Intracranial Haemorrhage in Adults

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Critical Alerts

Key Diagnostic Studies

Emergency Treatment Priorities

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Definition and Overview

Intracranial haemorrhage (ICH) encompasses bleeding within any compartment of the cranial vault, including the brain parenchyma (intracerebral haemorrhage), subarachnoid space (subarachnoid haemorrhage), subdural space (subdural haematoma), and epidural space (epidural haematoma). It represents a neurological emergency with significant mortality and morbidity, requiring rapid diagnosis through neuroimaging, immediate blood pressure optimization, urgent reversal of any anticoagulation, and early neurosurgical evaluation. [8]

Intracerebral haemorrhage is the most devastating form of stroke, with 30-day mortality rates of 30-50% and significant disability among survivors. [9] Subarachnoid haemorrhage, typically from ruptured berry aneurysms, carries 25-50% overall mortality with substantial morbidity from vasospasm and rebleeding. [3] Traumatic subdural and epidural haematomas require prompt surgical consideration to prevent herniation and death.

The prognosis for intracranial haemorrhage has improved modestly with advances in blood pressure management, anticoagulation reversal agents, and neurocritical care, though outcomes remain poor compared with ischaemic stroke. Early aggressive intervention focusing on preventing haematoma expansion, managing cerebral perfusion, and avoiding secondary brain injury is fundamental to optimizing outcomes. [10]

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Epidemiology

Incidence and Prevalence

Risk Factors

Intracerebral Haemorrhage:

Subarachnoid Haemorrhage:

Changing Epidemiology

The incidence of anticoagulation-related ICH is rising due to increased use of oral anticoagulants for atrial fibrillation and venous thromboembolism. Anticoagulation-associated ICH now accounts for 12-20% of all spontaneous ICH and carries higher mortality (50-65%) than non-anticoagulated ICH. [11] The introduction of direct oral anticoagulants (DOACs) has been associated with lower ICH risk compared with warfarin (relative risk reduction 50%), though specific reversal agents are required when bleeding occurs. [5,6]

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Classification

By Anatomical Location

Intracerebral Haemorrhage by Location

Intracerebral Haemorrhage Aetiology

Primary ICH (80-85%):

Secondary ICH (15-20%):

Cerebral Amyloid Angiopathy

Exam Detail: Boston Criteria for CAA Diagnosis [12]:

MRI Features Suggestive of CAA:

• Multiple strictly lobar microbleeds on GRE/SWI
• Cortical superficial siderosis
• White matter hyperintensities
• Perivascular spaces in centrum semiovale
• Recurrent lobar hemorrhages in elderly

Clinical Implications:

• High recurrence risk (10-20% annual)
• Anticoagulation generally contraindicated
• Antiplatelet use requires careful risk-benefit assessment
• Associated with Alzheimer's disease pathology

Subarachnoid Haemorrhage Classification

Aetiology:

Hunt and Hess Grading Scale [13]:

World Federation of Neurological Surgeons (WFNS) Grading Scale:

Modified Fisher Scale (CT Grading) [14]:

Thin = less than 1mm; Thick = ≥1mm or filling cisterns

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Pathophysiology

Intracerebral Haemorrhage Cascade

Phase 1: Initial Hemorrhage (0-4 hours)

The primary event involves rupture of small penetrating arteries weakened by chronic hypertension (lipohyalinosis, microaneurysms of Charcot-Bouchard) or amyloid deposition in vessel walls (CAA). Blood dissects into the parenchyma, creating immediate mechanical disruption and neuronal injury. [15]

Phase 2: Haematoma Expansion (0-24 hours)

Haematoma expansion occurs in 30-40% of patients within the first hours, particularly in those presenting within 3 hours of symptom onset. [2] This expansion is the primary target of acute intervention and is associated with:

• Elevated blood pressure
• Anticoagulation/coagulopathy
• "Spot sign" on CTA (active contrast extravasation)
• Irregular hematoma shape
• Early presentation

Exam Detail: Spot Sign as Predictor of Expansion:

