Stereo-EEG-guided network modulation for psychiatric disorders: Surgical considerations.

BACKGROUND: Deep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders. OBJECTIVE: /Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challenging disorder, we adopted an approach of inpatient intracranial monitoring borrowed from the epilepsy surgery field. METHODS: We implanted 3 patients with 4 DBS leads (bilateral pair in both the ventral capsule/ventral striatum and subcallosal cingulate) and 10 stereo-electroencephalography (sEEG) electrodes targeting depression-relevant network regions. For surgical planning, we used an interactive, holographic visualization platform to appreciate the 3D anatomy and connectivity. In the initial surgery, we placed the DBS leads and sEEG electrodes using robotic stereotaxy. Subjects were then admitted to an inpatient monitoring unit for depression-specific neurophysiological assessments. Following these investigations, subjects returned to the OR to remove the sEEG electrodes and internalize the DBS leads to implanted pulse generators. RESULTS: Intraoperative testing revealed positive valence responses in all 3 subjects that helped verify targeting. Given the importance of the network-based hypotheses we were testing, we required accurate adherence to the surgical plan (to engage DBS and sEEG targets) and stability of DBS lead rotational position (to ensure that stimulation field estimates of the directional leads used during inpatient monitoring were relevant chronically), both of which we confirmed (mean radial error 1.2±0.9 mm; mean rotation 3.6±2.6°). CONCLUSION: This novel hybrid sEEG-DBS approach allows detailed study of the neurophysiological substrates of complex neuropsychiatric disorders.

Targeting the Tumor Microenvironment in Brain Metastasis.

Dynamic interplay between cancer cells and the surrounding microenvironment is a feature of the metastatic process. Successful metastatic brain colonization requires complex mechanisms that ultimately allow tumor cells to adapt to the unique microenvironment of the central nervous system, evade immune destruction, survive, and grow. Accumulating evidence suggests that components of the brain tumor microenvironment (TME) play a vital role in the metastatic cascade. In this review, the authors summarize the contribution of the TME to the development and progression of brain metastasis. They also highlight opportunities for TME-directed targeted therapy.

Natural history of high-grade pediatric arteriovenous malformations: implications for management options.

PURPOSE: Cerebral arteriovenous malformations are a common cause of pediatric intracranial hemorrhage. Often, small, superficial, lesions are treated surgically; however, more complex, deeper, eloquently located lesions portend higher-risk features and suffer from limitations in treatment. We sought to examine our institution's experience with the natural history of these high-grade arteriovenous malformations to explore outcomes with conservative treatment. METHODS: A retrospective chart review was performed to identify all pediatric cases of intracranial arteriovenous malformations seen at our institution from 2005 to 2018. Subjects with Spetzler-Martin grade IV or V lesions, treated conservatively, were examined for primary outcomes including rupture rate, progression, and functional outcomes. RESULTS: A total of 14 patients were included in the study, of which, 78.57% were classified as Spetzler-Martin grade IV and 21.43% Spetzler-Martin grade V. All patients in this study were treated conservatively, with surveillance, followed for a mean of 32.17 months (range 9.43-79.10). 7.14% experienced delayed hemorrhage or re-rupture, 7.14% had hydrocephalus, and 14.29% had seizures. Neurological sequelae included weakness, visual impairment, speech impairment, sensory changes, and dystonia; functionally independent outcomes, defined as modified Rankin Score of 0-2, were seen in 85.71% of patients. CONCLUSION: Our experience suggests that patients with large, deep lesions have significant morbidity with high rates of rupture and subsequent neurologic deficits. However, intervention of these lesions may carry high risk, and the literature suggests such lesions may have less favorable outcomes when treated. We propose conservative treatment for high-grade arteriovenous malformations as a viable option with good functional outcomes in a cohort often without good options for conventional treatment.

Accuracy and Workflow Improvements for Responsive Neurostimulation Hippocampal Depth Electrode Placement Using Robotic Stereotaxy.

