Review of Primary Intracerebral Hemorrhage

Review of Primary

Intracerebral Hemorrhage

Réza Behrouz, DOAssistant Professor of Neurology

University of South Florida College of Medicine

85%ISCHEMIC

15%HEMORRHAGIC

STROKE

HEMORRHAGIC STROKE

1/3Subarachnoid

2/3Intracerebral

DEFINITION

Acute extravasation of blood into the brain

parenchyma

EPIDEMIOLOGY

•

More common in men–

Subarachnoid hemorrhage more common in women

•

Risk increases dramatically with age–

Risk doubles every 10 years after age 35

–

Mean age 60

•

2X in Blacks, Asians and Hispanics than Whites

Gebel JM et al. Intracerebral Hemorrhage. Neurologic Clinics. May 2000: 19 (2): 419 -

438.Broderick JP et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke.

1999;30:905-915

EPIDEMIOLOGY

•

US prevalence

37,000 ‐

52,000

•

US annual death rate

20,000

•

US overall annual cost $ 6 Billion


438.Broderick JP et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke.

1999;30:905-915

Roosevelt

Lenin

Al-Sabah

Sharon

PRESENTATION

•

Sudden onset focal neurological deficit–

85% during active

hours of the day

•

Smooth progression over time–

TIAs unusual

•

Elevated blood pressure (90%)–

Regardless of a pre-existing history of hypertension

Caplan LR. Intracerebral Hemorrhage.

Caplan’s Stroke: A Clinical Approach. Third Edition. 2000.Broderick JP et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke.

1999;30:905-915.

PRESENTATION

•

Nausea & emesis

~ 55 %

•

Early or abrupt change in LOC

~ 50 %

•

Headache ~ 40 %

•

Seizures

~ 10%

Caplan LR. Intracerebral Hemorrhage.

Caplan’s Stroke: A Clinical Approach. Third Edition. 2000.Broderick JP et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke.

1999;30:905-915.

PRIMARY SECONDARY

Unrelated to an underlying congenital or acquired brain lesions or

abnormalities

Related to

a pre-existing intracranial abnormality

Manno EM et al. Emerging Medical and Surgical Management Strategies in the Evaluation and Treatment of Intracerebral Hemorrhage. Mayo Clin Proc. March 2005;80(3):420-433.

PRIMARY HypertensionHypertensionCerebral Amyloid AngiopathyAnticoagulantsThrombolyticsDrug UseBleeding Diathesis

SECONDARYVascular MalformationsAneurysmsIntracranial NeoplasmCerebral InfarctionsVenous InfarctionMoyamoya DiseaseCerebral Vasculitis

Manno EM et al. Emerging Medical and Surgical Management Strategies in the Evaluation and Treatment of Intracerebral Hemorrhage. Mayo Clin Proc. March 2005;80(3):420-433.

Hypertension70%

AmyloidAngiopathy

20%

Anticoagulants (8%)

Drug Use

Bleeding Diathesis

HYPERTENSIVE HEMORRHAGE

•

HTN: the most important risk factor

•

Exact quantification of risk difficult to ascertain–

Smoking and excessive alcohol can increase the risk

•

Treatment of HTN decreases risk of ICH by

~ 50%

•

Recurrent risk of HH is 1-2% per year–

If blood pressure is well controlled


438.Hypertension Detection and Follow-up Program Cooperative Group. Five year findings.

JAMA

1982;247:633-8.


•

Rupture of deep-penetrating arteries

–

Originate from major cerebral arteries

–

Unprotected from direct effects of HTN

•

Diameter

–

100 -

600 μm

Mayer SA et al. Treatment of intracerebral hemorrhage. Lancet Neurology

2005;4:662-72.


StriatumThalamus

Pons

Lobar

Cerebellum


•

Charcot -

Bouchard aneurysms–

Not seen in all cases

•

Lipohyalinosis –

More plausible explanation

Qureshi AI et al. Spontaneous Intracerebral Hemorrhage.

N Eng J Med.

