American Journal of Medical Case Reports
ISSN (Print): 2374-2151 ISSN (Online): 2374-216X Website: Editor-in-chief: Samy, I. McFarlane
Open Access
Journal Browser
American Journal of Medical Case Reports. 2020, 8(2), 60-66
DOI: 10.12691/ajmcr-8-2-6
Open AccessArticle

Neurotoxicity Associated with Radiological Contrast Agents Used during Coronary Angiography: A Systematic Review

Pramod Theetha Kariyanna1, Lyudmila Aurora1, Amog Jayarangaiah2, Sushruth Das3, Jose Casillas Gonzalez1, Sudhanva Hegde1 and Isabel M. McFarlane1,

1Division of Cardiovascular Disease and Department of Internal Medicine, State University of New York, Downstate Medical Center, Brooklyn, New York, U.S.A.

2Trinity School of Medicine, 925 Woodstock Road, Roswell, GA 30075, U.S.A.

3Base PU College, Rajajinagar, Bangalore, India- 560010

Pub. Date: January 07, 2020

Cite this paper:
Pramod Theetha Kariyanna, Lyudmila Aurora, Amog Jayarangaiah, Sushruth Das, Jose Casillas Gonzalez, Sudhanva Hegde and Isabel M. McFarlane. Neurotoxicity Associated with Radiological Contrast Agents Used during Coronary Angiography: A Systematic Review. American Journal of Medical Case Reports. 2020; 8(2):60-66. doi: 10.12691/ajmcr-8-2-6


Contrast media enhances the visualization of the anatomic structures in radiological studies, allowing internal tissues such as blood vessels, kidney, ureters, adrenals and other organs to be identified. The evolution of contrast media highlights the efforts to develop less toxic chemical agents that possess low viscosity and osmolality. However, adverse effects such as idiosyncratic reactions, and organ specific damage are well characterized. Neurotoxicity, an important and dose related effect, appears to be due to disruption of the blood-brain-barrier by the high osmolarity of the contrast agent. From devastating cortical blindness to paralysis and seizures, an array of neurological manifestations has been described. In this systematic review, we describe the contrast-induced neurologic injury following coronary angiography and discuss the proposed mechanisms of injury leading to neurotoxicity.

neurotoxicity iodinated contrast media blood-brain barrier neurological injury coronary angiography cardiovascular risk factors types of contrast agents

