Isoflurane Conditioning Provides Protection against Subarachnoid Hemorrhage Induced Delayed Cerebral Ischemia through NF-kB Inhibition.

Delayed cerebral ischemia (DCI) is the largest treatable cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Nuclear Factor Kappa-light-chain-enhancer of Activated B cells (NF-kB), a transcription factor known to function as a pivotal mediator of inflammation, is upregulated in SAH and is pathologically associated with vasospasm. We previously showed that a brief exposure to isoflurane, an inhalational anesthetic, provided multifaceted protection against DCI after SAH. The aim of our current study is to investigate the role of NF-kB in isoflurane-conditioning-induced neurovascular protection against SAH-induced DCI. Twelve-week-old wild type male mice (C57BL/6) were divided into five groups: sham, SAH, SAH + Pyrrolidine dithiocarbamate (PDTC, a selective NF-kB inhibitor), SAH + isoflurane conditioning, and SAH + PDTC with isoflurane conditioning. Experimental SAH was performed via endovascular perforation. Anesthetic conditioning was performed with isoflurane 2% for 1 h, 1 h after SAH. Three doses of PDTC (100 mg/kg) were injected intraperitoneally. NF-kB and microglial activation and the cellular source of NF-kB after SAH were assessed by immunofluorescence staining. Vasospasm, microvessel thrombosis, and neuroscore were assessed. NF-kB was activated after SAH; it was attenuated by isoflurane conditioning. Microglia was activated and found to be a major source of NF-kB expression after SAH. Isoflurane conditioning attenuated microglial activation and NF-kB expression in microglia after SAH. Isoflurane conditioning and PDTC individually attenuated large artery vasospasm and microvessel thrombosis, leading to improved neurological deficits after SAH. The addition of isoflurane to the PDTC group did not provide any additional DCI protection. These data indicate isoflurane-conditioning-induced DCI protection after SAH is mediated, at least in part, via downregulating the NF-kB pathway.

Complex Morphologic Analysis of Cerebral Aneurysms Through the Novel Use of Fractal Dimension as a Predictor of Rupture Status: A Proof of Concept Study.

BACKGROUND: Aneurysm morphology has been correlated with rupture. Previous reports identified several morphologic indices that predict rupture status, but they measure only specific qualities of the morphology of an aneurysm in a semiquantitative fashion. Fractal analysis is a geometric technique whereby the overall complexity of a shape is quantified through the calculation of a fractal dimension (FD). By progressively altering the scale of measurement of a shape and determining the number of segments required to incorporate the entire shape, a noninteger value for the dimension of the shape is derived. We present a proof-of-concept study to calculate the FD of an aneurysm for a small cohort of patients with aneurysms in 2 specific locations to determine whether FD is associated with aneurysm rupture status. METHODS: Twenty-nine aneurysms of the posterior communicating and middle cerebral arteries were segmented from computed tomography angiograms in 29 patients. FD was calculated using a standard box-counting algorithm extended for use with three-dimensional shapes. Nonsphericity index and undulation index (UI) were used to validate the data against previously reported parameters associated with rupture status. RESULTS: Nineteen ruptured and 10 unruptured aneurysms were analyzed. Through logistic regression analysis, lower FD was found to be significantly associated with rupture status (P = 0.035; odds ratio, 0.64; 95% confidence interval, 0.42-0.97 per FD increment of 0.05). CONCLUSIONS: In this proof-of-concept study, we present a novel approach to quantify the geometric complexity of intracranial aneurysms through FD. These data suggest an association between FD and patient-specific aneurysm rupture status.

Anterior occipital condyle screw placement through the endonasal corridor: proof of concept study with cadaveric analysis.

PURPOSE: Odontoidectomy for ventral compressive pathology may result in O-C1 and/or C1-2 instability. Same-stage endonasal C1-2 spinal fusion has been advocated to eliminate risks associated with separate-stage posterior approaches. While endonasal methods for C1 instrumentation and C1-2 trans-articular stabilization exist, no hypothetical construct for endonasal occipital instrumentation has been validated. We provide an anatomic description of anterior occipital condyle (AOC) screw endonasal placement as proof-of-concept for endonasal craniocervical stabilization. METHODS: Eight adult, injected cadaveric heads were studied for placing 16 AOC screws endonasally. Thin-cut CT was used for registration. After turning a standard inferior U-shaped nasopharyngeal flap endonasally, 4 mm × 22 mm AOC screws were placed with a 0° driver using neuronavigation. Post-placement CT scans were obtained to determine: site-of-entry, measured from the endonasal projection of the medial O-C1 joint; screw angulation in sagittal and axial planes, proximity to critical structures. RESULTS: Average site-of-entry was 6.88 mm lateral and 9.74 mm rostral to the medial O-C1 joint. Average angulation in the sagittal plane was 0.16° inferior to the palatal line. Average angulation in the axial plane was 23.97° lateral to midline. Average minimum screw distances from the jugular bulb and hypoglossal canal were 4.80 mm and 1.55 mm. CONCLUSION: Endonasal placement of AOC screws is feasible using a 0° driver. Our measurements provide useful parameters to guide optimal placement. Given proximity of hypoglossal canal and jugular bulb, neuronavigation is recommended. Biomechanical studies will ultimately be necessary to evaluate the strength of AOC screws with plate-screw constructs utilizing endonasal C1 lateral mass or C1-2 trans-articular screws as inferior fixation points.

