Implantable Subdural Cortical Stimulation for Chronic Intractable Pain Treatment-The Mayo Experience and Review of Literature.

OBJECTIVES: Motor cortex stimulation (MCS) is an effective technique in treating chronic intractable pain for some patients. However, most studies are small case series (n < 20). Heterogeneity in technique and patient selection makes it difficult to draw consistent conclusions. In this study, we present one of the largest case series of subdural MCS. MATERIALS AND METHODS: Medical records of patients who underwent MCS at our institute between 2007 and 2020 were reviewed. Studies with at least 15 patients were summarized for comparison. RESULTS: The study included 46 patients. Mean age was 56.2 ± 12.5 years (SD). Mean follow-up was 57.2 ± 41.9 months. Male-to-female ratio was 13:33. Of the 46 patients, 29 had neuropathic pain in trigeminal nerve territory/anesthesia dolorosa; nine had postsurgical/posttraumatic pain; three had phantom limb pain; two had postherpetic pain, and the rest had pain secondary to stroke, chronic regional pain syndrome, and tumor. The baseline numeric rating pain scale (NRS) was 8.2 ± 1.8 of 10, and the latest follow-up score was 3.5 ± 2.9 (mean improvement of 57.3%). Responders comprised 67% (31/46)(NRS ≥ 40% improvement). Analysis showed no correlation between percentage of improvement and age (p = 0.352) but favored male patients (75.3% vs 48.7%, p = 0.006). Seizures occurred in 47.8% of patients (22/46) at some point but were all self-limiting, with no lasting sequelae. Other complications included subdural/epidural hematoma requiring evacuation (3/46), infection (5/46), and cerebrospinal fluid leak (1/46). These complications resolved with no long-term sequelae after further interventions. CONCLUSION: Our study further supports the use of MCS as an effective treatment modality for several chronic intractable pain conditions and provides a benchmark to the current literature.

Preliminary Experience with a Four-Lead Implantable Pulse Generator for Deep Brain Stimulation.

BACKGROUND: Implantable pulse generators (IPGs) store energy and deliver electrical impulses for deep brain stimulation (DBS) to treat neurological and psychiatric disorders. IPGs have evolved over time to meet the demands of expanding clinical indications and more nuanced therapeutic approaches. OBJECTIVES: The aim of this study was to examine the workflow of the first 4-lead IPG for DBS in patients with complex disease. METHOD: The engineering capabilities, clinical use cases, and surgical technique are described in a cohort of 12 patients with epilepsy, essential tremor, Parkinson's disease, mixed tremor, and Tourette's syndrome with comorbid obsessive-compulsive disorder between July 2021 and July 2022. RESULTS: This system is a rechargeable 32-channel, 4-port system with independent current control that can be connected to 8 contact linear or directionally segmented leads. The system is ideal for patients with mixed disease or those with multiple severe symptoms amenable to >2 lead implantations. A multidisciplinary team including neurologists, radiologists, and neurosurgeons is necessary to safely plan the procedure. There were no serious intraoperative or postoperative adverse events. One patient required revision surgery for bowstringing. CONCLUSIONS: This new 4-lead IPG represents an important new tool for DBS surgery with the ability to expand lead implantation paradigms for patients with complex disease.

Anterior nucleus of the thalamus seizure detection in ambulatory humans.

There is a paucity of data to guide anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) with brain sensing. The clinical Medtronic Percept DBS device provides constrained brain sensing power within a frequency band (power-in-band [PIB]), recorded in 10-min averaged increments. Here, four patients with temporal lobe epilepsy were implanted with an investigational device providing full bandwidth chronic intracranial electroencephalogram (cEEG) from bilateral ANT and hippocampus (Hc). ANT PIB-based seizure detection was assessed. Detection parameters were cEEG PIB center frequency, bandwidth, and epoch duration. Performance was evaluated against epileptologist-confirmed Hc seizures, and assessed by area under the precision-recall curve (PR-AUC). Data included 99 days of cEEG, and 20, 278, 3, and 18 Hc seizures for Subjects 1-4. The best detector had 7-Hz center frequency, 5-Hz band width, and 10-s epoch duration (group PR-AUC = .90), with 75% sensitivity and .38 false alarms per day for Subject 1, and 100% and .0 for Subjects 3 and 4. Hc seizures in Subject 2 did not propagate to ANT. The relative change of ANT PIB was maximal ipsilateral to seizure onset for all detected seizures. Chronic ANT and Hc recordings provide direct guidance for ANT DBS with brain sensing.

