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.

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.

Cosmetic considerations for placement of deep brain stimulation pulse generator: the submammary subfascial approach.

INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for a number of debilitating neurological diseases. However, the placement of an implantable pulse generator (IPG) can lead to significant cosmetic concerns for some patients. METHODS: We present a subfascial technique of DBS IPG implantation under the breast using a more concealed scar location. The technique is illustrated in a female patient who favored a more aesthetic placement of the DBS to treat essential tremor. Relevant literature of this approach from both breast augmentation and cardiac pacemaker implantation was reviewed. RESULTS: An excellent cosmetic outcome was demonstrated, and reviewing the literature, implanting under the pectoralis major fascia has the potential benefit of reducing complication rates associated with silicone implant placement in the plastic surgery literature when compared to other planes. CONCLUSIONS: The subfascial implantation of IPG was described. This plane, which is used routinely in breast augmentation, has the potential to decrease complication rates compared to placement in the subglandular plane. An inframammary incision provides patients with concerns about the scar and stigmata associated with an infraclavicular location of DBS generator a better cosmetic outcome.

Tonic Serotonin Measurements In Vivo Using N-Shaped Multiple Cyclic Square Wave Voltammetry.

Here, we present the development of a novel voltammetric technique, N-shaped multiple cyclic square wave voltammetry (N-MCSWV) and its application in vivo. It allows quantitative measurements of tonic extracellular levels of serotonin in vivo with mitigated fouling effects. N-MCSWV enriches the electrochemical information by generating high dimensional voltammograms, which enables high sensitivity and selectivity against 5-hydroindoleacetic acid (5-HIAA), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), histamine, ascorbic acid, norepinephrine, adenosine, and pH. Using N-MCSWV, in combination with PEDOT:Nafion-coated carbon fiber microelectrodes, a tonic serotonin concentration of 52 ± 5.8 nM (n = 20 rats, ±SEM) was determined in the substantia nigra pars reticulata of urethane-anesthetized rats. Pharmacological challenges with dopaminergic, noradrenergic, and serotonergic synaptic reuptake inhibitors supported the ability of N-MCSWV to selectively detect tonic serotonin levels in vivo. Overall, N-MCSWV is a novel voltammetric technique for analytical quantification of serotonin. It offers continuous monitoring of changes in tonic serotonin concentrations in the brain to further our understanding of the role of serotonin in normal behaviors and psychiatric disorders.

Clinical Characteristics of Patients with Gait Instability after MR-Guided Focused Ultrasound Thalamotomy.

Background: MRgFUS thalamotomy is an incisionless procedure which effectively treats patients with tremor, although the procedure can result in adverse side effects including gait instability. By determining whether certain pre-existing conditions predispose patients to developing gait instability, we will be able to better counsel patients regarding risk of MRgFUS thalamotomy. Methods: All patients diagnosed with essential tremor, mixed tremor syndrome, or tremor predominant Parkinson disease who underwent MRgFUS thalamotomy at Mayo Clinic, Rochester between 2017 and 2020 were retrospectively reviewed. Baseline demographic and clinical data was extracted, and gait symptoms were compared pre- versus post-operatively. Results: Of 45 patients who underwent MRgFUS thalamotomy, 42 had at least one follow-up visit within twelve months and were included in the study. 39 patients had essential tremor, 1 had tremor predominant Parkinson disease, and 2 had mixed tremor syndrome. 19 out of 42 patients (45%) had gait decline. There were 10 (24%) females, and median age was 77.6 years (IQR 71.5-83.2). Older age was not correlated with gait decline (p = 0.82). Patients with a history of neuropathy and joint replacements were more likely to have gait decline after MRgFUS thalamotomy (p = 0.0099 and p = 0.0376). Patients with pre-existing gait aids were not more likely to have gait instability (p = 0.20). Conclusion: Patients who undergo MRgFUS thalamotomy for each of the tremor conditions, have an increased risk of experiencing gait decline, when there is a pre-procedure history of peripheral neuropathy, or joint replacement surgery. Older age or pre-existing gait aid use is not associated with worsened gait outcomes. Highlights: Patients who undergo MRgFUS thalamotomy for tremor syndromes have a significantly increased risk of experiencing gait decline when there is comorbid peripheral neuropathy or joint replacementOlder age or pre-existing gait aid use is not associated with worsened gait outcomes.

