SPONTANEOUS INTRACEREBRAL

HEMORRHAGE

� Intracerebral hemorrhage is an acute and

spontaneous extravasation of blood into the

brain parenchyma that may extend into the

ventricles and subarachnoid space.ventricles and subarachnoid space.

� It is common:� 12-15 cases per 100 000 people per year

� 10% ~ 15% of all cases of stroke� 10% ~ 15% of all cases of stroke

� 6 month mortality is 30-50%

Primary (78% ~ Chronic Amyloid(78% ~ 88%)

Chronic hypertension

Amyloidangiopathy

SecondaryVascular

abnormalities (AVM,

aneurysm)

Tumor Coagulopathy

� Coagulation disorders

Anticoagulation /Thrombolytic therapyHemorrhagic transformation of cerebral infarct

LeukemiaThrombocytopeniaThrombocytopenia

� Delayed post-traumatic

� Post-operativeCarotid endarterectomyCraniotomy for evacuation SDHCraniotomy for excision AVM

� MalignantGlioblastoma multiformeLymphomaMetastasis (melanoma, choriocarcinoma,

renal cell carcinoma , bronchogenic carcinoma)renal cell carcinoma , bronchogenic carcinoma)

� BenignMeningiomaPituitary adenomaHemangioblastomaAcoustic neuromaCerebellar astrocytoma

30

74 2

ICH in young

Rp. AVM 30 %30

24

15

10Undet. 24%

HTN 15%

Aneurym 10%

Drug Abuse 7%

Tumor 4%

Moyamoya 2%

Non-modifiable

Male sex

Modifiable

HypertensionMale sex

Age

Asian and African Americans

• Japanese

Hypertension

Heavy alcohol consumption

Hypercholesterolemia

� Accounts for 60-70% of ICH

� Theory:

� Chronic hypertension causes

degeneration, fragmentation and fibrinoid degeneration, fragmentation and fibrinoid

necrosis of small perforating arteries

� Predisposes to rupture

CHARCOT-BOUCHARD ANEURYSMS

� Discrete arteriolar

microaneurysms

� Most common in the distal

BADJATIA AND ROSAND, INTRACEREBRALHEMORRHAGE. THE NEUROLOGIST, VOL. 11, NO. 6: NOVEMBER 2005

� Most common in the distal

portions of medium and

small arterioles

� Deposition of amyloid β peptide in small and medium sized blood vessels

� Results in fibrinoid necrosis

and microaneurysm formation

� Prevalence increases with age from ~ 9% in age 60-69 to 58% in age >90

�Lobar haemorrhages

�Chances of rebleed : 21% in 2 yrs

� Primary-immediate effects� Hemorrhage growth� Increased ICP

� Secondary effects� Edema

IschemiaEdema

� Ischemia

� Progression of hematoma

� Brott et al:▪ 103 pts � 26% within 1 hours, 38% within 20 hours

� Acute hypertension, local coagulation deficit may be associated

Brott, Stroke 1997;28:1-5

� Early Presentation

� Irregular shape

� Liver disease� Liver disease

� Hypertension

� Hyperglycemia

� Alcohol use

� Hypofibrinogenima

Priorities for Clinical Research in ICH:NINDS ICH Workshop; Stroke March 2005

� Volume more than60 cm3� Deep-93%� Lobar-71%

� Volumes 30-60 cm 3� Deep-60%� Deep-60%� Lobar-60%� Cerebellar-75%

� Volumes less than 30 cm3� Deep-23%� Lobar-7%� Cerebellar-57%

Broderick: Volume of ICH; Stroke Vol 24, No 7

� Classic clinical presentation: Onset of sudden focal neurological deficit which progresses over minutes to hours

� 50% present with headache /vomiting

� LOC , Seizures

� May have onset after exertion or intense emotional activity

� More often during routine activity

� May occur during trauma

� 25% pts � deterioration in the level of consciousness within the first 24 hrs

� Expansion of the hematoma : first 3 hrs� Expansion of the hematoma : first 3 hrs