Brain Vasculature Color-Labeling Using the Triple-Injection Method in Cadaveric Heads: A Technical Note for Improved Teaching and Research in Neurovascular Anatomy.

BACKGROUND: Color-labeling injections of cadaveric heads have revolutionized education and teaching of neurovascular anatomy. Silicone-based and latex-based coloring techniques are currently used, but limitations exist because of the viscosity of solutions used. OBJECTIVE: To describe a novel "triple-injection method" for cadaveric cranial vasculature and perform qualitative and semiquantitative evaluations of colored solution penetration into the vasculature. METHODS: After catheter preparation, vessel cannulation, and water irrigation of embalmed cadaveric heads, food coloring, gelatin, and silicone solutions were injected in sequential order into bilateral internal carotid and vertebral arteries (red-colored) and internal jugular veins (blue-colored). In total, 6 triple-injected embalmed cadaveric heads and 4 silicone-based "control" embalmed cadaveric heads were prepared. A qualitative analysis was performed to compare the vessel coloring of 6 triple-injected heads with that of 4 "control" heads. A semiquantitative evaluation was completed to appraise sizes of the smallest color-filled vessels. RESULTS: Naked-eye and microscope evaluations of embalmed experimental and control cadaveric heads revealed higher intensity and more distal color-labeling following the "triple-injection method" compared with the silicone-based method in both the intracranial and extracranial vasculature. Microscope assessment of 1-mm-thick coronal slices of triple-injected brains demonstrated color-filling of distal vessels with minimum diameters of 119 µm for triple-injected heads and 773 µm for silicone-based injected heads. CONCLUSION: Our "triple-injection method" showed superior color-filling of small-sized vessels as compared with the silicone-based injection method, resulting in more distal penetration of smaller caliber vessels.

C1 Lateral Mass Screw Placement Through Endonasal Corridor for Purpose of O-C1 Fusion: Morphometric Analysis in Cadaveric Specimens.

BACKGROUND: Odontoidectomy may pose some risks for O-C1 and/or C1-C2 instability, with previous authors reporting techniques for endonasal C1-C2 fusion. However, no technique for endonasal O-C1 fusion currently exists. We sought to describe the feasibility of endonasal anterior C1 (AC1) screw placement for endonasal O-C1 fusion. METHODS: Seven adult cadaveric heads were studied for endonasal placement of 14 C1 screws. Using thin-cut computed tomography (CT)-based "snapshot" neuronavigation assistance, 4 mm x 22 mm screws were placed in the C1 lateral mass using a 0° driver. Post-placement CT scans were obtained to determine site-of-entry measured from C1 anterior tubercle, screw angulation in axial and sagittal planes, and screw proximity to the central canal and foramen transversarium. RESULTS: Average site-of-entry was 16.57 mm lateral, 2.23 mm rostral, and 5.53 mm deep to the anterior-most portion of the C1 ring. Average axial angulation was 19.49° lateral to midline, measured at the C1 level. Average sagittal angulation was 13.22° inferior to the palatal line, measured from the hard palate to the opisthion. Bicortical purchase was achieved in 11 screws (78.6%). Partial breach of the foramen transversarium was observed in 2 screws (14.3%), violation of the O-C1 joint space in 1 (7.1%), and violation of the central canal in 0 (0%). Average minimum screw distances from the unviolated foramen transversaria and central canal were 1.97 mm and 4.04 mm. CONCLUSIONS: Navigation-assisted endonasal placement of AC1 screws is feasible. Additional studies should investigate the biomechanical stability of anterior C1 screw-plating systems, with anterior condylar screws as superior fixation point, compared to traditional posterior O-C1 fusion.

