8th August 2024

Stroke and Transient Ischaemic Attack

Stroke

Overview of stroke

This is a common neurological disorder with an incidence of 100,000 people per year in the UK. It is an acute onset vascular event resulting in damage to neurological tissue. The aetiology may be ischaemic or haemorrhagic. Strokes may be further classified by symptoms and signs according to the Oxfordshire Community Stroke Project (Bamford) classification, by the lobes affected, or by a number of clinical syndromes.

Ischaemic stroke

Aetiology of ischaemic stroke

Ischaemic stroke accounts for 80% of cases. Risk factors include increasing age, (family) history of stroke, smoking, hypertension, diabetes, atrial fibrillation, ischaemic heart disease, hypercholesterolaemia and sickle cell disease.

Ischaemic stroke may occur due to:

• Large vessel atherosclerosis resulting in thromboembolism
• Cardioembolism: atrial fibrillation, endocarditis, myocardial infarction, paradoxical systemic emboli
• Small vessel occlusion

Rarer aetiologies include:

• Venous infarction: this is caused by cerebral venous sinus thrombosis (CVST). Risk factors include oral contraception, dehydration, malignancy, thrombophilia and infection. It results in infarction with significant oedema and presents with headache, focal neurology and seizures. The pathology does not follow usual arterial infarct territories, and the empty delta sign on CT venogram is diagnostic. Patients are prone to haemorrhage but treatment is with anticoagulation (heparin then warfarin).
• Carotid and vertebral artery dissection: separation of the arterial walls results in haematoma formation. This may be spontaneous, related to trauma to the neck, which may be minor or not remembered (can include neck manipulation, sports and childbirth) or fibromuscular dysplasia. Resultant ischaemia is usually due to thromboembolism.
• Border zone infarct: a sudden drop in systemic blood pressure and subsequent intracerebral perfusion, for example with sepsis, may result in a border zone infarct in areas at the periphery of vascular territories.
• Inherited disorders including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an inherited disorder of the NOTCH3 gene resulting in migraine with aura, ischaemic events and cognitive impairment.
• Dolichoectasia (elongation and tortuosity) of the vertebrobasilar arteries, leading to thrombus formation.
• Moyamoya disease: a disease characterised by large vessel intracranial stenosis and subsequent collateral formation resulting in a classical ‘puff of smoke’ appearance on angiography. Unknown cause, highest prevalence in East Asian countries.
• In the context of systemic disease: vasculitis, thrombophilia.

Presentation of ischaemic stroke

The exact presentation varies depending on the vascular territory affected but, importantly, strokes cause sudden onset (within seconds) of negative symptoms. These include sensory deficit, motor deficit, speech impairment and visual impairment.

General clinical features according to the territory affected, as well as key stroke syndromes, are outlined below.

Anterior circulation (supplied by the internal carotid arteries, ICA):

Posterior circulation (vertebrobasilar circulation):

Assessment of ischaemic stroke

Timely diagnosis and management of stroke is crucial as the longer from the acute event, the more brain tissue is irreversibly damaged, and earlier initiation of treatment is associated with better outcomes.

• Recognition: using a validated score such as ROSIER (Recognition of Stroke in the Emergency Room) or FAST (Face Arm Speech Test) in the community.
• Assessment: a focused history from the patient or witness and an examination using the National Institutes of Health Stroke Scale (NIHSS) is performed to give an indication of stroke severity.
• Bedside tests: routine bloods including clotting, blood glucose to exclude mimic, ECG for arrhythmias.
• Imaging: immediate non-contrast CT head to exclude haemorrhage, consider CT angiography (CTA) if a large-vessel occlusion is suspected or the patient is a candidate for thrombectomy (see below).

Management of ischaemic stroke

Initial treatment should be supportive: monitor blood pressure, saturations, glucose and GCS, treat seizures if occurring, make nil by mouth until swallow assessment is performed. The patient should be admitted to a hyperacute stroke unit (HASU).