The "spot sign" represents active contrast extravasation within the hematoma on CTA, visualized as one or more small foci of contrast enhancement. Meta-analysis demonstrates: [2]

• Sensitivity for expansion: 51-63%
• Specificity: 85-90%
• Positive predictive value: 61%
• Patients with spot sign have 2.5× higher mortality

Imaging Criteria for Spot Sign:

• ≥1 focus of enhancement within hematoma
• Size 1-2mm or greater
• Density ≥120 HU
• Discontinuous from normal vasculature

Phase 3: Perihematomal Edema (24 hours - weeks)

Secondary injury develops through:

• Clot retraction releasing cytotoxic serum proteins
• Thrombin activation and inflammation
• Iron and haemoglobin breakdown products
• Blood-brain barrier disruption
• Mitochondrial dysfunction and oxidative stress

Perihematomal edema peaks at 10-14 days and may cause delayed neurological deterioration.

Phase 4: Resolution/Scarring (weeks-months)

• Macrophage infiltration and clot phagocytosis
• Glial scar formation
• Cavity formation
• Some functional recovery through neural plasticity

Subarachnoid Haemorrhage Pathophysiology

Acute Phase (Day 0-3): Early Brain Injury

Subacute Phase (Day 3-14): Delayed Cerebral Ischemia/Vasospasm

Vasospasm represents the major cause of delayed morbidity in SAH survivors, occurring in 70% of patients angiographically but causing symptomatic ischemia in 20-30%. [7,16]

Exam Detail: Mechanisms of Delayed Cerebral Ischemia:

The pathophysiology is multifactorial and extends beyond simple arterial narrowing:

1. Large Vessel Vasospasm:

   • Oxyhaemoglobin triggers prolonged contraction
   • Endothelin-1 elevation
   • Decreased nitric oxide availability
   • Structural vessel wall changes

2. Microcirculatory Dysfunction:

   • Microthrombosis
   • Cortical spreading ischemia
   • Blood-brain barrier breakdown

3. Inflammatory Response:

   • Cytokine release
   • Leukocyte infiltration
   • Complement activation

Vasospasm Timeline:

• Onset: Day 3-5 post-hemorrhage
• Peak: Day 7-10
• Resolution: Day 14-21
• Risk correlates with: Fisher grade, volume of blood, Hunt & Hess grade

Monitoring Modalities:

• Transcranial Doppler (TCD): Mean velocity > 120 cm/s suggests vasospasm; > 200 cm/s severe
• CT perfusion: Detects ischemia before infarction
• Clinical examination: Focal deficits, altered consciousness

Rebleeding Risk:

Hydrocephalus:

Subdural and Epidural Haematoma

Subdural Haematoma Pathophysiology:

Elderly and anticoagulated patients are particularly vulnerable due to brain atrophy (stretched bridging veins) and impaired coagulation.

Epidural Haematoma Pathophysiology:

Classic mechanism involves temporal bone fracture with middle meningeal artery laceration, though venous bleeding (dural sinuses) can also occur. The classic "lucid interval" (30-50% of cases) reflects initial accommodation of the hematoma followed by rapid expansion and herniation.

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Clinical Presentation

Intracerebral Haemorrhage

Cardinal Features:

Presentation by Location:

Clinical Pearl: Distinguishing ICH from Ischemic Stroke:

While clinical differentiation is unreliable (overlap ~20%), features suggesting hemorrhage include:

• More severe headache at onset
• Vomiting at onset
• Rapid progression of deficits over minutes
• Early depression of consciousness
• Very high blood pressure (SBP > 220)
• Prior use of anticoagulants

However: CT is essential for definitive diagnosis as clinical features cannot reliably distinguish hemorrhagic from ischemic stroke.

