Ricardo Galhardoni

Effects of deep brain stimulation on pain and other nonmotor symptoms in Parkinson disease

Objective: To prospectively evaluate the effect of subthalamic nucleus deep brain stimulation (STN-DBS) on the different characteristics of pain and other nonmotor symptoms (NMS) in patients with Parkinson disease (PD). Methods: Forty-four patients with PD and refractory motor symptoms were screened for STN-DBS. Patients were evaluated before and 1 year after surgery. The primary outcome was change in pain prevalence after surgery. Secondary outcome measures were changes in motor function (Unified Parkinsons Disease Rating Scale), characteristics of pain and other NMS using specific scales and questionnaires, and quality of life. Results: Forty-one patients completed the study. The prevalence of pain changed from 70% to 21% after surgery (p < 0.001). There were also significant improvements in pain intensity, NMS, and quality of life after STN-DBS (p < 0.05). Dystonic and musculoskeletal pain responded well to DBS, while central pain and neuropathic pain were not influenced by surgery. There was a strong correlation between the change in pain intensity and the improvement in quality of life (r = 0.708, p < 0.005). No correlation was found between pain improvement and preoperative response to levodopa or motor improvement during stimulation (r = 0.247, p = 0.197 and r = 0.249, p = 0.193, respectively) or with changes in other NMS. Conclusions: STN-DBS decreased pain after surgery, but had different effects in different types of PD-related pain. Motor and nonmotor symptom improvements after STN-DBS did not correlate with pain relief. Classification of evidence: This study provides Class IV evidence that in patients with idiopathic PD with refractory motor fluctuations, STN-DBS decreases the prevalence of pain and improves quality of life.

Subthalamic deep brain stimulation modulates small fiber–dependent sensory thresholds in Parkinson’s disease

TOC summary Subthalamic nucleus deep brain stimulation contributes to relieve pain associated with Parkinson’s disease and specifically modulates small fiber–mediated sensations. ABSTRACT The effects of deep brain stimulation of the subthalamic nucleus on nonmotor symptoms of Parkinson’s disease (PD) rarely have been investigated. Among these, sensory disturbances, including chronic pain (CP), are frequent in these patients. The aim of this study was to evaluate the changes induced by deep brain stimulation in the perception of sensory stimuli, either noxious or innocuous, mediated by small or large nerve fibers. Sensory detection and pain thresholds were assessed in 25 PD patients all in the off‐medication condition with the stimulator turned on or off (on‐ and off‐stimulation conditions, respectively). The relationship between the changes induced by surgery on quantitative sensory testing, spontaneous CP, and motor abilities were studied. Quantitative sensory test results obtained in PD patients were compared with those of age‐matched healthy subjects. Chronic pain was present in 72% of patients before vs 36% after surgery (P = .019). Compared with healthy subjects, PD patients had an increased sensitivity to innocuous thermal stimuli and mechanical pain, but a reduced sensitivity to innocuous mechanical stimuli. In addition, they had an increased pain rating when painful thermal stimuli were applied, particularly in the off‐stimulation condition. In the on‐stimulation condition, there was an increased sensitivity to innocuous thermal stimuli but a reduced sensitivity to mechanical or thermal pain. Pain provoked by thermal stimuli was reduced when the stimulator was turned on. Motor improvement positively correlated with changes in warm detection and heat pain thresholds. Subthalamic nucleus deep brain stimulation contributes to relieve pain associated with PD and specifically modulates small fiber–mediated sensations.

Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial.

BACKGROUND Data from previous studies suggest that botulinum toxin A has analgesic effects against peripheral neuropathic pain, but the quality of the evidence is low. We aimed to assess the safety and efficacy of repeated administrations of botulinum toxin A in patients with neuropathic pain. METHODS We did a randomised, double-blind, placebo-controlled trial at two outpatient clinics in France (Clinical Pain Centre, Ambroise Paré Hospital, APHP, Boulogne-Billancourt, and Neurological Centre, Hôpital Dupuytren, Limoges) and one in Brazil (Neurological Department, Hospital das Clínicas da FMUSP, São Paulo). Patients aged 18-85 years with peripheral neuropathic pain were randomly assigned (1:1) by block randomisation, according to a centralised schedule, to receive two subcutaneous administrations of botulinum toxin A (up to 300 units) or placebo, 12 weeks apart. All patients and investigators were masked to treatment assignment. The primary outcome was the efficacy of botulinum toxin A versus placebo, measured as the change from baseline in self-reported mean weekly pain intensity over the course of 24 weeks from the first administration. The primary efficacy analysis was a mixed-model repeated-measures analysis in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01251211. FINDINGS Between Oct 2, 2010, and Aug 2, 2013, 152 patients were enrolled, of whom 68 were randomly assigned (34 per group), and 66 (37 [56%] men) were included in the primary analysis (34 in the botulinum toxin A group and 32 in the placebo group). Botulinum toxin A reduced pain intensity over 24 weeks compared with placebo (adjusted effect estimate -0·77, 95% CI -0·95 to -0·59; p<0·0001). Pain on injection was the only adverse effect reported, and occurred in 19 (56%) participants in the botulinum toxin A group and 17 (53%) of those in the placebo group (p=1·0). Severe pain was experienced by ten (29%) participants in the botulinum toxin A group and 11 (34%) in the placebo group (p=0·8). INTERPRETATION Two administrations of botulinum toxin A, each of which comprised several injections, have a sustained analgesic effect against peripheral neuropathic pain. Several factors, such as the presence of allodynia and a limited thermal deficit, may be useful in predicting treatment response and should be investigated further. FUNDING Institut National de la Santé et de la Recherche Médicale (INSERM) and Fondation CNP (France).

