Glioblastoma (GBM) is an aggressive primary astrocytoma associated with short overall survival. Treatment for GBM primarily consists of maximal safe surgical resection, radiation therapy, and chemotherapy using temozolomide. Nonetheless, recurrence and tumor progression is the norm, driven by tumor stem cell activity and a high mutational burden. Focused ultrasound (FUS) has shown promising results in preclinical and clinical trials for treatment of GBM and has received regulatory approval for the treatment of other neoplasms. Here, we review the range of applications for FUS in the treatment of GBM, which depend on parameters, including frequency, power, pulse duration, and duty cycle. Low-intensity FUS can be used to transiently open the blood–brain barrier (BBB), which restricts diffusion of most macromolecules and therapeutic agents into the brain. Under guidance from magnetic resonance imaging, the BBB can be targeted in a precise location to permit diffusion of molecules only at the vicinity of the tumor, preventing side effects to healthy tissue. BBB opening can also be used to improve detection of cell-free tumor DNA with liquid biopsies, allowing non-invasive diagnosis and identification of molecular mutations. High-intensity FUS can cause tumor ablation via a hyperthermic effect. Additionally, FUS can stimulate immunological attack of tumor cells, can activate sonosensitizers to exert cytotoxic effects on tumor tissue, and can sensitize tumors to radiation therapy. Finally, another mechanism under investigation, known as histotripsy, produces tumor ablation via acoustic cavitation rather than thermal effects.

The synaptic cleft manifests enriched glycosylation, with structured glycans coordinating signaling between presynaptic and postsynaptic cells. Glycosylated signaling ligands orchestrating communication are tightly regulated by secreted glycan-binding lectins. Using the Drosophila neuromuscular junction (NMJ) as a model glutamatergic synapse, we identify a new Ca2+-binding (C-type) lectin, Lectin-galC1 (LGC1), which modulates presynaptic function and neurotransmission strength. We find that LGC1 is enriched in motoneuron presynaptic boutons and secreted into the NMJ extracellular synaptomatrix. We show that LGC1 limits locomotor peristalsis and coordinated movement speed, with a specific requirement for synaptic function, but not NMJ architecture. LGC1 controls neurotransmission strength by limiting presynaptic active zone (AZ) and postsynaptic glutamate receptor (GluR) aligned synapse number, reducing both spontaneous and stimulation-evoked synaptic vesicle (SV) release, and capping SV cycling rate. During high-frequency stimulation (HFS) mutants have faster synaptic depression and impaired recovery while replenishing depleted SV pools. Although LGC1 removal increases the number of glutamatergic synapses, we find LGC1 null mutants exhibit decreased SV density within presynaptic boutons, particularly SV pools at presynaptic active zones. Thus, LGC1 regulates NMJ neurotransmission to modulate coordinated movement.

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BACKGROUND AND OBJECTIVES: Robot-assisted pedicle screw placement is associated with greater accuracy, reduced radiation, less blood loss, shorter hospital stays, and fewer complications than freehand screw placement. However, it can be associated with longer operative times and an extended training period. We report the initial experience of a surgeon using a robot system at an academic medical center. METHODS: We retrospectively reviewed all patients undergoing robot-assisted pedicle screw placement at a single tertiary care institution by 1 surgeon from 10/2017 to 05/2022. Linear regression, analysis of variance, and cumulative sum analysis were used to evaluate operative time learning curves. Operative time subanalyses for surgery indication, number of levels, and experience level were performed. RESULTS: In total, 234 cases were analyzed. A significant 0.19-minute decrease in operative time per case was observed (r = 0.14, P = .03). After 234 operations, this translates to a reduction in 44.5 minutes from the first to last case. A linear relationship was observed between case number and operative time in patients with spondylolisthesis (−0.63 minutes/case, r = 0.41, P < .001), 2-level involvement (−0.35 minutes/case, r = 0.19, P = .05), and 4-or-more-level involvement (−1.29 minutes/case, r = 0.24, P = .05). This resulted in reductions in operative time ranging from 39 minutes to 1.5 hours. Continued reductions in operative time were observed across the learning, experienced, and expert phases, which had mean operative times of 214, 197, and 146 minutes, respectively (P < .001). General proficiency in robot-assisted surgery was observed after the 20th case. However, 67 cases were required to reach mastery, defined as the inflection point of the cumulative sum curve. CONCLUSION: This study documents the long-term learning curve of a fellowship-trained spine neurosurgeon. Operative time significantly decreased with more experience. Although gaining comfort with robotic systems may be challenging or require additional training, it can benefit surgeons and patients alike with continued reductions in operative time.

