Beta-triggered adaptive deep brain stimulation during reaching movement in Parkinson's disease.

Subthalamic nucleus (STN) beta-triggered adaptive deep brain stimulation (ADBS) has been shown to provide clinical improvement comparable to conventional continuous DBS (CDBS) with less energy delivered to the brain and less stimulation induced side effects. However, several questions remain unanswered. First, there is a normal physiological reduction of STN beta band power just prior to and during voluntary movement. ADBS systems will therefore reduce or cease stimulation during movement in people with Parkinson's disease and could therefore compromise motor performance compared to CDBS. Second, beta power was smoothed and estimated over a time period of 400 ms in most previous ADBS studies, but a shorter smoothing period could have the advantage of being more sensitive to changes in beta power, which could enhance motor performance. In this study, we addressed these two questions by evaluating the effectiveness of STN beta-triggered ADBS using a standard 400 ms and a shorter 200 ms smoothing window during reaching movements. Results from 13 people with Parkinson's disease showed that reducing the smoothing window for quantifying beta did lead to shortened beta burst durations by increasing the number of beta bursts shorter than 200 ms and more frequent switching on/off of the stimulator but had no behavioural effects. Both ADBS and CDBS improved motor performance to an equivalent extent compared to no DBS. Secondary analysis revealed that there were independent effects of a decrease in beta power and an increase in gamma power in predicting faster movement speed, while a decrease in beta event related desynchronization (ERD) predicted quicker movement initiation. CDBS suppressed both beta and gamma more than ADBS, whereas beta ERD was reduced to a similar level during CDBS and ADBS compared with no DBS, which together explained the achieved similar performance improvement in reaching movements during CDBS and ADBS. In addition, ADBS significantly improved tremor compared with no DBS but was not as effective as CDBS. These results suggest that STN beta-triggered ADBS is effective in improving motor performance during reaching movements in people with Parkinson's disease, and that shortening of the smoothing window does not result in any additional behavioural benefit. When developing ADBS systems for Parkinson's disease, it might not be necessary to track very fast beta dynamics; combining beta, gamma, and information from motor decoding might be more beneficial with additional biomarkers needed for optimal treatment of tremor.

Cost-effectiveness of surgery for degenerative cervical myelopathy in the United Kingdom.

PURPOSE: Degenerative cervical myelopathy (DCM) is the commonest cause of adult spinal cord dysfunction worldwide, for which surgery is the mainstay of treatment. At present, there is limited literature on the costs associated with the surgical management of DCM, and none from the United Kingdom (UK). This study aimed to evaluate the cost-effectiveness of DCM surgery within the National Health Service, UK. MATERIALS AND METHODS: Incidence of DCM was identified from the Hospital Episode Statistics (HES) database for a single year using five ICD-10 diagnostic codes to represent DCM. Health Resource Group (HRG) data was used to estimate the mean incremental surgery (treatment) costs compared to non-surgical care, and the incremental effect (quality adjusted life year (QALY) gain) was based on data from a previous study. A cost per QALY value of <£30,000/QALY (GBP) was considered acceptable and cost-effective, as per the National Institute for Health and Clinical Excellence (NICE) guidance. A sensitivity analysis was undertaken (±5%, ±10% and ±20%) to account for variance in both the cost of admission and QALY gain. RESULTS: The total number of admissions for DCM in 2018 was 4,218. Mean age was 62 years, with 54% of admissions being of working age (18-65 years). The overall estimated cost of admissions for DCM was £38,871,534 for the year. The mean incremental (per patient) cost of surgical management of DCM was estimated to be £9,216 (ranged £2,358 to £9,304), with a QALY gain of 0.64, giving an estimated cost per QALY value of £14,399/QALY. Varying the QALY gain by ±20%, resulted in cost/QALY figures between £12,000 (+20%) and £17,999 (-20%). CONCLUSIONS: Surgery is estimated to be a cost-effective treatment of DCM amongst the UK population.

Evoked resonant neural activity in subthalamic local field potentials reflects basal ganglia network dynamics.

