Treating Chronic, Intractable Pain with a Miniaturized Spinal Cord Stimulation System: 1-Year Outcomes from the AUS-nPower Study During the COVID-19 Pandemic.

Purpose: Spinal cord stimulation (SCS) is a highly effective treatment for chronic neuropathic pain. Despite recent advances in technology, treatment gaps remain. A small SCS system with a miniaturized implantable pulse generator (micro-IPG; <1.5 cm3 in volume) and an externally worn power source may be preferred by patients who do not want a large, implanted battery. We report here the long-term outcomes from the first-in-human study evaluating the safety and performance of a new neurostimulation system. Patients and Methods: This was a prospective, multi-center, open-label, single-arm study to evaluate this SCS system, in the treatment of chronic, intractable leg and low-back pain. Consented subjects who passed screening continued on to the long-term phase of the study. One-year, patient-reported outcomes (PRO's) such as pain (Numeric Rating Scale, NRS), functional disability, quality of life, and mood were captured. Results: Twenty-six (26) evaluable subjects with permanent implants were included in this analysis. The average leg pain NRS score decreased from 6.8 ± 1.2 at baseline to 1.1 ± 1.2 at the end of the study (p < 0.001), while the average low-back pain NRS score decreased from 6.8 ± 1.2 to 1.5 ± 1.2 (p < 0.001). The responder rate (proportion with ≥50% pain relief) was 91% in the leg(s) and 82% in the low back. There were significant improvements in functional disability (Oswestry Disability Index) and in mood (Beck Depression Inventory), demonstrating a 46% and 62% improvement, respectively (p < 0.001). Eleven-point Likert scales demonstrated the wearable to be very comfortable and very easy to use. Conclusion: There were considerable challenges conducting a clinical study during the COVID-19 pandemic, such as missed study programming visits. Nevertheless, subjects had significant PRO improvements through 1-year. The small size of the implanted device, along with a proprietary waveform, may allow for improved SCS outcomes and a drop in incidence of IPG-pocket pain.

Results From a Prospective, Clinical Study (US-nPower) Evaluating a Miniature Spinal Cord Stimulator for the Management of Chronic, Intractable Pain.

BACKGROUND: Chronic, intractable, neuropathic pain is readily treatable with spinal cord stimulation (SCS). Technological advancements, including device miniaturization, are advancing the field of neuromodulation. OBJECTIVES: We report here the results of an SCS clinical trial to treat chronic, low back and leg pain, with a micro-implantable pulse generator (micro-IPG). STUDY DESIGN: This was a single-arm, prospective, multicenter, postmarket, observational study. SETTING: Patients were recruited from 15 US-based comprehensive pain centers. METHODS: This open-label clinical trial was designed to evaluate the performance of the Nalu™ Neurostimulation System (Nalu Medical, Inc., Carlsbad, CA) in the treatment of low back and leg pain. Patients, who provided informed consent and were successfully screened for study entry, were implanted with temporary trial leads. Patients went on to receive a permanent implant of the leads and micro-IPG if they demonstrated a >= 50% reduction in pain during the temporary trial period. Patient-reported outcomes (PROs), such as pain scores, functional disability, mood, patient impression of change, comfort, therapy use profile, and device ease of use, were captured. RESULTS: At baseline, the average pain Visual Analog Scale (VAS) score was 72.1 ± 17.9 in the leg and 78.0 ± 15.4 in the low back. At 90 days following permanent implant (end of study), pain scores improved by 76% (VAS 18.5 ± 18.8) in the leg and 75% (VAS 19.7 ± 20.8) in the low back. Eighty-six percent  of both leg pain and low back pain patients demonstrated a >= 50% reduction in pain at 90 days following implant. The comfort of the external wearable (Therapy Disc and Adhesive Clip) was rated 1.16 ± 1.53, on average, at 90 days on an 11-point rating scale (0 = very comfortable, 10 = very uncomfortable). All PROs demonstrated statistically significant symptomatic improvement at 90 days following implant of the micro-IPG. LIMITATIONS:   Limitations of this study include the lack of long-term results (beyond 90 days) and a relatively small sample size of 35 patients who were part of the analysis; additionally, there was no control arm or randomization as this was a single-arm study, without a comparator, designed to document the efficacy and safety of the device. Therefore, no direct comparisons to other SCS systems were possible. CONCLUSIONS: This clinical study demonstrated profound leg and low back pain relief in terms of overall pain reduction, as well as the proportion of therapy responders. The study patients reported the wearable aspects of the system to be very comfortable.

