Clinical Programs, Conditions, and Case Presentations

Dystonia and Deep Brain Stimulation

Dystonia is a movement disorder characterized by twisting, repetitive movements which result in abnormal, often painful postures. The disorder may be categorized by age at presentation (< or > 26 years of age); anatomical distribution (focal, segmental, or generalized); and by underlying etiology (primary or idiopathic vs. secondary or symptomatic). Symptomatic dystonia may be caused by many disorders including static encephalopathy, stroke, traumatic brain injury, or any number of toxic, metabolic, or infectious insults to the cerebrum. Patients with primary dystonia exhibit no obvious structural brain abnormalities and relate no history of serious illness. A number of genetic abnormalities have now been associated with primary dystonia. The most common and most closely studied of these is the DYT1 mutation, which underlies the disorder formerly known as Dystonia Musculorum Deformans. This gene, which is highly prevalent in the Ashkenazi Jewish population, is a leading cause of disabling juvenile onset dystonia. The enzyme encoded by the DYT1 locus has been identified, but it is unclear how expression of the abnormal protein results in the dystonia phenotype or why only 30 percent of individuals who carry this gene become symptomatic.

Medical therapies for dystonia leave much to be desired. For years, anticholinergic medications have been the mainstay of medical therapy. A small sub-set of patients whose dystonia is caused by the DYT5 mutation will respond profoundly to levodopa. Additional medications such as oral baclofen, benzodiazepines, and tetrabenazine, are employed with modest results. Local injections of botulinum toxin (BotoxTM) can alleviate focal dystonias such as writer's Cramp, blepharospasm or torticollis, but this intervention is impractical in patients with generalized symptoms. Moreover, 10-15 percent of patients will not respond to BotoxTM initially, or will become resistant to repeat injections through the development of blocking antibodies. Surgical interventions include chronic intrathecal baclofen infusions via sub-cutaneously implanted programmable pumps, peripheral denervation, and central neuroablative procedures, in which specific targets within the basal ganglia and/or thalamus are destroyed. These interventions have been moderately successful but because they can often result in severe and irreversible adverse neurologic events, they are employed with great trepidation.

The application of deep brain stimulation for dystonia results from the success of this intervention for the treatment of Parkinson's disease and essential tremor, and the observation that ablative basal ganglia interventions can improve dystonia in select cases. Deep brain stimulation is superior to neuroablation for a number of reasons: 1- the effects of stimulation are reversible; 2- stimulation parameters can be customized for each patient, maximizing therapeutic results; 3- bilateral procedures are safer; and 4- because the brain tissue is not destroyed, the application of future therapies is not precluded. The major disadvantages of DBS are its cost and the need for long-term device maintenance.

Deep brain stimulating devices are implanted in two stages. During the first stage, quadripolar stimulating leads are inserted into the therapeutic targets with the assistance of a stereotactic guidance system. Initial coordinates for the targets, selected via MRI, are refined in the operating room by performing electrical recordings of the patient's brain. Patients must be awake or minimally sedated in order to obtain reliable recordings and to test the effects of stimulation during the surgery. During the second stage, which is performed under general anesthesia, the stimulating leads are connected, via extension cables, to programmable stimulators that are implanted subcutaneously at the chest wall. Programming of the devices begins one week after implantation is complete.

All available data demonstrate that DBS at the globus pallidus pars internus (GPi) significantly improves symptoms of torsion dystonia in the majority of patients thus far treated. Patients with primary dystonia respond more consistently and more robustly than do patients with secondary dystonia most likely due to the absence of structural brain abnormalities. Unlike Parkinson's disease, which responds soon after the onset of stimulation, dystonia may require weeks of stimulation before an improvement is evident. Moreover, the full benefit of stimulation may not be realized for 12-18 months after the onset of therapy. Complications thus far have been minor and few. No patient in Dr. Alterman and Tagliati's series has suffered an intracerebral hermorrhage or been made worse by surgery. Cognitive or speech abnormalities, which can be seen in the older Parkinson's population, have not been observed. Adolescents with the DYT1 gene defect have fared particularly well and currently represent the best candidates for surgery.

In May of 2005, the Dystonia Medical Research Foundation honored Mount Sinai Neurologist Michele Tagliati and Neurosurgeon Ron Alterman for their pioneering work in the use of deep brain stimulation (DBS) for the treatment of torsion dystonia. Over the last seven years, this team has employed DBS therapy in more than 80 dystonia patients, one of the largest series of such patients in the world. The results have been impressive overall and nothing short of spectacular in some cases. In fact, because the open-label results have been so compelling, the United States Food and Drug Administration granted DBS for dystonia a Humanitarian Device Exemption in April 2003. With the addition of Drs. Tagliati and Alterman to its staff, Mount Sinai has positioned itself to be a leader in the further development of DBS therapy for dystonia, Parkinson's disease, and many other indications that are currently under investigation.

Deep brain stimulation has revolutionized the treatment of dystonia, and it is fully expected that results will improve as the surgical technique is refined.

For More Information

Ron L. Alterman, M.D.
Tel: (212) 241-0050

Michele Tagliati, M.D.
Tel: (212) 241-4364.