Epidemiology and Pathophysiology of Intracerebral Hemorrhage Edward C. Jauch, MD MS FACEP 1

Edward C. Jauch, MD MS FACEP Assistant Professor Associate Director of Research Department of Emergency Medicine University of Cincinnati College of Medicine Faculty, Greater Cincinnati / Northern Kentucky Stroke Team 2 54 1 54

Global Objectives Review epidemiology of ICH Understand pathophysiology of ICH Discuss lessons from acute ischemic stroke Improve Emergency Medicine practice 54 2 54

A Clinical Case

Patient Initial Clinical History 57 yo male with sudden onset headache and left sided weakness Family calls 911 EMS transport to OLFH Hospital Enroute patients symptoms progress to full hemiplegia Initial VS: 210 / 120 mmHg, HR 110, R 24 54 3 54

Patient ED Presentation PMHX: HTN for 10 years, hyperlipidemia SHX: Smoking 30 years Meds: ACE inhibitor, ASA ROS: No recent illness or injuries, no new medications 54 3 54

Patient ED Presentation Physical examination: VS - 220 / 140 mmHg, HR 110, RR 22, T 98.6oC Uncomfortable WM, arouses to voice HEENT/CV/Lungs/Abd - WNL Neuro – LOC mildly depressed CN with L facial droop and partial gaze palsy, VFI Motor with dense L hemiplegia Sensory with mild L sensory loss Speech slurred but no significant aphasia NIHSS = 12 54 3 54

Key Questions What is your differential diagnosis? What are the most common ICH etiologies? What is the pathophysiology of ICH? What guidelines exist that govern the acute care of ICH patients? What can be learned regarding ICH management from acute ischemic stroke? How can the emergent care of ICH patients be enhanced? ABC’s. Patients with ICH can deteriorate quickly. Constantly reassess Imaging modality of choice

Patient ED Presentation Initial noncontrast CT scan Labs: CBC, chem 7 – WNL PT, PTT – WNL ECG – LVH with strain

Stroke Subtypes Hemorrhagic 26% Ischemic 71% Other 3% ICH 13% SAH Lacunar 19% Thromboembolic 6% Cardioembolic 14% Other 3% Unknown 32% Ischemic 71% Hemorrhagic 26% Up to 65,000 ICH per year in U.S. (NINCDS Stroke Data Bank: Foulkes, Stroke, 1988)

ICH Classifications Primary Secondary Hypertensive arteriopathies Cerebral amyloid angiopathies Secondary Neoplasms Structural lesions Anticoagulants or thrombolytic agents Drugs (cocaine, ephedra, etc) Traumatic brain injury

Location Lobar Nonlobar Cerebellar Intraventricular Associated with amyloid angiopathy Nonlobar Associated with hypertension Cerebellar Intraventricular

Lobar Hemorrhage Secondary to cerebral amyloid angiopathy Beta-amyloid deposition in vessels of cortex and leptomeninges Associated with aging Lobar hemorrhage in young due to AVM, cavernous hemangioma Amyloid in vessel wall Lobar hemorrhage is normotensive patient http://www.umassmed.edu/strokestop/module_one/359,44,Slide 44

Non-lobar Hemorrhage Non-lobar or hypertensive hemorrhage Location Associated with hypertensive arteriolosclerosis Location putamen, pons, thalamus, cerebellum Mortality 50% 30 day mortality Exam: sudden HA with focal findings on exam The second form of arteriolosclerosis is shown here. The arteriole here has an "onion skin" appearance typical of hyperplastic arteriolosclerosis. This lesion is most often associated with malignant hypertension

19 yo with ephedra induced ICH Risk Factors Age Gender (men > women) Race (blacks > whites) Prior stroke Hypertension Anticoagulant / thrombolytics Alcohol / cocaine 19 yo with ephedra induced ICH

Less Common Risk Factors Vascular malformations Arteriovenous malformations (AVM) Cavernous angiomas Intracranial aneurysms Infections Cerebral vasculitis Mycotic aneurysms Cerebral venous thrombosis

ICH Rate by Age Rate per 100,000 / year Age (years)

