Refining the predictive value of preoperative apparent diffusion coefficient (ADC) by whole-tumor analysis for facial nerve outcomes in vestibular schwannomas.

BACKGROUND: Apparent diffusion coefficient (ADC) in MRI has been shown to correlate with postoperative House-Brackmann (HB) scores in patients with vestibular schwannoma despite limited methodology. To rectify limitations of single region of interest (ROI) sampling, we hypothesize that whole-tumor ADC histogram analysis will refine the predictive value of this preoperative biomarker related to postoperative facial nerve function. METHODS: Of 155 patients who underwent resection of vestibular schwannoma (2014-2020), 125 patients were included with requisite clinical and radiographic data. After volumetric analysis and whole-tumor ADC histogram, regression tree analysis identified ADC cutoff for significant differences in HB grade. Outcomes were extent of resection, facial nerve function, hospital length of stay (LOS), and complications. RESULTS: Regression tree analysis defined three quantitative ADC groups (× 10-6 mm2/s) as high (> 2248.77; HB 1.7), mid (1468.44-2248.77; HB 3.1), and low (< 1468.44; HB 2.3) range (p 0.04). The mid-range ADC group had significantly worse postoperative HB scores and longer hospital LOS. Large tumor volume was independently predictive of lower rates of gross total resection (p <0.0001), higher postoperative HB score (p 0.002), higher rate of complications (p 0.04), and longer LOS (p 0.003). CONCLUSIONS: Whole-tumor histogram yielded a robust regression tree analysis that defined three ADC groups with significantly different facial nerve outcomes. This likely reflects tumor heterogeneity better than solid-tumor ROI sampling. Whole-tumor ADC warrants further study as a useful radiographic biomarker in patients with vestibular schwannoma who are considering surgical resection.

Sleep macro-architecture in patients with Parkinson's disease does not change during the first night of neurostimulation in a pilot study.

STUDY OBJECTIVES: A growing body of literature suggests that deep brain stimulation (DBS) to treat motor symptoms of Parkinson's disease (PD) may also ameliorate certain sleep deficits. Many foundational studies have examined the impact of stimulation on sleep following several months of therapy, leaving an open question regarding the time course for improvement. It is unknown whether sleep improvement will immediately follow onset of therapy or accrete over a prolonged period of stimulation. The objective of our study was to address this knowledge gap by assessing the impact of DBS on sleep macro-architecture during the first nights of stimulation. METHODS: Polysomnograms were recorded for three consecutive nights in 14 patients with advanced PD (10 male, 4 female; age: 53-74 years), with intermittent, unilateral subthalamic nucleus DBS on the final night or two. Sleep scoring was determined manually by a consensus of four experts. Sleep macro-architecture was objectively quantified using the percentage, latency, and mean bout length of wake after sleep onset (WASO) and on each stage of sleep (REM and NREM stages N1, N2, N3). RESULTS: Sleep was found to be highly disrupted in all nights. Sleep architecture on nights without stimulation was consistent with prior results in treatment naive patients with PD. No statistically significant difference was observed due to stimulation. CONCLUSIONS: These objective measures suggest that one night of intermittent subthreshold stimulation appears insufficient to impact sleep macro-architecture. CLINICAL TRIAL REGISTRATION: Name: Adaptive Neurostimulation to Restore Sleep in Parkinson's Disease; URL: https://clinicaltrials.gov/ct2/show/NCT04620551; Identifier: NCT04620551.

Brain Shift during Staged Deep Brain Stimulation for Movement Disorders.

