Seizures lecture

SeizuresOlivia Jagger

Academic Education F2

Learning Objectives

Define what we mean by seizures

Demonstrate achievement of learning objectives through

clinical cases

Understand the different types of seizures

Understand the causes of seizures

Know the emergency and longterm management of seizures

Know the complications of seizures and their management

Definitions - what does it all mean?

SeizureStatus

Epilepticus

Epilepsy

spontaneous uncontrolled

abnormal brain activity

Seizure >20 - 30minutes

OR

Multiple seizures frequent enough to prevent recovery between

episodes >20-30mins

tendency to have spontaneous uncontrolled

abnormal brain activity,

resulting in recurrent seizures

Pathophysiology

Action Potential

Pre-synaptic membrane

Post-synaptic membrane

Action Potential

excitatory

neurotransmitter

Ca2+

Na+

inhibitory

neurotransmitter

http://outreach.mcb.harvard.edu/animations/synaptic.swf

Pathophysiology

Glutamate is the major excitatory

neurotransmitter

GABA (gamma-

aminobutyric acid) is the

main inhibitory

neurotransmitter

Pathophysiology

Seizures are caused by abnormal synchronised

discharge of many neurons

Every individual has a seizure threshold

- the level of

excitability at which neurons will discharge

uncontrollably

In patients with epilepsy the seizure threshold is lowered and the neurons are

hyperexcitable

Triggers that push neuron excitationpast the seizure threshold include:

‣ Sleep deprivation

‣ Drugs

‣ Flickering lights‣ Infection / metabolic

disturbance

CauseIntracranial Extracranial

Underlying brain abnormality Pyrexia

• Raised intracranial pressure - cerebral tumour - cerebral odema → pregnant - eclampsia

Hypoxia

• Stroke - Thrombo-embolic - Haemorrhagic

• Biochemical ↑↓Sodium, Glucose ↓ Calcium, Magnesium ↑ Urate

Brain infections• Drugs - Prescribed / Recreational - Intoxication / Withdrawal

Intracranial Extracranial

Types of seizures

Absence

Myoclonic

Tonic-Clonic Tonic Atonic

Partial Generalised

Seizures

Simple Complex

no loss of conciousness

conciousness impaired

specific area in one cerebral hemisphere

both cerebral hemispheres

Tonic Clonic Seizures

• Prodrome• Aura• Sudden onset• Triggers

•Tonic Phase: stiffening, loss of consciousness, falls, cries out

• Clonic Phase: convulsion, jerking of arms and legs

•Excessive salivation (drooling or foaming)

•Biting of the tongue

•Loss of bowel and/or bladder control

•No breathing / random breaths

•Eye rolling

• Post-ictal• Drowsy• Confused• Agitated

Before During After

Convulsive seizure with tonic phase (stiffening) and clonic movements (jerking)

Febrile convulsions

• most common seizure disorder in childhood

• Peak age of onset 14-18 months

• Pyrexial

• Tonic-clonic

• <10 mins

• Don’t predispose to epilepsy

• ABCDE

• Rule out underlying infection

• Paediatric review if first fit

• REASSURE parents!

Presentation Management Risk Factors for Epilepsy

• First fit <9months

• Atypical seizure

• FH epilepsy

• Evidence of developmental delay

• Abnormal neurology on examination

Emergency Management

You are the F1 on call and you’re bleeped...

What is your initial management?

“Please come quickly a patient is having a

seizure and we don’t know what to do!”

Emergency Management

A

B

C

D

Airway

Breathing

Circulation

Disability

• Patent?• Give airway support if needed

• RR• O2 sats• give O2

• HR• BP• Cap refill• IV access and bleed• Head injury?• Infection?• Bleeding?• Temperature?• BM?

Start treating underlying cause

Management of seizuresStepwise approach

Benzodiazepine


Initial A,B, C, D

Phenytoin

Paralysis and Ventilation

Action Potential

Action Potential

Benzodiazepine - mechanism of action

If seizure does not resolve after a few minutes give a benzodiazepine

Reduces excessive neuronal firing

Enhances the inhibitory effect of GABAGAB

A

Benzodiazepines

Lorazepam 0.1mg/kg IV (2-4mg bolus repeated after 15 mins)

Diazepam 10-20mg rectally (repeated after 15 mins)

Midazolam 10mg buccally (repeated after 15 mins)

First lineIV Access

Second lineNo Access

Side Effects

• sedation• suppressed breathing• hypotension (worse with IV)


Phenytoin

Initial A,B, C, D


Benzodiazepine


Phenytoin - mechanism of action

Action Potential

Action Potential

Inhibits excitatory neuronal

transmission

Blocks voltage-sensitive sodium channels

If seizure does not resolve after benzodiazepine start a phenytoin infusion

Na+

Infusion dose

20mg/kg over 20 minutes

Phenytoin - Pharmacokinetics

Continuous BP and ECG monitoring

• Mainly hepatic break down• Zero order kinetics• Narrow therapeutic range• Risk of toxicity

