Causes of syncope and transient loss of consciousness

According to NICE, transient loss of consciousness (TLoC) affects up to half of the population in the UK.¹ Syncope and seizures are probably the commonest causes of TLoC in older people.³ There is a clear overlap between falls and TLoC. In one paper 19% of older people failed to recall the circumstances of their fall and 6% reported definitely blacking out.^4,5 Given a third of people aged over 65 years fall each year this suggests a significant number of older people may suffer from TLoC.

What is syncope

The epidemiology of syncope in old age has not been well studied.6 The age adjusted incidence rate is 7.2 per 1000 person-years among both men and women. The incidence of syncope rises with advancing age and is between 2€“6% for those above 80 years of age.⁷ The causes of syncope are usually divided into three different categories.⁸ Neurally mediated (reflex) syncope, orthostatic hypotension and cardiac syncope . These have differing underlying pathophysiologies and therefore treatments.

In older people the two commonest causes are orthostatic hypotension and carotid sinus hypersensitivity,5 but thought also needs to be given to cardiac arrhythmias and structural heart disease. Regardless of the cause the final pathway in syncope is the same ‘a transient reduction in cerebral perfusion causing loss of consciousness. Cerebral perfusion is dependent upon a systemic blood pressure, which in turn relies on cardiac output and peripheral vascular resistance. A reduction in one or both of these can therefore result in syncope.

Cardiac syncope is caused by a low cardiac output due to structural heart disease (for example aortic stenosis), arrhythmias or acute conditions reducing cardiac output (for example aortic dissection or a pulmonary embolism). Orthostatic hypotension is defined as a drop in systolic blood pressure of 20mmHg or diastolic blood pressure of 10mmHg within three minutes of standing up. It results in reduced cerebral perfusion and syncope or presyncope. There are multiple causes but medications are an important cause.⁹

Asymptomatic orthostatic hypotension is common in older people and so lying/standing blood pressure measurements have to be taken in context with the history. In addition, the presence of orthostatic hypotension can vary through the day with variable fluid status and vagal tone. Therefore the absence of a postural drop in blood pressure does not exclude the diagnosis, especially given a good history.The mechanism of neurally mediated syncope is poorly understood. In some cases of emotional upset, it is triggered in the central nervous system. In others, activation of receptors in various organs (for example ventricular wall, urinary bladder, oesophagus etc) lead to a reflex increase in vagus nerve activity and sympathetic withdrawal.^{10, 11}

The commonest cause of neurally mediated syncope in older people is carotid sinus hypersensitivity (CSH).⁵ The response to carotid sinus massage determines the subtype: cardio-inhibitory (three second pause), vasodepressor (50mmHg drop in blood pressure) or mixed (a combination of both). Like orthostatic hypotension, asymptomatic CSH is common in older people. Some people therefore distinguish between asymptomatic CSH and symptomatic carotid sinus syndrome.

Epilepsy or syncope?

Epilepsy is defined as a condition with recurrent seizures (at least two seizures 24 hours apart without any identifiable cause).¹² Seizure is a symptom, not a diagnosis, and is defined as a brief episode of abnormal brain electrical activity, which may produce behavioural consequences. Seizures can be caused by any pathological processes affecting the brain or can be secondary to a trigger (for example electrolyte imbalance) in which case they are called ‘provoked’ seizures. These are not expected to recur with an improvement in causative circumstances, and should not be labelled as epilepsy.¹³

Old age is the most common time to develop epilepsy.^{14, 15} The incidence of epilepsy is far higher than previously thought because of increased recognition and better diagnosis. In the UK 1% of the elderly population will have epilepsy and the annual incidence is 90 per 100,000 in people between the ages 65 and 69, and more than 150 per 100 000 for those over 80 years.¹⁶More than 60% of elderly people with epilepsy have an identifiable cause. The most common cause is cerebrovascular disease (one in three cases of epilepsy),13 and seizures may be a marker of increased risk for future stroke.¹⁷

Dementia increases the risk of epilepsy five to 10-fold.18 Brain trauma, central nervous system infections and brain tumours are uncommon causes of epilepsy in the elderly.19 In about 40% of older people the cause of epilepsy remains unknown despite investigations.²⁰ The most common type of epilepsy in the elderly (in 70% of cases) is partial seizures (beginning in a focal part of the brain) with or without secondary generalisation.13

When they cause an alteration in consciousness they are called complex partial seizures. Idiopathic generalised seizures (30% of epilepsy in the elderly) are mostly tonic-clonic seizures, with a smaller contribution from myoclonic jerks.The main differential diagnoses of epilepsy are syncope and transient global amnesia. History from a witness is the cornerstone for the diagnosis and is usually more valuable than abnormal investigations.¹³ Patients with a new onset of seizure should have a brain scan, preferably an MRI. EEG has a low sensitivity and specificity and a negative interictal EEG cannot rule out epilepsy. In one study, interictal epileptiform discharges were present in only 26% of patients of more than 60 years with new onset seizures.²¹ Video electroencephalographic monitoring can be requested if the diagnosis of epilepsy is still doubtful.

Initial assessment The most important first step in TLoC is to take a thorough history and examination (including lying/standing blood pressure). A 12 lead ECG is also useful. This may provide enough information to reach a definitive diagnosis (especially in the case of situational or vasovagal syncope). If a diagnosis can be confidently reached at this point there is probably no need for further investigations (unless attacks are very frequent or result in significant injury).The past medical history can give some pointers to potential diagnosis. The presence of cerebrovascular disease, dementia and neurosurgery, all increase the risk of seizures. The presence of a cardiac history or atrial fibrillation may point to an arrhythmia. Hypertension and multiple medications may point to orthostatic hypotension. It can sometimes be difficult to differentiate epilepsy from syncope but there are some key differences (Box 2).

