Publications by authors named "Kunal Agrawal"

20 Publications

  • Page 1 of 1

Transcranial Doppler to evaluate postreperfusion therapy following acute ischemic stroke: A literature review.

J Neuroimaging 2021 Jun 15. Epub 2021 Jun 15.

UCSD Comprehensive Stroke Center, Department of Neurosciences, University of California San Diego, San Diego, California, USA.

Cerebral vessel recanalization therapy, either intravenous thrombolysis or mechanical thrombectomy, is the main treatment that can significantly improve clinical outcomes after acute ischemic stroke. The degree of recanalization and cerebral reperfusion of the ischemic penumbra are dependent on cerebral hemodynamics. Currently, the main imaging modalities to assess reperfusion are MRI and CT perfusion. However, these imaging techniques cannot predict reperfusion-associated complications and are not readily available in many centers. It is also not feasible to repeat them frequently for sequential assessments, which is important because of the changing nature of cerebral hemodynamics following stroke. Transcranial Doppler sonography (TCD) is a valid, safe, and inexpensive technique that can assess recanalized vessels and reperfused tissue in real-time at the bedside. Post thrombectomy reocclusion, hyperperfusion syndrome, distal embolization, and remote infarction result in poor outcomes after mechanical or intravenous reperfusion therapy. Managing blood pressure following these endovascular treatments can also be a dilemma. TCD has an important role, with major clinical implications, in evaluating cerebral hemodynamics and collateral vessel status, guiding clinicians in making individualized decisions based on cerebral blood flow during acute stroke care. This review summarizes the most relevant literature on the role of TCD in evaluating patients after reperfusion therapy. We also discuss the importance of performing TCD in the first few hours following thrombolytic therapy in identifying hyperperfusion syndrome and embolic signals, predicting recurrent stroke, and detecting reocclusions, all of which may help improve patient prognosis. We recommend TCD during the hyperacute phase of stroke in comprehensive stroke centers.
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http://dx.doi.org/10.1111/jon.12887DOI Listing
June 2021

Intense Arm Rehabilitation Therapy Improves the Modified Rankin Scale Score: Association Between Gains in Impairment and Function.

Neurology 2021 04 15;96(14):e1812-e1822. Epub 2021 Feb 15.

From the Department of Neurology (S.C.C., J.L.S.), University of California, Los Angeles; California Rehabilitation Institute (S.C.C.), Los Angeles; Department of Neurology (S.C.C., V.L., L.D., J. See, R.A., A.M., R.J.Z., N.L.C., J.M.C.), Department of Psychological Science (J.H.), Institute for Software Research (W.S.), and Department of Statistics (M.T.S.), University of California, Irvine; Department of Physical Therapy (A.M.), Chapman University, Irvine, CA; Department of Allied Health Sciences (J.M.C.), University of North Carolina at Chapel Hill; Department of Stroke Rehabilitation Research (A.M.B.), Kessler Foundation; Department of Stroke Rehabilitation (A.M.B.), Kessler Institute for Rehabilitation, West Orange, NJ; Department of Physical Medicine and Rehabilitation (J.K.), MetroHealth System, Case Western Reserve University, Cleveland, OH; Brain Stimulation and Robotics Laboratory (D.E.), Burke Neurological Institute; Department of Telemedicine and Virtual Rehabilitation (D.P.), Burke Medical Research Institute, White Plains, NY; Abilities Research Center (D.P.), Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Clinical Neurosciences (K.A.), University of California, San Diego, La Jolla; Brooks Rehabilitation Clinical Research Center (K.N.), Brooks Rehabilitation, Jacksonville, FL; Department of Physical Medicine and Rehabilitation (E.J.R.), Northwestern University, Chicago, IL; Department of Neurology (D.L.T.), University of Washington, Seattle; Departments of Health Science and Research (M.L.W.) and Public Health Sciences (W.Z.), Medical University of South Carolina, Charleston; Department of Physical Medicine and Rehabilitation (R.Z.), Spaulding Rehabilitation Hospital, Massachusetts General Hospital, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Department of Neurology (J. Spilker, J.P.B.), University of Cincinnati, OH; Department of Rehabilitation Medicine (S.L.W.), Division of Physical Therapy Education, Emory University, Atlanta, GA; Atlanta VA Health Care System (S.L.W.), Center for Visual and Neurocognitive Rehabilitation, Decatur, GA; and NINDS (S.J.), NIH, Bethesda, MD.

Objective: To evaluate the effect of intensive rehabilitation on the modified Rankin Scale (mRS), a measure of activities limitation commonly used in acute stroke studies, and to define the specific changes in body structure/function (motor impairment) most related to mRS gains.

Methods: Patients were enrolled >90 days poststroke. Each was evaluated before and 30 days after a 6-week course of daily rehabilitation targeting the arm. Activity gains, measured using the mRS, were examined and compared to body structure/function gains, measured using the Fugl-Meyer (FM) motor scale. Additional analyses examined whether activity gains were more strongly related to specific body structure/function gains.

