Pain In Cerebral Palsy Research Articles

Assessment of spasticity-related pain in cerebral palsy and the efficacy of its treatment with incobotulinumtoxin A (literature review)

Pain in cerebral palsy (CP) occurs in 30–60% of cases. Pain associated with spasticity (PAS) is one of the most common causes of pain syndrome in cerebral palsy, which is often associated with impairment of the child’s daily life. Recently, more studies have been published on the use of botulinum toxin type A preparations to control PAS. The review article presents the results of a special pooled analysis of data on the analgesic effect of the drug Xeomin (incobotulinumtoxin A) in the treatment of PAS based on data from three phase III multicentre prospective comparative studies in children and adolescents with spastic forms of cerebral palsy. To evaluate PAS and the effect of incobotulinumtoxin A on it, a special questionnaire (Questionnaire on Pain caused by Spasticity, QPS) was used in these studies. The QPS reflects the child's pain associated with spasticity, which can be observed at rest and during various activities of the child.It was found that the children included in these studies reported the presence of PAS in more than 80% of cases with lower limb spasticity and in almost 70% of cases with upper limb spasticity. Parents or caregivers of these children observed an even higher prevalence of PAS. The use of incobotulinumtoxin A showed not only a pronounced antispastic effect, but also a significant reduction in the frequency and intensity of PAS in children and adolescents with cerebral palsy during normal daily activities, and during strenuous activities such as physical exercise and rehabilitation treatment. With repeated injection cycles of incobotulinumtoxin A, PAS continued to decrease, ensuring a reduction in pain even when physical activity became more difficult. Nowadays, injections with incobotulinumtoxin A can be considered as a routine therapeutic approach for the treatment of spasticity and increased muscle tone, but it is certainly an innovative method for effective pain reduction in cerebral palsy patients with lower and upper limb spasticity accompanied by PAS.

A First Clinical Trial on Botulinum Toxin-A for Chronic Muscle-Related Pain in Cerebral Palsy.

Objective: To test if botulinum toxin-A (BoNT-A) is effective in reducing chronic muscle-related pain in adults with spastic cerebral palsy (CP), as compared to placebo.Design: A single-center, double-blind, parallel, randomized placebo-controlled trial. The design included an interim analysis to allow for confirmatory analysis, as well as pilot study outcomes.Setting: Tertiary university hospital.Participants: Adults with spastic CP and chronic pain associated with spastic muscle(s).Intervention: Treatment was one session of electromyographically guided intramuscular injections of either BoNT-A or placebo normosaline.Main Study Outcomes: The primary outcome was the proportion who achieved a reduction of pain intensity of two or more steps on the Numerical Rating Scale 6 weeks after treatment.Results: Fifty individuals were screened for eligibility, of whom 16 were included (10 female, 6 male, mean age = 32 years, SD = 13.3 years). The randomization yielded eight participants per treatment arm, and all completed the study as randomized. The study was stopped at the interim analysis due to a low probability, under a preset threshold, of a positive primary outcome. Four individuals were treatment responders in the BoNT-A group for the primary outcome compared to five responders in the placebo group (p = 1.000). Adverse events were mild to moderate. In exploratory analysis, the BoNT-A group had a trend of continuing reduction of pain at the last follow-up, after the primary endpoint.Conclusions: This study did not find evidence that BoNT-A was superior to placebo at the desired effect size (number needed to treat of 2.5) at 6 weeks after treatment.Trial registration:ClinicalTrials.gov: NCT02434549

Recognizing chronic pain in cerebral palsy.

This commentary is on the original article by McKinnon et al. on pages 1293–1300 of this issue.

