What Have We Learned About Movement Disorders from Functional Neurosurgery?

Modern functional neurosurgery for movement disorders such as Parkinson's disease, tremor, and dystonia involves the placement of focal lesions or the application of deep brain stimulation (DBS) within circuits that modulate motor function. Precise targeting of these motor structures can be further refined by the use of electrophysiological approaches. In particular, microelectrode recordings enable the delineation of neuroanatomic structures. In the course of these operations, there is an opportunity not only to map basal ganglia structures but also to gain insights into how disturbances in neural activity produce movement disorders. In this review, we aim to highlight what the field has uncovered thus far about movement disorders through DBS. The work to date lays the foundation for future studies that will shed further light on dysfunctional circuits mediating diseases of the nervous system and how we might modulate these circuits therapeutically.

Left Vagus Stimulation Modulates Contralateral Subthalamic ß Power Improving the Gait in Parkinson's Disease.

BACKGROUND: Transcutaneous vagus nerve stimulation (VNS) showed early evidence of efficacy for the gait treatment of Parkinson's disease (PD). OBJECTIVES: Providing data on neurophysiological and clinical effects of transauricular VNS (taVNS). METHODS: Ten patients with recording deep brain stimulation (DBS) have been enrolled in a within participant design pilot study, double-blind crossover sham-controlled trial of taVNS. Subthalamic local field potentials (ß band power), Unified Parkinson's Disease Rating Scales (UPDRS), and a digital timed-up-and-go test (TUG) were measured and compared with real versus sham taVNS during medication-off/DBS-OFF condition. RESULTS: The left taVNS induced a reduction of the total ß power in the contralateral (ie, right) subthalamic nucleus and an improvement of TUG time, speed, and variability. The taVNS-induced ß reduction correlated with the improvement of gait speed. No major clinical changes were observed at UPDRS. CONCLUSIONS: taVNS is a promising strategy for the management of PD gait, deserving prospective trials of chronic neuromodulation. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cognitive Enhancement as Transformative Experience: The Challenge of Wrapping One's Mind Around Enhanced Cognition via Neurostimulation.

In this paper, the authors explore the question of whether cognitive enhancement via direct neurostimulation, such as through deep brain stimulation, could be reasonably characterized as a form of transformative experience. This question is inspired by a qualitative study being conducted with people at risk of developing dementia and in intimate relationships with people living with dementia (PLWD). They apply L.A. Paul's work on transformative experience to the question of cognitive enhancement and explore potential limitations on the kind of claims that can legitimately be made about individual well-being and flourishing, as well as limit the kind of empirical work-including the authors' own-that can hope to enlighten ethical discourse. In this paper, the authors advance the following theses: (1) it is sometimes reasonable to characterize cognitive enhancement as a transformative experience; (2) the testimonies of people intimately acquainted with dementia may still be relevant to evaluating cognitive enhancement even though cognitive enhancement may be a transformative experience; and (3) qualitative studies may still be useful in the ethical analysis of cognitive enhancement, but special attention may need to be given to how these are conducted and what kind of insights can be drawn from them.

Reduction of aggressive behaviour following hypothalamic deep brain stimulation: Involvement of 5-HT1A and testosterone.

BACKGROUND: Aggressive behaviour (AB) may occur in patients with different neuropsychiatric disorders. Although most patients respond to conventional treatments, a small percentage continue to experience AB despite optimized pharmacological management and are considered to be treatment-refractory. For these patients, hypothalamic deep brain stimulation (pHyp-DBS) has been investigated. The hypothalamus is a key structure in the neurocircuitry of AB. An imbalance between serotonin (5-HT) and steroid hormones seems to exacerbate AB. OBJECTIVES: To test whether pHyp-DBS reduces aggressive behaviour in mice through mechanisms involving testosterone and 5-HT. METHODS: Male mice were housed with females for two weeks. These resident animals become territorial and aggressive towards intruder mice placed in their cages. Residents had electrodes implanted in the pHyp. DBS was administered for 5 h/day for 8 consecutive encounters prior to the interaction with the intruder. After testing, blood and brains were recovered for measuring testosterone and 5-HT receptor density, respectively. In a second experiment, residents received WAY-100635 (5-HT1A antagonist) or saline injections prior to pHyp-DBS. After the first 4 encounters, the injection allocation was crossed, and animals received the alternative treatment during the next 4 encounters. RESULTS: DBS-treated mice showed reduced AB that was correlated with testosterone levels and an increase in 5-HT1A receptor density in the orbitofrontal cortex and amygdala. Pre-treatment with WAY-100635 blocked the anti-aggressive effect of pHyp-DBS. CONCLUSIONS: This study shows that pHyp-DBS reduces AB in mice via changes in testosterone and 5-HT1A mechanisms.