Primary Dural Repair via an Endoscopic Endonasal Corridor: Preliminary Development of a 3D-Printed Model for Training.

Objectives Endonasal suturing is an investigational method for dural repair that has been reported to decrease the incidence of cerebrospinal fluid fistula. This method requires handling of single-shaft instrumentation in the narrow endonasal corridor. In this study, we designed a low-cost, surgical model using three-dimensional (3D) printing technology to simulate dural repair through the endonasal corridor and subsequently assess the utility of the model for surgical training. Methods Using an Ultimaker 2+ printer, a 3D-printed replica of the cranial base and nasal cavity was fitted with tissue allograft to recapitulate the dural layer. Residents, fellows, and attending surgeons were asked to place two sutures using a 0-degree endoscope and single-shaft needle driver. Task completion time was recorded. Participants were asked to fill out a Likert scale questionnaire after the experiment. Results Twenty-six participants were separated into groups based on their prior endoscope experience: novice, intermediate, and expert. Twenty-one (95.5%) residents and fellows rated the model as "excellent" or "good" in enhancing their technical skills with endoscopic instrumentation. Three of four (75%) of attendings felt that the model was "excellent" or "good" in usefulness for training in dural suturing. Novice participants required an average of 11 minutes for task completion, as compared with 8.7 minutes for intermediates and 5.7 minutes for experts. Conclusion The proposed model appears to be highly effective in enhancing the endoscopic skills and recapitulating the task of dural repair. Such a low-cost model may be especially important in enhancing endoscopic facility in countries/regions with limited access to cadaveric specimens.

Case Report of Transgender Patient with Gonadotropic Dysfunction Secondary to Craniopharyngioma: Toward Improving Understanding of Biopsychosocial Dynamics of Gender Identity in Neurosurgical Care.

BACKGROUND: There is a paucity of information in the literature linking possible neuroendocrinologic repercussions of anterior pituitary insufficiency from tumor-associated mass effect with gender identity in transindividuals. The authors present the case of a 26-year-old transgender woman who was found to have a sellar/suprasellar neoplasm after reporting loss of vision in a bitemporal distribution. CASE DESCRIPTION: Magnetic resonance imaging demonstrated a 2.6-cm complex cystic and solid sellar/suprasellar mass, suggestive of craniopharyngioma, intimately associated with the pituitary stalk. Importantly, this radiographic diagnosis was made 2 years following the initiation of gender-affirming hormone therapy (HT). Laboratory testing following radiographic diagnosis demonstrated evidence of diffuse anterior pituitary insufficiency with decreased morning cortisol, free thyroxine, insulin-like growth factor-1, and testosterone. Following optimization with the endocrinology team, the patient was taken to the operating room for expanded endonasal resection of tumor with lumbar drain insertion and nasoseptal flap coverage. Gross total resection was achieved with marked improvement in vision noted following surgery. The patient continued her HT following surgery. CONCLUSIONS: In hindsight, the neuroendocrinologic manifestations of the craniopharyngioma may have influenced distressing pubertal experiences that distanced her from her assigned male sex, as well as the desired effects of feminization HT in this patient, ultimately delaying her presentation to the neurosurgery service and diagnosis of craniopharyngioma. As the first report of the neurosurgical evaluation and treatment of a transgender patient with anterior pituitary insufficiency secondary to craniopharyngioma, this case examines the biopsychosocial interplay between the development of gender identity and the neuroendocrinologic manifestations of craniopharyngioma.

Development and validation of Egyptian developmental screening chart for children from birth up to 30 months.