(171) Evaluating the Pain and Discomfort Scale to Assess Spasticity-Related Pain in Cerebral Palsy

Assessing pain among individuals with communicative impairments and developmental disabilities is a clinical challenge. In this preliminary study, we addressed, in part, the issue of the association between chronic pain and spasticity in cerebral palsy (CP). Specifically, we evaluated the measurement performance of a proxy-reported spasticity rating scale (Multiple Sclerosis Spasticity Scale–MSSS) and the feasibility of a range of motion examination procedure (Pain Examination Procedure–PEP) using direct-observation to code behavioral reactivity during the exam (Pain and Discomfort Scale – PADS). Fifteen individuals with CP (mean age=10.9 years, range=6.2-17.2 years; GMFCS=3-5; male=46%) were evaluated pre- (T1) and post- (T2) intrathecal baclofen pump (ITB) surgical implant to treat spasticity. The PEP protocol was successfully completed for all participants in the clinical setting. Cronbach's alpha for the MSSS was 0.96. PADS change scores (T1 to T2) were significantly correlated with MSSS change scores (r=0.80, p=0.006). The strong positive correlation suggests the PADS/PEP protocol may be measuring spasticity-related pain and discomfort, providing initial construct validity evidence between an objective/direct and subjective/indirect assessment method for pain and spasticity in CP. T1 PADS scores were also highly positively correlated with both PADS change and MSSS change scores (r=-0.72, p=0.006; r=-0.85, p=0.002), providing preliminary evidence of the predictive utility of a pre-ITB surgery PADS/PEP protocol. This was not a random sample, therefore the results are specific to the sample and may not hold for the population of individuals living with CP. Given the absence of self-report, we cannot be certain and do not claim to have measured the pain experience of the individuals in the sample. Future work should continue to examine the PADS as a potential pain behavior assessment tool to provide a direct assessment option for the study of pain among individuals with CP and related developmental disabilities. Supported by NICHD Grant No. 73126

(184) Feasibility of a Contact Heat Evoked Potentials Approach in Female Patients with Cerebral Palsy

Our scientific understanding of chronic pain in cerebral palsy (CP) in relation to somatosensory function is limited. There is some evidence that some individuals with CP have reduced sensitivity for non-painful touch, increased sensitivity to painful touch (pressure), and enhanced pain evoked potentials compared to controls. The goal of this pilot study was to establish initial feasibility of a contact heat approach for detecting and measuring heat-evoked potentials in CP. To reduce variance associated with gender differences, we recruited a purposeful sample of females only for the pilot (N=20, 50% CP, mean age = 20.6, range = 16-22). Six trials of 20 heat stimuli were applied to the target dermatomes for the distal volar forearm (C5 dermatome) and the distal lateral malleolus (L5 dermatome). An 11-point pain numeric rating scale (NRS) was used after each stimulus trial. Overall, initial results indicated the approach was feasible in the CP sample. All participants completed the protocol, with the exception of one CP participant. Small sample size notwithstanding, for descriptive purposes evoked potential latencies and amplitudes did not correlate with NRS ratings at either stimulation site. This is consistent with prior published findings for individuals with and without developmental disability. The NRS ratings were more variable in the CP group. A z-score proportions test was significant for arms (Z = 1.95, p

Preoperative treatment of spasticity with botulinum neurotoxin A to reduce pain in cerebral palsy: is it worthwhile?

This commentary is on the original article by Will et al. on pages 1074–1079 of this issue.

A population-based data-linkage study of prescribed pain medications dispensed to persons with cerebral palsy

