Neuroblastoma: Practice Essentials, Background, Relevant Anatomy (original) (raw)

Practice Essentials

Neuroblastoma (NB) is a poorly differentiated neoplasm derived from neural crest cells. It is the most common cancer in infants and the most common extracranial solid tumor in childhood. Median age at diagnosis is 17 months; 90% of patients are younger than 5 years at diagnosis, and less than 5% are adolescents or adults. [1, 2] Neuroblastoma accounts for 7% of pediatric malignancies but for more than 10% of childhood cancer-related mortality. [3]

Neuroblastomas originate in the adrenal medulla and paraspinal or periaortic regions. [2] Its presentation varies, depending on the primary site of origin, metastatic burden, and metabolically active by-products, but 65% of primary neuroblastomas occur in the abdomen—40% in the adrenal gland—so most children present with abdominal symptoms, such as fullness or distension.

Neuroblastoma is remarkable in that it has a documented spontaneous rate of resolution and is also one of the few tumors in which the surgical capsule can be violated yet a good outcome might be achieved, even if residual tumor is left behind.

Signs and symptoms

Abdominal symptoms such as fullness or distention are the most common symptoms. However, children with localized disease are typically asymptomatic. Children with disseminated neuroblastoma are generally sick and may have systemic manifestations, including the following:

• Unexplained fevers
• Weight loss
• Anorexia
• Failure to thrive
• General malaise
• Irritability
• Bone pain

Infants often present with consequences of compression of the sympathetic ganglia in the thoracic region, such as Horner syndrome (myosis, anhydrosis, and ptosis) or superior vena cava syndrome. Older children typically present with abdominal symptoms; the most common physical examination finding is a nontender, firm, irregular abdominal mass that crosses the midline.

See Presentation for more detail.

Diagnosis

Recommended laboratory studies include the following:

• Complete blood cell (CBC) count and differential
• Urine collection for catecholamines and urinalysis
• Erythrocyte sedimentation rate
• Vanillylmandelic acid–to–homovanillic acid (VMA-to-HVA) ratio

Neuron-specific enolase (NSE), lactate dehydrogenase (LDH), and ferritin are markers useful in the identification of active disease.

Standard diagnostic imaging modalities include the following:

• Plain abdominal radiography (kidneys, ureters, bladder [KUB])
• Renal/bladder ultrasonography
• Bone scintigraphy
• Computed tomography (CT) or magnetic resonance imaging (MRI)

Biopsy is the sine qua non in the diagnostic evaluation of neuroblastoma.

See Workup for more detail.

Treatment

Treatment of neuroblastoma is risk based. [2]

Low-risk neuroblastoma:

• Observation, with or without biopsy
• Surgical resection, then observation
• Chemotherapy, with or without surgery, for symptomatic disease or unresectable progressive disease after surgery
• Radiation therapy (for emergency treatment only)

Intermediate-risk neuroblastoma:

• Multiple-agent chemotherapy (eg, doxorubicin, cyclophosphamide, cisplatin or carboplatin, and etoposide)
• Chemotherapy is often given before definitive resection
• Surgery and observation (in infants).
• Radiation therapy (if needed)

High-risk neuroblastoma:

• Chemotherapy, surgery, tandem cycles of myeloablative therapy and hematopoietic stem cell transplantation, radiation therapy, and dinutuximab, with granulocyte-macrophage colony-stimulating factor (GM-CSF) and isotretinoin.
• Eflornithine, to reduce the risk of relapse after at least partial response to prior multiagent therapy

See Treatment for more detail.

Background

Virchow first described neuroblastoma in 1864; at that time, it was referred to as a glioma. [4] In 1891, Marchand histologically linked neuroblastoma to sympathetic ganglia. [5] More substantial evidence of the neural origins of neuroblastoma became apparent in 1914, when Herxheimer showed that fibrils of the tumor stained positively with special neural silver stains. [6]

In 1927, Cushing and Wolbach further characterized neuroblastoma by describing the transformation of malignant neuroblastoma into its benign counterpart, ganglioneuroma. [7] Everson and Cole reported that this type of transformation is rare in children older than 6 months. [8] In 1957, Mason published a report of a child with neuroblastoma whose urine contained pressor amines. [9] This discovery further contributed to the understanding of neuroblastoma and its possible sympathetic neural origin.

