OBJECTIVE: To identify characteristics of acute stroke patients associated with late arrival to h... more OBJECTIVE: To identify characteristics of acute stroke patients associated with late arrival to hospital. BACKGROUND: Treatment of stroke is highly time dependent. Time from symptom onset to hospital arrival or “onset-to-door time” (OTD) is a major factor in determining eligibility for IV TPA. Since the inception of Get with The Guidelines-Stroke (GWTG-Stroke) program, percentage of patients arriving within the time window have remained unchanged despite public health efforts. DESIGN/METHODS: OTD for stroke patients treated at a primary stroke center serving a multiethnic urban community in New York City from 2005 to 2013 were analyzed. Patients were excluded if stroke onset occurred within an institution (e.g. hospital, nursing home) and or if patient presented for evaluation after one week from onset. Utilizing data collected from GWTG-Stroke program, predictors of OTD beyond 4.5 hours were analyzed using multivariable logistic regression. RESULTS: 2629 stroke patients were treate...
Background and Purpose: Coronavirus disease 2019 (COVID-19) has been associated with an increased... more Background and Purpose: Coronavirus disease 2019 (COVID-19) has been associated with an increased incidence of thrombotic events, including stroke. However, characteristics and outcomes of COVID-19 patients with stroke are not well known. Methods: We conducted a retrospective observational study of risk factors, stroke characteristics, and short-term outcomes in a large health system in New York City. We included consecutively admitted patients with acute cerebrovascular events from March 1, 2020 through April 30, 2020. Data were stratified by COVID-19 status, and demographic variables, medical comorbidities, stroke characteristics, imaging results, and in-hospital outcomes were examined. Among COVID-19-positive patients, we also summarized laboratory test results. Results: Of 277 patients with stroke, 105 (38.0%) were COVID-19-positive. Compared with COVID-19-negative patients, COVID-19-positive patients were more likely to have a cryptogenic (51.8% versus 22.3%, P <0.0001) stro...
Background and Purpose: Triage of patients with emergent large vessel occlusion stroke to primary... more Background and Purpose: Triage of patients with emergent large vessel occlusion stroke to primary stroke centers followed by transfer to comprehensive stroke centers leads to increased time to endovascular therapy. A Mobile Interventional Stroke Team (MIST) provides an alternative model by transferring a MIST to a Thrombectomy Capable Stroke Center (TSC) to perform endovascular therapy. Our aim is to determine whether the MIST model is more time-efficient and leads to improved clinical outcomes compared with standard drip-and-ship (DS) and mothership models. Methods: This is a prospective observational cohort study with 3-month follow-up between June 2016 and December 2018 at a multicenter health system, consisting of one comprehensive stroke center, 4 TSCs, and several primary stroke centers. A total of 228 of 373 patients received endovascular therapy via 1 of 4 models: mothership with patient presentation to a comprehensive stroke center, DS with patient transfer from primary str...
Objective: To determine the impact of on-site endovascular coverage on outcome in anterior large ... more Objective: To determine the impact of on-site endovascular coverage on outcome in anterior large vessel stroke. Rationale: Availability of on-site endovascular service decreases time to treatment of large vessel stroke. Since expansion to a satellite hospital in July 2009, time to treatment has decreased. We hypothesize that expansion was associated with improved discharge outcomes in patients with anterior circulation large vessel strokes. Methods: A retrospective chart review of consecutive patients before and after the initiation of the program was conducted. Adults presenting with an NIHSS > 8, within 6 hours from stroke onset, and with carotid terminus or middle cerebral artery occlusion were included. Exclusion criteria were INR or creatinine >3 and premorbid modified Rankin Scale (mRS) >1. Comparison was made between groups before and after program initiation. Modified Rankin at discharge was set as primary outcome. Secondary outcomes included admission-discharge delta NIHSS, discharge disposition, mortality, and stroke volume on MRI or CT scan. Results: 70 patients were included in the study, 30 admitted before July 2009, and 40 after. There was no difference between patient demographics except higher coronary artery disease and hypertension in patients treated prior to program expansion (p<0.05). Only 2/30 patients received endovascular treatment prior to July 2009 versus 30/40 after (p<0.05). Patients treated following program initiation were less likely to be dependent (OR: 0.14; 95% CI: 0.019-1) and more likely to be discharged home (OR: 0.233; 95% CI: 0.062-0.876) after adjusting for age and admission NIHSS. In addition there was a 4-point increase in median admission-discharge NIHSS change in patients treated after program initiation (p=0.007). Discussion: For every 30 minutes until reperfusion, the probability of good recovery after large vessel stroke is decreased by about 10%. Transfer delays impede the benefit of endovascular recanalization. In the absence of strategic air transportation systems, rapid deployment of an endovascular team decreases time to recanalization and improves patient outcomes in anterior large vessel stroke. Disclosure: Dr. Shwe has nothing to disclose. Dr. Ortega-Gutierrez has nothing to disclose. Dr. Walker has nothing to disclose. Dr. Boniece has nothing to disclose. Dr. Berenstein has nothing to disclose. Dr. Fifi has nothing to disclose.
