The presence of microbleeds might increase the risk of ICH recurrence in warfarin users, although there are no prospective data. In a pooled analysis of ICH and ischemic stroke or transient isch- emic attack patients, microbleeds were more frequent in war- farin users with ICH than in nonwarfarin users (OR, 2.7; 95% CI, 1.6 4.4; P<0.001) but were not more frequent in warfarin users with ischemic stroke or transient ischemic attack (OR, OR, 0.01), and the presence of microbleeds was associated with a higher risk of subsequent ICH (OR, 12.1; 95% CI, 3.4 The optimal timing for resumption of anticoagulation after ICH, if necessary, is uncertain, and no randomized trial data are available to guide the decision. Several observational studies of patients with anticoagulant-related ICH found low rates of cardioembolic events while not receiving anti- coagulation therapy or recurrent ICH when anticoagulation but the results are limited by relatively small sample sizes and short durations of follow-up. A larger study of 234 patients with warfarin-related ICH followed up for a median of 34 weeks found that the risk of rebleeding with early resumption of anticoagulation exceeded the risk of thromboembolism from withholding it, whereas later, the opposite was true.294 A survival model based on these data found that the total risk of ischemic plus hemorrhagic stroke was minimized when anticoagulation was reinitiated after 10 weeks, and the authors suggested a delay of at least 1 month after ICH.294 In practice, the timing often depends on the indication for anticoagulation. In patients with pros- thetic heart valves, early resumption of anticoagulation may be necessary because of the high risk of embolism.


In patients with pros- thetic heart valves, early resumption of anticoagulation may be necessary because of the high risk of embolism. Although there are conflicting reports regarding the risk of ICH recur- rence with antiplatelet use, particularly in patients with lobar or percutaneous left atrial appendage closure303 might be safer alternatives to warfarin in some patients with atrial fibrillation. Antiplatelet agents do not appear to dramatically increase the risk of and therefore appear to be gener- ally safe for use after ICH, including ICH caused by CAA. Although dabigatran, rivaroxaban, and apixaban are reported to convey a lower risk of ICH than warfarin in atrial fibrilla- their usefulness as alternatives to warfarin after ICH remains to be determined. Meta-analyses suggest that aspirin use is associated with modest increases in ICH incidence305 but the absolute ICH risk in unselected populations appears to be small relative to the absolute numbers of MIs and ischemic A small observational study found that antiplatelet use was common after ICH and did not appear to be associated with an increase in the risk of ICH recurrence in 127 survivors of lobar hemorrhage (HR, 0.8; 95% CI, 0.3 2.3; P=0.73) and 80 survivors of deep hemorrhage (HR, 1.2; 95% There are conflicting reports regarding the use of statins in patients with ICH.308 312 In the Stroke Prevention With Aggressive Reduction in Cholesterol Levels (SPARCL) study, the benefit of high-dose atorvastatin in reducing recurrent ischemic stroke was offset in part by an increased risk of ICH.


Meta-analyses suggest that aspirin use is associated with modest increases in ICH incidence305 but the absolute ICH risk in unselected populations appears to be small relative to the absolute numbers of MIs and ischemic A small observational study found that antiplatelet use was common after ICH and did not appear to be associated with an increase in the risk of ICH recurrence in 127 survivors of lobar hemorrhage (HR, 0.8; 95% CI, 0.3 2.3; P=0.73) and 80 survivors of deep hemorrhage (HR, 1.2; 95% There are conflicting reports regarding the use of statins in patients with ICH.308 312 In the Stroke Prevention With Aggressive Reduction in Cholesterol Levels (SPARCL) study, the benefit of high-dose atorvastatin in reducing recurrent ischemic stroke was offset in part by an increased risk of ICH. Secondary analysis found that statin treatment, increasing age, and having ICH as the qualifying stroke for study enrollment were factors associated with later ICH However, a meta-analysis of 31 randomized controlled trials that included 91 588 statin-treated patients found no significant association between statin use and ICH all-cause mortality were significantly reduced with statin A Markov analysis evaluating the risks and ben- efits of statin therapy in patients with prior ICH concluded that if statin use does increase the risk of ICH, avoidance of statins should be considered in patients with ICH, particu- larly those with lobar ICH.311 Concordant with these con- clusions, statin use and age were independently associated with the presence and number of microbleeds, especially in cortical locations, in ICH patients.313 In contrast, continued statin use after ICH was associated with early neurologi- cal improvement and reduced 6-month mortality in a small There are no data on whether the reported propensity for ICH with statin use is dose depen- dent.