Evoked resonant neural activity (ERNA) is induced by subthalamic deep brain stimulation (DBS) and was recently suggested as a marker of lead placement and contact selection in Parkinson's disease. Yet, its underlying mechanisms and how it is modulated by stimulation parameters are unclear. Here, we recorded local field potentials from 27 Parkinson's disease patients, while leads were externalised to scrutinise the ERNA. First, we show that ERNA in the time series waveform and spectrogram likely represent the same activity, which was contested before. Second, our results show that the ERNA has fast and slow dynamics during stimulation, consistent with the synaptic failure hypothesis. Third, we show that ERNA parameters are modulated by different DBS frequencies, intensities, medication states and stimulation modes (continuous DBS vs. adaptive DBS). These results suggest the ERNA might prove useful as a predictor of the best DBS frequency and lowest effective intensity in addition to contact selection. Changes with levodopa and DBS mode suggest that the ERNA may indicate the state of the cortico-basal ganglia circuit making it a putative biomarker to track clinical state in adaptive DBS.

Subthalamic Nucleus Stimulation-Induced Local Field Potential Changes in Dystonia.

BACKGROUND: Subthalamic nucleus (STN) stimulation is an effective treatment for Parkinson's disease and induced local field potential (LFP) changes that have been linked with clinical improvement. STN stimulation has also been used in dystonia although the internal globus pallidus is the standard target where theta power has been suggested as a physiomarker for adaptive stimulation. OBJECTIVE: We aimed to explore if enhanced theta power was also present in STN and if stimulation-induced spectral changes that were previously reported for Parkinson's disease would occur in dystonia. METHODS: We recorded LFPs from 7 patients (12 hemispheres) with isolated craniocervical dystonia whose electrodes were placed such that inferior, middle, and superior contacts covered STN, zona incerta, and thalamus. RESULTS: We did not observe prominent theta power in STN at rest. STN stimulation induced similar spectral changes in dystonia as in Parkinson's disease, such as broadband power suppression, evoked resonant neural activity (ERNA), finely-tuned gamma oscillations, and an increase in aperiodic exponents in STN-LFPs. Both power suppression and ERNA localize to STN. Based on this, single-pulse STN stimulation elicits evoked neural activities with largest amplitudes in STN, which are relayed to the zona incerta and thalamus with changing characteristics as the distance from STN increases. CONCLUSIONS: Our results show that STN stimulation-induced spectral changes are a nondisease-specific response to high-frequency stimulation, which can serve as placement markers for STN. This broadens the scope of STN stimulation and makes it an option for other disorders with excessive oscillatory peaks in STN. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Pain in Parkinson's disease and the role of the subthalamic nucleus.

Pain is a frequent and poorly treated symptom of Parkinson's disease, mainly due to scarce knowledge of its basic mechanisms. In Parkinson's disease, deep brain stimulation of the subthalamic nucleus is a successful treatment of motor symptoms, but also might be effective in treating pain. However, it has been unclear which type of pain may benefit and how neurostimulation of the subthalamic nucleus might interfere with pain processing in Parkinson's disease. We hypothesized that the subthalamic nucleus may be an effective access point for modulation of neural systems subserving pain perception and processing in Parkinson's disease. To explore this, we discuss data from human neurophysiological and psychophysical investigations. We review studies demonstrating the clinical efficacy of deep brain stimulation of the subthalamic nucleus for pain relief in Parkinson's disease. Finally, we present some of the key insights from investigations in animal models, healthy humans and Parkinson's disease patients into the aberrant neurobiology of pain processing and consider their implications for the pain-relieving effects of subthalamic nucleus neuromodulation. The evidence from clinical and experimental studies supports the hypothesis that altered central processing is critical for pain generation in Parkinson's disease and that the subthalamic nucleus is a key structure in pain perception and modulation. Future preclinical and clinical research should consider the subthalamic nucleus as an entry point to modulate different types of pain, not only in Parkinson's disease but also in other neurological conditions associated with abnormal pain processing.

No Adverse Effects following Off-Label Magnetic Resonance Imaging in a Patient with Two Deep Brain Stimulation Systems: A Case Report.

Magnetic resonance imaging (MRI) in patients with implanted deep brain stimulation (DBS) systems is subject to strict guidelines in order to ensure patient safety. Criteria include limits on the number of implanted leads. Here, we describe the case of a 29-year-old patient with generalized dystonia implanted with 4 DBS electrodes and 2 implantable pulse generators, who had an off-label spinal MRI without regard for manufacturer guidance yet suffered no adverse effects. This suggests that manufacturer guidelines might be overly restrictive with regards to limits on implanted DBS hardware. Further research in this area is needed to widen access to this fundamental imaging modality for patients with DBS.