OBJECTIVE: To identify characteristics of acute stroke patients associated with late arrival to h... more OBJECTIVE: To identify characteristics of acute stroke patients associated with late arrival to hospital. BACKGROUND: Treatment of stroke is highly time dependent. Time from symptom onset to hospital arrival or “onset-to-door time” (OTD) is a major factor in determining eligibility for IV TPA. Since the inception of Get with The Guidelines-Stroke (GWTG-Stroke) program, percentage of patients arriving within the time window have remained unchanged despite public health efforts. DESIGN/METHODS: OTD for stroke patients treated at a primary stroke center serving a multiethnic urban community in New York City from 2005 to 2013 were analyzed. Patients were excluded if stroke onset occurred within an institution (e.g. hospital, nursing home) and or if patient presented for evaluation after one week from onset. Utilizing data collected from GWTG-Stroke program, predictors of OTD beyond 4.5 hours were analyzed using multivariable logistic regression. RESULTS: 2629 stroke patients were treated from January 2005 to December 2013. A total of 587 patients were excluded due to stroke onset within an institution and 101 patients due to presentation one week after stroke onset. Among the remaining 1941 patients, OTD was documented in 58[percnt] to be beyond 4.5 hours. Patients that were men (OR,1.29; 95[percnt] CI,1.07-1.58), with history of atrial fibrillation/flutter (OR,1.31; 95[percnt] CI,1.02-1.71), and experiencing TIA (OR,3.47; 95[percnt] CI,2.54-4.75) were significantly more likely to arrive within 4.5 hours. Conversely, diabetic patients were less likely to arrive within 4.5 hours (OR,0.63; 95[percnt] CI,0.50-0.78). Asian patients presented at rates similar to White patients while Black/African-American (OR,0.77; 95[percnt] CI,0.57-1.03) and Hispanic (OR,0.88; 95[percnt] CI,0.68-1.14) patients were marginally less likely to arrive on time. CONCLUSIONS: Factors associated with delay presentation in patients suffering acute stroke include non-white, female and presence of diabetes. Further studies and educational programs are needed to better understand and address these factors. Disclosure: Dr. Matos-Diaz has nothing to disclose. Dr. Liang has nothing to disclose. Dr. Walker has nothing to disclose. Dr. Lucido has nothing to disclose. Dr. Boniece has nothing to disclose.
Objective: To reduce the time to treament of acute ischemic strokes in the inpatient setting Back... more Objective: To reduce the time to treament of acute ischemic strokes in the inpatient setting Background: Urgent assessment and management of acute stroke is critical. A shorter time to treatment is directly associated with better patient outcomes. Studies have shown that management is prolonged in the inpatient setting compared to the emergency department (ED). Design/Methods: We did a retrospective cohort study of strokes ending in t-PA administration or endovascular intervention between 2010-2013. ED and inpatient data were compared. Variables assessed were time to neurological evaluation, time to CT-scan, time to t-PA, time from CT-scan to t-PA and time to endovascular intervention. The variables were compared using a one-tailed Student’s t-test. Once areas of delay were identified, procedure modifications were proposed. Results: 122 stroke codes included (ED=106, Inpatient=16). There was no difference in time to neurological evaluation (ED=2.80 minutes, inpatient=4.43 minutes; p=0.19). Time to CT-scan was significantly increased in the inpatient group (32.25 versus 14.93 minutes, p=<0.001). Time to t-PA was significantly prolonged in the inpatient group (80.3 versus 59.32 minutes, p=0.01). There was no difference in the time from CT-head to t-PA (p=0.09) or in the time to endovascular intervention (p=0.21). Conclusion/Proposal: In the inpatient setting there was a significant delay in the time to CT-scan and to t-PA; the main source of delay was time to CT-scan. There are many possible reasons for the delay: location of the CT-scanner, unfamiliarity with strokes by non-neurology staff, ready availability of t-PA. We proposed to target house staff education and t-PA availability. We developed a “stroke-code” checklist to be distributed to house staff from different services after a small explanatory lecture. We also developed an order form to create a zero wait time for t-PA, allowing the RN/PCA to be the first one served in the pharmacy. Once these interventions take place, we will assess if treatment times were reduced. Disclosure: Dr. Liang has nothing to disclose. Dr. Garcia Santibanez has nothing to disclose. Dr. Walker has nothing to disclose. Dr. Boniece has nothing to disclose.