Phenytoin - Side Effects

•Gum hypertrophy•Nausea / vomiting

•Headaches•Skin rashes•Hypotension

•Arrhythmias (bradycardia)•Bone marrow suppression

- Megaloblastic anaemia•Teratogenicity

•Ataxia•Nytagmus•Drowsiness•Dysphasia

•Coma death•Arrhythmias (bradycardia)•Hypotension

Monitor serum levels, FBC, LFTsIf IV: BP and ECG (especially QT

interval)

At therapeutic levels At toxic levels


Initial A,B, C, D


Benzodiazepine


Phenytoin

If seizure not resolved following initial

management patient may need paralysis and

ventilation

Should be done in ITU by an expert

* Never spend long than 20 minutes with a patient with a seizure before calling an

anaesthetist! *

Longterm Management - Drugs

Absence

Myoclonic

Tonic-Clonic Tonic Atonic

Partial Generalised

Seizures

Simple Complex1st line carbamazepine /2nd line sodium valproate

1st line sodium valproate /

2nd line levetiracetam


2nd line lamotrigine1st line sodium valproate


2nd line levetiracetam


2nd line lamotrigine

1st line sodium valproate

1st line carbamazepine /2nd line sodium valproate


2nd line ethosuximide


2nd line ethosuximide

Summary of longterm drug therapy

Type of Seizure 1st line drug 2nd line drug

PARTIAL Simple and

Complex

Carbamazepine(Inhibits sodium channels reducing action potential

propagation )

Sodium Valproate

GENERAL

Absence Sodium Valproate(Inhibits GABA

transaminase so enhances inhibitory affect

of GABA)

Ethosuximide (Calcium channel

inhibitor)

Myoclonic

Sodium Valproate Levetiracetam(Mechanism of

action unknown)

Tonic-Clonic

Sodium Valproate Lamotrigine(Inhibits sodium

channels reducing action potential

propagation)

Tonic Sodium Valproate

Atonic Sodium Valproate

Sodium Valproate - mechanism of action

Action Potential

Action Potential

Reduces excessive neuronal firing

Enhances the inhibitory effect of GABAGABA

Inhibits GABA transaminase (inhibits GABA breakdown)

Sodium Valproate - side effects

• Thinning and curling of hair• Hepatotoxicity (P450 inhibitor)• Weight gain• Thrombocytopaenia• Pancreatitis• Teratogenicity

•Significantly increased risk of birth defects with

Sodium Valproate

•The relative risk is 2-5x higher than other antiepileptic drugs

•Extreme caution in women of childbearing age

At therapeutic levels In Pregnancy

Cytochrome P450 Enzymes

• P450 cytochromes are the major enzymes involved in drug metabolism

• mainly act in the liver

INHIBITORS

Sodium Valproate

INDUCERS

Phenytoin / Carbamazapine

P450 inducers speed up the metabolism of drugs

(decrease drug availability)

P450 inhibitors lead to build up of

unmetabolised drugs (increase drug

availability)

Longterm Management - Surgery

Surgery may be considered when there is:

•A mass lesion in the brain•Uncontrolled epilepsy

Living well with Epilepsy

• Safety Advice

• Ensure treatment compliance

• Have a predetermined plan for seizure emergencies and rescue treatment

• First fit - cannot drive for 6 months

• Second or further fits - cannot drive for 12 months

• Medication change in the last 6 months - cannot drive for 6 months

• ‘night-time’ only seizures - they can drive, if they have not had a ‘day time’ seizure for 3 years

Lifestyle Driving

Todd’s Paresis

Complications

Brain Injury

Physical Injury

Sudden Unexpected Death in Epilepsy

Clinical Case 1

• A 70kg 27 year old male presents with five minutes of generalised tonic-clonic seizures.

• The immediate management would be:

A. 4mg Lorazepam IV

B. Maintain a clear airway

C. Call an anaesthetist

D. 20mg Diazepam rectally

Clinical Case 1

• Following an ABCD assessment, with attainment of IV access, he continues to fit.

• The appropriate management would be:

A. Lorazepam IV

B. Phenytoin IV

C. Midazolam buccally

D. Diazepam rectally

Clinical Case 1

• 20 minutes after the administration of 4mg lorazepam he continues to fit.

• The appropriate management would be:

A. Lorazepam IV

B. Phenytoin IV

C. Move to ITU for paralysis and assisted ventilation

D. hold him down to prevent injury

Clinical Case 1• His seizure resolves with an IV Phenytoin infusion. Baseline

investigations are unremarkable. He is discharged home for follow up in the ‘first fit’ clinic.

• What advice should he be given about driving?

A. He cannot drive for 6 months

B. He cannot drive for 12 months

C. He can continue to drive until he has been reviewed by a Neurologist in clinic

D. He cannot drive again until he retakes his driving test

Clinical Case 2An ambulance brings a 15 month old boy to ED following a seizure.

