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