Patients with acute intracerebral hemorrhage present with similar stroke symptoms as ischemic stroke and subarachnoid hemorrhage patients can. For this reason you cannot accurately rely on symptoms and presentation to delineate ischemic vs hemorrhgaic stroke and thus imaging within 30 minutes of arrival has become standard emergency management.

Some symptoms are found more often in patients with hemorrhagic stroke and include

• Headache

• Changes in level of consciousness

• Progressive decline

• Nausea and vomiting

CT has become the standard acute care imaging given its high quality images, availability and cost, and time to aquire images. Several centers continue to utilize MRI imaging for stroke symptoms which has similar sensitivities although you can imagine this is not available on demand in a majority of hospitals or universities. 

Volume Calculation

Although many hemorrhages are not spherical or oval in nature the best and easiest method for calculation of ICH volumes remains the ABC/2 method.

• You need to find the axial image with the largest viewable hemorrhage and then measure the longest axis of the hemorrhage which is A. 

• Next you will measure on the same image as above the maximal perpendicualr measurement of the hemorrhage which is B.

• The height of the hemorrhage can be calculated by several methods, the 2 most common are indicated below

  • On coronal imaging find the image which largest vertical height and measure as C.

  • On axial imaging, take the number of slices with at least 25% of the maximal hemorrhage size and divide by slice thickness in cm. Many modern CTs utilize 0.5cm slice thickness thus your number of slices is doubled for C.

• Multiple AxBxC then divide by 2. This is an estimated volume in mL. Know that the more non-spheriod the hemorrhage is the volume will be more inaccurate. 

CTA

Vascular imaging is frequently recommended for several reasons in patients with intracerebral hemorrhage, although its benefits are not defined. One key benefit from vascular imaging is evaluation for vascular abnormalities which may have been the cause of the hemorrhage, although these are found <5% of the time when routinely looked for in all patients. There are several risk factors that increase the chances of finding a vascular cause to the hemorrhage;

• Age < 65

• Females

• Non-smokers

• Lobar location of ICH

• Presense of intraventricular hemorrhage

• Absense of history of hypertension or coagulopathy

Some of the abnormalities that may lead to intracerebral hemorrhage include arteriovenous malformation, arteriovenous fistula, cerebral venous thrombosis, moya-moya pattern disease, and rarely aneurysm.

Spot Sign

Another reason to perform CT angiography upon admission is to evaluate for the spot sign. Many patients present to the hospital within the first minutes or hours after onset of symptoms and suffer neurological deterioration often from hematoma expansion. Hematoma expansion occurrs early and often leads to significantly worse outcomes compared to patients that do not experience any expansion. This is seen when comparing contrasted images with a "spot" of contrast within the hemorrhage that does not resolve with delayed imaging. Repeated CTs done 3-6 hours later then demonstrate significant increase in the size of the hemorrhage. About 1/3 of all ICH patients will experience hematoma expansion (often as 6mL increase or 33%). Despite the identification of a spot size, and risk of hematoma expansion there is currently not a defined intervention known to improve outcomes or limit the expansion but this remains a high area of interest in many studies. A representative case of a spot sign is shown at the end of the imaging examples. 

The ICH Score was developed by Claude Hemphill III MD et al. at UCSF in 2001 after studying ICH patients for several years. They identified the most predictive factors of mortality at 30 days and thus the score was created. These factors and the ICH Score are listed below in the table. The total score and mortality can be seen in the chart below with scores of 3 or higher having >50% 30-day mortality. Despite the predicitve capabilites of this score it is recommended to be used as a severity score and not one to limit offered care or surgery as early DNR orders are associated with significantly increased mortality.