Spontaneous regression of microscopic clusters of neuroblastoma cells, called neuroblastoma in situ, was noted to occur quite commonly. According to Beckwith and Perrin in 1963, regression occurs nearly 40 times more often than clinically apparent neuroblastoma. [10]

Neuroblastoma is one of the small, blue, round cell tumors of childhood. Other such tumors include the following:

Relevant Anatomy

During the fifth week of embryogenesis, primitive sympathetic neuroblasts migrate from the neural crest to the site where the adrenal anlage eventuates into the developing embryo. These neuroblasts migrate along the entire sympathetic chain; therefore, neuroblastoma can arise anywhere along the sympathetic nervous system, in the adrenal glands and in the paraspinal nerves from the neck to the pelvis. [2] The name neuroblastoma is derived from the fact that the cells resemble primitive neuroblasts.

Pathophysiology

Embryologically, tumors of the sympathetic nervous system differentiate along one of two distinct pathways: the pheochromocytoma line or the sympathoblastoma line. [11] The sympathoblastomas, also called neurocristopathies, include the well-differentiated ganglioneuroma, the moderately differentiated ganglioneuroblastoma, and the malignant neuroblastoma. All of these tumors arise from primordial neural crest cells, which ultimately populate the sympathetic chain and the adrenal medulla. [12]

Amplification of the MYCN oncogene occurs in 20% of primary neuroblastoma tumors and 50% of high-risk tumors; it is associated with high rates of metastasis and a poor prognosis in children older than 1 year but not in children younger than 1 year. [13] The precise role of MYCN in nonamplified tumors is unknown.

Hyperdiploid tumor DNA is associated with a favorable prognosis. N-myc amplification is associated with a poor prognosis In 2000, Maris et al reported from the Children's Cancer Group (CCG) that 1p deletion independently predicted a lower event-free survival but not overall survival. The clinical relevance of 14q LOH is unclear at this time.

Allelic loss of 11q is present in 35-45% of primary tumors. Notably, this aberration is rarely seen in tumors with MYCN amplification yet remains highly associated with other high-risk features.

Bosse and colleagues identified Glypican-2 (GPC2) as a molecule specifically expressed by neuroblastoma cells and not by normal tissues. GPC2 expression has been detected on the cell surface in the majority of high-risk neuroblastoma, and such expression correlated with worse prognosis of neuroblastoma patients. GPC2 expression is driven by somatic gain of chromosome 7q (where the GPC2 gene is located) and by MYCN amplification. Additionally, Bosse et al developed a GPC2-directed antibody-drug conjugate with a potent cytotoxic activity against GPC2-expressing neuroblastoma cells, which may represent a promising immunotherapeutic target for high-risk neuroblastoma. [14]

Etiology

About 1-2% of patients with neuroblastoma have a family history of the disease. Germline mutations associated with a genetic predisposition to neuroblastoma in these cases include the following [2] :

• ALK mutation - Point mutations in the tyrosine kinase domain of the ALK gene are found in about 75% of familial neuroblastoma cases; somatic activating point mutations in ALK are also seen in about 9% of sporadic neuroblastoma cases. In addition, co-amplification of ALK and MYCN (the two genes are near each other on chromosome 2) occurs in a small proportion of neuroblastoma cases
• PHOX2B mutation - Germline loss-of-function PHOX2B mutations have been identified in rare patients with sporadic neuroblastoma and Ondine curse (congenital central hypoventilation) and/or Hirschsprung disease. Somatic PHOX2B mutations are found in about 2% of patients with sporadic neuroblastoma.
• Deletion at the 1p36 or 11q14-23 locus

Increased risk of malignancies including neuroblastoma have been noted in children with various cancer predisposition syndromes, including Costello syndrome, Noonan syndrome, and neurofibromatosis type 1. [15]

Malignant transformation and maintenance of the dedifferentiated state of neural crest cells may result from failure of those cells to respond to normal signals that are responsible for normal morphologic differentiation. The factors involved in the cascade of events are poorly understood but most likely involve one or more ligand-receptor pathways. One of the most studied pathways is the nerve growth factor (NGF) and its receptor (NGFR). The dedifferentiated state of neuroblastoma leads to the variable presentations commonly observed in patients with neuroblastoma.