Subarachnoid Haemorrhage

Classic Presentation:

Sentinel Headache ("Warning Leak"):

A sentinel headache represents minor aneurysmal leak preceding major rupture, occurring in 20-50% of SAH patients retrospectively. These are often dismissed as migraine or tension headache. Key features suggesting sentinel leak: [3]

• Sudden onset severe headache unlike prior headaches
• Associated with brief LOC, nausea, or neck stiffness
• Resolves over hours to days
• Occurs days to weeks before major SAH

Neurological Signs by Aneurysm Location:

Terson Syndrome:

Vitreous or subhyaloid (preretinal) hemorrhage occurring in 10-40% of SAH patients. Indicates severe SAH and associated with poorer outcomes. Fundoscopy may reveal crescent-shaped hemorrhage layering inferiorly.

Subdural Haematoma Presentation

Risk Factors for Chronic SDH:

• Age > 65 years
• Anticoagulation/Antiplatelet use
• Alcohol use disorder
• Coagulopathy
• CSF shunts
• Repeated minor head trauma

Epidural Haematoma Presentation

Classic Triad (only 30-50%):

1. Lucid interval after initial LOC
2. Progressive deterioration
3. Ipsilateral pupil dilation (uncal herniation)

Clinical Course:

• Initial concussion with brief LOC
• "Lucid interval" (minutes to hours)
• Headache, vomiting, progressive obtundation
• Ipsilateral pupil dilation (CN III compression)
• Contralateral hemiparesis
• Death if untreated

Clinical Pearl: "Talk and Die" Syndrome:

Patients who are initially conscious after head injury but subsequently deteriorate and die. Most commonly due to:

1. Epidural hematoma (most classic)
2. Acute subdural hematoma
3. Delayed intracerebral contusion expansion

Key point: Patients with any head injury and risk factors must be observed with serial neurological examinations. A normal initial GCS does not guarantee a benign course.

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Herniation Syndromes

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Red Flags and Danger Signs

Immediate Life Threats

Poor Prognostic Indicators

ICH Score (Validated Mortality Predictor) [17]:

Additional Poor Prognostic Factors:

• Hematoma expansion > 33% or > 6mL
• Spot sign positive
• Anticoagulation use
• Hyperglycemia at presentation
• Early withdrawal of care (confounds mortality data)

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Differential Diagnosis

Sudden Severe Headache

Acute Focal Neurological Deficit

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Diagnostic Approach

Neuroimaging

CT Head Non-Contrast (First-Line, Gold Standard):

CT Sensitivity for SAH [3]:

CT Angiography (CTA):

MRI Brain:

Digital Subtraction Angiography (DSA):

Gold standard for:

• Aneurysm characterization when CTA equivocal
• AVM/DAVF assessment
• Vasculitis evaluation
• CTA-negative SAH (10-15% initially negative require repeat)

Lumbar Puncture for SAH

Indications:

• High clinical suspicion for SAH with negative or equivocal CT
• CT performed > 6 hours after onset (decreased sensitivity)

Timing:

• Optimal: 6-12 hours after symptom onset (allows xanthochromia to develop)
• Must wait adequate time for RBC lysis and bilirubin formation

CSF Findings in SAH:

Traumatic Tap vs. SAH:

Xanthochromia Detection:

• Visual inspection (less sensitive)
• Spectrophotometry (gold standard, detects oxyhaemoglobin and bilirubin)
• Must process CSF protected from light within 1-2 hours

ICH Volume Estimation (ABC/2 Method) [18]

Volume (mL) = (A × B × C) / 2

Where:

• A = Maximum hemorrhage diameter (cm) on largest slice
• B = Diameter perpendicular to A on same slice (cm)
• C = Number of slices with hemorrhage × slice thickness (cm)

For C: Count slices where hemorrhage is > 50% of maximum area; for 25-50%, count as 0.5

Volume Thresholds:

• 30 mL supratentorial: Associated with higher mortality

• 60 mL supratentorial: Very poor prognosis

• 15 mL infratentorial: Consider surgery

Laboratory Studies

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Treatment

General Principles of Management

Blood Pressure Management

Intracerebral Hemorrhage:

Exam Detail: INTERACT2 Trial Summary [1]:

• 2,839 patients with spontaneous ICH and SBP 150-220 mmHg
• Intensive (target less than 140 within 1 hour) vs. Guideline (less than 180)
• Primary outcome (death/disability): OR 0.87, p=0.06 (borderline)
• Safe; ordinal shift analysis favored intensive treatment
• Current guidelines recommend SBP less than 140 if presenting 150-220 mmHg

