Seizure and Epilepsy Flashcards
Describe the epidemiology of seizures?
Affects ~ 50mil ppl worldwide
Incidence
- Pooled incidence rate 61.4 per 100 000 person years
- Low-mid incoome countries higher incidence than high income countries
(higher driven by resource, avail to care, healthcare & social bckgrd)
- Bimodally distr (<1y.o. & >60y.o.)
- If properly treated, abt 70-80% ppl w epilepsy cld lead normal lives
In SG
- Est prevalence: 3.5-5.0 per 1000 population
- Mean age of first seizure onset 11.1y
- Indians 6.4 per 1000 // Chinese 5.2 per 1000 // Malays 2.8 per 1000
What are the mortality risks w epilepsy?
2-3x increased risk of premature death
- Highest within first 12mo of Dx
Epilepsy related:
Status epilepticus
Unintentional injuries (drowning, head injuries, burns)
Suicide
- Bidirectional r/s bet depression & epilepsy (may hv biochem link)
Sudden unexplained death in epilepsy (SUDEP)
- Direct corr bet uncontrolled seizure & SUDEP (wna address uncontrolled seizures)
- Incidence 1.2 per 1000 person years
- Peak for those aged 20-40y
- Mostly unwitnessed & sleep related
a. Many indi w SUDEP found in prone pos w evi of recent seizure
b. Rare cases occuring durg video EEG monitoring suggest that SUDEP preceded by convulsion, followed shortly by apnoea, asystole
- Risk factors: presence & freq of GTC seizures, nocturnal seizures, lack of seizure freedom
- Managed by basal edu session at Dx of epilepsy to understand importance of getting seizure control
What is epilepsy?
A long term disease characterised by any of the following
1. At least 2 unprovoked seizures occuring >24h apart
2. One unprovoked seizure & probability of further seizures sim to general recurrence (min 60%) after tow unprovoked seizures, occurring over the next 10y (if one seuzire puts you @ higher risk than general population w 2 seizures)
3. Diagnosis of an epilepsy syndrome
Not curable but is manageable
What is a seizure?
A transient occurence of signs and/or symptoms due to abnormal xs of synchronous neuronal activity in brain
What are the various ways to classify seizures?
Acute vs Remote vs Unprovoked
By location and tissue involvement (ILAE Classification) - generalised tissues vs focal seizures
Describe the aetiology of seizures/epilepsy.
Infection/inflamm
- CNS infection (meningitis, encephalitis, neurocysticerosis)
- Febrile illness
Metabolic disorders/issues
- Hyponatremia
- Hypocalcemia
- Hypomagnesemia
- Hypoglycemia
Structural problems
- Brain condition that induce injury or scarring
- Stroke
- Traumatic brain injury
- Hippocampal sclerosis, brain tumour, vascular malformation, glial scarring
Blood related
- BP
- Stress
- Genetics (20%)
- Neurodegenerative (concomitant conditions)
- Alzheimer’s disease
Chemicals/drugs
- Illicit (cocaine, amphetamines)
- Antimicrobials: carbapenems, penicillins, cephalosporins
- Analgesics: opioids
- Antipsychotics, antidepressants (e.g. clozapine, bupropion, TCAs, SSRI)
- Immunosuppressants: cyclosporine, hydrocortisone, tacrolimus
- Other: baclofen
- Alc withdrawal & intoxication
- Benzodiazepine withdrawal
Discuss the propensity of drug induced seizures.
Depends on
- Effects on neurotransmission (push into hyperexcitation or decrease inhib)
- Time course (e.g. whether it increases seizure risk durg use or on withdrawal)
- [ ] of drug reaching the brain (cross BBB?)
- Susceptibility of the indi pt
Susceptibility factors
- Hx of seizures
- Structural or fnal brain abnormalities
- Concurrent drug use
Rare that seizures can be ascribed primarily to the effects of a drug. They contribute to a shift in excitatory/inhib balance in indi –> seizure. (lower seizure potential, ppt seizure rather than incite seizure)
What are the criteria for acute vs remote seizures?
Acute
- Result from some immediately recognisable stimulus or cause i.e. that occur in the presence or close timely association (abt a week) w an acute brain insult (metabolic, toxic, structural, infectious, hypoxic, etc.)
