Application of novel non-invasive ophthalmic imaging to visualize peripapillary wrinkles, retinal folds and peripapillary hyperreflective ovoid mass-like structures associated with elevated intracranial pressure.

Background: Elevated intracranial pressure (ICP) is a serious and potentially life-threatening condition, for which clinically useful non-invasive measures have been elusive, in some cases due to their inadequate sensitivity and specificity. Our aim was to evaluate novel non-invasive ophthalmic imaging of selected pathological features seen in elevated ICP, namely peripapillary hyperreflective ovoid mass-like structures (PHOMS), peripapillary wrinkles (PPW) and retinal folds (RF) as potential biomarkers of elevated ICP. Methods: This single-center pilot study included subjects with untreated or incompletely treated high ICP. The retinas of these subjects were evaluated with averaged en-face optical coherence tomography (OCT), OCT retinal cross-sections (OCT B-scans), adaptive optics scanning light ophthalmoscopy (AOSLO), and fundus photos. Results: Seven subjects were included in the study. 6 subjects with high ICP (5 idiopathic intracranial hypertension, 1 medication induced, 30.8 ± 8.6 years, 75% female, 5 with papilledema) and 1 control (20-25 years) were included. PHOMS, PPW and RF were present in all subjects with papilledema, but neither in the high ICP subject without papilledema nor in the control subject. Averaged en-face OCT scans and AOSLO were more sensitive for PPW and RF than OCT B-scans and commercial fundus photos. Conclusion: PPW, RF and PHOMS volume have potential as non-invasive biomarkers of ICP. Novel imaging modalities may improve sensitivity. However, lack of automated image acquisition and processing limits current widespread adoption in clinical settings. Further research is needed to validate these structures as biomarkers for elevated ICP and improve clinical utility.

Percutaneous Disc Biopsy versus Bone Biopsy for the Identification of Infectious Agents in Osteomyelitis/Discitis.

PURPOSE: To determine whether sampling of the disc or bone is more likely to yield positive tissue culture results in patients with vertebral discitis and osteomyelitis (VDO). MATERIALS AND METHODS: Retrospective review was performed of consecutive patients who underwent vertebral disc or vertebral body biopsy at a single institution between February 2019 and May 2023. Inclusion criteria were age ≥18 years, presumed VDO on spinal magnetic resonance (MR) imaging, absence of paraspinal abscess, and technically successful percutaneous biopsy with fluoroscopic guidance. The primary outcome was a positive biopsy culture result, and secondary outcomes included complications such as nerve injury and segmental artery injury. RESULTS: Sixty-six patients met the inclusion criteria; 36 patients (55%) underwent disc biopsy, and 30 patients (45%) underwent bone biopsy. Six patients required a repeat biopsy for an initially negative culture result. No significant demographic, laboratory, antibiotic administration, or pain medication use differences were observed between the 2 groups. Patients who underwent bone biopsy were more likely to have a history of intravenous drug use (26.7%) compared with patients who underwent disc biopsy (5.5%; P = .017). Positive tissue culture results were observed in 41% of patients who underwent disc biopsy and 15% of patients who underwent bone biopsy (P = .016). No vessel or nerve injuries were detected after procedure in either group. CONCLUSIONS: Percutaneous disc biopsy is more likely to yield a positive tissue culture result than vertebral body biopsy in patients with VDO.

EGCG-like non-competitive inhibitor of DYRK1A rescues cognitive defect in a down syndrome model.

Overexpression of the chromosome 21 DYRK1A gene induces morphological defects and cognitive impairments in individuals with Down syndrome (DS) and in DS mice models. Aging neurons of specific brain regions of patients with Alzheimer's disease, DS and Pick's disease have increased DYRK1A immunoreactivity suggesting a possible association of DYRK1A with neurofibrillary tangle pathology. Epigallocatechin-3-gallate (EGCG) displays appreciable inhibition of DYRK1A activity and, contrary to all other published inhibitors, EGCG is a non-competitive inhibitor of DYRK1A. Prenatal exposure to green tea polyphenols containing EGCG protects from brain defects induced by overexpression of DYRK1A. In order to produce more robust and possibly more active analogues of the natural compound EGCG, here we synthetized new EGCG-like molecules with several structural modifications to the EGCG skeleton. We replaced the ester boun of EGCG with a more resistant amide bond. We also replaced the oxygen ring by a methylene group. And finally, we positioned a nitrogen atom within this ring. The selected compound was shown to maintain the non-competitive property of EGCG and to correct biochemical and behavioral defects present in a DS mouse model. In addition it showed high stability and specificity.