ATACH-2 Trial Summary [19]:

• 1,000 patients with ICH and GCS ≥5
• Intensive (110-139 mmHg) vs. Standard (140-179)
• No difference in death/disability at 90 days
• More renal adverse events with intensive treatment
• Suggests SBP target ~140 is optimal; going lower adds no benefit

Current Recommendation:

• If SBP 150-220: Target less than 140 mmHg within 1 hour
• If SBP > 220: Consider more aggressive reduction with close monitoring
• Avoid rapid drops > 60 mmHg or to less than 130 mmHg

Antihypertensive Agents:

Subarachnoid Hemorrhage:

Anticoagulation Reversal

Warfarin Reversal [4,11]:

4-Factor PCC Dosing by INR:

DOAC Reversal [5,6]:

Exam Detail: REVERSE-AD Trial (Idarucizumab) [5]:

• 503 patients with serious bleeding or requiring urgent surgery on dabigatran
• Idarucizumab normalized dTT within minutes in 98%
• Effective hemostasis in 67.7% of bleeding patients
• Half-life ~10 hours; redosing rarely needed

ANNEXA-4 Trial (Andexanet Alfa) [6]:

• 352 patients with major bleeding on factor Xa inhibitors
• Good/excellent hemostasis in 82%
• Thrombotic events in 10% at 30 days (use judiciously)
• High dose for apixaban/rivaroxaban taken less than 8h ago or unknown timing

Heparin Reversal:

• Protamine sulfate: 1 mg per 100 units UFH (max 50 mg)
• Give slowly IV (anaphylaxis risk, especially with prior protamine/NPH insulin exposure)
• LMWH: Protamine partially effective (60-80%)

Platelet Dysfunction/Thrombocytopenia:

ICP Management

Tier 1 (First-Line):

Tier 2 (Osmotherapy):

Target: ICP less than 20-22 mmHg; Cerebral Perfusion Pressure (CPP) > 60-70 mmHg

Tier 3 (Refractory ICP):

Seizure Management

Prophylaxis (Controversial in ICH):

Treatment of Seizures:

Surgical Management

Intracerebral Hemorrhage Indications [10,21]:

Exam Detail: STICH Trials Summary [21]:

STICH I (2005):

• 1,033 patients with supratentorial ICH
• Early surgery vs. initial conservative treatment
• No overall benefit from early surgery
• Post-hoc: Possible benefit in lobar hemorrhage less than 1 cm from surface

STICH II (2013):

• 601 patients with superficial lobar ICH (≤1 cm from surface)
• Early surgery vs. initial conservative treatment
• No significant benefit (unfavorable outcome 59% vs. 62%, p=0.37)
• Trend toward benefit if no IVH and GCS 9-12

MISTIE III (Minimally Invasive Surgery + tPA) [22]:

• 506 patients with ICH ≥30 mL
• Catheter-based aspiration with alteplase
• No mortality/functional benefit at 365 days
• Reduced clot volume but did not translate to better outcomes

ENRICH Trial (ongoing/recent):

• Testing early minimally invasive surgery for ICH
• May refine surgical indications

Subarachnoid Hemorrhage - Aneurysm Treatment [3]:

Timing: Early treatment (within 24-72 hours) preferred to prevent rebleeding. [3]

External Ventricular Drain (EVD):

• Indicated for: Hydrocephalus, IVH with decreased consciousness, ICP monitoring
• Reduces ICP through CSF drainage
• VP shunt needed in 20-30% of SAH survivors

CLEAR III Trial (IVH) [23]:

• 500 patients with IVH and obstruction of 3rd/4th ventricle
• EVD + alteplase vs. EVD + saline
• No difference in good functional outcome
• Reduced mortality but increased survivors with severe disability

Subdural Hematoma Surgery:

Epidural Hematoma Surgery:

Most symptomatic EDH requires emergent surgery due to rapid progression risk.

