The Parkinson disease pain classification system: Results from an international mechanism-based classification approach

Pain is a common nonmotor symptom in patients with Parkinson disease (PD) but the correct diagnosis of the respective cause remains difficult because suitable tools are lacking, so far. We developed a framework to differentiate PD- from non-PD-related pain and classify PD-related pain into 3 groups based on validated mechanistic pain descriptors (nociceptive, neuropathic, or nociplastic), which encompass all the previously described PD pain types. Severity of PD-related pain syndromes was scored by ratings of intensity, frequency, and interference with daily living activities. The PD-Pain Classification System (PD-PCS) was compared with classic pain measures (ie, brief pain inventory and McGill pain questionnaire [MPQ], PDQ-8 quality of life score, MDS-UPDRS scores, and nonmotor symptoms). 159 nondemented PD patients (disease duration 10.2 6 7.6 years) and 37 healthy controls were recruited in 4 centers. PDrelated pain was present in 122 patients (77%), with 24 (15%) suffering one or more syndromes at the same time. PD-related nociceptive, neuropathic, or nociplastic pain was diagnosed in 87 (55%), 25 (16%), or 35 (22%), respectively. Pain unrelated to PD was present in 35 (22%) patients. Overall, PD-PCS severity score significantly correlated with pain’s Brief Pain Inventory and MPQ ratings, presence of dyskinesia and motor fluctuations, PDQ-8 scores, depression, and anxiety measures. Moderate intrarater and interrater reliability was observed. The PD-PCS is a valid and reliable tool for differentiating PD-related pain from PD-unrelated pain. It detects and scores mechanistic pain subtypes in a pragmatic and treatment-oriented approach, unifying previous classifications of PD-pain.Fil: Mylius, Veit. Universitat Phillips; Alemania. Center for Neurorehabilitation; Suiza. Kantonsspital St; SuizaFil: Perez Lloret, Santiago. Universidad Abierta Interamericana. Secretaría de Investigación. Centro de Altos Estudios En Ciencias Humanas y de la Salud - Sede Buenos Aires.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; ArgentinaFil: Cury, Rubens G.. Universidade de Sao Paulo; BrasilFil: Teixeira, Manoel J.. Universidade de Sao Paulo; BrasilFil: Barbosa, Victor R.. Universidade de Sao Paulo; BrasilFil: Barbosa, Egberto R.. Universidade de Sao Paulo; BrasilFil: Moreira, Larissa I.. Universidade de Sao Paulo; BrasilFil: Listik, Clarice. Universidade de Sao Paulo; BrasilFil: Fernandes, Ana M.. Universidade de Sao Paulo; BrasilFil: de Lacerda Veiga, Diogo. Universidade de Sao Paulo; BrasilFil: Barbour, Julio. Universidade de Sao Paulo; BrasilFil: Hollenstein, Nathalie. Universidade de Sao Paulo; BrasilFil: Oechsner, Matthias. Center for Neurological Rehabilitation; SuizaFil: Walch, Julia. Kantonsspital St; SuizaFil: Brugger, Florian. Kantonsspital St; SuizaFil: Hägele Link, Stefan. Kantonsspital St; SuizaFil: Beer, Serafin. Center for Neurorehabilitation; SuizaFil: Rizos, Alexandra. King's College Hospital; Reino UnidoFil: Chaudhuri, Kallol Ray. The Maurice Wohl Clinical Neuroscience Institute; Reino Unido. King's College Hospital; Reino UnidoFil: Bouhassira, Didier. Université Versailles-Saint-Quentin; Francia. Hôpital Ambroise Paré; FranciaFil: Lefaucheur, Jean Pascal. Université Paris-Est-Créteil; FranciaFil: Timmermann, Lars. Universitat Phillips; AlemaniaFil: Gonzenbach, Roman. Center for Neurorehabilitation; SuizaFil: Kägi, Georg. Kantonsspital St; SuizaFil: Möller, Jens Carsten. Universitat Phillips; Alemania. Center for Neurological Rehabilitation; SuizaFil: Ciampi de Andrade, Daniel. Universidade de Sao Paulo; Brasi

Effects of deep brain stimulation on sensory and pain thresholds in dystonic patients

