Spontaneous Intra-cerebral Hemorrhage

Objective

• Epidemiology

• Etiology/ Risk Factors

• Clinical Manifestation H&P

• Diagnostic procedures

• Treatment

• Prognosis/Outcome

Epidemiology

• Each year in US, 37,000-52,400 people suffer an ICH

• SICH accounts for 10-15% of all strokes• SICH is associated with higher mortality

than either ischemic stroke or SAH• Only 38% of affected persons surviving 1

year

Epidemiology

• Variation in incidence is seen among diff. Sex, age groups, & races

• Circardian & circannual pattern of SICH onset in morning and winter has been reported

Broderick, NEJM, 1992

Etiology

• Primary ICH 80%• Secondary 20%

+ Congenital

+ Acquired - Vascular - Coagulopathy

- Neoplasm - Pregnancy

- Drugs - Unknown

- Trauma**

- Hemorrhagic ischemic stroke

Primary SICH (80%)

• Sponataneous rupture of small vessels damaged by HTN or amyloid angiopathy

• Hypertensive bleed – certain location

• Charcoat- Bouchard aneurysm,

lipohyalinosis

Cerebral Amyloid Angiopathy (CAA)

• Recurrent lobar Hg in elderly

• B-amyloid protein is deposited in media & adventitia of cortical and leptomeningeal vessels

• Apo-lipoprotein E genotype

• Hereditary ICH with amyloidosis-Dutch type is rare AD of CAA

CAA

Secondary SICH (20%)

• Vascular anomalies are 2nd most common cause of SICH

• Structural vascular lesions are most common cause of SICH in children.

• Aneurysm• AV malformation• Cavernoma/cavernous

haemangioma• Dural Arteriovenous fistula

Vascular anomaly

SAH-Aneurysm

AVM

Tumor

• Tumor hemorrhage occur in 10% of all primary or metastatic tumor

+ Primary

GBM, hemangioblastoma, oligodendroglioma

+ Metastatic tumor

Melanoma, renal cell Ca, lung, thyroid ,Breast and prostate cancer

Other Causes of ICH• Liver failure and coagulopathy• Drug abuse ( Cocaine, ecstasy, amphetamine)

- Most common cause of stroke in young adult. - Vascular anomaly is seen in 10/11 patients with SICH+ - Diagnostic work-up is needed in these patients

• Drugs ( Sympathomimetic, Gingko,….)• Moya-Moya disease.• Pregnancy• Rare causes ( infection, DIC,..)• Unknown + McEvoy, Lancet, 1998

Risk Factors• Non- modifiable ( age, sex, race, ..)• Modifiable Risk factors - Hypertension *

- Moderate/Heavy alcohol intake** - Anticoagulant Treatment** - Cigarette smoking (SAH, associated with ICH) - DM ( associated with ICH>SAH) - ? Hypocholesterolemia, Hepatitis C*** ** Juvela, Stroke, 1995 * SHEP, JAMA, 1991 ***Karibe, J Clin Neurosci, 2001

Prevention of SICH

• Hypertension treatment• Control of alcohol intake and

sympathomimetic drug abuse• Careful monitoring of anticoagulation level

in patients taking warfarin• Diligent selection of patient for

thrombolytic treatment for MI & acute ischemic stroke

Clinical ManifestationInitial presentation

• Sudden onset of focal neurologic deficit with H/A, Nausea, vomiting, & altered LOC.

• Elevated Blood pressure (90%)

• Seizures occurs in 10% of patients

• Type of focal deficits depend on hematoma location

SICH Location

Hematoma Location

Clinical Manifestation• Basal ganglia (50%) Contralateral hemiparesis, sensory loss, conjugate gaze toward Hg site

• Lobar regions (20-50%) Contralateral hemiparesis or sensory loss, aphasia, neglect, or confusion

