Intracerebral Hemorrhage

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1 Review of Primary Intracerebral Hemorrhage Réza Behrouz, DO Assistant Professor of Neurology University of South Florida College of Medicine

2 STROKE 85% ISCHEMIC 15% HEMORRHAGIC

3 HEMORRHAGIC STROKE 1/3 Subarachnoid 2/3 Intracerebral

4 DEFINITION Acute extravasation of blood into the brain parenchyma

5 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): Broderick JP et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke. 1999;30:

6 EPIDEMIOLOGY US prevalence 37,000 52,000 US annual death rate 20,000 US overall annual cost $ 6 Billion Gebel JM et al. Intracerebral Hemorrhage. Neurologic Clinics. May 2000: 19 (2): Broderick JP et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke. 1999;30:

7 Roosevelt Lenin Al-Sabah Sharon

8 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 Broderick JP et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke. 1999;30:

9 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 Broderick JP et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke. 1999;30:

10 PRIMARY Unrelated to an underlying congenital or acquired brain lesions or abnormalities SECONDARY 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):

PRIMARY Hypertension Hypertension Cerebral Amyloid Angiopathy Anticoagulants Thrombolytics Drug Use Bleeding Diathesis SECONDARY Vascular Malformations Aneurysms Intracranial Neoplasm Cerebral

11 PRIMARY Hypertension Hypertension Cerebral Amyloid Angiopathy Anticoagulants Thrombolytics Drug Use Bleeding Diathesis SECONDARY Vascular Malformations Aneurysms Intracranial Neoplasm Cerebral Infarctions Venous Infarction Moyamoya Disease Cerebral 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):

12 Anticoagulants (8%) Drug Use Amyloid Angiopathy 20% Bleeding Diathesis Hypertension 70%

13 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 Gebel JM et al. Intracerebral Hemorrhage. Neurologic Clinics. May 2000: 19 (2): Hypertension Detection and Follow-up Program Cooperative Group. Five year findings. JAMA 1982;247:633-8.

14 HYPERTENSIVE HEMORRHAGE Rupture of deep-penetrating arteries Originate from major cerebral arteries Unprotected from direct effects of HTN Diameter μm Mayer SA et al. Treatment of intracerebral hemorrhage. Lancet Neurology 2005;4:

15 HYPERTENSIVE HEMORRHAGE Lobar Striatum Thalamus Pons Cerebellum

16 HYPERTENSIVE HEMORRHAGE 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, 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):

AMYLOID ANGIOPATHY Different than systemic

History of cognitive decline Mayer SA et al.

17 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 Mayer SA et al. Treatment of intracerebral hemorrhage. Lancet Neurology 2005;4:

AMYLOID ANGIOPATHY Diagnosis at autopsy Lobar micro-hemorrhages Most are clinically silent Strongly suggests the diagnosis Age > 70 History of

18 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 Mayer SA et al. Treatment of intracerebral hemorrhage. Lancet Neurology 2005;4:

19 AMYLOID ANGIOPATHY Beta/A4-amyloid in vessel wall unstained Fluorescent stained Mayer SA et al. Treatment of intracerebral hemorrhage. Lancet Neurology 2005;4:

20 COAGULOPATHY Warfarin Increases risk 5-10 times AR % 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 : Gebel JM et al. Intracerebral Hemorrhage. Neurologic Clinics. May 2000: 19 (2):

21 COAGULOPATHY Predictors for Warfarin-related ICH Age Inadequate blood pressure control Intense anticoagulation Severe leukoareosis Cerebral amyloid angiopathy Hart RG et al. Oral anticoagulants and intracerebral hemorrhage. Facts and hypotheses. Stroke : Gebel JM et al. Intracerebral Hemorrhage. Neurologic Clinics. May 2000: 19 (2):

22 THROMBOLYTICS 6.4% with IV rtpa NINDS tpa study 0.6 % with placebo (p<0.001) 10.9% with IA thrombolysis PROACT II study 3.1 % with control (p=0.06) NINDS & rt-pa Stroke Study Group. Tissue Plasminogen Activator for acute ischemic stroke. N Engl J Med Dec 24; Furlan A et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA Dec 1;282(21):

23 THROMBOLYTICS Influential factors NIHSS > 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: Larrue V et al. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australian Acute Stroke Study (ECASS II). Stroke 2001 Feb;32(2):

