Prevalence of Concomitant Neurological Disorders and Long-Term Outcome of Patients Hospitalized for Intracerebral Hemorrhage with Versus without Cerebral Amyloid Angiopathy.

BACKGROUND: Patients with intracerebral hemorrhage (ICH) related to cerebral amyloid angiopathy (CAA) are at increased risk of developing epilepsy and cognitive disorders such as Alzheimer's disease (AD), mild cognitive impairment (MCI), and vascular dementia. In a retrospective cohort observation study of patients hospitalized for ICH with CAA versus ICH without CAA, we evaluated the prevalence of neurological comorbidities at admission and the risk of new diagnosis of epilepsy, relevant cognitive disorders, and mortality at 1 year. METHODS: In the TriNetX health research network, adult patients aged ≥ 55 years hospitalized with a diagnosis of ICH were stratified based on presence or absence of concomitant CAA diagnosis. Demographics and medical comorbidities were compared by using χ2 test and Student's t-test. After 1:1 propensity score matching, 1-year survival was assessed with Kaplan-Meier curves. The 1-year risk of new diagnosis of epilepsy, AD, MCI, vascular dementia, and dementia unspecified was assessed with Cox proportional hazards estimate. RESULTS: The study included a total of 1757 patients with ICH and CAA and 53,364 patients with ICH without CAA. Patients with CAA were older compared with those without CAA (74.1 ± 7.5 vs. 69.8 ± 8.8 years, p ≤ 0.001). Compared with ICH without CAA, patients with ICH and CAA had higher baseline prevalence of cerebral infarction (30% vs. 20%), nontraumatic ICH (36% vs. 7%), nontraumatic subarachnoid hemorrhage (14% vs. 5%), epilepsy (11% vs. 6%), and AD (5% vs. 2%) with significance at p < 0.001. After propensity score matching, a total of 1746 patients were included in both cohorts. In the matched cohorts, compared with patients with ICH without CAA, patients with ICH and CAA had lower 1-year all-cause mortality (479 [27%] vs. 563 [32%]; hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.71-0.90) and higher risk of new diagnosis of epilepsy (280 [18%] vs. 167 [11%]; HR 1.70; 95% CI 1.40-2.06), AD (101 [6%] vs. 38 [2%]; HR 2.62; 95% CI 1.80-3.80), MCI (85 [5%] vs. 35 [2%]; HR 2.39; 95% CI 1.61-3.54), vascular dementia (117 [7%] vs. 60 [4%]; HR 1.92; 95% CI 1.41-2.62), and dementia unspecified (245 [16%] vs. 150 [9%]; HR 1.70; 95% CI 1.39-2.08). CONCLUSIONS: Among patients admitted for ICH, patients with CAA have lower mortality but have 2-3 times more risk of diagnosis of epilepsy and dementia at 1 year, compared with those without CAA.

Kidney impairment and outcomes in acute ischaemic stroke.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk of stroke and mortality. AIMS: To evaluate the clinical and imaging features and outcomes of patients with and without kidney impairment among t admitted for acute ischaemic stroke (AIS). METHODS: AIS patients with brain magnetic resonance imaging (MRI) were included in the study. Kidney impairment was defined by an admission estimated glomerular filtration rate < 60 mL/min/1.73 m2 . Cerebral microbleeds (CMB) and white matter hyperintensities (WMH) were evaluated using the Microbleed Anatomical Rating Scale and Fazekas scales, respectively. Primary outcomes were defined by modified Rankin Scale (mRS) and discharge disposition. Multivariate logistic regression analysis was performed to evaluate factors associated with the presence of kidney impairment and poor discharge outcomes. RESULTS: Of the 285 patients with AIS, 80 had kidney impairment on admission. Patients with kidney impairment were older (mean age ± standard deviation: 74.7 ± 12.9 vs 64.4 ± 13.8 years, P < 0.0001) and had more neurological deficits on National Institutes of Health Stroke Scale (NIHSS) score (median 8.5 vs 5, P = 0.02). In unadjusted analysis, patients with kidney impairment were less likely to have a good functional outcome (mRS 0-2: 36% vs 57%, P = 0.002) and good discharge outcome (home or inpatient rehabilitation: 68% vs 82%, P = 0.008). On multivariate analysis, kidney impairment was associated with higher NIHSS score (odds ratio (OR) = 1.04; 95% confidence interval (CI) = 1.002-1.08) and severe WMH (OR = 1.99; 95% CI = 1.06-3.77) suggestive of small vessel disease, but kidney impairment was not associated with poor discharge outcome (OR = 1.62; 95% CI = 0.75-3.53). CONCLUSION: Presence of kidney impairment at the time of stroke presentation, regardless of previous renal function, is associated with more neurological deficits and severe WMH on MRI.

Bilateral Cerebral Hyperperfusion Syndrome Following Carotid Artery Stenting in Stroke - A Case Report.