Results: At baseline (160 ± 48 days poststroke), patients (n = 77) had median mRS score of 3 (interquartile range, 2-3), decreasing to 2 [2-3] 30 days posttherapy ( < 0.0001). Similarly, the proportion of patients with mRS score ≤2 increased from 46.8% at baseline to 66.2% at 30 days posttherapy ( = 0.015). These findings were accounted for by the mRS score decreasing in 24 (31.2%) patients. Patients with a treatment-related mRS score improvement, compared to those without, had similar overall motor gains (change in total FM score, = 0.63). In exploratory analysis, improvement in several specific motor impairments, such as finger flexion and wrist circumduction, was significantly associated with higher likelihood of mRS decrease.

Conclusions: Intensive arm motor therapy is associated with improved mRS in a substantial fraction (31.2%) of patients. Exploratory analysis suggests specific motor impairments that might underlie this finding and may be optimal targets for rehabilitation therapies that aim to reduce activities limitations.

Clinical Trial: Clinicaltrials.gov identifier: NCT02360488.

Classification Of Evidence: This study provides Class III evidence that for patients >90 days poststroke with persistent arm motor deficits, intensive arm motor therapy improved mRS in a substantial fraction (31.2%) of patients.
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http://dx.doi.org/10.1212/WNL.0000000000011667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105969PMC
April 2021

Cost-Effectiveness of Using LDL-Direct Versus Lipid-Panel as Part of the Inpatient Stroke Workup.

J Stroke Cerebrovasc Dis 2021 Feb 8;30(2):105417. Epub 2020 Dec 8.

UC San Diego Hospital, 200 West Arbor Dr., San Diego, CA 92103, United States; Stroke Center - University of California, San Diego, United States.

Objective: To investigate whether utilizing a LDL-direct laboratory test rather than a lipid panel to determine LDL-C as part of the inpatient stroke and TIA workup is more cost-effective to the patient and hospital system. A retrospective analysis was conducted on all patients admitted to UCSD La Jolla and Hillcrest Hospital and discharged with a final diagnosis of ischemic stroke or transient ischemic attack between 7/2016 and 6/2019. A cost-analysis was extrapolated based on the current cost of each test as provided by the UCSD hospital billing department as of June 2020. Patients started on a statin, who were not on one prior to admission, were also analyzed to highlight the importance of an accurate LDL-C on management of dyslipidemia.

Results: A total of 1245 patients were included in the study with 87% representing Ischemic strokes and 13% transient ischemic attacks. Over the three-year period, a total savings of $77,545 would be achieved if LDL-direct were used in place of a lipid-panel, representing an overall cost savings of 33%. Over the same time-frame, 536 (43%) patients were started on a statin that were not previously on one.

Conclusions: Ordering a LDL-direct test should be considered over a lipid panel to evaluate LDL-C as it may prove to be the most cost effective approach to both the patient and Healthcare system.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105417DOI Listing
February 2021

Moyamoya Presenting after Whole Body Cryotherapy.

Acta Neurol Taiwan 2020 Jun;29(2):64-66

University of California, San Diego, Department of Neurosciences, Stroke Center.

Background Purpose: Moyamoya syndrome is the progressive stenosis of intracranial carotids with secondary collateralization. Whole body cryotherapy (WBC) involves external cooling and is used in holistic and sports medicine, its neurologic effects are unknown.

Case Report: We report a first case of symptoms of moyamoya syndrome presenting following WBC and diagnosed with classic MRI ( "Brush Sign", "Ivy sign") and digital subtracted angiography.

Conclusion: WBC may provoke symptoms of moyamoya syndrome possibly through hyperventilation or vasoconstriction. Practitioners should be aware of possible consequences of WBC in patients with poor cerebrovascular reserve.
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June 2020

A Stroke Care Model at an Academic, Comprehensive Stroke Center During the 2020 COVID-19 Pandemic.

J Stroke Cerebrovasc Dis 2020 Aug 8;29(8):104927. Epub 2020 May 8.

Department of Neurosciences, University of California San Diego, 200 W. Arbor Drive, San Diego, CA 619-543-7760, United States.

Background And Purpose: The COVID-19 pandemic has required the adaptation of hyperacute stroke care (including stroke code pathways) and hospital stroke management. There remains a need to provide rapid and comprehensive assessment to acute stroke patients while reducing the risk of COVID-19 exposure, protecting healthcare providers, and preserving personal protective equipment (PPE) supplies. While the COVID infection is typically not a primary cerebrovascular condition, the downstream effects of this pandemic force adjustments to stroke care pathways to maintain optimal stroke patient outcomes.

