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Scholarly Works (69 results)

  • Article
  • Peer Reviewed
UC San Francisco Previously Published Works (2018)

Objective

Although numerous arteriovenous malformation (AVM) grading scales consider eloquence in risk assessment, none differentiate the types of eloquence. The purpose of this study was to determine if eloquence subtype affects clinical outcome.

Methods

This is a retrospective review of a prospectively collected clinical database of brain AVMs treated with microsurgery in the period from 1997 to 2017. The only inclusion criterion for this study was the presence of eloquence as defined by the Spetzler-Martin grading scale. Eloquence was preoperatively categorized by radiologists. Poor outcome was defined as a modified Rankin Scale (mRS) score 3-6, and worsening clinical status was defined as an increase in the mRS score at follow-up. Logistic regression analyses were performed.

Results

Two hundred forty-one patients (49.4% female; average age 33.9 years) with eloquent brain AVMs were included in this review. Of the AVMs (average size 2.7 cm), 54.4% presented with hemorrhage, 46.2% had deep venous drainage, and 17.0% were diffuse. The most common eloquence type was sensorimotor (46.1%), followed by visual (27.0%) and language (22.0%). Treatments included microsurgery alone (32.8%), microsurgery plus embolization (51.9%), microsurgery plus radiosurgery (7.9%), and all three modalities (7.5%). Motor mapping was used in 9% of sensorimotor AVM cases, and awake speech mapping was used in 13.2% of AVMs with language eloquence. Complications occurred in 24 patients (10%). At the last follow-up (average 24 months), 71.4% of the patients were unchanged or improved and 16.6% had a poor outcome. There was no statistically significant difference in the baseline patient and AVM characteristics among the different subtypes of eloquence. In a multivariate analysis, in comparison to visual eloquence, both sensorimotor (OR 7.4, p = 0.004) and language (OR 6.5, p = 0.015) eloquence were associated with poor outcomes. Additionally, older age (OR 1.31, p = 0.016) and larger AVM size (OR 1.37, p = 0.034) were associated with poor outcomes.

Conclusions

Unlike visual eloquence, sensorimotor and language eloquence were associated with worse clinical outcomes after the resection of eloquent AVMs. This nuance in AVM eloquence demands consideration before deciding on microsurgical intervention, especially when numerical grading systems produce a score near the borderline between operative and nonoperative management.
    Cover page: Does eloquence subtype influence outcome following arteriovenous malformation surgery?
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2015)

    Aim

    To evaluate the feasibility of implanting 3D-printed brain aneurysm model in human cadavers and to assess their utility in neurosurgical research, complex case management/planning, and operative training.

    Methods

    Two 3D-printed aneurysm models, basilar apex and middle cerebral artery, were generated and implanted in four cadaveric specimens. The aneurysms were implanted at the same anatomical region as the modeled patient. Pterional and orbitozygomatic approaches were done on each specimen. The aneurysm implant, manipulation capabilities, and surgical clipping were evaluated.

    Results

    The 3D aneurysm models were successfully implanted to the cadaveric specimens' arterial circulation in all cases. The features of the neck in terms of flexibility and its relationship with other arterial branches allowed for the practice of surgical maneuvering characteristic to aneurysm clipping. Furthermore, the relationship of the aneurysm dome with the surrounding structures allowed for better understanding of the aneurysmal local mass effect. Noticeably, all of these observations were done in a realistic environment provided by our customized embalming model for neurosurgical simulation.

    Conclusion

    3D aneurysms models implanted in cadaveric specimens may represent an untapped training method for replicating clip technique; for practicing certain approaches to aneurysms specific to a particular patient; and for improving neurosurgical research.
      Cover page: Implantation of 3D-Printed Patient-Specific Aneurysm Models into Cadaveric Specimens: A New Training Paradigm to Allow for Improvements in Cerebrovascular Surgery and Research.
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2005)