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit


[1]  Quader MA, Sawmiller CJ, Sumpio BE. Radio Contrast Agents: History and Evolution. Textbook of Angiology. 2000: 775-783.
[2]  Junck, L., Marshall, W. H. Neurotoxicity of radiological contrast agents. Annals of Neurology 1983; 13(5), 469-484.
[3]  Sterrett PR, Bradley IM, Kitten GT, Janssen HF, Hollowdy LJ: Cerebrovasculature permeability changes following experimental cerebral angiography. J Neurol Sci 30: 385-403, 1976.
[4]  Lalli AF Contrast media reactions: data analysis and hypothesis. Radiology 134: 1-12, 1980.
[5]  Mayher WE, Daniel EF, Allen MB: Acute meningeal reaction following Pantopaque myelography. J Neurosurg 34: 396-404, 197 1.
[6]  Rapoport SI, Thompson HK, Bidinger JM: Equi-osmolal opening of the blood-brain barrier in the rabbit by different contrast media. Acta Radiol [Diagn] (Stockh) 15:21-32, 1974.
[7]  Hanson, H-A, Johansson B, Blomstrand C: Ultrastructural studies on cerebrovascular permeability in acute hypertension. Acta Neuropathol (Berl) 32:187-198, 1975.
[8]  Herrschaft H, Gleim F, Schmidt H: Effects of angiographic contrast media on regional cerebral blood flow an.
[9]  Johansson B: Blood-brain barrier dysfunction in acute arterial hypertension after papaverine induced vasodilatation. Acta Neurol Scand 50: 573-580, 1974.
[10]  Rapoport SI, Thompson HK, Bidinger JM: Equi-osmolal opening of the blood-brain barrier in the rabbit by different contrast media. Acta Radiol [Diagn] (Stockh) 15:21-32, 1974.
[11]  Sage MR, Wilcox J, Evil1 CA, Benness GT: Comparison and evaluation of osmotic blood-brain barrier disruption following intracarotid mannitol and methylglucamine iothalamate. Invest Radiol 17: 276-281, 1982.
[12]  Lagemann VK: Pharmakokinetik angiographischer Kontrastmittel unter besonderer Berucksichtigung des extravasalen Raumes: eine experimentelle Grundlagenstudie an Hunden zur Charakterisierung der Angiographica. 11. Mitteilung: Pharmakokinetik eines angiographischen Kontrastmittels unter den Bedingungen einer selektiven-"angiographischer"-Applikation. Fortschr Geb Rontgenstr Nuklearmed 123: 515-521, 1975
[13]  Rapoport SI: The Blood-Brain Barrier in Physiology and Medicine. New York, Raven, 1976.
[14]  Rapoport SI, Fredericks WR, Ohno K, Pettigrew KD: Quantitative aspects of reversible osmotic opening of the bloodbrain barrier. Am J Physiol 238:R421-R431, 1980.
[15]  Stewart BH, Dimond RL, Ferguson CT, Shepard PB: Experimental renal arteriography: comparison of spinal cord and renal toxicity from iothalamate and diatrizoate compounds. J Urol 94: 695-700, 1965.
[16]  Lynch PR, Harrington GJ, Michie C: Cardiovascular reflexes associated with cerebral angiography. Invest Radiol 4: 156-160, 1909.
[17]  McAfee JG: A survey of complications of abdominal aortography. Radiology 68:825-838, 1957.
[18]  Broman T, Olsson 0: The tolerance of cerebral blood-vessels to a contrast medium of the Diodrast group. Acra Radiol [Suppl) (Stockh) 30:326-342, 1948.
[19]  Greenberg MK, Vance SC: Focal seizure disorder complicaring iodophendylare myelography (letter). Lancet 1:3 12-313, 1980 Greenberg MK, Vance SC: Focal seizure disorder complicaring iodophendylare myelography (letter). Lancet 1:3 12-313, 1980.
[20]  Efsen F: Spinal cord lesion as a complication of abdominal aortography. Acta Radiol {Diagn] (Stuckh) 4:47-60, 1906.
[21]  Killen DA, Foster JH: Spinal cord injury as a complication of contrast angiography. Surgery 59:969-981, 1966.
[22]  Margolis G: Pathogenesis of contrast media injury: insights provided by neuroroxicity studies. Invest Radiol 5:392-406, 1970.
[23]  Mani RL, Eisenberg RL: Complications of catheter cerebral arteriography: analysis of 5,000 procedures. 111. Assessment of arteries injected, contrast medium used, duration of procedure, and age of patient. AJR 131:871-874, 1978.
[24]  Talle K, Lundervold A: EEG, ECG, and other recordings in cerebral angiography. Acta Radiol [Suppl] (Stockh) 335: 250-256, 1973.
