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Abstract BACKGROUND: Early and mid-term safety and efficacy of aneurysm treatment with the Pipeline Embolization Device (PED) has been well demonstrated in prior studies. OBJECTIVE: To present 5-yr follow-up for patients treated in the Pipeline for Uncoilable or Failed Aneurysms clinical trial. METHODS: In our prospective, multicenter trial, 109 complex internal carotid artery (ICA) aneurysms in 107 subjects were treated with the PED. Patients were followed per a standardized protocol at 180 d and 1, 3, and 5 yr. Aneurysm occlusion, in-stent stenosis, modified Rankin Scale scores, and complications were recorded. RESULTS: The primary endpoint of complete aneurysm occlusion at 180 d (73.6%) was previously reported. Aneurysm occlusion for those patients with angiographic follow-up progressively increased over time to 86.8% (79/91), 93.4% (71/76), and 95.2% (60/63) at 1, 3, and 5 yr, respectively. Six aneurysms (5.7%) were retreated. New serious device-related events at 1, 3, and 5 yr were noted in 1% (1/96), 3.5% (3/85), and 0% (0/81) of subjects. There were 4 (3.7%) reported deaths in our trial. Seventy-eight (96.3%) of 81 patients with 5-yr clinical follow-up had modified Rankin Scale scores ≤2. No delayed neurological deaths or hemorrhagic or ischemic cerebrovascular events were reported beyond 6 mo. No recanalization of a previously occluded aneurysm was observed. CONCLUSION: Our 5-yr findings demonstrate that PED is a safe and effective treatment for large and giant wide-necked aneurysms of the intracranial ICA, with high rates of complete occlusion and low rates of delayed adverse events.

Hydrocephalus is a common disorder caused by the buildup of cerebrospinal fluid (CSF) in the brain. Treatment typically involves the surgical implantation of a pressure-regulated silicone tube assembly, known as a shunt. Unfortunately, shunts have extremely high failure rates and diagnosing shunt malfunction is challenging due to a combination of vague symptoms and a lack of a convenient means to monitor flow. Here, we introduce a wireless, wearable device that enables precise measurements of CSF flow, continuously or intermittently, in hospitals, laboratories or even in home settings. The technology exploits measurements of thermal transport through near-surface layers of skin to assess flow, with a soft, flexible, and skin-conformal device that can be constructed using commercially available components. Systematic benchtop studies and numerical simulations highlight all of the key considerations. Measurements on 7 patients establish high levels of functionality, with data that reveal time dependent changes in flow associated with positional and inertial effects on the body. Taken together, the results suggest a significant advance in monitoring capabilities for patients with shunted hydrocephalus, with potential for practical use across a range of settings and circumstances, and additional utility for research purposes in studies of CSF hydrodynamics.

Abstract BACKGROUND: Mixed lineage leukemia-1 (Mll1) epigenetically regulates gene expression patterns that specify cellular identity in both embryonic development and adult stem cell populations. In the adult mouse brain, multipotent neural stem cells (NSCs) in the subventricular zone generate new neurons throughout life, and Mll1 is required for this postnatal neurogenesis but not for glial cell differentiation. Analysis of Mll1-dependent transcription may identify neurogenic genes useful for the direct reprogramming of astrocytes into neurons. OBJECTIVE: To identify Mll1-dependent transcriptional modules and to determine whether genes in the neurogenic modules can be used to directly reprogram astrocytes into neurons. METHODS: We performed gene coexpression module analysis on microarray data from differentiating wild-type and Mll1-deleted subventricular zone NSCs. Key developmental regulators belonging to the neurogenic modules were overexpressed in Mll1-deleted cells and cultured cortical astrocytes, and cell phenotypes were analyzed by immunocytochemistry and electrophysiology. RESULTS: Transcriptional modules that correspond to neurogenesis were identified in wild-type NSCs. Modules related to astrocytes and oligodendrocytes were enriched in Mll1-deleted NSCs, consistent with their gliogenic potential. Overexpression of genes selected from the neurogenic modules enhanced the production of neurons from Mll1-deleted cells, and overexpression of Brn4 (Pou3f4) in nonneurogenic cortical astroglia induced their transdifferentiation into electrophysiologically active neurons. CONCLUSION: Our results demonstrate that Mll1 is required for the expression of neurogenic but not gliogenic transcriptional modules in a multipotent NSC population and further indicate that specific Mll1-dependent genes may be useful for direct reprogramming strategies.

