Intracerebral hemorhage Diagnosis and management

About ICH - Diagnosis and management, Discussed the clinical presentation, evaluation, radiological features and management including recent guidelines

1. INTRACEREBRAL HEMORRAGHE Co-Ordinator: Dr.Meenakshisundaram.U Presenter: Dr.M.Ramesh Babu STROKE SYMPOSIUM

2. Introduction Intracerebral hemorrhage is defined as an acute and spontaneous bleeding within the brain parenchyma that may extend into the ventricles and subarachnoid space. ( ICH, IVH, SAH) Third most frequent cause of stroke, following cerebral embolism and thrombotic disease.

3. General Rules of ICH ICH occurred at a younger age than brain infarction. The major cause of ICH was hypertension, often severe. Symptoms of ICH began abruptly. Loss of consciousness was a nearly constant feature. Headache always accompanied ICH, and was usually severe. The most common locations for ICH were the putamen, internal capsule, lobar, thalamus, cerebellum and pons. CT Brain imaging of choice , MRI helps in detecting the old haemorrhage. ICH was invariably fatal or devastating, with few, if any, intact survivors. CT

4. Epidemiology It is common: 12-15 cases per 100 000 people per year 10%~15% of all stroke cases Asian countries have a higher incidence ( 20-30%) of intracerebral hemorrhage than other regions of the world. A higher incidence of intracerebral hemorrhage has been noted in Chinese, Japanese, and other Asian populations, possibly due to environmental factors (eg, a diet rich in fish oils) and/or genetic factors.

5. Epidemiology Intracerebral hemorrhage has a 30-day mortality rate of ~ 50 % . Pontine or other brainstem intracerebral hemorrhage has a mortality rate of 75% at 24 hours. Incidence of intracerebral hemorrhage increases in individuals older than 55 years and doubles with each decade until age 80.

6. Etiology Hypertensive ICH ( 70 - 80%) Non-hypertensive ICH Vascular malformation: AVM, Aneurysm, Cavernous hemangioma Bleeding disorders/anticoagulant Amyloid angiopathy Trauma Tumor Drug abuse: amphetamine, cocaine, PPA

7. Tumors commonly a/w ICH Malignant Glioblastoma multiforme , Lymphoma Metastasis (melanoma, choriocarcinoma, renal cell carcinoma , bronchogenic carcinoma) Benign Meningioma , Pituitary adenoma H ema ngi o bl as t om a , Acoustic neuroma Cerebellar astrocytoma

8. Risk Factors for underlying Vascular Abnormalities Age <65 years, Female sex, Nonsmoker, Lobar ICH, Intraventricular extension, Absence of a history of hypertension or coagulopathy

9. History Comments Time of symptom onset (or time the patient was last normal) Vascular risk factors Hypertension, diabetes, hypercholesterolemia, and smoking Medications Anticoagulants, antiplatelet agents, decongestants, antihypertensive medications, stimulants (including diet pills), sympathomimetics Recent trauma or surgery Carotid endarterectomy or carotid stenting in particular, as ICH may be related to hyperperfusion after such procedures Dementia Associated with amyloid angiopathy Alcohol or illicit drug use Cocaine and other sympathomimetic drugs are associated with ICH, stimulants Seizures Liver disease May be associated with coagulopathy Cancer and hematologic disorders. May be associated with coagulopathy

10. Physical Examination Comments Vital signs Fever is associated with early neurologic deterioration. 19 Higher initial blood pressure is associated with early neurologic deterioration and increased mortality. 216 A general physical exam focusing on the head, heart, lungs, abdomen, and extremities. A thorough but time urgent neurologic exam A structured exam such as the National Institutes of Health Stroke Scale (NIHSS) can be completed in minutes and provides a quantification that allows easy communication of the severity of the event to other caregivers. Glasgow Coma Score (GCS) is similarly well known, easily computed, and the initial GCS is a strong predictor of long term outcome. 167, 215 These can be supplemented as needed.

