2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association

HomeStrokeVol. 53, No. 72022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessReview ArticlePDF/EPUB2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association Steven M. Greenberg, MD, PhD, FAHA, Chair, Wendy C. Ziai, MD, MPH, FAHA, Vice Chair, Charlotte Cordonnier, MD, PhD, Dar Dowlatshahi, MD, PhD, FAHA, Brandon Francis, MD, MPH, Joshua N. Goldstein, MD, PhD, FAHA, J. Claude Hemphill III, MD, MAS, FAHA, Ronda Johnson, MBA, Kiffon M. Keigher, MSN, ACNP-BC, RN, SCRN, William J. Mack, MD, MS, FAHA, J. Mocco, MD, MS, FAHA, Eileena J. Newton, MD, Ilana M. Ruff, MD, Lauren H. Sansing, MD, MS, FAHA, Sam Schulman, MD, PhD, Magdy H. Selim, MD, PhD, FAHA, Kevin N. Sheth, MD, FAHA, Nikola Sprigg, MD, Katharina S. Sunnerhagen, MD, PhD and on behalf of the American Heart Association/American Stroke Association Steven M. GreenbergSteven M. Greenberg Search for more papers by this author , Wendy C. ZiaiWendy C. Ziai Search for more papers by this author , Charlotte CordonnierCharlotte Cordonnier Search for more papers by this author , Dar DowlatshahiDar Dowlatshahi Search for more papers by this author , Brandon FrancisBrandon Francis Search for more papers by this author , Joshua N. GoldsteinJoshua N. Goldstein Search for more papers by this author , J. Claude Hemphill IIIJ. Claude Hemphill III Search for more papers by this author , Ronda JohnsonRonda Johnson Search for more papers by this author , Kiffon M. KeigherKiffon M. Keigher Search for more papers by this author , William J. MackWilliam J. Mack *AHA Stroke Council Scientific Statement Oversight Committee on Clinical Practice Guideline liaison. Search for more papers by this author , J. MoccoJ. Mocco †AANS/CNS liaison. Search for more papers by this author , Eileena J. NewtonEileena J. Newton Search for more papers by this author , Ilana M. RuffIlana M. Ruff ‡AHA Stroke Council Stroke Performance Measures Oversight Committee liaison. Search for more papers by this author , Lauren H. SansingLauren H. Sansing Search for more papers by this author , Sam SchulmanSam Schulman Search for more papers by this author , Magdy H. SelimMagdy H. Selim Search for more papers by this author , Kevin N. ShethKevin N. Sheth *AHA Stroke Council Scientific Statement Oversight Committee on Clinical Practice Guideline liaison. Search for more papers by this author , Nikola SpriggNikola Sprigg Search for more papers by this author , Katharina S. SunnerhagenKatharina S. Sunnerhagen Search for more papers by this author and on behalf of the American Heart Association/American Stroke Association Search for more papers by this author Originally published17 May 2022https://doi.org/10.1161/STR.0000000000000407Stroke. 2022;53:e282–e361Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: May 17, 2022: Ahead of Print Top 10 Take-Home Messages for the Management of Patients With Spontaneous Intracerebral Hemorrhage GuidelineThe organization of health care systems is increasingly recognized as a key component of optimal stroke care. This guideline recommends development of regional systems that provide initial intracerebral hemorrhage (ICH) care and the capacity, when appropriate, for rapid transfer to facilities with neurocritical care and neurosurgical capabilities.Hematoma expansion is associated with worse ICH outcome. There is now a range of neuroimaging markers that, along with clinical markers such as time since stroke onset and use of antithrombotic agents, help to predict the risk of hematoma expansion. These neuroimaging markers include signs detectable by noncontrast computed tomography, the most widely used neuroimaging modality for ICH.ICHs, like other forms of stroke, occur as the consequence of a defined set of vascular pathologies. This guideline emphasizes the importance of, and approaches to, identifying markers of both microvascular and macrovascular hemorrhage pathogeneses.When implementing acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome.ICH while anticoagulated has extremely high mortality and morbidity. This guideline provides updated recommendations for acute reversal of anticoagulation after ICH, highlighting use of protein complex concentrate for reversal of vitamin K antagonists such as warfarin, idarucizumab for reversal of the thrombin inhibitor dabigatran, and andexanet alfa for reversal of factor Xa inhibitors such as rivaroxaban, apixaban, and edoxaban.Several in-hospital therapies that have historically been used to treat patients with ICH appear to confer either no benefit or harm. For emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy appears to have no benefit for outcome, whereas the use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome. Similar considerations apply to some prophylactic treatments historically used to prevent medical complications after ICH. Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis, and prophylactic antiseizure medications in the absence of evidence for seizures do not improve long-term seizure control or functional outcome.Minimally invasive approaches for evacuation of supratentorial ICHs and intraventricular hemorrhages‚ compared with medical management alone‚ have demonstrated reductions in mortality. The clinical trial evidence for improvement of functional outcome with these procedures is neutral, however. For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (>15 mL) in addition to previously recommended indications of neurological deterioration, brainstem compression, and hydrocephalus.The decision of when and how to limit life-sustaining treatments after ICH remains complex and highly dependent on individual preference. This guideline emphasizes that the decision to assign do not attempt resuscitation status is entirely distinct from the decision to limit other medical and surgical interventions and should not be used to do so. On the other hand, the decision to implement an intervention should be shared between the physician and patient or surrogate and should reflect the patient’s wishes as best as can be discerned. Baseline severity scales can be useful to provide an overall measure of hemorrhage severity but should not be used as the sole basis for limiting life-sustaining treatments.Rehabilitation and recovery are important determinants of ICH outcome and quality of life. This guideline recommends use of coordinated multidisciplinary inpatient team care with early assessment of discharge planning and a goal of early supported discharge for mild to moderate ICH. Implementation of rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours after moderate ICH; however, early aggressive mobilization within the first 24 hours after ICH appears to worsen 14-day mortality. Multiple randomized trials did not confirm an earlier suggestion that fluoxetine might improve functional recovery after ICH. Fluoxetine reduced depression in these trials but also increased the incidence of fractures.A key and sometimes overlooked member of the ICH care team is the patient’s home caregiver. This guideline recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.PreambleSince 1990, the American Heart Association (AHA)/American Stroke Association (ASA) has translated scientific evidence into clinical practice guidelines with recommendations to improve cerebrovascular health. These guidelines, which are based on systematic methods to evaluate and classify evidence, provide a foundation for the delivery of quality cerebrovascular care. The AHA/ASA sponsors the development and publication of clinical practice guidelines without commercial support, and members volunteer their time to the writing and review efforts.Clinical practice guidelines for stroke provide recommendations applicable to patients with or at risk of developing cerebrovascular disease. The focus is on medical practice in the United States, but many aspects are relevant to patients throughout the world. Although it must be acknowledged that guidelines may be used to inform regulatory or payer decisions, the core intent is to improve quality of care and align with patients’ interests. Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances and should not replace clinical judgment; furthermore, the recommendations set forth should be considered in the context of individual patient values, preferences, and associated conditions.The AHA/ASA strives to ensure that guideline writing groups contain requisite expertise and are representative of the broader medical community by selecting experts from a broad array of backgrounds, representing different sexes, races, ethnicities, intellectual perspectives, geographic regions, and scopes of clinical practice and by inviting organizations and professional societies with related interests and expertise to participate as endorsers. The AHA/ASA has rigorous policies and methods for development of guidelines that limit bias and prevent improper influence. The complete policy on relationships with industry and other entities (RWI) can be found at https://professional.heart.org/-/media/phd-files/guidelines-and-statements/policies-devolopment/aha-asa-disclosure-rwi-policy-5118.pdf?la=en.Beginning