Specific management depends on time of onset:

Secondary prevention:

• Antiplatelet or anticoagulant: clopidogrel monotherapy lifelong or consider DOAC after 14 days if indicated (e.g. in AF)
• Carotid endarterectomy within 2 weeks if there is significant symptomatic stenosis, defined as >50% symptomatic stenosis using the NASCET criteria or > 70% stenosis using the ECST criteria. If there is contralateral stenosis, elective surgery may be offered after two to four weeks
• High-intensity statin therapy
• Control of vascular risk factors, including diabetes, hypertension and smoking

Further investigations and identifying an underlying cause

• MRI scan: diffusion-weighted imaging (DWI) is sensitive for an acute infarct
• Cardiac monitoring: to identify arrhythmias; consider Holter (ambulatory) monitor if suspicion of an embolic source (e.g. bilateral infarcts) but no arrhythmia has been captured during admission
• Echo: to identify vegetations, which can be a source of emboli; consider bubble echo to identify patent foramen ovale as source of paradoxical embolus
• Carotid Doppler: for large vessel atherosclerosis or dissection
• Bloods: in a younger patient, consider additional bloods such as a vasculitis screen and HIV and syphilis serology. Test for conditions such as polycythaemia, thrombophilia or sickle cell disease if appropriate

Complications of ischaemic stroke

• Malignant transformation: if a patient suffers a large MCA or cerebellar stroke the resulting oedema may cause raised intracranial pressure and herniation, which requires immediate neurosurgical discussion.
• Haemorrhagic transformation: large infarcts have a tendency to bleed, particularly if given thrombolysis. Monitor for neurological deterioration and immediately repeat a CT brain if this occurs.

Image Source: Wikimedia Commons (2016). DWE MRI of cerebral infarctio, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:DWE_MRI_of_cerebral_infarction.png (Accessed: 16 January 2024)

Haemorrhagic stroke

Aetiology and pathophysiology of haemorrhagic stroke

Approximately 20% of strokes are haemorrhagic.

The biggest risk factors are increasing age, hypertension, and use of antiplatelets or anticoagulants. Other risk factors include male sex, heavy alcohol use, stimulant drug use (cocaine), vascular malformations and cerebral malignancy, cerebral amyloid angiopathy (CAA), bleeding disorders, cerebral vasculitis and increased aneurysm risk (e.g. in connective tissue diseases or autosomal dominant polycystic kidney disease).

Haemorrhagic stroke may occur due to:

• Spontaneous intracerebral haemorrhage, risk factors for which are listed above, but most common aetiologies are hypertensive (resulting small vessel disease affecting deep perforating vessels leads to haemorrhage within the deep structures of the brain, such as the basal ganglia) and CAA (deposition of amyloid beta-peptide deposits in blood vessels results in lobar haemorrhage affecting cortical vessels. CT may demonstrate typical ‘finger-like’ projections and subarachnoid extension).
• Subarachnoid haemorrhage (SAH): mostly due to aneurysm rupture.

Pathology due to traumatic haemorrhage (e.g. subdural or extradural haematoma) is not usually considered a stroke.

Presentation and management of haemorrhagic stroke

The presentation is similar to ischaemic stroke. Clues that a stroke may be haemorrhagic include meningism, severe headache, reduced or progressive loss of consciousness and seizures.

