Progression of Neuropathic Pain after Acute Spinal Cord Injury: A Meta-Analysis and Framework for Clinical Trials.

The translation of therapeutic interventions to humans with spinal cord injury with the goal of promoting growth and repair in the central nervous system could, inadvertently, drive mechanisms associated with the development of neuropathic pain. A framework is needed to evaluate the probability that a therapeutic intervention for acute spinal cord injury modifies the progression of neuropathic pain. We analyzed a large, longitudinal dataset from the European Multi-Center Study about Spinal Cord Injury (EMSCI) and compared these observations with a previously published Swedish/Danish cohort. A meta-analysis was performed to produce aggregate estimates for the transition period between 1-6 months and the transition period between 1-12 months after injury. A secondary analysis used logistic regression to explore associations between the progression of neuropathic pain and demographics, pain characteristics, and injury characteristics. For overall neuropathic pain, 72% presenting with pain symptoms at one month reported persisting symptoms at six months, and 23% who did not have neuropathic pain at one month later had it develop. From 1-12 months, there was a similar likelihood of pain persisting (69%) and slightly higher rate of pain developing (36%). Characteristics that were significantly associated with the progression of pain included age and sensory and motor preservation. We provide historical benchmarks for estimating the progression of neuropathic pain during the first year after acute SCI. This information will be useful for comparison and evaluating safety during early phase acute spinal cord injury trials.

Survey of young patients with polio and a foreign background at a Swedish post-polio outpatient clinic.

Nowadays, polio survivors aged under 60 years are non-native Swedes which pose new aspects and challenges to a post-polio outpatient clinic. To analyze the medical data, walking aids, occupational, and family situation in non-native polio survivors aged less than 60 years at a Swedish post-polio outpatient clinic. Retrospective data analysis. Data were retrieved from medical records at the post-polio outpatient clinic. Actual age, age at acute polio infection, walking capacity, pain, concomitant diseases, working and family situation, and ethnical origin were analyzed. Data are presented in numbers and percentage. 153 patients were included. Mean age was 45 (17-60) years, and mean age at acute polio infection was 2 (0-12) years. Paresis of the lower extremities was the most common disability. 10 % were wheelchair dependent. Pain occurred in 70 % with a mean intensity of 55 measured with the visual analog scale. Hypertension was the most common concomitant disease. Half of the polio survivors were working at least part time, and roughly half were singles. Data were comparable with data earlier published in Swedish native polio survivors. Non-native polio survivors aged under 60 years showed similarities in age at acute polio infection, paresis, prevalence, and intensity of pain when compared with native Swedish polio survivors. They were, however, younger, and were less often working and married/cohabitants than native Swedish polio survivors. The results of this study underline the importance of social and vocational rehabilitation tailoring rehabilitation suitable for polio survivors with a foreign background.

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

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

Immunoglobulin g for the treatment of chronic pain: report of an expert workshop.

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.

Phenotypes and predictors of pain following traumatic spinal cord injury: a prospective study.

UNLABELLED: Pain is a serious consequence of spinal cord injury (SCI). Our aim was to investigate the temporal aspects of different types of pain following traumatic SCI and to determine possible predictors of neuropathic pain. Prospective data on 90 patients were collected at 1, 6, and 12 months after traumatic SCI. The patients completed questionnaires on pain severity, descriptors, and impact and underwent clinical examination with bedside sensory testing. Eighty-eight patients completed the 12-month follow-up. Approximately 80% of patients reported any type of pain at all 3 time points. Neuropathic pain related to SCI increased over time, and musculoskeletal pain decreased slightly, with both being present in 59% of patients at 12 months; other neuropathic pain not related to SCI and visceral pain were present in 1 to 3%. At-level neuropathic pain present at 1 month resolved in 45% and below-level pain resolved in 33%. Early (1 month) sensory hypersensitivity (particularly cold-evoked dysesthesia) was a predictor for the development of below-level, but not at-level, SCI pain at 12 months. In conclusion, the present study demonstrates phenotypical differences between at-level and below-level SCI pain, which is important for future studies aiming to uncover underlying pain mechanisms. PERSPECTIVE: The finding that early sensory hypersensitivity predicts later onset of below-level central neuropathic pain may help to identify patients at risk of developing neuropathic pain conditions after traumatic spinal cord injury. Information about onset of pain may help to identify different phenotypes in neuropathic pain conditions.