A Prospective, Multicenter, Observational Study of Surgical vs Nonsurgical Management for Pituitary Apoplexy.

CONTEXT: Pituitary apoplexy (PA) has been traditionally considered a neurosurgical emergency, yet retrospective single-institution studies suggest similar outcomes among patients managed medically. OBJECTIVE: We established a multicenter, international prospective registry to compare presentation and outcomes in PA patients treated with surgery or medical management alone. METHODS: A centralized database captured demographics, comorbidities, clinical presentation, visual findings, hormonal status, and imaging features at admission. Treatment was determined independently by each site. Key outcomes included visual, oculomotor, and hormonal recovery, complications, and hospital length of stay. Outcomes were also compared based on time from symptom onset to surgery, and from admission or transfer to the treating center. Statistical testing compared treatment groups based on 2-sided hypotheses and P less than .05. RESULTS: A total of 100 consecutive PA patients from 12 hospitals were enrolled, and 97 (67 surgical and 30 medical) were evaluable. Demographics, clinical features, presenting symptoms, hormonal deficits, and imaging findings were similar between groups. Severe temporal visual field deficit was more common in surgical patients. At 3 and 6 months, hormonal, visual, and oculomotor outcomes were similar. Stratifying based on severity of visual fields demonstrated no difference in any outcome at 3 months. Timing of surgery did not affect outcomes. CONCLUSION: We found that medical and surgical management of PA yield similar 3-month outcomes. Although patients undergoing surgery had more severe visual field deficits, we could not clearly demonstrate that surgery led to better outcomes. Even without surgery, apoplectic tumor volumes regress substantially within 2 to 3 months, indicating that surgery is not always needed to reduce mass effect.

Matched-pair analysis of patients with ischemic stroke undergoing thrombectomy using next-generation balloon guide catheters.

BACKGROUND: Balloon guide catheters (BGCs) have not been widely adopted, possibly due to the incompatibility of past-generation BGCs with large-bore intermediate catheters. The next-generation BGC is compatible with large-bore catheters. We compared outcomes of thrombectomy cases using BGCs versus conventional guide catheters. METHODS: We conducted a retrospective study of 110 thrombectomy cases using BGCs (n=55) and non-BGCs (n=55). Sixty consecutive thrombectomy cases in whom the BOBBY BGC was used at a single institution between February 2021 and March 2022 were identified. Of these, 55 BGC cases were 1:1 matched with non-BGC cases by proceduralists, age, gender, stent retriever + aspiration device versus aspiration-only, and site of occlusion. First-pass effect was defined as Thrombolysis In Cerebral Infarction 2b or higher with a single pass. RESULTS: The BGC and non-BGC cohorts had similar mean age (67.2 vs 68.9 years), gender distribution (43.6% vs 47.3% women), median initial National Institutes of Health Stroke Scale score (14 vs 15), and median pretreatment ischemic core volumes (12 mL vs 11.5 mL). BGC and non-BGC cases had similar rates of single pass (60.0% vs 54.6%), first-pass effect (58.2% vs 49.1%), and complications (1.8% vs 9.1%). In aspiration-only cases, the BGC cohort had a significantly higher rate of first-pass effect (100% vs 50.0%, p=0.01). BGC was associated with a higher likelihood of achieving a modified Rankin Scale score of 2 at discharge (OR 7.76, p=0.02). No additional procedural time was required for BGC cases (46.7 vs 48.2 min). CONCLUSION: BGCs may be safely adopted with comparable procedural efficacy, benefits to aspiration-only techniques, and earlier functional improvement compared with conventional guide catheters.

Multidisciplinary Stroke Pathway for Children Supported With Ventricular Assist Devices.

