1. INTRODUCTION:

Brain haemorrhages, including intracerebral haemorrhage( ICH) and subarachnoid haemorrhage( SAH), are associated with high rates of mortality and morbidity.¹ ICH is a common neurological complaint defined as bleeding into the brain parenchyma..² Although traumatic ICH is the most frequent type, this review focuses on non-traumatic ICH bleeding that occurs without trauma or identifiable causes such as arteriovenous malformations, cerebral aneurysms, or tumors.³ Non-traumatic ICH is further classified into primary and secondary forms.

The most common causes of primary ICH are hypertensive damage to small arteries (arteriolosclerosis) and cerebral amyloid angiopathy.⁴ The potential mechanisms that contribute to neurological complications include haemorrhage, ischemia, and compression caused by the expanding arteriovenous malformation (AVM).⁵

Currently, no effective treatments exist for secondary brain injuries (SBIs) that follow haemorrhage, including oxidative stress, inflammatory responses, neuronal apoptosis, and thrombin formation.¹ Stroke was the second leading cause of death and the third leading cause of combined death and disability, including weakness, paralysis, and reduced cognitive ability, and aphasia which occurred worldwide in 2019.^6,7 While the incidence of ICH increases with an ageing population. A significant number of cases also occur in individuals under 50 years of age.^2,8 Ischemic lesions related to small vessel disease are often observed in acute ICH, and primary ICH shares common risk factors and vascular pathology with ischemic stroke. Poorly controlled blood pressure and vascular abnormalities that cause rupture of small penetrating arteries are major contributors to ICH; however, improved hypertension management has led to a reduction in ICH cases.⁷ The affected vessel develops a “blister-like” bulge that may become fragile and rupture unexpectedly. When this occurs, blood leaks into the space surrounding the brain, causing a subarachnoid haemorrhage (SAH). This type of haemorrhage is a medical emergency, as it can result in stroke, coma, or even death.⁹ ICH is categorised based on its location within the brain. “Deep intracerebral haemorrhages are most frequently found in the basal ganglia and internal capsule (35%–70%), followed by the brainstem (5%–10%) and cerebellum (5%–10%). “Lobar” ICH, which accounts for 15%–30% of cases, involves haemorrhage in cortical-subcortical regions and may spread across one or more lobes.³ ICH is a significant public health concern, accounting for 10%–15% of strokes in Europe and North America, and 20%–30% in Asia.¹⁰ Neuroimaging studies have significantly advanced our understanding of this disorder.¹¹ Neurologists play a key role in managing ICH patients, particularly in emergency departments and intensive care units.²

Any condition or factor that affects the central nervous system and is classified as an acute brain injury (ABI)—such as traumatic brain injury (TBI)—involves two key components: Primary brain injury, which occurs at time of the insult and is irreversible. Secondary brain injury (SBI), which refers to physiological events that develop after the initial injury and contribute to additional damage to nervous tissue.¹²

Intracerebral haemorrhage results in damage to both grey matter (GM) and white matter (WM). Common clinical syndromes include contralateral hemiplegia due to corticospinal and corticonuclear tract damage, hemidysesthesia from central thalamic radiation involvement, and hemianopia resulting from optic radiation damage following deep basal ganglia hemorrhage.¹³ Over recent decades, various interventions such as invasive and minimally invasive hematoma evacuation, aggressive blood pressure control, and hemostatic therapies have shown clinical benefits.¹⁰ This review aims to summarize the pathophysiology, diagnostic approaches, and management strategies for ICH, focusing on blood pressure control, coagulopathy treatment, CAA treatment, and surgical interventions.

2. Epidemiology:

In the early 21st century, the incidence of stroke has likely increased, partly due to the growing use of antithrombotic therapy in elderly individuals with atrial fibrillation.¹⁴ According to the Global Burden of Disease Study 2010, the global number of haemorrhagic strokes rose by 47% between 1990 and 2010. The majority of ICH cases (80%) and related deaths (63%) occurred in low- and middle-income regions such as Africa, Central, and Southeast Asia. Although the occurrence of haemorrhagic stroke has decreased by 8% in high-income nations, it has increased by as much as 22% in low-income regions. ICH is more prevalent in men, occurs more frequently during the winter months, and shows a strong age-related increase in incidence. Among individuals aged 35–54, the annual ICH rate per 100,000 people was 5.9 in men and 5.1 in women.^15,16

