MUMJ Clinical Review15 CLINICAL REVIEW Intracerebral Hemorrhage: Pathophysiology, Diagnosis and Management Fabio Magistris, BMSc Stephanie Bazak, BScH Jason Martin ABSTRACT Stroke is one of the leading causes of death globally and in Canada. There are two major classifications of stroke: ischemic and hemorrhagic. Intracerebral hemorrhage (ICH) вЂ“ a subtype of hemorrhagic stroke вЂ“ is associated with substantial morbidity and mortality. The varied clinical presentation of ICH, ranging from minor neurological deficits to fatal herniation syndromes arises from parenchymal damage, elevated intracranial pressure and cardiopulmonary instability. Diagnosis is based on clinical presentation, laboratory investigations and imaging, which include computed tomography (CT), magnetic resonance imaging (MRI) and angiography. Validated clinical scoring systems for stroke, such as the ICH and FUNC scores, allow for improved prognosis assessment. Management is comprised of surgical, endovascular and medical interventions. Surgical clipping and endovascular coiling are used as a preventative measure for cerebral aneurysms, while the current medical therapies attempt to limit the neurological sequelae following stroke by limiting the extent of parenchymal involvement. Currently there are no proven therapies for brain protection, although this is currently a major target for research. Thus, stratification of hemorrhagic stroke based on clinical, laboratory and imaging findings enables appropriate treatment and assessment of patients at risk of hematoma expansion in order to prevent clinical deterioration and adverse sequelae. S INTRODUCTION troke is one of the leading causes of death in Canada, accounting for approximately 14,000 deaths annually1 and is a significant source of morbidity. Stroke can be classified into ischemic and hemorrhagic, with the former representing the vast majority of cases (87%).2 In hemorrhagic stroke, bleeding can occur within the cerebral parenchyma or within the meninges. Intracerebral hemorrhage (ICH) is defined as bleeding into the brain parenchyma. The current review excluded epidural hematoma, subdural hematoma and subarachnoid haemorrhage but includes intraventricular hemorrhage. Prognoses of hemorrhagic strokes depend on the initial clinical presentation, rapidity of diagnosis and time to initiation of intervention. This paper is a non-systematic review of the current literature on intracranial hemorrhage (ICH). An overview of the epidemiology, common risk factors, pathogenesis, clinical manifestations, diagnosis and treatment approach to ICH are presented. EPIDEMIOLOGY The World Health Organization (WHO) estimates that 15 million patients worldwide suffer from stroke annually. Approximately one third of these cases die, one third are left disabled and one third have a good outcome.3 High blood pressure is a contributing factor in more than 12.7 million strokes annually worldwide. 3 Incidence is greater among the elderly and those of African and Asian decent.4,5 The overall incidence of new or recurrent hemorrhagic strokes in the United States is 795,000 people pear year. The majority of these are new strokes (approximately 610,000).6 In 2000, stroke accounted for 7% of all deaths in Canada.7 Generally, ICH accounts for ~10% of all strokes and is associated with a 50% case fatality rate.8 Since 1980, the incidence of hypertensive ICH has declined, reflecting improved blood-pressure control in the population.9 16 Clinical Review RISK FACTORS Modifiable Modifiable risk factors for ICH include hypertension, anticoagulant therapy, thrombolytic therapy, high alcohol intake, previous history of stroke, and illicit drug use (particularly cocaine).10 Hypertension is by far the most common cause of hemorrhagic stroke, accounting for up to 60% of all ICH cases. Moreover, approximately two thirds of patients with ICH have a history of hypertension. Hypertensive ICH results from tiny aneurysms that rupture and result in intracranial hemorrhage.9,11 Anticoagulation therapy causes a seven to tenfold increase in risk for hemorrhagic stroke.12 Intracranial aneurysms are commonly acquired lesions found in 1-6% of postmortem autopsies.13 Most do not rupture throughout a personвЂ™s lifetime and remain undiagnosed. However, 27,000 new cases of subarachnoid hemorrhage following a ruptured aneurysm occur in the United States annually, accounting for 5-15% of hemorrhagic stroke cases.13 The process of aneurysm formation and their rupture is incompletely understood. However, hypertension and smoking have been clearly documented to be associated with ruptured cerebral aneurysms and both evidenced to cause structural defects by inducing endovascular changes.13, 14 The tunica media layer is often implicated, causing focal weakness in the vessel wall that can