Leka Sivakumar

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.

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.

Dabigatran Therapy in Acute Ischemic Stroke Patients Without Atrial Fibrillation

Background and Purpose— Acute ischemic stroke patients are at risk of early recurrence. We tested the feasibility and safety of initiating dabigatran in patients, within 24 hours of minor stroke in patients without atrial fibrillation. Methods— Minor stroke patients (National Institutes of Health Stroke Scale score ⩽3) without atrial fibrillation and evidence of acute infarction on magnetic resonance imaging were treated with dabigatran. Treatment began within 24 hours of onset and was continued for 30 days. The primary end point was symptomatic hemorrhagic transformation. Results— A total of 53 patients with median (interquartile range) age of 68 (57–77) years and National Institutes of Health Stroke Scale score of 1 (0–2) were enrolled. Baseline diffusion-weighted imaging volume was 0.8 (0.3–2.4) mL. No patients experienced symptomatic hemorrhagic transformation. Three patients had evidence of asymptomatic petechial hemorrhagic transformation on day 7, which remained stable at day 30, while continuing dabigatran. Conclusions— Dabigatran treatment within 24 hours of minor stroke is feasible. A larger randomized trial is required to confirm the safety and efficacy of this treatment approach. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT 01769703.

Early Rivaroxaban Use After Cardioembolic Stroke May Not Result in Hemorrhagic Transformation: A Prospective Magnetic Resonance Imaging Study.

Background and Purpose— Early anticoagulation after cardioembolic stroke remains controversial because of the potential for hemorrhagic transformation (HT). We tested the safety and feasibility of initiating rivaroxaban ⩽14 days after cardioembolic stroke/transient ischemic attack. Methods— A prospective, open-label study of patients with atrial fibrillation treated with rivaroxaban ⩽14 days of transient ischemic attack or ischemic stroke (National Institute of Health Stroke Scale <9). All patients underwent magnetic resonance imaging <24 hours of rivaroxaban initiation and day 7. The primary end point was symptomatic HT at day 7. Results— Sixty patients (mean±SD age 71±19 years, 82% stroke/18% transient ischemic attack) were enrolled. Median (interquartile range) time from onset to rivaroxaban was 3 (5) days. At treatment initiation, median National Institute of Health Stroke Scale was 2 (4), and median diffusion-weighted imaging volume was 7.9 (13.7) mL. At baseline, HT was present in 25 (42%) patients (hemorrhagic infarct [HI]1=19, HI2=6). On follow-up magnetic resonance imaging, no patients developed symptomatic HT. New asymptomatic HI1 developed in 3 patients, and asymptomatic progression from HI1 to HI2 occurred in 5 patients; otherwise, HT remained unchanged at day 7. Conclusions— These data support the safety of rivaroxaban initiation ⩽14 days of mild–moderate cardioembolic stroke/transient ischemic attack. Magnetic resonance imaging evidence of petechial HT, which is common, does not appear to increase the risk of symptomatic HT.

Dynamic Evolution of Diffusion-Weighted Imaging Lesions in Patients With Minor Ischemic Stroke

Background and Purpose— Diffusion-weighted imaging (DWI) lesion volume on magnetic resonance imaging is increasingly being used as a surrogate outcome measure in clinical trials. We aimed to characterize the evolution of DWI lesion volumes within 30 days of symptom onset after minor stroke. Methods— Minor stroke patients with DWI lesions on magnetic resonance imaging within 48 hours of symptom onset were prospectively followed with magnetic resonance imaging brain scan at 7 and 30 days. Change in the lesion volume was defined as the difference between day 30 Fluid-Attenuated Inversion Recovery and baseline DWI lesion volumes. Results— Three patterns of infarct evolution were observed: reduction (72 [63%]), no change (26 [23%]), and growth (16 [14%]). Patients with infarct reduction at 30 days had larger baseline DWI lesion volumes (2.5 [0.9–8.5] mL) than those with stable infarcts (0.5 [0.3–0.9] mL; P=0.01). Complete DWI reversal at day 30, was seen in only 6 (5.3%) patients. Conclusions— The most common pattern of infarct evolution in patients with minor stroke is a reduction in volume, but complete resolution is uncommon.

White matter hyperintensity volume predicts persistent cognitive impairment in transient ischemic attack and minor stroke.

Background Temporary and permanent cognitive changes following transient ischemic attack/minor stroke have been described previously. It is unknown if persisting cognitive deficits in these patients are correlated with acute infarction identified using magnetic resonance imaging. Aims We tested the hypothesis that persistent cognitive impairment after transient ischemic attack/minor stroke can be predicted by the volume of diffusion-weighted imaging lesions. Methods Acute transient ischemic attack/minor stroke (NIH stroke scale score ≤ 3) patients were prospectively recruited within 72 h of onset. Patients underwent Montreal cognitive assessment and magnetic resonance imaging, including diffusion-weighted imaging and Fluid-Attenuated Inverse Recovery sequences, at baseline, days 7 and 30. Cognitive testing was repeated at day 90. Diffusion-weighted imaging lesion and Fluid-Attenuated Inverse Recovery chronic white matter hyperintensity volumes were measured planimetrically. Cognitive impairment was defined a priori as Montreal cognitive assessment score < 26. Results One hundred fifteen patients were imaged at a median (inter-quartile range) of 24.0 (16.6) h after onset. Acute ischemic lesions were present in 91 (79%) patients. Cognitive impairment rates were similar in patients with (47/91, 52%) and without diffusion-weighted imaging lesions (13/24, 54%; p = 0.83). Although linear regression indicated no relationship between acute diffusion-weighted imaging lesion volume and day 30 Montreal cognitive assessment scores (β = −0.163, [−2.243, 0.334], p = 0.144), white matter hyperintensity volumes at baseline were predictive of persistent cognitive deficits after 30 days (β = 2.24, [1.956, 45.369], p = 0.005). Conclusions In most transient ischemic attack/minor stroke patients who suffer acute cognitive impairment post event, deficits are temporary. Deficits after 30 days of onset are correlated with chronic white matter hyperintensity, suggesting subclinical cognitive impairment and/or impaired ability to compensate for the effects of acute ischemic infarcts.

Factors associated with cognitive decline in transient ischemic attack patients.

Chronic cerebrovascular disease and large ischemic stroke are both associated with cognitive impairment. Much less is known about the acute cognitive sequelae of transient ischemic attack (TIA). Although often overlooked, there is increasing evidence that cognitive impairment does occur following TIA. In some patients, cognitive changes persist after resolution of focal neurological deficits, but the temporal profile of these symptoms is unknown. In addition, clinical and imaging correlates of cognitive impairment after TIA have not been systematically studied. This under-studied and recognized problem has significant implications for TIA patient management. In this review, we summarize the evidence currently available and identify future research priorities.

Response to Letter Regarding Article, “Serial Montreal Cognitive Assessments Demonstrate Reversible Cognitive Impairment in Patients With Acute Transient Ischemic Attack and Minor Stroke”

We thank Dr Regal for his interest and comments regarding our article.1 It is important to consider delirium in the differential diagnosis of stroke and to recognize that delirium can occur in the acute phase of ischemic stroke.2 We do agree that delirium and transient ischemic attack/minor stroke patients both exhibit rapid early neurological improvement. As pointed out by Dr Regal, these conditions are distinct from dementia and minimal cognitive impairment. Unlike the patients included in Dr Regal’s study, however, our patients demonstrated …