BACKGROUND: Revascularization of the symptomatic carotid artery is performed with endarterectomy or stenting. Rarely, patients may develop cerebral hyperperfusion syndrome (CHS) following revascularization. This usually occurs in the cerebral hemisphere ipsilateral to revascularized carotid stenosis. CHS rarely involves the contralateral hemisphere. OBJECTIVE: To present a case of CHS involving bilateral cerebral hemispheres following carotid artery stenting in acute ischemic stroke. CASE DESCRIPTION: A 66-year-old woman presented with right side weakness and aphasia. National Institutes of Health stroke scale score was 27. CT angiogram/perfusion showed high grade left internal carotid artery (ICA) stenosis, left middle cerebral artery (MCA) occlusion, and increased time to peak in left MCA territory. She underwent mechanical thrombectomy with complete reperfusion. Left carotid artery stenting was performed for 85% cervical ICA stenosis with thrombus. She neurologically deteriorated and required intubation after the procedure. Follow-up CT perfusion at 18 hours after thrombectomy showed increased cerebral blood flow and early time to peak in bilateral MCA territories. CT head showed parenchymal hematoma in the left subcortical area with extension to the ventricle. Fluid-attenuated inversion recovery MRI on day 4 showed diffuse white matter hyperintensities in the entire right hemisphere, and left temporal and frontal lobes suggestive of vasogenic edema. CONCLUSION: This case highlights bilateral cerebral hyperperfusion syndrome characterized by neurological worsening, imaging findings of parenchymal hemorrhage, vasogenic edema and increased cerebral blood flow without any new ischemic lesions. The involvement of bilateral hemispheres in the absence of significant contralateral carotid stenosis is unique in this case.

Sex and racial disparity in utilization and outcomes of t-PA and thrombectomy in acute ischemic stroke.

BACKGROUND/PURPOSE: Racial/ethnic and sex disparity may occur in stroke throughout the continuum of care. Endovascular therapy (EVT) became standard of care in 2015 for eligible patients with acute ischemic stroke (AIS). We evaluated for racial and sex differences in t-PA and EVT utilization and outcomes in 2016 in the National Inpatient Sample. METHODS: Treatment rates for t-PA, EVT, and t-PA+EVT and outcomes including home discharge, in-hospital mortality and prolonged length of stay (pLOS) were evaluated by sex and race. Multivariate survey-logistic regression was performed to evaluate outcomes. RESULTS: The study had 468,630 patients - 49.3% men, 50.7% women; 69.3% whites, and 30.7% non-whites. There was no difference in treatment utilization by sex, women vs men for t-PA (7.65% vs 7.76%; aOR:1.02; 95% CI:0.97-1.07), EVT (1.74% vs 1.67%; aOR:1.09; 95% CI:0.99-1.20) and t-PA+EVT (0.57% vs 0.57%; aOR:1.01; 95% CI:0.85-1.21); and by race, non-white vs white for t-PA (7.62% vs 7.74%; aOR:0.98; 95% CI:0.93-1.05), EVT (1.62% vs 1.74%; aOR:0.91; 95% CI:0.78-1.07), and t-PA+EVT(0.59% vs 0.56%; aOR:1.05; 95% CI:0.84-1.30). Compared to men, women treated with t-PA had less home discharge (37.2% vs 46.3%; aOR:0.81; 95% CI:0.72-0.90), more in-hospital mortality (5.7% vs 3.9%; aOR:1.37; 95% CI:1.06-1.77) and less pLOS (8.3% vs 9.6%; aOR:0.82; 95% CI:0.69-0.98); women treated with EVT had less home discharge (15.8% vs 23.7%; aOR:0.69; 95% CI:0.52-0.91). Compared to whites, non-whites treated with t-PA had lower odds of home discharge (42.1% vs 41.6%; aOR:0.79; 95% CI:0.69-0.90), less in-hospital mortality (3.7% vs 5.3%; aOR:0.65; 95% CI:0.49-0.87), and higher pLOS (11.4% vs 7.9%; aOR:1.3; 95% CI:1.07-1.56); non-whites treated with EVT had less home discharge (18%vs 20.2%; aOR:0.70; 95% CI:0.51-0.97) and higher pLOS (35.1% vs 24%; aOR:1.52; 95% CI:1.16-1.99). CONCLUSION: Sex and racial disparity exists for outcomes of t-PA and EVT despite no difference in utilization rates.

Hypertension is a Leading Cause of Nontraumatic Intracerebral Hemorrhage in Young Adults.