11. Hypertensive Hemorrhage Accounts for 60-70% of ICH Theory: Chronic hypertension causes degeneration, fragmentation and fibrinoid necrosis of small perforating arteries Predisposes to rupture The hypertensive vascular lesion that leads to arteriolar rupture in most cases appears to arise from an arterial wall altered by the effects of hypertension , i.e., the change referred to in a preceding section as segmental lipohyalinosis and the false aneurysm ( microaneurysm ) named for Charcot and Bouchard

12. The most common cause of ICH is hypertension, but the blood pressure does not need to be elevated to malignant ranges It is difficult to know how much, if any, of the blood pressure elevation is secondary to raised ICP (the Cushing response), and what the level of blood pressure was before the bleed. Acute fluctuations in blood pressure and flow, and chronic degenerative changes are both important in the etiology of Hypertensive ICH. Acute changes in blood pressure and blood flow can precipitate rupture of penetrating arteries in the absence of prior hypertension It is not known whether the size, location, and clinical picture differs in normotensive individuals who have an acute spike in blood pressure from those who have chronic hypertension.

13. Charcot - Bouchard Aneurysm Discrete arteriolar microaneurysms Most common in the distal portions of medium and small arterioles

14. Amyloid Angiopathy Especially in the elderly Deposition of amyloid β peptide in small and medium sized blood vessels Results in fibrinoid necrosis and microaneurysm formation Prevalence increases with age from ~ 9% in age 60-69 to 58% in age >90 Lobar (Occipital & Parietal) haemorrhages - Quite large & Multiple Chances of rebleed : 21% in 2 yrs Amyloid-laden arteries are most often found in the occipital and parietal regions

15. Multiple, nearly simultaneous intracerebral hemorrhages raise the possibility of amyloid angiopathy or a bleeding diathesis

16. Bleeding Diathesis The most consistent risk factor for intracranial or systemic bleeding is prolongation of the INR beyond the therapeutic range. Features of anticoagulant-induced ICH differs from others by: Hemorrhage often develops gradually and insidiously during many hours, or even days (6/14 patients with anticoagulant-related ICH had an insidious clinical course). 17 Hematoma growth is greater in patients with oral anticoagulant-related hemorrhage than in patients who had other spontaneous (that is non-traumatic, not associated with vascular malformations or aneurysms) causes. The cerebellum and cerebral lobes are involved more frequently than in hypertensive ICH. Oral anticoagulant-related hemorrhages have a high morbidity and mortality rate. If a patient on anticoagulants develops neurological symptoms, the cause is anticoagulant-related hemorrhage until proven otherwise

17. Timing of re-instituting anticoagulants The timing of re-instituting anticoagulants must be based on the situation in the individual patient. Some studies show that waiting 3 weeks or more after hemorrhage to restart led to fewer recurrent brain infarctions than expected. In other patients restarting anticoagulation early (within 7–10 days) led to less recurrent hemorrhage than anticipated. The treating clinician must weigh the risk of recurrent embolization (that is the benefit from anticoagulation) versus the risk of rebleeding. When the risk of rembolization is high and the risk of rebleeding low, then early reinstitution is recommended . When the risk of embolization is small (atrial fibrillation with normal left atrial size and no past brain infarcts) and the risk of rebleeding is substantial (poorly controlled hypertension ) then a much longer delay, or using an antiplatelet rather than an anticoagulant seems prudent. Anticoagulation of patients with lobar ICH had more risk and less potential gain than patients with deep hemorrhages (in whom hypertension could usually be controlled).

18. Drugs Related A variety of commonly abused substances are known to cause ICH. Clinicians should always think of the possibility of drug-related hemorrhage in young normotensive patients . Hemorrhage often develops within a few minutes of drug use . The most frequent presenting symptoms are headache, confusion, and seizures . Despite large-volume ICHs, few focal signs are present in such patients . This phenomena explained by frequent coexistence of brain edema, infarcts, and a diffuse vasculopathy. Angiography - Chronic amphetamine users and other patients with amphetamine-related ICH. Most common are segmental areas of constriction, irregularity, and occasionally fusiform dilatation . The focal vascular abnormalities in superficial cortical arterial branches and are often referred to as beading .

19. Pathophysiology Primar y immediate effect Hemorrhage growth Increase ICP Secondary effect Downstream effect Edema Ischemia Progression of Hematoma

20. Hemorrhage Growth Predictors Early Presentation Irregular shape Liver disease Hypertension Hyperglycemia Alcohol use ( causes platelet dysfunction, red. coagulation factors, inc. blood pressure) Hypofibrinogenemia Priorities for Clinical Research in ICH: NINDS ICH Workshop; Stroke March 2005

21. Clinical Features Alteration in level of consciousness (~ 50%) Nausea and vomiting (~ 40-50%) Headache (~40%) Seizures[3](~6-7%) Focal neurological deficits

22. Headache : was much more frequent with larger lesions, and was often absent or minimal in patients with small lesions. Most common in patients with lobar and cerebellar hematomas, locations near the meningeal surface, and was common in patients with meningeal signs. Patients with small, deep hematomas almost never develop headache during their course of illness. In many patients, headache occurs as the hematoma enlarges and is accompanied by vomiting and decreased alertness

23. Decreased level of Consciousness accompanies only large hematomas and those found in the brainstem. Diminished alertness in patients with ICH is caused by mass effect and increased ICP, or direct involvement of the brainstem reticular activating system. Decreased level of consciousness has been found to be an important adverse prognostic sign .