• Thalamus (10-15%) Contralateral hemiparesis, sensory loss, Downward & inward deviation

of eyes, reduced vertical gaze

• Pons (5-12%)– Quadriparesis, facial weakness, decreased level consciousness, small

reactive pupil

• Cerebellum (1-5%)– Ataxia, miosis, gaze paresis

Vital signsLevel of conscious

Pupil examcranial nerve exam

cerebellar examMotor Sensory

Clinical ManifestationInitial presentation

• Hydrocephalus

• Raised ICP

• Herniation syndrome

Clinical ManifestationHematoma enlargement

• ¼ patients further deterioration in LOC within the 1st 24 hours after onset

• Hematoma enlargement occurs in 18-38% of ICH patients scanned within 3 hr of onset*

• After 3 hr, only 11% of patients show hematoma enlargement.

• Mechanism: ? Rupture of surrounding veins.**• Potential predictors of hematoma enlargement: Thalamic ICH, large initial Hg, SBP>160, DM *Brut, Broderick, Stroke, 1997, **Kazui, Stroke,1996

Clinical ManifestationPerihamatoma edema

• Typically develops over 1st 3-96 hours

• Vasogenic & cytotoxic edema occur initially

• Interstitial and osmotic edema develop later

• RBC breakdown product and thrombin

Predictors of Mortality in ICH

• GCS at presentation(<8)* • Hematoma size (> 60ml)*• Pulse pressure • MABP• Glucose • Intraventricular rupture*• Hematoma enlargement• Relative volume edema Gebel, Stroke, 2002

Emergency Evaluation of ICHfirst 15 minutes

• ABCs• Consult Neurology• Document HX&PE

- Especially time last known to be normal

- Not when symptoms first noted …• Blood work ( CBC, PT,INR,toxicology)• EKG, CXR• Send for imaging

Diagnostic Procedure

• CT scan

• MRI

• Cerebral angiography

CT Scan• CT Head is the imaging

procedure of choice in the initial evaluation of suspected ICH (level of evidence I, grade A recommendation).

• Hematoma Location & size=

AXBXC/2

• HCP, edema, Herniation, IVH

MRI scan

• Identify Brain tumor •

Cerebral Angiogram

Cerebral Angiogram

Goals of ICH therapy• Prevent hematoma enlargement + Up to 1/3 of patients, time dependent + There are no proven ways to stop bleeding

- Blood pressure treatment

- Hemostatic agents - Surgery.

• Limit injury ( neuroprotection) + Raised ICP - Hyperventilation, osmotic agent, - ICP monitors, ventricular drainage - Surgery: open decompression ,endoscopic

+ Glycemia : Same argument as ischemi stroke

+ Core body temperature : Same Rx

Medical Treatment

• Critical care

• Seizure prophylaxis

• Blood pressure management

• Management of Intracranial Hypertension

ICU admission

• Risk of clinical deterioration after SICH is greatest during 1st 24 hours

• Maintain Euvolemia & normoglycemia

• Enteral nutrition

• DVT prophylaxis

• Gastric cytoprotection

• PT, OT, & speech therapy

Seizure prophylaxis

• Seizure more frequent in ICH than ischemic stroke*

• Most seizures occur within 1st 24 hours

• Risk of seizure depend on hematoma location*/**

• Epilepsy is more likely in late-onset siezure (>2 wks after SICH)*

* Bladin, Arch Neurol, 2000 * *Cervoni,Neurosurg Rev,1994

Acute ICH- Blood Pressure

• No Studies showing clear benefit• Highest BPs associated with ICH Growth• Generally more aggressive than for ischemic

stroke - Balancing risk of continued hemorrhage from

too high BP with risk of ischemia in setting of ICP from too low BP Stroke. 1999; 30:905-915

Guideline for the management of spontaneous intracerebral hemorrhage

Acute ICH-Blood Prssure

ICP

• ICP in herniation syndrome& death• Goal to Keep ICP<20mmhg, and CPP> 70 mmhg

• ICP moniter in patient with GCS <9

• Treatment of raised ICP:

- Head elevation - CSF drainage

- Osmotic therapy - Hyperventilation

- Sedation - Surgery

Acute ICH- Hemostatic Agent

• Donar Blood products -HMC reversal protocols for patients on

antithrombotic agents• Anti-fibrinolytic agents

• rFVIIa (Novoseven) - seem safe in phase II study - Phase IIb study with suggestion of efficacy?

