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1.  Quality of life in patients with TIA and minor ischemic stroke 
Neurology  2015;85(22):1957-1963.
We investigated health-related quality of life (HRQOL) in patients with TIA and minor ischemic stroke (MIS) using Neuro-QOL, a validated, patient-reported outcome measurement system.
Consecutive patients with TIA or MIS who had (1) modified Rankin Scale (mRS) score of 0 or 1 at baseline, (2) initial NIH Stroke Scale score of ≤5, (3) no acute reperfusion treatment, and (4) 3-month follow-up, were recruited. Recurrent stroke, disability by mRS and Barthel Index, and Neuro-QOL scores in 5 prespecified domains were prospectively recorded. We assessed the proportion of patients with impaired HRQOL, defined as T scores more than 0.5 SD worse than the general population average, and identified predictors of impaired HRQOL using logistic regression.
Among 332 patients who met study criteria (mean age 65.7 years, 52.4% male), 47 (14.2%) had recurrent stroke within 90 days and 41 (12.3%) were disabled (mRS >1 or Barthel Index <95) at 3 months. Any HRQOL impairment was noted in 119 patients (35.8%). In multivariate analysis, age (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01–1.04), initial NIH Stroke Scale score (adjusted OR 1.39, 95% CI 1.17–1.64), recurrent stroke (adjusted OR 2.10, 95% CI 1.06–4.13), and proxy reporting (adjusted OR 3.94, 95% CI 1.54–10.10) were independent predictors of impaired HRQOL at 3 months.
Impairment in HRQOL is common at 3 months after MIS and TIA. Predictors of impaired HRQOL include age, index stroke severity, and recurrent stroke. Future studies should include HRQOL measures in outcome assessment, as these may be more sensitive to mild deficits than traditional disability scales.
PMCID: PMC4664119  PMID: 26537051
2.  Dichotomous “Good Outcome” Indicates Mobility More Than Cognitive or Social Quality of Life 
Critical care medicine  2015;43(8):1654-1659.
Worthwhile interventions for intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) generally hinge on whether they improve the odds of “good outcome.” While good outcome is correlated with mobility, correlations with other domains of health-related quality of life (HRQoL), such as cognitive function (CF) and social functioning, are not well described. We tested the hypothesis that good outcome is more closely associated with mobility than other domains.
We defined “good outcome” as 0 through 3 (independent ambulation or better) vs. 4 through 5 (dependent) on the modified Rankin Scale (mRS) at one, three and 12 months. We simultaneously assessed the mRS and HRQoL using web-based computer adaptive testing in the domains of mobility, CF (executive function and general concerns), and satisfaction with social roles and activities (SRA). We compared the area under the curve (AUC) between different HRQoL domains.
Neurological intensive care unit with web-based follow-up
Measurement and Main Results
We longitudinally followed 114 survivors with data at one month, 62 patients at three months, and 58 patients at 12 months. At one month, AUC was highest for mobility (0.957, 95% CI 0.904 – 0.98), higher than CF - general concerns (0.819, 95%CI 0.715-0.888, P=0.003 compared to mobility), satisfaction with SRA (0.85, 95%CI 0.753-0.911, P=0.01 compared to mobility) and CF - executive function (0.879, 95%CI 0.782-0.935, P=0.058 compared to mobility). Optimal specificity and sensitivity for ROC analysis were approximately 1.5 SD below the US population mean.
HRQoL assessments reliably distinguished between good and poor outcome as determined by the mRS. “Good outcome” indicated HRQoL about 1.5 SD below the US population mean. Associations were weaker for CF and social function than mobility.
PMCID: PMC4506199  PMID: 25978337
outcomes assessment; intracerebral hemorrhage; subarachnoid hemorrhage; quality of life; critical care; internet
3.  Neurochecks as a Biomarker of the Temporal Profile and Clinical Impact of Neurologic Changes after Intracerebral Hemorrhage 
We sought to determine whether a quantitative neurocheck biomarker could characterize the temporal pattern of early neurologic changes after intracerebral hemorrhage (ICH), and the impact of those changes on long-term functional outcomes.
