Rf Wk5 Epilepsy Ppt

An Introduction to Epilepsy

Rebecca Liu

Consultant Neurologist

Royal Free Hospital

May 2010

An introduction to

Epilepsy

Rebecca Liu

Consultant Neurologist

May 2010

Case Scenario

• A 37 year old lorry driver brought into

A+E one night. Had been unwell with

gastroenteritis and complaining of

abdominal pain. Wife found him collapsed

on bathroom floor and observed

generalised twitching movements of all

limbs. When he came around, slightly

dazed. He had been incontinent of urine.

Has he had a seizure?

• Yes

• No

• Not sure

What would you do next?

• Order an EEG

• Order a CT / MRI Brain scan

• Perform an ECG

• Other

Would you stop him driving?

• Yes

• No

Learning Objectives

• Be aware that epilepsy can be classified in terms of seizure type and syndrome.

• Be able to take a focused seizure history

• Recognise that epilepsy is a CLINICAL diagnosis

• Consider possible differential diagnoses

• Be able to investigate and devise a structured

management plan for patients with epilepsy

• Be able to counsel patient on lifestyle issues

• Have a protocol for managing Status Epilepticus

Plan

• Definition and classification

• Epidemiology

• Clinical presentations and videos

• Break

• Management of epilepsy

• Special interest women and epilepsy

Status Epilepticus

• QUIZ

Definition

“ the occurrence of recurrent and

unprovoked transient paroxysms of

excessive or uncontrolled discharges of

neurons, which may be caused by a

number of different aetiologies, leading

to a change in perception or behaviour”

Epidemiology

• Incidence = no. of new cases / time

(year)/population in the middle of that

period– 50-70 per 100,000 in developed societies

• Bimodal peak incidences

0 10 20 30 40 50 60 70 80

Age (years)

150

100

50Inc

ide

nc

e p

er

10

0,0

00

Incidence Rate of Epilepsy

Why is epilepsy important?

• Commonest serious disorder of the brain

Prevalence (no. of cases at a given time/population) = 1:131

• Lifetime risk of having a seizure is 3-5%

• High rate of misdiagnosis

• Epilepsy poorly managed:

– 70% with epilepsy should be seizure free

Impact of Epilepsy

Physical

Social

Psychological

Physical Impact

• Three times more likely to die than normal

• Due to : underlying disease

accidents

status epilepticus

sudden Unexpected Death (SUDEP)

Psychological and Social Impact

• Suicide risk - 5 times the general population

rate

• Often underachieve at school

• Social isolation and stigmatisation

• Low rates of marriage

• High unemployment, unable to drive

Classification

Seizure classification

Syndromic classification

Classification of seizures

(ILAE 1981)

Generalized Focal


Generalized Focal


Generalized (primary generalized)

Myoclonic jerks

Absence “petit mal”

Tonic

Clonic

Atonic

Tonic Clonic

QuickTime™ and aYUV420 codec decompressorare needed to see this picture.


Generalized Focal


Partial / focal / localisation-related

Simple partial (no impairment of awareness)

Complex partial (impairment of awareness)

Secondarily generalized tonic clonic seizure

Seizure types

Temporal lobe seizures

Aura

epigastric rising sensation

déjà vu, jamais vu

olfactory sensation

gustatory sensation

auditory hallucinations

Temporal lobe seizures

Ictal phenomenon

automatisms

oral

limb

videoQuickTime™ and a

YUV420 codec decompressorare needed to see this picture.

Seizure types

Pre-motor

Jacksonian

seizures

Frontal lobe seizures

Supplementary

Motor seizuresPre-frontal

seizures

Speech

arrest or

dysphasia

video


Seizure types

Post-ictal phenomena

• Drowsiness, confusion

• Headache

• Todd‟s paresis / hemianopia /

dysphasia

Syndromic classification

Site of seizure onset

Presumed aetiologySymptomatic

Cryptogenic

Idiopathic

Influences management and prognosis

Idiopathic generalised

epilepsies

Childhood Absence Epilepsy

Juvenile Myoclonic Epilepsy

• Juvenile Absence Epilepsy

• GTCS On Awakening

• Eyelid myoclonia with absences

Symptomatic focal epilepsies

• Hippocampal (mesial temporal)

sclerosis

Hippocampal sclerosis

Volume loss on T1-weighted scan

Signal increase on T2-weighted scan

Secondary causes of epilepsy

Unknown

Metabolic

(alcohol)Autoimmune

Malformations of cortical

development (congenital)