Spontaneous intracerebral haemorrhage represents about 10–15% of all stroke cases and is categorised into primary and secondary types. Primary ICH, which comprises about 78–88% of cases, is mainly due to chronic hypertension and cerebral amyloid angiopathy (CAA), while secondary ICH results from vascular malformations, coagulation disorders, tumors, or neoplasms.¹⁷ Despite advances in understanding the condition, there is still no definitive treatment. Incidence is also influenced by ethnicity; for instance, African Americans experience a rate of 50 per 100,000 compared to 28 per 100,000 in Caucasians. Among Japanese individuals, the rate is even higher, at 55 per 100,000. Age-specific incidence rises dramatically, from 11 per 100,000 in people under 55 to approximately 200 at ages 55–64, 700 at 65–74, 1,400 at 75–84, and 2,500 at age 85 and older.⁴

Hypertension is the leading risk factor, contributing to about 65% of ICH cases.⁷ Primary ICH commonly causes rupture of small arterioles, often due to prolonged hypertension and its damaging effects on vessel walls.² Elevated blood pressure is frequently observed following stroke, especially in ICH. Systolic blood pressure (SBP) readings over 140mm Hg were found in 75% of ICH cases, compared to 67% in ischemic stroke and 100% in subarachnoid haemorrhage.¹⁷ It has been called the "silent killer" because patients with hypertension usually have no symptoms at all for about 15 to 20 years. Even without showing any symptoms, the disease slowly leads to cardiovascular issues and early death. Hypertension plays a significant role in causing kidney failure, heart disease, and stroke.¹⁸ CAA, which becomes more prevalent with age, is the second most common risk factor. It involves the deposition of amyloid protein in cortical arterioles, a rare process in the basal ganglia and brainstem.³ Other contributing factors identified in previous studies include Older age, excessive alcohol consumption, and reduced low-density lipoprotein cholesterol (LDL-C) levels.²

The damage from ICH results from both the dissection of brain tissue by blood and the mass effect of accumulating blood. Patients tend to have favorable outcomes when hematomas are smaller than 10ml. In contrast, hematomas larger than 60ml and those associated with coma carry a mortality rate exceeding 90%. Hematoma enlargement usually takes place within the first six hours following symptom onset, with up to 38% expanding within the initial three hours, underscoring the critical need for timely medical intervention.⁴ Leukoaraiosis, or white matter ischemic disease (WMD), is another risk factor, likely due to its link with hypertension. The presence of WMD in ICH patients is often associated with larger hematoma volumes and an increased likelihood of hematoma expansion.³

Etiology of Nontraumatic Intracerebral Haemorrhage (ICH):

Approximately 70% to 80% of all ICH cases are due to primary intracerebral haemorrhage. The majority of these (40%-60%) are caused by rupture of diseased small penetrating arteries that have been weakened by long-standing hypertension. Secondary intracerebral haemorrhage (ICH) arises from a diverse range of structural and physiological abnormalities.¹⁹

Table 1. Etiological classification of ICH.

Primary ICH

Secondary ICH

Hypertension

Cerebral amyloid angiopathy

Coagulopathy

Vascular malformation

Hematoma formation

Oxidative stress

Moyamoya

Ischemic stroke

Tumor

3. Pathophysiology:

In the early stages of injury, the rupture of a blood vessel can lead to hematoma formation, resulting in mechanical damage through compression of the brain parenchyma and disruption of its structural architecture due to mass effect.⁷ In cases of hypertensive ICH, the rupture of small arterioles typically less than 100 microns in diameter is referred to as lipohyalinosis. This condition is characterized by subintimal fibroblast proliferation, Replacement of medial vascular muscle cells in larger vessels with collagen, and the accumulation of lipid-laden macrophages.² These pathological vessels become structurally stiff and fragile compared to normal vasculature.²⁰

Figure.2. Pathophysiological mechanism of ICH.

The involved arterioles frequently undergo dilation and may form Charcot-Bouchard aneurysms. Thin-walled microaneurysms, when exposed to increased pressure, particularly within the thalamic, pontine, or striatal vessels supplied by larger pial arteries are highly susceptible to rupture. In most cases, ICH results from the rupture of these microaneurysms or arteriosclerotic weakening of the vessel wall.²¹

3.1 Cerebral amyloid angiopathy (CAA):

Cerebral amyloid angiopathy (CAA) results from the deposition of β-amyloid peptides in the walls of small arteries in the brain. This deposition damages the vascular smooth muscle, making the vessels fragile and impairing their ability to regulate blood flow.²² In younger individuals, intracerebral haemorrhage (ICH) is more commonly linked to vascular malformations, whereas in older adults, it is more often associated with CAA.⁷