Initial assessment is the same as for ischaemic stroke, including the importance of swift diagnosis and management. Specific considerations for haemorrhagic stroke include:

• Assessment: haemorrhage will usually be seen on CT
• Initial treatment:
  • Rapid blood pressure control using IV labetalol, target 140 mmHg systolic
  • Rapid reversal of anticoagulation; not for aspirin or other antiplatelets
  • Discuss with neurosurgery
• SAH: additionally treated with nimodipine PO/NG (nasogastric) to reduce vasospasm; ultimately requires neurosurgical management with endovascular coiling, if there is an appropriate aneurysm target, to prevent re-bleeding
• Identifying the cause:
  • MRI may demonstrate an arteriovenous malformation (AVM); microbleeds suggest CAA
  • SAH: cerebral angiography (CTA, MRA [MR angiography] or digital subtraction angiography) to identify aneurysms
• Secondary prevention is with adequate control of hypertension and other risk factors. Statins are contra-indicated post haemorrhagic stroke

Image Source: Wikimedia Commons (2008). Intracerebral, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Intracerebral.jpg (Accessed: 16 January 2024)

Image Source: Wikimedia Commons (2006). Subarachnoid haemorrhage, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Subarachnoid_haemorrhage.jpg (Accessed: 16 January 2024)

Image Source: Wikimedia Commons (2016). Trauma subdural arrows, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Trauma_subdural_arrows.jpg (Accessed: 16 January 2024)

Image Source: Wikimedia Commons (2011). 13049 2011 Article 474 Fig2 HTML, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:13049_2011_Article_474_Fig2_HTML.webp (Accessed: 16 January 2024)

Stroke mimics

Common stroke mimics to consider in the differential include TIA, hypoglycaemia, migraine, seizure and postictal state, conversion disorders, malignancy, sepsis, vasculitis, Bell’s palsy or decompensation of prior stroke and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS).

Vertigo

It may be difficult to discern a posterior circulation stroke from its differentials. For persistent vertigo in the absence of other neurology, the HINTS (head impulse, nystagmus, test of skew) examination can be used to differentiate central from peripheral causes. However, often an MRI scan is required. Key differentials and features include:

References

• Caplan LR. Overview of the evaluation of stroke. In: Kasner SE, Dashe JF, editors. UpToDate. [Internet]. Waltham (MA): UpToDate Inc; 2021. [Aug 3 2021; cited January 21 2022]. Available from: https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke
• Caplan LR. Posterior circulation cerebrovascular syndromes. In: Biller J, Dashe JF, editors. UpToDate. [Internet]. Waltham (MA): UpToDate Inc; 2021. [June 8 2021; cited January 21 2022]. Available from: https://www.uptodate.com/contents/posterior-circulation-cerebrovascular-syndromes
• Charnnarong Suwanwela N. Moyamoya disease: Etiology, clinical features and diagnosis. In: Biller J, Nordli DR, Tung GA, editors. UpToDate. [Internet]. Waltham (MA): UpToDate Inc; 2020. [Oct 21 2020; cited March 7 2022]. Available from: https://www.uptodate.com/contents/moyamoya-disease-etiology-clinical-features-and-diagnosis#H21
• Furman JM. Causes of Vertigo. In: Aminoff MJ, Deschler DG, Wilterdink JL, editors. UpToDate. [Internet]. Waltham (MA): UpToDate Inc; 2021. [March 23 2021; cited January 21 2022]. Available from: https://www.uptodate.com/contents/causes-of-vertigo
• Jones M. Stroke due to spontaneous intracerebral haemorrhage. In: BMJ Best Practice. [Internet]. London: BMJ Publishing Group, 2021 [August 17 2021; cited January 21 2022]. Available from: https://bestpractice.bmj.com/topics/en-gb/3000109
• Jones M, Power R. Ischaemic stroke. In: BMJ Best Practice. [Internet]. London: BMJ Publishing Group, 2021 [June 04 2021; cited January 21 2022]. Available from: https://bestpractice.bmj.com/topics/en-gb/3000114
• Logmore M, Wilkinson I, Baldwin A, Wallin E. Oxford Handbook of Clinical Medicine. 9th edition. Oxford: Oxford University Press. 2014
• Markus H, Pereira A, Cloud G. Stroke medicine [Internet]. Oxford: Oxford University Press; 2016 [cited 2022 Feb 3]. Available from: https://oxfordmedicine.com/view/10.1093/med/9780198737889.001.0001/med-9780198737889
• National Institute for Health and Care Excellence. Stroke and transient ischaemic attack in over 16s: diagnosis and initial management. London: NICE, 2019 [May 1 2019; cited January 21 2022]. Available from: https://www.nice.org.uk/guidance/ng128
• O’Ferrall E. Mitochondrial myopathies: Clinical features and diagnosis. UpToDate [Internet]. Shefner JM, Hahn S, editors. UpToDate. 2021 [cited 2022 Feb 5]. Available from: https://www.uptodate.com/contents/mitochondrial-myopathies-clinical-features-and-diagnosis
• Oliveira-Filho J, Mullen MT. Initial assessment and management of acute stroke. In: Kasner SE, Edlow JA, Dashe JF, editors. UpToDate. [Internet]. Waltham (MA): UpToDate Inc; 2021. [March 5 2021; cited January 21 2022]. Available from: https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke

