Seizures & Epilepsy

Seizures are episodes of abnormal, excessive neuronal discharge in the brain, and epilepsy is a chronic disorder defined by a predisposition to recurrent unprovoked seizures.

Definition

A seizure (from Latin sacire = "to take possession of") is a sudden burst of electrical activity in the brain leading to changes in movement, behaviour, feeling and/or consciousness ^[1]. More formally (ILAE 2014), it is the transient occurrence of signs and symptoms due to abnormal, excessive or synchronous neuronal discharges of neurons residing primarily in the cerebral cortex ^[2]^[3].

Key points to understand from first principles:

Normal brain function relies on a delicate balance between excitatory (mainly glutamate, acting on NMDA/AMPA receptors) and inhibitory (mainly GABA, acting on GABA-A/B receptors) neuronal networks. When this balance tips towards excitation — whether from increased excitatory drive, failure of inhibitory mechanisms, or changes in intrinsic neuronal properties — neurons begin firing excessively and synchronously. This synchronous discharge is the seizure.
A convulsion refers specifically to a seizure with prominent motor (tonic-clonic) components. Not all seizures are convulsions (e.g., absence seizures have no motor component), and not all convulsive movements are seizures (e.g., rigors, myoclonus).

Epilepsy (from Greek epilambanein = "to seize" or "to take hold of") is a brain disorder that causes recurring, unprovoked seizures ^[1]. It represents an enduring tendency (≥ 60% recurrence risk) to develop unprovoked seizures ^[2]^[3]^[4].

ILAE 2014 Operational Definition of Epilepsy (High Yield)

Epilepsy is defined by any of:

≥ 2 unprovoked or reflex seizures occurring > 24 hours apart ^[1]^[2]^[3]
1 unprovoked or reflex seizure with a probability of further seizures ≥ 60% over the next 10 years (similar to recurrence risk after 2 unprovoked seizures) ^[1]^[2]^[3]
Diagnosis of an epilepsy syndrome ^[1]^[2]^[3]

Epilepsy is considered resolved when:

Patient has been seizure-free for the last 10 years with no seizure medicines for the last 5 years ^[2]^[3]
Patient had an age-dependent epilepsy syndrome but is now past the applicable age ^[2]^[3]

Term	Definition	Key Point
Provoked (acute symptomatic) seizure	Seizure occurring at the time of or in close temporal association with a documented brain insult (up to 2–4 weeks after event) ^[3]^[4]	Temporary, reversible lowering of seizure threshold → NOT epilepsy unless it becomes a recurrent process beyond the acute illness
Unprovoked seizure	Seizure in the absence of temporary/reversible factors causing ↓ seizure threshold ^[2]^[4]	Implies an enduring epileptogenic abnormality
Reflex seizure	Seizure triggered by specific extrinsic (e.g., photic stimuli, acoustic) or intrinsic (e.g., thinking, reading) stimuli ^[2]^[4]	NOT regarded as provoked → recurrent reflex seizures qualify as epilepsy, because the tendency to respond repeatedly to such stimuli with seizures already meets the conceptual definition ^[3]
Cryptogenic seizure	Seizure with a presumed yet unidentified structural cause ^[2]^[4]	Now replaced by "unknown" in ILAE 2017
Remote symptomatic seizure	Due to chronic, irreversible conditions (e.g., old stroke, tumours) that ↑ risk of seizures ^[2]^[4]	These ARE unprovoked — the insult is remote, not acute

Status epilepticus (SE) — a medical emergency:

Continuous seizure lasting ≥ 5 minutes (either clinical or EEG activity), OR
≥ 2 epileptic seizures without full recovery of consciousness between attacks ^[3]^[5]
Can be convulsive (tonic-clonic) or non-convulsive (alteration of awareness ranging from confusion to coma without motor manifestation — diagnosed with EEG) ^[3]

Why 5 minutes?

Most self-limited seizures terminate within 2–3 minutes. After 5 minutes, the seizure is unlikely to self-terminate and excitotoxic neuronal injury begins (glutamate-mediated calcium influx → mitochondrial failure → cell death). This is why the threshold for pharmacological intervention is 5 minutes.

Epilepsy syndrome: a distinctive combination of clinical features, signs and symptoms, and electrographic (EEG) patterns that cluster together, providing genetic, therapeutic, and prognostic value ^[3]. Examples include juvenile myoclonic epilepsy (JME) and genetic epilepsy with febrile seizures plus (GEFS+).

Epidemiology

Risk Factors

Understanding risk factors helps you identify who is at risk and what questions to ask in history:

Category	Examples	Mechanism
Metabolic	Hypoglycaemia, hypocalcaemia, hyponatraemia, hypomagnesaemia, uraemia, hepatic encephalopathy	Electrolyte/metabolic derangements alter neuronal membrane potential and excitability
Structural (acute)	Stroke (esp. lobar haemorrhage), SAH, SDH, TBI, brain abscess	Direct cortical irritation by blood products, oedema, or tissue disruption
Infectious	Meningitis, encephalitis	Inflammation and neuronal injury in the cortex
Drugs/Toxins	Drug intoxication & withdrawal (alcohol, benzodiazepines, barbiturates), cocaine, amphetamines	Drugs may be pro-convulsant (lowering threshold) or their withdrawal removes inhibition (e.g., alcohol withdrawal removes GABA enhancement)
Fever	Febrile seizures in children 6m–5y	Fever lowers the seizure threshold, possibly via IL-1β and other cytokine-mediated effects on neuronal excitability

Category	Examples	Mechanism
Genetic (30–50%)	Channelopathies (Na⁺, K⁺, Ca²⁺ channel mutations), SCN1A (Dravet syndrome)	Altered ion channel function → abnormal neuronal excitability
Structural	Cortical dysplasia, tuberous sclerosis, hippocampal sclerosis, previous stroke, CNS tumours, TBI, neurodegenerative disease	Abnormal cortical architecture or gliosis creates epileptogenic foci
Metabolic	Glucose transporter deficiency, creatine deficiency, mitochondrial cytopathies	Impaired neuronal energy metabolism → excitotoxicity
Immune	Anti-NMDA receptor encephalitis	Antibodies against NMDA receptors → loss of inhibitory control
Infectious	TB, HIV, malaria, neurocysticercosis	Chronic CNS inflammation and scarring

Relevant Anatomy and Neurophysiology

The cerebral cortex is where seizures originate. Understanding cortical anatomy is essential because the clinical manifestation of a seizure depends on the cortical area involved — this is the principle of semiology (seizure semiology = the clinical signs produced by seizure activity in a specific brain region).

Cortical Lobes and Their Functions

Lobe	Key Function	Seizure Manifestation When Involved
Frontal	Motor (primary motor cortex, supplementary motor area), executive function, behaviour, urinary continence	Contralateral clonic jerking (Jacksonian march), asymmetric tonic posturing (supplementary motor area seizures), behavioural arrest, versive head/eye turning, urinary incontinence
Temporal	Memory (hippocampus), emotion (amygdala), audition, language (dominant hemisphere)	Epigastric rising sensation, déjà vu/jamais vu, fear, olfactory/gustatory hallucinations → behavioural arrest → oral automatisms (lip-smacking, chewing, swallowing) → impaired awareness ^[1]
Parietal	Somatosensory, spatial awareness, visuospatial processing	Contralateral tingling/numbness, distortion of body image, visual-spatial disturbance
Occipital	Vision (primary visual cortex)	Elementary visual hallucinations (flashing lights, colours), contralateral visual field loss

Classical Example: Temporal Lobe Epilepsy (TLE)

Classical example: temporal lobe epilepsy due to hippocampal sclerosis ^[1]:

Autonomic (epigastric sensation), cognition (déjà/jamais vu) or emotional (fear) seizures followed by behavioural arrest with progressive impaired awareness + automatism (chewing, lip-smacking, swallowing, tongue movement)/mannerism ^[1]
Why epigastric rising sensation? → The insular cortex (involved in visceral sensation) is closely connected to the medial temporal structures; seizure spread to the insula produces this characteristic aura
Why automatisms? → Seizure activity in the temporal lobe disrupts normal cortical control, releasing primitive motor patterns from subcortical structures

Aetiology

Acute symptomatic seizure may be caused by virtually any acute brain insult ^[2]^[4]:

Category	Causes	Pathophysiology
Vascular	Stroke (esp. lobar haemorrhage), SAH, SDH, cerebral venous sinus thrombosis	Blood products (iron, haemosiderin) are directly epileptogenic to cortex; peri-infarct oedema causes cortical irritation
Traumatic	TBI (contusion, DAI, EDH/SDH)	Cortical contusion → haemorrhage → gliosis; DAI disrupts networks
Infectious	Brain abscess, meningitis, encephalitis	Inflammation → ↑ cytokines (IL-1β, TNF-α) → ↑ glutamate release and ↓ GABA function
Metabolic	Hypoglycaemia (< 2.5 mmol/L), hypocalcaemia (ionised Ca < 1.0), hyponatraemia (< 120 mmol/L), hypomagnesaemia, uraemia, hepatic failure	HypoGly: neurons depend entirely on glucose for ATP — ATP depletion → failure of Na⁺/K⁺-ATPase → depolarisation. HypoNa: ↓ extracellular Na⁺ → relative ↑ intracellular Na⁺ → neuronal swelling and ↑ excitability. HypoCa: ↓ Ca²⁺ → ↑ Na⁺ channel sensitivity → ↓ threshold for depolarisation
Drugs/Toxins	Drug intoxication: cocaine, amphetamines, tramadol, theophylline. Drug withdrawal: alcohol, benzodiazepines, barbiturates. Herbal medications (e.g., 麻黃 = ephedra) ^[5]	Cocaine/amphetamines → ↑ monoamines → excitotoxicity. Alcohol withdrawal: chronic alcohol enhances GABA; abrupt cessation → ↓ GABA + upregulated NMDA receptors → unopposed excitation
Eclampsia	Seizures in pregnancy with pre-eclampsia	Cerebral vasospasm + endothelial dysfunction → cerebral oedema (posterior reversible encephalopathy)
Fever	Febrile seizures (children 6m–5y)	See paediatric section below

This is a classic exam table — the aetiology of epilepsy varies with age ^[2]^[4]:

Age Group	Common Causes
< 1 year	Hypoxia, hypoglycaemia, hypocalcaemia, kernicterus, birth trauma, ICH, congenital anomalies (e.g., cortical malformations, inborn errors of metabolism)
1–5 years	Intracranial infections, febrile seizures
5–20 years	Idiopathic epilepsy (genetic), head injury, hippocampal sclerosis, cortical dysplasia
20–60 years	Cerebral tumours, alcohol, drugs and toxins, CNS infections, AVM
> 60 years	Cerebrovascular disease (post-stroke epilepsy), neurodegenerative diseases (dementia), systemic illnesses, brain metastases

Causes of Epilepsy in the Elderly (GC Lecture High Yield)

Post-stroke epilepsy is a high-yield topic for HKUMed exams ^[7]:

Risk factors: haemorrhage, cortical involvement, large area of stroke ^[7]
Neurodegenerative diseases / dementia ^[7]
Intracranial lesions — brain tumours, vascular malformations ^[7]

Category	Examples	Key Points
Genetic (30–50%)	Channelopathies (SCN1A, KCNQ2), chromosomal abnormalities	Epilepsy is direct result of a known or presumed genetic defect and seizures are the core symptoms ^[3]^[5]
Structural	Tuberous sclerosis, cortical dysplasia, hippocampal sclerosis, previous stroke (30–50%), CNS tumours, TBI, neurodegenerative diseases	Lesion visible on neuroimaging + compatible electroclinical data ^[2]^[3]
Metabolic	Glucose transporter deficiency, creatine deficiency syndrome, mitochondrial cytopathies	Impaired neuronal energy metabolism ^[3]^[5]
Immune	Anti-NMDA receptor encephalitis	Autoantibodies against neuronal surface antigens ^[3]^[5]
Infectious	TB, HIV, malaria, neurocysticercosis	Chronic CNS infection → inflammation → scarring ^[3]^[5]
Unknown	Previously termed "cryptogenic"	Replaced the term cryptogenic which means the nature of underlying cause is not currently known ^[3]^[5]

In general, 62% of epilepsy is idiopathic, 9% stroke, 9% head trauma, 6% alcohol, 4% neurodegenerative disease, 3.5% static encephalopathy, 3% brain tumour, 2% infection ^[4].

ILAE 2017 Framework for Classification of Epilepsy

The ILAE 2017 classification provides a multi-level diagnostic framework ^[2]^[3]:

Level 1: Seizure Type Classification (ILAE 2017)

Focal vs Generalised — The Key Distinction

Focal seizures: arise in networks limited to one hemisphere. May be very localised or more widely distributed. Can be aware (previously "simple partial") or with impaired awareness (previously "complex partial").
Generalised seizures: originate at some point within, and rapidly engage, bilaterally distributed networks.
Focal seizures can spread to bilateral tonic-clonic seizure (secondary generalisation) ^[1]
The old terms "simple partial", "complex partial", and "secondarily generalised tonic-clonic" have been replaced but you will still see them in clinical practice and older references.