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 2015
The aim of this study is to describe a case of pathologically proven cerebral amyloid angiopathy-... more The aim of this study is to describe a case of pathologically proven cerebral amyloid angiopathy-related inflammation (CAA-I) without cerebral microbleeds (CMBs) and its clinical course. CAA-I is an uncommon variant of cerebral amyloid angiopathy. Keys to diagnosis rely on the physician's awareness of this entity, CMBs on magnetic resonance imaging (MRI), an often favorable response to immunosuppression, and ultimately brain biopsy. CAA-I with no CMBs is rarely reported. A 76-year-old woman presented with 4 weeks of headaches and was found to have visual neglect on the left part of the visual field. MRI of the brain showed sulcal/gyriform hyperintensity with associated leptomeningeal enhancement in the right occipital lobe on fluid-attenuated inversion recovery (FLAIR) imaging. No CMBs or large parenchymal FLAIR lesions were seen on MRI. Biopsy was consistent with CAA-I. The patient's headaches resolved spontaneously and no immunosuppression was initiated. The patient remain...
Journal of Stroke and Cerebrovascular Diseases, 2015
Outcomes of acute stroke management are time dependent. Intravenous tissue plasminogen activator ... more Outcomes of acute stroke management are time dependent. Intravenous tissue plasminogen activator (t-PA) is indicated within 3-4.5 hours of symptom onset and endovascular intervention within 6 hours. Time to treatment may depend on the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s location. This study seeks to determine whether there is a difference in the timing of key aspects of stroke codes between the emergency room and the inpatient setting. Stroke codes ending in t-PA administration or endovascular intervention between 2010 and 2013 were included. Emergency room stroke codes were compared with those in the inpatient setting. Data were obtained from the Yarmon Stroke Center log. The variables were time to neurological evaluation, time to computed tomography (CT) scan, time to t-PA administration, time from CT scan to t-PA, and time to endovascular intervention. The variables were compared using the t test. One hundred twenty-two stroke codes were included (106 from emergency room and 16 from inpatient setting). There was no difference in the time to neurological evaluation (P = .19). The time to CT scan and to t-PA administration was significantly increased in the inpatient group (P ≤ .001 and P = .01, respectively). There was no difference in the time from CT scan to t-PA (P = .09) and in the time to endovascular intervention (P = .21). Our results show that in the inpatient setting, there was a significant delay in the time to CT scan and to t-PA administration and that the source of the delay is the time to CT scan.
Extraskeletal myxoid chondrosarcomas usually arise deep in the proximal extremities and limb gird... more Extraskeletal myxoid chondrosarcomas usually arise deep in the proximal extremities and limb girdles. Patients with this type of sarcoma have high rates of local recurrence and metastases, but do not typically have paraneoplastic syndromes. We report an unusual case of a 49-year-old man with anti-Hu syndrome in the setting of an extraskeletal myxoid chondrosarcoma. This case shows the importance of searching for antineural antibodies in oncologic patients with new neurologic deficits, and of having a judicious workup for occult malignancies in patients with known antineural antibodies.