Early Experience With a Novel Miniaturized Spinal Cord Stimulation System for the Management of Chronic Intractable Pain of the Back and Legs.

INTRODUCTION: A novel, spinal cord stimulation (SCS) system with a battery-free miniaturized implantable pulse generator (IPG) was used in this feasibility study. The system uses an external power source that communicates bidirectionally with the IPG (< 1.5 cm3). Human factors, subject comfort, and effects on low back and leg pain were evaluated in this first-in-human study. MATERIALS AND METHODS: A prospective, multicenter, open-label clinical trial was initiated to evaluate the safety and performance of a novel miniaturized stimulator in the treatment of chronic, intractable leg and low-back pain. Eligible subjects were recruited for the study and gave consent. Subjects who passed the screening/trial phase (defined as ≥ 50% decrease in pain) continued to the long-term implant phase and were followed up at predefined time points after device activation. Interim clinical and usability outcomes were captured and reported at 90 days. RESULTS: Results of 22 subjects who chose a novel pulsed stimulation pattern therapy using the battery-free IPG (< 1.5 cm3) are described here. At 90-days follow-up, the average pain reduction was 79% in the leg (n = 22; p < 0.0001) and 76% in the low back (n = 21; p < 0.0001) compared with baseline. Responder rates (≥ 50% pain relief) at 90 days were 86% in leg pain (19/22) and 81% in low-back pain (17/21). Subjects rated the level of comfort of the external wearable power source to be 0.41 ± 0.73 at 90 days on an 11-point rating scale (0 = very comfortable, 10 = very uncomfortable). DISCUSSION: These interim results from the ongoing study indicate the favorable efficacy and usability of a novel, externally powered, battery-free SCS IPG (< 1.5 cm3) for leg and low-back pain. Study subjects wore the external power source continuously and found it comfortable, and the system provided significant pain relief. These preliminary findings warrant further investigation. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is ACTRN12618001862235.

Effects of Sub-threshold Transcutaneous Auricular Vagus Nerve Stimulation on Cingulate Cortex and Insula Resting-state Functional Connectivity.

Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive alternative to vagus nerve stimulation (VNS) with implantable devices, has shown promise in treating disorders such as depression, migraine, and insomnia. Studies of these disorders with resting-state functional magnetic resonance imaging (MRI) (rsfMRI) have found sustained changes in resting-state functional connectivity (rsFC) in patients treated with low frequency (1-20 Hz) taVNS. A recent study has reported reductions in pain scores in patients with rheumatoid arthritis after a 12-week treatment of high-frequency (20 kHz) sub-threshold taVNS. However, no studies to date have examined the effects of high-frequency sub-threshold taVNS on rsFC. The objective of this study was to determine whether high-frequency sub-threshold taVNS induces changes in rsFC using seed regions from the cingulate cortex and insula, brain regions that play a key role in interoception and processing of pain. With a single-blind placebo-controlled repeated measures experimental design, rsfMRI scans were acquired before and after 15 min of either sub-threshold taVNS treatment or a sham control. Significant taVNS-related changes in functional connections to the cingulate cortex were detected between the anterior cingulate cortex and right superior temporal gyrus and between the midcingulate cortex and right inferior parietal lobule. In addition, significant changes in functional connections to the insula were detected between the posterior insula and right precuneus and between the anterior insula and right cuneus gyrus. These results suggest that high-frequency sub-threshold taVNS can lead to sustained effects on the rsFC of brain regions involved in interoception and processing of pain in a cohort of healthy subjects. This study lays the foundation for future rsfMRI studies of high-frequency sub-threshold taVNS in clinical populations.