BACKGROUND Synthetic computed tomography (sCT) can be created from magnetic resonance imaging (MRI) utilizing newer software. sCT is yet to be explored as a possible alternative to routine CT (rCT). In this study, rCT scans and MRI-derived sCT scans were obtained on a cadaver. Morphometric analysis was performed comparing the 2 scans. The ExcelsiusGPS robot was used to place lumbosacral screws with both rCT and sCT images. OBSERVATIONS In total, 14 screws were placed. All screws were grade A on the Gertzbein-Robbins scale. The mean surface distance difference between rCT and sCT on a reconstructed software model was –0.02 ± 0.05 mm, the mean absolute surface distance was 0.24 ± 0.05 mm, and the mean absolute error of radiodensity was 92.88 ± 10.53 HU. The overall mean tip distance for the sCT versus rCT was 1.74 ± 1.1 versus 2.36 ± 1.6 mm (p = 0.24); mean tail distance for the sCT versus rCT was 1.93 ± 0.88 versus 2.81 ± 1.03 mm (p = 0.07); and mean angular deviation for the sCT versus rCT was 3.2° ± 2.05° versus 4.04°± 2.71° (p = 0.53). LESSONS MRI-based sCT yielded results comparable to those of rCT in both morphometric analysis and robot-assisted lumbosacral screw placement in a cadaver study.

INTRODUCTION: Favorable safety and effectiveness outcomes were presented previously for the Neuroform Atlas Stent following the completion of its pre-market study (ATLAS trial [Safety and Effectiveness of the Treatment of Wide Neck, Saccular, Intracranial Aneurysms with the Neuroform Atlas Stent System]) in anterior and posterior cohorts.METHODS: The ATLAS post-approval study was a multicenter, prospective, single-arm, open-label study of wide neck (neck ≥ 4mm or dome-to-neck ratio <2) intracranial aneurysms in the anterior and posterior circulations treated with the Neuroform Atlas Stent and approved coils. The primary effectiveness endpoint was complete occlusion (Raymond-Roy class 1) on angiography in the absence of retreatment or significant parent artery stenosis (>50%) through 3 years post-procedure. The primary safety endpoint was occurrence of major stroke, ipsilateral stroke, or neurological death through 3 years post-procedure. Independent adjudication of primary endpoint outcomes was completed by an Imaging Core Laboratory and Clinical Events Committee.RESULTS: A total of 146 anterior and 101 posterior cohort subjects from the pre-market study population were enrolled for continued follow-up. Subject demographics and aneurysm anatomy were representative of pivotal trial findings. For anterior subjects, the mean aneurysm size was 6.1±2.4 mm and the mean dome-to-neck ratio was 1.2±0.3 mm. In posterior subjects, the mean aneurysm size was 7±2.7 mm and the mean dome-to-neck ratio was 1.2±0.4 mm. At 3-year follow-up, the percent of target aneurysm progressive occlusion rated the same or better was 84.4% (95% CI, 67.2% -94.7%) of anterior subjects and 90.0% (95% CI, 73.5% -97.9%) of posterior subjects. A primary safety event was reported in 0.7% (1/146) of anterior and 1.0% (1/101) of posterior subjects, respectively, with no neurological deaths.CONCLUSIONS: The results of the ATLAS post-approval study demonstrate durable treatment effectiveness and favorable safety outcomes.

BACKGROUND AND OBJECTIVES: Flow diversion of intracranial aneurysms results in high occlusion rates. However, 10% to 20% remain persistently filling at 1 year. Often, these are retreated, but benefits of retreatment are not well established. A better understanding of the long-term rupture risk of persistently filling aneurysms after flow diversion is needed. METHODS: Our institutional database of 974 flow diversion cases was queried for persistently filling saccular aneurysms of the clinoidal, ophthalmic, and communicating segments of the internal carotid artery treated with the pipeline embolization device (PED, Medtronic). Persistent filling was defined as continued flow into the aneurysm on 1 year catheter angiogram. The clinical record was queried for retreatments and delayed ruptures. Clinical follow-up was required for at least 2 years. RESULTS: Ninety-four persistent aneurysms were identified. The average untreated aneurysm size was 5.6 mm. A branch vessel originated separately in 55% of cases from the body of the aneurysm in 10.6% of cases and from the neck in 34% of cases. Eighteen percent of aneurysms demonstrated >95% filling at 1 year, and 61% were filling 5% to 95% of their original size. The mean follow-up time was 4.9 years, including 41 cases with >5 years. No retreatment was undertaken in 91.5% of aneurysms. There were no cases of delayed subarachnoid hemorrhage. CONCLUSION: Among saccular internal carotid artery aneurysms treated with PED that demonstrated persistent aneurysm filling at 1 year, there were no instances of delayed rupture on long-term follow-up. These data suggest that observation may be appropriate for continued aneurysm filling at least in the first several years after PED placement.

Low-intensity focused ultrasound (LIFU) uses ultrasonic pulsations at lower intensities than ultrasound and is being tested as a reversible and precise neuromodulatory technology. Although LIFU-mediated blood-brain barrier (BBB) opening has been explored in detail, no standardized technique for blood-spinal cord barrier (BSCB) opening has been established to date. Therefore, this protocol presents a method for successful BSCB disruption using LIFU sonication in a rat model, including descriptions of animal preparation, microbubble administration, target selection and localization, as well as BSCB disruption visualization and confirmation. The approach reported here is particularly useful for researchers who need a fast and cost-effective method to test and confirm target localization and precise BSCB disruption in a small animal model with a focused ultrasound transducer, evaluate the BSCB efficacy of sonication parameters, or explore applications for LIFU at the spinal cord, such as drug delivery, immunomodulation, and neuromodulation. Optimizing this protocol for individual use is recommended, especially for advancing future preclinical, clinical, and translational work.