Deep Brain Stimulation in Parkinson Disease: A Meta-analysis of the Long-term Neuropsychological Outcomes.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidum internus (GPi) improves motor functions in patients with Parkinson's disease (PD) but may cause a decline in specific cognitive domains. The aim of this systematic review and meta-analysis was to assess the long-term (1-3 years) effects of STN or GPi DBS on four cognitive functions: (i) memory (delayed recall, working memory, immediate recall), (ii) executive functions including inhibition control (Color-Word Stroop test) and flexibility (phonemic verbal fluency), (iii) language (semantic verbal fluency), and (iv) mood (anxiety and depression). Medline and Web of Science were searched, and studies published before July 2021 investigating long-term changes in PD patients following DBS were included. Random-effects model meta-analyses were performed using the R software to estimate the standardized mean difference (SMD) computed as Hedges' g with 95% CI. 2522 publications were identified, 48 of which satisfied the inclusion criteria. Fourteen meta-analyses were performed including 2039 adults with a clinical diagnosis of PD undergoing DBS surgery and 271 PD controls. Our findings add new information to the existing literature by demonstrating that, at a long follow-up interval (1-3 years), both positive effects, such as a mild improvement in anxiety and depression (STN, Hedges' g = 0,34, p = 0,02), and negative effects, such as a decrease of long-term memory (Hedges' g = -0,40, p = 0,02), verbal fluency such as phonemic fluency (Hedges' g = -0,56, p < 0,0001), and specific subdomains of executive functions such as Color-Word Stroop test (Hedges' g = -0,45, p = 0,003) were observed. The level of evidence as qualified with GRADE varied from low for the pre- verses post-analysis to medium when compared to a control group.

Is punishment backward? On neurointerventions and forward-looking moral responsibility.

This article focuses on justified responses to "immoral" behavior and crimes committed by patients undergoing neuromodulation therapies. Such patients could be held morally responsible in the basic desert sense-the one that serves as a justification of severe practices such as backward-looking moral outrage, condemnation, and legal punishment-as long as they possess certain compatibilist capabilities that have traditionally served as the quintessence of free will, that is, reasons-responsiveness; attributability; answerability; the abilities to act in accordance with moral reasons, second-order volitions, or Deep Self. Recently leading compatibilist neuroethicists added the condition of not feeling alienated from desires motivating a person's action. This article argues against such attempts to determine conditions under which patients undergoing neuromodulation should be subject to negative reactive attitudes and legal punishment. Compatibilism should not be used to justify basic desert moral responsibility and legal punishment. Instead, a new way of thinking about the function of moral responsibility attribution is proposed for patients with neuromodulation. Their compatibilist capabilities should serve as important indicators for determining appropriate, forward-looking courses of action, such as quarantining and restorative treatment, to ensure the public safety and well-being of the patients.

Deep brain stimulation in the ALIC-BNST region targeting the bed nucleus of stria terminalis in patients with obsessive-compulsive disorder: effects on cognition after 12 months.