Novel spinal cord stimulation system with a Battery-Free micro-implantable pulse generator.

Spinal cord stimulation (SCS) is effective for the treatment of chronic intractable pain of the trunk and limbs. The mechanism of action may be based, at least in part, upon the gate control theory; however, new waveforms may suggest other mechanisms. Although benefits of the SCS technology generally outweigh the complications associated with SCS, some complications such as infection and skin erosion over the implant can result in device removal. Additional reasons for device removal, such as pocket pain and battery depletion, have driven technological innovations including battery-free implants and device miniaturization. The neurostimulation system described here was specifically designed to address complications commonly associated with implantable batteries and/or larger implantable devices. The benefits of the small size are further augmented by a minimally invasive implant procedure. Usability data show that patients found this novel neurostimulation system to be easy to use and comfortable to wear. What is more, clinical data demonstrate that the use of this system provides statistically significant reduction in pain scores with responder rates (defined as ≥50% reduction in pain) of 78% in the low back and 83% in the leg(s). Advances in miniaturization technology arose from the considerable shrinkage of the integrated circuit, with an increase in performance, according to Moore's law (1965). However, commensurate improvements in battery technology have not maintained a similar pace. This has prompted some manufacturers to place the battery outside, against the skin, thereby allowing a massive reduction in the implant volume, with the hopes of fewer device-related complications.

Effects of sub-threshold transcutaneous auricular vagus nerve stimulation on cerebral blood flow.

Transcutaneous auricular vagus nerve stimulation (taVNS) has shown promise as a non-invasive alternative to vagus nerve stimulation (VNS) with implantable devices, which has been used to treat drug-resistant epilepsy and treatment-resistant depression. Prior work has used functional MRI to investigate the brain response to taVNS, and more recent work has also demonstrated potential therapeutic effects of high-frequency sub-threshold taVNS in rheumatoid arthritis. However, no studies to date have measured the effects of high-frequency sub-threshold taVNS on cerebral blood flow (CBF). The objective of this study was to determine whether high-frequency (20 kHz) sub-threshold taVNS induces significant changes in CBF, a promising metric for the assessment of the sustained effects of taVNS. Arterial spin labeling (ASL) MRI scans were performed on 20 healthy subjects in a single-blind placebo-controlled repeated measures experimental design. The ASL scans were performed before and after 15 min of either sub-threshold taVNS treatment or a sham control. taVNS induced significant changes in CBF in the superior posterior cerebellum that were largely localized to bilateral Crus I and Crus II. Post hoc analyses showed that the changes were driven by a treatment-related decrease in CBF. Fifteen minutes of high-frequency sub-threshold taVNS can induce sustained CBF decreases in the bilateral posterior cerebellum in a cohort of healthy subjects. This study lays the foundation for future studies in clinical populations, and also supports the use of ASL measures of CBF for the assessment of the sustained effects of taVNS.

Biplanar X-Ray Methods for Stereotactic Intraoperative Localization in Deep Brain Stimulation Surgery.

BACKGROUND: Efficacy in deep brain stimulation (DBS) is dependent on precise positioning of electrodes within the brain. Intraoperative fluoroscopy, computed tomography (CT), or magnetic resonance imaging are used for stereotactic intraoperative localization (StIL), but the utility of biplanar X-ray has not been evaluated in detail. OBJECTIVE: To determine if analysis of orthogonal biplanar X-rays using graphical analysis (GA), ray tracing (RT), and/or perspective projection (PP) can be utilized for StIL. METHODS: A review of electrode tip positions comparing postoperative CT to X-ray methods was performed for DBS operations containing orthogonal biplanar X-ray with referential spheres and pins. RESULTS: Euclidean (Re) errors for final DBS electrode position on intraoperative X-rays vs postoperative CT using GA, RT, and PP methods averaged 1.58 mm (±0.75), 0.74 mm (±0.45), and 1.07 mm (±0.64), respectively (n = 56). GA was more accurate with a ventriculogram. RT and PP predicted positions that correlated with third ventricular structures on ventriculogram cases. RT was the most stable but required knowledge of the geometric setup. PP was more flexible than RT but required well-distributed reference points. A single case using the O-arm demonstrated Re errors of 0.43 mm and 0.28 mm for RT and PP, respectively. In addition, these techniques could also be used to calculate directional electrode rotation. CONCLUSION: GA, RT, and PP can be employed for precise StIL during DBS using orthogonal biplanar X-ray. These methods may be generalized to other stereotactic procedures or instances of biplanar imaging such as angiograms, radiosurgery, or injection therapeutics.

