SUBJECTS
In this non-randomized study, a total of 15 PD patients were recruited through a convenience sampling method, whose pain was refractory to medical therapy and other conservative treatments. The etiology of pain was determined by history and neurological physical findings, imaging diagnosis using MRI and CT, and responsiveness to nerve block and medications. The study was approved by the Institutional Review Boards at each respective center. The PI and sub-investigators referred subjects to the study from their own practices, if the patients were eligible to be implanted with the SCS system and were interested in participation. Patients were included in the study if they had chronic pain of predominantly neuropathic origin that was refractory to conventional treatments such as analgesic drugs and nerve blocks. In addition, patients were eligible if their pain had not improved even with adequate dopaminergic drug administration and adjustment of DBS parameters (if the patients had previously received DBS). Most patients had fluctuating pain in conjunction with motor fluctuations. For example, the patients' pain increased when they were off dopaminergic drugs and/or when DBS was turned off. Overall, the causes of pain in the patients enrolled in this study were as follows: 5 cases after lumbar spine surgery, 4 cases of radicular pain due to compression fractures (spinal surgery was not indicated because of severe osteoporosis or spinal scoliosis), 1 case of radicular pain due to severe spinal scoliosis, 3 cases of postural abnormalities (in this group pain occurred by standing for a long time with scoliosis and bent posture), and 2 cases with unknown etiology (Table 1). Exclusion criteria included: 1) active suicidal ideation, 2) substance abuse/addiction history, 3) chronic illness / cancer diagnosis, 4) life-threatening illness, 5) implanted devices such as a cardiac pacemaker, and 6) participating in another clinical study. DBS was not included in the exclusion criteria.
Table 1. Demographic Information
SCS INTERVENTION
N
|
Average Age
|
Average PD Duration (Y)
|
Type of PD Initially
|
Indication for SCS
|
DBS Prior
|
Leads and Location
|
Follow up Period (Months)
|
15
|
74
|
17
|
Tremor Dominant: 2
|
Pain multiple sites: 7
|
No: 7
|
Thoracic: 14
|
Range: 4-33
|
|
|
|
Akinetic Rigid: 13
|
Low back pain only: 6
|
Yes: 8
|
Cervical: 1
|
Average: 22
|
|
|
|
|
Leg Pain: 2
|
|
|
|
A total of 15 patients were included in the study with a mean age of 74 (SD 5.2) and an average PD duration of 17 years (SD 8.7) (Table 1). All participants had a history of concurrent pain conditions. 7 patients had no DBS therapy prior to the study, while 8 had undergone DBS prior to initiation. One or two percutaneous electrodes were implanted in the epidural space on the dorsal midline at the level of the thoracic or cervical spine and connected to an implantable pulse generator (Abbott Proclaim Elite5 or Abbott Prodigy); 1 Abbott Lamitrode lead in 5 patients, 1 Abbott Octrode lead in 1 patient, 2 Abbott Octrode leads in 3 patients, 1 Abbott Octrode lead with 1 Abbott Lamitrode lead in 4 patients, and 2 Medtronic Octad leads in 2 patients, in which a Medtronic IPG was previously used and changed to an Abbott IPG with a conversion connector. Lead choice (e.g, company and type of lead used) was determined based on differing protocols of the Japanese hospital systems. Participants were set to one of three stimulation modes according to their preference: the continuous tonic stimulation, the continuous Burst stimulation (40Hz, 500Hz, 1000μs), or the cycle mode (on time of 10-15 sec, off time of 15-30 sec) with Burst (40Hz, 500Hz, 1000μs). While traditional spinal cord stimulation has been delivered in a tonic fashion, the majority of patients in this study opted for the relatively newer, “burst SCS” in either a continuous or cycle mode timeframe. The burst SCS stimulation, demonstrated by De Ridder, is characterized by a five-pulse train with an intraburst frequency of 500 Hz, with a 40 Hz passive recharging model. In order to ensure proper electrode placement, a low-frequency tonic stimulation was first applied to induce a paresthesia or alternate sensory experience such as tingling in the primary area of the patient’s pain (e.g, lower back). Next, the stimulation waveform was changed to the stimulation parameter that the patient had chosen (e.g, burst stimulation, burst stimulation with cycle mode, tonic stimulation). The intensity of the stimulation was set to 60-70% of the threshold for paresthesias evoked by burst during intraoperative testing. All patients did not feel stimulation-induced paresthesias after the intensity was reduced to 60-70% of the threshold for paresthesias, except for one patient who chose either the continuous tonic (2.6mA, 10Hz, 350μs) or the continuous Burst (0.15mA) stimulation based on his severity of pain. The patients had different levels of pain that were altered by the action of both dopaminergic drugs and DBS. Therefore, the effects of SCS were evaluated "on-medication" and "on-DBS" under the condition that the dopaminergic drugs and DBS were sufficiently controlled so that there were no off-period painful sensations. The careful and adequate administration of dopaminergic drugs (or DBS programming) prevented the appearance of off-period painful sensations and controlled other motor and non-motor symptoms in Parkinson’s disease. In total, there were 8 patients who had previously received DBS and 7 patients who received only drug treatment (anti-Parkinsonian drugs and other agents for neuropathic pain). All patients underwent bilateral subthalamic deep brain stimulation (STN-DBS). Patients who received DBS were combined with anti-Parkinson drugs medication. In patients who received DBS, the therapeutic effect of SCS was evaluated at “on-medication” and “on-DBS”. In patients who received only drug therapy, the therapeutic effect of SCS was evaluated in the "on-medication" state. The exact configuration for each patient and stimulation parameters can be found in Table 2.