BackgroundPopulation-based surveys to investigate pain in cerebral palsy (CP) can be costly and results limited by recruitment bias, recall issues, and differences between self-reports and parental accounts. Secondary data analysis may provide a cost-effective alternative to study this issue and its impact in this population.
 ObjectiveInvestigate factors associated with dispensing of prescribed pain medications for those with CP.
 MethodsData from the Northern Ireland CP Register were linked with the Enhanced Prescribing Database, a database of prescriptions dispensed by community pharmacies, to investigate dispensing of prescribed pain medications (non-steroidal antiinflammatories, opioids, non-opioids) between 2010 and 2014. The sample comprised 1,430 individuals with CP and 699,645 with no diagnosis of CP, born 1981-2008.
 FindingsPain medications were dispensed to 61% of the CP population and 51% of the general population (p < 0.05). Individuals with CP displayed increased odds of receiving opioid analgesics compared to the general population (OR 2.81, 95%CI 2.32 to 3.40). Among those with CP, likelihood of being dispensed prescribed pain medications was greater amongst females (OR 1.34, 95%CI 1.06 to 1.70), younger age individuals (OR 1.60, 95%CI 1.02 to 2.51), those with reduced motor function (GMFCS V: OR 2.60, 95%CI 1.52 to 4.47), having seizures (OR 2.55, 95%CI 1.68 to 3.87), and living in deprived areas (OR 2.06, 95%CI 1.41 to 3.24).
 ConclusionDispensing of pain medications in CP is associated with clinical factors, though even after adjustment for these, living in deprived areas influences uptake of pain medication.

Pathophysiology of chronic pain in cerebral palsy: implications for pharmacological treatment and research.

Pain conditions in cerebral palsy have differing mechanisms and will not respond to the same treatments. Novel analgesics under development include inhibitors of ion channels, nerve growth factor, and calcitonin gene-related peptide.

Pain in cerebral palsy: a neglected comorbidity.

This commentary is on the original article by Westbom et al. on pages 858–863 of this issue.

Associations between recurrent musculoskeletal pain and visits to the family doctor (GP) and specialist multi-professional team in 74 Norwegian youth with cerebral palsy.

Musculoskeletal pain in cerebral palsy (CP) is common, but probably undertreated. The aim of the study was to explore if recurrent musculoskeletal pain (RMP) related to the CP condition was associated with visits to the family doctor [general practitioner (GP)] and specialist habilitation centre in youth with CP. Seventy-four youth with CP (mean age 16.5 years, 40 boys) from the same geographical area were assessed by clinical examination, semi-structured interview on pain (adolescent and parent together), the two questions on pain from the Child Health Questionnaire (parents only) and a structured interview on health care services. Gross Motor Function Classification System was level I 39%, level II 23%, level III 8% and levels IV and V 30%. Thirty-five participants (47%) had visited their GP last year, and 49 (66%) had visited the specialist habilitation centre. The presence of RMP (n = 58; 78%) was not significantly associated with having visited the GP or the specialist habilitation centre. Still, in participants with RMP, increasing pain severity was associated with having visited the GP. Rest, massage, change of position and oral drugs were the most common measures taken to relieve RMP. Three adolescents with RMP did not take any measures to relieve pain. Youth with RMP do take measures to relieve pain, but usually not in the direction of consulting the health care services available unless the pain is severe. Both youth with CP and their caregivers should be encouraged to discuss RMP with their professional network of care.

Knee Pain and Patellofemoral Symptoms in Patients With Cerebral Palsy.

Knee pain in cerebral palsy (CP) is associated with increased patellofemoral forces present when walking with flexed knees. In typically developing children, knee pain and patellofemoral dysfunction are associated with obesity, genu valgum, femoral anteversion, and external tibial torsion. These problems are also common in CP, and may contribute to knee problems in this population. The purposes of this study were to define the prevalence of knee pain and patellofemoral dysfunction in children with CP, and to identify physical and gait characteristics (using 3-dimensional gait analysis data) that predispose them to such problems. Retrospective review of 121 children with CP, Gross Motor Function Classification System level I to IV, who underwent computerized gait analysis testing. Demographics, range of motion, body mass index and hip, knee, and ankle kinematics were compared between subjects with and without knee pain. Twenty-five of 121 subjects (21%) reported knee pain at the time of testing. Three of 121 subjects (2%) had a history of patellar subluxation/dislocation. Age and sex were significantly related to presence of knee pain. The likelihood of knee pain was almost 5 times higher in females (odds ratio=4.9, [95% confidence interval, 1.8-13.3], P=0.002), with a prevalence of 40% (17/42) in females versus 10% (8/79) in males. The likelihood of knee pain increased with age by approximately 13% per year (odds ratio=1.13, [95% confidence interval, 1.00-1.28], P=0.058). Malignant malalignment syndrome showed a potential relationship to more severe knee pain (P=0.05), which warrants further investigation. Body mass index, pes valgus, and degree of stance knee flexion showed no statistically significant relationships to knee pain (P>0.16). The prevalence of knee pain in ambulatory patients with CP is approximately 21%. Patellar subluxation (2%) and dislocation are rare in these patients. Knee pain is not always related to crouch, femoral anteversion, external tibial torsion, genu valgum, or pes valgus. Knee pain in these patients is more prevalent in females, and increases with increasing age. Level III-case-control study.

