CORRESPONDENCE
Carly Johnco, PhD* Eric A. Storch, PhD*‡§¶k# Departments of *Pediatrics ‡Psychology §Psychiatry and Behavioral Neurosciences ¶Health Policy and Management University of South Florida Tampa, Florida kRogers Behavioral Health–Tampa Bay Tampa, Florida #All Children's Hospital Johns Hopkins Medicine St. Petersburg, Florida REFERENCES 1. Servello D, Zekaj E, Saleh C, Lange N, Porta M. Deep brain stimulation in Tourette syndrome: what does the future hold? A cohort of 48 patients. Neurosurgery. 2016;78(1):91-100. 2. McGuire JF, Piacentini J, Brennan EA, et al. A meta-analysis of behavior therapy for Tourette syndrome. J Psychiatr Res. 2014;50:106-112. 3. Dutta N, Cavanna AE. The effectiveness of habit reversal therapy in the treatment of Tourette syndrome and other chronic tic disorders: a systematic review. Funct Neurol. 2013;28(1):7-12. 4. Zheng W, Li XB, Xiang YQ, et al. Aripiprazole for Tourette's syndrome: a systematic review and meta-analysis. Hum Psychopharmacol. 2016;31(1):11-18. 5. Gilbert DL, Jankovic J. Pharmacological treatment of Tourette syndrome. J Obsessive Compuls Relat Disord. 2014;3(4):407-414. 6. Sandor P. Pharmacological management of tics in patients with TS. J Psychosom Res. 2003;55(1):41-48. 7. Martinez-Ramirez D, Hu W, Bona AR, Okun MS, Wagle Shukla A. Update on deep brain stimulation in Parkinson's disease. Transl Neurodegener. 2015; 4:12. 8. Benabid AL, Chabardes S, Seigneuret E. Deep-brain stimulation in Parkinson's disease: long-term efficacy and safety: what happened this year? Curr Opin Neurol. 2005;18(6):623-630. 9. Holtzheimer PE, Mayberg HS. Deep brain stimulation for psychiatric disorders. Annu Rev Neurosci. 2011;34:289-307. 10. Altinay M, Estemalik E, Malone DA Jr. A comprehensive review of the use of deep brain stimulation (DBS) in treatment of psychiatric and headache disorders. Headache. 2015;55(2):345-350. 11. Goodman WK, Alterman RL. Deep brain stimulation for intractable psychiatric disorders. Annu Rev Med. 2012;63(1):511-524. 12. Morishita T, Fayad S, Higuchi MA, Nestor K, Foote K. Deep brain stimulation for treatment-resistant depression: systematic review of clinical outcomes. Neurotherapeutics. 2014;11(3):475-484. 13. Fitzgerald PB, Segrave RA. Deep brain stimulation in mental health: review of evidence for clinical efficacy. Aust N Z J Psychiatry. 2015;49 (11):979-993. 14. Greenberg BD, Gabriels LA, Malone DA Jr, et al. Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience. Mol Psychiatry. 2010;15(1):64-79. 15. Schrock LE, Mink JW, Woods DW, et al. Tourette syndrome deep brain stimulation: a review and updated recommendations. Mov Disord. 2015;30(4): 448-471. 16. Mink JW, Walkup J, Frey KA, et al. Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome. Mov Disord. 2006;21(11):1831-1838. 17. Servello D, Porta M, Sassi M, Brambilla A, Robertson MM. Deep brain stimulation in 18 patients with severe Gilles de la Tourette syndrome refractory to treatment: the surgery and stimulation. J Neurol Neurosurg Psychiatry. 2008;79(2): 136-142. 18. Air EL, Ostrem JL, Sanger TD, Starr PA. Deep brain stimulation in children: experience and technical pearls. J Neurosurg Pediatr. 2011;8(6): 566-574.