A compact stereotactic system for image-guided surgical intervention.

Objective. Stereotactic technology enables fine navigation to small structures in the human body. While current stereotactic systems facilitate accurate targeting, they are mechanically cumbersome and limited in scope. Here, we hypothesized that a stereotactic system could be developed with a reduced footprint while maintaining broad targeting capabilities in order to improve versatility in frame placement location and surgical workflow.Approach. We designed a stereotactic system around the center-of-arc principle, with mechanical properties that would enable a compact design and ample targeting and trajectory maneuverability. To examine the opportunity for a low-cost rapidly-deployable system we developed two fabrication variants, one using three dimensional (3D)-printing and the other using conventional machining. Mechanical and image-guided accuracies were tested in phantom studies using magnetic resonance imaging (MRI) and computed tomography. Using human cadaver head specimens, we assessed the system's surgical workflow and its ability to reliably and accurately implant electrodes in deep brain stimulation (DBS) surgery.Main results. We developed a small 7.7 × 5.4 cm2device platform that rigidly mounts to curvilinear bone and supports the attachment of surgical instrumentation. Attachment of two surgical instruments, an imaging localizer and a compact targeting device, demonstrated successful MRI-guided intervention in phantom studies with a vector error of 1.79 ± 0.41 mm. Evaluation of the 3D-printed system for DBS surgery confirmed ease of device platform attachment and instrument functionality, as well as demonstrated a surgical targeting accuracy of 1.83 ± 0.15 mm. In addition, we found the surgical time to be 78.3 ± 5.4 min for bilateral electrode implantation.Significance. We developed a light and compact stereotactic system whose accuracy is on par with those used clinically. This technology is suitable for clinical translation and its flexibility in positioning will seamlessly expand the capabilities for stereotaxy to treat a wide range of conditions, both within neurosurgery and beyond.

Deep brain stimulation for orthostatic tremor: A single-center case series.

BACKGROUND: Orthostatic tremor (OT) is a high-frequency weight-bearing tremor of the legs and trunk associated with progressive disability and is often refractory to medications. Case reports suggest that thalamic deep brain stimulation (DBS) is effective. We report 5 female patients with medication-refractory OT who underwent bilateral thalamic DBS at the Mayo Clinic and assess factors associated with a successful DBS outcome. METHODS: Demographic, clinical, electrophysiology, and DBS data were abstracted. Outcomes were change in tremor-onset latency, standing time, standing ADLs, and patient and clinician global impression of change (PGIC; CGIC). RESULTS: All 5 patients had improved standing time (72 vs 408 seconds, p ≤ 0.001) and improved standing ADLs after surgery, without change in tremor-onset latency (16 vs 75 seconds, p = 0.14). Maximal benefit was reached up to 3 years after surgery and sustained for up to 6 years. CGIC was "much improved" in all; PGIC was "much improved" in 4 and "minimally improved" in 1. There were no major complications. Postoperative electrophysiology (n = 1) showed lower tremor amplitude and slower tremor ramp-up on vs off stimulation. CONCLUSIONS: Bilateral thalamic DBS improved OT symptoms with benefit lasting up to 6 years. A modest increase in standing time of several minutes was associated with meaningful improvement in standing ADLs. Microlesional effect and bilateral stimulation are likely favorable features, while baseline standing time of several minutes may be unfavorable. These findings may inform clinician and patient counseling and require confirmation in larger studies.

Advances in neurochemical measurements: A review of biomarkers and devices for the development of closed-loop deep brain stimulation systems.

Neurochemical recording techniques have expanded our understanding of the pathophysiology of neurological disorders, as well as the mechanisms of action of treatment modalities like deep brain stimulation (DBS). DBS is used to treat diseases such as Parkinson's disease, Tourette syndrome, and obsessive-compulsive disorder, among others. Although DBS is effective at alleviating symptoms related to these diseases and improving the quality of life of these patients, the mechanism of action of DBS is currently not fully understood. A leading hypothesis is that DBS modulates the electrical field potential by modifying neuronal firing frequencies to non-pathological rates thus providing therapeutic relief. To address this gap in knowledge, recent advances in electrochemical sensing techniques have given insight into the importance of neurotransmitters, such as dopamine, serotonin, glutamate, and adenosine, in disease pathophysiology. These studies have also highlighted their potential use in tandem with electrophysiology to serve as biomarkers in disease diagnosis and progression monitoring, as well as characterize response to treatment. Here, we provide an overview of disease-relevant neurotransmitters and their roles and implications as biomarkers, as well as innovations to the biosensors used to record these biomarkers. Furthermore, we discuss currently available neurochemical and electrophysiological recording devices, and discuss their viability to be implemented into the development of a closed-loop DBS system.