in 2017, numerous modifications to AHA/ASA guidelines have been implemented to make guidelines shorter and enhance user-friendliness. Guidelines are written and presented in a modular knowledge chunk format; each chunk includes a table of recommendations, a brief synopsis, recommendation-specific supportive text, and, when appropriate, flow diagrams or additional tables. Hyperlinked references are provided to facilitate quick access and review. Other modifications to the guidelines include the addition of Knowledge Gaps and Future Research segments in some sections and a web guideline supplement (Online Data Supplement) for useful but noncritical tables and figures.Joseph P. Broderick, MD, FAHAChair, AHA Stroke Council Scientific Statement Oversight Committee1. IntroductionApproximately 10% of the 795 000 strokes per year in the United States are intracerebral hemorrhages (ICHs),1 defined by brain injury attributable to acute blood extravasation into the brain parenchyma from a ruptured cerebral blood vessel. The clinical impact of ICH appears disproportionately high among lower-resource populations both in the United States and internationally. In US-based studies, ICH incidence has been reported to be ≈1.6-fold greater among Black than White people2 and 1.6-fold greater among Mexican American than non-Hispanic White people.3 Internationally, ICH incidence is substantially higher in low- and middle-income versus high-income countries, both as a proportion of all strokes and in absolute incidence rates.4,5Several additional features of ICH make it a greater public health threat than conveyed by incidence numbers alone. ICH is arguably the deadliest form of acute stroke, with early-term mortality about 30% to 40% and no or minimal trend toward improvement over more recent time epochs.6–9 Incidence of ICH increases sharply with age and is therefore expected to remain substantial as the population ages, even with counterbalancing public health improvements in blood pressure (BP) control.8 Another growing source of ICH is more widespread use of anticoagulants,10 a trend likely to counterbalance the reduced ICH risk associated with increasing prescription of direct oral anticoagulants (DOACs) relative to vitamin K antagonists (VKAs).11ICH thus remains in need of novel treatments and improved application of established approaches for every aspect of the disease: primary and secondary prevention, acute inpatient care, and poststroke rehabilitation and recovery. This guideline seeks to synthesize data in the ICH field into practical recommendations for clinical practice.1.1. Methodology and Evidence ReviewThe recommendations listed in this guideline are, whenever possible, evidence based and supported by extensive evidence review. A search for literature derived from research principally involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline was conducted between October 2020 and March 2021. Additional trials published between March 2021 and November 2021 that affected the content, Class of Recommendation (COR), or Level of Evidence (LOE) of a recommendation were included when appropriate. For specific search terms used‚ readers are referred to the Online Data Supplement, which contains the final evidence tables summarizing the evidence used by the guideline writing group to formulate recommendations. In addition, the guideline writing group reviewed documents related to subject matter previously published by the AHA/ASA. References selected and published in the present document are representative and not all inclusive.Each topic area was assigned a primary writer and a primary and sometimes secondary reviewer. Author assignments were based on the areas of expertise of the members of the guideline writing group and their lack of any RWI related to the section material. All recommendations were fully reviewed and discussed among the full guideline writing group to allow diverse perspectives and considerations for this guideline. Recommendations were then voted on, and a modified Delphi process was used to reach consensus. Guideline writing group members who had RWI that were relevant to certain recommendations were recused from voting on those particular recommendations. All recommendations in this guideline were agreed to by between 88.9% and 100% of the voting guideline writing group members.1.2. Organization of the Writing GroupThe guideline writing group consisted of vascular neurologists, neurocritical care specialists, neurological