Treatment of DYT-1 Generalized Dystonia by Stimulation of the Internal Globus Pallidus
Abstract & commentary
Source: Coubes P, et al. Treatment of DYT1-generalised dystonia by stimulation of the internal globus pallidus. Lancet 2000;355:2220-2221.
For more than four decades, stereotaxic neurosurgical procedures have been performed on patients with severe generalized dystonia. Many of these early approaches were performed by Irving Cooper, usually by conducting unilateral or bilateral cryothalamotomies. Although many patients often experienced benefit from surgery, the improvements often waned with time so that approximately one in four patients who underwent bilateral stereotaxic cryothalamotomies suffered permanent dysarthria as a sequel. In the last five years, several reports have raised hope that the ventrolateral globus pallidus might be a better target for patients with severe generalized dystonia. Patients have been treated with bilateral pallidotomies with mild-to-moderate improvements in dystonia. However, the operative risk of ablative surgery and the possibility of inducing irreversible neurobehavioral changes in young patients have tempered enthusiasm for this approach.
In this landmark paper, Coubes and colleagues report seven patients with dystonia musculorum deformans-1 generalized dystonia (DYT-1) treated with bilateral globus pallidus deep brain stimulators. Electrodes were implanted stereotactically in a single operation into the posteroventral internal pallidum. Operations were performed under general anesthesia without electrophysiologic guidance. After confirmation of electrode placement by MRI, impulse generators were implanted into the patient’s abdominal cavity. The average age of patients at the time of surgery was 14.5 years (range, 8-27) and all patients were severely disabled by dystonia. Their scores on the Burke-Fahn-Marsden scale (the standard clinical rating scale for dystonia) ranged from 24 (mild-to-moderate dystonia) to 97.5 (wheelchair-bound, totally dependent).
All patients improved gradually over three months, and improvements were sustained over at least one year of follow-up. Improvement in the Burke-Fahn-Marsden scale ranged from 60% to 100%. Videotapes of the patients were presented at the American Academy of Neurology (AAN) meeting in April in San Diego. It is difficult to overestimate the magnitude of the improvement in this group of patients. Six children became able to walk alone, achieving full functional independence. They were also able to return to school and resume normal lives. Painful dystonic cramping disappeared completely. In one particularly dramatic videotape segment, a young girl who was wheelchair bound and severely distorted by dystonic spasms was subsequently able to ride a bicycle without difficulty. There were no adverse events reported from surgery or stimulation, although one patient suffered a unilateral infection requiring removal of the hardware and reimplantation.
The degree of improvement and the appearance of the videotapes of these patients are sufficiently dramatic that there has been a change in the treatment algorithm for patients with severe intractable DYT-1 dystonia. At our movement disorders center and at others, bilateral globus pallidus stimulation is becoming the standard treatment for patients with severe DYT-1 dystonia who are refractory to medications. It also appears that children who undergo this operation, before they develop scoliosis or contractures, do better with the surgery.
Commentary
While these results are encouraging, several important questions remain to be answered. Long-term follow-up on these patients is not yet available, and the possibility remains that some of them may not sustain the dramatic benefits that have been observed. It is also not yet clear why patients improve gradually over a period of months. A similar pattern of delayed improvement has also been observed in several dystonia patients who underwent bilateral pallidotomy.
All seven patients reported in this series had DYT-1 dystonia. In their AAN presentation (Neurology 2000; 54(7 Suppl 3):A1-557), the authors reported eight additional patients with severe generalized dystonia (due to hypoxia, Hallervorden-Spatz, and other causes) who underwent the procedure. In these patients, benefits were more modest than in the DYT-1 patients, although these patients still experienced meaningful functional improvement from the operation.
The cost of this procedure (> $50,000), and the need for a dedicated stereotaxic neurosurgical team, may limit this operation to quaternary care academic medical centers. —Steven Frucht
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content