The NICE guidelines suggest if epilepsy is suspected the patient should be referred to a specialist in epilepsy, and seen within two weeks. Likewise if syncope is suspected and there are any ‘red flags’ the patient should be referred for ‘specialist cardiovascular assessment’. Who these specialists are, is not defined but, in the case of older people, may well be a geriatrician, rather than a neurologist or cardiologist.

If, after initial assessment, the diagnosis is not one of: vasovagal syncope, situational syncope, orthostatic hypotension or epilepsy then the guidelines suggest referring for cardiovascular assessment.

Cardiovascular assessment and syncope

Following onward referral the next investigation will depend on the likely, or possible, underlying cause. If the event occurred during exercise then an exercise ECG would be the next step. If structural heart disease is suspected (eg. a heart murmur suggesting aortic stenosis) then an echocardiogram, or other imaging, will be ordered. If an arrhythmia is suspected (due to an abnormal resting ECG) then ambulatory ECG is the next step. Sometimes the diagnosis is not clear and patients will have both an echocardiogram and an ambulatory ECG.In terms of ambulatory ECG, the guidelines suggest differing first line interventions depending on the frequency of syncopal events.

If blackouts are several times a week then a 24 or 48 hour ECG is suggested. If they are every 1-2 weeks then an external event recorder is recommended. If they are less frequent than every two weeks then the guidelines suggest offering an implantable event recorder, unless there is evidence of a conduction abnormality on 12 lead ECG. In reality, most people are offered a non-invasive investigation before proceeding to an implantable recorder.

In the event of an unexplained collapse in someone older than 60 years with a normal ECG, the first investigation (ie. before ambulatory ECG) should be carotid sinus massage (CSM),^{1, 22, 23} as CSH is the second commonest cause of syncope after orthostatic hypotension. This is usually performed on a tilt table, as it allows beat-to-beat blood pressure monitoring (to allow diagnosis of vasodepressor CSH) and there is a higher positive test rate in the erect, rather than the supine position. If CSM is negative then the next step is an ambulatory ECG. In people younger than 60 ambulatory ECG is offered first (as CSH is rare in younger people).Tilt table testing is a useful investigation for selected people with syncope. It involves lying the patient supine, connected to a heart and blood pressure monitor, and then tilting them head-up at 70 degrees for 40 minutes.²⁴

This puts the body under orthostatic stress and can cause syncope or pre-syncope in a controlled environment. It is not generally required to confirm the diagnosis of vasovagal syncope in the presence of a clear history. However, a tilt table test may be offered to people with neurocardiogenic syncope to see if there is a marked asystolic response (which may respond to pacing) or in cases where the cause of TLoC is unclear.

Tilt table testing is also useful in diagnosing postural orthostatic tachycardia syndrome (POTS). This condition results in an abnormal increase in heart rate on head up tilt, with no change in blood pressure. It seldom causes syncope but can cause presyncope and falls in older people. Despite using all the available tests, in 10% of older patients the mechanism of syncope will remain unclear.⁸ If the cause of syncope is uncertain, consideration of psychogenic non-epileptic seizures (PNES) or psychogenic pseudo syncope may be considered.¹ 

Treatment of TLoC

Treatment obviously depends upon the underlying cause of TLoC. In neurally mediated syncope education and lifestyle changes are the cornerstone of the non-pharmacological management. Cardiac pacing is the treatment of choice in cardio-inhibitory CSH, when a three second pause has been documented. In cases of orthostatic intolerance, including postural hypotension, expansion of extracellular fluid volume and withdrawal of any offending drugs should be the main strategy.

Pharmacological interventions with the alpha agonist midodrine (5-20mg three times daily) or mineralocorticoid fludrocortisone (0.1-0.3mg once daily) may also be useful, but both are unlicensed indications with a limited evidence base.

In cases of cardiovascular syncope the treatment, again, will depend on the cause. Cardiac pacing is indicated in brady-arrhythmias including sinus node dysfunction, AV blocks and unexplained syncope with BBB. Surgical treatment is indicated in patients with syncope secondary to severe aortic stenosis or atrial myxoma. The introduction of transcatheter aortic valve implantation (TAVI) has made aortic valve replacement for symptomatic aortic stenosis an option for frailer older people who would previously have been deemed unfit for major cardiac surgery.²⁵

Antiepileptic treatment

All elderly people with more than one well witnessed unprovoked event should be offered antiepileptic drug treatment. Patients with a high risk of recurrence, for example with a structural lesion on brain scan or with an epileptiform activity on EEG, can be considered for drug treatment after their first seizure.²⁰

Drug treatment offers control in around 80% of the elderly patients with epilepsy. All antiepileptic drugs, except ethosuximide, are effective for partial seizures with or without secondary generalisation. Sodium valproate has a broad spectrum of activity and is the drug of choice. None of the newer antiepileptic medications are more efficacious then the established agents, although lamotrigine, gabapentin and levetiracetam are better tolerated.¹⁴

Summary

TLoC is a common phenomenon in older people. The list of differentials is wide, but syncope and epilepsy are the commonest causes. The key to an accurate diagnosis is often a comprehensive history, although investigations are needed in many cases to confirm the exact cause.

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M L Sardar (Registrar, Geriatric Medicine, Tunbridge Wells Hospital, Pembury, Kent).

James C Milton (Consultant, Geriatric Medicine, Tunbridge Wells Hospital, Pembury, Kent).

Conflict of interest: none declared

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