SAH-Specific Management

Nimodipine [7]:

• Dose: 60 mg PO/NG every 4 hours × 21 days
• Mechanism: L-type calcium channel blocker; neuroprotective
• Evidence: Reduces poor outcomes (death/dependency) by ~40%
• Note: IV nimodipine associated with hypotension; oral preferred
• Adjust to 30 mg q4h if hypotension occurs

Vasospasm Prevention and Treatment:

Exam Detail: Triple-H Therapy (Historical):

• Hypertension, Hypervolemia, Hemodilution
• Previously standard for vasospasm treatment
• Modern approach emphasizes:
  • Euvolemia (not hypervolemia - increases complications without proven benefit)
  • Induced hypertension (after aneurysm secured)
  • Hemoglobin optimization (avoid severe anemia and excessive transfusion)

Endovascular Options for Vasospasm:

• Intra-arterial vasodilators (verapamil, nicardipine, milrinone)
• Balloon angioplasty
• Reserved for refractory cases after medical optimization

Other SAH Complications:

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Disposition

ICU Admission

All patients with intracranial hemorrhage require ICU admission, preferably in a dedicated Neurological/Neurosciences ICU with: [10]

• Continuous blood pressure monitoring (arterial line preferred)
• Frequent neurological assessments (q1 hour initially)
• ICP monitoring capability
• EVD management expertise
• Rapid access to neurosurgical intervention
• Osmotherapy protocols
• Experienced neurocritical care team

Neurosurgery Consultation

Immediate consultation required for:

• All ICH (surgical decision-making, ICP monitoring)
• All SAH (aneurysm treatment planning)
• Subdural/epidural hematoma with surgical indications
• Any hemorrhage with signs of herniation
• Hydrocephalus requiring EVD

Transfer Considerations

Transfer to comprehensive stroke/neurosurgical center if:

• Aneurysm requiring endovascular or surgical intervention
• ICH with potential surgical indications
• EVD/ICP monitoring needed and unavailable
• Specialized neurocritical care expertise required

Pre-transfer stabilization:

• Secure airway if GCS ≤8
• Initiate blood pressure management
• Begin anticoagulation reversal
• Do not delay transfer for repeat imaging

Goals of Care

Key Principles:

1. Early family communication - Keep family informed of severity and prognosis
2. Avoid premature prognostication - ICH scores have limitations; outcomes variable
3. Do not withdraw care early - AHA recommends full aggressive treatment for at least 24-48 hours before major care decisions [10]
4. Self-fulfilling prophecy - Early withdrawal of care is associated with mortality and may bias prognostic data
5. Shared decision-making - Once prognosis is clearer, involve family in goals of care
6. Palliative care involvement - When appropriate for comfort-focused care

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Prognosis and Outcomes

ICH Outcomes

Predictors of Poor Outcome:

• ICH Score ≥3
• Hematoma volume > 30 mL (supratentorial)
• Intraventricular extension
• Infratentorial location
• Low GCS at presentation
• Older age
• Anticoagulation
• Hematoma expansion
• Withdrawal of care (self-fulfilling)

SAH Outcomes

Long-term SAH Complications:

• Cognitive impairment (40-50%)
• Fatigue (50-70%)
• Depression/Anxiety (30-40%)
• Headache (20-40%)
• Unable to return to prior work (30-50%)

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Special Populations

Anticoagulated Patients

Key Principles:

• Highest priority: STOP and REVERSE anticoagulation immediately [4,11]
• Higher mortality without reversal (doubled)
• Do not wait for repeat imaging to start reversal
• Use specific reversal agents (PCC for warfarin, idarucizumab for dabigatran)
• Higher risk of hematoma expansion

Elderly Patients

• Higher prevalence of CAA (lobar hemorrhage)
• More likely on anticoagulation
• Higher mortality at any given ICH score
• Increased frailty impacts surgical candidacy
• More likely to have chronic SDH from minimal trauma

Young Patients (less than 45 years)

• Higher likelihood of underlying vascular lesion (AVM, aneurysm)
• More aggressive imaging workup essential
• Higher probability of good recovery if survive
• Consider genetic/rheumatologic evaluation