Transient ischaemic attack (TIA)

TIA

TIA is defined as a transient episode of focal neurological dysfunction due to ischaemia without acute infarction; aetiology is as per ischaemic stroke. It resolves within 24 hours and cannot be explained by other causes.

TIAs present with the same clinical features as stroke, depending on which vascular territory is affected, including speech or visual impairment and sensory or motor deficit. History (by the patient or a witness) is key to diagnosis.

Assessment and management of TIA

TIA is an emergency due to the high risk of stroke, however many patients can be managed as outpatients:

Admission should be considered if a patient has high risk features such as crescendo TIA (>1 TIA in a week), high risk of a cardioembolic source (new AF) or ongoing neurological symptoms (potential stroke).

Investigations should include:

• Routine bloods including clotting, blood sugar level to exclude mimic, ECG to exclude arrhythmia
• CT head is only recommended if an alternative cause is suspected or to exclude haemorrhage in patients taking anticoagulants
• Further investigations will be requested from TIA clinic:
  • MRI scan: if DWI demonstrates an acute infarct, the diagnosis is stroke
  • Consideration of carotid Doppler, echo and 24 hour tape as per ischaemic stroke

Management is as follows:

• Immediate treatment: on suspicion of TIA, give 300 mg aspirin (unless haemorrhage suspected)
• Secondary prevention:
  • Antiplatelet or anticoagulant: clopidogrel monotherapy lifelong or anticoagulation if in AF
  • High-intensity statin therapy
  • Carotid endarterectomy if significant stenosis on symptomatic side (as per stroke)
  • Control of vascular risk factors: diabetes, hypertension, smoking

TIA mimics

Important differentials to consider include: stroke, hypoglycaemia, migraine, seizure and postictal state, conversion disorders, malignancy, sepsis, multiple sclerosis, vasculitis, transient global amnesia and differentials of vertigo as previously discussed.

References

• Jones M, Power R. Transient ischaemic attack. In: BMJ Best Practice. [Internet]. London: BMJ Publishing Group, 2021 [July 13 2021; cited January 21 2022]. Available from: https://bestpractice.bmj.com/topics/en-gb/3000090
• Logmore M, Wilkinson I, Baldwin A, Wallin E. Oxford Handbook of Clinical Medicine. 9th edition. Oxford: Oxford University Press. 2014
• National Institute for Health and Care Excellence. Stroke and transient ischaemic attack in over 16s: diagnosis and initial management. London: NICE, 2019 [May 1 2019; cited January 21 2022]. Available from: https://www.nice.org.uk/guidance/ng128

Chronic neurological disability

Following a stroke or other intracranial event many patients are left with high levels of morbidity or disability. Key to managing patients with chronic neurological disability is the joined-up working of a multidisciplinary team (MDT).

Cognitive impairment

Chronic neurological conditions such as stroke can be life changing. Up to 75% of patients are left with some degree of cognitive impairment following a stroke. This may be global or in a specific domain. Two thirds of patients suffer from post-stroke fatigue at six months; no therapy has been proven beneficial for this.

