epilepsy and sleep disorder case

Question 1

what are anti epileptics used for?

Answer 1

used to prevent or control epilepsy commonly known as seizures.

Question 2

what is a seizure?

Answer 2

a seizure is a sudden burst of uncontrolled electrical activity in the brain that occurs when neutrons becomes excessively active.

Question 3

how are seizures classified?

Answer 3

generally classified into 2 major groups depending on where they begin in the brain.
FOCAL SEIZURE: affects initially one portion of the brain typically one hemisphere and may occur with or without impairment of awareness
GENERALISED SEIZURES: affects both sides of the brain at the same time and almost always causes loss of consciousness

Question 4

how can seizures be viewed?

Answer 4

seizures can be viewed as the result of an imbalance between inhibitory and excitatory processes in the brain that produce either too little inhibition or too much excitation.

Question 5

how does neutrons pass signals to one another?

Answer 5

the main form of communication among neutrons occurs through the travelling wave electrical excitation called action potential. an action potential is the synchronising of opening and closing of ion channels.

when at res the inside of the neurone is slightly more negative than the outside.an action potential starts when voltage gated sodium channels ope allowing positively charged sodium ions to rush into the cell thus reversing the polarisation of the membrane.

membrane depolarisation leads to the opening of high voltage activated calcium channels which then allows calcium ions to enter the neurone therefore triggering glutamate from the vesicles into the synaptic cleft.

next glutamate binds to two types of receptors on the post-synaptic neurone

1) AMPA receptors that upon binding to glutamate, opens and permits entry of the sodium ions.
2) NMDA receptors that open and permit entry of calcium ions

in addition calcium may enter through low-voltage activated calcium channels also known as t-type calcium channels which open in response to small depolarisation at or below resting membrane potential

all the influx of positively charged ions, again leads to depolarisation and propagation of action potential. if there is too much glutamate around neurone, this can lead to hyper-excitability and seizures may result in seizures. this doesn’t usually happen because there are also inhibitory neurone around that reduce excitable impulses. these inhibitory neurones release neurotransmitters GABA which binds to GABA-A receptors on the excitatory neurone. causes them to open and allow negatively charged chloride ions to enter in.

this causes an membrane potential to be more negative inside than outside and therefore limiting the neurones ability to respond to further stimulation. once GABA dissociates with GABA-A receptor, it becomes removed from the synaptic cleft by re-uptake through GABA-transporter- 1 and it is degraded by an enzyme GABA-T. too little glutamate can also cause hyper excitability in neurones which can also cause seizures

Question 6

what is the aim for anti epileptic drugs

Answer 6

the therapeutic intervention is simply to lower neural excitability and/or enhance neural inhibition.

Question 7

describe how blocking voltage gated sodium channel will help epileptic patients?

Answer 7

one way is to prevent excessive firing of an action potential in neurones by blocking the voltage gated sodium channels. this reduces the amount of sodium from entering the neurone.

examples of these drugs includes Carbamazepine, Oxcarbazepine, Lamotrigine, phenytoin, topiramate, valproic acid and zonisamide

Question 8

describe how blocking calcium channels will help epileptic patients?

Answer 8

it slows down hyper activity neurones by blocking calcium channels. works by inhibiting high voltage activated calcium channels.

examples of these drugs includes lamotrigine and topiramate and drugs that inhibit low voltage activated t-type calcium channels such as valproic acid and zonisamide

note- a lot of anti-epileptics drugs act on more than one target which can inhibit both calcium and sodium channels

topiramate has been shown to also inhibit excitatory neurotransmitters by blocking AMPA receptors

Question 9

how does Gabapentin and pregabalin work as an anti epileptic drug?

Answer 9

they work by exerting their effects by interacting with high voltage activated calcium channels. however gabapentin and pregabalin bind to a subunit of the high voltage activated calcium channel called alpha-2-delta 1. because the presynaptic channels that contain this specific subunit of alpha-2-delta-1. this appears to modulate the release of excitatory neurotransmitters such as glutamate.
inhibition of alpha-2-delta-1 containing calcium channels by gabapentin and pregabalin is one of the main reasons for their anti epileptic effects

Question 10

how does Levetiracetam work an an anti-epileptic?