result in aneurysmal ballooning at arterial bifurcations.13 Common locations of aneurysms are presented in Figure 1.18 Figure 1. Common locations of cerebral aneurysms are near the anterior communicating and anterior cerebral arteries, at the junctions near the middle cerebral artery and at the junction between the basilar and posterior cerebral artery.18 Volume 10 No. 1, 2013 Non-Modifiable Non-modifiable risk factors for hemorrhagic stroke include advanced age, negroid ethnicity, cerebral amyloidosis, coagulopathies, vasculitis, arteriovenous malformations (AVMs), and intracranial neoplasms.9,10,11,15 Intracranial hemorrhage associated with hereditary cerebral amyloid angiopathy (CAA) is caused by mutations in the amyloid precursor protein (APP) or cystatin C protein (CST3) genes inherited in an autosomal dominant pattern. 16 Although often asymptomatic, cerebral amyloid angiopathy (CAA) is an important cause of primary lobar intracerebral hemorrhage in the elderly.10 Coagulopathies predisposing to excessive bleeding can be due to inherited factor deficiencies or due to acquired liver pathology. Acquired coagulopathies causing ICH may stem from the use of anticoagulants, platelet antagonists and natural remedies with anticoagulant properties amongst others. Some drugs without anticoagulant properties are known to cause intracerebral hemorrhages. These include amphetamines Phencyclidine and Cocaine. In children, the most common cause of ICH are vascular malformations (AVMs), about tenth as frequent as cerebral aneurysms in adults with spontaneous intracranial haemorrhage. There are a number of other causes that are beyond the scope of this paper and have been reviewed in detail elsewhere. 9,11,17 PATHOGENESIS ICH consists of three distinct phases: (1) initial hemorrhage, (2) hematoma expansion, and (3) peri-hematoma edema.19 The initial hemorrhage is caused by rupture of cerebral arteries influenced by the aforementioned risk factors. The disease outcome depends primarily on the latter two phases of progression. Hematoma expansion, occurring hours after initial symptom onset, involves an increase in intracranial pressure (ICP) that disrupts the integrity of the local tissue and the blood-brain barrier. Additionally, obstructed venous outflow induces the release of tissue thromboplastin, resulting in local coagulopathy2. In over a third of patients, hematoma expansion is associated with hyperglycemia,20, 21,22 hypertension,23 and anticoagulation.24-26 The initial size of the hemorrhage and the rate of hematoma expansion are important prognostic variables in predicting neurologic deterioration. Hematoma size >30 ml is associated with greatly increased mortality.27 Following the expansion, cerebral edema forms around the hematoma, secondary to inflammation and disruption of the blood-brain barrier. This peri-hematoma edema is the primary etiology for neurological deterioration and develops over days following the initial insult. In up to 40% of ICH cases, the hemorrhage extends into the cerebral ventricles causing intraventricular hemorrhage (IVH).28 This is associated with acute obstructive hydrocephalus and substantially worsened prognosis.2,28 ICH and accompanying edema may also disrupt or compress adjacent MUMJ Clinical Review17 brain tissue, leading to neurological dysfunction. Substantial displacement of brain parenchyma may cause elevation of intracranial pressure (ICP) with the potential outcome of fatal herniation syndromes.29 CLINICAL MANIFESTATION Rapid recognition of ICH is crucial. Rapid clinical progression during the first several hours can quickly lead to neurological deterioration and cardio-pulmonary instability. The classic presentation in ICH is the progressive onset of focal neurological deficits over minutes to hours with accompanying headache, nausea, vomiting, decreased level of consciousness and elevated blood pressure.2,30 Comparatively, in ischemic stroke and subarachnoid hemorrhage, there is typically a more abrupt progression of focal deficits.2 Symptoms of headache and vomiting are also observed less often in ischemic stroke compared with ICH.30 Symptoms of ICH are typically due to increased ICP. This is often evidenced through the presence of CushingвЂ™s triad вЂ“ hypertension, bradycardia and irregular respiration вЂ“ triggered by the CushingвЂ™s reflex.31 Dysautonomia is also frequently present in ICH, accounting for hyperventilation, tachypnea, bradycardia, fever, hypertension and hyperglycemia.2,27 Stroke can often be confused with other neurological conditions that mimic stroke in their clinical presentation. The most common stroke-mimics are seizure, syncope and sepsis. Sensory symptoms such as vertigo, dizziness and headaches are non-discriminatory between stroke and non-stroke.32 Furthermore, ICH is particularly