24 DRUGS 1% of all cases Culprits Cocaine, Amphetamines, Ephedrines Mainly young patients Predisposing factors Hypertension, AVM Gebel JM et al. Intracerebral Hemorrhage. Neurologic Clinics. May 2000: 19 (2):

25 DIAGNOSIS Emergent diagnosis Size, volume and location Hydrocephalus / herniation Intraventricular extension Door to CT < 25 min Smith EE st al. Hemorrhagic Stroke. Neuroimaging Clin of N Am. 15 (2005)

26 DIAGNOSIS - CT Disappears Within 2 to 4 weeks Severe anemia Reduces attenuation Smith EE st al. Hemorrhagic Stroke. Neuroimaging Clin of N Am. 15 (2005)

27 DIAGNOSIS - MRI Limitations Time Patient monitoring Recommended Almost all patients with ICH Structural abnormalities Time course Smith EE st al. Hemorrhagic Stroke. Neuroimaging Clin of N Am. 15 (2005)

28 ACUTE MANAGEMENT! Stop Hemorrhage Stabilize Hemodynamics Complications

29 COAGULOPATHY Successful reversal INR < 1.4 Time is important Early reversal of coagulopathy is critical Mayer SA et al. Treatment of intracerebral hemorrhage. Lancet Neurology 2005;4:

30 COAGULOPATHY Vitamin K 10 mg IV FFP 15 ml/kg 6 units Repeat INR in 4 hours Administer FFP if >1.4 - otherwise every 6 hours Mayer SA et al. Treatment of intracerebral hemorrhage. Lancet Neurology 2005;4:

COAGULOPATHY Heparin reversal Protamine sulfate 10-50 mg IV over 1-3 minutes OR 1 mg for every 100 units of Heparin Platelet transfusion 4-8 units Goal

31 COAGULOPATHY Heparin reversal Protamine sulfate mg IV over 1-3 minutes OR 1 mg for every 100 units of Heparin Platelet transfusion 4-8 units Goal platelet count > 100,000 Use in ASA/Clopidogrel-related ICH controversial Mayer SA et al. Treatment of intracerebral hemorrhage. Lancet Neurology 2005;4:

32 BLOOD PRESSURE MAP < 130 mmhg With a history of hypertension Ideally between 90 to 110 mmhg CPP > 70 mmhg Agents Nicardipine (5-15 mg/hr), Labetolol (2-8 mg/min), Esmolol Hydralazine and Nitroprusside NOT recommended in acute ICH Mayer SA et al. Optimizing blood pressure in neurological emergencies. Neurocritical Care : Broderick JP et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke. 1999;30:

33 COMPLICATIONS Hematoma expansion Intra-parenchymal Intra-ventricular Hydrocephalus Edema and herniation Seizures

HEMATOMA EXPANSION 25% deteriorate in first 24 h Expansion of hematoma Worsening cerebral edema Expansion: 38-46% first 24 hours 24-72 hours Not a monophasic process Predictive factors Uncertain

34 HEMATOMA EXPANSION 25% deteriorate in first 24 h Expansion of hematoma Worsening cerebral edema Expansion: 38-46% first 24 hours hours Not a monophasic process Predictive factors Uncertain Uncorrected coagulopathy Admission SBP > 200 mmhg Admission hyperglycemia Fibotte JJ et al. Warfarin, hematoma expansion and outcome of intracerebral hemorrhage. Neurology 2004;63: Mayer SA et al. Neurological deterioration in non-comatose patients with supratentorial intracerebral hemorrhage. Neurology 1994;44:

35 INTRAVENTRICULAR EXTENSION 20-40% Deep hemorrhages Large Hemorrhages Symptoms Meningismus Alteration of consciousness Volume of IVE Proportionally affects mortality

36 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 Qureshi AI et al. Spontaneous Intracerebral Hemorrhage.

