Archive for September, 2013
There is no evidence that impaired blood flow or blockage in the veins of the neck or head is involved in multiple sclerosis, says a McMaster University study.
The research, published online by PLOS ONE today, found no evidence of abnormalities in the internal jugular or vertebral veins or in the deep cerebral veins of any of 100 patients with multiple sclerosis (MS) compared with 100 people who had no history of any neurological condition.
The study contradicts a controversial theory that says that MS, a chronic, neurodegenerative and inflammatory disease of the central nervous system, is associated with abnormalities in the drainage of venous blood from the brain. In 2008 Italian researcher Paolo Zamboni said that angioplasty, a blockage clearing procedure, would help MS patients with a condition he called chronic cerebrospinal venous insufficiency (CCSVI). This caused a flood of public response in Canada and elsewhere, with many concerned individuals lobbying for support of the ‘Liberation Treatment’ to clear the veins, as advocated by Zamboni.
“This is the first Canadian study to provide compelling evidence against the involvement of CCSVI in MS,” said principal investigator Ian Rodger, a professor emeritus of medicine in the Michael G. DeGroote School of Medicine. “Our findings bring a much needed perspective to the debate surrounding venous angioplasty for MS patients.”
In the study all participants received an ultrasound of deep cerebral veins and neck veins as well as a magnetic resonance imaging (MRI) of the neck veins and brain. Each participant had both examinations performed on the same day. The McMaster research team included a radiologist and two ultrasound technicians who had trained in the Zamboni technique at the Department of Vascular Surgery of the University of Ferrara.
The research was funded by a collection of private donors including the Harrison McCain Foundation, W. Garfield Weston Foundation, Charity Intelligence and St. Joseph’s Healthcare Foundation as well as many concerned individuals.
The search for the cause of multiple sclerosis, a debilitating disease that affects up to a half million people in the United States, has confounded researchers and medical professionals for generations. But Steven Schutzer, a physician and scientist at Rutgers New Jersey Medical School, has now found an important clue why progress has been slow — it appears that most research on the origins of MS has focused on the wrong part of the brain.
Look more to the gray matter, the new findings published in PLOS ONEsuggest, and less to the white. That change of approach could give physicians effective tools to treat MS far earlier than ever before.
Until recently, most MS research has focused on the brain’s white matter, which contains the nerve fibers. And for good reason: Symptoms of the disease, which include muscle weakness and vision loss, occur when there is deterioration of a fatty substance called myelin, which coats nerves contained in the white matter and acts as insulation for them. When myelin in the brain is degraded, apparently by the body’s own immune system, and the nerve fiber is exposed, transmission of nerve impulses can be slowed or interrupted. So when patients’ symptoms flare up, the white matter is where the action in the brain appears to be.
But Schutzer attacked the problem from a different direction. He is one of the first scientists to analyze patients’ cerebrospinal fluid (CSF) by taking full advantage of a combination of technologies called proteomics and high-resolution mass spectrometry. “Proteins present in the clear liquid that bathes the central nervous system can be a window to physical changes that accompany neurological disease,” says Schutzer, “and the latest mass spectrometry techniques allow us to see them as never before.” In this study, he used that novel approach to compare the cerebrospinal fluid of newly diagnosed MS patients with that of longer term patients, as well as fluid taken from people with no signs of neurological disease.
The advanced analytic tools used in Schutzer’s research were developed at Pacific Northwest National Laboratory in Richland, Washington, a Department of Energy facility. Richard Smith, the lab’s director of proteomics research and one of Schutzer’s co-investigators, says, “We have been developing these techniques over the past decade and they have matured in the past couple of years, enabling Dr. Schutzer and our team to do the current work.”
What Schutzer found startled another of his co-investigators, Patricia K. Coyle of Stony Brook University in New York, one of the leading MS clinicians and researchers in the country. The proteins in the CSF of the new MS patients suggested physiological disruptions not only in the white matter of the brain where the myelin damage eventually shows up. They also pointed to substantial disruptions in the gray matter, a different part of the brain that contains the axons and dendrites and synapses that transfer signals between nerves.
Several scientists had in fact hypothesized that there might be gray matter involvement in early MS, but the technology needed to test their theories did not yet exist. Schutzer’s analysis, which Coyle calls “exquisitely sensitive,” provides the solid physical evidence for the very first time. It includes a finding that nine specific proteins associated with gray matter were far more abundant in patients who had just suffered their first attack than in longer term MS patients or in the healthy controls. “This evidence indicates gray matter may be the critical initial target in MS rather than white matter,” says Coyle. “We may have been looking in the wrong area.”
According to Coyle, that realization presents exciting possibilities. One, she says, is that patients who suffer attacks that appear related to MS could have their cerebrospinal fluid tested quickly. If proteins that point to early MS are found, helpful therapy could begin at once, before the disease can progress further.
Coyle says Schutzer’s findings may also lead one day to more effective treatments for MS with far fewer side effects. Without specific knowledge of what causes multiple sclerosis, patients now need to take medications that can broadly weaken their immune systems. These drugs slow the body’s destruction of myelin in the brain, but also degrade the immune system’s ability to keep the body healthy in other ways. By suggesting an exciting new direction for MS research, Schutzer and his team may have set the stage for more targeted treatments that attack MS while preserving other important immune functions.
Schutzer sees an even broader future for the work he is now doing. He also has used advanced analysis of cerebrospinal fluid to identify physical markers for neurological ailments that include Lyme disease, in which he has been a world leader in research for many years, as well as chronic fatigue syndrome. He says, “When techniques are refined, more medical conditions are examined, and costs per patient come down, one day there could be a broad panel of tests through which patients and their doctors can get early evidence of a variety of disorders, and use that knowledge to treat them both more quickly and far more effectively than is possible now. “
There has been an “explosion of new and innovative” therapies for neurologic conditions such as stroke, epilepsy, Parkinson disease and multiple sclerosis, Loyola University Medical Center neurologist Dr. Jose Biller writes in the August issue of the journal Neurologic Clinics.
Biller is editor of the August issue, which includes 14 articles describing the latest data on new and emerging therapies for neurologic conditions. Five of the articles are written by Loyola physicians:
Sarkis Morales Vidal, MD and Sean Ruland, DO: “Platelet Antiaggregants in Stroke Prevention.”
Adriana Sofia Ploneda Perilla and Michael J. Schneck, MD: “Unanswered Questions in Thrombolytic Therapy for Acute Ischemic Stroke.”
Michael Star, MD and Murray Flaster, MD, PhD: “Advances and Controversies in the Management of Cerebral Venous Thrombosis.”
Jorge J. Asconape: “Epilepsy.”
Douglas Anderson, MD and Ninith Kartha, MD: “Deep Brain Stimulation in Nonparkinsonian Movement Disorders and Emerging Technologies, Targets and Therapeutic Promises in Deep Brain Stimulation.”
Matthew McCoyd, MD: “Update on Therapeutic Options for Multiple Sclerosis.”
In the preface, Biller writes that the August issue of Neurologic Clinics is intended to provide timely and practical information to physicians treating neurologic disorders. He concludes: “There is every reason to believe that future advances in neurologic therapy are sure to come.”
Biller is chair of the Department of Neurology of Loyola University Chicago Stritch School of Medicine.