Seizures symposium Flashcards

Question

Why is the brain prone to seizure activity?

Answer 1

Action potentials rely on positive feedback & are unstable Single neuron can fire spontaneously without external stimulation Network of excitatory neurons connected in a convergent or divergent pathway can be explosive. Stimulation of any one cell can lead to a chain reaction due to the progressive spread of activity over a large area Brain requires at least as much inhibition as excitation to avoid this Epilepsy represents a failure of inhibitory regulation, either focally or generally

Answer 2

Point mutation in Na+ channel (beta subunit) --> abnormally slow inactivation --> repolarisation is impaired. Example is generalised epilepsy with febrile seizures in infants Defect in KCNQ2 or KCNQ3 channel subunit --> impaired activation --> impaired action potential repolarisatin. Example is benign familial neonatal convulsions

Answer 3

Array of electrodes on the scalp which gives information about the electrical activity of a large number of neurons in the cerebral cortex Help determine location of a seizure Rhythmic oscillations - without sensory inputs the various neural networks feedback upon themselves When aroused, neuronal activity becomes desynchronised Hyperexcitation of a seizure --> synchronous activity on EEG

Answer 4

Originate within a small group of 1000 neutrons Synchronised paroxysmal depolarising shift overcomes inhibition Increased extracellular K+ due to neuronal damage or reduced uptake by astrocytes, plus glutamate release from neurons or astrocytes During PDS, trains of action potentials occur

Answer 5

Spread to other brain regions along normal neuronal pathway & may show secondary generalisation if activity spreads to thalamus

Answer 6

Reach cerebral cortex via normal neuronal pathways from thalamus Pathways originate in brainstem & are normally involved in regulating sleep/wake cycle & arousal of cerebral cortex Ca2+ channels & inhibitory GABA receptors in thalamic neutrons have been implicated in spike & wave seizures showing inhibition is preserved

Answer 7

Increased membrane excitability Increased efficiency of excitatory synaptic transmission (glutamate) Decreased efficiency of inhibitory synaptic transmission (GABA)

Answer 8

``` Phenytoin Lamotrigine Carbamazepine Zonisamide Lacosamide ```

Answer 9

AMPA receptor antagonist Non-competitive blockade of AMPA glutamate receptor Reduce spread / generalisation of seizure Well tolerated with improved alertness

Answer 10

Blocks T-type calcium channels in the thalamus, which are involved in bursting & intrinsic oscillations

Answer 11

``` Sodium valproate Benzodiazepines - lorzepam Barbiturates Tiagabine Vigabatric ```

Answer 12

High affinity synaptic vesicle protein 2A ligand Modulates neurotransmitter release Rapidly titrated & effective Mood lowering / agitation side effects

Answer 13

``` Good efficacy, easy & rapid to titrate No drug-drug interactions No cognitive side effects No bone marrow suppression No affective / drowsy side effects Different routes of administration Cost effective ```

Answer 14

``` Single mode of action Less selective effects More side effects in cognition / sedation More drug interactions Kinetics / narrow therapeutic range Cheaper ```

Answer 15

``` Broad spectrum More selective actions Less sedating side effects Psychiatric side effects Less long-term toxicity Fewer drug interactions Easier titration 10 X more expensive ```

Answer 16

Sodium valproate | Iamotrigine

Answer 17

Carbamazepine | Iamotrigine

Answer 18

Phenytoin Carbamazepine Gabapentin / pregabalin

Answer 19

``` Drowsiness Ataxia Hyperactivity Personality change Cognitive impairment Tolerance / dependence ```

Answer 20

``` Ataxia Diplopia Nystagmus Gingival hyperplasia Osteomalacia Cerebellar atrophy ```

Answer 21

``` Sedation Nausea / vomiting Tremor Hair thinning Weight gain Menstrual irregularities Encephalopathy ```