CAA typically affects lobar regions or the subarachnoid space, particularly over the cortical convexities, and is frequently associated with cerebral microbleeds (CMBs) or superficial siderosis. Several studies have indicated that individuals carrying the APOE ε2 or ε4 alleles are at a higher risk of developing CAA and subsequent ICH.¹⁵

3.2 Hematoma formation:

In intracerebral haemorrhage (ICH), bleeding initially occurs from a ruptured vessel, leading to the formation of a hematoma that directly compresses the surrounding brain tissue and disrupts cellular structure. This hematoma exerts a mass effect, which raises intracranial pressure, decreases cerebral perfusion, and results in ischemic injury.¹⁰ While the exact mechanisms behind hematoma expansion are not fully understood, most rebleeding episodes take place within the first 24hours.²³ Hematoma enlargement is a serious complication in the acute phase, with up to 40% of hematomas increasing in size within the first few hours after onset. Hematoma expansion is considered a complex process influenced by impaired blood clotting due to activation of inflammatory pathways, increased activity of matrix metalloproteinases (MMPs), compromise of the blood–brain barrier (BBB), abrupt elevations in intracranial pressure leading to tissue distortion, and venous congestion due to impaired drainage all contribute to early hematoma expansion. Additionally, higher plasma concentrations of cellular fibronectin (c-FN) and the pro-inflammatory cytokine interleukin-6 (IL-6) have been linked with this process. Several studies suggest that hematoma expansion occurs in 18–30% of patients scanned within three hours of ICH onset.²⁴

3.3 Oxidative stress (OS):

An imbalance in the production of reactive metabolites (antioxidants) and free radicals is known as oxidative stress. Important cells and biomolecules may be hampered by this imbalance, which could impact how well the body functions as a whole.²⁵

Figure 3. Oxidative stress cascade in ICH.

Oxidative stress is recognised as an important contributor to secondary brain injury (SBI) after intracerebral haemorrhage (ICH). It arises mainly from excessive generation of free radicals, especially reactive oxygen species (ROS), which play a key role in various stages of the pathophysiological response after ICH.²⁶

The body typically relies on antioxidant defence mechanisms to maintain a balance between the generation and elimination of these free radicals. However, when ROS production exceeds the capacity of the scavenging systems or when clearance is impaired, it results in cellular damage and death.¹

Excessive accumulation of ROS may cause harmful consequences, including macromolecular damage, disrupted cell signalling, neuronal death, and tissue injury, all contributing to SBI. Following ICH, there is a marked rise in ROS levels, creating an imbalance between oxidative and antioxidative processes. Through oxidative stress, neuronal injury occurs, and the BBB integrity is compromised, which further deteriorates neurological outcomes.²⁷

3.4 Inflammation:

Inflammatory processes play a significant role in brain injury following intracerebral haemorrhage (ICH), largely through the activation of microglia and macrophages. These immune cells constantly monitor the surrounding microenvironment and help maintain the stability of neurons, the blood-brain barrier (BBB), and the extracellular matrix. In response to cerebral haemorrhage, microglia/macrophages are rapidly activated and begin releasing large quantities of inflammatory mediators, which can contribute to BBB disruption, edema, and neuronal cell death.¹

Microglia also serve as the brain’s primary phagocytic system, facilitating hematoma clearance through the activation of pathways such as Nrf2 and peroxisome proliferator-activated receptor gamma (PPARγ), thereby protecting other brain cells from ICH-induced damage. Important inflammatory cytokines implicated in the process include interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Anti-inflammatory agents have been shown to reduce BBB disruption and perihematomal edema by decreasing these cytokine levels following ICH. Additionally, NLRP3 inflammasomes contribute to the maturation and release of pro-inflammatory cytokines such as interleukin 1β (IL-1β) and interleukin 18 (IL-18). Inhibition of inflammasome activity has shown potential benefits in ICH treatment.²⁸

Figure 4. Inflammatory mechanism in ICH.