difficult to diagnose because symptoms of syncope, coma, neck stiffness, seizure, diastolic blood pressure (BP) of >110 mmHg, nausea, vomiting, and headache are typically present in ischemic stroke but usually absent in ICH.32 As a result, early neuroimaging becomes vital in the diagnosis of ICH. The most common symptoms of hemorrhagic and ischemic stroke are acute onset, limb weakness, speech disturbances and facial weakness (Table 1). Table 1. Common clinical stroke symptoms in order of decreasing frequency. These symptoms are used to differentiate stroke from neurological conditions that mimic stroke Symptoms Cases Acute onset Arm weakness Leg weakness Speech disturbances Facial weakness Limb parasthesia Visual disturbances Facial parasthesia Vertigo Impaired limb coordination Convulsive fits (%) 96 63 54 53 23 20 11 9 6 5 1 DIAGNOSIS Clinical As with any medical emergency, a thorough and focused history eliciting specific risk factors and preceding events is critical for every patient presenting with stroke-like symptoms. Important risk factors include any recent trauma, hypertension, prior strokes, diabetes, smoking, alcohol, overthe-counter, prescription or recreational drugs (specifically cocaine, warfarin, aspirin, and other anticoagulants), hematologic disorders, liver disease, neoplasm, infections and AVM.33 Although risk factors and patient comorbidities have implications for clinical management and outcome, clinical presentation alone is insufficient to reliably differentiate stroke from other clinical entities.2 The difficulty for most physicians lies in the ability to distinguish stroke from those that mimic it such as syncope, sepsis and seizures. To improve diagnostic accuracy in stroke diagnosis, tools such as the ROSIER Scale (Table 2) have been developed for use in the emergency room to help reduce the number of unnecessary referrals for nonstroke cases.32 The ROSIER Scale is a rapid stroke assessment tool that uses clinical signs such as asymmetrical weakness, speech and visual disturbances, to help rule out stroke mimics. The ROSIER scale ranges from -2 to +5 points, with any patient scoring greater than 0 having a 90% likelihood of stroke. The ROSIER scale has a sensitivity of 92%, specificity of 86%, positive predictive value (PPV) of 88%, and negative predictive value (NPV) of 91%.32 Although tools such as the ROSIER scale have helped to improve diagnostic accuracy for stroke in general in the emergency department to 80-95%32, no signs or symptoms reliably distinguish ICH from ischemic stroke. Therefore, neurological imaging plays an increasingly important role in the diagnosis of ICH.32-35 Laboratory investigations for diagnosis and prognosis assessment consist of CBC, electrolytes, a hemostasis screen including INR and PT, a ОІ-HCG test in women of childbearing age and a toxicology screen to test for cocaine and other prescription drugs.33,36 Patients with an elevated PT or INR due to anticoagulant therapy have a greater risk of hematoma expansion and, when possible, their anticoagulation therapies should be, at least temporarily, reversed. Table 2. The ROSIER Scale is a rapid stroke assessment tool that uses clinical signs to help rule out stroke mimics. The scale ranges from -2 to +5 points, with any patient scoring greater than 0 being likely to have a stroke Components Asymmetrical facial weakness Asymmetrical arm weakness Asymmetrical leg weakness Speech disturbances Visual field defect Seizure Loss of consciousness Points 1 1 1 1 1 -1 -1 18 Clinical Review Imaging The primary purpose of diagnostic imaging is to differentiate between ischemic and hemorrhagic strokes and to rule out other CNS lesions.35 Computed tomography (CT) and magnetic resonance imaging (MRI) are both first line imaging modalities, supported by level 1 evidence (RCTвЂ™s).37 If an MRI can be ordered as quickly as the CT, it should be considered first. 35 In patients with contraindications to MRI, namely those with metallic fragments or devices in the brain, eyes or spinal canal, a CT scan should be obtained.2 CT may be superior at showing ventricular extension, while MRI better detects structural lesions, edema, and herniation.2 The noncontrast CT (NCCT) is the most readily available tool providing rapid feedback and is thus commonly used in emergency departments. It is thought to be nearly 100% sensitive for detecting clinically relevant acute hemorrhages. Moreover, it may elucidate hematoma location and expansion and the presence of edema.38 MRIs are most frequently utilized as follow-up investigations to identify secondary causes of ICH, such as arteriovenous malformation (AVM), amyloid angiopathy, or associated neoplasm. With advances in imaging, CT angiography (CTA) has proven to be a useful tool in predicting hematoma expansion in patients with