Mood disorders

Up to a third of patients suffer from depression at some point following a stroke and a quarter from anxiety. Mood disturbance and emotional lability may be transient and related to the event, resolving as function and life return to normal. However, depression can negatively impact rehabilitation, reduce independence and functional outcomes and increase mortality.

• Detection: patients should routinely be assessed for mood and cognition disorders throughout follow up, with access to psychological services as part of the MDT.
• Pharmacotherapy: SSRIs are often first line pharmacological treatment in the management of depression but treatment should follow current guidance and be guided by patient discussion.

Communication disorders

Following a stroke, patients may be left with a degree of aphasia, alexia, acalculia or agraphia, impacting independence and quality of life. Key types of aphasia are:

Capacity

Following a stroke, patients may lose capacity to make certain decisions in the short or long-term. It is important that disorders of communication are not confused with lack of capacity. The MDT, particularly speech and language therapists (SLT), must be involved to assist with assessing capacity and help with decision making. This is to ensure all efforts are taken to provide the information in a way understandable to the patient and to understand responses which may not be verbal.

Nutrition and hydration

Difficulty with nutrition and hydration may stem from reduced functional ability affecting cooking and feeding or due to impaired coordination of muscles used in swallowing.  Dysphagia affects up to 50% of people in the acute phase following a stroke. It is associated with significant morbidity, including from aspiration pneumonia, malnutrition and prolonged hospitalisation and as a consequence increased mortality.

All patients with suspected stroke should be assessed with a swallow screen within four hours. If swallowing is deemed to be impaired at this point or if concerns develop during the admission, involve SLT to assess the dysphagia and dieticians to advise on nutrition.

Interventions include:

• 1ˢᵗ line: nasogastric tube (NGT) insertion if swallow deemed to be unsafe >24 hours
• 2ⁿᵈ line: if persisting dysphagia >4 weeks (or in anticipation of dysphagia in some neurological conditions such as motor neurone disease), consider percutaneous endoscopic gastrostomy (PEG) insertion, which confers reduced risk of treatment failure compared to long-term NGT use. Main side effects of PEG insertion include aspiration and infection; pneumoperitoneum is a common, benign finding and, in the absence of peritonitis, should resolve spontaneously in days

Image Source: Wikimedia Commons (2014). Diagram showing the position of a nasogastric tube CRUK 340, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Diagram_showing_the_position_of_a_nasogastric_tube_CRUK_340.svg (Accessed: 17 January 2024)

Image Source: Wikimedia Commons (2014). Diagram showing the position of a percutaneous endoscopic gastrostomy (PEG) feeding tube CRUK 341, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Diagram_showing_the_position_of_a_percutaneous_endoscopic_gastrostomy_(PEG)_feeding_tube_CRUK_341.svg (Accessed: 17 January 2024)

Reduced mobility and pressure ulcers

In chronic neurological conditions, mobility may be reduced due to flaccid or spastic paralysis. Functional limitation can result in disuse atrophy, increased dependence, falls and fractures, increased risk of venous thromboembolism, predisposition to infection such as pneumonia, mood disturbance and pressure ulcers. Manage with comprehensive MDT and family input.

Pressure ulcers

People with chronic neurological disability may be at increased risk of pressure sores through various factors: reduced mobility and inability to reposition themselves, reduced sensation, incontinence, nutritional deficiency and cognitive impairment.

• Prevention:
  • On admission, assess risk of pressure sores using a validated assessment tool (e.g. Waterlow);
  • Frequent skin assessment, repositioning, nutritional supplementation if inadequate intake, barrier creams and pressure redistributing devices.
• Management:
  • Document pre-existing sores and raise safeguarding concerns if required;
  • Assess severity (see classification system below);
  • Choose dressings based on the degree of maceration, exudate and signs of infection: hydrocolloid dressings promote healing and alginate dressings are considered if significant exudate;
  • Consider Tissue Viability Nurse involvement;
  • Debridement if significant necrosis;
  • Consider systemic antibiotics if evidence of sepsis, spreading cellulitis or underlying osteomyelitis.