Methods: The University of California San Diego (UCSD) Health System encompasses two academic, Comprehensive Stroke Centers (CSCs). The UCSD Stroke Center reviewed the national COVID-19 crisis and implications on stroke care. All current resources for stroke care were identified and adapted to include COVID-19 screening. The adjusted model focused on comprehensive and rapid acute stroke treatment, reduction of exposure to the healthcare team, and preservation of PPE.

Aims: The adjusted pathways implement telestroke assessments as a specific option for all inpatient and outpatient encounters and accounts for when telemedicine systems are not available or functional. COVID screening is done on all stroke patients. We outline a model of hyperacute stroke evaluation in an adapted stroke code protocol and novel methods of stroke patient management.

Conclusions: The overall goal of the model is to preserve patient access and outcomes while decreasing potential COVID-19 exposure to patients and healthcare providers. This model also serves to reduce the use of vital PPE. It is critical that stroke providers share best practices via academic and vetted social media platforms for rapid dissemination of tools and care models during the COVID-19 crisis.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205687PMC
August 2020

PREMISE: Posterior Circulation Results Comparing Embolectomy to Medical Intervention in Stroke Emergencies.

Cureus 2019 Oct 25;11(10):e6000. Epub 2019 Oct 25.

Neurosciences, University of California San Diego School of Medicine, San Diego, USA.

Background Intravenous (IV) tissue plasminogen activator (rt-PA) is a proven therapy for stroke in the acute treatment window. Recent published data has shown efficacy for embolectomy for acute ischemic strokes within up to six, 16 and 24 hours in the anterior circulation but there is no guideline for optimal therapy for patients with posterior circulation stroke, specifically basilar artery occlusion (BAO) outside the standard IV rt-PA treatment window. Aim To evaluate differences in outcomes between maximal medical treatment versus thrombectomy in BAO. Method We retrospectively evaluated prospectively collected acute stroke code patients from our stroke registry from 7/2004 to 7/2016. Patients who received IV rt-PA were excluded. Patients with evidence of posterior circulation ischemia and a hyper dense artery sign on initial non-contrast CT were included as a surrogate for direct vessel data before 2014. Patients after 9/2014 were selected by evidence of BAO on vessel imaging. All patients were categorized either as endovascular therapy or standard medical treatment alone. Demographics, hospital discharge location and Modified Rankin Scale (mRS) at 90 days were compared. Two-sample t-test and Fisher's exact test compared continuous and categorical variables across groups respectively. Results A total of 18 patients were included (three embolectomy and 15 medical therapy only). There were no significant differences in demographic data (age, gender, race, ethnicity, blood pressure, diabetes mellitus, hypertension, atrial fibrillation, tobacco use, alcohol use and initial NIHSS). Results for outcome and efficacies showed no statistical difference between medical management and endovascular intervention for functional outcome mRS (0-3) at 90 days (p = 0.2) and discharge location of home/inpatient rehabilitation vs other locations (p = 0.52). Conclusions Our single-center review showed the expected transition from predominantly medically treated posterior circulation BAOs, to a mixed pattern including embolectomy. Although the sample size was small, this study also illustrates the lack of clear efficacy data for optimal treatment strategies, and the ongoing treatment challenges in posterior circulation stroke population in a population of patients outside the rt-PA window.
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http://dx.doi.org/10.7759/cureus.6000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876905PMC
October 2019

RAcial Disparities in Ich after IV-tPA and Neurointerventional Treatment (RADIANT).

J Stroke Cerebrovasc Dis 2020 Feb 26;29(2):104474. Epub 2019 Nov 26.

University of California, Department of Neurosciences, Stroke Center, San Diego, California.

Objective: To study the rate of symptomatic intracerebral hemorrhage (SxICH) and major systemic hemorrhage (MSH) after acute stroke treatments among different ethnicities/races.

Background: Studies have reported ethnic/racial disparities in intravenous tPA treatment (IV tPA). The adverse outcome of tPA and/or intra-arterial intervention (IA) among different ethnicities/races requires investigation.

Methods: We retrospectively reviewed all patients from an IRB-approved registry between June 2004 and June 2018. Patients who received IV tPA, IA, or both for acute stroke were identified and classified into 2 ethnic groups: non-Hispanics or Hispanics (NH/H) and 4 racial groups: Asian, Black, Other (Native Americans and Pacific Islanders), and White (A/B/O/W).

Results: We identified 916 patients that received acute therapy (A/B/O/W: n = 50/104/16/746, H/NH: n = 184/730). For those received IV tPA only (n = 759), IA only (n = 85), and IV tPA+IA (n = 72), the SxICH rate was 4.3%, 4.7%, and 6.9%; the MSH rate was 1.3%, 0%, and 0%, respectively. No significant difference in the rate of SxICH or MSH among different racial or ethnic groups was found after either therapy. Asian race (OR 14.17, P = .01), in association with age, international normalized value (INR), and Partial thromboplastin time (PTT) (OR 1.06, 46.52, and 1.18, P = .020, 0.037, and 0.042, respectively), was predictive of SxICH after IV tPA. There was a significant correlation between age and National Institute of Health Stroke Scale with SxICH (P < .01, P = .02, respectively). Age, INR, and PTT were independent predictors of SxICH after IV tPA (OR 1.06, 46.52, and 1.18, P = .02, 0.04, and 0.04, respectively).

