Letters COMMENT & RESPONSE
Deep Brain Stimulation for Parkinson Disease in Elderly Individuals To the Editor Patient selection criteria for deep brain stimulation (DBS) in Parkinson disease have been constantly refined and age is certainly a critical factor. DeLong et al1 proposed that the results of their study, showing little difference in postoperative complication rates, length of hospital stay, or mortality rates within 90 days of surgery in older vs younger patients, could support an expansion of the therapeutic window greater than the traditional age cutoff. However, critical concerns in most experienced centers relate to motor and cognitive outcomes rather than postoperative complications (assuming the patient is otherwise a good operative risk). Previous studies have shown worsening of activities of daily living scores, as well as axial motor scores in the ON medication state in older patients despite improvement in motor complications, a trend toward worsening of overall ON scores and less ability to reduce medication doses, and worsening or unchanged scores on several quality-of-life items (eg, mobility, activities of daily life, cognition, emotion, and communication) in older patients in contrast to improvement in younger patients.2,3 In our opinion, it is not possible to suggest an expansion in the age window for DBS based on the current study because it neither addressed important axial motor and cognitive outcomes nor quality of life. Moreover, this study did not assess choice of targets, number of sides operated on, or their timing (with staged procedures). Unilateral thalamic DBS is often performed in elderly tremor-dominant patients; indeed, the age window for this choice is already expanded in most centers performing DBS. Furthermore, this retrospective study could not rule out a selection bias from healthier older individuals being chosen for DBS. Another study found a correlation between in-hospital mortality, increasing age, and number of comorbidities; age served as a surrogate for medical comorbidities in multivariate regression.4 Although many of these limitations were acknowledged by DeLong et al,1 we feel that they were underemphasized. We believe that the current study is misleading and cannot be used to support an expansion of the age window for DBS candidacy. Instead, centers offering DBS should continue to emphasize cognitive status, motor phenotypes, and levodopa response, as well as other medical comorbidities. The findings of this study,1 showing little difference in postoperative complications between younger and older patients, rather than encouraging an expansion of the age range for DBS, should instead be interpreted as reassuring support for the cautious and informed selection process that is currently used by most centers. Camila C. Aquino, MD, MSc Andres M. Lozano, MD, PhD, FRCSC, FRSC Anthony E. Lang, MD, FRCPC jamaneurology.com
Author Affiliations: Morton and Gloria Shulman Movement Disorders Center and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, Toronto, Ontario, Canada (Aquino, Lang); Division of Neurosurgery, Toronto Western Hospital and University of Toronto, Toronto, Ontario, Canada (Lozano). Corresponding Author: Anthony E. Lang, MD, FRCPC, Toronto Western Hospital, 399 Bathurst St, 7th Floor, McLaughlin Pavilion, Toronto, ON M5T 2S8, Canada ([email protected]). Conflict of Interest Disclosures: None reported. Additional Contributions: Alfonso Fasano, MD, and Renato Munhoz, MD, of Toronto Western Hospital provided valuable input to this letter. They did not receive compensation for their contributions. 1. DeLong MR, Huang KT, Gallis J, et al. Effect of advancing age on outcomes of deep brain stimulation for Parkinson disease. JAMA Neurol. 2014;71(10):1290-1295. 2. Russmann H, Ghika J, Villemure J-G, et al. Subthalamic nucleus deep brain stimulation in Parkinson disease patients over age 70 years. Neurology. 2004; 63(10):1952-1954. 3. Derost P-P, Ouchchane L, Morand D, et al. Is DBS-STN appropriate to treat severe Parkinson disease in an elderly population? Neurology. 2007;68(17): 1345-1355. 4. Rughani AI, Hodaie M, Lozano AM. Acute complications of movement disorders surgery: effects of age and comorbidities. Mov Disord. 2013;28(12): 1661-1667.