OBJECTIVE: To evaluate the etiology and discharge outcome of nontraumatic intracerebral hemorrhage (ICH) in young adults admitted to a comprehensive stroke center. METHODS: A retrospective chart review was performed on patients with a discharge diagnosis of nontraumatic ICH admitted from 7/1/2011 to 6/30/2016. Data was collected on demographics, clinical history, ICH score, hemorrhage location, do-not-resuscitate (DNR) orders, likely etiology, and discharge disposition. Categorical data was reported as percentage. Chi-squared test was performed to evaluate association of location of ICH, etiology of ICH, and ICH score with the discharge outcome. RESULTS: Sixty-three patients met the study criteria, with mean age 35.4 ± 6.4 years including 26 (41%) women and 40 (64%) whites. Headache (65%) and change in mental status (48%) were the most common presenting symptoms. Hemorrhage was most commonly seen in the deep structures in 29 (46%) patients followed by lobar ICH in 14 (22%) patients. The most common etiology of ICH was hypertension in 23 (37%) patients, followed by vascular abnormalities in 18 (29%) patients. Forty-two (67%) had good outcome defined as discharge to home (n = 25) or acute inpatient rehabilitation (n = 17). Twenty-one (33%) patients had bad outcome with discharge to skilled nursing facility (n = 6), hospice (n = 1) or died in the hospital (n = 14). Hospital DNR orders were noted in 11 (18%) patients. Higher ICH score (P < .0001) and use of DNR orders (P < .0001) were associated with bad outcome. All 11 patients with DNR orders died in the hospital. Location or etiology of hemorrhage were not associated with discharge outcome. CONCLUSIONS: Hypertension, a modifiable risk factor, is a major cause of nontraumatic ICH in young adults. Aggressive management of hypertension is essential to halt the recent increased trends of ICH due to hypertension. Early DNR orders may need to be cautiously used in the hospital.

Cerebral Microbleeds are an Independent Predictor of Hemorrhagic Transformation Following Intravenous Alteplase Administration in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Intravenous alteplase (rt-PA) increases the risk of hemorrhagic transformation of acute ischemic stroke. The objective of our study was to evaluate clinical, laboratory, and imaging predictors on forecasting the risk of hemorrhagic transformation following treatment with rt-PA. We also evaluated the factors associated with cerebral microbleeds that increase the risk of hemorrhagic transformation. METHODS: Consecutive patients with acute ischemic stroke admitted between January 1, 2009 and December 31, 2013 were included in the study if they received IV rt-PA, had magnetic resonance imaging (MRI) of the brain on admission, and computed tomography or MRI of the brain at 24 (18-36) hours later to evaluate for the presence of hemorrhagic transformation. The clinical data, lipid levels, platelet count, MRI, and computed tomography images were retrospectively reviewed. RESULTS: The study included 366 patients, with mean age 67 ± 15 years; 46% were women and 88% were white. The median National Institutes of Health Stroke Scale (NIHSS) score was 6 (interquartile range 3-15). Hemorrhagic transformation was observed in 87 (23.8%) patients and cerebral microbleeds were noted in 95 (25.9%). Patients with hemorrhagic transformation tended to be older, nonwhite, have atrial fibrillation, higher baseline NIHSS score, lower cholesterol and triglyceride levels, and cerebral microbleeds and nonlacunar infarcts. Patients with cerebral microbleeds were more likely to be older, have hypertension, hyperlipidemia, previous history of stroke, and prior use of antithrombotics. On multivariate analysis race, NIHSS score, nonlacunar infarct, and presence of cerebral microbleeds were independently associated with hemorrhagic transformation following treatment with rt-PA. CONCLUSIONS: Presence of cerebral microbleeds is an independent predictor of hemorrhagic transformation of acute ischemic stroke following treatment with rt-PA.

Global SUMOylation facilitates the multimodal neuroprotection afforded by quercetin against the deleterious effects of oxygen/glucose deprivation and the restoration of oxygen/glucose.

The putative neuroprotective properties of various flavonoids have long been reported. Among this class of chemicals, quercetin, a major flavone/flavonol naturally occurring in plants, deserves focused attention because of the myriad of beneficial effects observed in various in vitro and in vivo models of central nervous system damage/degeneration. However, the mechanisms governing the beneficial outcomes mediated by quercetin remain to be elucidated. In an effort to define the underlying molecular mechanisms, our study employed human/rat neuroblastoma cell lines (SHSY5Y and B35, respectively) and E18-derived rat primary cortical neurons upon which the effects of various flavonoids were examined. Of note, increases in the levels of global SUMOylation, a post-translational modification with the Small Ubiquitin-like MOdifier (SUMO) were pronounced. Quercetin treatment increased SUMOylation levels in both SHSY5Y cells and rat cortical neurons in a dose and time-dependent manner, possibly via the direct inactivation of certain SENPs (SUMO-specific isopeptidases). Of particular interest, cells treated with quercetin displayed increased tolerance to oxygen/glucose deprivation exposure, an in vitro model of ischemia. SHSY5Y cells treated with quercetin also increased the expression of Nrf2 (via a decrease in the levels of Keap1), heme oxygenase-1 (HO-1), and nitric oxide synthase 1 (NOS1), which provide further protection from oxidative stress. In addition, the increased SUMOylation of HIF-1α was noted and deemed to be significant. We hypothesize that SUMOylated HIF-1α plays a fundamental role in the protection afforded and may underlie some of quercetin's ability to protect cells from oxygen/glucose deprivation-induced cell death, via an up-regulation of HO-1 and NOS1, which ultimately leads to the induction of pro-life NOS1/protein kinase G signaling. Quercetin acts to increase survival in the face of ischemia via an increase of SENP3 expression, the possible inactivation of SENPs 1/2, and via a decrease in KEAP1 levels (thereby increasing Nrf2 stability). These changes may then lead to increase in HIF-1α SUMOylation and HO-1 activation, followed by an up-regulation of NOS1/PKG signaling. Pathways altered via quercetin treatment within our experimental system are represented by blue arrowheads. Solid black arrows represent relationships that have been explored while a dotted arrow represents a relationship that has yet to be confirmed.