Conclusions: There was no significant difference in the rate of SxICH or MSH after IV tPA, IA, or IV tPA+IA among different racial or ethnic groups. Larger studies are needed to elucidate the race specific causes of SxICH and MSH after acute stroke treatment.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.104474DOI Listing
February 2020

Timing of symptomatic intracerebral hemorrhage after rt-PA treatment in ischemic stroke.

Neurol Clin Pract 2019 Aug;9(4):304-308

Department of Neurosciences, Stroke Center, University of California San Diego, San Diego, CA.

Background: We investigated patterns in the time from recombinant tissue-type plasminogen activator (rt-PA) treatment to symptomatic intracranial hemorrhage (sICH) onset in acute ischemic stroke.

Methods: We retrospectively reviewed all admitted "stroke code" patients from 2003 to 2017 at the University of California San Diego Medical Center from a prospective stroke registry. We selected patients that received IV rt-PA within 4.5 hours after onset/last known well and had sICH prehospital discharge. sICH diagnosis was made by prospective review. Endovascular-treated patients were excluded, given the variability of practice. sICH was prospectively defined as any new radiographic (CT/MRI) hemorrhage after rt-PA treatment and any worsened neurologic examination. Time to sICH was the time from rt-PA administration start to documented STAT head CT order time with the first evidence of new hemorrhage. Charts were reviewed for examination time metrics, demographics, clinical history, and neuroimaging.

Results: sICH was identified in 28 rt-PA-only treated patients. The mean time to sICH was 18.28 hours (range 2.4-34 hours). Median time to sICH was 18.25 hours. sICH was correlated with increased age ( = 0.02) and increased NIH Stroke Scale ( = 0.01).

Conclusions: Our findings suggest that rt-PA patients have the highest risk of post rt-PA sICH within the first 24 hours after treatment. This supports monitoring of rt-PA-treated patients in specialized settings such as neuro-intensive care units or stroke units. Our findings suggest that the probability of sICH is low 36 hours post rt-PA. Future larger studies are warranted to identify the patterns of bleeding after rt-PA administration.
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http://dx.doi.org/10.1212/CPJ.0000000000000632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745738PMC
August 2019

Efficacy of Home-Based Telerehabilitation vs In-Clinic Therapy for Adults After Stroke: A Randomized Clinical Trial.

JAMA Neurol 2019 Sep;76(9):1079-1087

National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.

Importance: Many patients receive suboptimal rehabilitation therapy doses after stroke owing to limited access to therapists and difficulty with transportation, and their knowledge about stroke is often limited. Telehealth can potentially address these issues.

Objectives: To determine whether treatment targeting arm movement delivered via a home-based telerehabilitation (TR) system has comparable efficacy with dose-matched, intensity-matched therapy delivered in a traditional in-clinic (IC) setting, and to examine whether this system has comparable efficacy for providing stroke education.

Design, Setting, And Participants: In this randomized, assessor-blinded, noninferiority trial across 11 US sites, 124 patients who had experienced stroke 4 to 36 weeks prior and had arm motor deficits (Fugl-Meyer [FM] score, 22-56 of 66) were enrolled between September 18, 2015, and December 28, 2017, to receive telerehabilitation therapy in the home (TR group) or therapy at an outpatient rehabilitation therapy clinic (IC group). Primary efficacy analysis used the intent-to-treat population.

Interventions: Participants received 36 sessions (70 minutes each) of arm motor therapy plus stroke education, with therapy intensity, duration, and frequency matched across groups.

Main Outcomes And Measures: Change in FM score from baseline to 4 weeks after end of therapy and change in stroke knowledge from baseline to end of therapy.

Results: A total of 124 participants (34 women and 90 men) had a mean (SD) age of 61 (14) years, a mean (SD) baseline FM score of 43 (8) points, and were enrolled a mean (SD) of 18.7 (8.9) weeks after experiencing a stroke. Among those treated, patients in the IC group were adherent to 33.6 of the 36 therapy sessions (93.3%) and patients in the TR group were adherent to 35.4 of the 36 assigned therapy sessions (98.3%). Patients in the IC group had a mean (SD) FM score change of 8.36 (7.04) points from baseline to 30 days after therapy (P < .001), while those in the TR group had a mean (SD) change of 7.86 (6.68) points (P < .001). The covariate-adjusted mean FM score change was 0.06 (95% CI, -2.14 to 2.26) points higher in the TR group (P = .96). The noninferiority margin was 2.47 and fell outside the 95% CI, indicating that TR is not inferior to IC therapy. Motor gains remained significant when patients enrolled early (<90 days) or late (≥90 days) after stroke were examined separately.

