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)
ILAE (international League against Epilepsy) classifications
based on?
1) mode of onset (where) 1/ 2 hemispheres
2) impairment of consciousness?
3) other features of seizure
- affects tx and prognostic
1) Based on mode of onset (where):
Focal: seizure begin only in 1 hemisphere
□ Secondarily generalised: begin in 1 hemi – spread to other
Generalised: seizure begin in both hemisphere
2) Impairment of consciousness
Loss of awareness of external stimuli or inability to respond to external stimuli in a purposeful and appropriate manner
With or w/o dyscognitive features (simple vs complex if loss of consciousness)
clinical characteristics (sx) of seizure depends on
- site of focus
- degree of irritability of area of brain surrounding the focus
- intensity of impulse
phases of seizure
1) prodromal
2) aura
3) ictal
4) postictal
prodromal
sx: confusion, anxiety, irritability, headache, tremor, and anger or other mood disturbances
duration: Occur hr/ days before seizure
aura
sx: depends on seizure type, severity, affected brain region
(vision, smell, taste, sound, N, tingle, automatism - repeated blink, smack lips)
is a focal aware seizure/ inital stage of generalised
X in absence seizure
ictal
Depend on type of seizure, electrical movement of brain
sx: Convulsion, loss of conscious, twitch, memory lapse, confusion
post-ictal phase
some recover immediately, others may require minutes, hours or days until baseline (30mins-hr - days after seizure)
length of the post-ictal stage depends directly on the seizure type, severity, and region of the brain affected
sx: malaise, migraine, N, drowsy, arm/leg weakness
focal seizure clinical presentation depends on___
depends on location of brain affected
frontal (motor, consciousness)
temporal (common, smell, automatism)
parietal (sensory disturbances)
occipital (visual fields)
frontal lobe
motor: clonic movements (jerk)
speech arrest (dysarthria)
affects consciousness (complex vs partial)
surgery??
temporal (common, smell, automatism)
most common site for seizure
smell
emotions
abdominal discomfort
automatism
staring
lose awareness
occipital (visual fields)
experience flashing bright lights or other visual changes
- on the left side of his or her visual field (if occurring in the right cortex)
- or on the right side (if occurring in the left cortex)
parietal (sensory disturbances)
- flashback
- visual, auditory, gustatory, olfactory hallucinations
- affective sx: fear, depression, anger, irritability
autonomic BP, HR, sweat, salivation, pallor
Generalised seizures
Tonic-clonic “grand mal”
status epilepticus if > 5mins
1) tonic (stiff, may decr/ stop breathe)
2) clonic (jerk limbs and face)
- 1min, after that brain is extremely hyperpolarised, insensitive to sitmuli
- incontinence, noisy/ laboured breathing
- following: headache, lethargic, confused (recovery mins-hrs)
clonic, tonic, myoclonic
clonic: jerk asymm, irregular (nenonates, infants)
tonic: loss of consciousness, rigid posture 10-20s
* lennox-gastaut syndrome + learning disability
myoclonic: rapid, brief contraction of body muscles
Absence “petit mal”
lapse in awareness
few secs, never preceded by auras, begin freq + end abruptly ~~ diff from complex partial seizures
child > adults
3Hz spike waves
Atonic
“drop attack”
all postural tone suddenly lost
shortep, followed by immediate recovery
any age
assoc w/: diffuse cerebral damage and learning disability
* lennox-gastaut syndrome, myoclonic astatic epilepsy
electroclinical syndrome by age of onset
infancy: west, dravet syndrome
childhood: febrile seizure, * lennox-gastaut syndrome, childhood absence
adol/ adults: generalised TC, juvenile myoclonic epil, progressive myoclonic epi
DIAGNOSIS OF EPILEPSY
1) hx taking
2) investigations: neurologic examination, lab values
3) concomitant medical conditions
1) hx taking
- Onset, duration, characteristics of seizure
□ Person who observed events - Pt: details of aura, preservation of consciousness, post-ictal state