Another score that was developed for prediction in ICH patients was the FUNC Score. This was developed by Natalia Rost MD et al at Mass General in 2008 with an opposite aim from that of the ICH score, functional recovery. They studied ICH patients and identified predictors of functional recovery (GOS ≥ 4, moderare disability = disabled but independant, can work in sheltered setting). Many of these factors are similar to that of the ICH score but in opposite direction (age, ICH volume, GCS, ICH location), while pre-ICH cognitive impairment is also taken into account

Acute lowering of blood pressure has been at the core of ICH management since guidelines and neurocritical care were developed. This was based largely on the belief that lowering blood pressure acutely will lead to reduced rates of hematoma expansion and therefore improved outcomes (given rates of hematoma expansion and poor outcomes are higher in those with elevated pressures). INTERACT and ATACH were trials that were done with small populations and demonstrated safety with rapid reduction in blood pressure and the possibility that it may lead to reduction in hematoma expansion and improved outcomes. Given these results, INTERACT-2 and ATACH-2 were completely with very similar results, but different conclusions.

INTERACT-2 (Craig Anderson et al. 2013) 

• 2839 patients with ICH within 6 hours and SBP 150-220

• SBP lowered to either <180 (guideline) or <140 (treatment)

• Patient population - 67% from China, median SBP 179, median NIHSS 10, GCS 14, mean volume 15mL

• Results - 52 vs 56% had primary outcome (p = 0.06, mRS 4-6, severe disability - death), secondary outcome with ordinal analysis demonstrated improved outcome in mRS 0-1 (p = 0.04)

• Conclusion - Rapid reduction did not lead to reduction in death and disability, but ordinal analysis demonstrates improved functional outcomes 

• Commentary - This study demonstrates improved functional outcomes despite its failure to demonstrate significance in primary outcome. There is concern that the patient population represents a more mild ICH population given volume, GCS/NIHSS, SBP and overall severity of illness. This study also failed to change rates of hematoma expansion between the 2 groups (evaluated in small subset of patients at 24 hours) [15-18mL vs 16-20mL]

ATACH-2 (Adnan Qureshi et al. 2016)

• 1000 patients with ICH within 4.5 hours and SBP > 180

• SBP lowered to 140-179 (standard) vs 110-139 (intensive)

• Patient population - 54% from Asia, 13% Black, 8% Hispanic, median volume 10mL (but 10% > 30mL), SBP 200

• Results - No difference in primary outcome of death and disability (39% vs 38%), no difference in secondary outcomes including hematoma expansion 

• Conclusion - Trial does not support the reduction of SBP to 110-139 in patients with acute ICH

• Commentary - Although this population was smaller than that in INTERACT-2, it included patients with higher mean SBPs upon arrival, and still failed to show any improvements in outcomes or hematoma expansion. Most of the patients were treated to well below their upper limit of BP parameters. There also was noted an increase in the rates of AKI, which was concerning given the slightly higher SBP in this population. This study also put into question the validity of improved outcome in INTERACT-2

There continue to remain 2 main tribes of thought in ICH blood pressure management. The believers of INTERACT-2 with improved outcomes, and the skeptics (may be a third group that believes in individualized parameters). There have been no high quality trials since these were completed and most of what has been published since has been subgroup analysis of these major trials and single center data. The guidelines remain unchanged with the following recommendations

• For patients with ICH and SBP <220 it appears safe to rapidly lower SBP <140 and this may result in improved functional outcomes

• For patients with ICH and SBP >220, recommendations are to moderately reduce SBP

More reading on the topic can be found in these readings:

Intensive Blood Pressure Lowering in Intracerebral Hemorrhage

Optimal Blood Pressure After Intracerebral Hemorrhage

The Case of Differing Perspectives

First and foremost you need to know about your anticoagulants before you can create a strategy about reversal as often your approach to reversal depends on the drug used, time since last dose, and patient factors. Please check out the pharmacology page for more info

Anticoagulation and Antiplatelets 

Anticoagulant Reversal for Intracerebral Hemorrhage

Patients with any intracranial hemorrhage require immediate and rapid correction of their coagulopathy. I have often seen patients that weren't reversed because they were "not sick" or "doing fine" until they weren't. Remember that hematoma expansion occurs early in patients with intracerebral hemorrhage and those on anticoagulants are at higher risk for hematoma expansion and thus wornsed outcomes. 