BACKGROUND: Detecting developmental delay in children is an ongoing world commitment, especially for those below three years. To accurately assess the development of children; a culturally appropriate screening tool must be used. Egypt lacks such tool and multiple studies have shown that western tools are not suitable in other cultures. OBJECTIVES: To develop and validate an easy, rapid, culturally appropriate and applicable screening chart for early detection of developmental delay among Egyptian children from birth up to 30 months and develop a Z-score chart for motor and mental development follow up based on our Egyptian screening chart. METHODS: A cross sectional randomized study was carried out on 1503 Egyptian children of both genders aged from birth up to 30 months assumed to have normal development according to the inclusion and exclusion criteria. They were selected from vaccination centers and well-baby clinics. Developmental milestones from Baroda development screening test (BDST) were applied on them after items were translated and adapted to Egyptian culture. Egyptian children developmental milestones scores were analyzed and carefully prepared in tables and charts. A 97% pass level of developmental achievements represents the threshold below which children are considered delayed. A Z-score chart for motor and mental development follow up was designed by calculating each age group achievement. The developed Egyptian developmental screening chart (EDSC) was validated against Ages and Stages Questionnaires (ASQ-3) as a reference standard in another different sample of 337 children in different age groups. RESULTS: The developed EDSC is represented in a chart format with two curves 50% and 97% pass level. Children considered delayed when the score below 97% pass level. Results revealed a statistically significant difference between EDSC and BDST at 50% and 97% pass levels. A Z-score chart for motor and mental development follow up was designed by calculating each age group achievement. EDSC sensitivity and specificity were calculated 84.38 (95% CI [67.21%-94.72%]) and 98.36 (95% CI [96.22%-99.47%]) respectively with an overall test accuracy 97.03 (95% CI [94.61%-98.57%]) (p ≤ .001). Agreement between EDSC and ASQ-3 was high (kappa score was 0.827) with negative and positive agreement 98.36 and 84.38, respectively. CONCLUSIONS: Extensive revision of the BDST was needed in order to create and validate a more culturally appropriate Egyptian screening chart. This is the first study to create and validate an Egyptian-specific screening tool, to be rapid and easy to use in Egypt for early detection of developmental delay and enabling early intervention practices. A Z-score curve is reliable for follow up motor and mental development by calculating each age group achievement.

Cadmium and iron removal from phosphoric acid using commercial resins for purification purpose.

Three commercial resins bearing sulfonic, amino phosphonic, or phosphonic/sulfonic reactive groups have been tested for the removal of iron and cadmium from phosphoric acid solutions. The sorption properties are compared for different experimental conditions such as sorbent dosage (0.5-2.5 g L-1), phosphoric acid concentration (from bi-component solutions, 0.25-2 M), and metal concentrations (i.e., in the range 0.27-2.7 mmol Cd L-1 and 0.54 mmol Fe L-1) with a special attention paid to the impact of the type of reactive groups held on the resins. The sulfonic-based resin (MTC1600H) is more selective for Cd (against Fe), especially at high phosphoric acid concentration and low sorbent dosage, while MTS9500 (aminophosphonic resin) is more selective for Fe removal (regardless of acid concentration and sorbent dosage). Equilibrium is reached within 2-4 h. The resins can be ranked in terms of cumulative sorption capacities according the series: MTC1600H > MTS9570 > MTS 9500. Sulfuric acid (0.5-1 M) can be efficiently used for the desorption of both iron and cadmium for MTC1600H, while for MTS9570 (phosphonic/sulfonic resin) sulfuric acid correctly desorbs Cd (above 96% at 1 M concentration), contrary to Fe (less than 30%). The aminophosphonic resin shows much poorer efficiency in terms of desorption. The sulfonic resin (i.e., MTC1600H) shows much higher sorption capacity, better selectivity, comparable uptake kinetics (about 2 h equilibrium time), and better metal desorption ability (higher than 98% with 1 M acid concentration, regardless of the type of acid). This conclusion is confirmed by the comparison of removal properties in the treatment of different types of industrial phosphoric acid solutions (crude, and pre-treated H3PO4 solutions). The three resins are inefficient for the treatment of crude phosphoric acid, and activated charcoal pre-treatment (MTC1600H reduced cadmium content by 77%). However, MTC1600H allows removing over 93% of Fe and Cd for H3PO4 pre-treated by TBP solvent extraction, while the others show much lower efficiencies (< 53%).

Comparative efficacy of autologous versus cadaveric saphenous vein grafts in cerebral revascularization surgery.