A novel re-attachable stereotactic frame for MRI-guided neuronavigation and its validation in a large animal and human cadaver model.

OBJECTIVE: Stereotactic frame systems are the gold-standard for stereotactic surgeries, such as implantation of deep brain stimulation (DBS) devices for treatment of medically resistant neurologic and psychiatric disorders. However, frame-based systems require that the patient is awake with a stereotactic frame affixed to their head for the duration of the surgical planning and implantation of the DBS electrodes. While frameless systems are increasingly available, a reusable re-attachable frame system provides unique benefits. As such, we created a novel reusable MRI-compatible stereotactic frame system that maintains clinical accuracy through the detachment and reattachment of its stereotactic devices used for MRI-guided neuronavigation. APPROACH: We designed a reusable arc-centered frame system that includes MRI-compatible anchoring skull screws for detachment and re-attachment of its stereotactic devices. We validated the stability and accuracy of our system through phantom, in vivo mock-human porcine DBS-model and human cadaver testing. MAIN RESULTS: Phantom testing achieved a root mean square error (RMSE) of 0.94 ± 0.23 mm between the ground truth and the frame-targeted coordinates; and achieved an RMSE of 1.11 ± 0.40 mm and 1.33 ± 0.38 mm between the ground truth and the CT- and MRI-targeted coordinates, respectively. In vivo and cadaver testing achieved a combined 3D Euclidean localization error of 1.85 ± 0.36 mm (p < 0.03) between the pre-operative MRI-guided placement and the post-operative CT-guided confirmation of the DBS electrode. SIGNIFICANCE: Our system demonstrated consistent clinical accuracy that is comparable to conventional frame and frameless stereotactic systems. Our frame system is the first to demonstrate accurate relocation of stereotactic frame devices during in vivo MRI-guided DBS surgical procedures. As such, this reusable and re-attachable MRI-compatible system is expected to enable more complex, chronic neuromodulation experiments, and lead to a clinically available re-attachable frame that is expected to decrease patient discomfort and costs of DBS surgery.

Global network modulation during thalamic stimulation for Tourette syndrome.

Background and objectives: Deep brain stimulation (DBS) of the thalamus is a promising therapeutic alternative for treating medically refractory Tourette syndrome (TS). However, few human studies have examined its mechanism of action. Therefore, the networks that mediate the therapeutic effects of thalamic DBS remain poorly understood. Methods: Five participants diagnosed with severe medically refractory TS underwent bilateral thalamic DBS stereotactic surgery. Intraoperative fMRI characterized the blood oxygen level-dependent (BOLD) response evoked by thalamic DBS and determined whether the therapeutic effectiveness of thalamic DBS, as assessed using the Modified Rush Video Rating Scale test, would correlate with evoked BOLD responses in motor and limbic cortical and subcortical regions. Results: Our results reveal that thalamic stimulation in TS participants has wide-ranging effects that impact the frontostriatal, limbic, and motor networks. Thalamic stimulation induced suppression of motor and insula networks correlated with motor tic reduction, while suppression of frontal and parietal networks correlated with vocal tic reduction. These regions mapped closely to major regions of interest (ROI) identified in a nonhuman primate model of TS. Conclusions: Overall, these findings suggest that a critical factor in TS treatment should involve modulation of both frontostriatal and motor networks, rather than be treated as a focal disorder of the brain. Using the novel combination of DBS-evoked tic reduction and fMRI in human subjects, we provide new insights into the basal ganglia-cerebellar-thalamo-cortical network-level mechanisms that influence the effects of thalamic DBS. Future translational research should identify whether these network changes are cause or effect of TS symptoms.

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.

A Diamond-Based Electrode for Detection of Neurochemicals in the Human Brain.

