Exertional syncope is one of the most clinically dangerous presentations in primary care — the differential diagnosis includes conditions that can cause sudden cardiac death without further warning. Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young athletes in the UK and affects approximately 1 in 500 of the general population, most of whom are undiagnosed. The mechanism is dynamic left ventricular outflow tract obstruction worsened by exertion and dehydration, causing severe reduction in cardiac output during exercise. The ECG in HCM shows LVH, deep Q waves (particularly in leads II, III, V5–V6), and lateral T-wave inversion — it is abnormal in 90% of HCM cases, making the ECG the most important first investigation. Aortic stenosis is the most common cause of exertional syncope in elderly patients — the classic triad of exertional syncope, exertional chest pain, and exertional dyspnoea (the "SAD" triad) in an elderly patient with an ejection systolic murmur radiating to the carotids is aortic stenosis until proven otherwise. Any patient with this presentation needs urgent echocardiography. The Brugada syndrome is a channelopathy (sodium channel gene SCN5A mutation in 20%) that causes ventricular fibrillation predominantly at rest or during fever — the ECG shows a characteristic coved-type ST elevation in leads V1–V3 with RBBB morphology. It is responsible for a significant proportion of unexplained sudden cardiac deaths in young adults (particularly South-East Asian males — "sudden unexplained death syndrome"). GPs who identify a Brugada pattern on ECG must refer urgently to cardiology for electrophysiological risk stratification and consideration of ICD implantation.

The witness account is the single most important diagnostic information in TLoC — the patient is unconscious during the episode and cannot reliably describe what happened. A witness who can describe: whether the patient went pale or flushed, whether there were any movements (tonic-clonic, myoclonic, dystonic posturing), whether the eyes were open or closed, how long the episode lasted, and how quickly the patient recovered, provides critical diagnostic information that cannot be obtained by any investigation. GPs should specifically request: "Can I speak to the person who witnessed the episode?" before accepting a patient's self-report alone. Video recording of episodes (on a mobile phone) is extremely valuable and should be encouraged for recurrent unexplained TLoC. The distinction between convulsive syncope and epilepsy is one of the most common and most consequential diagnostic errors in primary care — approximately 25% of all patients diagnosed with epilepsy have been misdiagnosed, and the majority of misdiagnoses are patients with vasovagal syncope with brief convulsive movements (convulsive syncope). Convulsive syncope occurs because cerebral hypoperfusion during a simple faint can cause brief myoclonic jerks or tonic posturing — these are a normal consequence of transient cerebral ischaemia, not evidence of epileptic activity. The distinguishing features are: (1) convulsive syncope lasts <30 seconds and is immediately preceded by presyncope features (pallor, sweating); (2) epileptic tonic-clonic seizures last 1–3 minutes with no preceding pallor; (3) post-ictal confusion lasting >5 minutes strongly supports epilepsy over syncope. NICE CG109 specifically warns against diagnosing epilepsy based solely on witnessing convulsive movements without considering the context. The consequences of misdiagnosis are severe: unnecessary anti-epileptic drugs, driving ban, employment restrictions, and psychological impact.

The postural blood pressure measurement is both mandatory (NICE CG109) and frequently omitted in primary care TLoC assessments — it must be measured lying after 5 minutes of rest, then at 1 minute and 3 minutes after standing. A drop of ≥20 mmHg systolic (or ≥10 mmHg diastolic) with symptoms confirms orthostatic hypotension. Orthostatic hypotension is one of the most common and most reversible causes of syncope — it affects approximately 20% of community-dwelling elderly adults and is caused by dehydration, antihypertensive medications (particularly alpha-blockers, ACE inhibitors, diuretics), Parkinson's disease, multiple system atrophy, diabetes (autonomic neuropathy), and prolonged bed rest. Adjusting antihypertensive medications in a patient with orthostatic hypotension syncope can immediately prevent further events. The carotid sinus massage (CSM) restriction to specialist settings is important — CSM carries a small but real risk of carotid plaque embolisation causing stroke (estimated at 1 in 1000 procedures). It should never be performed in general practice and should not be attempted in patients with carotid bruits, recent stroke, or known carotid stenosis. The lateral tongue bite specificity for epilepsy is clinically important — biting the tip or front of the tongue is non-specific (common in any fall) but biting the lateral border of the tongue (side of the tongue) has a specificity of approximately 96% for generalised tonic-clonic seizures, because the tonic phase of a seizure causes forced jaw closure with lateral tongue deviation. When a witness or patient reports a lateral tongue bite, epilepsy is the diagnosis until proven otherwise. Ask specifically: "Where on the tongue was the bite?" — this is often not volunteered.

