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Clinical Reasoning: Patient With Prior Spinal Cord Injury Who Developed Altered Mental Status After a Fall

Dessy, Alexa; Bhagat, Dhristie; Czeisler, Barry M
An 18-year-old male with a history of complete traumatic spinal cord injury (SCI) at C5-C7 three years prior presented with unresponsiveness and hypoxia after a fall. There were no overt signs of bruising or swelling. After extensive and unrevealing initial workup, MRI brain without contrast showed numerous diffusely scattered punctate foci of diffusion restriction and evidence of numerous microhemorrhages. A full body skeletal survey revealed mildly impacted, nondisplaced, incomplete fractures in the distal femoral metaphyses bilaterally. This case presentation discusses specific considerations for patients with SCI, reviewing the differential diagnosis, workup and management of altered mental status after minor falls or other trauma in this population.
PMID: 36175149
ISSN: 1526-632x
CID: 5334552

Social Determinants of Health Attenuate the Relationship Between Race and Ethnicity and White Matter Hyperintensity Severity but not Microbleed Presence in Patients with Intracerebral Hemorrhage

Bauman, Kristie M; Yaghi, Shadi; Lewis, Ariane; Agarwal, Shashank; Changa, Abhinav; Dogra, Siddhant; Litao, Miguel; Sanger, Matthew; Lord, Aaron; Ishida, Koto; Zhang, Cen; Czeisler, Barry; Torres, Jose; Dehkharghani, Seena; Frontera, Jennifer A; Melmed, Kara R
BACKGROUND:The association between race and ethnicity and microvascular disease in patients with intracerebral hemorrhage (ICH) is unclear. We hypothesized that social determinants of health (SDOHs) mediate the relationship between race and ethnicity and severity of white matter hyperintensities (WMHs) and microbleeds in patients with ICH. METHODS:We performed a retrospective observational cohort study of patients with ICH at two tertiary care hospitals between 2013 and 2020 who underwent magnetic resonance imaging of the brain. Magnetic resonance imaging scans were evaluated for the presence of microbleeds and WMH severity (defined by the Fazekas scale; moderate to severe WMH defined as Fazekas scores 3-6). We assessed for associations between sex, race and ethnicity, employment status, median household income, education level, insurance status, and imaging biomarkers of microvascular disease. A mediation analysis was used to investigate the influence of SDOHs on the associations between race and imaging features. We assessed the relationship of all variables with discharge outcomes. RESULTS:We identified 233 patients (mean age 62 [SD 16]; 48% female) with ICH. Of these, 19% were Black non-Hispanic, 32% had a high school education or less, 21% required an interpreter, 11% were unemployed, and 6% were uninsured. Moderate to severe WMH, identified in 114 (50%) patients, was associated with age, Black non-Hispanic race and ethnicity, highest level of education, insurance status, and history of hypertension, hyperlipidemia, or diabetes (p < 0.05). In the mediation analysis, the proportion of the association between Black non-Hispanic race and ethnicity and the Fazekas score that was mediated by highest level of education was 65%. Microbleeds, present in 130 (57%) patients, was associated with age, highest level of education, and history of diabetes or hypertension (p < 0.05). Age, highest level of education, insurance status, and employment status were associated with discharge modified Rankin Scale scores of 3-6, but race and ethnicity was not. CONCLUSIONS:The association between Black non-Hispanic race and ethnicity and moderate to severe WMH lost significance after we adjusted for highest level of education, suggesting that SDOHs may mediate the association between race and ethnicity and microvascular disease.
PMID: 34918215
ISSN: 1556-0961
CID: 5084672

Hemorrhagic Conversion Of Ischemic Stroke Is Associated With Hematoma Expansion [Meeting Abstract]

Palaychuk, Natalie; Changa, Abhinav; Dogra, Siddhant; Wei, Jason; Lewis, Ariane; Lord, Aaron; Ishida, Koto; Zhang, Cen; Czeisler, Barry M.; Torres, Jose L.; Frontera, Jennifer; Dehkharghani, Seena; Melmed, Kara R.
ISI:000788100600385
ISSN: 0039-2499
CID: 5243802

