Seizures/Epilepsy Flashcards
(40 cards)
1
Q
Definition of epilepsy
A
- Defining the “heightened tendancy for recurrent spontaneous seizures”
- Recurrent unprovoked seizures (≥2 at least 24 hours apart)
- ≥1 seizure with a relatively high recurrence risk (≥60% over a decade) - evidence for heightened risk from clinical, EEG, neuroimaging)
- Electro-clinical syndrome
2
Q
Features of partial/focal seizures based on lobe of invovlement:
A
- Frontal lobe
- Hypermotor behaviour - cycling, peddling, pelvic thrusting, more likely to happen during sleep
- Temporal lobe - most commonly involved in adult onset
- Mesial - autonomic, dysmnesic, deja vu, gustatory, olfactry
- Lateral/posterior neocortical - auditory, complex visual, dysphasia
- Parietal lobe - somatosensory → can propagate to temporal lobe also
- Occipital → simple visual, can propagate to temporal lobe also
3
Q
Types of generalised seizures
A
- Absence - brief behavioural arrest, automatisms
- Myoclonic - sudden brief jerks or twitching of limbs/axial muscles, usually with preserved consciousness
- Tonic - co-contraction of agonist/antagonist muscles, <15 seconds in duration
- Atonic - e.g. loss of muscle tone and falling
- Clonic seizures - repeptitive jerking movements
- Generalised tonic-clonic - initial tonic posturing phase following by clonic limb movements
4
Q
Epilepsy risk factors:
A
- Febrile seizures
- Significant head trauma
- CNS infections
- Family history of epilepsy
- History of pregnancy complications
- Learning or physical disabilities/milestone delay
5
Q
AED options in focal seizures (with or without secondary generalisation):
A
- Na+ channel antagonists
- Carbamazepine, has been the go to for focal epilepsy - note makes juvenile myoclonic seizures worse
- Phenytoin
- Oxcarbazepine
- Lamotrigine
Sanad Trial:
- Lamotrigine clinically better than carbamazepine for time to treatment failure outcomes. Cost effective alternative for patients diagnosed with focal seizures.
Sanad 2
- Did not support use of levetiracetam or zonisamide as first line treatment for focal epilepsy. Lamotrigine is standard therapy.
6
Q
AED options in generalised epilepsy
A
- Sodium valproate
- Levetiracetam
- Topiramate
- Lamotrigine
- Penobarbital
Sanad Study:
- Valproate better tolerated than topiramate, and more efficacious than lamotrigine in generalised and unclassifiable epilepsy and should be considered first line. Need to consider risks in women of childbearing ability.
Sanad 2:
- Levetiracetam not clinically effective or cost effective compared to valproate in generalised or non-classifiable epilepsy.
7
Q
Features of epileptiform activity on an EEG
A
- Spikes (50-70ms), sharp waves (70-200ms), or spike-wave discharges distinct from background activity
- An epileptiform pattern → recurrence risk 30-70% in the first year
- EEG with an epileptiform discharge after a single seizure - treatment may be considered before a diagnosis of epilepsy is made
- Low sensitivity (50%), diagnostic yield increases with serial EEGs
Examples of specific patterns
- Generalised 3-4Hz delta activity = encephalopathy
- Burst suppression pattern of background activity = anaesthesia, coma
- Psuedoperiodic, sharp-slow wave complexes in the right anterior temporal region, with diffuse background slow wave activity, maximal bitemporally = HSV encephalitis
8
Q
Examples of AEDs with sodium channel blocking abilty
A
- Carbamazepine
- Oxcarbazepine
- Phenytoin
- Lamotrigine
- Lacosamide (slow channels only)
- Topiramate (has other actions outside of sodium blocking also)
9
Q
Examples of AEDs with GABA enhancing activity
A
- Sodium valproate
- Clobazam
- Phenobarbital
- Primidone
- Clonazepam
- Topiramate
10
Q
Examples of AEDs with calcium channel blocking abilities:
A
T type calcium channels
- Sodium valproate
- Ethosuxamide
Others (A2D of VGCC)
- Gabapentin
- Pregabalin
11
Q
AED used for absence seizures
A
- Ethosuximide
12
Q
Last resort AEDS:
A
- Vigabatran - GABA transaminase inhibitor - increases GABA in brain. ⅓rd get visual field deficits
-
Felbamate
- Blocks NMDA and augments GABA function - though not well understood in humans,
- Mainly used to treat Lennox-Gastaut syndrome, can be used for focal seizures but not recommended as first line therapy
- Metabolised in liver, 50% excreted unchanged in kidneys
- Associated with fatal aplastic anaemia and hepatic failure
13
Q
Examples of AEDS which are hepatic enzyme inducers.