Secondary analysis found that statin treatment, increasing age, and having ICH as the qualifying stroke for study enrollment were factors associated with later ICH However, a meta-analysis of 31 randomized controlled trials that included 91 588 statin-treated patients found no significant association between statin use and ICH all-cause mortality were significantly reduced with statin A Markov analysis evaluating the risks and ben- efits of statin therapy in patients with prior ICH concluded that if statin use does increase the risk of ICH, avoidance of statins should be considered in patients with ICH, particu- larly those with lobar ICH.311 Concordant with these con- clusions, statin use and age were independently associated with the presence and number of microbleeds, especially in cortical locations, in ICH patients.313 In contrast, continued statin use after ICH was associated with early neurologi- cal improvement and reduced 6-month mortality in a small There are no data on whether the reported propensity for ICH with statin use is dose depen- dent. It remains unclear whether statins should be continued or discontinued in ICH patients. Prevention of Recurrent ICH: Recommendations When stratifying a patient s risk for recurrent ICH may affect management decisions, it is reasonable to consider the following risk factors for ICH recur- rence: (1) lobar location of the initial ICH; (2) older age; (3) presence and number of microbleeds on gra- dient echo MRI; (4) ongoing anticoagulation; and (5) presence of apolipoprotein E 2 or 4 alleles (Class IIa; Level of Evidence B). (Revised from the previous guideline) BP should be controlled in all ICH patients (Class I; Level of Evidence A). (Revised from the previ- ous guideline) Measures to control BP should begin immediately after ICH onset (Class I; Level of Evidence A).


(Revised from the previ- ous guideline) Measures to control BP should begin immediately after ICH onset (Class I; Level of Evidence A). (New recommendation) A long-term goal of BP <130 mmHg systolic and 80 mmHg diastolic is reasonable (Class IIa; Level of Evidence B). (New recommendation) Lifestyle modifications, including avoidance of alco- hol use greater than 2 drinks per day, tobacco use, and illicit drug use, as well as treatment of obstruc- tive sleep apnea, are probably beneficial (Class IIa; Level of Evidence B). (Revised from previous guideline) Avoidance of long-term anticoagulation with warfa- rin as a treatment for nonvalvular atrial fibrillation is probably recommended after warfarin-associated spontaneous lobar ICH because of the relatively high risk of recurrence (Class IIa; Level of Evidence B). (Unchanged from the previous guideline) Anticoagulation after nonlobar ICH and antiplate- let monotherapy after any ICH might be considered, particularly when there are strong indications for these agents (Class IIb; Level of Evidence B). (Revised from the previous guideline) The optimal timing to resume oral anticoagula- tion after anticoagulant-related ICH is uncertain. Avoidance of oral anticoagulation for at least 4 weeks, in patients without mechanical heart valves, might decrease the risk of ICH recurrence (Class IIb; Level of Evidence B). (New recommendation) If indicated, aspirin monotherapy can probably be restarted in the days after ICH, although the optimal timing is uncertain (Class IIa; Level of Evidence B). (New recommendation) The usefulness of dabigatran, rivaroxaban, or apixa- ban in patients with atrial fibrillation and past ICH to decrease the risk of recurrence is uncertain (Class IIb; Level of Evidence C). (New recommendation) There are insufficient data to recommend restric- tions on the use of statins in ICH patients (Class IIb; Level of Evidence C).


(New recommendation) There are insufficient data to recommend restric- tions on the use of statins in ICH patients (Class IIb; Level of Evidence C). (Unchanged from the previous guideline) Hemphill et al Management of Spontaneous ICH 2049 Rehabilitation and Recovery Knowledge of differences in the natural history of recovery patterns and prognosis for residual disability and function- ing between ICH and ischemic stroke is complicated by the lower rate of ICH compared with ischemic stroke and the lumping of subarachnoid hemorrhage and ICH together in many studies. There are also problems associated with the insensitivity of many of the outcome measures used in rehabilitation to allow detection of clinically meaning- ful differences between groups. Even so, there is grow- ing evidence that patients with ICH make slightly greater and faster gains in recovery than patients with ischemic In general, recovery is more rapid in the first few weeks but may continue for many months after ICH,28,316 with approximately half of all survivors remaining dependent on others for activities of daily living.30 However, patients vary in their speed and degree of recovery, and there is no hard rule as to when recovery ends. Cognition, mood, motivation, and social support all influence recovery, and it is difficult to separate intrinsic from adaptive recovery.