� Worsening cerebral edema : 24 ~ 48 hrs

� Late progression of edema: 2 ~ 3 weeks

� Mortality rate : 23% ~ 58% in 6 months

(1)GCS score on admission

(2)Hematoma volume & its progression

(3)Presence of IVH(3)Presence of IVH

(4) Use of anticoagulants

(5) Location of bleed

� Broderick et al: mortality rate at 1 month

� GCS < 9 , volume > 60 ml � 90%

� GCS ≥ 9 , volume < 30 ml � 17%

Hemphill et al. Stroke 2001, 32:891-97

CT

� Superior to MRI in acutely

ill / stuporous pt.

� IVH

MRI

� Superior in detecting

underlying structural

lesions ( AVM etc. )� IVH

� CECT –

AVM/Aneurysm/Tumor

� CT Angio

lesions ( AVM etc. )

� Gradient Echo MRI -as

accurate as CT for

identification of acute

hemorrhage & more

accurate for identification

of Chronic hemorrhage

� SAH

� Abnormal calcification

� Obvious vascular malformation� Obvious vascular malformation

� Blood in unusual location, such as sylvian fissure

� No obvious cause of bleeding such as isolated IVH

Zhu XL, Chan MS, Poon WS. Spontaneous intracranial haemorrhage:which patients need diagnostic cerebral angiography? A prospectivestudy of 206 cases and review of the literature. Stroke. 1997;28:1406–1409.

� Potential treatments of ICH � Stopping or slowing the initial bleeding;

� Removing blood from the parenchyma or ventricles;

� Management of complications of blood in the brain, including increased ICP and decreased CPP

� Good clinical practice: � Management of airways, oxygenation, circulation, glucose

level, fever, nutrition, and DVT prevention.

� Lack of definitive randomized trials of either medical or surgical therapies for ICH, great variability in care

� McKissock et al Primary Intracerebral haematoma: a controlled trial of surgical and conservative treatment in 180 unselected cases Lancet 1961; ii: 221-6

� Auer LM et al Endoscopic surgery versus medical treatment for spontaneous intracerebral haematoma. A randomized study J Neurosurg 1989; 70: 530-5

� Batjer Hhet al Failure of surgery to improve outcome in hypertensive putaminalhaemorrhage. A prospective randomised trial. Arch Neurol 1990; 47: 1103-6

� Juvela S et al The treatment of spontaneous intracerebral haemorrhage. A prospective randomised trial of surgical and conservative treatment. J Neurosurg1989; 70: 755-8

� Chen X et al A prospective randomised trial of surgical and conservative treatment of hypertensive intracerebral haemorrhage. Acta Acad Shanghai Med. 1992; 19: 237-40

� Morgenstern LB et al Surgical treatment for intracerebral hemorrhage(STICH). A single-center, randomised clinical trial. Neurology 1998; 51: 1359-63

� Zuccarello M et al Early surgical treatment for intracerebral hemorrage. A randomized feasibility study. Stroke 1999; 30(9):1833-9

� Cheng X-C et al. The randomised multicentric prospective controlled trial in the standard treatment of hypertensive intracerebral hematomas: the comparison of surgical therapeutic outcomes with conservative therapy. Chin JClin Neurosci 2001; 9: 365-8

� Hosseini H et al Stereotactic aspiration of deep intracerebral haematomas under computed � Hosseini H et al Stereotactic aspiration of deep intracerebral haematomas under computed tomographic control, a multicentric prospective randomised trial.

Cerebrovasc Dis 2003;16S4:57.

� Hattori N et al Impact of Stereotactic evacuation on activities of daily living during thechronic period following spontaneous Putaminal hemorrhage: a randomized study. J Neurosurg

2004; 101: 417-20

� Teernstra et al Stereotactic treatment of intracerebral hematoma by means of a plasminogenactivator: a multicenter randomized controlled trial (SICHPA). Stroke 2003; 34: 968-74

� Mendelow AD et al Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 2005;

365:387 - 397.

