Lesser-Known Aspects of Deep Brain Stimulation for Parkinson's Disease: Programming Sessions, Hardware Surgeries, Residential Care Admissions, and Deaths.

OBJECTIVE: The long-term treatment burden, duration of community living, and survival of patients with Parkinson's disease (PD) after deep brain stimulation (DBS) implantation are unclear. This study aims to determine the frequency of programming, repeat hardware surgeries (of the intracranial electrode, implantable pulse generator [IPG], and extension-cable), and the timings of residential care and death in patients with PD treated with DBS. MATERIALS AND METHODS: In this cross-sectional, population-based study, individual-level data were collected from the Australian government covering a 15-year period (2002-2016) on 1849 patients with PD followed from DBS implantation. RESULTS: The mean DBS implantation age was 62.6 years and mean follow-up 5.0 years. Mean annual programming rates were 6.9 in the first year and 2.8 in subsequent years. 51.4% of patients required repeat hardware surgery. 11.3% of patients had repeat intracranial electrode surgery (including an overall 1.1% of patients who were completely explanted). 47.6% of patients had repeat IPG/extension-cable surgery including for presumed battery depletion. 6.2% of patients had early repeat IPG/extension-cable surgery (within one year of any previous such surgery). Thirty-day postoperative mortality was 0.3% after initial DBS implantation and 0.6% after any repeat hardware surgery. 25.3% of patients were admitted into residential care and 17.4% died. The median interval to residential care and death was 10.2 years and 11.4 years, respectively. Age more than 65 years was associated with fewer repeat hardware surgeries for presumed complications (any repeat surgery of electrodes, extension-cables, and early IPG surgery) and greater rates of residential care admission and death. CONCLUSIONS: Data from a large cohort of patients with PD treated with DBS found that the median life span after surgery is ten years. Repeat hardware surgery, including of the intracranial electrodes, is common. These findings support development of technologies to reduce therapy burden such as enhanced surgical navigation, hardware miniaturization, and improved battery efficiency.

Programming Parameters and Techniques in Trigeminal Ganglion Stimulation for Intractable Facial Pain.

OBJECTIVES: Atypical facial pain syndromes are challenging disorders to manage and often incur limited benefit with surgery for classical trigeminal neuralgia presentations, such as microvascular decompression or ablative procedures. Neurostimulation of the trigeminal ganglion and peripheral nerves can be effective at treating atypical presentations of trigeminal facial pain affecting the V1-3 dermatomes, and the surgical techniques are well described. The stimulation parameters, however, have thus far received limited description; we therefore sought to describe programming strategies. MATERIALS AND METHODS: We performed a retrospective chart review, examining patients that underwent trigeminal ganglion stimulation (TGS) and nerve branch stimulation for atypical facial pain and trigeminal neuropathic pain, and describe the programming strategies in detail. RESULTS: We describe the use of high-frequency stimulation (1000 Hz), with alteration in pulse width (60-220 msec) and amplitude (0.5-3 V) to achieve effective treatment of refractory trigeminal facial pain. These parameters differ from existing published parameters for trigeminal nerve branch stimulation. We also describe the programming of specific contacts on each lead to target specific aspects of the individual patients' facial pain. CONCLUSIONS: The use of effective programming strategies is critical to the success of neurostimulation surgical treatments; however, the critical details in programming strategies typically receive limited description. We report on the use of several successful programming strategies for TGS, to assist pain providers in successfully applying these surgical techniques in these difficult to manage atypical facial pain syndromes.

Utilization of Concurrent Dorsal Root Ganglion Stimulation and Dorsal Column Spinal Cord Stimulation in Complex Regional Pain Syndrome.