Cognition, mood, motivation, and social support all influence recovery, and it is difficult to separate intrinsic from adaptive recovery. A simple prognostic score that uses age, ICH volume and location, level of con- sciousness at admission, and pre-ICH cognitive impairment has been shown to predict independence at 90 days.30 Such scores are useful across all patients, but prognostic imaging techniques may also be useful with lesions in specific func- Given that ICH is often located in lobar regions and complicated by intraventricular extension, some patients with specific cognitive deficits or delayed recovery that is dis- proportionate to the size of the lesion may require specialized therapy in rehabilitation.27 The provision of stroke rehabilitation services has received considerable attention in recent years. In part this represents a need to tailor services to ensure optimal recov- ery for patients, and in part it is attributable to fiscal pres- sures on costly health services. Given strong evidence for the benefits of well-organized, multidisciplinary inpatient (stroke unit) care in terms of improved survival, recovery, and returning home compared with care provided in conven- tional nondedicated stroke wards,319 efforts have been made to extend this service model of coordinated care into the community. Specifically, early supported hospital discharge and home-based rehabilitation programs have been shown to whereas home-based therapy for stable patients has been shown to produce comparable outcomes to conventional outpatient rehabilitation.320 Comprehensive stroke units that include rehabilitation services demonstrate improved outcomes compared with other models of stroke The majority of studies do not differentiate ICH patients from those with ischemic stroke. However, a recent random- ized trial in 364 patients in China was specific to ICH, in which a 3 stage in-hospital rehabilitation program was com- pared to standard ward and medical care.


However, a recent random- ized trial in 364 patients in China was specific to ICH, in which a 3 stage in-hospital rehabilitation program was com- pared to standard ward and medical care. Improvement was significantly greater for the rehabilitation group, measured by Fugl-Meyer and Barthel scales over 6 months, with the greatest improvement evident in the first month after stroke.322 A similar result was seen in an Australian trial of very early mobilization in 72 patients, but the number of ICH patients was too small to make any sensible comparisons to those with The success of rehabilitation depends on caregiver train- ing and support; however, the likely configuration of services in any region will depend on available resources and fund- ing options. A key portion of rehabilitation should include education for the patient and caregiver regarding secondary stroke prevention and means to achieve rehabilitation goals. Rehabilitation programs should consider lifestyle changes, depression, and caregiver burden as important issues to address with the patient and caregivers. Rehabilitation and Recovery: Recommendations Given the potentially serious nature and complex pattern of evolving disability and the increasing evi- dence for efficacy, it is recommended that all patients with ICH have access to multidisciplinary rehabilita- tion (Class I; Level of Evidence A). (Revised from the previous guideline) Where possible, rehabilitation can be beneficial when begun as early as possible and continued in the community as part of a well-coordinated ( seam- less ) program of accelerated hospital discharge and home-based resettlement to promote ongoing recov- ery (Class IIa; Level of Evidence B). (Unchanged from the previous guideline) Future Considerations As documented above, the acute treatment of spontaneous ICH remains under intense investigation. Thanks largely to acute lowering of BP can now be considered safe and potentially effective for improving outcome in most instances of ICH.


Thanks largely to acute lowering of BP can now be considered safe and potentially effective for improving outcome in most instances of ICH. Ongoing and future studies in this area, such as ATACH II,324 will seek to solidify the evidence for efficacy of BP lowering and refine the BP ranges and targets that should be applied in practice. These studies will also address other outstanding questions, such as whether the spot sign or other neuroimaging findings identify patients more likely to benefit from BP lowering.325 Although current evidence does not establish a general strategy of early surgery for supratentorial ICH, studies will continue to seek subgroups of patients who benefit. Another major focus in future years will be determining whether minimally invasive surgery231 can provide the advantages of hematoma removal with less surgical trauma and there- fore greater net benefit to patients. Another rational but still unproven approach to acute ICH treatment is neuroprotec- tion of surrounding brain tissue from the toxic effects of the hematoma. The translation of biological data on neuro- protection from animals to human ICH patients may face the same difficulties encountered by the ischemic stroke neuroprotection field, such as identifying the correct animal model system and a clinically relevant time frame for treat- Emerging methods such as prehospital administra- tion of candidate neuroprotectants327 should increase the range of feasible treatment approaches and time windows for acute ICH.


