Any of the following: 1. 2 or more seizures >24 h apart 2. 1 unprovoked seizure + 60% or more recurrence risk after 2 unprovoked seizures (over next 10 years) 3. Epilepsy syndrome diagnosis

Epilepsy Flashcards by Lin Weilin

*What is a seizure?

Transient episode (s/sx) due to abnormal excessive/synchronous brain activity

How well did you know this?

Not at all

Perfectly

*What is epilepsy?

Any of the following:

2 or more seizures >24 h apart
1 unprovoked seizure + 60% or more recurrence risk after 2 unprovoked seizures (over next 10 years)
Epilepsy syndrome diagnosis

How well did you know this?

Not at all

Perfectly

*What are some possible CNS insults that can provoke seizures in normal individuals?

Metabolic (Na, Ca, Mg, Glucose)
Infectious/Inflammation (fevers)
Structural (stroke, traumatic brain injury)
Toxic (illicit drugs, alcohol, BZD withdrawal)
(MIST)

How well did you know this?

Not at all

Perfectly

*What is the pathophysiology of seizures/epilepsy?

Hyperexcitability + Hypersynchronization

How well did you know this?

Not at all

Perfectly

What are some factors contributing to Hyperexcitability ?

More ion channels
Metabolic abnormalities
Excessive excitatory neurotransmitter
Insufficient inhibitory neurotransmitter

How well did you know this?

Not at all

Perfectly

Examples of excitatory neurotransmitters?

glutamine, acetylcholine, histamine, cytokines,

How well did you know this?

Not at all

Perfectly

Examples of inhibitory neurotransmitters?

GABA, dopamine

How well did you know this?

Not at all

Perfectly

Focal onset refers to __ in the context of epilepsy.

Seizures beginning in only 1 hemisphere

How well did you know this?

Not at all

Perfectly

Generalized onset refers to __ in the context of epilepsy.

Seizures beginning in both hemispheres

How well did you know this?

Not at all

Perfectly

Dyscognitive features refers to __ in the context of epilepsy.

Impairment of consciousness

How well did you know this?

Not at all

Perfectly

*How does ILAE classify seizures?

Focal/generalized
Dyscognitive features Y/N
Other features

How well did you know this?

Not at all

Perfectly

*For a conscious patient with focal onset seizures, what are the possible motor symptoms they may present with?

Clonic movement

Speech arrest

How well did you know this?

Not at all

Perfectly

*For a conscious patient with focal onset seizures, what are the possible sensory symptoms they may present with?

Feelings of numbness/tingling
Visual disturbances
Rising epigastric sensation

How well did you know this?

Not at all

Perfectly

*For a conscious patient with focal onset seizures, what are the possible autonomic symptoms they may present with?

HR, pallor, BP, Sweating, salivation

HPBSS

How well did you know this?

Not at all

Perfectly

*For focal onset seizures without dyscognitive features, what are the possible psychic/somatosensory symptoms they may present with?

Hallucinations
Flashbacks
Affective symptoms (i.e. fear, depression, anger and irritability)
(HAF)

How well did you know this?

Not at all

Perfectly

*For focal onset seizures with dyscognitive features, what are the possible symptoms they may present with?

Aura
Impaired consciousness
Automatisms (i.e. lip smacking, chewing or picking at their clothing unpurposefully)

How well did you know this?

Not at all

Perfectly

*What is the tonic phase of generalized tonic-clonic (GTC) seizures characterized by?

Stiffening of limbs

Breathing may decrease or stop, possibly leading to cyanosis

How well did you know this?

Not at all

Perfectly

*What is the clonic phase of generalized tonic-clonic (GTC) seizures characterized by?

Jerking of limbs and face
Usually lasts 1minute 
Breathing typically resumes (may be noisy/ labored/ irregular)
Incontinence may occur
Biting of tongue or inside of mouth
(J1 BIB)

How well did you know this?

Not at all

Perfectly

*How would a patient feel after a GTC seizure event?

Headache
Sleepy
Lethargic
Confused

How well did you know this?

