Ischaemic Stroke
Definition
Ischaemic stroke is an episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction resulting from the obstruction of a nutrient artery (1). It represents a profound disruption of cerebral function precipitated by the cessation or critical reduction of blood flow to a region of the brain, leading to a time-sensitive cascade of cellular events and neuronal death (7).
Epidemiology
In Malaysia, stroke is the third leading cause of death and a primary cause of significant disability (2). In 2019, there were 47,911 new stroke cases and 19,928 stroke-related deaths recorded (2). Worryingly, there is a substantial increase in stroke incidence among individuals under 65, with the most significant rise seen in the 35-39 age group (2, 3). This trend is linked to a rising prevalence of risk factors like diabetes, hypertension, and hyperlipidaemia in the Malaysian population (2). Ischaemic strokes constitute the vast majority of cases, accounting for approximately 76-80.5% of all strokes in Malaysia (5, 6). Globally, ischaemic strokes account for about 87% of all cerebrovascular accidents (7).
Pathophysiology
The pathophysiology of ischaemic stroke is a time-critical process encapsulated by the phrase "Time is Brain" (7). The process begins with the obstruction of a cerebral artery, most commonly due to a thrombus that forms on an atherosclerotic plaque (thrombotic stroke) or an embolus that travels from another part of the body, frequently the heart in cases of atrial fibrillation (embolic stroke) (7). A less common subtype, lacunar stroke, results from the occlusion of small, deep-penetrating arteries, often due to lipohyalinosis associated with chronic hypertension and diabetes (7).
This arterial occlusion immediately halts the supply of oxygen and glucose to the dependent brain tissue, leading to a rapid depletion of adenosine triphosphate (ATP) (7). This energy failure partitions the affected tissue into two zones:
The Ischaemic Core: The area with the most severe blood flow reduction where cell death (necrosis) occurs within minutes due to catastrophic ion pump failure (7). This damage is irreversible (7).
The Ischaemic Penumbra: A surrounding area of moderately reduced blood flow where neurons are functionally silent but structurally intact and viable for a limited period (7). The penumbra is the primary target of all acute reperfusion therapies (7).
If blood flow is not restored, the penumbra is progressively recruited into the expanding infarct core, driven by a toxic cascade of events including excitotoxicity (massive glutamate release), oxidative stress, sterile inflammation, and various programmed cell death pathways (7).
Classification
Ischaemic strokes are classified based on their aetiology, which has direct implications for management:
Thrombotic Stroke: Caused by a thrombus forming on an atherosclerotic plaque within a cerebral artery (7).
Embolic Stroke: Occurs when an embolus from a distant site (e.g., heart, aortic arch) lodges in a cerebral artery (7). Cardioembolism, particularly from atrial fibrillation, is a major cause (7).
Lacunar Stroke: Infarction in deep subcortical structures due to occlusion of small penetrating arteries (7).
Cryptogenic Stroke: A stroke of undetermined aetiology after a comprehensive diagnostic workup has failed to identify a clear cause (7).
Clinical Presentation
The classic presentation of a stroke is the sudden onset of focal neurological deficits (7). The F.A.S.T. (Face, Arm, Speech, Time) and B.E. F.A.S.T. (Balance, Eyes, Face, Arm, Speech, Time) acronyms are vital for rapid public recognition (7). For a house officer, a more detailed assessment is required.
Diagnostic Clues: The hallmark is the acute onset of symptoms corresponding to a specific arterial territory.
Common Symptoms (>50%):
Unilateral weakness or numbness of the face, arm, or leg (hemiparesis/hemianaesthesia) (7).
Speech difficulty, including slurred speech (dysarthria) or problems with language production or comprehension (aphasia) (7).
Sudden confusion or altered mental state (7).
Less Common Symptoms (10-50%):
Sudden visual disturbance, such as loss of vision in one or both eyes (hemianopia or amaurosis fugax) or double vision (diplopia) (7).
Sudden trouble walking, dizziness, vertigo, or loss of balance and coordination (ataxia), particularly in posterior circulation strokes (7).
⚠️ Red Flag Signs & Symptoms:
Sudden, severe headache, often described as the "worst headache of my life," although more classic for haemorrhagic stroke, can occur (7).
Decreased level of consciousness may indicate a large territory stroke with significant cerebral oedema or a brainstem stroke.
Signs of herniation (e.g., Cushing's triad, unilateral pupillary dilatation) require immediate neurosurgical consultation.