Comparison of surgery plus medical vs medical treatment for outcome: death or dependence at end of follow-up Prasad K, Shrivastava A. Surgery for primary supratentorial intracerebral haemorrhage (Cochrane

Review) In: The Cochrane Library Issue 4, 2000. Surgery was associated with statistically significant

reduction in the odds of being dead or dependent at final follow up.

Prasad, K. et al. Stroke 2009;40:e624-e626

� International surgical trial in ICH (STICH) with 1,033 patients showed no difference in outcome, but some potential benefit in subgroup with lobar ICHsubgroup with lobar ICH

� ISTICH-II will include only lobar ICH with a subset analysis of those treated with rFVIIa

Mendelow AD, et al. for the STICH Investigators. Lancet.

2005;365:387-397.

� 1995 – 2003

� 83 centers in 27 countries� 83 centers in 27 countries

� 1033 pts

� 503 early surgery and 530 initial conservative t/t

� Results

�Favorable outcome at 6 months

122 (26%) with surgery 118 (24%) with

initial conservative t/t (p=0.414)initial conservative t/t (p=0.414)

�Mortality 36% vs. 37%

� Conclusion

No overall benefit from early surgery

compared with initial conservative treatment

Early surgery Initial conservative

t/tGCS 5-8 99 (20%) 106 (20%)GCS 5-8 99 (20%) 106 (20%)

9-12 199 (40%) 211 (40%)13-15 205 (41%) 213 (40%)

SiteLobar 196 (39%) 214 (40%)BG/Thalamic 210 (42%) 224 (42%)Both 94 (19%) 90 (17%)

Early surgery Initial conservative t/t

Volume (ml) 40 (24-63) 37 (23-60)Volume (ml) 40 (24-63) 37 (23-60)

Surgery 465 (94%) 140 (26%)Craniotomy 346 (75%) 119 (85%)Stereotaxy 34 (7 %) 3 (2 %)Endoscopy 31 (7 %) 7 (5 %) Other 54 (11%) 11 (8 %)

� The STICH results do not significantly change current practice.

� Patients with a subcortical or cerebellar hematoma at least 3 cm and impaired consciousness should be operated on.operated on.

� Comatose patients (GCS 8) with ICH in the basal ganglia or thalamus very unlikely benefit from clot removal.

� Minimally invasive methods may be useful if done early after ICH onset, but control of hemostasis may be difficult.

� To establish whether earlier surgical evacuation of lobar ICH will improve outcome compared initial conservative treatment.

� To better define the indications for early surgery.

� This will overcome two of the criticisms of STICH (timing was too late and sometimes location was too deep).

� Inclusion:

� Spontaneous lobar ICH on CT Scan

� Patient randomised within 48 hours of ictus � Patient randomised within 48 hours of ictus

� Surgeon is in equipoise

� Best EYE score of 2 or more & M5/M6

� Volume of haematoma 10 - 100ml

� Exclusion:

� Aneurysm, tumour, trauma, angiographically proven AVM .

� Brain stem / cerebellar haemorrhage.

� Intraventricular haemorrhage , Hydrocephalus .

� Surgery cannot be performed within 12 hours.

� Unreversed clotting or coagulation problems.

� Severe pre-existing physical or mental disability or severe co-morbidity

� Patient randomized within 48 hours of ictus .

� If randomized to early surgery this should be undertaken within 12 hours.

� CT scan at about five days (+/- 2 days) .� CT scan at about five days (+/- 2 days) .

� 600 patients will be recruited 30 months.

� FU will take 6 months with analysis and reporting taking 1 year.

� Outcome will be measured at 6 months via a postal questionnaire incl. the GOS, MRS, EuroQol and Barthel.