The generation and propagation of the human alpha rhythm.

The alpha rhythm is the longest-studied brain oscillation and has been theorized to play a key role in cognition. Still, its physiology is poorly understood. In this study, we used microelectrodes and macroelectrodes in surgical epilepsy patients to measure the intracortical and thalamic generators of the alpha rhythm during quiet wakefulness. We first found that alpha in both visual and somatosensory cortex propagates from higher-order to lower-order areas. In posterior cortex, alpha propagates from higher-order anterosuperior areas toward the occipital pole, whereas alpha in somatosensory cortex propagates from associative regions toward primary cortex. Several analyses suggest that this cortical alpha leads pulvinar alpha, complicating prevailing theories of a thalamic pacemaker. Finally, alpha is dominated by currents and firing in supragranular cortical layers. Together, these results suggest that the alpha rhythm likely reflects short-range supragranular feedback, which propagates from higher- to lower-order cortex and cortex to thalamus. These physiological insights suggest how alpha could mediate feedback throughout the thalamocortical system.

Trigeminal and sphenopalatine ganglion stimulation for intractable craniofacial pain--case series and literature review.

INTRODUCTION: Facial pain is often debilitating and can be characterized by a sharp, stabbing, burning, aching, and dysesthetic sensation. Specifically, trigeminal neuropathic pain (TNP), anesthesia dolorosa, and persistent idiopathic facial pain (PIFP) are difficult diseases to treat, can be quite debilitating and an effective, enduring treatment remains elusive. METHODS: We retrospectively reviewed our early experience with stimulation involving the trigeminal and sphenopalatine ganglion stimulation for TNP, anesthesia dolorosa, and PIFP between 2010-2014 to assess the feasibility of implanting at these ganglionic sites. Seven patients received either trigeminal and/or sphenopalatine ganglion stimulation with or without peripheral nerve stimulation, having failed multiple alternative modalities of treatment. The treatments were tailored on the physical location of pain to ensure regional coverage with the stimulation. RESULTS: Fluoroscopy or frameless stereotaxy was utilized to place the sphenopalatine and/or trigeminal ganglion stimulator. All patients were initially trialed before implantation. Trial leads implanted in the pterygopalatine fossa near the sphenopalatine ganglion were implanted via transpterygoid (lateral-medial, infrazygomatic) approach. Trial leads were implanted in the trigeminal ganglion via percutaneous Hartel approach, all of which resulted in masseter contraction. Patients who developed clinically significant pain improvement underwent implantation. The trigeminal ganglion stimulation permanent implants involved placing a grid electrode over Meckel's cave via subtemporal craniotomy, which offered a greater ability to stimulate subdivisions of the trigeminal nerve, without muscular (V3) side effects. Two of the seven overall patients did not respond well to the trial and were not implanted. Five patients reported pain relief with up to 24-month follow-up. Several of the sphenopalatine ganglion stimulation patients had pain relief without any paresthesias. There were no electrode migrations or post-surgical complications. CONCLUSIONS: Refractory facial pain may respond positively to ganglionic forms of stimulation. It appears safe and durable to implant electrodes in the pterygopalatine fossa via a lateral transpterygoid approach. Also, implantation of an electrode grid overlying Meckel's cave appears to be a feasible alternative to the Hartel approach. Further investigation is needed to evaluate the usefulness of these approaches for various facial pain conditions.

Deep brain stimulation for the treatment of severe, medically refractory obsessive-compulsive disorder.

