An

An introduction to Introduction to Epilepsy Epilepsy

Rebecca Rebecca LiuLiu Consultant Neurologist Consultant Neurologist May 2010
Royal Free Hospital
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

Incidence Rate of Epilepsy

150

Incidence per 100,000

100

50

10

20

30

40

50

60

70

80

Age (years)

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

Classification of seizures

Generalized

Focal

Classification of seizures
Generalized

(primary generalized)

Myoclonic jerks Absence petit mal Tonic Clonic Atonic Tonic Clonic

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Classification of seizures

Generalized

Focal

Classification of seizures
Partial

/ focal / localisation-related

Simple partial (no impairment of awareness) Complex partial (impairment of awareness)

Secondarily generalized tonic clonic seizure

Seizure types

Seizure types

Temporal lobe seizures

Aura
epigastric rising sensation dj vu, jamais vu olfactory sensation gustatory sensation auditory hallucinations

Temporal lobe seizures

Ictal phenomenon automatisms
oral limb

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video

Seizure types

Frontal lobe seizures

Pre-motor Jacksonian seizures Supplementary Motor seizures Pre-frontal seizures

Speech arrest or dysphasia

video

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Seizure types

Post-ictal phenomena
Drowsiness, confusion Headache Todds paresis / hemianopia / dysphasia

Syndromic classification
Site of seizure onset

Presumed aetiology
Symptomatic 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

Malformations of cortical development (congenital)
Neoplasms Unknown

Trauma

Metabolic (alcohol)

Autoimmune

Vascular (strokes, AVMs)

Infections

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

History taking and Diagnosis

Situation, triggers warning duration movement accompanying features post ictal state direct questions for other events psychiatric history drugs / alcohol

History taking and Diagnosis

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

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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
25 uV Fp2-F8

F8-T4
T4-T6 T6-O2 Fp1-F7 F7-T3 T3-T5 T5-O1 ECG1 1 sec

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 brain
Blood, calcium Assessing acutely unwell patient

CT and MRI of Brain Tumour

CT

MRI - T1

MRI - T2

Malformations of Cortical Development

Periventricular heterotopia

Band heterotopia

Schizencephaly

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 AED
1. 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

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 individuals 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

1989 - Vigabatrin 1991 - Lamotrigine 1993 - Gabapentin 2000 - Levetiracetam 2005 - Pregabalin 2006 - Zonisamide 2007 - Rufinamide 2008 - lacosamide 2009 - Eslicarbazepine

1993 - Piracetam
1995 - Topiramate

1998 - Tiagabine
2000 - Oxcarbazepine

Choice of AED - Partial seizures

Simple partial
Complex partial Secondarily generalised

Carbamazepine Lamotrigine Oxcarbazepine Sodium Valproate Topiramate Levetiracetam

Choice of AED - Generalised seizures

Tonic Clonic Tonic-Clonic Absence Myoclonic Atonic

Valproate Lamotrigine Topiramate Levetiracetam Ethosuximide Clonazepam

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 Carbamazepine Lamotrigine Valproate Polytherapy

2.5% risk of MCM 2.7% 2.3% 5.9% 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?

Choice of AED - Generalised seizures

Tonic Clonic Tonic-Clonic Absence Myoclonic Atonic

Valproate Lamotrigine Topiramate Levetiracetam Ethosuximide Clonazepam

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

Pathophysiology of Status Epilepticus

Shorvon SD JNNP 2001

Treatment of tonic-clonic status epilepticus

ABC 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 Early Status

Lorazepam 4mg iv bolus/ Diazepam 10mg iv

Lorazepam 4mg can be repeated

Established Status

Phenytoin iv 15mg/kg at rate of 50mg/min or Phenobarbitone 10mg/kg at100mgs/min

ITU Refractory Status

General anaesthesia with either: Propofol, Thiopentone Initiate / continue maintenance AED Treat complications, Establish cause EEG monitoring Taper and stop after 12 hours

Case 1- Data Interpretation

An 84-year-old gentleman with hypertension had two secondary generalised convulsions over a twoyear 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?

Choice of AED - Partial seizures

Simple partial
Complex partial Secondarily generalised

Carbamazepine Lamotrigine Oxcarbazepine Sodium Valproate Topiramate Levetiracetam

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 Todds 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 hairdressers 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