Epilepsy Flashcards
Define a seizure
Transient occurrence of signs or symptoms due to abnormal electrical activity in the brain, leading to a disturbance of consciousness, behaviour, emotion, motor function or sensation
Most important excitatory neurotransmitter Via which receptor? How does it work?
Glutamate via NMDA R
Cation channel (Na/ Ca in, K out)
Depolarises membrane
More likely to fire AP
Most important inhibitory neurotransmitter Via which receptor? How does this work?
GABA via GABAa R
CL- channel
Hyperpolarises membrane
Less likely to fire AP
Pathology of seizures
Normal brain - inhibitory and excitatory sides are in balance
A seizure: manifestation of abnormal XS excitation & synchronisation of a group of neurones within brain
Caused by: loss of inhibitory (GABA mediated) signals OR too strong excitatory (NMDA/ glutamate) signals
- genetic variation (brain chemistry/ R structure)
- exogenous activation receptors (drugs)
- acquired changes brain chemistry (drug withdrawal, metabolic changes (decreased Na/ glucose)
- damage any of these networks (strokes/ tumours)
Symptoms and signs of seizure
- Often an aura prior e.g. headache/ funny sensations/ de ja vu
- Generalised seizures - loss of consciousness often, changes in muscle tone, tongue biting
May also: - For tonic-clonic seizures - initial hypertonic phase, followed rapid clonus (shaking/ jerking)
OR - For atonic seizures - lose all muscle tone (don’t fit)
- Post- ictal period minutes- hours (reduced consciousness)
Define epilepsy
Tendency toward recurrent seizures unprovoked by a systemic or neurological insult
Criteria, one of:
- 2+ unprovoked (or reflex) seizures occurring more than 24hrs apart
- 1 unprovoked/ reflex seizure & a probability of further seizures similar to general recurrence risk after 2 unprovoked (_>60% over next 10yrs)
- diagnosis of an epilepsy syndrome
- made by a specialist in an epilepsy or first fit clinic
What is a reflex seizure? List some types
Seizure brought on by a particular stimulus: Photogenic Concentrating Eating Hot water immersion Reading Orgasm Movement
Classification of seizure types
Focal onset - one side of brain affected (can eventually spread to both sides) - aware or impaired awareness - motor or nonmotor onset
Generalised onset (bilateral spread rapidly) - impaired awareness or LOC - motor (tonic-clonic, other motor) or nonmotor (absence - odd behaviour/ vacant e.g. typical/ atypical/ myoclonus/ eyelid myoclonic)
Unknown onset - motor (tonic-clonic/ other motor) or nonmotor - unclassified
What is a generalised seizure?
Originate at some point within -> rapidly engage bilaterally
CN include cortical & subcortical structures but not necessarily the entire cortex
Old term= grand mal
Old term for absence seizure = petit mal
What is a focal seizure?
Originates within networks limited to one hemisphere, may be discretely localised or more widely distributed (can eventually become bilateral)
Old term = partial seizure
What is a provoked seizure?
Seizure as a result of another medical condition, e.g.:
- drug use/ withdrawal
- alcohol withdrawal
- head trauma & IC bleeding
- metabolic disturbances (hyponatraemia/ hypoglycaemic)
- CNS infections
- febrile seizures infants
- uncontrolled hypertension
Unlikely need ongoing AED treatment if cause treated
Differentials for seizures
- syncopal-episodes e.g. vasovagal syncope
- cardiac issues e.g. reflex anoxic seizures, arrhythmias
- movement disorders e.g. parkinsons, huntingtons
- TIAs
- migraines
- non-epileptic attack disorders (old term= pseudo- seizures)
Initial management of a seizure
A-E assessment:
- Airway
- breathing (O2 sats)
- circulation (high HR, BP normally high, can go low drugs)
- disability (consciousness level)
- Execute recovery position
Start a timer
Get help
What is status epilepticus?
A seizure lasting _>5mins or multiple seizures without complete recovery _>5mins
Medical emergency
How to treat status epilepticus
Wait and if needed move on to next step
- Wait 5 minutes
- Benzodiazepine (full dose, give gradually)
- Benzodiazepines again
- phenytoin (or Levetriacetam) loading dose
- Call intensive care/ anaesthetics
- Thiopentone/ general anaesthesia
How do benzodiazepines work? Side effects, examples for use in status epilepticus
Class of GABAa agonists
End in -apam
Increased CL conductance = more negative resting potential, less likely to fire (work best when membrane positive e.g during seizure)
❌addictive, CVS collapse overdose, airway issues
Treatment of SE:
IV lorazepam (long acting)
Diazepam rectally
IM/ Buccal/ intranasal midazolam (mid-acting)
Investigations for epilepsy
Electroencephalograph:
Record electrical activity of brain, can trigger seizure to record e.g. sleep deprivation - need capture episode or unusual activity
Many healthy ppl have abnormal EEGs
MRI:
Vascular/ structural abnormalities/ big IC bleed - only required when unsure about diagnosis of epilepsy syndrome
List the 6 main anti-epileptic drugs (AEDs)
Carbamazepine Phenytoin Valproate Lamotrigine Levetiracetam Benzodiazepines for seizure termination
Which AEDs act by sodium channel blockade? How does this work?
Phenytoin
Carbamazepine
Valproate
Lamotrigine
Block Na channels in central neurones - slows recovery of neurones from inactive to closed state
- reduces neuronal transmission
Side effects of carbamazepine (tegretol)
Suicidal thoughts
Joint pain
Bone marrow failure
Side effects of phenytoin
Used mainly in status epilepticus or as an adjunct in generalised seizures
Zero order kinetics - eliminated at constant rate so care when adjusting dose
Bone marrow suppression
Hypotension
Arrhythmias (IV use)
Side effects of Na valproate (Epilim, depakote)
Mix of GABAa effects & Na channel blockade & Ca channel blockade
First line for generalise d
Liver failure
Pancreatitis
Lethargy
Teratogenic
When is lamotrigine used?
Primarily a Na channel blocker
May also affect Ca channels
Used often when valproate contraindicated in generalised epilepsy
How does levetiracetam (keppra) work? When can it be used?
Synaptic vesicle glycoprotein binder - stops release of neurotransmitters into synapse and reduces neuronal activity
Option for focal seizures and generalised seizures
Anecdotally being used more frequently, easy dosing and well tolerated
safe in pregnancy
General side effects of AEDs
Largely common across all: Tiredness/ drowsiness Nausea and vomiting Mood changes Suicidal ideation Osteoporosis - older ppl Congenital malformations - greatest with valproate
Rashes including Steven Johnson syndrome (can be life threatening, muco-cutaneous breakdown)
Many can cause anaemia, thrombocytopenia or bone marrow failure
What is required from patients on AEDs?
If also on warfarin need close monitoring
Ideally shouldn’t consume alcohol
Carbamazepine/ phenytoin May decrease effectiveness Of oral contraceptive pills and some antibiotics
Valproate can increase palms concentrations of other AEDs
AEDs which are CYP enzyme inducers
Phenytoin Carbamazepine Barbituates Rifampicin Alcohol (chronic) Sulphonylureas
AEDs which are CYP enzymes inhibitors
Omeprazole Disulfram Erythromycin Valproate Isoniazd Ciprofloxacin Ethanol (acute) Sulphonamides
When can an epileptic patient drive?
Temporarily lose license and need to be seizure free (with meds) for one year before reapplying
For bus/ lorry/ coach need to be seizure free for 5 years off medication for a single seizure or 10years if had multiple
Patients responsibility to inform DVLA
