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Spetzler was born in Germany and moved to the United States at age 11. He received his Bachelor of Science degree from Knox College in Galesburg, Illinois, and his M.D. from Northwestern Medical School in Chicago. He completed post-graduate training at Wesley Memorial Hospital—Northwestern in Chicago, Illinois and a residency in neurosurgery at the University of California, San Francisco.

In 1983, Spetzler was named Chair of the Division of Neurological Surgery at the Barrow Neurological Institute. He was named director in 1986.

Spetzler played a dominant role in the use of the standstill operation in treating large or dangerous cerebral aneurysms.

Partial list:

• Surgery of the Cerebellopontine Angle. Nicholas C. Bambakidis (Author), Cliff A. Megerian (Author), Robert F. Spetzler (Author). Pmph USA; 2009. ISBN 1607950014
• Medicine, Miracles, and Manifestations: A Doctor's Journey Through the Worlds of Divine Intervention, Near-Death Experiences, and Universal Energy. John L. Turner (Author), Robert F. Spetzler (Foreword). Career Press; 2009. ISBN 1601630603
• The Color Atlas of Microneurosurgery W. Koos (Author), Robert Spetzler (Author), Johannes Lang (Author), J. Zabramski (Author), Robert F. Spetzler (Author), Joseph M. Zabramski (Author). Thieme; 2000. ISBN 0865777802.
• Pediatric Neurovascular Disease: Surgical, Endovascular and Medical Management. Michael Alexander (Editor), Robert Spetzler (Editor). Thieme; 2005. ISBN 1588903680

Partial list:

• The Anatomy of the Callosomarginal Artery: Applications to Microsurgery and Endovascular Surgery. Cavalcanti DD, Albuquerque FC, Silva BF, Spetzler RF, Preul MC. Neurosurgery. 28 January 2010. PMID 20124934
• Safety of carotid endarterectomy while on clopidogrel (Plavix). Wait SD, Abla AA, Killory BD, Starke RM, Spetzler RF, Nakaji P. J Neurosurg. 29 January 2010. PMID 20113164
• Miniaturized handheld confocal microscopy for neurosurgery: results in an experimental glioblastoma model. Sankar T, Delaney PM, Ryan RW, Eschbacher J, Abdelwahab M, Nakaji P, Coons SW, Scheck AC, Smith KA, Spetzler RF, Preul MC. Neurosurgery. 2010 Feb;66(2):410-7; discussion 417-8.PMID 20087141
• Cerebral cavernous malformations. Incidence and familial occurrence. Rigamonti D, Hadley MN, Drayer BP, Johnson PC, Hoenig-Rigamonti K, Knight JT, Spetzler RF. N Engl J Med. 11 August 1988;319(6):343-7. PMID 3393196
• Preliminary personal experiences with the application of near-infrared indocyanine green videoangiography in extracranial vertebral artery surgery. Bruneau M, Sauvageau E, Nakaji P, Vandesteene A, Lubicz B, Chang SW, Balériaux D, Brotchi J, De Witte O, Spetzler RF. Neurosurgery. 2010 Feb;66(2):305-11; discussion 311.PMID 20087130
• Using ex vivo proton magnetic resonance spectroscopy to reveal associations between biochemical and biological features of meningiomas. Pfisterer WK, Nieman RA, Scheck AC, Coons SW, Spetzler RF, Preul MC. Neurosurg Focus. 2010 Jan;28(1):E12.PMID 20043716
• Supracerebellar infratentorial approach to cavernous malformations of the brainstem: surgical variants and clinical experience with 45 patients. de Oliveira JG, Lekovic GP, Safavi-Abbasi S, Reis CV, Hanel RA, Porter RW, Preul MC, Spetzler RF. Neurosurgery. 2010 Feb;66(2):389-99.PMID 20042987