Parkinsonism and Related Disorders 20 (2014) 662e664
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Short communication
Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson’s disease Jean Pellaprat a, b, *, Fabienne Ory-Magne c, Cindy Canivet c, Marion Simonetta-Moreau a, b, c, Jean-Albert Lotterie a, b, d, Fatai Radji c, Christophe Arbus a, b, e, Angélique Gerdelat a, b, c, Patrick Chaynes f, Christine Brefel-Courbon a, b, c, g a
INSERM, UMR 825, Toulouse, France Université de Toulouse, UPS, UMR 825, Toulouse, France Centre Hospitalier Universitaire de Toulouse, Service de Neurologie, Toulouse, France d Centre Hospitalier Universitaire de Toulouse, Service de Médecine Nucléaire, Toulouse, France e Centre Hospitalier Universitaire de Toulouse, Service de Psychiatrie, Toulouse, France f Centre Hospitalier Universitaire de Toulouse, Service de Neurochirurgie, Toulouse, France g Service de Pharmacologie Clinique, Faculté de Médecine, Toulouse, France b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 20 December 2013 Received in revised form 14 February 2014 Accepted 11 March 2014
Background: In Parkinson’s disease (PD), chronic pain is a common symptom which markedly affects the quality of life. Some physiological arguments proposed that Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) could improve pain in PD. Methods: We investigated in 58 PD patients the effect of STN-DBS on pain using the short McGill Pain Questionnaire and other pain parameters such as the Bodily discomfort subscore of the Parkinson’s disease Questionnaire 39 and the Unified Parkinson’s Disease Rating Scale section II (UPDRS II) item 17. Results: All pain scores were significantly improved 12 months after STN-DBS. This improvement was not correlated with motor improvement, depression scores or L-Dopa reduction. Conclusions: STN-DBS induced a substantial beneficial effect on pain in PD, independently of its motor effects and mood status of patients. Ó 2014 Elsevier Ltd. All rights reserved.
Keywords: Subthalamic deep brain stimulation (STNDBS) Parkinson’s disease Pain
1. Introduction More than 50% of the patients with Parkinson’s disease (PD) experience chronic pain [1]. Painful sensations are highly variable in PD but, according to a pathophysiological approach, two main different types of pain can be distinguished: nociceptive pain mainly related to motor symptoms (dystonias, cramps, painful dyskinesias, etc.) caused by pathological activation of nociceptors (with intact somatosensory pathways) and neuropathic pain (classically described as burning, tingling, etc.), related to central pain processing dysfunction [1,2]. In PD, pain management remains a matter of debate and there is not specific treatment for pain related to PD. Some physiological and clinical data support the idea that STN-DBS could improve painful sensation in PD [3,4]. For
* Corresponding author. Université de Toulouse, UPS, UMR, Inserm U825, Pavillon Baudot, CHU Purpan, 31059 Toulouse, France. Tel.: þ33 5 62 74 62 02. E-mail address: [email protected] (J. Pellaprat). http://dx.doi.org/10.1016/j.parkreldis.2014.03.011 1353-8020/Ó 2014 Elsevier Ltd. All rights reserved.
example, STN-DBS raised pain thresholds in painful PD patients, restored better functioning of the lateral discriminative pain system [3] and improved pain indicators (visual analogue scale and item 17 of UPDRS) [4]. In this prospective study, we aimed to evaluate the effect of STN-DBS on pain perception in PD patients, using a valid and reliable questionnaire [5], the short McGill Pain Questionnaire e Pain Questionnaire of Saint Antoine (MPQ-QDSA) which allows a multidimensional, qualitative and quantitative pain assessment. Moreover, we investigated correlations between pain and motor status, depression and dopaminergic treatment changes after STN-DBS. 2. Methods 2.1. Patients From January 2008 to January 2011, all patients with clinical diagnosis of PD according to UKPDSBB (UK Parkinson’s Disease Society Brain Bank) criteria and who underwent STN-DBS in Toulouse University Hospital were prospectively enrolled in this observational cohort study. Ethic committee approval and written informed consent were obtained.