Mediation of Reduced Hippocampal Volume by Cerebral Amyloid Angiopathy in Pathologically Confirmed Patients with Alzheimer's Disease.

BACKGROUND: Hippocampal atrophy in cerebral amyloid angiopathy (CAA) has been reported to be similar to that in Alzheimer's disease (AD). OBJECTIVE: To evaluate if CAA pathology partly mediates reduced hippocampal volume in patients with AD. METHODS: Patients with a clinical diagnosis of AD and neuropathological confirmation of AD+/-CAA in the National Alzheimer's Coordinating Center database were included in the study. The volumes of temporal lobe structures were calculated on T1-weighted imaging (T1-MRI) using automated FreeSurfer software, from images acquired on average 5 years prior to death. Multivariate regression analysis was performed to compare brain volumes in four CAA groups. The hippocampal volume on T1-MRI was correlated with Clinical Dementia Rating sum of boxes (CDRsb) score, apolipoprotein E (APOE) genotype, and hippocampal atrophy at autopsy. RESULTS: The study included 231 patients with no (n = 45), mild (n = 70), moderate (n = 67), and severe (n = 49) CAA. Among the four CAA groups, patients with severe CAA had a smaller mean left hippocampal volume (p = 0.023) but this was not significant when adjusted for APOE ɛ4 (p = 0.07). The left hippocampal volume on MRI correlated significantly with the hippocampal atrophy grading on neuropathology (p = 0.0003). Among patients with severe CAA, the left hippocampal volume on T1-MRI: (a) decreased with an increase in the number of APOE ɛ4 alleles (p = 0.04); but (b) had no evidence of correlation with CDRsb score (p = 0.57). CONCLUSION: Severe CAA was associated with smaller left hippocampal volume on T1-MRI up to five years prior to death among patients with neuropathologically confirmed AD. This relationship was dependent on APOE ɛ4 genotype.

Standard clinical and imaging-based small vessel disease parameters associated with mild stroke versus non-mild stroke.

Background: Mild stroke has variable outcomes, and there is an ongoing debate regarding whether the administration of thrombolytics improves outcomes in this subgroup of stroke patients. Having a better understanding of the features of mild stroke may help identify patients who are at risk of poor outcomes. Objective: The objective of this study is to evaluate the association of clinical and imaging-based small vessel disease features (white matter hyperintensities and cerebral microbleeds) with stroke severity and clinical outcomes in patients with mild stroke. Methods: In this retrospective study, mild stroke was defined as a National Institute of Health stroke scale (NIHSS) score <5. Clinical, laboratory and imaging data were compared between patients with mild stroke versus non-mild stroke (NIHSS≥5). Multivariate logistic regression analysis was performed to identify predictors of mild stroke and poor discharge outcome. Results: Among 296 patients included in the study, 131 patients (44%) had mild stroke. On multivariate analysis, patients with mild stroke were three times more likely to have sensory symptoms [odds ratio (OR) = 2.9; 95% confidence interval (CI) = (1.2-6.8)] and four times more likely to have stroke due to small vessel disease (OR = 3.7; 95%CI = 1.4-9.9). Among patients with mild stroke, higher age (OR = 1.1; 95%CI = 1.02-1.1), presence of cerebral microbleed (OR = 4.5; 95%CI = 1.5-13.8), vertigo (OR = 7.3; 95%CI = 1.2-45.1) and weakness (OR = 5.0; 95%CI = 1.2-20.3) as presenting symptoms were more likely to have poor discharge outcome. Conclusion: Sensory symptoms and stroke due to small vessel disease are more common in mild stroke than non-mild stroke. Among patients with mild stroke, presence of cerebral microbleeds on imaging and symptoms of muscle weakness are associated with poor discharge outcome. Larger studies are needed to assess the impact of cerebral microbleed on mild stroke outcomes and risk stratify the benefit of thrombolytics in this group.

Imaging features of small vessel disease in cerebral amyloid angiopathy among patients with Alzheimer's disease.