Abstract The vulnerability of neurons to the damaging events that occur during a period of ischem... more Abstract The vulnerability of neurons to the damaging events that occur during a period of ischemia can be modulated by a wide range of peptide growth factors and by agents that modify intracellular signal transduction systems both in vivo and in vitro. Analysis of the molecular mechanism of these protective effects can help to establish how signaling cascades influence the sensitivity of neurons to ischemia. We have established two in vitro models of ischemia and used these to explore the ability of peptide growth factors to confer protection on neural cells. Using the rat PC12 cell line, we have established a model of ischemia that includes a combination of hypoglycemia and anoxia. We also established an in vitro model of ischemia using primary cultured hippocampal neurons that has been used to study both anoxia and nitric oxide toxicity. In both models, peptide growth factors are neuroprotective. Although each of the growth factors we have studied is known to activate PKC, its activation does not mimic the effects of the peptide growth factors in either model. Indeed, down-regulation of PKC or pharmacologic inhibition of PKC made PC12 cells resistant to ischemic damage. Likewise, down-regulation of PKC or inhibition of PKC activity made hippocampal neurons more resistant both to ischemia and nitric oxide toxicity. In contrast, activation of the cyclic adenosine monophosphate (cAMP) dependent protein kinases (PKA) confers protection in both model systems. The effects of PKA activation were not additive with those of the growth factors. The effects of the growth factors were equivalent in PC12 lines that contained normal levels of the PKA, or were deficient in this enzyme. Thus, there appears to be two signal transduction pathways that contribute to neural protection in both PC12 cells and hippocampal neurons. One pathway is under the control of peptide growth factors, and a second can be initiated by activation of PKA. In PC12 cells, the protective effects of nerve growth factor (NGF) are mediated through the trk receptor and are dependent on the activation of the N-kinase, a member of the MAP kinase family and a key regulator of NGF-dependent differentiation. Thus, in two quite distinct model systems, PKC appears to have a deleterious effect on neuronal survival, whereas activation of the cAMP-dependent protein kinase appears to be neuroprotective. A significant fraction of the neuronal death that occurs in hippocampal neurons during anoxia is caused by the generation of nitric oxide. Inhibition of nitric oxide synthase (NOS) reduced the extent of neuronal death, and additions of agents that generate nitric oxide is neurotoxic. Growth factors can protect against nitric oxide toxicity, and one of the major mechanisms used by peptide growth factors to protect these neurons against ischemia is to make them resistant to nitric oxide that is generated during periods of ischemia. If nitric oxide is an important mediator of ischemic damage in vivo, the source of nitric oxide must be identified. We therefore examined the expression of both the constitutive form of nitric oxide synthase (cNOS) and the inducible form of nitric oxide synthase (iNOS) after ischemia. Using in situ hybridization and the histochemical nicotinamide-adenine-dinucleotide phosphate-reduced form (NADPH) diaphorase reaction, we were able to demonstrate that pyramidal neurons in CA1, CA3, CA4, and granule cells in the dentate gyrus express cNOS. In contrast to a number of instances where neurons that express NOS are resistant to neurodegeneration, neurons in the CA1 region of the hippocampus express cNOS, but are very vulnerable to ischemia. Although NOS is not normally expressed in astrocytes, transient ischemia induces the expression of iNOS in astrocytes, as indicated by both immunohistochemistry and NADPH diaphorase histochemistry. Thus, the synthesis of nitric oxide by either neurons or astrocytes might contribute to cell death during ischemia.
Reduction or elimination of nitric oxide (NO) production in cortical neurons by NO synthase (NOS)... more Reduction or elimination of nitric oxide (NO) production in cortical neurons by NO synthase (NOS) inhibitors during glu- tamate toxicity in vitro or during focal cerebral ischemia in viva can prevent neuronal cell death. In contrast, growth factors can prevent neuronal degeneration induced by treat- ment with glutamate or potassium cyanide. We have deter- mined whether NO mediates hippocampal cell
Nerve growth factor (NGF), which has been shown to act as a morphological and neurochemical diffe... more Nerve growth factor (NGF), which has been shown to act as a morphological and neurochemical differentiating factor in PC12 cells, also protects PC12 cells from the toxicity of serum withdrawal and ischemia. By using a previously established in vitro model of ischemia, which incorporates the combination of anoxia with glucose deprivation (Boniece and Wagner: J Neurosci 13:4220-4228, 1993), we have been able to study the signal transduction pathways upon which NGF-induced survival is dependent. Here we demonstrate that inhibitors of the N-kinase and NGF-induced neuritogenesis, 6-thioguanine and 2-aminopurine, prevent the protective effects of NGF, while they have little, if any, effect on the protection conferred by epidermal growth factor (EGF) or dbcAMP. This suggests that only NGF acts by a mechanism that depends strongly on the N-kinase. Furthermore, the methyltransferase inhibitor 5&#39;-deoxy-5&#39;-methylthioadenosine (MTA), which also inhibits NGF-induced neuritogenesis, inhibits the protective effect of NGF but not the protective effects of EGF or dbcAMP. Thus, the neuroprotective effect of NGF requires some of the same signal transduction steps used by NGF to promote differentiation and neurite formation. Furthermore, we found that exposure of PC12 cells to retinoic acid, which promotes the differentiation and inhibits the growth of PC12 cells, also improves cell survival during ischemia. In addition, a combination of NGF and retinoic acid was more effective than either agent alone. It is likely that these two agents confer protection by independent pathways.