Not at all

Perfectly

*How long will full recovery take post a GTC seizure event?

Minutes to hours (depending on severity of episode)

How well did you know this?

Not at all

Perfectly

*What are the characteristics of a generalized clonic seizure?

Clonic jerking is asymmetrical and irregular

How well did you know this?

Not at all

Perfectly

Which patient group is most likely to present with generalized clonic seizures?

neonates, infants or young children

How well did you know this?

Not at all

Perfectly

*What are the characteristics of a generalized tonic seizure?

Sudden loss of consciousness and rigid posture of entire body
Lasts 10-20 seconds

How well did you know this?

Not at all

Perfectly

Which patient group is most likely to present with generalized tonic seizures?

Any age with diffuse cerebral damage and learning disability
Association with other seizure types i.e. Lennox Gastaut syndrome

How well did you know this?

Not at all

Perfectly

*What are the characteristics of a generalized myoclonic seizure?

Involves rapid, brief contractions of bodily muscles, usually occurring on both sides of the body concurrently - On occasion, may involve just one arm or one foot

*What are the characteristics of a generalized absence seizure?

Basic lapse in awareness that begins and ends abruptly | - Often mistaken as persistent staring

Which patient group is most likely to present with generalized absence seizures?

- More common in children than in adults | - First onset usually occurs at 4-12 years old; rarely after 20 years old

It is important to differentiate generalized absence seizures from __ as the patient may be __.

1. Complex partial seizures/ Focal onset seizures with dyscognitive features 2. prescribed the wrong medication

Absence seizures differ from Focal onset seizures with dyscognitive features as they (absence seizures) __.

Absence seizures are: 1. no proceeding auras 2. short duration (seconds, rather than minutes) 3. begin and end abruptly 4. Characteristic '3Hz spike waves' in EEG

*What are the characteristics of a generalized atonic seizure?

Most severe: all postural tone suddenly lost, collapsing to the ground (drop attacks) Short episode Immediate recovery (MSI)

Which patient group is most likely to present with generalized atonic seizures?

Any age Always associated with diffuse cerebral damage and learning disability Common in severe symptomatic epilepsies i.e. Lennox Gastaut syndrome

A young patient was reported to frequently stare at teachers and classmates by the parents. What kind of seizure condition is likely?

Absence seizures (Generalized onset)

A young patient presents at the clinic and shows multiple injuries i.e. falls, burns. What kind of seizure condition is likely?

Atonic seizures (Generalized onset)

Which positive symptom in a seizure is often used as a surrogate for impaired awareness?

Urinary incontinence

Which positive symptom in a seizure may suggest GTC seizures?

Muscle soreness (due to high levels of motor activity)

When a patient presents with dyscognitive features, it is important to rule out __.

syncope (fainting possible due to block in O2 supply)

When a patient describes a moving tingling sensation in fingers, it is important to rule out __.

Transient ischaemic attack (TIA stroke)

Patients that present with seizure-like jerking without EEG abnormalities may in fact not have seizures but instead have __.

Psychogenic nonepileptic seizures

__ have many overlapping non-specific symptoms with seizures and should be ruled out.

Migraines

*An epileptiform EEG __ while a normal EEG __. electro-encephalo-graphy (EEG)

1. confirms diagnosis of seizures/epilepsy | 2. does not exclude possibility of epilepsy

*What are limitations of EEG?

1. Not all epileptic patients have abnormal EEG (false negative) 2. Normal patients may have abnormal EEG (false positive)

*What is the purpose of an MRI with gadolinium in the context of epilepsy?

To rule out structural abnormalities (i.e. focal leisons)

Who should receive an MRI with gadolinium?

Adults 1st seizure Focal neurological deficit Suggestive of focal onset seizure

*Why would a patient undergo biochemical/toxicology testing?

To rule out electrolyte abnormalities

Although serum prolactin is correlated with seizure activity, it is not used routinely due to __.

considerable variability

__ tests should be raised following a GTC seizure event as it has good correlation.

Creatinine Kinase (CK)

How should we begin with pharmacotherapy workup for a patient presenting with their 1st 'seizure' event?