Key Seizure Types Explained

A. Focal Seizures

Sub-type	Features	Pathophysiological Basis
Focal aware (previously "simple partial")	Patient remains aware throughout. Motor (contralateral jerking), sensory (tingling), autonomic (flushing, piloerection), or psychic (déjà vu, fear) symptoms depending on cortical region	Seizure activity remains confined; does not disrupt bilateral consciousness networks
Focal with impaired awareness (previously "complex partial")	Impaired awareness + automatisms (e.g., lip-smacking, fumbling) + behavioural arrest ^[1]	Seizure spreads to involve temporal/limbic circuits → disrupts awareness (reticular activating system and bilateral temporal connections)
Focal to bilateral tonic-clonic (previously "secondarily generalised")	Focal onset → bilateral tonic-clonic convulsion	Seizure propagates via corpus callosum and subcortical pathways to both hemispheres

Focal impaired awareness seizures (complex partial seizure): ^[1]

Seizure semiology depends on location involved
Automatism, abnormal posturing, head/eye version
Impaired awareness

B. Generalised Seizures

Sub-type	Features	Pathophysiological Basis
Generalised tonic-clonic (GTCS)	Tonic phase (sustained contraction, 10–20s) → clonic phase (rhythmic jerking, 30–60s) → postictal phase	Bilateral cortical activation → tonic: sustained depolarisation; clonic: rhythmic alternating excitation/inhibition
Absence (typical)	Brief (5–30s) staring episodes with behavioural arrest, ± subtle automatisms. 3 Hz spike-and-wave on EEG	Thalamocortical circuit: T-type Ca²⁺ channels in thalamic relay neurons generate rhythmic bursting → bilateral cortical synchronisation
Myoclonic	Brief, shock-like jerks. No loss of consciousness	Brief burst of cortical excitation; too short to disrupt consciousness
Atonic ("drop attacks")	Sudden loss of muscle tone → falls	Sudden widespread cortical inhibition or disruption of motor output
Tonic	Sustained muscle contraction (no clonic phase)	Sustained bilateral cortical/subcortical excitation without rhythmic inhibitory breaks
Clonic	Rhythmic jerking without preceding tonic phase	Bilateral rhythmic cortical excitation/inhibition

Level 2: Epilepsy Type

Focal epilepsy: predominantly focal seizures
Generalised epilepsy: predominantly generalised seizures
Combined generalised and focal epilepsy: both types (e.g., Dravet syndrome, Lennox-Gastaut syndrome)
Unknown: insufficient information

Level 3: Epilepsy Syndromes

Key epilepsy syndromes to know for exams:

Syndrome	Age of Onset	Seizure Type	EEG	Prognosis
West syndrome (Infantile spasms)	3–12 months	Epileptic spasms (flexor/extensor/mixed)	Hypsarrhythmia (chaotic, high-amplitude, disorganised)	Poor — often evolves to Lennox-Gastaut; a/w developmental regression
Lennox-Gastaut syndrome	1–7 years	Multiple types (tonic, atonic, atypical absence)	Slow spike-and-wave (< 2.5 Hz)	Poor — refractory epilepsy, cognitive decline
Childhood absence epilepsy (CAE)	4–10 years	Typical absence	3 Hz generalised spike-and-wave	Good — 70% remit by adolescence
Juvenile myoclonic epilepsy (JME)	12–18 years	Morning myoclonic jerks + GTCS ± absence	4–6 Hz generalised polyspike-and-wave	Good seizure control but lifelong — high relapse if AED withdrawn
Benign epilepsy with centrotemporal spikes (BECTS / Rolandic epilepsy)	3–13 years	Focal motor (face/arm) ± GTCS, often nocturnal	Centrotemporal spikes	Excellent — self-limited, resolves by puberty
Genetic epilepsy with febrile seizures plus (GEFS+)	Variable	Febrile seizures persisting beyond 6y + afebrile seizures	Variable	Variable

GC Lecture Clinical Contexts (High Yield Exam Scenarios)

From GC 081 lecture slides ^[1]:

"A 66/M presenting with acute right frontal stroke and recurrent left arm involuntary movement → Acute symptomatic seizure due to stroke; not epilepsy"
"A 25/M with recurrent epigastric sensation/déjà vu followed by behavioural arrest. MRI brain showing hippocampal sclerosis → Focal epilepsy (temporal lobe epilepsy) due to hippocampal sclerosis"
"A 18/F with a history of recurrent jerky movement in the morning, presenting with GTCS. MRI normal → Generalised epilepsy; epilepsy syndrome (Juvenile myoclonic epilepsy)"
"A 82/F with known dementia presenting with GTCS → Generalised epilepsy due to neurodegenerative disease"

Clinical Features

A. Symptoms

The clinical features of seizures are best understood through the concept of semiology — the clinical signs reflect which cortical area is seizing. I'll organise by phase:

An aura is actually a focal aware seizure — it is the first clinical manifestation and tells you where the seizure originates.

Aura Type	Cortical Origin	Pathophysiological Basis
Epigastric rising sensation	Temporal lobe (insular cortex connection)	Insular cortex mediates visceral sensation; seizure discharge here produces the "rising" feeling in the epigastrium
Déjà vu / Jamais vu	Temporal lobe (hippocampus/parahippocampus)	Abnormal activation of memory circuits → false sense of familiarity (déjà vu) or unfamiliarity (jamais vu)
Fear / dread	Temporal lobe (amygdala)	Amygdala is the fear centre — seizure discharge here produces intense fear
Olfactory hallucinations (unpleasant smell, e.g., burning rubber)	Temporal lobe (uncus) — "uncinate fits"	Uncus processes olfactory input
Gustatory hallucinations	Temporal lobe / insular cortex	Taste cortex is in the insula and frontal operculum
Visual hallucinations (simple: flashing lights)	Occipital lobe	Primary visual cortex (V1) discharge → elementary visual phenomena
Somatosensory symptoms (tingling, numbness)	Parietal lobe (postcentral gyrus)	Primary somatosensory cortex — seizure discharge produces contralateral paraesthesiae
Auditory hallucinations (buzzing, ringing)	Superior temporal gyrus	Primary auditory cortex

"Aura": hallucinations, rising sensation in epigastrium, fear/anger, nausea/vomiting ^[6]

Focal Seizures (Aware)

Motor: contralateral clonic jerking, which may spread sequentially along the motor homunculus — this is the Jacksonian march (e.g., thumb → hand → arm → face). Named after Hughlings Jackson who first described this cortical march.
Head/eye version: versive head/eye turning — usually contralateral to the seizure focus (frontal eye field involvement) ^[1]
Asymmetric tonic posturing: supplementary motor area seizures (medial frontal lobe) — the "fencing posture" (one arm extended, contralateral arm flexed)

Focal Seizures (Impaired Awareness)

Behavioural arrest (patient "freezes") ^[1]
Automatisms: chewing, lip-smacking, swallowing, tongue movement, fumbling with objects, picking at clothes ^[1]
- Why automatisms? → When the temporal lobe seizes, higher cortical control is disrupted, and subcortical/brainstem motor patterns are "released"
Impaired awareness — patient is unresponsive, may appear confused ^[1]
Duration: typically 1–3 minutes (longer than absence seizures)

Generalised Seizures

Type	Ictal Features	Mechanism
GTCS	Tonic phase: sudden sustained contraction of all muscles, may produce a cry (forced expiration through a closed glottis), jaw clenching (→ tongue biting, classically lateral tongue biting), urinary incontinence. Eyes may be open and deviated upward. Clonic phase: rhythmic jerking of all limbs, gradually slowing in frequency	Tonic: sustained excitatory discharge. Clonic: rhythmic inhibitory (GABAergic) interruptions of the excitatory discharge. Over time, inhibition gains dominance → seizure terminates
Absence	Behavioural arrest (staring), subtle automatisms (eyelid flutter, lip-smacking). Abrupt onset and offset. No postictal confusion. Can occur many times per day	3 Hz thalamocortical oscillation — T-type Ca²⁺ channels in thalamic relay neurons generate rhythmic spike-and-wave
Myoclonic	Brief, sudden, shock-like jerks — typically bilateral, often in arms. Often in the morning (JME)	Brief cortical discharge — too short to cause LOC
Atonic	Sudden loss of tone → head drop or fall ("drop attacks"). Brief (1–2s)	Sudden widespread cortical/subcortical inhibition of motor pathways

Other important ictal features:

Tongue biting: classically lateral tongue biting is highly specific for epileptic seizures (vs. tip-of-tongue biting which may occur in syncope) — because during the tonic phase, the jaw clamps shut and the tongue, which is pushed laterally by the tonic contraction, gets caught between the teeth
Urinary incontinence: loss of cortical control of the pontine micturition centre during generalised seizure. Can also occur in syncope (less common)
Fixed dilated pupils: sympathetic activation during generalised seizure ^[6]
Cyanosis: tonic contraction of respiratory muscles → inability to breathe → desaturation
Up-rolling eyeballs ^[6]

Represents the recovery period of the brain ^[3]. The postictal state results from active inhibitory mechanisms (GABA-mediated), neuronal exhaustion, and metabolic depletion.

Feature	Pathophysiological Basis
Postictal confusion	Global cortical suppression from neuronal exhaustion + active GABAergic inhibition
Headache	Vascular changes + muscle contraction during the tonic-clonic phase
Fatigue	Massive metabolic expenditure during seizure → ATP depletion
Muscle soreness and weakness	Intense muscle contraction during tonic-clonic phase → rhabdomyolysis in severe cases
Sleep (patient sleeps and wakes refreshed)	Active cortical suppression → natural transition to sleep
Todd's paralysis (postictal paresis)	Postictally a period of worsened neurologic function related to the location of the seizure in the brain ^[3]. Thought to be due to focal cortical exhaustion/depression. Mimicker of TIA or stroke ^[3]. E.g., patients with a simple motor seizure involving the left arm may have postictal weakness lasting for minutes to hours ^[3]
Transient aphasia	If seizure involved dominant temporal/frontal lobe
Hemianopia	If seizure involved occipital lobe
Memory loss	Hippocampal involvement
Sensory loss	Parietal lobe involvement

Seizure vs Syncope — Key Differentiating Features (High Yield)

From GC 089 lecture slides and senior notes ^[6]^[8]:

Feature	Seizure	Syncope
Risk factors	Fever, head injury, sleep deprivation, substance/alcohol use/withdrawal, PMHx/FHx of seizure	Cardiac diseases, drugs, Hx of NPC with RT
Onset	Sudden	Gradual
Prodrome	Aura: hallucinations, rising sensation in epigastrium, fear/anger, N/V	Situational elements, signs of SNS activation (sweating)
Event	More convulsive: limb twitching, up-rolling eyeballs, tongue biting, incontinence, fixed dilated pupils. Injury common	Less convulsive. Incontinence rare. Injury rare
Post-event	Postictal confusion. Todd's paralysis (postictal paresis)	Quick recovery

Important: Syncope CAN Cause Convulsive Movements

A common mistake is to assume that any convulsive movement = epileptic seizure. Convulsive syncope occurs when cerebral hypoperfusion is sufficiently prolonged (> 10–15 seconds) → cortical anoxia → release of brainstem motor activity → brief myoclonic jerks or even tonic-clonic movements. The key differentiator is the context (provoked by standing, preceded by vagal symptoms) and rapid recovery without postictal confusion.

During the seizure (ictal examination — if witnessed):

Focal motor signs: contralateral clonic activity, head/eye version, asymmetric tonic posturing
Automatisms: oral (lip-smacking, chewing) or manual (fumbling, picking) ^[1]
Impaired awareness / unresponsiveness
Cyanosis (respiratory compromise during tonic phase)
Fixed dilated pupils

After the seizure (postictal examination):

Drowsiness / confusion
Lateral tongue bite (examine the tongue!)
Evidence of urinary incontinence
Todd's paralysis (transient focal weakness/aphasia)
Posterior shoulder dislocation (classically associated with bilateral GTCS — because the internal rotators overpower the external rotators during tonic contraction)
Injuries: head lacerations, fractures

General examination (looking for the cause):

From paediatric lecture and examination guides ^[5]^[9]:

Examination	Looking For	Why
Vital signs	Temperature (fever → febrile seizure or CNS infection) ^[5]	Fever lowers seizure threshold
Dysmorphic features	Angelman syndrome ^[5], Down syndrome, etc.	Genetic syndromes associated with epilepsy
Neurocutaneous markers	Café-au-lait spots (neurofibromatosis type 1), ash-leaf spots (tuberous sclerosis), port-wine stain (Sturge-Weber syndrome) ^[5]	Neurocutaneous syndromes are associated with structural brain lesions causing epilepsy
Fundoscopy	Papilloedema (→ raised ICP from SOL) ^[5]	Tumours, hydrocephalus, abscess
Head circumference	Macrocephaly (hydrocephalus), microcephaly (congenital brain malformation) ^[5]	Structural abnormalities
Fontanelles (infants)	Bulging or tense fontanelles ^[5]	Raised ICP → meningitis, hydrocephalus
Meningeal signs	Kernig's / Brudzinski ^[5]	Meningitis / encephalitis
Neurological examination	Focal neurological deficits ^[5], asymmetric reflexes, tone abnormalities	Localising sign → structural lesion
Neurodevelopmental assessment	Developmental delay, slowing or regression ^[5]^[9]	Progressive encephalopathy, metabolic disease
Abdominal examination	Hepatosplenomegaly ^[5]	Glycogen storage disease ^[5], lysosomal storage disease
Cardiac examination	Murmurs, arrhythmias	Cardiac syncope mimicking seizure; tuberous sclerosis → cardiac rhabdomyoma
Dermatological exam with Wood's lamp	Signs of neurocutaneous syndromes ^[9]	Ash-leaf spots of tuberous sclerosis may be subtle and only visible under UV

"CAREFUL HISTORY IS MOST IMPORTANT" ^[1] — this is emphasised on the GC lecture slide. The diagnosis of seizure is fundamentally clinical, based on a detailed history from the patient AND witnesses.