The translation of biological data on neuro- protection from animals to human ICH patients may face the same difficulties encountered by the ischemic stroke neuroprotection field, such as identifying the correct animal model system and a clinically relevant time frame for treat- Emerging methods such as prehospital administra- tion of candidate neuroprotectants327 should increase the range of feasible treatment approaches and time windows for acute ICH. As targeted treatments for acute ICH continue to be ana- lyzed, it is important to note that many of the gains seen in Writing Group Disclosures Writing Group Member Employment Research Grant Other Research Support Speakers Bureau/ Honoraria Expert Witness Ownership Interest Consultant/ Advisory Board Other J. Claude Hemphill III University of California, San Francisco NIH/NINDS* None None None None None None Steven M. Greenberg Massachusetts General Hospital Avid Radiopharmaceuticals ; NIH ; NINDS ; None None None None None None Craig S. Anderson The George Institute for Global Health, University of Sydney; Royal Prince Alfred Hospital The National Health and Medical Research (NHMRC) of Australia None Takeda China*; Covidien*; Bayer* None None Pfizer*; The Medicines Company* None Kyra Becker University of Washington School of Medicine NINDS None None None None None None Bernard R. Bendok Northwestern Medical Faculty Foundation NIH None None None None None None Mary Cushman University of Vermont NIH/NHLBI ; NIH/NINDS None None None None None None Gordon L Fung University of California San Francisco Medical Center None None None None None None None Joshua N. Goldstein Massachusetts General Hospital CSL Behring ; NIH*; NINDS None None None None CSL Behring* None R. Loch Macdonald Independent Medical Practitioner Brain Aneurysm Foundation*; Canadian Institutes of Health Research*; Heart and Stroke Foundation of Canada*; Physicians Services Incorporated Foundation* None None None Edge Therapeutics* Actelion Pharmaceuticals* None Pamela H. Mitchell University of Washington NIH None None None None None None Phillip A. Scott University of Michigan NIH/NINDS None None None None None None Magdy H. Selim Harvard Medical Faculty Physicians NIH/NINDS None None None None Daiichi-Sankyo* None Daniel Woo University of Cincinnati NINDS None None None None None None This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit.


A relationship is considered to be significant if (a) the person receives $10000 or more during any 12-month period, or 5% or more of the person s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition. *Modest. Significant. Disclosures ICH outcome have resulted from improved hospital care. Improvements in hospital care tend to be incremental rather than revolutionary but can sum to substantial benefits to patients and remain a key part of future ICH research. Acute ICH treatment, like acute ischemic stroke treatment, is fundamentally limited in its ability to reduce stroke-related disability; for this reason, it is improved ICH prevention and recovery that has the greatest potential for reducing overall disease burden. In the area of ICH prevention, BP control can be considered as established treatment.273,328 There remains no disease-modifying treatment for prevention of CAA-related ICH; however, this is a major goal for ongoing and future tri- als. Another important question to be addressed is the possible role of the newer direct OACs in patients at increased ICH risk and the identification of the subgroup that might derive the greatest benefit from the reduced tendency of these agents to trigger intracranial bleeding.72,73,304 Finally, there are no spe- cific treatments or therapies established for enhancing post- ICH recovery, which highlights a tremendous opportunity for improving outcome from this devastating form of stroke. Hemphill et al Management of Spontaneous ICH 2051 References 1. Zahuranec DB, Gonzales NR, Brown DL, Lisabeth LD, Longwell PJ, Eden SV, Smith MA, Garcia NM, Hoff JT, Morgenstern LB. Presentation of intracerebral haemorrhage in a community.


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Effects of glucose level on early and long-term mortality after intracerebral haemorrhage: the Acute Brain Bleeding Analysis Study. Diabetologia. 2010;53:429 434. doi: 10.1007/s00125-009-1617-z. Reviewer Disclosures Reviewer Employment Research Grant Other Research Support Speakers Bureau/Honoraria Expert Witness Ownership Interest Consultant/ Advisory Board Other Sepideh Amin-Hanjani University of Illinois at Chicago NIH/NINDS (Site PI on MISTIE 3 trial)* None None None None None None Charlotte Cordonnier Lille University Hospital (France) None None None None None None None Matthew L. Flaherty University of Cincinnati Academic Health Center NINDS (Coinvestigator on NINDS-funded grants NS030678, (Principal Investigator, NINDS 2P50NS044283, STOP-IT Study ) Novo Nordisk (Principal Investigator of NINDS-funded STOP-IT Study, study drug supplied by Novo Nordisk)* CSL Behring* None Sense Diagnostics, LLC CSL Behring* None Eric E. Smith University of Calgary None None None None None None None This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be significant if (a) the person receives $10000 or more during any 12-month period, or 5% or more of the person s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition. *Modest. Significant. 17. B jot Y, Aboa-Eboul C, Hervieu M, Jacquin A, Osseby GV, Rouaud O, Giroud M. The deleterious effect of admission hyperglycemia on sur- vival and functional outcome in patients with intracerebral hemorrhage. Stroke. 2012;43:243 245. doi: 10.1161/STROKEAHA.111.632950. 18.


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