Several groups have pointed out that cognitive function may decline slightly with DBS, but deterioration is not as prominent in some spheres of performance, such as speed of processing, with stimulation of the globus pallidus compared to subthalamic stimulation. Hemorrhage into the basal ganglia and local infection near the stimulator has occurred in a small number of patients after surgery. Depression and suicides also appear as adverse events in some trials. One remarkable case had a severe depressive emotional state and affect that could be turned on and off with stimulation; the electrode tip had migrated from the intended site at the subthalamic nucleus into the mesencephalon but the mechanism of depression is obscure (Bejjani et al). We have encountered a few instances of serious delirium after electrode implantation as in the series reported by Carlson and colleagues (and rarely during the procedure if the patient is awake).
Recently, DBS has been introduced early in the course of illness, when the patient is still largely responsive to l-dopa and before severe motor complications such as dyskinesias arise. These patients are, of course, younger and have had a shorter duration of disease. In a trial conducted by Schuepbach and coworkers, in patients with mean durations of illness of 7.5 years and 52 years of age, there was a significant and sustained benefit in quality of life measures, motor complications and “on time,” for subthalamic DBS.
The stimulator is inserted in a pouch that is created near the rostral pectoral muscle and inferior to the clavicle. An external controller allows the stimulator to be adjusted for which 4 electrodes on either side are activated and their polarity, voltage applied, frequency of pulses, and pulse duration are manipulated. Patients with implanted electrodes require frequent initial contact with a physician experienced in programming the stimulator. Some patients can make minor adjustments or even turn off the stimulator on their own with a small control device that has preset limits. The stimulator battery must be exchanged periodically, the duration of service depending on the voltage used over time and other parameters of use. A comprehensive review of the subject has been given by Okun, including comments on the controversies regarding the differences in cognitive disturbance and the reduction in l-dopa doses comparing stimulation of the globus pallidus with the subthalamic nucleus.
Presumably, the mechanism of DBS is that high- frequency electrical impulses disrupt local neuronal activity, producing the functional equivalent of an ablative lesion, but the effects of deep brain stimulation may be more complex by way of stimulating neurotransmitter release.
The cerebral implantation of fetal dopaminergic tissue provided a modest improvement in motor function for a limited period (Spencer et al; Freed et al). The study by Freed and colleagues found a small improvement on a global scale that measured functional, psychologic, and neurologic aspects only in younger patients but the effect waned by 1 year. The effect has not been satisfactorily reproduced. These procedures are hampered by many difficulties, mainly in obtaining tissue and the failure of grafts to survive but also the problem of uncontrollable dyskinesias in some patients. Another provocative approach has been the delivery of neural trophic factors directly or in a viral vector through a small catheter; at least two trials have failed to show benefit. Similarly, the implantation of stem cells is being explored but has several obstacles.
Techniques of focused ultrasound energy to produce ablative lesions in deep nuclei are being developed. So far, they have found use for the treatment of essential tremor, such as in the trial conducted by Elias et al with thalamic lesions (ventral intermediate nucleus).