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Written by: Yung Bing Yong
The brain is the primary organ of the centre nervous system that controls our body and houses our mind. It is metabolically active and dependent on a continuous supply of oxygenated blood. If the blood supply is interrupted, the brain could not function normally, resulting a rapid appearance of focal or global disturbance of cerebral functions and its consequent neurological symptoms. If deprived of oxygen for 20s, the brain falls into unconsciousness as the electrical activity cease due to energy depletion. This can become irreversible if it extends beyond 5 min when permanent damage has been made.
In this PBL scenario, a 67-year-old Caucasian woman who has a 15 pack-year smoking history arrived in A&E with ipsilateral weakness of both her right upper and lower limb, difficulty speaking and is known with atrial fibrillation and hypertension. Her current medication is warfarin and amlodipine. Clinical presentation and further investigation suggests that she had a stroke.
To further understand the cases in more details, four learning objectives below are proposed in attempt to cover the knowledge necessary to explain the scenario in this PBL:
- Describe the blood supply of the brain.
- Explore the epidemiology of strokes.
- Explain the value of CT with and without contrast in this PBL scenario.
- Consider the treatment and prognosis of the patient.
Term to be clarified:
(a) Warfarin: An anticoagulant to reduce the risk of blood clotting by inhibiting vitamin K epoxide reductase. It
decrease the levels of active vitamin K and thus lowered the efficiency of blood coagulation cascade.
- Amlodipine: A calcium channel blocker. It works by blocking calcium influx into smooth muscles cells of the wall
of blood vessels. As a result, vasoconstriction is inhibited and thus reducing the blood pressure.
- Aphasia: Difficulty in using language. It is categorised into four main types:
- Expressive aphasia – patients know what to say, but are having trouble saying what they mean.
- Receptive aphasia – patients are having difficulty making sense of the words or diagrams.
- Anomic aphasia – patients are facing problems recalling words, names or numbers. (“speaking in a
- Global aphasia – patients cannot speak, understand speech, read, or write. It is the combination of
expressive and receptive aphasia.
- Pack year: unit for measuring the smoking history of a person as to be used in risk factor estimation.
1 pack year= 20 cigarettes per day.
Formula: No. of pack year =
- Equivocal plantar response: normal and consistent plantar reflex of both legs. Plantar reflex is a reflex elicited
when the sole of the foot is stimulated with a blunt instrument. The toes flex as a
result. This is to disregard the Babinski sign (the toes extend and fans out), which
indicating the presence of spinal cord injury.
- Describe the blood supply of the brain.
The brain constitutes just about 2% of the body weight but demands 20% of the available oxygen and 15% of the cardiac output. Blood is supplied to the brain via two sets of branches from the dorsal aorta, which forms the anterior and posterior circulations. The anterior circulation supplies the forebrain and the deep structures such as the basal ganglia, thalamus, and internal capsule entering through the carotid canal and foramen lacerum by making a stepwise turn; whereas the posterior circulation supplies the structures of the posterior fossa (posterior cortex, midbrain, cerebellum and brainstem) entering the skull cavity through the foramen magnum.
The anterior circulation carries 80% of the blood supply of the brain. Once entering the brain, the internal carotid artery (ICA) passes through the cavernous sinus and branches off as the middle cerebral artery (MCA) and anterior cerebral artery (ACA). The two anterior cerebral arteries are anastomosed by the anterior communicating artery. The remaining 20 % of the arterial supply of the brain derived from the posterior circulation comprises the vertebral, basilar and posterior cerebral arteries (PCAs).
The two circulations are united at the base of the midbrain around the optic chiasm by a network of arteries called the Circle of Willis (Fig. 2).
Looking at the anterior circulation of the Circle of Willis, which arises from the ICA, the ophthalmic artery can be observed. It supplies the orbit, the eye muscles and the retina, and eventually connects to the external carotid arteries.
The MCA is the largest and thus the most important branch of the ICA due to its clinical relevance as the common site of stroke. It receives 80% of the carotid blood flow and its proximal part gives off deep branches- lateral and medial striate arteries supply corpus striatum and the internal capsule regions of the brain. Occlusion of these deep arteries is the chief cause of classic stroke, and the most common location is the putamen and internal capsule.