[25]  Wishart DL: Complications in vertebral angiography as compared to nonvertebral, cerebral angiography in 447 studies AJR 113:527-537, 1971.
[26]  Silverman SM, Bergman PS, Bender MB: The dynamics of transient cerebral blindness: report of nine episodes following vertebral angiography. Arch Neurol 4: 333-348, 1961.
[27]  Studdard WE, Davis DO, Young SW: Cortical blindness after cerebral angiography: case report. J Neurosurg 54:240-244, 1981.
[28]  Vik-Mo H, Todnem K, Følling M, Rosland GA. Transient visual disturbance during cardiac catheterization with angiography. Catheterization and Cardiovascular Diagnosis. 1986; 12(1): 1-4.
[29]  Henzlova MJ, Coghlan HC, Dean LS, Taylor JL. Cortical blindness after left internal mammary artery to left anterior descending coronary artery graft angiograph. Catheterization and Cardiovascular Diagnosis. 1988; 15(1): 37-39.
[30]  Antonellis J, Kostopoulos K, Rambaouni A, et al. Cortical Blindness Following Coronary Arteriography: A Rare But Self-Cured Complication. Angiology. 1996; 47(8): 803-806.
[31]  Sticherling C, Berkefeld J, Auch-Schwelk W, Lanfermann H. Transient bilateral cortical blindness after coronary angiography. The Lancet. 1998; 351(9102): 570.
[32]  Moll S, Peters A, Dietz R. Severe agitation and hyperventilation after contrast media application during coronary angiography. Catheterization and Cardiovascular Interventions. 1999; 46(2): 200-201.
[33]  Yıldız A, Yencilek E, Apaydın FD, Duce MN, Özer C, Atalay A. Transient partial amnesia complicating cardiac and peripheral arteriography with nonionic contrast medium. European Radiology. 2003; 13(S06): L113-L115.
[34]  Velden J, Milz P, Winkler F, Seelos K, Hamann GF. Nonionic Contrast Neurotoxicity after Coronary Angiography Mimicking Subarachnoid Hemorrhage. European Neurology. 2003; 49(4): 249-251.
[35]  Schulte-Altedorneburg G, Rüb K, Scheglmann K. Simultaneous ischemic and neurotoxic brain damage after coronary angiography. Neurological research. 2004; 26(1): 79-82.
[36]  Hagemann G, Ugur T, Neumann R, Witte OW, Mentzel H-J. Cortical Blindness After Catheter Angiography. Neurocritical Care. 2005; 3(1):059-060.
[37]  Yazici M, Ozhan H, Kinay O, et al. Transient cortical blindness after cardiac catheterization with iobitridol. Texas Heart Institute journal. 2007; 34(3): 373-375.
[38]  González IA, Tapia C, Hernández-Luis C, San Román JA. Contrast Neurotoxicity Following Percutaneous Revascularization. Revista Española de Cardiología (English Edition). 2008; 61(8): 894-896.
[39]  Borghi C, Saia F, Marzocchi A, Branzi A. The conundrum of transient cortical blindness following coronary angiography. Journal of Cardiovascular Medicine. 2008; 9(10): 1063-1065.
[40]  Alp B, Bozbuğa N, Tuncer M, Yakut C. Transient Cortical Blindness after Coronary Angiography. Journal of International Medical Research. 2009; 37(4): 1246-1251.
[41]  Yetimalar, Y., Duraklı, M., Kurt, T., Seçil, Y., Gürgör, N., & Başoğlu, M. (2005). Transient Cortical Blindness Following Coronary Angiography. Neuro-Ophthalmology, 29(3), 125-127.
[42]  Ertugrul Okuyan, Halil Ibrahim Biter, Suleyman S. Yildiz, Mustafa H. Dinckal 2019. Transient cortical blindness following coronary angiography: A rare complication. Am J Case Rep 2010; 11: 205-207.
[43]  Mouine, N., Ndom, M. S., el Hankari, T., & Zbir, E. M. (2010). Transient cortical blindness after coronary angiography: report of 2 cases. Journal of Men’s Health, 7(4), 431-433.
[44]  Clarke T, Johnson P, Webster D, Gilbert D, Barton E. Transient cortical blindness post angiography a case report. West Indian Medical Journal. 2011; 60(3): 357-359.
[45]  Law S, Panichpisal K, Demede M, et al. Contrast-Induced Neurotoxicity following Cardiac Catheterization. Case Reports in Medicine. 2012; 2012: 1-4.
[46]  Ozbek K, Hasbek E, Koc F. Delirium due to contrast toxicity after coronary angioplasty. Anadolu Kardiyoloji Dergisi/The Anatolian Journal of Cardiology. August 2012.
[47]  Liao M-T, Lin T-T, Lin L-Y, Hwang J-J, Tseng C-D. Contrast-Induced Encephalopathy after Percutaneous Coronary Intervention. Acta Cardiol Sin 2013; 29: 277280.