To the Editor We read with great interest the article by DeLong et al1 regarding deep brain stimulation (DBS), an established surgical solution for the motor symptoms of Parkinson disease.2 They conducted a large nonrandomized clinical trial in which they demonstrated that comparable results are achieved with DBS in patients older than 75 years, contrary to popular belief. We consider this study a significant milestone: it lucidly shows us that despite our preconceptions, we can achieve decent results in elderly individuals for the treatment of PD and, more broadly, in the neurosurgical domain. However, before this study is used as a model for future trials, we would like to make 3 methodological observations. First, the authors chose a follow-up period of 90 days, which is sufficient for short-term complications. However, long-term complications may still occur but would be unaccounted for. Without further exploration of the relationship between age and the long-term complications of DBS, the evidence here is somewhat incomplete. Second, we would like to emphasize that the simple absence of increased postoperative complication risk is not the whole story. For example, we must not forget that patients older than 75 years are likely to be at advanced stages of Parkinson disease, exceeding the stage where maximal benefit can be reaped from DBS.3 Moreover, elderly patients have more comorbidity including malignancy and dementia. Therefore, gains from DBS may be reduced and careful cost-benefit analysis is required before the therapeutic window can be expanded. Third, we were a little concerned regarding the discrepancy between the group sizes of those 75 years and younger and those older than 75 years. This may have been accounted for by an appropriate power calculation; however, this was not mentioned. Regardless, in(Reprinted) JAMA Neurology March 2015 Volume 72, Number 3
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a NCSU Hunt Library User on 05/14/2015
367
Letters
creasing the sample size of the older-than-75-years group would have likely strengthened this study. Finally, these simple considerations are not criticisms, but rather careful additions to a well-conducted study for a welldeserved population. Weiyu Ye, BA Joseph M. Norris, BSc, BMBS Author Affiliations: School of Clinical Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, England (Ye); Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, England (Norris). Corresponding Author: Weiyu Ye, BA, School of Clinical Medicine, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0SP, England ([email protected]). Conflict of Interest Disclosures: None reported. 1. DeLong MR, Huang KT, Gallis J, et al. Effect of advancing age on outcomes of deep brain stimulation for Parkinson disease. JAMA Neurol. 2014;71(10):1290-1295. 2. Buttery PC, Barker RA. Treating Parkinson’s disease in the 21st century: can stem cell transplantation compete? J Comp Neurol. 2014;522(12):2802-2816. 3. Groiss SJ, Wojtecki L, Südmeyer M, Schnitzler A. Deep brain stimulation in Parkinson’s disease. Ther Adv Neurol Disord. 2009;2(6):20-28.
In Reply We appreciate the constructive comments by Aquino et al and Ye and Norris regarding our study1 on the effect of advancing age on outcomes of deep brain stimulation (DBS) surgery. While DBS has evolved into a routine and effective therapy for patients with advanced Parkinson disease (PD), consideration of DBS therapy for patients of advanced age is less likely owing to a number of factors including medical issues and the actual Parkinson symptoms being treated. Van Den Eeden and colleagues2 showed that the incidence of PD has the largest increase after age 70 years. Combined with an ever-increasing life span, there is a large and growing population of possible candidates for DBS for treatment of PD. This study was aimed at studying the differences in postoperative complications of this expanding elderly population and younger patients with PD. However, we do not underestimate the importance of the preoperative evaluation, especially in an elderly cohort. Specifically, while our study was limited by a short follow-up (90 days) and a smaller number of patients older than 75 years compared with those younger than 75 years, as outlined by Ye and Norris, we feel these data were adequate for assessing conclusions regarding postoperative surgical complications. First, most short-term complications occur in the immediate postoperative period.3 Thus, we feel that a 90-day period captures an appropriate follow-up for the purposes of this study. Second, while there were fewer patients older than 75 years compared with those younger than 75 years in our cohort, our statistical analyses were significantly different. Finally, this discrepancy highlights the effect age has on current surgical candidate selection.
