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BUDGET REQUEST Senator HARKIN. We are now going to shift to our afternoon panel, panel IV, Dr. Murray Goldstein,

Director of the National Institute of Neurological Disorders and Stroke; Dr. Snow, the Director of the National Institute on Deafness and Other Communication Disorders; Dr. Ruth Kirschstein, Director of the National Institute of General Medical Sciences; Dr. Carl Kupfer, the Director of the National Eye Institute; and Dr. Franklin Williams, Director of the National Institute on Aging.

Dr. Goldstein, we have your request for $583.3 million, which is a 7.7-percent increase from 1991. About $30.8 million I notice, or 74 percent of this growth, is for extramural research project grants. The funding for centers, training, and intramural research is held relatively flat. I keep repeating myself with every institute that comes up here. I'm making a point. (Laughter.]

DECADE OF THE BRAIN Again, I have not seen you since the showing of the movie "Awakenings."

Dr. GOLDSTEIN. That's right, sir.

Senator HARKIN. I was very moved by that, and now with Congressman Conte gone, we will all have a little added responsibility to help complete the Decade of the Brain research agenda.

So, Dr. Goldstein, welcome back to the subcommittee and please proceed.

Dr. GOLDSTEIN. Thank you very much, Senator. I have submitted my formal statement for the record and so I will not trouble you by reading it, but rather highlight some more recent developments.

As you know, sir, the Neurological Institute is one of the focal points at NIH for brain research. We have set ourselves two objectives for the Decade of the Brain. The first objective is understanding the human brain. Let me tell you what I mean by that. We really do not know how our brain works. An example. Every dayat least it happens to me-I meet somebody. I recognize him, but I can't remember his name. I do not think the problem is aging or Alzheimer's disease. I just can't remember his name at that moment, but 15 minutes later, I remember it clearly.

Senator HARKIN. I tell you it's the politician's worst fear. [Laughter.)

Dr. GOLDSTEIN. We're working on it. (Laughter.]

Fifteen minutes later, I do remember his name. It wasn't that my memory was impaired, it was that the mechanism for recall wasn't working adequately.


What is the mechanism for recall? Interesting question. Do we ever forget anything, or is it all stored away and is it our mechanism for recall that isn't working properly? Those are intriguing questions. I am sorry I do not have any answers, but that is what I mean when I say understanding the human brain.

The second issue we address is a more clinical one. Most neurological diseases do not kill, they cripple. They leave the victim with 15 to 20 years of a decrease in quality of his or her life, sometimes a disastrous decrease. In addition, it exsanguinates the emotions and resources of the family who have to provide care for the person whom they love. Our clinical research objective is aimed toward the issue of quality of life, what can we do to make it better for those patients with neurological disease.

Inherent and important in that is once a brain cell is destroyed or gone, it is gone forever. And so, the key to the issue is not treatment. The key to the issue is prevention to make sure we do not lose those brain cells since we are not going to get them back.

Let me give you two examples of things that have happened relatively recently which we consider tremendous success stories.


The first occurred shortly after our last hearings, and that was the treatment of acute spinal cord injury. I think you know about that. For the first time in the history of man we have developed and evaluated a successful treatment for acute spinal injury. It has now become part of the regular practice of medicine in this country and all over the world. If one can treat somebody with a spinal cord injury within 8 hours of that injury, we will absolutely, remarkably diminish the amount of neurological deficit. I have been careful not to say prevent paraplegia because there is a whole spectrum of results depending on the extent of the initial damage. But fundamentally those young men and women and they are generally young men and women-have remarkable improvement, namely, prevention of the fact that they were going to have to spend their lives in a wheelchair.


The second important event occurred 2 weeks ago. The fourth leading killer in this country remains stroke. One of the most common causes of stroke is an obstruction in one of the neck arteries to the brain. Surgeons for 20 years have been operating on those vessels in order to take out the obstruction in the neck artery. It is called a carotid, meaning the carotid artery, endarterectomy, meaning they cut out the bad part in the artery and sew the ends together. Carotid endarterectomy has become the third most common surgical procedure in the United States, and until 2 weeks ago, nobody really knew whether it did any good?

We launched a randomized controlled trial 3 years ago in which a group of patients received the best medical treatment available and part of the group of patients also had

a carotid endarterectomy. All patients had had the warning symptoms of stroke. The issue was would this surgical procedure be better than medical treatment alone in preventing a stroke.