Systolic Blood Pressure & Incidence Incidence Rate/100,000 Systolic Blood Pressure (mmHg)

Ethnicity of ICH Risk Age and sex adjusted rate U.S. 15 per 100,000 World wide 10-20 per 100,000 Higher in African American and Japanese Rates 13.5 per 100,000 Caucasian 38 per 100,000 AA 55 per 100,000 Japanese

Anticoagulation and Thrombolytic Related Hemorrhage Warfarin anticoagulation 6-11 fold increased risk of ICH Higher levels with increased risk Most occur in therapeutic range Thrombolysis and Symptomatic ICH 6.4% in thrombolysis treatment group tPA related hemorrhages typically lobar 20% occur outside area of infarct 0.6% in placebo group

Mortality and Morbidity Estimated lifetime cost $123,565 Of the 37,000-65,000 ICH per year 35-52% were dead at 1 month 50% of deaths occurred within 48 hours 10% independent at 30 days 20% independent at 6 months

30 Day Outcome of ICH No. cases Modified Oxford Handicap Scale

Clinical Presentation Symptoms and signs 82% change in mental status >75% hemiparesis/plegia 63% headache 22% vomiting 2/3 progression of symptoms, 1/3 maximal at onset

Clinical Presentation by Location Lobar Headache (headache location related to ICH site) Motor, sensory deficit, or VF deficits (not all) Deep Unilateral motor, sensory, VF loss Aphasia (D) or neglect (ND) Cerebellum Nausea, vomiting, ataxia, coma Pontine Coma, quadriplegia, pinpoint pupils

ICH Progression Symptoms often progress, associated with ICH growth 26% with 33% or greater growth in 1 hour 12% with 33% or greater growth 1-20 hours This gives us a window of therapeutic opportunity

Prognostic Information Volume of hemorrhage Clinical presentation Intraventricular extension (Kothari, Stroke)

Hematoma Volume Calculation Formula for volume of an ellipsoid 4/3Л (A/2)(B/2)(C/2) Simplified ABC/2

Prognosis Worse Better Volume > 60 cm3 and GCS < 9 91% dead at 30 days Patients with volume over 30 cm3 only 1 / 71 independent at 30 days Intraventricular extension Better Volume < 30 cm3 and GCS 9 or higher 19% dead at 30 days (Broderick, Stroke)

Pathophysiology Initial hemorrhage into surrounding tissues causes: Cytotoxic and vasogenic edema formation in the perihematomal parenchyma Neurotoxicity from released serum proteins Elevated intracranial pressure due to Hematoma mass effect Perihematomal edema Intraventricular extension and hydrocephalus Results in decreased perfusion

Current Recommendations for Management of Intracerebral Hemorrhage Emergency Medicine representation New guidelines due 2005 (Broderick, Stroke 1999) Edward C. Jauch, MD MS FACEP 30

Emergent Evaluation Baseline labs Neuroimaging CBC, coags, electrolytes Neuroimaging CT remains gold standard Identify ICH Identify complications (hydrocephalus, herniation) MRI / MRA Useful to evaluate for structural abnormalities AVM, aneurysms Angiography Rarely emergently indicated Identify vascular issues preoperatively in occult ICH

Medical Management ABC’s Blood pressure control ICP management Other Hyperventilation Osmotherapy No role for glycerol, corticosteroids, hemodilution Other Prevention of hyperthermia Fluid management (CVP at 5-12 mm Hg) Modifications for age, comorbidities, size, severity, location Seizure control Find somebody to take the patient

Blood Pressure Management No definitive data (yet) Hypertension very common MAP > 140 in 34%, > 120 in 78% Many return to baseline over first 24 hours Prospective Retrospective Case Series Results Meyer et al. 1962 Lower BP good Dandapani et al. 1995 Qureshi et al. 1999 Lower BP bad Brott T et al 1995 Hematoma enlargement not associated with degree of HTN   (Dr. Aninda Acharya, St.Louis University, Internet Stroke Center)

Blood Pressure Management 34 (Broderick, Stroke 1999) Edward C. Jauch, MD MS FACEP