OBJECTIVE: To identify characteristics of acute stroke patients associated with late arrival to h... more OBJECTIVE: To identify characteristics of acute stroke patients associated with late arrival to hospital. BACKGROUND: Treatment of stroke is highly time dependent. Time from symptom onset to hospital arrival or “onset-to-door time” (OTD) is a major factor in determining eligibility for IV TPA. Since the inception of Get with The Guidelines-Stroke (GWTG-Stroke) program, percentage of patients arriving within the time window have remained unchanged despite public health efforts. DESIGN/METHODS: OTD for stroke patients treated at a primary stroke center serving a multiethnic urban community in New York City from 2005 to 2013 were analyzed. Patients were excluded if stroke onset occurred within an institution (e.g. hospital, nursing home) and or if patient presented for evaluation after one week from onset. Utilizing data collected from GWTG-Stroke program, predictors of OTD beyond 4.5 hours were analyzed using multivariable logistic regression. RESULTS: 2629 stroke patients were treate...
Background and Purpose: Coronavirus disease 2019 (COVID-19) has been associated with an increased... more Background and Purpose: Coronavirus disease 2019 (COVID-19) has been associated with an increased incidence of thrombotic events, including stroke. However, characteristics and outcomes of COVID-19 patients with stroke are not well known. Methods: We conducted a retrospective observational study of risk factors, stroke characteristics, and short-term outcomes in a large health system in New York City. We included consecutively admitted patients with acute cerebrovascular events from March 1, 2020 through April 30, 2020. Data were stratified by COVID-19 status, and demographic variables, medical comorbidities, stroke characteristics, imaging results, and in-hospital outcomes were examined. Among COVID-19-positive patients, we also summarized laboratory test results. Results: Of 277 patients with stroke, 105 (38.0%) were COVID-19-positive. Compared with COVID-19-negative patients, COVID-19-positive patients were more likely to have a cryptogenic (51.8% versus 22.3%, P <0.0001) stro...
Background and Purpose: Triage of patients with emergent large vessel occlusion stroke to primary... more Background and Purpose: Triage of patients with emergent large vessel occlusion stroke to primary stroke centers followed by transfer to comprehensive stroke centers leads to increased time to endovascular therapy. A Mobile Interventional Stroke Team (MIST) provides an alternative model by transferring a MIST to a Thrombectomy Capable Stroke Center (TSC) to perform endovascular therapy. Our aim is to determine whether the MIST model is more time-efficient and leads to improved clinical outcomes compared with standard drip-and-ship (DS) and mothership models. Methods: This is a prospective observational cohort study with 3-month follow-up between June 2016 and December 2018 at a multicenter health system, consisting of one comprehensive stroke center, 4 TSCs, and several primary stroke centers. A total of 228 of 373 patients received endovascular therapy via 1 of 4 models: mothership with patient presentation to a comprehensive stroke center, DS with patient transfer from primary str...
Objective: To determine the impact of on-site endovascular coverage on outcome in anterior large ... more Objective: To determine the impact of on-site endovascular coverage on outcome in anterior large vessel stroke. Rationale: Availability of on-site endovascular service decreases time to treatment of large vessel stroke. Since expansion to a satellite hospital in July 2009, time to treatment has decreased. We hypothesize that expansion was associated with improved discharge outcomes in patients with anterior circulation large vessel strokes. Methods: A retrospective chart review of consecutive patients before and after the initiation of the program was conducted. Adults presenting with an NIHSS > 8, within 6 hours from stroke onset, and with carotid terminus or middle cerebral artery occlusion were included. Exclusion criteria were INR or creatinine >3 and premorbid modified Rankin Scale (mRS) >1. Comparison was made between groups before and after program initiation. Modified Rankin at discharge was set as primary outcome. Secondary outcomes included admission-discharge delta NIHSS, discharge disposition, mortality, and stroke volume on MRI or CT scan. Results: 70 patients were included in the study, 30 admitted before July 2009, and 40 after. There was no difference between patient demographics except higher coronary artery disease and hypertension in patients treated prior to program expansion (p<0.05). Only 2/30 patients received endovascular treatment prior to July 2009 versus 30/40 after (p<0.05). Patients treated following program initiation were less likely to be dependent (OR: 0.14; 95% CI: 0.019-1) and more likely to be discharged home (OR: 0.233; 95% CI: 0.062-0.876) after adjusting for age and admission NIHSS. In addition there was a 4-point increase in median admission-discharge NIHSS change in patients treated after program initiation (p=0.007). Discussion: For every 30 minutes until reperfusion, the probability of good recovery after large vessel stroke is decreased by about 10%. Transfer delays impede the benefit of endovascular recanalization. In the absence of strategic air transportation systems, rapid deployment of an endovascular team decreases time to recanalization and improves patient outcomes in anterior large vessel stroke. Disclosure: Dr. Shwe has nothing to disclose. Dr. Ortega-Gutierrez has nothing to disclose. Dr. Walker has nothing to disclose. Dr. Boniece has nothing to disclose. Dr. Berenstein has nothing to disclose. Dr. Fifi has nothing to disclose.