Environmental and paternal exposures linked to neuroblastoma have not been identified. [16]

Epidemiology

Frequency

Neuroblastoma is the most common cancer in infants. Approximately 700-800 cases are diagnosed each year in the United States, accounting for about 6% of cancers in children. [1] Clinical frequency is approximately one case per 8000-10,000 children.

Neuroblastoma is more common in whites and is slightly more prevalent in boys than in girls (male-to-female ratio of 1.3:1). In rare cases, neuroblastoma is detected by prenatal ultrasound. About 37% of cases are diagnosed in infancy, and nearly 90% of cases are diagnosed before the age of 5 years. Median age at diagnosis is 19 months. [2] Neuroblastoma is rare in people over the age of 10 years. [1] Neuroblastoma is thought to occur sporadically, with 1-2% of cases considered familial.

Prognosis

For more than 40 years, the age at diagnosis and the stage have been the dominant independent variables used as prognostic factors in children with neuroblastoma. In 1984, Shimada et al classified neuroblastoma by relating its histopathologic features to its clinical behavior. [17] To this end, Shimada et al divided neuroblastoma into favorable and unfavorable categories, depending on the degree of neuroblast differentiation, Schwannian stromal content, mitosis-karyorrhexis index, and age at diagnosis. In 1999, the Shimada classification was modified to the International Neuroblastoma Pathology Classification system.

Because of the various approaches to risk stratification, efforts have been made to develop a consensus approach that will allow comparison of patients around the world. In 2009, the International Neuroblastoma Risk Group (INRG) Task Force published a classification based on the review of a large number of patients from Europe, Japan, the United States, Canada, and Australia diagnosed with neuroblastoma between 1974 and 2002. [18] The Task Force identified the following as the most highly statistically significant and clinically relevant factors:

• Tumor stage
• Patient age
• Tumor histologic category
• Grade of tumor differentiation
• DNA ploidy
• Copy-number status of the MYCN oncogene
• Chromosome 11q status

On the basis of those factors the Task Force identified four broad prognostic clinical categories (see Workup/Risk Groups), which correlated with 5-year event-free survival (EFS) rates as follows [18] :

• Very low risk: EFS > 85%
• Low risk: EFS > 75% to 85%
• Intermediate risk: EFS 50% to 75%
• High risk: EFS < 50%

The Children's Oncology Group (COG) subsequently developed a process called the Neuroblastoma Risk Stratification System (NRSS), which is used for treatment stratification. The NRSS, which was most recently revised in 2021 (see Workup/Risk Groups) classifies patients into low-, intermediate-, or high-risk categories. [19] Five-year EFS and overall survival (OS) rates are as follows:

• Low risk: EFS 90.7% ± 1.1%, OS 97.9% ± 0.5%
• Intermediate risk: EFS 85.1% ± 1.4%, OS 95.8% ± 0.8%
• High risk: EFS 51.2% ± 1.4%, OS 62.5% ± 1.3%

Other variables carry varying degrees of prognostic significance. These include the site of the primary tumor, serum ferritin levels, neuron-specific enolase (NSE) level, and nutritional status.