INTRODUCTION: Complex regional pain syndrome (CRPS) can be effectively treated with spinal cord stimulation (t-SCS). There is also evidence that dorsal root ganglion (DRG) stimulation may be superior to t-SCS in CRPS. However, there has been no published data, to our knowledge, that looked at the concurrent use of t-SCS and DRG stimulation for treatment of CRPS. METHODS: Our study includes four patients with severe CRPS who had all been implanted with a t-SCS. While all these patients had positive results from their t-SCS, they all had areas which lacked coverage, giving them incomplete pain relief. These patients also underwent successful trial and implantation of DRG-S. All four patients reported further improvement in their residual pain and function with DRG-S (>60%), and even superior pain relief (>80%) with concurrent use of t-SCS and t-SCS. RESULTS: All patients had a diagnosis of lower extremity CRPS-1. After DRG-S implantation, multiple attempts were made in each patient to use DRG-S alone by temporarily turning the t-SCS off. However, in each attempt, all patients consistently reported superior pain relief and improvement in function with the concurrent use of t-SCS and DRG, as compared to DRG alone. The average numeric rating scale pain score decreased from approximately 7 in the regions not covered by t-SCS to 3 after DRG-S implantation, and to 1.25 with concurrent use t-SCS and DRG-S. CONCLUSION: Both t-SCS and DRG-S have been shown to be effective in treatment of patients with CRPS. In our study, concurrent use of t-SCS and DRG-S provided significant improvement in pain and function as compared to using either device alone. This suggests the potential that combination therapy with t-SCS and DRG-S may be beneficial in patients with CRPS. Further prospective studies are required to evaluate this concept.

Defensive Implantable Cardioverter-Defibrillator Programming Is Safe and Reduces Inappropriate Therapy　- Comparison of 3 Programming Strategies in 1,471 Patients.

BACKGROUND: Careful device programming is necessary to reduce inappropriate antitachycardia pacing (ATP) and shock therapy in recipients of implantable cardioverter-defibrillators (ICD). This retrospective study investigated the safety and efficacy of a therapy-reducing programming strategy in comparison with conventional strategies in consecutive ICD recipients of a university cardiac center. Methods and Results: All 1,471 ICD recipients from 2000 to 2015 were analyzed. Individual ICD programming (IND) was used from 2000 to 2005 followed by standard-three-zone programming (STD) until 2010. From 2010 to 2015 therapy-reducing long detection time programming (RED) was established. The mean follow-up was 2.4±1.6, 2.3±1.6 and 1.7±1.2 years in the IND, STD and RED groups, respectively. Switchover from IND to STD revealed a significant reduction in inappropriate ATP (P=0.024) and shock therapy (P<0.001). Further reduction of 58% (RR=0.42, 95% confidence interval [CI]: 0.17-1.04; P=0.061) in inappropriate ATP and 29% (RR=0.71, 95% CI: 0.29-1.72; P=0.452) in inappropriate shock therapy was achieved by switchover from STD to RED. Kaplan-Meier analysis revealed a significant difference in time until first inappropriate ATP and shock therapy among the 3 groups, being lowest in the RED group (P≤0.001). There was no difference in overall mortality (P=0.416). CONCLUSIONS: Defensive ICD programming with prolonged detection times is safe and significantly reduced inappropriate ICD therapies.

Paresthesia-Free High-Density Spinal Cord Stimulation for Postlaminectomy Syndrome in a Prescreened Population: A Prospective Case Series.

OBJECTIVE: Spinal cord stimulation (SCS) traditionally is thought to require paresthesia, but there is evidence that paresthesia-free stimulation using high-density (HD) parameters might also be effective. The purpose of this study is to evaluate relative effectiveness of conventional, subthreshold HD, and sham stimulation on pain intensity and quality of life. METHODS: Fifteen patients with response to conventional stimulation (60 Hz/350 µsec) were screened with a one-week trial of subthreshold HD (1200 Hz/200 µsec/amplitude 90% paresthesia threshold) and enrolled if there was at least 50% reduction on visual analog scale (VAS) for pain. Subjects were randomized into two groups and treated with four two-week periods of conventional, subthreshold HD, and sham stimulation in a randomized crossover design. RESULTS: Four of 15 patients responded to subthreshold HD stimulation. Mean VAS during conventional, subthreshold HD, and sham stimulation was 5.32 ± 0.63, 2.29 ± 0.41, and 6.31 ± 1.22, respectively. There was a significant difference in pain scores during the blinded crossover study of subthreshold HD vs. sham stimulation (p < 0.05, Student's t-test). Post hoc analysis revealed that subjects reported significantly greater attention to pain during conventional stimulation compared with subthreshold HD stimulation (p < 0.05, Student's t-test). All subjects reported a positive impression of change for subthreshold HD stimulation compared with conventional stimulation, and there was a trend toward greater likelihood for response to subthreshold HD stimulation in comparison with sham stimulation (p = 0.07, Fisher's exact test). At the end of the trial, all subjects elected to continue to receive subthreshold HD stimulation rather than conventional stimulation. CONCLUSIONS: Paresthesia are not necessary for pain relief using commercially available SCS devices, and may actually increase attention to pain. Subthreshold HD SCS represents a viable alternative to conventional stimulation among patients who are confirmed to have a clinical response to it.