The disability experienced by the stroke patient depends on the area of brain tissues damaged due to cerebrovascular accident in one particular or more blood supply of the brain. Figure 4 illustrated the functional areas supplied by individual cerebral vasculature.
Figure 5, on the other hand gives a few examples of possible symptoms caused by damage from strokes in different areas. In the interest of this PBL scenario, damage in Broca’s area lead to expressive aphasia; damage in Wernicke’s area provokes receptive aphasia; damage in both respective area will then prompt to global aphasia.
Having compared the homunculus of the somatosensory and motor cortex as shown above (Fig. 6) to the functional area supplied by cerebral arteries (Fig. 4), the legs to the hips is on the medial surface of the cerebral cortex that is supplied by the ACA. Therefore, even though, the MCA is occluded in this scenario, there is not complete paralysis in the legs.
- Explore the epidemiology of strokes.
Stroke occurs approximately 152,000 times a year in the UK in which men are at a 25% higher risk of having a stroke and at a younger age compared to women.
It is defined as the temporary or permanent loss of function of brain tissues caused by interruption of the vascular supply. It is subdivided into:
- Haemorrhagic stroke: Aneurism of blood vessels in the brain that burst.
- Ischemic stroke: Blood vessels in the brain are either clog by local atherosclerosis or thromboembolism.
- Transient ischemic attack (TIA): Same pathophysiology as ischemic stroke, but occurrence last less than 24 hours. Therefore, it is always a retrospective diagnosis.
Risk factors of stroke can be classified into:
Modifiable risk factors
Non-modifiable risk factors
Age > 75
Direct or indirect causes:
Ischemic stroke– Atheroscelerosis, hypertension, atrial fibrillation, valve disorder, sickle cells, thrombocytosis Haemorrhagic stroke– Aneurysm, head trauma, arteriovenous malformation, chronic hypertension, drug
- Explain the basic principle of CT with and without contrast in this PBL scenario.
Ideally, when stroke is suspected, a brain CT scan is arranged immediately to differentiate the type of stroke: Haemorrhagic or ischemic stroke, which determine the treatment option that are significantly different.
In practice, non-contrast CT is usually not sensitive in diagnosing ischaemic stroke or cerebral infarction in an emergency situation but is a quick method to identify acute haemorrhage in the brain, as a pool of blood will show up in white and disqualify the use of thrombolytic or clot-buster. As the time passes (first 24 hours) loss of grey-white differentiation would be shown on the CT that could suggest signs of infarction. This is the why the patient in this case did not present any sign of stroke at 7:05am on the head CT.
To better diagnosing ischaemic stroke, recent advances in CT technology, be it the contrast CT called CT angiography provide additional data to visualise the cerebral vasculature shortly after an intravenous contrast bolus.
If an ischaemic stroke is diagnosed as in the case of this PBL, and it has been less than four and a half hours since symptoms started, Alteplase will be given intravenously, while haemorrhagic stroke can be managed with surgical repair.
- Consider the treatment and prognosis of the patient.
Treatment for ischaemic stroke
(1) Immediate Care
- Thrombolytic (within golden 3-4.5 hours): Tissues plasminogen activator (tPA); Alteplase; Urokinase
- Intravenous fibrinolytic therapy
- Surgery: carotid endoterectomy/ angioplasty
- Ultrasound-enhanced thrombolysis
Life after stroke can be very difficult and challenging. Rehabilitation is necessary to improve quality of life and the eventual outcome, if not full function of the body.
- Speech & language therapy helps people who have problems producing or understanding speech.
- Physiotherapy helps with relearning movement and co-ordination of muscles.
- Psychological care helps with common mental health problems such as depression.
- Occupational therapy helps with assessing patients’ home and improving their abilities to carry out daily activities such as dressing and eating.