Qualitative development of the ‘Questionnaire on Pain caused by Spasticity (QPS),’ a pediatric patient‐reported outcome for spasticity‐related pain in cerebral palsy

Purpose To develop a patient-reported outcome measure for spasticity-related pain in children/adolescents (age 2–17 years) with cerebral palsy (CP), the ‘Questionnaire on Pain caused by Spasticity (QPS).’MethodsUsing a semi-structured interview guide, concept elicitation interviews on spasticity-related pain in upper and lower limbs were conducted in 21 children and caregiver pairs. Data were used to modify initial QPS modules and develop six draft modules, which were subsequently refined and finalized in four consecutive cognitive interview waves (12 children and caregiver pairs).ResultsTo accommodate the broad range in the children’s communication skills, QPS child/adolescent modules were developed in both interviewer-administered and self-administered formats. With the additional parent modules, three QPS modules were developed for each of the upper and lower limb applications. Information gained from the parent/caregiver modules complements the child/adolescent assessment. Parents report observed signs and frequency of pain in the same situations used to capture the child/adolescent reports of pain severity (e.g., rest, usual daily activities, active mobilization, and physically difficult activities). Participating children/adolescents and parents/caregivers reported that the final QPS instruments were comprehensive, relevant to the child’s spasticity-related experience, and easy to understand and complete.ConclusionsThe QPS is a novel instrument for the assessment of spasticity-related pain in children/adolescents with CP that was developed with direct patient input. Its modules allow the use of this instrument in children/adolescents with varied levels of impairment and communication skills.

Unraveling the sources of chronic pain in cerebral palsy

This commentary is on the original article by van der Slot et al. on pages 836‐842 of this issue.

Kinematic Determinants of Anterior Knee Pain in Cerebral Palsy: A Case-Control Study

Sheehan FT, Babushkina A, Alter KE. Kinematic determinants of anterior knee pain in cerebral palsy: a case-control study. ObjectiveTo quantify the role patellofemoral and tibiofemoral kinematics may play in development of anterior knee pain (AKP) in individuals with cerebral palsy (CP). DesignCase-control. SettingClinical research center. ParticipantsKnees from individuals with diagnosed CP (n=20) and control knees (n=40) were evaluated. Controls were matched for sex and age based on the group average. Matching by height and weight was a secondary priority. Subjects in the control cohort were asymptomatic with no history of lower leg abnormalities, surgery, or major injury. Only individuals who were physically capable of sustaining slow, cyclic knee flexion-extension for 2.5 minutes and had no contraindications to magnetic resonance imaging were enrolled. Both groups were samples of convenience. InterventionsNot applicable. Main Outcome MeasuresThree-dimensional patellofemoral and tibiofemoral joint kinematics, acquired during active leg extension, under volitional control. ResultsParticipants with CP and AKP (n=8) demonstrated significantly greater patellofemoral extension, valgus rotation, and superior and posterior displacement relative to controls and to the subgroup of participants with CP and no AKP (n=12). Patellofemoral extension discriminated AKP in individuals with CP with 100% accuracy. ConclusionsIn quantifying the 3-dimensional, in vivo knee joint kinematics during a volitional extension task, kinematic markers that discriminate AKP in individuals with CP were identified. This provides an ability to predict which individuals with CP are most likely to develop AKP and could enable aggressive conservative treatment, aimed at reducing patella alta and excessive patellofemoral extension, to be prescribed before considering surgical options. The current findings will likely lead to improved clinical diagnostics and interventions for individuals with CP, with the ultimate goal of helping maintain, if not improve, functional mobility throughout the lifespan.