OBJECTIVE: To identify characteristics of acute stroke patients associated with late arrival to h... more OBJECTIVE: To identify characteristics of acute stroke patients associated with late arrival to hospital. BACKGROUND: Treatment of stroke is highly time dependent. Time from symptom onset to hospital arrival or “onset-to-door time” (OTD) is a major factor in determining eligibility for IV TPA. Since the inception of Get with The Guidelines-Stroke (GWTG-Stroke) program, percentage of patients arriving within the time window have remained unchanged despite public health efforts. DESIGN/METHODS: OTD for stroke patients treated at a primary stroke center serving a multiethnic urban community in New York City from 2005 to 2013 were analyzed. Patients were excluded if stroke onset occurred within an institution (e.g. hospital, nursing home) and or if patient presented for evaluation after one week from onset. Utilizing data collected from GWTG-Stroke program, predictors of OTD beyond 4.5 hours were analyzed using multivariable logistic regression. RESULTS: 2629 stroke patients were treated from January 2005 to December 2013. A total of 587 patients were excluded due to stroke onset within an institution and 101 patients due to presentation one week after stroke onset. Among the remaining 1941 patients, OTD was documented in 58[percnt] to be beyond 4.5 hours. Patients that were men (OR,1.29; 95[percnt] CI,1.07-1.58), with history of atrial fibrillation/flutter (OR,1.31; 95[percnt] CI,1.02-1.71), and experiencing TIA (OR,3.47; 95[percnt] CI,2.54-4.75) were significantly more likely to arrive within 4.5 hours. Conversely, diabetic patients were less likely to arrive within 4.5 hours (OR,0.63; 95[percnt] CI,0.50-0.78). Asian patients presented at rates similar to White patients while Black/African-American (OR,0.77; 95[percnt] CI,0.57-1.03) and Hispanic (OR,0.88; 95[percnt] CI,0.68-1.14) patients were marginally less likely to arrive on time. CONCLUSIONS: Factors associated with delay presentation in patients suffering acute stroke include non-white, female and presence of diabetes. Further studies and educational programs are needed to better understand and address these factors. Disclosure: Dr. Matos-Diaz has nothing to disclose. Dr. Liang has nothing to disclose. Dr. Walker has nothing to disclose. Dr. Lucido has nothing to disclose. Dr. Boniece has nothing to disclose.
Objective: To reduce the time to treament of acute ischemic strokes in the inpatient setting Back... more Objective: To reduce the time to treament of acute ischemic strokes in the inpatient setting Background: Urgent assessment and management of acute stroke is critical. A shorter time to treatment is directly associated with better patient outcomes. Studies have shown that management is prolonged in the inpatient setting compared to the emergency department (ED). Design/Methods: We did a retrospective cohort study of strokes ending in t-PA administration or endovascular intervention between 2010-2013. ED and inpatient data were compared. Variables assessed were time to neurological evaluation, time to CT-scan, time to t-PA, time from CT-scan to t-PA and time to endovascular intervention. The variables were compared using a one-tailed Student’s t-test. Once areas of delay were identified, procedure modifications were proposed. Results: 122 stroke codes included (ED=106, Inpatient=16). There was no difference in time to neurological evaluation (ED=2.80 minutes, inpatient=4.43 minutes; p=0.19). Time to CT-scan was significantly increased in the inpatient group (32.25 versus 14.93 minutes, p=<0.001). Time to t-PA was significantly prolonged in the inpatient group (80.3 versus 59.32 minutes, p=0.01). There was no difference in the time from CT-head to t-PA (p=0.09) or in the time to endovascular intervention (p=0.21). Conclusion/Proposal: In the inpatient setting there was a significant delay in the time to CT-scan and to t-PA; the main source of delay was time to CT-scan. There are many possible reasons for the delay: location of the CT-scanner, unfamiliarity with strokes by non-neurology staff, ready availability of t-PA. We proposed to target house staff education and t-PA availability. We developed a “stroke-code” checklist to be distributed to house staff from different services after a small explanatory lecture. We also developed an order form to create a zero wait time for t-PA, allowing the RN/PCA to be the first one served in the pharmacy. Once these interventions take place, we will assess if treatment times were reduced. Disclosure: Dr. Liang has nothing to disclose. Dr. Garcia Santibanez has nothing to disclose. Dr. Walker has nothing to disclose. Dr. Boniece has nothing to disclose.