Answer 10

it is an high voltage activated calcium channel blocker. works by binding to SV2A protein that is bound to the walls of the vesicles that contains glutamate. this binding impairs the synaptic release of glutamate and thus decrease in neural excitability.
FELBAMATE inhibits excitatory neurotransmission by blocking NMDA receptors.

Question 11

what drugs act on the GABA system?

Answer 11

benzodiazepines and barbiturates which work by binding to GABA-A receptors therefore prolonging the opening of the channel and permitting greater influx of negatively charged chloride ions into the neurone

Tiagabine which is a selective inhibitor of the GABA transporter. it blocks the GABA reuptake therefore permitting more GABA to be available for receptor binding on the post synaptic neurone.

Vigabatrin which irreversibly inhibit GABA-amino transferas. the enzyme is responsible for catabolism of GABA therefore increasing concentration of GABA in the brain.

Question 12

what are side effects associated with anti epileptics?

Answer 12

sedation, dizziness
visual field loss or double vision 
cognitive problems
peripheral oedema 
liver toxicity

Question 13

what is the first line for seizures for generalised seizures:

Answer 13

First line: sodium valproate

Second line: lamotrigine or carbamazepine

Question 14

what is the first line for focal seizures?

Answer 14

First line: carbamazepine or lamotrigine

Second line: sodium valproate or levetiracetam

Question 15

what is meant by absence seizure

Answer 15

Absence seizures typically happen in children. The patient becomes blank, stares into space and then abruptly returns to normal. During the episode they are unaware of their surroundings and won’t res

Question 16

what is the first line treatment is absence seizures?

Answer 16

First line: sodium valproate or ethosuximide

Question 17

what is meant by atonic seizures?

Answer 17

Atonic seizures are also known as drop attacks. They are characterised by brief lapses in muscle tone. These don’t usually last more than 3 minutes. They typically begin in childhood. They may be indicative of Lennox-Gastaut syndrome

Question 18

what is the treatment of atonic seizures?

Answer 18

First line: sodium valproate

Second line: lamotrigine

Question 19

what is meant by myoclonic seizures

Answer 19

Myoclonic seizures present as sudden brief muscle contractions, like a sudden “jump”. The patient usually remains awake during the episode. They occur in various forms of epilepsy but typically happen in children as part of juvenile myoclonic epilepsy.

Question 20

what is the management of myoclonic seizures?

Answer 20

First line: sodium valproate

Other options: lamotrigine, levetiracetam or topiramate

Question 21

how to diagnose and investigate a seizure?

Answer 21

An electroencephalogram (EEG) can show typical patterns in different forms of epilepsy and support the diagnosis. Perform an EEG after the second simple tonic-clonic seizure. Children are allowed one simple seizure before being investigated for epilepsy.

An MRI brain can be used to visualise the structure of the brain. It is used to diagnose structural problems that may be associated with seizures and other pathology such as tumours. It should be considered when:

The first seizure is in children under 2 years
Focal seizures
There is no response to first line anti-epileptic medications

Additional investigations can be considered to exclude other pathology that may cause seizures:

ECG to exclude problems in the heart.
Blood electrolytes including sodium, potassium, calcium and magnesium
Blood glucose for hypoglycaemia and diabetes
Blood cultures, urine cultures and lumbar puncture where sepsis, encephalitis or meningitis is suspected

Question 22

what is the general advise for people who are epileptic

Answer 22

Patients and families presenting with seizures need to be given advice about safety precautions, recognising, managing and reporting further seizures. It is important to avoid situations where a seizure may put the child in danger, with advise to:

Take showers rather than baths
Be very cautious with swimming unless seizures are well controlled and they are closely supervised
Be cautious with heights
Be cautious with traffic
Be cautious with any heavy, hot or electrical equipment
Older teenagers with epilepsy will need to avoid driving unless they meet specific criteria regarding control of their epilepsy. These rules change frequently so it is always worth looking them up if advising patients.

