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Epilepsy - Coggle Diagram
Epilepsy
DX
complex
generally require 2 or more seizures
EEG
gold standard
hard to catch
24 hr monitoring
trigger
sleep deprivation
sites
frontal
temporal
occipital
can do central and parietal as well
patient hx
in depth description by witness
blood tests
to rule out other conditions
MRI
genetic testing
1 in 5 misdiagnosed
non-epileptic attack disorder
AETIOLOGY
structural
genetic
10%
Dravet
epileptic encephalopathy
intractable seizures
cognitive
behavioural
motor
SCN1A/8A
sodium channels
develops within 1st year
febrile convulsions
type
generalised tonic clonic
focal
atypical absence
tx
epidiolex
Angelman
Rett
MeCP2
x-linked
most males dont survive in utero
1 in 10,000 females
features
breathing issues
involuntary hand movements
loss of speech/muscle tone
seizures
CHD2 myoclonic encephalopathy
infantile spasms
Lennox Gastaut
metabolic
infectious
immune
unknown
acquired epilepsy
90%
temporal lobe
most common in adults
risk factors
seizures
febrile status epilepticus
status epilepticus
brain insult
stroke
TBI
pathogenesis
trauma
epileptogenesis
cell loss
excitotoxicity
glial cell activation
synaptic re-organisation
gene dysregulation
animal models
chemoconvulsant
kainic acid
induces status epilepticus
activates glutamate receptors
excitation
epileptogenic phase
spontaneous, unprovoked seizures
cell loss in hippocampus
aberrant neurogenesis
mossy fibre sprouting
chronic neuroinfl.
PTZ
pilocarpine
electrical stimulation
low mortality
high reproducibility
kindling model
repeated electrical stimulation
spontaneous seizures will begin
low intensity
genetic models
transgenic mice
dravet
angelman
rett
cdh2 ee
human induced pleuropotent stem cells/organoids
TX
need for improvement
vulnerable neurons + prolonged seizures
activity dependent cell death
hippocampus
cortex
amygdala
thalamus
high frequency of tonic clonic
volumetric changes in
hippocampus
cortex
frequent generalised seizures
cognitive impairment
functionally significant in
those with status epilepticus
children: early onset + severe
rapid intellectual decline
^ tendency for cognitive decline in later life
selecting
individualised
age
gender
concomitant therapies
MOA
enhancing GABA
benzodiazepines
increase potency of GABA
increased frequency of channel opening
barbiturates
increase efficacy of GABA
increase duration of channel opening
tiagabine
inhibits GABA reuptake via GAT1
vigabatrin
blocks GABA degradation via GAD
Sodium channel inactivation
stabilisation of inactive state of channel
phenytoin
tonic-clonic
focal
iamotrigine
most seizure types
carbamazepine
tonic-clonic seizures
focal seizures
affected cells are less excitable
fewer channels are available
normal AP's can continue
^membrane depolarisation/repetitive firing
increase in inactive channels
therefore these are voltage&use dependent
calcium channel inactivation
channels
high threshold
slow inactivation
lead to calcium influx into neuron
neurotransmitter release
glutamate
at axon terminal
gabapentin/pregabalin
bind to alpha 2 delta subunit
reduce calcium influx
attenuates neurotransmitter release
valproate
weak inh. of GABA-T & succinic semi-aldehyde
^GABA
inh. voltage gated sodium channels
inh. t-type calcium channels
simple monocarboxylic acid
may also act as histone deacetylase inh.
effects on gene expression
not given to women of child-bearing age
pharmacokinetics
absorption
most oral
some available for
IV
IM
PR
metabolism
most
hepatic enzymes
P450
excreted
kidneys
gabapentin
no metabolism
elimination
half-time
dosing freq.
phenobarbital
2-7days
SE's
CNS
sedation/fatigue
unsteadiness/dizziness
reduced co-ordination
anxiety, depression
cognitive impairments
retinal nerve atophy
systemic
altered met. of other drugs
hypersensitivity reaction
nausea
paradoxical
nervousness, irritability
excitement, hyperactivity
worsening of seizures
newer AED's
inh. of neurotransmitter release
levetiracetam
binds to SV2A
involved in synaptic vesicle docking and fusion
brivaracetam
higher affinity than levetiracetam
blocking of glutamate release more than GABA in glutamatergic neurons
non-pharmacological
vagus nerve stimulation
ketogenic diet
surgical resection
STAGES
prodromal
hours to days before
anxiety
irritability
mood changes
pre-ictal
aura
deja vu
specific smell
fear
rising sensation in stomach
ictal
from pre-ictal till end of seizure
post-ictal
recovery phase
CLASSIFICATION
Focal
aware/impaired awareness
motor onset
tonic
atonic
clonic
myoclonic
hyperkinetic
epileptic spasms
automatisms
nonmotor onset
behaviour arrest
emotional
cognitive
sensory
autonomic
Generalised
motor
tonic
atonic
clonic
myoclonic
tonic-clonic
myoclonic tonic-clonic
myoclonic atonic
epileptic spasms
nonmotor
typical
atypical
myoclonic
eyelid myoclonia
Unknown
motor
tonic clonic
epileptic spasms
nonmotor
behaviour arrest