Repetitive transcranial magnetic stimulation in chronic pain: a review of the literature.

OBJECTIVE To review the literature on the analgesic effects of repetitive transcranial magnetic stimulation (rTMS) in chronic pain according to different pain syndromes and stimulation parameters. DATA SOURCES Publications on rTMS and chronic pain were searched in PubMed and Google Scholar using the following key words: chronic pain, analgesia, transcranial magnetic stimulation, neuropathic pain, fibromyalgia, and complex regional pain syndrome. STUDY SELECTION This review only included double-blind, controlled studies with >10 participants in each arm that were published from 1996 to 2014 and written in English. Studies with relevant information for the understanding of the effects of rTMS were also cited. DATA EXTRACTION The following data were retained: type of pain syndrome, type of study, coil type, target, stimulation intensity, frequency, number of pulses, orientation of induced current, number of session, and a brief summary of intervention outcomes. DATA SYNTHESIS A total of 33 randomized trials were found. Many studies reported significant pain relief by rTMS, especially high-frequency stimulation over the primary motor cortex performed in consecutive treatment sessions. Pain relief was frequently >30% compared with control treatment. Neuropathic pain, fibromyalgia, and complex regional pain syndrome were the pain syndromes more frequently studied. However, among all published studies, only a few performed repetitive sessions of rTMS. CONCLUSIONS rTMS has potential utility in the management of chronic pain; however, studies using maintenance sessions of rTMS and assessing the effects of rTMS on the different aspects of chronic pain are needed to provide a more solid basis for its clinical application for pain relief.

Envelhecimento bem-sucedido: trajetórias de um constructo e novas fronteiras

This article focuses on different conceptions of su ccessful aging, emphasizing the process of aging as a heterogeneous experience that implies different strategies for achieving wellbeing and qu ality of life. Studies valuing the aging process as part of the course of human life and the role of subjectivity and health self-perception, as key con cepts for understanding wellbeing and health in old age, were selected. Dat a in the literature suggest that the experience of successful aging values elde rly peoples own perceptions: they are the protagonists of intervent ions and possess judgment about wellbeing and quality of life. Even in the pr esence of comorbidities and diminished functional ability, it is possible t o identify elderly people who report high levels of satisfaction and good qua lity of life. We propose questions that seek to improve investigations and e laborate this construct within gerontology, bearing in mind the size and co mplexity of this topic.Este artigo enfoca diferentes concepcoes de envelhecimento bem-sucedido, enfatizando o processo de envelhecimento como uma experiencia heterogenea, que implica diferentes estrategias para a obtencao de bem-estar e qualidade de vida. Foram selecionados estudos que valorizam o processo de envelhecimento como parte do curso de vida humano, o papel da subjetividade e a auto-avaliacao em saude, como conceitos-chave para compreender o bem-estar e saude na velhice. Os dados da literatura sugerem que a experiencia do envelhecimento bem-sucedido valoriza a percepcao dos proprios idosos, protagonistas de intervencoes e dotados de julgamentos sobre bem-estar e qualidade de vida. Mesmo na presenca de co-morbidades e diminuicao da funcionalidade e possivel identificar idosos que referem altos niveis de satisfacao e boa qualidade de vida. Propomos questoes que buscam aprimorar investigacoes e a elaboracao deste constructo em gerontologia, tendo em vista a amplitude e complexidade do tema.

Sensory abnormalities and pain in Parkinson disease and its modulation by treatment of motor symptoms.

Pain and sensory abnormalities are present in a large proportion of Parkinson disease (PD) patients and have a significant negative impact in quality of life. It remains undetermined whether pain occurs secondary to motor impairment and to which extent it can be relieved by improvement of motor symptoms. The aim of this review was to examine the current knowledge on the mechanisms behind sensory changes and pain in PD and to assess the modulatory effects of motor treatment on these sensory abnormalities. A comprehensive literature search was performed. We selected studies investigating sensory changes and pain in PD and the effects of levodopa administration and deep brain stimulation (DBS) on these symptoms. PD patients have altered sensory and pain thresholds in the off‐medication state. Both levodopa and DBS improve motor symptoms (i.e.: bradykinesia, tremor) and change sensory abnormalities towards normal levels. However, there is no direct correlation between sensory/pain changes and motor improvement, suggesting that motor and non‐motor symptoms do not necessarily share the same mechanisms. Whether dopamine and DBS have a real antinociceptive effect or simply a modulatory effect in pain perception remain uncertain. These data may provide useful insights into a mechanism‐based approach to pain in PD, pointing out the role of the dopaminergic system in pain perception and the importance of the characterization of different pain syndromes related to PD before specific treatment can be instituted.

