Lecture 4: Epilepsy Flashcards
What is epilepsy?
At least two unprovoked seizures occuring >24 hours apart. A collection of more than 40 diseases, which all give rise to recurrent seizures
What is a seizure?
A transient occurrence of signs and/or symptoms due to abnormal excessive or snchronous neuronal activity in the brain. Some seizures can hardly be noticed, while others are totally disabling. This generllay depends on area of the brain in which the seizure occurs. A seizure can happen for several reasons including diabetes, stroke etc.
What are generaslised seizures?
Arisisng within and rapidly engaging bilateraly distributed networks - both hemispheres in the brain
What are the types of generalised seizures?
- Absence seizures - alterened aareness that is short term. There is 2 main types; typical and atypical. Typical absence last less that 10 seconds. Atypical last up to 30 seconds, they have a slow onset and slow osfset.
- Clonic seizures: bilateral rhythmic jerking
- Tonic: bilaterally increased tone in limbs
- Atonic: sudden loss of muscle tone
- Myoclonic: single or series of muscel contractions
- Tonic-clonic: most common, combines bilaterally ruthmic jerking and stiffness of body.
- Status epilepticus
What is status epilepticus?
A condition resulting either from the failure of the mechanims responsible for seziure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures. It is a condition that can have long term consquesnses including neauronal death, neauronal injury, and alteration of neauronal networks, depending on the type and duration of seizures. Can be life threatening
What are focal seizures?
Originating in networks limited to one hemisphere
May be just an aura, a smell, vision.
May be motor - issues with toes/ fingers/ face twitching.
Can be autonomic - related to the autonomic system
Can effect awareness and responsiveness
Focal seizures may develop into bilateral convulisive seizures
What causes epilepsy?
- Genetic: dravets syndromed, mutations in the gene SCN1a - sodium channel. Sodium channel are involved in action potentials leading to abnormal activity leading to seizures
- Structural: acquired, due to traumatic brain injury from ie car crash or genetic
- Metabolic eg glutamate transporter deficiency (GLUT1)
- Immune: Rasmussen syndrome, an autoimmune disease
- Infectious: Bacterial and viral encephalitis - leading cause
- Unknown: 1/3 of all diagnosis are unknown
What are the co-morbidities associated with epilepsy?
Stroke, migraine/ headaches, dementia, traumatic brain injury, cerebral palsy, autism, multiple sclerosis, ADHD
What are the underlying causes of seizures?
Stage 1: initiation - abnormal voltage gated channels, so increase in neuronal excitability
Stage 2: Synchronisation - abnormal receptor operated channels
Stage 3: Propagation - recruitment of neurons via anatomical connections
What is the main excitatory neaurotrasmitter?
Glutamate
What is the main inhibitory neaurotrasmitter?
GABA
What is the underlying aetiology of seizures?
Increasing glutamate or reducing GABA activity
What are the strategies for the treatment of epilepsy?
- Inhibition of voltage gated Na channels
- Inhibition of voltage gated Ca channels
- Promote inhibitory neaurotransmission
What drugs inhibit voltage gated Na channels? How do they work?
- Phenytoin
- Carbamazapine
- Lamotrigine - also have a weaker effect on high voltage activated calcium channels
- Oxcarbazepine
They stabalise the inactive state of sodium channels - so it remains in its inactivated state for longer so cant be reactivated to cause more action potentials
What drugs enhance GABA action and what is there action?
- Benzodiazapenes: Incraeses frequency of opening of GABAa channles
- Phenobarbitol: Increase the probability of openeing GABAa channles, so channel will be open for longer, so incraese chloride influx and reduced excitabilty. May also inhibit glutamate receptors
- Vigabatrin: Inhits GABA transaminase (enzyme that breaks down GABA)
- Tiagabine: Inhibits GABA transanimase