BACKGROUND AND PURPOSE: Cerebral small vessel disease biomarkers including white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces (ePVS) are under investigation to identify those specific to cerebral amyloid angiopathy (CAA). In subjects with Alzheimer's disease (AD), we assessed characteristic features and amounts of WMH, lacunes, and ePVS in four CAA categories (no, mild, moderate and severe CAA) and correlated these with Clinical Dementia Rating sum of boxes (CDRsb) score, ApoE genotype, and neuropathological changes at autopsy. METHODS: The study included patients with a clinical diagnosis of dementia due to AD and neuropathological confirmation of AD and CAA in the National Alzheimer's Coordinating Center (NACC) database. The WMH, lacunes, and ePVS were evaluated using semi-quantitative scales. Statistical analyses compared the WMH, lacunes, and ePVS values in the four CAA groups with vascular risk factors and AD severity treated as covariates, and to correlate the imaging features with CDRsb score, ApoE genotype, and neuropathological findings. RESULTS: The study consisted of 232 patients, of which 222 patients had FLAIR data available and 105 patients had T2-MRI. Occipital predominant WMH were significantly associated with the presence of CAA (p = 0.007). Among the CAA groups, occipital predominant WMH was associated with severe CAA (ß = 1.22, p = 0.0001) compared with no CAA. Occipital predominant WMH were not associated with the CDRsb score performed at baseline (p = 0.68) or at follow-up 2-4 years after the MRI (p = 0.92). There was no significant difference in high grade ePVS in the basal ganglia (p = 0.63) and centrum semiovale (p = 0.95) among the four CAA groups. The WMH and ePVS on imaging did not correlate with the number of ApoE ε4 alleles but the WMH (periventricular and deep) correlated with the presence of infarcts, lacunes and microinfarcts on neuropathology. CONCLUSION: Among patients with AD, occipital predominant WMH is more likely to be found in patients with severe CAA than in those without CAA. The high-grade ePVS in centrum semiovale were common in all AD patients regardless of CAA severity.

Tremor Induced by Cyclosporine, Tacrolimus, Sirolimus, or Everolimus: A Review of the Literature.

Calcineurin inhibitors such as cyclosporine and tacrolimus are immunosuppressant drugs that are known to induce tremors. Non-calcineurin inhibitors such as sirolimus and everolimus have also reportedly been accompanied by tremors, albeit less likely. However, the prevalence rates reported in the literature are notably wide, and the risk profiles for these drug-induced tremors are less understood. We searched PubMed to extract data on the risk of tremors with these drugs when prescribed for various transplant and non-transplant indications. We ascertained whether the risk of drug-induced tremor is influenced by the underlying diagnosis, dosing formulations, drug concentrations, and blood monitoring. We extracted data on treatment strategies and outcomes for tremors. Articles were primarily screened based on English language publications, abstracts, and studies with n ≥ 5, which included case series, retrospective studies, case-controlled studies, and prospective studies. We found 81 eligible studies comprising 33 cyclosporine, 43 tacrolimus, 6 sirolimus, and 1 everolimus that discussed tremor as an adverse event. In the pooled analysis of studies with n > 100, the incidence of tremor was 17% with cyclosporine, 21.5% with tacrolimus, and 7.8% with sirolimus and everolimus together. Regarding the underlying diagnosis, tremor was more frequently reported in kidney transplant (cyclosporine 28%, tacrolimus 30.1%) and bone marrow transplant (cyclosporine 40%, tacrolimus 41.9%) patients compared with liver transplant (cyclosporine 9%, tacrolimus 11.5%) and nontransplant indications (cyclosporine 21.5%, tacrolimus 11.3%). Most studies did not report whether the risk of tremors correlated with drug concentrations in the blood. The prevalence of tremors when using the twice-daily formulation of tacrolimus was nearly the same as the once-daily formulation (17% vs 18%). Data on individual-level risk factors for tremors were lacking. Except for three studies that found some benefit to maintaining magnesium levels, there were minimal data on treatments and outcomes. A large body of data supports a substantive and wide prevalence of tremor resulting from tacrolimus use followed by cyclosporine, especially in patients receiving a kidney transplant. However, there is little reporting on the patient-related risk factors for tremor, risk relationship with drug concentrations, treatment strategies, and outcomes.

