Dural arteriovenous fistula in the setting of cerebral venous sinus thrombosis and COVID-19 infection.

OBJECTIVE: The aim of this study was to examine the presence of concurrent venous thrombosis and COVID-19 infections in patients with dural arteriovenous fistulas (dAVFs). METHODS: An analysis of all patients diagnosed with dAVF via cerebral angiography by the senior author was conducted, with special attention given to the presence of cerebral venous sinus thrombosis (CVST) and COVID-19 infection. General demographics, clinical presentation, presence of CVST, and COVID-19 infection status were reported. RESULTS: A total of 30 patients with dAVFs were included in this study. Three patients were diagnosed with COVID-19 (10%), with one of these patients developing CVST (33%) at 6 months postinfection. Of the 27 patients not infected with COVID-19, one was diagnosed with a likely chronic CVST at the time of presentation of dAVF (4%). A total of 11 case reports and 3 retrospective studies describing patients diagnosed with CVST at or after diagnosis of dAVFs have been reported in the literature. The incidence of dAVFs in patients with CVST has been reported as 2.4%, and the incidence of dAVF has reportedly increased five- to tenfold since the COVID-19 pandemic. CONCLUSIONS: COVID-19 infections may pose as an emerging risk factor for the development of CVST and subsequent dAVF development. To the authors' knowledge, this study presents the first cases in the literature describing a temporal relationship between COVID-19 and development of a dAVF with CVST. The effect of both COVID-19 and associated vaccines should be further assessed in future studies to examine its impact as an effect modifier on the association of dAVF and CVST.

Transmaxillary approach for resection of maxillary division trigeminal schwannoma at foramen rotundum.

BACKGROUND: The foramen rotundum and anterior cavernous sinus have traditionally been accessed by transcranial approaches that are limited by the high density of critical neurovascular structures. The transmaxillary approach provides an entirely extradural route to the foramen rotundum and anterior cavernous sinus. METHOD: This patient with neurofibromatosis and facial pain with trigeminal schwannoma at the foramen rotundum was successfully treated by transmaxillary resection of the tumor. This approach allowed for a direct extradural access to the pathology, with bony decompression and tumor resection, avoiding transcranial routes. CONCLUSION: The transmaxillary approach provides a safe and entirely extradural corridor to access smaller localized skull base lesions at and surrounding the cavernous sinus.

Nervus intermedius: Microsurgical and anatomic relationships to the cerebellopontine angle neurovascular complex.

Background: The nervus intermedius (NI) comprises fibers originating from the trigeminal, superior salivary, and solitary tract nuclei, which join the facial nerve (cranial nerve [CN] VII). Neighboring structures include the vestibulocochlear nerve (CN VIII), the anterior inferior cerebellar artery (AICA), and its branches. Microsurgical procedures at the cerebellopontine angle (CPA) benefit from understanding NI anatomy and relationships, especially for the microsurgical treatment of geniculate neuralgia, where the NI is transected. This study sought to characterize common relationships between the NI rootlets, CN VII, CN VIII, and the meatal loop of AICA at the internal auditory canal (IAC). Methods: Seventeen cadaveric heads underwent retrosigmoid craniectomy. Following complete unroofing of the IAC, the NI rootlets were individually exposed to identify their origins and insertion points. The AICA and its meatal loop were traced to assess their relationship with the NI rootlets. Results: Thirty-three NIs were identified. The median number of NI rootlets was 4 per NI (interquartile range, 3-5). The rootlets mainly originated from the proximal premeatal segment of CN VIII (81 of 141, 57%) and inserted onto CN VII at the IAC fundus (89 of 141, 63%). When crossing the acoustic-facial bundle, the AICA most frequently passed between the NI and CN VIII (14 of 33, 42%). Five composite patterns of neurovascular relationships were identified regarding NI. Conclusion: Although certain anatomical trends can be identified, the NI has a variable relationship with the adjacent neurovascular complex at the IAC. Therefore, anatomical relationships should not be used as the sole method of NI identification during CPA surgery.

Security breach: peripheral nerves provide unrestricted access for toxin delivery into the central nervous system.

We explore the hypothesis that a potential explanation for the initiation of motor neuron disease is an unappreciated vulnerability in central nervous system defense, the direct delivery of neurotoxins into motor neurons via peripheral nerve retrograde transport. This further suggests a mechanism for focal initiation of neuro-degenerative diseases in general, with subsequent spread by network degeneration as suggested by the Frost-Diamond hypothesis. We propose this vulnerability may be a byproduct of vertebrate evolution in a benign aquatic environment, where external surfaces were not exposed to concentrated neurotoxins.

