Title: Reflections on the life and work of Ayub K Ommaya, MD, ScD (h.c.), FRCS, FACS
Alexander Ommaya, DSc
Abstract: Ayub Khan Ommaya, MD was one of Pakistan's most honored physicians, a well known neurosurgeon, and a tireless research scientist. His invention, the Ommaya reservoir, was the first subcutaneous reservoir that allowed for repeated intrathecal injections. Before this invention patients had to suffer repeated lumbar punctures for intrathecal drug administration and chemotherapy. Dr. Ommaya also published the first coma score for classification of traumatic brain injury. Contemporary concussion classification systems follow Dr. Ommaya’s original approach.
Dr. Ommaya’s research provided the experimental data needed to model traumatic brain injury. His Centripetal theory was foundational to the biomechanics of traumatic brain injury. This work allowed for improved modeling of brain injury by engineers in their design of safety equipment in automobiles. His sustained interest in traumatic injury also lead to the creation of the National Center for Injury Prevention and Control through his friendship with Congressman Lehman, then chair of the House Appropriations Subcommittee on Transportation.
Dr. Ommaya also did early work with the Computed Tomography Scanner. His work with Sir Godfrey Hounsfield to determine the spatial resolution of the CT scanner opened the door for its use in stereotactic surgery. Spinal angiography was also pioneered by Ommaya, Di Chiro, and Doppman. This work allowed for the visualization of arteries and veins and allowed for understanding of spinal cord arteriography. The same team reported the treatment of spinal cord AVMs by percutaneous embolization of an intercostal artery using stainless steel pellets. This was one of the first reports of interventional neuroradiology. Dr. Ommaya made several significant contributions to many areas that concern Neurological surgeons, treatment of cancer, hydrocephalus, traumatic brain injury, and Arterio-Venous Malformations.
Early Life
Dr. Ayub K. Ommaya, the youngest son of four children, was born on April 14, 1930 in Mian Channu, Pakistan. His father Nadir Khan was a Jemadar in the British Indian Calvary (Bengal Lancers) and his mother Ida was a housewife. Ayub’s father fought in France during World War I, and was determined to find a wife there. He met Ayub’s mother in Eu, France in 1922. Ayub’s father died when he was 13, his oldest brother Jan joined the Army to help support the family and eventually rose to the rank of Brigadier General (figure 1). Finances were a challenge to the family after Ayub’s father passed away.
When Ayub was a young student, he was unsatisfied that the school library would only let students take out 3 books every two weeks. Ayub found a way to sneak books from the bottom shelf of the library, the only shelf accessible through the locked gate. In short time Ayub had read all these books, including encyclopedias and other reference books. At the age of 14, Ayub read a magazine article concerning the experiments of Dr. Wilder Penfield, the distinguished Canadian pioneer neurosurgeon, which focused on surgical treatment of epilepsy and electrical stimulation of the brain. The article described how different experiences were associated with stimulation of the brain. After reading this article and after discussions with his brother Jan, Ayub decided that he should focus on neurosurgery.
Ayub completed his premedical studies at Gordon College, Rawalpindi, Pakistan, and his medical studies at King Edward Medical College in Lahore. While at medical school he received the Harper-Nelson Gold Medal for outstanding academic achievement. In addition to his medical studies, Ayub found time to establish himself as a champion debater, boxer, and swimmer. Ayub won a regional swimming competition and then won the national competition in 1953. He also developed a remarkable tenor voice, and briefly studied opera in Venice, Italy, prior to taking a Rhodes scholarship at Balliol College, Oxford. During his stay at Oxford in addition to a developing interest in mechanisms of brain injury he won the James Willis Kirkaldy Oxford University Prize in 1956. He was also awarded the Hunterian Professorship at the Royal College of Surgeons in 1964.