ICH. Wada et al. (2007) demonstrated foci of contrast enhancement in 91% of expanded hematomas.39 CTA and contrast-enhanced CT may identify patients at risk for hematoma expansion through this novel discovery of the вЂ�spot signвЂ™ (Figure 2).38 The spot sign has helped enhance visualization of hematoma expansion with the ability to stratify risk of hemorrhagic stroke. The literature has noted a particularly high specificity (85-89%) of the spot sign for ICH, with negative predictive values of 76-96% and a positive likelihood ratio of 2.7-8.5.39-42 In the absence of CTA, it would be difficult to accurately detect structural causes of the hemorrhage, such as bleeding from a cerebral aneurysm or a vascular malformation. If no Volume 10 No. 1, 2013 underlying aneurysm or lesion is noted using 3D-CTA, the peripheral enhancement on source images of 3D-CTA supports the assertion that these foci represent active hemorrhage from secondarily damaged or torn perforations.39 In a study by Park et al. (2010), the mean duration of hospital admission for patients exhibiting the spot sign was 47.37 days, whereas those lacking the sign were admitted for 37.11 days (p < 0.001). Mortality rates between two groups also differed significantly over the 90 days following admission (40.5% vs.13.4%, p < 0.001).43 Thus, this association between the spot sign and hematoma expansion may reflect the role of a spot sign as a reliable radiologic predictor of clinical deterioration and poor outcomes in spontaneous ICH. PROGNOSIS Approximately half of all ICH-related mortality occurs within the first 24 hours after the initial hemorrhage.44 Mortality approaches 50% at 30 days.19,36 Factors associated with poor outcomes include large hematoma volume (>30 mL), posterior fossa location, older age, mean arterial blood pressure (MAP) >130 mmHg at admission36,44 and a score of below 4 on the Glasgow Coma Scale (GCS) on admission. The same factors are also the most powerful predictors of mortality at 30 days. Hematoma expansion has also been shown to be an independent predictor of diminished functional outcomes, neurological deterioration20,21,45 and mortality.2,46 In a study by Alvarez-SabГn et al. (2004) increased levels of matrix metalloproteinase (MMP)-9 and MMP-3 at 24 hours are associated with increased peri-hematomal edema and mortality, respectively.2,47 The ICH score and FUNC score are two clinical grading scales used to prognosticate patients with hemorrhagic stroke. The ICH Score predicts 30-day mortality using factors including age, ICH volume, GCS score and presence of IVH (Table 3).48 In a study by Hemphill et al. (2001), all 26 patients with an ICH score of 0 survived and all 6 patients Figure 2. Patient with spot sign demonstrating extravasation and hematoma expansion. A. Unenhanced CT demonstrates left posterior putaminal and internal capsule hematoma with mild surrounding edema. B. A small focus of enhancement is seen peripherally, consistent with the spot sign (black arrow). C. Post-contrast CT demonstrates enlargement of the spot sign, consistent with extravasation (white arrow). D. Unenhanced CT image 1 day after presentation reveals hematoma enlargement and intraventricular hemorrhage.39 MUMJ Clinical Review19 with an ICH Score of 5 died within the 30 days.48 The limitation of the ICH score is that it is solely used to prognosticate survival at 30 days without accounting for functional outcome. The ICH score should thus be used in combination with the FUNC score to assess functional outcome. Table 3. The ICH Score predicts 30-day mortality using factors including GCS score, ICH volume, presence of intraventricular hemorrhage (IVH), and age. The scale ranges from 0 to 6 points. In the original study all patients with a score of 0 survived and all patients with a score of 5 died within 30 days. The limitation of the ICH score that is does not account for functional outcome Component GCS score 3-4 5-12 13-15 ICH volume (cm3) >30 <30 IVH Yes No Infratentorial origin of ICH Yes No Age (y) >80 <80 Points 2 1 0 1 0 1 0 1 0 1 0 Another prognostic tool is the FUNC (Functional outcome risk stratification) score. The patient is assessed for risk of functional impairment at 90 days post-stroke. The FUNC scores range from zero to eleven based on ICH volume, age, site of ICH, GCS score and pre-ICH cognitive impairment49 (Table 4). A greater score is associated with a greater chance of functional independence, defined as GCS в‰Ґ4 at 90 days.49 According to Rost et al. (2008), no patient with a FUNC score в‰¤4 achieved functional independence and over 80% of those with a maximal FUNC score of 11 reached functional independence at 90 days.49 The limitation, however, is that only scores at the extreme ends seem to be clinically useful as scores in the mid-range have little predictive