epilepsy Flashcards
epilepsy mortality
- Risk of premature death incr 2-3x (highest within first 12mnths of diagnosis)
- Epilepsy-related death
□ Sudden unexplained death in epilepsy (SUDEP)
□ Status epilepticus
□ Unintentional injuries (drown, head injuries, burns)
□ Suicide. Depression comorbidity
SUDEP risk factors
◊ Presence and freq of generalised tonic-clonic seizures
◊ Nocturnal seizures
◊ Lack of seizure freedom
- mostly unwitness and sleep-related (prone position)
convulsion –> apnoea –> asystole
seizure
○ Transient occurrence of signs and sx due to abnormal excessive or synchronous neuronal activity in brain
epilepsy
= Enduring predisposition to generate epileptic seizures
- At least 2 unprovoked seizures occurring > 24h apart
- ONE unprovoked seizure and probability of further seizure (similar to general recurrence risk ~60%) after 2 unprovoked seizures
a. Occurring over the next 10 yrs
symptomatic seizures ACUTE
- Seizures that result from immediately recognizable stimulus/ cause
That occur in presence/ close timely association (~wk) with an acute brain insult
lower risk of subsequent epilepsy
REMOTE SX SEIZURES
- Seizures that occur longer than 1 wk following a disorder that is known to incr risk of developing epilepsy
unprovoked seizures
Seizure occur in absence of potentially responsible clinical condition or beyond the interval estimated for occurrence of acute sx seizures
X2 > 24hr apart = epilepsy
etiology of acute sx seizures
- metabolic
- toxic sub/ drugs
- structural
- infection/ inflammation
metabolic cause of acute sx seizure
hypoglycemia
ion balance(hyponatremia, hypomag, hypocalc)
Hypoxia
toxic cause of acute sx seizure
illicit drugs (cocaine): direct CNS effect
alcohol (withdrawal/ intoxication)
Drugs: lower threshold
□ tricyclic antidep, carbapenems, baclofen
Benzodiazepine withdrawal
□ Incr GABA
structural cause of acute sx seizure
Trauma brain injury, stroke (haemorrhagic/ ischemic)
infection/ inflamm cause of sx seizures
CNS infection
□ Meningitis, encephalitis
Febrile illness – inflamm, sepsis
non-epileptic events
Abnormal paroxysmal psychic, sensory and/or motor manifestations which resemble to epileptic seizures.
Not related to abnormal epileptiform discharges
- psychogenic non-epileptic seizure (PNES)
- physiological non-epileptic events
psychogenic non-epileptic seizure (PNES)
Partial alteration of lvl of consciousness with partial preservation of awareness
Psychological distress but in EEG no electrical activity
*Caused Involuntary by :
i. Stressful psychological exp
ii. Emotional trauma (PTSD, psych problems)
Physiological non-epileptic events
a. Sx of paroxysmal systemic disorder
b. Eg:
i. Convulsive syncope, migraine aura, non-ictal dysautonomia
ii. Hypoglycemia
iii. Movement disorders, balance disorder, sleep disorders
iv. Intoxication
v. Transient ischemic attacks
vi. Panic attacks
seizure are neurons synchronously active due to
- hyperexcitability
- hypersynchronisation
hyperexcitability
enhanced predisposition of a neuron to depolarise
1) voltage or ligand gated K, Na, Ca, Cl ion channels
2) abnormalities in INTRA, EXTRAcell sub (Na, K, O2, glucose)
○ Too much excitatory
*Glutamate –> NMDA receptor (to let Ca in)
* fast or long-lasting activation
○ Too little inhibitory
* GABA –> GABA receptors (let cl- ion in)
* dysfunctional GABA receptor, not able to inhibit signal
excitatory and inhibitory neurotransmitters
Excess excitatory neurotransmitters: glutamate (CNS), acetylcholine (NMJ), histamine, cytokines
Insuff inhibitory neurotransmitters: GABA, dopamine
hypersynchronisation
§ Synchronised paroxysmal discharges occurring in a large pop of neurons within cortex, self-enhancing
§ Hippocampal sclerosis;
□ Intrinsic reorganisation of local circuits: Hippocampus, neocortex, thalamus
□ Contribute to synchronisation and promote generation of epileptiform activit
steps of epilepsy (reflected in EEG)
1) short in circuit
- paroxysmal depolarisation (SPIKE)
2) drive normal neighbours
- repeated depol of large enough grp of neurons, incr extracell K+ conc
- drives depol of surrounding neurons
(SLOW WAVE)
3) failure of inhibition
- loss of hyperpolarisation
- excess glutamate, incr in intracell Ca2+
- recurrent excitatory feedback ciruit
epilepsy long term changes
1) incr Ca2+ over time – struc and functional neuronal changes
- 2nd messenger activation
- change in gene expression
- Ca2+ activation: cell death pathway, destroy inhibitory neurons
2) hippocampus, longterm potentiation (scar epilepsy)
good for memories, bad for seizures
epilepsy etiology
structural > genetics > other factors
> infectious > metabolic > neurodegenerative
structural cause of epilepsy
- Hippocampal sclerosis – intrinsic reorg, more syncronisation
- Brain tumor, vascular malformation, glial scarring (stroke, TBI)
genetics cause of epilepsy
Dravet syndrome (SCN1A mutation)
neurodegenerative cause of epilepsy
ALZHEIMER’S disease
metabolic cause of epilepsy
inborn error of metabolism
mitochondrial disorders
infectious cause of epilepsy
bacterial meningitis
encephalitis
neurocysticercosis (parasites)