Neurosurgical Career
Ayub completed his neurosurgical training under Dr. Joseph Pennybacker at Nuffield College of Surgical Sciences in London and at the Radcliffe Infirmary in Oxford. After his neurosurgical training, Dr. Ommaya came to America and began working as a researcher and clinician at the Surgical Neurology Branch of the NIH. His good friend Dr. Baruch Blumberg, who later received the Nobel Prize, arranged for his invitation to NIH. He also was a clinical professor at George Washington University.
Ayub was well known for his surgical skill and in 1977 he completed a difficult removal of a spinal Arterio-Venous Malformation (AVM) which received attention in the lay press.8 During the 18 hour operation the patient was placed in total body hypothermia and total circulatory arrest for 45 minutes. The hypothermia was needed to slow metabolism and protect the brain and organs from reduced oxygen supply while Ayub surgically embolized and removed an AVM which was located near the medulla. Ayub was the honorary physician to the President of Pakistan and he received Pakistan’s highest civilian award the Star of Achievement. Ayub was a man of diverse talents and also appeared with Peter Ustinov, Nick Nolte, and Susan Sarandon in the movie Lorenzo's Oil released in 1992.
Many Firsts
Ayub’s invention, the Ommaya reservoir, was the first subcutaneous reservoir that allowed for repeated intrathecal injections.13 , 7 Before his invention patients had to suffer repeated lumbar punctures for intrathecal drug administration. Spinal angiography was pioneered by Ommaya, Di Chiro, and Doppman. This work allowed for the visualization of arteries and veins and allowed for understanding of spinal cord arteriography. The same team reported the treatment of spinal cord AVMs by percutaneous embolization of an intercostal artery using stainless steel pellets. This was one of the first reports of interventional neuroradiology.9
Ayub’s models and work in traumatic injury were foundational to the biomechanics of traumatic brain injury. 20, 21, 23, 24, 25, 26, 27 This work allowed for improved modeling of brain injury by engineers in their design of safety equipment in automobiles. Ayub also published the first coma score for classification of traumatic brain injury. 17 The most widely used contemporary classification systems follow the Ommaya approach. 10 Ayub’s friendship with Congressman Lehman, then chair of the House Appropriations Subcommittee on Transportation, lead to the creation of the National Center for Injury Prevention and Control.32 Each of these efforts involved collaborators who were vital to their successful conclusion.
Ayub worked with Sir Godfrey Hounsfield to determine the spatial resolution of the CT scanner which opened the door for its use in stereotactic surgery.15, 28 Ayub also invented the first spinal fluid driven artificial organ.17
Interventional Neuroradiology
The work of Di Chiro, Ommaya, and Doppman was critical to the development of spinal angiography. 4,5 The visualization of arteries and veins allowed for understanding of the pathophysiology of spinal AVMs in addition to classification of lesions. Di Chiro, Ommaya, and Doppman also reported one of the earliest interventional radiology approaches using stainless steel pellets to treat a spinal cord AVM. 6 This percutaneous embolization approach was noted as less traumatic than surgical treatment by the authors and represented another step forward in pecutaneous vascular embolization as an addition the surgical armamentarium for treating certain vascular disorders of the central nervous system.
CSF Rhinorrhea
Before Ommaya’s work CSF rhinorrhea was classified as traumatic and spontaneous. The second category was essentially a waste basket which did not assist in guiding treatment approaches.14,18 Ommaya classified non traumatic rhinorrhea as resulting from high pressure leaks (tumors & hydrocephalis) and normal leaks (congenital abnormalities, focal atrophy, oysteomyelitic). Nontraumatic rhinorrhea is a challenge in diagnosis and choice of surgical approach. Of importance to successful surgical outcome is the demonstration of fistula. Among the non traumatic group, CSF rhinorrhea occurring with primary empty sella (PES) was first reported by Ommaya.31
Biomechanics of Traumatic Brain Injury
Ommaya’s cetripedal theory identified that the effects always begin at the surface of the brain in mild injury and extend inward to affect the diencephalic- mesencephalic core in more severe injury.20 His work showed that both translational and rotational acceleration produce focal lesions but that only rotational acceleration produced diffuse axonal injury. When damage is found in the rostral brainstem it is also associated with diffuse hemispheric damage. Prior to his work it was believed that that the mechanism of consciousness was linked to primary brainstem injury. However, the brainstem and mesencephalon are the last structure to be affected in severe injury, and rotational rather than translational forces produce concussion. Contact phenomenon contribute to the development of focal lesions, e.g. frontal and temporal lesions due to contact with the sphenoid bone.18 Magnetic resonance imaging (MRI) studies have supported these theories. 11, 12 They have confirmed that the distribution of lesions follows a centripetal pattern that follows injury severity identified by the Glascow Coma Score.