OBJECTIVE: Cerebral bypasses are performed for the purpose of either flow augmentation for ischemic cerebrovascular disease or flow replacement for vessel sacrifice during complex aneurysm or tumor surgery. Saphenous vein grafts (SVGs) are commonly used interposition grafts. The authors of this study sought to compare the efficacy of autologous versus cadaveric SVGs in a large series of cerebral bypasses using interposition vein grafts with long-term angiographic follow-up. METHODS: All intracranial bypass procedures performed between 2001 and 2018 were reviewed. Demographic, clinical, angiographic, and operative data were recorded and then analyzed according to SVG type. RESULTS: A total of 308 consecutive intracranial bypasses were performed during the study period, 53 (17.2%) of which were bypasses with an interposition SVG (38 autologous, 15 cadaveric). At a median follow-up of 2.2 months (IQR 0.2-29.1), 39 (73.6%) bypasses were patent (26 [68.4%] autologous, 13 [86.7%] cadaveric, p = 0.30). Comparing autologous and cadaveric SVG recipients, there were no statistically significant differences in age (p = 0.50), sex (p > 0.99), history of smoking (p = 0.75), hypertension (p > 0.99), diabetes mellitus (p = 0.13), indication for bypass (p = 0.27), or SVG diameter (p = 0.65). While there were higher intraoperative (autologous, 100.0 ml/min, IQR 84.3-147.5; cadaveric, 80.0 ml/min, IQR 47.3-107.8; p = 0.11) and postoperative (autologous, 142.2 ml/min, IQR 76.8-160.8; cadaveric, 92.0 ml/min, IQR 69.2-132.2; p = 0.42) volumetric flow rates in the autologous SVGs compared to those in the cadaveric SVGs, the difference between the two groups did not reach statistical significance. In addition, the blood flow index, or ratio of postoperative to intraoperative blood flow, for each bypass was similar between the groups (autologous, 1.3, IQR 0.9-1.6; cadaveric, 1.5, IQR 1.0-2.3; p = 0.37). Kaplan-Meier estimates showed no difference in bypass patency rates over time between autologous and cadaveric SVGs (p = 0.58). CONCLUSIONS: Cadaveric SVGs are a reasonable interposition graft option in cerebral revascularization surgery when autologous grafts are not available.

2D parametric contrast time-density analysis for the prediction of complete aneurysm occlusion at six months' post-flow diversion stent.

OBJECTIVE: Indications for the treatment of cerebral aneurysms with flow diversion stents are expanding. The current aneurysm occlusion rate at six months ranges between 60 and 80%. Predictability of complete vs. partial aneurysm occlusion is poorly defined. Here, we evaluate the angiographic contrast time-density as a predictor of aneurysm occlusion rate at six months' post-flow diversion stents. METHODS: Patients with unruptured cerebral aneurysms proximal to the internal carotid artery terminus treated with single flow diversion stents were included. 2D parametric parenchymal blood flow software (Siemens-Healthineers, Forchheim, Germany) was used to calculate contrast time-density within the aneurysm and in the proximal adjacent internal carotid artery. The area under the curve ratio between the two regions of interests was assessed at baseline and after flow diversion stents deployment. The area under the curve ratio between completely vs. partially occluded aneurysms at six months' follow-up was compared. RESULTS: Thirty patients with 31 aneurysms were included. Mean aneurysm diameter was 8 mm (range 2-28 mm). Complete occlusion was obtained in 19 aneurysms. Younger patients (P = 0.006) and smaller aneurysms (P = 0.046) presented higher chance of complete obliteration. Incomplete occlusion of the aneurysm was more likely if the area under the curve contrast time-density ratio showed absolute (P = 0.001) and relative percentage (P = 0.001) decrease after flow diversion stents deployment. Area under ROC curve was 0.85. CONCLUSION: Negative change in the area under the curve ratio indicates less contrast stagnation in the aneurysm and lower chance of occlusion. These data provide a real-time analysis after aneurysm treatment. If validated in larger datasets, this can prompt input to the surgeon to place a second flow diversion stents.

Role of Resistivity Index Analysis in the Prediction of Hemodynamically Significant Venous Sinus Stenosis in Patient With Idiopathic Intracranial Hypertension.

BACKGROUND: The resistivity index (RI) in cerebral venous sinus stenosis (VSS) has not been studied in patients with idiopathic intracranial hypertension (IIH). OBJECTIVE: To evaluate the role of RI measured by quantitative magnetic resonance venogram (QMRV) as a noninvasive tool in the diagnosis of venous hypertension associated with VSS in IIH. METHODS: Retrospective evaluation of 13 consecutive IIH patients who underwent venous sinus stenting at our institution between 2013 and 2018.Patients' demographics, clinical presentation, cerebral mean venous sinus pressure (MVP), and RI both pre- and poststenting were recorded. The baseline RI was also compared to a control group. RESULTS: Among 13 patients of IIH, 11 had unilateral VSS in dominant sinus, whereas 2 had bilateral VSS. RI was significantly higher in IIH patients compared to the control group in the superior sagittal (SSS) and transverse sinuses (TS) (0.21 vs 0.11, P = .01 and 0.22 vs 0.13, P = .03, respectively). The MVP (in mm Hg) decreased significantly after venous sinus stenting in the SSS (41.9 to 22.5, P < .001) and TS (39.4 to 19.5, P < .001), which was also associated with a significant reduction of the RI (0.22 vs 0.17, P < .01 in SSS and 0.23 vs 0.17, P = .03 in TS) poststenting. CONCLUSION: RI calculated using QMRV can serve as a noninvasive tool to aid in the diagnosis of hemodynamically significant VSS. The study had a small sample size, and larger multicenter studies would be required to validate the results further.

