Hyperacute Imaging of Intracerebral Hemorrhage Is NonContrast CT

Hyperacute Imaging of Intracerebral Hemorrhage: Is Non-Contrast CT Enough? Nerses Sanossian, MD Associate Professor of Neurology University of Southern California

Overview • Intracerebral hemorrhage overview • Role of neuroimaging – Types of imaging available • CT based • MRI based • Other modalities – Imaging characteristics of ICH – Clinical implications of imaging ICH

Intracerebral hemorrhage • 10 to 15% of the 795, 000 strokes per year in the United States • 6 month mortality of 30– 50% • Only 20% of patients regain functional independence at 6 months • Accounts for a greater proportion of early presentation – 23% of <2 hour cases seen

Hypertensive ICH

Why does it matter? • In a typical acute stroke every minute the brain looses 1 – 1. 9 million neurons – 14 billion synapses – 7. 5 miles myelinated fibers • Over 1/3 of patients with brain hemorrhage will deteriorate prior to initial evaluation 2 1 Saver, Stroke 2006; 2 Sanossian, Stroke 2010

Why is Time Important?

Common Sites of ICH • • • Cerebral Basal ganglia Thalamus Pons Cerebellum

Secondary Causes of ICH • Trauma • Arteriovenous malformation • Intracranial aneurysm • Coagulopathy • Haemorrhagic conversion of cerebral infarct • Dural sinus thrombosis • Intracranial neoplasm • Cavernous angioma • Dural arteriovenous fistula • Venous angioma • Cocaine or sympathomimetic drug exposure • CNS vasculitis

Imaging Clues to Secondary ICH

Diagnosis of ICH • Neuroimaging • Clinical Features – Can a diagnosis be made with reasonable certainty before neuroimaging?

Diagnosis of ICH • Neuroimaging • Clinical Features – Can a diagnosis be made with reasonable certainty before neuroimaging? • No • Prehospital ICH screen in 1700 cases • 1 The training set model accuracy is 74% – sensitivity 65%, specificity 83% with C= 0. 81 • 1 Validation set accuracy is 67% – sensitivity 76%, specificity 58% with C= 0. 73 1 Sanossian, Liebskind, Starkman et al. Stroke 2016 (Abs)

Imaging of ICH • Non-contrast CT (imaging acquisition) – Size – Location (IVH or SAH as well) – Descriptive (border, shape) – Associated findings (fracture) – Edema (presence, extent) • Contrast-enhanced CT (CTA, delayed CTA) – Spot sign – Enhancement

Speed of Acquisition • Ischemic Stroke Guidelines – Target door to imaging: 25 minutes – Target door to read: 40 minutes • Non-contrast CT likely to be faster • Contrast-enhanced CT slight delay • MRI longer delay – Is multimodal or advance imaging worth the wait in acute ICH?

Contrast-Enhanced CT/CTA • Is Spot sign = contrast extravasation • Extravasation • Contrast collection – Collapsed vessel – Small microaneurysm Becker et al. Stroke 1999; 30: 2025 -2032

Figure. A 67 -year-old man on warfarin therapy for atrial fibrillation and daily aspirin intake presents with syncope and increasing unresponsiveness (admission INR, 2. 7). 48 -second delayed acquisition Josser E. Delgado Almandoz et al. Stroke. 2009; 40: 29943000 Copyright © American Heart Association, Inc. All rights reserved.

Spot Sign Score Josser E. Delgado Almandoz et al. Stroke. 2009; 40: 29943000 Score Risk of expansion Mortality 0 2% 23% 1 33% 42% 2 50% 3 94% 63% 4 100% 71%

Presence of Spot Sign • Higher risk for expansion, poor outcome, mortality • Could be selected for therapy with – Factor VII • STOP-IT – More aggressive BP reduction – More aggressive anticaogulation reversal

Spot Sign Mimics Figure 1. 38 -year-old male with a right frontal oligodendroglioma (patient 2, Table 2). Steve Gazzola et al. Stroke. 2008; 39: 1177 -1183 Copyright © American Heart Association, Inc. All rights reserved.

