Mahesh Kate

Serial Montreal Cognitive Assessments Demonstrate Reversible Cognitive Impairment in Patients With Acute Transient Ischemic Attack and Minor Stroke

Background and Purpose— Cognitive changes after ischemic stroke are often overlooked, particularly acutely and in patients with mild or transient deficits. We assessed patients with transient ischemic attack (TIA)/minor stroke with serial cognitive screening tests. We tested the hypothesis that mild acute deficits are transient and improve after TIA/minor stroke. Methods— Patients with acute TIA/minor ischemic stroke, without a history of cognitive impairment, presenting with a National Institute of Health Stroke Scale score ⩽3 were assessed <72 hours of onset. Patients were administered the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) at days 1, 7, 30, and 90. Cognitive impairment was defined as MoCA <26 and MMSE ⩽26. Results— One hundred patients with a median (interquartile range) National Institute of Health Stroke Scale score of 1 (2) and median age of 68 (20) years were included. Baseline median MoCA score (26 [4]) was lower than the MMSE (29 [2]; P<0.0001). Cognitive impairment was detected in 54 of 100 patients (54%) with MoCA and 16 of 100 (16%; P=0.001) with MMSE. MoCA scores improved at day 7 (27 [5]), day 30 (28 [2]), and day 90 (28 [2]; P<0.0001). Resolution of cognitive deficits was because of resolution of recall deficits. Conclusions— Acute temporary cognitive impairment after TIA/minor stroke is common. The MoCA is sensitive to these changes, but the MMSE is not. Routine cognitive assessment after TIA/minor stroke may be warranted and relevant to return to activities even when other neurological deficits are not evident.

Cerebral Perfusion and Blood Pressure Do Not Affect Perihematoma Edema Growth in Acute Intracerebral Hemorrhage

Background and Purpose— The pathogenesis of perihematoma edema in intracerebral hemorrhage (ICH) is unknown but has been hypothesized to be ischemic. In the ICH Acutely Decreasing Arterial Pressure Trial (ICH ADAPT), perihematoma cerebral blood flow (CBF) was reduced but was unaffected by blood pressure (BP) reduction. Using ICH ADAPT data, we tested the hypotheses that edema growth is associated with reduced CBF and lower systolic BP. Methods— Noncontrast computed tomographic scans in patients with ICH were obtained at baseline, 2 hours, and 24 hours after randomization to target systolic BPs of <150 or <180 mm Hg. Computed tomography perfusion imaging was performed at 2 hours, and mean relative CBF was calculated in visibly edematous perihematoma tissue. Edema volumes were measured using a Hounsfield unit threshold of 5 to 23 at each time-point. Results— Patients were randomized at a median (interquartile range) of 7.4 (12.8) hours after onset. Treatment groups (n=34, <150 and n=33, <180 target) were balanced with respect to baseline systolic BP and acute ICH volume. Relative edema growth at 24 hours in the <150 group (0.11±0.19) was similar to that in the <180 group (0.09±0.16 mL; P=0.727). Absolute CBF was lower in the edematous region (35.67±13.1 mL/100 g per minute) when compared with that in the contralateral tissue (43.7±11.7 mL/100 g per minute; P<0.0001). Linear regression indicated that neither systolic BP change (&bgr;=–0.022; 95% confidence interval, –0.002 to 0.001) nor perihematoma relative CBF (&bgr;=–0.144; 95% confidence interval, –0.647 to 0.167) predicted edema growth. Conclusions— Lower perihematoma CBF and BP treatment do not exacerbate edema growth. These data do not support a cytotoxic edema pathogenesis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00963976.