Toxic Metabolic Encephalopathy in Hospitalized Patients with COVID-19

Frontera, Jennifer A; Melmed, Kara; Fang, Taolin; Granger, Andre; Lin, Jessica; Yaghi, Shadi; Zhou, Ting; Lewis, Ariane; Kurz, Sebastian; Kahn, D Ethan; de Havenon, Adam; Huang, Joshua; Czeisler, Barry M; Lord, Aaron; Meropol, Sharon B; Troxel, Andrea B; Wisniewski, Thomas; Balcer, Laura; Galetta, Steven
BACKGROUND:Toxic metabolic encephalopathy (TME) has been reported in 7-31% of hospitalized patients with coronavirus disease 2019 (COVID-19); however, some reports include sedation-related delirium and few data exist on the etiology of TME. We aimed to identify the prevalence, etiologies, and mortality rates associated with TME in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients. METHODS:We conducted a retrospective, multicenter, observational cohort study among patients with reverse transcriptase-polymerase chain reaction-confirmed SARS-CoV-2 infection hospitalized at four New York City hospitals in the same health network between March 1, 2020, and May 20, 2020. TME was diagnosed in patients with altered mental status off sedation or after an adequate sedation washout. Patients with structural brain disease, seizures, or primary neurological diagnoses were excluded. The coprimary outcomes were the prevalence of TME stratified by etiology and in-hospital mortality (excluding comfort care only patients) assessed by using a multivariable time-dependent Cox proportional hazards models with adjustment for age, race, sex, intubation, intensive care unit requirement, Sequential Organ Failure Assessment scores, hospital location, and date of admission. RESULTS:Among 4491 patients with COVID-19, 559 (12%) were diagnosed with TME, of whom 435 of 559 (78%) developed encephalopathy immediately prior to hospital admission. The most common etiologies were septic encephalopathy (n = 247 of 559 [62%]), hypoxic-ischemic encephalopathy (HIE) (n = 331 of 559 [59%]), and uremia (n = 156 of 559 [28%]). Multiple etiologies were present in 435 (78%) patients. Compared with those without TME (n = 3932), patients with TME were older (76 vs. 62 years), had dementia (27% vs. 3%) or psychiatric history (20% vs. 10%), were more often intubated (37% vs. 20%), had a longer hospital length of stay (7.9 vs. 6.0 days), and were less often discharged home (25% vs. 66% [all P < 0.001]). Excluding comfort care patients (n = 267 of 4491 [6%]) and after adjustment for confounders, TME remained associated with increased risk of in-hospital death (n = 128 of 425 [30%] patients with TME died, compared with n = 600 of 3799 [16%] patients without TME; adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.02-1.52, P = 0.031), and TME due to hypoxemia conferred the highest risk (n = 97 of 233 [42%] patients with HIE died, compared with n = 631 of 3991 [16%] patients without HIE; aHR 1.56, 95% CI 1.21-2.00, P = 0.001). CONCLUSIONS:TME occurred in one in eight hospitalized patients with COVID-19, was typically multifactorial, and was most often due to hypoxemia, sepsis, and uremia. After we adjustment for confounding factors, TME was associated with a 24% increased risk of in-hospital mortality.
PMCID:7962078
PMID: 33725290
ISSN: 1556-0961
CID: 4817682

Anticoagulation use and Hemorrhagic Stroke in SARS-CoV-2 Patients Treated at a New York Healthcare System