Background: Traumatic vertebral artery dissections (tVADs) occur in up to 20% of patients with head trauma, yet data on their presentation and associated sequelae are limited. Aims and Objectives: To characterize the tVAD population and identify factors associated with clinical outcomes. Materials and Methods: We retrospectively analyzed all cases of tVAD at our institution from January 2004 to December 2018 with respect to mechanism of injury, clinical presentation, anatomic factors, associated pathologies, and relevant outcomes. Results: Of the 123 patients with tVAD, the most common presenting symptoms were neck pain (n=76, 67.3%), headache (57.5%), and visual changes (29.6%). 101 cases (82.1%) were unilateral, and 22 cases (17.9%) were bilateral. V2 was the most involved anatomic segment (83 cases, 70.3). 30 cases (25.4%) led to stroke, and 39 cases (31.7%) had a concomitant cervical fracture. The anatomic segment and number of segments involved, and baseline clinical and demographic characteristics were not associated with risk of stroke. Patients with associated fractures were older (50.3 years v. 36.4 years, p=0.0233), had a higher comorbid disease burden (CCI 1 vs. CCI 1, p<0.0007), were more likely to smoke (OR 3.0 [1.2178, 7.4028], p=0.0202), be male (OR 7.125 [3.0181, 16.8236], p<0.0001), and have mRS≥3 at discharge (OR 3.0545 [1.0937, 8.5752], p=0.0449). On multivariable regression, only fracture independently predicted mRS≥3 at discharge (OR 5.6898 [1.5067, 21.4876], p=0.010). Conclusion: tVADs may be associated with stroke and/or cervical fracture. Presenting symptoms predict stroke, but baseline demographic and clinical characteristics do not. Comorbid cervical fractures, not stroke, drive negative outcomes

The surgical management of Cushing’s disease is often complicated by difficulties detecting corticotropic adenomas. Various diagnostic modalities are used when conventional magnetic resonance imaging (MRI) is negative or inconclusive. We sought to analyze our use of two such modalities in the surgical management of Cushing’s disease: (1) cavernous/inferior petrosal sinus sampling (central venous sampling, CVS) for adrenocorticotropic hormone and (2) dynamic MRI (dMRI). We conducted a single-center, retrospective review of all patients with Cushing’s disease treated by a single neurosurgeon with endonasal transsphenoidal surgery. Accuracy of adenoma localization with CVS and dMRI was analyzed. Ninety-one consecutive patients were included. Pathology confirmed an adenoma in 66. Preoperative dMRI and CVS were performed in 40 and 37 patients, respectively, with 20 undergoing both studies. Surgical pathology was positive for adenoma in 31 dMRI patients, 25 CVS patients, and 13 who underwent both. Among patients with pathology confirming an adenoma, dMRI identified a lesion in 96.8 % and correctly lateralized the lesion in 89.7 %, while CVS correctly lateralized in 52.2–65.2 % (depending on location of sampling). Among patients with both studies, dMRI and CVS correctly lateralized in 76.9 and 61.5–69.2 %, respectively. Accuracy of CVS improved if only patients with symmetric venous drainage were considered. In this mixed population of Cushing’s disease patients, dMRI was more accurate than CVS at localizing adenomas, supporting the use of advance MRI techniques in the work-up of Cushing’s disease. CVS, however, remains an important tool in the workup of Cushing’s syndrome.