J. Pellaprat et al. / Parkinsonism and Related Disorders 20 (2014) 662e664 2.2. Clinical assessments Patients were evaluated one week before and 12 months after STN-DBS, as part of their regular pre and post surgery follow-up care. Pain assessment was based on: 1) The short auto questionnaire MPQ-QDSA consisting of 8 sensory (throbbing, sharp, stabbing, gnawing, nagging, burning, tingling and heavy) and 7 affective (tiring-exhausting, fearful, obsessive, sickening, irritating, exasperating and depressing) items scored from 0 (no pain) to 4 (severe pain). Sensory, affective and total scores of the MPQ-QDSA were calculated; 2) The bodily discomfort item of the specific questionnaire of quality of life, the Parkinson’s disease Questionnaire-39 (PDQ-39); 3) The item 17 of UPDRS part II (pain related to PD) in ON medication condition; 4) The item 35 of UPDRS part IV (the presence of early morning dystonia). The location of pain was recorded in 4 areas: head/neck, trunk, upper and lower limbs. Before STN-DBS, motor assessment (UPDRS Part III) was performed in “OFF” drug condition (after an interruption of antiparkinsonian medication of at least 12 h) and in the best “ON” drug condition (after the administration of a single suprathreshold dose of levodopa, 150% of the morning dose). After STN-DBS, motor assessment was evaluated in OFFdrug-OFFDBS and in OFFdrug-ONDBS. STN-DBS was switched OFF or ON for at least 2 h before motor evaluation. Depressive symptoms were measured by the Montgomery-Asberg Depression Rating Scale (MADRS). The prescriptions of dopaminergic treatments, analgesic drugs (acetaminophen, pregabalin, tramadol, gabapentin and non-steroidal anti-inflammatory drugs), antidepressants and benzodiazepines were recorded. Antiparkinsonian treatment was calculated as a levodopa equivalent daily dose (LEDD). 2.3. Statistical analysis Baseline and post STN-DBS quantitative variables were compared using a Wilcoxon signed-rank test and the McNemar test was used to compare the presence of early morning dystonia and the location of pain, before and after STN-DBS. Bonferroni-Holm correction was applied. Correlation analyses were performed using a simple (Spearman test) and a multiple regression analysis. The dependent variable was the changes of the three MPQ-QDSA scores (before e after STN-DBS). The independent variables were: 1) The motor improvement (OFFdrug-OFFDBS e OFFdrug-ONDBS); 2) The depression changes (MADRS before - MADRS after STNDBS); 3) The levodopa equivalent dosage change (before - after STN-DBS). Clinical values were expressed as means standard deviation (SD). A p value
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Short communication
Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson’s disease Jean Pellaprat a, b, *, Fabienne Ory-Magne c, Cindy Canivet c, Marion Simonetta-Moreau a, b, c, Jean-Albert Lotterie a, b, d, Fatai Radji c, Christophe Arbus a, b, e, Angélique Gerdelat a, b, c, Patrick Chaynes f, Christine Brefel-Courbon a, b, c, g a
INSERM, UMR 825, Toulouse, France Université de Toulouse, UPS, UMR 825, Toulouse, France Centre Hospitalier Universitaire de Toulouse, Service de Neurologie, Toulouse, France d Centre Hospitalier Universitaire de Toulouse, Service de Médecine Nucléaire, Toulouse, France e Centre Hospitalier Universitaire de Toulouse, Service de Psychiatrie, Toulouse, France f Centre Hospitalier Universitaire de Toulouse, Service de Neurochirurgie, Toulouse, France g Service de Pharmacologie Clinique, Faculté de Médecine, Toulouse, France b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 20 December 2013 Received in revised form 14 February 2014 Accepted 11 March 2014
Background: In Parkinson’s disease (PD), chronic pain is a common symptom which markedly affects the quality of life. Some physiological arguments proposed that Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) could improve pain in PD. Methods: We investigated in 58 PD patients the effect of STN-DBS on pain using the short McGill Pain Questionnaire and other pain parameters such as the Bodily discomfort subscore of the Parkinson’s disease Questionnaire 39 and the Unified Parkinson’s Disease Rating Scale section II (UPDRS II) item 17. Results: All pain scores were significantly improved 12 months after STN-DBS. This improvement was not correlated with motor improvement, depression scores or L-Dopa reduction. Conclusions: STN-DBS induced a substantial beneficial effect on pain in PD, independently of its motor effects and mood status of patients. Ó 2014 Elsevier Ltd. All rights reserved.
