American Heart Association

Monthly Archives: June 2016

Cortical Neuronal Damage in Atherosclerotic Large Artery Disease

Russell Mitesh Cerejo, MD

Yamauchi H, Kagawa S, Kishibe Y, Takahashi M, Higashi T. Progressive Cortical Neuronal Damage and Chronic Hemodynamic Impairment in Atherosclerotic Major Cerebral Artery Disease. Stroke. 2016

In their paper, the authors set out to determine whether selective cortical neuronal damage manifests as a decrease in BZRs in the normal appearing cerebral cortex of patients with atherosclerotic ICA or MCA occlusive disease, and furthermore whether these changes can be correlated with chronic hemodynamic impairment at baseline or hemodynamic deterioration. They studied 80 patients with atherosclerotic ICA or MCA disease with 17 having TIAs, and 38 having completed stroke.

The authors found that the BZR index in 40 patients was increased during follow-up (mean 26±20 months). In multivariable logistic regression analyses, increases in the BZR index were associated with the decreased cerebral blood flow at baseline and an increased oxygen extraction fraction during follow-up. They hypothesize that misery perfusion at baseline is associated with subsequent development of ischemic cortical neuronal damage. The contribution of the increased BZR index at baseline suggests that patients with misery perfusion have already suffered some ischemic cortical neuronal damage and may be at particular risk for progressive cortical neuronal damage.
They also found that increases in the oxygen extraction fraction during follow-up were associated with a lack of statin use. They suggest that revascularization procedures can improve hemodynamic impairment and thus may be beneficial to patients vulnerable to selective neuronal damage. 

Bone Marrow Derived Mononuclear Cells Improve Functional Outcomes in Animal Models of Ischemic Stroke

Mark R. Etherton, MD, PhD

Despite the advent of efficacious treatments for acute ischemic stroke, in the form of intravenous tPA and endovascular thrombectomy, post stroke disability is frequent. The prevalence of post stroke disability has served as the impetus for significant research into modalities to augment post stroke recovery. One promising approach is cellular therapy; including bone marrow derived mono-nuclear cells (BMMNCs), which have shown beneficial effects in animal models of ischemic stroke.

In this study, the authors conducted a systematic review of manuscripts using intravenous BMMNCs in animal models of ischemic stroke and performed a meta-analysis of histological and behavioral outcomes. They identified 22 studies in which the majority had assessments of common variables pertaining to infarct size and motor/functional outcomes.
While there was obvious heterogeneity among the individual studies with regards to methodologies and outcomes assessed. The pooled analysis was possible, in part, because the authors identified important shared approaches in the selection of specific animal models, timing of BMMNC injection, and outcome variables assessed (e.g. reduction in infarct size, cylinder test). BMMNC treated animals had significantly reduced infarct size (standardized mean difference -3.3, 95% CI: -4.3, -2.3) and enhanced performance on tests of sensorimotor function (cylinder test SMD -2.4, 95%CI: -3.1, -1.6).

This meta-analysis serves as an important summary of the pre-clinical data for one subtype of cellular therapy in ischemic stroke. BMMNCs have beneficial effects on infarct size and behavioral outcomes in animal models of ischemic stroke. Ideally, this study will serve as a platform on which future studies can build to target clinical trials for cellular therapies in human post stroke recovery.

High BP at time of Stroke Associated with Increased Risk of Recurrent Stroke in the Young

Alexander E. Merkler, MD

Mustanoja S, Putaala J, Gordin D, Tulkki L, Aarnio K, Pirinen J, et al. Acute-Phase Blood Pressure Levels Correlate With a High Risk of Recurrent Strokes in Young-Onset Ischemic Stroke. Stroke. 2016

Hypertension is one of the most important stroke risk factors and one in four adults has hypertension. Lowering blood pressure is associated with a decreased risk of cardiovascular mortality and recurrent strokes in the elderly. Although risk factors for stroke in the young are different, the prevalence of hypertension in young adults has already doubled in the past two decades, making it a significant risk factor for cardiovascular mortality even in young patients. In this study, Dr Mustanoja et al. evaluate whether acute blood pressure recordings during an ischemic stroke are associated with recurrent stroke.

The authors performed a retrospective single-center study of 1004 patients with acute ischemic stroke <50 years of age. Of these patients, 39% had pre-stroke hypertension and 36% used antihypertensive treatment. Over a median follow-up period of 8.9 years, 14% suffered a recurrent stroke (including ischemic and hemorrhagic). Patients with recurrent stroke had a significantly higher admission SBP, DBP, pulse pressure (PP), and mean arterial pressure (MAP) than patients without recurrent stroke. Using a cox proportional hazards model, having a SBP³160mmHg was significantly associated with a higher risk of recurrent stroke (Hazard ratio 3.3 (95% CI, 2.1-4.6) as compared to patients with an admission SBP<160mmHg. In addition, those patients with an admission SBP160mmHg were more likely to have a recurrent event earlier those patients with a SBP<160mmHg (at 13.9 versus 16.2 years). Similar findings were seen for DBP³100mmHg.

Certain limitations apply; for example, although the authors state that the their findings were unchanged irrespective of whether patients used anti-hypertensive treatment post-stroke, it’s unclear which agent, the duration of the agent, and most importantly, the efficacy of the agent. In addition, the findings may not be entirely generalizable as the study was conducted on only Caucasians at a single center in Scandanavia.

Despite these limitations, the results emphasize the importance of hypertension in stroke in the young and the necessity to aggressively control elevated blood pressure in adults of any age.

Perfusion MRI in Perinatal Stroke

Russell Mitesh Cerejo, MD

Watson CG, Dehaes M, Gagoski BA, Grant PE, Rivkin MJ. Arterial Spin Labeling Perfusion Magnetic Resonance Imaging Performed in Acute Perinatal Stroke Reveals Hyperperfusion Associated With Ischemic Injury. Stroke. 2016

In their paper, the authors described a novel method to assess perfusion in perinatal strokes in the ischemic as well as penumbra tissue. 
They included subjects less than 28 days old at time of diagnosis, and included both arterial and venous infarcts. MRI was carried out on 3T scanners with arterial spin labeling (ASL) techniques used for non-contrast perfusion imaging. Out of 25 neonates that participated, 16 were males (64%). Median gestational age at birth was 38.7 weeks (range: 35.7-41.9), median (estimated) age at stroke was 1 day (i.e., second day of life) (range: 0-8), and median age at MRI was 3 days (range: 0-16). The median time from symptom onset to MRI acquisition was 2 days (range: 0-8).

Arterial ischemic stroke was present in 11 (44%), while venous infarction was found in 9 (36%). Five patients (20%) had both arterial and venous stroke. Hyperperfusion was seen in 73% of arterial ischemic strokes, 11% with venous stroke, and 80% with both. Hypoperfusion was observed in 33% with venous and none with arterial stroke. Perfusion was normal in 45% with venous and 20% with both. In nearly all patients presenting with clinical or electrographic seizures, EEG abnormalities were present in the same hemisphere as the stroke; this clinical feature did not differ by stroke type.

This study demonstrates that perfusion imaging can be obtained in neonates with acute stroke, and often reveals hyperperfusion in the infarct core. Penumbra in arterial infarcts is seldom found. Hyperperfusion may be due to post-stroke reperfusion or to neuronal hyperexcitability of stroke-associated seizure.