It is recommended that rescue personnel are adequately trained to recognize stroke signs early on and to manage the patient at this stage, during which the following are necessary:

Furthermore, it is important to collect essential informations such as the time of onset of symptoms and medical and pharmacological history.

American Heart Association / American Stroke Association (AHA/ASA) (class I, level B) recommends using assessment tools in order to quantify objectively the severity of each individual case [3]. The National Institutes of Health Stroke Scale (NIHSS) could be a valuable tool [4, 5]. However, patients with cerebral hemorrhage suffer from an altered state of consciousness, and this aspect limits the usefulness of the NIHSS. For this reason it seems more appropriate to use the ICH score [6, 7].

Clinical presentation alone is not sufficient to differentiate hemorrhagic stroke from ischemic stroke, as both are characterized by acute onset of neurological symptoms. However, there are some elements that can point to hemorrhagic stroke: severe headache, vomiting, Blod Pressure (BP) systolic values > 220 mmHg, level of vigilance reduced even to coma level, and progression of symptoms within hours or minutes [8].

For the differential diagnosis of acute ischemia and cerebral hemorrhage, the brain CT scan is still considered the gold standard according to the guidelines of the leading national and international scientific societies (AHA/ASA, European Stroke Organization (ESO); Stroke Prevention an Educational Awareness Diffusion (SPREAD)) [3, 9, 10]. In fact, although gradient echo and T2 susceptibility-weighted MRI is more sensitive than CT scan in identifying hyperacute cerebral hemorrhage [11, 12], its use is limited by several factors including execution time, cost, distance from the emergency area, and patient intolerance [13].

Intraparenchymal brain hemorrhage may be primary (80 % of cases, associated with hypertension or amyloid angiopathy) or secondary (associated with arteriovenous malformations (AVMs), aneurysms, tumors, cerebral venous thrombosis). Since this difference involves some prognostic and therapeutic implications, a more detailed diagnosis is needed if a secondary form is suspected.

The AHA/ASA guidelines suggest which factors should raise suspicion for a secondary hemorrhage and which are the most appropriate investigations: [3] young age (<65 years); female gender; absence of risk factors such as cigarette smoking, hypertension, or coagulopathy; atypical location of the lesion (lobar); or intraventricular hemorrhage extension [14, 15].

The following medical examinations must be carried out if a more detailed diagnosis is needed: brain MRI, Magnetic Resonance Angiography (MRA), and CT angiography with venous sequences. If there is a high clinical or radiological suspicion, DSA is recommended (class IIa, level of evidence B-AHA/ASA) [3].

The high percentage of patients who suffer early clinical deterioration after the onset of cerebral hemorrhage is partly due to the increase in hematoma volume during the first hours. Such an event negatively influences the prognosis and is associated with an increased risk of mortality. It is therefore important to identify patients at high risk of hematoma expansion.

For this purpose, the AHA/ASA guidelines (class IIB, level of evidence B) recommend that CT angiography and brain CT scan are performed with contrast medium [3], which allows detection of the so-called spot sign, i.e., contrast medium uptake in the area of the hematoma, whose presence correlates with the risk of the hemorrhagic lesion expanding [16, 17].

The AHA/ASA guidelines suggest that a panel of standard blood tests are performed in emergency in the case of cerebral hemorrhage [3]: blood count, serum electrolytes, urea, creatinine, blood glucose (hyperglycemia is associated with a worse outcome), liver function, International Normalized Ratio (INR), activated partial thromboplastin time (aPTT) (useful for determining the level of coagulation, especially in patients on anticoagulant therapy), and troponin (an increase in troponin has proven to be associated with a worse outcome) [18, 19].

Once the patient has been diagnosed, the ESO guidelines recommend prompt admission to a stroke or intensive care unit with dedicated medical and nursing staff [9]. Patients treated in these specific settings show lower mortality and disability rates compared to patients admitted to general wards [20].

