Middlebrooks, Erik H

BACKGROUND AND OBJECTIVES: The anterior nucleus of the thalamus (ANT) is a common target for deep brain stimulation (DBS) for drug-resistant epilepsy (DRE). However, the surgical approach to the ANT remains challenging because of its unique anatomy. This study aims to summarize our experience with the posterior temporo-parietal extraventricular (TPEV) approach targeting the ANT for DBS in DRE. METHODS: We performed a retrospective analysis of patients with DRE who underwent ANT-DBS using the TPEV approach between January 2011 and February 2021. Subjects with at least 6-month follow-up were eligible. The final lead position and number of active contacts targeting the anteroventral nucleus (AV) of the ANT were assessed using Lead-DBS. Mean seizure frequency reduction percentage and responder rate (≥50% decrease in seizure frequency) were determined. RESULTS: Thirty-one patients (mean age: 32.9 years; 52% female patients) were included. The mean follow-up period was 27.6 months ± 13.9 (29, 16-36). The mean seizure frequency reduction percentage was 65% ± 26 (75, 50-82). Twenty-six of 31 participants (83%) were responders, P < .001. Two subjects (6%) were seizure-free for at least 6 months at the last evaluation. Antiepileptic drugs dose and/or number decreased in 17/31 subjects (55%). The success rate for placing at least 1 contact at AV was 87% (27/31 patients) bilaterally. The number of active contacts at the AV was significantly greater in the responder group, 3.1 ± 1.3 (3, 2-4) vs 1.8 ± 1.1 (2, 1-2.5); P = .041 with a positive correlation between the number of active contacts and seizure reduction percentage; r = 0.445, R 2 = 0.198, P = .012. CONCLUSION: The TPEV trajectory is a safe and effective approach to target the ANT for DBS. Future studies are needed to compare the clinical outcomes and target accuracy with the standard approaches.

2071 Background: Despite advances in our understanding of brain cancer, the ability to discern between infiltrated and non-infiltrated tissue with current adjuncts, remains elusive. Isocitrate dehydrogenase (IDH) mutation is unique to IDH-mut glioma cells and can be used as a surrogate for tumor infiltration. Further, emerging evidence has shown unique signatures in brain cancer lipidomic profiling, with lipid metabolism playing a key role in brain cancer biology. Here, we aimed to evaluate the impact of desorption electrospray ionization-mass spectrometry (DESI-MS) as a near real-time method to determine infiltration status and the use of DESI-MS to perform intra-operative histological diagnosis. Methods: This is a prospective multi-institution cohort study using intra-operative DESI-MS on freshly obtained tumor samples to evaluate 2-hydroxyglutarate (2HG), with post-hoc validation by review by a board-certified neuropathologist. For tumor cell estimation and tissue diagnosis, high-throughput DESI-MS was used for rapid analysis of high-density arrays using lipidomic profiling. Analysis of the data was performed using a pre-written algorithm employing a combination of Python- and MATLAB-based custom software allowing results in less than a second per sample. Results: A total of 496 tumor biopsies from 72 patients have been analyzed. Earlier iterations focused on absolute quantitation of 2HG in 247 biopsies from 49 patients to determine IDH genotype yielding sensitivity, specificity, and accuracy values of 89, 100, and 94% for core biopsies (71). Improvement in accuracy was obtained with relative measurement of 2HG in comparison to glutamate allowing for detection of IDH-mut infiltration at the margin, resulting in 93% sensitivity, 100% specificity, and 98% accuracy with turnover times averaging 3 minutes in 183 biopsies from 23 patients. Margin assessment beyond the limits of neuro-navigation and surgeon assessment showed tumor infiltration in 88% of margin biopsies from IDH mutant tumors (30 of 34 biopsies) with 100% accuracy. Intra-operative tissue diagnosis was pursued in 66 unique tumor samples using DESI-MS lipidomic profiling, including samples of normal brain parenchyma, gliomas, meningiomas and pituitary adenomas, split into two microarray sets (36 and 40 samples). Using estimated principal components as input features, high accuracy ( > 90%; ROC AUCs ≥ 0.89) was obtained for supervised tissue classification using simple machine learning algorithms. Conclusions: We present a novel system for intra-operative evaluation of tumor infiltration at the margin in gliomas and for intra-operative tissue diagnosis of brain cancer. Our method identified tumor infiltration beyond the surgical margins and serves as a foundation for future uses employing DESI-MS to allow for molecularly guided surgery in IDH-mut gliomas.

AbstractBackground and purposeCerebral amyloid angiopathy (CAA) is a common cause of intracranial hemorrhage (ICH), which is a risk factor for seizures. The incidence and risk factors of seizures associated with a heterogeneous cohort of CAA patients have not been studied.MethodsWe conducted a retrospective study of patients with CAA treated at Mayo Clinic Florida between 1 January 2015 and 1 January 2021. CAA was defined using the modified Boston criteria version 2.0. We analyzed electrophysiological and clinical features, and comorbidities including lobar ICH, nontraumatic cortical/convexity subarachnoid hemorrhage (cSAH), superficial siderosis, and inflammation (CAA with inflammation [CAA‐ri]). Cognition and mortality were secondary outcomes. Univariate and multivariate analyses were performed to determine risk of seizures relative to clinical presentation.ResultsTwo hundred eighty‐four patients with CAA were identified, with median follow‐up of 35.7 months (interquartile range = 13.5–61.3 months). Fifty‐six patients (19.7%) had seizures; in 21 (37.5%) patients, seizures were the index feature leading to CAA diagnosis. Seizures were more frequent in females (p = 0.032) and patients with lobar ICH (p = 0.002), cSAH (p = 0.030), superficial siderosis (p < 0.001), and CAA‐ri (p = 0.005), and less common in patients with microhemorrhage (p = 0.006). After controlling for age and sex, lobar ICH (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.1–4.2), CAA‐ri (OR = 3.8, 95% CI = 1.4–10.3), and superficial siderosis (OR = 3.7, 95% CI = 1.9–7.0) were independently associated with higher odds of incident seizures.ConclusionsSeizures are common in patients with CAA and are independently associated with lobar ICH, CAA‐ri, and superficial siderosis. Our results may be applied to optimize clinical monitoring and management for patients with CAA.

