epilepsy

Question 1

What regulates the function of ion channels ( eg. Na+ and Ca2+ channels)?

Answer 1

beta subunit

Question 2

what is the structure of Na+ and Ca2+ channels?

Answer 2

four 6 membrane spanning regions

Question 3

What is the structure of a K+ channel?

Answer 3

6,2,4,or 7 membrane spanning regions

Question 4

define a seizure

Answer 4

abnormal EXCESSIVE and SYNCHRONOUS electrical discharge of brain neuronal network

( bunch of neurons firing at the same time)

Question 5

What is ( seizure related) aura?

Answer 5

a part of the ictal phase of the seizure ( very short lasting- can be just seconds) -

a sensation that the seizure is coming

Question 6

What is ( seizure related) prodrome?

Answer 6

it occurs before the seizure in the pre-ictal phase.

pt. doesn’t feel well for hours or days but it’s not technically part of the synchronous electrical activity (seizure).

Question 7

Based on ILAE classification what is a partial seizure ?

Answer 7

A seizure localized to one hemisphere

Question 8

Based on ILAE classification what is a generalized seizure ?

Answer 8

a seizure which involves both hemispheres and si usually subcortical ( i.e. not in the cortex) therefore they can spread.

Question 9

Based on ILAE classification what is a simple partial seizure?

Answer 9

a localized seizure w/o impairment/loss of consciousness.

Could have motor or sensory manifestations

Question 10

Based on ILAE classification what is a complex partial seizure?

Answer 10

a localized seizure w/ impairment ( but not total loss) of consciousness

e.g. of symptoms: staring into space , automatism ( lip smacking and tongue movement–> indicates that the temporal lobe is involved)

Question 11

Based on ILAE classification what two types of seizures can be classified as generalized?

Answer 11

convulsive and non-convulsive

Question 12

What does the figure 4 sign indicate?

Answer 12

• can be seen in a partial focal seizure that became a 2˚ generalized seizure or at a focal stage.

-Secondary Motor Area ( SMA) is involved
which is locate in the mesial part of the frontal and parietal lobes.

Question 13

What is an absence seizure?

Answer 13

a complex seizure common especially in children.

it can be typical or atypical

Symptoms: Pt is doing something then stops and stares and then continue what they were doing but have no recollection of the seizure or what happened during it.

Question 14

what can occur during the tonic phase of epileptic seizures?

Answer 14

an eplieptic cry: which results from respiratory: pharyngeal muscles contract.

Question 15

What is a tonic-clonic seizure?

Answer 15

tonic- muscles tense up and clonic repeated contracture: i.e. contraction and relaxation of muscles

Question 16

How are hyponeutremia and Seizures related?

Answer 16

Seizures can be caused by hyponeutremia but just because someone has hyponeutremia doesn’t mean they will have a seizure.

Question 17

What are the 3 ILAE classifications of epileptic syndromes?

Answer 17

• idiopathic: presumed genetic etiology
• symptomatic: consequence of a known or suspected disorder of CNS
• Cryptogenic: unknown cause

Question 18

What are geraliztd spike and wave complexes in an EEG constant with?

Answer 18

idiopathic generalized epilepsy

Question 19

how can you characterize the functionality resulting from a channelopathy ( 2), and the major ( 2) ways a mutation comes about.is inherited?

Answer 19

• channelopathy can result in either a gain or loss of fnc.

-they are usually autosomal dominant or
de Novo mutations

• rarely autosomal recessive

Question 20

How many variations does the alpha subunit of Na+ channels in mammals have?

Answer 20

9 variations

Question 21

Where are the Nav1.1 and Nav1.3 variants of the Na+ chanel found?

Answer 21

in the cell bodies ( mostly in CNS)

Question 22

Where are the Nav1.2 variant of the Na+ channel found?

Answer 22

unmyelinated axons and dentrites ( mostly in the CNS)

Question 23

Where are the Nav1.6 variant of the Na+ channel found?

Answer 23

myelinated axons and dentrites ( mostly in the CNS)

Question 24

what 3 mutations are seen in the Nav1.1 channel?

Answer 24

missense, nonsense, in-frame deletion, truncation mutations.

Question 25

what are symptoms of severe myoclonic epilepsy of infancy ( SMEI or Dravet Syndrome) in the first and second years of life?

Answer 25

1st year

• seizures assoc w/ elevated body temp ( fever or bathing)
• progressively prolonged and cluster seizures
• status epilepticus

2nd Year of life

• psychomotor delay
• ataxia (Uncoordinated movement –>inability to coordinate movements)
• cognitive impairment

Question 26

Where do most channelopathies occur in epilepsy pts?

Answer 26

in Na+ channels

there are lots of mutations in several ion channels
but Na+ has the most

and chanelopathies are commonly the cause of epilepsy but not always.

Question 27

how are generalized epilepsy w/ febrile seizures plus and Severe myoclonic epilepsy of infancy related?

Answer 27

GEFS + is a milder than SMEI and they are on the same spectrum of NA+ channelopathies.

Question 28

what happens to cognitive abilities and what is pathophysiology of generalized epilepsy w/ febrile seizures plus ?

Answer 28

no impairment of cognitive abilities

pathophysiology is usu missense–> loss of fnc of fast inactivation –> gain of fnc of Na+ channel –> persistent Na+current

Tx: anti epileptic medswuich can bind to mutant channels and stabilize folding of proteins

Question 29

what is the goal and examples of treatments for Severe mycolonic epilepsy of infancy?

Answer 29

Goal of tx: to reestablish GABAergic transmission

Tigabine: decreases reuptake of GABA

Benzodiazepines: Increase in response to postsynaptic GABA receptors

Question 30

Define a febrile sesizure ( ILAE definition) ( 4 points)

Answer 30

• occurs after l mo. of age
• assoc w. febrile illness not caused by infection of CNS
• w/o previous neonatal seizures or a previous unprovoked seizure
• doesn’t meet criteria for other acute symptomatic seizures

Question 31

a channelopathy in which channel is a major cause of febrile seizures?

Answer 31

a mutation in the Nav1.1 channel–>

• reduction of peak Na+ currents
• and pos. shift in voltage dependence of activation.

Question 32

what is used to treat epilepsy?

Answer 32

• Antiepileptic drugs to decrease hyper excitability

a. Na+ channel blockers ( stabilizes and block)
b. increasing inhibitory fnc of neurons ( GABAergic meds)

• Epilepsy surgery if localized ( and they fail to respond to 2 meds) and not localized in eloquent cortex

Question 33

where do most K+ channelopathies occur?

Answer 33

In M current ( i.e. a voltage-gated K+ channel likely to be open during depolarization and is regulated by G-protein coupled receptors)

Question 34

what is pathophysiology of Benign Familial Neonatal convulsion?

Answer 34

-missense mutation–> impaired flux of K+ ( loss of fnc)–> decreased M current

Question 35

what happens in a channelopathy of the large pore-forming subunit?

Answer 35

mutation –> large K+ flux ( gain of fnc)

manifests as generalized or paroxysmal dyskinesia

Question 36

what is the pathophysiology of T-Type Ca2+channels? and where doe these channelopathies usually occur?

Answer 36

mutations–> gain of fnc–>excessive synchronous rhythmic burst firing–>idiopathic generalized epilepsy

occurs mostly in thalamic cells

Question 37

what can channelopathies in the CL- channel ( specifically mutation in CLCN2 gene) lead to?

Answer 37

idiopathic generalized epilepsy

Question 38

Why can T-type Ca channels have rhythmic burst-firing?

Answer 38

b/c of the cycle btw activation during small depolarization and inactivation during maintained depolarization.