“My clinical and research career has been focused on the clinical applications of deep brain stimulation and the understanding of the mechanisms of deep brain stimulation and neurostimulation,” Ali R Rezai, Stanley D and Joan H Ross chair in Neuromodulation, The Ohio State University, Wexner Medical Center, Columbus, USA, tells NeuroNews. Rezai is also past president of the Congress of Neurological Surgeons (CNS) and president of North American Neuromodulation Society (NANS) 2011–2013
What drew you to neurosurgery and neuroscience?
During medical school, I was fascinated with the human brain and nervous system and became very interested in nervous system disorders. It is one of the major frontiers for discovery and innovation and there is a lot that needs to be done in this area to help patients who are afflicted with neurological conditions.
Which advances in neuromodulation have shaped your career?
The development of cardiac pacemakers in the 1960s and beyond revolutionised the way heart diseases are treated. In the same fashion, neurological pacemakers and neuromodulation are transforming the way neurological conditions are being treated.
One of the exciting advances in neuromodulation has been the development of the brain pacemaker systems and the surgical treatments involved in deep brain stimulation. The modern application of deep brain stimulation dates from the late 1980s and was developed by the French neurosurgeon Alim-Louis Benabid, who used stimulation in place of lesioning for the treatment of tremor. This ushered in the popular use of deep brain stimulation with over 100,000 patients receiving implants since then. It is now FDA-approved in the USA for the treatment of Parkinson’s disease, essential tremor, dystonia and obsessive compulsive disorder.
Deep brain stimulation is a major area of my interest and expertise. My clinical and research career has been focused on the clinical applications of deep brain stimulation and the understanding of the mechanisms of deep brain stimulation and neurostimulation. I have had the opportunity to be involved in multiple clinical trials including those treating Parkinson’s, dystonia, tremor, obsessive compulsive disorder, depression, traumatic brain injury, epilepsy, and Alzheimer’s disease.
Who were your mentors in the field and what do you still remember from their wisdom?
I have been fortunate to have the opportunity to learn and work with some of the pioneers in stereotactic and functional neurosurgery and neuromodulation. They include specialists like Michael Apuzzo and Patrick Kelly who advanced and popularised the use of computers and stereotactic neurosurgery, as well as Ron Tasker and Andres Lozano who taught me the foundational elements of intraoperative physiology and deep brain stimulation surgery.
I would also have to say that some of my greatest mentors have been my patients because of what I have learned from them just by listening carefully and through observation. Many of these patients have severe, intractable conditions and disabilities that have progressively taken away their quality of life, independence, and occupational and social functioning. Despite these adversities, they are courageous and do not give up in their quest to seek ways of getting better. I am also impressed by the number of patients who volunteer for clinical trials that may not directly benefit them but may help others who are afflicted and assist us in our future work.
What are the key things to keep in mind when developing standards of practice in neuromodulation?
Neuromodulation is a broad category of therapies that involves implantable devices and external neuromodulation approaches that provide precise stimulation or infusion to specific targets in the brain, spinal cord and the peripheral nervous system. These approaches are applied for specific disease symptoms such as chronic pain, headaches, tremors and other movement disorders, incontinence, as well as psychiatric, behavioural and cognitive disorders.
Neuromodulation provides additional options and hope for patients who have tried various medications and other treatments and yet are becoming progressively disabled with worsening of their functioning and quality of life.
A key feature for the future of neuromodulation is the use of a strong scientific rationale for new applications, the design of clinical trials which are different than pharmaceutical trials or studies in cardiology and other specialties, the development of registries and the importance of neuromodulation outcome studies linked to quality of life and economic benefit measures as compared to other treatments. Additional aspects include the standardisation of the neuromodulation procedures, reimbursements and the use of these procedures earlier in the course of the disease rather than as an end-stage therapeutic approach.
What are the three most important innovations in neuroscience in the last 10 years?
The neurological frontier is among the most important for medical exploration and discovery. The growing recognition of the scope, impact and importance of preventing, diagnosing, treating and curing disorders of the nervous system has inspired a new generation of developments in the neurosciences.
Among many innovations, we have seen an increased understanding of underlying genetic influences, neurobiology, neuropathology and neural circuitry and brain networks governing functions and being impaired in disorders of the nervous system. This progress, along with innovations in imaging, surgical technique, therapeutic implantable devices, stem cells and gene therapy, has positioned neuroscience as the emerging primary discipline for progress in global organised medicine and has greatly improved our understanding of brain networks.
From your research and experience, what motivates you?
The most significant motivator for me is when I see how our therapies concretely help our patients—when they stop a disabling tremor, lessen rigidity and stiffness, improve walking, relieve a headache and years of chronic pain and anxiety, and calm the electrical storm in the brain that causes seizures. There is tremendous opportunity ahead of us to do more and help more patients and that is what keeps us going. It is gratifying for our team to seek remedies for these conditions so that people can regain functioning that has been taken away from them by these diseases and enjoy better quality of life.
Neuromodulation is being tested as a potential treatment for various different diseases. In your view what are the research priorities in the area of neuromodulation, and why?
In addition to the use of deep brain stimulation for movement disorders, it also has a vast potential to treat patients with cognitive and behavioural disorders, including depression, anxiety, addictions, Alzheimer’s disease, eating disorders, traumatic brain injury, and other conditions such as stroke and sight restoration. Another important priority is to make the current generation neuromodulation devices for treatment less invasive, smaller, and with smart features that have closed-loop capabilities.