Hospitalisation for degenerative cervical myelopathy in England: insights from the National Health Service Hospital Episode Statistics 2012 to 2019.

PURPOSE: Degenerative cervical myelopathy (DCM) is the most common cause of adult spinal cord dysfunction worldwide. However, the current incidence of DCM is poorly understood. The Hospital Episode Statistics (HES) database contains details of all secondary care admissions across NHS hospitals in England. This study aimed to use HES data to characterise surgical activity for DCM in England. METHODS: The HES database was interrogated for all cases of DCM between 2012 and 2019. DCM cases were identified from 5 ICD-10 codes. Age-stratified values were collected for 'Finished Consultant Episodes' (FCEs), which correspond to a patient's hospital admission under a lead clinician. Data was analysed to explore current annual activity and longitudinal change. RESULTS: 34,903 FCEs with one or more of the five ICD-10 codes were identified, of which 18,733 (53.6%) were of working age (18-64 years). Mean incidence of DCM was 7.44 per 100,000 (SD ± 0.32). Overall incidence of DCM rose from 6.94 per 100,000 in 2012-2013 to 7.54 per 100,000 in 2018-2019. The highest incidence was seen in 2016-2017 (7.94 per 100,000). The median male number of FCEs per year (2919, IQR: 228) was consistently higher than the median female number of FCEs per year (2216, IQR: 326). The rates of both emergency admissions and planned admissions are rising. CONCLUSIONS: The incidence of hospitalisation for DCM in England is rising. Health care policymakers and providers must recognise the increasing burden of DCM and act to address both early diagnoses and access to treatment in future service provision plans.

Why are neurosurgeons sued? A single-center, half-decade review.

Purpose:The burden of medicolegal claims in neurosurgery is increasing in the UK. Trepidation associated with malpractice claims has the potential to negatively impact surgical practice and patient safety. What are the causes of these claims and can we address them? The aim of this study was to identify the incidence and total burden of litigation claims related to neurosurgery in a London tertiary center.Methods:We retrospectively reviewed all consecutive cases of claims in neurosurgery that were reported to NHSR between March 2013 and April 2018 by St George's Hospital legal department. This was an extension of previous study by Mukherjee et al., who studied the medicolegal claims in our institution in the preceding 9-year period (2004-2013).Results:There were 18 litigation claims against neurosurgery. Claims were reviewed for clinical event, cause, likelihood of pay-out and legal outcome. Eleven claims were settled in court and seven were settled without court proceeding. All claims were spinal cases, 56% emergency admissions. Causes included faulty surgical technique (39%), delayed treatment (33%), delayed diagnosis/misdiagnosis (17%), and lack of information (11%) with a likelihood of financial success of 43%, 67%, 33%, and 100%, respectively. The highest median pay-outs were for lack of information (£2.8 million) and faulty surgical technique (£1 million). When compared to the preceding 9-year period, there a modest reduction in claims per year, despite an increase in workload. Distribution of litigation causes remained similar but overall financial burden was higher.Conclusion:Spinal surgery has the highest malpractice claim risk in neurosurgical practice. Our review shows that faulty surgical technique is the leading cause of neurosurgical claims. Claims against lack of information, although less frequent, resulted in the highest median pay-out. This study reinforces previously published data that good surgical technique and thorough process of informed consent may reduce litigation in neurosurgery.

The Cumulative Effect of Transient Synchrony States on Motor Performance in Parkinson's Disease.