E764 | VOLUME 78 | NUMBER 5 | MAY 2016
19. Leckman JF, Zhang H, Vitale A, et al. Course of tic severity in Tourette syndrome: the first two decades. Pediatrics. 1998;102(1 pt 1):14-19. 20. Erenberg G, Cruse RP, Rothner AD. The natural history of Tourette syndrome: a follow-up study. Ann Neurol. 1987;22(3):383-385. 21. Bloch MH, Peterson BS, Scahill L, et al. Adulthood outcome of tic and obsessivecompulsive symptom severity in children with Tourette syndrome. Arch Pediatr Adolesc Med. 2006;160(1):65-69. 22. Champion LM, Fulton WA, Shady GA. Tourette's syndrome and social functioning in a Canadian population. Neurosci Biobehav Rev. 1988;12(3): 255-257. 23. Storch EA, Merlo LJ, Lack C, et al. Quality of life in youth with Tourette's syndrome and chronic tic disorder. J Clin Child Adolesc Psychol. 2007;36(2): 217-227. 24. Carter AS, O'Donnell DA, Schultz RT, Scahill L, Leckman JF, Pauls DL. Social and emotional adjustment in children affected with Gilles de la Tourette's Syndrome: associations with ADHD and family functioning. J Child Psychol Psychiatry. 2000;41(2):215-223. 25. Storch EA, Murphy TK, Chase RM, et al. Peer victimization in youth with Tourette's syndrome and chronic tic disorder: relations with tic severity and internalizing symptoms. J Psychopathol Behav Assess. 2007;29(4):211-219. 26. Maciunas RJ, Maddux BN, Riley DE, et al. Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome. J Neurosurg. 2007;107(5):1004-1014. 27. Welter ML, Mallet L, Houeto JL, et al. Internal pallidal and thalamic stimulation in patients with Tourette syndrome. Arch Neurol. 2008;65(7):952-957. 28. Ackermans L, Duits A, van der Linden C, et al. Double-blind clinical trial of thalamic stimulation in patients with Tourette syndrome. Brain A J Neurol. 2011; 134(pt 3):832-844. 29. Maddux B, Riley D, Whitney CM, Maciunas RJ. Double-blind trial of thalamic DBS for Tourette syndrome: one-year follow-up. Neurology. 2007;68(suppl 1):A155. 30. Muller-Vahl KR, Cath DC, Cavanna AE, et al. European clinical guidelines for Tourette syndrome and other tic disorders, part IV: deep brain stimulation. Eur Child Adolesc Psychiatry. 2011;20(4):209-217.
10.1227/NEU.0000000000001222
In Reply: Evaluating Risks and Benefit of Deep Brain Stimulation for Treatment-Refractory Tourette Syndrome We thank Drs Johnco and Storch for their comments and their great interest in our article.1 We welcome this occasion to clarify several critical points raised by the authors to allow a more balanced evaluation of deep brain stimulation (DBS) in refractory Tourette syndrome (TS). COMPLICATION RATE The authors underline the high rate of complications observed in our study and state that “[a]lthough promising, enthusiasm should be somewhat tempered, given that there was evidence of adverse effects of DBS in up to 29% of patients.” This statement confirms our own opinion, which we stated and underlined several times in our article, which contains a subsection titled Warnings in which we detailed and commented on the high rate of complications. In the Conclusion section, we stated that “DBS holds a promising future for movement and for behavioral disorders.” However, we stated equally that “great attention should be paid to the selection
www.neurosurgery-online.com
Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
CORRESPONDENCE
of patients and target choice, alongside constant technological improvement of the complex DBS device.” AGE OF SURGERY Drs Johnco and Storch write, “Servello et al. . .posed the question of whether DBS should be considered a last-line or bridging treatment for children and adolescents until remission, despite there being only 10 documented cases of DBS in patients ,18 years of age.” And “[g]iven the lack of firmly established efficacy for TS in adults, the rates of documented adverse effects, and the common pattern of symptom remission or reduction during adolescence and young adulthood. . ., we have concerns about prematurely advocating the use of DBS in young populations.” They continue, “it is also important to consider the potential negative impact on psychosocial functioning of multiple invasive surgeries on a child (potentially) with limited improvement, adverse effects, or complications.” We agree fully that more data are urgently needed in patients ,18 years of age treated with DBS to be more conclusive on this highly important and debated point. However, one should keep in mind that every surgical intervention harbors the risk of complications, regardless of the age at surgery. Additionally, one should keep in mind that every conventional medical treatment for psychiatric diseases harbors serious adverse effects. We believe further that it remains highly speculative to avoid surgical treatment exclusively on the basis on the fear of complications, whereas it is certain that a refractory patient will have a compromised future. Although we are aware that findings of case reports cannot be generalized, we refer to our recently published article2 in which we reported the case of a young TS patient. This TS patient could pass through the critical age of puberty thanks to DBS. Without DBS, this patient certainly would have been seriously impaired.