A decade ago, reversal was an easier question as most patients were on wafarin for anticoagulation. Direct thrombin and Xa inhibitors were largely pushed out to patients given their comparison of stroke and cerebrovascular events, safety and ease of prescription (not requiring blood level monitoring), and most importantly to us, less major hemorrhagic events. 

There are several drugs for us to "reverse" a patient with wafarin, namely fresh frozen plasma (FFP), vitamin K, and prothrombin complex concentrates (PCC). All patients on warfarin should recieve IV vitamin K. This takes about 24 hours for effect as your are supplying the liver with substrate to make futher factors needed for clotting. Several studies have shown that PCCs are superior to FFP leading to improved outcomes (Likely from reduced time to reversal of coagulopathy, and less side effects of drug). Patients on direct Xa inhibitors have a direct reversal, andexanet alpha, although this drug is extremely extensive and to date has not been shown to improve outcomes in ICH even if it may lead to less hemorrhage expansion. Given this information many centers continue to utilize PCCs for factor replacement in these patients. 

Most of the patients that are being reversed are anticoagulated for atrial fibrillation. These patients can be reversed and do not need to have anticoagulation restarted. Studies are unclear whether patients benefit from resumption of anticoagulation (less ischemic stroke risk, but increased chance of recurrent hemorrhage). The ASPIRE trial is currently enrolling patients attempting to answer this question. When your patient has another indication they still should be reversed, but require more thought. The one patient that requires collaboration and likely to least amount of time reversed are patients with LVADs. They are becoming more and more prominent as this surgery is more available, and require wafarin compared with the safer newer drugs. Reversal is still recommended, but initiation of heparin infusion may be considered as earlier as 24 hours after hemorrhage stabilization as this can be started/stopped depending on your patient. 

Antiplatelet Reversal in Intracerbral Hemorrhage

Reversal of any underlying coagulopathy should be done with patients with ICH, although there is a caviet to this statement. The PATCH trial was a comparison of patients on antiplatelets (mostly aspirin) that recieved platelet transfusion vs those receving standard care in which those recieving transfusions fared worse and suffered worse clinical outcomes (mRS). It is still recommended that if your patient will need emergency placement of an EVD or require surgery that platelets are given, although there is no direct evidence for this approach, it remains as a consensus from surgeons. 

Patients with low platelets or thrombocytopenia are much more difficult to make clinical decisions on. Whether the platelets are acutely vs chronically low, what the etiology of the thrombocytopenia is, and if any additional coagulation abnormalities exist, all significantly matter. Therefore, there is not a recommend number above which patients do better. Often neurosurgeons will ask for >75k or >100k, especially if there is a drain in place or just underwent surgery. This is often a time when consideration of thromboelastography (TEG) with platelet mapping may provider further insight. 

Conclusions

• All intracerebral hemorrhage patients should have coagulopathy reversed

• wafarin = vitamin K, and PCCs

• direct Xa inhibitors  = andexanet alpha, although PCCs considered

• antiplatelets = no reversal unless requiring surgery

• consider TEG when not straight forward answer/reversal

Seizures are a common result from acute intracerebral hemorrhage and result in either acute seizures of those that present post-hopsital during recovery or afterwards as a result of chronic brain injury. Acute seizures happen in roughly 10% of patients and most happen at ictus (the event) or immediately afterwards. Given that this happens infrequently and drugs are not benign, it is not recommend to prophylax patients with anticonvulsive medications. Several studies demonstrated worse outcomes when this was more common practice and levetiracetam appears less harmful it is still not recommended routinely. It is less likely that subcortical hemorrhages cause significant seizures although this can occur. Injuries to the cerebellum and brainstem should not result in seizure.

