Sachin Agarwal

Seizure burden in subarachnoid hemorrhage associated with functional and cognitive outcome

Objective: To assess the relationship between seizure burden on continuous EEG (cEEG) and functional as well as cognitive outcome 3 months after subarachnoid hemorrhage (SAH). Methods: The study included all consecutive patients with a spontaneous SAH admitted to the Columbia University Medical Center Neurological Intensive Care Unit and monitored with cEEG between 1996 and 2013. Seizure burden was defined as the duration, in hours, of seizures on cEEG. Cognitive outcomes were measured with the Telephone Interview for Cognitive Status (TICS, ranging from 0 to 51, indicating poor to good global mental status). Results: Overall, 402 patients with SAH were included with a median age of 58 years (interquartile range [IQR] 46–68 years). The median duration of cEEG monitoring was 96 hours (IQR 48–155 hours). Seizures were recorded in 50 patients (12%), in whom the median seizure burden was 6 hours (IQR 1–13 hours). At 3 months, in multivariate analysis, seizure burden was associated with unfavorable functional and cognitive outcome. Every hour of seizure on cEEG was associated with an odds ratio of 1.10 (95% confidence interval [CI] 1.01–1.21, p = 0.04) to 3-month disability and mortality, and the TICS-score decreased, on average, by 0.16 points (adjusted coefficient −0.19, 95% CI −0.33 to −0.05, p = 0.01). Conclusion: In this study, after adjusting for established predictors, seizure burden was associated with functional outcome and cognitive impairment 3 months after SAH.

Racial and ethnic differences in subclinical myocardial function: the Multi-Ethnic Study of Atherosclerosis

Background Racial/ethnic differences in the incidence and severity of heart failure (HF) are not well understood, but may be related to pre-existing variations in myocardial function. Objective To examine racial/ethnic differences in regional myocardial function among asymptomatic individuals free of known cardiovascular disease. Design, setting and patients The Multi-Ethnic Study of Atherosclerosis is a prospective, observational study of individuals without baseline cardiovascular disease, representing four major racial/ethnic groups. A total of 1099 study participants underwent cardiac MRI with tissue tagging; for each study, peak systolic strain (Ecc) and strain rate (SRs) were determined in four left ventricular (LV) regions. Main outcome measures Multiple linear regression was used to analyse the relationship between race/ethnicity and regional strain (Ecc and SRs) while adjusting for cardiovascular risk factors. Results Compared with other racial/ethnic groups, Chinese-Americans had the greatest magnitude of Ecc in a majority of LV regions (−19.60±3.78, p<0.05); Chinese-Americans also had the greatest absolute values for SRs in all regions, reflecting higher rate of systolic contraction (−2.01±0.76, p<0.05). Conversely, African-Americans had the lowest Ecc values (−17.50±4.00, p<0.05) in the majority of wall regions while Hispanics demonstrated the lowest rate of contractility in all wall regions (−1.44±0.50, p≤0.001) in comparison with the other racial/ethnic groups. These race-based differences remained significant in the majority of LV wall regions after adjusting for multiple variables, including hypertension and LV mass. Conclusions Important race-based differences in regional LV systolic function in a large cohort of asymptomatic individuals have been demonstrated. Further research is needed to investigate the possible mechanisms related to the race/ethnicity-based variations found in this study.

Intraventricular hemorrhage expansion in patients with spontaneous intracerebral hemorrhage

Objective: To evaluate whether delayed appearance of intraventricular hemorrhage (dIVH) represents an independent entity from intraventricular hemorrhage (IVH) present on admission CT or is primarily related to the time interval between symptom onset and admission CT. Methods: A total of 282 spontaneous intracerebral hemorrhage (ICH) patients, admitted February 2009–March 2014 to the neurological intensive care unit of a tertiary care university hospital, were prospectively enrolled in the ICH Outcomes Project. Multivariate logistic regression was used to determine associations with acute mortality and functional long-term outcome (modified Rankin Scale). Results: A cohort of 282 ICH patients was retrospectively studied: 151 (53.5%) had intraventricular hemorrhage on initial CT scan (iIVH). Of the remaining 131 patients, 19 (14.5%) developed IVH after the initial CT scan (dIVH). The median times from symptom onset to admission CT were 1.1, 6.0, and 7.4 hours for the dIVH, iIVH, and no IVH groups (Mann-Whitney U test, dIVH vs iIVH, p < 0.001) and median time from onset to dIVH detection was 7.2 hours. The increase in ICH volume following hospital admission was larger in dIVH than in iIVH and no IVH patients (mean 17.6, 0.2, and 0.4 mL). After controlling for components of the ICH score and hematoma expansion, presence of IVH on initial CT was associated with discharge mortality and poor outcome at 3, 6, and 12 months, but dIVH was not associated with any of the outcome measures. Conclusions: In ICH patients, associated IVH on admission imaging is commonly encountered and is associated with poor long-term outcome. In contrast, dIVH on subsequent scans is far less common and does not appear to portend worse outcome.