We enrolled cases of spontaneous ICH in a prospective observational study. Patients underwent a baseline Glasgow Coma Scale (GCS) assessment, then hourly neurochecks utilizing the GCS in a neuroscience intensive care unit. We identified a period of heightened neurologic instability by analyzing the average hourly rate of GCS change over 5 days from symptom onset. We used a multivariate regression model to test whether those early GCS score changes were independently associated with 3 month outcome measured by the modified Rankin Scale (mRS).
We studied 13,025 hours of monitoring from 132 cases. The average rate of neurologic change declined from 1.0 GCS points per hour initially to a stable baseline of 0.1 GCS points per hour beyond 12 hours from symptom onset (p<0.05 for time intervals before 12 hours). Change in GCS score within the initial 12 hours was an independent predictor of mRS at three months (odds ratio 0.81 [95% confidence interval 0.66–0.99], p=0.043) after adjustment for age, hematoma volume, hematoma location, initial GCS, and intraventricular hemorrhage.
Neurochecks are effective at detecting clinically important neurologic changes in the intensive care unit setting that are relevant to patients’ long-term outcomes. The initial 12 hours is a period of frequent and prognostically important neurologic changes in patients with ICH.
PMCID: PMC4558336  PMID: 26143415
5.  Predictors of 30 Day Readmission after Intracerebral Hemorrhage: A single-center approach for identifying potentially modifiable associations with readmission 
Critical care medicine  2013;41(12):10.1097/CCM.0b013e318298a10f.
To determine if patient demographics or severity of illness predict hospital readmission within 30 days following spontaneous intracerebral hemorrhage (ICH), to identify readmission associations that may be modifiable at the single center level, and to determine the impact of readmission on outcomes.
We collected demographic, clinical, and hospital course data for consecutive patients with spontaneous ICH enrolled in an observational study. Readmission within 30 days was determined retrospectively by an automated query with manual confirmation. We identified the reason for readmission and tested for associations between readmission and functional outcomes using modified Rankin Scale (mRS, a validated functional outcome measure from 0, no symptoms to 6, death) scores before ICH and at 14 days, 28 days, and three months after ICH.
Neurologic intensive care unit of a tertiary care hospital.
Critically ill patients with spontaneous ICH.
Patients received standard critical care management for ICH.
Measurements and Main Results
Of 246 patients (mean age 65 years, 51% female), 193 (78%) survived to discharge. Of these, 22 (11%) were re-admitted at a median of 9 [interquartile range (IQR) 4–15] days. The most common readmission diagnoses were infections after discharge (N=10) and vascular events (N=6). Age, history of stroke and hypertension, severity of neurologic deficit at admission, APACHE acute physiology score, ICU and hospital length of stay, ventilator free days, days febrile, and surgical procedures were not predictors of readmission. History of coronary artery disease was associated with readmission (p=0.03). Readmitted patients had similar mRS and severity of neurologic deficit at 14 days but higher (worse) mRS scores at three months (median [IQR], 5 [3–6] vs. 3 [1–4], p=0.01).
Severity of illness and hospital complications were not associated with 30-day readmission. The most common indication for readmission was infection after discharge, and readmission was associated with worse functional outcomes at three months. Preventing readmission after ICH may depend primarily on optimizing care after discharge and improve functional outcomes at three months.
PMCID: PMC3841230  PMID: 23963121
Intracerebral hemorrhage; critical care; readmission; quality metric; outcomes
6.  Intracerebral Hemorrhage and Delirium Symptoms. Length of Stay, Function, and Quality of Life in a 114-Patient Cohort 
Rationale: The prognostic significance of delirium symptoms in intensive care unit (ICU) patients with focal neurologic injury is unclear.
Objectives: To determine the relationship between delirium symptoms and subsequent functional outcomes and quality of life (QOL) after intracerebral hemorrhage.
Methods: We prospectively enrolled 114 patients. Delirium symptoms were routinely assessed twice daily using the Confusion Assessment Method for the ICU by trained nurses. Functional outcomes were recorded with modified Rankin Scale (scored from 0 [no symptoms] to 6 [dead]), and QOL outcomes with Neuro-QOL at 28 days, 3 months, and 12 months.