However, few centers have developed specific management protocols for ensuring that treatment of hemorrhagic stroke is initiated rapidly, in comparison to treatment of ischemic stroke. The Neurocritical Care Society emphasizes the usefulness of prompt treatment of hypertension and coagulopathy, which must already be started in the emergency department [21].

Cerebral hemorrhage frequently occurs in patients receiving anticoagulant or antiplatelet therapy and in patients suffering from congenital or acquired deficiency of clotting factors or congenital or acquired quantitative or qualitative platelet abnormalities.

For patients with deficiency of coagulation factors or platelet disorders, AHA/ASA guidelines recommend the infusion of involved factors in the first case and of platelets in the second (class I, level of evidence C) [3].

It is not yet clear which is the cutoff value of platelets, below which the transfusion of platelet concentrates is recommended. According to the SPREAD guidelines, 50,000/mm³ should be considered the cutoff [10], although cases must be evaluated individually since there may be conditions which require transfusion for higher values (patients requiring neurosurgery, particularly extensive hemorrhage).

For patients on intra venous (IV) heparin therapy, IV administration of protamine sulfate is recommended at a dosage of 1 mg/100 U of heparin (maximum dose 50 mg). The dose must be corrected according to the time elapsed since administration of the heparin (class IIb, level of evidence C – AHA/ASA) [3, 22]. Similar doses may be administered to patients on low molecular weight heparin therapy (LMWH), but their effectiveness in reversing the effect of the drug may be incomplete [21].

If the brain hemorrhage occurs in a patient on anticoagulant therapy with vitamin K antagonists, the administration of vitamin K is definitely indicated (class I, level of evidence C – AHA/ASA) [3], but its effect on the correction of INR is not evident in the early hours after administration. The vitamin starts to work 2 h after administration and reaches maximum effect 24 h afterward [23].

For immediate correction of INR, fresh frozen plasma can be used. Fresh plasma needs cross matching and is associated with the risk of allergic reaction or transmission of viral infections. Furthermore, very high volumes of plasma are often needed [24].

Prothrombin complex concentrate (PCC) is available both in a 3-factor formulation (II, IX, X) and in a 4-factor formulation (which also contains the VII). It requires no cross matching, can be administered quickly and in small volumes (20–40 ml), and is very fast in normalizing INR (within minutes) [25].

This profile of safety and efficacy according to the AHA/ASA is preferable to fresh frozen plasma (class IIb, level of evidence B) [3]. There is an associated risk of thrombotic events, but it is not particularly high [25].

The recombinant activated factor VII (rFVIIa) quickly normalizes INR, but it does not replace all the vitamin K-dependent factors, nor does it restore adequate thrombin generation [26]. For this reason it is not recommended by the AHA/ASA guidelines (class III, level of evidence C) [3].

Instead, ESO 2014 guidelines emphasize the absence of trials that directly compare the effectiveness of fresh frozen plasma, prothrombin complex, and rFVIIa, and therefore they do not give any recommendation on the type of hemostatic agent to be used [9].

There is no unanimous opinion about the target INR value to be reached: it ranges from <1.3 to <1.5 [27].

For patients treated with the new oral anticoagulants, there are currently no pharmacological agents that have been proven effective in reversing these molecules. Activated carbon is effective in reducing absorption of the drug, if the last dose was taken within two hours. PCC and rFVIIa seem to be useful in reversing the activity of direct thrombin inhibitors (dabigatran) [28].

Hemodialysis has been suggested as an effective option for removing dabigatran, but is less effective on rivaroxaban and apixaban because of their high protein binding (class IIb, level of evidence C – AHA/ASA) [3]. The ESO guidelines do not express any recommendation because of the scarcity of studies on the subject [9].