Deep brain stimulation (DBS), a surgical technique to treat certain neurologic and psychiatric conditions, relies on pre-determined stimulation parameters in an open-loop configuration. The major advancement in DBS devices is a closed-loop system that uses neurophysiologic feedback to dynamically adjust stimulation frequency and amplitude. Stimulation-driven neurochemical release can be measured by fast-scan cyclic voltammetry (FSCV), but existing FSCV electrodes rely on carbon fiber, which degrades quickly during use and is therefore unsuitable for chronic neurochemical recording. To address this issue, we developed durable, synthetic boron-doped diamond-based electrodes capable of measuring neurochemical release in humans. Compared to carbon fiber electrodes, they were more than two orders-of-magnitude more physically-robust and demonstrated longevity in vitro without deterioration. Applied for the first time in humans, diamond electrode recordings from thalamic targets in patients (n = 4) undergoing DBS for tremor produced signals consistent with adenosine release at a sensitivity comparable to carbon fiber electrodes. (Clinical trials # NCT01705301).

Centromedian-Parafascicular Complex Deep Brain Stimulation for Tourette Syndrome: A Retrospective Study.

Deep brain stimulation (DBS) of the thalamic centromedian/parafascicular (CM-Pf) complex has been reported as a promising treatment for patients with severe, treatment-resistant Tourette syndrome (TS). In this study, safety and clinical outcomes of bilateral thalamic CM-Pf DBS were reviewed in a series of 12 consecutive patients with medically refractory TS, 11 of whom met the criteria of postsurgical follow-up at our institution for at least 2 months. Five patients were followed for a year or longer. Consistent with many patients with TS, all patients had psychiatric comorbidities. Tic severity and frequency were measured by using the Yale Global Tic Severity Scale (YGTSS) over time (average, 26 months) in 10 subjects. One patient was tested at 2-week follow-up only and thus was excluded from group YGTSS analysis. Final YGTSS scores differed significantly from the preoperative baseline score. The average (n=10) improvement relative to baseline in the total score was 54% (95% CI, 37-70); average improvement relative to baseline in the YGTSS Motor tic, Phonic tic, and Impairment subtests was 46% (95% CI, 34-64), 52% (95% CI, 34-72), and 59% (95% CI, 39-78), respectively. There were no intraoperative complications. After surgery, 1 subject underwent wound revision because of a scalp erosion and wound infection; the implanted DBS system was successfully salvaged with surgical revision and combined antibiotic therapy. Stimulation-induced adverse effects did not prevent the use of the DBS system, although 1 subject is undergoing a trial period with the stimulator off. This surgical series adds to the literature on CM-Pf DBS and supports its use as an effective and safe therapeutic option for severe refractory TS.

Combat-related intradural gunshot wound to the thoracic spine: significant improvement and neurologic recovery following bullet removal.

The vast majority of combat-related penetrating spinal injuries from gunshot wounds result in severe or complete neurological deficit. Treatment is based on neurological status, the presence of cerebrospinal fluid (CSF) fistulas, and local effects of any retained fragment(s). We present a case of a 46-year-old male who sustained a spinal gunshot injury from a 7.62-mm AK-47 round that became lodged within the subarachnoid space at T9-T10. He immediately suffered complete motor and sensory loss. By 24-48 hours post-injury, he had recovered lower extremity motor function fully but continued to have severe sensory loss (posterior cord syndrome). On post-injury day 2, he was evacuated from the combat theater and underwent a T9 laminectomy, extraction of the bullet, and dural laceration repair. At surgery, the traumatic durotomy was widened and the bullet, which was laying on the dorsal surface of the spinal cord, was removed. The dura was closed in a water-tight fashion and fibrin glue was applied. Postoperatively, the patient made a significant but incomplete neurological recovery. His stocking-pattern numbness and sub-umbilical searing dysthesia improved. The spinal canal was clear of the foreign body and he had no persistent CSF leak. Postoperative magnetic resonance imaging of the spine revealed contusion of the spinal cord at the T9 level. Early removal of an intra-canicular bullet in the setting of an incomplete spinal cord injury can lead to significant neurological recovery following even high-velocity and/or high-caliber gunshot wounds. However, this case does not speak to, and prior experience does not demonstrate, significant neurological benefit in the setting of a complete injury.

Minimally invasive convection-enhanced delivery of biologics into dorsal root ganglia: validation in the pig model and prospective modeling in humans. Technical note.

