Deep Brain Stimulation of Bilateral Centromedian Thalamic Nuclei in Pediatric Patients with Lennox-Gastaut Syndrome: An Institutional Experience.

BACKGROUND: Surgical management of pediatric patients with nonlesional, drug-resistant epilepsy, including patients with Lennox-Gastaut syndrome (LGS), remains a challenge given the lack of resective targets in most patients and shows seizure freedom rates <50% at 5 years. The efficacy of deep brain stimulation (DBS) is less certain in children than in adults. This study examined clinical and seizure outcomes for pediatric patients with LGS undergoing DBS targeting of the centromedian thalamic nuclei (CMTN). METHODS: An institutional review board-approved retrospective analysis was performed of patients aged ≤19 years with clinical diagnosis of LGS undergoing bilateral DBS placement to the CMTN from 2020 to 2021 by a single surgeon. RESULTS: Four females and 2 males aged 6-19 years were identified. Before surgery, each child experienced at least 6 years of refractory seizures; 4 children had experienced seizures since infancy. All took antiseizure medications at the time of surgery. Five children had previous placement of a vagus nerve stimulator and 2 had a previous corpus callosotomy. The mean length of stay after DBS was 2 days. No children experienced adverse neurologic effects from implantation; the mean follow-up time was 16.3 months. Four patients had >60% reduction in seizure frequency after surgery, 1 patient experienced 10% reduction, and 1 patient showed no change. No children reported worsening seizure symptoms after surgery. CONCLUSIONS: Our study contributes to the sparse literature describing CMTN DBS for children with drug-resistant epilepsy from LGS. Our results suggest that CMTN DBS is a safe and effective therapeutic modality that should be considered as an alternative or adjuvant therapy for this challenging patient population. Further studies with larger patient populations are warranted.

Epilepsy-Related Mortality After Laser Interstitial Thermal Therapy in Patients With Drug-Resistant Epilepsy.

OBJECTIVES: The purpose of this report was to study the incidence of sudden unexpected death in epilepsy (SUDEP) after laser interstitial thermal therapy (LITT) for drug-resistant epilepsy (DRE). METHODS: A prospective observational study of consecutive patients treated with LITT between 2013 and 2021 was conducted. The primary outcome was the occurrence of SUDEP during postoperative follow-up. Surgical outcome was classified according to the Engel scale. RESULTS: There were 5 deaths, including 4 SUDEPs, among 135 patients with a median follow-up duration of 3.5 (range 0.1-9.0) years and a total of 501.3 person-years at risk. The estimated incidence of SUDEP was 8.0 (95% CI 2.2-20.4) per 1,000 person-years. Three SUDEPs occurred in patients with poor seizure outcomes, whereas 1 patient was seizure-free. Compared with pooled historical data, SUDEP occurred at a higher rate than in cohorts treated with resective surgery and at a rate similar to nonsurgical controls. DISCUSSION: SUDEP occurred early and late after mesial temporal LITT. The SUDEP rate was comparable with rates reported in epilepsy surgery candidates who did not receive intervention. These findings reinforce targeting seizure freedom to decrease SUDEP risk, including early consideration for further intervention. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that LITT is not effective in reducing SUDEP incidence in patients with DRE.

Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex.

Rodent studies have demonstrated that synaptic dynamics from excitatory to inhibitory neuron types are often dependent on the target cell type. However, these target cell-specific properties have not been well investigated in human cortex, where there are major technical challenges in reliably obtaining healthy tissue, conducting multiple patch-clamp recordings on inhibitory cell types, and identifying those cell types. Here, we take advantage of newly developed methods for human neurosurgical tissue analysis with multiple patch-clamp recordings, post-hoc fluorescent in situ hybridization (FISH), machine learning-based cell type classification and prospective GABAergic AAV-based labeling to investigate synaptic properties between pyramidal neurons and PVALB- vs. SST-positive interneurons. We find that there are robust molecular differences in synapse-associated genes between these neuron types, and that individual presynaptic pyramidal neurons evoke postsynaptic responses with heterogeneous synaptic dynamics in different postsynaptic cell types. Using molecular identification with FISH and classifiers based on transcriptomically identified PVALB neurons analyzed by Patch-seq, we find that PVALB neurons typically show depressing synaptic characteristics, whereas other interneuron types including SST-positive neurons show facilitating characteristics. Together, these data support the existence of target cell-specific synaptic properties in human cortex that are similar to rodent, thereby indicating evolutionary conservation of local circuit connectivity motifs from excitatory to inhibitory neurons and their synaptic dynamics.