Introdução: Diferente dos sintomas motores, os efeitos da Estimulação Cerebral Profunda (ECP) sobre os sintomas não motores das distonias ainda é desconhecido. O objetivo desde estudo foi analisar os efeitos da ECP sobre os limiares sensitivos e de dor experimental em um estudo duplo cego ligado/desligado, cross-over e comparar estes resultados com os de voluntários saudáveis (VS). Método: Dezesseis pacientes com distonia idiopática (39,9 13 anos, n = 14 generalizados, n = 2 segmentares) com ECP no globo pálido interno realizaram uma bateria de teste de sensibilidade quantitativa (TSQ) e uma avaliação do sistema modulatório descendente de dor (modulação condicionada de dor, MCD). Resultados de regiões corporais com mais e menos distonia foram comparados nas condições de estimulação ligada e desligada. Os resultados do TSQ e do MCD dos pacientes foram comparados aos de VS com idade e sexo semelhantes. Resultados: A resposta de modulação descendente de dor (MCD) dos pacientes distônicos (0,66 1,99) foi anormalmente elevada quando comparada à dos VS (-0,43 0,29, p = 0,0001). Os parâmetros do TSQ dos VS diferiram dos pacientes distônicos, nos quais o limiar de detecção do frio e a dor reportada no supralimiar de estimulação ao frio foram 54,8% e 95,7% maiores nos pacientes distônicos, respectivamente. A MCD durante a ECP ligada correlacionou-se a um escore de incapacidade de Burke-Fahn-Marsden (BFM) maior (r = 0,598; p = 0,014). Enquanto os limiares sensitivos e de dor não foram diferentes com a ECP ligada/desligada, a modulação de dor dos pacientes distônicos foi marcadamente menor e parece ser mais pronunciada pela ECP. Conclusão: A ECP não parece promover mudanças nos limiares sensitivos e de dor na distonia. Pacientes distônicos têm limiares sensitivos e modulação descendente de dor diferente dos VS, o que está em linha com a teoria de perda da discriminação espacial na distoniaIntroduction: Unlike motor symptoms, the effects of deep brain stimulation (DBS) on non-motor symptoms associated with dystonia remain unknown. The objective of this study was to assess the effects of DBS on evoked experimental pain and sensory thresholds in a cross-over, double-blind on/off study, and compare these results with those of healthy volunteers (HV). Methods: Sixteen patients with idiopathic dystonia (39.9 13 years old, n = 14 generalized, n=2 segmental) with DBS of the globus pallidus internus underwent a battery of quantitative sensory testing (QST) and assessment using a pain top-down modulation system (conditioned pain modulation, CPM). Results for the more and less dystonic body regions were com QST and CPM results were compared to age- and sex-matched HV. Results: Descending pain modulation CPM response in dystonic patients (0.66 1.99) was abnormally high compared to HV (-0.43 0.29 parameters differed from those of dystonic patients, in which the cold detection threshold and the pain rating to suprathreshold cold stimulation were 54.8% and 95.7% higher in dystonic patients, respectively. On-DBS abnormal CPM correlated with higher Burke-Fahn-Marsden (BFM) disability score (r = 0.598; p = 0.014). While sensory and pain thresholds were not affected by DBS on/off condition, pain modulation was remarkably low in dystonic patients and seemed to be more pronounced by DBS. Conclusion: DBS does not seem to promote changes in sensory and pain thresholds in dystonia. Dystonic patients had different sensory thresholds and top-down modulation of pain when compared to HV which is in line with the lack of spatial discrimination in dystoni

