Stroke disease

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Stroke disease - a neurological deficit of presumed vascular origin lasting more than 24 hrs. In practice, stroke disease is a manifestation of many pathological processes giving a similar clinical picture[1].



Stroke is a major cause of death (about 9% worldwide) and morbidity. Efforts should be focused on stroke prevention through blood pressure control, smoking cessation, reduction of cholesterol, anti-coagulation for atrial fibrillation, anti-platelet agents and surgery for selected patients. To date attributable factors for stroke disease explain only 60% of presentations, a much lower explanation rate than we have for ischaemic heart disease.


There are two main types which can be differentiated by CT scanning which in cases potentially suitable for thrombolysis is done immediately after clinical assessment. Increasingly urgent CT cranial angiography, cerebral MRI and/or cerebral vessel MRA is being offered to subgroups with ischaemic stroke as part of acute initial treatment determining work up.

  • Infarction 80% (a strong argument has been made that the new gold standard for this is the characteristic changes on diffusion weighted MRI of cerebral ischaemia[2])
  • Haemorrhage 20%

Clinically can present from collapse to clinically silent (a fair proportion of strokes occur when patient is asleep).

  • Hemiparesis
  • Dysphasia
  • Dysarthria
  • Ataxia
  • Nausea
  • Vomiting

Infarction vs Haemorrhage

  • Headache equally likely with both
  • Need CT scan to differentiate
  • Coma and prognosis tend to be worse with haemorrhage
  • Haemorrhage is more common in some Asian populations, in Japan, the ratios are ischaemic stroke 61 %, ICH 25 % and SAH 11 %[3].


For cerebral infarction, the Bamford Classification of infarcts is used, and can be useful for communication of stroke type and in terms of prognosis as below:


Clinical presentation TACS/PACS/TIA in anterior circulation

  • Distal artery – lower limb weakness
  • Proximal artery– more severe hemiplegia & frontal lobe signs
    • Middle cerebral artery
      • Main stem
      • Deep perforators
        • Cortical sparing
        • Contralateral hemimotor loss
      • Superior trunk
        • Contralateral motor and sensory with leg sparring
        • Temporal lobe unaffected
        • Inferior quadrantic hemianopia
        • Visuospatial disorder (non dominant hemisphere)
        • Wernickes type dysphasia (dominant hemisphere)

Total anterior circulation stroke (TACS)

A large stroke anterior/middle cerebral artery

  • New cortical dysfunction eg dysphasia and
  • New sensory/motor deficit 2/3 areas face/hand/leg and
  • Homonymous hemianopia

Could be associated with:

  • Amarosis fugax (blindness in one eye) if embolic/thrombotic

Partial anterior circulation stroke (PACS)

A smaller cortical stroke with either 2 out of 3 components of TACS or

  • New higher cerebral dysfunction or
  • Motor and sensory disturbance less than TACS
LogoKeyPointsBox.pngClinical presentation of POCS/TIA in posterior circulation

Swelling of brainstem can lead to obstructed exit of CSF from IVth ventricle and thus hydrocephalus. Monitor and CT scan/refer if possible

  • Subclavian artery
    • Rarely if severely stenosed or blocked blood may reverse flow down vertebral artery to supply the arm - the subclavian steal syndrome. Seen when arm is exercised. Can be diagnosed radiologically.

Posterior circulation stroke (POCS)

  • Ipsilateral cranial nerve palsies with contralateral motor/sensory deficit or
  • Bilateral motor/sensory deficit
  • Disorder of conjugate eye movements
  • Cerebellar dysfunction without ipsilateral long tract signs
  • Isolated homonymous field defect

Lacunar stroke (LACS)

Small vessel subcortical stroke

  • Pure motor
  • Pure Sensory
  • Sensorimotor
  • Ataxic hemiparsesis

Transient ischaemic attack

- a neurological deficit of presumed vascular origin lasting less than 24 hrs

  • Usually embolic in nature
  • Classically last 20 minutes
  • Is a major risk factor for impending stroke

Pathophysiology of stroke

  • Ischaemic core of dead cells surrounded by penumbra of potentially viable cells.
  • Ischaemia leads to loss of cell membrane function. Glutamate release leads to influx of calcium ions.
  • Local loss of cerebral autoregulation with increased flow around the peripheries of the infarct.
  • Cerebral oedema develops and is manifest by loss of sulci on CT and decreasing GCS. Cheyne stokes respirations. Brainstem herniation and raised ICP.