      Background: The primary aim of this study is to demonstrate the feasibility of utilizing doxycycline to suppress matrix metalloproteinase-9 (MMP-9) in brain arteriovenous malformations (AVMs). Methods: Ex-vivo treatment of AVM tissues: Intact AVM tissues were treated with doxycycline for 48 hours. Active and total MMP-9 in the medium were measured. Pilot trial: AVM patients received either doxycycline (100 mg) or placebo twice a day for one week prior to AVM resection. Active and total MMP-9 in BVM tissues were measured. Results: Ex-vivo treatment of AVM tissues: Doxycycline at 10 and 100 mu g/ml significantly decreased MMP-9 levels in AVM tissues ex-vivo (total: control vs 10 vs 100 mu g/ml = 100 +/- 6 vs 60 +/- 16 vs 61 +/- 9%; active: 100 +/- 8 vs 48 +/- 16 vs 59 +/- 10%). Pilot trial: 10 patients received doxycycline, and 4 patients received placebo. There was a trend for both MMP-9 levels to be lower in the doxycycline group than in the placebo group (total: 2.18 +/- 1.94 vs 3.26 +/- 3.58, P = .50; active: 0.48 +/- 0.48 vs 0.95 +/- 1.01 ng/100 mu g protein, P = .25). Conclusions: A clinically relevant concentration of doxycycline decreased MMP-9 in ex-vivo AVM tissues. Furthermore, there was a trend that oral doxycycline for as short as one week resulted in a decrease in MMP-9 in AVM tissues. Further studies are warranted to justify a clinical trial to test effects of doxycycline on MMP-9 expression in AVM tissues.

        Cover page: Suppression of MMP-9 by doxycycline in brain arteriovenous malformations
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2005)

        BACKGROUND: The primary aim of this study is to demonstrate the feasibility of utilizing doxycycline to suppress matrix metalloproteinase-9 (MMP-9) in brain arteriovenous malformations (AVMs). METHODS: Ex-vivo treatment of AVM tissues: Intact AVM tissues were treated with doxycycline for 48 hours. Active and total MMP-9 in the medium were measured. Pilot trial: AVM patients received either doxycycline (100 mg) or placebo twice a day for one week prior to AVM resection. Active and total MMP-9 in BVM tissues were measured. RESULTS: Ex-vivo treatment of AVM tissues: Doxycycline at 10 and 100 microg/ml significantly decreased MMP-9 levels in AVM tissues ex-vivo (total: control vs 10 vs 100 microg/ml = 100 +/- 6 vs 60 +/- 16 vs 61 +/- 9%; active: 100 +/- 8 vs 48 +/- 16 vs 59 +/- 10%). Pilot trial: 10 patients received doxycycline, and 4 patients received placebo. There was a trend for both MMP-9 levels to be lower in the doxycycline group than in the placebo group (total: 2.18 +/- 1.94 vs 3.26 +/- 3.58, P = .50; active: 0.48 +/- 0.48 vs 0.95 +/- 1.01 ng/100 microg protein, P = .25). CONCLUSIONS: A clinically relevant concentration of doxycycline decreased MMP-9 in ex-vivo AVM tissues. Furthermore, there was a trend that oral doxycycline for as short as one week resulted in a decrease in MMP-9 in AVM tissues. Further studies are warranted to justify a clinical trial to test effects of doxycycline on MMP-9 expression in AVM tissues.

          Cover page: Suppression of MMP-9 by doxycycline in brain arteriovenous malformations.
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2012)

          Background and purpose

          Our recently proposed point scoring model includes the widely-used Spetzler-Martin (SM)-5 variables, along with age, unruptured presentation, and diffuse border (SM-Supp). Here we evaluate the SM-Supp model performance compared with SM-5, SM-3, and Toronto prediction models using net reclassification index, which quantifies the correct movement in risk reclassification, and validate the model in an independent data set.

          Methods

          Bad outcome was defined as worsening between preoperative and final postoperative modified Rankin Scale score. Point scores for each model were used as predictors in logistic regression and predictions evaluated using net reclassification index at varying thresholds (10%-30%) and any threshold (continuous net reclassification index >0). Performance was validated in an independent data set (n=117).

          Results

          Net gain in risk reclassification was better using the SM-Supp model over a range of threshold values (net reclassification index=9%-25%) and significantly improved overall predictions for outcomes in the development data set, yielding a continuous net reclassification index of 64% versus SM-5, 67% versus SM-3, and 61% versus Toronto (all P<0.001). In the validation data set, the SM-Supp model again correctly reclassified a greater proportion of patients versus SM-5 (82%), SM-3 (85%), and Toronto models (69%).

          Conclusions

          The SM-Supp model demonstrated better discrimination and risk reclassification than several existing models and should be considered for clinical practice to estimate surgical risk in patients with brain arteriovenous malformation.
            Cover page: Evaluating Performance of the Spetzler-Martin Supplemented Model in Selecting Patients With Brain Arteriovenous Malformation for Surgery
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2015)

            Purpose

            To describe a newly recognized clinical syndrome consisting of ptosis, diplopia, vertical gaze limitation, and abduction weakness that can occur after orbital roof removal during orbito-zygomatic-pterional craniotomy.