Acute Postoperative Seizures and Engel Class Outcome at 1 Year Postselective Laser Amygdalohippocampal Ablation for Mesial Temporal Lobe Epilepsy.

BACKGROUND: MRI-guided laser interstitial thermal therapy (MRgLITT) for mesial temporal lobe epilepsy is a safe, minimally invasive alternative to traditional surgical approaches. Prognostic factors associated with efficacy are debated; preoperative epilepsy duration and semiology seem to be important variables. OBJECTIVE: To determine whether acute postoperative seizure (APOS) after MRgLITT for mesial temporal lobe epilepsy is associated with seizure freedom/Engel class outcome at 1 year. METHODS: A single-institution retrospective study including adults undergoing first time MRgLITT for mesial temporal lobe epilepsy (2010-2019) with ≥1-year follow-up. Preoperative data included sex, epilepsy duration, number of antiepileptics attempted, weekly seizure frequency, seizure semiology, and radiographically verified anatomic lesion at seizure focus. Postoperative data included clinical detection of APOS within 7 days postoperatively, and immediate amygdala, hippocampal, entorhinal, and parahippocampal residual volumes determined using quantitative imaging postprocessing. Primary outcome was seizure freedom/Engel classification 1 year postoperatively. RESULTS: Of 116 patients, 53% (n = 61) were female, with an average epilepsy duration of 21 (±14) years, average 6 failed antiepileptics (±3), and weekly seizure frequency of 5. APOS was associated with worse Engel class ( P = .010), conferring 6.3 times greater odds of having no improvement vs achieving seizure freedom at 1 year. Residual amygdala, hippocampal, entorhinal, and parahippocampal volumes were not statistically significant prognostic factors. CONCLUSION: APOS was associated with a lower chance of seizure freedom at 1 year post-MRgLITT for mesial temporal lobe epilepsy. Amygdala, hippocampal, entorhinal, and parahippocampal residual volumes after ablation were not significant prognostic factors.

Local connectivity and synaptic dynamics in mouse and human neocortex.

We present a unique, extensive, and open synaptic physiology analysis platform and dataset. Through its application, we reveal principles that relate cell type to synaptic properties and intralaminar circuit organization in the mouse and human cortex. The dynamics of excitatory synapses align with the postsynaptic cell subclass, whereas inhibitory synapse dynamics partly align with presynaptic cell subclass but with considerable overlap. Synaptic properties are heterogeneous in most subclass-to-subclass connections. The two main axes of heterogeneity are strength and variability. Cell subclasses divide along the variability axis, whereas the strength axis accounts for substantial heterogeneity within the subclass. In the human cortex, excitatory-to-excitatory synaptic dynamics are distinct from those in the mouse cortex and vary with depth across layers 2 and 3.

Effects of laser interstitial thermal therapy for mesial temporal lobe epilepsy on the structural connectome and its relationship to seizure freedom.

OBJECTIVE: Laser interstitial thermal therapy (LITT) is a minimally invasive surgery for mesial temporal lobe epilepsy (mTLE), but the effects of individual patient anatomy and location of ablation volumes affect seizure outcomes. The purpose of this study is to see if features of individual patient structural connectomes predict surgical outcomes after LITT for mTLE. METHODS: This is a retrospective analysis of seizure outcomes of LITT for mTLE in 24 patients. We use preoperative diffusion tensor imaging (DTI) to simulate changes in structural connectivity after laser ablation. A two-step machine-learning algorithm is applied to predict seizure outcomes from the change in connectomic features after surgery. RESULTS: Although node-based network features such as clustering coefficient and betweenness centrality have some predictive value, changes in connection strength between mesial temporal regions predict seizure outcomes significantly better. Changes in connection strength between the entorhinal cortex (EC), and the insula, hippocampus, and amygdala, as well as between the temporal pole and hippocampus, predict Engel Class I outcomes with an accuracy of 88%. Analysis of the ablation location, as well as simulated, alternative ablations, reveals that a more medial, anterior, and inferior ablation volume is associated with a greater effect on these connections, and potentially on seizure outcomes. SIGNIFICANCE: Our results indicate (1) that seizure outcomes can be retrospectively predicted with excellent accuracy using changes in structural connectivity, and (2) that favorable connectomic changes are associated with an ablation volume involving relatively mesial, anterior, and inferior locations. These results may provide a framework whereby individual pre-operative structural connectomes can be used to optimize ablation volumes and improve outcomes in LITT for mTLE.