surgeons, an emergency physician, a hematologist, a rehabilitation medicine physician, a board-certified acute care nurse practitioner, a fellow-in-training, and a lay/patient representative. The writing group included representatives from the AHA/ASA, the American Association of Neurological Surgeons/Congress of Neurological Surgeons, and the American Academy of Neurology. Appendix 1 of this document lists guideline writing group members’ relevant RWI and other entities. For the purposes of full transparency, the guideline writing group members’ comprehensive disclosure information is available online.1.3. Document Review and ApprovalThis document was reviewed by the AHA Stroke Council Scientific Statement Oversight Committee, the AHA Science Advisory and Coordinating Committee, and the AHA Executive Committee; reviewers from the American Academy of Neurology, the Society of Vascular and Interventional Neurology, and the American Association of Neurological Surgeons/Congress of Neurological Surgeons; and 53 individual content reviewers. Appendix 2 lists reviewers’ comprehensive disclosure information.1.4. Scope of the GuidelineThis guideline addresses the diagnosis, treatment, and prevention of ICH in adults and is intended to update and replace the AHA/ASA 2015 ICH guideline.12 This 2022 guideline is limited explicitly to spontaneous ICHs that are not caused by head trauma and do not have a visualized structural cause such as vascular malformation, saccular aneurysm, or hemorrhage-prone neoplasm. These hemorrhages without a demonstrated structural or traumatic cause are often referred to as primary ICH (see further comment on this terminology in Section 2.1, Small Vessel Disease Types). This guideline thus does not overlap with AHA/ASA guidelines or scientific statements on the treatment of arteriovenous malformations,13 aneurysmal subarachnoid hemorrhage,14 or unruptured saccular aneurysms.13,15 This guideline does, however, address imaging approaches to ICH that help differentiate primary ICH from these secondary causes.This guideline aims to cover the full course of primary ICH (Figure 1), from the location and organization of emergency care (Section 3), initial diagnosis and assessment (Section 4), and acute medical and surgical interventions (Sections 5.1, 5.2, and 6) to further inpatient care of post-ICH complications (Sections 5.3–5.5), goals of care assessment (Section 7), rehabilitation and recovery (Section 8), and secondary prevention of recurrent ICH (Section 9). Because of the substantial differences in pathogenesis and course between ICH and ischemic stroke, the writing group sought, when possible, to base its recommendations on data derived specifically from ICH patient groups. Some aspects of inpatient medical care and post-ICH rehabilitation are likely to be similar between patients with ICH and patients with ischemic stroke, however. Readers are therefore referred to relevant AHA/ASA guidelines and scientific statements for ischemic stroke in these overlapping areas.16,17Table 1 is a list of associated AHA/ASA guidelines and scientific statements that may be of interest to the reader.Table 1. Associated AHA/ASA Guidelines and StatementsTitleOrganizationPublication yearAHA/ASA guidelines 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke AssociationAHA/ASA2021 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice GuidelinesACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA2017 Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke AssociationAHA/ASA2016 Guidelines for the Management of Patients With Unruptured Intracranial Aneurysms: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke AssociationAHA/ASA2015 Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke AssociationAHA/ASA2015 Guidelines for the Primary Prevention of Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke AssociationAHA/ASA2014 Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke AssociationAHA/ASA2012AHA/ASA scientific statements Care of the Patient With Acute Ischemic Stroke (Prehospital and Acute Phase of Care): Update to the 2009 Comprehensive Nursing Care Scientific Statement: A Scientific Statement From the American Heart AssociationAHA/ASA2021 Management of Brain Arteriovenous Malformations: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke AssociationAHA/ASA2017 Prevention of Stroke in Patients With Silent Cerebrovascular Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke AssociationAHA/ASA2017 Palliative and End-of-Life Care in Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke AssociationAHA/ASA2014AAPA indicates American Association of Physician Assistants; ABC, Association of Black Cardiologists; ACC, American College of Cardiology; ACPM, American College of Preventive Medicine; AGS, American Geriatrics Society; AHA, American Heart Association; APhA, American Pharmacists Association; ASA, American Stroke Association; ASH, American Society of Hypertension; ASPC, American Society for Preventive Cardiology; NMA, National Medical Association; and PCNA, Preventive Cardiovascular Nurses Association.Download figureDownload PowerPointFigure 1. Guideline overview for primary ICH. ICH indicates intracerebral hemorrhage. Recommendations on the topics above can be found in the guideline in the sections indicated: *Sections 3 and 5. †Section 4. ‡Sections 5 and 6. §Section 7. ∥Section 5. #Section 8. **Section 9.Another area where this ICH guideline interfaces with prior ischemic stroke guidelines is the challenging area of antithrombotic agent use in patients after ICH who are at risk for both recurrent ICH and ischemic stroke (Section 9.1.3, Management of Antithrombotic Agents). This guideline does not attempt to reassess the extensive literature on assessment of future ischemic stroke risk and instead refers the reader to existing AHA guidelines on primary and secondary ischemic stroke prevention.18,19This ICH guideline has a new section on assessment of ICH risk in individuals with no prior ICH but with neuroimaging findings such as cerebral microbleeds or cortical superficial siderosis suggestive of a hemorrhage-prone microvasculopathy. This topic, which was also previously discussed in an AHA scientific statement on the wider area of silent cerebrovascular disease,20 does not fall strictly under the heading of ICH management. This guideline writing group nonetheless included the section (9.2, Primary ICH Prevention in Individuals With High-Risk Imaging Findings) because of its close relationship to the considerations used for secondary prevention of recurrent ICH (Section 9.1, Secondary Prevention) and the high frequency with which these small hemorrhagic lesions are detected as incidental findings on magnetic resonance imaging (MRI) performed for other indications. Evidence on how to interpret and act on incidental hemorrhagic lesions remains limited but is likely to grow with the widespread incorporation of blood-sensitive MRI methods into research studies and clinical practice.1.5. COR and LOERecommendations are designated with both a COR and an LOE. The COR indicates the strength of recommendation, encompassing the estimated magnitude and certainty of benefit in proportion to risk. The LOE rates the quality of scientific evidence supporting the intervention on the basis of the type, quantity, and consistency of data from clinical trials and other sources (Table 2).Table 2. Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care (Updated May 2019)*Table 2. Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care (Updated May 2019)*AbbreviationsAbbreviationMeaning/PhraseADLactivities of daily livingAFatrial fibrillationAHAAmerican Heart AssociationaPCCactivated prothrombin complex concentrateASAAmerican Stroke AssociationATACH-2Antihypertensive Treatment of Acute Cerebral Hemorrhage IIAVERTA Very Early Rehabilitation TrialBPblood pressureCAAcerebral amyloid angiopathyCLEAR IIIClot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase IIICLOTSClots in Legs or Stockings After StrokeCORClass of RecommendationCPPcerebral perfusion pressureCTcomputed tomographyCTAcomputed tomography angiographyDBPdiastolic blood pressureDIAGRAMDiagnostic Angiography to Find Vascular MalformationsDNARdo not attempt resuscitationDOACdirect oral anticoagulantDSAdigital subtraction angiographyDVTdeep vein thrombosisEDemergency departmentEIBPLearly intensive blood pressure loweringEMSemergency medical servicesERICHEthnic/Racial Variations of Intracerebral HemorrhageEVDexternal ventricular drain/drainageFFPfresh-frozen plasma4-F PCC4-factor prothrombin complex concentrateGCSGlasgow Coma ScaleHEhematoma expansionHRhazard ratioICHintracerebral hemorrhageICPintracranial pressureICUintensive care unitINCHInternational Normalized Ratio (INR) Normalization in Coumadin Associated Intracerebral HemorrhageINRinternational normalized ratioINTERACT2The Second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage TrialIPCintermittent pneumatic compressionIVCinferior vena cavaIVHintraventricular hemorrhageIVTintraventricular thrombolysisLMWHlow-molecular-weight heparinLOELevel of