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SARS-CoV-2 Is Not Detected in the Cerebrospinal Fluid of Encephalopathic COVID-19 Patients

Placantonakis, Dimitris G; Aguero-Rosenfeld, Maria; Flaifel, Abdallah; Colavito, John; Inglima, Kenneth; Zagzag, David; Snuderl, Matija; Louie, Eddie; Frontera, Jennifer Ann; Lewis, Ariane
Neurologic manifestations of the novel coronavirus SARS-CoV-2 infection have received wide attention, but the mechanisms remain uncertain. Here, we describe computational data from public domain RNA-seq datasets and cerebrospinal fluid data from adult patients with severe COVID-19 pneumonia that suggest that SARS-CoV-2 infection of the central nervous system is unlikely. We found that the mRNAs encoding the ACE2 receptor and the TMPRSS2 transmembrane serine protease, both of which are required for viral entry into host cells, are minimally expressed in the major cell types of the brain. In addition, CSF samples from 13 adult encephalopathic COVID-19 patients diagnosed with the viral infection via nasopharyngeal swab RT-PCR did not show evidence for the virus. This particular finding is robust for two reasons. First, the RT-PCR diagnostic was validated for CSF studies using stringent criteria; and second, 61% of these patients had CSF testing within 1 week of a positive nasopharyngeal diagnostic test. We propose that neurologic sequelae of COVID-19 are not due to SARS-CoV-2 meningoencephalitis and that other etiologies are more likely mechanisms.
PMCID:7759491
PMID: 33362695
ISSN: 1664-2295
CID: 4731452

The National Institutes of Health COVID-19 NeuroDatabank and NeuroBiobank: A National Resource for Learning, Discovery, and Progress

Troxel, Andrea B; Frontera, Jennifer A; Mendoza-Puccini, Carolina
Patients suffering from COVID-19 experience a wide range of symptoms and sequelae, including increasingly recognized neurological problems. A concerted effort is necessary to identify and characterize these issues, whether newly appearing as a result of COVID-19 disease or exacerbations of underlying conditions. A national resource to collect information and/or biospecimens regarding neurological complications of COVID-19 offers an opportunity for broad representation, harmonization, and rapid learning, all while ensuring robust protection of confidential information through the use of global unique identifiers to protect patient privacy.
PMCID:7843568
PMID: 33519693
ISSN: 1664-2295
CID: 4799602

Redefining Early Neurological Improvement After Reperfusion Therapy in Stroke

Agarwal, Shashank; Cutting, Shawna; Grory, Brian Mac; Burton, Tina; Jayaraman, Mahesh; McTaggart, Ryan; Reznik, Michael; Scher, Erica; Chang, Andrew D; Frontera, Jennifer; Lord, Aaron; Rostanski, Sara; Ishida, Koto; Torres, Jose; Furie, Karen; Yaghi, Shadi
BACKGROUND AND PURPOSE/OBJECTIVE:Early neurologic improvement (ENI) in patients treated with alteplase has been shown to correlate with functional outcome. However, the definition of ENI remains controversial and has varied across studies. We hypothesized that ENI defined as a percentage change in the National Institute of Health Stroke Scale (NIHSS) score (percent change NIHSS score) at 24-hours would better correlate with favorable outcomes at 3 months than ENI defined as the change in NIHSS score (delta NIHSS score) at 24 hours. METHODS:Retrospective analysis of prospectively collected single-center quality improvement data was performed of all acute ischemic stroke (AIS) patients treated with alteplase. We examined delta NIHSS score and percent change NIHSS score in unadjusted and adjusted logistic regression models as predictors of a favorable outcome at 3 months (defined as mRS 0-1). RESULTS:Among 586 patients who met the inclusion criteria, 194 (33.1%) had a favorable outcome at 3 months. In fully adjusted models, both delta NIHSS score (OR per point decrease 1.27; 95% confidence interval [CI] 1.19-1.36) and percent change NIHSS score (OR per 10 percent decrease 1.17; 95% CI 1.12-1.22) were associated with favorable functional outcome at 3 months. Receiver operating characteristic (ROC) curve comparison showed that the area under the ROC curve for percent change NIHSS score (.755) was greater than delta NIHSS score (.613) or admission NIHSS (.694). CONCLUSIONS:Percentage change in NIHSS score may be a better surrogate marker of ENI and functional outcome in AIS patients after receiving acute thrombolytic therapy. More studies are needed to confirm our findings.
PMID: 31836356
ISSN: 1532-8511
CID: 4241792

Predicting symptomatic intracranial haemorrhage after mechanical thrombectomy: the TAG score