Association of deep white matter hyperintensity with left ventricular hypertrophy in acute ischemic stroke.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) are associated with the presence of left ventricular hypertrophy (LVH). It is unclear if periventricular WMH (PV-WMH) and or deep WMH (D-WMH) are associated with LVH. We evaluated the association of PV-WMH and D-WMH with common transthoracic echocardiogram abnormalities, including LVH in acute ischemic stroke. METHODS: PV-WMH and D-WMH were graded on a 0-3 score based on the Fazekas scale. Patients were categorized into clinically significant PV-WMH and D-WMH (score 2-3) and controls (score 0-1). Multivariate logistic regression analysis was performed to determine abnormalities on echocardiogram associated with PV-WMH and D-WMH. RESULTS: Among 272 patients, 137 patients had PV-WMH and 93 patients had D-WMH with a score of 2-3 on Fazekas scale. Compared to controls, patients with PV-WMH (mean age±standard deviation: 60.8±14.4 vs. 73.8±11.2 years) and D-WMH (63.4±14.4 vs. 75.0±11.1 years) were older. Compared to controls, PV-WMH was associated with history of stroke (22 [16%] vs. 37 [27%], p = .03) and valvular calcification (33 [24%] vs. 61 [45%], p = .0005); D-WMH was associated with history of atrial fibrillation (25 [14%] vs. 22 [24%], p = .04), valvular calcification (50 [28%] vs. 44 [47%], p = .001), and LVH (30 [17%] vs. 25 [27%], p = .049). In multivariate analysis, PV-WMH was associated with age (odds ratio [OR] = 1.09; 95% confidence interval [CI] = 1.06-1.12) and stroke history (OR = 2.1; 95% CI = 1.1-4.1), and D-WMH was associated with age (OR = 1.07; 95% CI = 1.05-1.10) and LVH (OR = 2.0; 95% CI = 1.0-4.0). CONCLUSION: LVH is associated with D-WMH but not with PV-WMH. Although valvular calcification is common, it is likely age related than due to WMH.

Recurrent intracerebral hemorrhage in patients with cerebral amyloid angiopathy: a propensity-matched case-control study.

OBJECTIVE: Cerebral amyloid angiopathy (CAA) can present with intracerebral hemorrhage (ICH), convexity subarachnoid hemorrhage (SAH), and rarely acute ischemic stroke (AIS). The objective of our study was to compare the readmission rates for recurrent ICH, SAH, and AIS among patients admitted for ICH with and without CAA. METHODS: Using the National Readmissions Database 2016-2018 we identified patients admitted for ICH with and without a concomitant diagnosis of CAA. Primary outcome of the study was readmission due to ICH. Secondary outcomes included readmissions due to AIS and SAH. Survival analysis was performed, and Kaplan-Meier curves were created to assess for readmissions. RESULTS: The study consisted of 194,290 patients with ICH, 8247 with CAA and 186,043 without CAA as a concomitant diagnosis. After propensity matching, we identified 7857 hospitalizations with CAA and 7874 without CAA. Patients with CAA had higher risk of readmission due to ICH as compared to those without CAA [hazards ratio (HR) 3.44, 95% confidence interval (CI) 2.55-4.64, P < 0.001] during the mean follow-up period of 181.4 (SD ± 106.4) days. Patients with CAA were also more likely to be readmitted due to SAH (HR 2.52, 95% CI 1.18-5.37, P 0.017) but not due to AIS (HR 0.74, 95% CI 0.54-1.01, P 0.061). Age (HR 0.96 per year increase in age, 95% CI 0.94-0.98, P < 0.001) and Medicare payer (HR 3.31; 95% CI 1.89-5.78, P < 0.001) were independently associated with readmissions due to ICH. DISCUSSION: Patients admitted for ICH with a concomitant diagnosis of CAA are three times more likely to have readmissions for recurrent ICH compared to patients without CAA.

Neurological deterioration and computed tomography perfusion changes with increased time to peak in lacunar stroke.

OBJECTIVES: Lacunar strokes can have fluctuations and progression in the acute period leading to poor outcomes. Our study sought to evaluate if, in lacunar strokes, neurological deterioration (ND) was associated with blood pressure (BP) variations, stroke size, or increased time to peak (TTP) on admission computed tomography perfusion (CTP). METHODS: Patients with lacunar stroke who had magnetic resonance imaging and CTP performed were enrolled in the study. ND was defined as ≥1-point worsening on a modified National Institutes of Health Stroke Scale (NIHSS) score or the Medical Research Council scale compared to baseline assessment. The difference in BP between the day of admission and the day of ND was calculated. Multivariate logistic regression analysis, adjusted for pertinent clinical and imaging covariates, was performed to determine predictors of ND. RESULTS: Among 409 patients screened, 49 were eligible for the study. There was no difference in age, gender, race, medical history, admission BP, and the modified NIHSS score between patients with and without ND. In unadjusted analysis, patients with ND tended to have increased TTP in the stroke area compared to the control (12 [63%] vs. 11 [37%], P = 0.07). On multivariate analysis adjusted for covariates, presence of an increased TTP on CTP was a predictor of ND (odds ratio [95% confidence interval] = 4.80 [1.15-20.10], P = 0.03). CONCLUSION: The presence of an increased TTP on CTP corresponding to the stroke lesion on diffusion-weighted imaging is a predictor of ND in patients with lacunar stroke. Larger studies are needed to confirm our findings.

Clinical and Imaging Features Associated with the Utilization of Comfort Measures Only in Acute Ischemic Stroke.