trials with a priori target selection to systematically assess the efficacy of DBS treatment.” In medicine, larger randomized, double-blind trials are always desirable. However, one should keep in mind that DBS is experimental in psychiatric diseases and that large clinical trials are regrettably rare in DBS (whatever its indication). The reasons are multiple (eg, the difficulty in standardizing a highly complex surgical procedure, the strictly defined eligibility criteria for refractory patients to be considered for DBS, and the important financial aspects of DBS).2 TARGET SELECTION The authors write that the “a standardized approach to target selection based on symptom phenotypes is needed to methodically assess efficacy and to provide accurate, evidence-based, generalizable results.” We believe rather that target selection cannot be standardized, considering the large phenotypic variability of TS. Standardized target choice in TS, given the aforementioned large phenotypic variability, may even be counterproductive. Instead, we think that target selection should be based on the specific symptomatology of each patient; unavoidably, targeting selection may have different results in every single patient. In conclusion, we underline that DBS treatment represents the last therapeutic option and needs to be balanced against the severity of the disease, the natural evolution of the disease, and the disease-related morbidity risks. Disclosure The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.
Domenico Servello, MD Christian Saleh, MD Edvin Zekaj, MD Mauro Porta, MD Departments of Neurosurgery and Neurology IRCCS Galeazzi Hospital Milan, Italy
TS COMORBIDITIES The authors write, “The high rate of untreated severe comorbid psychiatric diagnoses is another important issue to consider for accurate evaluation of DBS candidates. . .. Unfortunately, no information was provided on whether these conditions had also been refractory to evidence-based treatments conducted by an experienced therapist.” In all TS patients with comorbidities, we have adopted a treatment for each of the associated comorbidities as outlined by Jankovic and Kurlan.3 Patients chosen for DBS were refractory to medical and behavioral treatments. DBS TRIALS The authors write “there is a clear need for further methodologically rigorous studies before any conclusions can be reached” and propose “larger randomized, double-blind, sham-controlled
NEUROSURGERY
REFERENCES 1. Servello D, Zekaj E, Saleh C, Lange N, Porta M. Deep brain stimulation in Tourette syndrome: what does the future hold? A cohort of 48 patients. Neurosurgery. 2016;78(1):91-100. 2. Zekaj E, Saleh C, Porta M, Servello D. Temporary deep brain stimulation in Gilles de la Tourette syndrome: a feasible approach? Surg Neurol Int. 2015;6: 122. 3. Jankovic J, Kurlan R. Tourette syndrome: evolving concepts. Mov Disord. 2011;26 (6):1149-1156. 10.1227/NEU.0000000000001223
VOLUME 78 | NUMBER 5 | MAY 2016 | E765
Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
Carly Johnco, PhD* Eric A. Storch, PhD*‡§¶k# Departments of *Pediatrics ‡Psychology §Psychiatry and Behavioral Neurosciences ¶Health Policy and Management University of South Florida Tampa, Florida kRogers Behavioral Health–Tampa Bay Tampa, Florida #All Children's Hospital Johns Hopkins Medicine St. Petersburg, Florida REFERENCES 1. Servello D, Zekaj E, Saleh C, Lange N, Porta M. Deep brain stimulation in Tourette syndrome: what does the future hold? A cohort of 48 patients. Neurosurgery. 2016;78(1):91-100. 2. McGuire JF, Piacentini J, Brennan EA, et al. A meta-analysis of behavior therapy for Tourette syndrome. J Psychiatr Res. 2014;50:106-112. 3. Dutta N, Cavanna AE. The effectiveness of habit reversal therapy in the treatment of Tourette syndrome and other chronic tic disorders: a systematic review. Funct Neurol. 2013;28(1):7-12. 4. Zheng W, Li XB, Xiang YQ, et al. Aripiprazole for Tourette's syndrome: a systematic review and meta-analysis. Hum Psychopharmacol. 2016;31(1):11-18. 5. Gilbert DL, Jankovic J. Pharmacological treatment of Tourette syndrome. J Obsessive Compuls Relat Disord. 2014;3(4):407-414. 