thanks, Meir, you're the researcher of the group.  Always send such
interesting articles!

~Tamar Mag Raine
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IM: tamarmag48
Oakland Mayor's Commission on People with disabilities


> [Original Message]
> From: Meir Weiss <[log in to unmask]>
> To: <[log in to unmask]>
> Date: 1/2/2005 4:09:06 AM
> Subject: Emailing: Brainstorm for Parkinson's
>
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> https://www.hadassah.org/pageframe.asp?section=news&page=per.html&header
> =per&size=50
> Medicine:
> Brainstorm for Parkinson's
> By Wendy Elliman
>
> It's a disabling disease, but Hadassah physicians have developed a
> deep-brain stimulation technique that ameliorates Parkinson's symptoms.
>
>
> Photo by Debbi Cooper
>
> Larisa Korvan is hoping desperately that Hadassah neurosurgeon Zvi
> Israel will add her to his waiting list. Although the procedure for
> which she hopes to qualify is only a few years old, although its cost is
> not covered by her health insurance, and although it will require her
> spending at least eight waking hours lying rock-still while surgeons
> drill her skull and reach into her brain, she wants this as much as she
> has ever wanted anything. "My Parkinson's symptoms were beginning while
> I was still in Ukraine," she says. "But it wasn't until after we moved
> to Israel 12 years ago that they became bad enough for me to take
> notice."
> Steady progression of the disease has now frozen Korvan's face into the
> typical, expressionless mask of Parkinson's disease. It has made her
> muscles rigid, her balance poor and all but taken away her fine-motor
> control. She suffers constant tremors and increasing difficulty in
> walking.
>
> While medication controlled the symptoms of this chronic movement
> disorder for several years, their side effects have become almost as
> debilitating as the illness itself.
>
> "I'm only in my sixties," she says. "I have children and grandchildren
> to live for. This new procedure is my only solution."
>
> A decade ago, as Korvan's illness was taking hold, this solution did not
> exist for her or for millions of others (about a million and a half in
> the United States; about two per thousand in Israel) afflicted by the
> crippling, progressive neurodegenerative disorder. Its development owes
> much to the work of Israeli physiologist Dr. Hagai Bergman of the Hebrew
> University-Hadassah Medical School, a member of the team that would be
> involved in Korvan's treatment. It was Dr. Bergman, probing the
> subthalamic nucleus, an area deep in the brain only millimeters in
> diameter, who discovered it to be overactive in Parkinson's disease and
> that when inactivated, all major symptoms are ameliorated.
>
> "Neurosurgeons have been searching for surgical solutions to Parkinson's
> for a hundred years," says Dr. Israel, of the neurosurgery department at
> the Hadassah-Hebrew University Medical Center at Ein Karem. "Parkinson's
> surgery, however, hit a long hiatus in 1967 with the appearance of
> L-dopa. L-dopa is a very successful medication but it, too, has side
> effects and ultimately loses its effectiveness."
>
> In 1982, a chance occurrence set in motion a shift back to surgery, but
> in a new form that has already restored to thousands of Parkinson's
> victims their quality of life. In that year, California emergency rooms
> were suddenly seeing young patients suffering an acute and irreversible
> syndrome that resembled Parkinson's. It turned out all were drug users
> who had bought from a batch in which a certain chemical had been mixed.
> The chemical was isolated and used to create, for the first time, a
> laboratory model of Parkinson's. Investigation could now begin in
> earnest.
>
> Among the researchers was Dr. Bergman, then in the United States doing
> postdoctoral study. Working with monkeys, he ablated or burned away the
> overactive subthalamic nucleus and strikingly reduced their Parkinson's
> symptoms. In 1993, ablation was replaced by the less risky procedure of
> delivering electrical stimuli to the subthalamic nucleus via implanted
> electrodes.
>
> The Food and Drug Administration approved this technique in 2001, and
> the three years since have seen an exponential growth in this therapy
> worldwide.
>
> In summer 2001, Dr. Israel returned to Israel following a two-year
> fellowship at the Oregon Health and Sciences University in Portland.
> Armed mainly with determination-no additional budget was available-he
> set about creating a deep-brain stimulation program that has made
> Hadassah Israel's leading functional neurosurgery center.
>
> "I started by building a multidisciplinary team," Dr. Israel explains.
> "It comprises myself, three neurologists, a neuropsychologist, a
> physiotherapist and Dr. Bergman. It's a team that has proven very
> productive in both research and clinical work."
>
> His next step was acquiring the equipment. A $180,000 grant from the
> Nash Family Foundation bought microrecording equipment. The navigation
> computer, which the team uses to locate the subthalamic nucleus,
> however, dates from 1997. "To calculate programming coordinates and
> design a treatment plan should take 10 minutes," Dr. Israel says. "It
> often takes up to two hours because of this dated hardware. We need
> $130,000 to replace it."
>
> In January 2003, the team performed its first deep-brain stimulation.
> Like the 15 performed since then, this treatment, which still is too new
> to have more than a 10-year follow-up, was a complete success.
> "Neurologists tend to be very conservative," says Dr. Israel, "but we're
> receiving referrals from all Israel's major neurology centers, as well
> as referrals from abroad."