1. Is it a Seizure? 2. First? 3. Provoked/Cause? 4. Need for AED? (risk of recurrence and patient factors) (SFPCN)

The risk of seizure recurrence is increased if patients have: __, __, __, __.

1. Epileptiform EEG 2. Structural abnormalities (brain imaging) 3. Prior brain insult (stroke/trauma) 4. Nocturnal seizure (ESPN)

The risk of recurrence after 2 unprovoked seizures is __, which is also usually the point we advise patients to start AED treatment.

~70%

Individualizing the pharmacologicals for the patient should be based on __, __ and __.

1. seizure type/epilepsy syndrome 2. co-morbidities and co-medications 3. Patient preference/lifestyle/job (SCP)

When rapid titration is required, i.e. acute treatment of Status epilepticus, the use of __ or __ would not be appropriate due to their slow titration

Lamotrigine | Topiramate

When seizure patients also complain of migraines, the use of __ or __ is suitable.

Topiramate | Valproate

When seizure patients have depression/anxiety, __ should be used with caution.

Levetiracetam

AEDs with many DDIs i.e. __ or __ should be avoided if the patient is on concurrent drugs that also have complex DDIs i.e. HIV tx/immunosuppressants)

Carbamazepine | Phenytoin

For female epileptic patients with childbearing potential, __ or __ are good options.

Levetiracetam/Lamotrigine

__ may cause speech/thinking retardation (cognitive impairment) especially when newly started, and may not be a suitable AED for patients mentally intensive careers.

Topiramate

When initiating AEDs, we should start patient on a __, appropriate AED. If Seizures continue with no drug SEs, we should __.

1. low dose, 1st line | 2. gradually increase AED dose

If seizures continue despite max doses, we should conduct __, __, __.

Diagnosis Review Adherence Check Appropriate drug Check (DAA)

*When should we consider substitution of AEDs?

1st AED causes ADRs or Not tolerated at low doses or Not effective

*When should we consider adding on of AEDs (combination therapy)?

1st AED tolerated but with a suboptimal response

*Non-pharmacological options for seizure patients include: __

Ketogenic diet Vagus nerve stimulation (VNS) Responsive neurostimulator system (RNS) Surgery

*What are some psychosocial challenges faced by epileptic patients?

``` Caregiver burden Employment Driving prohibition Social stigma (CEDS) ```

*What are some possible seizure triggers?

``` Hyperventilation Sensory stimuli (i.e. Photostimulation) Drugs Infection Stress (Physical and emotional) Hormonal changes Electrolyte imbalance Sleep deprivation (HS DISHES) ```

Hormonal changes are possible seizure triggers. They may occur during __, __, __.

time of menses, puberty, or pregnancy

Drugs are possible seizure triggers. Examples include:

Theophylline, alcohol, high dose phenothiazines, antidepressants (especially bupropion), tramadol, carbapenems

Electrolyte imbalance is a possible seizure trigger. Examples include: Hyper/Hypo: __ Hypo: __

Hyper/Hypo: Na | Hypo: Ca, Mg, Glucose

*If we observe a person having a seizure >5min, we should __.

Call 995 for an ambulance

*If we observe a person having a seizure, __ would be appropriate.

``` Easing person to floor in prone position Place soft/flat under head Clearing the area around the person Loosening ties/items around neck to prevent choking Remove spectacles Time the seizure ```

*If we observe a person having a seizure that is turning blue with cyanosis, should we engage in CPR?

No. CPR should only be initiated if the person collapses (i.e. no jerking but no breathing either)

*What are the treatment options for New onset, Focal onset epilepsy?

``` Levetiracetam (ILAE Level A) Phenytoin (ILAE Level A) Carbamazepine (ILAE Level A) Valproate (ILAE Level B) Topiramate Lamotrigine (ILAE Level A, elderly) Gabapentin (ILAE Level A, elderly) (LPCVT LG) ```

*What are the treatment options for New onset, Generalized onset epilepsy?