Measurements and Main Results: Thirty-one (27%) patients had delirium symptoms (“ever delirious”), 67 (59%) were never delirious, and the remainder (14%) had persistent coma. Delirium symptoms were nearly always hypoactive, were detected mean 6 days after intracerebral hemorrhage presentation, and were associated with longer ICU length of stay (mean 3.5 d longer in ever vs. never delirious patients; 95% confidence interval, 1.5–8.3; P = 0.004) after correction for age, admit National Institutes of Health (NIH) Stroke Scale, and any benzodiazepine exposure. Delirium symptoms were associated with increased odds of poor outcome at 28 days (odds ratio, 8.7; 95% confidence interval, 1.4–52.5; P = 0.018) after correction for admission NIH Stroke Scale and age, and with worse QOL in the domains of applied cognition–executive function and fatigue after correcting for the NIH Stroke Scale, age, benzodiazepine exposure, and time of follow-up.
Conclusions: After focal neurologic injury, delirium symptoms were common despite low rates of infection and sedation exposure, and were predictive of subsequent worse functional outcomes and lower QOL.
PMCID: PMC3919076  PMID: 24102675
delirium; outcomes; quality of life
7.  MRI Versus CT for Identification and Quantification of Intraventricular Hemorrhage 
Intraventricular hemorrhage (IVH) may be difficult to detect especially when in small amounts, and may affect outcomes. The objective of this study was to compare the sensitivity of MRI versus CT for the identification and quantification of IVH.
Patients with primary intracerebral hemorrhage were enrolled into a prospective registry between December 2006 and June 2013. Diagnostic and surveillance neuroimaging studies were analyzed for the presence of IVH and quantified by Graeb score. In subjects who developed IVH and underwent both MRI and CT, each MRI was paired with the CT scan done at the closest time point, and Graeb scores were compared with the Wilcoxon signed rank test for related samples.
There were 289 subjects in the cohort, with IVH found in 171. 68 pairs of MRI and CT were available for comparison. CT failed to detect IVH in 3% of cases, whereas MRI was 100% sensitive. MRI and CT yielded equal Graeb scores in 72% of pairs, and MRI Graeb score was higher in 24% (p=0.007).
MRI identifies small volumes of IVH in cases not detected by CT, and yields higher estimates of intraventricular blood volume. These data indicate that consideration of technical differences is needed when comparing images from the two modalities in the evaluation for IVH.
PMCID: PMC4214254  PMID: 25085346
MRI; magnetic resonance imaging; CT; computed tomography; intraventricular hemorrhage; intracerebral hemorrhage
8.  Surveillance neuroimaging and neurologic examinations affect care for intracerebral hemorrhage 
Neurology  2013;81(2):107-112.
We tested the hypothesis that surveillance neuroimaging and neurologic examinations identified changes requiring emergent surgical interventions in patients with intracerebral hemorrhage (ICH).
Patients with primary ICH were enrolled into a prospective registry between December 2006 and July 2012. Patients were managed in a neuroscience intensive care unit with a protocol that included serial neuroimaging at 6, 24, and 48 hours, and hourly neurologic examinations using the Glasgow Coma Scale and NIH Stroke Scale. We evaluated all cases of craniotomy and ventriculostomy to determine whether the procedure was part of the initial management plan or occurred subsequently. For those that occurred subsequently, we determined whether worsening on neurologic examination or worsened neuroimaging findings initiated the process leading to intervention.
There were 88 surgical interventions in 84 (35%) of the 239 patients studied, including ventriculostomy in 52 (59%), craniotomy in 21 (24%), and both in 11 (13%). Of the 88 interventions, 24 (27%) occurred subsequently and distinctly from initial management, a median of 15.9 hours (8.9–27.0 hours) after symptom onset. Thirteen (54%) were instigated by findings on neurologic examination and 11 (46%) by neuroimaging. Demographics, severity of hemorrhage, and hemorrhage location were not associated with delayed intervention.
More than 25% of surgical interventions performed after ICH were prompted by delayed imaging or clinical findings. Serial neurologic examinations and neuroimaging are important and effective surveillance techniques for monitoring patients with ICH.
PMCID: PMC3770177  PMID: 23739227
9.  Pearls & Oy-sters: Bilateral thalamic involvement in West Nile virus encephalitis 
Neurology  2014;83(2):e16-e17.
