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mental, or generalized); and by underlying etiology (primary or idiopathic vs. sec- ondary 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 dys- tonia exhibit no obvious structural brain abnormalities and relate no history of seri- ous illness. A number of genetic abnormal- ities have now been associated with prima- ry dystonia. The most common and most closely studied of these is the DYT1 muta- tion, which underlies the disorder former- ly known as Dystonia Musculorum
MRI demonstrating DBS electrodes in the globus pallidus of a dystonia patient
Deformans. This gene, which is highly prevalent in the Ashkenazi Jewish popula- tion, 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% 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 tox- in (BotoxTM) can alleviate focal dystonias such as writer’s cramp, blepharospasm or torticollis, but this intervention is imprac- tical in patients with generalized symp- toms. Moreover, 10-15% of patients will not respond to BotoxTM initially, or will become resistant to repeat injections through the development of blocking anti- bodies. Surgical interventions include chronic intrathecal baclofen infusions via sub-cutaneously implanted programmable pumps, peripheral denervation, and cen- tral 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 dysto- nia 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, maximiz- ing therapeutic results; 3- bilateral proce- dures 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
Drawing of implanted DBS system
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) sig- nificantly improves symptoms of torsion dystonia in the majority of patients thus far treated. Patients with primary dystonia re- spond 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
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DBS: A Success Story
of stimulation, dystonia may require weeks of stimulation before an improvement is evi- dent. Moreover, the full benefit of stimula- tion 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 suf- fered 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 ob- served. Adolescents with the DYT1 gene de- fect have fared particularly well and currently represent the best candidates for surgery.
In an article subtitled “Mind over muscle,” Carolyn Feibel, staff writer from The Record of Hackensack, NJ, described the journey of Kari Weiner of Montclair, New Jersey, from the chaotic intensification of Kari’s dystonia symptoms—uncontrollable violent flailing of her limbs (even to the point that her shoulder came out of its socket), seizures of painful spasms, locking of her legs into rigid positions— to her surgery by Dr. Alterman, to her months of therapy, to her finally tossing her wheelchair into the garbage. Dr. Alterman op- erated on Kari when she was 13 years old, when she had already been in a wheelchair for six years and after her parents realized that medications were not helping her symptoms. Kari and her family noticed immediate lessening of her spasms as soon as the surgery was com- pleted. Over the next four years, surgeries to repair leg muscles that the dystonia had tight- ened and twisted and physical therapy to help her walk again prepared Kari for her final achievement of discarding her crutches and returning to school full-time. She was then 16 years old. Nicknamed the “Energizer Bunny” by her mother, Kari says that people call her the “bionic woman.” “I really run on batteries.” Always aware that the batteries which Dr. Alterman placed inside her chest cavity are essential to her functioning normally, Kari has to avoid microwaves and metal detectors which can turn off the batteries and thus cause her symptoms to return. She must also have the batteries replaced every 20 months. Those are small prices to pay for being able to live without the debilitating symptoms of dystonia.
Deep brain stimulation has revolutionized the treatment of dystonia, and it is fully expected that results will improve as the surgical technique is refined.
If you are interested in learning more about DBS for dystonia or for other conditions, contact Dr. Alterman at 212-241-0050 or Dr. Tagliati at 212-241-4364.
To read the complete story of Kari Weiner, go to the advanced search page of northjersey.com.
Retirement of Bo Yi Yang, PhD
Dr. Bo-Yi Yang, Assistant Professor of Neurosurgery, joined the faculty in 1995 and retired in November. He per- formed intraoperative neurophysio- logical monitoring, diagnostic testing, and neurophysiological research, working closely with Dr. Don Weisz, Director of Intraoperative Monitoring. The Department of Neurosurgery celebrated his career and imminent retirement at a luncheon on November 18th. Faculty and staff of the Department, nurses from the operating room, scientists from his research collabora- tions, and many other friends he had made at Mount Sinai came to honor Bo-Yi. To show the Department’s appreciation for his service, the neurosurgery faculty, nurses, and staff presented Dr. Yang with a Canon digital SLR camera with two lenses and fil- ters. The camera will allow Dr. Yang to re-
Pittsburgh, and, for the last nine years, Mount Sinai. Dr. Yang’s career in China was temporarily suspended when the onset of the Cultural Revolution coincided with his com- pleting of the PhD thesis. During the ten years of the Revolution, aca- demics, including Dr. Yang, were sent to the countryside and forced to do manual labor. After the Revolution, Dr. Yang’s studies resumed when the Chinese government sent him to the United States for further education as a visiting scholar. Following his time at Irvine and Stanford, Dr. Yang returned to Fudan University where he quickly moved from Instructor to Full Professor and Chairman of the Department of Physiology and Biophysics. Dr. Post and Dr. Yang Dr. Weisz and Dr. Yang worked together for 13 years turn to his longtime passion of photography during his retirement years. Dr. Weisz spoke of his friendship and pro- fessional association with Dr. Yang over the past 25 years. For 13 of the 25 years they worked together at four different institu- tions — University of California at Irvine, Stanford University, University of
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