TraumaNeoplasms

InfectionsVascular

(strokes, AVMs)

Diagnosing Epilepsy

History taking and Diagnosis

• Epilepsy is a clinical diagnosis

• Take time over the history

• Collateral history of paramount importance

• Investigations are supportive not diagnostic


– Situation, triggers

– warning

– duration

– movement

– accompanying features

– post ictal state

– direct questions for other events

– psychiatric history

– drugs / alcohol


• Identify early risk factors for epilepsy

– Birth and delivery

– Developmental milestones

– Febrile seizures

– Meningitis/encephalitis

– Significant head injury

– Family history

If not epilepsy, what is it?

Differential diagnosis of blackouts

• Syncope

• Vasovagal, cardiac

• Psychogenic

• Panic attacks

• Dissociative seizures / non-epileptic

• Other

• Migraine

• Hypoglycaemia

• Cataplexy

• increased ICP

Differential diagnosis of focal

seizures

• TIA

• Transient global amnesia

• Tonic spasms of MS

• Focal dystonias

• Migraine

• Parasomnias - non REM, REM, periodic limb movements

• Hypoglycaemia

• Depersonalisation / Panic attacks

Seizures Vs Syncope

Video


Investigations

• Blood tests

• ECG

• EEG

• MRI

• Others:

– Ictal video - hand held home video or video

EEG, ambulatory ECG, CSF

Investigation

• Bloods

– glucose

– electrolytes esp Na / Ca / Mg

– renal

– liver

– full blood count

EEG

1 sec

25 uV

Fp2-F8

F8-T4

T4-T6

T6-O2

Fp1-F7

F7-T3

T3-T5

T5-O1

ECG1

Investigation

• EEG

• highest yield during seizure (but can be negative in SPS and frontal lobe seizures)

– overall 50% yield

– up to 80% with sleep EEG

– Photosensitivity / hyperventilation

– Depth EEG recording (pre-surgical evaluation)

• Never start AED Treatment on basis of abnormal EEG unless findings match history.

Generalized

epilepsy

Brain Imaging

MRI brain Low grade tumours

Abnormal blood vessels

Developmental abnormalities, scars

• Cause can determine prognosis and treatment

• Essential in selecting patients for epilepsy surgery

CT brainBlood, calcium

Assessing acutely unwell patient

CT and MRI of Brain Tumour

CT MRI - T1 MRI - T2

Malformations of Cortical

Development

Periventricular

heterotopia

SchizencephalyBand

heterotopia

Investigation

• Others when refractory or when

diagnosis uncertain:

• Gold standard = Video-EEG Telemetry

• Prolonged ECG (24 hr >>>Reveal)

Management

• Information / Epilepsy Nurse Specialist

• Lifestyle counselling

• Medications

• Surgery

Information

• Stigma

• Concordance

• Morbidity including SUDEP

• Family

Information

• Lifestyle

– Safety

– Trigger avoidance, alcohol

– Driving - DVLA regulations

– work

Treatments

• Medical

• Surgical

Medication

• starting

• choosing

• continuing

• compliance

• stopping

Medication

• Starting - when?

• Clear provoked seizure - alcohol X

– 2 or more seizures

– Single unprovoked seizure ?

• Likely to recur - EEG / MRI/ Focal deficit/LD

• Severe initial seizure

• Lifestyle considerations

Goals of AED Treatment

• Complete seizure freedom

• No adverse effects

• User friendly

– Once or twice daily

– No drug interactions

• Maintenance of normal lifestyle

Medication

• Choosing an AED1. Seizure type and Epilepsy Syndrome

2. Individual characteristics

• Gender - OCP/ teratogenesis

• Age

• Co-morbidity - renal / liver disease

• Lifestyle

• Impact of adverse effects

• NICE Epilepsy guidelines www.nice.org.uk

SIGN www.sign.ac.uk

http://www.nice.org.uk/

http://www.sign.ac.uk/

Medication golden rules

• Aim for monotherapy

• “Start Low and Go Slow”

• Aim for the lowest effective maintenance dose

• Warn about side effects

• Be aware of potential drug interactions

• Do not overuse AED blood levels!