MRI and tractography techniques to localize the ventral intermediate nucleus and dentatorubrothalamic tract for deep brain stimulation and MR-guided focused ultrasound: a narrative review and update.

The thalamic ventral intermediate nucleus (VIM) can be targeted for treatment of tremor by several procedures, including deep brain stimulation (DBS) and, more recently, MR-guided focused ultrasound (MRgFUS). To date, such targeting has relied predominantly on coordinate-based or atlas-based techniques rather than directly targeting the VIM based on imaging features. While general regional differences of features within the thalamus and some related white matter tracts can be distinguished with conventional imaging techniques, internal nuclei such as the VIM are not discretely visualized. Advanced imaging methods such as quantitative susceptibility mapping (QSM) and fast gray matter acquisition T1 inversion recovery (FGATIR) MRI and high-field MRI pulse sequences that improve the ability to image the VIM region are emerging but have not yet been shown to have reliability and accuracy to serve as the primary method of VIM targeting. Currently, the most promising imaging approach to directly identify the VIM region for clinical purposes is MR diffusion tractography.In this review and update, the capabilities and limitations of conventional and emerging advanced methods for evaluation of internal thalamic anatomy are briefly reviewed. The basic principles of tractography most relevant to VIM targeting are provided for familiarization. Next, the key literature to date addressing applications of DTI and tractography for DBS and MRgFUS is summarized, emphasizing use of direct targeting. This literature includes 1-tract (dentatorubrothalamic tract [DRT]), 2-tract (pyramidal and somatosensory), and 3-tract (DRT, pyramidal, and somatosensory) approaches to VIM region localization through tractography.The authors introduce a 3-tract technique used at their institution, illustrating the oblique curved course of the DRT within the inferior thalamus as well as the orientation and relationship of the white matter tracts in the axial plane. The utility of this 3-tract tractography approach to facilitate VIM localization is illustrated with case examples of variable VIM location, targeting superior to the anterior commissure-posterior commissure plane, and treatment in the setting of pathologic derangement of thalamic anatomy. Finally, concepts demonstrated with these case examples and from the prior literature are synthesized to highlight several potential advantages of tractography for VIM region targeting.

Chronic subdural cortical stimulation for phantom limb pain: report of a series of two cases.

Phantom limb pain is a complex, incompletely understood pain syndrome that is characterized by chronic painful paresthesias in a previous amputated body part. Limited treatment modalities exist that provide meaningful relief, including pharmacological treatments and spinal cord stimulation that are rarely successful for refractory cases. Here, we describe our two-patient cohort with recalcitrant upper extremity phantom limb pain treated with chronic subdural cortical stimulation. The patient with evidence of cortical reorganization and almost 60 years of debilitating phantom limb pain experienced sustained analgesic relief at a follow-up period of 6 months. The second patient became tolerant to the stimulation and his pain returned to baseline at a 1-month follow-up. Our unique case series report adds to the growing body of literature suggesting critical appraisal before widespread implementation of cortical stimulation for phantom limb pain can be considered.

The Impact of Mirth-Inducing Ventral Striatal Deep Brain Stimulation on Functional and Effective Connectivity.

Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is an investigational therapy for treatment-resistant obsessive-compulsive disorder. The ability of VC/VS DBS to evoke spontaneous mirth in patients, often accompanied by smiling and laughter, is clinically well documented. However, the neural correlates of DBS-evoked mirth remain poorly characterized. Patients undergoing VC/VS DBS surgery underwent intraoperative evaluation in which mirth-inducing and non-mirth-inducing stimulation localizations were identified. Using dynamic causal modeling (DCM) for fMRI, the effect of mirth-inducing DBS on functional and effective connectivity among established nodes in limbic cortico-striato-thalamo-cortical (CSTC) circuitry was investigated. Both mirth-inducing and non-mirth-inducing VC/VS DBS consistently resulted (conjunction, global null, family-wise error-corrected P < 0.05) in activation of amygdala, ventral striatum, and mediodorsal thalamus. However, only mirth-inducing DBS resulted in functional inhibition of anterior cingulate cortex. Dynamic causal modeling revealed that mirth-inducing DBS enhanced effective connectivity from anterior cingulate to ventral striatum, while attenuating connectivity from thalamus to ventral striatum relative to non-mirth-inducing stimulation. These results suggest that DBS-evoked mood elevation is accompanied by distinct patterns of limbic thalamocortical connectivity. Using the novel combination of DBS-evoked mood alteration and functional MRI in human subjects, we provide new insights into the network-level mechanisms that influence affect.

Thalamic deep brain stimulation for orthostatic tremor: A multicenter international registry.

BACKGROUND: We report the accumulated experience with ventral intermediate nucleus deep brain stimulation for medically refractory orthostatic tremor. METHODS: Data from 17 patients were reviewed, comparing presurgical, short-term (0-48 months), and long-term (≥48 months) follow-up. The primary end point was the composite activities of daily living/instrumental activities of daily living score. Secondary end points included latency of symptoms on standing and treatment-related complications. RESULTS: There was a 21.6% improvement (P = 0.004) in the composite activities of daily living/instrumental activities of daily living score, which gradually attenuated (12.5%) in the subgroup of patients with an additional long-term follow-up (8 of 17). The latency of symptoms on standing significantly improved, both in the short-term (P = 0.001) and in the long-term (P = 0.018). Three patients obtained no/minimal benefit from the procedure. CONCLUSIONS: Deep brain stimulation of the ventral intermediate nucleus was, in general, safe and well tolerated, yielding sustained benefit in selected patients with medically refractory orthostatic tremor. © 2017 International Parkinson and Movement Disorder Society.

Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor.

Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson's disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal modelling revealed a correlation between therapeutic effectiveness and attenuated within-region inhibitory connectivity in cerebellum. Finally, specific subregions of sensorimotor cortex were identified in which deep brain stimulation-evoked activation correlated with the presence of unwanted paraesthesias. These results suggest that thalamic deep brain stimulation in tremor likely exerts its effects through modulation of both olivocerebellar and thalamocortical circuits. In addition, our findings indicate that deep brain stimulation-evoked functional activation maps obtained intraoperatively may contain predictive information pertaining to the therapeutic and adverse effects induced by deep brain stimulation.media-1vid110.1093/brain/aww145_video_abstractaww145_video_abstract.

Stimulation-Induced Transient Nonmotor Psychiatric Symptoms following Subthalamic Deep Brain Stimulation in Patients with Parkinson's Disease: Association with Clinical Outcomes and Neuroanatomical Correlates.

BACKGROUND: The clinical and neurobiological underpinnings of transient nonmotor (TNM) psychiatric symptoms during the optimization of stimulation parameters in the course of subthalamic nucleus deep brain stimulation (STN-DBS) remain under intense investigation. METHODS: Forty-nine patients with refractory Parkinson's disease underwent bilateral STN-DBS implants and were enrolled in a 24-week prospective, naturalistic follow-up study. Patients who exhibited TNM psychiatric manifestations during DBS parameter optimization were evaluated for potential associations with clinical outcome measures. RESULTS: Twenty-nine TNM+ episodes were reported by 15 patients. No differences between TNM+ and TNM- groups were found in motor outcome. However, unlike the TNM- group, TNM+ patients did not report improvement in subsyndromal depression or quality of life. TNM+ episodes were more likely to emerge during bilateral monopolar stimulation of the medial STN. CONCLUSIONS: The occurrence of TNM psychiatric symptoms during optimization of stimulation parameters was associated with the persistence of subsyndromal depression and with lower quality of life ratings at 6 months. The neurobiological underpinnings of TNM symptoms are investigated yet remain difficult to explain.