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 2015
The aim of this study is to describe a case of pathologically proven cerebral amyloid angiopathy-... more The aim of this study is to describe a case of pathologically proven cerebral amyloid angiopathy-related inflammation (CAA-I) without cerebral microbleeds (CMBs) and its clinical course. CAA-I is an uncommon variant of cerebral amyloid angiopathy. Keys to diagnosis rely on the physician's awareness of this entity, CMBs on magnetic resonance imaging (MRI), an often favorable response to immunosuppression, and ultimately brain biopsy. CAA-I with no CMBs is rarely reported. A 76-year-old woman presented with 4 weeks of headaches and was found to have visual neglect on the left part of the visual field. MRI of the brain showed sulcal/gyriform hyperintensity with associated leptomeningeal enhancement in the right occipital lobe on fluid-attenuated inversion recovery (FLAIR) imaging. No CMBs or large parenchymal FLAIR lesions were seen on MRI. Biopsy was consistent with CAA-I. The patient's headaches resolved spontaneously and no immunosuppression was initiated. The patient remain...
Journal of Stroke and Cerebrovascular Diseases, 2015
Outcomes of acute stroke management are time dependent. Intravenous tissue plasminogen activator ... more Outcomes of acute stroke management are time dependent. Intravenous tissue plasminogen activator (t-PA) is indicated within 3-4.5 hours of symptom onset and endovascular intervention within 6 hours. Time to treatment may depend on the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s location. This study seeks to determine whether there is a difference in the timing of key aspects of stroke codes between the emergency room and the inpatient setting. Stroke codes ending in t-PA administration or endovascular intervention between 2010 and 2013 were included. Emergency room stroke codes were compared with those in the inpatient setting. Data were obtained from the Yarmon Stroke Center log. The variables were time to neurological evaluation, time to computed tomography (CT) scan, time to t-PA administration, time from CT scan to t-PA, and time to endovascular intervention. The variables were compared using the t test. One hundred twenty-two stroke codes were included (106 from emergency room and 16 from inpatient setting). There was no difference in the time to neurological evaluation (P = .19). The time to CT scan and to t-PA administration was significantly increased in the inpatient group (P ≤ .001 and P = .01, respectively). There was no difference in the time from CT scan to t-PA (P = .09) and in the time to endovascular intervention (P = .21). Our results show that in the inpatient setting, there was a significant delay in the time to CT scan and to t-PA administration and that the source of the delay is the time to CT scan.
Extraskeletal myxoid chondrosarcomas usually arise deep in the proximal extremities and limb gird... more Extraskeletal myxoid chondrosarcomas usually arise deep in the proximal extremities and limb girdles. Patients with this type of sarcoma have high rates of local recurrence and metastases, but do not typically have paraneoplastic syndromes. We report an unusual case of a 49-year-old man with anti-Hu syndrome in the setting of an extraskeletal myxoid chondrosarcoma. This case shows the importance of searching for antineural antibodies in oncologic patients with new neurologic deficits, and of having a judicious workup for occult malignancies in patients with known antineural antibodies.