Montalvo, Mayra; Mistry, Eva; Chang, Andrew Davey; Yakhkind, Aleksandra; Dakay, Katarina; Azher, Idrees; Kaushal, Ashutosh; Mistry, Akshitkumar; Chitale, Rohan; Cutting, Shawna; Burton, Tina; Mac Grory, Brian; Reznik, Michael; Mahta, Ali; Thompson, Bradford B; Ishida, Koto; Frontera, Jennifer; Riina, Howard A; Gordon, David; Parella, David; Scher, Erica; Farkas, Jeffrey; McTaggart, Ryan; Khatri, Pooja; Furie, Karen L; Jayaraman, Mahesh; Yaghi, Shadi
BACKGROUND:There is limited data on predictors of symptomatic intracranial haemorrhage (sICH) in patients who underwent mechanical thrombectomy. In this study, we aim to determine those predictors with external validation. METHODS:and t tests to identify independent predictors of sICH with p<0.1. Significant variables were then combined in a multivariate logistic regression model to derive an sICH prediction score. This score was then validated using data from the Blood Pressure After Endovascular Treatment multicentre prospective registry. RESULTS:We identified 578 patients with acute ischaemic stroke who received thrombectomy, 19 had sICH (3.3%). Predictive factors of sICH were: thrombolysis in cerebral ischaemia (TICI) score, Alberta stroke program early CT score (ASPECTS), and glucose level, and from these predictors, we derived the weighted TICI-ASPECTS-glucose (TAG) score, which was associated with sICH in the derivation (OR per unit increase 1.98, 95% CI 1.48 to 2.66, p<0.001, area under curve ((AUC)=0.79) and validation (OR per unit increase 1.48, 95% CI 1.22 to 1.79, p<0.001, AUC=0.69) cohorts. CONCLUSION/CONCLUSIONS:High TAG scores are associated with sICH in patients receiving mechanical thrombectomy. Larger studies are needed to validate this scoring system and test strategies to reduce sICH risk and make thrombectomy safer in patients with elevated TAG scores.
PMID: 31427365
ISSN: 1468-330x
CID: 4046642

Stroke Risk Following Infection in Patients with Continuous-Flow Left Ventricular Assist Device

Cho, Sung-Min; Moazami, Nader; Katz, Stuart; Bhimraj, Adarsh; Shrestha, Nabin K; Frontera, Jennifer A
BACKGROUND:Infection has been associated with stroke in patients with left ventricular assist devices (LVAD); however, little data exist on the timing, type and mortality impact of infection-related stroke. METHODS:Prospectively collected data of HeartMate II (N = 332) and HeartWare (N = 70) LVAD patients from a single center were reviewed. Only strokes (ischemic or hemorrhagic) that occurred within 6 weeks following a LVAD infection were considered in analyses. The association between LVAD infections (wound, pump pocket, driveline and/or bloodstream infection [BSI]), specific pathogens and ischemic and hemorrhagic strokes was evaluated using multivariable logistic regression analysis. The impact of infection-related stroke on cumulative survival was assessed using Kaplan-Meier analysis. RESULTS:Of 402 patients, LVAD infection occurred in 158 (39%) including BSI in 107 (27%), driveline infection in 67 (17%), wound infection in 31 (8%) and pump pocket infection in 24 (6%). LVAD infection-related stroke occurred in 20/158 (13%) patients in a median of 4 days (0-36 days) from documented infection. In multivariable analysis, ischemic stroke was associated with wound infection (aOR 9.0, 95% CI 2.4-34.0, P = 0.001) and BSI (aOR 7.7, 95% CI 0.9-66.0, P = 0.064), and hemorrhagic stroke was associated with BSI in 100% of cases (P = 0.01). There was no association with driveline or pump pocket infection. The cumulative survival rate among patients with infection-related stroke was significantly lower compared to those with LVAD infection but no stroke (log-rank P < 0.001). There was a trend toward shorter stroke-free survival among patients with LVAD infection. CONCLUSIONS:LVAD infections, particularly BSI, are significantly associated with stroke, and infection-related stroke conferred significantly lower cumulative survival.
PMID: 30644037
ISSN: 1556-0961
CID: 3595252

Reversal and Resumption of Antithrombotic Therapy in LVAD- Associated Intracranial Hemorrhage