Mental health, health related quality of life and recurrent musculoskeletal pain in children with cerebral palsy 8–18 years old

Purpose: To extend knowledge on mental health with children’s self-report and explore mental health and health related quality of life (HRQL) in a context of recurrent musculoskeletal pain in cerebral palsy (CP). Method: Eighty-three participants, mean age 14.2 ± 2.8 years, were assessed with clinical examination, interview and questionnaires. Gross motor function was GMFCS level I 42%, level II 42%, level III 12% and level IV–V 5%. Children self-reported mental health on SDQ (Strengths and Difficulty Questionnaire), HRQL on PedsQL (Pediatric Quality of Life), and pain on CHQ (Child Health Questionnaire). Mothers proxy-reported on the same questionnaires and reported own mental health on GHQ (General Health Questionnaire). Results: Both self-reported mental health and HRQL was better than proxy-reported. Recurrent musculoskeletal pain was associated with more mental health problems and reduced HRQL in self-reports, but not in proxy-reports. Conclusions: In CP, the importance of child-report on mental health and HRQL when possible, in addition to parent proxy-report, cannot be overstated. Close co-operation between (re)habilitation and child psychiatry is urgent. Further research on self-reported mental health and impact of mental health problems is warranted together with a focus on the impact of recurrent musculoskeletal pain on participation.Implications for RehabilitationChildren with cerebral palsy experience musculoskeletal pain that is associated with more self-reported mental health problems and lower HRQL.Because mothers tend to not recognise these associations, self-report (when possible) is essential.A bio-psycho-social perspective in both individual and family approach is important because of the associations mentioned and because parents report that their children have a high prevalence of mental health problems.Assessment of HRQL has the potential to capture both pain and mental health problems, and should be an integrated part of the systematic clinical follow-up.

Intérêt de la toxine botulique pour les suites opératoires en chirurgie des membres chez l’enfant infirme moteur cerebral

Purpose of the study Spasticity can be the cause of pain in cerebral palsy (CP) children who may suffer increased postoperative pain after orthopedic surgery. Moreover, symptoms can be worsened by abnormal movements, cast immobilization or anxiety. Spasticity must therefore be treated after surgery in CP children. A randomized study has demonstrated that when these children undergo surgical tenotomy, preoperative injections of botulinum toxin have a beneficial effect in terms of pain relief. The aim of this study was to assess the benefit regarding pain and comfort provided by preoperative use of botulinum toxin in total-body CP children undergoing bone surgery. Material and methods Two successive groups of nine total-body CP children were compared in a retrospective study. All patients underwent an orthopedic surgery involving a bone or a multilevel procedure. The second group was treated before surgery with multisite injections of botulinum toxin. The main outcome criteria studied were: efficiency and adverse effects of botulinum toxin, duration of hospital stay and pain, length of level III analgesic treatment (morphine), sleep quality, and skin lesions under cast immobilization. The two groups were similar for mean age (8.7 ± 2.04 versus 10.9 ± 4.37 years) and mean body weight (20 ± 5.6 versus 26 ± 7.7 kg). Mean botulinum toxin (Botox ®/kg) in the second group was 11.6 U (range 9.7 - 14.8). Average time from preoperative botulinum toxin injections to surgery was 27 days (range 23-31). Results There was no significant difference between the two groups, except for the botulinum toxin treatment. The Aschworth scale confirmed the clinical efficiency of the preoperative injections, with no adverse effects. After the surgical procedure, all patients but two had cast immobilization (orthopedic traction, in botulinum group). The mean duration was six weeks in both groups. There was no significant difference in duration of the hospital stay: 7.33 ± 1.5 versus 7.88 ± 1.7 days and duration of level III analgesic treatment (4.33 ± 1.9 versus 4.16 ± 2.5 days). The duration of pain symptoms decreased significantly from 6.87 ± 2.9 to 2.22 ± 1.7 days and sleep quality improved from 7/9 to 1/9 patients with disturbed sleep. Four under-cast skin lesions were noted in the first group but none in the bolulinum group. Discussion We cannot confirm that botulinum toxin before bone surgery induces lesser consumption of analgesic drugs. Our results do however support the hypothesis that treatment of spasticity using preoperative injections of botulinum toxin decreases the duration of postoperative pain and improves the children's comfort. Moreover, postoperative under-cast skin lesions can be prevented. This work suggests that improved patient comfort and pain relief could be achieved by using multisite botulinum toxin injections before orthopedic surgery in spastic total-body CP children.

