Overview & Epidemiology

1. What is a Stroke?

The World Health Organisation’s classical definition (Hatano 1976) is still clinically useful: stroke is a rapidly developing clinical sign of focal (or global) disturbance of cerebral function, lasting more than 24 hours or leading to death, with no apparent cause other than of vascular origin. The American Heart Association (Sacco et al. 2013) updated this to require imaging or pathological evidence of brain, retinal, or spinal cord injury due to a vascular cause — capturing rapidly recovering events that nonetheless leave tissue damage on MRI (formerly “TIAs”).

Time-based definitions (<24 h vs ≥24 h) have been superseded by tissue-based definitions: if there is infarction on DWI MRI, it is a stroke regardless of how quickly the clinical deficit resolved.

2. Ischaemic vs Haemorrhagic

Strokes are classified by mechanism into two great families with very different physiology, treatment, and prognosis.

The bedside neurological exam cannot reliably distinguish ischaemic from haemorrhagic stroke — non-contrast CT (or MRI) is mandatory before any treatment, because the therapy for ischaemia (lysis, antithrombotics) is catastrophic if given to a haemorrhage.

3. Global Burden

The Global Burden of Disease Study (Lancet 2021) places stroke in the front rank of human disease:

Stroke is the leading cause of long-term adult disability and the second-leading cause of death worldwide (after ischaemic heart disease). Age-standardised mortality has declined since 1990 in high-income countries due to better hypertension control and acute stroke care, but absolute numbers continue to rise globally because of population aging.

Striking demographic features:

• Geographic gradient — ~85% of strokes occur in low- and middle-income countries.
• Sex difference — men have higher incidence at younger ages, women catch up after menopause; lifetime risk is higher in women, and women have worse outcomes (older, more often live alone, more cardioembolic strokes from AF).
• Race/ethnicity — in the USA, Black Americans have ~2× the stroke incidence and onset ~10 years earlier than White Americans.
• Young stroke is rising — stroke in adults <55 has risen ~40% in recent decades, partly attributable to increasing prevalence of obesity, diabetes, and hypertension in younger populations.

4. Risk Factors

The INTERSTROKE study (O’Donnell et al., Lancet 2010, 2016) found that 10 modifiable risk factors account for ~90% of the population-attributable risk of stroke. The dominant ones, in order of attributable fraction:

Non-modifiable risk factors: age (incidence doubles each decade after 55), sex, race/ethnicity, family history (especially monogenic causes — CADASIL, sickle-cell, Fabry, MELAS, fibromuscular dysplasia).

5. Time is Brain

Saver (2006) calculated the cost of delay in large-vessel ischaemic stroke:

In a typical large-vessel occlusion, the brain ages ~3.6 years for every hour of untreated ischaemia. The pre-treatment delays in the stroke chain (recognition, transport, door-to-imaging, door-to-needle, door-to-puncture) translate directly into permanent lost function. This single calculation has reorganised stroke care worldwide around minimising every minute.

The therapeutic time window has lengthened in recent years thanks to imaging-based patient selection (DAWN, DEFUSE-3, EXTEND), but the principle remains: earlier is always better, regardless of window.

6. FAST — Recognise Stroke at the Bedside

The FAST mnemonic was designed to put stroke recognition into the hands of bystanders and untrained responders. It captures the three commonest presenting deficits and the fact that time itself is the fourth element:

BE-FAST adds two prefix items to capture posterior-circulation strokes that FAST often misses (~14% false-negative rate):

Sensitivity / specificity for FAST in pre-hospital screening: ~80% / ~85%. Specifically missed presentations include isolated vertigo, isolated visual-field loss, and isolated cognitive change — reasons to stay broad-minded when symptoms are sudden and focal.

7. The Stroke Chain of Survival

Modern stroke systems organise the response into a chain whose weakest link sets outcome:

1. 01

   Recognition

   Bystander or first responder identifies stroke via FAST/BE-FAST.

2. 02

   Activation

   Emergency services dispatched; pre-notification of the receiving stroke centre.

3. 03

   Triage

   Pre-hospital severity scale (LAMS, RACE, C-STAT) routes large-vessel occlusion to a thrombectomy-capable centre.

4. 04

   Imaging

   Non-contrast CT to exclude haemorrhage; CTA to identify large-vessel occlusion; CT perfusion or MRI for late-window selection.

5. 05

   Reperfusion

   IV thrombolysis (alteplase or tenecteplase) within 4.5 h; mechanical thrombectomy up to 24 h with appropriate imaging.

6. 06

   Stroke unit care

   Neurological monitoring, BP/glucose targets, dysphagia screen, DVT prophylaxis, complications management.

7. 07

   Rehabilitation

   Multidisciplinary therapy starting within 24–48 h; intensity drives recovery.

8. 08

   Secondary prevention

   Antithrombotic, statin, BP, lifestyle, mechanism-specific (carotid revascularisation, AF anticoagulation).

8. A Brief History

• ~400 BCE — Hippocrates describes “apoplexy” (Greek for “struck down”), the term that survived into the 20th century.
• 17th c. — Johann Jakob Wepfer (1620–1695) shows on autopsy that apoplexy can be due to either brain bleed or arterial blockage — the first ischaemic / haemorrhagic distinction.
• 1835 — Carswell illustrates atherosclerotic plaque in cerebral arteries.
• 1928 — Pickering coins the term “cerebrovascular accident.”
• 1971 — Ambrose & Hounsfield’s CT scanner enables the first non-invasive haemorrhage/infarct distinction.
• 1989 — First DWI MRI sequences detect ischaemic injury within minutes.
• 1995 — NINDS rt-PA trial: alteplase within 3 h improves outcomes — the birth of acute reperfusion therapy.
• 2008 — ECASS-3 extends the IV-tPA window to 4.5 h.
• 2015 — MR CLEAN, ESCAPE, EXTEND-IA, SWIFT-PRIME, REVASCAT establish endovascular thrombectomy for proximal large-vessel occlusion.
• 2018 — DAWN and DEFUSE-3 push the thrombectomy window to 24 h with imaging selection.
• 2020s — Tenecteplase begins replacing alteplase (single bolus, equal/superior efficacy); mobile stroke units bring CT to the patient.

9. Where This Course Goes

The remainder of the course descends into the mechanistic and clinical detail behind the picture sketched here: