[2009 Dec] Are researchers ignorant to the fact that aluminum causes hemochromatosis?
Researcher's labour of love leads to MS breakthrough
Nov. 20, 2009
Elena Ravalli was a seemingly healthy 37-year-old when she began to
experience strange attacks of vertigo, numbness, temporary vision loss and
crushing fatigue. They were classic signs of multiple sclerosis, a potentially
debilitating neurological disease.
It was 1995 and her husband, Paolo Zamboni, a professor of medicine at the
University of Ferrara in Italy, set out to help. He was determined to solve the
mystery of MS – an illness that strikes people in the prime of their lives but
whose causes are unknown and whose effective treatments are few.
What he learned in his medical detective work, scouring dusty old books and
using ultra-modern imaging techniques, could well turn what we know about MS on
its head: Dr. Zamboni's research suggests that MS is not, as widely believed, an
autoimmune condition, but a vascular disease.
More radical still, the experimental surgery he performed on his wife offers
hope that MS, which afflicts 2.5 million people worldwide, can be cured and even
largely prevented.
“I am confident that this could be a revolution for the research and diagnosis
of multiple sclerosis,” Dr. Zamboni said in an interview.
Not everyone is so bullish: Skeptics warn the evidence is too scant and
speculative to start rewriting medical textbooks. Even those intrigued by the
theory caution that MS sufferers should not rush off to get the surgery –
nicknamed the “liberation procedure” – until more research is done.
U.S. and Canadian researchers are trying to test Dr. Zamboni's premise.
For the Italian professor, however, the quest was both personal and professional
and the results were stunning.
Fighting for his wife's health, Dr. Zamboni looked for answers in the medical
literature. He found repeated references, dating back a century, to excess iron
as a possible cause of MS. The heavy metal can cause inflammation and cell
death, hallmarks of the disease. The vascular surgeon was intrigued –
coincidentally, he had been researching how iron buildup damages blood vessels
in the legs, and wondered if there could be a similar problem in the blood
vessels of the brain.
Using ultrasound to examine the vessels leading in and out of the brain, Dr.
Zamboni made a startling find: In more than 90 per cent of people with multiple
sclerosis, including his spouse, the veins draining blood from the brain were
malformed or blocked. In people without MS, they were not.
He hypothesized that iron was damaging the blood vessels and allowing the heavy
metal, along with other unwelcome cells, to cross the crucial brain-blood
barrier. (The barrier keeps blood and cerebrospinal fluid separate. In MS,
immune cells cross the blood-brain barrier, where they destroy myelin, a crucial
sheathing on nerves.)
More striking still was that, when Dr. Zamboni performed a simple operation to
unclog veins and get blood flowing normally again, many of the symptoms of MS
disappeared. The procedure is similar to angioplasty, in which a catheter is
threaded into the groin and up into the arteries, where a balloon is inflated to
clear the blockages. His wife, who had the surgery three years ago, has not had
an attack since.
The researcher's theory is simple: that the underlying cause of MS is a
condition he has dubbed “chronic cerebrospinal venous insufficiency.” If you
tackle CCSVI by repairing the drainage problems from the brain, you can
successfully treat, or better still prevent, the disease.
“If this is proven correct, it will be a very, very big discovery because we'll
completely change the way we think about MS, and how we'll treat it,” said
Bianca Weinstock-Guttman, an associate professor of neurology at the State
University of New York at Buffalo.
The initial studies done in Italy were small but the outcomes were dramatic. In
a group of 65 patients with relapsing-remitting MS (the most common form) who
underwent surgery, the number of active lesions in the brain fell sharply, to 12
per cent from 50 per cent; in the two years after surgery, 73 per cent of
patients had no symptoms.
“ I am confident that this could be a revolution for the research and diagnosis
of multiple sclerosis ”— Dr. Paolo Zamboni
Augusto Zeppi, a 40-year-old resident of the northern Italian city of Ferrara,
was one of those patients. Diagnosed with MS nine years ago, he suffered severe
attacks every four months that lasted weeks at a time – leaving him unable to
use his arms and legs and with debilitating fatigue. “Everything I was dreaming
for my future adult life, it was game over,” he said.