Frameless Robotic-Assisted Deep Brain Stimulation With the Mazor Renaissance System.

BACKGROUND: Robotic-assisted stereotactic systems for deep brain stimulation (DBS) have recently gained popularity because of their abilities to automate arduous human error-prone steps for lead implantation. Recent DBS literature focuses on frame-based robotic platforms, but little has been reported on frameless robotic approaches, specifically the Food and Drug Administration-approved Mazor Renaissance Guidance System (Mazor Robotics Ltd). OBJECTIVE: To present an initial case series for patients undergoing awake DBS with the Mazor Renaissance Guidance System and evaluate operative variables and stereotactic accuracy. METHODS: Retrospective data collection at a single institution was conducted for an initial 35 consecutive patients. Patient demographics and operative variables, including case times, microelectrode recording passes, and postoperative complications, were obtained by chart review. Implant accuracy was evaluated through measuring radial and vector (x, y) errors using the Mazor software. Pneumocephalus volumes were calculated using immediate postoperative T1-weighted MRI scans. RESULTS: Total operating room (245 ± 5.5 min) and procedural (179 ± 4.7) times were comparable with previous awake DBS literature. The radial error for center tract implants was 1.3 ± 0.1 mm, with smaller error in the first (1.1 ± 0.2) vs second (1.7 ± 0.3) implants of bilateral DBS (P = .048). Vector error analysis demonstrated larger shifts posteriorly for first implants and medially for second implants. Pneumocephalus volumes (12.4 ± 2.2 cm3) were not associated with increased microelectrode recording passes, radial error, or complications. CONCLUSION: Frameless robotic-assisted DBS is a safe and efficient new technology that has been easily adopted into the workflow at our institution.

Tribute to William Edward Hunt and Robert McDonald Hess Jr.: Pioneers in the Clinical Classification of Ruptured Intracranial Aneurysms.

William Edward Hunt (1921-1999) and Robert McDonald Hess Jr. (1931-2019) were pioneers in revolutionizing the early surgical management of ruptured intracranial aneurysms. Early on in his career as a professor of neurosurgery at Ohio State University, Dr. Hunt adopted a systematic method to identify clinical symptoms of patients presenting with subarachnoid hemorrhage as candidates for either immediate or delayed surgery. As an Ohio State University neurosurgery resident, Dr. Hess was an active key collaborator in Dr. Hunt's aneurysm studies. Described as a modification of the Botterell classification system, the Hunt-Hess scale grading the survival risk of undergoing immediate intracranial aneurysm surgery was implemented and validated across an 18-year consecutive patient series at White Cross Hospital, Columbus, Ohio. Dr. Hunt and Dr. Hess demonstrated that for patients with subarachnoid hemorrhage on admission with Hunt-Hess grades I and II, indicating retained consciousness and minimal neurological deficits, immediate surgical management afforded a <20% mortality rate. In comparison, patients with grade III or higher had a >50% mortality rate, suggesting that conservative management should be instead pursued. As the principal investigator, Dr. Hunt was widely regarded internationally as an expert in the field of treating intracranial aneurysms, eventually serving as a World Federation of Neurosurgical Societies (WFNS) committee member to also publish a universal subarachnoid hemorrhage grading scale. To pay tribute to Drs. Hunt and Hess for their substantial contributions, we present historical vignettes of their lives along with highlighting the role of the Hunt-Hess classification system in transforming management of ruptured aneurysms.

Controlling Signal Artifact With Software Threshold Imaging for Magnetic Resonance-Guided Laser Interstitial Thermal Therapy.

BACKGROUND: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) uses intraoperative temperature mapping and thermal damage estimates to guide ablations of intracranial targets. In select cases, signal artifact presents at the target site and impairs intraprocedural decision-making by obscuring the visualization of both temperature imaging and the thermal damage estimate calculation. To date, the etiology and impact of signal artifact are unknown. However, user-selected MRgLITT software settings may play a role in generating artifact. OBJECTIVE: To assess the effect of the thresholding feature in MRgLITT software on signal artifact generation during intracranial ablations. METHODS: Ablations were performed with the Visualase MRI-guided Laser Ablation System (Medtronic). For each LITT procedure, raw thermal data were extracted at a reference threshold of 40 and reprocessed at 5 additional threshold values ranging from 35 to 60. Artifact growth rates relative to threshold values were derived using simple linear regressions and then assessed within the context of laser power and duration using Pearson correlations. RESULTS: A total of 33 patients were included, with 28 artifact-containing and 5 artifact-free cases. For artifact-containing cases, a 13% increase in artifact area occurred for every 1-point increase in threshold (R2 > 0.99). Artifact growth rates were not correlated with laser power (r = 0.15, P = .44) or duration (r = 0.0049, P = .98). One of the 5 artifact-free cases developed artifact at a threshold of 60. CONCLUSION: Artifact generation is likely multifactorial involving tissue properties and software settings. Operators can minimize software-introduced artifact by reducing threshold values.

