Epilepsy E-book

Question 1

Focal Seizures 1st line treatment:

Answer 1

• Carbamazepine: either immediate or prolonged release formulations (Tegretol)
§ Immediate release: Initially 100–200 mg 1–2 times a day, increased in steps of 100–200 mg every 2  weeks; usual dose 0.8–1.2 g daily in divided doses; increased if necessary up to 1.6–2 g daily in divided doses
§ Prolonged release: Initially 100–400 mg daily in 2 divided doses, increased in steps of 100–200 mg every 2 weeks, dose should be increased slowly; usual dose 0.8–1.2 g daily in 2 divided doses, increased if necessary up to 1.6–2 g daily in 2 divided doses
• Lamotrigine (can be used as a monotherapy or as an adjunct to valproate)
§ Monotherapy: Initially 25 mg once daily for 14 days, then increased to 50 mg
once daily for further 14 days, then increased in steps of up to 100 mg every
7–14 days; maintenance 100–200 mg daily in 1–2 divided doses; increased if necessary up to 500 mg daily, dose titration should be repeated if restarting after interval of more than 5 days
§ Adjunct with valproate: Initially 25 mg once daily on alternate days for 14
days, then 25 mg once daily for further 14 days, then increased in steps of up to 50 mg every 7–14 days; maintenance 100–200 mg daily in 1–2 divided doses, dose titration should be repeated if restarting after interval of more than 5 days

Question 2

Focal Seizures 2nd line treatment:

Answer 2

• Levetiracetam monotherapy: Initially 250 mg once daily for 1–2 weeks, then increased to 250 mg twice daily, then increased in steps of 250 mg twice daily (max. per dose 1.5 g twice daily), adjusted according to response, dose to be increased every 2 weeks
• Oxcarbazepine monotherapy: Initially 300 mg twice daily, then increased in steps of up to 600 mg daily, adjusted according to response, dose to be adjusted at weekly intervals; usual dose 0.6–2.4 g daily in divided doses
• Sodium Valproate: Initially 600 mg daily in 1–2 divided doses, then increased in steps of 150–300 mg every 3 days; maintenance 1–2 g daily, alternatively maintenance 20–30 mg/kg daily;
maximum 2.5 g per day

Question 3

The following drugs may be considered for adjunctive treatment

Answer 3

carbamazepine, clobazam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, sodium valproate, or topiramate

Question 4

Tonic Seizures

Clinical features:

Answer 4

• In a tonic seizure, a person’s muscle tone is greatly increased causing the body, arms, or legs to become suddenly stiff or tense. There are 2 types of tonic seizures, focal and generalised, depending on the location of the seizures start point in the brain
• When it starts in one area of the brain:
o Stiffening of a part of the body may begin in one area and stay local. These are called
focal tonic seizures
• When it starts on both sides of the brain:
o The whole body or both sides of the body may become stiff or tense from the beginning. These are called generalized tonic seizures

Question 5

Symptoms of tonic seizures

Answer 5

• A person may be aware or have only a small change in awareness during a seizure.
• If the respiratory muscles are included a stridor or loud cry may be heard.
• Usually occur during sleep.
• Short, usually less than 20 seconds.
• A person may fall if they are standing when a tonic seizure starts

Question 6

Tonic Seizures 1st line treatment:

Answer 6

Sodium Valproate (except for woman of childbearing age)

• Initially 600 mg daily in 1–2 divided doses, then increased in steps of 150–300 mg every 3 days; maintenance 1–2 g daily, alternatively maintenance 20–30 mg/kg daily; maximum 2.5 g per day

Question 7

Tonic Seizures 2nd line treatment:

Answer 7

Lamotrigine as adjunctive (if sodium valproate not suitable)
• Initially 25 mg once daily for 14 days, then increased to 50 mg once daily for further 14 days, then increased in steps of up to 100 mg every 7–14 days; maintenance 100–200 mg daily in 1–2 divided doses; increased if necessary up to 500 mg daily, dose titration should be repeated if restarting after interval of more than 5 days

Question 8

Do not use… in tonic seizures

Answer 8

carbamazepine, gabapentin, oxcarbazepine, pregabalin, tiagabine or vigabatrin

Question 9

Tonic-Clonic Seizures (Grand Mal) Clinical features:

Answer 9

• Tonic-clonic seizures are the type of epileptic seizure most people recognise.
• Previously called grand-mal seizures
• Typically, generalised onset
o Affects both sides of the brain from the start
o Focal tonic-clonic seizure
• Can start in one side of brain and spread to affect both
o Called focal to bilateral tonic-clonic seizure
o Can have symptoms of a focal seizure immediately before you lose consciousness
o Symptom examples:
§ Feeling frightened
§ Having a rising sensation in your stomach
§ Smelling something that’s not there
• Typically, last between 1 and 3 minutes
o If longer than 5 minutes can turn into status epilepticus

Question 10

There are 2 phases in a tonic-clonic seizure: the ‘tonic’ phase, followed by the ‘clonic’ phase.