Objectives: Up to 10% of acute ischemic stroke (AIS) patients can die in the first 30 days. Older age and a higher National Institutes of Health Stroke Scale (NIHSS) score are associated with transition to comfort measures only (CMO) in AIS. There are insufficient data on specific stroke etiology, infarct location, or vascular territory for the association of AIS with the use of CMO. We therefore evaluated the clinical and imaging factors associated with utilization of CMO and their outcomes. Methods: AIS patients seen in an academic comprehensive stroke center in the United States between July 1, 2015, and June 30, 2016, were subgrouped based on the use of CMO orders (CMO vs. non-CMO) during hospitalization. Clinical, laboratory, and imaging data were analyzed. Multivariable logistic regression analysis was performed, adjusting for pertinent covariates. Results: The study consisted of 296 patients, 27 (9%) patients were transitioned to CMO. Compared with non-CMO patients, those with CMO were older (mean ± standard deviation: 66 ± 15 vs. 75 ± 11 years, p = 0.002). Hemorrhagic transformation of AIS was more likely in CMO (17% vs. 41%, p = 0.0030) compared with non-CMO patients. On multivariate analysis, severe stroke measured by the NIHSS score (odds ratio [OR] = 1.2; 95% confidence interval [CI] = 1.1-1.4), infarction of the insular cortex (OR = 12.9; 95% CI = 1.4-118.4), and presence of cerebral edema with herniation (OR = 9.4; 95% CI = 2.5-35.5) were associated with transition to CMO. Conclusions: The presence of severe stroke, infarction of the insular cortex, and cerebral edema with herniation were associated with utilization of CMO in AIS. Impairment of multiple neurological functions served by the insular cortex could play a role in transition to CMO.

Benefits of an interdisciplinary stroke clinic: addressing a gap in physical therapy at post-stroke neurology follow-up.

BACKGROUND AND PURPOSE: An interdisciplinary stroke clinic (ISC) can improve communication and identify people post-stroke who have not reached their full recovery potential. We describe the characteristics of participants who underwent physical therapy (PT) evaluation in addition to their outpatient neurology evaluation and identify the association of assessment scales that predicted referral for additional rehabilitation. METHODS: Participants' post-stroke seen in the ISC were included in the study. The PT evaluation included the Berg Balance Scale (BBS), Ten-Meter Walk Test (10MWT), Six-Minute Walk Test (6MWT), and Short Form-Stroke Impact Scale (SF-SIS). Multivariable logistic regression analysis was performed to identify factors associated with referral for additional rehabilitation. RESULTS: The study consisted of 148 participants with a mean age of 63 (SD ± 15) years; 58% were women and 76% were Whites. Additional rehabilitation was recommended for 59% of participants. In multivariate analysis, reduced speed on comfortable 10MWT (OR = 0.06; 95%CI = 0.01-0.51) and lower SF-SIS score (OR = 0.76; 95%CI = 0.66-0.87) were significantly associated with referral for additional PT or occupational therapy. CONCLUSION: A significant number of post-acute stroke survivors were found to be appropriate for additional rehabilitation when assessed clinically by a neurologic physical therapist in an ISC. The measures that most closely correlated with this in-person clinical evaluation were 10MWT and SF-SIS.IMPLICATIONS FOR REHABILITATIONAn interdisciplinary stroke clinic can improve communication and identify people post-stroke who have not reached their full recovery potential.In a pilot study, a significant number of post-acute stroke survivors were found to be appropriate for additional rehabilitation when assessed clinically by a neurologic physical therapist in an interdisciplinary stroke clinic.Reduced speed on comfortable Ten-Meter Walk Test and lower Short Form-Stroke Impact Scale scores were associated with referral for additional rehabilitation.

Diffusion weighted imaging in acute ischemic stroke: A review of its interpretation pitfalls and advanced diffusion imaging application.

Diffusion weighted imaging (DWI) is a widely used imaging technique to evaluate patients with stroke. It can detect brain ischemia within minutes of stroke onset. However, DWI has few potential pitfalls that should be recognized during interpretation. DWI lesion could be reversible in the early hours of stroke and the entire lesion may not represent ischemic core. False negative DWI could lead to diagnosis of DWI negative stroke or to a missed stroke diagnosis. Ischemic stroke mimics can occur on DWI with non-cerebrovascular neurological conditions. In this article, the history of DWI, its clinical applications, and potential pitfalls for use in acute ischemic stroke are reviewed. Advanced diffusion imaging techniques with reference to Diffusion Kurtosis Imaging and Diffusion Tensor Imaging that has been studied to evaluate ischemic core are discussed.

Disparities in diagnosis of cerebral amyloid angiopathy based on hospital characteristics.

