was found on fatigue. The walking distance improved more in the pyridostigmine group than in the placebo group (by 7.2 m (6.0%); p<0.01). Subgroup analysis showed that a significant improvement in walking performance was only found in subjects with normal sized motor units. Quadriceps strength improved more in the pyridostigmine group than in the placebo group (by 6.7 Nm (7.2%); p = 0.15). No effect of pyridostigmine was found on jitter.

Conclusions: Pyridostigmine in the prescribed dose did not reduce fatigue in subjects with postpoliomyelitis syndrome. However, it may have a limited beneficial effect on physical performance, especially in subjects with neuromuscular transmission defects in normal sized motor units.

Outcome of Research: More research required.

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Title: Use of Medication in People with Post-Polio Syndrome
Author: Susan Perlman, MD
Affiliation: University of California Los Angeles (UCLA)
Journal: NEW - PUT DETAILS IN CITATION FIELD
Citation: Polio Network News (Now called Polio-Polio Health)

WINTER 1999, VOL. 15, No. 1
Publication Year and Month: 1999 12

Abstract: Until we better understand the causes of post -polio syndrome, we will have no curative medication. At best, we can use medication to treat the symptoms and to improve the quality of life, and we can avoid using medication that could make the symptoms worse. Certain other diseases (elevated blood cholesterol levels, high blood pressure, heart disease, and cancers) require use of medications with side effects that can exacerbate symptoms of post-polio syndrome. These should be used, but with careful monitoring of the polio survivor's functioning.

Conclusions: Polio survivors and their physicians should scrutinize all medications - current and newly added - used to treat various medical problems to be assured that related conditions, such as fibromyalgia, elevated cholesterol, high blood pressure, etc., are appropriately treated, but with minimal effect on polio-related symptoms.

Outcome of Research: Not applicable

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Title: Bromocriptine In The Treatment Of Post-Polio Fatigue: A pilot study with implications for the pathophysiology of fatigue
Author: Richard L. Bruno, Ph.D., Jerald R. Zimmerman, M.D., Susan Creange, M.A., Todd Lewis, Ph.D., Terry Molzen, M.A., and Nancy M. Frick, M.Div, Lh.D.
Affiliation: Post-Polio Rehabilitation and Research Service; Kessler Institute for Rehabilitation, Department of Physical Medicine and Rehabilitation; UMDNJ/New Jersey Medical School, Harvest Center; Hackensack, New Jersey
Journal: American Journal of Physical Medicine & Rehabilitation
Citation: American Journal of Physical Medicine and Rehabilitation, 1997 (in press)
Publication Year and Month: 1997

Abstract: Objective: Determine the effectiveness of bromocriptine in the treatment of severe and disabling post-polio fatigue.
Design: Placebo-controlled drug trial in a pilot series of patients.
Setting: Outpatient rehabilitation hospital.
Patients: Of 83 patients without comorbidities who completed treatment with the Post-Polio Service, 5 of 8 patients who had paralytic polio and continued to report moderate to severe daily fatigue after complying with conservative treatments for post-polio fatigue agreed to be studied.
Intervention: Placebo was given for four weeks followed by increasing doses of bromocriptine mesylate (Parlodel®) administered at noon for 28 days reaching a total dose of 12.5 mg/day.
Main Outcome Measures: Daily logs of subjective fatigue and cognitive difficulties.
Results: Three of the subjects reported symptom improvement on bromocriptine but not on placebo. However, all subjects experienced nausea on bromocriptine, likely eliminating blinding. Drug responders had clinically impaired performance on neuropsychological tests of attention and information processing speed. Logged daily difficulty with attention, cognition, word finding memory, staying awake and fatigue on awakening were significantly negatively correlated with days on bromocriptine, but not with days on placebo, in drug responders.
Conclusions: A double-blind, placebo-controlled multicenter study will be needed to confirm bromocriptine's effectiveness in treating attentionally-impaired polio survivors whose severe and disabling fatigue does not responded to conservative treatment.

Conclusions: This pilot study of severely fatigued polio survivors suggests that bromocriptine may be of use in the treatment of post-polio fatigue that has not responded to conservative therapies. However, the small sample size and methodological limitations make this suggestion merely tentative. Since nausea was universally experienced, all subjects may have realized that they were receiving active drug and were thereby biased toward reporting reductions in symptoms. The percentage of days on which side effects were experienced on bromocriptine was higher in the responders (48%) than non-responders (34%). Although the placebo phase was not compromised, the bromocriptine phase of the study may have been as unblinded as an open-label drug trial. Reductions in morning fatigue and fatigue-related cognitive symptoms as the dose of bromocriptine increased were not paralleled by drug-related improvements in neuropsychologic test scores, most likely since the same form of the tests was administered on placebo and on bromocriptine. Subjects repeatedly taking the same test would be expected to demonstrate a learning effect and have their test scores improve. This has been seen even in polio survivors with severe fatigue who were repeatedly administered the same neuropsychologic tests over the course of several hours [4] It was also surprising that drug responders noticed no reduction in fatigue during the afternoon, since bromocriptine was administered at noon so that a peak blood level would be reached at 3:00 PM when many polio survivors report hitting an afternoon "wall" of fatigue. Since the pharmacokinetics of bromocriptine could differ from the time course of its pharmacological effect, as is seen with D2 receptor antagonists, moving the dose of drug to before sleep or upon awakening may prolong any beneficial effect of the drug into the afternoon. [18]

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Title: An Open Trial of Pyridostigmine in Post-poliomyelitis Syndrome
Author: Daria A. Trojan and Neil R. Cashman