1. Key Statistics About Neuroblastoma. American Cancer Society. Available at https://www.cancer.org/cancer/neuroblastoma/about/key-statistics.html. April 28, 2021; Accessed: January 31, 2024.
2. PDQ Pediatric Treatment Editorial Board. Neuroblastoma Treatment (PDQ®): Health Professional Version. August 22, 2023. [QxMD MEDLINE Link]. [Full Text].
3. Irwin MS, Park JR. Neuroblastoma: Paradigm for Precision Medicine. Pediatr Clin North Am. 2015 Feb. 62(1):225-256. [QxMD MEDLINE Link].
4. Virchow R. Hyperplasie der Zirbel und der Nebennieren. Die Krankhaften Geschwulste. Vol 2: 1864-65.
5. Marchand F. Beitrage zur Kenntniss der normalen und pathologischen Anatomie der Glandula carotica und der Nebennieren. Festschrift fur Ruduloph. Vichows Arch. 1891. 5:578.
6. Herxheimer G. Ueber Turmoren des Nebennierenmarkes, insbesondere das Neuroblastoma sympaticum. Beitr Pathol Anat. 1914. 57:112.
7. Cushing H, Wolback SB. The transformation of a malignant paravertebral sympathicoblastoma into a benign ganglioneuoma. Am J Pathol. 1927. 3:203.
8. Everson TC, Cole WH. Spontaneous regression of neuroblastoma. Everson TC, Cole WH, eds. Spontaneous Regression of Cancer. Philadelphia, Pa: WB Saunders; 1966. 88.
9. Mason GA, Hart-Mercer J, Millar EJ, Strang LB, Wynne NA. Adrenaline-secreting neuroblastoma in an infant. Lancet. 1957 Aug 17. 273(6990):322-5. [QxMD MEDLINE Link].
10. Beckwith JB, Perrin EV. In situ neuroblastomas: A contribution to the natural history of neural crest tumors. Am J Pathol. 1963 Dec. 43:1089-104. [QxMD MEDLINE Link].
11. Knudson AG Jr, Strong LC. Mutation and cancer: neuroblastoma and pheochromocytoma. Am J Hum Genet. 1972 Sep. 24(5):514-32. [QxMD MEDLINE Link].
12. Bosse KR, Maris JM. Advances in the translational genomics of neuroblastoma: From improving risk stratification and revealing novel biology to identifying actionable genomic alterations. Cancer. 2016 Jan 1. 122 (1):20-33. [QxMD MEDLINE Link]. [Full Text].
13. Powers JT, Tsanov KM, Pearson DS, Roels F, Spina CS, Ebright R, et al. Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma. Nature. 2016 Jul 14. 535 (7611):246-51. [QxMD MEDLINE Link]. [Full Text].
14. Bosse KR, Raman P, Zhu Z, et al. Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma. Cancer Cell. 2017 Sep 11. 32 (3):295-309.e12. [QxMD MEDLINE Link]. [Full Text].
15. Barr EK, Applebaum MA. Genetic Predisposition to Neuroblastoma. Children (Basel). 2018 Aug 31. 5 (9):[QxMD MEDLINE Link].
16. Mallepalli S, Gupta MK, Vadde R. Neuroblastoma: An Updated Review on Biology and Treatment. Curr Drug Metab. 2019. 20 (13):1014-1022. [QxMD MEDLINE Link].
17. Shimada H, Chatten J, Newton WA Jr, et al. Histopathologic prognostic factors in neuroblastic tumors: definition of subtypes of ganglioneuroblastoma and an age-linked classification of neuroblastomas. J Natl Cancer Inst. 1984 Aug. 73(2):405-16. [QxMD MEDLINE Link].
18. Cohn SL, Pearson AD, London WB, Monclair T, Ambros PF, Brodeur GM, et al. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol. 2009 Jan 10. 27 (2):289-97. [QxMD MEDLINE Link]. [Full Text].
19. Irwin MS, Naranjo A, Zhang FF, Cohn SL, London WB, Gastier-Foster JM, et al. Revised Neuroblastoma Risk Classification System: A Report From the Children's Oncology Group. J Clin Oncol. 2021 Oct 10. 39 (29):3229-3241. [QxMD MEDLINE Link]. [Full Text].
20. Stigliani S, Coco S, Moretti S, Oberthuer A, Fischer M, Theissen J, et al. High genomic instability predicts survival in metastatic high-risk neuroblastoma. Neoplasia. 2012 Sep. 14(9):823-32. [QxMD MEDLINE Link]. [Full Text].
21. Rufini V, Calcagni ML, Baum RP. Imaging of neuroendocrine tumors. Semin Nucl Med. 2006 Jul. 36(3):228-47. [QxMD MEDLINE Link].
22. Mullassery D, Sharma V, Salim A, Jawaid WB, Pizer BL, Abernethy LJ, et al. Open versus needle biopsy in diagnosing neuroblastoma. J Pediatr Surg. 2014 Oct. 49(10):1505-7. [QxMD MEDLINE Link].
23. Beiske K, Burchill SA, Cheung IY, Hiyama E, Seeger RC, Cohn SL, et al. Consensus criteria for sensitive detection of minimal neuroblastoma cells in bone marrow, blood and stem cell preparations by immunocytology and QRT-PCR: recommendations by the International Neuroblastoma Risk Group Task Force. Br J Cancer. 2009 May 19. 100 (10):1627-37. [QxMD MEDLINE Link]. [Full Text].
24. Van Maerken T, Vandesompele J, Rihani A, De Paepe A, Speleman F. Escape from p53-mediated tumor surveillance in neuroblastoma: switching off the p14(ARF)-MDM2-p53 axis. Cell Death Differ. 2009 Dec. 16(12):1563-72. [QxMD MEDLINE Link].
25. Schleiermacher G, Javanmardi N, Bernard V, Leroy Q, Cappo J, Rio Frio T, et al. Emergence of new ALK mutations at relapse of neuroblastoma. J Clin Oncol. 2014 Sep 1. 32(25):2727-34. [QxMD MEDLINE Link].
26. Brodeur GM, Seeger RC, Barrett A, et al. International criteria for diagnosis, staging, and response to treatment in patients with neuroblastoma. J Clin Oncol. 1988 Dec. 6(12):1874-81. [QxMD MEDLINE Link].