• Lab guidance range may differ from individual‟s „therapeutic range‟

Anti-epileptic drugs in the UK

• „Oldies‟

– Acetazolamide

– Carbamazepine

– Clobazam

– Ethosuximide

– Phenobarbitone

– Phenytoin

– Primidone

– Sodium Valproate

Newer anti-epileptic drugs in the

UK

• 2000 - Levetiracetam

• 2005 - Pregabalin

• 2006 - Zonisamide

• 2007 - Rufinamide

• 2008 - lacosamide

• 2009 - Eslicarbazepine

•1989 - Vigabatrin

•1991 - Lamotrigine

•1993 - Gabapentin

•1993 - Piracetam

•1995 - Topiramate

•1998 - Tiagabine

•2000 - Oxcarbazepine

Simple partial

Complex partial

Secondarily

generalised

Carbamazepine

Lamotrigine

Oxcarbazepine

Sodium Valproate

Topiramate

Levetiracetam

Choice of AED - Partial seizures

Tonic

Clonic

Tonic-Clonic

Absence

Myoclonic

Atonic

Valproate

Lamotrigine

Topiramate

Levetiracetam

Ethosuximide

Clonazepam

Choice of AED - Generalised seizures

Response to Treatment

• 47% remit with first AED

• 11% with second AED

• 9% with third AED

• <5% subsequently

Stopping AED Treatment

• After seizure free for >2 years

• Recurrence risk - range 11-41%

• Guided by epilepsy syndrome, other risk

factors

Stopping AED Treatment

Stopping AEDs

driving

employment

lifestyle

Continuing AEDs

Side effects

Teratogenic risks

Employment

Surgical Treatment

• Usually undertaken for medically refractory

seizures

• Aim is to remove the epileptic focus or interrupt

the pathways of seizure spread

• 60-70% seizure free after temporal lobectomy

Hippocampal

Sclerosis

Post-temporal

lobectomy

Special situations

• Women and Epilepsy

• Status Epilepticus

Women and Epilepsy

Case Scenario

15 year old girl

Two generalised tonic-clonic seizures 6 weeks

apart

Early morning myoclonic jerks

Otherwise perfectly well

Has boyfriend!

What is her syndromic diagnosis?

What are the particular considerations for women of

childbearing age who have epilepsy?

Consider

• AEDs and appearance

• Female hormones and seizure control

• Interaction with the OCP

• Effect of AEDs / epilepsy on fertility

• Teratogenic effects of AEDs

• Seizure control during and after pregnancy

• AEDs and breastfeeding

Contraception

• Enzyme inducers e.g. phenytoin, carbamazepine reduce OC levels

• OCP reduces levels of lamotrigine

• Solution: take at least 50mcg oestradiol

reduced contraceptive efficacy

Depo-Provera recommended

Teratogenic effects of AEDs

• Effect on embyronic and fetal development

Major malformations

Minor abnormalities

Neurocognitive delay

Malformation Risks of AEDs

• No AED 2.5% risk of MCM

• Carbamazepine 2.7%

• Lamotrigine 2.3%

• Valproate 5.9%

• Polytherapy 5.4%

Malformation Risks of AEDs

Overall

• Generally reassuring, overall MCM rate ~90%

• If need AED treatment, aim for monotherapy

• VPA associated with higher relative risk of

MCMs, esp if polytherapy

Women and Epilepsy

Case Scenario

15 year old girl

Two generalised tonic-clonic seizures 6 weeks

apart

Early morning myoclonic jerks

Otherwise perfectly well

Has boyfriend!

Will you treat her?

What with?

Tonic

Clonic

Tonic-Clonic

Absence

Myoclonic

Atonic

Valproate

Lamotrigine

Topiramate

Levetiracetam

Ethosuximide

Clonazepam

Choice of AED - Generalised seizures

Special situations - Status Epilepticus

• Epileptic activity persists for >30 minutes

• Prolonged seizures / no recovery in between.