Closing the Loop With Cortical Sensing: The Development of Adaptive Deep Brain Stimulation for Essential Tremor Using the Activa PC+S.

Deep Brain Stimulation (DBS) is an important tool in the treatment of pharmacologically resistant neurological movement disorders such as essential tremor (ET) and Parkinson's disease (PD). However, the open-loop design of current systems may be holding back the true potential of invasive neuromodulation. In the last decade we have seen an explosion of activity in the use of feedback to "close the loop" on neuromodulation in the form of adaptive DBS (aDBS) systems that can respond to the patient's therapeutic needs. In this paper we summarize the accomplishments of a 5-year study at the University of Washington in the use of neural feedback from an electrocorticography strip placed over the sensorimotor cortex. We document our progress from an initial proof of hardware all the way to a fully implanted adaptive stimulation system that leverages machine-learning approaches to simplify the programming process. In certain cases, our systems out-performed current open-loop approaches in both power consumption and symptom suppression. Throughout this effort, we collaborated with neuroethicists to capture patient experiences and take them into account whilst developing ethical aDBS approaches. Based on our results we identify several key areas for future work. "Graded" aDBS will allow the system to smoothly tune the stimulation level to symptom severity, and frequent automatic calibration of the algorithm will allow aDBS to adapt to the time-varying dynamics of the disease without additional input from a clinician. Additionally, robust computational models of the pathophysiology of ET will allow stimulation to be optimized to the nuances of an individual patient's symptoms. We also outline the unique advantages of using cortical electrodes for control and the remaining hardware limitations that need to be overcome to facilitate further development in this field. Over the course of this study we have verified the potential of fully-implanted, cortically driven aDBS as a feasibly translatable treatment for pharmacologically resistant ET.

Robustness of Beta Desynchronization from Chronically Implanted Cortical Electrodes on Multiple Time Scales.

Adaptive deep brain stimulation (aDBS) promises a significant improvement in patient outcomes, compared to existing deep brain stimulation devices. Fully implanted systems represent the next step to the clinical adoption of aDBS. We take advantage of a unique longitudinal data set formed as part of an effort to investigate aDBS for essential tremor to verify the long term reliability of electrocorticography strips over the motor cortex as a source of bio-markers for control of adaptive stimulation. We show that beta band event related de-synchronization, a promising bio-marker for movement, is robust even when used to trigger aDBS. Over the course of several months we show a minor increase in beta band event related de-synchronization in patients with active deep brain stimulation confirming that it could be used in chronically implanted systems.Clinical relevance - We show the promise and practicality of cortical electrocorticography strips for use in fully implanted, clinically translatable, aDBS systems.

Signature morpho-electric, transcriptomic, and dendritic properties of human layer 5 neocortical pyramidal neurons.

In the neocortex, subcerebral axonal projections originate largely from layer 5 (L5) extratelencephalic-projecting (ET) neurons. The unique morpho-electric properties of these neurons have been mainly described in rodents, where retrograde tracers or transgenic lines can label them. Similar labeling strategies are infeasible in the human neocortex, rendering the translational relevance of findings in rodents unclear. We leveraged the recent discovery of a transcriptomically defined L5 ET neuron type to study the properties of human L5 ET neurons in neocortical brain slices derived from neurosurgeries. Patch-seq recordings, where transcriptome, physiology, and morphology were assayed from the same cell, revealed many conserved morpho-electric properties of human and rodent L5 ET neurons. Divergent properties were often subtler than differences between L5 cell types within these two species. These data suggest a conserved function of L5 ET neurons in the neocortical hierarchy but also highlight phenotypic divergence possibly related to functional specialization of human neocortex.