The cut flow index revisited: utility of intraoperative blood flow measurements in extracranial-intracranial bypass surgery for ischemic cerebrovascular disease.

OBJECTIVE: In extracranial-intracranial (EC-IC) bypass surgery, the cut flow index (CFI) is the ratio of bypass flow (ml/min) to donor vessel cut flow (ml/min), and a CFI ≥ 0.5 has been shown to correlate with bypass patency. The authors sought to validate this observation in a large cohort of EC-IC bypasses for ischemic cerebrovascular disease with long-term angiographic follow-up. METHODS: All intracranial bypass procedures performed at a single institution between 2003 and 2018 were reviewed. Demographic, clinical, angiographic, and operative data were recorded and analyzed according to bypass patency with univariate and multivariate statistical analyses. RESULTS: A total of 278 consecutive intracranial bypasses were performed during the study period, of which 157 (56.5%) were EC-IC bypasses for ischemic cerebrovascular disease. Intraoperative blood flow measurements were available in 146 patients, and angiographic follow-up was available at a mean of 2.1 ± 2.6 years after bypass. The mean CFI was significantly higher in patients with patent bypasses (0.92 vs 0.64, p = 0.003). The bypass patency rate was 83.1% in cases with a CFI ≥ 0.5 compared with 46.4% in cases with a CFI < 0.5 (p < 0.0001). Adjusting for age, sex, diagnosis, and single versus double anastomosis, the CFI remained a significant predictor of bypass patency (p = 0.001; OR 5.8, 95% CI 2.0-19.0). A low CFI was also associated with early versus late bypass nonpatency (p = 0.008). CONCLUSIONS: A favorable CFI portends long-term EC-IC bypass patency, while a poor CFI predicts eventual bypass nonpatency and can alert surgeons to potential problems with the donor vessel, anastomosis, or recipient bed during surgery.

Motor Cortex Stimulation for Deafferentation Pain.

PURPOSE OF REVIEW: Since the early 1990s, motor cortex stimulation (MCS) has been a unique treatment modality for patients with drug-resistant deafferentation pain. While underpowered studies and case reports have limited definitive, data-driven analysis of MCS in the past, recent research has brought new clarity to the MCS literature and has helped identify appropriate indications for MCS and its long-term efficacy. RECENT FINDINGS: In this review, new research in MCS, repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) are analyzed and compared with historical landmark papers. Currently, MCS is effective in providing relief to 40-64% of patients, with decreasing analgesic effect over time addressed by altering stimulation settings. rTMS and tDCS, two historic, non-invasive stimulation techniques, are providing new alternatives for the treatment of deafferentation pain, with rTMS finding utility in identifying MCS responders. Future advances in electrode arrays, neuro-navigation, and high-definition tDCS hold promise in providing pain relief to growing numbers of patients. Deafferentation pain is severe, disabling, and remains a challenge for patients and providers alike. Over the last several years, the MCS literature has been revitalized with studies and meta-analyses demonstrating MCS effectiveness and providing guidance in identifying responders. At the same time, rTMS and tDCS, two time-honored non-invasive stimulation techniques, are finding new utility in managing deafferentation pain and identifying good MCS candidates. As the number of potential therapies grow, the clinician's role is shifting to personalizing treatment to the unique pain of each patient. With new treatment modalities, this form of personalized medicine is more possible than ever before.

Middle cerebral artery flow velocity increases more in patients with delayed intraparenchymal hemorrhage after Pipeline.

OBJECTIVE: Pipeline Embolization Devices (PED) are commonly used for endovascular treatment of cerebral aneurysms but can be associated with delayed ipsilateral intraparenchymal hemorrhage (DIPH). The role that altered intracranial hemodynamics may play in the pathophysiology of DIPH is poorly understood. We assess middle cerebral artery (MCA) flow velocity changes after PED deployment. MATERIALS AND METHODS: Patients with aneurysms located proximal to the internal carotid artery terminus treated with PED at our institution between 2015 and 2016 were retrospectively reviewed. Patients were included if MCA flow velocities were measured using transcranial Doppler. Bilateral MCA flow velocities, ratio of ipsilateral to contralateral MCA flow velocity, and bilateral MCA pulsatility index before and after PED deployment were assessed. RESULTS: 10 patients of mean age 52 years were included. Two patients had DIPH within 48 hours after PED deployment. We observed that these two patients had a higher increase in ipsilateral MCA mean flow velocity after treatment compared with patients without DIPH (39.5% vs 5.5%). Additionally, before PED deployment, patients with DIPH had a higher ipsilateral MCA pulsatility index (1.55 vs 0.98) and a higher ratio of ipsilateral to contralateral MCA mean flow velocity (1.35 vs 1.04). CONCLUSIONS: After PED, ipsilateral MCA mean flow velocity increases more in patients with DIPH. These flow velocity changes suggest the possible role of altered distal intracranial hemodynamics in DIPH after PED treatment of cerebral aneurysms. Further data are required to confirm this observation.