Deep brain stimulation is a rapidly expanding therapy initially designed for the treatment of movement disorders and pain syndromes. The therapy includes implantation of electrodes in specific targets of the brain, delivering programmable small and safe electric impulses, like a pacemaker, that modulates both local and broad neurologic networks. The effects are thought to primarily involve a focus in the brain, probably inhibitory, which then restores a network of neural circuitry. Psychiatric diseases can be refractory and severe, leading to high medical costs, significant morbidity, and even death. Whereas surgery for psychiatric disease used to include destructive procedures, deep brain stimulation allows safe, reversible, and adjustable treatment that can be tailored for each patient. Deep brain stimulation offers new hope for these unfortunate patients, and the preliminary results are promising.

CyberKnife radiosurgery can control recurrent epidermoid cysts of the central nervous system.

Epidermoid cysts of the central nervous system may be difficult to resect and recurrent lesions may be impossible to control with open surgery. We identified three patients with recurrent epidermoids treated with radiosurgery at Stanford. One patient with a middle fossa lesion that had been resected twice in six years, presented with a 4.5 cubic centimeter recurrence and was treated with radiosurgery. Follow-up scans over three years showed no additional growth. Two patients had spinal lesions. One had undergone numerous, unsuccessful procedures in the three years before the radiosurgical treatment and subsequent open resection of a 3.8 cubic centimeter recurrence. His scans remain unremarkable eight years after treatment. The other, with acaudaequina mass, had required five open resections in 11 years. Following the last resection, the residual was treated radiosurgically. The lesion eventually increased in size, but became symptomatic only after seven years. A second course of radiosurgery was delivered. We believe that stereotactic radiosurgery can be safe for some epidermoid cysts of the central nervous system, decreases their growth rate, and may facilitate subsequent open surgery. It should be considered for select individuals with recurrent or unresectable lesions.

Recurrent seizures related to motor cortex stimulator programming.

Objective. Motor cortex stimulation (MCS) is increasingly being utilized for the treatment of intractable pain. While the risks of MCS are relatively low, focal or generalized seizures may be produced during programming of MCS systems. Occasionally, patients may experience seizures hours after programming. In order to understand this phenomenon better, we undertook a retrospective analysis of five patients in whom seizures limited the efficacy of MCS. Methods. A retrospective chart review was performed in five patients who underwent MCS between 2002 and 2006 and who had persistent seizures that limited programming. Results. The initial seizure during programming in these patients occurred at amplitudes of between 4.8 and 6.6 V. Four patients experienced generalized tonic-clonic seizures and one patient experienced focal seizures. Subsequent seizures occurred at amplitudes of between 4.4 and 5.5 V, with a tendency for seizure thresholds to progressively decrease. All five patients experienced at least one seizure occurring many minutes to hours after programming, with no side-effects initially observed once the final settings had been programmed. Four out of five patients were programmed with frequencies documented at between 70 and 90 Hz; documentation on frequency was unavailable for the remaining patient. One patient never achieved adequate pain relief and had the MCS system explanted. Conclusions. Despite the overall safety of MCS for the treatment of chronic pain, seizures during and after programming are a serious risk that should be anticipated. In this group of patients, seizures were associated only with stimulus rates between 70 and 90 Hz. No patient developed chronic epilepsy from the stimulation.

Bilateral subthalamic nucleus deep brain stimulation improves certain aspects of postural control in Parkinson's disease, whereas medication does not.