[48]  Obermann M, Moeller-Hartmann C, Naegel S. Neurotoxic cerebral oedema following coronary angiography. Journal of Neurology, Neurosurgery & Psychiatry. 2012; 84(4): 458-459.
[49]  Kocabay G, Karabay CY, Kalayci A, et al. Contrast-induced neurotoxicity after coronary angiography. Herz. 2013; 39(4): 522-527.
[50]  Khan SM, Ho DW, Lazar JM, Marmur J. Cerebral contrast retention after difficult cardiac catheterization: Case report. SAGE Open Medical Case Reports. 2014; 2: 2050313X1453028.
[51]  Gollol Raju NS. Contrast induced neurotoxicity following coronary angiogram with Iohexol in an end stage renal disease patient. World Journal of Clinical Cases. 2015; 3(11): 942.
[52]  McElnea E, Gallagher D, Khaldoon Al-Tahs, Kiernan T. A Case of Transient Loss of Vision Following Coronary Angiography: Etiology, Investigation and Management. Journal of Medical Cases. 2013; 7(9): 379-383.
[53]  Spina R, Simon N, Markus R, Muller DW, Kathir K. Contrast-induced encephalopathy following cardiac catheterization. Catheterization and Cardiovascular Interventions. 2016; 90(2): 257-268.
[54]  Abela L, Magri Gatt K, Farrugia J, Mallia M. Contrast induced spinal myoclonus after percutaneous coronary intervention. Journal of Cardiology Cases. 2017; 16(3): 97-100.
[55]  Contrast-Induced Encephalopathy in Patients with End-Stage Renal Disease: A Case Report and Literature Review. 2018.
[56]  Dattani A, Au L, Tay KH, Davey P. Contrast-Induced Encephalopathy following Coronary Angiography with No Radiological Features: A Case Report and Literature Review. Cardiology. 2018; 139(3): 197-201.
[57]  Yen C-C, Sung S-F, Hsu Y-H. Clinical presentations of contrast-induced encephalopathy in end-stage renal disease. Internal Medicine Journal. 2018; 48(5): 604-605.
[58]  Tomdio A, Koromia GA, Patwardhan M, Pitzalis M. TRANSIENT CORTICAL BLINDNESS DUE TO CONTRAST-INDUCED NEUROTOXICITY AFTER CARDIAC CATHETERIZATION. Journal of the American College of Cardiology. 2018; 71(11): A2243.
[59]  Heemelaar JC, van der Hoeven NW, Muller FF, Appelman Y. Acute-onset coma after iso-osmolar iodinated contrast injection: a case report of contrast-induced encephalopathy after elective coronary angiography. Johnson T, Milasinovic D, Kanakakis J, Yousef Abumuaileq RR, Cassa MP, Patel P, eds. European Heart Journal - Case Reports. 2018; 2(4).
[60]  Witten DM, Hirsch FD, Hartmann GW: Acute reactions to urographic contrast medium: incidence, clinical characteristics, and relationship to history of hypersensitivity states. AJR 119832-840, 1973.
[61]  Olivecrona H: Complications of cerebral angiography. Neuroradiology 14: 175-181, 1977.
[62]  Seaman WB, Buenger RE, Fischer HW, Hilal SK, Gottschalk A, Laser E, Viamonte M Jr, Turner AF: Prevention and Management of Adverse Reactions to Intravascular Contrast Media. American College of Radiology, 1977.
[63]  Hammargren LL, Geise AW, French LA: Protection against cerebral damage from intracarotid injection of Hypaque in animals. J Neurosurg 23:418-424, 1965.
[64]  Harris AB: Steroids and blood-brain barrier alterations in sodium acetrizoate injury. Arch Neurol 17:282-295, 1967.
[65]  Murphy DJ: Cerebrovascular permeability after meglumine iorhalaniate administration. Neurology (Minneap) 23. 926-936, 1973.
[66]  Sessions RT, Killen DA, Foster JH: Low molecular weight dextran as a protective agent against the toxic effects of Urokon. Am Sug 28:455-460, 1962.
[67]  Waldron IIL 11, Bridenbaugh RB, Dempsey EW: Alterations at the cellular level in the brain following repeated angiography: protective effect of corticosteroids. J Can Assoc Radiol 26: 82-87, 1975.
[68]  Whetsell WO Jr, Lockard I: Responses to intracarotid Hypaque in rabbits with and without low molecular weight dextran. J Neuropathol Exp Neurol 25:283-295, 1966.
[69]  Shehadi WH: Committee report. Contrast media in diagnostic radiology: recommendations for labels, package inserts, and dosage determination. AJR 129: 167-170, 1977.