Some studies have investigated the efficacy of rFVIIa on intracranial hemorrhages in patients who were not taking anticoagulant or antiplatelet therapy. Although a limitation in the extension of hematoma volume was observed, which was associated with a better clinical outcome, this method is not recommended in AHA/ASA, ESO, and SPREAD guidelines (class III, level of evidence A – AHA/ASA) [3, 9, 10] as it involves an excessive risk of thromboembolism [29].

As for the prophylaxis of deep vein thrombosis (DVT), there is no indication for the use of elastic graduated compression stockings. The recent CLOTS3 study has demonstrated the effectiveness of the use of intermittent pneumatic compression [30] which in fact is included in the recommendations of ESO and AHA/ASA guidelines (class I, level of evidence A) [3, 9].

According to AHA/ASA guidelines, the administration of LMWH can be taken into consideration once it has been documented that the bleeding has stopped, 4–5 days after onset of the hemorrhage [3], while ESO 2014 guidelines emphasize the fact that there is no evidence of the benefits of prophylaxis with LMWH and that no conclusive indication can be derived from available studies regarding the timing of its introduction [9]. It seems that such therapy is not associated with an increased risk of hemorrhage [31].

AHA/ASA (class IIa, level of evidence C) guidelines recommend the administration of systemic anticoagulants or the use of indwelling or temporary vena cava filter if there is symptomatic DVT or pulmonary embolism during brain hemorrhage [3]. The choice between these two options depends on several factors: the time elapsed from onset of hemorrhage, the stability of the hematoma, the cause of the hemorrhage, and the overall clinical condition of the patient [32].

High blood pressure is common in patients with cerebral hemorrhage and it is due to various factors: preexisting hypertension, neuroendocrine response to stress, and response to increased intracranial pressure. This condition can cause an increase in hematoma volume, deterioration of neurological conditions, increased mortality rate, and risk of disability [33].

It has been documented that performing perfusion CT on patients who are undergoing intensive treatment for hypertension (systolic BP target <140 mmHg) does not show any reduction of blood flow in the area around the hematoma [34]. In the INTERACT studies 1 and 2, the safety and efficacy of aggressive blood pressure treatments (with Systolic Blood Pressure (SBP) target <140 mmHg), during the early stages of cerebral hemorrhage, was compared with the standard treatment (with target SBP <180 mmHg). The studies demonstrated that this approach is safe, and furthermore the patients who received the more aggressive treatment achieved better functional recovery and a better quality of life. There is no evidence however of a positive impact on the increase in hematoma volume [35, 36].

Based on the results obtained, the AHA/ASA 2015 and ESO 2014 guidelines consider the intensive treatment of hypertension to be safe and potentially effective (class I, level of evidence A) [3, 9].

According to AHA/ASA guidelines, reaching the target 140 mmHg is probably not very feasible for patients with initial SBP > 220 mmH [3]. In this case they recommend an aggressive treatment to reduce blood pressure by continuous intravenous infusion of drugs, with continuous monitoring of BP.

SPREAD 2012 guidelines contain the following recommendations: [10]

The AHA/ASA guidelines make no specific recommendations regarding the pharmacological agent to be used [3], while SPREAD guidelines mention labetalol, urapidil, furosemide, and nitroprussiate, all medications administered intravenously in divisible doses [10].

High blood glucose levels at onset of cerebral hemorrhage are correlated with an increased risk of death and disability; correction is therefore recommended in patients without diabetes [37]. However, treatment with continuous infusion of insulin is not indicated since it involves an excessive risk of hypoglycemia.

It is still unclear which blood glucose target to maintain in the acute phase, but it is advisable to monitor patients closely (three times a day), even those without diabetes, in order to avoid both hyper- and hypoglycemia (class I, level of evidence C – AHA/ASA) [3]. Correction with insulin is always indicated for blood glucose values > 200 mg/dl.

Hyperpyrexia has proven to be an independent negative prognostic factor [38]. Despite this premise, it has not been demonstrated that drug treatment benefits outcome in real terms [39].