PURPOSE: The aim of this study was to evaluate cognitive effects 12 months after Deep Brain Stimulation (DBS) of the Bed Nucleus of Stria Terminalis (BNST) in patients with refractory Obsessive-Compulsive Disorder (OCD). METHODS: Eight patients (5 female; mean ± SD age 36 ± 15) with OCD were included. A neuropsychological test battery covering verbal and spatial episodic memory, executive function, and attention was administered preoperatively and 12 months after surgery. Medical records were used as a source for descriptive data to probe for any changes not covered by standardized checklists and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the primary outcome measure. RESULTS: At 12 months, seven patients showed response to DBS: three were full responders (i.e., Y-BOCS ≥ 35% improvement), and four were partial responders (Y-BOCS 25-34% improvement). Relative to baseline, there was a slight decline on visuo-spatial learning (p = 0.027), and improved performance on the Color-Word Interference inhibition/switching subtest (p = 0.041), suggesting improvement in cognitive flexibility. CONCLUSIONS: DBS in the BNST for treatment refractory OCD generates very few adverse cognitive effects and improves cognitive flexibility after 12 months of stimulation. The improvement in Y-BOCS and the absence of major cognitive side effects support the BNST as a potential target for DBS in severe OCD.

Intraoperative Local Field Potential Beta Power and Three-Dimensional Neuroimaging Mapping Predict Long-Term Clinical Response to Deep Brain Stimulation in Parkinson Disease: A Retrospective Study.

BACKGROUND: Directional deep brain stimulation (DBS) leads allow a fine-tuning control of the stimulation field, however, this new technology could increase the DBS programming time because of the higher number of the possible combinations used in directional DBS than in standard nondirectional electrodes. Neuroimaging leads localization techniques and local field potentials (LFPs) recorded from DBS electrodes implanted in basal ganglia are among the most studied biomarkers for DBS programing. OBJECTIVE: This study aimed to evaluate whether intraoperative LFPs beta power and neuroimaging reconstructions correlate with contact selection in clinical programming of DBS in patients with Parkinson disease (PD). MATERIALS AND METHODS: In this retrospective study, routine intraoperative LFPs recorded from all contacts in the subthalamic nucleus (STN) of 14 patients with PD were analyzed to calculate the beta band power for each contact. Neuroimaging reconstruction obtained through Brainlab Elements Planning software detected contacts localized within the STN. Clinical DBS programming contact scheme data were collected after one year from the implant. Statistical analysis evaluated the diagnostic performance of LFPs beta band power and neuroimaging data for identification of the contacts selected with clinical programming. We evaluated whether the most effective contacts identified based on the clinical response after one year from implant were also those with the highest level of beta activity and localized within the STN in neuroimaging reconstruction. RESULTS: LFPs beta power showed a sensitivity of 67%, a negative predictive value (NPV) of 84%, a diagnostic odds ratio (DOR) of 2.7 in predicting the most effective contacts as evaluated through the clinical response. Neuroimaging reconstructions showed a sensitivity of 62%, a NPV of 77%, a DOR of 1.20 for contact effectivity prediction. The combined use of the two methods showed a sensitivity of 87%, a NPV of 87%, a DOR of 2.7 for predicting the clinically more effective contacts. CONCLUSIONS: The combined use of LFPs beta power and neuroimaging localization and segmentations predict which are the most effective contacts as selected on the basis of clinical programming after one year from implant of DBS. The use of predictors in contact selection could guide clinical programming and reduce time needed for it.

Quality of Life and Motor Outcomes in Patients With Parkinson's Disease 12 Months After Deep Brain Stimulation in China.

