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Open Access Publications from the University of California

Scholarly Works (37 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2015)

Two interventions for the treatment and prevention of ischemic stroke are investigated. Remote ischemic conditioning (RIC) holds significant potential for the prevention of delayed ischemic neurological deficits following aneurysmal subarachnoid hemorrhage (aSAH). Using a matched cohort analysis, lower-limb RIC demonstrated a positive effect on the functional outcomes of patients with aSAH. Differential expression and methylation analysis following RIC in aSAH patients identified genes enriched for cell cycle and inflammatory responses, potential biomarkers for the determination of an effective RIC dose. A reliable, minimally invasive rat model of SAH and vasospasm has been developed, allowing for the study of neuroprotective treatments without the confounding effects of invasive surgery.

Encephaloduroarteriosynangiosis (EDAS) for patients with intracranial atherosclerosis (IAS) also has great potential as a treatment for ischemic stroke. Patients with IAS are particularly susceptible to intraoperative variations in cerebral perfusion. The strict anesthesia protocol established for EDAS procedures was effective in reducing the intraoperative variability of targeted physiological parameters, while achieving established hemodynamic goals. Investigation into the perfusion profile following EDAS in IAS patients demonstrated a shift of the perfusion profile in the surgical site towards an increased probability of arterial components, with decreased postsurgical neurological events. A reliable mouse model of ischemic stroke and EDAS has been developed, allowing for the study of neovascularization following ischemic infarction and for therapies to enhance perfusion.

Differences in brain structure, including white matter, must be considered to achieve a model of ischemic stroke and maximize translational benefits. A minimally invasive endovascular canine model of ischemic stroke was developed, allowing visualization of the cerebrovasculature, and producing infarcts consistent with invasive models. The higher proportion of white matter in canine brain allows for the hyperacute detection of ischemic white matter changes by clinical MR imaging and its correlation to immunohistochemical changes. As early as four hours after insult, imaging shows extraaxonal edema of white fiber tracts, and immunohistochemistry studies demonstrate changes to oligodendroctyes. A direct link between the preclinical model and clinical state, with consideration for the therapeutic interventions of RIC and EDAS, disease state, and outcomes measured will maximize translational success.

    Cover page: Preclinical and Clinical Stroke - A Bidirectional Approach between Insult and Intervention
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2014)
      Cover page: Letter to the Editor: Indirect bypass in nonmoyamoya intracranial arterial stenosis. Author reply.
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2015)
      Stroke is the third leading cause of death in developed nations. Up to 88% of strokes are ischemic in nature. Extracranial carotid artery atherosclerotic disease is the third leading cause of ischemic stroke in the general population and the second most common nontraumatic cause among adults younger than 45 years. This article provides comprehensive, evidence-based recommendations for the management of extracranial atherosclerotic disease, including imaging for screening and diagnosis, medical management, and interventional management.
        Cover page: Management of Extracranial Carotid Artery Disease
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2013)
        Despite recent advances, cerebral vasospasm and delayed cerebral ischemia (DCI) still represent a major cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (aSAH). Although a significant portion of the morbidity and mortality associated with aSAH is related to the initial hemorrhagic ictus, cerebral vasospasm and DCI are still the leading cause of poor outcomes and death in the acute posthemorrhage period, causing long-term disability or death in more than one in five of all patients who have suffered aSAH and initially survived.Management of patients following aSAH includes four major considerations: (1) prediction of patients at highest risk for development of DCI, (2) prophylactic measures to reduce its occurrence, (3) monitoring to detect early signs of cerebral ischemia, and (4) treatments to correct vasospasm and cerebral ischemia once it occurs. The authors review the pertinent literature related to each, including both the current management guidelines supported by the literature as well as novel management strategies that are currently being investigated.
          Cover page: Management of Arterial Vasospasm Following Aneurysmal Subarachnoid Hemorrhage
          • Thesis
          • Peer Reviewed
          UCLA Electronic Theses and Dissertations (2015)

          Object: Encephaloduroarteriosynangiosis (EDAS) is a form of revascularization that has shown promising early results in the treatment of adult patients with moyamoya disease (MMD) and more recently in patients with intracranial atherosclerotic arterial steno-occlusive disease (ICASD). Herein we present the long-term results of a single-center experience with EDAS for adult MMD and ICASD.

          Methods: Patients with ischemic symptoms despite intensive medical therapy were considered for EDAS. All patients undergoing EDAS were included. Clinical data from a retrospective dataset and a prospective cohort were collected, including recurrence of TIA and/or stroke, functional status, and death. Perren revascularization and ASITN collateral grades were recorded from angiograms.

          Results: 107 EDAS were performed in 82 adults, 36 ICASD & 46 MMD. During a median follow-up of 22 months, 2 (2.4%) patients had strokes, only in the ICASD group. The probability of stroke-free survival at 2 years in the ICASD group was 94.3% (95%CI 80-98.6%). There were no strokes in the MMD group. The probability of TIA-free survival at 2 years was 89.4% (95%CI 74.7-96%) in ICASD and 99.7% (95%CI 87.5-99.9%) in MMD. There were no hemorrhages or stroke-related deaths. Angiograms in 85.7% of ICASD and 92% of MMD patients demonstrated Perren grade 3 and improvement in ASITN grade in all cases.

          Conclusions: EDAS is well tolerated in adults with MMD and ICASD and improves collateral circulation to territories at risk. The rates of stroke after EDAS are lower than those reported with other treatments, including intensive medical therapy in patients with ICASD.

