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A. Epidemiology

  1. Intracerebral hemorrhage accounts for ~15% of strokes
  2. ~45,000 new cases per year in USA
  3. One year survival ~38% for hemorrhagic stroke; 6 month mortality ~50%
  4. Primary Intracerebral Hemorrhage
    1. ~85% of cases of cerebral hemorrhage
    2. Mainly due to spontaneous rupture of small cerebral vessels
    3. Hypertension and cerebral amyloid angiopathy most common causes
  5. Secondary Intracerebral Hemorrhage
    1. Due to vascular abnormalities
    2. Mainly arteriovenous malformations (AVM) and aneurysms
  6. Most Common Locations
    1. Cerebral lobes
    2. Basal ganglia
    3. Thalamus
    4. Brainstem (mainly pons)
    5. Cerebellum

B. Causes of Cerebral Hemorrhage

  1. Hypertension 60%
    1. Increased risk even with treatment
    2. Higher incidence in blacks and Japanese (~2X risk over whites)
  2. Cerebral Amyloid 15% [4]
    1. Lobar intracerebral hemorrhages occur
    2. Risk for initial and recurrent lobar hemorrhage linked to apolipoprotein E genotype
    3. Thus, carriers of Apo E e2 or e4 genotypes had 3.8X increased risk for recurrence [4]
  3. Arteriovenous Malformation (AVM; see below) [13,14]
    1. Complex tangles of abnormal arteries and veins
    2. Responsible for ~5% of hemorrhagic strokes
    3. Prevalence is ~0.01% of population in USA
    4. Usually present age <40 years, male = female
    5. Rate of intracranial hemorrhage with AVM is 40-75% overall
    6. Risk of bleed increased with aneurysms, drainage to deep venous sinuses, deep location, single draining vein, venous stenosis [13]
    7. Discussed in detail below
  4. Subarachnoid Hemorrhage (SAH) [3]
    1. ~80% due to rupture of intracranial aneurysm
    2. ~20% nonaneurysmal hemorrhage (including perimesenceaphlic SAH) - better prognosis
    3. Modifiable Risk Factors: cigarette smoking, hypertension, cocaine, heavy alcohol use
  5. Ruptured Intracranial Aneurysm [3,12]
    1. Berry aneurysm
    2. Mycotic aneurysm
    3. Can bleed and/or rupture
  6. Primary Intracranial Aneurysm Rupture Rates at 5 Years [3,11]
    1. Aneurysms <7mm: Anterior Circulation: 0% ; Posterior Circulation 2.5%
    2. Aneurysms 7-12 mm: Anterior Circulation: 2.6% ; Posterior Circulation 14.5%
    3. Aneurysms 13-24 mm: Anterior Circulation: 14.5% ; Posterior Circulation 18.4%
    4. Aneurysms >24 mm: Anterior Circulation: 40% ; Posterior Circulation 50%
    5. Anterior included internal carotid, anterior communicating, anterior cerebral, middle cerebral arteries
    6. Posterior included vertebrobasilar system and posterior communicating artery
  7. Trauma
  8. Hemorrhagic Infarcts 10%
  9. Brain Tumors 10% (melanoma metastases, glioblastoma, others)
  10. Clotting Abnormalities
    1. Warfarin (Coumadin®) and related agents
    2. Aspirin: increase in hemorrhagic strokes by ~12 events per 10,000
    3. Heparins and related agents
    4. Thrombolytic Therapy - bolus higher risk than slow infusion [7]
    5. Hemophilia
    6. Excessive use of alcohol
    7. Factor XIII alpha gene polymorphisms
    8. Other Factor Deficiency
  11. Drugs
    1. Cocaine, amphetamines
    2. Possible: low dose oral contraceptives containing norgestrel and levonorgestrel
    3. Phenylpropanoloamine 3-16X increased risk factor for CNS hemorrhage in women [16,17]
    4. Phenylpropanolamine has been withdrawn from the market in USA [16]
  12. Infection
  13. Vasculitis
  14. Increased risk of hemorrhagic and thromboembolic stroke in peripartum period
  15. Most frequent sites: Basal ganglia (putamen) > Cerebellum / Pons > Frontal
  16. Cerebellar and pontine hemorrhages are neurosurgical emergencies

