Cerebral Venous Thrombosis in COVID-19: A New York Metropolitan Cohort Study.

BACKGROUND AND PURPOSE: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection is associated with hypercoagulability. We sought to evaluate the demographic and clinical characteristics of cerebral venous thrombosis among patients hospitalized for coronavirus disease 2019 (COVID-19) at 6 tertiary care centers in the New York City metropolitan area. MATERIALS AND METHODS: We conducted a retrospective multicenter cohort study of 13,500 consecutive patients with COVID-19 who were hospitalized between March 1 and May 30, 2020. RESULTS: Of 13,500 patients with COVID-19, twelve had imaging-proved cerebral venous thrombosis with an incidence of 8.8 per 10,000 during 3 months, which is considerably higher than the reported incidence of cerebral venous thrombosis in the general population of 5 per million annually. There was a male preponderance (8 men, 4 women) and an average age of 49 years (95% CI, 36-62 years; range, 17-95 years). Only 1 patient (8%) had a history of thromboembolic disease. Neurologic symptoms secondary to cerebral venous thrombosis occurred within 24 hours of the onset of the respiratory and constitutional symptoms in 58% of cases, and 75% had venous infarction, hemorrhage, or both on brain imaging. Management consisted of anticoagulation, endovascular thrombectomy, and surgical hematoma evacuation. The mortality rate was 25%. CONCLUSIONS: Early evidence suggests a higher-than-expected frequency of cerebral venous thrombosis among patients hospitalized for COVID-19. Cerebral venous thrombosis should be included in the differential diagnosis of neurologic syndromes associated with SARS-CoV-2 infection.

Multi-Center Study of Diffusion-Weighted Imaging in Coma After Cardiac Arrest.

BACKGROUND: The ability to predict outcomes in acutely comatose cardiac arrest survivors is limited. Brain diffusion-weighted magnetic resonance imaging (DWI MRI) has been shown in initial studies to be a simple and effective prognostic tool. This study aimed to determine the predictive value of previously defined DWI MRI thresholds in a multi-center cohort. METHODS: DWI MRIs of comatose post-cardiac arrest patients were analyzed in this multi-center retrospective observational study. Poor outcome was defined as failure to regain consciousness within 14 days and/or death during the hospitalization. The apparent diffusion coefficient (ADC) value of each brain voxel was determined. ADC thresholds and brain volumes below each threshold were analyzed for their correlation with outcome. RESULTS: 125 patients were included in the analysis. 33 patients (26%) had a good outcome. An ADC value of less than 650 × 10(-6) mm(2)/s in ≥10% of brain volume was highly specific [91% (95% CI 75-98)] and had a good sensitivity [72% (95% CI 61-80)] for predicting poor outcome. This threshold remained an independent predictor of poor outcome in multivariable analysis (p = 0.002). An ADC value of less than 650 × 10(-6) mm(2)/s in >22% of brain volume was needed to achieve 100% specificity for poor outcome. CONCLUSIONS: In patients who remain comatose after cardiac arrest, quantitative DWI MRI findings correlate with early recovery of consciousness. A DWI MRI threshold of 650 × 10(-6) mm(2)/s in ≥10% of brain volume can differentiate patients with good versus poor outcome, though in this patient population the threshold was not 100% specific for poor outcome.

Unplanned Transfers from Hospital Wards to the Neurological Intensive Care Unit.