Global hypoperfusion

with infarction of watershed areas where circulations overlap. Seen in shock/hypotensive states

Vessel occlusion

  • Thrombosis-in-situ
  • Embolism

Thrombus formation in situ

  • Plaque rupture and thrombosis
  • Vasculitis
  • Cervical artery dissection

Embolism from the heart

Embolism from the carotid

  • Ipsilateral carotid - Carotid plaque

Other classifications

Risk Factors for stroke

Population attributable risks for either acute myocardial infarction or stroke internationally


It has been possible with such public health interventions to reduce the incident of stroke by over 30% over 12 years and interestingly dementia in the last 6 of those years by 7% in Western populations[5]


Carotid endarterectomy for those with Carotid territory TIA/Stroke and ipsilateral Carotid stenosis > 70%


Blood tests

  • FBC ? polycythaemia, platelets
  • ESR ? temporal arteritis / vasculitis
  • U&E
  • Glucose and HbA1C including in non diabetics
  • Cholesterol
  • Prothrombin time
  • Partial Thromboplastin time



See main article Imaging in stroke

  • CT scan
  • MRI scan

Additional Investigations



Where there is disability there is good evidence for best supportive care in a stroke unit as opposed to a general ward

Ischaemic stroke



  • Less than 6 hrs from onset (there is some evidence around the margins for benefit. Best benefit less than 4.5 hours onset. For small to medium size ischaemic strokes of unknown time of onset MRI mismatch between positive diffusion-weighted imaging and negative hyperintensity of flair defines effectively such strokes)
  • Stable neurology
  • CT scan excludes bleed
  • Giving t-PA reduces disability but at an increase in bleeds. Tenecteplase has similar outcomes. Its optimal dose is not defined and currently alteplase is standard of care.

Relative contraindications

  • Minor neurological deficit
  • NIHSS > 22 National Institute of Health stroke scale
  • Patient comatose
  • Deficit rapidly improving
  • BP > 185/110
  • Seizure at stroke onset
  • Abnormal CT
  • Prolonged PT/PTT
  • Thrombocytopenia
  • Recent surgery/MI/stroke
  • Haemorrhage
Inteventional thrombectomy

This has a place in proven proximal vessel occlusion after alteplase[6] or tenecteplase (25mg rather than 40mg may be most promising dose). Mechanical thrombectomy is superior to alteplase alone in those with unknown time of onset, severe stroke, and large vessel occlusion. This has lead to further consolidation of acute stroke treatment centres as happened when acutePCI was developed in myocardial infarction. Generally the combined treatment has better outcomes up to 6 hours. Thrombectomy alone as of 2018 is not a convincing strategy, as is the case with PCI. In patients with ischaemic but not infarcted brain benefit in selected cases can extend to between 16 to 24 hours of late thrombolectomy.

Clot busting in perspective

At least one health commissioner in England had suggested that most strokes can be cured by thrombolysis. This gives a very unrealistic picture to patients and indeed the UK FAST stroke campaign of 2013 onwards, while successful for those who had sustained a major stoke actually increased time to appropriate medical assessment for those with transient symptoms. This is the group where most can be done to prevent any disability by rapid work up and intervention in days, usually as an outpatient.

In all trials 3% to 15% of patients with stroke are eligible for or get thrombolysis. This figure might push 20% where real time MRI is available. The real life benefit for those presenting early with appropriate acute investigation with first ischaemic stroke are now proven.

A reasonable statement from current evidence is NNT = 8 NNH = 16

The treatment is logical, but is at the stage of enthusiasm - much of the Stroke literature is very positive.

The time-limit on thrombolysis and age for risk benefit have been better defined.

The results of treatment are variable.

An effort to educate or persuade the population to treat stroke as an urgent event needing direct attendance to hospital has been made in England, with some success.


Selected neurosurgical intervention is likely to be beneficial in posterior fossa intracranial haemorrhage. Surgical intervention with intracerebral haemorrhage is unlikely to be benefical[7]

Blood pressure control

This has a very limited role in treating acute stroke despite many years of study. The ENOS trial showed that raised BP (systolic 140-220mmHg) within 48 hours in patients with either haemorrhagic or non-haemorrhagic stroke was not worth treating with either pre-existing oral antihypertensive therapy or GTN infusion in the first 7 days after a stroke[8]. It will still be common to treat BPs above 220mmHg in the first 48 hours with drugs such as labetolol. As of 2018 observational data suggest that extremes of BP should be avoided in patients presenting with acute ischaemic stroke. While there is no convincing evidence that active BP reduction results in improved outcomes in ischaemic stroke patients, intervention at BP of 185/110 mmHg or greater in patients treated with alteplase or mechanical thrombectomy to maintain BP ≤ 180/105 mmHg for at least 24 hours is standard practice. Acute BP goals for spontaneous cerebral haemorrhage remain unclear despite a number of randomized controlled trials.



