Surgical considerations for tremor and dystonia
ABSTRACTDeep brain stimulation (DBS) is among the most effective approaches for the treatment of patients with advanced movement disorders. In patients with essential tremor, stimulation typically targets the ventral intermediate nucleus of the thalamus. Results of several studies have shown that over a follow-up period of 1 to 5 years, the severity of tremor decreases by an average of approximately 50% from baseline. Ongoing research continues to define the optimal stimulation parameters for patients with tremor, including frequency, voltage, and pulse width. In patients with dystonia, DBS typically targets the globus pallidus internus or the subthalamic nucleus. Long-term prospective clinical trials demonstrated reductions in motor severity rating scale scores of approximately 50% to 80% over follow-up periods of 2 to 3 years. Serious adverse events were uncommon, and included lead failures and infections. Appropriate candidates for DBS treatment of dystonia include patients with an unequivocal diagnosis of dystonia and significant disability. Several issues in the use of DBS for movement disorders remain unresolved, including the intensity of appropriate medical management before undergoing DBS, the importance of intraoperative mapping, optimal stimulator programming, and the time course of the beneficial effects of treatment.
Patient selection
Appropriate patients for DBS include those with an unequivocal diagnosis of dystonia and significant disability. Etiology and type of dystonia should also be considered. Patients with secondary dystonia (eg, due to structural brain lesions or heredodegenerative disorders) generally do not respond to DBS as well as patients with primary dystonias. A possible exception is tardive dystonia, which is caused by past exposure to dopamine receptor–blocking drugs. Although it is a secondary dystonia, tardive dystonia may respond well to DBS. Data on this point remain limited. Moreover, with tardive dystonia (as well as Sydenham chorea and poststroke hemiballismus), there may be spontaneous remission. DBS in these conditions should therefore be considered when enough time has elapsed that the likelihood of spontaneous remission is low.1
Not all dystonic symptoms have been shown to respond equally to DBS. Evidence of effectiveness is stronger and more consistent for limb and axial dystonia than for dystonic impairment of speech and swallowing. Phasic dystonia (jerky or rhythmic movements) appears to respond better than fixed postures. A critical point is that fixed postures not caused by electrically active muscle contraction will not respond to DBS. For example, bony deformity of the spine, joint disease, or tendon shortening cannot be expected to improve with DBS. The situation is complicated, since such conditions may develop as secondary consequences of dystonia. The potential for their development may warrant earlier rather than later DBS surgery in childhood-onset PGD.10
UNRESOLVED ISSUES IN DBS FOR DYSTONIA
How aggressively should other therapies be tried before starting DBS?
Pharmacologic options include a range of oral, intramuscular, and intrathecal agents. Injection of botulinum toxin to denervate affected muscles is a mainstay of treatment for focal or segmental dystonia, but often fails to improve symptoms because of the involvement of a large number of muscles, complexity of the movement pattern, or the development of neutralizing antibodies.8 With the exception of levodopa-responsive PGD, other pharmacologic therapy for PGD is generally of limited effectiveness for controlling symptoms of dystonia.9 Oral or intrathecal baclofen may improve symptoms, but often produces unacceptable sedation.
How important is intraoperative microelectrophysiology?
Although contemporary imaging techniques are important in the correct placement of stimulating electrodes, the available techniques do not always provide sufficient resolution to delineate the STN or GPi. The accuracy of electrode placement may also be influenced by distortions caused by lack of homogeneity among magnetic resonance images, brain shift, and signal deflections from cannulae or electrodes.14 These errors may result in significant deviation of electrode placement from the intended target. Microelectrode recording and micro-stimulation may be used to map the target region and refine the surgical target. It is widely, but not universally, held that this strategy contributes to superior accuracy and outcomes; it ordinarily requires an awake procedure, which is not always feasible in patients with severe dystonia or in pediatric patients.11
How should be programming (stimulator adjustment) be performed?
Research continues to refine our understanding of how electrical parameters such as voltage, frequency, and pulse width affect clinical outcomes in patients undergoing DBS for dystonia. Some programming approaches, such as long pulse width and high frequency, that were once generally accepted are now widely questioned. Another major unresolved question is: “How long should it take to see the results of stimulation?” In the clinical studies described above, continued improvement was generally observed over months or even years, and, in most patients, stimulators are incrementally adjusted over an extended period. However, some patients may experience much more rapid onset of benefit.
Long-term DBS management of dystonia
Unlike DBS for Parkinson disease or even essential tremor, DBS for dystonia is performed in young patients. This creates special challenges in pediatric patients, who can be expected to grow and develop after device implantation. As a result, children may require additional surgeries to reposition devices.
In addition, the most widely used devices require repeated battery replacement surgeries, although newer rechargeable devices are becoming available.
Finally, there is a nontrivial incidence of hardware-related complications when devices are used continuously for many years. Although individual dystonia patients vary in the acuity of their response to the cessation of stimulation,6 deterioration can be acute and dramatic. In long-term studies of bilateral pallidal stimulation described above, hardware failures were the most commonly reported adverse events, including unilateral or bilateral lead fracture.7,9 These appear to be more frequent in patients with dystonia than in other movement disorders.
SUMMARY AND CONCLUSIONS
Deep brain stimulation produces marked and long-lasting improvement in motor function and disability in patients with hyperkinetic disorders. In patients with essential tremor, stimulation usually targets the VIM of the thalamus. Reduction in tremor is most closely related to stimulation frequency and voltage, whereas pulse width has little effect on treatment outcome. In patients with dystonia, stimulation typically targets the GPi or STN. Long-term prospective clinical trials demonstrated significant reductions in motor severity rating scale scores. Selecting patients for DBS requires careful consideration of a range of factors, including the specific clinical presentation, treatment history, and social support. Areas of current investigation include optimal stimulation programming, intraoperative mapping, and the long-term efficacy and safety of stimulation.