Ommaya Reservoir
Ayub Ommaya first reported the Ommaya reservoir in 1963. The reservoir is subcutaneous implant for repeated intrathecal injections, to treat hydrocephalus and malignant tumors. 13, 16 The reservoir was the first medical port to use silicone which is biologically inert and self sealing. The Ommaya reservoir allows delivery of intermittent bolus injections for chemotherapy to the tumor bed. Agents are injected percutaneously into the reservoir and delivered to the tumor by compression of the reservoir. The Ommaya reservoir provided a great improvement for treatment which reduces the risk of infection.
Creation of the National Center for Injury Prevention and Control
While the Chief Medical Advisor for the Department of Transportation in the 1980’s, Ayub commissioned a report, Injury in America, from the Institute of Medicine (IOM) in 1985.3 This report and efforts by Congressman William Lehman and Dr. Ommaya lead to the creation of the Center for Disease Control's, National Center for Injury Prevention and Control which began to provide synthesis, direction, and funding for the field. Congressman William Lehman and Ayub became friends when he cared for his daughter. They had many discussions focusing on the need for a center that emphasized injury prevention and research. Congressman Lehman, then chair of the House Appropriations Subcommittee on Transportation, was responsible for the initial $10 million awarded to the CDC to establish a new Center for Injury Control. 2 The FY 2008 budget for the center is $134 Million, and it funds basic and applied injury research. Ayub served on the National Advisory Committee for the Center for 15 years.
Spinal Fluid Driven Artificial Organ
Ayub has two children who suffer from Type 1 diabetes. Motivated by his personal experience with the disease, Ayub focused on the problem of transplantation of islet cells for the treatment of diabetes. A major challenge facing survival of islet cells is immune rejection. Ayub thought that the CSF would provided an ideal setting for transplanted islets due to the immune protection provided by the blood brain barrier. He developed an artificial organ which would house transplanted islets, and the cells could be nourished by the CSF. Ayub, Illani Atwater, and collegues identified that ventricular-peritoneal CSF shunts provided an immune protected site for the transplantation of mouse and rat islets in dogs and llamas.22, 30 Ayub and collegues also identified that CSF glucose mirrors blood glucose. Islets cells were able to survive in this system and function in the llama model, but further work on the model is needed.1 Unfortunately Ayub was not able to complete this research.
The role of emotions in consciousness
Ayub focused much of his career on the study of consciousness, the brain, and mind. This interest derived from his reading of Pennfield’s work on surgical treatment of epilepsy. His work in traumatic brain injury was influenced by his interest in how consciousness is altered and how it recovers after traumatic injury. Key to his observations is the role of the limbic system and emotion as foundational for consciousness.29 In his view, emotion is the trigger to action and other aspects of rationality are tools to justify action. Ayub saw consciousness as an emergent property of the evolution of neural structures. Consciousness is the result of evolutionary forces directed to improving the efficiency of mental function. The reintegration of thought and action after traumatic injury provided the experimental context for Ayub’s thoughts.
