Pontine hemorrhage accounts for up to 10% of all cerebral hemorrhages¹⁾, representing the most catastrophic type, with mortality rates exceeding 30%^2,3). The primary cause is hypertension⁴⁾; however, it can also be triggered by other conditions such as vascular malformations⁵⁾, particularly in patients without risk factors for atherosclerotic diseases and without a history of anticoagulant therapy. Clinically, patients may present with altered consciousness, cranial nerve deficits, respiratory difficulties, and motor impairments⁶⁾.

The diagnosis is established by imaging studies, with computed tomography (CT) scans to determine the location and extent of hemorrhage, both of which are prognostic indicators⁷⁾. Pontine intracerebral hemorrhage can also be associated with electrocardiographic changes and increased cardiac biomarkers⁸⁾, thus closely resembling acute coronary syndrome. This similarity in diagnosis has profound therapeutic implications, as the usual management of acute coronary syndrome, such as urgent coronary angiography, percutaneous coronary intervention, and the administration of antiplatelet or anticoagulant therapy, is absolutely contraindicated in intracerebral hemorrhage because of the risk of hematoma expansion and worsening neurological deficits. These cardiac manifestations are thought to result from neurogenic mechanisms related to autonomic dysregulation and catecholamine excess rather than primary coronary artery disease. Therefore, early and accurate differentiation between pontine ICH–related neurogenic cardiac injury and true ACS is essential^9,10). This review summarizes the relevant pathophysiological, clinical, diagnostic, and therapeutic aspects of pontine hemorrhage presenting with ACS-like features (Table 1).

The average age at which intracerebral hemorrhage occurs is 61 years; but a variation may be seen in relation to the patient's ethnicity. A global incidence of 23.05 cases per 100,000 people is seen. The incidence increases with age, doubling the risk every 10 years, without considering gender, which does not have a significant impact as a risk factor^11,12).

The incidence rate is highest among Asians, intermediate in Black populations, and lowest in White populations^11,12). The higher rate in Black individuals compared to White individuals is attributed to deep cerebral and brainstem hemorrhages, as hypertension is the primary risk factor for this type of hemorrhage. In the White population, there is better hypertension control; however, the incidence remains due to the increased use of antithrombotic therapies¹¹⁾.

Beyond the epidemiology of intracerebral hemorrhage itself, cardiac complications are frequently observed and contribute significantly to morbidity and mortality. About 10–20% of patients with acute cerebral hemorrhage have been documented to have neurogenic stress cardiomyopathy, especially those with significant neurological damage. Up to 50–70% of patients with cerebral hemorrhage experience electrocardiographic abnormalities, which frequently resemble acute coronary syndrome. These abnormalities include ST-segment alterations, Twave inversion, QT prolongation, and atrioventricular conduction problems.Furthermore, even in the absence of obstructive coronary artery disease, increases in cardiac biomarkers like troponin and creatine kinase-MB have been reported in 15-30% of instances.There have also been reports of clinically significant arrhythmias, such as bradyarrhythmias, ventricular ectopy, and atrial fibrillation, especially in brainstem and subarachnoid hemorrhages.The significance of acknowledging cardiac involvement as a frequent and clinically significant sign of intracerebral hemorrhage rather than as a separate cardiac disorder is highlighted by these epidemiological findings^16,20,30,31).

Hypertension remains the primary risk factor for intracerebral hemorrhage, particularly for deep and brainstem hemorrhages, and is also implicated in specific etiologies such as cerebral amyloid angiopathy and anticoagulant-associated hemorrhage. Anticoagulant therapy, especially warfarin, increases the risk of intracerebral bleeding by two- to five-fold depending on treatment intensity, while antiplatelet therapy carries a smaller but measurable risk, particularly with dual antiplatelet regimens^11,12). Additional factors that increase hemorrhagic risk include the presence of cerebral microbleeds on MRI, poorly controlled blood pressure, advanced age, high alcohol intake, Black ethnicity, and low total and low-density lipoprotein cholesterol levels, which have been associated with greater hemorrhage severity and mortality. Certain medications, such as selective serotonin reuptake inhibitors, have also been linked to increased intracranial bleeding risk due to platelet dysfunction^13,14). These risk factors often interact, with younger Black individuals demonstrating higher susceptibility, whereas risk patterns may differ in very elderly populations.