The implantable loop recorder (ILR) is the most diagnostically powerful investigation for unexplained recurrent syncope — it is a small (the size of a USB stick) subcutaneous device inserted under local anaesthetic in the left parasternal area that continuously records the cardiac rhythm for up to 3 years and can be interrogated remotely. Studies (including the ISSUE-3 trial) show that ILR identifies a diagnosable cardiac arrhythmia in approximately 35–60% of patients with unexplained syncope after conventional non-invasive investigations are normal. NICE CG109 specifically recommends ILR for unexplained TLoC after initial investigations. The key clinical principle is that a 24-hour Holter monitor is frequently ordered for suspected arrhythmic syncope but has a very low diagnostic yield (2–10%) because arrhythmic syncope is episodic — the probability of catching an arrhythmia in 24 hours when events occur monthly is very low. ILR extends the monitoring window to 3 years and dramatically increases the diagnostic yield. The prolactin timing requirement is critical — serum prolactin must be drawn within 10–20 minutes of the episode (not 1 hour, not at the next blood draw) to have diagnostic value. The prolactin surge from ictal hypothalamic stimulation peaks at 15–20 minutes and returns to baseline within 60 minutes. Practically, this means that for planned tilt table tests or in-hospital telemetry monitoring where an event is witnessed and a blood draw can be arranged promptly, prolactin is a useful investigation. In general practice, by the time a patient presents post-episode, prolactin measurement is too late unless the patient presents within 20 minutes of the event.

The DVLA driving restrictions for TLoC are a medicolegal requirement that GPs must advise patients about and document at every TLoC assessment — failure to advise and document is a significant medicolegal risk. The key principles from the DVLA "Assessing Fitness to Drive" guidance (updated 2022): (1) Vasovagal syncope with a clear identifiable provoking factor (pain, venepuncture, prolonged standing in the heat) and clear prodromal warning — no restriction required, as the patient has warning and can pull over safely. (2) Vasovagal syncope without a provoking factor or without adequate warning — cease driving for 4 weeks, and do not resume until the diagnosis is secure and the patient is either in remission or able to receive adequate warning. (3) Unexplained TLoC — cease driving until the cause is identified. (4) First seizure (whether epileptic or first syncope being investigated for epilepsy) — cease driving for 6 months (Group 1) or 5 years (Group 2 LGV/PSV). The occupational safety documentation is equally important — a lorry driver, train driver, bus driver, pilot, surgeon, or anyone operating dangerous machinery who has an unexplained TLoC must be advised immediately to notify their employer and cease the relevant occupational activity. GPs are not required to notify employers directly, but the advice must be documented. For bus/lorry/PSV drivers with confirmed epilepsy or unexplained TLoC, DVLA notification by both the patient and the GP (with patient consent) is appropriate. The documentation standard is: "Patient advised regarding DVLA driving restrictions — not to drive until [specific condition met or date]. Patient agreed to notify DVLA and will not drive in the interim."

Physical counterpressure manoeuvres (PCMs) are the most evidence-based and most under-taught interventions for vasovagal syncope — the randomised controlled PC-Trial (van Dijk et al. Lancet 2006) demonstrated that teaching patients to perform leg crossing + muscle tensing or hand gripping at the onset of prodromal symptoms reduced syncope recurrence by 39% and the proportion of patients with complete syncope by 50%, with an NNT of approximately 4. These manoeuvres work by rapidly increasing venous return (leg crossing compresses the leg veins, forcing blood centrally) and peripheral vascular resistance (isometric hand gripping activates the sympathetic nervous system), counteracting the vasovagal reflex and preventing the critical fall in cardiac output. The technique must be actively taught — simply telling a patient "lie down when you feel faint" is insufficient. A GP who spends 5 minutes teaching PCMs gives the patient a tool that prevents future events without any pharmacological risk. Tilt table training is a related technique (standing against a wall for progressively longer periods, daily, to desensitise the vasovagal reflex over weeks) — it was recommended in older NICE guidance and is still used in some syncope clinics, though evidence for standalone tilt training is less robust than for PCMs. Fludrocortisone for vasovagal syncope is a reasonable choice but requires monitoring — it causes sodium and water retention (increasing intravascular volume and therefore cardiac preload, which reduces syncope susceptibility) but at the cost of potassium wasting. U&E and BP monitoring at 4 and 12 weeks after initiation is mandatory. It should not be prescribed in patients with heart failure, significant renal impairment, or poorly controlled hypertension.