4. Risk Factors:

The incidence of intracerebral haemorrhage (ICH) increases significantly with advancing age. Data show that as age rises, so does the occurrence of ICH. Among young and middle-aged adults, females tend to have a lower in-hospital mortality rate compared to males. In contrast, older men are at greater risk of ICH-related complications, which may contribute to higher mortality rates.⁷ Excessive alcohol consumption and cocaine use are known risk factors for this severe type of stroke. Additionally, the use of aspirin and other antiplatelet agents is associated with an increased risk of ICH. High doses of aspirin, particularly in elderly individuals with uncontrolled hypertension or a history of epistaxis, may further elevate this risk.²⁹

Chronic kidney disease (CKD), which is more prevalent in older adults, is closely linked to vascular pathology. Chronic kidney disease (CKD) leads to platelet dysfunction and plays a role in promoting fluid retention and elevated blood pressure. The decline in glomerular filtration rate is often due to small-vessel disease in the kidneys, which correlates with small-vessel disease in the central nervous system. CKD, especially in its end stages, has been associated with more severe strokes, larger ICH volumes, greater ventricular involvement, and a higher likelihood of recurrence.³⁰

4.1 Cerebral microbleeds (CMBs):

Cerebral microbleeds (CMBs) are observed in about 5% to 23% of older adults and are frequently linked to conditions such as hypertension, diabetes, and smoking. Their presence may heighten the risk of intracerebral haemorrhage (ICH), especially in those undergoing treatment with warfarin or antiplatelet agents. As a result, when prescribing antithrombotic therapy for individuals with CMBs, it is essential to carefully weigh the potential therapeutic benefits against the associated bleeding risks.¹⁶

Table 2. Risk factors for ICH.

Modifiable risk factors	Non-modifiable risk factor
Hypertension	Old age
smoking	Sex
Excessive alcohol consumption	Cerebral amyloid angiopathy
Decreased low-density lipoprotein cholesterol, low triglycerides	Cerebral microbleeds
anticoagulation	Chronic kidney disease
Use of an antiplatelet agent
Sympathomimetic drugs

5. Diagnosis of ICH:

Intracerebral haemorrhage (ICH) is a life-threatening medical emergency that demands prompt and accurate diagnosis.⁸ Several clinical and neuroimaging features are known to predict outcomes in patients with ICH. These include hematoma volume, Glasgow Coma Scale (GCS) score, the presence of intraventricular haemorrhage (IVH), patient age, and the location of the haemorrhage, particularly if it is infratentorial.¹⁹ Disruption of the blood–brain barrier. which can be readily detected using contrast-enhanced magnetic resonance imaging or computed tomography, serves as a key diagnostic marker for malignant gliomas, meningiomas, and brain metastases, as well as for certain less common tumors lacking an intact BBB.³¹

5.1 Computed tomography (CT):

The widespread availability of CT scanning has made the diagnosis of intracerebral haemorrhage (ICH) relatively simple, and it remains the most frequently used neuroimaging method.² Non-contrast CT (NCCT) can quickly and reliably detect acute ICH, typically appearing as a hyperdense area within the brain parenchyma. Compared to other imaging techniques, NCCT is more cost-effective and widely accessible, particularly in emergency departments across hospitals in the United States. It is the recommended first-line imaging modality for evaluating patients with acute neurological symptoms suspected of ICH.¹⁹

However, NCCT does have certain limitations. Its sensitivity is reduced when detecting subacute or chronic haemorrhages, and it offers limited insight into the underlying cause, such as cerebral amyloid angiopathy (CAA) or vascular abnormalities.

5.2 Computed Tomography Angiography:

Computed tomography angiography is performed alongside NCCT to identify underlying vascular pathologies such as aneurysms, arteriovenous malformations, or other intracranial arteriopathies.³² They help identify patients with active contrast extravasation, which is a predictor of hematoma expansion and worse outcomes.² CTA provides high-resolution images of cerebral arteries by using helical scanning techniques on multidetector scanners at 1.5 mm slice thickness. Using iodine-based contrast administered intravenously, images are acquired as contrast passes through the intracranial arteries. CTA occasionally can detect the presence of a tumor blush if the image acquisition occurs after the arterial contrast phase. Disadvantages of CTA are the risk of radiation, contrast-induced nephropathy, and life-threatening allergic reactions.¹⁹

5.3 Magnetic Resonance Imaging (MRI):

Magnetic resonance imaging (MRI) is a noninvasive diagnostic tool that assists physicians in detecting and managing various medical conditions, including intracerebral haemorrhage (ICH).³³ Magnetic Resonance Imaging (MRI) demonstrates exceptionally high sensitivity, specificity, and diagnostic accuracy, close to 100% for detecting intracerebral haemorrhage (ICH) during both the hyperacute and acute phases. Compared to computed tomography (CT), MRI is also more accurate in detecting chronic ICH. Specific MRI sequences, such as echo-planar gradient-echo (GRE) and susceptibility-weighted imaging (SWI), are especially valuable in the hyperacute phase, as haemorrhages can increasingly obscure the underlying brain tissue after 24 hours.