Mechanical circulatory support (MCS), including ventricular assist device (VAD) support, is a leading cause of stroke in children; however, existing pediatric stroke recommendations do not apply to many pediatric VAD patients. We sought to develop a multidisciplinary pathway to improve timely and effective acute stroke care and examine the early performance of the pathway in expediting stroke care. Stakeholders from pediatric heart failure, cardiac intensive care, neurology, interventional radiology, neuroradiology, neurosurgery, pharmacy, and adult VAD care convened at Stanford University in August 2017 to discuss the challenges of providing high-quality acute stroke care to children on VAD support, and to develop multidisciplinary acute stroke pathways. Stakeholders identified multiple barriers to providing timely acute stroke care to pediatric VAD patients. These include delayed recognition of stroke, and lack of clarity related to the optimal imaging technique, when to emergently reverse antithrombotic therapy (AT), pediatric indications for thrombectomy and cranial decompression, and strategies to avoid unnecessary serial CTS. Four stroke pathways were created including evaluation and management of the pediatric patient with (1) an acute neurologic change before an imaging diagnosis; (2) an arterial ischemic stroke (AIS); (3) an intracerebral hemorrhage (ICH); and (4) a subdural hematoma (SDH). With the implementation of the stroke pathway, the median time-to-first-CT image decreased by 43 minutes from 66 to 23 minutes ( P < 0.001) while the proportion with a CT within 30 minutes increased from 0% to 67% ( P < 0.001). Despite a variety of challenges, multidisciplinary consensus can be achieved on a rapid stroke management pathway for children on VAD support that addresses important barriers to timely stroke care. Although too few stoke events occurred to differentiate clinical outcomes, the time-to-first-CT image was significantly shorter after pathway implementation.

Pituitary macroadenoma causing vision loss in Wyburn-Mason syndrome: illustrative case.

BACKGROUND: Wyburn-Mason syndrome (WMS) is a neurocutaneous disorder consisting of vascular malformations of the brain, eye, and skin. These include characteristically high-flow intracranial and intraorbital arteriovenous malformations (AVMs) that present commonly with visual deterioration, headache, and hemiplegia. Complete removal of these lesions is challenging. Most patients are followed closely, and intervention occurs only in the setting of worsening symptoms secondary to AVM growth or hemorrhage. Here the authors present the first known case of a patient with WMS and a pituitary macroadenoma. OBSERVATIONS: A 62-year-old man with a 30-year history of WMS with right basal ganglia and orbital AVMs and right eye blindness presented for new-onset left-sided vision loss. A pituitary adenoma was identified compressing the optic chiasm and left optic nerve. Magnetic resonance imaging and digital subtraction angiography studies were obtained for surgical planning, and the patient underwent an endoscopic transnasal transsphenoidal resection, with significant postoperative vision improvement. LESSONS: Given the variable presentation and poor characterization of this rare syndrome, patients with WMS presenting with new symptoms must undergo evaluation for growth and hemorrhage of known AVMs, as well as new lesions. Further, in patients undergoing intracranial surgery, extensive preoperative imaging and planning are crucial for safe and successful procedures.

Venous thromboembolism rates and risk factors following endoscopic skull base surgery.

BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal perioperative complication. The objective of this study was to assess the rate and risk factors for VTE in endoscopic skull base surgery (ESBS). METHODS: This was a retrospective review of adults undergoing ESBS at a tertiary academic center. Incidence of VTE in the 30-day postoperative period was recorded. Logistic regression analyses identified factors associated with VTE. RESULTS: A total of 1122 ESBS cases performed at Stanford University School of Medicine between 2009 and 2019 were studied. Almost all cases (96.1%) did not employ perioperative VTE chemoprophylaxis. The overall incidence of VTE was 2.3% (26/1122). Malignant pathologies had a higher rate of VTE compared with nonmalignant pathologies (4.5% vs 2.0%, odds ratio [OR] 2.85, 95% confidence interval [CI] 1.22-6.66). Factors associated with an increased risk of VTE included a Caprini score greater than 5 (OR 1.53, 95% CI 1.28-1.83); multiple preoperative endocrinopathies such as the syndrome of inappropriate antidiuretic hormone secretion (SIADH) (OR 22.48, 95% CI 3.93-128.70), adrenal insufficiency (OR 5.24, 95% CI 1.82-15.03), hypercortisolism (OR 4.46, 95% CI 1.47-13.56), and hypothyroidism (OR 3.69, 95% CI 1.66-8.20); each 10-hour increment of lumbar drain duration (OR 1.16, 95% CI 1.08-1.25); and each 10-hour increment for duration of hospitalization (OR 1.05, 95% CI 1.03-1.06). CONCLUSIONS: The incidence of VTE following ESBS is relatively low at 2.3%. Factors with a higher association of VTE include malignancy, preoperative endocrinopathies, higher Caprini score, prolonged lumbar drain duration, and prolonged hospitalization. Larger, multi-institutional studies are needed to validate these findings and to better refine clinical decision-making regarding perioperative VTE prophylaxis.

Improved Ophthalmic Outcomes Following Venous Sinus Stenting in Idiopathic Intracranial Hypertension.