BACKGROUND: Long-term levodopa use is frequently associated with fluctuations in motor response and can have a serious adverse effect on the quality of life (QoL) of patients with Parkinson's disease (PD). Deep brain stimulation (DBS) is effective in improving symptoms of diminished levodopa responsiveness. QoL improvements with DBS have been shown in several randomized control trials, mostly in Europe and the United States; however, there is a need for evidence from regions around the world. OBJECTIVE: The study aimed to demonstrate improvement in PD-related QoL in patients undergoing DBS in a prospective, multicenter study conducted in China. MATERIALS AND METHODS: To evaluate the effect of neurostimulation on the QoL of patients with PD, a Parkinson's Disease Questionnaire (PDQ-8); Unified Parkinson's Disease Rating Scale (UPDRS) I, II, III, and IV; and EuroQol 5-dimension questionnaire (EQ-5D) were administered at baseline and 12 months after DBS implantation. The mean change and percent change from baseline were reported for these clinical outcomes. RESULTS: Assessments were completed for 85 of the 89 implanted patients. DBS substantially improved patients' QoL and function. Implanted patients showed statistically significant mean improvement in PDQ-8 and UPDRS III (on stimulation/off medication). In the patients who completed the 12-month follow-up visit, the percent change was -22.2% for PDQ-8 and -51.6% for UPDRS III (on stimulation/off medication). Percent change from baseline to 12 months for UPDRS I, II, III, and IV and EQ-5D were -16.8%, -39.4%, -18.5%, and -50.0% and 22.7%, respectively. The overall rate of incidence for adverse events was low at 15.7%. Favorable outcomes were also reported based on patient opinion; 95.3% were satisfied with DBS results. CONCLUSIONS: These data were comparable to other studies around the world and showed alignment with the ability of DBS to meaningfully improve the QoL of patients with PD. More studies investigating DBS therapy for patients with PD are necessary to accurately characterize clinical outcomes for the global PD population. CLINICAL TRIAL REGISTRATION: The ClinicalTrials.gov registration number for this study is NCT02937688.

Low-frequency oscillations link frontal and parietal cortex with subthalamic nucleus in conflicts.

Low-frequency oscillations (LFOs, 28 Hz) in the subthalamic nucleus(STN) are known to reflect cognitive conflict. However, it is unclear if LFOs mediate communication and functional interactions among regions implicated in conflict processing, such as the motor cortex (M1), premotor cortex (PMC), and superior parietal lobule (SPL). To investigate the potential contribution of LFOs to cognitive conflict mediation, we recorded M1, PMC, and SPL activities by right subdural electrocorticography (ECoG) simultaneously with bilateral STN local field potentials (LFPs) by deep brain stimulation electrodes in 13 patients with Parkinson's disease who performed the arrow version of the Eriksen flanker task. Elevated cue-related LFO activity was observed across patients during task trials, with the earliest onset in PMC and SPL. At cue onset, LFO power exhibited a significantly greater increase or a trend of a greater increase in the PMC, M1, and STN, and less increase in the SPL during high-conflict (incongruent) trials than in low-conflict (congruent) trials. The local LFO power increases in PMC, SPL, and right STN were correlated with response time, supporting the notion that these structures are critical hubs for cognitive conflict processing. This power increase was accompanied by increased functional connectivity between the PMC and right STN, which was correlated with response time across subjects. Finally, ipsilateral PMC-STN Granger causality was enhanced during high-conflict trials, with direction from STN to PMC. Our study indicates that LFOs link the frontal and parietal cortex with STN during conflicts, and the ipsilateral PMC-STN connection is specifically involved in this cognitive conflict processing.

Deep brain stimulation for movement disorder treatment: exploring frequency-dependent efficacy in a computational network model.

A large-scale computational model of the basal ganglia network and thalamus is proposed to describe movement disorders and treatment effects of deep brain stimulation (DBS). The model of this complex network considers three areas of the basal ganglia region: the subthalamic nucleus (STN) as target area of DBS, the globus pallidus, both pars externa and pars interna (GPe-GPi), and the thalamus. Parkinsonian conditions are simulated by assuming reduced dopaminergic input and corresponding pronounced inhibitory or disinhibited projections to GPe and GPi. Macroscopic quantities are derived which correlate closely to thalamic responses and hence motor programme fidelity. It can be demonstrated that depending on different levels of striatal projections to the GPe and GPi, the dynamics of these macroscopic quantities (synchronisation index, mean synaptic activity and response efficacy) switch from normal to Parkinsonian conditions. Simulating DBS of the STN affects the dynamics of the entire network, increasing the thalamic activity to levels close to normal, while differing from both normal and Parkinsonian dynamics. Using the mentioned macroscopic quantities, the model proposes optimal DBS frequency ranges above 130 Hz.