In ischaemic stroke:

  • Aspirin usually 300 mg/day and then reduced to 75 mg/d is the most resource effective beneficial treatment and despite trends is not statistically inferior to the alternative proven antiplatelet strategies studied in randomised controlled trials with both arms having active therapy published up to 2008[9].
  • Aspirin (50mg) and dipyridamole (200mg MR bd) is slightly superior to aspirin alone but has tendency to induce headache. It appears advantageous in heart failure[10].
  • Clopidogrel may be given in those unable to take aspirin and is as effective as aspirin and dipyridamole and is better tolerated than the combination[11]. It is more costly.
  • The combination of aspirin and clopidrogel is likely to be ineffective or harmful in long term stroke indications due to (intracranial) haemorrhage[12] . However net benefit is likely of short courses of up to 21 days dual therapy in some of the highest risk populations, but as of 2019 it is not known if say only ten days provides the optimal benefit and how to adjust for differential metabolism and other risk factors to get the 2% absolute gain[13].

Blood pressure control

  • Even a minimal reduction (5-6 mmHg) in diastolic blood pressure has been shown in several trials to result in a significant (41%) reduction in subsequent stroke rate
  • However in the acute stroke with loss of cerebral autoregulation BP control is kept to a minimum to maintain perfusion pressures especially in the setting of oedema and raised ICP. There is also indirect evidence that is suggestive that the mechanism for poor outcome with early mobilisation in the first 24 hours after stroke could be due to decreased cerebral perfusion[14].
  • It is traditional not to lower the BP aggressively in the first 2 weeks after stroke because of concerns that a high BP may be a beneficial adaptive response for perfusion of the ischaemic penumbra, and also not to lower the BP aggressively before a critical carotid stenosis has been excluded. Clinical evidence exists that hpertensive control early after stroke is of no benefit (see above)


Event comparison of the anticoagulants dabigatran etexilate, rivaroxaban and apixaban in the indication of non-rheumatic atrial fibrillation against warfarin
  • Warfarin for AF significant reduces stroke rate in primary prevention and secondary prevention after an ischaemic cerebrovascular event. Absolute benefit remains even though previous ischaemic stroke is known to increase bleeding risk by about 2.5 times (95% confidence interval: 1.3 to 4.8 times)[15].
  • Dabigatran etexilate, rivaroxaban and apixaban are all clinically superior to warfarin in the populations studied, predominantly because they reduce the rate of haemorrhagic stroke[16]. However, if available, their use is likely to be dictated by both resource effectiveness issues and individual patient, drug and service characteristics. As can be seen from the figure some agents increase the rate of gastro-intestinal haemorrhage or myocardial infarction.

Stroke Units

Organised care by experienced healthcare workers in stroke medicine works

  • VTE prophylaxis
  • Hydration
  • TEDs
  • Aspirin where indicated
  • Treat depression which is common
  • Rehabilitation without very early intensive mobilisation[14]