Symptoms during the tonic phase:

Answer 10

• Loss of consciousness
• Stiff muscles, people standing may fall to the floor
• Air pushing past voice box, sounds like crying out
• Biting down on tongue or inside mouth

Question 11

There are 2 phases in a tonic-clonic seizure: the ‘tonic’ phase, followed by the ‘clonic’ phase.

Symptoms during the clonic phase:

Answer 11

• Quick and rhythmic jerking limbs
• Loss of bladder and/or bowel control
• Breathing affected, mouth may turn blue

Question 12

Tonic-Clonic Seizures (Grand Mal) 1st line treatment

Answer 12

Sodium	Valproate	(except	for	woman	of	childbearing	age)	
• Initially	600	mg	daily	in	1-2	divided	doses,	then	increase	in	steps	of	150-300	mg	every	3	days;	 maintenance	1-2	g	daily, alternatively	maintenance	20-30	mg/kg	daily;	maximum	2.5	g	per	day

Question 13

Tonic-Clonic Seizures (Grand Mal) 2nd line treatment:

Answer 13

Lamotrigine
• Initially 25 mg once daily for 14 days, then increased to 50 mg once daily for further 14 days, then increased in steps of up to 100 mg every 7-14 days; maintenance 100-200 mg daily in 1-2 divided doses; increased if necessary up to 500 mg daily, dose titration should be repeated if restarting after interval of more than 5 days

Question 14

Emergency action for tonic-clonic seizures

Answer 14

Less than 5 minutes:
• Protect them by:
o Cushioning their head with something soft or your hands.
o Remove potentially harmful items around them or move them away.
• Avoid restraining them or putting anything in their mouth.
• Once the seizure stops, check airway, put into recovery position and monitor until they have
recovered.
• Ensure they get admitted into the hospital if it is their first seizure.

More than 5 minutes:
• In addition to above,
o First line - buccal midazolam (dose for patients 10 years and over is 10 mg).
o Second line - rectal diazepam (or if preferred can be 1st line) if midazolam unavailable (dose for adults is 0.5 mg/kg).

Question 15

Absence - Typical and Atypical

Answer 15

Absence seizures can be broken down into two different types; typical or atypical. Both are often short
(less than 15 seconds) and symptoms come and go very quickly. However, both seizures present slightly different. Absence typical epilepsy is characterised by abrupt, short (5-10 seconds ) cessations of physical movement and generally occur in childhood in children between 4-14 years old (Epilepsy
Foundation, 2019). They occur due to brief abnormal electrical activity in the brain. As it is a generalised onset seizure, it begins in both side of the brain at the same time. They usually affect only a person’s awareness of what is going on at the time with immediate recovery following the seizure, although in some people’s recovery time may vary.
The frequency of absence typical seizures can vary. A child may have multiple number of absence seizures (up to 100) in a given day. Due to its nature, it may be overlooked and often mistaken for daydreaming or not paying attention.
Typical absence seizures exhibit a classic ictal EEG pattern of bilateral symmetric 3Hz spike and wave, which allows it to be identified
quite easily.
Atypical absence seizures may be longer, have a slower onset and offset, and involve different symptoms. They typical last less than 20 seconds but can be longer.

Question 16

Symptoms – Absence Typical

Answer 16

• Person will stop all activity and may seem like they are staring off into space or just have a blank look
• Eyes may turn upwards and eyelids flutter
• Usually last 10 seconds
• If they are walking they may continue to walk, but not know what they are doing

Question 17

Symptoms – Absence Atypical

Answer 17

• Seizure will normally start off with gazing into space, typically with blank look.
• Change in muscle tone and movement.
• Continuous blinking that resembles the fluttering of the eyelids.
• Lip smacking or chewing movements.
• Pill-rolling, piano finger like hand motions. Some may rub their fingers together.
• Arms and legs may go limp which could cause people to fall.