Conclusions And Relevance: Activity-based training produced substantial gains in arm motor function regardless of whether it was provided via home-based telerehabilitation or traditional in-clinic rehabilitation. The findings of this study suggest that telerehabilitation has the potential to substantially increase access to rehabilitation therapy on a large scale.

Trial Registration: ClinicalTrials.gov identifier: NCT02360488.
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http://dx.doi.org/10.1001/jamaneurol.2019.1604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593624PMC
September 2019

Mapping a Reliable Stroke Onset Time Course Using Signal Intensity on DWI Scans.

J Neuroimaging 2019 07 1;29(4):476-480. Epub 2019 Apr 1.

Department of Neurosciences, University of San Diego Health, Stroke Center, San Diego, CA.

Background And Purpose: Identifying a last known well (LKW) time surrogate for acute stroke is vital to increase stroke treatment. Diffusion-weighted imaging (DWI) signal intensity initially increases from onset of stroke but mapping a reliable time course to the signal intensity has not been demonstrated.

Methods: We retrospectively reviewed stroke code patients between 1/2016 and 6/2017 from the prospective; Institutional review board (IRB) approved University of California San Diego Stroke Registry. Patients who had magnetic resonance imaging of brain from onset, with or without intervention, are included. All ischemic strokes were confirmed and timing from onset to imaging was calculated. Raw DWI intensity is measured using IMPAX software and compared to contralateral side for control for a relative DWI intensity (rDWI). LKW and magnetic resonance imaging (MRI) time were collected by chart review. Correlation is assessed using Pearson correlation coefficient between DWI intensity, rDWI, and time to MRI imaging. 1.5T, 3T, and combined modalities were examined.

Results: Seventy-eight patients were included in this analysis. Overall, there was statistically significant positive correlation (.53, P < .001) between DWI intensity and LKW time irrespective of scanner strength. Using 1.5T analyses, there was good correlation (.46, P < .001). 3T MRI analysis further showed comparatively stronger positive correlation (.66, P < .001).

Conclusions: There is good correlation between DWI intensity and minutes from onset to MRI. This suggests a time-dependent DWI intensity response and supports the potential use of DWI intensity measurements to extrapolate an LKW time. Further studies are being pursued to increase both experience and generalizability.
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http://dx.doi.org/10.1111/jon.12616DOI Listing
July 2019

"Encephalopathy Only Stroke Codes" (EoSC) Rarely Result in Stroke as Final Diagnosis.

Neurol Res Int 2019 11;2019:2105670. Epub 2019 Feb 11.

Department of Neurosciences, Stroke Center, University of California San Diego, San Diego, CA, USA.

Stroke codes prompted by isolated encephalopathy often result in nonstroke final diagnoses but require intensive stroke center resources. We assessed the likelihood of "Encephalopathy only Stroke Codes (EoSC)" resulting in a true stroke (EoSC CVA+) final diagnosis. 3860 patients were analyzed in a prospective stroke code registry from 2004 to 2016. EoSC was defined using a standard and an exploratory definition. Definition 1 included EoSC patients as stroke codes where NIHSS was nonzero for LOC questions (questions la, 1b, and lc) but remainder of the NIHSS was zero. Definition 2 included the same definition but allowed symmetric pairings on motor questions (5a/5b, 6a/6b, or Question 4 scoring a 3). Groups were assessed for final diagnosis of stoke (EoSC CVA+) or not stroke (EoSC CVA-). EoSC accounted for 60/3860 (1.55%) of total stroke codes. EoSC CVA+ was found in 5/3860 (0.13%) of all stroke codes, 5/60 (8.33%) of EoSC stroke codes, and 5/1514 (0.33%) of all strokes. For Definition 2, EoSC accounted for 96/3860 (2.5%) of total stroke codes. EoSC CVA+ was found in 9/3860 (0.23%) of all stroke codes, 9/96 (9.38%) of EoSC stroke codes, and 9/1514 (0.59%) of all strokes. On multivariable logistic regression analysis, diabetes was the highest predictor of stroke (p=0.05). Encephalopathy only Stroke Codes only rarely result in cases with a true final diagnosis of stroke (EoSC CVA+), accounting for 0.1-0.2% of all stroke codes and 8-9% of EoSC stroke codes. This may have important significance for mobilization of limited acute stroke code resources in the future.
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http://dx.doi.org/10.1155/2019/2105670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388344PMC
February 2019

The COAST stroke advance directive: A novel approach to preserving patient autonomy.

Neurol Clin Pract 2018 Dec;8(6):521-526

Department of Neurosciences (KM, BCM, KA), University of California San Diego; and Neurology and Neurological Sciences (IS), Stanford University, CA.