External links


  1. Donnan GA, Fisher M, Macleod M, Davis SM. Stroke. Lancet. 2008 May 10; 371(9624):1612-23.(Link to article – subscription may be required.)
  2. Oppenheim C, Lamy C, Touzé E, Calvet D, Hamon M, Mas JL, Méder JF. Do transient ischemic attacks with diffusion-weighted imaging abnormalities correspond to brain infarctions? AJNR. American journal of neuroradiology. 2006 Sep; 27(8):1782-7.
  3. Yamada Y, Metoki N, Yoshida H, Satoh K, Kato K, Hibino T, Yokoi K, Watanabe S, Ichihara S, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Nozawa Y. Genetic factors for ischemic and hemorrhagic stroke in Japanese individuals. Stroke. 2008 Aug; 39(8):2211-8. Epub 2008 Jun 19.(Link to article)
  4. Kivimäki M, Jokela M, Nyberg ST, Singh-Manoux A, Fransson EI, Alfredsson L, Bjorner JB, Borritz M, Burr H, Casini A, Clays E, De Bacquer D, Dragano N, Erbel R, Geuskens GA, Hamer M, Hooftman WE, Houtman IL, Jöckel KH, Kittel F, Knutsson A, Koskenvuo M, Lunau T, Madsen IE, Nielsen ML, Nordin M, Oksanen T, Pejtersen JH, Pentti J, Rugulies R, Salo P, Shipley MJ, Siegrist J, Steptoe A, Suominen SB, Theorell T, Vahtera J, Westerholm PJ, Westerlund H, O'Reilly D, Kumari M, Batty GD, Ferrie JE, Virtanen M. Long working hours and risk of coronary heart disease and stroke: a systematic review and meta-analysis of published and unpublished data for 603 838 individuals. Lancet (London, England). 2015 Aug 19.(Epub ahead of print) (Link to article – subscription may be required.)
  5. Hachinski V. Stoop to conquer: preventing stroke and dementia together. Lancet 389:1518, 15 April 2017(Link to article – subscription may be required.)
  6. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, van Walderveen MA, Staals J, Hofmeijer J, van Oostayen JA, Lycklama À Nijeholt GJ, Boiten J, Brouwer PA, Emmer BJ, de Bruijn SF, van Dijk LC, Kappelle LJ, Lo RH, van Dijk EJ, de Vries J, de Kort PL, van Rooij WJ, van den Berg JS, van Hasselt BA, Aerden LA, Dallinga RJ, Visser MC, Bot JC, Vroomen PC, Eshghi O, Schreuder TH, Heijboer RJ, Keizer K, Tielbeek AV, den Hertog HM, Gerrits DG, van den Berg-Vos RM, Karas GB, Steyerberg EW, Flach HZ, Marquering HA, Sprengers ME, Jenniskens SF, Beenen LF, van den Berg R, Koudstaal PJ, van Zwam WH, Roos YB, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW. A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke. The New England journal of medicine. 2015 Jan; 372(1):11-20.(Link to article – subscription may be required.)
  7. Mendelow AD, Gregson BA, Fernandes HM, Murray GD, Teasdale GM, Hope DT, Karimi A, Shaw MD, Barer DH. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet. 2005 Jan 29-Feb 4; 365(9457):387-97.(Link to article – subscription may be required.)
  8. Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial. Lancet. 2014 Oct 21.(Epub ahead of print) (Link to article – subscription may be required.)
  9. Kent DM, Thaler DE. Stroke Prevention -- Insights from Incoherence. The New England journal of medicine. 2008 Aug 27.(Epub ahead of print) (Link to article – subscription may be required.)
  10. Sacco RL, Diener HC, Yusuf S, Cotton D, Ounpuu S, Lawton WA, Palesch Y, Martin RH, Albers GW, Bath P, Bornstein N, Chan BP, Chen ST, Cunha L, Dahlöf B, De Keyser J, Donnan GA, Estol C, Gorelick P, Gu V, Hermansson K, Hilbrich L, Kaste M, Lu C, Machnig T, Pais P, Roberts R, Skvortsova V, Teal P, Toni D, Vandermaelen C, Voigt T, Weber M, Yoon BW. Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke. The New England journal of medicine. 2008 Aug 27.(Epub ahead of print) (Link to article – subscription may be required.)
  11. Sacco RL, Diener HC, Yusuf S, Cotton D, Ounpuu S, Lawton WA, Palesch Y, Martin RH, Albers GW, Bath P, Bornstein N, Chan BP, Chen ST, Cunha L, Dahlöf B, De Keyser J, Donnan GA, Estol C, Gorelick P, Gu V, Hermansson K, Hilbrich L, Kaste M, Lu C, Machnig T, Pais P, Roberts R, Skvortsova V, Teal P, Toni D, Vandermaelen C, Voigt T, Weber M, Yoon BW. Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke. The New England journal of medicine. 2008 Aug 27.(Epub ahead of print) (Link to article – subscription may be required.)
  12. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. The New England journal of medicine. 2006 Apr 20; 354(16):1706-17.(Link to article – subscription may be required.)
  13. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. Johnston SC, Easton JD, Farrant M, Barsan W, Conwit RA, Elm JJ, Kim AS, Lindblad AS, Palesch YY:Clinical Research Collaboration, Neurological Emergencies Treatment Trials Network, and the POINT Investigators. N Engl J Med. 2018 Jul 19;379(3):215-225. doi: 10.1056/NEJMoa1800410
  14. a b Bernhardt J, Langhorne P, Lindley RI, Thrift AG, Ellery F, Collier J, Churilov L, Moodie M, Dewey H, Donnan G. Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial. Lancet (London, England). 2015 Jul 4; 386(9988):46-55.(Link to article – subscription may be required.)
  15. Poli D, Antonucci E, Grifoni E, Abbate R, Gensini GF, Prisco D. Bleeding risk during oral anticoagulation in atrial fibrillation patients older than 80 years. Journal of the American College of Cardiology. 2009 Sep 8; 54(11):999-1002.(Link to article – subscription may be required.)
  16. Mega JL. A new era for anticoagulation in atrial fibrillation. The New England journal of medicine. 2011 Sep 15; 365(11):1052-4.(Link to article – subscription may be required.)