Factors that are associated with increased chance of seizures are

• younger age = more brain

• cortical blood

• temporal lobe involvment

Surgery remains one of the first things to think about in ICH patients. Often you are confronted with large (>30mL) hemorrhages that are causing or close to causing brainstem compression and uncal herniation syndrome. Surgery is indicated in all of these cases as an emergency evacuation of the space occupying mass, just like removal of an epidural hematoma. There are no clinical trials or studies in this group of patients as there is no "control" group. Those that are deemed in need of emergent surgery for ICH evacuation but never recieve it likely dont survive. 

In contrast, there is a group of patients that we have spent decades now trying to figure out how surgery can be useful. These are patients with smaller hemorrhages (< 30mL), have largely subcortical hemorrhages (thalamus, basal ganglia, etc) and don't have an immediate requirement for surgery for survival. Below I will summarize the most important trials that have been completed and my take on the studies. The bottom line is that there is no definative evidence to date that surgery in this group of patients leads to improved outcomes. 

STICH (David Mendelow et al. 2005)

• 1033 patients with acute spontaneous ICH, GCS > 5 and neurosurgeon uncertain of benefits to surgery 

• Compared early surgery (within 24 hours) vs conservative medical therapy

• Patient population - 80% GCS >9, 42% basal ganglia/thalamus, 38mL ICH volume

• Results - At 6 months, 122/468 (26%) in surgery group had favorable outcome compared with 118/496 (24%) in the medical group. 

• Conclusion - Evacuation of ICH did not lead to improvement in survival or outcomes when compared with standard medical care. 

• Commentary - This study remains one of the most talked about for everything other than the actual results. The most important inclusion criteria was uncertainty from a neurosurgeon. 140 patients in the conservative medical therapy group recieved craniotomy or burr hole from worsening! The outcome scale was derived just for this study and a novel score then based on presenting GCS, age and ICH volume (all part of ICH score). Much is also talked about how cortically based hemorrhages fared better with surgery, but this study was not powered to answer this question. Overall, most patients did poorly with only ~25% in both groups reaching favorable outcomes at 6 months.

STICH II (David Mendelow et al. 2013)

• 601 patients with acute cortical/lobar hemorrhage 10-100mL, and no IVH

• Compared hematoma evacuation within 12 hours compared with conservative medical therapy

• Patient population - median age 65, 57% male, 65% GCS ≥13, average volume 37mL

• Results - At 6 months, 174/297 (59%) in the surgery group compared with 178/286 (62%) had unfavorable outcomes based on prognosis-based dichotomized GOSE. 

• Conclusion - There was no significant difference in outcomes or mortality at 6 months in those recieving early surgery vs conservative care.

• Commentary - Although no significant difference between groups, the authors interpretation of the study was that surgery did not increase mortality and may lead to "clinically relevant survival" which is not demonstrated by their data. Again their results are imperfect given signifcant crossover with 62 conservative care patients receiving some type of hematoma evacuation surgery. This study again failed to demonstrate signifcant gains surgery can provide to routinely offer to patients with superficial hemorrhages and no IVH.

MISTIE III 

• 506 patients with spontaneous ICH > 30mL

• Compared minimally invasive catheter evacuation followed by thrombolysis (MISTIE) with standard medical care of ICH

• Patient population - median age 62, 61% male, 76% GCS ≥ 9, median NIHSS 19, ICH volume 45mL, 62% deep hemorrhages

• Results - At 365 days, 45% of surgical patients vs 41% of medical care patients had favorable mRS 0-3. 

• Conclusion - MISTIE technique did not improve favorable outcomes in patients compared to standard medical treatment.

• Commentary - This is the largest prospective minimally invasive study to date and still did not demonsrate benefit. Only 58% of the surgical patients reached the volume endpoint of ≤15mL, which may demonstrate why this is not a perfected treatment or surgery. In those that did reach this endpoint or even less, they had a significantly improved chance of favorable functional outcome (mRS). I may be biased but believe we will eventually identify surgical evacuation techniques that benefit ICH patients, but it is not ready to apply to everyone and continued clinical trials should continue.