Keywords: Subthalamic deep brain stimulation (STNDBS) Parkinson’s disease Pain
1. Introduction More than 50% of the patients with Parkinson’s disease (PD) experience chronic pain [1]. Painful sensations are highly variable in PD but, according to a pathophysiological approach, two main different types of pain can be distinguished: nociceptive pain mainly related to motor symptoms (dystonias, cramps, painful dyskinesias, etc.) caused by pathological activation of nociceptors (with intact somatosensory pathways) and neuropathic pain (classically described as burning, tingling, etc.), related to central pain processing dysfunction [1,2]. In PD, pain management remains a matter of debate and there is not specific treatment for pain related to PD. Some physiological and clinical data support the idea that STN-DBS could improve painful sensation in PD [3,4]. For
* Corresponding author. Université de Toulouse, UPS, UMR, Inserm U825, Pavillon Baudot, CHU Purpan, 31059 Toulouse, France. Tel.: þ33 5 62 74 62 02. E-mail address: [email protected] (J. Pellaprat). http://dx.doi.org/10.1016/j.parkreldis.2014.03.011 1353-8020/Ó 2014 Elsevier Ltd. All rights reserved.
example, STN-DBS raised pain thresholds in painful PD patients, restored better functioning of the lateral discriminative pain system [3] and improved pain indicators (visual analogue scale and item 17 of UPDRS) [4]. In this prospective study, we aimed to evaluate the effect of STN-DBS on pain perception in PD patients, using a valid and reliable questionnaire [5], the short McGill Pain Questionnaire e Pain Questionnaire of Saint Antoine (MPQ-QDSA) which allows a multidimensional, qualitative and quantitative pain assessment. Moreover, we investigated correlations between pain and motor status, depression and dopaminergic treatment changes after STN-DBS. 2. Methods 2.1. Patients From January 2008 to January 2011, all patients with clinical diagnosis of PD according to UKPDSBB (UK Parkinson’s Disease Society Brain Bank) criteria and who underwent STN-DBS in Toulouse University Hospital were prospectively enrolled in this observational cohort study. Ethic committee approval and written informed consent were obtained.
J. Pellaprat et al. / Parkinsonism and Related Disorders 20 (2014) 662e664 2.2. Clinical assessments Patients were evaluated one week before and 12 months after STN-DBS, as part of their regular pre and post surgery follow-up care. Pain assessment was based on: 1) The short auto questionnaire MPQ-QDSA consisting of 8 sensory (throbbing, sharp, stabbing, gnawing, nagging, burning, tingling and heavy) and 7 affective (tiring-exhausting, fearful, obsessive, sickening, irritating, exasperating and depressing) items scored from 0 (no pain) to 4 (severe pain). Sensory, affective and total scores of the MPQ-QDSA were calculated; 2) The bodily discomfort item of the specific questionnaire of quality of life, the Parkinson’s disease Questionnaire-39 (PDQ-39); 3) The item 17 of UPDRS part II (pain related to PD) in ON medication condition; 4) The item 35 of UPDRS part IV (the presence of early morning dystonia). The location of pain was recorded in 4 areas: head/neck, trunk, upper and lower limbs. Before STN-DBS, motor assessment (UPDRS Part III) was performed in “OFF” drug condition (after an interruption of antiparkinsonian medication of at least 12 h) and in the best “ON” drug condition (after the administration of a single suprathreshold dose of levodopa, 150% of the morning dose). After STN-DBS, motor assessment was evaluated in OFFdrug-OFFDBS and in OFFdrug-ONDBS. STN-DBS was switched OFF or ON for at least 2 h before motor evaluation. Depressive symptoms were measured by the Montgomery-Asberg Depression Rating Scale (MADRS). The prescriptions of dopaminergic treatments, analgesic drugs (acetaminophen, pregabalin, tramadol, gabapentin and non-steroidal anti-inflammatory drugs), antidepressants and benzodiazepines were recorded. Antiparkinsonian treatment was calculated as a levodopa equivalent daily dose (LEDD). 2.3. Statistical analysis Baseline and post STN-DBS quantitative variables were compared using a Wilcoxon signed-rank test and the McNemar test was used to compare the presence of early morning dystonia and the location of pain, before and after STN-DBS. Bonferroni-Holm correction was applied. Correlation analyses were performed using a simple (Spearman test) and a multiple regression analysis. The dependent variable was the changes of the three MPQ-QDSA scores (before e after STN-DBS). The independent variables were: 1) The motor improvement (OFFdrug-OFFDBS e OFFdrug-ONDBS); 2) The depression changes (MADRS before - MADRS after STNDBS); 3) The levodopa equivalent dosage change (before - after STN-DBS). Clinical values were expressed as means standard deviation (SD). A p value