� Many techniques� Ultrasonic aspiration

� High pressure fluid irrigation

� Endoscopic aspiration

� Modified nucleotome

� Catheter aspiration withinjection of thrombolytic agent(UK or tPA)

� Potential advantages

� Deep putaminal or thalamic haemorrhages may be accessible

� Less damage to overlying brain

� 77% reduction in ICH volume at 48 hours, with no bleeding- Saline irrigation and aspiration after 1 mgrtPA q8h

Vespa P, et al. Neurocritical Care. 2005;2:274.

Emergency diagnosis and

assessment of ICH and its

causes

Rapid neuroimaging with

CT or MRI is

recommended to

distinguish ischemic

stroke from ICH.

Class I, Level A

Medical treatment for ICH Patients with a severe

coagulation factor

deficiency or severe

thrombocytopenia should

receive appropriate factor

replacement therapy or

platelets, respectively.

Class I, Level C

Hemostasis/antiplatelets/DV

T prophylaxis

Patients with ICH whose INR

is elevated due to OAC should

have their warfarin withheld,

receive therapy to replace

vitamin K–dependent factors

and correct the INR, and

receive intravenous vitamin

K.

Class I, Level C

K.

Patients with ICH should have

intermittent pneumatic

compression for prevention of

venous thromboembolism in

addition to elastic stockings.

Class I, Level B

Inpatient management

and prevention of

secondary brain injury

General monitoring Initial monitoring and Initial monitoring and

management of ICH

patients should take

place in an intensive

care unit, preferably

one with physician and

nursing neuroscience

intensive care

expertise.

Class I, Level B

Management of

glucose

Glucose should be

monitored and

normoglycemia is

recommended

Class I, Level C

Seizures and

antiepileptic drugs

Patients with clinical

seizures should be

Class I, Level A

antiepileptic drugs seizures should be

treated with

antiepileptic drugs.

Patients with a change

in mental status who

are found to have

electrographic seizures

on EEG should be

treated with

antiepileptic drugs

Class I, Level C

Patients with cerebellar

hemorrhage who are

deteriorating

neurologically or who

Procedures/surgery—clot

removal

neurologically or who

have brainstem

compression and/or

hydrocephalus from

ventricular obstruction

should undergo surgical

removal of the

hemorrhage as soon as

possible.

Class I, Level B

Prevention of

recurrent ICH

After the acute ICH,

absent medical

contraindications, BP

should be well

controlled,

particularly for

Class I, Level A

particularly for

patients with ICH

location typical of

hypertensive

vasculopathy.

(Class II a; Level of Evidence:

B).

(Class II b; Level of Evidence:

B)

CT angiography, CT

venography, contrast-

enhanced CT, CEMRI, MRA &

CT angiography and contrast-

enhanced CT may be

considered to help identify enhanced CT, CEMRI, MRA &

MRV can be useful to

evaluate for underlying

structural lesions when there

is clinical or radiological

suspicion

considered to help identify

patients at risk for hematoma

expansion

(Class IIa; Level of Evidence: B)

PCCs have not shown improved outcome compared with FFP but may have fewer

complications compared with FFP and are reasonable to consider as an alternative

to FFP

(Class IIb; Level of Evidence: B)

The usefulness of platelet transfusions in ICH patients with a history

of antiplatelet use is unclear and is considered investigational

After documentation of cessation of bleeding, low-dose

subcutaneous low-molecular-weight heparin or unfractionated

heparin may be considered for prevention of venous

thromboembolism in patients with lack of mobility after 1 to 4 days

from onset

(Class III; Level of Evidence: A)

rFVIIa does not replace all clotting factors, and although the INR may be lowered,

clotting may not be restored in vivo; therefore, rFVIIa is not routinely

recommended as a sole agent for OAC reversal in ICH

Although rFVIIa can limit the extent of hematoma expansion in

noncoagulopathic ICH patients, there is an increase in thromboembolic risk with

rFVIIa and no clear clinical benefit in unselected patients.Thus rFVIIa is not

recommended in unselected patients

In patients presenting with a systolic BP of 150 to 220 mm Hg, acute lowering of systolic BP to 140 mm Hg is probably safe (Class IIa; Level of Evidence: B).(New recommendation)