Bilateral thalamic inflammation in the presence of a clinical picture suggestive of viral encephalitis should raise concern for West Nile virus infection.
PMCID: PMC4117177  PMID: 25002571
10.  Delayed intraventricular hemorrhage is common and worsens outcomes in intracerebral hemorrhage 
Neurology  2013;80(14):1295-1299.
To evaluate the incidence, characteristics, and clinical consequences of delayed intraventricular hemorrhage (dIVH).
Patients with primary intracerebral hemorrhage (ICH) were enrolled into a prospective registry between December 2006 and February 2012. Patients were managed, and serial neuroimaging obtained, per a structured protocol. Initial and delayed IVH were identified on imaging, along with ICH volumes, with outcomes blinded. Multivariate models were developed to test whether the occurrence of dIVH was a predictor of functional outcomes independent of known predictors, including the ICH score elements and ICH growth.
A total of 216 patients were studied, and 104 (48%) had IVH on initial imaging. Of the 112 with no IVH, 23 (21%) subsequently developed IVH. Emergent surgical intervention, mostly ventriculostomy placement, was required after discovery of dIVH in 10 (43%) of these 23. In multivariate models adjusting for all elements of the ICH score and hematoma growth, dIVH was an independent predictor of death at 14 days (p = 0.015) and higher modified Rankin Scale scores at 3 months (all p = 0.037). The effect of dIVH remained significant in a secondary analysis that adjusted for all other variables significant in the univariate analysis.
Similar to hematoma expansion dIVH is independently associated with death and poor outcomes. Because IVH is easily detected by serial neuroimaging and often requires emergent surgical intervention, monitoring for dIVH is recommended.
PMCID: PMC3656461  PMID: 23516315
11.  Blood Pressure Reduction, Decreased Diffusion on MRI, and Outcomes After Intracerebral Hemorrhage 
Decreased diffusion (DD) consistent with acute ischemia may be detected on MRI after acute intracerebral hemorrhage (ICH), but its risk factors and impact on functional outcomes are not well defined. We tested the hypotheses that DD after ICH is related to acute blood pressure (BP) reduction and lower hemoglobin (HGB) and presages worse functional outcomes.
Patients who underwent MRI were prospectively evaluated for DD by certified neuroradiologists blinded to outcomes. HGB and BP data were obtained via electronic queries. Outcomes were obtained at 14 days and 3 months with the modified Rankin Scale (mRS), a functional scale scored from 0 (no symptoms) to 6 (dead). We used logistic regression for dependence or death (mRS 4 to 6).
DD distinct from the hematoma was found on MRI in 36 of 95 patients (38%). DD was associated with greater BP reductions from baseline, and a higher risk of dependence or death at 3 months (OR 4.8, 95% CI 1.7 – 13.9, P=0.004) after correction for ICH Score (1.8 per point, 95%CI 1.2–3.1, P=0.01). Lower HGB was associated with worse ICH score, larger hematoma volume and worse outcomes, but not DD.
DD is common after ICH, associated with greater acute BP reductions, and associated with disability and death at 3 months in multivariate analysis. The potential benefits of acute BP reduction to reduce hematoma growth may be limited by DD. The prevention and treatment of cerebral ischemia manifested as DD is a potential method to improve outcomes.
PMCID: PMC3246540  PMID: 21980211
12.  Intracranial Hemorrhage 
Intracranial hemorrhage is a life-threatening condition, the outcome of which can be improved by intensive care. Intracranial hemorrhage may be spontaneous, precipitated by an underlying vascular malformation, induced by trauma, or related to therapeutic anticoagulation. The goals of critical care are to assess the proximate cause, minimize the risks of hemorrhage expansion through blood pressure control and correction of coagulopathy, and obliterate vascular lesions with a high risk of acute rebleeding. Simple bedside scales and interpretation of computed tomography scans assess the severity of neurological injury. Myocardial stunning and pulmonary edema related to neurological injury should be anticipated, and can usually be managed. Fever (often not from infection) is common and can be effectively treated, although therapeutic cooling has not been shown to improve outcomes after intracranial hemorrhage. Most functional and cognitive recovery takes place weeks to months after discharge; expected levels of functional independence (no disability, disability but independence with a device, dependence) may guide conversations with patient representatives. Goals of care impact mortality, with do-not-resuscitate status increasing the predicted mortality for any level of severity of intraparenchymal hemorrhage. Future directions include refining the use of bedside neuromonitoring (electroencephalogram, invasive monitors), novel approaches to reduce intracranial hemorrhage expansion, minimizing vasospasm, and refining the assessment of quality of life to guide rehabilitation and therapy.