Bursts of beta frequency band activity in the basal ganglia of patients with Parkinson's disease (PD) are associated with impaired motor performance. Here we test in human adults whether small variations in the timing of movement relative to beta bursts have a critical effect on movement velocity and whether the cumulative effects of multiple beta bursts, both locally and across networks, matter. We recorded local field potentials from the subthalamic nucleus (STN) in 15 PD patients of both genders OFF-medication, during temporary lead externalization after deep brain stimulation surgery. Beta bursts were defined as periods exceeding the 75th percentile amplitude threshold. Subjects performed a visual cued joystick reaching task, with the visual cue being triggered in real time with different temporal relationships to bursts of STN beta activity. The velocity of actions made in response to cues prospectively triggered by STN beta bursts was slower than when responses were not time-locked to recent beta bursts. Importantly, slow movements were those that followed multiple bursts close to each other within a trial. In contrast, small differences in the delay between the last burst and movement onset had no significant impact on velocity. Moreover, when the overlap of bursts between the two STN was high, slowing was more pronounced. Our findings suggest that the cumulative, but recent, history of beta bursting, both locally and across basal ganglia networks, may impact on motor performance.SIGNIFICANCE STATEMENT Bursts of beta frequency band activity in the basal ganglia are associated with slowing of voluntary movement in patients with Parkinson's disease. We show that slow movements are those that follow multiple bursts close to each other and bursts that are coupled across regions. These results suggest that the cumulative, but recent, history of beta bursting, both locally and across basal ganglia networks, impacts on motor performance in this condition. The manipulation of burst dynamics may be a means of selectively improving motor impairment.

Closed-Loop Deep Brain Stimulation for Essential Tremor Based on Thalamic Local Field Potentials.

BACKGROUND: High-frequency thalamic stimulation is an effective therapy for essential tremor, which mainly affects voluntary movements and/or sustained postures. However, continuous stimulation may deliver unnecessary current to the brain due to the intermittent nature of the tremor. OBJECTIVE: We proposed to close the loop of thalamic stimulation by detecting tremor-provoking movement states using local field potentials recorded from the same electrodes implanted for stimulation, so that the stimulation is only delivered when necessary. METHODS: Eight patients with essential tremor participated in this study. Patient-specific support vector machine classifiers were first trained using data recorded while the patient performed tremor-provoking movements. Then, the trained models were applied in real-time to detect these movements and triggered the delivery of stimulation. RESULTS: Using the proposed method, stimulation was switched on for 80.37 ± 7.06% of the time when tremor-evoking movements were present. In comparison, the stimulation was switched on for 12.71 ± 7.06% of the time when the patients were at rest and tremor-free. Compared with continuous stimulation, a similar amount of tremor suppression was achieved while only delivering 36.62 ± 13.49% of the energy used in continuous stimulation. CONCLUSIONS: The results suggest that responsive thalamic stimulation for essential tremor based on tremor-provoking movement detection can be achieved without any requirement for external sensors or additional electrocorticography strips. Further research is required to investigate whether the decoding model is stable across time and generalizable to the variety of activities patients may engage with in everyday life. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Neurophysiological Correlates of Trait Impulsivity in Parkinson's Disease.

BACKGROUND: Impulsivity is common in people with Parkinson's disease (PD), with many developing impulsive compulsive behavior disorders (ICB). Its pathophysiological basis remains unclear. OBJECTIVES: We aimed to investigate local field potential (LFP) markers of trait impulsivity in PD and their relationship to ICB. METHODS: We recorded subthalamic nucleus (STN) LFPs in 23 PD patients undergoing deep brain stimulation implantation. Presence and severity of ICB were assessed by clinical interview and the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS), whereas trait impulsivity was estimated with the Barratt Impulsivity Scale (BIS-11). Recordings were obtained during the off dopaminergic states and the power spectrum of the subthalamic activity was analyzed using Fourier transform-based techniques. Assessment of each electrode contact localization was done to determine the topography of the oscillatory activity recorded. RESULTS: Patients with (n = 6) and without (n = 17) ICB had similar LFP spectra. A multiple regression model including QUIP-RS, BIS-11, and Unified PD Rating Scale-III scores as regressors showed a significant positive correlation between 8-13 Hz power and BIS-11 score. The correlation was mainly driven by the motor factor of the BIS-11, and was irrespective of the presence or absence of active ICB. Electrode contact pairs with the highest α power, which also correlated most strongly with BIS-11, tended to be more ventral than contact pairs with the highest beta power, which localize to the dorsolateral motor STN. CONCLUSIONS: Our data suggest a link between α power and trait impulsivity in PD, irrespective of the presence and severity of ICB. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Postoperative Externalization of Deep Brain Stimulation Leads Does Not Increase Infection Risk.