Postural control requires precise integration of sensory inputs and motor output, but clinical assessments of postural control do not differentiate between these. Previously, we found that this differentiation is important in Parkinson's disease (PD) as there was a dissociated effect of medication versus pallidotomy on sensory aspects of postural instability. In this study, we address several questions that emerged from that work in 28 different patients with PD off and on medication, before and after bilateral subthalamic nucleus deep brain stimulation (B-STN DBS): (1) In a different cohort is there still an unusually large percentage of patients with postural instability in sensory-deprived conditions? (2) Are more specific measures of motor aspects of postural control using dynamic posturography (postural movement velocity [MV] and reaction time [RT]) abnormal in PD as seen clinically using the Postural Instability and Gait Disorder score of the Unified Parkinson's Disease Rating Scale? (3) What is the effect of B-STN DBS versus medication on sensory versus motor aspects of postural instability in PD? The results included (1) substantially more patients (39%) versus controls (5%) exhibited postural instability in conditions of limited sensory feedback; (2) postural MV and postural RT were abnormal off medication preoperatively (N(subset) = 23; P < 0.001 for both); (3) B-STN DBS improved abnormal sensory aspects of postural instability (P < 0.05) and postural MV (P = 0.005), whereas medication did not. Neither B-STN DBS nor medication improved postural RT. For the group as a whole, STN DBS plus medication was better therapy than medication preoperatively for sensory aspects of postural control (P = 0.003).

Improvement in a quantitative measure of bradykinesia after microelectrode recording in patients with Parkinson's disease during deep brain stimulation surgery.

It is widely accepted that patients with Parkinson's disease experience immediate but temporary improvement in motor signs after surgical implantation of subthalamic nucleus (STN) deep brain stimulating electrodes before the electrodes are activated, although this has never been formally studied. Based on anecdotal observations that limb mobility improved just after microelectrode recording (MER) during deep brain stimulation (DBS) procedures, we designed a prospective study to measure upper extremity bradykinesia using a quantitative measure of angular velocity. Measurements were made pre- and post-MER and during intraoperative DBS. Analysis of 98 STN DBS procedures performed on 61 patients showed that MER did not create adverse clinical symptoms despite concerns that MER increases morbidity. Quantitative upper extremity bradykinesia improved after MER alone, and further improvement was seen during intraoperative DBS. Electrophysiological data from each case were then compared to the improvement in bradykinesia post-MER alone and a significant correlation was found between the improvement in arm bradykinesia, the number of passes through the STN with somatosensory driving, and also with the number of arm cells with somatosensory driving in the STN, but not with total number of passes, total number of passes through the STN, or total number of cells with somatosensory driving in the STN. This study demonstrates that there is a significant improvement in upper extremity bradykinesia just after MER, before inserting or activating the DBS electrode in patients with Parkinson's disease who undergo STN DBS.

Intra-operative STN DBS attenuates the prominent beta rhythm in the STN in Parkinson's disease.

Power spectra from local field potentials (LFPs) recorded post-operatively from the deep brain stimulation (DBS) macroelectrode show prominence of the beta rhythm (11-30 Hz) in untreated Parkinson's disease (PD). Dopaminergic medication and movement attenuate this beta band in PD. In this pilot study of six sides in four patients, we recorded LFPs from the DBS electrode in untreated PD patients in the operating room. In all cases, there was a peak in the time-frequency spectrogram in the beta frequency range when the patients were at rest, which was associated with attenuation in the same range with movement. The actual frequency range and the strength of the beta peak varied among cases. In two patients, intra-operative constraints permitted recording of LFPs at rest, before and immediately after subthalamic nucleus (STN) DBS. In both patients we documented that STN DBS caused a significant attenuation in power in the beta band at rest that persisted for 15-25 s after DBS had been turned off (P < 0.01). From one case, our data suggest that the beta rhythm attenuation was most prominent within the STN itself. This study shows for the first time that STN DBS attenuates the power in the prominent beta band recorded in the STN of patients with PD. These pilot findings raise the interesting possibility of using this biomarker for closed loop DBS or neuromodulation.

Quantitative measurements of alternating finger tapping in Parkinson's disease correlate with UPDRS motor disability and reveal the improvement in fine motor control from medication and deep brain stimulation.