A
- Phenytoin
- Carbamazepine
- Oxcarbazepine
- Phenobarbital
- Topiramate is a weak inducer
14
Q
Examples of AEDS which are hepatic enzyme inhibitors
A
Sodium vaproate
15
Q
Examples of AEDS that are renally excreted:
A
- Levetiracetam
- Gabapentin, pregabalin
16
Q
Examples of AEDS which demonstrate non-linear kinetics
A
- Phenytoin - increase in the daily dose beyond 300mg → disproportionate increase in serum concentration. If seizures not controlled at this dose, an increment of 100mg → >30mg/L serum concentration → clinical toxicity. Smaller increments more appropriate.
- Gabapentin is the opposite → increaseing doses → falling levels
17
Q
Notes on benzodiazepines as AEDs
A
- Bind to the GABA(A) receptor, facilitate attachement of GABA to its binding site on receptor
- Effective for focal and generalised seizures. Clobazam used as adjunctive therapy in Lennox-Gastaut syndrome.
- Usefullness limited in chronic treatment of epilepsy due to development of tolerance
- Can get withdrawal seizures on sudden discontination
- Side effects - sedation, irritability, ataxia, depression
18
Q
Notes on levetiracetam:
A
- Modulates neurotransmitter release by binding synaptic vesicular protein SV2A
- Monitor for depression - can lead to suicidal ideation
- Renally excreted, may want to avoid in renal impairment (but can dose adjust)
19
Q
Notes on carbazmazepine as an AED:
A
- Binds to voltage-gated sodium channels switching them to an inactivated state
- 70% protein bound
- Metabolised in liver by CYP3A4
- Potent, broad spectrum inducer of CYP system
- Many interactions with other AEDS - metabolism of carbamazepine increased by phenytoin → reduced effect
- Potential life-threatening effects:
- SJS/TEN (usually first eight weeks of therapy - screen patients of Asian ancestry for the HLAB1502 allele due to increased risk)
- Bone marrow suppression -leukopaaenia in 7% adults - may be transient. Aplastic anaemia rare → idiosyncratic, non dose related, usually within 3 to 4 months of starting therapy
- Hyponatraemia (SIADH)
20
Q
Notes on ethosuximide:
A
- Diminishes T-type calcium currents
- Effective for abscence seizures - no activity against generalised tonic-clonic or focal seizures
- Metabolised in liver CYP3A - no significant reactions reported with other drugs
- Side effects - nausea, vomiting, sleep disturbance, drowsiness, hyperactivity
21
Q
Notes on gabapentin:
A
- Binds to alpha-2-delta subunit of voltage gated calcium channel
- Add on therapy for refactory focal seizures
- Absorbed by means of a saturable amino acid transport system in the gut → more frequent dosing → increased bioavailability
- Not bound to plasma protein
- Not metabolised → excreted unchanged in urine. Dose adjustments required in renal impairment
- Should be taken 2 hours after the use of antacides → concurrent administration decreases bioavailability
- Adverse effects → major = sedation, use with caution with benzodiazepines and opioids. Also dizziness, ataxia, weight gain.
22
Q
Notes on lacosamide:
A
- Slow inactivation of voltage dependent sodium channels
- Completely absorbed after oral administration with 100% bioavailability and is eliminated by renal excretion
- Generally well tolerated - possible PR prolongation reported so caution with abnormal ECG/cardiovascular disease
23
Q
Notes on lamotrigine
A
- Sodium channel blockers
- Total absorption orally
- Plasma concentrations linear to dose
- 55% bound to plasma protein
- Liver metabolism - glucoronide conjugates excreted in urine
- Hormone replacement and contraceptives → increase clearance → reduced concetrations when taking, increased concentrations during “placebo week” (only estrogen containing OCPs)
- Clearance increased in pregnancy may → seizures
- Action increased by valproate, reduced by phenytoin, carbamazepine, rifampicin, phenobarbital
- Side effects - rash and nausea (rash more likely if rash with other antiseizure drugs), small risk of SJS/TEN, DRESS rare.