Computer-Guided Deep Brain Stimulation Programming for Parkinson's Disease.

OBJECTIVE: Pilot study to evaluate computer-guided deep brain stimulation (DBS) programming designed to optimize stimulation settings using objective motion sensor-based motor assessments. MATERIALS AND METHODS: Seven subjects (five males; 54-71 years) with Parkinson's disease (PD) and recently implanted DBS systems participated in this pilot study. Within two months of lead implantation, the subject returned to the clinic to undergo computer-guided programming and parameter selection. A motion sensor was placed on the index finger of the more affected hand. Software guided a monopolar survey during which monopolar stimulation on each contact was iteratively increased followed by an automated assessment of tremor and bradykinesia. After completing assessments at each setting, a software algorithm determined stimulation settings designed to minimize symptom severities, side effects, and battery usage. RESULTS: Optimal DBS settings were chosen based on average severity of motor symptoms measured by the motion sensor. Settings chosen by the software algorithm identified a therapeutic window and improved tremor and bradykinesia by an average of 35.7% compared with baseline in the "off" state (p < 0.01). CONCLUSIONS: Motion sensor-based computer-guided DBS programming identified stimulation parameters that significantly improved tremor and bradykinesia with minimal clinician involvement. Automated motion sensor-based mapping is worthy of further investigation and may one day serve to extend programming to populations without access to specialized DBS centers.

Intensity Modulation: A Novel Approach to Percept Control in Spinal Cord Stimulation.

OBJECTIVE: Spinal cord stimulation (SCS) can be effective for neuropathic pain, but clinical benefit is sometimes inadequate or is offset by stimulation-induced side-effects, and response can be inconsistent among patients. Intensity-modulated stimulation (IMS) is an alternative to tonic stimulation (TS) that involves continuous variation of stimulation intensity in a sinusoidal pattern between two different values, sequentially activating distinct axonal populations to produce an effect that resembles natural physiological signals. The purpose of this study is to evaluate the effect of IMS on the clinical effect of SCS. METHODS: Seven patients undergoing a percutaneous SCS trial for postlaminectomy syndrome were enrolled. Thresholds for perception, pain relief, and discomfort were measured and used to create patient-specific models of axonal activation and charge delivery for both TS and IMS. All participants underwent three two-min periods of blinded stimulation using TS, IMS, and placebo, and were asked to describe the effect on quality of the sensory percept and pain relief. RESULTS: All participants perceived IMS differently from placebo, and five noted significant differences from TS that resulted in a more comfortable sensation. TS was described as electric and tingling, whereas IMS was described as producing a focal area of deep pressure with a sense of motion away from that focus. The anatomic location of coverage was similar between the two forms of stimulation, although one participant reported better lower back coverage with IMS. Computer modeling revealed that, compared with TS, IMS involved 36.4% less charge delivery and produced 78.7% less suprathreshold axonal activation. CONCLUSIONS: IMS for SCS is feasible, produces a more comfortable percept than conventional TS, and appears to provide a similar degree of pain relief with significantly lower energy requirements. Further studies are necessary to determine whether this represents an effective alternative to tonic SCS for treatment of neuropathic pain.

Threshold Evolution as an Analysis of the Different Pulse Frequencies in Rechargeable Systems for Spinal Cord Stimulation.