Validation of cerebral arteriovenous malformation hemodynamics assessed by DSA using quantitative magnetic resonance angiography: preliminary study.

BACKGROUND: The hemodynamic evaluation of cerebral arteriovenous malformations (AVMs) using DSA has not been validated against true flow measurements. OBJECTIVE: To validate AVM hemodynamics assessed by DSA using quantitative magnetic resonance angiography (QMRA). MATERIALS AND METHODS: Patients seen at our institution between 2007 and 2016 with a supratentorial AVM and DSA and QMRA obtained before any treatment were retrospectively reviewed. DSA assessment of AVM flow comprised AVM arterial-to-venous time (A-Vt) and iFlow transit time. A-Vt was defined as the difference between peak contrast intensity in the cavernous internal carotid artery and peak contrast intensity in the draining vein. iFlow transit times were determined using syngo iFlow software. A-Vt and iFlow transit times were correlated with total AVM flow measured using QMRA and AVM angioarchitectural and clinical features. RESULTS: 33 patients (mean age 33 years) were included. Nine patients presented with hemorrhage. Mean AVM volume was 9.8 mL (range 0.3-57.7 mL). Both A-Vt (r=-0.47, p=0.01) and iFlow (r=-0.44, p=0.01) correlated significantly with total AVM flow. iFlow transit time was significantly shorter in patients who presented with seizure but A-Vt and iFlow did not vary with other AVM angioarchitectural features such as venous stenosis or hemorrhagic presentation. CONCLUSIONS: A-Vt and iFlow transit times on DSA correlate with cerebral AVM flow measured using QMRA. Thus, these parameters may be used to indirectly estimate AVM flow before and after embolization during angiography in real time.

Cerebral Aneurysm Size and Distal Intracranial Hemodynamics: An Assessment of Flow and Pulsatility Index Using Quantitative Magnetic Resonance Angiography.

BACKGROUND: The relationship between cerebral aneurysm size and risk of rupture is well documented, but the impact of aneurysms on distal intracranial hemodynamics is unknown. OBJECTIVE: To examine the relationship between aneurysm size and distal intracranial hemodynamics prior to treatment. METHODS: Patients seen at our institution between 2006 and 2015 with cerebral aneurysms within the internal carotid artery (ICA) segments (proximal to ICA terminus) were retrospectively reviewed. Patients were included if the aneurysm was unruptured, and were excluded if a contralateral aneurysm was present. Flows within bilateral ICAs and middle cerebral arteries (MCA) were measured prior to any treatment using quantitative magnetic resonance angiography. Pulsatility index (PI = [systolic - diastolic flow velocity]/mean flow velocity) within each vessel was then calculated. Hemodynamic parameters were analyzed with respect to aneurysm size. RESULTS: Forty-two patients were included. Mean aneurysm size was 13.5 mm (range 2-40 mm). There was a significant correlation between aneurysm size and ipsilateral MCA PI (P = .006; r = 0.441), MCAipsilateral/ICAipsilateral PI ratio (P = .003; r = 0.57), and MCAipsilateral/MCAcontralateral PI ratio (P = .008; r = 0.43). Mean PI in the ipsilateral ICA was 0.38 (range 0.17-0.77) and ipsilateral MCA was 0.31 (range 0.08-0.83), and mean PI in contralateral ICA was 0.35 (range 0.19-0.57) and MCA was 0.30 (range 0.07-0.89). CONCLUSION: Larger aneurysm size correlates with higher ipsilateral MCA PI, demonstrating that aneurysms affect distal intracranial hemodynamics.

Contrast Time-Density Time on Digital Subtraction Angiography Correlates With Cerebral Arteriovenous Malformation Flow Measured by Quantitative Magnetic Resonance Angiography, Angioarchitecture, and Hemorrhage.