24
Q
Notes on phenobarbital
A
- Binds to GABA A receptor - enhances effect of GABA
- Metabolised by liver CYP system, 25% excreted renally, unchanged
- CYP inducer
- Reduces the effects of most forms of hormonal contraceptives
- Frequent adverse effects - sedation, mood changes, reduced concentration
- Chronic use - decreased bone density, Dupuytren’s contractures, frozen shoulder
- Teratogenic
25
Notes on phenytoin:
* Blocks sodium channels
* Metabolised in liver
* Potent inducer of CYP - reduces the effects of most hormonal contraceptives
* Side effects: gingival hypertropy, body hair increase, rash, folic acid depletion, decreased bone density. Neurotoxic - confusion, slurred speech, doplopia, ataxia
* Has been associated with SJS/TEN - more common in HLAB1502 allele (Asians)
* Very poor absorption with nasoenteric feeds
26
Notes on pregabalin:
* Like gabapentin - binds alpha-2-delta subunit of VGCC
* Renally excreted virtually unchanged
* Not a substrate/inducer/inhibitor of the CYP system
* Not bound to plasma proteins
* Linear pharmacokinetics
* Side effects - dizziness, somnolence, ataxia. Also weight gain, peripheral oedema, blurred or double vision
27
Notes on topiramate:
* Blocks sodium channels, also enhances activity of GABA, antagonises the NMDA glutamate receptor
* Metabolised to a minor degree in liver, mostly eliminated in the urine
* Serum levels decline during pregnancy
* May increase phenytoin concentration
* Adverse effects
* Impaired cognition
* Weight loss
* Metabolic acidosis (inhibitory effect on carbonic anhydrase → renal bicarbonate loss) → tachypnoea, calcium phosphate nephrolithiasis
* Acute myopia and secondary angle glaucoma
28
Notes on valproate:
* Increases GABA, also some blocking action at sodium receptors
* Focal and generalised seizures (probably most effective agent for generalised tonic-clonic seizures)
* Tightly protein bound
* Metabolised in liver
* Moderate inhibitor of CYP system
* Oral contraceptives can reduce levels of valproate
* Adverse effects:
* Associated with weight gain, insulin resistance, metabolic syndrome, PCOS
* Hyperammonaemia if used in paitents with urea cycle disorders - contraindicated
* Thrombocytopaenia and coagulation disorders
* Teratogenic
* Pancreatitis rare complications
* LFT derangement - cases of hepatic failure reported
29
Notes on Perampanel
* Glutaminergic AMPA antagonist
* Adjunctive for focal seizures
* _Side effects:_
* Dizziness, ataxia
* Weight gain
* Hostility and aggression
* Not available in NZ
30
Notes on cannabidiol in management of epilepsy
* 6 positive RCTs as adjunctive in selected paediatric treatment-resistant epilepsies
* Tuberous sclerosis complex
* Dravet syndrome
* Lennox-Gastaut Syndrome
* CBD interacts with clobazam - synergistict efficacy but greater adverse effects (sedation and LFTs)
31
Notes on mTOR inhibitors in management of epilepsy
* Everolimus and sirolimus
* Used for Tuberous Sclerosis complex epilepsy
* Most effective \< 18 years
32
Notes on Vagus Nerve Stimulation in Management of epilepsy
* 25% reduction in seizure frequency in medically-refractive epilepsy - considered when refractive to medications and not suitable for surgery
33
Notes on ketogenic diets in management of epilepsy
* Established benefit in children with drug-resistant epilepsy, evidence uncertain for adults
34
Notes on teratogenicity and AEDs and management of epilepsy in pregnancy
* Lamotrigine safest , levetiracetam relatively favourable
* Folate not proven protective in preventing AED induced teratogenicity but still advised
**If possible avoid in women of childbearing potential:**
* Polytherapy
* Phenobarbitone
* Valproate
**Concentrations of AEDs reduced in pregnancy for the following drugs:**
* Lamotrigine - early reduction but more so 2nd and 3rd trimesters
* Levetiracetam
* Lacosamide
* Oxcarbazepine
* Zonisamide
* Topiramate → reduced 3rd trimester, rebound post-partum
35
Notes on autoimmune epilepsy
* Can use APE2 score → if ≥4 should have neural specific antibody evaluation
36
Notes on SUDEP
* Sudden Unexplained Death in Epilepsy
* Mean age 35 years, probably related to unwitnessed seizure activity
* A/W AED polytherapy likely confounded with refactory seizures
37
Notes on juvenile myoclonic epilepsy
* Childhood seizure syndrome. Usually “grow out” but should be advised to avoid hazardous careers
* Typical history → 18 year old boy with recurrent morning myoclonus and abscences after sleep deprivation
* Treatment: valproate for boys, lamotrigine for girls
38
AEDs that cause weight gain and weight loss
**Weight gain**
* Sodium valproate
* Also lamotrigine, carbamazepine, phenytoin
**Weight loss**
* Topiramate
39
Notes on medial temporal sclerosis
* Think of if given a coronal image in a seizure question
40
Notes on neurocysticercosis
* Infectious parasitic disease caused by a tapeworm found in pork
* Typically manifests as seizures - probably the most common parasitic disease of the human nervous system