INTRODUCTION: Pulse frequency (Fc) is one of the most important parameters in neurostimulation, with Pulse Amplitude (Pw) and Amplitude (I). Up to certain Fc, increasing the number of pulses will generate action potentials in neighboring neural structures and may facilitate deeper penetration of the electromagnetic fields. In addition, changes in frequency modify the patient's sensation with stimulation. MATERIALS/METHODS: Fifty patients previously implanted with rechargeable current control spinal cord stimulation. With pulse width fixed at 300 µsec, we stimulated at 26 different Fc values between 40 and 1200 Hz and determine the influence of these changes on different stimulation thresholds: perception threshold (Tp ), therapeutic perception (Tt), and discomfort threshold (Td). Simultaneously, paresthesia coverage of the painful area and patient's sensation and satisfaction related to the quality of stimulation were recorded. RESULTS: Pulse Fc is inversely proportional to stimulation thresholds and this influence is statistically significant (p < 0.05). As Pulse Fc increased from 40 to 1200 Hz, the mean threshold decreases from 7.25 to 1.38 mA (Tp ), 8.17 to 1.63 (Tt ), and 9.20 to 1.85 (Td). Significant differences for Tp and Tt began at 750 Hz (Tp , Tt ) and at 650 Hz for Td. No significant influence was found regarding paresthesia coverage. As expected, Fc affects significantly patient's sensation and satisfaction. DISCUSSION: Changes in Fc affect the quality of paresthesias. Within the evaluated parameters higher frequencies are inversely proportional to stimulation thresholds and Tt. It seems that Fc is a vital parameter to achieve therapeutic success. CONCLUSIONS: Changes in Fc is a useful parameter to modulate the patient's sensory perception. Fc can be successfully used to adjust the quality of the paresthesias and to modify patient's subjective sensation. We showed that as the frequency increases, the patient's satisfaction with the perceived sensation decreases, suggesting that higher Fc may need to be set up at subthreshold amplitude to achieve positive response.

Intrathecal Baclofen Dosing Regimens: A Retrospective Chart Review.

OBJECTIVES: To examine dosing patterns in patients receiving baclofen via intrathecal baclofen pumps to assess for common patterns by diagnosis, ambulation ability, and affected limbs distribution. MATERIALS AND METHODS: This trial study included 25 patients with baclofen pumps selected from the 356 patients enrolled in our center's baclofen pump program. Selection was done by splitting all patients into diagnostic categories of stroke, multiple sclerosis, traumatic/anoxic brain injury, cerebral palsy, and spinal cord injury, and then, five patients were randomly selected from each diagnosis.A systematic chart review was then conducted for each patient from Jan 1, 2008, through September 16, 2013, to look at factors including mean daily dose at end of study, and among those implanted during the study mean initial stable dose and time to initial stable dose. RESULTS: Analysis of mean daily dose across diagnoses found significant differences, with brain injury, cerebral palsy, and spinal cord injury patients having higher doses while multiple sclerosis and stroke patients required lower doses. Nonambulatory patients strongly trended to have higher daily doses than ambulatory patients. Similar trends of mean initial stable dose being higher in a similar pattern as that of end mean daily dose were seen according to diagnoses and ambulatory status, although statistical significance could not be achieved with the small sample size. CONCLUSION: Significant differences in dosing were found between diagnoses and trended to differ by ambulatory status at the end of the study, and similar trends could be observed in achieving initial stable dose.

Is the introduction of another variable to the strength-duration curve necessary in neurostimulation?

INTRODUCTION: Neurostimulation is the process and technology derived from the application of electricity with different parameters to activate or inhibit nerve pathways. Pulse width (Pw) is the duration of each electrical impulse and, along with amplitude (I), determines the total energy charge of the stimulation. OBJECTIVES: The aim of the study was to test Pw values to find the most adequate pulse widths in rechargeable systems to obtain the largest coverage of the painful area, the most comfortable paresthesia, and the greatest patient satisfaction. MATERIAL AND METHODS: A study of the parameters was performed, varying Pw while maintaining a fixed frequency at 50 Hz. Data on perception threshold (Tp ), discomfort threshold (Td ), and therapeutic threshold (Tt ) were recorded, applying 14 increasing Pw values ranging from 50 µsec to 1000 µsec. Lastly, the behavior of the therapeutic range (TR), the coverage of the painful area, the subjective patient perception of paresthesia, and the degree of patient satisfaction were assessed. RESULTS: The findings after analyzing the different thresholds were as follows: When varying the Pw, the differences obtained at each threshold (Tp , Tt , and Td ) were statistically significant (p < 0.05). The differences among the resulting Tp values and among the resulting Tt values were statistically significant when varying Pw from 50 up to 600 µsec (p < 0.05). For Pw levels 600 µsec and up, no differences were observed in these thresholds. In the case of Td , significant differences existed as Pw increased from 50 to 700 µsec (p ≤ 0.05). The coverage increased in a statistically significant way (p < 0.05) from Pw values of 50 µsec to 300 µsec. Good or very good subjective perception was shown at about Pw 300 µsec. CONCLUSIONS: The patient paresthesia coverage was introduced as an extra variable in the chronaxie-rheobase curve, allowing the adjustment of Pw values for optimal programming. The coverage of the patient against the current chronaxie-rheobase formula will be represented on three axes; an extra axis (z) will appear, multiplying each combination of Pw value and amplitude by the percentage of coverage corresponding to those values. Using this new comparison of chronaxie-rheobase curve vs. coverage, maximum Pw values will be obtained different from those obtained by classic methods.