Diagnosis of seizure suggested by transient occurrence of: ^[1]

Abnormal behaviour
Involuntary movements
Recurrent / stereotypical attack

Structured History

1. History of the event itself:

What was the patient doing when it happened? (position, activity, context)
Any warning symptoms (aura)?
What happened during the event? (Ask the witness: convulsive movements, bilateral vs unilateral, head/eye turning, automatisms, tongue biting, incontinence, colour change, duration)
What happened after? (confusion, drowsiness, focal weakness, headache, how long to return to normal?)

From GC 089 syncope history taking ^[8]:

"Patient and witness interview: Scenario, precipitating factors, prodrome/associated symptoms; duration, convulsion, incontinence, tongue biting, cyanosis; recovery (postictal drowsiness), post-syncopal symptoms, retrograde amnesia; previous events"

2. Seizure precipitants/triggers ^[3]:

Majority of patients with epilepsy have no identifiable or consistent trigger
Possible triggers include fever, lack of sleep, menstrual period, strong emotions, intense exercise, loud music and flashing lights ^[3]

3. Past medical history ^[3]^[5]:

Previous episodes of seizures (number, semiology)
Febrile seizures in infancy
Birth history, developmental milestones, vaccination history (paediatrics) ^[5]
Previous stroke, TBI, CNS infection

4. Drug history ^[3]^[5]:

Compliance on AEDs ^[5]
Recent AED drug levels ^[5]
Drug interactions ^[5]
Intake of herbal medications (e.g., 麻黃) ^[5]
Any contingency plan at home (PR Valium) ^[5]
Drugs that lower seizure threshold (comprehensive list from Felix Lai notes ^[3]):
- Analgesics: NSAIDs/Opioids/Triptans
- Antimicrobials: Antiviral/Antiretroviral/Antimalarial/Cephalosporin/Fluoroquinolones
- Anticholinergics, Antihistamines, Antiemetics (Metoclopramide/Ondansetron)
- Psychiatric medications: Antipsychotics/MAOI/SSRI/SNRI/TCA
- CVS drugs: Antiarrhythmics/β-blockers
- Respiratory drugs: Salbutamol/Terbutaline/Theophylline/Montelukast
- Immunosuppressants: Azathioprine/Cyclosporine/Mycophenolate/Tacrolimus

5. Family history ^[3]^[5]:

Epilepsy
Febrile seizures
Sudden cardiac death (to consider cardiac syncope in DDx)

6. Social history ^[5]:

Alcoholism
Previous head trauma
Driving status, occupation (important for counselling)
Impact on daily activities

7. Explore common reasons for breakthrough seizures ^[5]:

Drugs-related (Compliance/Dosage/Correct drugs/Drug interactions)
Triggering factors
Disease progression

Febrile Seizures (Paediatric Focus)

Febrile seizure (發熱性痙攣/發燒抽筋): fever ≥ 38°C in children between 6 months – 5 years, in absence of (1) CNS infection/inflammation, (2) metabolic disturbances, (3) history of afebrile seizure ^[2]

Feature	Simple Febrile Seizure	Complex Febrile Seizure
Duration	< 15 minutes	> 15 minutes
Recurrence within 24h	Does not recur within 24h	Recurs within 24h
Type	Usually brief GTCS	May be focal, prolonged, or recurrent
Recurrence risk	~30–40%	Higher
Risk of subsequent epilepsy	Slight ↑ (1–2% cf 0.4% in other children)	4–12%

Differential Diagnosis of "Seizure-like" Episodes (Overview)

This will be covered in detail in the DDx section, but for completeness of clinical features, the key mimickers include ^[4]^[2]:

Mimicker	Key Features	Mechanism
Expiratory apnoea syncope ('blue breath-holding' spells)	Trigger: anger/crying → hold breath in expiration → go blue, stiff then limp ± LOC → rapid recovery	Prolonged expiration → ↓ venous return → ↓ CO → cerebral hypoperfusion
Reflex asystolic syncope ('pallid breath-holding' spells)	Trigger: sudden pain/head trauma/cold food/fright → stop breathing → go pale, stiff ± brief GTCS → rapid recovery (may be ≥ 1h if severe). MoA: excess vagal stimulation → cardiac asystole	Cardioinhibitory vagal reflex
Vasovagal syncope	Trigger: hot stuffy environment, prolonged standing, fear → predominantly vasodepressor	Paradoxical vagal activation → ↓ BP and/or ↓ HR
Cardiac syncope	e.g., Long QT syndrome (LQTS)	Arrhythmia → ↓ CO → cerebral hypoperfusion

To tie everything together, here is a first-principles summary of how the pathophysiology produces the clinical features:

High Yield Summary

Key Definitions:

Seizure = transient symptoms from abnormal excessive/synchronous neuronal activity
Epilepsy = ≥ 2 unprovoked seizures > 24h apart, OR 1 seizure + ≥ 60% recurrence risk, OR epilepsy syndrome
Status epilepticus = seizure ≥ 5 minutes or ≥ 2 seizures without recovery of consciousness between
Resolved epilepsy = seizure-free 10y + off AEDs 5y, or past age-dependent syndrome age

Seizure Types (ILAE 2017):

Focal (aware / impaired awareness / → bilateral tonic-clonic)
Generalised (tonic-clonic, absence, myoclonic, atonic, tonic, clonic)
Unknown

Aetiology varies by age:

Neonates: hypoxia, metabolic, congenital
Children: febrile seizures, infections, genetic
Young adults: idiopathic/genetic, hippocampal sclerosis, trauma
Adults: tumours, alcohol, drugs
Elderly: stroke, neurodegeneration, metastases

ILAE 2017 Aetiological Categories: Genetic, Structural, Metabolic, Immune, Infectious, Unknown

Key Clinical Features:

Aura = focal aware seizure (epigastric sensation, déjà vu, fear = temporal lobe)
Focal impaired awareness = automatisms + behavioural arrest (temporal lobe epilepsy)
GTCS: tonic → clonic → postictal confusion
Todd's paralysis = postictal paresis mimicking stroke
Lateral tongue biting = specific for epileptic seizure
Febrile seizure: 6m–5y, fever ≥ 38°C, r/o CNS infection

History is most important for diagnosis — ask patient AND witnesses

Active Recall - Seizures & Epilepsy (Definition, Epidemiology, Aetiology, Classification, Clinical Features)

Differential Diagnosis of Seizures & Epilepsy

1. Non-Epileptic Events Mimicking Seizures (Adults)

These are conditions that produce transient LOC, abnormal movements, or altered awareness but are NOT caused by abnormal excessive neuronal discharge. Understanding the mechanism of each helps you differentiate them from true seizures ^[6]^[4]^[11].

Syncope = sudden transient loss of consciousness and postural tone with spontaneous recovery, due to ↓ global cerebral perfusion ^[8]. LOC occurs within ≤ 10 seconds of hypoperfusion to the reticular activating system (RAS) in the midbrain ^[8].

This is the single most important differential because syncope is far more common than seizures (~1–6% of hospital admissions ^[8]), and prolonged syncope can produce convulsive syncope (brief myoclonic jerks from cortical anoxia), which is frequently mistaken for epilepsy.

Sub-type	Mechanism	Key Features
Neurocardiogenic / vasovagal (60%)	Exaggerated vagal activation → ↓ HR (cardioinhibitory) and/or ↓ BP (vasodepressor) → ↓ cerebral perfusion	Situational trigger (standing, heat, pain, emotion, micturition, cough, eating, drinking cold liquid). Prodrome: nausea, lightheadedness, sweating, pallor. Brief LOC. Recovery slow (a few minutes) with nausea, malaise, sweating, flushing ^[8]
Cardiac syncope (15%)	Arrhythmia or outflow obstruction → ↓ CO → ↓ perfusion	Sudden onset, in any position ± a/w exertion (especially LVOT obstruction e.g., HOCM, aortic stenosis). Often no prodrome, or preceded by palpitation, chest pain. Extreme "death-like" pallor. Rapid recovery ( < 1 min) ^[8]. May be premonitory sign of severe cardiac disease (30% mortality if cardiac cause) ^[8]
Postural hypotension (15%)	Impaired physiological vasoconstriction on standing → hypotension	Occurs on standing; more common in elderly, autonomic neuropathy (diabetes), medications (antihypertensives, diuretics)

Convulsive Syncope — A Classic Pitfall

When cerebral hypoperfusion lasts > 10–15 seconds, cortical anoxia triggers release of brainstem motor activity → brief myoclonic jerks or even tonic posturing. This is "hypoxic brain seizure" ^[12] (also called convulsive syncope). It does NOT represent epilepsy. The critical differentiators are: (1) clear situational/postural trigger, (2) prodromal vagal symptoms, (3) < 15 seconds of convulsive movements ^[5], (4) rapid recovery without postictal confusion.

The GC Interactive Tutorial (Neuro-Epilepsy case) explicitly asks students to "obtain from clinical history and signs that can distinguish between syncope and epileptic seizures" and to "identify any precipitating, exacerbating or risk factors which can provoke syncope and seizures" ^[10].

Children have several age-specific conditions that are commonly mistaken for seizures ^[2]^[5]:

Condition	Age	Trigger	Mechanism	Key Features
Expiratory apnoea syncope ("blue breath-holding spells")	6m–5y	Anger, crying	Hold breath in expiration → ↓ venous return → ↓ CO → cerebral hypoperfusion	Go blue, stiff then limp ± LOC; rapid recovery ^[2]
Reflex asystolic syncope ("pallid breath-holding spells")	6m–5y	Sudden pain, head trauma, cold food, fright, fever	Excess vagal stimulation → cardiac asystole	Stop breathing → go pale, stiff ± brief GTCS; usually rapid recovery but may be ≥ 1h if severe ^[2]
Vasovagal syncope	Older children / adolescents	Hot stuffy environment, prolonged standing, fear	Vasodepressor ± cardioinhibitory	Lightheadedness → pallor → LOC → rapid recovery ^[2]
Cardiac syncope	Any	Exertion	Arrhythmia (e.g., LQTS) or structural heart disease → ↓ CO	Sudden LOC, may have palpitation; family history of sudden death ^[2]
Shaking chills / rigors	Any	Fever	Muscle contraction to generate heat	Can be stopped by holding hands/feet; child is irritable but consolable (vs. seizures which cannot be stopped by holding; child is inconsolable) ^[5]
Benign myoclonus of infancy	< 1y	None	Normal developmental phenomenon	Brief jerks during wakefulness; normal EEG
Sandifer syndrome	Infants	Feeding	Dystonic posturing secondary to GORD	Abnormal posturing (head turning, arching) temporally related to feeds
Self-gratification / masturbation	Infants–toddlers	None	Normal behaviour	Rhythmic movements; stops when distracted; normal EEG
Night terrors	3–8y	Sleep	Partial arousal from non-REM sleep	Screaming, inconsolable, eyes open but unresponsive; no memory of event

Differentiating Chills/Rigors from Seizures in Children (High Yield for Paediatrics)

From Felix Lai Paediatrics notes ^[5]:

Chills and rigors = Able to stop the seizure by holding their hands or feet / Irritable but consolable (likely related to discomfort)
Seizures = Cannot be stopped by holding their hands or feet / Inconsolable

This is a practical bedside test that examiners love to ask about.

When you have confirmed a true seizure, you must determine whether it is provoked (and therefore potentially reversible) before labelling the patient with epilepsy. This is the second layer of differential diagnosis.