In contrast to intracerebral hemorrhage–specific risk factors, acute coronary syndrome is primarily associated with traditional atherosclerotic and metabolic risk factors. These include advanced age, male sex, long-standing hypertension, diabetes mellitus, dyslipidemia—particularly elevated low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol—cigarette smoking, obesity, sedentary lifestyle, and a family history of premature coronary artery disease. Additional contributors include chronic kidney disease, prior ischemic heart disease, peripheral vascular disease, and inflammatory states. Most importantly, in patients who report with intracerebral hemorrhage and ACS-like electrocardiographic or biomarker abnormalities, the presence or absence of these traditional ACS risk factors may help differentiate real myocardial ischemia from neurogenic cardiac symptoms, may help differentiate true myocardial ischemia from neurogenic cardiac manifestations, as summarized in Table 2. A thorough evaluation of vascular risk profiles, neurological symptoms, and early neuroimaging is essential to direct optimal care and avoid potentially harmful antithrombotic or invasive cardiac medications.

In brainstem hemorrhages, hypertension is the most common cause⁴⁾, followed by less frequent etiologies such as vascular malformations⁵⁾, anticoagulation, and amyloid angiopathy¹⁵⁾.

These hemorrhages can have implications for cardiac function, which may range from electrocardiographic changes¹⁶⁾ to wall motion abnormalities (WMA)^9,17). However, the mechanism by which a central nervous system (CNS) injury may lead to cardiac stress is not fully understood. It is believed that norepinephrine (NA) may play a significant role in this pathophysiology^9,10).

However, stress-induced cardiomyopathy after intracerebral hemorrhage has a complex pathogenesis that goes beyond catecholamine excess. Experimental and clinical studies have demonstrated that sympathetic surges lead to alterations in β-adrenergic receptor density and signaling, resulting in myocardial stunning and impaired contractility^9,18). Excessive catecholamine exposure promotes cyclic adenosine monophosphate (cAMP)–mediated intracellular signaling dysfunction, contributing to transient systolic dysfunction despite the absence of coronary obstruction.

Furthermore, abnormalities in the internal processing of calcium play a significant role. The excessive entry of calcium into the cell through the action of catecholamine leads to impaired excitation contraction coupling, mitochondria dysfunction, and oxidative stress^9,18,21). Abnormal processing of the re-entry of calcium into the sarcoplasmic reticulum and the entry of calcium through L-type channels contributes to the worsening of the shock of the heart. This will cause the abnormalities of the wall motion in the reversible form of cardiomyopathy.

Also postulated are alterations at a microvascular level, such as spasm of the coronary microvasculature and endothelial dysfunction, that could account for periods of myocardial hypoperfusion associated with pontine hemorrhage-related cardiac dysfunction when there is no fixed coronary disease^16,20). In aggregate, these pathophysiologies account for cases of pontine hemorrhage-related cardiac dysfunction that have ACS-like manifestations but satisfy reversibility criteria when treated supportively, illustrating once again that neurogenic cardiac injury differs from true ACS.

Hypotheses that initially arose pertaining to this subject proposed that higher concentrations of this particular neurotransmitter might result in an indirect vasoconstriction of the coronary arteries or possibly exert a toxic effect on the heart because the neural cells that innervate the coronary arteries are derived from the brain stem⁸⁾.

Evidence currently exists to support a modified and cumulative neurocardiovascular pathway based on an autonomic central nervous system imbalance, as opposed to the traditional hypothalamic and/or corticotrophin releasing hormone factors¹⁸⁾. Acute bleeding within the central nervous system, including the brain stem, insular cortex, hypothalamus, and limbic circuits, will interrupt autonomic centers, resulting in an imbalance between the autonomic and sympathoadrenal systems with the consequent excess of systemic catecholamines from the sympathoneural terminals and the adrenal medulla.