Topiramate Lamotrigine Valproate (TLV)

What are the possible treatment add-on options for refractory, Focal onset epilepsy?

``` Clobazam Lacosamide Pregabalin Perampanel Any other new onset agent (CLP P) ```

*What are the treatment add-on options for refractory, Generalized onset epilepsy?

Clobazam Levetiracetam Any other new onset agent

What are good treatment options for an elderly patient with New onset, Focal onset epilepsy? (assuming no other co-morbidities)

Gabapentin | Lamotrigine

The majority of AEDs work on the voltage gated Na channels. __ has a special MOA as it acts on SV2A (glutamate) while __ works on the AMPA receptor (Na) Other AEDs i.e. __ work on the GABA receptor (Cl) as well. SV2A - synaptic vesicle glycoprotein 2A

1. Keppra (Levetiracetam) 2. Perampanel 3. Phenytoin

What is the usual maintenance dose for Phenytoin?

300-400mg/day (or 5-7mg/kg/day)

What is the usual maintenance and Max dose for Sodium valproate?

600-2000mg/day (or 20-30 mg/kg/day) | Max: 60 mg/kg/day

What is the usual maintenance dose for Carbamazepine?

800-1200mg/day

What is the usual maintenance dose for phenobarbitone/phenobarbital?

60-180mg/day

What is the usual maintenance dose for Lamotrigine?

100-200mg/day

What is the usual maintenance dose for Topiramate?

200-400mg/day

What is the usual maintenance dose for Levetiracetam?

1000-3000mg/day

*The 1st generation AEDs include: __, __, __ and __.

Carbamazepine Phenytoin Phenobarbitone/phenobarbital Valproate

*The 1st generation AEDs are all eliminated via __.

the hepatic route

*The 1st generation AEDs are all __, which is relevant in the context of hypo-albuminemia or ESRF because of an __.

1. highly protein bound | 2. increased free fraction drug (increased effects)

* Of the 1st generation AEDs, all are potent inducers except __, which is a potent inhibitor

Valproate

*Gabapentin and pregabalin are both mainly eliminated via __.

Renal route

*Lamotrigine is mainly eliminated via __.

Hepatic route

*Levetiracetam is mainly eliminated via __.

Hepatic route

*Topiramate is mainly eliminated via __.

Renal route (30-55%)

*Clobazam (3rd gen AED) is mainly eliminated via __.

Renal route

*Among the 2nd gen AEDs, __ has few interactions while __ has dose-dependent interactions.

1. Lamotrigine | 2. Topiramate

*Among the 2nd gen AEDs, __ has significant (55%) protein binding while __ has a low level (15%) of protein binding.

1. Lamotrigine | 2. Topiramate

What are the key times to note when it comes to a patient taking potent CYP inducer/inhibitor?

During initiation and discontinuation

*What are some drugs that may have DDIs with AEDs in general?

``` Chemotherapy agents Antidepressants and antipsychotics Immunosuppressants Antiretroviral (i.e. HIV) medications (CAIA) ```

*Potent Enzyme inducing AEDs affect the reproductive hormones which would affect the patient's __. We can also expect a similar effect on __ drugs that the patient takes.

1. sexual function | 2. oral-contraceptives

*In the long term, AEDs may have effects on __ health and may affect __ risk

1. bone | 2. vascular

*Phenytoin has good bioavailability and complete absorption. However, its absorption is reduced when given at __. Therefore, we should __.

1. doses of >400mg | 2. limit dose per setting to 400mg

__'s absorption is reduced by NGT and feeds interaction. We should space out 1-2 hours between feeds and dosing.

Phenytoin

*There is a need to correct for __ when administering phenytoin for a patient __.

1. albumin level | 2. with albumin <40g/L

*__ can be displaced from albumin by endogenous compounds and other drugs.