Cerebral amyloid angiopathy (CAA) categorized as a cerebral small vessel disease can cause lobar intracerebral hemorrhage (ICH), convexity subarachnoid hemorrhage (SAH) and ischemic stroke (IS). The purpose of this study was to evaluate the differences in the diagnosis of CAA based on hospital characteristics and to assess the discharge outcomes of patients with CAA admitted for IS, ICH and SAH. Adult patients admitted with secondary diagnosis of CAA were identified in National Inpatient Sample in 2016 and 2017. Multivariable logistic regression analysis was performed to evaluate outcomes. A total of 16,040 patients had a secondary diagnosis of CAA. Among CAA patients, 1810 (11.3%) patients were admitted for IS, 4765 (29.7%) for ICH and 490 (3.1%) for SAH. Diagnosis of CAA was five-fold higher among patients admitted to urban teaching hospitals (aOR = 5.4;95% CI = 4.1-7.2) compared to rural hospitals and two-fold higher in large bed size hospitals (aOR = 2.3;95% CI = 2.0-2.7) compared to small bed size hospitals. Compared to non-CAA group, patients with history of CAA had lower odds of in-hospital mortality among patients admitted for ICH (10% vs 23%, aOR = 0.35; 95%CI = 0.27-0.44) and SAH (6% vs 19%, aOR = 0.24; 95%CI = 0.10-0.55); and higher odds of discharge to home among patients admitted for ICH (17% vs 18%, aOR = 1.27; 95%CI = 1.05-1.53). CAA diagnosis is less common in rural and small bed size hospitals compared to urban and large bedside hospitals, respectively. Patients with CAA admitted for ICH have better discharge outcomes compared to non-CAA patients admitted for ICH.

Nonabducent Cranial Neuropathies in Cerebral Venous Sinus Thrombosis: A Case Report and Literature Review.

INTRODUCTION: Cerebral venous sinus thrombosis (CVST) can rarely present with cranial neuropathies other than abducent nerve palsy. The authors report a case and review the literature for nonabducent cranial neuropathies in CVST. CASE REPORT: A 22-year-old woman with a history of oral contraceptive use developed right-sided headache, blurred vision, and dizziness for 4 days. Magnetic resonance venogram showed complete thrombosis of the right transverse sinus, sigmoid sinus, and internal jugular vein, and partial thrombosis of the superior sagittal sinus, left transverse sinus, and superior part of the left internal jugular vein. Hypercoagulable workup revealed heterozygous factor V Leiden mutation. About 2 weeks after symptom onset, she developed right facial droop and left eye ptosis. Examination revealed bilateral papilledema, partial left ptosis, complete right abducent, and right peripheral facial palsies. Acetazolamide 250 mg 2 times per day was initiated for the treatment of headache. Three days after starting acetazolamide left ptosis, right facial and abducent palsies improved that continued to get better with only slight deficits at discharge 4 weeks from symptom onset. Follow-up computed tomography venogram on day 24 showed partial recanalization of CVST. CONCLUSION: A systematic review identified 26 patients from 21 articles with nonabducent cranial neuropathies. Seven patients had lower motor neuron facial palsy, 13 patients had hearing loss or vertigo with vestibulocochlear involvement, and 6 patients had other mixed cranial nerve palsies with CVST. They are usually associated with transverse sinus and/or sigmoid sinus thrombosis. They have a good prognosis with improvement and complete resolution of cranial neuropathies in most cases usually in 1 month.

Age differences in utilization and outcomes of tissue-plasminogen activator and mechanical thrombectomy in acute ischemic stroke.

BACKGROUND AND PURPOSE: U.S. demographics is shifting towards older population. Older stroke patients likely receive less tissue-plasminogen activator (t-PA) and mechanical thrombectomy (MT) compared to younger patients. The objective of this study is to evaluate extent of difference in utilization of t-PA and MT and outcomes of stroke between three age groups -18-45 (young adults), 46-80 (middle/old), and > 80 (oldest old) years. METHODS: It is a retrospective cross-sectional observational study. Primary outcomes were rates of stroke intervention and effect of age on stroke intervention. Secondary outcomes were in-hospital mortality, discharge to home, and prolonged length of stay. Multivariate survey-logistic regression was performed to evaluate outcomes. RESULTS: Among 487,105 patients in the study 4.8% were young adults, 66.6% middle/old, and 28.6% oldest old. Compared to young adults, middle/old received 19% (OR = 0.81; 95%CI = 0.72-0.91) less t-PA alone; and 33% (OR = 0.67; 95%CI = 0.53-0.83) less MT alone; oldest old received 25% less t-PA alone (OR = 0.75; 95%CI = 0.66-0.86) and 51% (OR = 0.49; 95%CI = 0.38-0.63) less MT alone. Compared to young adults, in-hospital mortality was three-fold higher among middle/old (OR = 3.5; 95%CI = 1.3-9.6), and seven-fold higher among oldest old (OR = 7.5; 95%CI = 2.8-20.5) for t-PA alone; discharge to home reduced by 40% in middle/old (OR = 0.6; 95%CI = 0.4-0.7) and by 80% in oldest old (OR = 0.2; 95%CI = 0.1-0.2) for t-PA alone and similarly for MT alone. CONCLUSIONS: Oldest old receive one-fourth less t-PA and half less MT compared to young adults. Oldest old patients who received t-PA alone or MT alone had remarkably worse outcomes for in-hospital mortality and discharge to home than young adults did.