� If SBP is 200 mm Hg or MAP is 150 mm Hg

� Aggressive reduction and frequent monitoring (5 minutes)

� If SBP is 180 mm Hg or MAP is 130 mm Hg with elevated ICP

� Monitoring ICP

� Reducing BP to keep CPP >60 mm Hg

� If SBP is 180 mm Hg or MAP is 130 mm Hg no ICP issues,

� Modest reduction of BP (~MAP of 110/BP 160/90)

� Using intermittent or continuous IV meds

� Evaluate every 15 minutes.

(Class II a; Level of

Evidence: B)

(Class III; Level of

Evidence: B)

Continuous EEG

monitoring is probably

Prophylactic

anticonvulsantmonitoring is probably

indicated in ICH patients

with depressed mental

status out of proportion

to the degree of brain

injury

anticonvulsant

medication should not be

used

(Class II a; Level of Evidence: B)

Ventricular drainage as treatment

for hydrocephalus is reasonable in

patients with decreased level of

consciousness

(Class II b; Level of Evidence: C)

Patients with a GCS score of 8,

those with clinical evidence of

transtentorial herniation, or those

with significant IVH or

hydrocephalus might be considered

for ICP monitoring and treatment. for ICP monitoring and treatment.

(Class IIb; Level of Evidence: B)

Although intraventricular

administration of rtPA in IVH

appears to have a fairly low

complication rate, efficacy and

safety of this treatment is uncertain

and is considered investigational

(Class IIb; Level of Evidence: B) (Class IIb; Level of Evidence: C)

For patients presenting with lobar

clots >30 mL and within 1 cm of the

surface, evacuation of

For most patients with ICH, the

usefulness of surgery is uncertain .

Specific exceptions to this surface, evacuation of

supratentorial ICH by standard

craniotomy might be considered

Specific exceptions to this

recommendation have been

described.

The effectiveness of minimally

invasive clot evacuation utilizing

either stereotactic or endoscopic

aspiration with or without

thrombolytic usage is uncertain and

is considered investigational

(Class III; Level of Evidence: B) (Class III; Level of Evidence: C)

Although theoretically

attractive, no clear evidence

at present indicates that

ultra-early removal of

Initial treatment of these

patients with ventricular

drainage alone rather than

surgical evacuation is not ultra-early removal of

supratentorial ICH improves

functional outcome or

mortality rate. Very early

craniotomy may be harmful

due to increased risk of

recurrent bleeding

surgical evacuation is not

recommended

(Class IIa; Level of Evidence: B)

Aggressive full care early after ICH onset and

postponement of new DNR orders until at

least the second full day of hospitalization is least the second full day of hospitalization is

probably recommended

� (Class II a; Level of Evidence: B)

Risk factors for recurrence: lobar location of the initial

ICH, older age, ongoing anticoagulation, presence of

the apolipoprotein E 2 or 4 alleles, and greaterthe apolipoprotein E 2 or 4 alleles, and greater

number of microbleeds on MRI

After the acute ICH period, a goal target of a normal

BP of <140/90 (<130/80 if diabetes or chronic kidney

disease) is reasonable

Avoidance of long-term anticoagulation as treatment

for nonvalvular atrial fibrillation is probably

recommended after spontaneous lobar ICH because of

the relatively high risk of recurrence

(Class IIa; Level of Evidence: B)

Avoidance of heavy alcohol use can be beneficial

(Class IIb; Level of

Evidence:B)

(Class IIb; Level of

Evidence:C)

Anticoagulation after

nonlobar ICH and

antiplatelet therapy after all

ICH might be considered,

particularly when there are

definite indications for these

agents

There is insufficient data to

recommend restrictions on

use of statin agents or

physical or sexual activity