B. Symptoms and Signs

  1. Sudden Headache (HA)
  2. Described as worst HA of life in ~35% of cases
  3. Nausea and vomiting with occasional low back pain
  4. Seizures - usually at presentation or within 24 hours of hemorrhage
  5. Effects of initial hemorrhage
    1. May trigger vasospasm with possible additional stroke
    2. Vasospasm may also exacerbate symptoms of a hemorrhagic stroke
    3. Cerebral edema from initial bleed induces additional neuronal damage
    4. Deterioration occurs in ~25% of patients with good initial level of consciousness
  6. Communicating hydrocephalus may develop
  7. Vasospasm and communicating hydrocephalus are much more common with subarachnoid hemorrhage (SAH) than with brain parenchymal hemorrhage
  8. Large hematoma usually present with decreased level of consciousness
  9. Electrolyte abnormalities often occur

C. Diagnosis

  1. Emergency computerized tomographic (CT) scan without contrast essential
    1. Rule out other mass lesions as cause of symptoms: tumor, brain abscess
    2. Intensive care unit monitoring generally required
  2. CT Scan
    1. Hemorrhage, swelling, midline shift, herniation, radiolucency (wedge shaped)
    2. Vascular Distribution, Ring enhancement (usually seen in abscess / tumor)
    3. CT Scan will miss ~10% of SAH
    4. If SAH is strongly suspected even with negative CT scan, perform lumbar puncture
    5. Blood in ventricles is a very poor prognostic sign
  3. History and Physical Examination
    1. Precision based on clinical grounds is very poor in determining stroke type
    2. Radiographic evaluation is critical in nearly all cases
    3. Acute onset of focal neurological deficit - immediate evaluation
    4. Change in mental status is an indication for emergent evaluation
    5. Level of consciousness is major prognostic indicator
    6. If patient is communicative and stable, concurrent with CT scan
    7. Elucidate risk factors for CVA
    8. Level of consciousness at presentation is major prognostic factor
    9. Glascow coma scale (GCS, see below) is determined
  4. Magnetic Resonance Angiography (MRA) and Imaging
    1. Flow settings (Gradient Echo, MR angiography) detects vessel occlusion
    2. Detection of collateral circulation in setting of carotid occlusion
    3. Newer methods can detect early changes due to ischemia (often within 3-6 hours)
    4. Detects reperfusion areas after thrombolytic therapy
  5. Aneurysms and Risk of Hemorrhage [12]
    1. Aneurysms >10mm have ~11X increased risk of rupture than <10mm aneurysms
    2. Rupture rate is 6% in first year for aneurysms >24mm
    3. Patients with history of SAH have high risk of rupture of small (<10mm) aneurysms
  6. Doppler Ultrasound Duplex Scan of carotids
    1. Evaluates carotid atherosclerotic disease
    2. Accurate for carotid stenoses of 60% or greater
  7. Invasive (rarely required for hemorrhage)
    1. Angiography is the "Gold Standard" and may detect small aneurysm, AVM
    2. Xenon blood flow study
    3. MR with angiography is approaching angiography in evaluating larger vessels
    4. Technetium 99m blood flow scan is rarely used clinically
    5. Indium 111 CSF Study for hydrocephalus only
  8. In patients with suspected SAH and negative CT scan, lumbar puncture is required to rule out SAH and is positive for blood in ~10% of CT negative cases [3]

