November 9, 1998
Volume 51, No. 11
Doctors developing treatments for little-known dystonia
Dystonia is a little-known yet fairly common movement disorder that causes muscles to pull or spasm. The condition's effects may be felt in the neck and shoulders, vocal cords, eyelids, arms or legs, or be more generalized.
Because its effects are so varied and symptoms may mimic other conditions, dystonia is difficult to diagnose, said Marian Evatt, assistant professor of neurology and a dystonia specialist. Writer's cramp, one of the better-known forms of the disorder, is commonly misdiagnosed as carpal tunnel syndrome, tennis elbow, arthritis, strain or stress. And cervical dystonia of the neck is often misdiagnosed as a pinched nerve.
"Stress-reducing treatments alone won't relieve the abnormalities within the basal ganglia--the brain region responsible for controlling movement," Evatt said. "Nor will it correct the recently identified genetic flaws in the DYT1 gene associated with early-onset torsion dystonia. But accurate diagnosis and a careful treatment plan can dramatically improve the quality of life."
Physician-scientists in the Movement Disorders Program of Department of Neurology lead one of the region's most active centers for treating and studying dystonia. Two patients at Emory are among the first in the world to receive deep-brain stimulation for dystonia. Approved by the Food & Drug Administration for tremor and epilepsy, the treatment involves surgical implantation into the neck of a pacemaker-type device that delivers controlled electrical stimulation to brain regions associated with dystonia, particularly the pallidum. Physicians can end or reverse treatment, or adjust stimulation frequencies for patients as needed.
Initial outcomes look good in the first few dystonia patients to undergo another type of surgery for the disorder. Emory neurologists use the microelectrode brain-mapping procedure originally pioneered by them for Parkinson's disease to identify those few brain cells associated with dystonia. Neurology chair Mahlon DeLong and colleague Jerrold Vitek are guided by the electrical charges of single nerve cells as they pinpoint troublesome cells in the pallidum for neurosurgeon Roy Bakay to remove. The team uses this same procedure to target cells within the brain's thalamus.
So far at Emory, 12 dystonia patients have undergone pallidotomy and two have undergone thalamotomy as part of clinical trials.
The biological warfare agent and deadly neurotoxin that causes food poisoning "offers significant pain relief for some dystonia patients and may restore function for others," Evatt said. Marketed by Allergan as botulinum toxin type A (Botox), injections of minute amounts of the toxin have given thousands of patients relief from disabling symptoms. Botulinum toxin weakens a muscle enough to reduce a spasm but doesn't cause paralysis. Rather, it acts as a nerve blocker by preventing the release of chemical transmitters that activate muscles.
Evatt and colleague Alan Freeman administer Botox to dystonia patients with involuntary limb movements, abnormal head turning and other generalized forms of the disorder. Emory eye surgeon Ted Wojno uses the treatment to open the eyes of functionally blind patients, and ear, nose and throat specialist William Grist treats patients with spasmodic dysphonia with Botox to restore their voices.
Effects of the toxin usually wear out within a few months, so patients must be re-injected several times a year. And benefits may subside altogether as resistance grows after several injections.
The amount of the toxin required for Botox formulations is so small that until a few years ago Allergen's entire raw stock took up the space of a two-liter soda bottle. That single batch of toxin-producing bacterium was begun and maintained for some 20 years, but Botox is now created in a continuous process as an advanced type A bulk toxin.