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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.

PREPARED STATEMENT

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 81⁄2 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:]

STATEMENT OF DR. MURRAY GOLDSTEIN

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 headinjury.

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 methods to block or enhance nerve cell activity for therapeutic effect. For instance, in stroke patients, damaged nerve cells can spill out dangerous levels of excitatory amino acids and produce toxic supercharged molecules of oxygen known 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 excitotoxins may be at work in head injury and neuro-AIDS. Greater attention can now be given to study of the selective

vulnerability and degeneration of nerve cell populations. Our Institute's research objective is to prevent brain cell degeneration or arrest it in the very earliest stage of diseases such as Alzheimer's disease and Parkinson's disease. Aged, nonhuman primates are an important research model for Alzheimer's disease, helping to elucidate the development of nerve 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 term effects of deprenyl and the value of tocopherol--a component of vitamin

E--in combination with deprenyl to treat people with Parkinson's disease are being evaluated in an ongoing clinical trial. Study of tissues from people with amyotrophic lateral sclerosis, or Lou Gehrig's disease, has provided a lead to evaluate the use of branched-chain amino acids for this disease.

One third of the people who will have a stroke this year will become permanently disabled: stroke is the most common cause of disability requiring rehabilitation. The NINDS research effort on stroke will be enriched by a newly established intramural program. We also have ongoing clinical trials to evaluate clot-dissolving agents--tPA and heparinoids--for their effectiveness in limiting brain damage from ischemic stroke. We are working with a time-frame of only 90 minutes to three hours to determine whether tPA must be given as an emergency measure in order to be effective. Studies are also underway to elucidate risk factors and prevent stroke in those people at risk for an initial insult or recurrence. Within the past year, the NINDS found that aspirin and warfarin were so effective in preventing stroke in people with atrial fibrillation that as many as 30,000 people could be spared from a stroke this year, at a potential health care savings of $200 million. Early results from another, ongoing study have related ethnic differences in risk factors to differences in stroke type and outcome. NINDS has revised and reissued a program announcement to encourage new studies in Blacks, other minorities, and women to improve our understanding of different risk factors and types of stroke in various populations.

Intramural scientists using magnetic resonance imaging (MRI) have evidence that multiple sclerosis (MS) progressively attacks the central nervous system even when patients may be relatively symptom-free. This finding will change the way many patients are treated, especially in the early stages of the disease. In other work, intramural and extramural investigators are deciphering the immunologic processes related to MS and exploring new forms of treatment such as the possibility of a T-cell vaccine. At a minimum, 25 percent of all genetic disorders affect the brain and nervous system, some estimate that there are neurological consequences in 70 percent of all genetic disorders.

Neurogenetics research is brimming with

a proportional number of research opportunities. The chromosomal bases for

19 neurological or neuromuscular disorders are now known.

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neurofibromatosis 1 (NF-1) gene has been located on chromosome 17; ongoing research will clarify the gene's normal function and its role in the symptoms

of NF-1 and other disorders of cell growth such as cancer.

Scientists are

closing in on the genetic basis of some forms of epilepsy. Intramural
investigators are refining the optimal dose for enzyme replacement therapy in
Type 1 Gaucher's disease while continuing the development of methods to
repair or replace the defective gene. Dystrophin research has unexpectedly
revealed that other genes may be producing proteins that can "pinch hit" for
dystrophin and mitigate the symptoms of muscular dystrophy. Both genetic
linkage studies and studies of cell biochemistry are probing independently
the underlying causes of the various types of Batten's disease. In other
studies, researchers are working to isolate and sequence the gene for the
animal model of narcolepsy. While investigators continue work to localize
the genetic defect in Huntington's disease (HD), research to determine the
physiologic defect and possible therapies has progressed; preliminary efforts
are underway to test the efficacy of a drug called idebenone to protect at-
risk brain cells. Transgenic mice are also being developed as a genetic
model for HD--an invaluable tool for the expected wave of new studies once
the gene is found.

An estimated 10 to 15 percent of all children have mild cognitive
deficits or learning disabilities. This year, an estimated 9,000 babies will
develop cerebral palsy and several thousand more babies and children will
have to live with--or die from--the neurological consequences of their
mother's drug abuse. An ongoing multidisciplinary study to develop,
standardize, and validate a uniform classification system for the diagnosis
of children with higher cortical dysfunctions will facilitate research.
Improved treatments for epilepsy in the pediatric age group are a priority
for the Institute.

As evidenced by the advances and initiatives described here, we cannot separate progress in prevention, treatment, and diagnosis from the importance of basic neuroscience research. Neurochemistry and neurobiology are

providing important leads to understand cognition and behavior. NINDS grantees recently found that one possible mechanism for strengthening long term neural interactions appears to be the ability of the sending cell in

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