What is the differential diagnosis for loss of consciousness after ruling out seizure?

Differential Diagnosis for Loss of Consciousness After Ruling Out Seizure

Once seizure has been excluded, the differential diagnosis for transient loss of consciousness centers on syncope, which encompasses neurally-mediated (reflex) syncope, orthostatic hypotension, cardiac causes (arrhythmias and structural disease), and non-syncopal conditions including psychogenic pseudo-syncope. 1

Primary Categories of True Syncope

Neurally-Mediated (Reflex) Syncope

The most common category of syncope after excluding seizure includes: 1

• Vasovagal syncope (common faint) - both classical and non-classical presentations 1
• Carotid sinus syncope 1
• Situational syncope triggered by specific circumstances: 1
  • Acute hemorrhage
  • Cough, sneeze
  • Gastrointestinal stimulation (swallow, defecation, visceral pain)
  • Micturition (post-micturition)
  • Post-exercise
  • Post-prandial
  • Others (brass instrument playing, weightlifting)
• Glossopharyngeal neuralgia 1

Orthostatic Hypotension

This mechanism involves failure to maintain blood pressure upon standing: 1

• Primary autonomic failure syndromes - pure autonomic failure, multiple system atrophy, Parkinson's disease with autonomic failure 1
• Secondary autonomic failure - diabetic neuropathy, amyloid neuropathy 1
• Drug (and alcohol)-induced orthostatic syncope 1
• Volume depletion - hemorrhage, diarrhea, Addison's disease 1
• Post-exercise and post-prandial orthostatic hypotension 1

Cardiac Causes (Life-Threatening Priority)

Cardiac-related mechanisms represent the most lethal causes and require immediate specialist cardiovascular assessment. 1

Cardiac Arrhythmias: 1

• Sinus node dysfunction (including bradycardia/tachycardia syndrome)
• Atrioventricular conduction system disease
• Paroxysmal supraventricular and ventricular tachycardias
• Inherited syndromes (long QT syndrome, Brugada syndrome)
• Implanted device (pacemaker, ICD) malfunction
• Drug-induced proarrhythmias

Structural Cardiac or Cardiopulmonary Disease: 1

• Obstructive cardiac valvular disease
• Acute myocardial infarction/ischemia
• Obstructive cardiomyopathy
• Atrial myxoma
• Acute aortic dissection
• Pericardial disease/tamponade
• Pulmonary embolus/pulmonary hypertension

Cerebrovascular Causes

• Vascular steal syndromes 1

Non-Syncopal Conditions Mimicking Loss of Consciousness

Disorders Without True Impairment of Consciousness: 1

• Falls without loss of consciousness 1
• Psychogenic pseudo-syncope - anxiety, hysteria, panic attacks, major depression 1
• Cataplexy - partial or complete loss of muscular control triggered by emotions (usually laughter), with full recollection of events; most often occurs as part of narcolepsy 1
• Drop attacks ("maladie des genoux bleus") - sudden dropping to knees without apparent reason, immediate recovery, predominantly in women, with no or very brief loss of consciousness 1

Critical Distinguishing Features from Seizure

Brief seizure-like activity is common during syncope and should NOT be regarded as indicating epilepsy. 1 Key differences include: 1

Features Suggesting Syncope (Not Seizure):

• Tonic-clonic movements are always of short duration (<15 seconds) and start AFTER loss of consciousness 1
• Prodromal symptoms: nausea, vomiting, abdominal discomfort, feeling of cold, sweating, pallor (neurally-mediated) 1
• Rapid return to baseline - no prolonged confusion 1
• Usually short duration overall 1

Features That Would Suggest Seizure (Already Ruled Out):

• Prolonged tonic-clonic movements with onset coinciding with loss of consciousness 1
• Hemilateral clonic movements 1
• Clear automatisms (chewing, lip smacking, frothing) 1
• Tongue biting, blue face 1
• Prolonged confusion or aching muscles after the event 1

Pathophysiologic Mechanism

Syncope results from a 35% reduction in cerebral blood flow or complete disruption of cerebral perfusion for 5-10 seconds, causing transient brain ischemia. 1 All causes can be classified into three basic mechanisms: 1

1. Vasomotor instability - decreased vascular resistance, venous return, or both 1
2. Reduced cardiac output - pump failure, mechanical obstruction, or arrhythmias 1
3. Neurologically reduced cerebral perfusion - cerebrovascular disease or vasospasm 1

Initial Evaluation Requirements

The initial evaluation must include careful history, physical examination with orthostatic blood pressure measurements, and standard electrocardiogram (ECG). 1

Immediate Referral Indications:

• Suspected cardiac cause or unexplained loss of consciousness after initial assessment → specialist cardiovascular assessment 1
• Features suggesting epilepsy (if not already ruled out) → specialist neurologic assessment 1
• Uncomplicated faint, situational syncope, or orthostatic hypotension → ECG required but no immediate further investigation or specialist referral needed 1

Common Pitfalls to Avoid

• Misattributing brief myoclonic jerks during syncope as epilepsy - these are common in syncope due to transient brain ischemia and occur AFTER the patient has slumped to the floor 1
• Overlooking life-threatening cardiac causes in well-appearing patients - cardiac-related syncope carries the highest mortality risk 1
• Failing to measure orthostatic blood pressure - essential for diagnosing orthostatic hypotension 1
• Attributing syncope to psychiatric disorders without excluding other causes - psychiatric illness can coexist with organic causes of syncope 1
• Missing medication-induced causes - particularly drugs causing orthostatic hypotension or proarrhythmias 1