27. Monclair T, Brodeur GM, Ambros PF, Brisse HJ, Cecchetto G, Holmes K, et al. The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report. J Clin Oncol. 2009 Jan 10. 27 (2):298-303. [QxMD MEDLINE Link]. [Full Text].
28. Neuroblastoma Risk Groups. American Cancer Society. Available at https://www.cancer.org/cancer/types/neuroblastoma/detection-diagnosis-staging/risk-groups.html. April 28, 2021; Accessed: December 18, 2023.
29. Nitschke R, Smith EI, Shochat S, et al. Localized neuroblastoma treated by surgery: a Pediatric Oncology Group Study. J Clin Oncol. 1988 Aug. 6(8):1271-9. [QxMD MEDLINE Link].
30. Suzuki M, Kushner BH, Kramer K, Basu EM, Roberts SS, Hammond WJ, et al. Treatment and outcome of adult-onset neuroblastoma. Int J Cancer. 2018 Sep 1. 143 (5):1249-1258. [QxMD MEDLINE Link]. [Full Text].
31. Herd F, Basta NO, McNally RJQ, Tweddle DA. A systematic review of re-induction chemotherapy for children with relapsed high-risk neuroblastoma. Eur J Cancer. 2019 Feb 26. 111:50-58. [QxMD MEDLINE Link]. [Full Text].
32. Gains J, Mandeville H, Cork N, Brock P, Gaze M. Ten challenges in the management of neuroblastoma. Future Oncol. 2012 Jul. 8(7):839-58. [QxMD MEDLINE Link].
33. Ladenstein R, Pötschger U, Pearson ADJ, et al. Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial. Lancet Oncol. 2017 Apr. 18 (4):500-514. [QxMD MEDLINE Link].
34. Rujkijyanont P, Photia A, Traivaree C, Monsereenusorn C, Anurathapan U, Seksarn P, et al. Clinical outcomes and prognostic factors to predict treatment response in high risk neuroblastoma patients receiving topotecan and cyclophosphamide containing induction regimen: a prospective multicenter study. BMC Cancer. 2019 Oct 16. 19 (1):961. [QxMD MEDLINE Link]. [Full Text].
35. Berthold F, Faldum A, Ernst A, et al. Extended induction chemotherapy does not improve the outcome for high-risk neuroblastoma patients: results of the randomized open-label GPOH trial NB2004-HR. Ann Oncol. 2020 Mar. 31 (3):422-429. [QxMD MEDLINE Link]. [Full Text].
36. Bayeva N, Coll E, Piskareva O. Differentiating Neuroblastoma: A Systematic Review of the Retinoic Acid, Its Derivatives, and Synergistic Interactions. J Pers Med. 2021 Mar 16. 11 (3):[QxMD MEDLINE Link]. [Full Text].
37. Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010 Sep 30. 363(14):1324-34. [QxMD MEDLINE Link].
38. FDA grants accelerated approval to naxitamab for high-risk neuroblastoma in bone or bone marrow. Food and Drug Administration. Available at https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-naxitamab-high-risk-neuroblastoma-bone-or-bone-marrow. November 27, 2020; Accessed: December 18, 2023.
39. FDA approves eflornithine for adult and pediatric patients with high-risk neuroblastoma. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-eflornithine-adult-and-pediatric-patients-high-risk-neuroblastoma. December 14, 2023; Accessed: January 31, 2024.
40. Oesterheld J, Ferguson W, Kraveka JM, Bergendahl G, Clinch T, Lorenzi E, et al. Eflornithine as Postimmunotherapy Maintenance in High-Risk Neuroblastoma: Externally Controlled, Propensity Score-Matched Survival Outcome Comparisons. J Clin Oncol. 2023 Oct 26. JCO2202875. [QxMD MEDLINE Link]. [Full Text].
41. Mastrangelo S, Romano A, Attinà G, Maurizi P, Ruggiero A. Timing and chemotherapy association for 131-I-MIBG treatment in high-risk neuroblastoma. Biochem Pharmacol. 2023 Oct. 216:115802. [QxMD MEDLINE Link]. [Full Text].
42. Buckley SE, Chittenden SJ, Saran FH, Meller ST, Flux GD. Whole-body dosimetry for individualized treatment planning of 131I-MIBG radionuclide therapy for neuroblastoma. J Nucl Med. 2009 Sep. 50(9):1518-24. [QxMD MEDLINE Link].
43. Pai Panandiker AS, Beltran C, Billups CA, McGregor LM, Furman WL, Davidoff AM. Intensity modulated radiation therapy provides excellent local control in high-risk abdominal neuroblastoma. Pediatr Blood Cancer. 2012 Sep 28. [QxMD MEDLINE Link].
44. Russo C, Cohn SL, Petruzzi MJ, de Alarcon PA. Long-term neurologic outcome in children with opsoclonus-myoclonus associated with neuroblastoma: a report from the Pediatric Oncology Group. Med Pediatr Oncol. 1997 Apr. 28(4):284-8. [QxMD MEDLINE Link].
45. de Alarcon PA, Matthay KK, London WB, Naranjo A, Tenney SC, Panzer JA, et al. Intravenous immunoglobulin with prednisone and risk-adapted chemotherapy for children with opsoclonus myoclonus ataxia syndrome associated with neuroblastoma (ANBL00P3): a randomised, open-label, phase 3 trial. Lancet Child Adolesc Health. 2018 Jan. 2 (1):25-34. [QxMD MEDLINE Link]. [Full Text].
46. Nuchtern JG, London WB, Barnewolt CE, Naranjo A, McGrady PW, Geiger JD, et al. A prospective study of expectant observation as primary therapy for neuroblastoma in young infants: a Children's Oncology Group study. Ann Surg. 2012 Oct. 256 (4):573-80. [QxMD MEDLINE Link].