Tourette syndrome deep brain stimulation: a review and updated recommendations.

Deep brain stimulation (DBS) may improve disabling tics in severely affected medication and behaviorally resistant Tourette syndrome (TS). Here we review all reported cases of TS DBS and provide updated recommendations for selection, assessment, and management of potential TS DBS cases based on the literature and implantation experience. Candidates should have a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V) diagnosis of TS with severe motor and vocal tics, which despite exhaustive medical and behavioral treatment trials result in significant impairment. Deep brain stimulation should be offered to patients only by experienced DBS centers after evaluation by a multidisciplinary team. Rigorous preoperative and postoperative outcome measures of tics and associated comorbidities should be used. Tics and comorbid neuropsychiatric conditions should be optimally treated per current expert standards, and tics should be the major cause of disability. Psychogenic tics, embellishment, and malingering should be recognized and addressed. We have removed the previously suggested 25-year-old age limit, with the specification that a multidisciplinary team approach for screening is employed. A local ethics committee or institutional review board should be consulted for consideration of cases involving persons younger than 18 years of age, as well as in cases with urgent indications. Tourette syndrome patients represent a unique and complex population, and studies reveal a higher risk for post-DBS complications. Successes and failures have been reported for multiple brain targets; however, the optimal surgical approach remains unknown. Tourette syndrome DBS, though still evolving, is a promising approach for a subset of medication refractory and severely affected patients.

Anterior nuclear deep brain stimulation guided by concordant hippocampal recording.

OBJECT: Anterior nuclear (AN) stimulation has been reported to reduce the frequency of seizures, in some cases dramatically; however, it has not been approved by the US Food and Drug Administration. The anterior nucleus is difficult to target because of its sequestered location, partially surrounded by the ventricle. It has traditionally been targeted by using transventricular or lateral transcortical routes. Here, the authors report a novel approach to targeting the anterior nucleus and neurophysiologically confirming effective stimulation of the target, namely evoked potentials in the hippocampus. METHODS: Bilateral AN 3389 electrodes were placed in a novel trajectory followed by bilateral hippocampal 3391 electrodes from a posterior trajectory. Each patient was implanted bilaterally with a Medtronic Activa PC+S device under an investigational device exemption approval. Placement was confirmed with CT. AN stimulation-induced hippocampal evoked potentials were measured to functionally confirm placement in the anterior nucleus. RESULTS: Two patients had implantations by way of a novel AN trajectory with concomitant hippocampal electrodes. There were no lead misplacements. Postoperative stimulation of the anterior nucleus with a PC+S device elicited evoked potentials in the hippocampus. Thus far, both patients have reported a > 50% improvement in seizure frequency. CONCLUSIONS: Placing AN electrodes posteriorly may provide a safer trajectory than that used for traditionally placed AN electrodes. In addition, with a novel battery that is capable of electroencephalographic recording, evoked potentials can be used to functionally assess the Papez circuit. This treatment paradigm may offer increased AN stimulation efficacy for medically intractable epilepsy by assessing functional placement more effectively and thus far has proven safe.

Chronic subthreshold subdural cortical stimulation for the treatment of focal epilepsy originating from eloquent cortex.

Medically refractory epilepsy remains a major medical problem worldwide. Although some patients are eligible for surgical resection of seizure foci, a proportion of patients are ineligible for a variety of reasons. One such reason is that the foci reside in eloquent cortex of the brain and therefore resection would result in significant morbidity. This retrospective study reports our experience with a novel neurostimulation technique for the treatment of these patients. We identified three patients who were ineligible for surgical resection of the intracranially identified seizure focus because it resided in eloquent cortex, who underwent therapeutic trial of focal cortical stimulation delivered through the subdural monitoring grid. All three patients had a significant reduction in seizures, and two went on to permanent implantation, which resulted in long-term reduction in seizure frequency. In conclusion, this small case report provides some evidence of proof of concept of the role of targeted continuous neocortical neurostimulation in the treatment of medically refractory focal epilepsy, and provides support for ongoing investigations into this treatment modality.