24. Vomiting is an especially important sign in patients with ICH. In ICH and SAH, vomiting is usually caused by increased ICP or local distortion of the IVth ventricle. In the posterior circulation, vomiting usually reflects dysfunction of the vestibular nuclei , or the so-called vomiting center , in the floor of the IVth ventricle. Patients with cerebellar hemorrhage almost always vomit early in their clinical course.

25. Seizures : Lobar hemorrhages situated near the gray–white junction of the cortex, and putaminal hemorrhages that undercut the cerebral cortex are especially epileptogenic. When pts. with subcortical large and expanding ICHs are monitored using continuous EEG recordings, electrographic seizure discharges are often found. May present with “ non-convulsive seizures “

26. Other Symptoms and Signs: Neck stiffness is uncommon in putaminal hemorrhage, 31 but is often found in patients with caudate, thalamic, and cerebellar hemorrhages. 34 , 35 Fever is relatively common, but is often related to infectious complications, such as pulmonary and urinary tract infections. Subhyaloid retinal hemorrhages , common in SAH, are rare in ICH Cardiac arrhythmias and pulmonary edema develop in some patients with ICH, and are usually attributed to changes in ICP and catecholamine release, a similar pathogenesis to that used to explain cardiac findings in patients with SAH.

27. Keys to localization of ICH are as follows: 1. Motor signs – quadriparesis, hemiparesis, or no paresis 2. Pupillary function – asymmetry, size, and light reaction 3. Extraocular movements – supranuclear, nuclear, internuclear gaze palsies 4. Gait abnormalities – especially ataxia

28. Hemorrhages of the lateral basal ganglia, putamen, and internal capsule (Striatocapsular hemorrhage): Most common location of hypertensive ICH is the lateral basal ganglionic capsular region This location is the most common site for putaminal hemorrhage because it is supplied by the largest of the lateral lenticulostriate arteries These lesions have traditionally been referred to as putaminal hemorrhages because they most often begin in the putamen. The usual findings include C/L hemiparesis, C/L hemisensory loss, and conjugate deviation of the eyes toward lesion. The pupils are generally normal and gait is hemiparetic . Patients with a Left putaminal hemorrhage usually have a non-fluent aphasia . Right -sided lesions are a/w left visual neglect, motor impersistence, and constructional dyspraxia.

29. Large putaminal hemorrhages - Stupor increases as the lesion enlarges I/L pupil at first becomes smaller, and later, larger than the opposite pupil; Ipsilateral plantar response becomes extensor B/L horizontal gaze palsy develops The presence of any of these signs – ipsilateral Babinski’s sign, abnormal ipsilateral pupil, or ipsilateral gaze paresis – has a grim prognosis . These additional findings are caused by midline shift or compression of the rostral brain stem by the expanding hematoma. shows necropsy brain specimens of large putaminal hemorrhages

30. Lesions affecting the anterior limb of the internal capsule and anterior putamen and produce a milder, more transient hemiparesis without sensory abnormalities. Posterior third of the internal capsule and at the far posterior extreme of the putamen, sensory abnormalities predominate, with little or no hemiparesis . An inferior quadrantanopia or hemianopia may be present. Patients with lesions in the far posterior left putamen mayhave fluent Wernicke-like aphasia because of undercutting of the temporal lobe The most common and largest lesions affecting the anterior part of the posterior limb of the internal capsule are often referred to as the middle type , whereas the others are termed anterior or posterior types of putaminal hematomas.

31. Caudate Hemorrhage accounts for ~ 7% of ICH. Hematomas at this site frequently discharge quickly into the adjacent lateral ventricle , or may spread laterally toward the internal capsule or inferiorly toward the hypothalamus. Early ventricular dilatation by blood probably accounts for the most common symptoms of caudate hemorrhage ( headache, vomiting, decreased alertness, and stiff neck ). Some patients also are confused, disoriented, and have poor memory. The larger parenchymatous hematomas cause a C/L hemiparesis, conjugate deviation of the eyes to the side of the lesion, conjugate gaze palsy to the opposite side, and an I/L small pupil or Horner’s syndrome.