Proposed Approach to Thrombolysis in Dabigatran-Treated Patients Presenting with Ischemic Stroke

BACKGROUND Acute ischemic stroke thrombolysis in patients taking dabigatran is controversial because of a presumed increased risk of symptomatic hemorrhagic transformation. Using data from our local hematopathology laboratory, we developed a thrombolysis protocol for acute ischemic stroke patients taking dabigatran. METHODS A local thrombin time (TT)-dabigatran concentration relationship was calculated using dabigatran calibrators. The effect of dabigatran on activated partial thromboplastin time (aPTT) and prothrombin time (PT) (international normalized ratio [INR]) was also measured. A protocol was developed, in which a dabigatran concentration less than 10 ng/mL (corresponding to a TT<38 seconds or a normal aPTT) was selected as the upper limit for thrombolysis. Consecutive patients presenting with acute stroke were then enrolled in this prospective study. RESULTS In the 8 months after development of the protocol, 13 potential thrombolysis candidates taking dabigatran were assessed at a median (interquartile range) time of 192 (143) minutes. The median National Institutes of Health Stroke Scale score was 18 (20). The mean time from arrival to TT, aPTT, and PT (INR) results were 39±4.1 minutes, 21±6.5 minutes, and 21±6.5 minutes, respectively. Based on TT/aPTT, 4 patients were ineligible for thrombolysis. Six patients were not treated because of minor or resolving symptoms and another presented with intracerebral hemorrhage. Two patients were treated with intravenous tissue plasminogen activator (tPA), without symptomatic hemorrhagic transformation in either case. In 3 patients (42.8%), aPTT was normal, despite a prolonged TT. CONCLUSIONS Administration of intravenous tPA in dabigatran-treated patients is feasible. Although, the relationship between dabigatran concentrations and coagulation measures varies between laboratories, individual protocols, preferably based on TT, can be developed at acute stroke treatment centers.

Autoregulation of Cerebral Blood Flow Is Preserved in Primary Intracerebral Hemorrhage

Background and Purpose— Treatment of acute hypertension after intracerebral hemorrhage (ICH) is controversial. In the context of disrupted cerebral autoregulation, blood pressure (BP) reduction may cause decreased cerebral blood flow (CBF). We used serial computed tomography perfusion to test the hypothesis that CBF remains stable after BP reduction. Methods— Patients recruited within 72 hours of ICH were imaged with computed tomography perfusion before and after BP treatment. Change in perihematoma relative (r) CBF after BP treatment was the primary end point. Results— Twenty patients were imaged with computed tomography perfusion at a median (interquartile range) time from onset of 20.2 (25.7) hours and reimaged 2.1 (0.5) hours later, after BP reduction. Mean systolic BP in treated patients (n=16; 4 untreated as BP<target at baseline) decreased significantly between the first (168±21 mm Hg) and second (141±19 mm Hg; P<0.0001) computed tomography perfusion scans. The primary end point of rCBF was not affected by BP reduction (pretreatment=0.89±0.11; post-treatment=0.87±0.11 mL/100 g per minute; P=0.37). Linear regression showed no relationship between changes in systolic BP and perihematoma rCBF (&bgr;=0.001 [−0.002 to 0.003]; P=0.63). Conclusions— CBF remained stable after acute BP reduction, suggesting some preservation of cerebral autoregulation.

Reduction of Diffusion-Weighted Imaging Contrast of Acute Ischemic Stroke at Short Diffusion Times

Background and Purpose— Diffusion-weighted imaging (DWI) of tissue water is a sensitive and specific indicator of acute brain ischemia, where reductions of the diffusion of tissue water are observed acutely in the stroke lesion core. Although these diffusion changes have been long attributed to cell swelling, the precise nature of the biophysical mechanisms remains uncertain. Methods— The potential cause of diffusion reductions after stroke was investigated using an advanced DWI technique, oscillating gradient spin-echo DWI, that enables much shorter diffusion times and can improve specificity for alterations of structure at the micron level. Results— Diffusion measurements in the white matter lesions of patients with acute ischemic stroke were reduced by only 8% using oscillating gradient spin-echo DWI, in contrast to a 37% decrease using standard DWI. Neurite beading has recently been proposed as a mechanism for the diffusion changes after ischemic stroke with some ex vivo evidence. To explore whether beading could cause such differential results, simulations of beaded cylinders and axonal swelling were performed, yielding good agreement with experiment. Conclusions— Short diffusion times result in dramatically reduced diffusion contrast of human stroke. Simulations implicate a combination of neuronal beading and axonal swelling as the key structural changes leading to the reduced apparent diffusion coefficient after stroke.