All patients are graded in categories of those with the most severe obstruction of the carotid artery, those with middle degree obstruction, and those with very small obstruction. Two weeks ago, following an analysis of the data, we had to stop the trial. We could no longer ethically continue the trial. The upper third of patients, those with severe occlusion, had such remarkable positive results from surgery, we could no longer permit patients not to have surgery. Four hundred thousand physicians were informed overnight that the patients who were in the trial and their own patients, with 70 percent or more obstruction, should now be seriously considered for surgery to prevent stroke. It was unethical to go any further.


I use this as some of the real live examples of the Decade of the Brain and what we have to look forward to in the next 842 years of this remarkable opportunity that the Congress has given the people of the United States.

I would be delighted to try to respond to your questions, sir.
The statement follows:)


Each year, more people are hospitalized in the United States with brain

and other neurological disorders than with any other major disease group. Fortunately, steady progress during years of broad-based support for basic and clinical neuroscience research has brought us to a threshold; a threshold

in which knowledge of the brain and nervous system can be turned into

significant benefit for the millions of Americans who live with, or are at

risk for, a neurological or neuromuscular disorder.

During the past year,

the National Institute of Neurological Disorders and Stroke (NINDS), the

Federal agency with lead responsibility for research and training to

understand and treat brain and neuromuscular disorders, announced important

clinical findings which already are having important impact on patients with

stroke, spinal cord injury, Parkinson's disease, Gaucher's disease, and

febrile seizures. With encouragement from Congress and input from patients,

voluntary groups, and scientists and physicians concerned with nervous system

diseases, the National Advisory Neurological Disorders and Stroke Council has

prepared an "Implementation Plan for the Decade of the Brain" that

crystallizes the specific areas ripe for further progress in understanding,

preventing, and treating brain, other neurological, and neuromuscular disorders.

During the Decade of the Brain, the Institute will emphasize efforts to

understand and treat the injured brain and spinal cord--resulting from trauma

or disease.

We are beginning to move beyond symptomatic treatment into ways to actually intervene and arrest or even reverse the underlying disease processes. There exists a window of minutes to days after an initial injury in which damaged nerve cells may be salvaged with timely and appropriate treatment, and additional, secondary damage prevented. With acute spinal cord injury we have an eight-hour span during which high doses of

methylprednisolone--costing about $100--can prevent secondary injury and save

the teenager injured in a diving accident from lifelong neurological

disability. This finding was announced in March of 1990. High dose methylprednisolone is now being rapidly integrated into practice as the treatment of choice for acute spinal cord injury; treatment by emergency

medical teams soon after an accident is becoming more common. Plans are

underway to evaluate whether longer treatment with methylprednisolone or the use of a different steroid may provide even greater benefit. This year,

NINDS is establishing a pilot program of regional clinical research centers for head and spinal cord injury. These centers will develop improved therapies, promote research on restoration and preservation of function after injury, and provide the environment necessary for the recruitment and training of investigators for research on central nervous system trauma. The regional centers will add an important dimension to the NINDS research effort

in 1992 to improve the outcome for many of the estimated 10,000 Americans who

will have a spinal cord injury and the 500,000 who will experience a head


NINDS scientists and grantees are pursuing other avenues to "tease out"

the various chemical and cellular events triggered by injury to the nervous

system and devise nethods to block or enhance nerve cell activity for

therapeutic effect. For instance, in stroke patients, damaged nerve cells can spilt out dangerous levels of excitatory amino acids and produce toxic

supercharged molecules of oxygen knowa as free radicals. The next step is to

evaluate promising agents to neutralize these chemicals and prevent the progression of stroke. Research studies are also defining the role of free

radicals in Parkinson's disease and also the damaging interaction between

free radicals and blood vessels in the brain that can result from seizures.

Investigators are pursuing recent evidence that suggests the same mechanism

to secrete excitotoxias my be at work in head injury and neuro-AIDS.

Greater attention can aow be given to study of the selective

vulnerability and degeneration of nerve cell populations. Our laptitute's research objective is to prevent brain cell degeneration or arrest it in the very urliest stage of diseases such as Alzheimer', disease and Parkinson',

disease. Aged, nonhuman primates are an important research model for

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Alzheimer's disease, helping to elucidate the development of aerve cell

abnormalities and the deposition of amyloid protein in the plaques

characteristic of this disease. New genetic studies, neurochemical studies,

and the development of advanced imaging methodologies are being emphasized to

shed more light on the fundamental cause of Alzheimer's disease. 'The long ter effects of deprenyl and the value of tocopherol --, component of vitamin

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