Management of Increased ICP Definition ICP > 20 mm Hg for > 5 mins Treatment goal ICP < 20 mm Hg CPP > 70 mm Hg Recommendations ICP monitoring with GCS < 9 Management Osmotherapy Hyperventilation Ventricular drainage  

Management of ICP (Broderick, Stroke 1999) 36 (Broderick, Stroke 1999) Edward C. Jauch, MD MS FACEP

Seizure Therapy 25% will have seizure Much more common if lobar Most in first 72 hours Phenytoin is drug of choice Does not convey life long epilepsy

What can be Fixed? Stop the bleeding Remove the blood Reduce the edema Until now no option Remove the blood Multiple trials without clear impact Reduce the edema No treatment yet

Surgical Treatment Direct evacuation, endoscopic, stereotactic

Surgical Treatment Recommendations 7000 procedures a year in U.S. despite lack of data Largest surgical trial negative (in press) MISTIE trial of stereotactic evacuation with tPA (3/05) Surgery in 24 hrs, stable clot for 6 hrs 40 (Broderick, Stroke 1999)

The Potential Future With Novo 7 What Can We Learn From Acute Ischemic Stroke? 41

Time Will Always Mean Brain! (Lancet 2004; 363: 768–74)

Same Chain: No Weak Links Development: Protocol and pathway development Detection: Early recognition Dispatch: Early EMS activation Delivery: Transport & management Door: ED triage Data: ED evaluation & management Decision: Neurology input, therapy selection Drug: Thrombolytic & future agents Disposition: Admission or transfer How to introduce this section? What are the elements of stroke management involving the Emergency Department Also add “D” for Diagnosis 43

Emergent Triage and ED Evaluation Must be a Priority Challenges in trauma centers Sharing resources ED demands The diagnosis of stroke remains based on three important and integral elements: The history and physical Biochemical testing Neuroimaging

NINDS Recs: Same for ICH Door-to-MD: 10 minutes Door-to-Stroke 15 minutes Team notification: Door-to-CT scan: 25 minutes Door-to-Drug: 60 minutes (80% compliance) Door-to-Admission 3 hours I.) AT this National Symposium, experts developed in-hospital Time Intervals to allow the stroke patient to be treated and evaluated in a expedient manner. These recommendations Include: A.) Emergency department arrival to initial physician evaluation: 10 minutes B.) Emergency department arrival to Stroke Team Notification: 15 minutes C.) Emergency department arrival to CT Scan initiation: 25 minutes D.) And they recommended that 80% of eligible stroke patients presenting to the emergency department should be treated with tPA within 60 minutes. NEXT SLIDE (NINDS Stroke Symposium 2003)

There Will Be Major Barriers EM education of disease and treatment Timely radiology involvement Access to neurologic expertise Neurology does not admit ICH Neurosurgeons won’t rush in EM will be point person like tPA Post treatment management ICU beds Complications likely to occur early Cost Whose cost center “Drip and ship” model

Who Cares for Patients with ICH? Shortage of neurosurgeons Shortage of neurocritical care Neurologists not experienced with ICH Emergency Medicine primarily focused on stabilization Example – Cincinnati 30% neurosurgical shortage Nonoperative ICH to neurology Only 4 of 15 hospitals with neurosurgery coverage Only 1 level 1 trauma largely due to neurosurgery

Potential Solution: Utilize Primary Stroke Centers Patient care areas Acute stroke teams Written care protocols EMS participation Emergency Department participation Stroke unit* Neurosurgical services** Support services Organizational support Stroke center director Neuroimaging Laboratory Outcome & quality measures CME Secondary stroke center likely required for most ICH (Brain Attack Coalition, JAMA 2000)

ED Treatment and Patient Outcome

Questions. www. ferne. org ferne@ferne Questions?? www.ferne.org ferne@ferne.org Edward Jauch, MD, MS jauchec@ucmail.uc.edu (513) 558-0474 ferne_acep_2005_jauch_ich_epipath_cd 4/23/2017 6:52:28 PM 54 1 54