Affiliation: From the Department of Neurology, Montreal Neurological Institute and Hospital, McGill University, Montreal.
Journal:
Citation: The Canadian Journal of Neurological Sciences Volume 22, No. 3 August 1995 223-227
Publication Year and Month: 1995 08

Abstract: Background: One of the major symptoms of postpoliomyelitis syndrome (PPS) is disabling generalized fatigue. Subjects with PPS also report muscle fatiguability and display electrophysiologic evidence of anticholinesterase-responsive neuromuscular junction transmission defects, suggesting that anticholinesterase therapy may be useful in the management of disabling fatigue. Methods: We initiated an open trial of the oral anticholinesterase pyridostigmine, up to 180 mg per day, in 27 PPS patients with generalized fatigue and muscle fatiguability. Response to Pyridostigmine was assessed with the Hare fatigue scale, the modified Barthel index for activities of daily living, and a modified Klingman mobility index. Results: Two patients could not tolerate the medication. After one month of therapy, 16 patients (64%) reported a reduction in fatigue on the Hare fatigue scale; three of 16 showed improvement on the modified Barthel index for activities of daily living, and two of 16 experienced improvement on a modified Klingman mobility index. Pyridostigmine responders were significantly more fatigued than non-responders on the pre-treatment Hare score, but were not significantly different with regard to age, sex, age at acute poliomyelitis, or severity of acute poliomyelitis. Conclusions: Pyridostigmine may be useful in the management of fatigue in selected patients with PPS. Response to pyridostigmine may be predicted by severity of pre-treatment fatigue.

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Outcome of Research: Not applicable

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Title: Anticholinesterases in Post-Poliomyelitis Syndrome
Author: Daria A. Trojan and Neil R. Cashman
Affiliation: Department of Neurology, Montreal Neurological Institute and Hospital, McGill University
Journal: Annals of the New York Academy of Sciences
Citation: Reprinted from The Post-Polio Syndrome: Advances in the Pathogenesis and Treatment, Volume 753 of the Annals of the New York Academy of Sciences, May 25, 1995
Publication Year and Month: 1995 05

Abstract: New weakness, fatigue, and pain after decades of functional stability in those who have recovered from acute paralytic poliomyelitis constitutes post-poliomyelitis syndrome (PPS).[1-7] The cause of PPS is unknown, but it is thought to be due to a distal degeneration of enlarged post-polio motor units produced by terminal axonal sprouting during the recovery process after acute polio.[8,9] The symptoms of weakness and fatigue may be a direct result of this distal motor unit degeneration;[2,7-13] however, it is presently unclear how pain relates to disease of the motor unit. PPS is a slowly progressive motor neuron disease for which there is currently no specific treatment.[4]

Conclusions: Our studies indicate that a proportion of fatigued post-poliomyelitis patients can experience an amelioration of defects in neuromuscular junction transmission and of clinical fatigue with anticholinesterases. Because S-SFEMG response was significantly associated with clinical response to anticholinesterases, fatigue in PPS may be caused by defects in neuromuscular junction transmission in a proportion of patients. Preliminary studies in a small group of patients indicate that anticholinesterases may produce their clinical neuromuscular response by producing an increase in isokinetic strength in a proportion of patients. Our studies provide a physiological rationale for the use of anticholinesterases in PPS for the symptom of fatigue. However, further randomized, placebo-controlled, double-blinded trials are needed to establish definitively the benefits and risks of these agents.

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Title: Anticholinesterase-responsive neuromuscular junction transmission defects in post-poliomyelitis fatigue
Author: Daria A. Trojan, Daniel Gendron and Neil R. Cashman
Affiliation: Department of Neurology, McGill University, Montreal Neurological Institute and Hospital
Journal: Journal of the Neurological Sciences
Citation: 114 (1993) 170-177
Publication Year and Month: 1992 08

Abstract: Disabling generalized fatigue and muscle fatiguability are common features of post-poliomyelitis syndrome (PPS). In 17 fatigued PPS patients, we measured jitter on stimulation single-fiber electromyography (S-SFEMG) for at least 3.5 min before and after i.v. injection of 10 mg edrophonium. We observed reduction in jitter (defined as a significant difference in jitter means before and after edrophonium, unpaired t-test P < 0.05) in 7 patients, no change in 8, and a significant increase in 2 patients. Blinded to their edrophonium results, the 17 patients were treated with pyridostigmine 180 mg/day for 1 month, with a subjective improvement of fatigue in 9 patients, and with a significant reduction in mean Hare fatigue scores in the entire group of 17 patients (pre = 2.71, and post = 1.71; Wilcoxan signed rank sum test, P < 0.05). Edrophonium-induced reduction of jitter on S-SFEMG was significantly associated with pyridostigmine-induced subjective improvement of fatigue (Fisher's exact test, P < 0.04). A significant reduction in fatigue with pyridostigmine was observed only in the 7 patients who experienced a significant reduction in jitter with edrophonium (Wilcoxan signed rank sum test, P = 0.03). In addition, the 9 pyridostigmine responders experienced a significant reduction in jitter means pre- and post-edrophonium (100% vs. 88%, Bonferroni corrected, P < 0.01). We conclude that neuromuscular transmission as measured by jitter on S-SFEMG can improve with edrophonium in a proportion of PPS patients, and that generalized fatigue and muscle fatiguability in some patients with PPS may be due to anticholinesterase-responsive NMJ transmission defects.

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Outcome of Research: Not applicable

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