BACKGROUND: The aim of this study is to evaluate the characteristics of unplanned transfers of adult patients from hospital wards to a neurological intensive care unit (NICU). METHODS: We retrospectively reviewed consecutive unplanned transfers from hospital wards to the NICU at our institution over a 3-year period. In-hospital mortality rates were compared between patients readmitted to the NICU ("bounce-back transfers") and patients admitted to hospital wards from sources other than the NICU who were then transferred to the NICU ("incident transfers"). We also measured clinical characteristics of transfers, including source of admission and indication for transfer. RESULTS: A total of 446 unplanned transfers from hospital wards to the NICU occurred, of which 39% were bounce-back transfers. The in-hospital mortality rate associated with all unplanned transfers to the NICU was 17% and did not differ significantly between bounce-back transfers and incident transfers. Transfers to the NICU within 24 h of admission to a floor service accounted for 32% of all transfers and were significantly more common for incident transfers than bounce-back transfers (39 vs. 21%, p = .0002). Of patients admitted via the emergency department who had subsequent incident transfers to the NICU, 50% were transferred within 24 h of admission. CONCLUSIONS: Unplanned transfers to an NICU were common and were associated with a high in-hospital mortality rate. Quality improvement projects should target the triage process and transitions of care to the hospital wards in order to decrease unplanned transfers of high-risk patients to the NICU.

Quantitative CT densitometry for predicting intracerebral hemorrhage growth.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage growth independently predicts disability and death. We hypothesized that noncontrast quantitative CT densitometry reflects active bleeding and improves predictive models of growth. MATERIALS AND METHODS: We analyzed 81 of the 96 available baseline CT scans obtained <3 hours post-ICH from the placebo arm of the phase IIb trial of recombinant factor VIIa. Fifteen scans could not be analyzed for technical reasons, but baseline characteristics were not statistically significantly different. Hounsfield unit histograms for each ICH were generated. Analyzed qCTD parameters included the following: mean, SD, coefficient of variation, skewness (distribution asymmetry), and kurtosis ("peakedness" versus "flatness"). These densitometry parameters were examined in statistical models accounting for baseline volume and time-to-scan. RESULTS: The coefficient of variation of the ICH attenuation was the most significant individual predictor of hematoma growth (adjusted R(2) = 0.107, P = .002), superior to BV (adjusted R(2) = 0.08, P = .006) or TTS (adjusted R(2) = 0.03, P = .05). The most significant combined model incorporated coefficient of variation, BV, and TTS (adjusted R(2) = 0.202, P = .009 for coefficient of variation) compared with BV and TTS alone (adjusted R(2) = 0.115, P < .05). qCTD increased the number of growth predictions within ±1 mL of actual 24-hour growth by up to 47%. CONCLUSIONS: Heterogeneous ICH attenuation on hyperacute (<3 hours) CT imaging is predictive of subsequent hematoma expansion and may reflect an active bleeding process. Further studies are required to determine whether qCTD can be incorporated into standard imaging protocols for predicting ICH growth.

Emergency noninvasive angiography for acute intracerebral hemorrhage.

Spontaneous ICH is a devastating condition and is associated with significant mortality in the acute phase due to ongoing hemorrhage and hematoma expansion. A growing body of evidence suggests that there may be considerable utility in performing noninvasive vascular imaging during the acute-to-early phase of ICH. CTA has become widely available and is sensitive and specific for detecting vascular causes of secondary ICH such as aneurysms, arteriovenous malformations, dural arteriovenous fistulas, intracranial dissections, and neoplasm. CT venography can also diagnose dural sinus thrombosis presenting as hemorrhagic infarction. Recent data from stroke populations demonstrate a relatively low risk to patients when contrast is administered in the absence of a known serum creatinine. Detection of acute contrast extravasation within the hematoma ("spot sign") with CT angiography is predictive of subsequent hematoma expansion and is associated with increased morbidity and mortality. Risk stratification based on acute CTA can inform and expedite decision-making regarding intensive care unit admission, blood pressure control, correction of coagulopathy, and neurosurgical consultation. Noninvasive vascular imaging should be considered as an important component of the initial diagnostic work-up for patients presenting with acute ICH.

Effect of rebleeding on the course and incidence of vasospasm after subarachnoid hemorrhage.