value.49 Although these prognostic tool scores are important in the hospital setting, the AHA recommends prompt and aggressive full care upon ICH onset with postponement of new AND (вЂњAllow Natural DeathвЂќ) orders until at least the second full day of hospitalization.50 This is because there is evidence that a stated poor prognosis can lead to self-fulfilling prophecies of early death.50 Withdrawal of care is the strongest predictor of death after ICH44 and, thus, in the emergency setting new AND orders or withdrawal of care are not recommended.45 Table 4. The FUNC (Functional outcome risk stratification) score assesses the patient for risk of functional impairment at 90 days post-stroke. The scores range from 0 to 11 based on ICH volume, age, ICH location, GCS score, and pre-ICH cognitive impairment. A greater score is associated with a greater chance of functional independence, defined as GCS >4, at 90 days. Limitations include lack of predictive value for scores in the mid-range Component ICH volume (cm3) <30 30-60 >60 Age (y) <70 70-79 >80 ICH location Lobar Deep Infratentorial GCS score в‰Ґ9 в‰¤8 Pre-ICH cognitive impairment Absent Present Points 4 2 0 2 1 0 2 1 0 2 0 1 0 TREATMENT Surgical Two surgical interventions are available for treating aneurysms. The surgical approach entails placement of permanent alloy clips across the neck of the aneurysm through craniotomy access. The patient is typically under general anesthesia. This prevents blood flow from reaching the aneurysm and lowers the risk of rupture.14 The aneurysm can also be coiled through endovascular access while the patient is under general anesthesia or sedation.14 Intra-procedural neurologic function is observed through neurophysiological monitoring. Using fluoroscopy and digital subtraction angiography, a catheter is advanced through the femoral artery, aorta, carotid artery and into the aneurysm. A sufficient number of detachable coils are then positioned into the aneurysm to minimize the amount of blood filling the aneurysm.14,52-54 Systematic reviews have associated the use of coils with lower rates of inpatient mortality, shorter hospital stay and decreased treatment costs.14 Medical The patientвЂ™s vital signs must be immediately stabilized according to ATLS guidelines.34 Patients with ICH are often unable to protect their airway and may need endotracheal intubation (criteria for intubation, GCS <8). Rapid sequence intubation is the preferred approach with administration of 20 Clinical Review short-acting IV thiopental (1-5 mg/kg) or lidocaine (1 mg/kg) to prevent the increase in ICP that may result from tracheal stimulation.34,37 A chest X-ray and an EKG must be ordered to assess cardiopulmonary function. A CT scan must then be obtained to determine further management and to make a final diagnosis.34 With ICH there is often a need to transfer a patient to an intensive care unit for ICP monitoring and potential neurosurgical intervention. Physicians should determine whether the level of care required exceeds the capacity of their facility and if their patient needs to be transferred to the nearest tertiary stroke centre.2 Bleeding, seizures, blood pressure, and intracranial pressure must be monitored and actively controlled. A new AHA/ASA guideline states that glucose should be monitored and normoglycemia is recommended (Class I: Level of Evidence: C).50 Special attention should be given to the risk of iatrogenic hypoglycemia associated with increased risk of mortality.50 Antacids are administered to prevent associated gastric ulcers. Fever must be controlled and thromboembolic prophylaxis undertaken with compression stockings. Normothermia is recommended as even mild hyperthermia can accentuate the cellular damage in the area of ischemic penumbra poststroke. Following 1-2 days of treatment, heparin therapy can be considered for further thromboembolic prophylaxis when no increased risk of recurrent hemorrhage is suspected.27 Reversal of warfarin anticoagulation is undertaken to control bleeding and ICH. This must be accomplished as quickly as possible to stop further hematoma expansion. Agents for reversal therapy include intravenous vitamin K (VAK), fresh frozen plasma (FFP), prothrombin complex concentrates (PCC) and rFVIIa.55,56 Vitamin K should be given with either FFP or PCC as it requires more than six hours to normalize the INR. According to Huttner et al. (2006) the incidence of hematoma expansion in patients receiving PCCs (19%) was significantly lower than those receiving FFP (33%) or VAK (50%) (П‡2 P<0.01 for PCCs).55 Although the extent of hematoma growth did not significantly differ between the groups (p=0.36), more rapid INR reversal was achieved through treatment with PCCs as compared with FFP and VAK (П‡2 P<0.01). This suggests that the superior effect