BACKGROUND:Arteriovenous malformations (AVMs) in the basal ganglia, thalamus, and insula are considered inoperable given their depth, eloquence, and limited surgical exposure. Although many neurosurgeons opt for radiosurgery or observation, others have challenged the belief that deep AVMs are inoperable. Further discussion of patient selection, technique, and multimodality management is needed. OBJECTIVE:To describe and discuss the technical considerations of microsurgical resection for deep-seated AVMs. METHODS:Patients with deep AVMs who underwent surgery during a 14-year period were reviewed through the use of a prospective AVM registry. RESULTS:Microsurgery was performed in 48 patients with AVMs in the basal ganglia (n = 10), thalamus (n = 13), or insula (n = 25). The most common Spetzler-Martin grade was III− (68%). Surgical approaches included transsylvian (67%), transcallosal (19%), and transcortical (15%). Complete resection was achieved in 34 patients (71%), and patients with incomplete resection were treated with radiosurgery. Forty-five patients (94%) were improved or unchanged (mean follow-up, 1.6 years). CONCLUSION:This experience advances the notion that select deep AVMs may be operable lesions. Patients were highly selected for small size, hemorrhagic presentation, young age, and compactness—factors embodied in the Spetzler-Martin and Supplementary grading systems. Overall, 10 different approaches were used, exploiting direct, transcortical corridors created by hemorrhage or maximizing anatomic corridors through subarachnoid spaces and ventricles that minimize brain transgression. The same cautious attitude exercised in selecting patients for surgery was also exercised in deciding extent of resection, opting for incomplete resection and radiosurgery more than with other AVMs to prioritize neurological outcomes. ABBREVIATIONS:AVM, arteriovenous malformationMCA, middle cerebral arteryRS, Rankin Scale

Middle meningeal artery embolization (MMAE) is a treatment strategy increasingly used in the management of chronic subdural hematoma (CSDH). While frequently performed for the treatment of bilateral chronic subdural hematoma (bCSDH), outcomes of bilateral MMAE (bMMAE) have not often been independently reported in the literature. In this study, we document the outcomes and utility of bMMAE for the treatment of bCSDH at our institution. This is a retrospective cohort study of patients who underwent bMMAE at our institution between 2018 and 2024. Demographic, clinical, and outcome variables were compared using standard statistical approaches between reoperation and non-reoperation groups, and resolution and non-resolution groups. Twenty-eight patients underwent bMMAE for the treatment of CSDH. The median age was 75 years. Median radiographic follow-up was 8.0 months. At the time of last-follow-up, radiographic bilateral CSDH resolution was observed in 5 patients (17.9 %) and 10 patients (35.7 %) continued to have symptoms at last follow-up. Reoperation occurred in 5 patients (17.9 %). On univariate comparison between reoperation and non-reoperation cases, patients in the reoperation cohort were more likely to have persistent symptoms at last follow-up (80.0 % versus 26.1 %, p = 0.0410) and had a larger median pre-operative thickness (19.0 versus 13.0, p = 0.0498). There were no significant differences in outcome variables between resolution and non-resolution cases of bMMAE. bMMAE is a promising technique for the management of bCSDH with and without concomitant surgical evacuation. Further work is required for proper patient identification for bCSDH treatment options. •Bilateral MMA embolization for bilateral chronic subdural hematoma treatment.•Bilateral MMA embolization comparable to surgical evacuation outcomes.•Low risk of morbidity/mortality as for bilateral MMA embolization.•Bilateral MMAE patients requiring reoperation have more persistent symptoms.

ObjectiveDifferent technical and procedural methods have been introduced to develop low radiation dose protocols in neurointerventional examinations. We investigated the feasibility of minimizing radiation exposure dose by simply decreasing the detector dose during cerebral DSA and evaluated the comparative level of image quality using both subjective and objective methods.MethodsIn a prospective study of patients undergoing diagnostic cerebral DSA, randomly selected vertebral arteries (VA) and/or internal carotid arteries and their contralateral equivalent arteries were injected. Detector dose of 3.6 and 1.2 μGy/frame were selected to acquire standard dose (SD) and low dose (LD) images, respectively. Subjective image quality assessment was performed by two neurointerventionalists using a 5 point scale. For objective image quality evaluation, circle of Willis vessels were categorized into conducting, primary, secondary, and side branch vessels. Two blinded observers performed arterial diameter measurements in each category. Only image series obtained from VA injections opacifying the identical posterior intracranial circulation were utilized for objective assessment.ResultsNo significant difference between SD and LD images was observed in subjective and objective image quality assessment in 22 image series obtained from 10 patients. Mean reference air kerma and kerma area product were significantly reduced by 61.28% and 61.24% in the LD protocol, respectively.ConclusionsOur study highlights the necessity for reconsidering radiation dose protocols in neurointerventional procedures, especially at the level of baseline factory settings.