Category	Causes	How to Identify
Metabolic	HypoGly, hypoNa ( < 120 mmol/L → convulsions) ^[15], hypoCa, hypoMg, uraemia, hepatic encephalopathy	Bedside glucose, electrolytes, LFT, RFT. HypoNa symptoms: malaise, lethargy, headache → confusion, convulsion, coma ^[15]
Vascular	Stroke (esp. lobar haemorrhage), SAH, SDH, cerebral venous sinus thrombosis	CT brain (acute), MRI brain
Traumatic	TBI	History of trauma, CT brain
Infectious	Meningitis, encephalitis, brain abscess	Fever, meningeal signs, LP (after excluding raised ICP), CT/MRI
Drugs/Toxins	Drug intoxication (cocaine, amphetamines, tramadol, theophylline), drug withdrawal (alcohol, BZD, barbiturates)	Drug history, toxicology screen, serum alcohol. Alcohol withdrawal seizures: usually occur ~6–48h after last drink; usually GTCS, generally self-limiting ^[16]
Eclampsia	Seizures in pregnancy with pre-eclampsia	Pregnancy, hypertension, proteinuria
Fever	Febrile seizures (children 6m–5y)	Age, fever ≥ 38°C, exclude CNS infection

Alcohol Withdrawal Seizures — Key Points

Withdrawal seizures: usually occur ~6–48h after last drink ^[16]

Usually develop in alcoholics (15–25%)
Usually GTCS, generally self-limiting
Risk factors: previous Hx of withdrawal seizures, concurrent epilepsy, ↓K or ↓Mg ^[16]
Must rule out other causes (SDH, CNS infection, metabolic derangement) — alcoholics are prone to falls, infections, and metabolic derangements
Delirium tremens: usually occurs ~48–96h after last drink — later and more severe, with hallucinations, autonomic instability, and significant mortality (5–15%) ^[16]

Category	Diagnoses	Key Differentiating Features
Syncope	Vasovagal, cardiac, orthostatic, situational	Prodromal lightheadedness/sweating, brief LOC ( < 1 min), rapid recovery, position-dependent, pallor not cyanosis ^[5]^[6]^[8]
TIA	Carotid/vertebrobasilar territory	Negative symptoms (weakness, numbness, aphasia); no positive symptoms at onset; vascular risk factors ^[6]^[11]
Transient global amnesia	—	Pure amnesia, no LOC, no automatisms, no motor phenomena ^[6]^[11]
Hyperventilation / panic attack	—	Emotional trigger, overbreathing, perioral tingling, carpopedal spasm ^[6]^[11]
Metabolic encephalopathy	HypoGly, hepatic encephalopathy	Altered sensorium without paroxysmal onset; check glucose and LFTs ^[11]
Sleep disorders	Sleepwalking, narcolepsy-cataplexy	Temporal association with sleep; cataplexy triggered by emotion ^[11]
Movement disorders	Tics, startle, hemifacial spasm, choreoathetosis	Non-paroxysmal, suppressible (tics), no LOC, no postictal phase ^[11]
Psychiatric	PNES, panic attack	Prolonged, asynchronous, eyes closed, no postictal confusion, normal EEG during event. Video EEG = gold standard ^[4]^[11]
Migraine	Migraine with aura, hemiplegic migraine	Slow evolution of aura (minutes vs. seconds); followed by headache ^[11]^[13]
Provoked seizure	Metabolic, vascular, infectious, drugs/toxins, fever, eclampsia	Acute reversible cause identified; address the cause → seizures should not recur
Brain tumour	Primary or metastatic	Focal deficits, raised ICP signs, slow-growing tumours → chronic seizures ^[13]
NCSE	—	Unexplained altered consciousness; subtle motor signs; EEG required ^[17]
Paediatric	Breath-holding spells, rigors, Sandifer, benign myoclonus, night terrors	Age-specific features; self-limiting; chills can be stopped by holding the child's limbs ^[2]^[5]

High Yield Summary — Differential Diagnosis

The two key questions:

Is it a seizure or a mimic? → Syncope is the most common mimic. PNES is the most important psychiatric mimic.
If seizure, is it provoked or unprovoked? → Provoked = treat the cause. Unprovoked = epilepsy.

Top differentials to never miss:

Syncope (especially cardiac — 30% mortality if missed)
Hypoglycaemia (rapidly reversible, rapidly fatal if missed)
CNS infection (especially in febrile seizures in children — must exclude meningitis)
Intracranial lesion (tumour, SDH — CT/MRI in all first-time seizures)
Drug/alcohol withdrawal (especially alcohol — seizures at 6–48h, DT at 48–96h)
NCSE (commonly missed — EEG required)

Key clinical differentiators for seizure vs syncope:

Seizure: sudden onset, aura, tonic-clonic > 15s, lateral tongue biting, cyanosis, incontinence, postictal confusion (> 30 min), Todd's paralysis
Syncope: gradual onset with prodrome, pallor, convulsion < 15s, tip tongue biting (if any), rapid recovery ( < 5 min)

In children, also consider: breath-holding spells, rigors/chills (stopped by holding limbs), Sandifer syndrome, night terrors

Gold standard for PNES: Video EEG

Active Recall - Differential Diagnosis of Seizures & Epilepsy

References

^[1] Lecture slides: GC 081. Seizure and loss of consciousness Delirium and encephalopathy; epilepsy; coma and brain death; care of unconscious patients; electrophysiology I.pdf (slides on Definition, Learning objectives, Summary) ^[2] Senior notes: Adrian Lui Pediatrics Notes.pdf (p117–118, Diagnosis of a Seizure, Febrile seizures, Paroxysmal disorders) ^[3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p1170, Postictal signs and symptoms) ^[4] Senior notes: Ryan Ho Neurology.pdf (p90, 101, 105, Faints and Fits, Diagnosis of a Seizure, Approach to Epilepsy) ^[5] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p476, Differential diagnosis — syncope vs seizure table, chills vs seizures) ^[6] Senior notes: Maksim Medicine Notes.pdf (p257, Seizures & Epilepsy — clinical features table, non-epileptic seizures) ^[8] Senior notes: Ryan Ho Cardiology.pdf (p63, Syncope — mechanisms, comparison table) ^[10] Lecture slides: GC_Interactive tutorial (Neuro-Epilepsy case) student copy.pdf (Learning objectives) ^[11] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p1177, Q1 Differential diagnosis of seizure and epilepsy) ^[12] Senior notes: Block A - Introduction to CVS investigations (including ECG).pdf (p11, Hypoxic brain seizure) ^[13] Senior notes: Maksim Surgery Notes.pdf (p362, Brain tumours — seizures, Todd's paralysis) ^[14] Lecture slides: Febrile seizures: Clinical features and evaluation - UpToDate.pdf (p19, Differential diagnosis) ^[15] Senior notes: Ryan Ho Chemical Path.pdf (p6, Hyponatraemia — severity and symptoms) ^[16] Senior notes: Ryan Ho GI.pdf (p303, Alcohol withdrawal syndrome) ^[17] Senior notes: Ryan Ho Psychiatry.pdf (p75, Non-convulsive status epilepticus — features and diagnosis)

Diagnostic Criteria

Investigation Modalities

These are performed urgently in all first seizures to rule out provoked causes and other medical emergencies ^[2]^[4]^[6]:

Investigation	What It Detects	Key Findings & Interpretation
Random glucose / H'stix	Hypoglycaemia	< 2.5 mmol/L can cause seizures; must be checked immediately. Why? Neurons depend entirely on glucose for ATP — glucose depletion → Na⁺/K⁺-ATPase failure → depolarisation → seizure
Electrolytes (Na⁺, K⁺, Ca²⁺, Mg²⁺, PO₄³⁻)	Hyponatraemia, hypocalcaemia, hypomagnesaemia	HypoNa < 120 → seizures; HypoCa (↓ ionised) → ↑ Na⁺ channel excitability → seizures; HypoMg → ↓ seizure threshold (Mg²⁺ is an endogenous NMDA receptor blocker)
Urea / Creatinine (RFT)	Uraemic encephalopathy	Uraemic toxins impair cortical function
LFT	Hepatic encephalopathy	Hyperammonaemia → astrocyte swelling → cerebral oedema + altered neurotransmission
CBC + D/C	Infection, haematological malignancy	Leucocytosis → infection; pancytopenia → consider marrow infiltration
CRP / septic workup	CNS or systemic infection	Fever + raised inflammatory markers + seizure → consider meningitis/encephalitis
Toxicology screen (urine ± blood)	Drug intoxication or withdrawal	Cocaine, amphetamines, methadone, benzodiazepines, alcohol. "Substance abuse in adolescents/adults with unexplained generalised seizures" ^[2]^[4]
AED drug levels	Sub-therapeutic AED levels	Check in known epilepsy patients with breakthrough seizures — compliance issue? Drug interaction?
Serum prolactin	Differentiate true seizure from PNES	↑ 2–3× if true seizures ^[6] — must be taken within 10–20 minutes of the event. Why? Seizures cause hypothalamic-pituitary axis stimulation → transient prolactin release. PNES does not cause this rise. Sensitivity ~60%, specificity ~90% for GTCS

Prolactin for Seizure vs PNES (High Yield)

Prolactin ↑ 2–3× baseline if true seizures ^[6]. This is most useful for GTCS and focal seizures with impaired awareness. It is NOT elevated in absence seizures or PNES. Must be drawn within 10–20 minutes post-event, with a baseline sample for comparison. It is a useful adjunct but NOT diagnostic in isolation.

In children with febrile seizures ^[19]:

Simple febrile seizure: In a neurologically healthy child with a typical simple febrile seizure and reassuring examination, diagnostic testing is unnecessary in most cases — focus on identifying the febrile illness and parent education
CBC, electrolytes, blood sugar, calcium, and urea nitrogen are of very low yield in simple febrile seizures — measure only when history of vomiting, diarrhoea, abnormal fluid intake, improper formula mixing, or physical findings of lethargy/dehydration/oedema ^[19]
Complex febrile seizure / febrile status epilepticus: obtain CBC, electrolytes, blood glucose, calcium, and urea nitrogen + more individualised evaluation since the likelihood of an alternative aetiology is higher ^[19]

B. Electroencephalogram (EEG)

EEG is the single most useful neurophysiological test in epilepsy — but it has critical limitations that every student must understand ^[2]^[4]^[5]^[18]^[20].

Type	When to Use	Key Points
Routine interictal EEG	First-line in all suspected seizures	Captures brain activity between seizures. Abnormal in only 50% of first seizures ^[2]^[4] — this is the crucial limitation. A normal EEG does NOT exclude epilepsy
Sleep-deprived EEG	When routine EEG is normal but clinical suspicion remains	↑ Yield of abnormality if repeated or performed after sleep deprivation ^[2]^[4]. Sleep deprivation ↓ cortical inhibition → more likely to "unmask" epileptiform activity
Prolonged / Ambulatory EEG	When seizures are infrequent	Captures events over 24–72 hours in the patient's natural environment
Video EEG monitoring	If non-epileptic attacks are suspected ^[2]^[4]	Gold standard of diagnosis ^[2]^[4] — simultaneously records clinical behaviour and EEG. May catch synchronous EEG discharges at the same time of attacks (confirming epilepsy) OR show a normal EEG during a clinical "seizure" (confirming PNES)
Invasive depth electrodes	When surgery is indicated to localise the epileptic foci ^[2]^[4]	Intracranial electrodes (subdural grids, stereotactic depth electrodes) placed surgically. Used in pre-surgical evaluation for medically refractory epilepsy

EEG Pattern	Associated Condition	What It Looks Like
Generalised epileptiform activity	Generalised tonic-clonic seizure ^[5]	Bilateral synchronous spikes / polyspikes
3 Hz generalised spike-and-wave	Typical absence seizure ^[5]	Classic rhythmic 3 Hz pattern; provoked by hyperventilation
≤ 2.5 Hz generalised spike-and-wave	Atypical absence seizure ^[5]	Slower, more disorganised than typical absence
4–6 Hz generalised polyspike-and-wave	Juvenile myoclonic epilepsy (JME)	Polyspike bursts, often provoked by photic stimulation
Focal epileptiform activity or focal slowing	Focal impaired awareness seizure ^[5]	Localised to one region (e.g., temporal) — helps localise the epileptogenic focus
Hypsarrhythmia	Infantile spasms (West syndrome) ^[5]^[21]	Classic pattern: very high-voltage, random, slow waves and spikes in all cortical areas that vary in duration and location ^[21]. Chaotic, disorganised
Sharp epileptiform waves over temporal region (interictal)	Temporal lobe epilepsy / hippocampal sclerosis ^[4]	Well-defined sharp waves; ictal → rhythmic evolving discharge with characteristic buildup ^[4]
Diffuse slowing of background	Encephalopathy / delirium (not specific to epilepsy)	Generalised ↓ frequency — indicates diffuse cortical dysfunction, NOT epileptiform activity

Critical EEG Limitations (High Yield Exam Point)

EEG is an important Ix but NEVER relied on to r/o or confirm diagnosis ^[2]^[4]:

Abnormal in only 50% of first seizures → cannot be used to exclude dx of epilepsy nor as standalone proof of epilepsy dx ^[2]^[4]
Epileptiform activities can be found in healthy children without seizures ^[5] — false positives exist (~2–4% of normal population)
Not all cases of brain diseases are associated with EEG abnormalities ^[5]

Bottom line: EEG is an adjunct to clinical diagnosis, not a replacement. A patient with a compelling clinical history and a normal interictal EEG still has epilepsy. A patient with no seizure history but incidental EEG spikes does NOT have epilepsy.