Dynamic Detection of Spinal Cord Position During Postural Changes Using Near-Infrared Reflectometry.

INTRODUCTION: Motion of the spinal cord relative to a spinal cord stimulator epidural electrode array can cause suboptimal stimulation: either noxious, inefficient, or insufficient. Adaptive stimulation attempts to mitigate these effects by modulating stimulation parameters in a position-dependent fashion. Near-infrared (NIR) reflectometry is demonstrated to provide real-time direct measurement of spinal cord position at the site of stimulation, which can facilitate closed-loop adaptive stimulation during static and dynamic motion states. METHODS: A miniature sensor array consisting of an NIR light emitting diode flanked by phototransistors potted in epoxy was placed in the dorsal epidural space of a human cadaver at the T8 level via laminotomy. Turgor of the subarachnoid space was maintained by intrathecal infusion of saline. NIR reflectance was measured as the cadaver was rotated about its longitudinal axis on a gantry. NIR reflectance was correlated with gantry position and velocity. RESULTS: NIR reflectometry suggests gravitational force is the primary determinant of cord position in static, ordinal positions. Under dynamic motion conditions, there was statistically significant cross-correlation between reflectometry data and the tangential velocity squared, suggesting that centripetal force was the primary determinant of cord position as the gantry was rotated. Reflectometry data strongly correlated with a simple geometric model of anticipated spinal cord precession within the spinal canal. CONCLUSIONS: Spinal cord position during dynamic motion has been shown to differ from static predictions due to additional influences such as centripetal force. These findings underscore limitations in extrapolating spinal cord position from surrogates such as body position or body acceleration at sites remote from the stimulating electrodes. NIR reflectometry offers a real-time direct measure of spinal cord position in both static and dynamic motion states, which may facilitate closed-loop adaptive stimulation applications.

Low-frequency deep brain stimulation for movement disorders.

INTRODUCTION: Traditionally, deep brain stimulation (DBS) for movement disorders (MDs) is provided using stimulation frequencies equal to or above 100 Hz. However, recent evidence suggests that relatively low-frequency stimulation (LFS) below 100 Hz is an option to treat some patients with MDs. OBJECTIVES: We aimed to review the clinical and pathophysiological evidence supporting the use of stimulation frequencies below 100 Hz in different MDs. RESULTS: Stimulation of the subthalamic nucleus at 60 Hz has provided benefit in gait and other axial symptoms such as swallowing and speech. Stimulation of the pedunculopontine nucleus between 20 and 45 Hz can provide benefit in freezing of gait, cognition, and sleep quality in select patients with Parkinson's disease. Stimulation of the globus pallidus internus below 100 Hz in patients with dystonia has provided benefit at the beginning of the therapy, although progressively higher stimulation frequencies seem to be necessary to maintain the clinical benefit. Relative LFS can lower energy requirements and reduce battery usage-a useful feature, particularly in patients treated with high current energy. CONCLUSIONS: DBS at frequencies below 100 Hz is a therapeutic option in select cases of Parkinson's disease with freezing of gait and other axial symptoms, and in select patients with dystonia and other hyperkinetic movements, particularly those requiring an energy-saving strategy.