Sensorimotor dysfunction after limb fracture – An exploratory study

© 2016 European Pain Federation - EFIC ® Background: Chronic pain is often associated with sensorimotor dysfunction but little is known about the early impact of limb fracture on sensory and motor performance. This exploratory study sought to assess these changes in patients with recent wrist and ankle fractures. A secondary aim was to determine the incidence of Complex Regional Pain Syndrome (CRPS) and its clinical features. Methods: Fifty-three patients at a UK fracture centre underwent Quantitative Sensory Testing (QST), Motor Imagery (MI) and Body Perception Disturbance (BPD) assessments ≤5weeks post-fracture (Time 1). Subjective evaluation of recovery and clinical examination for CRPS was conducted 5weeks later (Time 2, 50 patients). Patient-reported outcomes of pain, psychological distress and limb function were collected at Times 1 and 2, and 6months after T1 (Time 3, 36 patients, postal questionnaire). Results: Quantitative sensory testing at Time 1 demonstrated cold and pressure-pain hyperalgesia in the fractured limb compared to the non-fractured side (

Neuromyelitis optica presenting with relapses under treatment with natalizumab: a case report

Introduction Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system. To date, optimal therapeutic approaches for neuromyelitis optica have yet to be defined. Natalizumab is highly effective in relapsing-remitting multiple sclerosis and might be considered as an option. Case presentation Here, we describe a 67-year-old Caucasian man with definite neuromyelitis optica with detection of anti-aquaporin-4 antibodies over the course of the disease. After initially discussing the diagnosis of multiple sclerosis at an outside hospital, our patient received interferon beta 1a as well as repeated corticosteroid pulses without success. Under subsequent therapy with natalizumab, he continued to present relapses. It was not until discontinuation of natalizumab, repeated cycles of plasma exchanges and initiation of therapy with rituxan that the disease course started to stabilize. Although B cells were completely depleted, our patient experienced another severe myelitis relapse during further follow-up and an additional immunosuppressive therapy with cyclophosphamide was started. Under this regimen, no further relapses occurred over the next 24 months. Conclusions This case adds further evidence to the previously discussed notion that natalizumab, while highly effective in multiple sclerosis, may not work sufficiently in neuromyelitis optica. It further advocates for repetitive testing of anti-aquaporin-4 antibodies before and after treatment initiation

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Complex regional pain syndrome : The matter of white matter?

Introduction: Many central pathophysiological aspects of complex regional pain syndrome (CRPS) are still unknown. Although brain-imaging studies are increasingly supporting the contribution of the central nervous system to the generation and maintenance of the CRPS pain, the brain's white-matter alterations are seldom investigated. Methods: In this study, we used diffusion tensor imaging to explore white-matter changes in twelve CRPS-type-1 female patients suffering from chronic right upper-limb pain compared with twelve healthy control subjects. Results: Tract-based spatial-statistics analysis revealed significantly higher mean diffusivity, axial diffusivity, and radial diffusivity in the CRPS patients, suggesting that the structural connectivity is altered in CRPS. All these measures were altered in the genu, body, and splenium of corpus callosum, as well as in the left anterior and posterior and the right superior parts of the corona radiata. Axial diffusivity was significantly correlated with clinical motor symptoms at whole-brain level, supporting the physiological significance of the observed white-matter abnormalities. Conclusions: Altogether, our findings further corroborate the involvement of the central nervous system in CRPS.Peer reviewe

¿Afecta el dolor al volumen local del cerebro? Aportaciones desde un modelo clínico de dolor agudo

