Epilepsy

Question 1

Define seizure

Answer 1

Clinical manifestation of abnormally excessive & hyper synchronous activity of neurons located mainly in cerebral cortex

Question 2

How are seizures classified?

Answer 2

• Generalized= initial activation of neurons throughout both hemispheres
• Partial= initial activation of limited number of neurons in part of 1 hemisphere
• Secondary generalized= partial seizure that spreads to involve majority of 2 cerebral hemispheres

Question 3

What are the manifestations of a partial seizure in the different lobes?

Answer 3

• Frontal= Jacksonian seizure- tingling in hand/arm, adverse seizures- eyes/head turn to one side
• Parietal= tingling/jerking of leg, arm, face
• Occipital= flashing lights/spots, vomiting
• Temporal= smell/taste, altered behaviour, deja vu, lip smacking, chewing movements

Question 4

What is status epilepticus?

Answer 4

• Life threatening
• Brain in state of persistent seizure= 30+mins OR 2+ without full recovery
• Confers greater risk for future unprovoked seizures

Question 5

What is the mechanism of a seizure?

Answer 5

• Excitation= ionic: Na+, Ca2+ influx, neurotransmitter: aspartate & glutamate release
• Inhibition= Ionic: Cl-, K+ efflux, neurotransmitter: GABA release
• Either can result in too much neuronal activity-seizure
• Initially localised hyper excitability spreads to surrounding neuronal networks
• Either inhibited or chain reaction-seizure

Question 6

What is the function of inhibitory interneurons?

Answer 6

• Allow activity to spread in one direction but not sideways

- Release neurotransmitter GABA

Question 7

Describe GABA

Answer 7

• γ-aminobutyric acid
• Major inhibitory neurotransmitter
• GABA(A)= ligand gated chloride channel receptor
• GABA(B)= G protein-coupled receptor

Question 8

What types of epilepsy are caused by a mutation in GABA(A) receptor subunits?

Answer 8

• Childhood absence epilepsy
• Pure febrile seizures
• Juvenile myoclonic epilepsy
• Generalized epilepsy with febrile seizures
• Dravet syndrome/ SMEI

Question 9

What are the modes of action for anti-epileptic drugs?

Answer 9

• Suppress a.p= Na channel blocker, K channel opener
• Enhance GABA transmission= GABA mimetics/uptake inhibitor
• Suppression of excitatory transmission= glutamate receptor antagonist

Question 10

Name some Benzodiazepines and describe them

Answer 10

• Clonazepam= generalized tonic-clonic, absence & partial seizures
• Clorazepate= partial seizures
• Diazepam/valium/lorazepam= SE given IV

Question 11

What is the mechanism of action for benzodiazepines

Answer 11

• Inc affinity of GABA for receptor
• Inc Cl- current
• Suppresses seizure focus by raising ap threshold
• Strengthens surrounding inhibition-prevents spread

Question 12

What are the negatives of using benzodiazepines?

Answer 12

• Sedation major side effect
• Problems with tolerance & dependance (avoid LT use)
• Respiratoy depression in IV use

Question 13

What is the mechanism of action for Phenytoin?

Answer 13

-When Na+ channels inactivated after depolarisation it binds to receptor so slows down recovery

Question 14

Describe epilepsy & pregnancy

Answer 14

• Very harmful to pregnant women
• Folic acid recommended
• Phenytoin/ valproic acid contraindicated

Question 15

What anti-epileptic drugs have mixed actions?

Answer 15

• gabapentin

- valproate (valproic acid)= tonic-clonic & absence, also used in bipolar

Question 16

How does valproate work?

Answer 16

• Inhibits Na+ channels
• Dec GABA turnover
• Blocks neurotransmitter release by blocking T-type Ca2+ channels

Question 17

What is foetal hydantoin syndrome?

Answer 17

• Pregnant & taking Phenytoin
• Intrauterine growth restriction- microcephaly
• Minor dysmorphic craniofacial features & limb defects
• Some have growth problems & developmental delay

Question 18

What is foetal Valproate syndrome?

Answer 18

-Congenital malformations in infants

Question 19

What is epilepsia partialis continua?

Answer 19

• Rare brain disorder
• Recurrent motor epileptic seizures- focal (face & hands)
• Due to large, acute brain lesion= stroke in adults, focal cortical inflammatory processes in children
• Medication & therapy resistant
• Goal to stop secondary generalization