Complications
Acute:
Cerebral Oedema and Raised Intracranial Pressure (ICP): Can lead to brain herniation and death, particularly in large infarcts.
Haemorrhagic Transformation: The ischaemic tissue can bleed, a risk increased by thrombolytic therapy (7).
Seizures: Can occur in the immediate post-stroke period (7).
Aspiration Pneumonia: Due to dysphagia (difficulty swallowing), which is a common and serious complication (7).
Venous Thromboembolism (VTE): Deep vein thrombosis and pulmonary embolism are risks due to immobility.
Chronic:
Neurological: Spasticity, chronic pain, post-stroke epilepsy (7).
Cognitive & Psychological: Post-stroke depression is very common, affecting about one-third of survivors (7). Vascular cognitive impairment and dementia are significant long-term risks (7).
Musculoskeletal: Contractures, shoulder subluxation, falls (7).
Functional: Reduced mobility, dependence in activities of daily living, social isolation (7).
Prognosis
Prognosis is highly variable and depends on stroke severity (often measured by the NIHSS score), patient's age, comorbidities, and time to treatment (7). In Malaysia, the 5-year survival rate for stroke is approximately 46.9%, which is lower than in many developed countries (5). A previous stroke or TIA is a strong predictor of recurrence, which carries a higher risk of severe disability and death (7, 5).
Differential Diagnosis
Subarachnoid or Intracerebral Haemorrhage: This is the most critical differential because of fundamentally different management. A sudden, severe headache, neck stiffness, photophobia, and vomiting at onset are more suggestive of a haemorrhage (7). An urgent non-contrast CT brain is mandatory to distinguish it from an ischaemic stroke (7).
Seizure with Post-ictal Paralysis (Todd's Palsy): This is a key differential, presenting as transient focal weakness after a seizure. The presence of tonic-clonic movements, tongue biting, or incontinence at onset points towards a seizure. The neurological deficit in Todd's palsy typically resolves within 48 hours.
Hypoglycaemia: This is a crucial stroke mimic that must be excluded immediately. It can perfectly replicate focal neurological deficits (7). A bedside blood glucose test provides the answer instantly; the deficits will resolve rapidly with glucose correction.
Migraine with Aura (Hemiplegic Migraine): This can present with unilateral weakness, sensory changes, or aphasia. However, it is typically distinguished by a preceding or accompanying headache with migrainous features (e.g., throbbing quality, photophobia, phonophobia) and a history of similar episodes. The progression of symptoms is often more gradual ("march") compared to the sudden onset of a stroke.
Investigations
Immediate & Bedside Tests
Capillary Blood Glucose: This is a mandatory and immediate test for every patient with suspected stroke to rule out hypoglycaemia (a key stroke mimic) (7), which would require urgent correction and alter the diagnosis entirely.
12-lead ECG: This is essential to immediately detect atrial fibrillation (a major cause of cardioembolic stroke) or signs of a concurrent myocardial infarction (7), both of which are critical for determining the underlying aetiology and guiding secondary prevention.
Diagnostic Workup
First-Line Investigations: An urgent Non-Contrast CT Brain (NCCT) is the absolute first-line imaging modality (1, 4). Its primary, non-negotiable purpose is to definitively rule out intracranial haemorrhage (the action), as its presence is an absolute contraindication to thrombolysis (the rationale) (7).
Gold Standard: While NCCT is for immediate triage, Magnetic Resonance Imaging (MRI) with Diffusion-Weighted Imaging (DWI) is the gold standard for diagnosis (7). It is highly sensitive for detecting cytotoxic oedema within minutes of ischaemic onset (the rationale), confirming the diagnosis and delineating the extent of the infarct with high precision (the action) (7).
Advanced Imaging (for selected patients): CT Angiography (CTA) or MR Angiography (MRA) is performed to visualise the head and neck arteries (7). This is crucial to identify a Large Vessel Occlusion (LVO) (the rationale), which would make the patient a candidate for mechanical thrombectomy (the action) (7). CT Perfusion (CTP) may be used in an extended time window to differentiate the salvageable penumbra from the irreversible infarct core (the rationale), helping to select patients for thrombectomy up to 24 hours from onset (the action) (7).
Monitoring & Staging
Full Blood Count: This is essential to identify thrombocytopenia (which increases bleeding risk with thrombolysis) or polycythaemia (a potential cause of stroke) (7), allowing for risk stratification before treatment.