His mother reports he suddenly started shaking his arms and legs and his eyes had a blank stare. This went on for what seemed like 5 minutes so she called 999. There is no vomiting, diarrhea or rash. He has no significant past medical history.

O/E Temperature 39C, slight cough and mild nasal congestion. Alert and interactive. Normal neurological examination.

The immediate management would be:

• Maintain a clear airway

• 10mg Diazepam rectally

• 5mls Calpol

• IV access and bloods

Clinical Case 2He was reviewed by a Paediatrician who found no evidence of

developmental delay or systemic infection. His temperature settled with Calpol.

The likely diagnosis is:

• Epilepsy

• Febrile Convulsion

A.Absence Seizure

B.Brain tumour

Clinical Case 2

• Which of the following are Risk Factors for development of epilepsy in febrile convulsions:

• (select as many as apply)

A. Family history of a febrile convulsion

B. Generalised seizure

C. Recurrent febrile seizures

D. Febrile seizure onset in first nine months

E. Evidence of developmental delay

Clinical Case 3•An 85 year old gentleman is brought in by his grandson with acute confusion and frank haematuria.

•Past medical history: Hypertension, Hypercholesterolaemia, AF and Epilepsy

•Drug History: Warfarin, Simvastatin, Sodium Valproate

•Which one initial investigation will most aid your diagnosis?

• Sodium Valproate level

• INR

• CT head

• Cystoscopy

Clinical Case 3

• Which of the following anti-epileptic drugs are INDUCERS of P450 cytochromes?

• (select as many apply)

A. Phenytoin

B. Carbamazepine

C. Sodium Valproate

D. Lamotrigine

Clinical Case 4

• A 37 year old man presented to the Emergency department following an epileptic seizure. He had suffered from epilepsy since childhood and takes sodium valproate and levertiracetam. Two hours following the seizure he complained that he was still unable to move his right arm.

• The likely diagnosis is:

A. Partial Seizure

B. Todd’s Paresis

C. TIA

D. Stroke

Clinical Case 4

• Which of the following statements are correct about Todd’s Paresis?


A. There is paralysis of limbs lasting several hours after a seizure

B. It is a type of lower motor neurone paralysis

C. It has to be differentiated from acute stroke

D. It usually resolves within 1-2 weeks

E. It is associated with dysphasia

AMK practice

• The most appropriate longterm drug for treatment of generalised tonic-clonic seizures is:

A. Sodium valproate

B. Lamotrigine

C. Ethosuximide

D. Carbemazepine

E. Lorazepam

AMK practiceThe most appropriate longterm drug for treatment of complex partial

seizures is:

(Select as many as apply)

• Phenytoin

A. Sodium valproate

B. Carbamazepine

B. Ethosuximide

C. Lamotrigine

AMK practice• A 30 year old lady is started on phenytoin for recurrent

tonic-clonic seizures. Past medical history includes prednisolone for brittle asthma. Two weeks later she returns to clinic and complains that her asthma has worsened since she began the phenytoin therapy.

• A likely reason for this new change is that phenytoin:

• interferes with absorption of the prednisone

• stabilizes cell membranes, preventing the prednisone from diffusing tothe site of action

• accelerates hepatic degradation of prednisone

• induce renal excretory pathways, accelerating urinary excretion of theprednisone

• Decreases hepatic degradation of prednisolone

AMK practice

• Select 3 drugs with similar proposed mechanisms of action:

A. Phenytoin

B. Carbamazepine

C. Lamotrigine

D. Sodium valproate

E. Ethosuximide

AMK practice• Which of the following statements about Phenytoin are

true:


A. It follows first-order kinetics

B. It follows zero-order kinetics

C. It is mainly metabolised by the kidneys

D. It has a narrow therapeutic window

E. It can cause bone marrow suppression

AMK practice• Symptoms of Phenytoin toxicity include:


A. Gingival hyperplasia

B. Nystagmus

C. Ataxia

D. Dysphasia

E. Bone marrow suppression

Seizures SummarySeizures are caused by abnormal synchronised discharge of many neurons

Seizures are classified as Partial (affect a small area of one cerebral hemisphere) and Generalised (affecting both cerebral hemispheres)

Anything that lowers the excitation threshold of neurons (makes them hyper excitable or reduces inhibition) can result in seizures

A seizure is an emergency ‘Status Epilepticus’ if it lasts >20 - 30minutes OR multiple seizures frequent enough to prevent recovery >20-30mins

The stepwise management of seizures is ABCD assessment, Benzodiazepine, Phenytoin, Paralysis and assisted ventilation

The first line drug for longterm management of generalised seizures is Sodium Valproate

The first line drug for the longterm management of partial seizures is Carbamazepine

Phenytoin displays zero-order kinetics and has potential for toxicity

Sodium Valoprate is 2-5x more teratogenic than any other anti-epileptic agent

Please send any questions that occur

to you later to [email protected]

et

Questions

Health & Medicine

Seizures lecture