32. Sensory findings are usually absent or minimal. The usual cause of caudate hemorrhage is hypertension , but AVMs are also common, especially in the young. Caudate hematomas have a better prognosis than comparable-sized putaminal hemorrhages. Symptoms and signs of caudate hemorrhage closely mimic SAH , but the CT appearance of blood in the caudate and lateral ventricles is distinctive.

33. Thalamic Hemorrhage : It occurs secondary to rupture of the Thalamoperforating artery . severe sensory loss on the entire contralateral body. If large or moderate in size, thalamic hemorrhage also produces a hemiplegia or hemiparesis by compression or destruction of the adjacent internal capsule. The sensory deficit involves all of the opposite side including the trunk and may exceed the motor weakness.

34. Fluent Aphasia - Lesions of the dominant side C/L N e gl e ct - lesi o ns o f t he nondominant side. Thal a mic h e m o rrha g e , b y vir t ue o f i t s extension into the subthalamus and high midbrain, may also cause a series of ocular disturbances- pseudoabducens palsies with one or both eyes turned asymmetrically inward and slightly downward, palsies of vertical and lateral gaze forced deviation of the eyes downward inequality of pupils absence of light reaction, skew deviation with the eye ipsilateral to the hemorrhage assuming a higher position than the contralateral eye, ipsilateral ptosis and miosis ( Horner syndrome ) Compression of the adjacent third ventricle leads to enlargement of the lateral ventricles that may require temporary drainage. early hydrocephalus is common

35. Pontine Hemorrhage Deep coma within a few minutes Locked in Syndrome Total paralysis with bilateral Babinski signs , Decerebrate rigidity , Small (1-mm) pupils that react to light. Lateral eye movements, evoked by head turning or caloric testing, are impaired or absent.

36. Cerebellar Hemorrhage Bleeding occurs from the distal branches of superior cerebellar or PICA vessels. Loss of consciousness at the onset is unusual . Repeated vomiting is a prominent feature Occipital headache, vertigo, and inability to sit, stand, or walk . A mild ipsilateral facial weakness, diminished corneal reflex, paresis of conjugate lateral gaze to the side of the hemorrhage, or an ipsilateral sixth-nerve weakness occur with larger hemorrhages. or extend into the cerebellar peduncle. Dysarthria and dysphagia may be prominent in some cases but usually are absent. Infrequent ocular signs :blepharospasm, involuntary closure of one eye, skew deviation, "ocular bobbing," and small, often unequal pupils that continue to react.

37. C/L hemiplegia and ipsilateral facial weakness occur if there is marked displacement and compression of the medulla against the clivus. The plantar reflexes are flexor in the early stages but extensor later . When these signs occur, hydrocephalus is usually found and may require drainage. C erebellar hemorrhage is the most amenable to surgical evacuation with good results.

38. Lobar Hemorrhage Bleeding in areas specifically in the subcortical white matter of one of the lobes of the cerebral hemisphere Not associated strictly with hypertension. Causes : anticoagulation or thrombolytic therapy; acquired coagulopathies, cranial trauma, arteriovenous, trauma, and, in the elderly, amyloidosis of the cerebral vessels. Most lobar hemorrhages are spherical or ovoid, but a few follow the contour of the subcortical white matter tracts and take the form of a slit (subcortical slit hemorrhage). M any of these are the result of a bleeding diathesis, such as thrombocytopenia.

39. Lab Tests Serum and Urine Tests Comments Complete blood count, electrolytes, blood urea nitrogen and creatinine, and Glucose Higher creatinine is associated with hematoma expansion. Higher serum glucose is associated with hematoma expansion and worse outcome (although there are no data to suggest that normalization improves outcome). Prothrombin time (PT) or international normalized ratio (INR) and an activated partial thromboplastin time (aPTT) Warfarin-related hemorrhages are associated with an increased hematoma volume, greater risk of expansion, and increased morbidity and mortality. 17, 197, 218 Toxicology screen in young or middle-aged patients to detect cocaine and other sympathomimetic drugs of abuse Cocaine and other sympathomimetic drugs are associated with ICH Urinalysis and urine culture and a pregnancy test in a woman of childbearing age.

