Spontaneous intracerebral hemorrhage


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ICH treatment is still difficult, controversial and still in progress

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Spontaneous intracerebral hemorrhage

  2. 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. 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. 4. Primary (78% ~ Chronic Amyloid (78% ~ 88%) Chronic hypertension Amyloid angiopathy Secondary Vascular abnormalities (AVM, aneurysm) Tumor Coagulopathy
  5. 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. 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. 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. 8. Non- modifiable Male sex Modifiable HypertensionMale sex Age Asian and African Americans • Japanese Hypertension Heavy alcohol consumption Hypercholesterolemia
  9. 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. 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. 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. 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. 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. 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. 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. 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. 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. 18. Hemphill et al. Stroke 2001, 32:891-97
  19. 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. 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. 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. 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. 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. 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
  25. 25. 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.
  26. 26. 1995 – 2003 83 centers in 27 countries83 centers in 27 countries 1033 pts 503 early surgery and 530 initial conservative t/t
  27. 27. 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
  28. 28. 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%)
  29. 29. 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 %)
  30. 30. 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.
  31. 31. 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).
  32. 32. 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
  33. 33. 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
  34. 34. 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.
  35. 35. Many techniques Ultrasonic aspiration High pressure fluid irrigation Endoscopic aspiration Modified nucleotome Catheter aspiration with injection of thrombolytic agent (UK or tPA)
  36. 36. 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.
  37. 37. 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
  38. 38. 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
  39. 39. 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
  40. 40. 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
  41. 41. 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
  42. 42. 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.
  43. 43. (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
  44. 44. (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
  45. 45. (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
  46. 46. 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.
  47. 47. (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
  48. 48. (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
  49. 49. (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
  50. 50. (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
  51. 51. (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
  52. 52. (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
  53. 53. (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