OBJECTIVE: Rebleeding of an aneurysm is a leading cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Whereas numerous studies have demonstrated the risk factors associated with rebleeding, few data on complications of rebleeding, including its effect on the development of delayed cerebral ischemia (DCI), are available. METHODS: A nested case-control study was performed on patients with rebleeding and control subjects matched for modified Fisher scale, Hunt-Hess grade, age, and sex previously entered into a prospective database. Rebleeding was defined as new hemorrhage apparent on repeat CT with or without new symptoms. Incidence and time course of DCI and hospital complications were compared. A secondary analysis of DCI and hospital complications was also performed on subjects surviving to postbleed day 7. RESULTS: We identified 120 patients with rebleeding and 359 control subjects from 1996 to 2011. The rebleeding rate was 8.6%. In both the primary and secondary analyses, there was no difference in the incidence of DCI or its time course (29% vs. 27%, p = 0.6; 7 ± 5 vs. 7 ± 6 days, p = 0.9 for primary analysis; 39% vs. 31%, p = 0.1, 7 ± 5 vs. 7 ± 6 days, p = 0.6 for the secondary analysis). In a multivariate logistic regression model, rebleeding was associated with the complications of hyponatremia, respiratory failure, and hydrocephalus. Patients with rebleeding had higher rates of mortality, brain death, and poor outcomes. CONCLUSIONS: Rebleeding after SAH is associated with multiple medical and neurologic complications, resulting in higher morbidity and mortality, but is not associated with change of incidence or timing of DCI.

Effect of mannitol and hypertonic saline on cerebral oxygenation in patients with severe traumatic brain injury and refractory intracranial hypertension.

BACKGROUND: The impact of osmotic therapies on brain oxygen has not been extensively studied in humans. We examined the effects on brain tissue oxygen tension (PbtO(2)) of mannitol and hypertonic saline (HTS) in patients with severe traumatic brain injury (TBI) and refractory intracranial hypertension. METHODS: 12 consecutive patients with severe TBI who underwent intracranial pressure (ICP) and PbtO(2) monitoring were studied. Patients were treated with mannitol (25%, 0.75 g/kg) for episodes of elevated ICP (>20 mm Hg) or HTS (7.5%, 250 ml) if ICP was not controlled with mannitol. PbtO(2), ICP, mean arterial pressure, cerebral perfusion pressure (CPP), central venous pressure and cardiac output were monitored continuously. RESULTS: 42 episodes of intracranial hypertension, treated with mannitol (n = 28 boluses) or HTS (n = 14 boluses), were analysed. HTS treatment was associated with an increase in PbtO(2) (from baseline 28.3 (13.8) mm Hg to 34.9 (18.2) mm Hg at 30 min, 37.0 (17.6) mm Hg at 60 min and 41.4 (17.7) mm Hg at 120 min; all p<0.01) while mannitol did not affect PbtO(2) (baseline 30.4 (11.4) vs 28.7 (13.5) vs 28.4 (10.6) vs 27.5 (9.9) mm Hg; all p>0.1). Compared with mannitol, HTS was associated with lower ICP and higher CPP and cardiac output. CONCLUSIONS: In patients with severe TBI and elevated ICP refractory to previous mannitol treatment, 7.5% hypertonic saline administered as second tier therapy is associated with a significant increase in brain oxygenation, and improved cerebral and systemic haemodynamics.

Electrographic seizures and periodic discharges after intracerebral hemorrhage.

OBJECTIVE: To determine the frequency and significance of electrographic seizures and other EEG findings in patients with intracerebral hemorrhage (ICH). METHODS: We reviewed 102 consecutive patients with ICH who underwent continuous electroencephalographic monitoring (cEEG). Demographic, clinical, radiographic, and cEEG findings were recorded. Using multivariate logistic regression analysis, we determined factors associated with 1) electrographic seizures, 2) periodic epileptiform discharges (PEDs), and 3) poor outcome (death, vegetative or minimally conscious state) at hospital discharge. RESULTS: Seizures occurred in 31% (n = 32) of patients with ICH, prior to cEEG in 19 patients. Eighteen percent (n = 18) of patients had electrographic seizures; only one of these patients also had clinical seizures while on cEEG. After controlling for demographic and clinical predictors, only an increase in ICH volume of 30% or more between admission and 24-hour follow-up CT scan was associated with electrographic seizures (33% vs 15%; OR 9.5, 95% CI 1.7 to 53.8). PEDs were less frequently seen in those with hemorrhages located at least 1 mm from the cortex (8% vs 29%; OR 0.2, 95% CI 0.1 to 0.7). PEDs were independently associated with poor outcome (65% vs 17%; OR 7.6, 95% CI 2.1 to 27.3). In patients with electrographic seizures, the first seizure was detected within the first hour of cEEG monitoring in 56% and within 48 hours in 94%. CONCLUSIONS: Seizures occurred in one third of patients with intracerebral hemorrhage (ICH) and over half were purely electrographic. Electrographic seizures were associated with expanding hemorrhages, and periodic discharges with cortical ICH and poor outcome. Further research is needed to determine if treating or preventing seizures or PEDs might lead to improved outcome after ICH.