40. Other Routine Tests Comments EKG To assess for active coronary ischemia or prior cardiac injury that may indicate poor cardiac function, and to obtain a baseline in the event of cardiopulmonary issues during hospitalization. Chest radiograph Neuroimaging CT/ CECT/ CTA/CTV, MRI with gadolinium, MRA/MRV can all be useful to evaluate for underlying structural lesions, including vascular malformations and/or tumors When there is clinical or radiologic suspicion

41. Imaging Superior to MRI in acutely ill / stuporous pt. Faster , Can detect early Hemorrhage CT good for 3 B’s (Blood, Brain, Bone) IVH CECT – A VM/A n eu rysm/ T u mor CT Angio, CE CT may be considered to help identify patients at risk for hematoma expansion A newer technique for determining haematoma expansion, the ‘ leakage sign ’, has higher sensitivity and specificity for presence & haematoma expansion than the spot sign CT MRI Superior in detecting underlying structural lesions ( AVM etc. ) Gradient Echo MRI -as accurate as CT for identification of acute hemorrhage within hours of onset as regions of marked signal loss due to susceptibility effects & more accurate for identification of Chronic hemorrhage

42. Stages of ICH in CT Hyper acute (0-24 hrs) :Hyperdense Acute (1-2 days) :Hyperdense Sub acute (3-28 days) : Isodense Chronic (> month) :Hypodense Chronic : Encephalomalacia CT contrast - Spot sign

43. Formula for Estimating ICH Hematoma Volume

44. Role of DSA SAH Abnormal calcification Obvious vascular malformation Blood in unusual location, such as sylvian fissure No obvious cause of bleeding such as isolated IVH

45. ICH Score Hemphill et al. Stroke 2001, 32:891-97

46. Secondary Deterioration 25% pts. deterioration in the level of consciousness within the first 24 hrs Expansion of the Hematoma : first 3 hrs Worsening cerebral edema : 24 ~ 48 hrs Late progression of edema: 2 ~ 3 weeks

47. Outcome Mortality rate : 23% ~ 58% in 6 months GCS score on admission Hematoma volume & its progression Location of bleed Presence of IVH Use of anticoagulants Broderick et al: mortality rate at 1 month GCS < 9 , volume > 60 ml ~ 90% GCS ≥ 9 , volume < 30 ml ~ 17% P utaminal hemorrhages, lesions larger than 140 mm 2 in one slice, In thalamic hemorrhage, lesions larger than 3.3 cm in maximal diameter, cerebellar lesions larger than 3 cm had a poor prognosis

48. Management of ICH Anti oedema measures Surgical Interventions Blood Pressure reduction Reversal of Coagulopathy

49. Medical Management Journal of Stroke 2017;19(1):28-39

50. Surgical Management A spontaneous cerebral hemorrhage presents two problems that require the involvement of the Neurosurgeon : 1. Preventing or treating any secondary damage caused by the bleed itself, due to intracranial hypertension 2. Identifying a possible vascular origin of the bleed and treating it to prevent subsequent bleeding Approach to surgical consideration is still important. Candidates must be selected carefully Can be divided into 3 groups: Massive, rapidly developing lesions that effectively kill or devastate patients before they reach the hospital. For these lesions, little can or should be done. Surgery is not indicated. Small hematomas, from which the patient will make an excellent spontaneous recovery. Treatment consists of controlling the etiological factors, such as hypertension, to prevent recurrences. Surgery is not indicated. Medium-sized hematomas (hematoma volumes between the two extremes), with developing mass effect after the patient reaches the hospital. Within this third group, medical measures and surgery are potentially most helpful

51. Size : Hematomas larger than 3 cm in their widest diameter have a higher mortality and a more delayed recovery Location : Cerebellar, lobar, and right putaminal hemorrhages are most accessible to surgical drainage. For deeper hemorrhages stereotactic drainage would be preferred. Mass effect and drainage : Size of the hematoma does not, by itself, solely determine mass effect. Older patients may have sufficient pre-existing atrophy to be able to accommodate a sizable hematoma without a critical rise in ICP or shift Surgical drainage would be indicated more strongly for lesions with greater mass effect and no spontaneous decompression.

52. Too early surgery can promote rebleeding which adversely affects outcome. The ideal time to operate is unknown . After 7–10 days, blood begins to be absorbed, and the lesion becomes softer again. Ideally, drainage should occur either early or after 7–10 days for technical reasons. In general, if the patient has survived the first week, improvement occurs as edema subsides.