MRI Imaging of ICH • Sensitivity and specificity for ICH in comparison to CT • Additional data obtained • Required sequences

Hemorrhage Visualized on Magnetic Resonance Imaging but Not on Computed Tomography Kidwell, C. S. et al. JAMA 2004; 292: 1823 -1830. Copyright restrictions may apply.

MRI Imaging of ICH

MRI Spot Sign Schindlbeck et al Stroke 2016

MRI for Etiology

MRI and ICH • Not feasible in the hyperactue setting • Yield in non-lobar ICH is low and does not change management • Sensitivity and specificity of MRI is compatible to CT for diagnosis of ICH, SAH and other intracranial hemorrhages – GRE, FLAIR

Patients with Hematoma Enlargement According to Intervals Between Initial Scan and Symptom Onset Proportion of patients (%) From: Kazui: Stroke, 27(10): 1783 -1787 40 35 30 25 20 15 10 5 0 Hematoma Enlargement 0 -3 hr 3 -6 hr 6 -12 hr 12 -24 hr 24 -48 hr

3 in 10 ICH patients Deteriorate Early • ICH in 23% of subjects • Independent predictors of clinical deterioration: • ICH on initial imaging (OR = 5. 75) • History of diabetes (OR = 1. 89) Sanossian N, Starkman S, Hamilton S: Stroke, 42(3) e 291, 2011 The NIH Field Administration of Stroke Therapy- Magnesium Phase 3 Clinical Trial

Hyperacute BP and Clinical Deterioration Systolic Blood Pressure Diastolic Blood Pressure 186 120 184 115 182 110 180 105 178 CD 176 100 CD No CD 95 174 90 172 170 85 168 80 Prehospital ED arrival Sanossian, Libeskind, Starkman et al. Cerebrovasc Dis 2013

Early Systolic BP and ICH Expansion 200 190 180 mm. Hg 170 * * ** 160 Expansion No Expansion 150 140 * p<0. 08 **p<0. 005 130 120 Prehospital ED arrival 15 min 1 hour 4 hours 8 hours 12 hours 16 hours 24 hours Sanossian N, Liebeskind DS, Starkman S: Cerebrovascular Diseases 33(S 2): 26, 2012

What Can We Do to Prevent Hematoma Expansion • Lower Blood Pressure – Associated with less hematoma expansion in observational studies – Direct clinical evidence? • Yes: the INTERACT study • Coagulate – Less hemorrhage expansion with r. FVII • No effect on clinical outcomes • No possible way to use in prehospital studies

INTERACT 2: Early Aggressive BP Reduction has borderline significance clinical outcome, but associated with less hematoma expansion Anderson CS, Heeley E, Huang Y: N Engl J Med 368: 2355 -2365, 2013

What Agents Can be Used • Beta Blockers – Labetalol • Nitrates – Nitroglycerine, nitroprusside • Calcium Channel Blockers – Nicardipine, nimodipine • ACE inhibitors • Alpha blockers

BP Reduction in ICH Guidelines • Treat SBP >180 mm Hg and/or mean arterial pressure >130 mm Hg • If Blood pressure is between 150 -220 it is safe to target SBP 140

Definiftive Treatment of ICH • Possible future directions – Recombinant Factor VII in select group – Hemicraniectomy (not craniotomy) – Endoscopic clot removal

Conclusion • Earl treatment before hematoma expansion • Hyperactue imaging – CT is sufficient for current therapeutic Rx • BP reduction – CTA/contrast CT is appropriate to select patinets at high risk of expansion • High risk treatments such as r. FVII in future • More aggressive BP reduction in future • No rationale for selecting MRI – Centers that lead with MRI imaging can use data from contrast bolus to predict hematoma enlargement