Posts Tagged 'treatment'

Questionable Hope for CCSVI

James Bowen, MD, Neurology, Multiple Sclerosis, Swedish Neuroscience Institute 

Once again, multiple sclerosis patients’ area buzz over a new theory and treatment for the disease. The theory is called chronic cerebrospinal venous insufficiency (CCSVI); and, this time, social media is driving the patient excitement.

CCSVI is based on a controversial idea that impaired venous drainage of the brain due to blockage in venous structures causes MS. Increase in venous pressure promotes leakage of blood across capillaries, with inflammation resulting from the iron deposition into the brain. In 2009 Paolo Zamboni, M.D., reported that virtually all MS patients in a study had abnormalities in the jugular or azygous veins, whereas no control patients had such findings. The Zamboni, or Liberation, procedure involves either angioplasty or stenting of the abnormal vein. Many MS patients are understandably enthusiastic about this theory and treatment.

There are, however, a number of problems with the CCSVI theory that patients and MS neurologists should consider.

• Diagnostic criteria for CCSVI are not standardized or accepted

• CCSVI does not seem to explain the distribution of white matter lesions or the relapsing and remitting course that most patients experience

• CCSVI does not explain the presence of inflammation in MS lesions

• Iron in MS lesions is contained within macrophages, not erythrocytes or free, as predicted by the CCSVI theory

• Other diseases with increased venous pressure do not resemble MS

• Venous drainage is highly redundant, so stricture of a vein usually does not increase venous pressure in the brain

• Changes in muscle tone or posture from neurological disease may explain some venous blockages; and neurological disease can lead to lower venous blood flow due to circulatory auto regulation

Studies that have been performed to date have not supported the CCSVI theory. Preliminary results from the Buffalo Neuroimaging Analysis Center at the University at Buffalo, The State University of New York, found 56 percent of patients with MS, 42 percent of those with neurological diseases other than MS, and 23 percent of controls met criteria for CCSVI. This group found a decrease in cerebral venous volume in MS patients compared to normal, whereas blockage in venous flow would be expected to induce vascular dilation and increased venous volume. At the recent ECTRIMS (European Committee for the Treatment and Research of Multiple Sclerosis) meeting in Sweden, groups from Gotteborg, Berlin, Padua, Amsterdam and London found no evidence for venous obstruction in MS patients compared to controls. A study from London, Ontario, found that venous blockage increased with age in both MS and controls. A study from Beirut, Lebanon, found venous changes in only 9 percent of patients after their first MS attack, increasing to 92 percent with advanced MS, possibly suggesting a late finding that is unrelated to the cause of the disease. Nevertheless, as anecdotal reports continue to circulate of individual patients with dramatic responses to treatment of CCSVI, the theory has been of great interest among MS patients and has become the subject of a significant number of studies.

Before CCSVI can be considered as contributing to MS, three criteria should be required.

1. Venous blockage must be shown to be increased in MS patients relative to healthy controls and other neurological diseases. This would demonstrate an association between CCSVI and MS, but not prove causation.

2. Treatment of CCSVI should stop the progression of MS symptoms in placebo controlled, blinded, multi-center studies. This would prove that CCSVI contributes to MS, but not prove causation.

3. MS should develop in humans or animals with venous blockage.

The scientific community is taking CCSVI very seriously. Most of the studies currently under way are testing whether MS patients have venous blockage. The National MS Society and the MS Society of Canada funded seven 24-month studies in June 2010, totaling $2,400,000 of ultrasound, MRI and angiographic techniques to determine whether venous blockage is specific to MS patients in both adult and pediatric populations. The MS Society of Italy is contributing £900,000 (nearly $1.3 million) to study the question. The Buffalo Neuroimaging Analysis Center is conducting a study of venous imaging, as well as a small treatment trial. Saskatchewan and MS Research Australia have also initiated large studies.

The risks of the Liberation procedure in MS are not entirely understood, though stent migration and fatal intracerebral bleeding have already been described. Only controlled studies will teach us the true complication rate. In the meantime, most MS neurologists are recommending that patients await the results of current studies before proceeding with this controversial treatment. 


Creating the future through research at SNI

Dan Rizzuto, PhD, Research Manager, Swedish Neuroscience Institute

Clinical research is an essential component of Swedish Neuroscience Institute (SNI). It provides our patients therapeutic options that would otherwise be unavailable to them and places our staff at the forefront of medical knowledge as they evaluate leading-edge drugs and medical devices. The majority of SNI investigations assess the safety and efficacy of new drugs and devices. These studies are typically sponsored by the federal government, or pharmaceutical and medical device companies, with oversight provided by the U.S. Food and Drug Administration. Investigator-initiated trials at SNI answer questions about current standard-of-care therapies. These trials play an important role in supporting evidence-based medicine and advancing patient care.