Vol 344, No 19. May 10, 2001.Manno EM et al. Emerging Medical and Surgical Management Strategies in the Evaluation and Treatment of Intracerebral Hemorrhage. Mayo Clin Proc. March 2005;80(3):420-433.

AMYLOID ANGIOPATHY

•

Different than systemic amyloidosis

•

~ 20 % of ICH cases > 70

•

Risk with advancing age

•

Lobar or cortical

•

Multiple

•

Recurrent –

Rate 5-15% per year

•

Less severe than HH

•

History of cognitive decline


2005;4:662-72.

AMYLOID ANGIOPATHY

•

Diagnosis at autopsy

•

Lobar micro-hemorrhages

•

Most are clinically silent

•

Strongly suggests the diagnosis–

Age > 70–

History of lobar hemorrhage

•

Reflects disease severity and recurrence risk


2005;4:662-72.

AMYLOID ANGIOPATHY

Beta/A4-amyloid in vessel Fluorescent stained wall unstained


2005;4:662-72.

COAGULOPATHY

•

Warfarin–

Increases risk 5 -

10 times

–

AR 0.3 -

1.7 % per year–

Doubles the mortality of ICH

•

Aspirin–

AR 0.2 % per year

•

Bleeding disorders

•

Mostly lobar

•

Hemorrhage develops gradually

Hart RG et al. Oral anticoagulants and intracerebral hemorrhage. Facts and hypotheses.

Stroke 1995. 26:1471-77.Gebel JM et al. Intracerebral Hemorrhage. Neurologic Clinics. May 2000: 19 (2): 419 -

438.

COAGULOPATHY

Predictors for Warfarin-related ICHAge

Inadequate blood pressure control

Intense anticoagulation

Severe leukoareosis

Cerebral amyloid angiopathy

Hart RG et al. Oral anticoagulants and intracerebral hemorrhage. Facts and hypotheses.

Stroke 1995. 26:1471-77.Gebel JM et al. Intracerebral Hemorrhage. Neurologic Clinics. May 2000: 19 (2): 419 -

438.

THROMBOLYTICS

6.4% with IV rTPA

NINDS tPA

study0.6 % with placebo (p<0.001)

10.9% with IA thrombolysis

PROACT II study3.1 % with control (p=0.06)

NINDS & rt-PA Stroke Study Group. Tissue Plasminogen

Activator for acute ischemic stroke.

N Engl

J Med.

1995 Dec 24; 333 1581-87Furlan

A et al. Intra-arterial prourokinase

for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse

in Acute Cerebral Thromboembolism. JAMA. 1999 Dec 1;282(21):2003-11

THROMBOLYTICS

Influential factorsNIHSS > 20

Age > 75

Edema and mass effect on baseline CT

Initial CT hypo-attenuation > 33% of MCA distribution

NINDS tPA

Study Group. Intracerebral

Hemorrhage After Intravenous t-PA Therapy for Ischemic Stroke. Stroke.

1997;28:2109-2118.Larrue

V et al. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen

activator: a secondaryanalysis of the European-Australian Acute Stroke Study (ECASS II).

Stroke 2001 Feb;32(2):438-41.

DRUGS

• 1% of all cases

• CulpritsCocaine, Amphetamines, Ephedrines

• Mainly young patients

• Predisposing factorsHypertension, AVM


438.

DIAGNOSIS

• Emergent diagnosisSize, volume and locationHydrocephalus / herniationIntraventricular extension

• Door to CT< 25 min

Smith EE st al. Hemorrhagic Stroke.

Neuroimaging Clin of N Am.

15 (2005) 259-272.

DIAGNOSIS -

CT

•Disappears Within 2 to 4 weeks

• Severe anemia Reduces attenuation



15 (2005) 259-272.

DIAGNOSIS -

MRI

• LimitationsTimePatient monitoring

• RecommendedAlmost all patients with ICH

• Structural abnormalities

• Time course



15 (2005) 259-272.