Prognostic Evaluation Based on Cortical Vein Score Difference in Stroke

Background and Purpose— Multimodal imaging in acute ischemic stroke defines the extent of arterial collaterals, resultant penumbra, and associated infarct core, yet limitations abound. We identified superficial and deep venous drainage patterns that predict outcomes in patients with a proximal arterial occlusion of the anterior circulation. Methods— An observational study that used computed tomography (CT) angiography to detail venous drainage in a consecutive series of patients with a proximal anterior circulation arterial occlusion. The principal veins that drain the cortex (superficial middle cerebral, vein of Trolard, vein of Labbé, and basal vein of Rosenthal) and deep structures were scored with a categorical scale on the basis of degree of contrast enhancement. The Prognostic Evaluation based on Cortical vein score difference In Stroke score encompassing the interhemispheric difference of the composite scores of the veins draining the cortices (superficial middle cerebral+vein of Trolard+vein of Labbé+basal vein of Rosenthal) was analyzed with respect to 90-day modified Rankin Scale outcomes. Results— Thirty-nine patients were included in the study. A Prognostic Evaluation based on Cortical vein score difference In Stroke score of 4 to 8 accurately predicted poor outcomes (modified Rankin Scale, 3–6; odds ratio, 20.53; P<0.001). On stepwise logistic regression analyses adjusted for CT Alberta stroke program early CT score, CT angiography collateral grading and National Institutes of Health Stroke Scale score, a Prognostic Evaluation based on Cortical vein score difference In Stroke score of 4 to 8 (odds ratio, 23.598; P=0.009) and an elevated admission National Institutes of Health Stroke Scale (odds ratio, 1.423; P=0.023) were independent predictors of poor outcome. Conclusions— The Prognostic Evaluation based on Cortical vein score difference In Stroke score, a novel measure of venous enhancement on CT angiography, accurately predicts clinical outcomes. Venous features on computed tomography angiography provide additional characterization of collateral perfusion and prognostication in acute ischemic stroke.

Quantitative susceptibility mapping using a superposed dipole inversion method: Application to intracranial hemorrhage.

To investigate gradient‐echo phase errors caused by intracranial hemorrhage (ICH) of low signal magnitude, and propose methods to reduce artifacts from phase errors in quantitative susceptibility mapping (QSM) of ICH.

Ischemia in Intracerebral Hemorrhage Is Associated With Leukoaraiosis and Hematoma Volume, Not Blood Pressure Reduction

Background and Purpose— Diffusion-weighted imaging (DWI) lesions have been identified both inside and outside the perihematoma region. We tested the hypotheses that larger hematoma volumes and blood pressure reduction are associated with DWI lesions. Methods— Hematoma and perihematoma edema volumes were measured using planimetric techniques in 117 intracerebral hemorrhage (ICH) patients who underwent DWI. Perihematoma and remote DWI lesion volumes were measured using apparent diffusion coefficient thresholds for moderate (<730×10−6 mm/s) and severe (<550×10−6 mm/s) ischemia. Acute blood pressure change over the first 24 hours was calculated. Results— The median (interquartile range) time to magnetic resonance imaging was 2 (1–5) days. Median hematoma volume was 9.8 (2.6–23.0) mL, and median perihematoma edema volume was 7.0 (2.9–18.6) mL. A small portion of the perihematoma region contained tissue below the thresholds for moderate (8.0 [2.9–14.5]%) and severe ischemia (1.1 [0.3–3.5]%). Ischemic perihematoma tissue volumes were correlated with hematoma volumes (R=0.52, P<0.001), but not maximal systolic blood pressure drop at 24 hours (R=−0.09, P=0.38). Remote DWI lesions were found in 17 (14.5%) patients (mean volume=0.44±0.3 mL). Patients with remote DWI lesions had higher rates of antiplatelet use (P=0.01), prior ICH (P=0.03), lobar ICH (0.04), and larger leukoaraiosis volumes (P=0.02). Maximal systolic blood pressure drop at 24 hours was similar in patients with (−20.5 [−55, −10] mm Hg) and without remote DWI lesions (−27 [−46, −13] mm Hg, P=0.96). Conclusions— Small DWI lesions within and outside the perihematoma region are common in primary ICH. Perihematoma DWI lesions were independently associated with larger hematoma volumes. Remote DWI lesions may be an epiphenomenon associated with the underlying microvascular pathogenesis. These data do not support a hemodynamic mechanism of ischemic injury after primary ICH.