EvidenceLOSlength of stayLVADleft ventricular assist deviceMISminimally invasive surgeryMISTIE IIIMinimally Invasive Surgery Plus rt-PA for Intracerebral Hemorrhage EvacuationMRAmagnetic resonance angiographyMRImagnetic resonance imagingmRSmodified Rankin ScaleMSUmobile stroke unitNCCTnoncontrast computed tomographyNDneurological deteriorationNICE-SUGARNormoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm RegulationNIHSSNational Institutes of Health Stroke ScaleNSAIDnonsteroidal anti-inflammatory drugORodds ratioPCCprothrombin complex concentratePEpulmonary embolismPREVAILEvaluation of the WATCHMAN Left Atrial Appendage [LAA] Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin TherapyPRoFESSPrevention Regimen for Effectively Avoiding Second StrokesPROGRESSPerindopril Protection Against Recurrent Stroke StudyPROTECT-AFWATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial FibrillationQASCQuality in Acute Stroke CareRCTrandomized controlled trialRRTrenal replacement therapyRWIrelationships with industry and other entitiesSAEserious adverse eventSBPsystolic blood pressureSPARCLStroke Prevention by Aggressive Reduction in Cholesterol LevelsSSRIsselective serotonin reuptake inhibitorsSTICHSurgical Trial in Intracerebral HemorrhageTBItraumatic brain injuryTXAtranexamic acidUFHunfractionated heparinVKAvitamin K antagonistVTEvenous thromboembolism2. General Concepts2.1. Small Vessel Disease TypesDespite our use of the term primary ICH to distinguish from ICH with a demonstrated structural cause (Section 1.4, Scope of the Guideline), these seemingly spontaneous hemorrhages are not truly primary but rather represent the consequence of defined underlying (and often co-occurring) vascular pathologies. The 2 common cerebral small vessel pathologies that account for the overwhelming majority of primary ICH are arteriolosclerosis and cerebral amyloid angiopathy (CAA). Each is a common age-related pathology, appearing at autopsy at moderate to severe extents in 30% to 35% of individuals enrolled in a longitudinal study of aging.21 Arteriolosclerosis (also referred to as lipohyalinosis) is detected as concentric hyalinized vascular wall thickening favoring the penetrating arterioles of the basal ganglia, thalamus, brainstem, and deep cerebellar nuclei (collectively referred to as deep territories). Its major associated risk factors are hypertension, diabetes, and age. CAA is defined by deposition primarily of the β-amyloid peptide in the walls of arterioles and capillaries in the leptomeninges, cerebral cortex, and cerebellar hemispheres (lobar territories). The primary risk factors for CAA are age and apolipoprotein E genotypes containing the ε2 or ε4 alleles.ICH occurs in a relatively small subset of those brains with advanced arteriolosclerosis or CAA, typically in deep territories for arteriolosclerosis and lobar territories for CAA, the brain locations favored by the underlying pathologies. Small, often asymptomatic cerebral microbleeds in these compartments are substantially more common, occurring in >20% of population-based individuals >60 years of age scanned with sensitive T2*-weighted MRI methods.22,23 The presence of multiple strictly lobar ICHs, microbleeds, or cortical superficial siderosis (chronic blood products over the cerebral subpial surface) has been pathologically validated as part of the Boston criteria to detect CAA-related hemorrhage with reasonably high specificity and sensitivity.24 Microbleeds associated with arteriolosclerosis tend to occur in deep territories but can appear in lobar territories as well.The underlying small vessel types of ICH have several practical implications for the formulation of ICH guidelines. They establish a hemorrhage-prone environment in which use of antithrombotic agents creates increased risk of ICH.25 It is important to note, however, that the small vessel pathologies that underlie ICH are also associated with increased risk of ischemic stroke,26 highlighting the complexity and importance of balancing the risks versus benefits of antithrombotic treatment. Among the cerebral small vessel diseases, CAA inferred by the Boston criteria appears to confer substantially greater risk for recurrent hemorrhage than arteriolosclerosis (recurrent ICH rates in a pooled analysis of 7.39%/y after CAA-related ICH versus 1.11%/y after non–CAA-related ICH).272.2. Mechanisms for ICH-Related Brain InjuryICH is understood to injure surrounding brain tissue through the direct pressure effects of an acutely expanding mass lesion and through secondary physiological and cel