C. Neuroimaging

CT/MRI brain in ALL first-time seizures for identification of any underlying structural cause ^[2]^[4]

Feature	Details
Role	1st line of imaging in acute or emergency setting ^[22]
What it detects	Haemorrhage, calcific lesions, skull fractures, large mass lesions, hydrocephalus ^[22]
Advantages	Fast (seconds), widely available, excellent for acute blood
Limitations	Poor at detecting posterior fossa lesions (surrounding bone density), white/grey matter abnormalities, subtle cortical malformations ^[6]
When to use	Emergency setting (first seizure in A&E), post-traumatic seizure, suspicion of acute haemorrhage
Contrast CT	If suspecting intracranial infection, tumour, inflammatory lesion or vascular pathologies ^[22]

Feature	Details
Role	Preferred neuroimaging study — more sensitive than CT for structural lesions ^[2]^[4]^[5]
What it detects	Brain malformations, dysplastic lesions, subtle temporal lobe pathology particularly in the hippocampus ^[5], tumours, gliosis, cortical dysplasia, demyelination
Advantages	No radiation, exquisite soft tissue contrast, sensitive to subtle lesions
Limitations	Time-consuming (~30–45 min), motion artefacts (may need sedation in children), loud, contraindicated with certain metallic implants
Key finding: hippocampal sclerosis	MRI: T2W-hyperintensity and atrophy of hippocampal region ^[4] — the hallmark of mesial temporal sclerosis, the most common cause of temporal lobe epilepsy
Contrast	Gadolinium contrast not routinely required but indicated when infection, inflammation, vascular malformation or tumour are suspected ^[5]
Especially important	In children < 2y or adults, when other Ix suggest focal onset, or refractory to 1st-line AED ^[2]^[4]

CT vs MRI — When to Choose What

Scenario	Modality	Rationale
A&E / acute seizure	Plain CT brain	Fast, detects acute blood/fractures
Suspected infection / tumour / vascular	Contrast CT or MRI	Enhancement = BBB disruption or extra-axial lesion
Stable first seizure workup	MRI brain (preferred)	More sensitive for structural causes
Refractory epilepsy	MRI with epilepsy protocol	Thin-cut coronal FLAIR through hippocampi; may add volumetric analysis
Pre-surgical evaluation	MRI + advanced techniques	fMRI (functional mapping), SPECT, PET/CT

Neuroimaging may not be necessary in children who have an obvious cause of seizure identified on history and physical examination ^[5] — e.g., a classic simple febrile seizure in a neurologically normal child.

For seizures specifically ^[22]:

Plain CT brain: 1st line of imaging in acute or emergency setting — detects haemorrhage or calcific lesions
Contrast CT brain: if suspecting intracranial infection, tumour, inflammatory lesion or vascular pathologies
MRI brain: clinically stable patients — no radiation, sensitive to subtle lesions (e.g., malformations) — ± contrast if suspecting intracranial infection, tumour, inflammatory lesion or vascular pathologies
SXR useless for seizures ^[22]
Advanced techniques for pre-op planning: SPECT, FDG-PET/CT, fMRI ^[22]

These are used primarily in pre-surgical evaluation for medically refractory epilepsy:

Modality	Role	Key Findings
SPECT (Single Photon Emission CT)	Assessment of epileptic foci ^[23]	Ictal (during seizure): ↑ perfusion at foci. Interictal (between seizures): ↓ perfusion at foci ^[23]. Change in blood flow to a specific region at onset of seizure indicates presence of seizure focus ^[23]
FDG-PET/CT	Identifies areas of hypometabolism between seizures	Interictal: ↓ glucose metabolism at epileptogenic focus (correlates with EEG focus). Used in pre-surgical planning
fMRI	Functional brain mapping	Maps eloquent cortex (motor, language) near proposed surgical resection site

SPECT and PET are complementary: SPECT is better for ictal localisation (injection during the seizure), while PET is better for interictal localisation (metabolic mapping at rest).

Indicated if suspected meningitis or encephalitis, if space-occupying lesions are ruled out ^[3]

LP Finding	Normal	Bacterial Meningitis	Viral Meningitis / Encephalitis	TB Meningitis
Opening pressure	6–20 cmH₂O	↑↑	Normal–↑	↑
Appearance	Clear	Turbid	Clear	Clear/fibrin web
WCC	< 5/mm³	↑↑ (neutrophils)	↑ (lymphocytes)	↑ (lymphocytes)
Protein	0.15–0.45 g/L	↑↑	Normal–↑	↑↑
Glucose	> 60% serum	↓↓	Normal	↓

Autoimmune encephalitis panel (e.g., anti-NMDA receptor antibodies) should be sent in CSF if autoimmune aetiology is suspected.

Contraindications to LP (must exclude before proceeding):

Signs of raised ICP (papilloedema, ↓ GCS, focal neurological deficit) — risk of tonsillar herniation
Coagulopathy
Local infection at LP site

Investigation	Purpose	When to Order	Key Findings
Glucose	R/o hypoglycaemia	All first seizures (STAT)	< 2.5 mmol/L → provoked seizure
Electrolytes (Na, K, Ca, Mg)	R/o metabolic cause	All first seizures	HypoNa < 120, HypoCa, HypoMg → provoked
LFT / RFT	R/o hepatic/uraemic encephalopathy	All first seizures	Deranged → provoked; also baseline before AEDs
CBC + D/C	R/o infection, haem malignancy	All first seizures	Leucocytosis, pancytopenia
Toxicology / alcohol	R/o drug-related seizure	Clinical suspicion	Positive screen → provoked
AED levels	Compliance, therapeutic range	Known epilepsy with breakthrough	Sub-therapeutic → adjust dose
Prolactin	Differentiate true seizure vs PNES	Within 10–20 min post-event	↑ 2–3× → true seizure
EEG	Classify, predict recurrence, syndrome	All first unprovoked seizures	Epileptiform discharges; syndrome-specific patterns
Video-EEG	Gold standard for PNES vs epilepsy	Suspected non-epileptic attacks	Normal EEG during clinical event → PNES
CT brain	Acute structural cause	Emergency / first seizure	Haemorrhage, mass, calcification
MRI brain	Structural cause (definitive)	All epilepsy (stable setting)	Hippocampal sclerosis, cortical dysplasia, tumour
SPECT	Localise epileptic focus (pre-surgical)	Refractory epilepsy	Ictal ↑ perfusion at focus
ECG	R/o cardiac syncope	All first seizures	Long QT, Brugada, heart block
LP	R/o CNS infection / autoimmune	Suspected meningitis/encephalitis	↑ WCC, ↑ protein, ↓ glucose; autoimmune antibodies
Genetic testing	Identify genetic cause	Intractable epilepsy, developmental delay	SCN1A, TSC1/2, HLA-B*1502
Metabolic screen	Identify metabolic cause	Neonates, infants, developmental regression	Organic acids, amino acids, lactate, ammonia

High Yield Summary — Diagnosis & Investigations

Diagnosis is CLINICAL — history from patient AND witness is the cornerstone.

ILAE 2014 criteria for epilepsy:

≥ 2 unprovoked seizures > 24h apart, OR
1 unprovoked seizure + ≥ 60% recurrence risk (abnormal EEG, structural brain pathology, focal deficit, intellectual disability, nocturnal seizure), OR
Epilepsy syndrome diagnosis

Key investigations in all first seizures:

Bedside glucose, electrolytes (Na, Ca, Mg), LFT/RFT, CBC, toxicology
CT brain (acute) → MRI brain (stable, more sensitive)
ECG (r/o cardiac cause)
EEG (classify, predict recurrence — but NEVER used alone to confirm or exclude)

EEG pitfalls:

Normal in 50% of first seizures → cannot exclude epilepsy
Epileptiform activity found in 2–4% of normal population → cannot confirm epilepsy alone
↑ Yield: repeat, sleep deprivation, within 24h of seizure

Video-EEG = gold standard for PNES vs epilepsy

MRI key finding: hippocampal T2 hyperintensity + atrophy = hippocampal sclerosis (most common cause of TLE)

SPECT: ictal ↑ perfusion at focus; interictal ↓ perfusion at focus

In simple febrile seizures: diagnostic testing generally unnecessary if neurologically normal child with reassuring examination

Active Recall - Diagnostic Criteria, Algorithm & Investigations for Seizures/Epilepsy

Part 1: Acute Seizure Management

Part 2: Management of Status Epilepticus (SE)

Status Epilepticus — MEDICAL EMERGENCY (High Yield SAQ)

Status epilepticus: continuous seizure lasting ≥ 5 minutes OR ≥ 2 epileptic seizures without full recovery of consciousness between attacks ^[4]^[6]

MEDICAL EMERGENCY! → the later a seizure is stopped, the more difficult it is to be stopped ^[2]^[4]

The earlier AED is given, the better the outcome! ^[2]

80% resolve if given ≤ 30 min; 75% resolve if given ≤ 60 min; 65% resolve if given ≤ 90 min ^[2]

Mortality: 3–20% (↑ if prolonged seizure or identified acute brain insult) ^[4]

ALWAYS start treatment when seizure lasts > 5 min ^[2]

Staged Management Protocol

Stage	Timing	Treatment	Key Points
Stage 1: Early SE	0–10 min	Benzodiazepines	1st-line for acute seizure cessation
Stage 2: Established SE	10–30 min	Long-acting AED	If seizure persists despite BZD
Stage 3: Refractory SE	Seizure despite BZD + 1 AED	General anaesthesia	ICU admission, EEG monitoring
Stage 4: Super-refractory SE	Seizure despite GA ≥ 24h	Ketamine, MgSO₄, immunotherapy, other	Consider autoimmune aetiology

Benzodiazepines ("benzo" = benzene ring + "diazepine" = 7-membered ring with 2 nitrogens) work by enhancing GABA-A receptor function — they bind to the benzodiazepine site on the GABA-A receptor, increasing the frequency of Cl⁻ channel opening → ↑ inhibition → seizure termination.

Drug	Route & Dose	Key Points
IV Lorazepam	4mg over 2 min, repeat once in 5–10 min (up to 8mg) — include dose given pre-hospital ^[6]	Preferred 1st-line: longer duration of action in the brain (less lipophilic → slower redistribution)
IV Diazepam	10mg over 2 min (if lorazepam N/A) ^[6]	Alternative; more lipophilic → faster onset but shorter effective duration (redistributes to fat quickly)
IM Midazolam	10mg ^[6]	If no IV access — excellent IM bioavailability; can also be given buccal/intranasal

In children ^[5]:

If IV/IM not available (seizure ≥ 5 min): PR Diazepam 0.5 mg/kg OR Buccal Midazolam 0.5 mg/kg
If IV available: IV Lorazepam 0.1 mg/kg slow IV over 3–5 minutes (max 4mg/dose), can repeat once (0.05 mg/kg) at 5–10 min (max 2 doses) OR IV Diazepam 0.1 mg/kg slow IV (max 10mg/dose, max 3 doses) ^[5]

If seizure persists after adequate BZD dosing, escalate to a loading dose of a long-acting AED:

Drug	Dose	Mechanism	Key Considerations
IV Phenytoin	15 mg/kg over 30 min ^[6]	Na⁺ channel blocker → stabilises inactive state of voltage-gated Na⁺ channels → ↓ repetitive firing	Undiluted (precipitates with dextrose), slow infusion (cardiotoxicity), use large vein ^[6]. S/E: Bradycardia, hypotension (Na channel blocker — requires cardiac monitoring), purple glove syndrome (distal limb oedema + discolouration → skin necrosis + limb ischaemia), allergy / SJS (cross-reactivity if HLA-B1502 +ve)* ^[6]
IV Valproate	20 mg/kg ^[6]	Multiple mechanisms: ↑ GABA, blocks Na⁺/Ca²⁺ channels, inhibits GABA transaminase	Check NH₃; C/I if liver failure; S/E: thrombocytopenia ^[6]. Safe in generalised epilepsy.
IV Levetiracetam	20 mg/kg ^[6]	Binds SV2A (synaptic vesicle glycoprotein) → ↓ neurotransmitter release	Good option for renal impairment ^[6]. Fewer drug interactions than phenytoin/valproate. Well-tolerated.

In children ^[5]:

2nd-line options: IV Phenytoin, IV Phenobarbital
Trial of IV pyridoxine should be given to children < 3 years old with a prior history of chronic active epilepsy or SE of unclear aetiology ^[5] — pyridoxine-dependent epilepsy is a treatable metabolic condition where pyridoxine (vitamin B6) is a cofactor for glutamic acid decarboxylase, the enzyme that converts glutamate to GABA. Without pyridoxine → ↓ GABA → intractable seizures.

HLA-B*1502 and Phenytoin/Carbamazepine — Hong Kong Relevance

Allergy / SJS (cross-reactivity if HLA-B1502 +ve)* ^[6]. The HLA-B*1502 allele is prevalent in ~8% of the Hong Kong Chinese population. It confers a high risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with carbamazepine and, to a lesser extent, phenytoin. Screen ALL patients of Southeast Asian descent before prescribing carbamazepine or phenytoin.