D. Glascow Coma Scale (GCS)

  1. Add Points from Three Categories
    1. Mild traumatic injury GCS 14-15
    2. Moderate 9-13 (lethargic or stuporous)
    3. Severe 3-8 (comatose)
  2. Eye Opening
    1. Spontaneous 4 points
    2. To speech 3 points
    3. To Pain 2 points
    4. None
  3. Motor Response
    1. Obeys 6
    2. Localizes 5
    3. Withdraws 4
    4. Abnormal flexion 3
    5. Extensor response 2
    6. None 1
  4. Verbal Response
    1. Oriented 5
    2. Confused 4
    3. Inappropriate 3
    4. Incomprehensible 2
    5. None 1
  5. Overall GCS Grading
    1. Grade I (GCS 15) - no motor deficits
    2. Grade II (GCS 13 or 14) - no motor deficits
    3. Grade III (GCS 13 or 14) - motor deficits present
    4. Grade IV (GCS 7-12) - based on GCS only
    5. Grade V (GCS 3-6) - based on GCS only

E. Acute Therapy of Hemorrhagic Stroke [1]

  1. Lower blood pressure slowly monitoring progress of patient (difficult to set a goal)
  2. Blood pressure should be lowered aggressively in a hypertensive emergency
  3. Treat swelling (cytotoxic edema) with furosemide, tachypnea, mannitol
  4. Glucocorticoids are not helpful in the treatment of swelling from hemorrhagic stroke
  5. Patients are managed in an intensive care units by neurosurgery / stroke specialists
  6. Anticonvulsants (usually phenytoin) for seizures
  7. Nimodipine (Nimodop®) administered to patients with SAH to reduce vasospasm
  8. Pegorgotein, a scavenger of oxygen free radicals, of no benefit in closed head injury [8]
  9. Recombinant activated factor VII (FVIIa, NovoSeven®) reduced growth of hematoma but did not improve clinical outcomes and did increase arterial thromboembolic events [18]
  10. Surgical Evacuation
    1. Neurosurgical procedure for selected patients
    2. Hematoma >3cm diameter
    3. Particularly in patients with GCS
    4. May be more aggressive in younger patients