Stereotactic radiosurgery (SRS) to a surgical cavity after brain metastasis resection is a promising treatment for improving local control. The optimal timing of adjuvant SRS, however, has yet to be determined. Changes in resection cavity volume and local progression in the interval between surgery and SRS are likely important factors in deciding when to proceed with adjuvant SRS. We conducted a retrospective review of patients with a brain metastasis treated with surgical resection followed by SRS to the resection cavity. Post-operative and pre-radiosurgery magnetic resonance imaging (MRI) was reviewed for evidence of cavity volume changes, amount of edema, and local tumor progression. Resection cavity volume and edema volume were measured using volumetric analysis. We identified 21 consecutive patients with a brain metastasis treated with surgical resection and radiosurgery to the resection cavity. Mean age was 57 yrs. The most common site of metastasis was the frontal lobe (38%), and the most common primary neoplasms were lung adenocarcinoma and melanoma (24% each). The mean postoperative resection cavity volume was 7.8 cm(3) and shrank to a mean of 4.5 cm(3) at the time of repeat imaging for radiosurgical planning (median 41 days after initial post-operative MRI), resulting in a mean reduction in cavity volume of 43%. Patients who underwent pre-SRS imaging within 1 month of their initial post-operative MRI had a mean volume reduction of 13% compared to 61% in those whose pre-SRS imaging was ≥1 month (p=0.0003). Post-resection edema volume was not related to volume reduction (p=0.59). During the interval between MRIs, 52% of patients showed evidence of tumor progression within the resection cavity wall. There was no significant difference in local recurrence if the interval between resection and radiosurgery was <1 month (n=8) versus ≥1 month (n=13, p=0.46). These data suggest that the surgical cavity after brain metastasis resection constricts over time with greater constriction seen in patients whose pre-SRS imaging is ≥1 month after initial post-operative imaging. Given that there was no difference in local recurrence rate, the data suggest there is benefit in waiting in order to treat a smaller resection cavity.

BackgroundAdmission neutrophil-lymphocyte ratio (NLR) is significantly correlated to clinical outcomes in acute ischemic stroke (AIS). We investigated follow-up NLR and temporal changes in NLR after endovascular thrombectomy (EVT) with respect to successful revascularization, clinical outcomes, symptomatic intracranial hemorrhage (sICH) and mortality.MethodsRetrospective analysis of EVT for anterior circulation emergent LVO was performed with both admission (NLR1) and 3–7 day follow-up NLR (NLR2) laboratory data. Patient demographics, National Institutes of Health Stroke Scale (NIHSS) presentations, reperfusion efficacy (modified Thrombolysis in Cerebral Infarction (mTICI) score), sICH, and clinical outcomes (modified Rankin Scale (mRS)) at 90 days were studied. Univariate analyses correlated NLR1, NLR2, and temporal change in NLR (NLR2-NLR1) with successful reperfusion (mTICI ≥2b), favorable outcomes (mRS ≤2), sICH, and mortality. Multivariable logistic regression model evaluated the independent effects of NLR2 on favorable outcomes.Results142 AIS patients with median NIHSS 17 underwent EVT within 24 hours, and met NLR laboratory inclusion criteria. Lower follow-up NLR2 and less temporal change in NLR over 3–7 days, but not admission NLR1, inversely correlated with successful reperfusion (p<0.05) and favorable clinical outcomes (p<0.001). Higher follow-up NLR2 and greater temporal change in NLR was significantly associated with sICH and mortality (p≤0.05). In multivariable logistic regression, lower follow-up NLR2 remained a predictor of favorable outcomes (OR 0.785, p=0.001), independent of age or successful reperfusion.ConclusionsFollow-up NLR is a readily available and modifiable biomarker that correlates with the degree of reperfusion after mechanical stroke thrombectomy. Lower follow-up NLR2 at 3–7 days is associated with successful reperfusion and an independent predictor of favorable clinical outcomes, with reduced risk for sICH and mortality.