Middlebrooks, Erik H.

3D time-of-flight (TOF) MR angiography (MRA) benefits from ultra-high-field MRI (≥7 T) due to improved contrast and increased signal-to-noise ratio. However, high-resolution TOF MRA at 7T usually requires longer acquisition times. In addition, relatively higher specific absorption rate (SAR) at 7T limits the choice of optimal pulse sequence parameters, especially if venous saturation is employed. Here, we illustrate the clinical application of ultra-high resolution cerebral 7T TOF MRA using compressed sensing in cases of artery of Percheron and lacunar infarcts, which showed superior resolution and exquisite details pertinent to the clinical diagnosis. The technical challenges associated with high-resolution 7T imaging were alleviated by optimization of sequence parameters and utilization of compressed sensing acceleration.

OBJECTIVE The authors hypothesized that the proximity of deep brain stimulator contacts to the anterior thalamic nucleus–mammillothalamic tract (ANT-MMT) junction determines responsiveness to treatment with ANT deep brain stimulation (DBS) in drug-resistant epilepsy and conducted this study to test that hypothesis. METHODS This retrospective study evaluated patients who had undergone ANT DBS electrode implantation and whose devices were programmed to stimulate nearest the ANT-MMT junction based on direct MRI visualization. The proximity of the active electrode to the ANT and the ANT-MMT junction was compared between responders (≥ 50% reduction in seizure frequency) and nonresponders. Linear regression was performed to assess the percentage of seizure reduction and distance to both the ANT and the ANT-MMT junction. RESULTS Four (57.1%) of 7 patients had ≥ 50% reduction in seizures. All 4 responders had at least one contact within 1 mm of the ANT-MMT junction, whereas the 3 patients with < 50% seizure improvement did not have a contact within 1 mm of the ANT-MMT junction. Additionally, the 4 responders demonstrated contact positioning closer to the ANT-MMT junction than the 3 nonresponders (mean distance from MMT: 0.7 mm on the left and 0.6 mm on the right in responders vs 3.0 mm on the left and 2.3 mm on the right in nonresponders). However, proximity of the electrode contact to any point in the ANT nucleus did not correlate with seizure reduction. Greater seizure improvement was correlated with a contact position closer to the ANT-MMT junction (R2 = 0.62, p = 0.04). Seizure improvement was not significantly correlated with proximity of the contact to any ANT border (R2 = 0.24, p = 0.26). CONCLUSIONS Obtained using a combination of direct visualization and targeted programming of the ANT-MMT junction, data in this study support the hypothesis that proximity to the ANT alone does not correlate with seizure reduction in ANT DBS, whereas proximity to the ANT-MMT junction does. These findings support the importance of direct targeting in ANT DBS, as well as imaging-informed programming. Additionally, the authors provide supportive evidence for future prospective trials using ANT-MMT junction for direct surgical targeting.

Abstract Objective Surgical access to the third ventricle can be achieved through various corridors depending on the location and extent of the lesion; however, traditional transcranial approaches risk damage to multiple critical neural structures. Methods Endonasal approach similar to corridor of the reverse third ventriculostomy (ERTV) was surgically simulated in eight cadaveric heads. Fiber dissections were additionally performed within the third ventricle along the endoscopic route. Additionally, we present a case of ERTV in a patient with craniopharyngioma extending into the third ventricle. Results The ERTV allowed adequate intraventricular visualization along the third ventricle. The extracranial step of the surgical corridor included a bony window in the sellar floor, tuberculum sella, and the lower part of the planum sphenoidale. ERTV provided an intraventricular surgical field along the foramen of Monro to expose an area bordered by the fornix anteriorly, thalamus laterally, anterior commissure anterior superiorly, posterior commissure, habenula and pineal gland posteriorly, and aqueduct of Sylvius centered posterior inferiorly. Conclusion The third ventricle can safely be accessed through ERTV either above or below the pituitary gland. ERTV provides a wide exposure of the third ventricle through the tuber cinereum and offers access to the anterior part as far as the anterior commissure and precommissural part of fornix and the whole length of the posterior part. Endoscopic ERTV may be a suitable alternative to transcranial approaches to access the third ventricle in selected patients.