Classifying chronic pain in dystonia: a multicenter study

Introdução: As distonias são associadas a sintomas não-motores incapacitantes como a dor crônica (DC). A DC é prevalente na distonia e impacta significativamente a qualidade de vida (QV). Não há uma ferramenta validada para avaliar a DC nas distonias, fato que dificulta o tratamento e manejo da dor. Objetivo: Desenvolver uma classificação de DC e sistema de pontuação para as distonias. Método: Um grupo multidisciplinar foi estabelecido para desenvolver a Dystonia-Pain Classification System (Dystonia-PCS) para classificar DC como relacionada ou não à distonia e fornecer um escore de gravidade de dor englobando intensidade de dor, frequência, e impacto na vida diária. Após, pacientes avaliados consecutivamente com distonias hereditárias/idiopáticas de qualquer distribuição, com ou sem DC foram recrutados num estudo de validação multicêntrico transversal. A Dystonia-PCS foi comparada com escalas clássicas de dor, humor, QV e distonia (Brief Pain Inventory-BPI, Douleur Neuropathique-4 questionnaire (DN4), Hospital Anxiety and Depression Scale, EuroQol-5D-3L e BurkeFahnMarsden Dystonia Rating Scale). Resultados: A DC esteve presente em 81 dos 123 pacientes recrutados. A DC principal foi diretamente relacionada à distonia em 82,7% dos pacientes, agravada pela distonia em 8,64%, e não-relacionada à distonia em 7,41%. A Dystonia-PCS teve excelente escore intra-avaliadores (ICC 0,941) e interavaliadores (ICC 0,867). Além disso, ela foi significativamente correlacionada ao subescore de dor da EuroQol-5D-3L ( = 0,635; p < 0,001), aos subescores de gravidade e interferência do BPI ( = 0,553; p < 0,001 e = 0,609; p < 0,001, respectivamente), e ao escore DN4 ( = 0,397; p < 0,001). Conclusão: A Dystonia-PCS é uma ferramenta confiável para categorizar e quantificar o impacto da DC nas distonias e pode melhorar o desenho de estudos clínicos e o manejo da DC na distoniaIntroduction: Dystonia is associated with disabling non-motor symptoms like chronic pain (CP). CP is prevalent in dystonia and significantly impacts the quality of life (QoL). There is no validated tool for assessing CP in dystonia, which substantially hampers pain treatment and management. Objective: To develop a CP classification and scoring system for dystonia. Methods: A multidisciplinary group was established to develop the Dystonia-Pain Classification System (Dystonia-PCS) to classify CP as related or unrelated to dystonia and to provide a pain severity score encompassing pain intensity, frequency, and impact on daily living. Then, consecutive patients with inherited/idiopathic dystonia of any distribution, with or without CP, were recruited in a cross-sectional multicenter validation study. Dystonia-PCS was compared to classic pain, mood, Qol, and dystonia scales (Brief Pain Inventory-BPI, Douleur Neuropathique-4 questionnaire-DN4, Hospital Anxiety, and Depression Scale, EuroQol-5D-3L and BurkeFahnMarsden Dystonia Rating Scale). Results: CP was present in 81 of 123 recruited patients with dystonia. The main chronic pain was directly related to dystonia in 82.7% of patients, aggravated by dystonia in 8.8%, and non-related to dystonia (7.5%). Dystonia-PCS had excellent intra-rater (ICC 0.941) and interrater (ICC 0.867) reliability. In addition, it correlated significantly with EuroQol-5D-3Ls pain subscore ( = 0.635, p < 0.001), BPI severity and interference subscores ( = 0.553, p < 0.001 and = 0.609, p < 0.001, respectively), and DN4 score ( = 0.397, p < 0.001). Conclusion: Dystonia-PCS is a reliable tool to categorize and quantify CP impact in dystonia and will help to improve clinical trial design and management of CP in dystoni

Acquired hepatocerebral degeneration: a case report

ABSTRACT Acquired hepatocerebral degeneration is an underdiagnosed neurologic syndrome characterized by parkinsonism, ataxia or other movement disorders and by neuropsychiatric and cognitive symptoms. It occurs in patients with chronic liver disease, especially those who develop portosystemic shunting and is often unrecognized as a cause of cognitive decline. Recently, its pathogenesis has been associated with manganese accumulation in basal ganglia and some treatments proposed. The aim of this article was to report a case and discuss some discoveries in connection with the disease

Exploring clinical outcomes in patients with idiopathic/inherited isolated generalized dystonia and stimulation of the subthalamic region