Impact of pain on quality of life in patients with post-polio syndrome.

OBJECTIVE: Post-polio syndrome is a neurological disorder occurring several years after an acute polio infection. The main symptoms are increased muscular weakness and atrophy, fatigue and pain. Pain is present more often in younger individuals and in females and, according to the visual analogue scale (VAS), the intensity of pain is relatively high. The aim of the present study was to analyse the impact of pain on quality of life in patients with post-polio syndrome. DESIGN: Transversal study. PATIENTS AND METHODS: Patients with post-polio syndrome underwent a thorough neurological and general examination. They were interviewed about the presence and intensity of pain during the previous 3 months, then completed the quality of life inventory Short-Form 36 (SF-36), which included questions about pain during the previous 4 weeks, and rated their pain intensity during the previous 24 h according to the VAS. RESULTS: Seventy-seven of the patients (68%) experienced pain at the examination. Pain was found to have a significant impact on the SF-36 subdomains Vitality and General health. A correlation was found between pain during the previous 3 months, the previous 4 weeks, and the previous 24 h. DISCUSSION: Pain is common in patients with post-polio syndrome. Although patients have a high mean VAS score the pain only affects quality of life for Vitality and General Health, but not for other physical and mental domains.

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

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

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

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

Post-polio syndrome, spinal cord injury and statin myopathy: double trouble or incorrect diagnosis? Two case reports.

OBJECTIVE: To discuss the importance of a thorough clinical examination and evaluation of symptoms in upper and lower motor neurone lesions. DESIGN: Case report. METHODS: Post-polio outpatient clinic, Danderyds University Hospital, Stockholm, Sweden. We describe here two patients with a past history of poliomyelitis, who were experiencing increasing muscular weakness. Clinical evaluation led to diagnoses of spinal cord injury and statin myopathy, respectively. CONCLUSION: In order to make a correct diagnosis it is essential to distinguish between lower and upper motor neurone lesions. In the case of a lower motor neurone disorder a neurophysiological examination is necessary for a correct diagnosis, and is a prerequisite for adequate treatment and rehabilitation.

Pain, especially neuropathic pain, in adults with spina bifida, and its relation to age, neurological level, completeness, gender and hydrocephalus.

STUDY DESIGN: Cohort study. OBJECTIVE: To investigate the prevalence of neuropathic pain in adults with spina bifida, to study the relationship between neuropathic pain, age at examination, gender, completeness of injury, neurological level and presence of hydrocephalus. METHODS: A total of 110 patients with spina bifida who visited the spinal cord injury outpatient clinic Spinalis were included. At the yearly check-up they underwent examination by a physiotherapist and a neurologist and were interviewed about pain character, temporal profile and localization. The patients were divided into 2 groups; spina bifida with (n = 57) and without hydrocephalus (n = 53). Pain was classified as neuropathic when it was in an area of decreased sensibility and had no correlation to movement and/or inflammatory signs. Results were analysed by chi2 analysis and Fisher's exact test. RESULTS: Twenty-two patients (20%) experienced nociceptive pain. Neuropathic pain was present in 11/110 (10%) patients, of these 62% experienced below level neuropathic pain. Neuropathic pain was present in 13% of male patients and 7% of female patients, 12% of patients with a lumbar level and 10% of patients with a thoracic level. Neuropathic pain was present in 9% of patients with a complete spinal cord injury, 14% of those with an incomplete spinal cord injury, 1,7% with hydrocephalus and 19% without hydrocephalus. CONCLUSION: The results suggest that neuropathic pain is present in spina bifida. Careful analysis and classification of a patient's pain is clinically important. Neuropathic pain is more common in patients without hydrocephalus and in older patients. Presence of neuropathic pain was not related to gender, completeness of injury, or neurological level.

