UMMC in Pivotal Study Evaluating New Technology to Treat Essential Tremor
If asked to name a neurological condition that causes trembling, many would say Parkinson's disease - but there is more than one correct answer. Eight times more common than Parkinson's and yet unrelated, the disorder known as essential tremor can lead to similarly debilitating and even embarrassing shaking that may prove resistant to drug therapy.
But patients with the most severe cases of essential tremor are looking with hope to University of Maryland Medical Center (UMMC), one of eight sites taking part in an international clinical trial to treat the disorder with an emerging noninvasive technique. It is an effort through the Departments of Neurology, Neurosurgery and Diagnostic Radiology.
Called MR-guided Focused Ultrasound (MRgFUS), the procedure uses focused ultrasound waves transmitted through the skull to lesion a group of cells called the VIM while an MRI scanner helps doctors visualize the brain and guide and continuously monitor the treatment. Preliminary results of the randomized trial have produced amazing improvements in a small number of essential tremor patients treated thus far at UMMC, with another phase of the study forthcoming.
“We’re a leader in this area,” explains Howard M. Eisenberg, M.D., the R.K. Thompson Professor of Neurosurgery and chair of the Department of Neurosurgery at University of Maryland School of Medicine. Dr. Eisenberg is UMMC’s principal investigator of the clinical trial, whose lead site is University of Virginia. He is working in collaboration with Paul Fishman, M.D., Ph.D., a professor of neurology at the University of Maryland School of Medicine, and Dheeraj Gandhi, MBBS, a professor of diagnostic radiology, neurology and neurosurgery at UM School of Medicine.
“Only a few sites in the U.S. are doing this, so it’s good for us and good for our patients,” he adds. “It’s exciting.”
GRAVE IMPACT ON QUALITY OF LIFE
Typically affecting the arms and hands on both sides of the body, essential tremor is a chronic and often progressive condition impacting an estimated 10 million International Essential Tremor Foundation (IETF). The involuntary, rhythmic trembling — once known as familial or hereditary tremor — may eventually involve the head, voice, trunk and legs. Its incidence increases with age, with about 4% of those 40 and older affected and higher prevalence among people in their 60s, 70s and beyond.
For most, the disorder’s impact remains mild and either goes untreated or is controlled with medications, Dr. Eisenberg says. But disability from essential tremor is common, and those affected are often anxious or self-conscious in social situations, according to the IETF. Well-known actress Katharine Hepburn was thought to be affected by the condition, as were playwright Eugene O’Neill and presidents John Adams and John Quincy Adams.
“Some can’t even drink a glass of water without holding it in two hands,” explains Dr. Eisenberg, who’s also a neurosurgeon at UMMC and whose other clinical interests include epilepsy, acoustic neuromas and gamma knife surgery. “There’s also the element of being embarrassed by it. It can affect almost all aspects of daily life, such as eating, drinking and writing.”
NON-SURGICAL TREATMENT ALTERNATIVE
Medications can control the worst effects of essential tremor for most patients and are always prescribed as first-line therapy. But when drugs fail or cause intolerable
side effects, second-line therapies include deep brain stimulation or DBS, in which doctors surgically implant an electrode into the brain and a stimulator battery under the collarbone.
MRgFUS, on the other hand, doesn’t involve surgery. Instead, patients lie in an MRI scanner with a head-immobilizing frame fitted with a transducer helmet. While the MR images help doctors visualize brain structures, focused ultrasound energy is aimed at the VIM. Temperature is monitored in real time with the MRI guidance, and no radiation is used. The entire procedure lasts two to four hours, Dr. Eisenberg says.
“You’re raising the temperature in a very restricted area of the brain and that destroys the tissue,” says Dr. Eisenberg, whose role as a consultant with the Focused Ultrasound Foundation and the equipment’s manufacturer, InSightec, proved instrumental in getting UMMC chosen as one of the clinical trial sites. “The ultrasound creates a heat lesion that you monitor through MRI.”
Because it’s noninvasive, unlike DBS, MRgFUS requires no incisions or battery and is also less likely to trigger complications such as infection or brain hemorrhage, he says. But DBS has the advantage of currently being approved for use on both sides of the brain; still-experimental MRgFUS can only currently be used on one side.
PRELIMINARY OUTCOMES PROMISING
But if preliminary UMMC results of the clinical trial — also being conducted in Canada, Japan and Korea in addition to the United States — are replicated, it may only be a matter of time before the FDA approves using MRgFUS on both sides of the brain. The phase 3 study assigned three-quarters of participants to MRgFUS treatment, while 25% received a sham treatment (those assigned a sham treatment can opt for the actual treatment after three months). Patients' essential tremor symptoms are evaluated just after treatment and at six and 12 months after treatment, with some tracked periodically for up to five years. Patients also complete questions numerous times during the course of the study.
At UMMC, 11 patients were added to the study, while 35 more have contacted the Medical Center hoping to be included in the second phase, according to Charlene Aldrich, RN, MSN, clinical research manager.
"I have a list of 20 other patients we are in the process of contacting now to let them know we will re-start screening (for inclusion) as soon as we get the approval in hand," Aldrich notes, adding that 50 additional patients were approved among U.S. sites for the study's second arm. "I get contacted almost daily."
Initial results were stunning: all treated patients showed immediate improvement in their tremor. Dr. Eisenberg predicts that the FDA will approve MRgFUS as a standard second-line essential tremor therapy on one side of the brain within a year or two; if results hold up long-term, perhaps treatment on both sides of the brain will then be approved, he says.
“They’re impressed — it’s pretty dramatic,” Dr. Eisenberg says. “The question isn’t the improvement (itself), but whether the effect is sustained.”