Background Deep Brain Stimulation (DBS) is an established treatment option for refractory dystonia, but the improvement among the patients is variable. Objective To describe the outcomes of DBS of the subthalamic region (STN) in dystonic patients and to determine whether the volume of tissue activated (VTA) inside the STN or the structural connectivity between the area stimulated and different regions of the brain are associated with dystonia improvement. Methods The response to DBS was measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) before and 7 months after surgery in patients with generalized isolated dystonia of inherited/idiopathic etiology. The sum of the two overlapping STN volumes from both hemispheres was correlated with the change in BFM scores to assess whether the area stimulated inside the STN affects the clinical outcome. Structural connectivity estimates between the VTA (of each patient) and different brain regions were computed using a normative connectome taken from healthy subjects. Results Five patients were included. The baseline BFM motor and disability subscores were 78.30 ± 13.55 (62.00–98.00) and 20.60 ± 7.80 (13.00–32.00), respectively. Patients improved dystonic symptoms, though differently. No relationships were found between the VTA inside the STN and the BFM improvement after surgery (p = 0.463). However, the connectivity between the VTA and the cerebellum structurally correlated with dystonia improvement (p = 0.003). Conclusions These data suggest that the volume of the stimulated STN does not explain the variance in outcomes in dystonia. Still, the connectivity pattern between the region stimulated and the cerebellum is linked to outcomes of patients

Development and validation of the dystonia-pain classification System : a multicenter study

Abstract: Background: Dystonia is associated with disabling nonmotor symptoms like chronic pain (CP), which is prevalent in dystonia and significantly impacts the quality of life (QoL). There is no validated tool for assessing CP in dystonia, which substantially hampers pain management. Objective: The aim was to develop a CP classification and scoring system for dystonia. Methods: A multidisciplinary group was established to develop the Dystonia-Pain Classification System (Dystonia- PCS). The classification of CP as related or unrelated to dystonia was followed by the assessment of pain severity score, encompassing pain intensity, frequency, and impact on daily living. Then, consecutive patients with inherited/idiopathic dystonia of different spatial distribution were recruited in a cross-sectional multicenter validation study. Dystonia-PCS was compared to validated pain, mood, QoL, and dystonia scales (Brief Pain Inventory, Douleur Neuropathique-4 questionnaire, European QoL-5 Dimensions-3 Level Version, and Burke–Fahn–Marsden Dystonia Rating Scale). Results: CP was present in 81 of 123 recruited patients, being directly related to dystonia in 82.7%, aggravated by dystonia in 8.8%, and nonrelated to dystonia in 7.5%. affected by this disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. Dystonia-PCS had excellent intra-rater (Intraclass Correlation Coefficient - ICC: 0.941) and inter-rater (ICC: 0.867) reliability. In addition, pain severity score correlated with European QoL-5 Dimensions-3 Level Version’s pain subscore (r = 0.635, P < 0.001) and the Brief Pain Inventory’s severity and interference scores (r = 0.553, P < 0.001 and r = 0.609, P < 0.001, respectively). Conclusions: Dystonia-PCS is a reliable tool to categorize and quantify CP impact in dystonia and will help improve clinical trial design and management of CP in patients affected by this disorder

The Parkinson`s disease pain classification system (PDPCS): results from an international mechanism-based classification approach

Abstract: Pain is a common non-motor symptom in patients with Parkinson’s disease (PD) but the correct diagnosis of the respective cause remains difficult because suitable tools are lacking, so far. We developed a framework to differentiate PD- from non-PD-related pain and classify PD-related pain into three groups based on validated mechanistic pain descriptors (nociceptive, neuropathic, or nociplastic), which encompasses the previously described PD pain types. Severity of PD-related pain syndromes was scored by ratings of intensity, frequency, and interference with daily living activities. The PD-Pain Classification System (PD-PCS) was compared with classic pain measures (ie, brief pain inventory (BPI) and McGill pain questionnaire (MPQ), PDQ-8 quality of life score, MDS-UPDRS scores, and non-motor symptoms). 159 non-demented PD patients (disease duration 10.2±7.6 years) and 37 healthy controls were recruited in four centers. PD-related pain was present in 122 patients (77%), with 24 (15%) suffering one or more syndromes at the same time. PD-related nociceptive, neuropathic, or nociplastic pain was diagnosed in 87 (55%), 25 (16%), or 35 (22%), respectively. Pain unrelated to PD was present in 35 (22%) patients. Overall, PD-PCS severity score significantly correlated with pain’s BPI and MPQ ratings, presence of dyskinesia and motor fluctuations, PDQ-8 scores, depression and anxiety measures. Moderate intra- and inter-rater reliability were observed. The PD-PCS is a valid and reliable tool for differentiating PD-related pain from PD-unrelated pain. It detects and scores mechanistic pain subtypes in a pragmatic and treatment-oriented approach, unifying previous classifications of PD-pain