OBJECTIVES: Externalization of deep brain stimulation (DBS) leads is performed to allow electrophysiological recording from implanted electrodes as well as assessment of clinical response to trial stimulation before implantable pulse generator (IPG) insertion. Hypothetically, lead externalization provides a route for inoculation and subsequent infection of hardware, though this has not been established definitively in the literature. We sought to determine if lead externalization affects the risk of infection in DBS surgery. MATERIALS AND METHODS: We present our center's experience of lead externalization and surgical site infection (SSI) in DBS surgery for movement disorders. Patients were divided into two cohorts: one in which leads were not externalized and IPGs were implanted at the time of electrode insertion, and one in which leads were externalized for six days while patients underwent electrophysiological recording from DBS electrodes for research. We compare baseline characteristics of these two cohorts and their SSI rates. RESULTS: Infective complications were experienced by 3/82 (3.7%) patients overall with one (1.2%) requiring complete hardware removal. These occurred in 1/36 (2.7%) in the externalized cohort and 2/46 (4.3%) in the nonexternalized cohort. The incidence of infection between the two cohorts was not significantly different (p = 1, two-tailed Fisher's exact test). This lack of significant difference persisted when baseline variation between the cohorts in age, hardware manufacturer, and indication for DBS were corrected by excluding patients implanted for dystonia, none of whom underwent externalization. We present and discuss in detail each of the three cases of infection. CONCLUSIONS: Our data suggest that externalization of leads does not increase the risk of infective complications in DBS surgery. Lead externalization is a safe procedure which can provide a substrate for unique neurophysiological studies to advance knowledge and therapy of disorders treated with DBS.

Spondylodiscitis following endovascular abdominal aortic aneurysm repair: imaging perspectives from a single centre's experience.

OBJECTIVE: Very few reports have previously described spondylodiscitis as a potential complication of endovascular aortic aneurysm repair (EVAR). We present to our knowledge the first case series of spondylodiscitis following EVAR based on our institution's experience over an 11-year period. Particular attention is paid to the key imaging features and challenges encountered when performing spinal imaging in this complex patient group. MATERIALS AND METHODS: Of 1,847 patients who underwent EVAR at our institution between January 2006 and January 2017, a total of 9 patients were identified with imaging features of spondylodiscitis (0.5%). All cross-sectional studies before and after EVAR were assessed by a Consultant Musculoskeletal Radiologist and a Musculoskeletal Radiology Fellow to evaluate for features of spondylodiscitis. RESULTS: All 9 patients had single-level spondylodiscitis involving lumbosacral levels adjacent to the aortic/iliac stent graft. Eight out of nine patients had an extensive anterior paravertebral phlegmon/abscess that was contiguous with the infected stent graft and native aneurysm sac ± anterior vertebral body erosion. Epidural disease was present in only 3 out of 9 patients and was a minor feature. MRI was non-diagnostic in 3 out of 9 patients owing to susceptibility artefact. 18F-FDG PET/CT accurately depicted the spinal level involved and adjacent paravertebral disease in patients with non-diagnostic MRI and was adopted as the follow-up modality in 3 out of 5 surviving patients. CONCLUSION: Spondylodiscitis is a rare complication post-EVAR. Imaging features of disproportionate anterior paravertebral disease and anterior vertebral body bony involvement suggest direct spread of infection posteriorly to the adjacent vertebral column. Use of MRI versus 18F-FDG PET/CT as the optimal imaging modality should be directed by the type of stent graft deployed.

High field structural MRI in the management of degenerative cervical myelopathy.

Introduction: This is a narrative overview of the pathophysiology, investigation and management of Degenerative Cervical Myelopathy (DCM). This review article also takes a look ahead to the impact high resolution MRI may have on treatment.Background: DCM is the most common cause of spinal dysfunction and yet it remains poorly understood. It is becoming increasingly common in our ageing population. Disc and facet joint abnormalities, osteophytes, spondylothisthesis and ligamentous hypertrophy all act together to produce spinal canal and neuronal foramina stenosis which in turn causes neural compromise. Its impact on the quality of life of this patient group and the wider economy is vast. Some patients with overt cord compression and MRI signal change in their cervical cord may only have subtle clinical signs whilst others with less striking imaging may be profoundly myelopathic. Who to operate on and when remains a neurosurgical dilemma in this group of patients.Methods: A number of articles with a broad variation in methodology were reviewed and referenced during the production of this paper.Results: This paper is a narrative review. The results presented in all the referenced articles were considered.Conclusion: The process of developing new imaging techniques will give a greater understanding of the causes of the symptoms of DCM and in a wider context facilitate further surgical and medical strategies that are more cost effective and beneficial to patients. The advent of 7T MRI or further optimisation of safer 3T MRI sequences may soon provide this opportunity and the diagnostic gap in spinal cord imaging can begin to close.