Remote
- Occur longer than 1 week following a disorder that is known to increase the risk of dev epilepsy
Unprovoked siezures
- Occur in the absence of a potentially responsible clinical condition or beyond the interval est for the occurrence of acute
What are non-epileptic events?
Abnormal paroxysmal psychic, sensory and/or motor manifestations which resemble (at least in part) to epileptic seizures but are not related to abnormal epileptiform discharges
- Psychogenic non-epileptic “seizures” (PNES):
- Partial alt of level of consciousness w a partial preservation of awareness
- Caused by stressful psychological xp or emotional trauma
- Involuntary - Physiological non-epiletptic events:
- Symptoms of a paroxysmal systemic disorder
- E.g. convulsive syncope, hypoglycemia, movement disorders, migraine aura, non-ictal dysautonomia, intoxications, TIA, balance disorder, sleep disorders, panic attacks
Describe the signs & symptoms of seizures
Generalised seizures
1. Tonic
- Stiff/flexed muscles (rigid)
- 10-20s
- All ages but charactersitic & defining seizure type in Lennox-Gastaut syndrome
- Often fall backwards
- Clonic
- Muscles rapidly contract & relax
- Assymmetrical, irregular
- Most freq in neonates, infants or young children - Tonic-clonic (Grandmal)
- Most common
- Tonic: muscles tense up, reduced RR, laboured breathing, cyanosis of nail beds, lips, face
- Clonic [1min]: jerking of limbs & face, return of perfusion to above irregular
- Incontinence, biting of tongue
- Full recovery: several min-h - Myoclonic
- Short muscle twitches
- Brief loss of consciousness but without convulsions
- Little postictal confusion - Atonic
- Muscles relaxed, flaccid
- Often fall forward
- Short episode, followed by immediate recovery
- Any age, always assoc w diffuse cerebral damage and learning disability
- Common in severe symptomatic epilepsies (esp in Lenno-Gastaut syndrome and in myoclonic astatic epilepsy) - Absence (Petit mal)
- Lose & regain consciousness quickly
- Mistaken for daydreaming, “spacing out”
- No warning, no after effects
- Children > adults
- First onset 4-12y.o., rarely after 20y.o.
- Brief staring spells
- Diff Dx w complex focal seizures
a. 3Hz spike and wave EEG
b. Never preceded by auras
c. Last s (rather than min)
d. Begin freq & end abruptly
Focal seizures
1. Partial focal seizures
- Involve strange sensations (hearing/smell/tasting)
- Affective symptoms (incl fear, depression, anger, irritability)
- Staring spells without consciousness
- Feelings of numbness or tingling
- Visual disturbances
- Rising epigastric sensation
- Sweating, salivation or pallor
- BP, HR
- Retained muscle tone
- Jerking mvmt (if neurons in muscle grps affected)
If starts in specific muscle grp & spreads to surrounding ones = Jacksonian March
Clonic movements (e.g. twitching or jerking) of arm, shoulder, face or leg
- Speech arrest (involve muscles of articulation- dysarthria)
- Complex focal seizures (consciousness impaired)
- Loss of consciousness, preceded by aura
- Complex ictal automatisms
- Postictal confusion
- Complete/impaired awareness, responsiveness
Describe the ILAE Classification of seizures.
Based on onset
1. Focal onset - begin only in one hemisphere
2. Generalised - begin in both hemispheres
3. Secondary generalised - begins in one hemisphere and spreads to other
Generalised usually impair consciousness - loss of awareness of xt stimuli or inability to respond to xt stimuli in a purposeful and appropriate manner
Describe the pathophysiology of seizures.