Demographic factors influence cognitive recovery after shunt for normal-pressure hydrocephalus.

Background:Several studies have reported that ventriculoperitoneal shunt insertion for treatment of normal-pressure hydrocephalus results in improvement of gait and, less frequently, improvement of cognition. We sought to identify the demographic factors associated with cognitive improvement after shunt insertion to improve assessment of prognosis for cognitive gains with treatment. Review Summary:We report cognitive testing before and after ventriculoperitoneal shunt insertion in 36 patients with normal pressure hydrocephalus, who previously had improvement of any clinical symptom—gait, urinary incontinence, cognition—after a diagnostic trial of continuous cerebrospinal fluid drainage. Conclusions:One third of patients met our definition of good cognitive improvement: improvement by at least 25% on at least half of the cognitive tests administered. There was a significant negative linear relationship between age and probability of good cognitive improvement. Additionally, the degree of cognitive improvement was found to be greater in women than men (P = 0.002). Age was found to be a better predictor of improvement on memory tests, while sex was a better predictor of improvement on nonmemory tests after shunt insertion.

Determinants of Long-term Neurological Recovery Patterns Relative to Hospital Discharge Among Cardiac Arrest Survivors

Objective: To explore factors associated with neurological recovery at 1 year relative to hospital discharge after cardiac arrest. Design: Observational, retrospective review of a prospectively collected cohort. Setting: Medical or surgical ICUs in a single tertiary care center. Patients: Older than 18 years, resuscitated following either in-hospital or out-of-hospital cardiac arrest and considered for targeted temperature management between 2007 and 2013. Interventions: None. Measurements and Main Results: Logistic regressions to determine factors associated with a poor recovery pattern after 1 year, defined as persistent Cerebral Performance Category Score 3–4 or any worsening of Cerebral Performance Category Score relative to discharge status. In total, 30% (117/385) of patients survived to hospital discharge; among those discharged with Cerebral Performance Category Score 1, 2, 3, and 4, good recovery pattern was seen in 54.5%, 48.4%, 39.5%, and 0%, respectively. Significant variables showing trends in associations with a poor recovery pattern (62.5%) in a multivariate model were age more than 70 years (odds ratio, 4; 95% CIs, 1.1–15; p = 0.04), Hispanic ethnicity (odds ratio, 4; CI, 1.2–13; p = 0.02), and discharge disposition (home needing out-patient services (odds ratio, 1), home requiring no additional services (odds ratio, 0.15; CI, 0.03–0.8; p = 0.02), acute rehabilitation (odds ratio, 0.23; CI, 0.06–0.9; p = 0.04). Conclusions: Patients discharged with mild or moderate cerebral dysfunction sustained their risk of neurological worsening within 1 year of cardiac arrest. Old age, Hispanic ethnicity, and discharge disposition of home with out-patient services may be associated with a poor 1 year neurological recovery pattern after hospital discharge from cardiac arrest.

Aortic plaque regression as determined by magnetic resonance imaging with high-dose and low-dose statin therapy

Objective We sought to compare the effects of high-dose with low-dose simvastatin therapy on aortic plaque morphology using transoesophageal magnetic resonance imaging (TEMRI). Methods Thirty-one patients with established moderate-to-severe atherosclerosis were recruited and randomized to 80 versus 20 mg/day simvastatin therapy. Aortic vessel wall and lumen volumes and areas were measured by TEMRI at baseline and 12 months. Results Significant differences were observed between the low-dose and high-dose statin therapy in reduction of low-density lipoprotein cholesterol (LDL-c) (10 mg/dl, P = 0.001), total cholesterol (16.2 mg/dl, P < 0.001), vessel wall area (19.0 mm2, P < 0.001) and volume (343.4 mm3, P < 0.001), as well as increase in lumen area (54.4 mm2, P < 0.001) and volume (1038 mm3, P < 0.001). LDL-c lowering was significantly associated with aortic wall area and volume reduction in both groups. Conclusion High-dose statin leads to greater LDL-c reduction, aortic vessel wall reduction and lumen increase than low-dose statin therapy in patients with at least moderate-documented atherosclerosis.

34 – Collagen Vascular and Infectious Diseases

Stroke is a relatively common complication of many inflammatory and collagen vascular diseases and a primary event in some. Strokes in this setting are often ascribed to inflammation of arteries, although other mechanisms, including emboli and coagulation disturbances, play a prominent role. This chapter reviews the current clinical understanding of the inflammatory diseases that may be associated with stroke. Because the central role of inflammatory mechanisms in atherosclerosis has also been recognized, the chapter concludes with some comments on the nature of inflammatory mechanisms in atherosclerotic stroke more generally.