Iatrogenic ICH management

• Warfarin associated ICH - FFP 20 ml/Kg

- FVIIa - Vit. K 1 mg (INR 4.5-10) 8-24 hr to correct PT

• Heparin associated ICH - Discontinue drug and give 1% protamine sulfate over 10-20 minutes

( 1mg neutralize 100 USP heparin unit)

• Thrombolytic associated ICH -10 units cryoprecipitate, 2 U FFP every 6 hrs for 24hrs with 4-6 units platelets

concentrate until fibrinogen levels are >11.1 mmol/L

rFVIIa for acute ICH

• FDA approved for hemophilia

- being used for emergent warfarin reversal rescue in uncontrollable bleeding

• International Randomized Trial

- 400 patients

- Placebo,40,80,160 mcg/KG

- Scan within 3 hours, drug within 4

hours

rFVIIa for acute ICHWorld Stroke Congress, Vancouver BC, June 2004

* NS increase in Thrombotic events, 5.6%( 7 strokes, 7MIs)

Outcome Placebo 40 mcg/Kg

80 mcg/Kg

160 mcg/Kg

Sig?

% ICH growth

29% 16% 14% 11% Yes

% mortality

29% 18% 18% 19% No

% Good outcome

31% 45% 47% 45% Yes

rFVII for acute ICH Recommended Uses

• ICH on warfarin

• ICH < 4 hours from onset

• ICH with expanding hematoma

- CTA can give answer with one scan

Thrombolytic therapy for ICH

• Thrombolytic agent to reduce ICH/IVH

• IVH complicates 40% of ICH obstructive HCP and mass effect

• Urokinase in EVD reduce mortality from 58% to 25% at 1 month*.

• Phase II trial in underway

*Naff, Stroke, 2000

Acute ICH-Surgery• No randomized trials showing benefit

- may reduce mortality in larger hemorrhage

- Std craniotomy, endoscopic and needle aspiration

Stroke.2000,31:2511. Neurology 2001;56:1294-1299

Neurology 2001; 56:766-772. Stroke.1999;2025-2032

Meta-analyses of Surgical TrialsMeta-analysis

Studies Analyzed

Odds of death or dependency with surgery

Conclusions

Hankey & Hon

McKissock, Juvela, Auer, Batjer

1.23(0.77-1.98) Insufficient evidence

Prasad et al McKissock, Juvela, Auer, Batjer

1.99(0.92-4.31) Insufficient evidence

Saver et al Juvela, Auer, Batjer

0.72 (0.38-1.44) Trends toward improved outcome

Fernandes

et al

McKissock, Juvela, Auer, Batjer, Chen, Morgenstern,

Zuccarello

1.20

(0.83-1.74)

Trends toward improved outcome

International Surgical TrialIntra-cerebral Hemorrhage (ISTICH)

Mendelow. Lancet 2005

• 1033 patients , within 72 hours• Preliminary results

- Good outcomes seen in

* 26.01% of “early surgery”group

* 23.8% of “ initial conservative “group

* Difference NS

- Patients with hematoma <1cm from cortical surface have better outcome

ICH Surgery Recommedation

Stroke.1999;30:905-915

Cerebellar ICH

• No randomized controlled studies.

• Several series reported good outcomes with evacuation of hematama:

- > 3 cm in size

- Brainstem compression/hydrocephalus

Surgical Treatment

Complications

• Neurological– Seizures 10%– Increased ICP

• Pulmonary– Aspiration– Pneumonia

• Cardiovascular– Cardiac arrhythmias– DVT/PE

• GI/GU– GI bleeding– Urinary tract infection– Bowel impaction– Malnutrition

• Integumentary– Pressure ulcers

• Musculoskeletal– Impaired mobility– Contractures– Heterotrophic ossification– Spasticity

• Psychcosocial– Depression – 60%– Loss of self esteem