37 EDEMA Chief complication in the first few days Can increase by 75% Increased mass effect Increased ICP Herniation Qureshi AI et al. Spontaneous Intracerebral Hemorrhage. N Eng J Med. Vol 344, No 19. May 10, 2001 Gebel JM et al. Relative edema volume is a predictor of outcome in patients with hyperacute intracerebral hemorrhage. Stroke 2002; 33:

38 EDEMA ICTUS Vasogenic Edema Cytotoxic Edema 0 30 min Hours to Days 10 Days TIME Qureshi AI et al. Spontaneous Intracerebral Hemorrhage. N Eng J Med. Vol 344, No 19. May 10, 2001

39 EDEMA / HERNIATION Hyperventilation Initial mode of therapy to gain immediate control Transient effect 20% Mannitol IV 0.5 to 1.0 g/kg IV bolus every 4 hours Hypertonic Saline IV 3% (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:

40 EDEMA / HERNIATION Pharmacological coma Pentobarbital Do not use corticosteroids Broderick JP et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke. 1999;30:

41 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: Passero S et al. Seizures after spontaneous supratentorial intracerebral hemorrhage. Epilepsia. 2002;

42 SEIZURES Early seizure Early < 14 days More common Taper AED off after one month if seizure free Late seizures Late > 14 days May need lifetime AED therapy AED prophylaxis may be beneficial No randomized trial has addressed the efficacy Use for lobar ICH Taper off after one month if seizure free Vespa PM et al. Acute seizures after intracerebral hemorrhage. Neurology 2003;60: Passero S et al. Seizures after spontaneous supratentorial intracerebral hemorrhage. Epilepsia. 2002;

43 EARLY SURGICAL EVACUATION May be performed as a life-saving measure Benefit in long-term outcome is questionable Ten studies (5 randomized) Conflicting results Overall, no proof that early surgery is superior to medical therapy Over 7000 annual surgeries are performed worldwide Broderick JP et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke. 1999;30:

44 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:

45 STICH Randomized, parallel group Primary ICH - GCS > 5 and hematoma diameter > 2 cm 1033 patients with supra-tentorial hemorrhage Uncertainty principle 1/2 allocated to early surgery + medical therapy Surgery within 72 hours 1/2 allocated to initial medical therapy Baseline characteristics well-matched Outcome assessed at 6 months months 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:

46 STICH Surgery Initial Conservative SURVIVAL 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:

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). Mendelow AD et al.

47 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). 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:

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

48 EARLY SURGICAL EVACUATION worldwide 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 Broderick JP et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke. 1999;30:

49 rfviia Hematoma growth Is a critical determinant of morbidity and mortality Ultra-early hemostatic therapy Arrests ongoing bleeding and minimizes hematoma growth rfviia Currently approved for hemorrhage in hemophiliacs resistant to Factor VIII or IX replacement therapy Causes local initiation of coagulation cascade after vascular damage. Mayer SA et al. Recombinant activated factor VII of racute intracerebral hemorrhage. N Eng J Med. 2005; 352:

50 rfviia Mayer SA et al. Recombinant activated factor VII of racute intracerebral hemorrhage. N Eng J Med. 2005; 352:

rfviia Limited hematoma growth by ~ 50 % (p = 0.01) Relative reduction in mortality 35% p = 0.

51 rfviia Limited hematoma growth by ~ 50 % (p = 0.01) Relative reduction in mortality 35% p = rfviia versus placebo Mayer SA et al. Recombinant activated factor VII of racute intracerebral hemorrhage. N Eng J Med. 2005; 352:

52 rfviia Mayer SA et al. Recombinant activated factor VII of racute intracerebral hemorrhage. N Eng J Med. 2005; 352:

53 rfviia

54 PROGNOSIS Thirty day mortality 30-50% Depends upon various factors With Warfarin on board ~ 70% Only ~ 25% will be independent in 6 months months Qureshi AI et al. Spontaneous Intracerebral Hemorrhage. N Eng J Med. Vol 344, No 19. May 10, 2001.

55 PROGNOSIS THE LAW OF 30 S ICH volume > 30 ml Mortality ~ 30 % In 30 days

56 ICH SCORE

57 ICH SCORE

58 FUTURE STUDIES Acute therapy ATACH - Antihypertensive therapy in ICH INTERACT - Effects of aggressive BP lowering DITCH - Intraventricular thrombolysis Genetics GOCHA - Genetics of Warfarin-related ICH Surgical intervention STICH II MISTIE - Intra-hematomal tpa and stereotactic evacuation

59 SUMMARY Epidemiology Pathophysiologic mechanisms Diagnostic methods Management schemes Prognosis New directions

60 THANK YOU

Stroke - Intracranial hemorrhage. Dr. Amitesh Aggarwal Associate Professor Department of Medicine

Stroke - Intracranial hemorrhage Dr. Amitesh Aggarwal Associate Professor Department of Medicine Etiology and pathogenesis ICH accounts for ~10% of all strokes 30 day mortality - 35 45% Incidence rates