Consent: an event or a memory in lumbar spinal surgery? A multi-centre, multi-specialty prospective study of documentation and patient recall of consent content.

STUDY DESIGN: Prospective, multi-centre, multi-specialty medical notes review and patient interview. PURPOSE: The consenting process is an important communication tool which also carries medico-legal implications. While written consent is a pre-requisite before spinal surgery in the UK, the standard and effectiveness of the process have not been assessed previously. This study assesses standard of written consent for elective lumbar decompressive surgery for degenerative disc disease across different regions and specialties in the UK; level of patient recall of the consent content; and identifies factors which affect patient recall. METHODS: Consent forms of 153 in-patients from 4 centres a, b, c, d were reviewed. Written documentation of intended benefits, alternative treatments and operative risks was assessed. Of them, 108 patients were interviewed within 24 h before or after surgeries to assess recall. RESULTS: The written documentation rates of the operative risks showed significant inter-centre variations in haemorrhage and sphincter disturbance (P = 0.000), but not for others. Analysis of pooled data showed variations in written documentation of risks (P < 0.0005), highest in infection (96.1%) and lowest in recurrence (52.3%). For patient recall of these risks, there was no inter-centre variation. Patients' recall of paralysis as a risk was highest (50.9%) and that of recurrence was lowest (6.5%). Patients <65 years old recalled risks better than those ≥65, significantly so for infection (29.9 vs 9.7%, P = 0.027). Patients consented >14 days compared to <2 days before their surgeries had higher recall for paralysis (65.2 vs 43.7%) and recurrence (17.4 vs 2.8%). Patient recall was independent of consenter grade. CONCLUSION: Overall, the standard of written consent for elective lumbar spinal decompressive surgery was sub-optimal, which was partly reflected in the poor patient recall. While consenter seniority did not affect patient recall, younger age and longer consent-to-surgery time improved it.

Routine radiographs one day after anterior cervical discectomy and fusion are neither necessary nor cost-effective.

OBJECTIVES: Anterior cervical discectomy and fusion (ACDF) is a common operative treatment of compressive pathology of the cervical spinal cord, when caused by one or more degenerated intervertebral discs or related osteophytes. In addition to intra-operative radiographs to confirm spinal level before discectomy and implant position after insertion, traditional practice is to obtain post-operative antero-posterior and lateral plain radiographs (XR) before hospital discharge, despite a paucity of evidence supporting their benefit to patient care. Minimising unnecessary radiation to radiosensitive neck structures is desirable, and furthermore, with increasing financial pressure on healthcare resources, routine investigations should be clinically justified and evidence-based. We aim to compare the utility of routine post-operative cervical spine X-rays following ACDF. METHODS: We compare two groups of consecutive patients undergoing ACDF in a single UK neurosurgical centre. The first group (n = 109) received routine post-operative XR imaging, and the second group (n = 113) received radiographs only when clinically indicated. RESULTS: There were no differences in post-operative complication rates (4.6% vs. 5.3%), or requirement for further imaging or of further operative intervention (1.8% vs. 0.9%). The group that did not have routine post-operative radiographs had a significantly shorter stay in hospital (median two days vs. three days). There were no patients in either group where post-operative XR changed clinical management and mandated revision surgery or further imaging. All cases requiring surgery or further imaging were identified by clinical deterioration. CONCLUSIONS: We suggest that the practice of obtaining routine radiographs of the cervical spine following ACDF should be abandoned, unless there is a clear clinical indication.

Thalamic Deep Brain Stimulation for Neuropathic Pain: Efficacy at Three Years' Follow-Up.