Within the field of neurology, there has been limited discussion of how to best respect patient autonomy in patients presenting with an acute stroke, who often have impairments in language and cognition. In addition to performing a detailed neurologic examination and providing a thorough timeline of their current presentation and medical history, these patients and their families are then asked to quickly make critical medical decisions regarding acute stroke therapies (thrombolysis and endovascular therapy). These discussions are often limited by time constraints and inadequate opportunities for patient education regarding acute stroke care. This article discusses some of the challenges of preserving patient autonomy in patients presenting with acute stroke and the advent of a stroke advance directive (Coordinating Options for Acute Stroke Therapy [COAST]) aimed to overcome these obstacles.
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http://dx.doi.org/10.1212/CPJ.0000000000000549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294541PMC
December 2018

The Sustained DeyeCOM Sign as a Predictor of Large Vessel Occlusions and Stroke Mimics.

J Stroke Cerebrovasc Dis 2018 Jun 15;27(6):1466-1470. Epub 2018 Feb 15.

Stroke Center, University of California at San Diego (UCSD), San Diego, California.

Introduction: Rapid imaging in acute stroke is critical and often occurs before full examination. Early, reliable examination findings clarify diagnosis and improve treatment times. The DeyeCOM sign has been described as a predictor of ischemic stroke. In this study, we evaluate a sustained DeyeCOM sign on serial computed tomography scans in prediction of large vessel occlusion.

Methods: Between April and June 2017, we retrospectively reviewed 46 patients with acute stroke from the University of California, San Diego Stroke Registry, who had both computed tomography and computed tomography angiography as part of their acute work-up. A DeyeCOM(+) sign was defined as a conjugate gaze deviation on imaging of at least 15°. DeyeCOM(++) was defined as sustained gaze deviation on both scans.

Results: Three groups of patients were observed: DeyeCOM(++), nonsustained gaze deviation, and no gaze deviation (DeyeCOM(--)). All patients in the DeyeCOM(++) (8 of 8, 100%) had large vessel occlusion. Of those with nonsustained gaze deviation, 2 of 7 (29%) had large vessel occlusion. No patients in the DeyeCOM(--) (0 of 31, 100%) had large vessel occlusion. The specificity and sensitivity of DeyeCOM(++) for large vessel occlusion was 100% (confidence interval [CI] .90-1.0) and 80% (CI .44-.97). The specificity and sensitivity of DeyeCOM(--) for absence of large vessel occlusion was 100% (CI .69-1.0) and 86% (CI .70-.95).

Conclusions: DeyeCOM(++) had 100% specificity for large vessel occlusion, whereas DeyeCOM(--) had a 100% specificity for absence of large vessel occlusion. Sustained DeyeCOM, whether positive or negative, is a strong predictor of ultimate diagnosis that could lead to quicker endovascular treatment times.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.12.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937983PMC
June 2018

Accuracy of Stroke Diagnosis in Telestroke-Guided Tissue Plasminogen Activator Patients.

J Stroke Cerebrovasc Dis 2016 Dec 2;25(12):2942-2946. Epub 2016 Sep 2.

University of California, San Diego, California.

Objectives: The objective of the study is to assess the accuracy of final diagnosis in telestroke-guided tissue plasminogen activator (rt-PA) patients compared with bedside evaluation using computed tomography (CT) or magnetic resonance imaging (MRI) as a surrogate for final stroke diagnosis. The overall goal was to determine if telestroke had similar diagnostic accuracy as bedside evaluations in diagnosing rt-PA-treated patients.

Materials And Methods: We analyzed all acute stroke code calls who received intravenous rt-PA at our center from October 2013 to June 2015. Calls were grouped into patients who were initially evaluated by telestroke at a spoke partner site (spoke) and patients evaluated in person at the hub. Patients receiving additional neurointervention were excluded to avoid confounding. Relevant variables included severity of stroke (National Institutes of Health Stroke Scale [NIHSS]), rt-PA times, presence of intracranial hemorrhage (ICH), and primary outcome of CT or MRI evidence of stroke after rt-PA administration. Post-rt-PA imaging used included CT or MRI within 72 hours after treatment.

Results: Overall, 80 patients received intravenous rt-PA (spoke [n = 23] and hub [n = 57]). There was no difference in mean NIHSS score prior to treatment (10.3 ± 9.2 and 9.8 ± 8.4; P = .936), "onset-to-treatment" time (143.6 ± 53.5 minutes and 141.0 ± 54.1 minutes; P = .915), and ICH rate (13% and 8.8%; adjusted P = .898). The presence of radiographic evidence of stroke at spoke versus hub was not different (78.3% and 66.7%; adjusted P = .338). The most commonly used radiographic modality was MRI (MRI: 80%, CT: 20%).

Conclusions: Using imaging as a surrogate for final diagnosis resulted in no difference in final stroke diagnosis rate between the groups, reinforcing that telestroke evaluations are as accurate as bedside evaluations in diagnosing acute stroke.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.08.009DOI Listing
December 2016

Visual Determination of Conjugate Eye Deviation on Computed Tomography Scan Predicts Diagnosis of Stroke Code Patients.

