FDA Panel Backs Deep Brain Stimulator for Tremors

http://www.reutershealth.com/news/docs/199703/19970317rga.html

     ROCKVILLE, MD, Mar 17 (Reuters) - The Food and Drug
     Administration's Neurological Devices panel on Friday voted 8-0
     to recommend approval of an implantable device known as a deep
     brain stimulator that helps control tremors in patients with
     Parkinson's disease and essential tremor.

     The panel was split on whether the device should be implanted on
     both sides of the brain, citing a lack of data. The $10,000
     device, called the Activa Tremor Control System, will be made and
     sold by Medtronic Inc., and will only be recommended for patients
     refractory to drug therapies for the conditions.

     The FDA does not have to follow the panel's advice, but usually
     does. Panel members said they thought results were more
     impressive in essential tremor than in Parkinson's. Even so, Dr.
     Mark Hallet, a panelist and clinical director of the National
     Institute for Neurological Disorders and Stroke, said that he
     felt "...the benefit is clear," for all tremors, outweighing any
     safety risk.

     Committee members were concerned, however, about the potential
     for intracranial hemorrhage during implantation. During trials
     that involved 418 patients, 13 had ICH. In addition, panel member
     Dr. Gilbert Gonzalez, a neurologist from the Mayo Clinic in
     Scottsdale, Ariz., said that he was not convinced that it was
     safe to implant a polyurethane device into the brain.

     With Activa, electrodes implanted in the brain -- usually in the
     thalamus -- are then connected to a pulse generator, which is
     implanted subcutaneously in the chest. Medtronic says that Activa
     is an option to drugs such as levodopa, and to surgical
     techniques such as thalamotomy. With the Activa system, there is
     little to no damage to the brain with implantation, according to
     Medtronic and to an FDA reviewer. And, patients can turn off the
     device at any time, by passing a hand-held magnet over the
     generator. This helps control side effects due to the impulses,
     which include paraesthesia, paresis and dysarthria.

     The firm presented data from two trials, both relatively small.
     All patients received an Activa implant, but patients and
     physicians were blinded as to whether stimulation was activated
     at time of evaluation. Panel members said they did not consider
     this a true randomization, but accepted the results anyway. In
     the studies, conducted in the U.S. and Europe, both Parkinson's
     and essential tremor patients had two-point drops on the
     four-point Unified Parkinson's Disease scale and the Tremor
     Rating Scale, said Medtronic clinical investigator Dr. William
     Koller of the University of Kansas.

     The firm studied 45 U.S. patients at several sites, all of whom
     received unilateral implantation. In the European study, 28
     patients got unilateral, and 18 got bilateral implantation.
     Koller said that ,for many essential tremor patients, results
     were so significant that it was "...like pushing the disease back
     twenty years."

     An FDA medical reviewer said that, at every follow-up point,
     57.7% of essential tremor patients had at least a two-point
     decrease on the symptom scale. For Parkinson's patients, at least
     60% of patients had a similar drop. The reviewer expressed
     concern that 7 of the Parkinson's patients had worsening tremors,
     and that most did not experience any improvement in other
     symptoms, or in ability to carry out activities of daily living
     such as bathing.

     But Medtronic and some panelists pointed out that tremor is only
     one symptom of Parkinson's and that Activa was not designed to
     address any other symptoms. Activa is already approved in Europe,
     Australia, and Canada for use in both essential tremor and
     Parkinson's.

     - Westport Newsroom 203 221 7648

---------------

New Brain Clue to Making Choices

http://www.reutershealth.com/news/rhdn/199703/1997031310.html

     NEW YORK, March 13 (Reuters) -- Scientists may have come close to
     understanding a biochemical process in the brain that influences
     the ability to make the right decisions -- to predict what
     behavioral choices may be most useful for survival.

     A series of experiments on monkeys reported in the journal
     Science indicate that brain cells which secrete the
     neurotransmitter dopamine play a key role in this process,
     signaling the best course of action for a given situation.

     The new explanation for how people come to read sensory clues
     around them and choose from a number of behaviors for maximum
     benefit are based on more than 15 years of primate experiments in
     Switzerland, says Dr. P. Read Montague, professor of neuroscience
     at Baylor College of Medicine in Houston, Texas.

     In these experiments by Montague's co-author Dr. Wolfram Schultz
     of the University of Fribourg, electrodes were attached to the
     brains of monkeys to record electrical activity in
     dopamine-secreting brain cells (neurons). The monkeys were
     trained to press a level in response to a certain pattern of
     light to receive a reward (a squirt of juice).

     "And the electrical activity in these neurons is known to reflect
     the delivery of this chemical, dopamine, to the frontal cortex.
     Dopamine is one of several neurotransmitters thought to regulate
     emotional response, and is suspected of playing a central role in
     schizophrenia, Parkinson's disease, and drug abuse," Montague
     says. "We think these dopamine neurons are making guesses at
     likely future rewards. The neuron is constantly making a guess at
     the time and magnitude of the reward."

     "If what it expects doesn't arrive, it doesn't change its firing.
     If it expects a certain amount of reward at a particular time and
     the reward is actually higher, it's surprised by that and
     increases its delivery of dopamine," he explains. "And if it
     expects a certain level (of reward) and it actually gets less, it
     decreases its level of dopamine delivery."

     Thus, says Montague, "what we see is that the dopamine neurons
     change the way they make electrical impulses in exactly the same
     way the animal changes his behavior. The way the neurons change
     their predictions correlates with the behavioral changes of the
     monkey almost exactly."

     Montague and MIT co-author Dr. Peter Dayan pulled together
     Schultz's findings and created a mathematical theory based on the
     idea of those neuronal guesses and then compared it to what was
     actually recorded in primates. "It dead-on predicts the way those
     cells are going to fire," Montague says.

     The researcher notes further evidence supporting the theory comes
     from recent brain-scan studies of people who are missing parts of
     their frontal cortex.

     "They're missing the part of their frontal cortex that provides
     input to these dopamine neurons in their midbrain," says
     Montague. "And interestingly enough, these people lack the
     ability to make correct decisions about the future when you give
     them psychological tasks asking them that -- which is exactly
     what you'd predict from the way we construe these neurons."

     Montague says the findings in primates may also increase our
     understanding of the brain mechanisms affected by drug abuse.
     "This is an important piece of the puzzle because we know
     dopamine is involved in the same systems that are usurped by
     drugs of abuse, like cocaine."

     SOURCE: Science (1997;275:1593-1598)







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