Synchronised paroxysmal electrical discharges in a large population of neurons due to imbal bet excitatory and inhibitory rece/ion channel fn which favour depolarisation
a. Hyperexcitability = enhanced predisposition of a neuron to depolarise
- Xs excitatory neurotransmitters: glutamate (main), acetylcholine, histamine, cytokines
- NMDA is the primary rece that resp –> opens Ca2+ channel –> inflex into cell –> depolarise
- Fast/long lasting activation of NMDA rece
- Increase extracellular K+, less K+ diffuses from ard neurons durg hyperpol state of cells –> neurons become partially depol (always ready to fire)
- Abnormaltities in intra/xtracellular sub (e.g. Na+, K+, O2, glucose etc) –> volage or ligand gated K+, Na+, Ca2_, Cl- ion channels
b. Inhibition
- Main inhibitory neurotransm: GABA > dopamine
- Binding of GABA to GABA rece –> open Cl- channel –> influx into cell –> hyperpolarise
- Dysfnal GABA rece unable to open –> unable to inhib depolarisation –> more excitatory
Xs synchronous depolarisation, usually starting from defined regions (foci) and spreading to other regions
May lead to long term changes in neurons in brain
- Increase in Ca2+ –> long term structural & fnal changes in neurons to beget seizures
- Ca2+ = 2nd messenger activation –> change in gene activation, turns on cell death pathways (destroy surrounding inhib neurons)
What is an important region of the brain in seizures?
Hippocampus
- Is an epileptic region, often involved in epilepsy (NOT seizure events)
- Hippocampal sclerosis:
Intrinsic reorganisation of local circuits - hippocampus, the neocortex and the thalamus. Contribute to synchronisation and promote generation of epileptiform activity.
What are the risk factors of seizure?
Alcohol
Hypoglycemia
Pyrexia
Sleep deprivation
How do we diagnose epilepsy/seizures?
Hx taking
From pt: onset, hx, prodrome, aura, preservation of consciousness, post-ictal state
From observer: onset, duration, characteristics
Neurologic exam
1. Scalp EEG
- Epileptiform discharges when seizure ongoing (otherwise delayed Dx)
- Normal EEG does not exclude epilepsy (not in window of capture)
- Not all epileptic pts hv abnormal EEG
50% chance of showing epileptiform activity in a first awake EEG // 80-90% sensitivity w repeated awake-sleep EEGs
- EEG can be abnormal in normal persons
(false +ve 0.5-1%)
- Video EEG
-Videomonitoring + EEG to corr clinical manifestation w any abnormal discharges
- Labour intensive & $$ –> selective
- Typically limited to diagnostic problems that cannot be resolved easily in routine EEG laboratory - Brain imaging - MRI w gadolinium
- Orderred for adult pt who presents w 1st seizure, pts w focal neurologic defecits, suggestion of focal onset seizures
- ID focal lesions: mesial temporal sclerosis, focal cortical dysplasia, remote injury, tumour, vascular malformation
Concomitant medical conditions
Biochem/toxicology
- Rule out electrolyte abnormalities
- Serum prolactin - considerable var, not used routinely
- Creatinine kinase (CK) - raised after GTC seizure
How do we approach a pt w 1st seizure?
- Was it a seizure?
- Neuro exam: EEG, signs & symptoms - Was it 1st seizure?
- What was the aetio? Unprovoked?
- Does the pt need ASM?
a. What is the risk of seizure recurrence?
b. Pt factors
c. Which ASM
Discuss the risk of seizure recurrence.
After 1st seizure, risk of 2nd seizure
- Within next 5y ~30%, out of this 30%, 80-90% had a second seizure within 2y
- Higher in presence of abnormalities on EEG
- Prior brain insult (e.g. stroke, brain trauma)
- Structural abnormality in brain imaging
- Nocturnal seizure
After 2 unprovoked seizures, risk of recurrent seizures at 4y ~70%
When do we start treatment?
High recurrence risk
Potential seizure morbidity
Weigh risk & benefit
Personal circumstances
Consider aetio, seizure type, specific syndromes, comorbidities, comedication, EEG findings, tolerability, lifestyle, work, family planning, need, preference
First Seizure Trial Group (FIRST) studt and Multicentre Study of Early Epilepsy and Single Seizures (MESS) study demonstrated that treatment after 1st seizure
- Reduced risk of 2nd seizure
- No effect on long term prognosis
- No evi of higher risk of death, injuries, or status epilepticus in pts allocated to deferred treatment
(If clear cut, go ahead w ASM)
What are the goals or epilepsy management?
Absence of epileptic seizures
Absence of ASM related S/E
Attainment of optimal QoL
Abt 2/3 of pts are able to achieve seizure freedom