Mood stability in Parkinson disease following deep brain stimulation: a 6-month prospective follow-up study.

BACKGROUND: Deep brain stimulation for Parkinson disease has been associated with psychiatric adverse effects including anxiety, depression, mania, psychosis, and suicide. OBJECTIVE: The purpose of this study was to evaluate the safety of deep brain stimulation in a large Parkinson disease clinical practice. METHODS: Patients approved for surgery by the Mayo Clinic deep brain stimulation clinical committee participated in a 6-month prospective naturalistic follow-up study. In addition to the Unified Parkinson's Disease Rating Scale, stability and psychiatric safety were measured using the Beck Depression Inventory, Hamilton Depression Rating Scale, and Young Mania Rating scale. Outcomes were compared in patients with Parkinson disease who had a psychiatric history to those with no co-morbid psychiatric history. RESULTS: The study was completed by 49 of 54 patients. Statistically significant 6-month baseline to end-point improvement was found in motor and mood scales. No significant differences were found in psychiatric outcomes based on the presence or absence of psychiatric comorbidity. CONCLUSIONS: Our study suggests that patients with Parkinson disease who have a history of psychiatric co-morbidity can safely respond to deep brain stimulation with no greater risk of psychiatric adverse effect occurrence. A multidisciplinary team approach, including careful psychiatric screening ensuring mood stabilization and psychiatric follow-up, should be viewed as standard of care to optimize the psychiatric outcome in the course of deep brain stimulation treatment.

Clinical evaluation of a stereotactic system for single-stage deep brain stimulation surgery under general anesthesia: technical note.

OBJECTIVE: Conventional frame-based stereotactic systems have circumferential base frames, often necessitating deep brain stimulation (DBS) surgery in two stages: intracranial electrode insertion followed by surgical re-preparation and pulse generator implantation. Some patients do not tolerate awake surgery, underscoring the need for a safe alternative for asleep DBS surgery. A frame-based stereotactic system with a skull-mounted "key" in lieu of a circumferential base frame received US FDA clearance. The authors describe the system's application for single-stage, asleep DBS surgery in 8 patients at their institution and review its workflow and technical considerations. METHODS: Eight patients underwent DBS lead insertion and IPG implantation in a single surgical preparation under general anesthesia using the system. Postoperative CT imaging confirmed lead placement. RESULTS: Eight patients underwent implantation of 15 total leads targeting the ventral intermediate nucleus (4 patients), globus pallidus internus (GPi; 3 patients), and subthalamic nucleus (STN; 1 patient). Intraoperative microelectrode recording was conducted for GPi and STN targets. Postoperative CT imaging revealed a mean ± SD radial error of 1.24 ± 0.45 mm (n = 15 leads), without surgical complications. CONCLUSIONS: The stereotactic system facilitated safe and effective asleep, single-stage DBS surgery, maintaining traditional lead accuracy standards.

Anatomical Parcellations of Brodmann's Areas 4 and 6: A Study on Cortical Thickness for Improved Neurosurgical Planning.

The cerebral cortex, comprising six layers known as the neocortex, is a sheet of neural tissue that contains regions for neurosurgical planning, including the primary motor cortex (PMC), the supplementary motor cortex (SMA), and the primary somatosensory cortex (PSC). However, knowledge gaps persist concerning the transition points between areas 3 to 4 and 4 to 6 and the SMA's extent. This study aims to develop a non-invasive protocol using T1/T2 weighted imaging to identify crucial anatomic borders around the primary and supplementary motor cortex for neurosurgical planning. A comprehensive literature search on the cytoarchitectonic borders of Brodmann's areas 3a, 4, and 6 was conducted, and relevant articles were selected based on their examination of these borders. The primary motor cortex was found to be the thickest region in the human brain, with discernible differences in thickness between areas 4 and 6. T2-weighted images revealed significant cortical thickness differences between the precentral and postcentral gyrus. Various methods have been employed to parcellate borders between cortical regions, including Laplace's equation and equi-volume models. A triple-layer appearance in the primary motor cortex and a novel method based on myelin content demonstrated consistent agreements with historically defined cytoarchitectonic borders. However, differentiating areas 4 and 6 from MR imaging remains challenging. Recent studies suggest potential methods for pre-surgically identifying the primary motor cortex and examining differences in cortical thickness in diseases. A protocol should be established to guide neurosurgeons in accurately identifying areas 4 and 6, possibly using imaging modalities superimposed on myelin maps for differentiation and determining area 6's anterior extent.