General anaesthesia — the patient must be in ICU with full monitoring ^[3]^[6]:

Drug	Notes
IV Midazolam (infusion)	Titratable, short-acting
IV Propofol (infusion)	Rapid onset; risk of propofol infusion syndrome (rhabdomyolysis, metabolic acidosis, cardiac failure) with prolonged use
IV Thiopental (infusion)	Barbiturate; potent but causes significant hypotension and immunosuppression

Maintain for ≥ 24 hours before gradual withdrawal ^[6]
EEG to monitor treatment response and look for NCSE ^[6]
Maintain high level of AED ^[6] — the goal is burst-suppression on EEG

Part 3: Long-term Management of Epilepsy

A. Non-Pharmacological Measures

Lifestyle changes: discourage from activities leading to ↑ risk of injury/mortality should seizure occur ^[2]^[4]^[6]:

Activity	Recommendation	Rationale
Driving	Prohibited until seizure-free for 3 months to 1 year ^[4]. Patients with diagnosed epilepsy are legally prohibited to drive in HK ^[5]	Sudden LOC while driving → fatal accident. Patients are obliged to notify the Transport Department regarding the diagnosis ^[5]
Operating high-risk power equipment	Avoid ^[4]	Risk of injury during LOC
Working at heights / hiking alone	Avoid ^[4]	Falls from height during seizure
Swimming / bathing alone	Swimming and diving under supervision is allowed. Avoid taking a bath — should take showers instead ^[5]. Use low bathtub water level ^[4]	Drowning is the biggest safety risk in epilepsy ^[24]
Cooking over fire alone	Use non-fire heat source ^[4]	Burns risk
Avoid triggers	Sleep deprivation, alcohol, recreational drug use ^[6]	These lower seizure threshold

"Note that diagnosis of epilepsy should be made as accurate as possible because of the huge impact on patient's life, e.g., job, insurance…" ^[2]^[4]

B. Antiepileptic Drugs (AEDs) — Chronic Therapy

Based on NICE guidelines ^[2]^[4]^[6]:

Scenario	Usual Practice	Exceptions
↑ Risk of seizures (e.g., post-head injury)	NO treatment	Start AED if head injury or surgery; high-risk conditions (AVM, brain tumour, SAH) ^[2]^[4]. Seizure prophylaxis for 1 week only post-severe TBI ^[25]
Single unprovoked seizure	NO treatment	Start AED if ↑↑ risk for recurrence: unequivocal epileptic activity on EEG; neurological deficits or structural abnormality on brain imaging; high-risk jobs or lifestyle ^[2]^[4]^[6]
≥ 2 unprovoked seizures	AED indicated ^[2]^[4]^[6]	Withhold AED if: seizures widely separated in time (> 1y); precipitating factors identified (e.g., alcohol, sleep deprivation); high probability of poor compliance (e.g., personality disorder) ^[4]

"≥ 2 unprovoked seizures" or "1 unprovoked seizure with high-risk features: epileptiform EEG, CNS structural disease (e.g., brain tumour, CNS infection), status epilepticus (> 5 min), high-risk occupations (e.g., pilot)" ^[6]

This is a critical distinction because using the wrong type of AED can worsen certain seizure types:

Category	Definition	Drugs	Can Treat
Broad-spectrum AED	Reasonable initial choices in most adult patients regardless of type of seizures/epilepsy syndromes ^[4]	Valproate (Epilim), Lamotrigine (Lamictal), Topiramate (Topamax), Levetiracetam (Keppra), Zonisamide ^[4]^[5]	Both generalised and focal seizures ^[5]
Narrow-spectrum AED	Restricted to focal epilepsy ± secondarily generalised seizures ^[4]	Carbamazepine (Tegretol), Oxcarbazepine, Phenytoin (Dilantin), Gabapentin, Pregabalin (Lyrica), Tiagabine, Vigabatrin ^[4]^[5]	Focal seizures only (including focal evolving to bilateral tonic-clonic) ^[5]
Absence-specific	For absence seizures only	Ethosuximide ^[4]	Typical absence seizures

Narrow-Spectrum AEDs Can Worsen Generalised Epilepsy!

Narrow-spectrum AEDs are less effective than broad-spectrum agents in idiopathic generalised epilepsy syndromes (e.g., JME, childhood absence epilepsy) and may even exacerbate some seizure types in these patients ^[4]. For example, carbamazepine can worsen absence seizures and myoclonic seizures. This is why seizure classification matters before choosing an AED.

Seizure Type	First-Line AED	Alternatives	Avoid
Focal ± bilateral tonic-clonic	Carbamazepine, Lamotrigine, Levetiracetam	Oxcarbazepine, Valproate, Topiramate, Phenytoin	Ethosuximide (ineffective)
Generalised tonic-clonic	Valproate (most effective), Lamotrigine, Levetiracetam	Topiramate, Phenytoin	—
Absence	Ethosuximide (if absence only), Valproate (if absence + GTCS)	Lamotrigine	Carbamazepine, Phenytoin, Vigabatrin (may worsen)
Myoclonic	Valproate, Levetiracetam	Topiramate, Lamotrigine (cautious — can worsen in some)	Carbamazepine, Phenytoin (may worsen)
JME	Valproate (best efficacy), Levetiracetam, Lamotrigine	Topiramate	Carbamazepine, Phenytoin
Infantile spasms	Vigabatrin (if tuberous sclerosis), ACTH/Prednisolone	—	—

Drug	Mechanism	Key Side Effects	Contraindications / Cautions
Valproate (Epilim)	Multiple: ↑ GABA (inhibits GABA transaminase), blocks Na⁺/Ca²⁺ channels	Weight gain, hair loss (curly regrowth), tremor, hepatotoxicity, pancreatitis, thrombocytopenia, hyperammonaemia, PCOS in women	TERATOGENIC — C/I in women of childbearing age unless no alternative (neural tube defects, cognitive impairment in offspring). CYP inhibitor → ↑ levels of other drugs
Lamotrigine (Lamictal)	Na⁺ channel blocker + ↓ glutamate release	SJS/TEN (especially if dose escalated too rapidly or with valproate), dizziness, headache	Must titrate slowly (start low, go slow). Valproate inhibits lamotrigine metabolism → ↓ dose of lamotrigine needed. Folic acid should also be started ^[10]
Levetiracetam (Keppra)	Binds SV2A → ↓ synaptic vesicle release	Behavioural/psychiatric: irritability, aggression, depression. Generally well-tolerated otherwise	Good in renal impairment (renal excretion, no hepatic metabolism). Minimal drug interactions
Carbamazepine (Tegretol)	Na⁺ channel blocker	Hyponatraemia (SIADH), rash, SJS/TEN (HLA-B*1502), diplopia, ataxia, aplastic anaemia (rare)	CYP inducer → ↓ efficacy of OCP, warfarin. HLA-B1502 screening required* in Asian populations. C/I in generalised epilepsy (may worsen absence/myoclonus)
Phenytoin (Dilantin)	Na⁺ channel blocker	Gingival hyperplasia, hirsutism, coarsened facies, acne, peripheral neuropathy, cerebellar atrophy (chronic), osteomalacia (↑ vitamin D metabolism), SJS/TEN	Zero-order kinetics at therapeutic range → small dose changes cause large changes in plasma level → requires TDM. CYP inducer. HLA-B1502 screening required*
Topiramate (Topamax)	Na⁺ channel blocker + GABA enhancer + carbonic anhydrase inhibitor + AMPA/kainate antagonist	Weight loss (useful vs valproate), cognitive slowing ("Dopamax"), word-finding difficulty, renal stones (carbonic anhydrase inhibition → ↓ urinary citrate), acute angle-closure glaucoma	Caution in renal stones. Teratogenic (cleft lip/palate)
Ethosuximide	T-type Ca²⁺ channel blocker (in thalamic relay neurons)	GI upset, headache, rash	Only effective for absence seizures (T-type Ca²⁺ channels are specifically involved in thalamocortical 3 Hz oscillations)
Phenobarbital	GABA-A receptor enhancer (↑ duration of Cl⁻ channel opening)	Sedation, cognitive impairment, behavioural disturbance (children), osteomalacia	CYP inducer. Still widely used in neonatal seizures and resource-limited settings
Gabapentin / Pregabalin	Bind α2δ subunit of voltage-gated Ca²⁺ channels → ↓ neurotransmitter release	Sedation, weight gain, peripheral oedema	Also used for neuropathic pain. Narrow-spectrum only
Vigabatrin	Irreversible GABA transaminase inhibitor → ↑ GABA in synapse	Irreversible visual field constriction (bilateral concentric) — requires regular perimetry	First-line for infantile spasms with tuberous sclerosis

General AED side effects (mnemonic: 3D 2A): Drowsiness, Dizziness, Diplopia, Ataxia, Amnesia ^[6]

CYP inducers: phenytoin, phenobarbitone, carbamazepine → ↓ efficacy of OC pills, warfarin ^[6] CYP inhibitor: valproate ^[6]

This is a high-yield exam topic and a critical clinical scenario:

Issue	Key Points
Teratogenicity	Valproate is the most teratogenic AED — neural tube defects (spina bifida), cognitive impairment, autism, craniofacial anomalies. Risk is dose-dependent (~10% major malformation rate at high doses). C/I in women of childbearing age unless no suitable alternative
Drug of choice in pregnancy	Lamotrigine and levetiracetam have the best safety profiles in pregnancy
Folic acid	Folic acid should also be started ^[10] — all women with epilepsy on AEDs should take high-dose folic acid (5 mg/day) pre-conception and throughout pregnancy to reduce neural tube defect risk
CYP induction → OCP failure	Phenytoin, carbamazepine, phenobarbitone induce CYP enzymes → ↓ OCP efficacy → advise barrier contraception or use non-enzyme-inducing AED
Lamotrigine levels in pregnancy	Lamotrigine clearance increases significantly in pregnancy (oestrogen induces glucuronidation) → may need dose increases; levels should be monitored

D. Epilepsy Surgery

Indicated when medical therapy fails ^[2]^[3]^[4]:

Surgery	Indication	Outcome
Standard anterior temporal lobectomy	TLE: most common cause of pharmacoresistant epilepsy ^[2]^[3]^[4]	60–70% seizure-free at 2–5 years (cf 0–10% with continued medical Tx) ^[2]^[4]
Amygdalohippocampectomy	Selective resection for mesial TLE	Comparable outcomes with less tissue removal
Focal cortical resection	Drug-resistant focal epilepsy with localised lesion ^[3]	C/I if located in eloquent regions because of unacceptable S/E (e.g., dysphasia, hemiplegia) ^[4]
Hemispherectomy	Catastrophic hemispheric epilepsy (e.g., Rasmussen encephalitis, hemimegalencephaly) in children	Can be curative; remarkable plasticity in young children
Corpus callosotomy	Drop attacks (atonic/tonic seizures) refractory to AEDs	Palliative — ↓ generalisation of seizures but does not eliminate the epileptic focus

Surgical complications ^[3]^[4]:

Short-term memory loss (if dominant temporal lobe resection)
Visual field defects (e.g., quadrantanopia — damage to Meyer's loop during temporal lobectomy)
Cognitive and psychological sequelae (e.g., depression) ^[3]
Rarely: infections, CN palsies, hemiparesis, death

Indications for referral to a paediatric epilepsy centre ^[24]:

Age younger than 2 years
Epilepsy not controlled within 2 years of onset or after trials of 2 medications
Intolerable adverse effects
Disabling seizures
Imaging demonstrating a focal unilateral lesion consistent with seizure signs and symptoms
Epileptic encephalopathy with lack of expected developmental progression, plateauing, or regression coincident with seizure onset
An aetiology that requires special dietary or medical management, e.g., glucose transporter deficiency, Dravet syndrome ^[24]

Modality	Mechanism	Indication
Vagus nerve stimulation (VNS)	Regular pulsed stimulation via vagus nerve → desynchronise cerebral activity + ↑ synthesis of inhibitory neurotransmission ^[2]^[4]	Drug-resistant epilepsy not suitable for resective surgery. ↓ Seizure frequency by ~50% in ~50% of patients
Deep brain stimulation (DBS)	Usually at anterior thalamus to abort seizure spread ^[2]^[4]	Drug-resistant focal epilepsy

Diet	Mechanism	Indication
Ketogenic diet (KD)	High-fat, very low-carbohydrate diet → chronic ketosis → ↑ GABA, ↓ neuronal excitability (multiple proposed mechanisms including ↑ mitochondrial function, ↓ mTOR pathway, anti-inflammatory effects)	Drug-resistant epilepsy, especially in children. First-line in glucose transporter type 1 deficiency (GLUT1-DS) and pyruvate dehydrogenase deficiency
Modified Atkins diet	Less restrictive version of KD	Adolescents/adults with drug-resistant epilepsy

G. Special Situations

Cannot use conventional anti-epileptics → keep using Magnesium sulfate ^[27]
MgSO₄ is superior to diazepam and phenytoin for eclamptic seizures (MAGPIE trial, Lancet 2002)
Continue MgSO₄ infusion until 24 hours after delivery ^[27]
Check knee jerk and respiratory rate every hour — loss of knee jerk is the first sign of magnesium toxicity (at 10 mEq) from the normal therapeutic level of 4–8 mEq ^[27]

High Yield Summary — Management

Acute seizure: ABC → glucose check → BZD if ≥ 5 min → if persistent: phenytoin/valproate/levetiracetam → if refractory: GA in ICU

Status epilepticus staged protocol (SAQ!):

Stage 1 (0–10 min): IV lorazepam 4mg (or IM midazolam 10mg if no IV)
Stage 2 (10–30 min): IV phenytoin 15mg/kg (or IV valproate/levetiracetam)
Stage 3 (refractory): GA — midazolam/propofol/thiopental, maintain ≥ 24h, EEG monitoring
Stage 4 (super-refractory): ketamine, MgSO₄, immunotherapy, dietary therapy, surgery

AED indications: ≥ 2 unprovoked seizures; single seizure + high recurrence risk; epilepsy syndrome

AED choice: Classify seizure type FIRST → broad-spectrum (valproate, lamotrigine, levetiracetam) for generalised; narrow-spectrum (carbamazepine) acceptable for focal only. Narrow-spectrum can WORSEN generalised epilepsy.