Intraoperative Characterization of Subthalamic Nucleus-to-Cortex Evoked Potentials in Parkinson's Disease Deep Brain Stimulation.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective tool for treating medically refractory Parkinson's disease (PD), but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials (EPs) in the primary motor cortex (M1), suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography (ECoG) from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed - one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the "start" and the "end" EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude (p < 0.05) and latency (p < 0.001), and the end, but not the start, EP magnitude has a significant relationship (p < 0.001, adjusted for random effects of subject) to ongoing high gamma (80-150 Hz) power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs.

Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex.

Viral genetic tools that target specific brain cell types could transform basic neuroscience and targeted gene therapy. Here, we use comparative open chromatin analysis to identify thousands of human-neocortical-subclass-specific putative enhancers from across the genome to control gene expression in adeno-associated virus (AAV) vectors. The cellular specificity of reporter expression from enhancer-AAVs is established by molecular profiling after systemic AAV delivery in mouse. Over 30% of enhancer-AAVs produce specific expression in the targeted subclass, including both excitatory and inhibitory subclasses. We present a collection of Parvalbumin (PVALB) enhancer-AAVs that show highly enriched expression not only in cortical PVALB cells but also in some subcortical PVALB populations. Five vectors maintain PVALB-enriched expression in primate neocortex. These results demonstrate how genome-wide open chromatin data mining and cross-species AAV validation can be used to create the next generation of non-species-restricted viral genetic tools.

Rebound effect in deep brain stimulation for essential tremor and symptom severity estimation from neural data.

Deep brain stimulation (DBS) is a safe and established treatment for essential tremor (ET). However, there remains considerable room for improvement due to concerns associated with the initial implant surgery, semi-regular revision surgeries for battery replacements, and side effects including paresthesia, gait ataxia, and emotional disinhibition that have been associated with continuous, or conventional, DBS (cDBS) treatment. Adaptive DBS (aDBS) seeks to ameliorate some of these concerns by using feedback from either an external wearable or implanted sensor to modulate stimulation parameters as needed. aDBS has been demonstrated to be as or more effective than cDBS, but the purely binary control system most commonly deployed by aDBS systems likely still provides sub-optimal treatment and may introduce new issues. One example of these issues is rebound effect, in which the tremor symptoms of an ET patient receiving DBS therapy temporarily worsen after cessation of stimulation before leveling out to a steady state. Here is presented a quantitative analysis of rebound effect in 3 patients receiving DBS for ET. Rebound was evident in all 3 patients by both clinical assessment and inertial measurement unit data, peaking by the latter at Tp = 6.65 minutes after cessation of stimulation. Using features extracted from neural data, linear regression was applied to predict tremor severity, with $R_{avg{\text{ }}}^2 = 0.82$. These results strongly suggest that rebound effect and the additional information made available by rebound effect should be considered and exploited when designing novel aDBS systems.

A tablet- and mobile-based application for remote diagnosis and analysis of movement disorder symptoms.

One significant hindrance to effective diagnosis of movement disorders (MDs) and analysis of their progression is the requirement for patients to conduct tests in the presence of a clinician. Here is presented a pilot study for diagnosis of essential tremor (ET), the world's most common MD, through analysis of a tablet- or mobile-based drawing task that may be selected at will, with the spiral- and line-drawing tasks of the Fahn-Tolosa-Marin tremor rating scale serving as our task in this work. This system replaces the need for pen-and-paper drawing tests while permitting advanced quantitative analysis of drawing smoothness, pressure applied, and other measures. Data is securely recorded and stored in the cloud, from which all analysis was conducted remotely. This will enable longitudinal analysis of patient disease progression without the need for excessive clinical visits. Several features were extracted and recursive feature elimination applied to rank the features' individual contribution to our classifier. Maximum cross-validated classification accuracy on a preliminary sample set was 98.3%. Future work will involve collecting healthy subject data from an age-controlled population and extending this diagnostic application to additional conditions, as well as incorporating regression-based symptom severity analysis. This highly promising new technology has the potential to substantially alleviate the demands placed on both clinicians and patients by bringing MD treatment more into line with the era of personalized medicine.