• Tonic-clonic and non convulsive status

epilepticus

• Medical emergency - in practice, treat after 5

minutes

Status Epilepticus

• More common in children, learning disability, structural lesion

• Affects ~5% adults with epilepsy

• Often 1st presentation of seizures

• 40% admitted to ITU have dissociative seizures

• Precipitants

• Significant morbidity and mortality

Shorvon SD JNNP 2001Pathophysiology of Status Epilepticus

Treatment of tonic-clonic status

epilepticus

• A B C

• Administer O2

• Take bloods: FBC, renal, liver function, Mg, Ca, anticonvulsant levels, toxicology?

• Give glucose if hypoglycaemia suspected

• Iv thiamine and glucose if alcoholism suspected

• Correct metabolic abnormalities

• Inotropes for hypotension

Premonitory

phase

Lorazepam 4mg can be

repeated Early Status

Phenytoin iv 15mg/kg at rate of 50mg/min or

Phenobarbitone 10mg/kg at100mgs/min

Established

Status

General anaesthesia with either:

Propofol, Thiopentone

Initiate / continue maintenance AED

Treat complications, Establish cause

EEG monitoring

Taper and stop after 12 hours

Refractory

Status

ITU

Lorazepam 4mg iv bolus/

Diazepam 10mg iv

Case 1- Data Interpretation

• An 84-year-old gentleman with hypertension had two secondary generalised convulsions over a two-year period.

• CT brain showed extensive small vessel cerbrovascular disease. He was on treatment with a thiazide diuretic and aspirin.

• Treatment was commenced with carbamazepine retard at 200 mg twice daily. Four weeks later he present to A/E with confusion, lethargy and dizziness.

• His routine bloods showed the following;

• FBC – normal

• Na+ 120

• K+ 4.2

• Urea 6.4

• Creatinine 98 •

• Describe the abnormality

• What is the most likely diagnosis?

• What medication change would you make to improve treatment?

Simple partial

Complex partial

Secondarily

generalised

Carbamazepine

Lamotrigine

Oxcarbazepine

Sodium Valproate

Topiramate

Levetiracetam

Choice of AED - Partial seizures

Case 2 – Data Interpretation

• A 75-year-old gentleman had been treated with phenytoin 300mg once daily for 7 years. He suffered approximately one seizure every 18 months and his phenytoin level was within the therapeutic range.

• However, after suffering three generalized tonic clonic seizures within six weeks his phenytoin had been increased to 350mg once daily.

• Five days after taking the increased dose he presented to A/E with unsteadiness, nausea and vomiting.

Case 2

• His blood test results were as follows;

• FBC normal

• Na+ 129

• K+ 4.4

• Urea 5.2

• Creatinine 104

• Phenytoin 25.1 mg/L (ref 10 – 20 mmol/L)

• What are the abnormalities?

• What is likely to be causing his symptoms?

• What is the mechanism of this phenomenon?

Question 1

• What is the commonest cause of new onset epilepsy in the elderly?

– Metastatic brain disease

– Small vessel cerebrovascular disease

– Primary brain tumour

– Electrolyte disturbance

– Herpes encephalitis

Question 2

• Which of these is most likely to represent a post-ictal phenomenon following a seizure of occipital lobe onset?

– Confusion

– Dysphasia

– Todd‟s paresis

– Psychosis

– Hemianopia

Question 3

• Which of these medications is most likely to

cause a Stevens-Johnson syndrome?

– Phenytoin

– Topiramate

– Lamotrigine

– Levetiracetam

– Phenobarbital

Clinical Case

• A 27 yo woman presents with 2 yr hx of

episodes of loss of consciousness

• 1st episode occurred while working in

hairdresser‟s

• Hx?

• Ix?

• Mx and Rx

Summary

• 1. Diagnosis is clinical• Eye-witness account essential

• Seizure and syndrome classification

• Diagnostic certainty before treatment

• 2. Investigations

• EEG, ECG, Brain imaging

• 3. Holistic management of patient• Counselling

• Treatment (individualised)

• Surgical referral if necessary

Rf Wk5 Epilepsy Ppt

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