(3) Secondary Prevention 3 in 10 stroke survivors will suffer another stroke or TIA. That is why secondary prevention is much importance. Seeing the fact that the patient as illustrated in this case has atrial fibrillation and is on warfarin but still encountered a stroke attack, a close monitor of warfarin INR should be done afterwards and possible increase in doses or change of medication. Healthy lifestyle that covers the diet and exercise should be recommended and implemented.
How well a patient does after acute ischaemic stroke depend on numerous factors, such as the area of brain tissues is damaged, the affected body function, and the time of appropriate treatment is received.
Generally, patient often improves in moving, talking and thinking in the weeks to months after a stroke and undergoes rehabilitation. However, they do suffer some sort of morbidity. Only roughly 30% of patients are neurologically normal or near normal. Fortunately, about 50% of patients are completely or almost completely independent in daily living.
- Adams HP Jr, et al. Guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1994; 25: 1901-1914.
- Brierley JB. Experimental hypoxic brain damage. Journal of Clinical Pathology 1977s3-11: 181-187.
- Bryan RN, et al. Diagnosis of acute cerebral infarction: Comparison of CT and MR imaging. AJNR Am J Neuroradiol 1991; 12: 611-620.
- Clarke DD, Sokoloff L. Regulation of Cerebral Metabolic Rate. Basic Neurochemistry: Molecular, Cellular and Medical Aspects, 6th edition. Philadelphia: Lippincott-Raven; 1999.
- Lee JM, Grabb MC, Zipfel GJ, Choi DW. Brain tissue responses to ischemia. J Clin Invest. 2000;106(6):723-731.
- MedlinePlus. Aphasia. Available at: http://www.nlm.nih.gov/medlineplus/aphasia.html. [Accessed 24th March 2015].
- Michael-Titus A, Revest P, Shortland P. STROKE AND HEAD INJURY. The Nervous System, 2nd edition: Elsevier Limited; 2010. pp. 200-209.
- NICE. Alteplase for treating acute ischaemic stroke (review of technology appraisal guidance 122). Available at: http://www. nice.org.uk/guidance/ta264/chapter/1-guidance. [Accessed 11 April 2015].
- Rull G. Thrombolytic Treatment of Acute Ischaemic Stroke. Available at http://www.patient.co.uk/doctor/thrombolytic-treatment-of-acute-ischaemic-stroke. [Accessed 11 April 2015].
- Stoke Association. State of the Nation Stroke Statistics-January 2015. Available at: http://www.stroke.org.uk/resource-sheet/state-nation-stroke-statistics. [Accessed 11 April 2015].
- Townsend N, et al. Coronary heart disease statistics 2012 edition. British Heart Foundation: London
- Xavier AR, et al. Neuroimaging of Stroke: A Review. South Med J. 2003;96(4). Available at: http://www.medscape.com/viewarticle/452843_2. [Accessed 11 April 2015]
 Lee JM, Grabb MC, Zipfel GJ, Choi DW. Brain tissue responses to ischemia. J Clin Invest. 2000;106(6):723-731.
 Clarke DD, Sokoloff L. Regulation of Cerebral Metabolic Rate. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Philadelphia: Lippincott-Raven; 1999.
 Townsend N, et al. Coronary heart disease statistics 2012 edition. British Heart Foundation: London
 Bryan RN, et al. Diagnosis of acute cerebral infarction: Comparison of CT and MR imaging. AJNR Am J Neuroradiol 1991; 12: 611-620.
 Adams HP Jr, et al. Guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1994; 25: 1901-1914.
 NICE. Alteplase for treating acute ischaemic stroke (review of technology appraisal guidance 122). Available at: http://www. nice.org.uk/guidance/ta264/chapter/1-guidance. [Accessed 11 April 2015].
 Stroke Association. State of the Nation Stroke Statistics-January 2015. Available at: http://www.stroke.org.uk/resource-sheet/state-nation-stroke-statistics. [Accessed 11 April 2015].
 Rull G. Thrombolytic Treatment of Acute Ischaemic Stroke. Available at http://www.patient.co.uk/doctor/thrombolytic-treatment-of-acute-ischaemic-stroke. [Accessed 11 April 2015].
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