368
In regard to the concerns mentioned by Aquino et al, we agree that cognitive status, motor phenotypes, levodopa response, and medical comorbidities should all continue to be emphasized and weighed by multidisciplinary teams evaluating candidates for DBS surgery. Careful preoperative examination of these factors can predict better outcomes including evaluation of axial motor scores while not taking medication, particularly for gait.4 Ultimately, elderly individuals are a heterogeneous group and our study supports that age should not be used to exclude them from a potentially powerful treatment if their disease is otherwise amenable to surgical intervention. Instead, all patients should be viewed on the basis of their medical issues, their disease symptoms (ie, tremor, dyskinesias, gait, and postural instability), and whether there is sufficient life span to offer a long-term benefit. We agree that the current results emphasize the careful (biased but unknown) selection of this retrospective cohort in selecting appropriate candidates, although neither the selection criteria nor critical aspects of the patient’s PD (ie, tremor, location of DBS, number of operated sides, and active contacts) are ascertainable from this format of analysis. Our data do show that short-term complication rates are comparable between the 2 age groups and multidisciplinary teams should reconsider age as a limiting factor for DBS, instead focusing on whether patients meet the standard medical criteria for surgical candidacy. Shervin Rahimpour, MD Dennis A. Turner, MD Shivanand P. Lad, MD, PhD Author Affiliations: Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina. Corresponding Author: Shivanand P. Lad, MD, PhD, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Box 3807, Durham, NC 27710 ([email protected]). Conflict of Interest Disclosures: Dr Lad has consulted for and received grant support from Medtronic and St Jude Medical. He serves as director of the Duke Neuro-Outcomes Center, which has received research funding from National Institutes of Health grant KM1 CA 156687, Medtronic, and St Jude Medical. No other disclosures were reported. Additional Contributions: Steven Cook, MD, and Patrick Hickey, DO, of Duke University provided valuable contributions in writing this letter. They did not receive compensation for the contributions. 1. DeLong MR, Huang KT, Gallis J, et al. Effect of advancing age on outcomes of deep brain stimulation for Parkinson disease. JAMA Neurol. 2014;71(10):1290-1295. 2. Van Den Eeden SK, Tanner CM, Bernstein AL, et al. Incidence of Parkinson’s disease: variation by age, gender, and race/ethnicity. Am J Epidemiol. 2003;157 (11):1015-1022. 3. Voges J, Waerzeggers Y, Maarouf M, et al. Deep-brain stimulation: long-term analysis of complications caused by hardware and surgery: experiences from a single centre. J Neurol Neurosurg Psychiatry. 2006;77(7):868-872. 4. Vesper J, Haak S, Ostertag C, Nikkhah G. Subthalamic nucleus deep brain stimulation in elderly patients: analysis of outcome and complications. BMC Neurol. 2007;7:7.
JAMA Neurology March 2015 Volume 72, Number 3 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a NCSU Hunt Library User on 05/14/2015
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Deep Brain Stimulation for Parkinson Disease in Elderly Individuals To the Editor Patient selection criteria for deep brain stimulation (DBS) in Parkinson disease have been constantly refined and age is certainly a critical factor. DeLong et al1 proposed that the results of their study, showing little difference in postoperative complication rates, length of hospital stay, or mortality rates within 90 days of surgery in older vs younger patients, could support an expansion of the therapeutic window greater than the traditional age cutoff. However, critical concerns in most experienced centers relate to motor and cognitive outcomes rather than postoperative complications (assuming the patient is otherwise a good operative risk). Previous studies have shown worsening of activities of daily living scores, as well as axial motor scores in the ON medication state in older patients despite improvement in motor complications, a trend toward worsening of overall ON scores and less ability to reduce medication doses, and worsening or unchanged scores on several quality-of-life items (eg, mobility, activities of daily life, cognition, emotion, and communication) in older patients in contrast to improvement in younger patients.2,3 In our opinion, it is not possible to suggest an expansion in the age window for DBS based on the current study because it neither addressed important axial motor and cognitive outcomes nor quality of life. Moreover, this study did not assess choice of targets, number of sides operated on, or their timing (with staged procedures). Unilateral thalamic DBS is often performed in elderly tremor-dominant patients; indeed, the age window for this choice is already expanded in most centers performing DBS. Furthermore, this retrospective study could not rule out a selection bias from healthier older individuals being chosen for DBS. Another study found a correlation between in-hospital mortality, increasing age, and number of comorbidities; age served as a surrogate for medical comorbidities in multivariate