BACKGROUND AND OBJECTIVES: Surgical approaches to the ventral brainstem and petroclival regions are complex, and standard retrosigmoid and subtemporal approaches are often inadequate. Retrosigmoid suprameatal tubercle (RSMTA) and anterior subtemporal transpetrosal (ASTA) approaches may provide extended surgical exposure with less brain retraction. The objective of this study was to evaluate advantages and disadvantages of RSMTA vs ASTA, and illustrate the surgical corridors and 3-dimensional microsurgical anatomy of the related structures. METHODS: Four silicone-injected adult cadaver heads (8 sides) were dissected to evaluate the accessibility of lesions located at the petrous apex, ventral brainstem, and pontomedullary region using ASTA and RSTMA. RESULTS: Both ASTA and RSMTA provide access from the petrous apex to the ventral lower pons and pontomedullary junction. A greater extent of safely resected bone was found in ASTA vs RSMTA. ASTA provides a larger surgical view to the ventrolateral midpons, peritrigeminal region, superior neurovascular complex, pontomesencephalic junction, and posterior cavernous sinus. Meanwhile, through cranial nerve V mobilization, RSMTA provides a larger surgical view to the lower half part of the pons, ventrolateral part of the pontomedullary junction, and middle and lower neurovascular structures. CONCLUSION: The choice of surgical approach is determined by considering the area where the lesion originates, lesion size, the anatomic structures to which it extends, and evaluation of the area that can be surgically exposed. Our study highlights the differences between these approaches and important surgical anatomic considerations.

Transient global amnesia (TGA) is a neurological condition characterized by temporary memory loss and classically associated with a reversible unilateral punctate focus of restricted diffusion in the cornu ammonis 1 (CA1) region of the hippocampus. Historically, the lesions were considered to be transient in nature with no long-term imaging abnormality. However, more recent studies have challenged the concept that there are no long-term neurological sequelae. In line with this evidence, we explore the role of ultra-high-resolution imaging using 7 Tesla MRI to evaluate for long-term imaging abnormalities in a 63-year-old woman with a typical clinical course and acute TGA imaging findings. The 7 Tesla MRI revealed a residual lesion on susceptibility-weighted imaging (SWI) with evidence of gliosis and volume loss at the site of the acute lesion in CA1 eight months after the acute episode. This case challenges the traditional mantra of TGA as a fully reversible condition with no long-term imaging findings, suggesting the need for further research using ultra-high-field MRI to determine TGA's potential long-term imaging sequelae and any association with neurocognitive sequelae.

OBJECTIVE Pseudoaneurysms (PSAs) are complex vascular lesions. Flow diversion has been proposed as an alternative treatment to parent artery occlusion that preserves laminar flow. The authors of the present study investigated the safety and short-term (< 1 year) and long-term (≥ 1 year) aneurysm occlusion rates following the treatment of intracranial and extracranial PSAs using the Pipeline embolization device (PED). METHODS An electronic database search for full-text English-language articles in Ovid MEDLINE and Epub Ahead of Print, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus was conducted following the PRISMA guidelines. Studies of any design including at least 4 patients with intracranial or extracranial PSAs treated using a PED were included in this analysis. The primary outcome of interest was the rate of peri- and postprocedural complications. Secondarily, the authors analyzed the incidence of complete aneurysm occlusion. RESULTS A total of 90 patients with 96 PSAs across 9 studies were included. The mean age was 38.2 (SD 15.14) years, and 37.8% of the patients were women. The mean PSA size was 4.9 mm. Most PSAs were unruptured, and the most common etiology was trauma (n = 32, 35.5%), followed by spontaneous formation (n = 21, 23.3%) and iatrogenic injury (n = 19, 21.1%). Among the 51 (53.1%) intracranial and 45 (46.9%) extracranial PSAs were 19 (19.8%) dissecting PSAs. Sixty-six (77.6%) PSAs were in the internal carotid artery and 10 (11.8%) in the vertebral artery. Thirty-three (34.4%) PSAs were treated with ≥ 2 devices, and 8 (8.3%) underwent adjunctive coiling. The mean clinical and angiographic follow-up durations were 10.7 and 12.9 months, respectively. The short-term (< 1 year) and long-term (≥ 1 year) complete occlusion rates were 79% (95% CI 66%–88%, p = 0.82) and 84% (95% CI 70%–92%, p = 0.95), respectively. Complication rates were 8% for iatrogenic dissection (95% CI 3%–16%, p = 0.94), 10% for silent thromboembolism (95% CI 5%–21%, p = 0.77), and 12% for symptomatic thromboembolism (95% CI 6%–23%, p = 0.48). No treatment-related hemorrhage was observed. The overall mortality rate at the last follow-up was 14%. CONCLUSIONS The complete occlusion rate for PSAs treated with the PED was high and increased over time. Although postprocedural complications and mortality were not insignificant, flow diversion represents a reasonably safe option for managing these complex lesions.