Radiofrequency thalamotomy for tremor produces focused and predictable lesions shown on magnetic resonance images.

Radiofrequency thalamotomy is a neurosurgical management option for medically-refractory tremor. In this observational study, we evaluate the MRI features of the resultant lesion, their temporal dynamics, and how they vary depending on surgical factors. We report on lesion characteristics including size and location, as well as how these vary over time and across different MRI sequences. Data from 12 patients (2 essential tremor, 10 Parkinson's disease) who underwent unilateral radiofrequency thalamotomy for tremor were analysed. Lesion characteristics were compared across five structural sequences. Volumetric analysis of lesion features was performed at early (<5 weeks) and late (>5 months) timepoints by manual segmentation. Lesion location was determined after registration of lesions to standard space. All patients showed tremor improvement (clinical global impressions scale) postoperatively. Chronic side-effects included balance disturbances (n = 4) and worsening mobility due to parkinsonism progression (n = 1). Early lesion features including a necrotic core, cytotoxic oedema and perilesional oedema were best demarcated on T2-weighted sequences. Multiple lesions were associated with greater cytotoxic oedema compared with single lesions (T2-weighted mean volume: 537 ± 112 mm³ versus 302 ± 146 mm³, P = 0.028). Total lesion volume reduced on average by 90% between the early and late scans (T2-weighted mean volume: 918 ± 517 versus 75 ± 50 mm³, t = 3.592, P = 0.023, n = 5), with comparable volumes demonstrated at ∼6 months after surgery. Lesion volumes on susceptibility-weighted images were larger than those of T2-weighted images at later timepoints. Radiofrequency thalamotomy produces focused and predictable lesion imaging characteristics over time. T2-weighted scans distinguish between the early lesion core and oedema characteristics, while lesions may remain more visible on susceptibility-weighted images in the months following surgery. Scanning patients in the immediate postoperative period and then at 6 months is clinically meaningful for understanding the anatomical basis of the transient and permanent effects of thalamotomy.

Clinical neurophysiological interrogation of motor slowing: A critical step towards tuning adaptive deep brain stimulation.

OBJECTIVE: Subthalamic nucleus (STN) beta activity (13-30 Hz) is the most accepted biomarker for adaptive deep brain stimulation (aDBS) for Parkinson's disease (PD). We hypothesize that different frequencies within the beta range may exhibit distinct temporal dynamics and, as a consequence, different relationships to motor slowing and adaptive stimulation patterns. We aim to highlight the need for an objective method to determine the aDBS feedback signal. METHODS: STN LFPs were recorded in 15 PD patients at rest and while performing a cued motor task. The impact of beta bursts on motor performance was assessed for different beta candidate frequencies: the individual frequency strongest associated with motor slowing, the individual beta peak frequency, the frequency most modulated by movement execution, as well as the entire-, low- and high beta band. How these candidate frequencies differed in their bursting dynamics and theoretical aDBS stimulation patterns was further investigated. RESULTS: The individual motor slowing frequency often differs from the individual beta peak or beta-related movement-modulation frequency. Minimal deviations from a selected target frequency as feedback signal for aDBS leads to a substantial drop in the burst overlapping and in the alignment of the theoretical onset of stimulation triggers (to âˆ¼ 75% for 1 Hz, to âˆ¼ 40% for 3 Hz deviation). CONCLUSIONS: Clinical-temporal dynamics within the beta frequency range are highly diverse and deviating from a reference biomarker frequency can result in altered adaptive stimulation patterns. SIGNIFICANCE: A clinical-neurophysiological interrogation could be helpful to determine the patient-specific feedback signal for aDBS.

Neurosurgical interventions for cancer pain.