Background/Objective:To study pain-brain morphometry associations as a function of post-surgery stages (anesthesia, pain and analgesia) in an acute pain model. Method:Impacted mandible third molar were extracted. Before surgery, an anatomical T1 scan was obtained. Regional brain volumen and subcortical nuclei shapes were obtained. Statistical analyses were done using multiple regression, being pain scores the predictors and voxel volumes, subcortical nuclei volumes and subcortical nuclei shapes, the outcomes. Results:Pain was significantly larger at pain than at anesthesia and analgesia stages, and was higher during anesthesia than during analgesia. Pain intensity was related to grey matter in several cortical (Insula, Mid Frontal and Temporal Gyruses, Precuneus, Anterior Cingulate), and subcortical nuclei (Hippocampus, Thalamus, Putamen, Amygdala), depending of the post-surgical stage. A larger number of brain areas showed significance at pain that at anesthesia and analgesia stages. Conclusions:The relationships of regional brain volumes and subcortical nuclei shapes with pain scores seemed to be unsteady, as they changed with the patient’s actual pain stage.Antecedentes/Objetivo: Se trata de determinar la asociación entre dolor percibido y morfometría cerebral en tres etapas postquirúrgicas (anestesia, dolor y analgesia), en un modelo de dolor agudo. Método: Se obtuvo una imagen cerebral estructural de alta resolución y posteriormente se extrajeron los terceros molares mandibulares impactados. Se realizó un análisis morfométrico para determinar volumen cerebral y forma de núcleos subcorticales. Se realizaron análisis de regresión múltiple, siendo la intensidad del dolor el predictor, y el volumen y la forma de los núcleos subcorticales, medidos pre-cirugía, las variables dependientes.Resultados:El dolor experimentado fue mayor en la etapa de dolor que en las de anestesia y analgesia, y mayor en anestesia que en analgesia. El dolor se asoció con el volumen de materiagris en áreas corticales (insula, giros frontal medial y temporal, precuneus y cingulado anterior) y subcorticales (hipocampo, tálamo, putamen y amígdala). El número de áreas asociadasal dolor experimentado fue mayor en la etapa de dolor que en las de anestesia y analgesia. Conclusiones: La relación entre volumen cerebral regional y forma de núcleos subcorticales con la intensidad del dolor no es fijo, sino que varía en función de la etapa post-quirúrgica (magnitud del dolor).This investigation was partially supported by Research Groups #CTS-138, #CTS-176 and #CTS-1028. (Junta de Andalucía, Spain)

Novel SCARB2 mutation in action myoclonus-renal failure syndrome and evaluation of SCARB2 mutations in isolated AMRF features

Background: Action myoclonus-renal failure syndrome is a hereditary form of progressive myoclonus epilepsy associated with renal failure. It is considered to be an autosomal-recessive disease related to loss-of-function mutations in SCARB2. We studied a German AMRF family, additionally showing signs of demyelinating polyneuropathy and dilated cardiomyopathy. To test the hypothesis whether isolated appearance of individual AMRF syndrome features could be related to heterozygote SCARB2 mutations, we screened for SCARB2 mutations in unrelated patients showing isolated AMRF features. Methods: In the AMRF family all exons of SCARB2 were analyzed by Sanger sequencing. The mutation screening of unrelated patients with isolated AMRF features affected by either epilepsy (n = 103, progressive myoclonus epilepsy or generalized epilepsy), demyelinating polyneuropathy (n = 103), renal failure (n = 192) or dilated cardiomyopathy (n = 85) was performed as high resolution melting curve analysis of the SCARB2 exons. Results: A novel homozygous 1 bp deletion (c.111delC) in SCARB2 was found by sequencing three affected homozygous siblings of the affected family. A heterozygous sister showed generalized seizures and reduction of nerve conduction velocity in her legs. No mutations were found in the epilepsy, renal failure or dilated cardiomyopathy samples. In the polyneuropathy sample two individuals with demyelinating disease were found to be carriers of a SCARB2 frameshift mutation (c.666delCCTTA). Conclusions: Our findings indicate that demyelinating polyneuropathy and dilated cardiomyopathy are part of the action myoclonus-renal failure syndrome. Moreover, they raise the possibility that in rare cases heterozygous SCARB2 mutations may be associated with PNP features

Cortical disinhibition occurs in chronic neuropathic, but not in chronic nociceptive pain

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the relationship between chronic neuropathic pain after incomplete peripheral nerve lesion, chronic nociceptive pain due to osteoarthritis, and the excitability of the motor cortex assessed by transcranial magnetic stimulation (TMS). Hence in 26 patients with neuropathic pain resulting from an isolated incomplete lesion of the median or ulnar nerve (neuralgia), 20 patients with painful osteoarthritis of the hand, and 14 healthy control subjects, the excitability of the motor cortex was tested using paired-pulse TMS to assess intracortical inhibition and facilitation. These excitability parameters were compared between groups, and the relationship between excitability parameters and clinical parameters was examined.</p> <p>Results</p> <p>We found a significant reduction of intracortical inhibition in the hemisphere contralateral to the lesioned nerve in the neuralgia patients. Intracortical inhibition in the ipsilateral hemisphere of neuralgia patients and in both hemispheres of osteoarthritis patients did not significantly differ from the control group. Disinhibition was significantly more pronounced in neuralgia patients with moderate/severe pain intensity than in patients with mild pain intensity, whereas the relative compound motor action potential as a parameter of nerve injury severity did not correlate with the amount of disinhibition.</p> <p>Conclusions</p> <p>Our results suggest a close relationship between motor cortex inhibition and chronic neuropathic pain in the neuralgia patients, which is independent from nerve injury severity. The lack of cortical disinhibition in patients with painful osteoarthritis points at differences in the pathophysiological processes of different chronic pain conditions with respect to the involvement of different brain circuitry.</p