Coagulation Profile (PT/INR, aPTT): This is a mandatory prerequisite before administering thrombolysis to rule out any underlying coagulopathy (the action), as a bleeding disorder would dramatically increase the risk of life-threatening intracranial haemorrhage (the rationale) (7).
Renal Profile & Electrolytes: This establishes a baseline for renal function to guide safe medication dosing (e.g., for anticoagulants) and to rule out electrolyte disturbances as a cause of confusion (7).
Management
Management Principles
The management of acute ischaemic stroke is governed by the "Time is Brain" principle and focuses on immediate stabilisation, rapid reperfusion to salvage the ischaemic penumbra, prevention of complications, and initiation of secondary prevention (7).
Acute Stabilisation (The First Hour)
Airway/Breathing: Ensure a patent airway. Administer supplemental oxygen via nasal prongs or face mask to maintain SpO2 >94% (the action), which is crucial to prevent secondary hypoxic brain injury and support the penumbra (the rationale).
Circulation: Secure two large-bore IV cannulas (e.g., G18) and start normal saline infusion. If hypotensive, administer a fluid bolus to restore perfusion (7). Aggressively manage blood pressure:
If eligible for thrombolysis: Lower BP to <185/110 mmHg and maintain it at <180/105 mmHg post-treatment (the action) to minimise the risk of haemorrhagic transformation (the rationale) (7). Labetalol or Nicardipine are commonly used.
If not eligible for thrombolysis: A strategy of "permissive hypertension" (up to 220/120 mmHg) is often adopted (the action) to maximise collateral blood flow to the penumbra (the rationale) (7).
Disability: Check capillary blood glucose immediately and correct if <3.5 mmol/L (7). Assess baseline neurological deficit using the NIHSS (National Institutes of Health Stroke Scale) to quantify stroke severity and determine eligibility for reperfusion therapies (7).
Exposure: Check for and manage fever aggressively with paracetamol, as hyperthermia is associated with worse neurological outcomes (7).
Definitive Therapy
This is guided by the Malaysian CPG for Ischaemic Stroke (1).
First-Line Treatment (Reperfusion):
Intravenous Thrombolysis (IVT): For eligible patients presenting within 4.5 hours of clear symptom onset, Intravenous Alteplase (rtPA) is the standard of care (1). The dose is 0.9 mg/kg (maximum 90mg), with 10% given as a bolus over 1 minute and the remaining 90% infused over 60 minutes (1). Tenecteplase (TNK) is an emerging alternative given as a single bolus, showing non-inferiority and potential benefits for LVO (7).
Mechanical Thrombectomy (MT): This is the standard of care for patients with an acute ischaemic stroke due to a Large Vessel Occlusion (LVO) in the anterior circulation (1, 7). It can be performed up to 6 hours from onset, and in selected patients with a favourable tissue profile on perfusion imaging, the window can be extended up to 24 hours (1, 7). Patients may receive IVT first if eligible (the "drip and ship" model) before transfer to a thrombectomy-capable centre (7).
Antiplatelet Therapy (for non-thrombolysed patients): Aspirin 300mg stat should be given once a haemorrhagic stroke has been excluded by imaging (1). For minor strokes (NIHSS ≤3) or high-risk TIAs, Dual Antiplatelet Therapy (DAPT) with Aspirin and Clopidogrel for 21 days is recommended, initiated within 24 hours (1, 7).
Supportive & Symptomatic Care
VTE Prophylaxis: Use intermittent pneumatic compression devices. Subcutaneous heparin should be avoided in the first 24 hours post-thrombolysis.
Dysphagia Screening: All patients must be kept Nil By Mouth (NBM) until a formal swallow assessment is performed (e.g., by a speech therapist or trained nurse) (1). This is critical to prevent aspiration pneumonia (7).
Glycaemic Control: Maintain blood glucose between 6-10 mmol/L. Avoid and actively treat both hypoglycaemia and significant hyperglycaemia (7).
Nutritional Support: If dysphagia is present, insert a nasogastric tube for feeding after 24 hours to ensure adequate nutrition.
Key Nursing & Monitoring Instructions
Strict hourly neurological observations using the Glasgow Coma Scale (GCS) and NIHSS for the first 24 hours.
Continuous cardiac monitoring for at least 24 hours to detect arrhythmias like AF.
