Post on 04-Oct-2014
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
Classification of seizures
Generalized Focal
Classification of seizures
Generalized (primary generalized)
Myoclonic jerks
Absence “petit mal”
Tonic
Clonic
Atonic
Tonic Clonic
QuickTime™ and aYUV420 codec decompressorare needed to see this picture.
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
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
QuickTime™ and aYUV420 codec decompressorare needed to see this picture.
QuickTime™ and aYUV420 codec decompressorare needed to see this picture.
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
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
QuickTime™ and aYUV420 codec decompressorare needed to see this picture.
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
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