53. The general criteria that lead the neurosurgeon to evacuate an intracranial space-occupying process are: Deterioration of consciousness Shift of the median line exceeding 5 mm. Unilateral disappearance of basal cisterns These general criteria are less reliable in the case of spontaneous intraparenchymal hematomas because extensive literature has demonstrated the usefulness of surgical treatment when the clinical condition of a patient with spontaneous deep hematoma is compromised . A multicentre trial ( STITCH I ) which was concluded in 2005 did not show any difference between the advantages derived from surgery and from conservative treatment of hematomas deeper than one centimetre from the cortical surface. A second trial ( STICH II ) [ 59 ], which ended in 2013, seemed to suggest a modest advantage derived from the surgical evacuation of lobar hematomas, but not for deep ones.

54. A multicentre trial ( MISTIE III ) is currently being carried out: the data seems promising, although it is not at the moment conclusive. The assessment of a Neurosurgeon is therefore necessary if the patient’s clinical condition deteriorates or if the CT scan shows a shift of the midline . However, the criteria are not standardized and coded clinical deterioration is still a parameter that requires clinical assessment regarding the possibility of surgical evacuation.

55. Surgical Management Journal of Stroke 2017;19(1):28-39

56. Timing of Surgery Cerebellar hemorrhage Brainstem compression Hydrocephalus from ventricular obstruction Intraventricular hemorrhage For patients presenting with lobar clots >30 mL For most patients with ICH, the usefulness of surgery is uncertain

57. Stereotactic ICH Aspiration Many techniques Ultrasonic aspiration High pressure fluid irrigation Endoscopic aspiration Modified nucleotome Catheter aspiration with injection of thrombolytic agent (UK or tPA)

58. Potential advantages Deep putaminal or thalamic haemorrhages may be accessible Less damage to overlying brain 77% reduction in ICH volume at 48 hours, with no bleeding - Saline irrigation and aspiration after 1 mg rtPA q8h

59. Indication for monitoring ICP - by means of intraparenchymal catheter or ventricular shunt is linked to the patient’s clinical condition (GCS <8), mass effect of the bleed and evidence of cerebral oedema on brain CT scan There are no randomized studies on the monitoring - thresholds of intracranial pressure ( ICP <20 mmHg ) and cerebral perfusion pressure ( CPP 50– 70 mmHg ) are taken from studies carried out on traumatic brain injury (TBI) patients.

60. Coagulopathy Reversal INR greater than 1.4 caused by warfarin Fresh- frozen plasma (FFP) Vitamin K Prothrombin complex concentrates ( PCC ) Recombinant activated factor 7 (rFVIIa)

61. Risk factors for Recurrent ICH Lobar ICH Older age Anticoagulation Apo E e2 or e4 alleles Increased number of “microbleeds” on MRI

62. Take Home Message ICH is the 3 rd most cause of stroke after embolic and thrombotic Asian population , age >55 yrs, female gender have high incidence of ICH Hypertension is the major cause and Putamen is most common site for H. ICH Early clinical diagnosis and CT imaging helps in prompt treatment and better outcome GCS <9 and Hemorrhage > 3 cms have poor prognosis Recent large-scale clinical trials have reported that early intensive blood pressure reduction can be a safe and feasible strategy for ICH, and have suggested a safe target range for systolic blood pressure. New medical therapies associated with warfarin and non-vitamin K antagonist oral anticoagulants have been developed to treat ICH Aggressive medical management and selection of patient with medium sized Hematomas and timing of surgery are potentially helpful in saving lifes.

63. References Caplan's Stroke, A Clinical Approach.2016.5th ed., Chapter 14: Intracerebral hemorrhage. Bradley's Neurology in Clinical Practice. 7th ed, Chapter No. 66 Intracerebral hemorrhage Adams & Victor's Principles of Neurology, 10E. AHA/ASA Guidelines 2015,Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Emergency Management in Neurology, Hemorrhagic Stroke, Series Editor , Elio Agostoni Milano, Italy Journal of Stroke 2017, Spontaneous Intracerebral Hemorrhage: Management, Jun Yup Kim, Hee-Joon Bae , Department of Neurology, Stroke Center, Seoul National University Bundang Hospital, College of Medicine, Seoul National University, Seongnam, Korea ,;19(1):28-39 .

64. Thank you