OBJECT: Chronic neuropathic pain is estimated to affect 3-4.5% of the worldwide population, posing a serious burden to society. Deep Brain Stimulation (DBS) is already established for movement disorders and also used to treat some "off-label" conditions. However, DBS for the treatment of chronic, drug refractory, neuropathic pain, has shown variable outcomes with few studies performed in the last decade. Thus, this procedure has consensus approval in parts of Europe but not the USA. This study prospectively evaluated the efficacy at three years of DBS for neuropathic pain. METHODS: Sixteen consecutive patients received 36 months post-surgical follow-up in a single-center. Six had phantom limb pain after amputation and ten deafferentation pain after brachial plexus injury, all due to traumas. To evaluate the efficacy of DBS, patient-reported outcome measures were collated before and after surgery, using a visual analog scale (VAS) score, University of Washington Neuropathic Pain Score (UWNPS), Brief Pain Inventory (BPI), and 36-Item Short-Form Health Survey (SF-36). RESULTS: Contralateral, ventroposterolateral sensory thalamic DBS was performed in sixteen patients with chronic neuropathic pain over 29 months. A postoperative trial of externalized DBS failed in one patient with brachial plexus injury. Fifteen patients proceeded to implantation but one patient with phantom limb pain after amputation was lost for follow-up after 12 months. No surgical complications or stimulation side effects were noted. After 36 months, mean pain relief was sustained, and the median (and interquartile range) of the improvement of VAS score was 52.8% (45.4%) (p = 0.00021), UWNPS was 30.7% (49.2%) (p = 0.0590), BPI was 55.0% (32.0%) (p = 0.00737), and SF-36 was 16.3% (30.3%) (p = 0.4754). CONCLUSIONS: DBS demonstrated efficacy at three years for chronic neuropathic pain after traumatic amputation and brachial plexus injury, with benefits sustained across all pain outcomes measures and slightly greater improvement in phantom limb pain.

Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Techniques, Side Effects, and Postoperative Imaging.

The pedunculopontine nucleus (PPN) region has received considerable attention in clinical studies as a target for deep brain stimulation (DBS) in Parkinson disease. These studies have yielded variable results with an overall impression of improvement in falls and freezing in many but not all patients treated. We evaluated the available data on the surgical anatomy and terminology of the PPN region in a companion paper. Here we focus on issues concerning surgical technique, imaging, and early side effects of surgery. The aim of this paper was to gain more insight into the reasoning for choosing specific techniques and to discuss shortcomings of available studies. Our data demonstrate the wide range in almost all fields which were investigated. There are a number of important challenges to be resolved, such as identification of the optimal target, the choice of the surgical approach to optimize electrode placement, the impact on the outcome of specific surgical techniques, the reliability of intraoperative confirmation of the target, and methodological differences in postoperative validation of the electrode position. There is considerable variability both within and across groups, the overall experience with PPN DBS is still limited, and there is a lack of controlled trials. Despite these challenges, the procedure seems to provide benefit to selected patients and appears to be relatively safe. One important limitation in comparing studies from different centers and analyzing outcomes is the great variability in targeting and surgical techniques, as shown in our paper. The challenges we identified will be of relevance when designing future studies to better address several controversial issues. We hope that the data we accumulated may facilitate the development of surgical protocols for PPN DBS.

Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Anatomy and Terminology.

Several lines of evidence over the last few years have been important in ascertaining that the pedunculopontine nucleus (PPN) region could be considered as a potential target for deep brain stimulation (DBS) to treat freezing and other problems as part of a spectrum of gait disorders in Parkinson disease and other akinetic movement disorders. Since the introduction of PPN DBS, a variety of clinical studies have been published. Most indicate improvements in freezing and falls in patients who are severely affected by these problems. The results across patients, however, have been variable, perhaps reflecting patient selection, heterogeneity in target selection and differences in surgical methodology and stimulation settings. Here we outline both the accumulated knowledge and the domains of uncertainty in surgical anatomy and terminology. Specific topics were assigned to groups of experts, and this work was accumulated and reviewed by the executive committee of the working group. Areas of disagreement were discussed and modified accordingly until a consensus could be reached. We demonstrate that both the anatomy and the functional role of the PPN region need further study. The borders of the PPN and of adjacent nuclei differ when different brainstem atlases and atlas slices are compared. It is difficult to delineate precisely the PPN pars dissipata from the nucleus cuneiformis, as these structures partially overlap. This lack of clarity contributes to the difficulty in targeting and determining the exact localization of the electrodes implanted in patients with akinetic gait disorders. Future clinical studies need to consider these issues.