Epilepsy Clinical Overview
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: This is bread-and-butter neurology. With a prevalence of active epilepsy around 4.2 per 1,000 people in Malaysia, you will encounter this frequently in the Emergency Department, on the wards, and in clinics. Mismanagement can lead to significant morbidity.
High-Yield Definition: "Epilepsy is a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring >24 h apart; (2) One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) Diagnosis of an epilepsy syndrome." (Source: ILAE 2014, adapted in Malaysian Consensus Guidelines).
Clinical One-Liner: Basically, it's a brain that is predisposed to having spontaneous seizures, and it's our job to figure out why and how to stop them.
II. Etiology & Risk Factors
Etiology: The cause is often broken down into broad categories based on the 2017 ILAE classification. Think:
Structural: The most common group here. Post-stroke, head injury, brain tumours, cortical dysplasia, or mesial temporal sclerosis.
Genetic: Known or presumed genetic mutations. Often presents as specific epilepsy syndromes in childhood (e.g., Juvenile Myoclonic Epilepsy).
Infectious: A very relevant cause in our region. Think neurocysticercosis, tuberculosis, viral encephalitis (like Japanese Encephalitis or Dengue), or bacterial meningitis sequelae.
Metabolic: Inborn errors of metabolism, mitochondrial diseases. Less common.
Immune: Autoimmune encephalitis (e.g., anti-NMDA receptor encephalitis). A rising cause, keep it in your differentials for new-onset refractory seizures.
Unknown: Still a large proportion of cases where we can't pinpoint a single cause.
Risk Factors (Malaysian Context):
Non-Modifiable: Family history of epilepsy, certain genetic syndromes.
Modifiable/Acquired:
Previous significant head trauma (major cause in our young population due to road traffic accidents).
Stroke (increasingly common cause in our ageing population).
Perinatal insults (birth asphyxia, low birth weight).
CNS infections.
III. Quick Pathophysiology
In simple terms, a seizure is a transient surge of abnormal, excessive, or synchronous electrical activity in the brain. The clinical features you see depend entirely on where this electrical storm starts and where it spreads.
Focal Onset: Starts in one area. If it stays there, you get focal aware seizures (patient knows what's happening). If it spreads and impairs consciousness, it's a focal impaired awareness seizure. If it spreads to both hemispheres, it becomes a focal to bilateral tonic-clonic seizure.
Generalised Onset: Starts in networks connected to both hemispheres simultaneously. This is why consciousness is lost early. The imbalance between excitatory (e.g., glutamate) and inhibitory (e.g., GABA) neurotransmission is the key mechanism. Our drugs work by either suppressing excitation or enhancing inhibition.
IV. Clinical Assessment
Red Flags & Immediate Actions:
Seizure > 5 minutes (Status Epilepticus): This is a medical emergency. Action: Start ABCDE approach, secure airway, give high-flow oxygen, check capillary blood sugar, secure IV access, and give IV Benzodiazepine as per protocol. Alert your senior immediately.
New Focal Neurological Deficit (Todd's Paresis vs. Stroke): Action: Urgent non-contrast CT Brain to rule out an acute bleed or large infarct.
Fever, Neck Stiffness, Altered Mental Status: Suggests meningoencephalitis. Action: Full septic workup, start empirical antibiotics/antivirals after discussing with your senior, and plan for a lumbar puncture if no contraindications.
First Seizure in an Older Adult (>40 years): High suspicion for a structural lesion. Action: Prioritise neuroimaging.
History: A good history from an eyewitness is gold standard.
Before (Pre-ictal): Was there a trigger (sleep deprivation, flashing lights, illness)? Was there an aura (e.g., rising epigastric sensation, déjà vu, strange smell)?
During (Ictal): Where did it start? (e.g., head turning, one-sided jerking suggests focal onset). Was there loss of consciousness? Stiffening (tonic), jerking (clonic)? Eyes open or closed? Tongue bite (lateral aspect is specific)? Incontinence? Duration?
After (Post-ictal): How long did it take to return to baseline? Was there confusion, drowsiness, or focal weakness (Todd's paresis)?
Pertinent Negatives: Ask about syncope triggers (prolonged standing, pain, micturition) and features (presyncope lightheadedness, sweating, gradual loss of tone) to rule out cardiogenic causes.
