Epilepsy Flashcards
Definition of epilepsy?
1) ≥2 unprovoked seizures occurring >24h apart
2) 1 unprovoked seizure & probability of further seizures similar to general recurrence risk (min. 60%) after 2 unprovoked seizures, occurring over next 10 years, or
3) Diagnosis of epilepsy syndrome
Pathophysiology of seizures
- Hyperexcitability from excessive excitatory neurotransmitters (e.g. glutamate, ACh, histamine, cytokines), insufficient inhibitory (e.g. GABA, dopamine), and abnormalities in intra-/extracellular substances (e.g. Na, K, glucose, O2)
- Hypersynchronization from hippocampal sclerosis
==> Instability in single neuronal cell membrane/group of cells around it which leads to seizure activity (synchronized paroxysmal discharges occurring in a large population of neurons within the cortex)
Etiologies of seizures
- Structural (e.g. stroke, traumatic brain injury; brain tumours, hippocampal sclerosis, vascular malformations)
- Metabolic (hypoNa/Ca/Mg/glycemia; inborn errors of metabolism, mitochondrial disorders)
- Infectious/Inflammation (CNS infection, febrile illness; bacterial meningitis, encephalitis)
- Neurodegenerative (e.g. Alzheimer’s)
- Genetic (e.g. Dravet syndrome with SCN1A mutations)
Status Epilepticus definition
≥ 5min of which a seizure is likely to be prolonged leading to continuous seizure activity (30min = neuronal injury)
What are focal seizures?
Seizures begin only in 1 hemisphere (with / without dyscognitive features). May or may not have impaired awareness.
e.g. Focal aware/motor (simple partial) ; Focal dyscognitive/impaired awareness (Complex partial)
Types of generalized onset seizures
- Tonic-clonic (GTC) / “Grand-mal” = Starts with stiffening of limbs (tonic) then jerking of limbs & face (clonic)
- Clonic = Jerking, often asymmetrical & irregular
- Tonic = Stiffening of body & sudden loss of consciousness, lasts 10-20s
- Myoclonic = Rapid, brief contractions of bodily muscles (usually faster than clonic), usually both sides concurrently
- Absence / “Petit-mal” = Lapse in awareness that begins and ends abruptly, lasts only a few seconds, frequent, no auras
- Atonic = Sudden loss of muscle tone, most severe form (classic drop attack, rag-doll), short ep followed by immediate recovery
Stages of seizure
1) Prodromal: May or may not occur, common Sx incl. confusion, anxiety, headache, etc.
2) Aura / Early ictal: May or may not occur, common Sx incl. bitter/acidic taste, dizziness, flickering vision, numbness, strange smells, tingling, etc.
3) Ictal: Variety of Sx such as arm/leg stiffening, lip-smacking, confusion, twitching
4) Post-itcal: Different recovery periods, typical Sx incl. arm/leg weakness, body soreness, drowsiness, headaches, nausea, etc.
When to start treatment?
- Diagnosis of epilepsy confirmed
Consider starting after first unprovoked seizure if:
- Signs of neurological deficit
- Electroencephalogram (EEG) shows unequivocal epileptic activity
- Discussion of risk of further seizures
- Brain imaging shows structural abnormality
When to discontinue ASM and how to discontinue?
Discontinue when seizure free >2 years. If increased risk of recurrence, wait >2y.
Withdraw ASMs slowly over 2-3 months. Benzodiazepines withdrawn over 6 months.
When is epilepsy considered resolved?
- Had age-dependent epilepsy but past applicable age
- Seizure-free for last 10 years and no ASMs for last 5 years
Safer ASMs in pregnancy?
Levetiracetam and Lamotrigine
Some ASMs can impair COC effectiveness (e.g. CBZ, OXC, PHT, TOP).
Oestrogen-containing COC and HRT can impair effectiveness of lamotrigine.
ASMs in lactation?
- ASMs usually benefits > risks, generally safe
- Phenobarb, Zonisamide, Ethosuximide reported higher infant levels
- No benzos except Lorazepam (shorter acting, nil active metabolites); but occasional use and low doses compatible with breastfeeding
1st line, 2nd line & adjuvant ASMs for GTC?
1st line: Valproate (not for females of child-bearing age)
2nd line: Lamotrigine, Levetiracetam
Adjuvant: Topiramate, Perampanel, Clobazam
1st line, 2nd line & adjuvant ASMs for Focal?
1st line: Lamotrigine, Levetiracetam
2nd line: Carbamazepine, Oxcarbazepine, Zonisamide, Lacosamide
Adjuvant: Topiramate (1st), Pregabalin, Valproate, Perampanel
1st line and 2nd line ASMs for Absence?
1st: Ethosuximide
2nd: Valproate, Lamotrigine, Levetiracetam