Fever after subarachnoid hemorrhage: risk factors and impact on outcome.

OBJECTIVE: To identify risk factors for refractory fever after subarachnoid hemorrhage (SAH), and to determine the impact of temperature elevation on outcome. METHODS: We studied a consecutive cohort of 353 patients with SAH with a maximum daily temperature (T(max)) recorded on at least 7 days between SAH days 0 and 10. Fever (>38.3 degrees C) was routinely treated with acetaminophen and conventional water-circulating cooling blankets. We calculated daily T(max) above 37.0 degrees C, and defined extreme T(max) as daily excess above 38.3 degrees C. Global outcome at 90 days was evaluated with the modified Rankin Scale (mRS), instrumental activities of daily living (IADLs) with the Lawton scale, and cognitive functioning with the Telephone Interview of Cognitive Status. Mixed-effects models were used to identify predictors of T(max), and logistic regression models to evaluate the impact of T(max) on outcome. RESULTS: Average daily T(max) was 1.15 degrees C (range 0.04 to 2.74 degrees C). The strongest predictors of fever were poor Hunt-Hess grade and intraventricular hemorrhage (IVH) (both p < 0.001). After controlling for baseline outcome predictors, daily T(max) was associated with an increased risk of death or severe disability (mRS > or = 4, adjusted OR 3.0 per degrees C, 95% CI 1.6 to 5.8), loss of independence in IADLs (OR 2.6, 95% CI 1.2 to 5.6), and cognitive impairment (OR 2.5, 95% CI 1.2 to 5.1, all p < or = 0.02). These associations were even stronger when extreme T(max) was analyzed. CONCLUSION: Treatment-refractory fever during the first 10 days after subarachnoid hemorrhage (SAH) is predicted by poor clinical grade and intraventricular hemorrhage, and is associated with increased mortality and more functional disability and cognitive impairment among survivors. Clinical trials are needed to evaluate the impact of prophylactic fever control on outcome after SAH.

Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage.

BACKGROUND: Although volume of intracerebral hemorrhage (ICH) is a predictor of mortality, it is unknown whether subsequent hematoma growth further increases the risk of death or poor functional outcome. METHODS: To determine if hematoma growth independently predicts poor outcome, the authors performed an individual meta-analysis of patients with spontaneous ICH who had CT within 3 hours of onset and 24-hour follow-up. Placebo patients were pooled from three trials investigating dosing, safety, and efficacy of rFVIIa (n = 115), and 103 patients from the Cincinnati study (total 218). Other baseline factors included age, gender, blood glucose, blood pressure, Glasgow Coma Score (GCS), intraventricular hemorrhage (IVH), and location. RESULTS: Overall, 72.9% of patients exhibited some degree of hematoma growth. Percentage hematoma growth (hazard ratio [HR] 1.05 per 10% increase [95% CI: 1.03, 1.08; p < 0.0001]), initial ICH volume (HR 1.01 per mL [95% CI: 1.00, 1.02; p = 0.003]), GCS (HR 0.88 [95% CI: 0.81, 0.96; p = 0.003]), and IVH (HR 2.23 [95% CI: 1.25, 3.98; p = 0.007]) were all associated with increased mortality. Percentage growth (cumulative OR 0.84 [95% CI: 0.75, 0.92; p < 0.0001]), initial ICH volume (cumulative OR 0.94 [95% CI: 0.91, 0.97; p < 0.0001]), GCS (cumulative OR 1.46 [95% CI: 1.21, 1.82; p < 0.0001]), and age (cumulative OR 0.95 [95% CI: 0.92, 0.98; p = 0.0009]) predicted outcome modified Rankin Scale. Gender, location, blood glucose, and blood pressure did not predict outcomes. CONCLUSIONS: Hematoma growth is an independent determinant of both mortality and functional outcome after intracerebral hemorrhage. Attenuation of growth is an important therapeutic strategy.