INTRODUCTION: Deep brain stimulation (DBS) is a routine neurosurgical procedure utilized to treat various movement disorders including Parkinson's disease (PD), essential tremor (ET), and dystonia. Treatment efficacy is dependent on stereotactic accuracy of lead placement into the deep brain target of interest. However, brain shift attributed to pneumocephalus can introduce unpredictable inaccuracies during DBS lead placement. This study aimed to determine whether intracranial air is associated with brain shift in patients undergoing staged DBS surgery. METHODS: We retrospectively evaluated 46 patients who underwent staged DBS surgery for PD, ET, and dystonia. Due to the staged nature of DBS surgery at our institution, the first electrode placement is used as a concrete fiducial marker for movement in the target location. Postoperative computed tomography (CT) images after the first electrode implantation, as well as preoperative, and postoperative CT images after the second electrode implantation were collected. Images were analyzed in stereotactic targeting software (BrainLab); intracranial air was manually segmented, and electrode shift was measured in the x, y, and z plane, as well as a Euclidian distance on each set of merged CT scans. A Pearson correlation analysis was used to determine the relationship between intracranial air and brain shift, and student's t test was used to compare means between patients with and without radiographic evidence of intracranial air. RESULTS: Thirty-six patients had pneumocephalus after the first electrode implantation, while 35 had pneumocephalus after the second electrode implantation. Accumulation of intracranial air following the first electrode implantation (4.49 ± 6.05 cm3) was significantly correlated with brain shift along the y axis (0.04 ± 0.35 mm; r (34) = 0.36; p = 0.03), as well as the Euclidean distance of deviation (0.57 ± 0.33 mm; r (34) = 0.33; p = 0.05) indicating statistically significant shift on the ipsilateral side. However, there was no significant correlation between intracranial air and brain shift following the second electrode implantation, suggesting contralateral shift is minimal. Furthermore, there was no significant difference in brain shift between patients with and without radiographic evidence of intracranial air following both electrode implantation surgeries. CONCLUSION: Despite observing volumes as high as 22.0 cm3 in patients with radiographic evidence of pneumocephalus, there was no significant difference in brain shift when compared to patients without pneumocephalus. Furthermore, the mean magnitude of brain shift was <1.0 mm regardless of whether pneumocephalus was presenting, suggesting that intracranial air accumulation may not produce clinical significant brain shift in our patients.

Pilot Study to Investigate the Use of In-Clinic Sensing to Identify Optimal Stimulation Parameters for Deep Brain Stimulation Therapy in Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) programming is time intensive. Recent advances in sensing technology of local field potentials (LFPs) may enable improvements. Few studies have compared the use of this technology with standard of care. OBJECTIVE/HYPOTHESIS: Sensing technology of subthalamic nucleus (STN) DBS leads in Parkinson's disease (PD) is reliable and predicts the optimal contacts and settings as predicted by clinical assessment. MATERIALS AND METHODS: Five subjects with PD (n = 9 hemispheres) with bilateral STN DBS and sensing capable battery replacement were recruited. An LFP sensing review of all bipolar contact pairs was performed three times. Contact with the maximal beta peak power (MBP) was then clinically assessed in a double-blinded fashion, and five conditions were tested: 1) entry settings, 2) off stimulation, 3) MBP at 30 µs, 4) MBP at 60 µs, and 5) MBP at 90 µs. RESULTS: Contact and frequency of the MBP power in all hemispheres did not differ across sessions. The entry settings matched with the contact with the MBP power in 5 of 9 hemispheres. No clinical difference was evident in the stimulation conditions. The clinician and subject preferred settings determined by MBP power in 7 of 9 and 5 of 7 hemispheres, respectively. CONCLUSIONS: This study indicates that STN LFPs in PD recorded directly from contacts of the DBS lead provide consistent recordings across the frequency range and a reliably detected beta peak. Furthermore, programming based on the MBP power provides at least clinical equivalence to standard of care programming with STN DBS.

Comparison of Monopolar Review to Fixed Parameter Fractionation in Deep Brain Stimulation.

Background: Technological advancements in deep brain stimulation (DBS) require methodological changes in programming. Fractionalization poses significant practical challenges for the most common approach for assessing DBS efficacy, monopolar review (MR). Objectives: Two DBS programming methods: MR and fixed parameter vertical and horizontal fractionalization (FPF) were compared. Methods: A two-phase process of vertical and horizontal FPF was performed. MR was conducted thereafter. After a short wash-out period, both optimal configurations determined by MR and FPF were tested in a double-blind randomized manner. Results: Seven PD patients were enrolled, providing 11 hemispheres to compare the two conditions. In all subjects, the blinded examiner selected a directional or fractionalization configuration. There was no significant difference in clinical benefits between MR and FPF. FPF was the preferred method for initial programming as selected by subject and clinician. Conclusions: FPF programming is a viable and efficient methodology that may be incorporated into clinical practice.

Evaluation of consensus sleep stage scoring of dysregulated sleep in Parkinson's disease.