As the pons shows close anatomical and functional connections to the autonomic nuclei of the medulla, damage to the pontine regions may provoke considerable disruptions in cardiovascular regulation besides the motor and cranial nerve dysfunctions. The pontine regions show ascending and transversal tracts that regulate the autonomic centers within the medulla, specifically the rostral ventrolateral medulla (RVLM), nucleus tractus solitarius (NTS), or nucleus ambiguus.Because the disruptions in the aforementioned tracts may result from pontine hemorrhage due to mass effect or perihematomal edema, the regulation of baroreceptor processing, the efferent vagal activities, or sympathetic tone may all become disturbed.The nucleus ambiguus is the source of parasympathetic fibers to the heart, while the NTS plays the central integrating role for the central afferents.

Disruption of pontomedullary connections by injuries of the pons and medulla may therefore lead to withdrawal of vagal stimulation and unopposed sympathetic activation. On the other hand, disruption of RVLM regulation, which plays a central role in sympathetic regulation of vasomotor tone, may lead to excessive sympathetic discharge of catecholaminergic fibers^18,22,23).

Excessive sympathetic discharge results in profound increases in plasma and myocardial catecholamine concentrations, which directly harm the myocardium through overestimation of β-adrenergic receptors, intracellular calcium accumulation, mitochondrial damage, and oxidative injury. These mechanisms are now established as the major underlying causes of stress-induced cardiomyopathy secondary to subarachnoid and intracerebral hemorrhage. Contrary to what has been previously reported with regard to catecholamine increase being insufficient, the current evidence clearly indicates a close correlation between the degree of sympathetic activation, markers of myocardial damage, and the degree of cardiac dysfunction following hemorrhagic brain injury. Thus, this revolution apparently locates catecholamine surge secondary to central autonomic network dysfunction as the major mechanism responsible for the neurocardiac damage following hemorrhage.

In 2012, Sugimoto et al. further expanded the questions surrounding this topic, as reduced estradiol levels with high concentrations of NA were significantly associated with wall motion abnormalities in patients with cerebral hemorrhage⁹⁾. They concluded that postmenopausal women might have a higher risk of experiencing WMA following subarachnoid hemorrhage.

Regarding the cardiac effects associated with brainstem hemorrhages, pulmonary edema¹⁶⁾, hypotension, altered ejection fraction, and hypokinesia have been reported in patients with WMA following a cerebral hemorrhage²⁰⁾. Additionally, electrocardiographic and enzymatic changes have been documented after CNS hemorrhage⁸⁾, including T-wave inversion, prolonged or depressed ST segments, and, less commonly, ST elevation⁵⁾, as well as the presence of AV block⁸⁾. Regarding enzyme levels, the peak within the first 72 hours following a subarachnoid hemorrhage with neurogenic stress cardiomyopathy (NSC) is lower compared to that in myocardial infarction (MI), although it may rise in up to 20% of patients without NSC²¹⁾ (Fig 1).

The brainstem consists of important nerve tracts, involving an interconnection between the central nervous system and the spinal cord. Most of the cranial nerves arise from it and it contains regulatory centers, an important aspecto of respiration²²⁾. Furthermore, the reticular formation, which is vital for the sleep-wake cycle, heart rhythm, and motor function, is located within this structure²³⁾.

All of this helps to understand the symptoms arising from brainstem involvement. Consequently, in pontine hemorrhages, one may observe alterations in consciousness, respiratory difficulties, motor impairment, and cranial nerve involvement, such as the third cranial nerve (oculomotor nerve), which manifests as pinpoint pupils and difficulty with eye movement⁶⁾. In cases of massive hemorrhage, the individual may experience decerebration and deep coma, possibly related to the interruption of the ascending reticular system²⁴⁾.