Distribution of electric field in patients with obsessive compulsive disorder treated with deep brain stimulation of the bed nucleus of stria terminalis.

BACKGROUND: Deep brain stimulation (DBS) is being investigated as a treatment for therapy-refractory obsessive compulsive disorder (OCD). Many different brain targets are being trialled. Several of these targets such as the ventral striatum (including the nucleus accumbens (NAc)), the ventral capsule, the inferior thalamic peduncle, and the bed nucleus of stria terminalis (BNST)) belong to the same network, are anatomically very close to one another, or even overlap. Data is still missing on how various stimulation parameters in a given target will affect surrounding anatomical areas and impact the clinical outcome of DBS. METHODS: In a pilot study of eleven participants with DBS of the BNST, we investigate through patient-specific simulation of electric field, which anatomical areas are affected by the electric field, and if this can be related to the clinical results. Our study combined individual patient's stimulation parameters at 12- and 24-month follow-up with image data from the preoperative MRI and postoperative CT. These data were used to calculate the distribution of electric field and create individual anatomical models of the field of stimulation. RESULTS: The individual electric stimulation fields by stimulation in the BNST were similar at both the 12- and 24-month follow-up, involving mainly anterior limb of the internal capsule (ALIC), genu of the internal capsule (IC), BNST, fornix, anteromedial globus pallidus externa (GPe), and the anterior commissure. A statistical significant correlation (p < 0.05) between clinical effect measured by the Yale-Brown Obsessive Compulsive Scale and stimulation was found at the 12-month follow-up in the ventral ALIC and anteromedial GPe. CONCLUSIONS: Many of the targets under investigation for OCD are in anatomical proximity. As seen in our study, off-target effects are overlapping. Therefore, DBS in the region of ALIC, NAc, and BNST may perhaps be considered to be stimulation of the same target.

Neuron matters: neuromodulation with electromagnetic stimulation must consider neurons as dynamic identities.

Neuromodulation with electromagnetic stimulation is widely used for the control of abnormal neural activity, and has been proven to be a valuable alternative to pharmacological tools for the treatment of many neurological diseases. Tremendous efforts have been focused on the design of the stimulation apparatus (i.e., electrodes and magnetic coils) that delivers the electric current to the neural tissue, and the optimization of the stimulation parameters. Less attention has been given to the complicated, dynamic properties of the neurons, and their context-dependent impact on the stimulation effects. This review focuses on the neuronal factors that influence the outcomes of electromagnetic stimulation in neuromodulation. Evidence from multiple levels (tissue, cellular, and single ion channel) are reviewed. Properties of the neural elements and their dynamic changes play a significant role in the outcome of electromagnetic stimulation. This angle of understanding yields a comprehensive perspective of neural activity during electrical neuromodulation, and provides insights in the design and development of novel stimulation technology.

Arching deep brain stimulation in dystonia types.

Although medical treatment including botulinum toxic injection is the first-line treatment for dystonia, response is insufficient in many patients. In these patients, deep brain stimulation (DBS) can provide significant clinical improvement. Mounting evidence indicates that DBS is an effective and safe treatment for dystonia, especially for idiopathic and inherited isolated generalized/segmental dystonia, including DYT-TOR1A. Other inherited dystonia and acquired dystonia also respond to DBS to varying degrees. For Meige syndrome (craniofacial dystonia), other focal dystonia, and some rare inherited dystonia, further evidences are still needed to evaluate the role of DBS. Because short disease duration at DBS surgery and absence of fixed musculoskeletal deformity are associated with better outcome, DBS should be considered as early as possible when indicated after careful evaluation including genetic work-up. This review will focus on the factors to be considered in DBS for patients with dystonia and the outcome of DBS in the different types of dystonia.

KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation.