Kvernland, Alexandra; Kumar, Arooshi; Yaghi, Shadi; Raz, Eytan; Frontera, Jennifer; Lewis, Ariane; Czeisler, Barry; Kahn, D Ethan; Zhou, Ting; Ishida, Koto; Torres, Jose; Riina, Howard A; Shapiro, Maksim; Nossek, Erez; Nelson, Peter K; Tanweer, Omar; Gordon, David; Jain, Rajan; Dehkharghani, Seena; Henninger, Nils; de Havenon, Adam; Grory, Brian Mac; Lord, Aaron; Melmed, Kara
BACKGROUND AND PURPOSE/OBJECTIVE:While the thrombotic complications of COVID-19 have been well described, there are limited data on clinically significant bleeding complications including hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this particular subset of patients are especially salient as therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19. METHODS:We conducted a retrospective cohort study of patients with hemorrhagic stroke (both non-traumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between March 1, 2020, and May 15, 2020, within a major healthcare system in New York, during the coronavirus pandemic. Patients with hemorrhagic stroke on admission and who developed hemorrhage during hospitalization were both included. We compared the clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital system between March 1, 2020, and May 15, 2020 (contemporary controls), and March 1, 2019, and May 15, 2019 (historical controls). Demographic variables and clinical characteristics between the individual groups were compared using Fischer's exact test for categorical variables and nonparametric test for continuous variables. We adjusted for multiple comparisons using the Bonferroni method. RESULTS:During the study period in 2020, out of 4071 patients who were hospitalized with COVID-19, we identified 19 (0.5%) with hemorrhagic stroke. Of all COVID-19 with hemorrhagic stroke, only three had isolated non-aneurysmal SAH with no associated intraparenchymal hemorrhage. Among hemorrhagic stroke in patients with COVID-19, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% of these patients versus 4.2% in contemporary controls (p ≤ .001) and 10.0% in historical controls (p ≤ .001). Compared to contemporary and historical controls, patients with COVID-19 had higher initial NIHSS scores, INR, PTT, and fibrinogen levels. Patients with COVID-19 also had higher rates of in-hospital mortality (84.6% vs. 4.6%, p ≤ 0.001). Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results. CONCLUSION/CONCLUSIONS:We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in patients with COVID-19 infection occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in patients with COVID-19.
PMCID:7444897
PMID: 32839867
ISSN: 1556-0961
CID: 4574182

Systemic Inflammatory Response Syndrome is Associated with Hematoma Expansion in Intracerebral Hemorrhage

Melmed, Kara R; Carroll, Elizabeth; Lord, Aaron S; Boehme, Amelia K; Ishida, Koto; Zhang, Cen; Torres, Jose L; Yaghi, Shadi; Czeisler, Barry M; Frontera, Jennifer A; Lewis, Ariane
OBJECTIVES/OBJECTIVE:Systemic inflammatory response syndrome (SIRS) and hematoma expansion are independently associated with worse outcomes after intracerebral hemorrhage (ICH), but the relationship between SIRS and hematoma expansion remains unclear. MATERIALS AND METHODS/METHODS:We performed a retrospective review of patients admitted to our hospital from 2013 to 2020 with primary spontaneous ICH with at least two head CTs within the first 24 hours. The relationship between SIRS and hematoma expansion, defined as ≥6 mL or ≥33% growth between the first and second scan, was assessed using univariable and multivariable regression analysis. We assessed the relationship of hematoma expansion and SIRS on discharge mRS using mediation analysis. RESULTS:Of 149 patients with ICH, 83 (56%; mean age 67±16; 41% female) met inclusion criteria. Of those, 44 (53%) had SIRS. Admission systolic blood pressure (SBP), temperature, antiplatelet use, platelet count, initial hematoma volume and rates of infection did not differ between groups (all p>0.05). Hematoma expansion occurred in 15/83 (18%) patients, 12 (80%) of whom also had SIRS. SIRS was significantly associated with hematoma expansion (OR 4.5, 95% CI 1.16 - 17.39, p= 0.02) on univariable analysis. The association remained statistically significant after adjusting for admission SBP and initial hematoma volume (OR 5.72, 95% CI 1.40 - 23.41, p= 0.02). There was a significant indirect effect of SIRS on discharge mRS through hematoma expansion. A significantly greater percentage of patients with SIRS had mRS 4-6 at discharge (59 vs 33%, p=0.02). CONCLUSION/CONCLUSIONS:SIRS is associated with hematoma expansion of ICH within the first 24 hours, and hematoma expansion mediates the effect of SIRS on poor outcome.
PMID: 34077823
ISSN: 1532-8511
CID: 4891632