Blood pressure reduction does not reduce perihematoma oxygenation: a CT perfusion study

Blood pressure (BP) reduction after intracerebral hemorrhage (ICH) is controversial, because of concerns that this may cause critical reductions in perihematoma perfusion and thereby precipitate tissue damage. We tested the hypothesis that BP reduction reduces perihematoma tissue oxygenation. Acute ICH patients were randomized to a systolic BP target of <150 or <180 mm Hg. Patients underwent CT perfusion (CTP) imaging 2 hours after randomization. Maps of cerebral blood flow (CBF), maximum oxygen extraction fraction (OEFmax), and the resulting maximum cerebral metabolic rate of oxygen (CMRO2max) permitted by local hemodynamics, were calculated from raw CTP data. Sixty-five patients (median (interquartile range) age 70 (20)) were imaged at a median (interquartile range) time from onset to CTP of 9.8 (13.6) hours. Mean OEFmax was elevated in the perihematoma region (0.44±0.12) relative to contralateral tissue (0.36±0.11; P<0.001). Perihematoma CMRO2max (3.40±1.67 mL/100 g per minute) was slightly lower relative to contralateral tissue (3.63±1.66 mL/100 g per minute; P=0.025). Despite a significant difference in systolic BP between the aggressive (140.5±18.7 mm Hg) and conservative (163.0±10.6 mm Hg; P<0.001) treatment groups, perihematoma CBF was unaffected (37.2±11.9 versus 35.8±9.6 mL/100 g per minute; P=0.307). Similarly, aggressive BP treatment did not affect perihematoma OEFmax (0.43±0.12 versus 0.45±0.11; P=0.232) or CMRO2max (3.16±1.66 versus 3.68±1.85 mL/100 g per minute; P=0.857). Blood pressure reduction does not affect perihematoma oxygen delivery. These data support the safety of early aggressive BP treatment in ICH.

Acute Blood Pressure Reduction in Patients With Intracerebral Hemorrhage Does Not Result in Borderzone Region Hypoperfusion

Background and Purpose— The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT) demonstrated blood pressure (BP) reduction does not affect mean perihematoma or hemispheric cerebral blood flow. Nonetheless, portions of the perihematoma and borderzones may reach ischemic thresholds after BP reduction. We tested the hypothesis that BP reduction after intracerebral hemorrhage results in increased critically hypoperfused tissue volumes. Methods— Patients with Intracerebral hemorrhage were randomized to a target systolic BP (SBP) of <150 or <180 mm Hg and imaged with computed tomographic perfusion 2 hours later. The volumes of tissue below cerebral blood flow thresholds for ischemia (<18 mL/100 g/min) and infarction (<12 mL/100 g/min) were calculated as a percentage of the total volume within the internal and external borderzones and the perihematoma region. Results— Seventy-five patients with intracerebral hemorrhage were randomized a median (interquartile range) of 7.8 (13.3) hours from onset. Acute hematoma volume was 17.8 (27.1) mL and mean SBP was 183±22 mm Hg. At the time of computed tomographic perfusion (2.3 [1.0] hours after randomization), SBP was lower in the <150 mm Hg (n=37; 140±18 mm Hg) than in the <180 mm Hg group (n=36; 162±12 mm Hg; P<0.001). BP treatment did not affect the percentage of total borderzone tissue with cerebral blood flow <18 (14.7±13.6 versus 15.6±13.7%; P=0.78) or <12 mL/100 g/min (5.1±5.1 versus 5.8±6.8%; P=0.62). Similar results were found in the perihematoma region. Low SBP load (fraction of time with SBP<150 mmHg) did not predict borderzone tissue volume with cerebral blood flow <18 mL/100 g/min (&bgr;=0.023 [−0.073, 0.119]). Conclusions— BP reduction does not increase the volume of critically hypoperfused borderzone or perihematoma tissue. These data support the safety of early BP reduction in intracerebral hemorrhage. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00963976.