Background: Robotic stereotaxy is increasingly common in epilepsy surgery for the implantation of stereo-electroencephalography (sEEG) electrodes for intracranial seizure monitoring. The use of robots is also gaining popularity for permanent stereotactic lead implantation applications such as in deep brain stimulation and responsive neurostimulation (RNS) procedures. Objective: We describe the evolution of our robotic stereotactic implantation technique for placement of occipital-approach hippocampal RNS depth leads. Methods: We performed a retrospective review of 10 consecutive patients who underwent robotic RNS hippocampal depth electrode implantation. Accuracy of depth lead implantation was measured by registering intraoperative post-implantation fluoroscopic CT images and post-operative CT scans with the stereotactic plan to measure implantation accuracy. Seizure data were also collected from the RNS devices and analyzed to obtain initial seizure control outcome estimates. Results: Ten patients underwent occipital-approach hippocampal RNS depth electrode placement for medically refractory epilepsy. A total of 18 depth electrodes were included in the analysis. Six patients (10 electrodes) were implanted in the supine position, with mean target radial error of 1.9 ± 0.9 mm (mean ± SD). Four patients (8 electrodes) were implanted in the prone position, with mean radial error of 0.8 ± 0.3 mm. The radial error was significantly smaller when electrodes were implanted in the prone position compared to the supine position (p = 0.002). Early results (median follow-up time 7.4 months) demonstrate mean seizure frequency reduction of 26% (n = 8), with 37.5% achieving ≥50% reduction in seizure frequency as measured by RNS long episode counts. Conclusion: Prone positioning for robotic implantation of occipital-approach hippocampal RNS depth electrodes led to lower radial target error compared to supine positioning. The robotic platform offers a number of workflow advantages over traditional frame-based approaches, including parallel rather than serial operation in a bilateral case, decreased concern regarding human error in setting frame coordinates, and surgeon comfort.

Understanding the complex pathophysiology of idiopathic intracranial hypertension and the evolving role of venous sinus stenting: a comprehensive review of the literature.

Idiopathic intracranial hypertension (IIH) is a disease defined by elevated intracranial pressure without established etiology. Although there is now consensus on the definition of the disorder, its complex pathophysiology remains elusive. The most common clinical symptoms of IIH include headache and visual complaints. Many current theories regarding the etiology of IIH focus on increased secretion or decreased absorption of cerebrospinal fluid (CSF) and on cerebral venous outflow obstruction due to venous sinus stenosis. In addition, it has been postulated that obesity plays a role, given its prevalence in this population of patients. Several treatments, including optic nerve sheath fenestration, CSF diversion with ventriculoperitoneal or lumboperitoneal shunts, and more recently venous sinus stenting, have been described for medically refractory IIH. Despite the availability of these treatments, no guidelines or standard management algorithms exist for the treatment of this disorder. In this paper, the authors provide a review of the literature on IIH, its clinical presentation, pathophysiology, and evidence supporting treatment strategies, with a specific focus on the role of venous sinus stenting.

Acute postoperative seizures as predictors of seizure outcomes after epilepsy surgery.

OBJECTIVES: This meta-analysis was performed to determine if acute postoperative seizures (APOS) predict epilepsy surgery outcomes. Additionally, we estimated pooled prevalence for APOS and explored if certain APOS characteristics predict surgical outcomes. METHODS: A systematic literature search was performed for studies reporting seizure outcomes after epilepsy surgery in patients with and without APOS. APOS were defined as seizure(s) occurring within 30days of surgery. After data extraction, pooled Mantel-Haenszel odds ratio (OR) with 95% confidence intervals (CI) was calculated for 1-year seizure-free outcome in patients with and without APOS using random-effects meta-analysis. Sub-group meta-analysis for pediatric studies, time of occurrence, and APOS semiology were also performed. A meta-regression was performed to explore source(s) of heterogeneity. RESULTS: Seventeen studies were included in the final synthesis. Pooled prevalence of APOS was found to be 22.58%. A significantly higher proportion of patients without APOS within 30days of surgery (73.49%) were seizure-free at ≥1-year (OR 4.20, 95% CI 2.97-5.93, p<0.0001) compared to those with APOS (38.96%). Among the pediatric studies (n=6) 77.14% of patients without APOS were seizure-free at ≥1-year, compared to 35.94% of those with APOS (OR 5.71, 95% CI 3.32-9.80, p<0.0001). Patients having APOS within 24h of surgery and APOS semiology different from habitual pre-surgical seizures were more likely to achieve seizure-free outcomes, but these results failed to achieve statistical significance. CONCLUSIONS: APOS reliably predict 1-year seizure outcomes after epilepsy surgery. This information should help counsel patients and families.