A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications

Frontera, Jennifer A; Yang, Dixon; Lewis, Ariane; Patel, Palak; Medicherla, Chaitanya; Arena, Vito; Fang, Taolin; Andino, Andres; Snyder, Thomas; Madhavan, Maya; Gratch, Daniel; Fuchs, Benjamin; Dessy, Alexa; Canizares, Melanie; Jauregui, Ruben; Thomas, Betsy; Bauman, Kristie; Olivera, Anlys; Bhagat, Dhristie; Sonson, Michael; Park, George; Stainman, Rebecca; Sunwoo, Brian; Talmasov, Daniel; Tamimi, Michael; Zhu, Yingrong; Rosenthal, Jonathan; Dygert, Levi; Ristic, Milan; Ishii, Haruki; Valdes, Eduard; Omari, Mirza; Gurin, Lindsey; Huang, Joshua; Czeisler, Barry M; Kahn, D Ethan; Zhou, Ting; Lin, Jessica; Lord, Aaron S; Melmed, Kara; Meropol, Sharon; Troxel, Andrea B; Petkova, Eva; Wisniewski, Thomas; Balcer, Laura; Morrison, Chris; Yaghi, Shadi; Galetta, Steven
BACKGROUND:Little is known regarding long-term outcomes of patients hospitalized with COVID-19. METHODS:We conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. RESULTS:Of 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N = 196 neurological patients and N = 186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 1.98, 95%CI 1.23-3.48, P = 0.02), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P = 0.01) and were less likely to return to work than controls (41% versus 64%, P = 0.04). Cognitive and Neuro-QOL metrics were similar between groups. CONCLUSIONS:Abnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.
PMCID:8113108
PMID: 34000678
ISSN: 1878-5883
CID: 4876752

Risk factors for intracerebral hemorrhage in patients with COVID-19

Melmed, Kara R; Cao, Meng; Dogra, Siddhant; Zhang, Ruina; Yaghi, Shadi; Lewis, Ariane; Jain, Rajan; Bilaloglu, Seda; Chen, Ji; Czeisler, Barry M; Raz, Eytan; Lord, Aaron; Berger, Jeffrey S; Frontera, Jennifer A
Intracerebral hemorrhage (ICH) can be a devastating complication of coronavirus disease (COVID-19). We aimed to assess risk factors associated with ICH in this population. We performed a retrospective cohort study of adult patients admitted to NYU Langone Health system between March 1 and April 27 2020 with a positive nasopharyngeal swab polymerase chain reaction test result and presence of primary nontraumatic intracranial hemorrhage or hemorrhagic conversion of ischemic stroke on neuroimaging. Patients with intracranial procedures, malignancy, or vascular malformation were excluded. We used regression models to estimate odds ratios and 95% confidence intervals (OR, 95% CI) of the association between ICH and covariates. We also used regression models to determine association between ICH and mortality. Among 3824 patients admitted with COVID-19, 755 patients had neuroimaging and 416 patients were identified after exclusion criteria were applied. The mean (standard deviation) age was 69.3 (16.2), 35.8% were women, and 34.9% were on therapeutic anticoagulation. ICH occurred in 33 (7.9%) patients. Older age, non-Caucasian race, respiratory failure requiring mechanical ventilation, and therapeutic anticoagulation were associated with ICH on univariate analysis (p < 0.01 for each variable). In adjusted regression models, anticoagulation use was associated with a five-fold increased risk of ICH (OR 5.26, 95% CI 2.33-12.24, p < 0.001). ICH was associated with increased mortality (adjusted OR 2.6, 95 % CI 1.2-5.9). Anticoagulation use is associated with increased risk of ICH in patients with COVID-19. Further investigation is required to elucidate underlying mechanisms and prevention strategies in this population.
PMID: 32968850
ISSN: 1573-742x
CID: 4605862