Heterozygous mutations in KMT2B are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving through a caudocranial pattern into generalized dystonia, with prominent oromandibular, laryngeal and cervical involvement. Although KMT2B-related disease is emerging as one of the most common causes of early-onset genetic dystonia, much remains to be understood about the full spectrum of the disease. We describe a cohort of 53 patients with KMT2B mutations, with detailed delineation of their clinical phenotype and molecular genetic features. We report new disease presentations, including atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype. In addition to the previously reported systemic features, our study has identified co-morbidities, including the risk of status dystonicus, intrauterine growth retardation, and endocrinopathies. Analysis of this study cohort (n = 53) in tandem with published cases (n = 80) revealed that patients with chromosomal deletions and protein truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants. Eighteen individuals had detailed longitudinal data available after insertion of deep brain stimulation for medically refractory dystonia. Median age at deep brain stimulation was 11.5 years (range: 4.5-37.0 years). Follow-up after deep brain stimulation ranged from 0.25 to 22 years. Significant improvement of motor function and disability (as assessed by the Burke Fahn Marsden's Dystonia Rating Scales, BFMDRS-M and BFMDRS-D) was evident at 6 months, 1 year and last follow-up (motor, P = 0.001, P = 0.004, and P = 0.012; disability, P = 0.009, P = 0.002 and P = 0.012). At 1 year post-deep brain stimulation, >50% of subjects showed BFMDRS-M and BFMDRS-D improvements of >30%. In the long-term deep brain stimulation cohort (deep brain stimulation inserted for >5 years, n = 8), improvement of >30% was maintained in 5/8 and 3/8 subjects for the BFMDRS-M and BFMDRS-D, respectively. The greatest BFMDRS-M improvements were observed for trunk (53.2%) and cervical (50.5%) dystonia, with less clinical impact on laryngeal dystonia. Improvements in gait dystonia decreased from 20.9% at 1 year to 16.2% at last assessment; no patient maintained a fully independent gait. Reduction of BFMDRS-D was maintained for swallowing (52.9%). Five patients developed mild parkinsonism following deep brain stimulation. KMT2B-related disease comprises an expanding continuum from infancy to adulthood, with early evidence of genotype-phenotype correlations. Except for laryngeal dysphonia, deep brain stimulation provides a significant improvement in quality of life and function with sustained clinical benefit depending on symptoms distribution.

Globus pallidus internus activity during simultaneous bilateral microelectrode recordings in status dystonicus.

Limited data are available regarding the electrophysiology of status dystonicus (SD). We report simultaneous microelectrode recordings (MERs) from the globus pallidus internus (GPi) of a patient with SD who was treated with bilateral deep brain stimulation (DBS). Mean neuronal discharge rate was of 30.1 ± 10.9 Hz and 38.5 Hz ± 11.1 Hz for the right and left GPi, respectively. On the right side, neuronal electrical activity was completely abolished at the target point, whereas the mean burst index values showed a predominance of bursting and irregular activity along trajectories on both sides. Our data are in line with previous findings of pallidal irregular hypoactivity as a potential electrophysiological marker of dystonia and thus SD, but further electrophysiological studies are needed to confirm our results.

Bilateral double beta peaks in a PD patient with STN electrodes.

Subthalamic local field potentials in the beta band are considered as potential biomarkers for closed-loop deep brain stimulation. To investigate the subthalamic beta band peak amplitudes in a Parkinson's disease patient over an extended period of time by using a novel and commercially available neurostimulator with permanent sensing capability. We recorded local field potentials of the subthalamic nucleus using the Medtronic Percept™ implantable neurostimulator at rest and during physical activity (gait) with and in response to deep brain stimulation. We found a double-peaked beta activity on both sides. Increasing stimulation and physical activity resulted in a decreased beta band amplitude, but was accompanied by the appearance of a second, and previously unrecognized peak at 13 Hz in the right hemisphere. Our results will support the investigation of distinct different peaks in the beta band and their relevance and usefulness as closed-loop biomarkers.

Investigation of Magnetoelectric Sensor Requirements for Deep Brain Stimulation Electrode Localization and Rotational Orientation Detection.