Strict blood pressure monitoring: every 15 minutes for the first 2 hours post-thrombolysis, then decreasing in frequency.
Maintain a strict input/output chart.
Inform medical staff immediately if:
GCS drops by ≥2 points.
There is any worsening of neurological deficits.
Systolic BP >180 mmHg or Diastolic BP >105 mmHg post-thrombolysis.
Patient develops a severe headache, nausea, or vomiting.
Long-Term Plan & Patient Education
Secondary Prevention: This is paramount. It includes lifelong antiplatelet therapy (e.g., Aspirin 75-150mg OD or Clopidogrel 75mg OD) for non-cardioembolic stroke (1, 7). For cardioembolic stroke (e.g., with AF), long-term anticoagulation (preferably with a DOAC) is indicated (7).
Risk Factor Management: Aggressive control of hypertension (target <130/80 mmHg), diabetes (target HbA1c <7%), and dyslipidaemia (high-intensity statin therapy for nearly all patients) (7).
Lifestyle Modification: Counsel on smoking cessation, a healthy diet, regular exercise, and weight management (7).
Rehabilitation: Arrange for a multidisciplinary team approach involving physiotherapy, occupational therapy, and speech therapy as soon as the patient is stable (7).
Patient Education: Educate the patient and family on recognising stroke symptoms (F.A.S.T.), the importance of medication adherence, and the follow-up plan.
When to Escalate
Call Your Senior (MO/Specialist) if:
You confirm a new case of acute ischaemic stroke, especially if the patient is within the time window for reperfusion therapy.
The patient's neurological status deteriorates (e.g., GCS drop, worsening NIHSS score).
Blood pressure remains refractory to treatment, especially post-thrombolysis.
The patient develops a severe headache, vomiting, or acute confusion post-thrombolysis (suspicion of intracranial haemorrhage).
Any acute complication arises (e.g., seizure, respiratory distress).
Referral Criteria:
All acute stroke patients require immediate discussion with the on-call physician/neurologist.
Refer to the Neurology team for all confirmed strokes.
Refer to the Neurosurgery team immediately if imaging shows a large infarct with significant mass effect, signs of herniation, or haemorrhagic transformation requiring surgical intervention.
Refer to the Interventional Neuroradiology team if the patient is a candidate for mechanical thrombectomy.
Refer to the Rehabilitation Medicine team early for planning of ongoing rehabilitative care.
References
Malaysian Society of Neurosciences. (2020). Clinical Practice Guidelines: Management of Ischaemic Stroke (3rd Edition). Journal of Cardiovascular, Neurovascular & Stroke, 3(1), 1-155. Retrieved from https://www.researchgate.net/publication/351357870_Clinical_Practice_Guidelines_Management_of_Ischaemic_Stroke_3rd_Edition_2020
Tan, K. S., & Venketasubramanian, N. (2022). Stroke Burden in Malaysia. Journal of the Neurological Sciences, 433(S1), 117811. Adapted from https://www.researchgate.net/publication/359456292_Stroke_Burden_in_Malaysia
Hwong, W. Y., et al. (2021). Trends of Stroke Incidence and 28-Day All-Cause Mortality after a Stroke in Malaysia: A Linkage of National Data Sources. Malaysian Journal of Medical Sciences, 28(3), 69-81. Adapted from https://www.researchgate.net/publication/351883112_Trends_of_Stroke_Incidence_and_28-Day_All-Cause_Mortality_after_a_Stroke_in_Malaysia_A_Linkage_of_National_Data_Sources
Ganasegeran, K., et al. (2021). Stroke Management and Rehabilitation. Saujana Health. Retrieved from https://saujanahealth.com.my/articles/stroke-management-and-rehabilitation/
Yusof, F. A., et al. (2024). Survival of Ischaemic and Haemorrhagic Stroke: Analysis of the Malaysian National Stroke Registry Data from 2009 to 2013. Malaysian Journal of Medical Sciences, 31(5), 1-13. Adapted from http://www.mjms.usm.my/MJMS31052024/MJMS31052024_14.pdf
CodeBlue. (2022, December 28). Malaysian Stroke Patients Take Average Seven Hours For Hospital Arrival. Retrieved from https://codeblue.galencentre.org/2022/12/malaysian-stroke-patients-take-average-seven-hours-for-hospital-arrival/
Ischaemic Stroke Comprehensive Overview.pdf. (Provided document).