Dorsal root ganglia (DRG) are critical anatomical structures involved in nociception. Intraganglionic (IG) drug delivery is therefore an important route of administration for novel analgesic therapies. Although IG injection in large animal models is highly desirable for preclinical biodistribution and toxicology studies of new drugs, no method to deliver pharmaceutical agents into the DRG has been reported in any large species. The present study describes a minimally invasive technique of IG agent delivery in domestic swine, one of the most common large animal models. The technique utilizes CT guidance for DRG targeting and a custom-made injection assembly for convection enhanced delivery (CED) of therapeutic agents directly into DRG parenchyma. The DRG were initially visualized by CT myelography to determine the optimal access route to the DRG. The subsequent IG injection consisted of 3 steps. First, a commercially available guide needle was advanced to a position dorsolateral to the DRG, and the dural root sleeve was punctured, leaving the guide needle contiguous with, but not penetrating, the DRG. Second, the custom-made stepped stylet was inserted through the guide needle into the DRG parenchyma. Third, the stepped stylet was replaced by the custom-made stepped needle, which was used for the IG CED. Initial dye injections performed in pig cadavers confirmed the accuracy of DRG targeting under CT guidance. Intraganglionic administration of adeno-associated virus in vivo resulted in a unilateral transduction of the injected DRG, with 33.5% DRG neurons transduced. Transgene expression was also found in the dorsal root entry zones at the corresponding spinal levels. The results thereby confirm the efficacy of CED by the stepped needle and a selectivity of DRG targeting. Imaging-based modeling of the procedure in humans suggests that IG CED may be translatable to the clinical setting.

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.

Increased cortical extracellular adenosine correlates with seizure termination.

OBJECTIVE: Seizures are currently defined by their electrographic features. However, neuronal networks are intrinsically dependent on neurotransmitters of which little is known regarding their periictal dynamics. Evidence supports adenosine as having a prominent role in seizure termination, as its administration can terminate and reduce seizures in animal models. Furthermore, microdialysis studies in humans suggest that adenosine is elevated periictally, but the relationship to the seizure is obscured by its temporal measurement limitations. Because electrochemical techniques can provide vastly superior temporal resolution, we test the hypothesis that extracellular adenosine concentrations rise during seizure termination in an animal model and humans using electrochemistry. METHODS: White farm swine (n = 45) were used in an acute cortical model of epilepsy, and 10 human epilepsy patients were studied during intraoperative electrocorticography (ECoG). Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS)-based fast scan cyclic voltammetry (FSCV) and fixed potential amperometry were obtained utilizing an adenosine-specific triangular waveform or biosensors, respectively. RESULTS: Simultaneous ECoG and electrochemistry demonstrated an average adenosine increase of 260% compared to baseline, at 7.5 ± 16.9 s with amperometry (n = 75 events) and 2.6 ± 11.2 s with FSCV (n = 15 events) prior to electrographic seizure termination. In agreement with these animal data, adenosine elevation prior to seizure termination in a human patient utilizing FSCV was also seen. SIGNIFICANCE: Simultaneous ECoG and electrochemical recording supports the hypothesis that adenosine rises prior to seizure termination, suggesting that adenosine itself may be responsible for seizure termination. Future work using intraoperative WINCS-based FSCV recording may help to elucidate the precise relationship between adenosine and seizure termination.

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.

Early experience of pre- and post-contrast 7.0T MRI in brain tumors.

We investigated the safety and clinical applicability of 7.0 Tesla (T) brain magnetic resonance imaging (MRI) in patients with brain tumors. Twenty-four patients with intraaxial or extraaxial brain tumors were enrolled in this study. 7.0T MRIs of T2*-weighted axial and T1-weighted coronal or sagittal images were obtained and compared with 1.5T brain MRIs. The T2*-weighted images from 7.0T brain MRI revealed detailed microvasculature and the internal contents of supratentorial brain tumors better than that of 1.5T brain MRI. For brain tumors located in parasellar areas or areas adjacent to major cerebral vessels, flow-related artifacts were exaggerated in the 7.0T brain MRIs. For brain tumors adjacent to the skull base, susceptibility artifacts in the interfacing areas of the paranasal sinus and skull base hampered the aquisition of detailed images and information on brain tumors in the 7.0T brain MRIs. This study shows that 7.0T brain MRI can provide detailed information on the intratumoral components and margins in supratentorial brain tumors. Further studies are needed to develop refined MRI protocols for better images of brain tumors located in the skull base, parasellar, and adjacent major cerebrovascular structures.