Psychometric validation of the Portuguese version of the Neuropathic Pain Symptoms Inventory

BackgroudIt has been shown that different symptoms or symptom combinations of neuropathic pain (NeP) may correspond to different mechanistic backgrounds and respond differently to treatment. The Neuropathic Pain Symptom Inventory (NPSI) is able to detect distinct clusters of symptoms (i.e. dimensions) with a putative common mechanistic background. The present study described the psychometric validation of the Portuguese version (PV) of the NPSI.MethodsPatients were seen in two consecutive visits, three to four weeks apart. They were asked to: (i) rate their mean pain intensity in the last 24 hours on an 11-point (0-10) numerical scale; (ii) complete the PV-NPSI; (iii) provide the list of pain medications and doses currently in use. VAS and Global Impression of Change (GIC) were filled out in the second visit.ResultsPV-NPSI underwent test-retest reliability, factor analysis, analysis of sensitivity to changes between both visits. The PV-NPSI was reliable in this setting, with a good intra-class correlation for all items. The factorial analysis showed that the PV-NPSI inventory assessed different components of neuropathic pain. Five different factors were found. The PV-NPSI was adequate to evaluate patients with neuropathic pain and to detect clusters of NeP symptoms.ConclusionsThe psychometric properties of the PV-NPSI rendered it adequate to evaluate patients with both central and peripheral neuropathic pain syndromes and to detect clusters of NeP symptoms.

The assessment and management of pain in the demented and non-demented elderly patient

Persistent pain is a frequent health problem in the elderly. Its prevalence ranges from 45% to 80%. Chronic diseases, such as depression, cardiovascular disease, cancer and osteoporosis have a higher prevalence in aged individuals and increase the risk of developing chronic pain. The presence of pain is known to be associated with sleep disorders in these patients, as well as functional impairment, decreased sociability and greater use of the health system, with consequent increase in costs. Alzheimers disease patients seem to have a normal pain discriminative capacity and they may probably have weaker emotional and affective experience of pain when compared to other types of dementia. Many patients have language deficits and thus cannot properly describe its characteristics. In more advanced cases, it becomes even difficult to determine whether pain is present or not. Therefore, the evaluation of these patients should be performed in a systematic way. There are three ways to measure the presence of pain: by direct questioning (self-report), by direct behavioral observation and by interviews with caregivers or informants. In recent years, many pain scales and questionnaires have been published and validated specifically for the elderly population. Some are specific to patients with cognitive decline, allowing pain evaluation to be conducted in a structured and reproducible way. The next step is to determine the type of painful syndrome and discuss the bases of the pharmacological management, the use of multiple medications and the presence of comorbidities demand the use of smaller doses and impose contra-indications against some drug classes. A multiprofessional approach is the rule in the management of these patients.

Into the Island: A new technique of non-invasive cortical stimulation of the insula

STUDY AIM We describe a new neuronavigation-guided technique to target the posterior-superior insula (PSI) using a cooled-double-cone coil for deep cortical stimulation. INTRODUCTION Despite the analgesic effects brought about by repetitive transcranial magnetic stimulation (TMS) to the primary motor and prefrontal cortices, a significant proportion of patients remain symptomatic. This encouraged the search for new targets that may provide stronger pain relief. There is growing evidence that the posterior insula is implicated in the integration of painful stimuli in different pain syndromes and in homeostatic thermal integration. METHODS The primary motor cortex representation of the lower leg was used to calculate the motor threshold and thus, estimate the intensity of PSI stimulation. RESULTS Seven healthy volunteers were stimulated at 10 Hz to the right PSI and showed subjective changes in cold perception. The technique was safe and well tolerated. CONCLUSIONS The right posterior-superior insula is worth being considered in future studies as a possible target for rTMS stimulation in chronic pain patients.

Neuropathic pain after brachial plexus avulsion--central and peripheral mechanisms.

ReviewThe pain that commonly occurs after brachial plexus avulsion poses an additional burden on the quality of life of patients already impaired by motor, sensory and autonomic deficits. Evidence-based treatments for the pain associated with brachial plexus avulsion are scarce, thus frequently leaving the condition refractory to treatment with the standard methods used to manage neuropathic pain. Unfortunately, little is known about the pathophysiology of brachial plexus avulsion. Available evidence indicates that besides primary nerve root injury, central lesions related to the abrupt disconnection of nerve roots from the spinal cord may play an important role in the genesis of neuropathic pain in these patients and may explain in part its refractoriness to treatment.ConclusionsThe understanding of both central and peripheral mechanisms that contribute to the development of pain is of major importance in order to propose more effective treatments for brachial plexus avulsion-related pain. This review focuses on the current understanding about the occurrence of neuropathic pain in these patients and the role played by peripheral and central mechanisms that provides insights into its treatment.SummaryPain after brachial plexus avulsion involves both peripheral and central components; thereby it is characterized as a mixed (central and peripheral) neuropathic pain syndrome.