of PCC is related to the more rapid INR reversal.55 Studies using recombinant factor VIIa (rFVIIa) have been disappointing and it is not commonly used clinically to treat bleeding. This product is currently being tested in patients with spot sign. Blood pressure should be controlled to prevent re-bleeding and hematoma expansion. A beta-blocker, such as Labetalol, and an ACE inhibitor, such as enalapril, are often used to achieve blood pressure control. Nitroprusside may raise intracranial pressure and should be avoided, except when necessary in patients with asthma or heart failure where betablocker administration is contraindicated.57 The decision to actively pursue hypertensive control depends on the systolic pressure, mean arterial pressure (MAP) and presence or absence of intracranial pressure on admission and is beyond the Volume 10 No. 1, 2013 scope of this paper but is covered by the 2010 AHA/ASA guidelines.50 Intracranial pressure (ICP) management relies on elevation of the head of the bed to 40 degrees to improve jugular venous outflow. More aggressive therapies, such as osmotic therapy (mannitol, hypertonic saline) require intracranial pressure and BP monitoring to maintain an adequate cerebral perfusion pressure greater than 70 mmHg.2,50 These are routinely used during transfer of patients from peripheral centres. Special attention should be given to the risk of iatrogenic hypotension caused by rapid and aggressive hypertensive therapy, which can induce cerebral ischemia.57 For seizure control, the 2010 AHA/ASA guidelines recommended that patients with seizures accompanied by change in mental status should be treated with a benzodiazepine for rapid seizure control and Phenytoin for long-term management.50 Figure 3 represents a flowchart for the approach to ICH identifying the various steps involved from presentation through diagnosis to treatment. Step 1 Patient must be assessed and stabilized if necessary according to ATLS guidelines. вЂў Patients with a GCS score under 9 require endotracheal intubation.33 Step 2 Clinical History вЂ“ Questions should be asked about any recent trauma, hypertension, prior strokes, diabetes, smoking, alcohol, over-the-counter, prescription or recreational drugs (specifically cocaine, warfarin, aspirin, other anticoagulants), hematologic disorders, liver disease, neoplasm, infections, or AVM.33 Step 3 Assess symptoms using the ROSIER Scale32 (scores >0, 90% chance of stroke) to diagnose, and the ICH48 (the greater the score, the poorer the outcome) and FUNC Scores49 (the greater the score, the greater the chance of functional independence) to prognosticate. Step 4 Lab test should be performed to guide diagnosis, assess risk factors for ICH and discover potential underlying causes. Sample tests include a CBC, electrolytes, a hemostasis screen including INR and PT, a pregnancy test, a toxicology screen, matrix metalloproteinase, chest X-ray and an ECG.2 Step 5 Diagnostic Imaging2,35 вЂ“ CT and MRI are both first-choice imaging modalities (both level 1evidence). Using CTA the вЂ�spot signвЂ™ can indicate risk for hematoma expansion is a warning for poorer outcomes unless treated quickly. Step 6 Treatment 2 (Note: this step may occur prior to other steps) вЂў Potential treatments in ICH: stopping or slowing initial bleed during the initial hours after onset (pharmacotherapy, surgical clipping, endovascular coiling) вЂў Management of symptoms, signs and complications such as elevated ICP, decreased cerebral perfusion and supportive management of patients with severe brain injury is required. Figure 3. Flowchart for the approach to stroke, specifically intracerebral hemorrhage (ICH), in the acute care setting starting with a focused history, lab testing, diagnostic imaging and acute treatment. MUMJ Clinical Review21 CONCLUSION Given the high mortality rate of ICH, early recognition and correct diagnosis is vital. While making the diagnosis, one must distinguish stroke mimics from actual stroke signs and identify common signs such as acute onset, limb weakness or speech disturbances. Among their diagnostic arsenals and prognostic tools, ICH can be assessed through the Rosier scale (diagnostic) and the ICH and FUNC scores (prognostic). However, such tools are limited in their interpretation of mid-range scores. Neurological imaging techniques, such as CT and MRI are playing an increasingly central role in the early diagnosis of ICH. The вЂ�spot signвЂ™ has been suggested as a marker of hematoma expansion as identified on CTA. A major limitation in stroke management is that no effective targeted therapy for hemorrhagic stroke yet exists. Rather, symptoms and complications are individually managed, with increased ICP and neurological deterioration being particularly important. The recent advent of endovascular coiling of aneurysms as a preventative measure against ICH has improved clinical outcomes in appropriately selected patient populations. 