Background: Ophthalmic outcomes following venous sinus stenting (VSS) in patients with idiopathic intracranial hypertension (IIH) are not well characterized. Materials and Methods: A retrospective chart review was conducted on 86 consecutive patients with IIH who underwent venous sinus stenting at Mayo Clinic, Rochester, Minnesota and Stanford Medical Center, Palo Alto, California between May 2015 and October 2021. Patients with raised intracranial pressure from a non-IIH etiology were excluded. Clinical symptoms and neuro-ophthalmological data, including best corrected visual acuity (BCVA), visual field mean deviation, papilledema, and optical coherence tomography (OCT) peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell inner plexiform layer (GC-IPL), were analyzed. Baseline measurements before VSS and 3 months or more postoperatively were compared. Results: Eighty-six subjects (82 female) were included in this study, with a median age of 33 (16-68) years and a median body mass index of 36.69 (22.30-62.00) kg/m2. 85/86 (98.8%) had attempted prior management with medication, and 12/86 (14%) had prior surgical management with optic nerve sheath fenestration, ventriculoperitoneal shunt, or bariatric surgery. Prior to VSS, 67/86 (77.9%) had papilledema, 85/86 (98.8%) had headaches, and 68/86 (79.1%) had pulsatile tinnitus. For patients with both pre- and post-VSS data available, the average papilledema grade was 1.76 (0-5) (n = 74) and the average OCT pRNFL was 186.34 (52.00-588.00) µm (n = 70), prior to VSS. A median of 4.0 (interquartile range 3.3-5.4) months after VSS, the average papilledema grade improved to 0.39 (0-2), p <0.001, and OCT pRNFL improved to 96.86 (47.00-168.00) µm, p <0.001. 28/86 (32.6%) patients no longer required medication for high intracranial pressure. 14/85 (16.5%) patients reported complete resolution of their headache and 55/71 (77.5%) reported improvement in headache quality. 40/68 (66.7%) reported complete resolution of pulsatile tinnitus. OCT GC-IPL, BCVA, and visual field mean deviation did not significantly change pre- vs post-VSS. Conclusions: Our large consecutive case series corroborates smaller prior studies in demonstrating the overall efficacy of VSS for patients with IIH. We found both ophthalmic improvements, as demonstrated by the significantly reduced papilledema and pRNFL, and overall clinical symptom improvement.

Direct brainstem somatosensory evoked potentials for cavernous malformations.

OBJECTIVE: Brainstem cavernous malformations (CMs) often require resection due to their aggressive natural history causing hemorrhage and progressive neurological deficits. The authors report a novel intraoperative neuromonitoring technique of direct brainstem somatosensory evoked potentials (SSEPs) for functional mapping intended to help guide surgery and subsequently prevent and minimize postoperative sensory deficits. METHODS: Between 2013 and 2019 at the Stanford University Hospital, intraoperative direct brainstem stimulation of primary somatosensory pathways was attempted in 11 patients with CMs. Stimulation identified nucleus fasciculus, nucleus cuneatus, medial lemniscus, or safe corridors for incisions. SSEPs were recorded from standard scalp subdermal electrodes. Stimulation intensities required to evoke potentials ranged from 0.3 to 3.0 mA or V. RESULTS: There were a total of 1 midbrain, 6 pontine, and 4 medullary CMs-all with surrounding hemorrhage. In 7/11 cases, brainstem SSEPs were recorded and reproducible. In cases 1 and 11, peripheral median nerve and posterior tibial nerve stimulations did not produce reliable SSEPs but direct brainstem stimulation did. In 4/11 cases, stimulation around the areas of hemosiderin did not evoke reliable SSEPs. The direct brainstem SSEP technique allowed the surgeon to find safe corridors to incise the brainstem and resect the lesions. CONCLUSIONS: Direct stimulation of brainstem sensory structures with successful recording of scalp SSEPs is feasible at low stimulation intensities. This innovative technique can help the neurosurgeon clarify distorted anatomy, identify safer incision sites from which to evacuate clots and CMs, and may help reduce postoperative neurological deficits. The technique needs further refinement, but could potentially be useful to map other brainstem lesions.

Cerebral Perfusion in Pediatric Stroke: Children Are Not Little Adults.