6. Sandor P. Pharmacological management of tics in patients with TS. J Psychosom Res. 2003;55(1):41-48. 7. Martinez-Ramirez D, Hu W, Bona AR, Okun MS, Wagle Shukla A. Update on deep brain stimulation in Parkinson's disease. Transl Neurodegener. 2015; 4:12. 8. Benabid AL, Chabardes S, Seigneuret E. Deep-brain stimulation in Parkinson's disease: long-term efficacy and safety: what happened this year? Curr Opin Neurol. 2005;18(6):623-630. 9. Holtzheimer PE, Mayberg HS. Deep brain stimulation for psychiatric disorders. Annu Rev Neurosci. 2011;34:289-307. 10. Altinay M, Estemalik E, Malone DA Jr. A comprehensive review of the use of deep brain stimulation (DBS) in treatment of psychiatric and headache disorders. Headache. 2015;55(2):345-350. 11. Goodman WK, Alterman RL. Deep brain stimulation for intractable psychiatric disorders. Annu Rev Med. 2012;63(1):511-524. 12. Morishita T, Fayad S, Higuchi MA, Nestor K, Foote K. Deep brain stimulation for treatment-resistant depression: systematic review of clinical outcomes. Neurotherapeutics. 2014;11(3):475-484. 13. Fitzgerald PB, Segrave RA. Deep brain stimulation in mental health: review of evidence for clinical efficacy. Aust N Z J Psychiatry. 2015;49 (11):979-993. 14. Greenberg BD, Gabriels LA, Malone DA Jr, et al. Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience. Mol Psychiatry. 2010;15(1):64-79. 15. Schrock LE, Mink JW, Woods DW, et al. Tourette syndrome deep brain stimulation: a review and updated recommendations. Mov Disord. 2015;30(4): 448-471. 16. Mink JW, Walkup J, Frey KA, et al. Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome. Mov Disord. 2006;21(11):1831-1838. 17. Servello D, Porta M, Sassi M, Brambilla A, Robertson MM. Deep brain stimulation in 18 patients with severe Gilles de la Tourette syndrome refractory to treatment: the surgery and stimulation. J Neurol Neurosurg Psychiatry. 2008;79(2): 136-142. 18. Air EL, Ostrem JL, Sanger TD, Starr PA. Deep brain stimulation in children: experience and technical pearls. J Neurosurg Pediatr. 2011;8(6): 566-574.
E764 | VOLUME 78 | NUMBER 5 | MAY 2016
19. Leckman JF, Zhang H, Vitale A, et al. Course of tic severity in Tourette syndrome: the first two decades. Pediatrics. 1998;102(1 pt 1):14-19. 20. Erenberg G, Cruse RP, Rothner AD. The natural history of Tourette syndrome: a follow-up study. Ann Neurol. 1987;22(3):383-385. 21. Bloch MH, Peterson BS, Scahill L, et al. Adulthood outcome of tic and obsessivecompulsive symptom severity in children with Tourette syndrome. Arch Pediatr Adolesc Med. 2006;160(1):65-69. 22. Champion LM, Fulton WA, Shady GA. Tourette's syndrome and social functioning in a Canadian population. Neurosci Biobehav Rev. 1988;12(3): 255-257. 23. Storch EA, Merlo LJ, Lack C, et al. Quality of life in youth with Tourette's syndrome and chronic tic disorder. J Clin Child Adolesc Psychol. 2007;36(2): 217-227. 24. Carter AS, O'Donnell DA, Schultz RT, Scahill L, Leckman JF, Pauls DL. Social and emotional adjustment in children affected with Gilles de la Tourette's Syndrome: associations with ADHD and family functioning. J Child Psychol Psychiatry. 2000;41(2):215-223. 25. Storch EA, Murphy TK, Chase RM, et al. Peer victimization in youth with Tourette's syndrome and chronic tic disorder: relations with tic severity and internalizing symptoms. J Psychopathol Behav Assess. 2007;29(4):211-219. 26. Maciunas RJ, Maddux BN, Riley DE, et al. Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome. J Neurosurg. 2007;107(5):1004-1014. 27. Welter ML, Mallet L, Houeto JL, et al. Internal pallidal and thalamic stimulation in patients with Tourette syndrome. Arch Neurol. 2008;65(7):952-957. 28. Ackermans L, Duits A, van der Linden C, et al. Double-blind clinical trial of thalamic stimulation in patients with Tourette syndrome. Brain A J Neurol. 2011; 134(pt 3):832-844. 29. Maddux B, Riley D, Whitney CM, Maciunas RJ. Double-blind trial of thalamic DBS for Tourette syndrome: one-year follow-up. Neurology. 2007;68(suppl 1):A155. 30. Muller-Vahl KR, Cath DC, Cavanna AE, et al. European clinical guidelines for Tourette syndrome and other tic disorders, part IV: deep brain stimulation. Eur Child Adolesc Psychiatry. 2011;20(4):209-217.