OBJECTIVE: Sleep dysregulation in Parkinson's disease (PD) has been hypothesized to occur, in part, from dysfunction in the basal ganglia-cortical circuit. Assessment of this relationship requires accurate sleep stage determination, a known challenge in this clinical population. Our objective was to optimize the consensus on the sleep staging process and reduce interrater variability in a cohort of advanced PD subjects. METHODS: Fifteen PD subjects were enrolled from three sites in a clinical trial that involved recordings from subthalamic nucleus (STN) deep brain stimulation (DBS) leads (NCT04620551). Video polysomnography (vPSG) data for a total of 45 nights were analyzed. Four experienced scorers independently scored data on initial review. Epochs with less than 75% consensus were flagged for secondary review. In secondary review of discordant epochs, two of the original scorers re-assessed epochs, from which the final consensus stage was derived. RESULTS: Sleep stage classification agreement averaged 83.10% across all sleep stages on initial scoring (IS), and on secondary consensus scoring (CS) review, agreement reached 96.58%. Greatest disagreement was noted in determination of awake epochs (33.6% of discordant epochs) and non-rapid-eye-movement stage 2 (N2) epochs (31.8% of discordant epochs). Scoring discrepancy was resolved with direct measurement of cortical frequency and amplitudes, physiologic context of the epoch, and video review. CONCLUSION: Our method of multi-level initial and then secondary consensus review scoring resulted in consensus scoring agreement superior to conventional standards. This work features a custom-engineered vPSG software and review platform for integration of consensus sleep stage scoring in a multi-site clinical trial.

Surgical outcomes in large vestibular schwannomas: should cerebellopontine edema be considered in the grading systems?

PURPOSE: Large (> 3 cm) vestibular schwannomas pose complexity in surgical management because of narrow working corridors and proximity to the cranial nerves, brainstem, and inner ear structures. With current vestibular schwannoma classifications limited in information regarding cerebellopontine edema, our retrospective series examined this radiographic feature relative to clinical outcomes and its possible role in preoperative scoring. METHODS: Of 230 patients who underwent surgical resection of vestibular schwannoma (2014-2020), we identified 107 patients with Koos grades 3 or 4 tumors for radiographic assessment of edema in the middle cerebellar peduncle (MCP), brainstem, or both. Radiographic images were graded and patients grouped into Koos grades 3 or 4 or our proposed grade 5 with edema. Tumor volumes, radiographic features, clinical presentations, and clinical outcomes were evaluated. RESULTS: The 107 patients included 22 patients with grade 3 tumors, 39 with grade 4, and 46 with grade 5. No statistical differences were noted among groups for demographic data or complication rates. Unlike grades 3 and 4 patients, grade 5 patients presented with worse hearing (p < 0.001), larger tumors (p < 0.001), lower rates of gross total resection (GTR), longer hospital stays, and higher rates of balance dysfunction. CONCLUSION: With edema detected in 43% of this cohort, special considerations are warranted for grade 5 vestibular schwannomas given the preoperative findings of worse hearing, lower GTR rates, longer hospital stays, and 96% who pursued postoperative balance therapy. We propose that grade 5 with edema offers a more nuanced interpretation of a radiographic feature that holds relevance to treatment selection and patient outcomes.

Automatic extraction of upper-limb kinematic activity using deep learning-based markerless tracking during deep brain stimulation implantation for Parkinson's disease: A proof of concept study.

Optimal placement of deep brain stimulation (DBS) therapy for treating movement disorders routinely relies on intraoperative motor testing for target determination. However, in current practice, motor testing relies on subjective interpretation and correlation of motor and neural information. Recent advances in computer vision could improve assessment accuracy. We describe our application of deep learning-based computer vision to conduct markerless tracking for measuring motor behaviors of patients undergoing DBS surgery for the treatment of Parkinson's disease. Video recordings were acquired during intraoperative kinematic testing (N = 5 patients), as part of standard of care for accurate implantation of the DBS electrode. Kinematic data were extracted from videos post-hoc using the Python-based computer vision suite DeepLabCut. Both manual and automated (80.00% accuracy) approaches were used to extract kinematic episodes from threshold derived kinematic fluctuations. Active motor epochs were compressed by modeling upper limb deflections with a parabolic fit. A semi-supervised classification model, support vector machine (SVM), trained on the parameters defined by the parabolic fit reliably predicted movement type. Across all cases, tracking was well calibrated (i.e., reprojection pixel errors 0.016-0.041; accuracies >95%). SVM predicted classification demonstrated high accuracy (85.70%) including for two common upper limb movements, arm chain pulls (92.30%) and hand clenches (76.20%), with accuracy validated using a leave-one-out process for each patient. These results demonstrate successful capture and categorization of motor behaviors critical for assessing the optimal brain target for DBS surgery. Conventional motor testing procedures have proven informative and contributory to targeting but have largely remained subjective and inaccessible to non-Western and rural DBS centers with limited resources. This approach could automate the process and improve accuracy for neuro-motor mapping, to improve surgical targeting, optimize DBS therapy, provide accessible avenues for neuro-motor mapping and DBS implantation, and advance our understanding of the function of different brain areas.

Use of Three-Dimensional Printed Brain Models During Deep Brain Stimulation Surgery Consultation for Patient Health Literacy: A Randomized Controlled Investigation.