Image Source: Wikimedia Commons (2012). Wound stage, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Wound_stage.jpg (Accessed: 17 January 2024)

Pain

Pain is often encountered by patients with chronic neurological disability. Following a stroke, this is most commonly musculoskeletal and is related to paralysis and immobility.

Headache

Common following a stroke or due to medications used, such as GTN (glyceryl trinitrate). Manage with simple analgesia.

Hemiplegic shoulder pain

Hemiplegic shoulder pain or subluxation is related to muscular flaccidity and poor handling. Management is with prevention, physiotherapy, positioning and simple analgesia.

Central post-stroke pain

A neuropathic pain syndrome occurring following stroke. Characterised by pain in the areas affected by the stroke and can cause allodynia, hyperalgesia or abnormal sensations. Managed with neuropathic agents; may need Pain Team input.

Spasticity

Common due to upper motor neurone damage. Caused by hyperexcitability of the stretch reflex, resulting in functional impairment, risk of infection related to skin breakdown, pain and the development of contractures.

• Prevention: physical rehabilitation using a variety of techniques
• Management:
  • Physical rehabilitation
  • IM botulinum toxin (type A) for focal spasticity – well tolerated with minimal side effects
  • Trial of oral baclofen or tizanidine – use is limited to generalised spasticity or progressive neurological conditions due to side effects of drowsiness, fatigue and weakness

Continence

Urinary incontinence affects half of patients admitted with an acute stroke, with a significant minority remaining incontinent one year post stroke. Functional urinary incontinence is related to physical limitations, aphasia and cognitive impairment. Short-term urinary catheterisation may be required for symptomatic retention while investigations are done to ascertain the cause. Faecal incontinence is less common and also often related to function, although faecal loading and infection must be ruled out.

References

• Berlowitz DR. Pressure ulcer. In: BMJ Best Practice. [Internet]. London: BMJ Publishing Group, 2021 [August 3 2021; cited January 21 2022]. Available from: https://bestpractice.bmj.com/topics/en-gb/378
• Clark DG. Approach to the patient with aphasia. In: Mendez MF, Wilterdink JL, editors. UpToDate. [Internet]. Waltham (MA): UpToDate Inc; 2021. [July 14 2020; cited January 21 2022]. Available from: https://www.uptodate.com/contents/approach-to-the-patient-with-aphasia
• Creutzfeldt CJ, Robinson MT. Neuropalliative care of stroke. In: Biller J, Morrison RS, Dashe JF, editors. UpToDate. [Internet]. Waltham (MA): UpToDate Inc; 2021. [December 6 2021; cited January 21 2022]. Available from: https://www.uptodate.com/contents/neuropalliative-care-of-stroke
• Improvement, NHS. Psychological care after stroke. Leicester: NHSI, 2011. [cited January 21 2022]. Available from: https://www.england.nhs.uk/improvement-hub/publication/psychological-care-after-stroke-improving-stroke-services-for-people-with-cognitive-and-mood-disorders/
• National Institute for Health and Care Excellence. Stroke and TIA. [Internet] London: NICE, 2021 [September 2021; cited January 21 2022]. Available from: https://cks.nice.org.uk/topics/stroke-tia/
• National Institute for Health and Care Excellence. Stroke and transient ischaemic attack in over 16s: diagnosis and initial management. London: NICE, 2019 [May 1 2019; cited January 21 2022]. Available from: https://www.nice.org.uk/guidance/ng128
• Stroke.org.uk. [Internet] London: Stroke Association, 2022 [cited January 21 2022]. Available from: https://www.stroke.org.uk/