Epilepsy pathophysiology and pharmacolgoy

Question 1

what is epilepsy?

Answer 1

a tendency to have recurrent seizures

Question 2

what are seizures?

Answer 2

episodes of altered consciousness brought about by signals flowing in the wrong way which cause wrong activity patterns in the brain.

Question 3

what is ictogenesis?

Answer 3

the development of a seizure

Question 4

what is ictal?

Answer 4

the seizure

Question 5

what is epileptogenesis?

Answer 5

the development of a seizure

Question 6

what is interictal?

Answer 6

the time between seizures

Question 7

what does paroxysmal mean?

Answer 7

sudden, violent outbursts

Question 8

what are 3 major causes of death in epilepsy?

Answer 8

1. status epilepticus
2. trauma
3. SUDEP

Question 9

what is status epilepticus?

Answer 9

when epileptic fits follow one another without recovery of consciousness between them

Question 10

what does SUDEP stand for?

Answer 10

Sudden Unexplained Death in Epilepsy

Question 11

how is epilepsy diagnosed?

Answer 11

1. looking at the patient/observations
2. feedback from others who have observed these things
3. baseline EEG to look for interictal activity

Question 12

what is interictal activity?

Answer 12

these are transient and abnormal focal neural discharges seen on electroencephalogram (EEG) - happens between seizures

Question 13

what are some co-morbidities with epilepsy i.e. conditions that arise with epilepsy?

Answer 13

1. Excess mortality
2. Memory deficits
3. Schizophrenia
4. Depression, stress, anxiety
5. Downward social movement

Question 14

what can cause epilepsy (epileptogenesis)?

Answer 14

1. genetic factors
2. brain injury e.g. stroke
3. brain infection e.g. measles and HPV
4. Brain disease e.g. tumours
5. Drugs (including alcohol!)

Question 15

what can cause seizures (ictogenesis)?

Answer 15

1. drugs
2. electrical stimulation
3. sensory triggers e.g. flashing light, sounds
4. metabolic imbalance e.g. pH levels change
5. hormonal state
6. brain state
7. temperature
8. fatigue/stress

Question 16

what effect do absence seizures have on the brain?

Answer 16

they compromise brain function as the discharge released blocks the flow of activity through the thalamus - known as compromised computation (where the brain can’t function well as it has been compromised)

Question 17

what are absence seizures?

Answer 17

when an individual blanks out and stares into space for a few seconds.

Question 18

what two synchronised activities in the brain are the basis of memory?

Answer 18

Long term potentiation and long term depression

Question 19

Is epilepsy the price we pay for cortical function and why?

Answer 19

yes, because the cortical function involves synchronised neuronal activation but when this is not so, due to signals flowing in the wrong direction because of neuronal binding problems, we get wrong activity patterns in the brain. This results in seizures as it is recurrent, which leads to epilepsy.

Question 20

since epilepsy is genetic, what does that mean for treatment?

Answer 20

it means we can develop medicines personalised to the patients genome with advances in genome sequencing.

Question 21

what surgeries are available for those with epilepsy?

Answer 21

1. resection (cutting out tissue or part of an organ)

2. brain stimulation (electrical or optogenetic)

Question 22

which anti epileptic drugs suppress neuronal excitation? (so signal is not generated)

Answer 22

1. phenytoin
2. sodium valproate
3. carbamazepine

Question 23

which anti-epileptic drugs enhance inhibition? (so signal is not transmitted)

Answer 23

1. benzodiazepines
2. barbiturates
3. tiagabine

Question 24

how does phenytoin work?

Answer 24

stabilizes inactive state of Na channels

Question 25

how does sodium valproate work?

Answer 25

inhibits Na channels

Question 26

how does carbamazepine work?

Answer 26

inhibits Na channels

Question 27

how does benzodiazepines work?

Answer 27

elongates GABAa channel opening time

Question 28

how does barbiturates work?

Answer 28

increases GABA current by increasing affinity for GABA

Question 29

how does tiagabine work?

Answer 29

blocks cellular GABA uptake

Question 30

how does Ethosuximide work?

Answer 30

target voltage-dependent Ca2+ channels (VDCCs) for treatment of absence seizures

Question 31

what do phenytoin, carbamazepine and phenobarbital interact with?

Answer 31

They induce the metabolism of :

• anticonvulsants
• warfarin
• oral contraceptives

Question 32

which are teratogenic (i.e. complicate issues in pregnancy causing deformities):

• anticonvulsants
• warfarin
• oral contraceptives?

Answer 32

anticonvulsants e.g. sodium valproate

-anticonvulsants are drugs used to prevent or reduce the severity of epileptic fits or other convulsions.

Question 33

what are some side effects to taking carbamazepine?

Answer 33

• diplopia (double vision)
• ataxia (the term for a group of disorders that affect co-ordination, balance and speech)
• drowsiness
• hyponatraemia
• agranulocytosis (low white blood cell count)
• aplastic anaemia (where the bone marrow and stem cells do not produce enough blood cells)

Question 34

Which has a more narrow therapeutic window phenytoin or carbamazepine?

Answer 34

phenytoin 10-20
carbamazepine 20-50

so phenytoin

Question 35

what are the side effects to taking phenytoin?

Answer 35

1. nystagmus
2. ataxia
3. gingival hyperplasia
4. hirsuitism

Question 36

what lifestyle change can a patient make to better their epileptic condition?

Answer 36

-go on a Ketogenic diet

Question 37

what is a Ketogenic diet?

Answer 37

a high-fat, adequate-protein, low-carbohydrate diet.

Question 38

how does a Ketogenic diet help with epilepsy?

Answer 38

The diet forces the body to burn fats rather than carbohydrates. Fat is converted into fatty acids and ketone bodies. Higher levels of ketone bodies in the blood leads to a reduction in the frequency of epileptic seizures.