BACKGROUND: Advanced therapies in neurosurgery, such as deep brain stimulation (DBS), would benefit from improved patient education materials. Three-dimensional (3D) printed anatomical models represent a recent development for improving patient education for neurosurgical procedures. METHODS: In this study, 40 patients undergoing DBS surgery consultation were randomly assigned to 1 of 2 groups: an experimental group, which received a demonstration of DBS therapeutic neuroanatomical targets in a 3D printed brain model plus standard patient education (PE), or a control group, which received standard PE alone. RESULTS: Patients in the DBS model plus PE group showed a significant increase in patient confidence and understanding of the brain structures targeted during a DBS procedure compared with patients in the PE-only group (P < 0.01). There was no difference in perceived risk, comfort, or anxiety related to the procedure. CONCLUSIONS: In the first randomized controlled study to our knowledge of 3D printed models for DBS consultation, our results demonstrate that patients had improved understanding of their therapy with the models. However, the models alone did not affect risk evaluation or comfort with surgery. A 3D printed brain model may help improve patient understanding of DBS surgery.

Using a Robotic-Assisted Approach for Stereotactic Laser Ablation Corpus Callosotomy: A Technical Report.

BACKGROUND: Corpus callosotomy for medically intractable epilepsy is an effective ablative procedure traditionally achieved using either standard open craniotomy or with less-invasive approaches. Advances in robotic-assisted stereotactic guidance for neurosurgery can be applied for LITT for corpus callosotomy. CLINICAL PRESENTATIONS: Two patients were included in this study. One was a 25-year-old female patient with extensive bi-hemispheric malformations of cortical development and medically refractory epilepsy, and the other was an 18-year-old male with medically refractory epilepsy and atonic seizures, who underwent a complete corpus callosotomy using robotic-assisted stereotactic guidance for LITT. RESULTS: Both patients underwent successful intended corpus callosotomy with volumetric analysis demonstrating a length disconnection of 74% and a volume disconnection of 55% for patient 1 and a length disconnection of 83% and a volume disconnection of 33% for patient 2. Postoperatively, both patients had clinical reductions in seizure. CONCLUSION: Our experience demonstrates that robotic guidance systems can safely and effectively be adapted for minimally invasive LITT corpus callosotomy.

Deep Brain Stimulation of the Ventral Intermediate Nucleus of the Thalamus in Writer's Cramp: A Case Report.

Background: Globus pallidus internus (GPi) deep brain stimulation (DBS) and thalamotomy are interventions for writer's cramp (WC). Ventralis intermedius nucleus (VIM) DBS is targeted for tremor, however, many aspects of VIM DBS remained underexplored in WC. Case Report: A 62-year-old man with WC underwent DBS. Dystonic tremor improved intraoperatively with ventralis oralis anterior (VoA)/ventral oralis posterior (VoP) and with subthalamic nucleus stimulation; although greatest benefit was obtained with VIM stimulation. Sustained benefit with VIM DBS at ten months post-operative was obtained. Discussion: This case demonstrates an intraoperative approach in target selection and supports benefits of VIM DBS for WC. Highlights: This case highlights the intraoperative approach and clinical effects of VIM DBS in the treatment of medically refractory writer's cramp (WC). We contextualize our results from this case with previous reports of VoA/VoP stimulation for WC.

Retrospective analysis of hemispheric structural network change as a function of location and size of glioma.

Gliomas are neoplasms that arise from glial cell origin and represent the largest fraction of primary malignant brain tumours (77%). These highly infiltrative malignant cell clusters modify brain structure and function through expansion, invasion and intratumoral modification. Depending on the growth rate of the tumour, location and degree of expansion, functional reorganization may not lead to overt changes in behaviour despite significant cerebral adaptation. Studies in simulated lesion models and in patients with stroke reveal both local and distal functional disturbances, using measures of anatomical brain networks. Investigations over the last two decades have sought to use diffusion tensor imaging tractography data in the context of intracranial tumours to improve surgical planning, intraoperative functional localization, and post-operative interpretation of functional change. In this study, we used diffusion tensor imaging tractography to assess the impact of tumour location on the white matter structural network. To better understand how various lobe localized gliomas impact the topology underlying efficiency of information transfer between brain regions, we identified the major alterations in brain network connectivity patterns between the ipsilesional versus contralesional hemispheres in patients with gliomas localized to the frontal, parietal or temporal lobe. Results were indicative of altered network efficiency and the role of specific brain regions unique to different lobe localized gliomas. This work draws attention to connections and brain regions which have shared structural susceptibility in frontal, parietal and temporal lobe glioma cases. This study also provides a preliminary anatomical basis for understanding which affected white matter pathways may contribute to preoperative patient symptomology.