Question 18

Pharmacological Management of Typical and Atypical Absence Seizures 1st line treatment:

Answer 18

Ethosuximide or Sodium Valproate. If risk of generalised tonic clonic seizure is high,
sodium valproate should be offered first, unless it is unsuitable
• Ethosuximide: For Adult:
o Initially 500 mg daily in 2 divided doses, then increased in steps of 250 mg every 5–7 days; usual dose 1–1.5 g daily in 2 divided doses, increased if necessary up to 2 g daily.
• Sodium Valproate (except for woman of childbearing age)
§ Initially 600 mg daily in 1-2 divided doses, then increased in steps of 150-300 mg
every 3 days; maintained 1-2 g daily, alternatively maintenance 20-30 mg/kg daily;
maximum 2.5 g per day.

Question 19

Pharmacological Management of Typical and Atypical Absence Seizures 2nd line treatment:

Answer 19

Lamotrigine

Question 20

Pharmacological Management of Typical and Atypical Absence Seizures 3rd line treatment:

Answer 20

if the above 1st and 2nd line are ineffective, (two first line anti-epileptic drugs (AEDs)):
combination of two or three AEDs as “add on”/adjunctive therapy. This can include ethosuximide, lamotrigine or sodium valproate. If adjunctive therapy fails to work or is not tolerated by the patient, they should be referred to a tertiary epilepsy specialist.

Question 21

Which medications should not be offered for management of Typical and Atypical Absence Seizures

Answer 21

Carbamazepine, Gabapentin, Oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin should not be offered.

Question 22

Myoclonic Seizures Clinical features and symptoms

Answer 22

• Brief, sudden and involuntary shock like muscle contracts involving the whole body, and just a few muscles or more than two contiguous regions

Symptoms
• Quick, uncontrolled muscle jerks.
• Jerky or rhythmic movements.
• Unusual clumsiness.

Question 23

In epilepsy, myoclonic seizures result in abnormal movements of the body; bilaterally. These occur in a variety of syndromes which are characterised by different symptoms.

Answer 23

• Juvenile myoclonic epilepsy: These seizures are usually characterized by the involvement of
the neck, shoulders and upper arms. In many patients, these seizures take place shortly after waking up. They often begin around puberty or in early adulthood. There is no association between this form of epilepsy and intelligence. They can be well controlled through medication in most cases however, the medication must be continued throughout the duration of their lives.
• Lennox-Gastaut syndrome: This is a rare syndrome that usually includes other types of seizures and often begins in early childhood. The myoclonic seizures usually involve the neck, shoulders, upper arms, and often the face. They may be quite strong and are difficult to control.
• Progressive myoclonic epilepsy: This is a rare amalgamation of myoclonic seizures and tonicclonic seizures and treatment is usually unsuccessful as the patient deteriorates over time.

Question 24

Myoclonic Seizures 1st line treatment:

Answer 24

Sodium	Valproate (except	for	woman	of childbearing	age)
• Adult: Initially	600 mg	daily	in	1–2	divided	doses,	then	increased	in	steps	of 150–300 mg	every	3 days;	 maintenance	 1–2 g	 daily,	 alternatively	 maintenance	 20–30 mg/kg	 daily;	 maximum 2.5 g	per	day

Question 25

Myoclonic Seizures 2nd line treatment:

Answer 25

Topiramate and levetiracetam (If sodium valproate is unsuitable but consideration should be given to the less favourable side-effect profile of Topiramate)
• Topiramate
o Initially 25 mg once daily for 1 week, dose to be taken at night, then increased in steps of 25–50 mg every 1–2 weeks, dose to be taken in 2 divided doses; usual dose 100–200 mg daily in 2 divided doses; maximum 500 mg per day
• Levetiracetam
o Initially 250 mg twice daily, then increased in steps of 500 mg twice daily (max. per dose 1.5 g twice daily), dose to be increased every 2–4 weeks

A combination of Topiramate and Levetiracetam may be used if monotherapy is ineffective or not tolerated. If adjunctive treatment fails, a tertiary epilepsy specialist should be consulted and may consider clobazam, clonazepam, zonisamide or piracetam.

Carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine and vigabatrin are not recommended for the treatment of myoclonic seizures

Question 26

Atonic Seizures Clinical features:

Answer 26

Atonic seizures (‘drop attacks’ or ‘drop seizures’) commonly leads to generalised seizure activity. This tends to be loss of muscle tone (tension of the muscles). When patients experience a seizure, they may fall down and injure themselves. Hence, head protection (e.g. helmet) may be required.
Seizure beginning in one part of the brain:
• Originates in one area of the brain, resulting in a loss of tone in one area of the body.
• Known as focal motor atonic seizure.
Seizure beginning on both sides of the brain:
• Usually, atonic seizures affect both sides of the brain.
• These are called generalized onset atonic seizures.
• Seizures can cause the patient to fall down and so they are known as “drop attacks” and this can lead to injury to the face nose and head in particular
• Usually a person having a generalized atonic seizure is not fully aware during the event.
People normally recover fairly quickly after experiencing an atonic seizure although some may need to rest for a bit. Additionally, they may or may not feel confused after the attack.

Question 27

Atonic Seizures symptoms

Answer 27

• Their upper body or head may slouch if they are sitting.
• Patient can go limp and immediately fall to the floor if they are standing.
• The whole body or parts of it may immediately become limp.
• They may drop whatever they are holding.
• Eyelids become droopy.
• They usually last for less than 15 seconds.
• Jerking-like movements

Question 28

Atonic Seizures 1st line treatment:

Answer 28

Sodium	Valproate (except	for	woman	of childbearing	age)
• Initially	 600 mg	 daily	 in	 1–2	 divided	 doses,	 then	 increased	 in	 steps	 of	 150–300 mg	 every	3 days;	 maintenance	 1–2 g	 daily,	 alternatively	 maintenance	 20–30 mg/kg	 daily;	maximum	2.5 g	per	day	
• If	ineffective,	offer	lamotrigine	as	adjunctive
o Adults:	Initially	25 mg	once	daily	for	14	days,	then	increased	to	50 mg	once	daily	for	further	 14	 days,	 then	 increased	 in	 steps	 of	 up	 to	 100 mg	 every	 7-14 days;	maintenance	 100–200 mg	 daily	 in	 1–2	 divided	 doses, dose	 titration	 should	 be	repeated	if restarting	after	interval	of	more	than	5	days

Question 29

Atonic Seizures 2nd line treatment:

Answer 29

Lamotrigine
• Initially 25 mg once daily on alternate days for 14 days, then 25 mg once daily for further 14 days, then increased in steps of up to 50 mg every 7–14 days; maintenance 100–200 mg daily in 1–2 divided doses, dose titration should be repeated if restarting after interval of more than 5 days

Question 30

Status Epilepticus

Answer 30

If a person has repeated seizures in which seizure activity does not stop or seizures follow on from each other without the person recovering in between, this is known as Status Epilepticus. There are 2 types; convulsive and non-convulsive. Convulsive status epilepticus is used
to describe prolonged or repeated tonic-clonic seizures, whereas non-convulsive describes long absence or complex partial seizures. Generalised tonic-clonic status
epilepticus is a medical emergency associated with high morbidity and mortality

Question 31

Status Epilepticus treatment

Answer 31

Adults should be managed with diazepam 10-20 mg rectally, which can be re-administered after 15 minutes, or midazolam 10 mg given buccally. If seizures continue give IV lorazepam 0.1 mg/kg (usually a 4 mg bolus, repeated once after 10-20 minutes) and give the patient their usual AED medication. For sustained control or if seizures continue give phenytoin infusion. In refractory status, patients should receive general anaesthesia with either propofol, midazolam or thiopental sodium, the anaesthetic should be continued for 12-24 hours after the last clinical seizure, then dose tapered.

Question 32

General common side effects of AEDs include:

Answer 32

Drowsiness
• Lack	of	energy
• Agitation
• Headaches
• Tremor
• Hair	loss	or	unwanted	hair	growth
• Swollen	gums
• Rash

Question 33

Specific side effects which patients should look out for when taking certain drugs are

Answer 33

• Carbamazepine – Dose related side effects such as headache, ataxia, drowsiness
• Lamotrigine – Steven Johnson syndrome with occurs within the first 8 weeks of treatment
• Sodium Valproate – Hepatic function presents as persistent vomiting, abdominal pain,
jaundice, and pancreatitis which presents with acute upper severe abdominal pain
• Ethosuximide – Fever, sore throat, mouth ulcers, bleeding (if experience any of these patient must have a FBC)
• Topiramate – Eye disorders such as displacement of the lens and iris