Additional areas of improvement include the development of biomarkers, advanced imaging and genetic screening to improve our ability to detect disorders like Alzheimer’s, Parkinson’s disease, chronic pain and many other neurological and behavioural disorders. This will facilitate disease management and the selection of the most appropriate patients for therapies, and will help us monitor the progress of preventive and treatment efforts.
Another challenge that we face is the ability to provide earlier access to innovative treatments and technologies, rather than use them as a last resort. In the case of neuromodulation implants, often patients have suffered with disease symptoms that have become treatment intractable for years before they finally receive these devices. I believe that innovative and cutting edge options will be available much earlier in a personalised and participatory fashion in the future.
What new techniques/technologies are you keeping an eye on?
An area of crucial importance in neuromodulation is the development of neurological sensors, neuroanalytics and the closed-loop feedback capabilities with neuromodulation implants. Up until now, neuromodulation implants have only been output open-loop devices with no feedback and input capabilities. Advances in sensing of neurological signal detection and processing, are enabling a new arena of responsive and adaptive neuromodulation therapies. These closed-loop capabilities are similar to cardiac devices that can detect a life-threatening heart rhythm and treat it. Areas of promise for closed loop application in neuromodulation are in deep brain stimulation for epilepsy and Parkinson’s disease, and spinal cord stimulation for chronic pain.
Another area of important development is the use of micro-implantable neuromodulation devices that are minimally invasive and not attached with connecting wires to pacemaker batteries in the chest or buttock region. These microstimulators are remotely powered and managed via handheld cell- phone-like devices. This is a specific area that I have been working on with my colleagues over the past few years. An example is the use of a micro dental implant-like device that stimulates the sphenopalatine ganglion for the treatment of cluster headaches. When the headaches start, the patient uses a handheld smart-phone-like device to treat the headache in a few minutes.
Yet another area of importance is the use of disease biomarkers to facilitate selection, monitoring and evaluation of patients undergoing neuromodulation therapies. These biomarkers can play an important role as surrogate markers for neuromodulation therapies.
As past president of the Congress of Neurological Surgeons (CNS) and president of North American Neuromodulation Society (NANS) 2011–2013, what are your goals for the societies that you preside over?
Our goals for NANS are to provide access to numerous neuromodulation educational programmes for our members. We will continue to strive to create greater opportunities for innovation and discovery, and to sharpen our focus on improving neuromodulation education through collaboration and partnerships with clinicians, scientists, and engineers to foster the growth and development of neuromodulation therapies for our patients. NANS has also begun to play a more prominent role in advocacy efforts to both promote the field and ensure that patients continue to receive access to neuromodulation therapies, and we look forward to expansion in that area.
What are your interests outside of medicine?
My work is a large component of my life, and it gives me a great deal of satisfaction and pleasure. I consider my research and delving into the understanding of human brain and behaviour stimulating and fun. Outside of work, I also enjoy music, reading, history and exercise. However, I must admit that being at the Ohio State University has sparked a new interest for me in college athletics and competition, and I have become a big college football and basketball fan.
- Stanley D and Joan H Ross Chair in Neuromodulation
- Associate dean of Neuroscience
- Professor of Neurosurgery, tenured
- Professor of Neuroscience
- Director, Neuroscience Program
- Director, Center for Neuromodulation
Honours and awards (selected)
- Innovator of the Year Award, Cleveland Clinic, 2007
- Best Article of the Year Award, CNS Spectrums, 2004
- Best Paper of the Year, American Psychiatric Association, 2004
- American Association of Neurological Surgeons William H Sweet Investigator Award, 1998
- Congress of Neurological Surgeons Clinical Fellowship Award, 1997
- Bottrell Fellowship Award in Neurosurgery, 1997
- Alpha Omega Alpha, 1989
- Dean’s Scholar, University of Southern California School of Medicine, 1988–1990
- Editorial board, Neurosurgery Journal
- Editorial board, World Neurosurgery Journal
- Editorial board, Stereotactic and Functional Neurosurgery Journal
- Editorial board, Neuromodulation Journal
- Editorial board, Neurological Research Journal
- Co-editor, World Neurosurgery journal supplement, 2013
- wCo-editor, Movement Disorders journal supplement, “Deep brain stimulation for Parkinson’s disease”, 2006
- Editor, Neurosurgery Clinics of North America: “Neurosurgery for Psychiatric Disorders”, 2003
Society positions (selected)
- President, North American Neuromodulation Society (NANS), 2011–2013
- President, Congress of Neurological Surgeons (CNS), 2012–2013
- Past president, American Society of Stereotactic and Functional Neurosurgery (ASSFN), June 2010–June 2012
- Annual Meeting Scientific Program chairman, North American Neuromodulation Society Meeting, 2009–2011
- Annual Meeting Program chairman, Congress of Neurological Surgeons Annual Meeting, 2010
- Vice-president, American Society of Stereotactic and Functional Neurosurgery (2008–2010)
- Executive Committee, Congress of Neurological Surgeons, 2002–2013
- Board of Directors, North American Neuromodulation Society, 2004–2013 Board of Directors, International Society of Reconstructive Neurosurgery, 2005–2013