Apart from the neurological deficits, pontine intracerebral hemorrhage can also have significant cardiac manifestations. These include a variety of arrhythmias such as sinus bradycardia, atrial fibrillation, ventricular ectopy, atrioventricular conduction abnormalities, and QT interval prolongation, which are due to autonomic dysfunction and neurogenic myocardial damage. Symptoms due to cardiac dysfunction can include chest discomfort, dyspnea, palpitations, and acute heart failure. In some instances, neurogenic pulmonary edema can occur, which can present with acute respiratory distress, hypoxia, and bilateral pulmonary infiltrates, further adding to the complexity of the clinical scenario and simulating primary cardiopulmonary pathology²⁴⁾.

Imaging plays a critical role in the early differentiation of pontine intracerebral hemorrhage from acute coronary syndrome in patients presenting with cardiac manifestations. Non-contrast computed tomography is the first-line modality for confirming hemorrhage, defining its location and extent, and guiding immediate management decisions. Early neuroimaging is essential to prevent inappropriate antithrombotic or invasive cardiac interventions that may worsen neurological outcomes^7,25).

The timely diagnosis of neurogenic heart failure and its careful differentiation from actual ACS are required in the care of pontine intracerebral hemorrhage patients who have the clinical manifestations of acute coronary syndrome. The characteristic features of stress-induced cardiomyopathy (SICMP) in intracranial hemorrhage include the performance of the myocardium, a subtle rise in the cards biomarkers, and the reversible changes in the electrocardiographic pattern, without the co-existing obstructive coronary artery atherosclerosis. In contrast, the main cause of actual ACS includes the erosion of the atherosclerotic plaque in the coronary arteries and the thrombosis.

Antiplatelet and anticoagulant therapy: Due to the high risk of hematoma expansion and further neurological deterioration, anticoagulants and antiplatelet therapy, which represent the mainstay of acute coronary syndrome treatment, are considered to be contradicted in the acute management of intracerebral hemorrhage. In the situation of suspected neurogenic cardiac injury, antithrombotic therapy may be delayed when there exists irrefutable proof of coronary occlusion that has been validated by cardiology consultation and imaging. Still, even then, the decision regarding antithrombotic therapy must be made on an individual basis after discussion among the neurology, neurosurgery, and cardiology staff.

Hemodynamic and supportive management is key to the management of SICMP associated with pontine hemorrhage. Blood pressure management should focus on preventing the expansion of the hematoma and preventing extreme hypotension that could impair cerebral perfusion. cardiac dysfunction is managed with supportive care and may include careful beta-blocker therapy to suppress sympathetic hyperactivity and fluid management to prevent pulmonary edema. Supportive care and intropic therapy would focus on refractory shock in cardiac dysfunction. Mechanical ventilation and oxygenation would then be required if there is associated respiratory distress related to brain stem damage. Continuous cardiac monitoring is necessary because of the high possibility of arrhythmia and autonomic dysfunction in cardiac SICMP. Neurological monitoring in an intensive care unit setting and prevention of secondary complications, including control of intracranial pressure, remain integral components of supportive management in pontine hemorrhage²⁶⁾.

Neurosurgical management: Neurosurgical decision-making in pontine hemorrhage focuses on patient selection and risk–benefit assessment rather than routine operative intervention. Neurological stabilization and the prevention of secondary brain injury remain the focus. Surgical intervention in pontine hemorrhage is still highly controversial, usually guided by the volume of hematoma, level of consciousness, rostrocaudal extension, and clinical deterioration. Most patients can be managed conservatively with monitoring in the intensive care environment; the main indication for surgical intervention, if ever, is highly selected where potential benefits outweigh the risks. Predictors influencing the decision between conservative and surgical management include patient age, level of consciousness, hemorrhage type, hematoma volume, rostrocaudal extent, hemodynamic instability, and bleeding duration, emphasizing the need for individualized treatment strategies²⁷⁾ (Table 3).

Inconsistency is perservered, ranging from early death to long-term survival without neurological déficits. It highly showed dependency on the severity of clinical manifestations and the presence of specific radiological markers. Bilateral extension of the hematoma, a Glasgow Coma Scale (GCS) score ≤ 8, hydrocephalus, male sex, and large hematoma volume play a crucial role in mortality during the first three months. A GCS score ≤ 8, pupillary alterations and hematoma volume were independently associated with functional outcomes at three months²⁸⁾.