F. Subarachnoid Hemorrhage (SAH) [2,3,5]

  1. Etiology and Prevalence
    1. Causes ~5% of strokes, with ~50% of patients <55 years old
    2. ~80% due to rupture of intracranial aneurysms
    3. ~1% of emergency room visits for headaches are SAH cases
    4. Most intracranial aneurysms are acquired with likely predisposing genetic contributions
    5. About 1 case per 10,000 persons per year in USA (27,000 per year)
    6. Fatal in around 50% of cases
    7. Smoking, hypertension, cocaine, large amounts of alcohol increase risk of SAH
  2. Symptoms [12]
    1. Sudden onset HA
    2. Warning ("Sentinal") HA occurs in ~35% of patients with SAH
    3. Worst HA of life (~25% of these patients have SAH)
    4. Nausea ± vomiting
    5. Cranial nerve deficits - particularly CN III and CN VI (increased ICP)
    6. Ischemic stroke-like symptoms
    7. Low back pain may occur
    8. Fatigue, weakness leading to obtundation
    9. May have spontaneous resolution of symptoms if bleed stops
    10. This "sentinal bleed" may herald second bleed
    11. Cerebral venous sinus thrombosis may also cause worst HA of life
    12. Over 90% of paitnets with SAH may have cardiac arrhythmias
  3. Hunt and Hess Grading Scale [5]
    1. Grade 1: asymptomatic or minimal HA and slight nuchal rigidity
    2. Grade 2: Moderate-to-severe HA, nuchal rigidity, and no neurologic deficit except cranial-nerve palsy
    3. Grade 3: drowsiness, confusion, or mild focal defects
    4. Grade 4: stupor, moderate-to-severe hemiparesis, and possibly, early decerebrate rigidity and vegetative disturbances
    5. Grade 5: deep coma, decerebrate rigidity, moribund appearance
  4. Evaluation [2]
    [Figure] "Circle of Willis"
    1. Rapid neurologic examination including fundoscopy
    2. Major concern for elevated intracranial pressure
    3. Radiographic Evaluation - CT generally available more rapidly than MRI
    4. MRI and CT appear to have same sensitivity
    5. Lumbar Puncture (LP) - in patients with suspected SAH and negative CT
  5. CT Scan
    1. ~95% sensitive for SAH (98% in first 12 hours, 93% in 24 hours)
    2. If CT is negative and suspicion continues to be high, then do lumbar puncture
    3. Alternatively, MRI may be used as a followup but is time consuming and expensive
  6. Magnetic Resonance Imaging (MRI) [9]
    1. More costly and time consuming than CT but can be more informative
    2. Magnetic resonance angiography (MRA) can be used to screen for aneurysms
    3. MRA screening of first degree relatives of patients with SAH is not recommended [15]
  7. Lumbar Pucture (LP)
    1. LP should be performed in patients with negative, equivocal, or inadequate CT or MRI
    2. Cerebrospinal fluid (CSF) pressure should always be measured
    3. Samples should always be sent for cell counts, gram stain and culture
    4. Elevated intracranial pressure (ICP) found in cerebral venous sinus thrombosis, pseudotumor and hydrocephalus
    5. Waiting ~6 hours after symptom onset for LP allows formation of bilirubin in CSF (yellow color) and assurance that erythrocytes in CSF are not due to trauma
    6. Presence of "true" blood in CSF is suggestive of SAH
    7. Traumatic LP will have very little blood in last tube collected but this is unreliable [2]
    8. High erythrocyte counts in last tube collected signifies presence of "true" blood in CSF
  8. Treatment [2,6]
    1. Early aneurysm treatment (48-72 hours after initial bleed) is strongly advocated
    2. Rate of recurrent hemorrhage is high (~5% in first 24 hours; ~2%/day after up to 40%)
    3. Vasospasm often occurs early and may be prevented with nimodipine (Nimotop®)
    4. Niomdipine given 60mg po q4 hours (as tolerated by blood pressure) for 3 weeks
    5. Endovascular coiling superior to neurosurgical clipping in patients with ruptured aneurysm who are candidates for either procedure [6]
    6. Endovascular coiling (usually requires general anesthesia) preferred in elderly patients
    7. Surgical clipping is required in most middle cerebral artery or complex aneurysms
    8. Surgery often delayed for patients with Grade IV or V SAH
    9. Maintain normal blood pressure (caution with nimodipine)
    10. Reverse antiplatelet agents (with transfusion) and correct coagulopathies
  9. Monitor for Complications
    1. Rebleeding occurs in ~40% of cases overall
    2. Mortality after rebleeding is ~80%
    3. Neurosurgical evacuation of bleed may be required if edema or mass effect occurs
    4. Increased ICP leads to progressive reduction in consciousness
    5. Increased intracranial pressure treatment may be needed
    6. Cerebral ischemia can occur due to elevated ICP, reduced arterial perfusion
    7. If clinical condition worsens, angiogram and emergent surgery may be required

