Intra-operatively, many STN neuronal action potentials were recorded, but only five were amenable to formal analysis based on the presence of a well isolated single unit recorded continuously for at least 20 seconds. These cells () demonstrated a mean firing frequency of 76 +/− 27 Hz (SD) and oscillatory firing patterns (significant spectral peaks at ~4 Hz and/or ~20 Hz in 4/5 cells) similar to that seen in idiopathic PD and in parkinsonian non-human primates.1
All five neurons had mean firing frequencies greater than 50 spikes/sec, which is above the 99% confidence interval for normative STN firing rates based on published data from non-human primates.1
Published data also indicate that oscillatory firing patterns are rare in the normal primate STN (found in 3.8% of cells1
). Therefore, it is very unlikely that 4 out of five cells picked at random from a population of normal STN neurons would have oscillatory activity (P<0.00001; Chi-square test). Post-operative MRI demonstrated that the leads were appropriately located with the active contacts at left lateral 10.5, AP-3.4, vert −3.8 and right lateral 12.1, AP - 0.7, vert −2.8, with respect to the mid-commissural point ().
Figure 1 Characteristic oscillatory activity recorded from an STN neuron. A, Segment of the raw signal recorded from a well-isolated neuron. B, Autocorrelogram for the same spike-train illustrating rhythmic peaks in firing probability ~50 milliseconds apart. (more ...)
Postoperative axial T2 weighted MRI in the plane of the dorsal STN (4 mm inferior to the intercommissural line). The leads are seen as signal voids, lateral to the anterior border of the red nucleus.
The patient tolerated the surgical procedure without incident. When evaluated after activation of the DBS, the patient reported a substantial reduction in the daily percentage of “off” time from 25% preoperatively to 0% per day postoperatively; this benefit persisted throughout the 40 months of observation. In addition, activation of the DBS allowed reduction in medications: levodopa was reduced from 700 mg to 400 mg daily; clozapine was reduced from 175 mg to 75 mg daily; while pramipexole (0.5 mg 3 times daily) and benztropine (2 mg twice daily), and quetiapine (50 mg twice daily) were discontinued altogether. At the 40 month visit, he continued to report stable motor benefit and denied any recent hallucinations.
Formal postoperative evaluations also showed improvement (). When evaluated 40 months after surgery, there was a 72% reduction in the UPDRS III score (lower scores reflect milder parkinsonsism) comparing the practically defined off-medication score preoperatively with the postoperative off-medication/on-stimulation score. There was also a 55% reduction in the on-medication score, comparing the preoperative on-medication score with the on-medication/on-stimulation score at 40 months. There were similar improvements in the stand-walk-sit test, in which shorter times reflect better mobility. For example, at 40 months, there was a 32% reduction in the timed stand-walk-sit test comparing the preoperative off-medication time with the off-medication/on-stimulation time. The on-medication/on-stimulation time was 29% shorter than the preoperative on-medication state (). At 40 months, no changes in stimulation parameters had been made since the initial months after placement.
UPDRS and Stand-walk-sit test
Surgery and STN DBS had little effect on the patient's neuropsychological status. Preoperative testing in the on-medication state showed a Wechsler Adult Intelligence Scale III verbal scale IQ of 77, performance scale IQ of 74, and full scale IQ of 74. Difficulties were noted on verbal articulation, fine motor dexterity, 3-step motor sequencing, visual-spatial organization, delayed recall of complex abstract visual stimuli, abstract problem solving, recognizing higher-order concepts and intruding extra words on list learning. Post-operatively, with the stimulators on and on-medication, the Wechsler Adult verbal scale IQ was 71, the performance scale IQ was 80, and the full scale IQ was 73.