Valproate

__ exhibits saturable protein binding. This has implications when interpreting drug levels for patients with hypoalbuminemia. (Free fraction increases linearly along with exponential increase in total drug level)

Valproate

__ has an active metabolite and the parent drug levels may not fully reflect the clinical situation. It may be necessary to let patients return to baseline before re-initiating the drug to account for the active metabolite.

Carbamazepine

*Carbamazepine undergoes CYP3A4 autoinduction increasing its clearance and decreasing its half-life over time. Maximal autoinduction occurs __. The clinical implication is __, which would reduce risk of SEs (i.e. ataxia).

1. 2-3wks post drug initiation | 2. avoid initiating target maintenance dose, instead start low and gradually increase over initial few weeks.

*Concentration dependent CNS SEs of AEDs may include:

``` Dizziness Fatigue Visual disturbances (usually double --/blurred vision) Ataxia Nystagmus Somnolence (DF VANS) ```

*Carbamazepine and valproate may cause GI SEs such as: __

N/V

*Levetiracetam may cause psychiatric SEs such as: __. We should pre-empt the patients and caregivers.

Behavioral disturbances i.e. irritability and aggression

*Topiramate may cause cognitive SEs such as: __

Reduced speech fluency

*Concentration dependent effects are particularly common during __ but patients may develop __.

1. initiation | 2. tolerance

__ may reduce risk of conc-dependent SEs but also reduces adherence.

Splitting daily doses into smaller doses

__ may reduce risk of conc dependent SEs only if the patients do not have day-time pre-dominant seizures.

Administering the largest AED dose at bedtime

__ is a good option to reduce risk of conc dependent SEs as it results in flatter peaks.

Sustained release preparation

*Gingival hyperplasia may be observed in almost half of all patients receiving chronic __ therapy

phenytoin

*Hirsutism is commonly observed in children and young adults on chronic __ therapy. Facial hirsutism may affect up to 30% of __.

1. phenytoin | 2. young females

*Alopecia occurs in 2-12% of patients receiving __.

sodium valproate

*Due to cosmetic concerns, we avoid starting newly diagnosed epilepsy patients on __ and __. Patients should be made aware of the SEs and alternative options.

Phenytoin and Valproate

*Encephalopathy is most commonly associated with prolonged __ treatment at high doses ( e.g. cerebellar atrophy). It may also occur with __.

1. phenytoin | 2. phenobarbitone

*Peripheral neuropathy occurs in 8.5-18% of patients experience sensory loss after long term __ treatment at high doses. May or may not improve with decrease in AED dose. May respond with folate supplementation. Also associated with __ and __.

1. phenytoin 2. carbamazepine 3. phenobarbitone

*Increased weight gain is often associated with __. Gradually reverses spontaneously with discontinuation of treatment.

sodium valproate

*Anorexia and weight loss is associated with __ and felbamate. It is reversible with discontinuation of drug. In fact, __ has been used as a weight loss agent.

topiramate

*Osteomalacia is attributed to hepatic metabolism of vitamin D and/or inhibition of calcium absorption. Often associated with __, __ and __ (hepatic enzyme inducers).

1. phenytoin 2. phenobarbitone 3. carbamazepine

*Neonatal congenital defects are associated with __, __, __. Also, __may cause cognition issues for the fetus.

phenytoin, phenobarbitone, topiramate | Valproate

*Isolated cases of blood dyscrasias are associated with __.

nearly all AEDs

*__ is Rare (<1%) and occurs predominantly in patients receiving phenytoin. It is also associated with carbamazepine and phenobarbitone

Megaloblastic anaemia

*__ has been associated with AED use. There should be no changes to ongoing therapy without first discussing with physician. Closer monitoring of symptoms is warranted. Compared to __, the risk of __ is significantly worse.

1. Suicidal ideation | 2. stopping AEDs or refusing to start AEDs

There is a strong association between carriage of HLA B*1502 and risk of __. This is relevant for Han Chinese and other Asian ethnic grps e.g. Malays, Indians, Thais).

CBZ induced SJS/TEN

*Current clinical guidelines recommend HLA B*1502 genotyping prior to starting __.

carbamazepine

*If patients are HLA B*1502 positive, avoid __ and __.

carbamazepine and phenytoin

HLA B*1502 genotyping prior to starting lamotrigine and phenytoin is not __/__/__.

not warranted not cost effective not well associated

*Risk of serious cutaneous reaction is for Lamotrigine higher with __, __ and concomitant __.

1. high starting doses 2. rapid dose escalation 3. valproate

*To reduce risk of Lamotrigine induced SJS/TEN, slow titration is warranted. with the 'slowest' titration if patient is on concomitant __ and the 'fastest' titration if patient is on concomitant __.

1. valproate (inhibitors) | 2. CBZ/Ph/Pbt (inducers)

State the dosing schedule for Lamotrigine if the patient is also on Valproate. Wk 1-2: __ Wk 3-4: __ Wk 5-maintenance: increase by __ Usual maintenance dose: __, 100-400mg/day with valproate and other drugs that induce glucuronidation (in 1 or 2 divided doses)

Wk 1-2: 25mg every other day Wk 3-4: 25mg/day Wk 5-maintenance: 25-50mg/1-2wk Usual maintenance dose: 100-200mg/day