ABSTRACT: Cerebral perfusion imaging provides useful information about the hemodynamic state of the brain that is relevant to a number of neurologic conditions, including stroke, epilepsy, and brain tumors. Multiple imaging modalities have been developed to evaluate brain perfusion, primarily by the use of different tracers to measure cerebral blood volume and cerebral blood flow. Here, we provide an overview of magnetic resonance imaging perfusion techniques; summarize the role of perfusion imaging in adult stroke; describe changes in cerebral blood flow over childhood; and discuss the relevance and future directions of perfusion imaging in pediatric cerebrovascular disorders and stroke.

Azetidinimines as a novel series of non-covalent broad-spectrum inhibitors of ß-lactamases with submicromolar activities against carbapenemases KPC-2 (class A), NDM-1 (class B) and OXA-48 (class D).

The occurrence of resistances in Gram negative bacteria is steadily increasing to reach extremely worrying levels and one of the main causes of resistance is the massive spread of very efficient ß-lactamases which render most ß-lactam antibiotics useless. Herein, we report the development of a series of imino-analogues of ß-lactams (namely azetidinimines) as efficient non-covalent inhibitors of ß-lactamases. Despite the structural and mechanistic differences between serine-ß-lactamases KPC-2 and OXA-48 and metallo-ß-lactamase NDM-1, all three enzymes can be inhibited at a submicromolar level by compound 7dfm, which can also repotentiate imipenem against a resistant strain of Escherichia coli expressing NDM-1. We show that 7dfm can efficiently inhibit not only the three main clinically-relevant carbapenemases of Ambler classes A (KPC-2), B (NDM-1) and D (OXA-48) with Ki's below 0.3 µM, but also the cephalosporinase CMY-2 (class C, 86% inhibition at 10 µM). Our results pave the way for the development of a new structurally original family of non-covalent broad-spectrum inhibitors of ß-lactamases.

Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting Activity.

Our previous study found that desmethylxanthohumol (1) inhibited α-glucosidase in vitro. Recently, further investigations revealed that dehydrocyclodesmethylxanthohumol (2) and its dimer analogue rottlerone (3) exhibited more potent α-glucosidase inhibitory activity than 1. The aim of this study was to synthesize a series of rottlerone analogues and evaluate their α-glucosidase and DPP-4 dual inhibitory activity. The results showed that compounds 4d and 5d irreversibly and potently inhibited α-glucosidase (IC50 = 0.22 and 0.12 µM) and moderately inhibited DPP-4 (IC50 = 23.59 and 26.19 µM), respectively. In addition, compounds 4d and 5d significantly promoted glucose consumption, with the activity of 5d at 0.2 µM being comparable to that of metformin at a concentration of 1 mM.

Intracerebral Hemorrhage Volume Reduction and Timing of Intervention Versus Functional Benefit and Survival in the MISTIE III and STICH Trials.

BACKGROUND: The extent of intracerebral hemorrhage (ICH) removal conferred survival and functional benefits in the minimally invasive surgery with thrombolysis in intracerebral hemorrhage evacuation (MISTIE) III trial. It is unclear whether this similarly impacts outcome with craniotomy (open surgery) or whether timing from ictus to intervention influences outcome with either procedure. OBJECTIVE: To compare volume evacuation and timing of surgery in relation to outcomes in the MISTIE III and STICH (Surgical Trial in Intracerebral Hemorrhage) trials. METHODS: Postoperative scans were performed in STICH II, but not in STICH I; therefore, surgical MISTIE III cases with lobar hemorrhages (n = 84) were compared to STICH II all lobar cases (n = 259) for volumetric analyses. All MISTIE III surgical patients (n = 240) were compared to both STICH I and II (n = 722) surgical patients for timing analyses. These were investigated using cubic spline modeling and multivariate risk adjustment. RESULTS: End-of-treatment ICH volume ≤28.8 mL in MISTIE III and ≤30.0 mL in STICH II had increased probability of modified Rankin Scale (mRS) 0 to 3 at 180 d (P = .01 and P = .003, respectively). The effect in the MISTIE cohort remained significant after multivariate risk adjustments. Earlier surgery within 62 h of ictus had a lower probability of achieving an mRS 0 to 3 at 180 d with STICH I and II (P = .0004), but not with MISTIE III. This remained significant with multivariate risk adjustments. There was no impact of timing until intervention on mortality up to 47 h with either procedure. CONCLUSION: Thresholds of ICH removal influenced outcome with both procedures to a similar extent. There was a similar likelihood of achieving a good outcome with both procedures within a broad therapeutic time window.

Spontaneous regression of a vein of Galen aneurysmal malformation in a pediatric patient: illustrative case.