21. REFERENCES 36. 1. Statistics Canada. (2011). Morality, Summary List of Causes 2008. Retrieved February 2013, from the World Wide Web: http://www5.statcan.gc.ca/bsolc/olc-cel/ olc-cel?catno=84F0209X&CHROPG=1&lang=eng. 2. Broderick J, Connolly S, Feldmann E., et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working group. Stroke. 2007; 38: 2001-23. 3. MacKay J, Mensah GA. Global Burden of Stroke. In: MacKay J, Mensah GA. The Atlas of Heart Disease and Stroke. Geneva: World Health Organization; 2004; p. 50-51. 4. Flaherty ML, Woo D, Haverbusch M., et al. Racial variations in location and risk of intracerebral hemorrhage. Stroke. 2005; 36: 934-7. 5. Mayer SA, Rincon F. Treatment of intracerebral haemorrhage. Lancet Neurol. 2005; 4: 662-72. 6. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. Jan 3 2012; 125(1):e2-e220. 7. Heart and Stroke Foundation of Canada (2003). The Growing Burden of Heart Disease and Stroke in Canada. Retrieved April 7, 2013, from World Wide Web: http://www.cvdinfobase.ca/cvdbook/En/Index.htm. 8. Gebel JM, Broderick JP. Intracerebral hemorrhage. Neurol Clin. 2000; 18: 419-38. 9. Lovelock CE, Molyneux AJ, Rothwell PM, Oxford Vascular Study. Change in incidence and aetiology of intracerebral haemorrhage in Oxfordshire, UK, between 1981 and 2006: a population-based study. Lancet Neurol. 2007; 6: 487. 10. Viswanathan A, Greenberg SM. Cerebral amyloid angiopathy in the elderly. Ann Neurol. 2011; 70:871. 11. Ariesen MJ, Claus SP, Rinkel GJ, et al. Risk factors for intracerebral hemorrhage in the general population: a systematic review. Stroke. 2003; 34:2060. 12. Robert G. Hart, Bradley S. Boop, David C. Anderson. Oral Anticoagulants and Intracranial Hemorrhage. Stroke. 1995; 26: 1471-7. 13. Schievink WI. Intracranial aneurysms. N Engl J Med. 1997;336:28-40. 14. Jonathan L. Brisman, Joon K. Song, David W. Newell. Cerebral aneurysms. N Engl J Med. 2006;355:928-39. 15. Garcia JH, Ho KL. Pathology of hypertensive arteriopathy. Neurosurg Clin N Am 1992; 3:497. 16. Hamaguchi T, Yamada M. Genetic factors for cerebral amyloid angiopathy. Brain Nerve. 2008 Nov; 60(11):1275-83. 17. Beslow LA, Licht DJ, Smith SE, et al. Predictors of outcome in childhood intracerebral hemorrhage: a prospective consecutive cohort study. Stroke 2010; 41: 313. 18. Neuroradiology Unit, S P Institute of Neurosciences, Solapur, India. (2011). Dr. Balaji AnvekarвЂ™s Neuroradiology Cases. Retrieved March 5, 2013, from the World Wide Web: http://www.neuroradiologycases.com/2011/11/imaging-in-sub-arachnoid-hemorrhage.html. 19. Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke. 1997;28:1-5. 20. Kazui S, Naritomi H, Yamamoto H, et al. Enlargement of spontaneous intracerebral hemorrhage: incidence and time course. Stroke. 1996;27:1783-7. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. Kazui S, Minematsu K, Yamamoto H, et al. Predisposing factors to enlargement of spontaneous intracerebral hematoma. Stroke. 1997;28:2370-5. Becker KJ, Baxter AB, Bybee HM, et al. Extravasation of radiographic contrast is an independent predictor of death in primary intracerebral hemorrhage. Stroke. 1999;30:2025-32. Ohwaki K, Yano E, Nagashima H, et al. Blood pressure management in acute intracerebral hemorrhage: relationship between elevated blood pressure and hematoma enlargement. Stroke. 2004; 35:1364-7. Toyoda K, Okada Y, Minematsu K, et al. Antiplatelet therapy contributes to acute deterioration of intracerebral hemorrhage. Neurology. 2005; 65: 1000-04. Yasaka M, Minematsu K, Naritomi H, et al. Predisposing factors for enlargement of intracerebral hemorrhage in patients treated with warfarin. Thromb Haemost. 2003; 89: 278-83. Flibotte JJ, Hagan N, OвЂ™Donnell J, et al. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology. 2004; 63: 1059-64. Elliott J, Smith M. The acute management of intracerebral hemorrhage: a clinical review. Anesth Analg. 2010; 110(5): 1419-27. Rincon F, Mayer SA. Clinical review: Critical care management of spontaneous intracerebral hemorrhage. Critical Care. 2008; 12: 237. Tiebosch, I.A.C.W.. Effects of anti-inflammatory treatments on stroke outcome in animal models. Geneeskunde Proefschriften, 2012. Sahni R, Weinberger J. Management of intracerebral hemorrhage. Vasc Health Risk Manag. 2007 October; 3(5): 701-9. Mayer, SA.; Chong, JY. Critical care management of increased intracranial pressure. Journal of Intensive Care Medicine. 2002;17 (2):55-67. Nor AM., Davis J., Sen B. et al. The recognition of stroke in the emergency room (ROSIER) scale: development and validation of a stroke recognition. Lancet Neruology. 