PMCID: PMC3361326  PMID: 22167847
intracranial hemorrhage; cerebral hemorrhage; subarachnoid hemorrhage; outcomes
14.  Anaemia and its treatment in neurologically critically ill patients: being reasonable is easy without prospective trials 
Critical Care  2010;14(3):149.
Most healthy humans have a haemoglobin concentration of 12 to 15 g/dL and most intensivists now transfuse packed red blood cells for haemoglobin <7 g/dL. Higher haemoglobin is associated with improved intermediate and clinical outcomes after subarachnoid hemorrhage (from ruptured brain aneurysm) or neurotrauma. An observational study in a recent issue shows that higher haemoglobin was associated with better functional outcomes in patients with spontaneous intracerebral haemorrhage; few patients received a packed red blood cell transfusion, so it is not known if that treatment is better than the disease. The mechanism of anaemia's purported impact on outcome is unclear, although altered metabolism in brain tissue that is sensitive to reduced oxygen delivery is plausible. These data may intensify the differences of opinion between intensivists: whether neurologic patients are better served by higher haemoglobin and potentially by more packed red blood cell transfusion, or simply need to be studied more in prospective clinical trials, remains unclear.
PMCID: PMC2911693  PMID: 20497614
15.  Red blood cell transfusion in patients with subarachnoid hemorrhage: a multidisciplinary North American survey 
Critical Care  2011;15(1):R30.
Anemia is associated with poor outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH). It remains unclear whether this association can be modified with more aggressive use of red blood cell (RBC) transfusions. The degree to which restrictive thresholds have been adopted in neurocritical care patients remains unknown.
We performed a survey of North American academic neurointensivists, vascular neurosurgeons and multidisciplinary intensivists who regularly care for patients with SAH to determine hemoglobin (Hb) concentrations which commonly trigger a decision to initiate transfusion. We also assessed minimum and maximum acceptable Hb goals in the context of a clinical trial and how decision-making is influenced by advanced neurological monitoring, clinician characteristics and patient-specific factors.
The survey was sent to 531 clinicians, of whom 282 (53%) responded. In a hypothetical patient with high-grade SAH (WFNS 4), the mean Hb concentration at which clinicians administered RBCs was 8.19 g/dL (95% CI, 8.07 to 8.30 g/dL). Transfusion practices were comparatively more restrictive in patients with low-grade SAH (mean Hb 7.85 g/dL (95% CI, 7.73 to 7.97 g/dL)) (P < 0.0001) and more liberal in patients with delayed cerebral ischemia (DCI) (mean Hb 8.58 g/dL (95% CI, 8.45 to 8.72 g/dL)) (P < 0.0001). In each setting, there was a broad range of opinions. The majority of respondents expressed a willingness to study a restrictive threshold of ≤8 g/dL (92%) and a liberal goal of ≥10 g/dl (75%); in both cases, the preferred transfusion thresholds were significantly higher for patients with DCI (P < 0.0001). Neurosurgeons expressed higher minimum Hb goals than intensivists, especially for patients with high-grade SAH (β = 0.46, P = 0.003), and were more likely to administer two rather than one unit of RBCs (56% vs. 19%; P < 0.0001). Institutional use of transfusion protocols was associated with more restrictive practices. More senior clinicians preferred higher Hb goals in the context of a clinical trial. Respondents were more likely to transfuse patients with brain tissue oxygen tension values <15 mmHg and lactate-to-pyruvate ratios >40.
There is widespread variation in the use of RBC transfusions in SAH patients. Practices are heavily influenced by the specific dynamic clinical characteristics of patients and may be further modified by clinician specialty and seniority, the use of protocols and advanced neurological monitoring.
PMCID: PMC3222066  PMID: 21244675

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