ACUTE MANAGEMENT

!StopHemorrhage

Stabilize Hemodynamics

Complications

COAGULOPATHY

•

Successful reversal

–

INR < 1.4

•

Time is important

–

Early reversal of coagulopathy is critical


2005;4:662-72.

COAGULOPATHY

Repeat INR in 4 hours Administer FFP if >1.4 -

otherwise every 6 hours

Vitamin K10 mg IV

FFP15 mL/kg

6 units


2005;4:662-72.

COAGULOPATHY

Heparin reversalProtamine sulfate 10-50 mg IV over 1-3 minutesOR 1 mg for every 100 units of Heparin

Platelet transfusion4-8 unitsGoal platelet count > 100,000Use in ASA/Clopidogrel-related ICH controversial


2005;4:662-72.

BLOOD PRESSURE

MAP

< 130 mmHg

With a history of hypertension

Ideally between 90 to 110 mmHgCPP > 70 mmHg

AgentsNicardipine (5-15 mg/hr), Labetolol (2-8 mg/min), EsmololHydralazine and Nitroprusside NOT recommended in acute ICH

Mayer SA et al. Optimizing blood pressure in neurological emergencies.

Neurocritical Care.

2004. 1: 287-99Broderick JP et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage.

Stroke.

1999;30:905-915

COMPLICATIONS

• Hematoma expansionIntra-parenchymal Intra-ventricular

•Hydrocephalus

•Edema and herniation

• Seizures

HEMATOMA EXPANSION

• 25% deteriorate in first 24 hExpansion of hematoma first 24 hoursWorsening cerebral edema

24 -

72 hours

• Expansion: 38 -

46%

• Not a monophasic process

• Predictive factors UncertainUncorrected coagulopathyAdmission SBP > 200 mmHgAdmission hyperglycemia

Fibotte JJ et al. Warfarin, hematoma expansion and outcome of intracerebral hemorrhage.

Neurology

2004;63:1059-1064.Mayer SA et al. Neurological deterioration in non-comatose patients with supratentorial intracerebral hemorrhage.

Neurology 1994;44:1379-84.

INTRAVENTRICULAR EXTENSION

• 20 - 40%Deep hemorrhagesLarge Hemorrhages

• SymptomsMeningismusAlteration of consciousness

• Volume of IVEProportionally affects mortality

ACUTE HYDROCEPHALUS

• Increased ICP

• Hydrocephalus

• External ventricular drain• Large IV blood on initial CT• Development of hydrocephalus

EDEMA

•

Chief complication in the first few days

• Can increase by 75%

• Increased mass effect

• Increased ICP

• Herniation


N Eng J Med.

Vol 344, No 19. May 10, 2001Gebel JM et al. Relative edema volume is a predictor of outcome in patients with

hyperacute intracerebral hemorrhage. Stroke 2002; 33:2636 -

41.

EDEMA

0 30 min Hours to Days

10 Days

TIME

ICTUSVasogenic

EdemaCytotoxic

Edema


N Eng J Med.

Vol 344, No 19. May 10, 2001

EDEMA / HERNIATION

•HyperventilationInitial mode of therapy to gain immediate controlTransient

effect

• 20% Mannitol IV0.5 to 1.0 g/kg IV bolus every 4 hours

• Hypertonic Saline IV3% (250 mL), 7.5% (100 mL) and 10% (75 mL) = 7.5 g NaCl

Broderick JP et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage.

Stroke.

1999;30:905-915

EDEMA / HERNIATION

• Pharmacological comaPentobarbital

•Do not use corticosteroids


Stroke.

1999;30:905-915

SEIZURES

• Presenting symptom in 10%

• Risk of development of epilepsy

5%

• Non-convulsing status epilepticus

1-2 %

EEG indicated in prolonged comatose states

• Lobar hemorrhage An independent risk factor for early seizures

Vespa PM et al. Acute seizures after intracerebral hemorrhage.

Neurology

2003;60:1441-46Passero S et al. Seizures after spontaneous supratentorial intracerebral hemorrhage. Epilepsia. 2002;431175-80.