Author

Byron D Joyner, MD, MPA Vice Dean for Graduate Medical Education and Designated Institutional Official Professor, Department of Urology, University of Washington School of Medicine; Pediatric Urologist, Seattle Children's Hospital

Byron D Joyner, MD, MPA is a member of the following medical societies: American Academy of Pediatrics, Society of University Urologists, Washington State Medical Association, Society of Urology Chairpersons and Program Directors, American College of Surgeons, American Urological Association, The Society of Federal Health Professionals (AMSUS), Massachusetts Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Brian H Kopell, MD Associate Professor, Department of Neurosurgery, Icahn School of Medicine at Mount Sinai; Director, Center for Neuromodulation, Co-Director, The Bonnie and Tom Strauss Movement Disorders Center, Department of Neurosurgery, Mount Sinai Health System

Brian H Kopell, MD is a member of the following medical societies: Alpha Omega Alpha, American Association of Neurological Surgeons, American Society for Stereotactic and Functional Neurosurgery, Congress of Neurological Surgeons, International Parkinson and Movement Disorder Society, North American Neuromodulation Society

Disclosure: Received income in an amount equal to or greater than $250 from: Medtronic; Abbott Neuromodulation; Turing Medical.

Acknowledgements

Natalya Lopushnyan Yale University School of Medicine

Disclosure: Nothing to disclose.