Intra-arterial thrombolytic therapy for acute anterior spinal artery stroke

Haynes, Joseph; Shapiro, Maksim; Raz, Eytan; Czeisler, Barry; Nossek, Erez
BACKGROUND AND IMPORTANCE/BACKGROUND:Spinal cord infarction is rare but can be extremely disabling. Prompt diagnosis and treatment of these infarcts is important for patient outcomes. While intravenous thrombolytic therapy is a well-established form of treatment in circumstances of cerebral stroke, it has only recently been successfully used in a few incidents of spinal cord ischemia. We present a case of anterior spinal artery (ASA) territory ischemia treated with ASA intra-arterial thrombolytic therapy. CLINICAL PRESENTATION/METHODS:A 52-year-old male presented with acute onset of severe lumbar pain, rapidly progressing paraplegia and loss of pain and temperature sensation, with preservation of proprioception and vibratory sensation at the L1 level and below on the right and at the L3 level and below on the left. MRI showed restricted diffusion involving the cord at and below L1 level, with normal cord T2 signal. Digital subtraction spinal angiography showed ASA cutoff in the descending limb at the level of L1. Intra-arterial tissue plasminogen activator (t-PA) combined with verapamil and eptifibatide was administered within the ASA and the patient had significant neurological improvement immediately postoperatively and at 8-month clinical follow-up. CONCLUSION/CONCLUSIONS:Direct ASA intra-arterial thrombolysis is feasible, and this drug combination might be an effective therapy for spinal stroke.
PMID: 33358345
ISSN: 1532-2653
CID: 4731222

A Prospective Study of Neurologic Disorders in Hospitalized COVID-19 Patients in New York City

Frontera, Jennifer A; Sabadia, Sakinah; Lalchan, Rebecca; Fang, Taolin; Flusty, Brent; Millar-Vernetti, Patricio; Snyder, Thomas; Berger, Stephen; Yang, Dixon; Granger, Andre; Morgan, Nicole; Patel, Palak; Gutman, Josef; Melmed, Kara; Agarwal, Shashank; Bokhari, Matthew; Andino, Andres; Valdes, Eduard; Omari, Mirza; Kvernland, Alexandra; Lillemoe, Kaitlyn; Chou, Sherry H-Y; McNett, Molly; Helbok, Raimund; Mainali, Shraddha; Fink, Ericka L; Robertson, Courtney; Schober, Michelle; Suarez, Jose I; Ziai, Wendy; Menon, David; Friedman, Daniel; Friedman, David; Holmes, Manisha; Huang, Joshua; Thawani, Sujata; Howard, Jonathan; Abou-Fayssal, Nada; Krieger, Penina; Lewis, Ariane; Lord, Aaron S; Zhou, Ting; Kahn, D Ethan; Czeisler, Barry M; Torres, Jose; Yaghi, Shadi; Ishida, Koto; Scher, Erica; de Havenon, Adam; Placantonakis, Dimitris; Liu, Mengling; Wisniewski, Thomas; Troxel, Andrea B; Balcer, Laura; Galetta, Steven
OBJECTIVE:To determine the prevalence and associated mortality of well-defined neurologic diagnoses among COVID-19 patients, we prospectively followed hospitalized SARS-Cov-2 positive patients and recorded new neurologic disorders and hospital outcomes. METHODS:We conducted a prospective, multi-center, observational study of consecutive hospitalized adults in the NYC metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between COVID-19 patients with and without neurologic disorders. RESULTS:Of 4,491 COVID-19 patients hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were: toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis, or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were RT-PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all P<0.05). After adjusting for age, sex, SOFA-scores, intubation, past history, medical complications, medications and comfort-care-status, COVID-19 patients with neurologic disorders had increased risk of in-hospital mortality (Hazard Ratio[HR] 1.38, 95% CI 1.17-1.62, P<0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, P<0.001). CONCLUSIONS:Neurologic disorders were detected in 13.5% of COVID-19 patients and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.
PMID: 33020166
ISSN: 1526-632x
CID: 4626712