regression.4 Although many of these limitations were acknowledged by DeLong et al,1 we feel that they were underemphasized. We believe that the current study is misleading and cannot be used to support an expansion of the age window for DBS candidacy. Instead, centers offering DBS should continue to emphasize cognitive status, motor phenotypes, and levodopa response, as well as other medical comorbidities. The findings of this study,1 showing little difference in postoperative complications between younger and older patients, rather than encouraging an expansion of the age range for DBS, should instead be interpreted as reassuring support for the cautious and informed selection process that is currently used by most centers. Camila C. Aquino, MD, MSc Andres M. Lozano, MD, PhD, FRCSC, FRSC Anthony E. Lang, MD, FRCPC jamaneurology.com
Author Affiliations: Morton and Gloria Shulman Movement Disorders Center and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, Toronto, Ontario, Canada (Aquino, Lang); Division of Neurosurgery, Toronto Western Hospital and University of Toronto, Toronto, Ontario, Canada (Lozano). Corresponding Author: Anthony E. Lang, MD, FRCPC, Toronto Western Hospital, 399 Bathurst St, 7th Floor, McLaughlin Pavilion, Toronto, ON M5T 2S8, Canada ([email protected]). Conflict of Interest Disclosures: None reported. Additional Contributions: Alfonso Fasano, MD, and Renato Munhoz, MD, of Toronto Western Hospital provided valuable input to this letter. They did not receive compensation for their contributions. 1. DeLong MR, Huang KT, Gallis J, et al. Effect of advancing age on outcomes of deep brain stimulation for Parkinson disease. JAMA Neurol. 2014;71(10):1290-1295. 2. Russmann H, Ghika J, Villemure J-G, et al. Subthalamic nucleus deep brain stimulation in Parkinson disease patients over age 70 years. Neurology. 2004; 63(10):1952-1954. 3. Derost P-P, Ouchchane L, Morand D, et al. Is DBS-STN appropriate to treat severe Parkinson disease in an elderly population? Neurology. 2007;68(17): 1345-1355. 4. Rughani AI, Hodaie M, Lozano AM. Acute complications of movement disorders surgery: effects of age and comorbidities. Mov Disord. 2013;28(12): 1661-1667.
To the Editor We read with great interest the article by DeLong et al1 regarding deep brain stimulation (DBS), an established surgical solution for the motor symptoms of Parkinson disease.2 They conducted a large nonrandomized clinical trial in which they demonstrated that comparable results are achieved with DBS in patients older than 75 years, contrary to popular belief. We consider this study a significant milestone: it lucidly shows us that despite our preconceptions, we can achieve decent results in elderly individuals for the treatment of PD and, more broadly, in the neurosurgical domain. However, before this study is used as a model for future trials, we would like to make 3 methodological observations. First, the authors chose a follow-up period of 90 days, which is sufficient for short-term complications. However, long-term complications may still occur but would be unaccounted for. Without further exploration of the relationship between age and the long-term complications of DBS, the evidence here is somewhat incomplete. Second, we would like to emphasize that the simple absence of increased postoperative complication risk is not the whole story. For example, we must not forget that patients older than 75 years are likely to be at advanced stages of Parkinson disease, exceeding the stage where maximal benefit can be reaped from DBS.3 Moreover, elderly patients have more comorbidity including malignancy and dementia. Therefore, gains from DBS may be reduced and careful cost-benefit analysis is required before the therapeutic window can be expanded. Third, we were a little concerned regarding the discrepancy between the group sizes of those 75 years and younger and those older than 75 years. This may have been accounted for by an appropriate power calculation; however, this was not mentioned. Regardless, in(Reprinted) JAMA Neurology March 2015 Volume 72, Number 3
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a NCSU Hunt Library User on 05/14/2015
367
Letters
creasing the sample size of the older-than-75-years group would have likely strengthened this study. Finally, these simple considerations are not criticisms, but rather careful additions to a well-conducted study for a welldeserved population. Weiyu Ye, BA Joseph M. Norris, BSc, BMBS Author Affiliations: School of Clinical Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, England (Ye); Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, England (Norris). Corresponding Author: Weiyu Ye, BA, School of Clinical Medicine, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0SP, England ([email protected]). Conflict of Interest Disclosures: None reported. 1. DeLong MR, Huang KT, Gallis J, et al. Effect of advancing age on outcomes of deep brain stimulation for Parkinson disease. JAMA Neurol. 2014;71(10):1290-1295. 2. Buttery PC, Barker RA. Treating Parkinson’s disease in the 21st century: can stem cell transplantation compete? J Comp Neurol. 2014;522(12):2802-2816. 3. Groiss SJ, Wojtecki L, Südmeyer M, Schnitzler A. Deep brain stimulation in Parkinson’s disease. Ther Adv Neurol Disord. 2009;2(6):20-28.