The overall mortality rate ranges from 30% to 90%, with favorable outcomes varying between 15% and 77%. Less favorable outcomes are seen in patients presenting with coma, pupillary alterations, abnormal respiratory patterns, and systemic hypotension upon admission^28,29). Acute hydrocephalus was associated with survival outcomes but not with functional outcomes. Elevated blood glucose levels and high white blood cell counts were potential predictors of survival in patients with pontine hemorrhage²⁸⁾. Extremely high systolic blood pressure (> 180 mmHg) at admission was associated with mortality in patients with hemorrhagic pontine brain injury²⁹⁾. The effectiveness of surgery remains debated^{28, 29)}.

Left ventricular systolic dysfunction occurs in 10% of patients with subarachnoid hemorrhage (SAH). Additionally, 17% of patients with SAH present with elevated serum troponin I and creatine kinase (CK-MB) levels^{30, 31)}. A relationship was observed between the severity of neurological injury and the likelihood of troponin release. The severity of neurological injury is strongly linked to myocardial necrosis, resulting in neurogenic causes of cardiac injury and dysfunction³⁰⁾.

The absence of a history of diabetes, prior hypertension, ophthalmoplegia, small hematoma volume, lack of intraventricular hemorrhage extension, and absence of hydrocephalus are indicators of improved functional outcome with rapid recovery²⁹⁾. Early diagnosis in this condition contributes to quick recognition and treatment of vasospasm, which playa n important aspecto in neurological outcomes and result in negligible extent of cardiac injury³¹⁾ (Table 4).

In addition to neuro-radiological factors, cardiac dysfunction has been recognized as an important predictor that modifies outcomes for intracerebral hemorrhage patients. Neurogenic cardiac injury, such as cardiomyopathy triggered by stress, arrhythmias, and myocardial proteins, has been reported to be linked to an increased rate of mortality within a hospital setting, increased stay within an intensive care unit, and higher rates of systemic complications. Patients with left ventricular systolic dysfunction or patients manifesting electrocardiogram changes necessitate extended hemodynamic support.

Cardiac biomarker abnormalities and autonomic dysregulation were associated with the severity of the central injury, and the relationship between the injured central and cardiac systems is obviously reciprocal. Cardiac abnormalities and the resultant fluctuations in heartbeat and/or circulation may impair cerebral perfusion, contributing to the acceleration of the secondary injury and to the occurrence of multiorgan dysfunction syndrome. On the other hand, the early detection and appropriate management of the neurolathyrism-related injury observed in the heart were able to increase short-term survival rates and stabilize the systemic alterations, and thus promote the recovery of the central system injury, emphasizing the importance of the active detection and management of the observed alterations in pontal and other intracerebral hemorrhages, since the alterations are no ‘epiphenomena’ but, on the contrary, independent determinants of the observed outcomes.

Pontine intracerebral hemorrhage could also closely resemble acute coronary syndrome by having neurogenic changes on an electrocardiogram, increased levels of cardiac biomarkers, and functional heart impairment. This condition is a challenge for a differential diagnosis due to important treatment differences between stress-induced cardiomyopathy and acute coronary syndrome. Therefore, a differential diagnosis between these two conditions based on a comprehensive analysis should be done to offer relevant treatment.

Misdiagnosis can result in unnecessary invasive cardiac work-ups or the premature administration of antiplatelet and anticoagulation therapies, with considerable risk of hematoma expansion and subsequent deterioration of neurologic status. With the identification of neurogenic cardiac dysfunction as a common and important presentation of pontine hemorrhage comes the ability to appropriately and promptly manage patients and avoid iatrogenic complications through meaningful optimization of neurologic and systematic outcomes. It is important to have a multidisciplinary approach involving neurology and neurosurgery and cardiovascular subspecialties in managing patients who present concurrently with neurologic findings and acute cardiac syndrome-type manifestations.