Stereotactic Brain Biopsy Hemorrhage Risk Factors and Implications for Postoperative Care at a Single Institution: An Argument For Postoperative Imaging.

OBJECTIVE: To determine preoperative factors contributing to postoperative hemorrhage after stereotactic brain biopsy (STB), clinical implications of postoperative hemorrhage, and the role of postoperative imaging in clinical management. METHODS: Retrospective review of STB (2005-2018) across 2 institutions including patients aged >18 years undergoing first STB. Patients with prior craniotomy, open biopsy, or prior STB were excluded. Preoperative variables included age, sex, neurosurgeon seniority, STB method. Postoperative variables included pathology, postoperative hemorrhage on computed tomography, immediate and 30-day postoperative seizure, infection, postoperative hospital stay duration, and 30-day return to operating room (OR). Analysis used the Fisher exact tests for categorical variables. RESULTS: Overall, 410 patients were included. Average age was 56.5 (±16.5) years; 60% (n = 248) were men. The majority of biopsies were performed by senior neurosurgeons (66%, n = 270); frontal lobe (42%, n = 182) and glioblastoma (45%, n = 186) were the most common location and pathology. Postoperative hemorrhage occurred in 28% (114) of patients with 20% <0.05 cm3 and 8% >0.05 cm3. Postoperative hemorrhage of any size was associated with increased rate of postoperative deficit within both 24 hours and 30 days, postoperative seizure, and length of hospital stay when controlling for pathology. Hemorrhages >0.05 cm3 had a 16% higher rate of return to the OR for evacuation, due to clinical deterioration as opposed to radiographic progression. CONCLUSIONS: Postbiopsy hemorrhage was associated with higher risk of immediate and delayed postoperative deficit and seizure. Postoperative computed tomography should be used to determine whether STB patients can be discharged same day or admitted for observation; clinical evaluation should determine return to OR for evacuation.

Concurrent Deep Brain Stimulation Reduces the Direct Cortical Stimulation Necessary for Motor Output.

BACKGROUND: Converging literatures suggest that deep brain stimulation (DBS) in Parkinson's disease affects multiple circuit mechanisms. One proposed mechanism is the normalization of primary motor cortex (M1) pathophysiology via effects on the hyperdirect pathway. OBJECTIVES: We hypothesized that DBS would reduce the current intensity necessary to modulate motor-evoked potentials from focally applied direct cortical stimulation (DCS). METHODS: Intraoperative subthalamic DBS, DCS, and preoperative diffusion tensor imaging data were acquired in 8 patients with Parkinson's disease. RESULTS: In 7 of 8 patients, DBS significantly reduced the M1 DCS current intensity required to elicit motor-evoked potentials. This neuromodulation was specific to select DBS bipolar configurations. In addition, the volume of activated tissue models of these configurations were significantly associated with overlap of the hyperdirect pathway. CONCLUSIONS: DBS reduces the current necessary to elicit a motor-evoked potential using DCS. This supports a circuit mechanism of DBS effectiveness, potentially involving the hyperdirect pathway that speculatively may underlie reductions in hypokinetic abnormalities in Parkinson's disease. © 2020 International Parkinson and Movement Disorder Society.

Evaluating angioarchitectural characteristics of glial and metastatic brain tumors with conventional magnetic resonance imaging.