It is popularly assumed that emotion disrupts cognition. However neurophysiology and Ayub’s TBI research emphasizes its fundamental inseparability. Ayub defined four steps in the evolution of consciousness. 1) reflex and avoidance reactions; 2) sensory inputs merged with multisensory neurons in the mesencephalon; 3) interactions formed between sensory and limbic systems and memory; and 4) reinforcement of thalamic neural centers which relays information between sensory and motor centers. Ayub discussed how the limbic system and emotion motivates action and focuses attention.
Final Years
In the last two years before his passing, and after it was clear his health was declining, his beloved wife and mother of his three youngest children Ghazali brought him back home to Pakistan (figure 3). Those who worked with Ayub remember him as a skillful surgeon who was absolutely unflappable in the operating room, and an astoundingly effective clinician, communicator, and educator. His manner with patients was an enlightening mixture of kindness, simplicity, and accuracy, all held together with a subtle wit and humor. He had the ability to render complex and sensitive clinical problems into clear and simple terms; he communicated this with clarity and compassion to his patients, and they believed in him and loved him for it.
Ayub was a single parent for many years caring for his 3 older children. During this time, Ayub made all the meals, spent time with his children, and was an excellent father. In addition he juggled work in the lab and as a neurosurgeon. He always spent time with people who needed his assistance, and he never stopped learning. He was an avid reader with an exceptionally curious mind, who spent his free time reading philosophy, politics, history, and religion. On July 11, 2008, Dr. Ayub Khan Ommaya passed away at his home in Islamabad, Pakistan, of complications related to Alzheimer‘s disease.
References
[1] Atwater I, Yanez A, Cea R, Navia A, Jeffs S, Arraya V, Szpak-Glasman M, Leighton X, Goping G, Bevilacqua JA, Moreno R, Brito J, Arriaza C, Ommaya A. Cerebral spinal fluid shunt is an immunologically privileged site for transplantation of xenogeneic islets. Transplant Proc. Jun;29(4):2111-5. 1997.
2 Bergman AB Ragnar Berfenstam's legacy. Inj Prev. Mar;6(1):4; 2000
3 Committee on Trauma Research Injury in America: A Continuing Public Health Problem. National Academy press: Washington, DC 1985
4 DiChiro, G. Doppman, J.L. and Ommaya, A.K.: Selective arteriography of arteriovenous aneurysms of the spinal cord. Radiology, 88: 1065-1077, June 1967.
5 Doppman, J.L., DiChiro, G. and Ommaya, A.K.: Selective Arteriography of the Spinal Cord. St. Louis, Missouri: Warren Green Publisher, 1969.
6 Doppman, J.L., DiChiro, G., and Ommaya, A.K.: Obliteration of spinal cord arteriovenous malformation by percutaneous embolization. Lancet, 1: 477, March, 1968.
7 Dudrick SJ. History of vascular access. J Parenter Enteral Nutr. 30(1 Suppl):S47-56. 2006
8 Holley J. Ayub K. Ommaya, 78; Neurosurgeon and Authority on Brain Injuries. Washington Post. Page B04; July 14, 2008
9 Huckman MS. Giovanni Di Chiro (1926-1997). AJNR Am J Neuroradiol. Jun-Jul;19(6):1007-10; 1998
10 Kelly JP, Rosenberg J. Practice parameter : the management of concussion in sport: report of the Quality Standard’s Subcommittee. Neurology;48:581–585; 1997