BACKGROUND: Digital subtraction angiography (DSA) currently provides angioarchitectural features of cerebral arteriovenous malformations (AVMs) but its role in the hemodynamic evaluation of AVMs is poorly understood. OBJECTIVE: To assess contrast time-density time (TT) on DSA relative to AVM flow measured using quantitative magnetic resonance angiography (QMRA). METHODS: Patients seen at our institution between 2007 and 2014 with a supratentorial AVM and DSA and QMRA obtained prior to any treatment were retrospectively reviewed. Regions of interest were selected on the draining veins at the point closest to the nidus. TT on DSA was defined as time needed for contrast to change image intensity from 10% to 100%, 100% to 10%, and 25% to 25%. TT was correlated to AVM total flow, angioarchitectural features, and hemorrhage. RESULTS: Twenty-eight patients (mean age 35.6 yr) were included. Six patients presented with hemorrhage. Mean AVM volume was 11.42 mL (range 0.3-57.7 mL). Higher total AVM flow significantly correlated with shorter TT100%-10% and TT25%-25% (P = .02, .02, respectively). Presence of venous stenosis correlated significantly with shorter TT100%-10% (P = .04) and TT25%-25% (P = .04). AVMs with a single draining vein exhibited longer TT25%-25% compared to those with multiple draining veins (P = .04). Ruptured AVMs had significantly shorter TT10%-100% compared to unruptured AVMs (P = .05). CONCLUSION: TT on DSA correlates with cerebral AVM flow measured using QMRA and with AVM angioarchitecture and hemorrhagic presentation. Thus, TT may be used to indirectly estimate AVM flow during angiography in real-time and may also be an indicator of important AVM characteristics associated with outflow resistance and increased rupture risk, such as venous stenosis.

Thresholds for Volume and Expansion in Intraparenchymal Hemorrhage: Predictors of Neurologic Deterioration and Mortality.

OBJECTIVE: Spontaneous intraparenchymal hemorrhage (IPH) is a common neurosurgical emergency, with hemorrhage size and expansion associated with poor clinical outcomes. In this study, radiologic risk factors and specific IPH volume thresholds were calculated to identify heightened risk of neurologic deterioration and mortality. METHODS: A consecutive review of all patients with nontraumatic IPH transferred to a tertiary academic neurosurgery service was performed over 2 years. IPH volume, hemorrhage location, presence of intraventricular hemorrhage, hydrocephalus, anticoagulant use, and neurologic status were reviewed. A maximum Youden index was calculated to determine thresholds of initial IPH volume and expansion most predictive of deterioration and mortality. RESULTS: A total of 202 transfers were studied. Both initial IPH volume at the outside hospital and IPH expansion were correlated with neurologic deterioration and death. The most predictive threshold for mortality was 32 mL of initial IPH volume (area under the curve 0.758, P < 0.001, confidence interval 1.012-1.035) and 1 mL of expansion. The threshold for neurologic deterioration was 18 mL of initial volume (area under the curve 0.690, P = 0.004, confidence interval 1.004-1.025) and 1 mL of expansion. Both intraventricular hemorrhage and hydrocephalus were independently associated with elevated risk for deterioration and mortality, while anticoagulant use was associated with neurologic deterioration. CONCLUSIONS: Volume and growth of IPH are significant predictors of neurologic deterioration and death. An initial volume over 32 mL is associated with increased mortality risk, whereas risk of neurologic deterioration appears to peak at a smaller volume of 18 mL. Any measurable IPH expansion suggests elevated risk of deterioration and mortality.

Transorbital Glue Embolization of a Recurrent Venous Varix Using Real-Time Image Guidance in the Neuroangiography Suite.

Orbital lesions are challenging to access due to their location amid critical anatomic structures. Here, we demonstrate direct transorbital cannulation of an orbital venous varix using image guidance. A 36-year-old male was diagnosed with a left orbital venous varix approximately 5 years ago at an outside institution. He subsequently underwent surgery for direct intraoperative embolization of the venous varix followed by surgical resection. The patient recently presented to us with left eye pain, proptosis, double vision, and conjunctival hemorrhage precipitated by straining or lying flat. Orbital magnetic resonance imaging showed recurrence of the venous varix, which was then confirmed with digital subtraction angiography and intraprocedural computed tomography (DynaCT, Siemens Healthineers, Erlangen, Germany). Due to scarring from the previous surgery, percutaneous transorbital embolization of the venous varix was planned. The needle trajectory was determined and also visualized in real-time using image guidance (Needle Guidance, Siemens Healthineers). Once the needle reached the desired target, n-butyl cyanoacrylate glue (Codman Neuro, San Jose, California) was injected until nearly the entire venous varix was occluded. There were no complications, and at his postoperative visit the patient reported resolution of all symptoms.