ICH treatment is still difficult, controversial and still in progress

1. SPONTANEOUS INTRACEREBRAL
HEMORRHAGE

2. 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.

3. It is common:
12-15 cases per 100 000 people per year
10% ~ 15% of all cases of stroke10% ~ 15% of all cases of stroke
6 month mortality is 30-50%

4. Primary
(78% ~ Chronic Amyloid
(78% ~
88%)
Chronic
hypertension
Amyloid
angiopathy
Secondary
Vascular
abnormalities
(AVM,
aneurysm)
Tumor Coagulopathy

5. Coagulation disorders
Anticoagulation /Thrombolytic therapy
Hemorrhagic transformation of cerebral infarct
Leukemia
ThrombocytopeniaThrombocytopenia
Delayed post-traumatic
Post-operative
Carotid endarterectomy
Craniotomy for evacuation SDH
Craniotomy for excision AVM

6. Malignant
Glioblastoma multiforme
Lymphoma
Metastasis (melanoma, choriocarcinoma,
renal cell carcinoma , bronchogenic carcinoma)renal cell carcinoma , bronchogenic carcinoma)
Benign
Meningioma
Pituitary adenoma
Hemangioblastoma
Acoustic neuroma
Cerebellar astrocytoma

7. 30
7
4 2
ICH in young
Rp.AVM 30 %
30
24
15
10
Undet. 24%
HTN 15%
Aneurym 10%
DrugAbuse 7%
Tumor 4%
Moyamoya 2%

8. Non-
modifiable
Male sex
Modifiable
HypertensionMale sex
Age
Asian and African
Americans
• Japanese
Hypertension
Heavy alcohol
consumption
Hypercholesterolemia

9. Accounts for 60-70% of ICH
Theory:
Chronic hypertension causes
degeneration, fragmentation and fibrinoiddegeneration, fragmentation and fibrinoid
necrosis of small perforating arteries
Predisposes to rupture

10. CHARCOT-BOUCHARD
ANEURYSMS
Discrete arteriolar
microaneurysms
Most common in the distal
BADJATIAAND ROSAND, INTRACEREBRAL
HEMORRHAGE. THE NEUROLOGIST,VOL.
11, NO. 6: NOVEMBER 2005
Most common in the distal
portions of medium and
small arterioles

11. 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

12. Primary-immediate effects
Hemorrhage growth
Increased ICP
Secondary effects
Edema
Ischemia
Edema
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

13. Early Presentation
Irregular shape
Liver diseaseLiver disease
Hypertension
Hyperglycemia
Alcohol use
Hypofibrinogenima
Priorities for Clinical Research in ICH:
NINDS ICHWorkshop; Stroke March 2005

14. 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; StrokeVol 24, No 7

15. 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

16. 25% pts deterioration in the level of
consciousness within the first 24 hrs
Expansion of the hematoma : first 3 hrsExpansion of the hematoma : first 3 hrs
Worsening cerebral edema : 24 ~ 48 hrs
Late progression of edema: 2 ~ 3 weeks

17. 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%

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

19. CT
Superior to MRI in acutely
ill / stuporous pt.
IVH
MRI
Superior in detecting
underlying structural
lesions ( AVM etc. )IVH
CECT –
AVM/Aneurysm/Tumor
CTAngio
lesions ( AVM etc. )
Gradient Echo MRI -as
accurate as CT for
identification of acute
hemorrhage & more
accurate for identification
of Chronic hemorrhage

20. SAH
Abnormal calcification
Obvious vascular malformationObvious vascular malformation
Blood in unusual location, such as sylvian fissure
No obvious cause of bleeding such as isolated IVH
Zhu XL, Chan MS, PoonWS. Spontaneous intracranial haemorrhage:
which patients need diagnostic cerebral angiography? A prospective
study of 206 cases and review of the literature. Stroke. 1997;28:
1406–1409.

21. 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

22. 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 putaminal
haemorrhage.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 Neurosurg
1989; 70: 755-8
ChenX et al A prospective randomised trial of surgical and conservative treatment of
hypertensive intracerebral haemorrhage. Acta AcadShanghai 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

23. Zuccarello M et al Early surgical treatment for intracerebral hemorrage. A randomized feasibility study.
Stroke 1999; 30(9):1833-9
ChengX-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. ChinJClin Neurosci 2001; 9: 365-8
Hosseini H et al Stereotactic aspiration of deep intracerebral haematomas under computedHosseini 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 the
chronic 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 plasminogen
activator: a multicenter randomized controlled trial (SICHPA). Stroke 2003; 34: 968-74
MendelowAD et al Early surgery versus initial conservative treatment in patients with
spontaneous supratentorial intracerebral haematomas in the International SurgicalTrial in
Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 2005;
365:387 - 397.

24. 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 wasassociated with statistically significant
reduction in the oddsof being dead or dependent at final follow up.
Prasad, K. et al. Stroke 2009;40:e624-e626

26. 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
MendelowAD, et al. for the STICH Investigators. Lancet.
2005;365:387-397.