SEIZURES• Early seizure

Early < 14 daysMore commonTaper AED off after one month if seizure free

• Late seizuresLate > 14 daysMay need lifetime AED therapy

• AED prophylaxis may be beneficialNo randomized trial has addressed the efficacyUse for lobar ICH Taper off after one month if seizure free

Vespa PM et al. Acute seizures after intracerebral hemorrhage.

Neurology

2003;60:1441-46Passero S et al. Seizures after spontaneous supratentorial intracerebral hemorrhage. Epilepsia. 2002;431175-80.

EARLY SURGICAL EVACUATION

• May be performed as a life-saving measure

• Benefit in long-term outcome is questionableTen studies (5 randomized) Conflicting resultsOverall, no proof that early surgery is superior to medical therapy

• Over 7000 annual surgeries are performed

worldwide


Stroke.

1999;30:905-915

Mendelow AD et al. Early surgey versus initial conservative treatment in patients with spontaneous supratentoral intracerebral hemorrhage in the international Surgical Trial in Intracerebral Haemorhage (STICH): a randomised trial. Lancet

2005;365:387-397.

Randomized, parallel groupPrimary ICH -

GCS > 5 and hematoma diameter > 2 cm

1033 patients with supra-tentorial hemorrhage“Uncertainty principle”1/2 allocated to early surgery + medical therapySurgery within 72 hours1/2 allocated to initial medical therapyBaseline characteristics well-matched

Outcome assessed at 6 months months

STICH


2005;365:387-397.

00.10.20.30.40.50.60.70.80.9

1

30 60 90 120 150 180 210 240

STICH


2005;365:387-397.

SURVIVAL

Surgery

Initial Conservative


2005;365:387-397.

STICH

Favorable outcome = BI >95 and mRS <2

Neither the absolute (2%) nor the relative benefit (10%)of early surgery was significant (p=0.414).

EARLY SURGICAL EVACUATION

•worldwide


Stroke.

1999;30:905-915

Patients with cerebellar ICH > 3 cm who are deteriorating, show signs of brainstem compression or hydrocephalus

Patients with lobar ICH that is 1 cm or less from the cortical surface

• Hematoma growth Is a critical determinant of morbidity and mortality

• Ultra-early hemostatic therapy Arrests ongoing bleeding and minimizes hematoma growth

• rFVIIaCurrently approved for hemorrhage in hemophiliacs

resistant

to Factor VIII or IX replacement therapy Causes local initiation of coagulation cascade after vascular damage.

rFVIIa

Mayer SA et al. Recombinant activated factor VII of racute intracerebral hemorrhage. N Eng J Med.

2005; 352:777-85.

rFVIIa


2005; 352:777-85.

rFVIIa


2005; 352:777-85.

•

Limited hematoma growth

by ~ 50 % (p = 0.01)

•

Relative reduction in

mortality 35%p = 0.025 -

rFVIIa versus

placebo

rFVIIa


2005; 352:777-85.

rFVIIa

• Thirty day mortality

30-50%

Depends upon various factorsWith Warfarin on board ~ 70%

• Only ~ 25% will be independent in 6 monthsmonths

PROGNOSIS


N Eng J Med.

Vol 344, No 19. May 10, 2001.

THE LAW OF 30’S

ICH volume > 30

mLMortality

~ 30

%

In

30

days

PROGNOSIS

ICH SCORE

ICH SCORE

Acute therapyATACH -

Antihypertensive therapy in ICHINTERACT -

Effects of aggressive BP loweringDITCH -

Intraventricular thrombolysis

GeneticsGOCHA -

Genetics of Warfarin-related ICH

Surgical interventionSTICH IIMISTIE -

Intra-hematomal tPA and stereotactic evacuation

FUTURE STUDIES

EpidemiologyPathophysiologic mechanismsDiagnostic methodsManagement schemesPrognosisNew directions

SUMMARY

THANK YOU

Documents

Review of Primary Intracerebral Hemorrhage