Abstract The vulnerability of neurons to the damaging events that occur during a period of ischem... more Abstract The vulnerability of neurons to the damaging events that occur during a period of ischemia can be modulated by a wide range of peptide growth factors and by agents that modify intracellular signal transduction systems both in vivo and in vitro. Analysis of the molecular mechanism of these protective effects can help to establish how signaling cascades influence the sensitivity of neurons to ischemia. We have established two in vitro models of ischemia and used these to explore the ability of peptide growth factors to confer protection on neural cells. Using the rat PC12 cell line, we have established a model of ischemia that includes a combination of hypoglycemia and anoxia. We also established an in vitro model of ischemia using primary cultured hippocampal neurons that has been used to study both anoxia and nitric oxide toxicity. In both models, peptide growth factors are neuroprotective. Although each of the growth factors we have studied is known to activate PKC, its activation does not mimic the effects of the peptide growth factors in either model. Indeed, down-regulation of PKC or pharmacologic inhibition of PKC made PC12 cells resistant to ischemic damage. Likewise, down-regulation of PKC or inhibition of PKC activity made hippocampal neurons more resistant both to ischemia and nitric oxide toxicity. In contrast, activation of the cyclic adenosine monophosphate (cAMP) dependent protein kinases (PKA) confers protection in both model systems. The effects of PKA activation were not additive with those of the growth factors. The effects of the growth factors were equivalent in PC12 lines that contained normal levels of the PKA, or were deficient in this enzyme. Thus, there appears to be two signal transduction pathways that contribute to neural protection in both PC12 cells and hippocampal neurons. One pathway is under the control of peptide growth factors, and a second can be initiated by activation of PKA. In PC12 cells, the protective effects of nerve growth factor (NGF) are mediated through the trk receptor and are dependent on the activation of the N-kinase, a member of the MAP kinase family and a key regulator of NGF-dependent differentiation. Thus, in two quite distinct model systems, PKC appears to have a deleterious effect on neuronal survival, whereas activation of the cAMP-dependent protein kinase appears to be neuroprotective. A significant fraction of the neuronal death that occurs in hippocampal neurons during anoxia is caused by the generation of nitric oxide. Inhibition of nitric oxide synthase (NOS) reduced the extent of neuronal death, and additions of agents that generate nitric oxide is neurotoxic. Growth factors can protect against nitric oxide toxicity, and one of the major mechanisms used by peptide growth factors to protect these neurons against ischemia is to make them resistant to nitric oxide that is generated during periods of ischemia. If nitric oxide is an important mediator of ischemic damage in vivo, the source of nitric oxide must be identified. We therefore examined the expression of both the constitutive form of nitric oxide synthase (cNOS) and the inducible form of nitric oxide synthase (iNOS) after ischemia. Using in situ hybridization and the histochemical nicotinamide-adenine-dinucleotide phosphate-reduced form (NADPH) diaphorase reaction, we were able to demonstrate that pyramidal neurons in CA1, CA3, CA4, and granule cells in the dentate gyrus express cNOS. In contrast to a number of instances where neurons that express NOS are resistant to neurodegeneration, neurons in the CA1 region of the hippocampus express cNOS, but are very vulnerable to ischemia. Although NOS is not normally expressed in astrocytes, transient ischemia induces the expression of iNOS in astrocytes, as indicated by both immunohistochemistry and NADPH diaphorase histochemistry. Thus, the synthesis of nitric oxide by either neurons or astrocytes might contribute to cell death during ischemia.
Reduction or elimination of nitric oxide (NO) production in cortical neurons by NO synthase (NOS)... more Reduction or elimination of nitric oxide (NO) production in cortical neurons by NO synthase (NOS) inhibitors during glu- tamate toxicity in vitro or during focal cerebral ischemia in viva can prevent neuronal cell death. In contrast, growth factors can prevent neuronal degeneration induced by treat- ment with glutamate or potassium cyanide. We have deter- mined whether NO mediates hippocampal cell
Nerve growth factor (NGF), which has been shown to act as a morphological and neurochemical diffe... more Nerve growth factor (NGF), which has been shown to act as a morphological and neurochemical differentiating factor in PC12 cells, also protects PC12 cells from the toxicity of serum withdrawal and ischemia. By using a previously established in vitro model of ischemia, which incorporates the combination of anoxia with glucose deprivation (Boniece and Wagner: J Neurosci 13:4220-4228, 1993), we have been able to study the signal transduction pathways upon which NGF-induced survival is dependent. Here we demonstrate that inhibitors of the N-kinase and NGF-induced neuritogenesis, 6-thioguanine and 2-aminopurine, prevent the protective effects of NGF, while they have little, if any, effect on the protection conferred by epidermal growth factor (EGF) or dbcAMP. This suggests that only NGF acts by a mechanism that depends strongly on the N-kinase. Furthermore, the methyltransferase inhibitor 5&#39;-deoxy-5&#39;-methylthioadenosine (MTA), which also inhibits NGF-induced neuritogenesis, inhibits the protective effect of NGF but not the protective effects of EGF or dbcAMP. Thus, the neuroprotective effect of NGF requires some of the same signal transduction steps used by NGF to promote differentiation and neurite formation. Furthermore, we found that exposure of PC12 cells to retinoic acid, which promotes the differentiation and inhibits the growth of PC12 cells, also improves cell survival during ischemia. In addition, a combination of NGF and retinoic acid was more effective than either agent alone. It is likely that these two agents confer protection by independent pathways.
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