□ Seizure diary - Positive identification of classical characteristics
□ aura, cyanosis, loss of consciousness
□ generalised stiffness of limbs, jerking of limbs
□ tongue biting, incontinence, confusion (post), muscle sore
differential diagnosis
syncope (no confusion, low BP, HR)
transient ischemic attack (stroke)
migraine
psychogenic nonepileptic seizures (PTSD)
2) EEG – Electroencephalogram
+ve: epileptiform discharges on EEG (not all epileptic pt will have abnormal EEG)
also have false +ve in asx adults
EEG finds out location
1) focal onset = 1 hemi
2) generalised onset = both hemi
video EEG: see clinical presentation and correlate to part of brain that was affected
MRI with gadolinium
present with 1st seizure. Focal neurologic deficits –> focal onset seizures
Identify focal lesions:
◊ Mesial temporal sclerosis
◊ Focal cortical dysplasia
◊ Remote injury (past stroke)
◊ Tumour
◊ Vascular malformation
Lab test (biochemical/ toxicology)
- Electrolyte abnormalities (acute sx seizures– ions, K, Na, glucose)
- Serum prolactin – considerable variability, not routine
- Creatine kinase – raised after GTC (muscle contraction)
3) Concomitant medical conditions
epilepsy is assoc with physical and psychiatric comorbidities
- poorer health outcomes
- incr health care needs
- decr QOL
- greater social exclusion
*Depression, ANX
* intellectual disability in children with epilepsy
risk of seizure recurrence
have 2nd seizure within 2 years
esp in:
- epileptiform abnormalities on EEG
- prior brain insult (stroke, brain trauma, infection, brain surgery)
- struc abnormality in brian imaging
- nocturnal seizure (1st seizure occurred during sleep)
when to start tx
after 2nd unprovoked seizure >24h
after 1st unprovoked + high risk for 2nd
* abnormal EEG
* abnormal brain imaging
* seizure during sleep
* brain trauma
consideration to start tx
recurrence risk
potential seizure morbidity
vs
risk of tx
personal circumstances
determinants to start tx
- cause, epilepsy syndrome, EEG findings
- seizure type
- tolerability
- work, qol, desire to bear children, driver’s license
Tx goals
Absence of epileptic seizures
Absence of ASM-related SE
Attain optimal QOL
non pharm
§ Ketogenic diet
§ Vagus nerve stimulation (VNS)
§ Responsive neurostimulator system
§ Surgery
Ketogenic diet
□ Pts who cannot tolerate or not responded well to ASM (antiseizure meds)
□ Low carb, high fat diet
- Induce ketosis (use fat as main source of energy, low carbs), prevent seizures (mostly young children)
- Challenging to adhere LT
Vagus nerve stimulation (VNS)
□ Intractable focal seizures
electrodes attached around left branch of vagus nerve – connected to stimulator
On demand stimulation: put magnet at sc-implant stimulator to deliver cyclical stimulation
Responsive neurostimulator system
□ Stimulator implanted in skull under scalp. Lead implanted in brain
- Reduce freq partial-onset seizures in pts:
◊ Undergone diagnostic testing that localised < 2 epileptogenic foci
◊ Refractory to >2 antiepileptic medications
◊ Have freq and disabling sx
□ Monitors electrical activity in brain, detects pt specific patterns –> deliver pulse of stimulation when sense activity that can cause seizure
Surgery
□ Selected forms of epilepsy (focal)
□ Advocated for early therapy in:
- Temporal lobe, frontal lobe removal
- frontal lobe epilsey w/ or w/o identifiable lesions on MRI scan
□ Achieve improvement of sx/ seizure-free status
□ Last option for certain refractory cases
seizure diary
- seizure freq, type
- how long they last
- change in AED
- AED SE
- seizure triggers
psychosocial issues
-social stigma
- employment
- no driving
- caregiver burden (esp with childhood epilepsy – developmental issues)
seizure triggers
hyperventilation
photostimulation
physical and emotional stress
sleep deprivation
sensory stimuli
infection
hormonal changes (menses, puberty, preg)
drugs
drugs that trigger seizure
TAPBOB
- theophylline (asthma, xanthines)
- alcohol
- phenothiazines (high dose – chlorpromazine, clozapine)
- antidep (bupropion)
- tramadol (opioids)
- carbapenems (beta-lactams)