Correct position and orientation of a directional deep brain stimulation (DBS) electrode in the patient's brain must be known to fully exploit its benefit in guiding stimulation programming. Magnetoelectric (ME) sensors can play a critical role here. The aim of this study was to determine the minimum required limit of detection (LOD) of a ME sensor that can be used for this application by measuring the magnetic field induced by DBS. For this experiment, a commercial DBS system was integrated into a head phantom and placed inside of a state-of-the-art Superconducting Quantum Interference Device (SQUID)-based magnetoencephalography system. Measurements were performed and analyzed with digital signal processing. Investigations have shown that the minimum required detection limit depends on various factors such as: measurement distance to electrode, bandwidth of magnetic sensor, stimulation amplitude, stimulation pulse width, and measurement duration. For a sensor that detects only a single DBS frequency (stimulation frequency or its harmonics), a LOD of at least 0.04 pT/Hz0.5 is required for 3 mA stimulation amplitude and 60 µµs pulse width. This LOD value increases by an order of magnitude to 0.4 pT/Hz0.5 for a 1 kHz, and by approximately two orders to 3 pT/Hz0.5 for a 10 kHz sensor bandwidth. By averaging, the LOD can be reduced by at least another 2 orders of magnitude with a measurement duration of a few minutes.

Subthalamic Nucleus Deep Brain Stimulation in Primary Meige Syndrome: A 1-Year Follow-Up Study.

OBJECTIVE: To investigate the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Meige syndrome. MATERIALS AND METHODS: Fifteen consecutive patients who underwent STN-DBS at the Peking University People's Hospital between September 2017 and June 2018 were included in this study. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement score and the BFMDRS disability score were obtained prior to surgery, and at specific time points after surgery. Patients' sleep status was also assessed before and after surgery. RESULTS: The BFMDRS movement scores decreased from 15.3 ± 4.6 to 5.2 ± 6.2 after STN-DBS, with a mean improvement of 68.6% (p < 0.05). The BFMDRS disability scores were also significantly decreased, from 6.9 ± 3.3 to 3.5 ± 2.9, with a mean improvement of 51.7% (p < 0.05). The eye, mouth, speech, and swallowing movement scores also decreased significantly after STN-DBS compared to baseline (p < 0.05). The sleep quality of the patients was also improved after surgery. CONCLUSIONS: These findings demonstrate that the STN is an effective brain target for the treatment of patients with Meige syndrome. STN-DBS was not only able to improve patients' motor symptoms, but also their sleep status.

Allergy Considerations in Implanted Neuromodulation Devices.

OBJECTIVES: Allergic reactions are rare and poorly understood complications of neuromodulation device implantation. There are currently no guidelines for management of allergic reactions to these devices and their components. Here we review the published cases of allergic reactions to implanted neuromodulatory devices and leverage the experiences of other specialties that deal with similar complications to formulate recommendations for prevention and management. MATERIALS AND METHODS: A review and assessment of the literature. RESULTS: Allergic reactions to a number of implantable devices have been observed and published. In dentistry and orthopedics, metals such as nickel are the most frequent cause of allergic reactions. In interventional cardiology, where devices closely resemble neuromodulatory devices, titanium, silicone, and polyurethanes are the most common causes of allergic reactions. In neurosurgery, allergic reactions to implantable neuromodulatory devices are rare, and we summarize 13 cases published to date. Such allergic reactions generally present as local dermatitis, erythema, and pruritus, which can be difficult to distinguish from surgical site infection. In one published case, symptoms resolved with corticosteroid treatment, but all other cases required explantation. The successful reimplantation with a modified device was reported in some cases. CONCLUSIONS: Patients should be screened for a personal history of contact allergy before implantation procedures. A multidisciplinary approach to suspected cases of postoperative allergic reactions involving collaboration between neurosurgeons and other implanting physicians, dermatologists or allergists, and device manufacturers is recommended. In cases where an allergic reaction is suspected, an infectious etiology should be ruled out first. Clinical suspicion can then be supported with the use of patch testing, interpreted by an experienced dermatologist or allergist. If patch testing supports an allergic etiology, the implanting physician and the device manufacturer can work together to modify the device for safe reimplantation.