Mathematical Modeling of Thermal Damage Estimate Volumes in MR-guided Laser Interstitial Thermal Therapy.

BACKGROUND AND PURPOSE: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive procedure that produces real-time thermal damage estimates (TDEs) of ablation. Currently, MRgLITT software provides limited quantitative parameters for intraoperative monitoring, but orthogonal TDE-MRI slices can be utilized to mathematically estimate ablation volume. The objective of this study was to model TDE volumes and validate using post-24 hours MRI ablative volumes. METHODS: Ablations were performed with the Visualase Laser Ablation System (Medtronic). Using ellipsoidal parameters determined for dual-TDEs from orthogonal MRI planes, TDE volumes were calculated by two definite integral methods (A and B) implemented in Matlab (MathWorks). Post-24 hours MRI ablative volumes were measured in OsiriX (Pixmeo) by two-blinded raters and compared to TDE volumes via paired t-test and Pearson's correlations. RESULTS: Twenty-two ablations for 20 patients with various intracranial pathologies were included. Average TDE volume calculated with method A was 3.44 ± 1.96 cm3 and with method B was 4.83 ± 1.53 cm3 . Method A TDE volumes were significantly different than post-24 hours volumes (P < .001). Method B TDE volumes were not significantly different than post-24 hours volumes (P = .39) and strongly correlated with each other (r = .85, R2 = .72, P < .0001). A total of eight of 22 (36%) method A versus 17 of 22 (77%) method B TDE volumes were within 25% of the post-24 hours ablative volume. CONCLUSION: We present a viable mathematical method integrating dual-plane TDEs to calculate volumes. Future algorithmic iterations will incorporate additional calculated variables that improve ablative volume estimations.

Suicide transport blockade of motor neuron survival generates a focal graded injury and functional deficit.

We describe a pre-clinical spinal cord motor neuron injury model that is minimal invasive, reproducible, focal and easily applied to small rodents. Retrograde axonal transport of a pro-apoptotic phosphatidylinosotol 3'-kinase inhibitor, wortmannin, via the sciatic nerve results in loss of ipsilateral lumbar motor neurons proportional to the level of drug administered. Motor neuron loss was detected by choline acetyltransferase (ChAT) immunostaining and with a transgenic thy1-eGFP marker. The short half-life of wortmannin generates minimal wound spread, and wortmannin does not affect axon transport, as determined by co-injection of a pseudorabies virus tracer. Using quantitative transcript analysis, we found that ChAT transcripts significantly decreased at 14 days post-delivery of 1 µg wortmannin, relative to sham controls, and remained low after 90 days. Smaller effects were observed with 200 ng and 100 ng wortmannin. Wortmannin also generated a transient and significant increase in astrocyte Gfap transcripts after 14 days with a return to control levels at 90 days. Treated mice had hind limb spasticity and a forced motor function defect that was quantified using a water exit test. Controls rapidly exit a shallow water tray, and wortmannin treated animals were up to 12-fold slower, a phenotype that persisted for at least 3 months. Thus the focal delivery of wortmannin to motor neurons generates a reproducible and scalable injury that can facilitate quantitative studies on neural regeneration and repair. The efficacy of sciatic nerve suicide transport can also explain neurotoxin-mediated selective loss of motor neurons in diseases such as amyotrophic lateral sclerosis. All procedures were performed at Rutgers under established Institutional Animal Care and Use protocols (eIACUC_TR201800022, approved on March 20, 2018).

Characterization of Magnetic Resonance Thermal Imaging Signal Artifact During Magnetic Resonance Guided Laser-Induced Thermal Therapy.