BACKGROUND: Vein of Galen aneurysmal malformations (VGAMs) are rare congenital intracranial vascular lesions that represent 30% of all pediatric vascular anomalies. These lesions are associated with severe manifestations, including congestive heart failure, hydrocephalus, and spontaneous hemorrhage. The mainstay of management is medical stabilization followed by endovascular embolization of the lesion. Although VGAM was first reported in 1937, there are few published cases demonstrating spontaneous regression of the lesion. OBSERVATIONS: The authors report the case of a 31-month-old female who presented with an incidentally found VGAM. After initial evaluation, including magnetic resonance imaging and angiography, the patient was lost to follow-up. Upon her return to the clinic at age 12 years, the previously identified VGAM was absent, indicative of involution of the lesion. The patient remained asymptomatic and met appropriate developmental milestones during this interval. LESSONS: This report adds a rare case of the spontaneous resolution of VGAM to the literature. This case may suggest the presence of VGAMs that are asymptomatic, undetected, and regress within the pediatric population. Future studies may benefit from identifying imaging and angiographic findings predictive of spontaneous regression. There may be a role for conservative management in particular cases of asymptomatic and medically stable children with VGAMs.

Efficacy and safety of embolization of dural arteriovenous fistulas via the ophthalmic artery.

INTRODUCTION: Dural arteriovenous fistulae (DAVF) are vascular lesions with arteriovenous shunting that may be treated with surgical obliteration or endovascular embolization. Some DAVF, such as anterior cranial fossa DAVF (AC-DAVF) derive their arterial supply from ophthalmic artery branches in nearly all cases, and trans-arterial embolization carries a risk of vision loss. We determined the efficacy and safety of trans-ophthalmic artery embolization of DAVF. MATERIALS AND METHODS: We performed a retrospective cohort study of all patients with DAVF treated by trans-ophthalmic artery embolization from 2012 to 2020. Primary outcome was angiographic cure of the DAVF. Secondary outcomes included vision loss, visual impairment, orbital cranial nerve injury, stroke, modified Rankin Scale at 90-days, and mortality. RESULTS: 12 patients met inclusion criteria (9 males; 3 females). 10 patients had AC-DAVF. Patient age was 59.7 ± 9.5 (mean ± SD) years. Patients presented with intracranial hemorrhage (4 patients), headache (4 patients), amaurosis fugax (1 patients), or were incidentally discovered (2 patients). DAVF Cognard grades were: II (1 patient), III (6 patients), and IV (5 patients). DAVF were embolized with Onyx (10 patients), nBCA glue (1 patient), and a combination of coils and Onyx (1 patient). DAVF cure was achieved in 11 patients (92%). No patients experienced vision loss, death, or permanent disability. One patient experienced a minor complication of blurry vision attributed to posterior ischemic optic neuropathy. 90-day mRS was 0 (10 patients) and 1 (2 patients). CONCLUSIONS: Trans-ophthalmic artery embolization is an effective and safe treatment for DAVF.

Thrombolysis for Evacuation of Intracerebral and Intraventricular Hemorrhage: A Guide to Surgical Protocols With Practical Lessons Learned From the MISTIE and CLEAR Trials.

BACKGROUND: Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) procedure was recently tested in a large phase III randomized trial showing a significant probability of functional benefit in those cases that reached the goal hematoma evacuation of ≤15 mL residual (or ≥70% removal). Benefit of thrombolysis was also identified in cases with large intraventricular hemorrhage, and achieving at least 85% volume reduction in the Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) III trial. OBJECTIVE: To protocolize steps in the MISTIE and CLEAR procedures in order to maximize hematoma evacuation and minimize complications. METHODS: We articulate data-driven lessons and expert opinions surrounding the factors of patient selection, catheter placement, and dosing, which impacted safety and surgical performance in the MISTIE and CLEAR trials. RESULTS: Modifiable factors to maximize evacuation efficiency include optimizing catheter placement and pursuing aggressive dosing to achieve treatment goals, while strictly adhering to the safety steps as articulated in the respective trials. Prognostic factors that are viewed as nonmodifiable include greater initial intracerebral hemorrhage volume with irregular shape, smaller intraventricular bleeds, and the uncommon but consequential development of new bleeding during the dosing period despite strict protocol adherence. CONCLUSIONS: Surgeon education in this tutorial is aimed at maximizing the benefit of the MISTIE and CLEAR procedures by reviewing case selection, safety steps, treatment objectives, and technical nuances. Key lessons include stability imaging, etiology screening, and technical adherence to the protocol in order to achieve defined thresholds of evacuation.