Analysis of long-standing nociceptive and neuropathic pain in patients with post-polio syndrome.

The purpose of this study was to analyze pain, both nociceptive and neuropathic, in patients with post-polio syndrome (PPS) and relate the pain to age at the initial polio infection, age at examination, to gender and disability. The study was conducted in a university hospital department. Patients with PPS were interviewed at their regular visits about pain, its character, intensity and localization. A clinical examination, including a thorough neurological examination, was performed. Data included age at time of polio infection, age at time of examination and gender. Pain intensity was measured with the VAS-scale and walking capability by the WISCI-scale. One hundred sixty-three (88 women, 75 men) patients were included in the study. Pain was present in 109 (67%). Pain was more frequently reported by women (82%) than by men (49%). 96 patients experienced nociceptive pain, 10 patients both neuropathic and nociceptive pain and three experienced pure neuropathic pain. Half of the patients with pain experienced pain in more than one body region. When neuropathic pain was present, another additional neurological disorder was diagnosed. Pain was more often found in younger patients (around 70%) than in older patients (around 50%). In summary pain is common in patients with PPS and most patients experienced nociceptive pain. Women have pain more often than men. Older patients experience pain more seldom than younger patients. Age at time of primary polio infection is important for the development of pain. When neuropathic pain is present, it is important to proceed with neurological examination to find an adequate diagnosis.

Spasticity and bone density after a spinal cord injury.

STUDY DESIGN: Descriptive, cross-sectional study. OBJECTIVE: To assess the relationship between spasticity and bone mineral density in the lower extremities in individuals with a motor complete spinal cord injury. METHODS: Eighteen individuals, matched for time since injury, gender, and age, were included in the study. Nine men had severe spasticity, and 9 men had spasticity that was either mild or not present. Comparisons regarding bone mineral density were made using dual energy X-ray absorptiometry. Regions of interest measured were total leg, pelvis, femoral neck and total hip. Between-group differences regarding fat and lean tissue were analysed. RESULTS: Background data, such as weight, height, standing and exercising habits, smoking and alcohol use, were similar in both groups. There was no difference between the groups regarding bone mineral density. All of the participants presented with osteoporosis or osteopaenia values at the hips. Participants with severe spasticity had larger muscle volume than those with none or mild spasticity. No correlations between bone mineral density and body composition with age or time since injury were seen. CONCLUSION: No difference in bone mineral density dependent on spasticity was detected in this study, but all included participants showed osteopaenia or osteoporosis at the hip, but not in full body values. Individuals with severe spasticity had greater muscle mass compared with those with no or mild spasticity.

Pain in a Swedish spinal cord injury population.

OBJECTIVE: To describe pain and associated variables in a prevalence group of persons with a sustained spinal cord injury (SCI) in the Swedish capital and its surroundings. SETTING: Spinalis SCI Unit (outpatient clinic), Stockholm, Sweden. DESIGN: Assessment over a 12-month period in a yearly health control. SUBJECTS: Four hundred and fifty-six SCI patients. RESULTS: Two hundred and ninety-one out of 456 SCI patients (63.7%) suffered from pain, and in 45.7% of these it was classified as being neurogenic. Aching pain was the most used descriptor (38.5%). The onset of pain was commonly within three months (73.5%). In 70.4% of patients pain occurred below the level of the lesion. Most patients identified pain as coming from one (55.0%) or two (28.2%) body regions. Rating of the general pain intensity on a visual analogue scale (VAS) was 46 out of 100 and rating of the worst pain intensity was 78 out of 100. Ninety-four out of 276 patients (32.3%) considered that their quality of life was significantly affected by pain. CONCLUSION: Pain was most common in patients with incomplete lesions (ASIA impairment grade D) and there was a correlation between pain and higher mean age at injury and between pain and female gender.