A population-based study of transient neurological attacks: incidence, clinical characteristics, investigation, aetiology and prognosis 

Stroke is the second most common cause of death worldwide and the commonest cause of dependency, creates a huge societal burden and is responsible for billions of pounds in health and social care costs. About 30% of strokes occur in individuals with a previous transient ischaemic attack (TIA) or minor stroke. Effective prevention would minimise the consequences. However, the diagnosis of TIA is difficult, particularly by non-experts. About 50% of patients with a suspected TIA or minor stroke have atypical TIAs or a non-vascular diagnosis (TIA/minor stroke mimics). Although there is some evidence that non-specific Transient Neurological Attacks (TNAs) have an increased risk of acute vascular events, the evidence is still both thin and controversial.
The aim of my thesis has been to evaluate the burden of TIA/minor stroke mimics, TNAs and all acute cerebrovascular events among all referrals from the general population to a TIA clinic; to determine the reliability of clinical diagnosis of TIA and non-specific TNA; to improve the classification of non-specific TNAs; and to predict the risk of stroke and other major vascular events after a non-specific TNA and TNA syndromes.
I have collected and analysed data from a population-based study, the Oxford Vascular Study (OXVASC). OXVASC is an ongoing prospective, population-based incidence study of all vascular diseases in all territories in Oxfordshire, UK, which started in 2002. The study population comprises approximately 92,728 individuals registered with nine GP practices and uses multiple overlapping methods of "hot" and "cold" pursuit to identify patients with acute vascular events.
The research described in this thesis has several clinically relevant findings which can contribute to improving the diagnosis and treatment of patients with suspected TIAs. First, I highlighted that TIA/minor stroke mimics (mimics) were responsible for one quarter of all suspected TIAs, had similar short- and long-term risk of acute cardiac events as did TIAs, and that the majority (70%) of mimics were complex neurological conditions. Second, I showed that TIA/minor ischaemic strokes are each more common than major ischaemic strokes and that TIA/minor ischaemic stroke patients together had two-thirds of all recurrent strokes and two-thirds of all myocardial infarctions and sudden cardiac deaths. Moreover, the 10 years' cumulative risk of stroke in patients with TIA, minor stroke and major stroke was very high and the risk of death among all cerebrovascular events was greater than 50%. Third, I found that the crude incidence rate of TNAs per 1000 people in OXVASC was slightly higher than the crude incidence rate of TIAs (0.73 versus 0.67) and increased with age. In addition, I reported that among TNA syndromes, transient isolated vertigo, unilateral sensory symptoms, migraine-aura like events and transient confusion had high incidence rates, whereas transient total paralysis and transient speech arrest had low incidence rates. Fourth, I showed that about one-third of TIAs seen in the first 10 years of OXVASC did not fulfil the classical criteria (NINDS-negative TIA) and had the same short- and long-term risk of stroke as NINDS-positive TIAs. Fifth, although the 90 days stroke risk after a TNA was lower than after a NINDS-positive TIA, in the post 90 days up to 10 years period the risk of recurrent stroke was not significantly different between the two groups. Sixth, the risks of stroke were higher than expected in the background population in all TNA categories (focal-TNA, non-focal TNA and focal plus non-focal TNA) and all TNA syndromes (isolated brainstem syndrome, migraine-like syndrome, isolated sensory syndromes, isolated visual disturbance, isolated speech disturbance, transient confusion and transient unresponsiveness) except transient amnesia. Moreover, non-focal TNAs and focal plus non-focal TNAs had a six times higher risk of stroke than expected and a similar risk to NINDS-positive TIAs. Finally, transient confusion and transient unresponsiveness had a relative risk of stroke nine times higher than expected and twice the risk of NINDS-positive TIAs.

Keywords: TNA
Stroke Epidemiology
TIA
Transient Neurological Attacks
Transient Neurological Attacks prognosis
TNA prognosis
Stroke
Advisor: Rothwell, P