Pregnancy

• Increased SAH risk during pregnancy/postpartum
• Eclampsia/HELLP as causes of ICH
• Multidisciplinary management essential (obstetrics, neurosurgery, anesthesia)
• Fetal monitoring during treatment
• Consider timing of delivery
• Avoid teratogenic medications

Patients Requiring Anticoagulation Long-Term

Post-ICH Anticoagulation Decisions:

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Quality Metrics

Performance Indicators

Documentation Requirements

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Prevention

Primary Prevention

Secondary Prevention (After ICH)

SAH Prevention

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Patient Education

For Families (Acute Phase)

Key Messages:

• "Your loved one has bleeding in/around the brain, which is very serious"
• "We are working to stop the bleeding from getting bigger and protect the brain"
• "They need intensive care and close monitoring; some patients need surgery"
• "The next 48-72 hours are critical for understanding how they might recover"
• "It is too early to predict outcomes with certainty"

Long-Term (Survivors)

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Exam-Focused Section

Common Examination Questions

MRCP/Clinical Examination:

1. "Describe your approach to a patient with sudden severe headache"
2. "What are the causes of intracerebral hemorrhage?"
3. "How do you distinguish SAH from other causes of headache?"
4. "What is the management of anticoagulation-associated ICH?"
5. "Describe the pathophysiology and management of vasospasm"

Emergency Medicine/Acute Care:

1. "A patient presents with acute onset hemiparesis. How do you differentiate ICH from ischemic stroke?"
2. "A patient on warfarin (INR 3.5) has confirmed ICH. Outline your management."
3. "Describe the indications for surgery in ICH"

Viva Points

Viva Point: Opening Statement: "Intracranial hemorrhage is bleeding within any compartment of the cranial vault—including intracerebral, subarachnoid, subdural, or epidural—and represents a neurological emergency with high mortality requiring immediate CT imaging, blood pressure optimization, anticoagulation reversal, and neurosurgical evaluation."

Key Facts to Mention:

• ICH mortality 30-50% at 30 days [9]
• INTERACT2: Intensive BP lowering (SBP less than 140) is safe and may be beneficial [1]
• 4-factor PCC preferred over FFP for warfarin reversal [4]
• Idarucizumab reverses dabigatran; andexanet alfa for factor Xa inhibitors [5,6]
• SAH: 85% aneurysmal; Hunt & Hess and Fisher grading prognostic [3,13,14]
• Nimodipine reduces poor outcomes in SAH by ~40% [7]
• STICH trials: Early surgery for supratentorial ICH not routinely beneficial [21]

Common Mistakes

Mistakes That Fail Candidates:

• ❌ Ordering tPA before CT in possible stroke (must exclude hemorrhage)
• ❌ Using FFP as first-line warfarin reversal instead of PCC
• ❌ Failing to consider LP when CT negative but SAH suspected
• ❌ Missing cerebellar hemorrhage as surgical emergency
• ❌ Not reversing anticoagulation immediately
• ❌ Giving IV nimodipine (causes severe hypotension; use oral)
• ❌ Over-aggressive BP lowering in SAH with unsecured aneurysm

Model Answers

Q: Describe your approach to a patient presenting with sudden severe headache.

A: "I would approach this systematically, recognizing this as a potential neurological emergency. First, I would assess the patient's airway, breathing, and circulation, and obtain vital signs including blood pressure. Key historical features I would seek include: the exact nature of onset (thunderclap suggests SAH), associated loss of consciousness, neck stiffness, photophobia, focal neurological symptoms, and history of anticoagulation use.

My examination would include GCS, full neurological examination, fundoscopy for papilledema or subhyaloid hemorrhage, and assessment for meningism.

The critical investigation is an urgent CT head without contrast, which has high sensitivity for SAH within 6 hours. If negative but clinical suspicion remains high, I would perform lumbar puncture after 6-12 hours to detect xanthochromia. If CT is positive for hemorrhage, I would obtain CTA to identify any underlying aneurysm or vascular malformation.

Immediate management priorities include blood pressure control, reversal of any anticoagulation, and early neurosurgical consultation. In line with AHA guidelines, I would target SBP less than 140 mmHg for intracerebral hemorrhage using nicardipine or labetalol."

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References

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2. Wada R, Aviv RI, Fox AJ, et al. CT angiography "spot sign" predicts hematoma expansion in acute intracerebral hemorrhage. Stroke. 2007;38(4):1257-1262. doi:10.1161/01.STR.0000259633.59404.f3

3. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43(6):1711-1737. doi:10.1161/STR.0b013e3182587839

4. Frontera JA, Lewin JJ 3rd, Rabinstein AA, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care. 2016;24(1):6-46. doi:10.1007/s12028-015-0222-x

5. Pollack CV Jr, Reilly PA, van Ryn J, et al. Idarucizumab for dabigatran reversal - full cohort analysis. N Engl J Med. 2017;377(5):431-441. doi:10.1056/NEJMoa1707278

6. Connolly SJ, Crowther M, Eikelboom JW, et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med. 2019;380(14):1326-1335. doi:10.1056/NEJMoa1814051

7. Dorhout Mees SM, Rinkel GJ, Feigin VL, et al. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2007;(3):CD000277. doi:10.1002/14651858.CD000277.pub3

8. Qureshi AI, Mendelow AD, Hanley DF. Intracerebral haemorrhage. Lancet. 2009;373(9675):1632-1644. doi:10.1016/S0140-6736(09)60371-8

9. van Asch CJ, Luitse MJ, Rinkel GJ, et al. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010;9(2):167-176. doi:10.1016/S1474-4422(09)70340-0

10. Greenberg SM, Ziai WC, Cordonnier C, et al. 2022 guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association/American Stroke Association. Stroke. 2022;53(7):e282-e361. doi:10.1161/STR.0000000000000407

11. Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46(7):2032-2060. doi:10.1161/STR.0000000000000069

12. Linn J, Halpin A, Demaerel P, et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology. 2010;74(17):1346-1350. doi:10.1212/WNL.0b013e3181dad605

13. Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg. 1968;28(1):14-20. doi:10.3171/jns.1968.28.1.0014

14. Frontera JA, Claassen J, Schmidt JM, et al. Prediction of symptomatic vasospasm after subarachnoid hemorrhage: the modified Fisher scale. Neurosurgery. 2006;59(1):21-27. doi:10.1227/01.NEU.0000218821.34014.1B

15. Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012;11(8):720-731. doi:10.1016/S1474-4422(12)70104-7

16. Macdonald RL, Schweizer TA. Spontaneous subarachnoid haemorrhage. Lancet. 2017;389(10069):655-666. doi:10.1016/S0140-6736(16)30668-7

17. Hemphill JC 3rd, Bonovich DC, Besmertis L, et al. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001;32(4):891-897. doi:10.1161/01.STR.32.4.891

18. Kothari RU, Brott T, Broderick JP, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke. 1996;27(8):1304-1305. doi:10.1161/01.STR.27.8.1304

19. Qureshi AI, Palesch YY, Barsan WG, et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med. 2016;375(11):1033-1043. doi:10.1056/NEJMoa1603460

20. Baharoglu MI, Cordonnier C, Al-Shahi Salman R, et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial. Lancet. 2016;387(10038):2605-2613. doi:10.1016/S0140-6736(16)30392-0

21. Mendelow AD, Gregson BA, Rowan EN, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet. 2013;382(9890):397-408. doi:10.1016/S0140-6736(13)60986-1

22. Hanley DF, Thompson RE, Rosenblum M, et al. Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet. 2019;393(10175):1021-1032. doi:10.1016/S0140-6736(19)30195-3

23. Hanley DF, Lane K, McBee N, et al. Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial. Lancet. 2017;389(10069):603-611. doi:10.1016/S0140-6736(16)32410-2

24. Steiner T, Al-Shahi Salman R, Beer R, et al. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage. Int J Stroke. 2014;9(7):840-855. doi:10.1111/ijs.12309