Scans showed that his two jugular veins were blocked, 60 and 80 per cent
respectively. In 2007, he was one of the first to undergo the experimental
surgery to unblock the veins. He had a second operation a year later, when one
of his jugular veins was blocked anew.
After the procedures, Mr. Zeppi said he was reborn. “I don't remember what it's
like to have MS,” he said. “It gave me a second life.”
Buffalo researchers are now recruiting 1,700 adults and children from the United
States and Canada. They plan to test MS sufferers and non-sufferers alike and,
using ultrasound and magnetic resonance imaging, do detailed analyses of blood
flow in and out of the brain and examine iron deposits.
Another researcher, Mark Haacke, an adjunct professor at McMaster University in
Hamilton, is urging patients to send him MRI scans of their heads and necks so
he can probe the Zamboni theory further. Dr. Haacke is a world-renowned expert
in imaging who has developed a method of measuring iron buildup in the brain.
“Patients need to speak up and say they want something like this investigated …
to see if there's credence to the theory,” he said.
MS societies in Canada and the United States, however, have reacted far more
cautiously to Dr. Zamboni's conclusion. “Many questions remain about how and
when this phenomenon might play a role in nervous system damage seen in MS, and
at the present time there is insufficient evidence to suggest that this
phenomenon is the cause of MS,” said the Multiple Sclerosis Society of Canada.
The U.S. society goes further, discouraging patients from getting tested or
seeking surgical treatment. Rather, it continues to promote drug treatments
used to alleviate symptoms, which include corticosteroids, chemotherapy agents
and pain medication.
Many people with multiple sclerosis, though, are impatient for results. Chatter
about CCSVI is frequent in online MS support groups, and patients are scrambling
to be part of the research, particularly when they hear the testimonials.
Kevin Lipp, a 49-year-old resident of Buffalo, was diagnosed with MS a decade
ago and has suffered increasingly severe attacks, especially in the heat. (Heat
sensitivity is a common symptom of MS.) His symptoms were so bad that he was
unable to work and closed his ice-cream shop.
Mr. Lipp was tested and doctors discovered blockages in both his jugular and
azygos veins. In January of this year, he travelled to Italy for surgery, which
cleared five blockages, and he began to feel better almost immediately.
“I felt good. I felt totally normal. I felt like I did years ago,” he said. He
has not had an attack since.
As part of the research project, Mr. Lipp's siblings have also been tested. His
two sisters, both of whom have MS, have significant blockages and iron deposits,
while his brother, who does not have MS, has neither iron buildup nor blocked
arteries.
While it has long been known that there is a genetic component to multiple
sclerosis, the new theory is that it is CCSVI that is hereditary – that people
are born with malformed valves and strictures in the large veins of the neck and
brain. These problems lead to poor blood drainage and even reversal of blood
flow direction that can cause inflammation, iron buildup and the brain lesions
characteristic of multiple sclerosis.
It is well-established that the symptoms of MS are caused by a breakdown of
myelin, a fatty substance that coats nerve cells and plays a crucial role in
transmitting messages to the central nervous system. When those messages are
blurred, nerves malfunction, causing all manner of woes, including blurred
eyesight, loss of sensation in the limbs and even paralysis.
However, it is unclear what triggers the breakdown of myelin. There are various
theories, including exposure to a virus in childhood, vitamin D deficiency,
hormones – and now, buildup of iron in the brain because of poor blood flow.
While he is convinced of the significance of his discovery, Dr. Zamboni
recognizes that medicine is slow to accept new theories and even slower to act
on them. Regardless, he can take satisfaction in knowing that the woman who
inspired the quest, and perhaps a dramatic breakthrough, has benefited
tremendously.
Dr. Zamboni's wife, Elena, has undergone a battery of scans and neurological
tests and her multiple sclerosis is, for all intents and purposes, gone.
“This is probably the best prize of the research,” he said.
André Picard is the public health reporter at The Globe and Mail. Avis Favaro is
the medical correspondent at CTV News.
With reports from Elizabeth St. Philip, CTV News