The Unified Parkinson's Disease Rating Scale (UPDRS) is the primary outcome measure in most clinical trials of Parkinson's disease (PD) therapeutics. Each subscore of the motor section (UPDRS III) compresses a wide range of motor performance into a coarse-grained scale from 0 to 4; the assessment of performance can also be subjective. Quantitative digitography (QDG) is an objective, quantitative assessment of digital motor control using a computer-interfaced musical keyboard. In this study, we show that the kinematics of a repetitive alternating finger-tapping (RAFT) task using QDG correlate with the UPDRS motor score, particularly with the bradykinesia subscore, in 33 patients with PD. We show that dopaminergic medication and an average of 9.5 months of bilateral subthalamic nucleus deep brain stimulation (B-STN DBS) significantly improve UPDRS and QDG scores but may have different effects on certain kinematic parameters. This study substantiates the use of QDG to measure motor outcome in trials of PD therapeutics and shows that medication and B-STN DBS both improve fine motor control.

Somatotopy in the basal ganglia: experimental and clinical evidence for segregated sensorimotor channels.

Growing experimental and clinical evidence supports the notion that the cortico-basal ganglia-thalamo-cortical loops proceed along parallel circuits linking cortical and subcortical regions subserving the processing of sensorimotor, associative and affective tasks. In particular, there is evidence that a strict topographic segregation is maintained during the processing of sensorimotor information flowing from cortical motor areas to the sensorimotor areas of the basal ganglia. The output from the basal ganglia to the motor thalamus, which projects back to neocortical motor areas, is also organized into topographically segregated channels. This high degree of topographic segregation is demonstrated by the presence of a well-defined somatotopic organization in the sensorimotor areas of the basal ganglia. The presence of body maps in the basal ganglia has become clinically relevant with the increasing use of surgical procedures, such as lesioning or deep brain stimulation, which are selectively aimed at restricted subcortical targets in the sensorimotor loop such as the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi). The ability to ameliorate the motor control dysfunction without producing side effects related to interference with non-motor circuits subserving associative or affective processing requires the ability to target subcortical areas particularly involved in sensorimotor processing (currently achieved only by careful intraoperative microelectrode mapping). The goal of this article is to review current knowledge about the somatotopic segregation of basal ganglia sensorimotor areas and outline in detail what is known about their body maps.

The functional organization of the sensorimotor region of the subthalamic nucleus.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is viewed by many as the ultimate therapy targeting severe advanced stages of Parkinson's disease (PD). A fundamental constituent of the mechanisms underlying the therapeutic effects of DBS is clearly the functional organization of the STN; however, there is limited understanding of the organization of this structure in humans. Data from primates suggest that different domains can be identified in the STN, including a sensorimotor area with a segregated body map, as well as nonmotor areas. Recent clinical studies have used microelectrode recording to investigate the presence of a body map in the sensorimotor STN of PD patients. This paper will review and compare experimental and clinical data regarding the functional organization of the STN and discuss the clinical implications for PD patients undergoing STN DBS.

Asymptomatic transient MRI signal changes after unilateral deep brain stimulation electrode implantation for movement disorder.

Deep brain stimulation (DBS) is an accepted treatment of movement disorders, but little research on tissue changes induced by these devices has been made. We report findings of MRI signal changes in patients with unilateral DBS implantation and no clinically detectable symptoms. A retrospective review of preoperative stereotactic MRI scans for staged placement of second-side DBS was performed in 38 patients to assess the frequency of signal changes along the previously implanted DBS track. No abnormal signal changes were noted in 23 patients (61%). Increased subcortical signals on T2-weighted fast spin echo MRI sequences along the DBS track were noted in 15 patients (39%) and varied from circumferential hyperintensity along the electrode track to significant involvement of the subcortical white matter. The changes were only detected in scans performed within 3 months of DBS implantation (15 of 27 patients). Despite these changes, the patients were totally asymptomatic. The etiology of the changes is unknown but may reflect a transient tissue response to the implantation of the electrode.

Patient-controlled deep brain stimulation can overcome analgesic tolerance.

We report a technique based on patient-controlled stimulation to restore analgesia after development of tolerance to deep brain stimulation (DBS). A 45-year-old female with neurogenic pain after cerebellar stroke underwent DBS implantation in the right ventralis caudalis (VC) thalamus with excellent stimulus-controlled analgesia for 29 months, followed by development of tolerance and loss of analgesia. Analgesia was restored when a stimulation module that allowed patient-controlled stimulation was implanted.