In Reply We appreciate the constructive comments by Aquino et al and Ye and Norris regarding our study1 on the effect of advancing age on outcomes of deep brain stimulation (DBS) surgery. While DBS has evolved into a routine and effective therapy for patients with advanced Parkinson disease (PD), consideration of DBS therapy for patients of advanced age is less likely owing to a number of factors including medical issues and the actual Parkinson symptoms being treated. Van Den Eeden and colleagues2 showed that the incidence of PD has the largest increase after age 70 years. Combined with an ever-increasing life span, there is a large and growing population of possible candidates for DBS for treatment of PD. This study was aimed at studying the differences in postoperative complications of this expanding elderly population and younger patients with PD. However, we do not underestimate the importance of the preoperative evaluation, especially in an elderly cohort. Specifically, while our study was limited by a short follow-up (90 days) and a smaller number of patients older than 75 years compared with those younger than 75 years, as outlined by Ye and Norris, we feel these data were adequate for assessing conclusions regarding postoperative surgical complications. First, most short-term complications occur in the immediate postoperative period.3 Thus, we feel that a 90-day period captures an appropriate follow-up for the purposes of this study. Second, while there were fewer patients older than 75 years compared with those younger than 75 years in our cohort, our statistical analyses were significantly different. Finally, this discrepancy highlights the effect age has on current surgical candidate selection.
368
In regard to the concerns mentioned by Aquino et al, we agree that cognitive status, motor phenotypes, levodopa response, and medical comorbidities should all continue to be emphasized and weighed by multidisciplinary teams evaluating candidates for DBS surgery. Careful preoperative examination of these factors can predict better outcomes including evaluation of axial motor scores while not taking medication, particularly for gait.4 Ultimately, elderly individuals are a heterogeneous group and our study supports that age should not be used to exclude them from a potentially powerful treatment if their disease is otherwise amenable to surgical intervention. Instead, all patients should be viewed on the basis of their medical issues, their disease symptoms (ie, tremor, dyskinesias, gait, and postural instability), and whether there is sufficient life span to offer a long-term benefit. We agree that the current results emphasize the careful (biased but unknown) selection of this retrospective cohort in selecting appropriate candidates, although neither the selection criteria nor critical aspects of the patient’s PD (ie, tremor, location of DBS, number of operated sides, and active contacts) are ascertainable from this format of analysis. Our data do show that short-term complication rates are comparable between the 2 age groups and multidisciplinary teams should reconsider age as a limiting factor for DBS, instead focusing on whether patients meet the standard medical criteria for surgical candidacy. Shervin Rahimpour, MD Dennis A. Turner, MD Shivanand P. Lad, MD, PhD Author Affiliations: Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina. Corresponding Author: Shivanand P. Lad, MD, PhD, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Box 3807, Durham, NC 27710 ([email protected]). Conflict of Interest Disclosures: Dr Lad has consulted for and received grant support from Medtronic and St Jude Medical. He serves as director of the Duke Neuro-Outcomes Center, which has received research funding from National Institutes of Health grant KM1 CA 156687, Medtronic, and St Jude Medical. No other disclosures were reported. Additional Contributions: Steven Cook, MD, and Patrick Hickey, DO, of Duke University provided valuable contributions in writing this letter. They did not receive compensation for the contributions. 1. DeLong MR, Huang KT, Gallis J, et al. Effect of advancing age on outcomes of deep brain stimulation for Parkinson disease. JAMA Neurol. 2014;71(10):1290-1295. 2. Van Den Eeden SK, Tanner CM, Bernstein AL, et al. Incidence of Parkinson’s disease: variation by age, gender, and race/ethnicity. Am J Epidemiol. 2003;157 (11):1015-1022. 3. Voges J, Waerzeggers Y, Maarouf M, et al. Deep-brain stimulation: long-term analysis of complications caused by hardware and surgery: experiences from a single centre. J Neurol Neurosurg Psychiatry. 2006;77(7):868-872. 4. Vesper J, Haak S, Ostertag C, Nikkhah G. Subthalamic nucleus deep brain stimulation in elderly patients: analysis of outcome and complications. BMC Neurol. 2007;7:7.
JAMA Neurology March 2015 Volume 72, Number 3 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a NCSU Hunt Library User on 05/14/2015
jamaneurology.com