BACKGROUND: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive procedure that utilizes intraoperative magnetic resonance thermal imaging (MRTI) to generate a thermal damage estimate (TDE) of the ablative area. In select cases, the MRTI contains a signal artifact or defect that distorts the ablative region. No study has attempted to characterize this artifact. OBJECTIVE: To characterize MRTI signal the artifact in select cases to better understand its potential relevance and impact on the ablation procedure. METHODS: All ablations were performed using the Visualase magnetic resonance imaging-guided laser ablation system (Medtronic). Patients were included if the MRTI contained signal artifact that distorted the ablative region during the first thermal dose delivered. Ablation artifact was quantified using MATLAB version R2018a (Mathworks Inc, Natick, Massachusetts). RESULTS: A total of 116 patients undergoing MRgLITT for various surgical indications were examined. MRTI artifact was observed in 37.0% of cases overall. Incidence of artifact was greater at higher powers (P < .001) and with longer ablation times (P = .024), though artifact size did not correlate with laser power or ablation duration. CONCLUSION: MRTI signal artifact is common during LITT. Higher powers and longer ablation times result in greater incidence of ablation artifact, though artifact size is not correlated with power or duration. Future studies should aim to evaluate effects of artifact on postoperative imaging and, most notably, patient outcomes.

Fads3 modulates docosahexaenoic acid in liver and brain.

Fatty acid desaturase 3 (FADS3) is the third member of the FADS gene cluster. FADS1 and FADS2 code for enzymes required for highly unsaturated fatty acid (HUFA) biosynthesis, but FADS3 function remains elusive. We generated the first Fads3 knockout (KO) mouse with an aim to characterize its metabolic phenotype and clues to in vivo function. All mice (wild type (WT) and KO) were fed facility rodent chow devoid of HUFA. No differences in overt phenotypes (survival, fertility, growth rate) were observed. Docosahexaenoic acid (DHA, 22:6n-3) levels in the brain of postnatal day 1 (P1) KO mice were lower than the WT (P < 0.05). The ratio of docosapentaenoic acid (DPA, 22:5n-3) to DHA in P1 KO liver was higher than in WT suggesting lower desaturase activity. Concomitantly, 20:4n-6 was lower but its elongation product 22:4n-6 was greater in the liver of P1 KO mice. P1 KO liver Fads1 and Fads2 mRNA levels were significantly downregulated whereas expression levels of elongation of very long chain 2 (Elovl2) and Elovl5 genes were upregulated compared to age-matched WT. No Δ13-desaturation of vaccenic acid was observed in liver or heart in WT mice expressing FADS3 as was reported in vitro. Taken together, the fatty acid compositional results suggest that Fads3 enhances liver-mediated 22:6n-3 synthesis to support brain 22:6n-3 accretion before and during the brain growth spurt.

Palmitic acid (16:0) competes with omega-6 linoleic and omega-3 ɑ-linolenic acids for FADS2 mediated Δ6-desaturation.

Sapienic acid, 16:1n-10 is the most abundant unsaturated fatty acid on human skin where its synthesis is mediated by FADS2 in the sebaceous glands. The FADS2 product introduces a double bond at the Δ6, Δ4 and Δ8 positions by acting on at least ten substrates, including 16:0, 18:2n-6, and 18:3n-3. Our aim was to characterize the competition for accessing FADS2 mediated Δ6 desaturation between 16:0 and the most abundant polyunsaturated fatty acids (PUFA) in the human diet, 18:2n-6 and 18:3n-3, to evaluate whether competition may be relevant in other tissues and thus linked to metabolic abnormalities associated with FADS2 or fatty acid levels. MCF7 cells stably transformed with FADS2 biosynthesize 16:1n-10 from exogenous 16:0 in preference to 16:1n-7, the immediate product of SCD highly expressed in cancer cell lines, and 16:1n-9 via partial ß-oxidation of 18:1n-9. Increasing availability of 18:2n-6 or 18:3n-3 resulted in decreased bioconversion of 16:0 to 16:1n-10, simultaneously increasing the levels of highly unsaturated products. FADS2 cells accumulate the desaturation-elongation products 20:3n-6 and 20:4n-3 in preference to the immediate desaturation products 18:3n-6 and 18:4n-3 implying prompt/coupled elongation of the nascent desaturation products. MCF7 cells incorporate newly synthesized 16:1n-10 into phospholipids. These data suggest that excess 16:0 due to, for instance, de novo lipogenesis from high carbohydrate or alcohol consumption, inhibits synthesis of highly unsaturated fatty acids, and may in part explain why supplemental preformed EPA and DHA in some studies improves insulin resistance and other factors related to diabetes and metabolic syndrome aggravated by excess calorie consumption.