Comparison of the impact of skull density ratio with alternative skull metrics on magnetic resonance-guided focused ultrasound thalamotomy for tremor.

OBJECTIVE: One of the key metrics that is used to predict the likelihood of success of MR-guided focused ultrasound (MRgFUS) thalamotomy is the overall calvarial skull density ratio (SDR). However, this measure does not fully predict the sonication parameters that would be required or the technical success rates. The authors aimed to assess other skull characteristics that may also contribute to technical success. METHODS: The authors retrospectively studied consecutive patients with essential tremor who were treated by MRgFUS at their center between 2017 and 2021. They evaluated the correlation between the different treatment parameters, particularly maximum power and energy delivered, with a range of patients' skull metrics and demographics. Machine learning algorithms were applied to investigate whether sonication parameters could be predicted from skull density metrics alone and whether including combined local transducer SDRs with overall calvarial SDR would increase model accuracy. RESULTS: A total of 62 patients were included in the study. The mean age was 77.1 (SD 9.2) years, and 78% of treatments (49/63) were performed in males. The mean SDR was 0.51 (SD 0.10). Among the evaluated metrics, SDR had the highest correlation with the maximum power used in treatment (ρ = -0.626, p < 0.001; proportion of local SDR values ≤ 0.8 group also had ρ = +0.626, p < 0.001) and maximum energy delivered (ρ = -0.680, p < 0.001). Machine learning algorithms achieved a moderate ability to predict maximum power and energy required from the local and overall SDRs (accuracy of approximately 80% for maximum power and approximately 55% for maximum energy), and high ability to predict average maximum temperature reached from the local and overall SDRs (approximately 95% accuracy). CONCLUSIONS: The authors compared a number of skull metrics against SDR and showed that SDR was one of the best indicators of treatment parameters when used alone. In addition, a number of other machine learning algorithms are proposed that may be explored to improve its accuracy when additional data are obtained. Additional metrics related to eventual sonication parameters should also be identified and explored.

Deep Brain Stimulator Device Infection: The Mayo Clinic Rochester Experience.

Background: Deep brain stimulator (DBS)-related infection is a recognized complication that may significantly alter the course of DBS therapy. We describe the Mayo Clinic Rochester experience with DBS-related infections. Methods: This was a retrospective study of all adults (≥18 years old) who underwent DBS-related procedures between 2000 and 2020 at the Mayo Clinic Rochester. Results: There were 1087 patients who underwent 1896 procedures. Infection occurred in 57/1112 (5%) primary DBS implantations and 16/784 (2%) revision surgeries. The median time to infection (interquartile range) was 2.1 (0.9-6.9) months. The odds of infection were higher with longer operative length (P = .002), higher body mass index (BMI; P = .006), male sex (P = .041), and diabetes mellitus (P = .002). The association between infection and higher BMI (P = .002), male sex (P = .016), and diabetes mellitus (P = .003) remained significant in a subgroup analysis of primary implantations but not revision surgeries. Infection was superficial in 17 (23%) and deep in 56 (77%) cases. Commonly identified pathogens were Staphylococcus aureus (65%), coagulase-negative staphylococci (43%), and Cutibacterium acnes (45%). Three device management approaches were identified: 39 (53%) had complete device explantation, 20 (27%) had surgical intervention with device retention, and 14 (19%) had medical management alone. Treatment failure occurred in 16 (23%) patients. Time-to-event analysis showed fewer treatment failures with complete device explantation (P = .015). Only 1 individual had complications with brain abscess at failure. Conclusions: Primary DBS implantations had higher rates of infection compared with revision surgeries. Complete device explantation was favored for deep infections. However, device salvage was commonly attempted and is a reasonable approach in select cases given the low rate of complications.