2005;4: 727-34. Kase, K. S. Vascular diseases of the nervous system: Intracranial hemorrhage. In Daroff: BradleyвЂ™s Neurology in Clinical Practice 6 ed. Philadelphia, PA: Elesvier Inc; 2012; p. 1054-69. Stone, CK., Humphries, RL. Current Diagnosis & Treatment Emergency Medicine 7e. McGraw-Hill Companies. 2011. Yew, KS., Cheng, E. Acute stroke diagnosis. American Family Physician, 2009; 80(1): 33-40. Broderick JP, Brott TG, Duldner JE, et al. Volume of intracerebral hemorrhage. A powerful and easy-to- use predictor of 30-day mortality. Stroke. 1993; 24: 987вЂ“93. Djulbegovic B, Loughran TP Jr, Hornung, CA et al. The quality of medical evidence in hematology-oncology. Am J Med. 1999; 106(2): 198-205. Nentwich, LM., Veloz, W. Neuroimaging in acute stroke. Emergency Medicine North America. 2012; 30: 659-80. Wada, R., Aviv, RI., Fox, AJ., et al. CT Angiography вЂњSpot SignвЂќ Predicts Hematoma Expansion in Acute Intracerebral Hemorrhage. Stroke. 2007; 38(4):1257-62. Delgado Almandoz, JE., Kelly HR., Schaefer, PW., et al. CT angiography spot sign predicts in-hospital mortality in patients with secondary intracerebral hemorrhage. Journal of NeuroInterventional Surgery. 2012; 4(6): 442-7. Brouwers, HB., Falcone, GJ., McNamara, KA., et al. CTA Spot Sign Predicts Hematoma Expansion in Patients with Delayed Presentation After Intracerebral Hemorrhage. Neurocritical Care. 2012; 17(3): 421-428. Delgado Almandoz, JE., Yoo, A. J., Stone, M. J., et al. The Spot Sign Score in Primary Intracerebral Hemorrhage Identifies Patients at Highest Risk of In-Hospital Mortality and Poor Outcome Among Survivors. Stroke. 2009; 41(1): 54-60. Park, SY., Kong, MH., Kim, JH., et al. Role of вЂњSpot SignвЂќ on CT Angiography to Predict Hematoma Expansion in Spontaneous Intracerebral Hemorrhage. Journal of Korean Neurosurgical Society. 2010; 48(5); 399. Fogelholm R, Murros K, Rissanen A, et al. Long term survival after primary intracerebral haemorrhage: a retrospective population based study. J Neurol Neurosurg Psychiatry. 2005; 76: 1534-8. Leira R, Davalos A, Silva Y, et al. Stroke Project, Cerebrovascular Diseases Group of the Spanish Neurological Society. Early neurologic deterioration in intracerebral hemor- rhage: predictors and associated factors. Neurology. 2004; 10(63): 461-7. Davis SM, Broderick J, Hennerici M, et al. Recombinant Activated Factor VII Intracerebral Hemorrhage Trial Investigators. Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology. 2006; 66: 1175-81. Alvarez-Sabin J, Delgado P, Abilleira S, et al. Temporal Profile of Matrix Metalloproteinases and Their Inhibitors After Spontaneous Intracerebral Hemorrhage: Relationship to Clinical and Radiological Outcome. Stroke. 2004; 35: 1316-22. Hemphill JC III, Bonovich DC, Besmertis L, et al. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001; 32(4): 891-7. Rost NS, Smith EE, Chang Y, et al. Prediction of functional outcome in patients with primary intracerebral hemorrhage: the FUNC score. Stroke 2008; 39(8): 2304-9. Morgenstern LB, Hemphill JC 3rd, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. Sep 2010; 41(9): 2108-29. Caceres, JA., Goldstein, J. N. Intracranial Hemorrhage. Emergency Medicine Clinics of North America. 2012; 30: 771-94. Jose I. Suarez, Robert W. Tarr, Warren R. Selman. Aneurysmal Subarachnoid Hemorrhage. N Engl J Med. 2006; 354: 387-96. Stephen Chang, Abhishek Srinivas, Kieran Murphy, Endovascular Management of a Patient after SAH. Tech Vasc Interventional Rad. 2005; 8: 108-17. 22 54. 55. Clinical Review Michael T. Froehler. Endovascular Treatment of Ruptured Intracranial Aneurysms. Curr Neurol Neurosci Re. 2013; 13: 326. Huttner HB, Schellinger PD, Hartmann M, et al. Hematoma growth and outcome in treated neurocritical care patients with intracerebral hemorrhage related to oral anticoagulant therapy: comparison of acute treatment strategies using vitamin K, fresh frozen plasma, and prothrombin complex concentrates. Stroke. Jun 2006; 37(6): 1465-70. 56. 57. Volume 10 No. 1, 2013 Boulis NM, Bobek MP, Schmaier A, et al. Use of factor ix complex in warfarinrelated intracranial hemorrhage. Neurosurgery. 1999; 45: 1113вЂ“18. Martins SCO, deFreitas GR, Pontes-Neto OM et al. Guidelines for acute ischemic stroke treatment вЂ“ Part II: Stroke treatment. Arq Neuropsiquiatr. 2012; 70(11): 88593. Author Biographies Fabio Magistris graduated from the University of Western Ontario with a degree in Medical Sciences before attending McMaster University. He is currently in his first year of the MD program. Stephanie Bazak graduated from Acadia University with a Bachelor of Science in Psychology. She is currently in her second year of medicine at McMaster University Jason Martin completed three years of the Medical Sciences program at the University of Western Ontario before attending McMaster University. He is currently in his second year of the MD program. He has an active interest in neuroradiology.