Cho, Sung-Min; Moazami, Nader; Katz, Stuart; Starling, Randall; Frontera, Jennifer A
BACKGROUND:Little data exists regarding reversal and resumption of antithrombotics following left ventricular assist device (LVAD)-associated intracranial hemorrhage (ICH). METHODS:Prospectively collected data of LVAD patients with ICH was reviewed. Coagulopathy reversal agents, antithrombotic regimens and thrombotic (venous thromboembolism, ischemic stroke, myocardial infarction) and hemorrhagic (recurrent ICH, gastrointestinal bleed, anemia requiring transfusion) complications were recorded. RESULTS:Of 405 patients, intracranial hemorrhage occurred in 39 (10%): 23 intracerebral hemorrhages, 10 subarachnoid hemorrhages, and 6 subdural hematomas. Of 27 patients who received antithrombotic reversal, 8 (30%) had inadequate coagulopathy reversal and 3 of these had hemorrhage expansion or died before repeat imaging. One (4%) had a thrombotic complication (deep vein thrombosis). Antithrombotic therapy was resumed in 17(100%) survivors in a median time 8 days for antiplatelet agents, and 14 days for warfarin. Recurrent intracranial hemorrhage occurred within a median of 7 days of antithrombotic resumption, while ischemic stroke occurred in a median of 428 days. Patients who resumed antiplatelets alone (N=4) had a trend toward more thrombotic events (1.37 vs. 0.14 events-per-patient-year [EPPY],P=0.08), including more fatal thrombotic events (0.34 EPPY vs. 0.08, P=0.89) compared to those resuming warfarin±antiplatelet (N=14). Non-fatal hemorrhage event rates were 0.34 EPPY in the warfarin±antiplatelet vs. 0 EPPY in the antiplatelet alone group (P=0.16). No fatal hemorrhagic events occurred. CONCLUSIONS:Reversal of anticoagulation appears safe following LVAD-associated intracranial hemorrhage, though inadequate reversal was common. Resumption of warfarin±antiplatelet was associated with fewer fatal and non-fatal thrombotic events compared to antiplatelets alone, though more non-fatal hemorrhage events occurred.
PMID: 30763560
ISSN: 1552-6259
CID: 3656352

Journal Club: Association between aspirin dose and subarachnoid hemorrhage from saccular aneurysms: A case-control study

Agarwal, Shashank; Zhou, Ting; Frontera, Jennifer
PMID: 31061211
ISSN: 1526-632x
CID: 3900862

How Does Preexisting Hypertension Affect Patients with Intracerebral Hemorrhage?

Valentine, David; Lord, Aaron S; Torres, Jose; Frontera, Jennifer; Ishida, Koto; Czeisler, Barry M; Lee, Fred; Rosenthal, Jonathan; Calahan, Thomas; Lewis, Ariane
BACKGROUND AND PURPOSE/OBJECTIVE:Patients with intracerebral hemorrhage (ICH) frequently present with hypertension, but it is unclear if this is due to pre-existing hypertension (prHTN) or to the bleed itself or associated pain. We sought to assess the relationship between prHTN and admission systolic blood pressure (aBP) and bleed severity. METHODS:We retrospectively assessed the relationship between prHTN and aBP and NIHSS in patients with ICH at 3 institutions. RESULTS:Of 251 patients, 170 (68%) had prHTN based on history of hypertension/antihypertensive use. Median aBP was significantly higher in those with prHTN (155 mm Hg (IQR 135-181) versus 139 mm Hg (IQR 124-158), P < .001). Patients with left ventricular hypertrophy (LVH) on electrocardiogram (ECG) or transthoracic echocardiogram (TTE) had significantly higher aBP than those without LVH (median aBP 195 mm Hg (IQR 155-216) for patients with LVH on ECG versus 147 mm Hg (IQR 129-163) for patients with no LVH on ECG, P < .001; median aBP 181 mm Hg (IQR 153-214) for patients with LVH on TTE versus 152 mm Hg (IQR 137-169) for patients with no LVH on TTE, P = .01). prHTN was associated with a higher median NIHSS (11 (IQR 3-20) for patients with history of hypertension/antihypertensive use versus 6 (IQR 1-14) for patients without this history (P = .02); 9 (IQR 3-19) versus 5 (IQR 2-13) for patients with/without LVH on ECG (P = .085); and 10 (IQR 5-18) versus 5 (IQR 1-13) for patients with/without LVH on TTE (P = .046). CONCLUSIONS:Patients with ICH who have prHTN have higher aBP and NIHSS, suggesting that prHTN may worsen reactive hypertension in the setting of ICH.
PMID: 30553645
ISSN: 1532-8511
CID: 3554632

Racial Disparity in the Development of Seizure as a Delayed Complication of Subdural Hematoma [Meeting Abstract]

Brown, Stacy C.; King, Zachary; Kuohn, Lindsey; Kamel, Hooman; Gilmore, Emily; Frontera, Jennifer; Falcone, Guido; Sheth, Kevin
ISI:000475965902155
ISSN: 0028-3878
CID: 4028972

Performance and Yield of MRI in Patients with Deep Intracerebral Hemorrhage [Meeting Abstract]

Moretti, Luke; Frontera, Jennifer; Lord, Aaron; Torres, Jose; Ishida, Koto; Czeisler, Barry; Lewis, Ariane
ISI:000475965903208
ISSN: 0028-3878
CID: 4029152