Primary and metastatic brain tumors can overlap in traditional imaging features detected on preoperative conventional magnetic resonance imaging (MRI). The research objective was to determine whether morphological vascular characteristics present in routine preoperative imaging using traditional MRI sequences are predictive of primary versus metastatic brain tumors; secondarily to determine association of conventional and vascular-related imaging parameters with intraoperative blood loss, pathological invasion, and World Health Organization (WHO) tumor grade. A retrospective review analyzed 100 consecutive intracranial tumor surgeries, 50 WHO grade II-IV gliomas and 50 intracranial metastases. Two blinded expert readers independently evaluated preoperative MRIs, obtained via standard morphological imaging sequences, for adjacent or intra-tumoral arterial aneurysm, peritumoral venous ectasia, prominence, or engorgement ("aberrant peritumoral vessels"), and prominent intra-tumoral flow voids. Multivariate analysis was performed to develop models predictive of glioma and glioblastoma (GBM). Aberrant peritumoral vessels and prominent intra-tumoral flow voids were statistically significant predictors of glioma in univariate analyses (p = 0.048, p = 0.001, respectively) and when combined in multivariate analysis (OR = 5.23, p = 0.001), particularly for GBM (OR = 9.08, p < 0.001). Multivariate modeling identified prominent intra-tumoral flow voids and FLAIR invasion as the strongest combined predictors of gliomas and GBM. Aberrant peritumoral vessels and larger tumor volume predicted higher intraoperative blood loss in all analyses. No vascular-related parameters predicted pathological invasion on multivariate analysis. Aberrant peritumoral vessels and prominent intra-tumoral flow voids were predictive of gliomas, specifically GBM. These vascular characteristics, evaluated on routine clinical preoperative MRI imaging, may aid in distinguishinggliomafrom brainmetastases andmay predict intraoperative blood loss.

Publisher Correction: Direct stimulation of somatosensory cortex results in slower reaction times compared to peripheral touch in humans.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Multicenter validation of automated trajectories for selective laser amygdalohippocampectomy.

OBJECTIVE: Laser interstitial thermal therapy (LITT) is a novel minimally invasive alternative to open mesial temporal resection in drug-resistant mesial temporal lobe epilepsy (MTLE). The safety and efficacy of the procedure are dependent on the preplanned trajectory and the extent of the planned ablation achieved. Ablation of the mesial hippocampal head has been suggested to be an independent predictor of seizure freedom, whereas sparing of collateral structures is thought to result in improved neuropsychological outcomes. We aim to validate an automated trajectory planning platform against manually planned trajectories to objectively standardize the process. METHODS: Using the EpiNav platform, we compare automated trajectory planning parameters derived from expert opinion and machine learning to undertake a multicenter validation against manually planned and implemented trajectories in 95 patients with MTLE. We estimate ablation volumes of regions of interest and quantify the size of the avascular corridor through the use of a risk score as a marker of safety. We also undertake blinded external expert feasibility and preference ratings. RESULTS: Automated trajectory planning employs complex algorithms to maximize ablation of the mesial hippocampal head and amygdala, while sparing the parahippocampal gyrus. Automated trajectories resulted in significantly lower calculated risk scores and greater amygdala ablation percentage, whereas overall hippocampal ablation percentage did not differ significantly. In addition, estimated damage to collateral structures was reduced. Blinded external expert raters were significantly more likely to prefer automated to manually planned trajectories. SIGNIFICANCE: Retrospective studies of automated trajectory planning show much promise in improving safety parameters and ablation volumes during LITT for MTLE. Multicenter validation provides evidence that the algorithm is robust, and blinded external expert ratings indicate that the trajectories are clinically feasible. Prospective validation studies are now required to determine if automated trajectories translate into improved seizure freedom rates and reduced neuropsychological deficits.

Use of Dexmedetomidine for Postoperative Pain Management Following Spine Fusion Surgery in a Highly Opioid-Tolerant Patient.

A 51-year-old man with metastatic renal cell carcinoma whose fentanyl requirement was 3000-4000 µg/h in inpatient hospice presented for a thoracic (T) vertebral 4-10 posterior spinal fusion for a lytic T7 compression fracture. He underwent total intravenous (IV) anesthesia with propofol, remifentanil, and ketamine; liposome bupivacaine was locally infiltrated at the end of the case. Following extubation on postoperative day (POD) 1, he had severe pain refractory to high-dose IV fentanyl patient control analgesia and ketamine infusion. His pain dramatically improved after a dexmedetomidine infusion was added and titrated to the analgesic effect. He participated in neurological examinations and fulfilled both surgical and pain management goals without side effects. Dexmedetomidine was successfully weaned off on POD 3.