27. 1995 – 2003
83 centers in 27 countries83 centers in 27 countries
1033 pts
503 early surgery and 530 initial conservative t/t

28. 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

29. Early surgery Initial
conservative
t/t
GCS 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%)
Site
Lobar 196 (39%) 214 (40%)
BG/Thalamic 210 (42%) 224 (42%)
Both 94 (19%) 90 (17%)

30. 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 %)

31. 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.

32. 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).

33. Inclusion:
Spontaneous lobar ICH on CT Scan
Patient randomised within 48 hours of ictusPatient randomised within 48 hours of ictus
Surgeon is in equipoise
Best EYE score of 2 or more & M5/M6
Volume of haematoma 10 - 100ml

34. Exclusion:
Aneurysm, tumour, trauma, angiographically provenAVM .
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

35. 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.

36. Many techniques
Ultrasonic aspiration
High pressure fluid irrigation
Endoscopic aspiration
Modified nucleotome
Catheter aspiration with
injection of thrombolytic agent
(UK or tPA)

37. 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 mg
rtPA q8h
Vespa P, et al. NeurocriticalCare. 2005;2:274.

38. 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

39. 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

40. Inpatient management
and prevention of
secondary brain injury
General monitoring Initial monitoring andInitial 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

41. 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

42. 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

43. 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.

44. (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 identifyenhanced 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

45. (ClassIIa; Level of Evidence: B)
PCCs have not shownimproved outcome comparedwith FFP but may have fewer
complicationscompared with FFPand 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 unclearand is considered investigational
After documentation of cessation of bleeding, low-dose
subcutaneous low-molecular-weight heparin or unfractionated
heparin may beconsidered for prevention of venous
thromboembolism in patients with lack of mobility after 1 to 4 days
from onset

46. (ClassIII; Level of Evidence: A)
rFVIIa does not replaceall clottingfactors, and although the INR may be lowered,
clottingmay notbe restored in vivo; therefore, rFVIIa is not routinely
recommendedas a sole agent for OAC reversal in ICH
Although rFVIIa can limit the extent of hematoma expansion in
noncoagulopathicICH patients, there is an increase in thromboembolicrisk with
rFVIIa and no clear clinical benefit in unselectedpatients.Thus rFVIIa is not
recommended in unselected patients

47. In patients presenting with a systolic BP of 150 to 220 mmHg, acute lowering of
systolicBP 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.

48. (Class II a; Level of
Evidence:B)
(Class III; Level of
Evidence:B)
Continuous EEG
monitoring is probably
Prophylactic
anticonvulsantmonitoring is probably
indicated inICH patients
with depressed mental
status out of proportion
to the degree of brain
injury
anticonvulsant
medication should not be
used

49. (Class II a;Level of Evidence: B)
Ventricular drainage as treatment
for hydrocephalus isreasonablein
patients with decreased level of
consciousness
(Class II b; Level of Evidence:C)
Patients with a GCS score of 8,
those with clinical evidenceof
transtentorial herniation, or those
with significant IVHor
hydrocephalus might be considered
for ICP monitoring andtreatment.for ICP monitoring andtreatment.
(Class IIb; Level of Evidence:B)
Although intraventricular
administration of rtPA in IVH
appears to have a fairly low
complicationrate, efficacy and
safety of this treatment is uncertain
andis considered investigational

50. (Class IIb; Level of Evidence: B) (Class IIb; Level of Evidence: C)
For patients presentingwith lobar
clots >30 mL and within1 cm of the
surface, evacuationof
For most patients with ICH, the
usefulness of surgery isuncertain .
Specific exceptions to thissurface, evacuationof
supratentorial ICH by standard
craniotomy might be considered
Specific exceptions to this
recommendation have been
described.
The effectiveness of minimally
invasive clotevacuation utilizing
either stereotactic or endoscopic
aspirationwith or without
thrombolytic usage is uncertain and
is consideredinvestigational

51. (ClassIII; Level of Evidence: B) (Class III; Level ofEvidence: C)
Although theoretically
attractive, no clear evidence
atpresentindicates that
ultra-early removal of
Initial treatmentof these
patients with ventricular
drainage alone rather than
surgical evacuation is notultra-early removal of
supratentorialICH improves
functional outcome or
mortality rate.Very early
craniotomymay be harmful
due to increased risk of
recurrentbleeding
surgical evacuation is not
recommended

52. (Class IIa; Level of Evidence: B)
Aggressive full care early after ICH onset and
postponementof new DNR orders until at
least the second full day of hospitalizationisleast the second full day of hospitalizationis
probably recommended

53. (Class II a; Level of Evidence:B)
Risk factors for recurrence: lobarlocation 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
Afterthe acute ICH period, a goal target of a normal
BPof <140/90(<130/80 if diabetes or chronic kidney
disease)is reasonable
Avoidance of long-term anticoagulation as treatment
for nonvalvularatrial fibrillation is probably
recommended after spontaneouslobar ICH because of
the relatively high risk of recurrence

54. (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
nonlobarICH and
antiplatelet therapy after all
ICH might be considered,
particularly when there are
definite indications for these
agents
There is insufficient datato
recommendrestrictions on
use of statin agents or
physicalor sexual activity