MRI is also highly useful in detecting underlying causes of intracerebral hemorrhage, such as small vessel disease (SVD) and cerebral amyloid angiopathy (CAA). For instance, imaging findings such as lobar macrohemorrhage, purely cortical microbleeds (CMBs), cortical superficial siderosis (cSS), and a multispot distribution of white matter signal abnormalities are typically associated with CAA. Meanwhile, the presence of CMBs in subcortical regions and white matter signal abnormalities in the basal ganglia often suggests SVD as the underlying etiology.³⁴ Additionally, changes in metabolites like N-acetylaspartate and total creatine within the peri-stroke area have been linked to white matter (WM) loss. The ratio of these metabolites can serve as a valuable early indicator of white matter injury (WMI) and cognitive decline in patients with cerebral ischemia. Magnetic resonance spectroscopy (MRS) can serve as a valuable technique for identifying white matter injury (WMI) before the appearance of structural abnormalities.¹³

6. Complications:

Following diagnosis, patients of intracerebral haemorrhage may experience several critical complications that significantly affect prognosis. The immediate threats are hematoma expansion, particularly within the first three to six hours of symptom onset, occurring in up to 38% of cases.⁴ This expansion increases intracranial pressure (ICP) and exerts a mass effect, leading to brain tissue compression, reduced cerebral perfusion, and also risk of brain herniation. If blood enters the ventricles, it can obstruct cerebrospinal fluid pathways, causing acute hydrocephalus, which further elevates ICP and worsens outcomes.¹⁰ In addition to mechanical injury, Secondary brain injury poses a significant challenge, primarily driven by oxidative stress and inflammatory pathways. Excessive production of reactive oxygen species after haemorrhage contributes to blood-brain barrier disruption, neuronal apoptosis, and perihematomal edema.^1,27 Activation of inflammatory pathways, including cytokines such as interleukin-6 and TNF-α, also worsens brain tissue damage.²⁸ Furthermore, the presence of white matter disease (WMD) in ICH patients has been associated with larger hematoma volumes and an increased risk of hematoma expansion.³ These complications often lead to long-term neurological deficits, such as motor impairments, sensory dysfunction, and cognitive decline, particularly due to white matter injury and structural brain disruption.¹³

7. Management of ICH:

7.1 Blood pressure management:

Most patients with intracerebral haemorrhage (ICH) present with hypertension, and persistent high blood pressure during the early hours of hospitalization is strongly linked to hematoma expansion. Poor outcomes such as death, functional dependence, and clinical deterioration are associated with elevated blood pressure.¹⁵ Managing blood pressure is a crucial and rational approach to reducing the risk of ongoing bleeding and is now a fundamental aspect of early intracerebral haemorrhage (ICH) treatment. The goal is to lower blood pressure quickly while avoiding hypotension. For this purpose, fast-acting, titratable agents such as nicardipine are commonly used in the initial phase of treatment.

During the acute phase, antihypertensive medications that may raise intracranial pressure, such as hydralazine, nitroprusside, and nitroglycerin, should be avoided.²² Recent findings from the fourth Intensive Ambulance-delivered Blood Pressure Reduction in Acute Stroke Trial (INTERACT4) highlight the benefits of rapid blood pressure control within the first few hours of ICH onset. These results offer strong evidence and mechanistic support for developing urgent, time-sensitive treatment protocols in the early management of ICH and ischemic stroke.³⁵

Maintaining blood pressure within a healthy range is crucial for protecting overall health and lowering the risk of serious conditions. Research shows that even a modest reduction of just 5 mmHg in blood pressure can lower the risk of stroke by 34%, reduce the risk of ischemic heart disease by 21%, and significantly decrease the chances of developing dementia, heart failure, and cardiovascular-related mortality.³⁶

7.2 Coagulopathy Reversal:

The incidence of oral anticoagulant therapy-related ICH (OAT-ICH) has increased and now accounts for nearly 25% of all ICH cases. It is associated with increased hematoma volumes and higher risk of hematoma expansion, making rapid anticoagulation reversal and blood pressure control critical.¹⁵ For warfarin reversal, prothrombin complex concentrates combined with vitamin K are preferred over fresh frozen plasma due to faster INR correction and better outcomes. In dabigatran-associated ICH, idarucizumab effectively reverses its anticoagulant effect, while for Factor Xa inhibitors, Andexanet alfa has shown promise but remains controversial due to high cost and limited evidence of clinical benefit over PCCs. Recombinant activated factor VII showed reduced hematoma growth in early trials, but failed to improve clinical outcomes, and is not routinely used.²²