PURPOSE OF REVIEW: Half of all cancer patients will develop cancer-related pain, and a fifth of these patients will continue to experience pain refractory to maximal pharmacological therapy. This, together with the opioid crisis, has prompted a resurgence in neurosurgical treatments. Neuromodulatory or neuroablative procedures are largely used for various nonmalignant, chronic pain conditions, but there is growing evidence to support their use in cancer pain. This review aims to cover the main neurosurgical treatments that may prove useful in the changing sphere of cancer pain treatment. RECENT FINDINGS: Neuromodulation techniques for pain have largely replaced neuroablation in neurosurgical practice due to the higher risk of inadvertent permanent neurological deficits from the latter. When compared to neuroablative approaches for severe treatment-refractory cancer pain, neuromodulation is more expensive (largely due to implant cost) and requires more follow-up, with greater engagement needed from the health service, the patient and their carers. Furthermore, neuroablation has a more rapid onset of effect. SUMMARY: Neuromodulation techniques for pain have largely replaced neuroablation in neurosurgical practice due to the higher risk of inadvertent permanent neurological deficits from the latter. Whilst this approach is beneficial when treating nonmalignant pain, neuromodulation in patients with pain related to advanced cancer still has a limited role. Neuroablative procedures are less expensive, require less follow-up, and can have a lower burden on health services, patients and their carers.

The aperiodic exponent of subthalamic field potentials reflects excitation/inhibition balance in Parkinsonism.

Periodic features of neural time-series data, such as local field potentials (LFPs), are often quantified using power spectra. While the aperiodic exponent of spectra is typically disregarded, it is nevertheless modulated in a physiologically relevant manner and was recently hypothesised to reflect excitation/inhibition (E/I) balance in neuronal populations. Here, we used a cross-species in vivo electrophysiological approach to test the E/I hypothesis in the context of experimental and idiopathic Parkinsonism. We demonstrate in dopamine-depleted rats that aperiodic exponents and power at 30-100 Hz in subthalamic nucleus (STN) LFPs reflect defined changes in basal ganglia network activity; higher aperiodic exponents tally with lower levels of STN neuron firing and a balance tipped towards inhibition. Using STN-LFPs recorded from awake Parkinson's patients, we show that higher exponents accompany dopaminergic medication and deep brain stimulation (DBS) of STN, consistent with untreated Parkinson's manifesting as reduced inhibition and hyperactivity of STN. These results suggest that the aperiodic exponent of STN-LFPs in Parkinsonism reflects E/I balance and might be a candidate biomarker for adaptive DBS.

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.

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.

Deep Brain Stimulation for Chronic Pain.

Deep brain stimulation (DBS) is a neurosurgical intervention well known for the treatment of movement disorders as well as epilepsy, Tourette syndrome, and obsessive-compulsive disorders. DBS was pioneered in the 1950s, however, as a tool for treating facial pain, phantom limb pain, post-stroke pain, and brachial plexus pain among other disease states. Various anatomic targets exist, including the sensory thalamus (ventral posterior lateral and ventral posterior medial), the periaqueductal gray and periventricular gray matter, and the anterior cingulate cortex.

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.

DyNeuMo Mk-1: Design and pilot validation of an investigational motion-adaptive neurostimulator with integrated chronotherapy.

There is growing interest in using adaptive neuromodulation to provide a more personalized therapy experience that might improve patient outcomes. Current implant technology, however, can be limited in its adaptive algorithm capability. To enable exploration of adaptive algorithms with chronic implants, we designed and validated the 'Picostim DyNeuMo Mk-1' (DyNeuMo Mk-1 for short), a fully-implantable, adaptive research stimulator that titrates stimulation based on circadian rhythms (e.g. sleep, wake) and the patient's movement state (e.g. posture, activity, shock, free-fall). The design leverages off-the-shelf consumer technology that provides inertial sensing with low-power, high reliability, and relatively modest cost. The DyNeuMo Mk-1 system was designed, manufactured and verified using ISO 13485 design controls, including ISO 14971 risk management techniques to ensure patient safety, while enabling novel algorithms. The system was validated for an intended use case in movement disorders under an emergency-device authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA). The algorithm configurability and expanded stimulation parameter space allows for a number of applications to be explored in both central and peripheral applications. Intended applications include adaptive stimulation for movement disorders, synchronizing stimulation with circadian patterns, and reacting to transient inertial events such as posture changes, general activity, and walking. With appropriate design controls in place, first-in-human research trials are now being prepared to explore the utility of automated motion-adaptive algorithms.

Hypothesis: Disrupted Regulation of the Intracranial Vascular and Cerebrospinal Fluid Circulations Causes Nocturia.