Stiff person spectrum disorder diagnosis, misdiagnosis, and suggested diagnostic criteria.

BACKGROUND: Stiff person spectrum disorder (SPSD) is heterogeneous, and accurate diagnosis can be challenging. METHODS: Patients referred for diagnosis/suspicion of SPSD at the Mayo Autoimmune Neurology Clinic from July 01, 2016, to June 30, 2021, were retrospectively identified. SPSD diagnosis was defined as clinical SPSD manifestations confirmed by an autoimmune neurologist and seropositivity for high-titer GAD65-IgG (>20.0 nmol/L), glycine-receptor-IgG or amphiphysin-IgG, and/or confirmatory electrodiagnostic studies (essential if seronegative). Clinical presentation, examination, and ancillary testing were compared to differentiate SPSD from non-SPSD. RESULTS: Of 173 cases, 48 (28%) were diagnosed with SPSD and 125 (72%) with non-SPSD. Most SPSD were seropositive (41/48: GAD65-IgG 28/41, glycine-receptor-IgG 12/41, amphiphysin-IgG 2/41). Pain syndromes or functional neurologic disorder were the most common non-SPSD diagnoses (81/125, 65%). SPSD patients more commonly reported exaggerated startle (81% vs. 56%, p = 0.02), unexplained falls (76% vs. 46%, p = 0.001), and other associated autoimmunity (50% vs. 27%, p = 0.005). SPSD more often had hypertonia (60% vs. 24%, p < 0.001), hyperreflexia (71% vs. 43%, p = 0.001), and lumbar hyperlordosis (67% vs. 9%, p < 0.001) and less likely functional neurologic signs (6% vs. 33%, p = 0.001). SPSD patients more frequently had electrodiagnostic abnormalities (74% vs. 17%, p < 0.001), and at least moderate symptomatic improvement with benzodiazepines (51% vs. 16%, p < 0.001) or immunotherapy (45% vs. 13% p < 0.001). Only 4/78 non-SPSD patients who received immunotherapy had alternative neurologic autoimmunity. INTERPRETATION: Misdiagnosis was threefold more common than confirmed SPSD. Functional or non-neurologic disorders accounted for most misdiagnoses. Clinical and ancillary testing factors can reduce misdiagnosis and exposure to unnecessary treatments. SPSD diagnostic criteria are suggested.

A motor association area in the depths of the central sulcus.

Cells in the precentral gyrus directly send signals to the periphery to generate movement and are principally organized as a topological map of the body. We find that movement-induced electrophysiological responses from depth electrodes extend this map three-dimensionally throughout the gyrus. Unexpectedly, this organization is interrupted by a previously undescribed motor association area in the depths of the midlateral aspect of the central sulcus. This 'Rolandic motor association' (RMA) area is active during movements of different body parts from both sides of the body and may be important for coordinating complex behaviors.

Underlying neurobiology and clinical correlates of mania status after subthalamic nucleus deep brain stimulation in Parkinson's disease: a review of the literature.

Deep brain stimulation (DBS) is a novel and effective surgical intervention for refractory Parkinson's disease (PD). The authors review the current literature to identify the clinical correlates associated with subthalamic nucleus (STN) DBS-induced hypomania/mania in PD patients. Ventromedial electrode placement has been most consistently implicated in the induction of STN DBS-induced mania. There is some evidence of symptom amelioration when electrode placement is switched to a more dorsolateral contact. Additional clinical correlates may include unipolar stimulation, higher voltage (>3 V), male sex, and/or early-onset PD. STN DBS-induced psychiatric adverse events emphasize the need for comprehensive psychiatric presurgical evaluation and follow-up in PD patients. Animal studies and prospective clinical research, combined with advanced neuroimaging techniques, are needed to identify clinical correlates and underlying neurobiological mechanisms of STN DBS-induced mania. Such working models would serve to further our understanding of the neurobiological underpinnings of mania and contribute valuable new insight toward development of future DBS mood-stabilization therapies.