J Stroke Cerebrovasc Dis 2016 Dec 26;25(12):2809-2813. Epub 2016 Aug 26.

Department of Neurology and Neurologic Sciences, University of California, San Diego, California.

Background: Head computed tomography (CT) is critical for stroke code evaluations and often happens prior to completion of the neurological exam. Eye deviation on neuroimaging (DeyeCOM sign) has utility for predicting stroke diagnosis and correlates with National Institutes of Health Stroke Scale (NIHSS) gaze score. We further assessed the utility of the DeyeCOM sign, without complex caliper-based eye deviation calculations, but simply with a visual determination method.

Methods: Patients with initial head CT and final diagnosis from an institutional review board-approved consecutive prospective registry of stroke codes at the University of California, San Diego, were included. Five stroke specialists and 1 neuroradiologist reviewed each CT. DeyeCOM+ patients were compared to DeyeCOM- patients (baseline characteristics, diagnosis, and NIHSS gaze score). Kappa statistics compared stroke specialists to neuroradiologist reads, and visual determination to caliper measurement of DeyeCOM sign.

Results: Of 181 patients, 46 were DeyeCOM+. Ischemic stroke was more commonly diagnosed in DeyeCOM+ patients compared to other diagnoses (P = .039). DeyeCOM+ patients were more likely to have an NIHSS gaze score of 1 or higher (P = .006). The NIHSS score of DeyeCOM+ stroke versus DeyeCOM- stroke patients was 8.3 ± 6.0 versus 6.7 ± 8.0 (P = .065). Functional outcomes were similar (P = .59). Stroke specialists had excellent agreement with the neuroradiologist (Κ = .89). Visual inspection had excellent agreement with the caliper method (Κ = .88).

Conclusions: Using a time-sensitive visual determination of gaze deviation on imaging was predictive of ischemic stroke diagnosis and presence of NIHSS gaze score, and was consistent with the more complex caliper method. This study furthers the clinical utility of the DeyeCOM sign for predicting ischemic strokes.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.07.039DOI Listing
December 2016

Cerebral Sinus Thrombosis.

Headache 2016 Sep 28;56(8):1380-9. Epub 2016 Jun 28.

Department of Neurology, School of Medicine, George Washington University, Washington, DC, USA.

Background: Although cerebral venous thrombosis/cerebral sinus thrombosis (CVT/CST) remains a relatively uncommon cause of stroke and other neurologic complications, the widespread availability of noninvasive brain imaging has led to an increase in its diagnosis.

Purpose: Through a review and description of its epidemiology, clinical features and treatment, to heighten awareness of CVT/CST.

Methodology: Via a systematic review of the more recently published medical literature relevant to the topic and focusing in particular on primary sources, we compiled data related to the incidence of CVT/CST and its diagnosis, treatment and prognosis.

Results: Thrombosis of a cerebral vein or sinus may occur in individuals of any age and may be caused by a myriad of prothrombotic conditions, both primary and acquired. The clinical presentation of CVT/CST is widely variable, but headache is present in the great majority of cases, and the predominant symptom in many. The headache associated with CVT/CST may be acute, severe, and even "thunderclap" in character, or it may be chronic, pervasive, and of lower intensity.

Conclusions: Given its eclectic epidemiology, its potential to produce a highly unfavorable clinical outcome, and evidence suggesting that specific treatment improves outcome, CVT/CST is a disorder whose salient features should be familiar to virtually all clinicians.
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http://dx.doi.org/10.1111/head.12873DOI Listing
September 2016

Spatially-global integration of closed, fragmented contours by finding the shortest-path in a log-polar representation.

Vision Res 2016 09 14;126:143-163. Epub 2015 Aug 14.

Department of Psychological Sciences, Purdue University, USA.

Finding the occluding contours of objects in real 2D retinal images of natural 3D scenes is done by determining, which contour fragments are relevant, and the order in which they should be connected. We developed a model that finds the closed contour represented in the image by solving a shortest path problem that uses a log-polar representation of the image; the kind of representation known to exist in area V1 of the primate cortex. The shortest path in a log-polar representation favors the smooth, convex and closed contours in the retinal image that have the smallest number of gaps. This approach is practical because finding a globally-optimal solution to a shortest path problem is computationally easy. Our model was tested in four psychophysical experiments. In the first two experiments, the subject was presented with a fragmented convex or concave polygon target among a large number of unrelated pieces of contour (distracters). The density of these pieces of contour was uniform all over the screen to minimize spatially-local cues. The orientation of each target contour fragment was randomly perturbed by varying the levels of jitter. Subjects drew a closed contour that represented the target's contour on a screen. The subjects' performance was nearly perfect when the jitter-level was low. Their performance deteriorated as jitter-levels were increased. The performance of our model was very similar to our subjects'. In two subsequent experiments, the subject was asked to discriminate a briefly-presented egg-shaped object while maintaining fixation at several different positions relative to the closed contour of the shape. The subject's discrimination performance was affected by the fixation position in much the same way as the model's.
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http://dx.doi.org/10.1016/j.visres.2015.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752937PMC
September 2016

Sexual function after strokes.