Initiating a research study at SNI begins with a physician identifying a research question or a sponsor asking a physician to investigate a new therapy. After the physician defines the study protocol, he or she presents an overview to the SNI Research Committee to ensure sufficient patient access, financial support and staffing resources are available. After the committee has approved the protocol, the Swedish Institutional Review Board performs its federally-required review, which is designed to protect the welfare of research participants.

As research manager, I oversee the financial and regulatory aspects of clinical research at SNI, including budget, contract negotiations with study sponsors and the assignment of study coordinators to assist with IRB submissions and patient visits. This allows the investigator to focus on providing patient care, overseeing patient safety and collecting efficacy data.

Research at SNI currently includes 54 active investigations across nine programs, and is supported by more than $2 million dollars in annual funding. Thirty-seven of these studies are sponsored and financially supported by pharmaceutical and device companies, eight are investigator-initiated and nine are funded by the federal government or other non-profit organizations.

Research at SNI has a very bright future with many new and exciting trials on the horizon. The movement disorders program has ramped up its first clinical trial of a Parkinson’s disease treatment, and the Ivy Center for Advanced Brain Tumor Treatment is at the forefront of developing personalized medicine for brain cancer patients. One of the most exciting developments involves the bridging of two disciplines: deep brain stimulation (DBS) and psychiatry. The DBS program and the Swedish psychiatry program are evaluating clinical trials that use DBS for treatment resistant obsessive compulsive disorder and major depression. DBS offers hope for the most severely affected of these patients who continue to exhibit severe symptoms even after adequate trials of currently available therapies.

As a neuroscience center of excellence, SNI is uniquely designed to meet the healthcare challenges of the 21st century and beyond. We pursue evidence-based medicine by combining an academic focus on learning and research with high-quality clinical programs. The power to meet these challenges resides within each of us, and I encourage you to think about how you can be a pioneer in the advancement of medicine through clinical research.

If you would like to participate in clinical research activities at SNI, please contact:

Dan Rizzuto, Ph.D.

Gamma Knife Radiosurgery for Treatment of Essential Tremor

Ronald Young, MD, Neurology, Swedish Neuroscience Institute

Essential tremor (ET) is the most common type of movement disorder, affecting approximate­ly four out of 1000 people, and is significantly more common, though less recognized, than Parkinson’s disease. ET affects men and women equally and is inherited as an autosomal-dominant condition in about 60 percent of cases.

Although often referred to as benign essen­tial tremor, it is hardly benign in patients who may not be able to write legibly, hold a glass of water or use a knife and fork. ET is primarily an action tremor of the upper extremities but may involve resting tremor of the head and neck and/or lower jaw, and also tremor of the voice. The latter may be so severe that speech becomes unintelligible.

Medication and surgical treatment options

Primidone and beta blockers are useful in re­ducing tremor in the early stages of ET, but as the tremor progresses, medical management often becomes less effective or side effects can prevent the use of adequate doses of medication. ET pa­tients then are candidates for surgical or radiosur­gical treatment.

The mainstay of the surgical treatment of ET is deep brain stimulation (DBS), in which an electrode is implanted in the ventral inter­mediate nucleus (VIM) of the thalamus. Neurosurgeons Peter Nora, M.D., and Ryder Gwinn, M.D., have been implant­ing DBS electrodes at Swedish Medical Center for several years. The treatment is effective, but it requires implantation of permanent hardware (wires and batteries) into the brain and chest wall. Patients who take anticoagulants or have severe cardio­vascular disease are not suitable candidates for DBS. These patients, however, may be candidates for radiosurgical treatment.

A new option for difficult-to-treat patients

A Gamma Knife® device is used to fo­cus high-energy gamma rays precisely on the VIM in a single outpatient treatment. This results in the death of the brain cells that generate ET. We recently published our experience in the radiosurgical treat­ment of more than 200 patients with ET. More than 80 percent of the treated pa­tients showed significant reduction in tremor, including nearly 50 percent who were entirely free of tremor. Patients could write legibly, drink without spilling and, in general, perform activities of daily living with minimal or no disability (see figure). These results are comparable to the data published for the use of DBS in the treat­ment of ET. Follow-up MRI scans in these patients demonstrated the development of lesions of about 6 mm in diameter precisely located in the VIM thalamus. Eight percent of patients developed lesions which were larger than expected. These large lesions occasionally resulted in sensory loss, hemi­paresis or speech difficulty. In about half of these patients, the neurological symptoms recovered over time, so the permanent rate of complications was about 4 percent. At present we have not been able to identify what factors may predict the development of an excessively large lesion.

Gamma Knife radiosurgery offers a means for the treatment of ET that is safe and effective without the need for implant­ed hardware. The rate of tremor relief and the complications compare favorably with DBS. Radiosurgery can be offered to all pa­tients who are candidates for surgical treat­ment of ET, but it is particularly useful for patients who are not candidates for DBS.

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