>
> The number of applicants increased in spring 2004, when Israel
> Television showed one of Dr. Israel's Parkinson's patients prior to
> surgery and again two weeks afterward. The dramatic improvement
> generated over a hundred inquiries a day for the week following the
> broadcast-Larisa Korvan's among them.
>
> "This treatment isn't appropriate for all patients," says Dr. Israel.
> "We must be careful in our selection. Depression, dementia or other
> illnesses will exclude some. Age may exclude others, although we try not
> to make it a limiting factor."
>
> None of this applies to Korvan. If her wish is realized, she will be
> admitted to Hadassah the day before the procedure and her medication
> will be halted. At 6:30 the next morning she will go to the operating
> room, where a three-dimensional frame will be fitted around the outside
> of her head. Her brain will be scanned and the image obtained combined
> with an earlier MRI.
>
> "We use this to program our path to the subthalamic nucleus," Dr. Israel
> explains. "Because all of us have differently shaped heads, the location
> of this tiny spot differs slightly in each of us. We must reach it with
> great precision to avoid damaging other brain structures and to achieve
> the best results."
>
> By about 9 o'clock, Dr. Israel will drill a small hole through the
> patient's anesthetized skull just above the hairline, getting the angle
> down to the deep brain exactly right.
>
> Once the channel is opened, he will insert about three inches of
> silicone-covered wire the thickness of a paper clip, four tiny
> electrodes at its end, and advance it gently down to the subthalamic
> nucleus. To check if it is accurately placed, he will ask Korvan to move
> and speak, so he can judge reactions and whether the tremors and
> rigidity decrease.
>
> Next will come what Dr. Israel calls "the plumbing." With one end of the
> silicone wire in place, the other, emerging from the skull, will be
> slipped under Korvan's skin and trained down the side of her head and
> neck to her upper chest. There it will be connected to its electrical
> generator, also implanted under the skin.
>
> It will be about seven hours since Dr. Israel drilled the hole. The
> patient will be taken to intensive care for overnight observation.
>
> "The initial effect of inserting the electrodes is to stun the
> overactive subthalamic nucleus cells, and the patient is thus often
> dramatically better," Dr. Israel says. "Within a week or two, however,
> the cells begin recovering, and its time for the generator to be
> programmed."
>
> Placing a hand-held electrical device over the generator in the
> patient's chest, Dr. Israel can fine-tune the electrical pulses it
> delivers deep into the brain. "I can make any one of the four electrodes
> or any combination of them produce stimuli of different strengths," he
> says. "It can take up to a couple of months to get the correct balance.
> During this time, medication has to be very carefully balanced.
> Eventually, some patients do so well they come off medication
> altogether. Those who can't usually need about 50 percent less than
> before, which means the side effects dramatically subside."
>
> Hadassah's deep-brain stimulation program is one worth investing in,
> says Dr. Israel, both for the relief it brings to patients and because
> it is one of few worldwide that intimately combines with a research arm.
> Microrecordings of each procedure are passed on to Dr. Bergman's lab.
> Research funds, however, are modest, and the cost of surgery-$26,000
> compared to about $100,000 in the United States-is not covered by
> Israel's strapped health funds, despite clear evidence that it becomes
> cost-effective within two and a half years.
>
> Futuristic as deep-brain stimulation is, the longer-term future therapy
> for Parkinson's and other neurological disorders is likely to be in a
> different realm altogether-that of stem cells.
>
> "Parkinson's disease results from degeneration of dopamine-producing
> nerve cells in the brain," says senior Hadassah neurologist Dr. Tamir
> Ben-Hur. "Dopamine stimulates and fine-tunes the motor system in the
> brain that controls the muscles. When its production is depleted, the
> motor system nerves can no longer control movement and coordination.
> Parkinson's patients have lost more than 50 percent of their
> dopamine-producing cells by the time symptoms appear."
>
> Dr. Ben-Hur is working with Dr. Benjamin Reubinoff to create cells that
> secrete dopamine and then implant them in the appropriate area of the
> brain. "We don't have to invent the wheel," he says. "There are
> encouraging results worldwide in transplanting fetal tissue to help
> Parkinson's patients. But with material from up to eight pregnancy
> terminations needed per patient, fetal tissue is ruled out for both
> logistical and ethical considerations. We must cultivate an alternate
> source of dopaminergic cells for transplant."
>
> Researchers worldwide are working on growing such cells from stem-cell
> lines. Drs. Ben-Hur and Reubinoff are building on work in which they
> successfully implanted into the brains of newborn mice laboratory-grown
> nerve cells derived from human embryonic stem cells. Recently, they
> implanted dopamine-creating cells grown from these stem cells into the
> brains of Parkinsonian rats and became first in the world to report some
> clinical effect from these transplanted cells.
>
> "There's still a long way to go," says Dr. Ben-Hur. "We must learn how
> to improve the yield of dopaminergic cells in culture and improve their
> delivery and survival in the brain after transplant."
>
> Here, perhaps, is where the two approaches to treating Parkinson's
> disease are to meet: Hadassah's neurologists will create the cells that
> secrete dopamine safely and efficiently, and its neurosurgeons will
> implant them deep into the human brain with the pinpoint precision
> required
>
>
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