Nocturia is a prevalent condition and may result from nocturnal polyuria, whereby overnight urine production is excessive. Anecdotal cases of idiopathic nocturnal polyuria in which cerebrospinal fluid (CSF) disorders were identified suggest a potential mechanism. The skull constrains three circulatory systems: the CSF, interstitial fluid, and vascular supply. For each, fluid dynamics (pressure, volume, and flow) are closely regulated and adapt to changes such as recumbency and circadian variation. Pathologies disrupting this regulation, and thus impairing intracranial fluid dynamics, will place the brain environment at risk. Hence, compensatory responses are needed to maintain safe limits and prevent neurological deficits. We hypothesise that a change in the fluid dynamics for the intracranial CSF, interstitial, or vascular circulation means that positional or circadian changes during sleep trigger compensatory hormonal responses to protect the brain, but these also cause nocturnal polyuria. Natriuretic hormones are candidate mediators for protection against excess intracranial pressure or volume. PATIENT SUMMARY: A need to pass urine during the night, which is called nocturia, may be because of excessive overnight urine production. We propose that changes in fluid dynamics in the brain caused by lying down or daily body rhythms may trigger the release of hormones that could be a factor in nighttime urine production. This hypothesis should be explored in further investigations.

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 Relative Merits of Posterior Surgical Treatments for Multi-Level Degenerative Cervical Myelopathy Remain Uncertain: Findings from a Systematic Review.

OBJECTIVES: To assess the reporting of study design and characteristics in multi-level degenerative cervical myelopathy (DCM) treated by posterior surgical approaches, and perform a comparison of clinical and radiographic outcomes between different approaches. METHODS: A literature search was performed in Embase and MEDLINE between 1995-2019 using a sensitive search string combination. Studies were selected by predefined selection criteria: Full text articles in English, with >10 patients (prospective) or >50 patients (retrospective), reporting outcomes of multi-level DCM treated by posterior surgical approach. RESULTS: A total of 75 studies involving 19,510 patients, conducted worldwide, were identified. Laminoplasty was described in 56 studies (75%), followed by laminectomy with (36%) and without fusion (16%). The majority of studies were conducted in Asia (84%), in the period of 2016-2019 (51%), of which laminoplasty was studied predominantly. Twelve (16%) prospective studies and 63 (84%) retrospective studies were identified. The vast majority of studies were conducted in a single centre (95%) with clear inclusion/exclusion criteria and explicit cause of DCM. Eleven studies (15%) included patients with ossification of the posterior longitudinal ligament exclusively with cohorts of 57 to 252. The clinical and radiographic outcomes were reported with heterogeneity when comparing laminoplasty, laminectomy with and without fusion. CONCLUSIONS: Heterogeneity in the reporting of study and sample characteristics exists, as well as in clinical and radiographic outcomes, with a paucity of studies with a higher level of evidence. Future studies are needed to elucidate the clinical effectiveness of posterior surgical treatments.

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.

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.

Neuromodulation techniques for cancer pain management.

PURPOSE OF REVIEW: Advanced pain management techniques may be indicated in 5-15% of cancer patients. Despite this, a recent review identified that, over the course of 1 year in England, only 458 patients received a procedure intended to provide analgesia and only 30 patients had intrathecal drug delivery (ITDD) devices implanted. This article describes the emerging evidence for ITDD in cancer pain and provides a narrative review of other neuromodulatory techniques (including spinal cord stimulation, peripheral nerve stimulation and acupuncture), approaches that might be employed to address this area of significant unmet clinical need. RECENT FINDINGS: Numerous studies have been published within the last year reporting positive outcomes associated with ITDD in cancer pain management. Neuromodulation represents an important strategy in the management of persistent pain. Whilst the nonmalignant pain evidence-base is rapidly growing, it remains sparse for cancer pain management. The growing cohort of cancer survivors may significantly benefit from neuromodulatory techniques. SUMMARY: ITDD and other neuromodulatory techniques for cancer pain management appear underutilised in the UK and offer the prospect of better treatment for cancer patients with refractory pain or intolerable side-effects from systemic analgesics.

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.