Valproate: C/I in women of childbearing age (teratogenic). Start folic acid 5mg with lamotrigine.

Drug-resistant epilepsy: Failure of ≥ 2 adequate AED trials → consider epilepsy surgery (60–70% cure for TLE)

HLA-B*1502: Screen before carbamazepine/phenytoin in HK population (SJS/TEN risk)

Withdrawal: After ≥ 2 years seizure-free; taper slowly over 2–3 months. Exception: JME = lifelong.

Eclampsia: MgSO₄ (NOT conventional AEDs); continue 24h post-delivery; monitor knee jerk.

Active Recall - Management of Seizures & Epilepsy

Complications of Seizures & Epilepsy

Complications can be divided into those arising from the seizures themselves, those arising from the underlying disease, those arising from treatment (AEDs and surgery), and those arising from the psychosocial burden of living with epilepsy. Understanding the pathophysiology of each complication is what makes them stick.

1. Acute Complications of Seizures

These are the immediate dangers during or shortly after a seizure. They stem from the fundamental problem: during a generalised tonic-clonic seizure, the brain loses voluntary control of the body for 1–3 minutes, and massive sympathetic discharge + sustained muscle contraction produce systemic consequences.

Injury	Mechanism	Clinical Significance
Tongue biting (classically lateral)	Tonic jaw clenching during the tonic phase catches the tongue between the teeth	Pain, bleeding, risk of infection; lateral tongue bite is a clinical marker that helps confirm a true epileptic seizure ^[6]
Head injury / lacerations	Sudden loss of consciousness and postural tone → unprotected fall	May cause concussion, skull fracture, subdural haematoma — particularly dangerous if seizing near hard surfaces or stairs
Posterior shoulder dislocation	During the tonic phase, internal rotators (subscapularis, pectoralis major, latissimus dorsi) overpower the smaller external rotators → the humeral head is driven posteriorly	Bilateral posterior shoulder dislocation is virtually pathognomonic for a seizure (or electrocution). Must obtain axillary lateral X-rays — posterior dislocations are easily missed on standard AP views
Vertebral compression fractures	Sustained tonic contraction of paraspinal muscles → axial loading of the vertebral bodies	Particularly in patients with osteoporosis; thoracic compression fractures most common
Burns / scalds	Seizure while cooking, bathing, or near heat sources	This is why patients are counselled to use non-fire heat sources and take showers instead of baths ^[4]^[5]
Drowning	LOC while in or near water	Drowning accidents are the biggest risk in children with epilepsy ^[24]. Supervised swimming only

Derangement	Mechanism
Lactic acidosis	Sustained muscle contraction → anaerobic glycolysis → lactate accumulation. Usually self-correcting once the seizure terminates
Hypoglycaemia	Massive increase in cerebral and muscular glucose consumption during a prolonged seizure. Especially dangerous in prolonged SE
Hyperthermia	Intense muscular activity generates heat; impaired central thermoregulation during SE. Worsens neuronal injury
Hyperkalaemia	Muscle cell destruction (rhabdomyolysis) + acidosis → K⁺ shift out of cells

Complication	Mechanism	Duration
Postictal confusion	Global cortical suppression from neuronal exhaustion + active GABAergic inhibition after seizure termination	Minutes to hours
Todd's paralysis (postictal paresis)	Postictally a period of worsened neurologic function related to the location of the seizure in the brain ^[3]. Focal cortical exhaustion/depression. Mimicker of TIA or stroke ^[3]	Minutes to hours; may be mistaken for stroke if not recognised
Postictal psychosis	Mechanism not fully understood; may relate to post-seizure dopaminergic upregulation	Hours to days; rare
Postictal headache	Vascular changes + meningeal irritation + muscle contraction	Hours

Status epilepticus is a MEDICAL EMERGENCY with mortality 3–20% ^[2]^[4]. Mortality rises with duration and if there is an identified acute brain insult.

The complications of SE itself are devastating and escalate with duration:

Complication	Mechanism	Time Threshold
Excitotoxic neuronal injury	Prolonged seizure → sustained glutamate release → NMDA receptor activation → Ca²⁺ influx → mitochondrial failure → neuronal apoptosis/necrosis	After ~5 minutes
Cerebral oedema	Excitotoxicity + failure of ion homeostasis → cytotoxic oedema; breakdown of BBB → vasogenic oedema	After ~30 minutes
Hippocampal sclerosis (long-term)	The hippocampus is particularly vulnerable to excitotoxic injury because of its high density of NMDA receptors. Prolonged SE → selective neuronal loss in CA1, CA3, and dentate hilus → gliosis → hippocampal sclerosis → which itself becomes a focus for future epilepsy (a vicious cycle)	Hours to days
Multi-organ failure	Sustained metabolic demand + lactic acidosis + rhabdomyolysis + hyperthermia + cardiovascular instability	Prolonged SE
Respiratory failure	Tonic contraction of respiratory muscles + aspiration + neurogenic pulmonary oedema + BZD/AED-induced respiratory depression	Any stage
DIC	Systemic inflammatory response + metabolic derangement in prolonged SE	Late/severe SE

"The later a seizure is stopped, the more difficult it is to be stopped" ^[2]^[4] — this is because prolonged seizure activity causes GABA-A receptor internalisation (fewer receptors on the neuronal surface → BZDs become less effective) while NMDA receptors are trafficked to the surface (↑ excitatory drive). This is the pharmacological rationale for the staged protocol.

3. Chronic Complications of Epilepsy

These are extremely common and frequently under-recognised:

Comorbidity	Prevalence in Epilepsy	Key Points
Learning disabilities	Up to half of children ^[24]	Beyond intellectual disability — specific difficulties in reading, mathematics, etc.
ADHD	~30% of children ^[24]	Attention deficit without hyperactivity is more common; girls and boys affected equally ^[24]
Anxiety	Up to 25% of children ^[24]	Often coexists with other comorbidities; higher risk with positive family history of mood disorders ^[24]
Depression	Common in adults and children	May be a direct effect of temporal lobe epilepsy, a side effect of AEDs (especially levetiracetam, phenobarbital), or a reaction to the burden of chronic disease
Autism	Risk is 7.4-fold higher in children with epilepsy ^[24]	Risk factors include intellectual disability, specific syndromes (West syndrome), and specific aetiologies (tuberous sclerosis, certain genetic disorders) ^[24]
Psychosis	Rare (ictal, postictal, or interictal)	Interictal psychosis of epilepsy may resemble schizophrenia; more common with temporal lobe epilepsy

This is the most feared chronic complication of epilepsy:

"Sudden unexpected death in epilepsy is a rare complication of epilepsy seen in approximately 1 child per 4,000 person-years" ^[24]. "All families of children with epilepsy should be counselled regarding this potential complication, especially those with frequent nocturnal convulsions" ^[24].

Feature	Details
Definition	Sudden, unexpected, witnessed or unwitnessed, non-traumatic, non-drowning death in a patient with epilepsy, with or without evidence of a seizure, excluding documented status epilepticus, where post-mortem examination does not reveal a structural or toxicological cause of death
Incidence	~1 in 1,000 adults with epilepsy per year; ~1 in 4,500 children per year. Much higher in drug-resistant epilepsy (~1 in 150/year)
Risk factors	Frequent nocturnal convulsions ^[24], drug-resistant epilepsy (especially GTCS), young adult males, polytherapy, non-compliance with AEDs, sleeping prone
Mechanism (proposed)	Post-ictal central apnoea (brainstem suppression → respiratory arrest) + post-ictal cardiac arrhythmia (autonomic instability) → cardiorespiratory arrest. May be related to serotonergic brainstem dysfunction
Prevention	Best protection = optimal seizure control (especially preventing GTCS). Nocturnal supervision, seizure detection devices, avoiding sleeping prone. Compliance with AEDs is critical

SUDEP — Must Counsel All Patients and Families

SUDEP is under-discussed by clinicians because of its sensitive nature, but failure to counsel is both ethically and medicolegally problematic. The key message: optimal seizure control with AED compliance is the single most important preventive measure. The risk is highest in uncontrolled GTCS, particularly nocturnal seizures.

4. Complications of Treatment

These are covered in detail in the management section but summarised here as complications:

AED	Notable Chronic Complications	Mechanism
Valproate	Teratogenicity (neural tube defects, cognitive impairment in offspring), hepatotoxicity, pancreatitis, PCOS, weight gain, hyperammonaemia	Teratogenicity: disrupts folate metabolism + histone deacetylase inhibition → abnormal gene expression during embryogenesis
Phenytoin	Gingival hyperplasia (fibrous overgrowth from ↑ fibroblast activity), hirsutism, coarsened facies, cerebellar atrophy (chronic toxicity), peripheral neuropathy, osteomalacia	Zero-order kinetics → easy to overshoot toxic range; CYP induction → ↓ vitamin D
Carbamazepine	Hyponatraemia (SIADH), SJS/TEN (HLA-B*1502), aplastic anaemia (rare)	ADH-like effect at collecting duct; immune-mediated hypersensitivity
Lamotrigine	SJS/TEN (especially with rapid dose escalation or co-administration with valproate)	Immune-mediated; valproate inhibits lamotrigine glucuronidation → ↑ lamotrigine levels
Levetiracetam	Behavioural/psychiatric: irritability, aggression, depression	Unknown; may relate to SV2A modulation affecting mood circuits
Topiramate	Cognitive slowing, word-finding difficulty, renal stones, acute angle-closure glaucoma	Carbonic anhydrase inhibition → ↓ urinary citrate → calcium phosphate stones
Phenobarbital	Sedation, cognitive impairment, behavioural disturbance in children, osteomalacia	GABA-A enhancement → sedation; CYP induction → ↓ vitamin D
Vigabatrin	Irreversible visual field constriction (bilateral concentric)	Retinal toxicity from GABA accumulation in retinal cells

Haemorrhagic disease of the newborn: Higher risk with enzyme-inducing AEDs (carbamazepine, phenytoin, phenobarbitone) → Mx: 1mg IM Vitamin K in the last month of gestation ^[6]

Epilepsy has a profound impact on quality of life beyond the seizures themselves:

Domain	Impact
Driving	Prohibited from driving if diagnosed: must be seizure-free for ≥ 5 years to drive ordinary motor vehicle, ≥ 10 years without meds for buses and large goods vehicles ^[6]. No mandatory reporting by doctors in HK, but need clear documentation. Counselling: encourage patient to disclose their condition to Transport Department ^[6]
Employment	Many occupations are restricted (pilot, commercial driver, heavy machinery operator, working at heights). Employment discrimination is common. Diagnosis should be as accurate as possible because of the huge impact on patient's life, e.g., job, insurance ^[4]
Education	Children with epilepsy have higher rates of learning difficulties, school absenteeism, and social isolation
Stigma	Epilepsy remains highly stigmatised in many societies, including Hong Kong. Fear of public seizures → social withdrawal
Relationships / family	Impact on family dynamics; parental anxiety; adolescent concerns about dating, pregnancy
Insurance	Difficulty obtaining life/health/travel insurance
Pregnancy	AED → risk of foetal malformation (cleft palate, spina bifida, congenital heart malformation, hypospadias) ^[6]. Highest risk with valproate and polytherapy. Changing to lamotrigine or levetiracetam, use monotherapy at lowest effective dose. Folic acid 5mg daily 3 months before conception until 3 months of gestation ^[6]. Anticipate breakthrough seizures postpartum due to stress and sleep deprivation ^[6]

Prognosis of febrile convulsion is generally good ^[5]:

Complication	Risk	Key Points
Recurrent febrile seizures	Risk of recurrence following first febrile seizure = 30% (1/3 of patients) ^[5]. 50–75% within 1 year; 90% within 2 years	Risk factors for recurrence: early age of onset ( < 18 months), family history of febrile seizures in 1st-degree relatives, low degree of fever prior to initial seizure ( < 38°C), brief duration between fever onset and initial seizure ( < 12 hours), background neurological abnormality, seizure recurrence within the same febrile illness ^[5]
Risk of developing epilepsy	Simple febrile seizure: 1–2% (vs 0.4% general population); Complex febrile seizure: 5–10% ^[5]	Risk factors for future epilepsy: complex febrile seizure, pre-existing neurological abnormality, positive family history of afebrile convulsion ^[5]. If 1 feature present = 6–8%; if all 3 features present = 49% ^[5]
Risk of intellectual deficit	Generally rare following febrile seizures ^[5]	ONLY in patients with pre-existing neurological or developmental abnormality and in those who developed subsequent afebrile convulsion ^[5]
No long-term neurological damage	In simple febrile seizures	NO evidence that any therapy will decrease possibility of future epilepsy ^[5]

High Yield Summary — Complications

Acute seizure complications: Physical injury (tongue biting, posterior shoulder dislocation, head injury, drowning, burns), aspiration pneumonia, rhabdomyolysis → AKI, lactic acidosis, hyperthermia, cardiac arrhythmias, neurogenic pulmonary oedema

Status epilepticus: Excitotoxic neuronal injury, cerebral oedema, hippocampal sclerosis (→ future epilepsy), multi-organ failure, respiratory failure, DIC. Mortality 3–20%.

