Motor cortical stimulation for parkinsonism in multiple system atrophy

Background: Functional neuroimaging studies have demonstrated disturbances in the activity of premotor and motor cortices in Parkinson disease and in animal models of parkinsonism that improve in response to effective basal ganglia surgical therapy. Techniques that directly alter the function of these cortical areas, such as transcranial magnetic stimulation, have been applied in patients with Parkinson disease, with transient improvement in their bradykinesia and gait dysfunction. Recently, a patient with refractory Parkinson disease was claimed to have obtained a marked bilateral clinical benefit from extradural unilateral motor cortical stimulation. We hypothesized that direct cortical stimulation could alleviate the disability of the treatment-refractory parkinsonian symptoms commonly present in MSA. Objective: To evaluate the efficacy of motor cortical stimulation in patients with refractory parkinsonism due to multiple system atrophy (MSA) Methods: Five patients with a diagnosis of MSA with predominant parkinsonism underwent surgery for subdural motor cortical stimulation. Main Outcome Measures: Changes in activities of daily living and motor subscores on the Unified Parkinson's Disease Rating Scale 12 hours after medication with-drawal. Scores at baseline and 3 to 6 months following surgery were compared. Results: All patients had a decline in motor scores at the follow-up evaluations despite the application of a variety of adjustments. The activities of daily living score mildly worsened by 9.7% (95% confidence interval, 32.3 to-13.0; P = .37) and the motor score worsened by 25.6% (95% confidence interval, 58.7 to -7.5; P = .06). Despite objective worsening over time and no deterioration when stimulation was immediately turned off, 3 patients still claimed subjective benefit and requested continued stimulation. No patients suffered adverse effects from the surgery or long-term stimulation, although I patient had a stimulation-induced seizure during the initial programming. The range of settings for 4 patients with bipolar configuration and 1 patient with monopolar configuration were as follows: amplitude, 3 to 3.6 V; pulse width, 40 to 90 milliseconds; and pulse rate, 145 to 185 Hz. Conclusions: Our data suggest that motor cortical stimulation using these parameters fails to improve the motor disability in MSA. Worsening of motor scores was likely a function of disease progression.