Globus Pallidus Stimulation and the Alleviation of Parkinsonian Symptoms

ABSTRACT & COMMENTARY
Source: Davis KD, et al. Globus pallidus stimulation activates the cortical motor system during alleviation of parkinsonian symptoms. Nature Med 1997;3:671-674.

It is now well known that stereotaxically placed lesions in the posteroventral globus pallidus (GP) ameliorate symptoms of akinesia and rigidity in patients with severe Parkinson’s disease (Latinen J. Neurosurg 1992;76:53-61). The rationale was that the GP excessively inhibited the motor thalamus, leading to reduced function in cerebral premotor and motor systems. Encouraging though the procedure may be, success has not been 100%, and complications have affected a number of patients. Against that background, Davis et al, with informed consent, implanted electrodes in GP in nine patients with contralateral rigidity and evaluated clinical and regional blood flow changes (using PET technology) during high-frequency stimulation. "Marked improvement" occurred in eight of the nine. The authors also implanted stimulators in the ventrointermediate nucleus (Vim) of the thalamus in a second group of six patients with contralateral tremor. With stimulation, tremor disappeared in five and was reduced in the sixth. Only one patient out of both groups experienced a brief sensory experience (a flash of light when Vim stimulation was initiated), and none had sustained paresthesias.

Among the patients with pallidal high-frequency stimulation, rigidity melted greatly within one minute of onset. CBF increased in the ipsilateral supplementary motor area and the putamen external segment. CBF decreased only in the ipsilateral cingulate motor area. Lower intensity stimulation induced no observable functional changes. Based on the clinical improvement and increased blood flow in the SMA during high frequency GP stimulation, the authors conclude that such stimulation blocked the chronic pre-stimulation inhibition of the GP on the SMA. Consistent with previous experiments, Vim stimulation blocked pre-existing contralateral tremor and induced decreased CBF in the contralateral SMA, cerebellum, and cingulate motor area, reflecting the reduced function in those zones secondary to blocking the tremor.

The specificity of the above procedures and their effects was strengthened by delivering high-frequency stimuli to the intact GP of four patients who previously had GPi pallidotomy of the contralateral hemisphere. All four presumably had akinesia-rigidity contralateral to the newly stimulated GPi and are reported as "having favorable results" comparable to those described in an above paragraph.

The authors conclude that high-frequency stimulation to the GP blocks its powerful inhibition of the SMA, a conclusion buttressed by earlier experience that low-frequency stimulation of the GP increases the motor abnormalities. Grafton and DeLong also attest to the efficacy of this procedure in their recent study on the subject (Nature Med 1997;3:602-603).

COMMENTARY

This well controlled and performed study provides one more step in developing new therapy for PD patients with either excess akinesia-rigidity or refractory tremor. Previous studies have not all reported such consistently successful results for which clear explanations have been difficult to make. Failure to destroy the specific and relatively small GPi area, chronic changes due to trans- synaptic degeneration following the initial procedure, or just biologic variation possibly explain the differences. Even given these promising results and their possible capacities to provide months or even years of relief cannot be considered as permanent escape from the imprisonment of PD. As Lewis Thomas said of the iron lung in relation to the early days of epidemic poliomyelitis, "It represented half-way technology even though it saved lives." Only cell molecular neurobiology will solve and prevent the occurrence and ultimate, relentless disability of PD. —fp