Cerebrovascular reactivity and vasospasm after subarachnoid hemorrhage: a pilot study.

The authors performed serial transcranial Doppler (TCD) and carbon dioxide reactivity (CO2R) testing in 20 aneurysmal subarachnoid hemorrhage patients to determine whether impaired cerebrovascular reactivity was associated with symptomatic vasospasm. Symptomatic vasospasm occurred in 9 of 14 patients with abnormal CO2R and in none of 6 patients with preserved reactivity (p = 0.011). Abnormal CO2R preceded the onset of vasospasm in 7 of 9 patients. Abnormal standard TCD testing was not associated with vasospasm.

Detection of electrographic seizures with continuous EEG monitoring in critically ill patients.

OBJECTIVE: To identify patients most likely to have seizures documented on continuous EEG (cEEG) monitoring and patients who require more prolonged cEEG to record the first seizure. METHODS: Five hundred seventy consecutive patients who underwent cEEG monitoring over a 6.5-year period were reviewed for the detection of subclinical seizures or evaluation of unexplained decrease in level of consciousness. Baseline demographic, clinical, and EEG findings were recorded and a multivariate logistic regression analysis performed to identify factors associated with 1) any EEG seizure activity and 2) first seizure detected after >24 hours of monitoring. RESULTS: Seizures were detected in 19% (n = 110) of patients who underwent cEEG monitoring; the seizures were exclusively nonconvulsive in 92% (n = 101) of these patients. Among patients with seizures, 89% (n = 98) were in intensive care units at the time of monitoring. Electrographic seizures were associated with coma (odds ratio [OR] 7.7, 95% CI 4.2 to 14.2), age <18 years (OR 6.7, 95% CI 2.8 to 16.2), a history of epilepsy (OR 2.7, 95% CI 1.3 to 5.5), and convulsive seizures during the current illness prior to monitoring (OR 2.4, 95% CI 1.4 to 4.3). Seizures were detected within the first 24 hours of cEEG monitoring in 88% of all patients who would eventually have seizures detected by cEEG. In another 5% (n = 6), the first seizure was recorded on monitoring day 2, and in 7% (n = 8), the first seizure was detected after 48 hours of monitoring. Comatose patients were more likely to have their first seizure recorded after >24 hours of monitoring (20% vs 5% of noncomatose patients; OR 4.5, p = 0.018). CONCLUSIONS: CEEG monitoring detected seizure activity in 19% of patients, and the seizures were almost always nonconvulsive. Coma, age <18 years, a history of epilepsy, and convulsive seizures prior to monitoring were risk factors for electrographic seizures. Comatose patients frequently required >24 hours of monitoring to detect the first electrographic seizure.

Quantification of lethargy in the neuro-ICU: the 60-Second Test.

The authors evaluated the 60-Second Test (SST), a brief test of mental concentration, as a supplement to the Glasgow Coma Scale (GCS) for monitoring verbally responsive patients in the neuro-intensive care unit. The SST demonstrated excellent reliability and was abnormal in 79% of patients assigned a top GCS score of 15. However, both tests had poor responsiveness to clinically identified changes in level of consciousness (LOC). The SST is sensitive to subtle alterations in LOC but, like the GCS, may have limitations as a monitoring tool in the neurocritical care setting.

Predictors and clinical impact of epilepsy after subarachnoid hemorrhage.