            Design

            Case series.

            Participants

            Eight study patients (7 women), 44 to 80 years of age, with neuro-ophthalmic symptoms after pterional craniotomy.

            Methods

            Case description of 8 study patients.

            Main outcome measures

            Presence of ptosis, diplopia, and gaze limitation.

            Results

            Eight patients had neuro-ophthalmic findings after pterional craniotomy for meningioma removal or aneurysm clipping. The cardinal features were ptosis, limited elevation, and hypotropia. Three patients also had limitation of downgaze and 2 patients had limitation of abduction. Imaging showed loss of the fat layers that normally envelop the superior rectus and levator palpebrae superioris. The muscles appeared attached to the defect in the orbital roof. Ptosis and diplopia developed in 2 patients despite Medpor titanium mesh implants. Deficits in all patients showed spontaneous improvement. In 2 patients, a levator advancement was required to repair ptosis. In 3 patients, an inferior rectus recession using an adjustable suture was performed to treat vertical diplopia. Follow-up a mean of 6.5 years later revealed that all patients had a slight residual upgaze deficit, but alignment was orthotropic in primary gaze.

            Conclusions

            After pterional craniotomy, ptosis, diplopia, and vertical gaze limitation can result from tethering of the superior rectus-levator palpebrae superioris complex to the surgical defect in the orbital roof. Lateral rectus function sometimes is compromised by muscle attachment to the lateral orbital osteotomy. This syndrome occurs in approximately 1% of patients after removal of the orbital roof and can be treated, if necessary, by prism glasses or surgery.
              Cover page: Vertical Diplopia and Ptosis from Removal of the Orbital Roof in Pterional Craniotomy
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2014)

              Object

              Management of unruptured arteriovenous malformations (AVMs) is controversial. In the first randomized trial of unruptured AVMs (A Randomized Trial of Unruptured Brain Arteriovenous Malformations [ARUBA]), medically managed patients had a significantly lower risk of death or stroke and had better outcomes. The University of California, San Francisco (UCSF) was one of the participating ARUBA sites. While 473 patients were screened for eligibility, only 4 patients were enrolled in ARUBA. The purpose of this study is to report the treatment and outcomes of all ARUBA-eligible patients at UCSF.

              Methods

              The authors compared the treatment and outcomes of ARUBA-eligible patients using prospectively collected data from the UCSF brain AVM registry. Similar to ARUBA, they compared the rate of stroke or death in observed and treated patients and used the modified Rankin Scale to grade outcomes.

              Results

              Of 74 patients, 61 received an intervention and 13 were observed. Most treated patients had resection with or without preoperative embolization (43 [70.5%] of 61 patients). One of the 13 observed patients died after AVM hemorrhage. Nine of the 61 treated patients had a stroke or died. There was no significant difference in the rate of stroke or death (HR 1.34, 95% CI 0.12-14.53, p = 0.81) or clinical impairment (Fisher's exact test, p > 0.99) between observed and treated patients.

              Conclusions

              The risk of stroke or death and degree of clinical impairment among treated patients was lower than reported in ARUBA. The authors found no significant difference in outcomes between observed and treated ARUBA-eligible patients at UCSF. Results in ARUBA-eligible patients managed outside that trial led to an entirely different conclusion about AVM intervention, due to the primary role of surgery, judicious surgical selection with established outcome predictors, and technical expertise developed at high-volume AVM centers.
                Cover page: Treatment and outcomes of ARUBA-eligible patients with unruptured brain arteriovenous malformations at a single institution.
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2012)

                Background and purpose

                The Val66Met polymorphism of brain-derived neurotrophic factor is associated with decreased brain-derived neurotrophic factor secretion and poor outcome after acute neurological injury. We hypothesized that the Met allele is associated with worsening of functional outcome after brain arteriovenous malformation resection.

                Methods

                Three hundred forty-one surgically treated patients with brain arteriovenous malformation with outcome data were genotyped for Val66Met. Outcome was change in modified Rankin Scale preoperatively versus postoperatively, dichotomized into poor (change >0) or good outcome (change ≤0). Likelihood ratio tests for interactions and logistic regression analysis were performed.