Question 23

sodium valproate

Answer 23

This is a first line option for most forms of epilepsy (except focal seizures). It works by increasing the activity of GABA, which has a relaxing effect on the brain. Notable side effects of sodium valproate include:

Teratogenic, so patients need careful advice about contraception
Liver damage and hepatitis
Hair loss
Tremor
There are a lot of warning about the teratogenic effects of sodium valproate and NICE updated their guidelines in 2018 to reflect this. It must be avoided in girls unless there are no suitable alternatives and strict criteria are met to ensure they do not get pregnant.

Question 24

Carbamazepine

Answer 24

This is first line for focal seizures. Notable side effects are:

Agranulocytosis
Aplastic anaemia
Induces the P450 system so there are many drug interactions

Question 25

Phenytoin-side effects

Answer 25

Notable side effects:

Folate and vitamin D deficiency
Megaloblastic anaemia (folate deficiency)
Osteomalacia (vitamin D deficiency)

Question 26

Ethosuximide- side effects

Answer 26

Notable side effects:

Night terrors
Rashes

Question 27

Lamotrigine- side effects

Answer 27

Notable side effects:

Stevens-Johnson syndrome or DRESS syndrome. These are life threatening skin rashes.
Leukopenia

Question 28

management of seizures

Answer 28

Put the patient in a safe position (e.g. on a carpeted floor)
Place in the recovery position if possible
Put something soft under their head to protect against head injury
Remove obstacles that could lead to injury
Make a note of the time at the start and end of the seizure
Call an ambulance if lasting more than 5 minutes or this is their first seizure.

Question 29

Management of status epileptics in the hospital

Answer 29

Secure the airway
Give high-concentration oxygen
Assess cardiac and respiratory function
Check blood glucose levels
Gain intravenous access (insert a cannula)
IV lorazepam, repeated after 10 minutes if the seizure continues
If the seizures persist the final step is an infusion of IV phenobarbital or phenytoin. At this point intubation and ventilation to secure the airway needs to be considered, along with transfer to the intensive care unit if appropriate.

Question 30

what is the presentation for some who has epilepsy?

Answer 30

• Syncope, where insufficient blood to the brain caused the patient to faint
• Hyperventilation
• Migraine
• Panic attack
• Pseudo seizure (non-epileptic attack), which is where a patient presents with a convulsion in the absence of abnormal electroactivity; it is thought to be a psychological issue
• Transient global amnesia
• Transient ischaemic attack

Question 31

what are some of the causes of epilepsy?

Answer 31

• Hypo/hyperglycaeimia
• Hypo/hypernatraemia
• Hypocalcaemia
• Hypomagneseamia
• Uraemia
• Drugs (phenothiazines, benzodiazepine withdrawal, antibiotics, antidepressants, EtOH, tramadol, antiepileptics, ciclosporin, cocaine, lithium, inteferons, barbiturates)
• Meningitis
• Encephalitis
• Head trauma
• Space Occupying Lesion
• Stroke / TIA
• Genetics (polygenetic)
• Epileptogenisis

Question 32

There are two broad categories of epilepsy: Generalised (global) and Partial (focal).

Answer 32

There are two broad categories of epilepsy: Generalised (global) and Partial (focal).
Generalised epilepsy affects the whole brain. The following types of epilepsy fall under this category:
• Absences (petit mal)
• Tonic-clonic (grand mal)
• Myoclonic (Juvenile myoclonic epilepsy)
• Tonic
• Akinetic – all muscle tone is lost, resulting in falls thus risk of head injury
Partial epilepsy affects a local area of the brain. The following types of epilepsy fall under this category:
• Simple – consciousness is maintained, so the patient is aware of the seizure
• Complex – impaired awareness
• Secondary generalised (aka Focal to bilateral tonic-clonic seizures) – starts local, then becomes generalised