G. Arteriovenous Malformation (AVM) [13,14]

  1. Complex tangles of abnormal arteries and veins
    1. Lack capillary bed and act essentially as fistulas
    2. May allow high-flow, rapid arteriovenous shunting
  2. Responsible for ~5% of hemorrhagic strokes
  3. Prevalence is ~0.01% of population in USA
    1. Usually present age <40 years, male = female
    2. Rate of intracranial hemorrhage with AVM is 40-75% overall
    3. Annual rate of hemorrhage is 1-4% after initial presentation
    4. For patients with initial bleed, annual risk of second bleed is 4.5-35%
  4. Increased Risk of Bleeding [13]
    1. Presence of aneurysms - in ~60% of AVMs, may require clipping independent of AVM
    2. Drainage to deep venous sinuses
    3. deep location,
    4. single draining vein
    5. venous stenosis
  5. About 66% of adults with AVM have learning disorders
  6. Spetzler-Martin AVM Scale
    1. AVM surgical risk graded by Spetzler-Martin Scale
    2. Diameter: <3cm - 1 point; 3-6cm 2 points; >6cm 3 points
    3. Location: noneloquent cortical tissue 0 points; adjacent to eloquent cortical tissue 1 point
    4. Venous draining: superficial only 0 points; deep 1 point
    5. Sum of scores equals grade
    6. Surgery generally good for grades 1-3; higher complication rates with grades 4, 5
  7. Treatment of AVMs
    1. Surgical risk by Spetzler-Martin Scale
    2. Microsurgical repair is best treatment:
    3. Radiosurgery including gamma knife or proton beam has been used
    4. Gamma knife radiosurgery reduces risk ~75% of bleeding of cerebral AVMs [10]
    5. Risk of surgery is persistant neurologic defects, and related to grade
    6. Surgery should be reserved for aneurysm or other high risk AVM
    7. Embolization may be curative in minority (mainly <1cm) of cases
    8. Embolic agent (Onyx glue) has improved rates of embolization
    9. Incompletely treated AVM may recur

H. Dural Venous Sinus Thrombosis [9]

  1. Thrombus formation within a major dural venous sinus which drains blood from brain
    1. Superior sagittal sinus
    2. Straight sinus
    3. Transverse sinus
    4. Sigmoid sinus
    5. Confluence of sinuses (torcular herophili)
  2. Dural sinus thrombosis leads to impairment of cortical and deep venous cerebral drainage
  3. Severe headache is usually present
  4. Risk Factors
    1. Dehydration
    2. Systemic and local infection
    3. Pregnancy
    4. Neoplastic invasion
    5. Trauma
    6. Hypercoagulability
  5. Complications
    1. Infarction of involved cerebral territories
    2. Venous infarctions may be hemorrhagic
    3. Multiple, simultaneous bilateral lesions can occur
  6. Diagnosis
    1. Magnetic resonance imaging (MRI) with blood imaging:
    2. MRI venography is method of choice (contrast enhancement used)
    3. Blood vessels in wall of thrombosed sinus are bright, outlining the sinus
  7. Treatment with anticoagulation is recommended but controversial

References

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  4. O'Donnell HC, Rosand J, Knudsen KA, et al. 2000. NEJM. 342(4):240 abstract
  5. Brisman JL, Song JK, Newell DW. 2006. NEJM. 355(9):928 abstract
  6. Molyneux AJ, Kerr RSC, Y LM, et al. 2005. Lancet. 366(9488):809 abstract
  7. Mehta SR, Eikelboom JW, Yusuf S. 2000. Lancet. 356(9228):449 abstract
  8. Young B, Runge JW, Waxman KS, et al. 1996. JAMA. 276(7):538 abstract
  9. Quint DJ. 2000. JAMA. 283(7):853 abstract
  10. Maruyama K, Kawahara N, Shin M, et al. 2005. NEJM. 352(2):146 abstract
  11. International Study of Unruptured Intracranial Aneurysms. 2003. Lancet. 361(9378):103
  12. Unruptured Intracranial Aneurysms Investigators. 1998. NEJM. 339(24):1725 abstract
  13. Fleetwood IG and Steinberg GK. 2002. Lancet. 359(9309):863 abstract
  14. Friedlander RM. 2007. NEJM. 356(2);2704
  15. Magnetic Resonance Angiography in Relatives of SAH Patients. 1999. NEJM. 341(18):1344 abstract
  16. Kernan WN, Viscoli CM, Brass LM, et al. 2000. NEJM. 343(25):1826 abstract
  17. Phenylpropanolamine. 2000. Med Let. 42(1094):113 abstract
  18. Mayer SA, Brun NC, Begtrup K, et al. 2008. NEJM. 358(20):2127 abstract