Desmopressin administration and rebleeding in subarachnoid hemorrhage: analysis of an observational prospective database

OBJECTIVERebleeding remains a frequent and catastrophic event leading to poor outcome after subarachnoid hemorrhage (SAH). Reduced platelet function after the initial bleed is associated with higher risk of early rebleeding. Desmopressin (DDAVP) is a well-known hemostatic agent, and recent guidelines already suggest its use in individuals exposed to antiplatelet drugs. The authors hypothesized that DDAVP administration in patients with SAH at admission would be associated with lower risks of rebleeding.METHODSThe authors performed an observational cohort study of patients enrolled in the Columbia University SAH Outcome Project between August 1996 and July 2015. The authors compared the rate of rebleeding between patients who were and those who were not treated with DDAVP. After adjustment for known predictors, logistic regression was used to measure the association between treatment with DDAVP and risks of rebleeding.RESULTSAmong 1639 patients with SAH, 12% were treated with DDAVP. The main indication for treatment was suspected exposure to an antiplatelet agent. The overall incidence of rebleeding was 9% (1% among patients treated with DDAVP compared with 8% among those not treated). After adjustment for antiplatelet use and known predictors, treatment with DDAVP was associated with a 45% reduction in the risks of rebleeding (adjusted OR 0.55, 95% CI 0.27-0.97). DDAVP was associated with a higher incidence of hyponatremia but not with thrombotic events or delayed cerebral ischemia.CONCLUSIONSTreatment with DDAVP was associated with a lower risk of rebleeding among patients with SAH. These findings support further study of DDAVP as first-line therapy for medical hemostasis in patients with SAH.

Early myoclonus following anoxic brain injury

Background It is unknown whether postanoxic cortical and subcortical myoclonus are distinct entities with different prognoses. Methods In this retrospective cohort study of 604 adult survivors of cardiac arrest over 8.5 years, we identified 111 (18%) patients with myoclonus. Basic demographics and clinical characteristics of myoclonus were collected. EEG reports, and, when available, raw video EEG, were reviewed, and all findings adjudicated by 3 authors blinded to outcomes. Myoclonus was classified as cortical if there was a preceding, time-locked electrographic correlate and otherwise as subcortical. Outcome at discharge was determined using Cerebral Performance Category. Results Patients with myoclonus had longer arrests with less favorable characteristics compared to patients without myoclonus. Cortical myoclonus occurred twice as often as subcortical myoclonus (59% vs 23%, respectively). Clinical characteristics during hospitalization did not distinguish the two. Rates of electrographic seizures were higher in patients with cortical myoclonus (43%, vs 8% with subcortical). Survival to discharge was worse for patients with myoclonus compared to those without (26% vs 39%, respectively), but did not differ between subcortical and cortical myoclonus (24% and 26%, respectively). Patients with cortical myoclonus were more likely to be discharged in a comatose state than those with subcortical myoclonus (82% vs 33%, respectively). Among survivors, good functional outcome at discharge was equally possible between those with cortical and subcortical myoclonus (12% and 16%, respectively). Conclusions Cortical and subcortical myoclonus are seen in every sixth patient with cardiac arrest and cannot be distinguished using clinical criteria. Either condition may have good functional outcomes.

Incorporating High-Frequency Physiologic Data Using Computational Dictionary Learning Improves Prediction of Delayed Cerebral Ischemia Compared to Existing Methods

Purpose Accurate prediction of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) can be critical for planning interventions to prevent poor neurological outcome. This paper presents a model using convolution dictionary learning to extract features from physiological data available from bedside monitors. We develop and validate a prediction model for DCI after SAH, demonstrating improved precision over standard methods alone. Methods 488 consecutive SAH admissions from 2006 to 2014 to a tertiary care hospital were included. Models were trained on 80%, while 20% were set aside for validation testing. Modified Fisher Scale was considered the standard grading scale in clinical use; baseline features also analyzed included age, sex, Hunt–Hess, and Glasgow Coma Scales. An unsupervised approach using convolution dictionary learning was used to extract features from physiological time series (systolic blood pressure and diastolic blood pressure, heart rate, respiratory rate, and oxygen saturation). Classifiers (partial least squares and linear and kernel support vector machines) were trained on feature subsets of the derivation dataset. Models were applied to the validation dataset. Results The performances of the best classifiers on the validation dataset are reported by feature subset. Standard grading scale (mFS): AUC 0.54. Combined demographics and grading scales (baseline features): AUC 0.63. Kernel derived physiologic features: AUC 0.66. Combined baseline and physiologic features with redundant feature reduction: AUC 0.71 on derivation dataset and 0.78 on validation dataset. Conclusion Current DCI prediction tools rely on admission imaging and are advantageously simple to employ. However, using an agnostic and computationally inexpensive learning approach for high-frequency physiologic time series data, we demonstrated that we could incorporate individual physiologic data to achieve higher classification accuracy.