``` State the dosing schedule for Lamotrigine if the patient is not taking concomitant inducers/inhibitors. Wk 1-2: __ Wk 3-4: __ Wk 5-maintenance: increase by __ Usual maintenance dose: __ ```

Wk 1-2: 25mg every day Wk 3-4: 50mg/day Wk 5-maintenance: 50mg/1-2wk Usual maintenance dose: 225-375mg/day (in 2 divided doses)

``` State the dosing schedule for Lamotrigine if the patient is taking concomitant inducers i.e. CBZ/Ph/Pbt. Wk 1-2: __ Wk 3-4: __ Wk 5-maintenance: increase by __ Usual maintenance dose: __ ```

Wk 1-2: 50mg every day Wk 3-4: 100mg/day (in 2 divided doses) Wk 5-maintenance: 100mg/1-2wk Usual maintenance dose: 300-500mg/day (in 2 divided doses)

*Cross sensitivity for skin reactions have been associated with __.

AEDs with aromatic ring structures

AEDs with aromatic ring structures include: Oxcarbazepine, __, __, __ and __.

Cbz Lamo Ph Pbt

AEDs WITHOUT aromatic ring structures include: __, __, __ and __.

``` Levetiracetam Gabapentin Valproate Topiramate (LGVT) ```

*A lack of efficacy in AEDs may be due to: __, __, __, __ or changes in __/__.

1. fast metabolizers 2. Compliance issues 3. inappropriate drug 4. interactions (drug/food) 5. change in physiology (age/pregnancy) 6. change in formulation

*Toxicity in AEDs may be due to __, __ or changes in __.

1. slow metabolizers 2. interactions (drug/food) 3. change in physiology (liver/renal)

The population derived reference ranges are __: 10-20 mg/L Valproate: __ mg/L __: 4-12 mg/L Phenobarbitone: __ mg/L But we should always treat the patient and NOT the level.

1. Phenytoin 2. 50-100 3. Carbamazepine 4. 15-40

*Oral contraceptives may lower __ concentrations, resulting in breakthrough seizures.

Lamotrigine

*A patient is concerned regarding her AED drugs and breastfeeding the baby. What is your response?

Taking anti epileptic drugs is not an absolute contraindication to breastfeeding. All breastfeeding women on AED therapy should be encouraged to breastfeed

*When a seizure lasts __, it is likely to be prolonged (status epilepticus). When a seizure lasts __, it may cause long term consequences.

1. >5min | 2. >30min

*The initial treatment for status epilepticus is __ with __ preferred.

Benzodiazepines | IM/SC (non-oral ROA)

*As the initial treatment for status epilepticus is usually insufficient, treatment for the second therapy phase may include: __ / __ or __ if the previous 2 options are unavailable.

IV Valproate/IV Levetiracetam | IV Phenobarbital