Physical Examination:
Often normal between seizures.
Look for post-ictal signs: confusion, drowsiness.
Check for tongue bite (lateral border), evidence of incontinence.
Full neurological examination: search for any focal deficits that might point to a structural lesion.
Look for neurocutaneous stigmata (e.g., ash-leaf spots of Tuberous Sclerosis, café-au-lait macules of Neurofibromatosis).
Clinical Pearl: When a patient presents with a first seizure, your most important job is not just to stop the fit, but to answer the question: "Is this a provoked or unprovoked seizure?" A seizure due to severe hypoglycemia is provoked and is not epilepsy. A seizure out of the blue is unprovoked and requires a full workup.
V. Diagnostic Workflow
Differential Diagnosis:
Syncope (Vasovagal or Cardiogenic):
Points For: Clear trigger, pre-syncopal symptoms, rapid recovery.
Points Against: Prolonged post-ictal confusion, lateral tongue bite, focal neurological signs.
How to Differentiate: Detailed history is key. ECG to look for arrhythmias or prolonged QT.
Psychogenic Non-Epileptic Seizures (PNES):
Points For: Eyes closed during event, asynchronous thrashing movements, pelvic thrusting, crying, long duration with minimal post-ictal state.
Points Against: Stereotypical, brief tonic-clonic pattern, significant post-ictal confusion.
How to Differentiate: Video-EEG monitoring is the gold standard. Serum lactate/prolactin may be elevated post-epileptic seizure but not typically in PNES.
Metabolic/Toxic Disturbances:
Points For: Known diabetic with hypoglycemia, uremia in a renal patient, history of substance abuse.
Points Against: Normal blood parameters in an otherwise well patient.
How to Differentiate: Bedside glucose, renal profile, liver function tests, calcium, magnesium.
Investigations Plan:
Bedside / Initial (First 30 Mins):
Capillary Blood Glucose: To rule out hypoglycemia, the most critical reversible cause.
ECG: Rule out arrhythmias causing syncope. Look for prolonged QT which can be associated with seizures.
First-Line Labs & Imaging:
Bloods: Full blood count, renal profile, liver function test, serum calcium, magnesium. To rule out metabolic causes and establish a baseline before starting Anti-Epileptic Drugs (AEDs).
Neuroimaging (CT/MRI Brain): MRI is superior for identifying subtle structural causes. A non-contrast CT is often the first modality in the emergency setting to rule out acute bleeds or large tumours. Indicated for almost all adults with a first unprovoked seizure.
Confirmatory / Gold Standard:
Electroencephalogram (EEG): The gold standard to detect epileptiform discharges, which supports the diagnosis and helps classify the epilepsy type (focal vs. generalised). A normal EEG does not rule out epilepsy. Sleep deprivation prior to the test increases the yield.
VI. Staging & Severity Assessment
We primarily use the ILAE 2017 Classification which has three levels:
Seizure Type: Classify the event itself (e.g., Focal to Bilateral Tonic-Clonic, Generalised Absence, etc.). This is based on the history.
Epilepsy Type: Based on seizure type and EEG findings, we classify the epilepsy as Focal, Generalised, Combined Generalised & Focal, or Unknown.
Epilepsy Syndrome: If the clinical features, age of onset, and EEG findings fit a recognised pattern (e.g., Juvenile Myoclonic Epilepsy, Lennox-Gastaut Syndrome), we make a syndromic diagnosis.
Impact on Management: The epilepsy type is the most critical factor for choosing the right AED. A drug for focal epilepsy (like Carbamazepine) can worsen generalised epilepsy.
VII. Management Plan
Immediate Stabilisation (Status Epilepticus - Seizure > 5 mins):
(Based on Malaysian Consensus Guidelines 2017 - always check local hospital protocol)
Airway, Breathing, Circulation: Secure airway (jaw thrust, NP airway), give 10-15L/min O2 via face mask, establish IV access.
First Line (0-10 mins): IV Diazepam 10mg slow bolus (rate <5mg/min). Can repeat once if seizures persist.
Second Line (10-30 mins): If no response, start IV Phenytoin loading dose of 15-18 mg/kg at a slow infusion rate (≤50 mg/min) with cardiac monitoring. Caution: Hypotension and arrhythmias.