The AHA/ASA guidelines recognize a level of evidence C for the treatment of hyperpyrexia [3]. ESO guidelines are aligned with respect to early treatment while explicitly advising against the preventive treatment of hyperpyrexia outside clinical trials [9].

The frequency of epileptic seizures during cerebral hemorrhage is approximately 16 %. They mainly occur during the first week after onset and when there is lobar hemorrhage [40, 41].

Prophylactic treatment with antiepileptic drugs is not recommended as it may result in a worsening of outcome (class II, level of evidence B – AHA/ASA) [3]. SPREAD and AHA/ASA guidelines recommend drug treatment for seizures (class I, level of evidence A – AHA/ASA) [3, 9] which are detected by an EEG recording in patients with impaired consciousness (class I, level of evidence C – AHA/ASA) [3], even when the seizures are subclinical. Continuous Electro Encephalo Gram (EEG) monitoring is therefore recommended in patients who have a reduced state of consciousness that cannot be justified on the basis of the hematoma’s characteristics (class IIa, level of evidence C – AHA/ASA) [3].

The most common complications are pneumonia (5.6 %), aspiration (2.6 %), respiratory failure (2 %), pulmonary embolism (1.3 %), and sepsis (1.7 %). Approximately 50 % of deaths after stroke are due to medical complications. Dysphagia is the main risk factor for pneumonia, so AHA/ASA guidelines recommend assessment of swallowing disorders using a standardized test such as the water swallowing test (class I, level of evidence B) [3, 42].

The detection of high levels of troponin during the first 24 h after admission (about 15 % of patients) is associated with increased mortality; AHA/ASA guidelines therefore recommend screening for myocardial ischemic events by performing ECG and dosing troponin (class IIa, level of evidence C) [3].

Intracranial hypertension is due to hydrocephalus from ventricular flood or mass effect of the hematoma. For this reason, if the hematomas are small and there is minimum ventricular flooding, no treatment is needed.

Intracranial pressure (ICP) can be measured by means of either parenchymal or ventricular catheters; if necessary, the latter can also be used to drain fluid. These devices, particularly ventricular catheters, carry the risk of rebleeding or infectious complications.

Increase in intracranial pressure and decrease in cerebral perfusion pressure are related to a higher mortality rate and worse functional outcome [43]. In the absence of studies that clearly define the indication for ICP monitoring, AHA/ASA and SPREAD guidelines recommend monitoring and possibly treating intracranial pressure in patients with GCS score <8 related to the mass effect of the hematoma and if there is high-severity ventricular flooding, hydrocephalus, or clinical manifestations of transtentorial herniation (class IIb, level of evidence C – AHA/ASA) [3, 10].

The ESO 2014 guidelines point out that in the absence of randomized controlled trials, it is impossible to formulate an indication for ICP monitoring [9]. They also highlight that a low rate of complications has been reported [44].

If there is intracranial hypertension, the AHA/ASA guidelines strongly recommend the following therapy: [3] elevate the patient’s head 30° above the bed and administer a mild sedation; avoid the use of collars or devices that compress the neck veins; and use osmotic agents such as mannitol or hypertonic solutions, which are considered more effective [45]. Corticosteroids, on the other hand, are considered to be contraindicated (class III, level of evidence B) [3].

In the case of hydrocephalus secondary to obstruction of the flow of cerebrospinal fluid, CSF drainage may be considered, especially in patients with a reduced level of consciousness (class IIa, level of evidence B – AHA/ASA) [3].

Intraventricular hemorrhage occurs in about 45 % of cases of intracerebral hemorrhage. Drainage via a ventricular derivation catheter may be useful; it is however often ineffective due to the difficulty in maintaining patency. To overcome this obstacle, fibrinolytic drugs can be administered intraventricularly recombinant tissue Plasminogen Activator (rtPA), but they may increase the risk of rebleeding.

Endoscopic evacuation has been used as an alternative. However, the safety and effectiveness of this procedure have not yet been proven [46, 47].