The domperidone-QTc warning is a specific and important prescribing safety point — the MHRA issued a drug safety update in 2014 restricting domperidone to a maximum dose of 10 mg TDS for a maximum of 7 days, and specifically contraindicated it in patients with QTc prolongation, hepatic impairment, and patients taking QTc-prolonging drugs. The reason is that domperidone blocks cardiac hERG potassium channels (like many QTc-prolonging drugs), causing torsades de pointes and ventricular fibrillation. The combination of domperidone + a QTc-prolonging antibiotic (e.g. clarithromycin, azithromycin) or antifungal (fluconazole) is particularly dangerous — clarithromycin inhibits CYP3A4, which is the primary metabolic pathway for domperidone, causing plasma domperidone levels to rise dramatically. GPs must check for this combination on the medication list before prescribing. Post-micturition syncope in elderly men is a common, underdiagnosed, and easily treatable form of situational syncope — it occurs when an elderly man rises from a warm bed at night (already in a vasovagal-susceptible state from warmth-induced vasodilation) to urinate, combines standing from recumbency (orthostatic component), and the act of micturition (Valsalva-equivalent with subsequent reflex vasodilation). Management is simple: advise sitting to urinate at night, maintain adequate hydration, and rise slowly from the bed. This advice, given once, prevents recurrence in the majority of patients.

The ankle dorsiflexion exercise before rising (the "foot pump" manoeuvre) is evidence-based and highly practical — contracting the calf muscles in the lying position activates the calf muscle venous pump (which normally relies on walking to return blood from the lower limbs to the central circulation), increasing venous return before the patient stands. Studies in elderly patients with orthostatic hypotension show that ankle dorsiflexion exercises before rising significantly reduce the magnitude of the orthostatic BP drop. It takes 10 seconds, has no adverse effects, costs nothing, and can be started immediately. GPs should demonstrate it at the consultation. SUDEP (Sudden Unexpected Death in Epilepsy) is a topic that epilepsy specialist nurses should discuss with all patients with diagnosed epilepsy — it affects approximately 1 in 1000 adult epilepsy patients per year and is the most common epilepsy-related cause of death. The risk is substantially reduced by: optimal seizure control (taking medication consistently), avoiding seizure triggers (sleep deprivation, alcohol, missed doses), sleeping with a partner or installing a seizure alarm, and not sleeping prone. GPs referring for first seizure or managing diagnosed epilepsy should ensure patients are connected with an epilepsy specialist nurse who can provide SUDEP counselling — this is a national epilepsy quality standard. The STARS charity (Syncope Trust And Reflex anoxic Seizures) is a UK-specific organisation that provides excellent patient resources for vasovagal syncope and reflex anoxic seizures (the equivalent in children) — providing their contact details to patients with confirmed vasovagal syncope substantially improves patient understanding and self-management.

The sodium valproate pregnancy prevention programme (the MHRA Valproate Pregnancy Prevention Programme, implemented in 2018) is a specific prescribing safety requirement — valproate causes neural tube defects (spina bifida), facial abnormalities, developmental delay, and autism spectrum disorder in approximately 10% of children exposed in utero (foetal anti-convulsant syndrome, FACS). Every woman of childbearing potential prescribed valproate must be enrolled in the pregnancy prevention programme: annual risk acknowledgement form signed, contraception counselled and documented, annual specialist review. GPs prescribing valproate on repeat prescription must check that the programme requirements are met at every medication review. Failure to comply with the programme requirements is a prescribing safety incident. The enzyme-inducing AED and contraception interaction is equally important — phenytoin, carbamazepine, phenobarbital, oxcarbazepine, and topiramate (at higher doses) induce hepatic CYP enzymes and dramatically reduce plasma concentrations of all estrogen-based hormonal contraceptives (COC, patch, vaginal ring), making them ineffective for contraception. Women on enzyme-inducing AEDs who wish to use hormonal contraception must use: COCP with ≥50 μg ethinylestradiol (not standard dose — insufficient in the presence of enzyme induction), or — preferably — non-hormonal contraception (copper IUD), or progestogen-only injections (Depo-Provera — not affected by enzyme induction because of the large depot reservoir). This counselling must be documented and ideally confirmed by a pharmacist or specialist nurse.