Third Line (Refractory SE): If seizures continue, this is now Refractory Status Epilepticus. Escalate to your senior/specialist immediately. Options include IV Midazolam infusion, Propofol, or Phenobarbitone in an ICU setting.
Definitive Treatment (The Ward Round Plan):
Initiate AED after a second unprovoked seizure. Decision after a first seizure is individualised.
Choice of First-Line AED (General Guide):
Focal Epilepsy: Carbamazepine (Tegretol), Levetiracetam (Keppra), Lamotrigine.
Generalised Epilepsy (Tonic-Clonic): Sodium Valproate (Epilim) is very effective. Levetiracetam and Lamotrigine are alternatives. Crucially, avoid Carbamazepine.
Absence Seizures: Ethosuximide or Sodium Valproate.
Juvenile Myoclonic Epilepsy: Sodium Valproate is first-line.
Important Consideration: In women of childbearing potential, Sodium Valproate should be avoided if possible due to its high teratogenicity. Discuss with a specialist.
Dosing: Start low, go slow. Titrate up to the lowest effective dose that controls seizures without causing side effects.
Non-Pharmacological: Advise on seizure triggers (sleep deprivation, alcohol), driving restrictions (must be seizure-free for at least 1 year to drive), and first aid for seizures for family members.
Long-Term & Discharge Plan:
Referral to a neurologist/physician clinic for follow-up.
Ensure patient has adequate medication supply (e.g., 3 months).
Emphasise medication adherence is critical.
Provide contact information for the Malaysian Epilepsy Society for patient support.
VIII. Complications
Immediate:
Status Epilepticus: Can lead to permanent brain damage or death. Management: Aggressive ABC support and escalating AEDs.
Trauma: Head injury, fractures, or dislocations from falls during a seizure. Management: Standard trauma assessment and care.
Short-Term:
Aspiration Pneumonia: From aspiration during the ictal or post-ictal state. Management: Antibiotics and supportive care.
AED Side Effects: Drowsiness, dizziness, rash (risk of SJS with Lamotrigine/Carbamazepine, especially in HLA-B*1502 positive patients). Management: Monitor and switch AED if necessary.
Long-Term:
Sudden Unexpected Death in Epilepsy (SUDEP): Rare but serious risk, especially in patients with poorly controlled generalised tonic-clonic seizures. Management: Emphasise adherence to AEDs to achieve seizure freedom.
Cognitive & Psychological Issues: Depression, anxiety, and memory problems are common. Management: Screen for these and refer to psychiatry/psychology if needed.
IX. Prognosis
Good for many. Around 70% of patients can become seizure-free with appropriate AED treatment.
Poor Prognostic Factors:
Identifiable structural brain lesion.
Failure to respond to the first two appropriate AEDs (Drug-Resistant Epilepsy).
Associated intellectual disability.
X. How to Present to Your Senior
"Dr, for review please. This is [Patient Name], a [Age]-year-old [man/woman] in [Bed Number], with no prior medical history, who was brought in for a first-episode seizure. The eyewitness, his [son], described a sudden loss of consciousness with generalised body stiffening and jerking lasting about 2 minutes, followed by 15 minutes of confusion. On examination, he is now drowsy but rousable, GCS 14/15, with no focal deficits. My main differential is a first unprovoked seizure, likely generalised tonic-clonic type. I have sent off the initial bloods including magnesium and calcium, and done an ECG which is normal sinus rhythm. I would like to ask about arranging for a CT brain and an outpatient EEG."
XI. Summary & Further Reading
Top 3 Takeaways:
A seizure lasting >5 minutes is Status Epilepticus. Manage it as a medical emergency with the ABCs and IV benzodiazepines.
The most important initial step is to differentiate a provoked from an unprovoked seizure.
The choice of long-term AED depends critically on the epilepsy type (focal vs. generalised). Get the classification right.
Key Resources:
Malaysian CPG: Look for the "Consensus Guidelines on the Management of Epilepsy, 4th Edition (2024)" by the Malaysian Society of Neurosciences. The 2017 edition is also a key reference.
UpToDate: Search for "Evaluation and management of the first seizure in adults" and "Overview of the management of epilepsy in adults."
ILAE Website: For the official 2017 classification of seizure types. (ilae.org)