10.1227/NEU.0000000000001222
In Reply: Evaluating Risks and Benefit of Deep Brain Stimulation for Treatment-Refractory Tourette Syndrome We thank Drs Johnco and Storch for their comments and their great interest in our article.1 We welcome this occasion to clarify several critical points raised by the authors to allow a more balanced evaluation of deep brain stimulation (DBS) in refractory Tourette syndrome (TS). COMPLICATION RATE The authors underline the high rate of complications observed in our study and state that “[a]lthough promising, enthusiasm should be somewhat tempered, given that there was evidence of adverse effects of DBS in up to 29% of patients.” This statement confirms our own opinion, which we stated and underlined several times in our article, which contains a subsection titled Warnings in which we detailed and commented on the high rate of complications. In the Conclusion section, we stated that “DBS holds a promising future for movement and for behavioral disorders.” However, we stated equally that “great attention should be paid to the selection
www.neurosurgery-online.com
Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
CORRESPONDENCE
of patients and target choice, alongside constant technological improvement of the complex DBS device.” AGE OF SURGERY Drs Johnco and Storch write, “Servello et al. . .posed the question of whether DBS should be considered a last-line or bridging treatment for children and adolescents until remission, despite there being only 10 documented cases of DBS in patients ,18 years of age.” And “[g]iven the lack of firmly established efficacy for TS in adults, the rates of documented adverse effects, and the common pattern of symptom remission or reduction during adolescence and young adulthood. . ., we have concerns about prematurely advocating the use of DBS in young populations.” They continue, “it is also important to consider the potential negative impact on psychosocial functioning of multiple invasive surgeries on a child (potentially) with limited improvement, adverse effects, or complications.” We agree fully that more data are urgently needed in patients ,18 years of age treated with DBS to be more conclusive on this highly important and debated point. However, one should keep in mind that every surgical intervention harbors the risk of complications, regardless of the age at surgery. Additionally, one should keep in mind that every conventional medical treatment for psychiatric diseases harbors serious adverse effects. We believe further that it remains highly speculative to avoid surgical treatment exclusively on the basis on the fear of complications, whereas it is certain that a refractory patient will have a compromised future. Although we are aware that findings of case reports cannot be generalized, we refer to our recently published article2 in which we reported the case of a young TS patient. This TS patient could pass through the critical age of puberty thanks to DBS. Without DBS, this patient certainly would have been seriously impaired.
trials with a priori target selection to systematically assess the efficacy of DBS treatment.” In medicine, larger randomized, double-blind trials are always desirable. However, one should keep in mind that DBS is experimental in psychiatric diseases and that large clinical trials are regrettably rare in DBS (whatever its indication). The reasons are multiple (eg, the difficulty in standardizing a highly complex surgical procedure, the strictly defined eligibility criteria for refractory patients to be considered for DBS, and the important financial aspects of DBS).2 TARGET SELECTION The authors write that the “a standardized approach to target selection based on symptom phenotypes is needed to methodically assess efficacy and to provide accurate, evidence-based, generalizable results.” We believe rather that target selection cannot be standardized, considering the large phenotypic variability of TS. Standardized target choice in TS, given the aforementioned large phenotypic variability, may even be counterproductive. Instead, we think that target selection should be based on the specific symptomatology of each patient; unavoidably, targeting selection may have different results in every single patient. In conclusion, we underline that DBS treatment represents the last therapeutic option and needs to be balanced against the severity of the disease, the natural evolution of the disease, and the disease-related morbidity risks. Disclosure The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.
Domenico Servello, MD Christian Saleh, MD Edvin Zekaj, MD Mauro Porta, MD Departments of Neurosurgery and Neurology IRCCS Galeazzi Hospital Milan, Italy
TS COMORBIDITIES The authors write, “The high rate of untreated severe comorbid psychiatric diagnoses is another important issue to consider for accurate evaluation of DBS candidates. . .. Unfortunately, no information was provided on whether these conditions had also been refractory to evidence-based treatments conducted by an experienced therapist.” In all TS patients with comorbidities, we have adopted a treatment for each of the associated comorbidities as outlined by Jankovic and Kurlan.3 Patients chosen for DBS were refractory to medical and behavioral treatments. DBS TRIALS The authors write “there is a clear need for further methodologically rigorous studies before any conclusions can be reached” and propose “larger randomized, double-blind, sham-controlled
NEUROSURGERY
REFERENCES 1. Servello D, Zekaj E, Saleh C, Lange N, Porta M. Deep brain stimulation in Tourette syndrome: what does the future hold? A cohort of 48 patients. Neurosurgery. 2016;78(1):91-100. 2. Zekaj E, Saleh C, Porta M, Servello D. Temporary deep brain stimulation in Gilles de la Tourette syndrome: a feasible approach? Surg Neurol Int. 2015;6: 122. 3. Jankovic J, Kurlan R. Tourette syndrome: evolving concepts. Mov Disord. 2011;26 (6):1149-1156. 10.1227/NEU.0000000000001223
VOLUME 78 | NUMBER 5 | MAY 2016 | E765
Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