La douleur chez le sujet adulte infirme moteur cérébral

Introduction Pain is the main problem in patients with cerebral palsy. To improve the quality of life of people with cerebral palsy, a good knowledge of the clinical syndrome is necessary. Method We reviewed the published data of the APIB study. We analysed data about pain, especially its correlation with age, motor handicap, and depressive syndrome. We also reviewed the literature to survey the pain syndrome in such a situation. Results A total of 562 patients responded to the APIB survey (mean age 36 ± 14 years). Of these, 75% complained about physical pain. Pain was significantly associated with age, motor handicap, depressive syndrome, and sleep disorders. Discussion A study of the literature confirms our results on pain in cerebral palsy from the APIB survey. The main localisations of pain are the spine, and scapular and pelvic girdles. Pain syndromes of the upper and lower limbs are also frequent, with much due to overuse. Some rare causes include heterotopic ossifications. Conclusion A good knowledge of the characteristics of the pain syndromes in people with cerebral palsy is important because of the great prevalence of this problem in this population. Better knowledge will help prevent the pain and improve quality of life.

Pain in cerebral palsy: the relation of coping strategies to adjustment

Pain is a serious secondary problem for many persons with cerebral palsy (CP). Cognitive–behavioral models of pain hypothesize that how patients cope with painful episodes plays an important role in their adjustment to chronic pain. The utility of this model, however, has never been tested in persons with CP-related pain. Fifty adults with CP and chronic pain were interviewed to assess pain experience, the interference of pain on activities (BPI), depressive symptoms (CES-D), and coping strategies used for the pain (CSQ and CPCI). The results indicated that pain-contingent rest and catastrophizing were both significantly associated with pain interference and depressive symptoms even when controlling for pain severity. These findings support a cognitive–behavioral model of chronic pain as it might be applied to persons with CP. The results also support the need for research to determine if, and to what extent, cognitive–behavioral interventions that provide training in specific coping responses reduce depressive symptoms and pain interference in persons with CP.

Utilization of a Neural Network in the Elaboration of an Evaluation Scale for Pain in Cerebral Palsy

An interesting aspect of neural networks is shown in the elaboration of an evaluation scale for pain in cerebral palsy with severe mental retardation. Because of the diversity of cases, the number of items had to be limited in the final step of statistical validation. Classical analysis on prior data did not allow to decide whether the variability in results is more likely due to the type of disability (i.e., the possibility of pain expression) than to the actual presence of pain. A neural network was used to find implicit relations between the data, with the advantage of having total control on the variables' status by applying variations in the network architecture. This allowed for the rapid identification more significant item combinations as a function of degree of relationship to pain in cerebral palsy.