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Neurology Today:
doi: 10.1097/01.NT.0000360735.80901.4f
Department: Bookshelf

More Than Science Fiction — The Back Story for Deep Brain Stimulation: Deep Brain Stimulation: A New Treatment Shows Promise in the Most Difficult Cases.

FORD, BLAIR MD

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Dr. Ford is professor of clinical neurology and medical director of the Center for Movement Disorders Surgery in the departments of neurology and neurological surgery at Columbia University.

By Jamie Talan. 176 pages. Dana Press 2009

The story of deep brain stimulation (DBS) is an extraordinary tale of surgical innovation and scientific vision. It is a story of relentless technological progress, driven by larger-than-life pioneers and their courageous patients, who submitted themselves to unproven therapies in the hope of relief from intractable illness. Thanks to their contributions, DBS is now a standard advanced therapy that has revolutionized the treatment of Parkinson disease (PD). Tens of thousands of patients worldwide have undergone brain electrode implantation to control symptoms of PD, dystonia, tremor, and increasingly, psychiatric disorders.

Even 20 years after French neurosurgeon Alim-Louis Benabid, MD, demonstrated that continuous electrical stimulation could stop a trembling limb, the notion of placing electrodes and wires into a human brain, and flipping a switch to control movements and behavior, seems straight out of science fiction.

Deep Brain Stimulation author Jamie Talan, an accomplished science writer who has written for Newsday, The Los Angeles Times, and Neurology Today, reaches out to many of the top researchers and experts in the field. She condenses over a century of scientific progress into a spellbinding narrative, going back to the “first documented meeting between electrode and brain” in 1870, when experimenters believed they were recording the thoughts of monkeys.

Talan tackles the new and future frontiers of DBS, including its applications to depression, Tourette syndrome, obsessive-compulsive disorder, and states of minimal consciousness. Her final chapters, “Patients, Parameters and Risks” and “Ethics and the Future,” describe the complicated ethical pitfalls in this unique field of modern medicine.

Written in a clear scientifically literate style that will reach all readers, Talan's narrative is grounded in the real-life scenarios of patients with neurological and psychiatric disease. The main participants in this narrative are patients, neuroscientists, and surgeons, so too are the medical technology industry, governmental regulators, and medical ethicists.

Talan begins her story at the moment DBS appeared on the radar, when all of these stakeholders intersected in the same chamber at the US FDA hearing in March 1997. A patient with crippling essential tremor dramatically demonstrated the effect of DBS by turning off his stimulators in front of the committee members. Within six months, DBS was an approved therapy.

The story continues through the development of the modern stereotactic apparatus, the mapping experiments of Wilder Penfield, MD, the development of a schematic model of the basal ganglia, and the many triumphs and pitfalls of lesion-based surgery that dominated the field for more than four decades. Dr. Penfield, more than anyone, captured the imagination of the public and scientific community with his careful mapping of the human cortex, but his work did not lead directly to the development of DBS, and it is somewhat of an artifact of hindsight that conflates Dr. Penfield's work with basal ganglia ablation surgery, the forerunner of DBS.

Figure. DR. BLAIR FO...
Figure. DR. BLAIR FO...
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The seminal figure in the development of DBS does not appear in the story, but he made the critical observation that lesions of the basal ganglia could stop tremors without causing paralysis. Russell Meyer, MD, pioneering neurosurgeon from the University of Iowa, was not only the first to treat PD by “attacking the basal ganglia,” as he wrote in 1951, but he also proposed a brain circuit scheme that was remarkably prescient; it consisted of parallel loops connecting the globus pallidus, thalamus, and cortex, a direct forerunner of the corticopallidothalamic circuit elucidated 30 years later by Mahlon DeLong, MD, and colleagues.

As Deep Brain Stimulation describes, for much of its history, this technology was advanced by clinicians, and not neuroscientists. Surgically-created lesions of the basal ganglia were made and revised on a purely empirical basis, and the results were not evaluated in a scientific manner. In that pre-DBS era, surgeons obliterated pieces of brain without the aid of neuroimaging. They published nonrandomized case series with limited follow-up, and biased results. As the story of DBS reminds us, medical progress is messy and evolves with caution and recklessness, serendipity, near-misses, and eureka moments.

At times during the development of DBS, a critical breakthrough occurred by pure chance. The most famous example is that of Irving Cooper, MD, who accidentally severed the anterior choroidal artery in a patient, only to discover that when the patient awoke, his tremor was cured. At many other points, researchers got an idea essentially correct but missed a critical detail, or were simply unaware that what they were searching for had already been discovered. The spirit of these times — with all of its ingenuity, hubris, and hope — was personified by Cooper — or “King Coop,” as Talan names him.

Despite the attempts of neuroscientists to provide a neurophysiological rationale for the surgical treatment of movement disorders, neurosurgeons were always one step ahead, empirically placing lesions where no one had dared to go. Progress happened through trial and error, and not according to a prior understanding of brain circuitry. The field of DBS is now maturing from its clinical phase to a firmer ground of patient safety and scientific validity, even as the ethical consequences of DBS become more entangled.

Only in the current era, as innovative clinicians expand the indications for DBS, is the selection of brain targets determined by functional imaging studies, as exemplified by the work of neurologist Helen Mayberg, MD. The newer applications, such as depression and obsessive-compulsive disorder, involve brain networks that remain uncharted and fraught with ethical considerations. What are investigators to do, asks Talan, when a depressed patient threatens to kill himself if he is not accepted for DBS therapy?

Throughout this remarkable story of progress and promise, Talan maintains her science writer's skepticism. Sometimes, though, she seems un-ironically accepting of the claims and platitudes that always come with medical innovation: “I still have Parkinson disease but I say I have got 50 percent of it beat.”

Around the edges of the narrative are the human casualties of innovation, with their crushed hopes and surgical complications, such as the man who loses his speech as a result of surgery, or the young woman afflicted with chronic pain who experiences only temporary relief before her agony returns for ever. When failures occur, Deep Brain Stimulation quickly shifts from patient to surgeon: the human cost of progress tends to drop out of sight as the researchers shrug and conclude: “We need to be working harder at research to find the best target.”

In summary, Deep Brain Stimulation is a fascinating, thought-provoking story of one of the most important and promising advances in all of medicine. It is a multilayered tribute to the innovators who continue to advance the field, as well as the brave patients who choose hope in the face of uncertain risk. The story of DBS contains valuable lessons about the nature of medical innovation, and about the ethical complexities that lie ahead as the technology advances. The mysteries of the brain remain far from human understanding but the electrode-brain interface is with us to stay.

©2009 American Academy of Neurology

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