AbstractDrug‐resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and immunomodulatory potential, therapies with biologics such as mesenchymal stem cells (MSCs) offer a potential therapeutic benefit for structural causes of epilepsy, such as hippocampal sclerosis. In this article, we report a systematic review of the literature evaluating the preclinical and clinical studies of MSCs for DRE. Medline, Ovid EMBASE, Scopus, and the Cochrane Databases were searched electronically from their dates of inception to November 2021 using the following keywords: ((“mesenchymal”) AND (“stem cell”)) AND ((“epilepsy”) OR (“convulsion”) OR (“seizures”)). This review followed Preferred Reporting Items for Systemic Reviews and Meta‐Analyses (PRISMA) guidelines. The initial query identified 488 studies representing 323 unique manuscripts. After application of selection criteria, 15 studies were included in this systematic review; 11 were preclinical studies and 4 were clinical studies. All preclinical studies were performed in rodents and all clinical studies were phase 1 trials. Thus far, therapy with MSCs appears to be safe for use in humans, as no severe adverse events related directly to the therapy were reported. Furthermore, MSC therapy appears to provide a statistically significant clinical benefit by reducing the seizure burden of patients, reducing the electrophysiological biomarkers of epilepsy, and improving their comorbidities, such as depression and anxiety. In addition, animal studies reveal that the therapy exerts its effect by reducing aberrant mossy fiber sprouting (reduce excitatory pathways) and increasing γ‐aminobutyric acid (GABA)ergic interneurons (increase inhibitory pathways). Both preclinical and clinical studies have shown MSC therapy to be safe and preliminary effective, thus warranting further studies to investigate its therapeutic potential.

Abstract Objective Surgical access to the third ventricle can be achieved through various corridors depending on the location and extent of the lesion; however, traditional transcranial approaches risk damage to multiple critical neural structures. Methods Endonasal approach similar to corridor of the reverse third ventriculostomy (ERTV) was surgically simulated in eight cadaveric heads. Fiber dissections were additionally performed within the third ventricle along the endoscopic route. Additionally, we present a case of ERTV in a patient with craniopharyngioma extending into the third ventricle. Results The ERTV allowed adequate intraventricular visualization along the third ventricle. The extracranial step of the surgical corridor included a bony window in the sellar floor, tuberculum sella, and the lower part of the planum sphenoidale. ERTV provided an intraventricular surgical field along the foramen of Monro to expose an area bordered by the fornix anteriorly, thalamus laterally, anterior commissure anterior superiorly, posterior commissure, habenula and pineal gland posteriorly, and aqueduct of Sylvius centered posterior inferiorly. Conclusion The third ventricle can safely be accessed through ERTV either above or below the pituitary gland. ERTV provides a wide exposure of the third ventricle through the tuber cinereum and offers access to the anterior part as far as the anterior commissure and precommissural part of fornix and the whole length of the posterior part. Endoscopic ERTV may be a suitable alternative to transcranial approaches to access the third ventricle in selected patients.

Abstract Tremor is a common symptom in multiple sclerosis and can present as a severe postural and action tremor, leading to significant disability. Owing to the diffuse and progressive nature of the disease, it has been challenging to characterize the pathophysiology underlying multiple sclerosis tremor. Deep brain stimulation of the ventralis intermedius and the ventralis oralis posterior thalamic nuclei has been used to treat medically refractory multiple sclerosis tremors with variable results. The aim of this study was to characterize multiple sclerosis tremor at the network level by applying modern connectomic techniques to data from a previously completed single-centre, randomized, single-blind prospective trial of 12 subjects who were treated with unilateral dual-lead (ventralis intermedius + ventralis oralis posterior) thalamic deep brain stimulation. Preoperative T1-weighted MRI and postoperative head CTs were used, along with applied programming settings, to estimate the volume of tissue activated for each patient. The volumes of tissue activated were then used to make voxel-wise and structural connectivity correlations with clinically observed tremor suppression. The volume of the tissue-activated analyses identified the optimal region of stimulation at the ventralis oralis posterior ventralis intermedius border intersecting with the dentato-rubro-thalamic tract. A regression model showed strong connectivity to the supplemental motor area was positively associated with tremor suppression (r = 0.66) in this cohort, whereas connectivity to the primary motor cortex was negatively associated with tremor suppression (r = −0.69), a finding opposite to that seen in ventralis intermedius deep brain stimulation for essential tremor. Comparing the structural connectivity to that of an essential tremor cohort revealed a distinct network that lies anterior to the essential tremor network. Overall, the volumes of tissue activated and connectivity observations converge to suggest that optimal suppression of multiple sclerosis tremor will likely be achieved by directing stimulation more anteriorly toward the ventralis oralis posterior and that a wide field of stimulation synergistically modulating the ventralis oralis posterior and ventralis intermedius nuclei may be more effective than traditional ventralis intermedius deep brain stimulation at suppressing the severe tremors commonly seen in complex tremor syndromes such as multiple sclerosis tremor.