7.3 Treatment of CAA:

Since no definitive treatment currently exists, the management of the disease primarily focuses on preventing initial and recurrent episodes of intracerebral haemorrhage (ICH), similar to the approach used for other types of spontaneous ICH. To date, only a limited number of clinical trials have investigated medications aimed at reducing Aβ amyloid buildup in cerebral amyloid angiopathy. Ponezumab, a selective anti-Aβ40 antibody, was developed to inhibit or reverse Aβ aggregation and deposition. However, a phase 2 clinical trial showed that this agent did not enhance vascular reactivity or reduce the occurrence of cerebral microbleeds in humans. A phase 2 clinical trial (NCT00056238) assessed the safety and tolerability of NC-758 Cerebril, developed by Bellus Health, Inc., an anti-Aβ agent, in patients of lobar haemorrhage potentially associated with cerebral amyloid angiopathy (CAA). Nevertheless, findings on the effectiveness of this drug have yet to be published.³⁷

7.4 Surgery Interventions:

Surgical treatment remains one of the most effective approaches for removing clots and relieving the mass effect caused by hematomas. Techniques for evacuating hematomas include traditional open craniotomy and image-guided stereotactic aspiration.¹⁰ In this approach, a catheter is surgically inserted into the hematoma, followed by the administration of 1 mg of tissue plasminogen activator (tPA) every 8 hours, up to nine doses, to dissolve and aspirate the clot over three days. While this method has shown a modest reduction in mortality, it has not demonstrated significant improvement in overall clinical outcomes. Patients who underwent near-complete hematoma evacuation experienced greater benefits, and centers with higher patient enrollment achieved better success rates in clot removal.²²

The ENRICH trial suggests that minimally invasive trans-sulcal parafascicular surgery may be appropriate for treating lobar ICHs ranging from 30 to 80 mL within 24 hours of symptom onset, aiming to achieve a hematoma volume below 15 mL in patients between 18 and 80 years of age who have no significant pre-existing disabilities. The SWITCH trial compared decompressive craniectomy with medical therapy in patients suffering from severe deep ICH within 72 hours of stroke onset. Evidence suggests that decompressive craniectomy, even when performed without clot removal, may offer benefits to patients aged 18–75 years who have hematoma volumes ranging from 30 to 100 mL located in the basal ganglia or thalamus. For patients with decreased consciousness, ventricular drainage is recommended to lower mortality. Additionally, monitoring and managing intracranial pressure in such patients may further help reduce death rates and improve recovery outcomes.⁷

8. CONCLUSION:

Intracerebral haemorrhage (ICH) remains one of the most severe types of stroke with high mortality and morbidity. Effective and early diagnosis using imaging modalities like CT and MRI, along with rapid blood pressure management and hematoma control, is critical for improving outcomes. Although progress has been made in both surgical and medical therapies, a definitive cure is still lacking. Future research should focus on molecular targets involved in hematoma expansion and secondary brain injury mechanisms, such as oxidative stress and inflammation. An integrated, multidisciplinary strategy is crucial for achieving the best possible outcomes in patient care.

ETHICS AND CONSENT:

This review article is based on previously published studies and does not involve any studies with human participants or animals performed by the authors. No ethical approval was required.

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Received on 16.09.2025 Revised on 12.12.2025

Accepted on 28.01.2026 Published on 06.07.2026

Available online from July 20, 2026

Asian J. Pharm. Res. 2026; 16(3):347-354.

DOI: 10.52711/2231-5691.2026.00051

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

	T1 sequence MR	T2 sequence MR	Gradient-echo sequence MR
Hyperacute (<24h)	Hypointense/isointense	Isointense/hyperintense center with peripheral hypointensity and hyperintense rim of vasogenic edema	Marked hypointensity
Acute (1-3 days)	Isointense/slightly hypointense	Hypointense with hyperintense rim	Marked hypointensity
Early subacute (3-7 days)	Hyperintense	Hypointense	Hypointense
Late subacute (7-28 days)	Hyperintense	Hyperintense	Hypointense
Chronic (>1 month)	Hypointense	Hypointense	Hyperintense/isointense core with hypointense rim