                Results

                A significant interaction (P=0.03) of Val66Met genotype and hemorrhagic presentation existed; thus, ruptured and unruptured patients were considered separately. The Met allele was associated with increased risk of poor outcome among patients presenting unruptured (OR, 2.15; 95% CI, 1.02-4.55; P=0.045) but not ruptured (OR, 0.54; 95% CI, 0.19-1.53; P=0.25), adjusting for covariates.

                Conclusions

                The Val66Met polymorphism is associated with worsened surgical outcome in patients with unruptured brain arteriovenous malformation, a group that currently has no good risk predictors. Further studies replicating these findings are needed.
                  Cover page: Brain-Derived Neurotrophic Factor Val66Met Polymorphism Predicts Worse Functional Outcome After Surgery in Patients With Unruptured Brain Arteriovenous Malformation
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2015)

                  Background

                  Arteriovenous malformation (AVM) patients present in 4 ways relative to hemorrhage: (1) unruptured, without a history or radiographic evidence of old hemorrhage (EOOH); (2) silent hemorrhage, without a bleeding history but with EOOH; (3) ruptured, with acute bleeding but without EOOH; and (4) reruptured, with acute bleeding and EOOH.

                  Objective

                  We hypothesized that characteristics and outcomes in the unrecognized group of silent hemorrhage patients may differ from those of unruptured patients.

                  Methods

                  Two hundred forty-two patients operated-on since 1997 were categorized by hemorrhage status and hemosiderin positivity in this cohort study: unruptured (group 1), silent hemorrhage (group 2), and ruptured/reruptured (group 3/4). Group 3/4 was combined because hemosiderin cannot distinguish acute hemorrhage from older silent hemorrhage.

                  Results

                  Hemosiderin was found in 45% of specimens. Seventy-five patients (31.0%) had unruptured AVMs, 30 (12.4%) had silent hemorrhage, and 137 (56.6%) had ruptured/reruptured AVMs. Deep drainage, posterior fossa location, preoperative modified Rankin Scale (mRS) score, outcome, and macrophage score were different across groups. Only the macrophage score was different between the groups without clinical hemorrhage. Outcomes were better in silent hemorrhage patients than in those with frank rupture (mean mRS scores of 1.2 and 1.7, respectively).

                  Conclusion

                  One-third of patients present with silent AVM hemorrhage. No clinical or anatomic features differentiate these patients from unruptured patients, except the presence of hemosiderin and macrophages. Silent hemorrhage can be diagnosed using magnetic resonance imaging with iron-sensitive imaging. Silent hemorrhage portends an aggressive natural history, and surgery halts progression to rerupture. Good final mRS outcomes and better outcomes than in those with frank rupture support surgery for silent hemorrhage patients, despite the findings of ARUBA.
                    Cover page: Silent arteriovenous malformation hemorrhage and the recognition of "unruptured" arteriovenous malformation patients who benefit from surgical intervention.
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2017)
                    In vivo measurement of blood velocity fields and flow descriptors remains challenging due to image artifacts and limited resolution of current imaging methods; however, in vivo imaging data can be used to inform and validate patient-specific computational fluid dynamics (CFD) models. Image-based CFD can be particularly useful for planning surgical interventions in complicated cases such as fusiform aneurysms of the basilar artery, where it is crucial to alter pathological hemodynamics while preserving flow to the distal vasculature. In this study, patient-specific CFD modeling was conducted for two basilar aneurysm patients considered for surgical treatment. In addition to velocity fields, transport of contrast agent was simulated for the preoperative and postoperative conditions using two approaches. The transport of a virtual contrast passively following the flow streamlines was simulated to predict post-surgical flow regions prone to thrombus deposition. In addition, the transport of a mixture of blood with an iodine-based contrast agent was modeled to compare and verify the CFD results with X-ray angiograms. The CFD-predicted patterns of contrast flow were qualitatively compared to in vivo X-ray angiograms acquired before and after the intervention. The results suggest that the mixture modeling approach, accounting for the flow rates and properties of the contrast injection, is in better agreement with the X-ray angiography data. The virtual contrast modeling assessed the residence time based on flow patterns unaffected by the injection procedure, which makes the virtual contrast modeling approach better suited for prediction of thrombus deposition, which is not limited to the peri-procedural state.
                      Cover page: Computational Fluid Dynamics modeling of contrast transport in basilar aneurysms following flow-altering surgeries.
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