Handb Clin Neurol 2015 ;130:289-95

Department of Neurology, George Washington University Medical School, Washington, DC, USA.

Strokes are the second leading cause of death and the third leading cause of disability worldwide. Thanks in part to better and more available diagnosis, treatment, and rehabilitation, the vast majority of stroke patients tend to survive strokes, particularly in the industrialized world. Motor disability and cognitive changes such as aphasia and visuospatial disorders are most often considered among the major contributors to stroke burden. This chapter discusses disorders of sexual functions as another frequent sequel of strokes. Strokes generally induce hyposexuality, but in some instances they may be followed by hypersexuality. There is some evidence suggesting that lesions of either hemisphere affect sexual activities, but for different reasons: aphasia and depression after left-hemisphere lesions, a deficit in arousal and perhaps visuospatial disorders after right-hemisphere lesions. Psychologic, psychosocial, and physical factors, as well as medications, play an important role. A better understanding of the psychosocial and physiologic mechanisms underlying sexual functioning can provide insight into improving sexual activity and therefore quality of life in patients affected by strokes and other brain lesions.
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http://dx.doi.org/10.1016/B978-0-444-63247-0.00016-XDOI Listing
August 2015

Cognitive changes associated with endocrine therapy for breast cancer.

Maturitas 2010 Nov 4;67(3):209-14. Epub 2010 Aug 4.

Division of Genitourinary Malignancies, Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.

Endocrine therapy in the setting of breast cancer has undoubtedly advanced clinical outcomes in this disease, but treatment with endocrine therapy is accompanied by a wide spectrum of side effects. It is of prime importance to understand and characterize these toxicities to facilitate clinical decision-making. Somewhat surprisingly, there is a relative paucity of data pertaining to cognitive changes associated with endocrine therapy. In this article we review cognitive associated with two classes of endocrine therapy: (1) selective estrogen receptor modulators (SERMs; tamoxifen and raloxifene) and (2) aromatase inhibitors (AIs; anastrozole, letrozole, and exemestane). Companion studies to the Multiple Outcome of Raloxifene Evaluation (MORE), the Study of Tamoxifen and Raloxifene (STAR) and National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trials provide relevant data to understand the effect of SERMs on cognition. In contrast, substudies of the Arimidex, Tamoxifen Alone or in Combination (ATAC), Tamoxifen and Exemestane Adjuvant Multinational (TEAM) and Breast International Group (BIG) 1-98 trials juxtapose cognitive effects of AIs against those of tamoxifen. These and other studies are examined herein to provide a comprehensive overview of the effect of endocrine therapy on cognition.
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http://dx.doi.org/10.1016/j.maturitas.2010.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253817PMC
November 2010

Shared visual attention and memory systems in the Drosophila brain.

PLoS One 2009 Jun 19;4(6):e5989. Epub 2009 Jun 19.

Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.

Background: Selective attention and memory seem to be related in human experience. This appears to be the case as well in simple model organisms such as the fly Drosophila melanogaster. Mutations affecting olfactory and visual memory formation in Drosophila, such as in dunce and rutabaga, also affect short-term visual processes relevant to selective attention. In particular, increased optomotor responsiveness appears to be predictive of visual attention defects in these mutants.

Methodology/principal Findings: To further explore the possible overlap between memory and visual attention systems in the fly brain, we screened a panel of 36 olfactory long term memory (LTM) mutants for visual attention-like defects using an optomotor maze paradigm. Three of these mutants yielded high dunce-like optomotor responsiveness. We characterized these three strains by examining their visual distraction in the maze, their visual learning capabilities, and their brain activity responses to visual novelty. We found that one of these mutants, D0067, was almost completely identical to dunce(1) for all measures, while another, D0264, was more like wild type. Exploiting the fact that the LTM mutants are also Gal4 enhancer traps, we explored the sufficiency for the cells subserved by these elements to rescue dunce attention defects and found overlap at the level of the mushroom bodies. Finally, we demonstrate that control of synaptic function in these Gal4 expressing cells specifically modulates a 20-30 Hz local field potential associated with attention-like effects in the fly brain.

Conclusions/significance: Our study uncovers genetic and neuroanatomical systems in the fly brain affecting both visual attention and odor memory phenotypes. A common component to these systems appears to be the mushroom bodies, brain structures which have been traditionally associated with odor learning but which we propose might be also involved in generating oscillatory brain activity required for attention-like processes in the fly brain.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0005989PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694981PMC
June 2009