Table 2. Lead locations and stimulation parameters
Patient
|
DBS Prior
|
Lead Locations
|
Stimulation Parameter
|
1
|
No
|
T7-T9
T10-T12
|
Proclaim Elite5 (Abbott), 5-6-(at T8 level) 9-(at T10 level) 15+16+ (at T12 level), 0.5mA Burst (40Hz, 500Hz, 1000us), Cycle mode(on time 15 sec, off time 15 sec)
|
2
|
No
|
T8-9
T10-11
|
Prodigy(Abbott), 3-8+, 0.5mA, Burst (40Hz, 500Hz, 1000us)
|
3
|
No
|
C2-C5
|
Proclaim Elite5 (Abbott), 2-4+, 0.4mA, Burst (40Hz, 500Hz, 1000us), Cycle mode(on time 30sec, off time 90 sec)
|
4
|
No
|
T6-T8
|
Proclaim Elite5 (Abbott), 3-4-12+13+, 0.8mA, Burst (40Hz, 500Hz, 1000us)
|
5
|
No
|
T10-T11
T11-T12
|
Proclaim Elite5 (Abbott), 15-16-(at T12 level) 11+12+ (at T10 level) 0.15mA, Burst (40Hz, 500Hz, 1000us)
|
6
|
No
|
T8-T10
|
Proclaim Elite5 (Abbott), 2-10-(at T8/9 level) 3+11+ (at T9 level) 0.15mA, Burst (40Hz, 500Hz, 1000us)
|
7
|
No
|
T9-T11
|
Proclaim Elite5 (Abbott), 2-4+(at T9/10 level) 2.6mA, tonic 2.6mA 10Hz 350us or 0.15mA, Burst (40Hz, 500Hz, 1000us), (Switching from Burst mode to tonic SCS mode when severe pain is occurred)
|
8
|
Yes
|
T8-T9
T10-T11
|
Proclaim Elite5 (Abbott), 1-2-7+8+, 1.45mA, Burst (40Hz, 500Hz, 1000us), Cycle mode(on time 10sec, off time 30 sec)
|
9
|
Yes
|
T7-T9
|
Proclaim Elite5 (Abbott), 6-7+13-14-15+16+, 0.6mA, Burst (40Hz, 500Hz, 1000us), Cycle mode (on time 10sec, off time 30 sec)
|
10
|
Yes
|
T9-T10
|
Proclaim Elite5 (Abbott), 3-2+4+ (at T9/10 level), 0.40mA, Burst (40Hz, 500Hz, 1000us), Cycle mode (on time 30sec, off time 90 sec)
|
11
|
Yes
|
T9-T10
|
Proclaim Elite5 (Abbott), 2-1+3+ (at T9 level), 0.20mA, Burst (40Hz, 500Hz, 1000us)
|
12
|
Yes
|
T6-T9
|
Proclaim Elite5 (Abbott),10-12+ (at T7 level), 0.80mA, Burst (40Hz, 500Hz, 1000us), Cycle mode (on time 30sec, off time 90 sec)
|
13
|
Yes
|
T5-T7
T9-T11
|
Proclaim Elite5 (Abbott),11-10+12+ (at T9/10 level), 3.0-4.5mA, tonic 40Hz 350us
|
14
|
Yes
|
T2-T4
|
Proclaim Elite5 (Abbott),4-5-6+7+ (at T3 level), 0.75mA, Burst (40Hz, 500Hz, 1000us)
|
15
|
Yes
|
T9-T10
T10-T11
|
Proclaim Elite5 (Abbott),11-13+ (at T9/10 level), 0.35mA, Burst (40Hz, 500Hz, 1000us), Cycle mode (on time 15sec, off time 45 sec)
|
CLINICAL OUTCOMES
Patients were asked to complete the Visual Analogue Scale for pain (VAS), the revised Unified Parkinson's Disease Rating Scale (MDS-UPRS), Self-Rating Depression Scale (SDS), Hamilton Depression Rating Scale (HAMD), Profile of Mood State (POMS-II), 10M (10-meter) walking test, and a Timed Up and Go (TUG) at each clinic visit. Each participant had a family member or close friend present during clinic visits to help answer questionnaires.
STATISTICAL ANALYSIS
Mean and standard deviations were calculated for two separate groups, those who had DBS prior to entering the study, and those that did not. Paired two-tailed t-tests were calculated comparing pre-intervention means and post-intervention means within each group (Table 3). As a sensitivity analysis, we also performed a Wilcoxon sign rank test for certain parameters.
Table 3. Outcome Measures Pre and Post Stimulation Therapy
Outcome
|
DBS Prior
|
Pre stimulation (SD)
|
Post stimulation (SD)
|
P-value (t-test, two-tailed)
|
Sample Size (n)
|
VAS Scores
|
No
|
8.9 (1.4)
|
3.8 (2.6)
|
0.00021
|
7
|
Yes
|
8.5 (1.4)
|
3.3 (2.5)
|
.00031
|
8
|
Outcome
|
Stimulation Parameter
|
Pre stimulation
|
Post stimulation
|
P-value (t-test, two-tailed)
|
Sample Size (n)
|
VAS Scores
|
Continuous Burst
|
9.4 (0.8)
|
4.9 (2.5)
|
0.002
|
6
|
Cycle Mode Burst
|
7.8 (1.4)
|
2.6 (2.0)
|
.0001
|
7
|
1 Significant value defined as p-value <0.05
|
Table 4. Baseline Characteristics On and Off Medications
Outcome
|
DBS Prior
|
Off Meds and Off DBS
|
On Meds and On DBS
|
Sample Size (n)
|
Hoehn and Yahr
|
No
|
4.9 (0.4)
|
4.3 (0.5)
|
7
|
Yes
|
4.8 (0.5)
|
3.8 (0.5)
|
8
|