OBJECTIVE: To determine the frequency, predictors, and impact on outcome of epilepsy developing during the first year after subarachnoid hemorrhage (SAH). METHODS: The authors prospectively analyzed 247 of 431 patients with SAH treated over a period of 5 years who were alive with follow-up at 12 months. Epilepsy was defined as two or more unprovoked seizures after hospital discharge. RESULTS: New-onset epilepsy occurred in 7% (n = 17) of patients; an additional 4% (n = 10) had only one seizure after discharge. Independent predictors of epilepsy included subdural hematoma (OR 9.9, 95% CI 1.9 to 52.8) and cerebral infarction (OR 3.9, 95% CI 1.4 to 11.3). Unlike those without seizures, patients who developed epilepsy failed to experience functional recovery on the modified Rankin Scale (mRS) between 3 and 12 months after SAH. At 12 months epilepsy was independently associated with severe disability (score >/= 3) on the mRS (OR 10.3, 95% CI 2.5 to 42.0), increased instrumental disability on the Lawton Instrumental Activities of Daily Living scale (OR 4.9; 95% CI 1.1 to 22.2), reduced quality of life on the Sickness Impact Profile (OR 4.5; 95% CI 1.1 to 18.0), and increased state anxiety on the Spielberger Anxiety Inventory (OR 4.8; 95% CI 1.1 to 20.4). Epilepsy was not associated with cognitive impairment, depression, or subjective life satisfaction. CONCLUSION: Epilepsy occurred in 7% of patients with SAH, was predicted by subdural hematoma and cerebral infarction, and was associated with poor functional recovery and quality of life. Our findings indicate that focal pathology, rather than diffuse injury from hemorrhage, is the principal cause of epilepsy after SAH.

Global and domain-specific cognitive impairment and outcome after subarachnoid hemorrhage.

BACKGROUND: Cognitive dysfunction is the most common form of neurologic impairment after subarachnoid hemorrhage (SAH). OBJECTIVE: To evaluate the impact of global and domain-specific cognitive impairment on functional recovery and quality of life (QOL) after SAH. METHODS: One hundred thirteen patients (mean age 49 years; 68% women) were evaluated 3 months after SAH. Three simple tests of global mental status and neuropsychological tests to assess seven specific cognitive domains were administered. Four aspects of outcome (global handicap, disability, emotional status, and QOL) were compared between cognitively impaired and unimpaired patients with analysis-of-covariance models controlling for age, race/ethnicity, and education. Multiple linear regression was used to evaluate the relative contribution of global and domain-specific cognitive status for predicting concurrent modified Rankin Scale (mRS) and Sickness Impact Profile (SIP) scores. RESULTS: Impairment of global mental status on the Telephone Interview of Cognitive Status (TICS) was associated with poor performance in all seven cognitive domains (all p < 0.0005) and was the only cognitive measure associated with poor recovery in all four aspects of outcome (all p < or = 0.005). Cognitive impairment in four specific domains was also associated with functional disability or reduced QOL. After accounting for global cognitive impairment with the TICS, however, neuropsychological testing did not contribute additional predictive value for concurrent mRS or SIP total scores. CONCLUSIONS: Cognitive impairment impacts broadly on functional status, emotional health, and QOL after SAH. The TICS may be a useful alternative to more detailed neuropsychological testing for detecting clinically relevant global cognitive impairment after SAH.

Predictors of functional disability and mortality after status epilepticus.

The authors identified predictors of functional disability and mortality after status epilepticus in a multivariate analysis of 83 episodes in 74 patients. Twenty-one percent (14/85) of episodes were fatal. Increased age (OR = 1.1; 95% CI, 1.0 to 1.1) and acute symptomatic seizures (OR = 6.0; 95% CI, 1.2 to 30.3) were predictors of mortality. Functional outcome at discharge deteriorated in 23% (16/69) of nonfatal episodes. Increased length of hospitalization (OR = 1.04; 95% CI, 1.0 to 1.1) and acute symptomatic seizures (OR = 3.9; 95% CI, 1.0 to 14.7) were predictors of functional disability.