11 Levin HS, Mendelsohn D, Lilly MA, Yeakley J, Song J, Scheibel RS, Harward H, Fletcher JM, Kufera JA, Davidson KC, Bruce D. Magnetic resonance imaging in relation to functional outcome of pediatric closed head injury: a test of the Ommaya-Gennarelli model. Neurosurgery;40(3):432-40; 1997
12 Levin HS, Williams D, Crofford MJ, High WM Jr, Eisenberg HM, Amparo EG, Guinto FC Jr, Kalisky Z, Relationship of depth of brain lesions to consciousness and outcome after closed head injury. J Neurosurg; Dec;69(6):861-6; 1988
13 Ommaya AK, Subcutaneus reservoir and pump for sterile access to ventricular cerebrospinal fluid. Lancet.;2:98 3–984; 1963
14 Ommaya AK, DiChiro G, Baldwin M, Pennybacker JB. Non-traumatic cerebrospinal fluid rhinorrhoea J. Neurol. Neurosurg. Psychiat.,; 31, 214-225; 1968
15 Ommaya AK, Murray G, Ambrose J, Richardson A, Hounsfield G. Computerized axial tomography: estimation of spatial and density resolution capability. Br J Radiol.;49(583):604-11; 1976
16 Ommaya AK. Implantable devices for chronic access and drug delivery to the central nervous system. Cancer Drug Deliv;1(2):169-79; 1984
17 Ommaya AK. Spinal fluid driven artificial organ. United States Patent and Trademark Office. Patent number: 5385582. Jan 31, 1995
18 Ommaya AK. Trauma to the nervous system. Hunterian Lecture. Ann. Roy. Coll. Surg. Eng., 39, 317-347; 1966
19 Ommaya, A. K.. Cerebrospinal fluid rhinorrhea. Neurology 15, 107-113; 1964
20 Ommaya, A.K. and Gennarelli, R.A.: Cerebral concussion and traumatic unconsciousness. Brain., 97: 633-654, 1974.
21 Ommaya, A.K. and Yarnell, P.: Subdural hematoma after whiplash injury. Lancet, 2: 237-239, August, 1969
22 Ommaya, A.K., Atwater, I., Coonrod, B.A., et. Al. Novel Transplantation Approach: Islet Xenografts in C.S.F. Shunts in Dogs. Transplantation Proceedings, December, 1994.
23 Ommaya, A.K., Fass, F., and Yarnell, P.: Whiplash injury and brain damage: An experimental study. J.A.M.A., 204: 285-289, April, 1968.
24 Ommaya, A.K., Hirsch, A.E., and Martinez., J.: The role of “whiplash” in cerebral concussion. Proceedings of the 10th Stapp Car Crash Conference, New York: Society of Automotive Engineers, 197-203, November, 1966.
25 Ommaya, A.K., Hirsch, A.E., Flamm, E.S., and Mahone, R.M.: Cerebral concussion in the monkey: An experimental model. Science, 153: 211-212; 1966.
26 Ommaya, A.K., Hirsch, A.E., Harris, E., and Yarnell, P.: Scaling of experimental data in cerebral concussion in sub-human primates to concussive threshold for man. Proceedings of the 11th Stapp Car Crash Conference, New York: Society of Automotive Engineers, 47-52, October, 1967.
27 Ommaya, A.K., Rockoff, S.D., and Baldwin, M.: Experimental concussion: A first report. J. Neurosurg., 21: 249-267;1964.
28 Ommaya, A.K.: Computerized axial tomography of the head: The EMI-Scanner, a new device for direct examination of the brain “in-Vivo.” Surg. Neurol. 1: 217-222, 1973.
29 Ommaya, Ayub K. Emotion and the Evolution of Neural Complexity. WESScom: The Journal of the Washington Evolutionary Systems Society 3(1):8-17; 1993
30 Ommaya, A.K., Atwater, I.J., Yanez, A., et. Al. Llama Glama: Unique model for evaluation of xenogenic islet transplants in a CSF driven artificial organ. Transplantation Proceedings, 1995.
31 Syed BA. Nontraumatic (spontaneous) cerebrospinal fluid rhinorrhea from cribriform fistula associated with primary empty sella: report of two cases and literature review. Ann Saudi Med. Jan;20(1):43-6; 2000
32 Zaldivar R.A. Low key Rep. Lehman savvy on deal-making ex-salesman acts as State’s rainmaker. Miami Herald. p. 1A ; November 20, 1989.