SUDEP: ~1/1,000 adults/year, higher in drug-resistant GTCS. Risk factors: nocturnal GTCS, poor AED compliance, sleeping prone. Prevention = seizure control.

Chronic epilepsy complications:

Cognitive impairment (~25% of children)
Psychiatric comorbidities: depression, anxiety, ADHD (~30%), autism (7.4× risk)
Poor bone health (enzyme-inducing AEDs → ↓ vitamin D)

Treatment complications:

AED side effects (teratogenicity with valproate; SJS with carbamazepine/lamotrigine/phenytoin; cognitive slowing with topiramate; visual field loss with vigabatrin)
Surgery complications: memory loss, visual field defects, depression

Febrile seizure prognosis: Generally good. Recurrence risk 30%. Epilepsy risk: simple 1–2%, complex 5–10%.

Psychosocial: Driving restrictions (seizure-free ≥ 5y in HK), employment limitations, stigma, insurance difficulties, pregnancy risks

Active Recall - Complications of Seizures & Epilepsy

References

^[1] Lecture slides: GC 081. Seizure and loss of consciousness Delirium and encephalopathy; epilepsy; coma and brain death; care of unconscious patients; electrophysiology I.pdf (slide on Surgical management — complications) ^[2] Senior notes: Adrian Lui Pediatrics Notes.pdf (p126, TLE surgery complications, Status Epilepticus) ^[3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p1176, Surgical treatment complications) ^[4] Senior notes: Ryan Ho Neurology.pdf (p109, TLE surgery complications, SE mortality) ^[5] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p491, Counselling of febrile seizure — recurrence risk, epilepsy risk, intellectual deficit risk) ^[6] Senior notes: Maksim Medicine Notes.pdf (p257–259, Pregnancy and epilepsy, Driving, AED side effects) ^[10] Lecture slides: GC_Interactive tutorial (Neuro-Epilepsy case) student copy.pdf (Case scenario — side effects, driving, refractory seizure, pregnancy) ^[24] Lecture slides: Paediatrics in Review - Seizures in Children.pdf (p24–26, Comorbidities table, SUDEP) ^[28] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p810, TSC — seizure associated with developmental delay)

High Yield Summary

Key Definitions:

Seizure = transient symptoms from abnormal excessive/synchronous neuronal activity
Epilepsy = ≥ 2 unprovoked seizures > 24h apart, OR 1 seizure + ≥ 60% recurrence risk, OR epilepsy syndrome
Status epilepticus = seizure ≥ 5 minutes or ≥ 2 seizures without recovery of consciousness between
Resolved epilepsy = seizure-free 10y + off AEDs 5y, or past age-dependent syndrome age

Seizure Types (ILAE 2017):

Focal (aware / impaired awareness / → bilateral tonic-clonic)
Generalised (tonic-clonic, absence, myoclonic, atonic, tonic, clonic)
Unknown

Aetiology varies by age:

Neonates: hypoxia, metabolic, congenital
Children: febrile seizures, infections, genetic
Young adults: idiopathic/genetic, hippocampal sclerosis, trauma
Adults: tumours, alcohol, drugs
Elderly: stroke, neurodegeneration, metastases

ILAE 2017 Aetiological Categories: Genetic, Structural, Metabolic, Immune, Infectious, Unknown

Key Clinical Features:

Aura = focal aware seizure (epigastric sensation, déjà vu, fear = temporal lobe)
Focal impaired awareness = automatisms + behavioural arrest (temporal lobe epilepsy)
GTCS: tonic → clonic → postictal confusion
Todd's paralysis = postictal paresis mimicking stroke
Lateral tongue biting = specific for epileptic seizure
Febrile seizure: 6m–5y, fever ≥ 38°C, r/o CNS infection

History is most important for diagnosis — ask patient AND witnesses

High Yield Summary — Differential Diagnosis

The two key questions:

Is it a seizure or a mimic? → Syncope is the most common mimic. PNES is the most important psychiatric mimic.
If seizure, is it provoked or unprovoked? → Provoked = treat the cause. Unprovoked = epilepsy.

Top differentials to never miss:

Syncope (especially cardiac — 30% mortality if missed)
Hypoglycaemia (rapidly reversible, rapidly fatal if missed)
CNS infection (especially in febrile seizures in children — must exclude meningitis)
Intracranial lesion (tumour, SDH — CT/MRI in all first-time seizures)
Drug/alcohol withdrawal (especially alcohol — seizures at 6–48h, DT at 48–96h)
NCSE (commonly missed — EEG required)

Key clinical differentiators for seizure vs syncope:

Seizure: sudden onset, aura, tonic-clonic > 15s, lateral tongue biting, cyanosis, incontinence, postictal confusion (> 30 min), Todd's paralysis
Syncope: gradual onset with prodrome, pallor, convulsion < 15s, tip tongue biting (if any), rapid recovery ( < 5 min)

In children, also consider: breath-holding spells, rigors/chills (stopped by holding limbs), Sandifer syndrome, night terrors

Gold standard for PNES: Video EEG

High Yield Summary — Diagnosis & Investigations

Diagnosis is CLINICAL — history from patient AND witness is the cornerstone.

ILAE 2014 criteria for epilepsy:

≥ 2 unprovoked seizures > 24h apart, OR
1 unprovoked seizure + ≥ 60% recurrence risk (abnormal EEG, structural brain pathology, focal deficit, intellectual disability, nocturnal seizure), OR
Epilepsy syndrome diagnosis

Key investigations in all first seizures:

Bedside glucose, electrolytes (Na, Ca, Mg), LFT/RFT, CBC, toxicology
CT brain (acute) → MRI brain (stable, more sensitive)
ECG (r/o cardiac cause)
EEG (classify, predict recurrence — but NEVER used alone to confirm or exclude)

EEG pitfalls:

Normal in 50% of first seizures → cannot exclude epilepsy
Epileptiform activity found in 2–4% of normal population → cannot confirm epilepsy alone
↑ Yield: repeat, sleep deprivation, within 24h of seizure

Video-EEG = gold standard for PNES vs epilepsy

MRI key finding: hippocampal T2 hyperintensity + atrophy = hippocampal sclerosis (most common cause of TLE)

SPECT: ictal ↑ perfusion at focus; interictal ↓ perfusion at focus

In simple febrile seizures: diagnostic testing generally unnecessary if neurologically normal child with reassuring examination

High Yield Summary — Management

Acute seizure: ABC → glucose check → BZD if ≥ 5 min → if persistent: phenytoin/valproate/levetiracetam → if refractory: GA in ICU

Status epilepticus staged protocol (SAQ!):

Stage 1 (0–10 min): IV lorazepam 4mg (or IM midazolam 10mg if no IV)
Stage 2 (10–30 min): IV phenytoin 15mg/kg (or IV valproate/levetiracetam)
Stage 3 (refractory): GA — midazolam/propofol/thiopental, maintain ≥ 24h, EEG monitoring
Stage 4 (super-refractory): ketamine, MgSO₄, immunotherapy, dietary therapy, surgery

AED indications: ≥ 2 unprovoked seizures; single seizure + high recurrence risk; epilepsy syndrome

Valproate: C/I in women of childbearing age (teratogenic). Start folic acid 5mg with lamotrigine.

Drug-resistant epilepsy: Failure of ≥ 2 adequate AED trials → consider epilepsy surgery (60–70% cure for TLE)

HLA-B*1502: Screen before carbamazepine/phenytoin in HK population (SJS/TEN risk)

Withdrawal: After ≥ 2 years seizure-free; taper slowly over 2–3 months. Exception: JME = lifelong.

Eclampsia: MgSO₄ (NOT conventional AEDs); continue 24h post-delivery; monitor knee jerk.

High Yield Summary — Complications

Status epilepticus: Excitotoxic neuronal injury, cerebral oedema, hippocampal sclerosis (→ future epilepsy), multi-organ failure, respiratory failure, DIC. Mortality 3–20%.

SUDEP: ~1/1,000 adults/year, higher in drug-resistant GTCS. Risk factors: nocturnal GTCS, poor AED compliance, sleeping prone. Prevention = seizure control.

Chronic epilepsy complications:

Cognitive impairment (~25% of children)
Psychiatric comorbidities: depression, anxiety, ADHD (~30%), autism (7.4× risk)
Poor bone health (enzyme-inducing AEDs → ↓ vitamin D)

Treatment complications:

AED side effects (teratogenicity with valproate; SJS with carbamazepine/lamotrigine/phenytoin; cognitive slowing with topiramate; visual field loss with vigabatrin)
Surgery complications: memory loss, visual field defects, depression

Febrile seizure prognosis: Generally good. Recurrence risk 30%. Epilepsy risk: simple 1–2%, complex 5–10%.

Psychosocial: Driving restrictions (seizure-free ≥ 5y in HK), employment limitations, stigma, insurance difficulties, pregnancy risks

Seizures & Epilepsy

Definition

Critical Distinctions

Seizure Recurrence Risk

Epidemiology

Global

Age Distribution

Hong Kong Relevance

Risk Factors

For Provoked Seizures

For Epilepsy

Risk Factors Modifying Recurrence

Relevant Anatomy and Neurophysiology

The Cerebral Cortex as the Seizure Generator

Neuronal Excitability: The Basis of Seizures

The Concept of Seizure Threshold

Seizure Propagation

Aetiology

Causes of Provoked (Acute Symptomatic) Seizures

Causes of Epilepsy by Age (High Yield)

ILAE 2017 Classification of Epilepsy Aetiology (6 Categories)

Structural Causes — More Detail

Classification

Clinical Features

A. Symptoms

1. Pre-ictal Phase (Prodrome / Aura)

2. Ictal Phase (During the Seizure)

3. Postictal Phase

B. Signs

History Taking Framework

Febrile Seizures (Paediatric Focus)

Epidemiology

Classification

Clinical Features

Diagnosis

Management

Differential Diagnosis of "Seizure-like" Episodes (Overview)

Non-Epileptic Events in Children [2]

Non-Epileptic Events in Adults [6]

Pathophysiology Summary: From Ion Channel to Clinical Feature

Active Recall - Seizures & Epilepsy (Definition, Epidemiology, Aetiology, Classification, Clinical Features)

References

The Core Clinical Question

Framework for the Differential Diagnosis

1. Non-Epileptic Events Mimicking Seizures (Adults)

A. Syncope (Most Important DDx)

B. Psychogenic Non-Epileptic Seizures (PNES)

C. Metabolic Encephalopathy

D. Transient Ischaemic Attack (TIA)

E. Transient Global Amnesia (TGA)

F. Sleep Disorders

G. Movement Disorders

H. Migraine

I. Hyperventilation Syndrome / Panic Attack

2. Non-Epileptic Events Mimicking Seizures (Children)

3. Febrile Seizures — A Special Category

4. Causes of Provoked (Acute Symptomatic) Seizures — The "Seizure but Not Epilepsy" Differential

5. Non-Convulsive Status Epilepticus — A Commonly Missed Diagnosis

6. Brain Tumours Presenting as Seizures

Master Summary Table: Differential Diagnosis of Seizures & Epilepsy

Approach to Differential Diagnosis: Practical Algorithm

Active Recall - Differential Diagnosis of Seizures & Epilepsy

Diagnostic Criteria

Step 1: Was This a Seizure? (Clinical Diagnosis)

Step 2: Is This Epilepsy? (ILAE 2014 Operational Definition)

Step 3: Classify the Seizure → Epilepsy Type → Syndrome → Aetiology

Diagnostic Algorithm

Investigation Modalities

Guiding Principle

A. Bedside and Blood Investigations

B. Electroencephalogram (EEG)

Purpose

Types of EEG

Key EEG Findings and Interpretation

Optimising EEG Yield

C. Neuroimaging

CT Brain

MRI Brain

D. Advanced / Nuclear Medicine Imaging

E. ECG