            Cover page: EDAS for Adult Intracranial Arterial Steno-Occlusive Disease. Long-Term Single Center Experience With 107 Operations
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2015)
            The authors report the treatment of a rare type of dural arteriovenous fistula of the paracavernous venous plexus. These fistulas can mimic carotid-cavernous fistulas in both imaging characteristics and clinical presentation, but the anatomical differences require differences in management. The authors describe an integrated open surgical and direct endovascular embolization approach and review of the literature pertaining to the anatomy of and treatment options for paracavernous fistulas.
              Cover page: Integrated open surgical and endovascular embolization treatment of a paracavernous venous plexus fistula: case report.
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2005)

              A new angiographic finding in intracranial aneurysms embolized with Matrix coils is described. Two illustrative cases with a well-defined radiolucent separation between the coil mass and the parent artery are presented. To the best of our knowledge, this is the first report in humans of this finding. On the basis of prior histopathologic studies, this finding, which we call the "white-collar sign," may indicate the formation of a thick connective tissue barrier between aneurysm and artery that prevents any further aneurysmal filling.

                Cover page: Angiographic evidence of aneurysm neck healing following endovascular treatment with bioactive coils.
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2015)

                Background

                The objective of this study is to characterize the relationship between ICP and EEG METHODS: Simultaneous ICP and EEG data were obtained from burst-suppressed patients and segmented by EEG bursts. Segments were categorized as increasing/decreasing and peak/valley to investigate relationship between ICP changes and EEG burst duration. A generalized ICP response was obtained by averaging all segments time-aligned at burst onsets. A vasodilatation index (VDI) was derived from the ICP pulse waveform and calculated on a sliding interval to investigate cerebrovascular changes post-burst.

                Results

                Data from two patients contained 309 bursts. 246 ICP segments initially increased, of which 154 peaked. 63 ICP segments decreased, and zero reached a valley. The change in ICP (0.54 ± 0.85 mmHg) was significantly correlated with the burst duration (p < 0.001). Characterization of the ICP segments showed a peak at 8.1 s and a return to baseline at 14.7 s. The VDI for increasing segments was significantly elevated (median 0.56, IQR 0.31, p < 0.001) and correlated with burst duration (p < 0.001).

                Conclusions

                Changes in the ICP and pulse waveform shape after EEG burst suggest that these signals can be related within the context of neurovascular coupling.

                Significance

                Existence of a physiological relationship between ICP and EEG may allow the study of neurovascular coupling in acute brain injury patients.
                  Cover page: Characterization of the Relationship Between Intracranial Pressure and Electroencephalographic Monitoring in Burst-Suppressed Patients
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2014)

                  Background

                  Remote ischemic conditioning (RIC) is a powerful endogenous mechanism whereby a sublethal ischemic stimulus confers a protective benefit against a subsequent severe ischemic insult. RIC has significant potential clinical implications for the prevention of delayed ischemic neurological deficit after aneurysmal subarachnoid hemorrhage (aSAH). Although RIC has been extensively investigated in animal models, it has not been fully evaluated in humans.

                  Objective

                  To assess the feasibility and safety of RIC for aSAH in a phase I clinical trial.

                  Methods

                  Consecutive patients hospitalized for treatment of an aSAH who met the inclusion/exclusion criteria were approached for consent. Enrolled patients received up to 4 RIC sessions on nonconsecutive days. Primary end points were the development of a symptomatic deep venous thrombosis, bruising, or injury to the limb and request to stop by the patient or surrogate. The secondary end points were the development of new neurological deficits or cerebral infarct, demonstrated by brain imaging after enrollment, and neurological deficit and condition at follow-up.

                  Results

                  Twenty patients were enrolled and underwent 76 RIC sessions, 75 of which were completed successfully. One session was discontinued when the patient became confused. No patient developed a deep venous thrombosis or injury to the preconditioned limb. No patient developed delayed ischemic neurological deficit during enrollment. At follow-up, median modified Rankin Scale score was 1 and Glasgow Outcome Scale score was 5.

                  Conclusion

                  The RIC procedure was well tolerated and did not cause any injury. RIC for aSAH warrants investigation in a subsequent pivotal clinical trial.
                    Cover page: Phase I Clinical Trial for the Feasibility and Safety of Remote Ischemic Conditioning for Aneurysmal Subarachnoid Hemorrhage
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2015)
                    The electronic health record (EHR) contains a diverse set of clinical observations that are captured as part of routine care, but the incomplete, inconsistent, and sometimes incorrect nature of clinical data poses significant impediments for its secondary use in retrospective studies or comparative effectiveness research. In this work, we describe an ontology-driven approach for extracting and analyzing data from the patient record in a longitudinal and continuous manner. We demonstrate how the ontology helps enforce consistent data representation, integrates phenotypes generated through analyses of available clinical data sources, and facilitates subsequent studies to identify clinical predictors for an outcome of interest. Development and evaluation of our approach are described in the context of studying factors that influence intracranial aneurysm (ICA) growth and rupture. We report our experiences in capturing information on 78 individuals with a total of 120 aneurysms. Two example applications related to assessing the relationship between aneurysm size, growth, gene expression modules, and rupture are described. Our work highlights the challenges with respect to data quality, workflow, and analysis of data and its implications toward a learning health system paradigm.
                      Cover page: An integrated, ontology-driven approach to constructing observational databases for research
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