Because of the absence of firm evidence of their effectiveness, the AHA/ASA guidelines assign a level B evidence [3] both to endoscopic treatment and to intraventricular administration of fibrinolytics [46, 47].

There is no clear evidence that surgery offers better results compared to the medical treatment of supratentorial parenchymal hemorrhages [48]. In fact, according to SPREAD and AHA/ASA guidelines, surgical treatment of supratentorial hemorrhage should be limited to cases where the patient’s neurological status deteriorates (class IIb, level of evidence A – AHA/ASA) [3, 10].

Furthermore, according to AHA/ASA guidelines, the evacuation of supratentorial hematoma in patients who suffer rapid neurological deterioration should be considered a lifesaving measure (class IIb, level of evidence C) [3].

On the other hand, based on the results of one meta-analysis [49], ESO guidelines suggest that, if performed early, surgery might offer greater benefits for patients with a better state of vigilance (GCS 9–12) [9].

As for cerebellar hemorrhages, surgical evacuation of hematoma is unanimously recommended for patients who are likely to suffer from neurological deterioration or brain stem compression [50] (class I, level of evidence B – AHA/ASA) [3].

It is also highlighted that applying Cerebrospinal Fluid (CSF) drainage as the first phase of treatment is contraindicated (class III, level of evidence C – AHA/ASA) [3]. Unlike cerebellar hemorrhage, evacuation of brain stem hemorrhage can be a harmful procedure.

Decompressive craniectomy, with or without evacuation, could reduce mortality in patients suffering from supratentorial bleeding with one or more of the following characteristics: coma, large hematoma with midline shift, and high intracranial pressure refractory to other medical therapies.

However, there are not sufficient data available in literature to determine its effectiveness [51] (class IIb, level of evidence C – AHA/ASA) [3].

The PROGRESS study shows that reducing blood pressure (with perindopril and indapamide) decreases the risk of recurrence of cerebral hemorrhage, as well as other vascular events [54].

The Secondary Prevention of Small Subcortical Strokes (SPS3) study shows that maintaining systolic blood pressure <130 mmHg reduces the risk of recurrence, especially in patients suffering from known small vessel disease [55]. AHA/ASA and ESO guidelines therefore recommend controlling blood pressure as secondary prevention (class I, level of evidence A – AHA/ASA) [3, 9].

The best time to start treatment remains unclear, although the INTERACT2 study has demonstrated that it is safe to start treatment early [36].

There are no randomized trials that give indications about when to reintroduce anticoagulant therapy after a hemorrhagic cerebral event. The decision must be made by assessing the relationship between hemorrhagic risk and thromboembolic risk in each individual patient.

The indications of the SPREAD 2012 guidelines are as follows [10]:

AHA/ASA guidelines suggest avoiding administration of warfarin for patients suffering from non-valvular atrial fibrillation and previous warfarin-related lobar hemorrhage (class IIa, level of evidence B) [3]. As regards when to resume therapy, the guidelines suggest 4 weeks unless the patient has a mechanical heart valve (class IIb, level of evidence B) [3].

ESO guidelines do not give any suggestions regarding indications and appropriate timing for resuming anticoagulation therapy after cerebral hemorrhage and highlight the need for randomized trials on the topic [9].

There are no accurate data regarding resumption of antiplatelet therapy. However, the risk of myocardial infarction and ischemic stroke is higher than the risk of rebleeding in both deep and lobar locations [56]. According to AHA/ASA guidelines, therefore, therapy may if necessary be reintroduced the day after the cerebral hemorrhage (class IIa, level of evidence B) [3].

No advantage has been demonstrated in using the new oral anticoagulants (dabigatran, rivaroxaban, apixaban) as opposed to administering warfarin to patients with previous brain hemorrhage, who are suffering from non-valvular atrial fibrillation [57] (class IIb, level of evidence C – AHA/ASA) [3].