Epilepsy

K J GOH Division of Neurology Department of Medicine University of Malaya

Goh KJ, Neurology, UM

Epilepsy
Introduction
Terminology Classification

Diagnosis
History and physical examination Laboratory investigations

Prognosis
Remission of seizures Mortality
Goh KJ, Neurology, UM

Epilepsy
Introduction
Terminology Classification

Diagnosis
History and physical examination Laboratory investigations

Prognosis
Remission of seizures Mortality
Goh KJ, Neurology, UM

Terminology
Epileptic seizure - clinical manifestations of an abnormal, excessive and synchronous electrical activity of the neurons in the cerebral cortex. This may be an alteration in behaviour or perception Epilepsy chronic clinical disorder in there is recurrent epileptic seizures

Goh KJ, Neurology, UM

Introduction
Epilepsy is the commonest chronic serious neurological disorder Prevalence of 0.5 1.0 per cent in the general population Age adjusted incidence of 30 50 per 100 000, higher at extremes of ages

Goh KJ, Neurology, UM

Classification
Epileptic seizure
Classification based on clinical and electroencephalographic (EEG), both ictal and interictal, features

Epilepsy and epileptic syndrome

Classification based on clinical history, physical examination, seizure type, EEG and other laboratory findings

Goh KJ, Neurology, UM

Goh KJ, Neurology, UM

Classification of seizures
Partial
simple complex secondarily generalised

Generalised
Absence Myoclonic Tonic, Clonic, Tonic-clonic TonicAtonic Unclassified

Goh KJ, Neurology, UM

Goh KJ, Neurology, UM

Goh KJ, Neurology, UM

Classification of Epileptic Syndromes

Localisation related
idiopathic symptomatic cryptogenic

Generalised
idiopathic symptomatic cryptogenic

Undetermined and special syndromes

Goh KJ, Neurology, UM

Revision of classification
Difficulty in pigeon-holing epileptic disorders pigeoninto the various dichotomies viz. focal vs. generalised; idiopathic vs. symptomatic Lack of localising information less useful when evaluating for epilepsy surgery New diagnostic scheme of 5 axes (Engel, 2001)

Goh KJ, Neurology, UM

Proposed Diagnostic Scheme*

Axis 1: ictal phenomenology description of the clinical seizure Axis 2: defining the seizure type Axis 3: syndromic diagnosis (when possible) Axis 4: aetiology (when possible) Axis 5: degree of impairment (optional)
* Engel, Epilepsia, 2001
Goh KJ, Neurology, UM

Epilepsy
Introduction
Terminology Classification

Diagnosis
History and physical examination Laboratory investigations

Prognosis
Remission of seizures Mortality
Goh KJ, Neurology, UM

Epilepsy
Introduction
Terminology Classification

Diagnosis
History and physical examination Laboratory investigations

Prognosis
Remission of seizures Mortality
Goh KJ, Neurology, UM

History
Diagnosis of epilepsy usually depends on an accurate description of the ictal event Seizure history
Precipitants Prodrome (warning symptoms) Ictal episode PostPost-ictal symptoms

Other history medical, family, social and drug history

Goh KJ, Neurology, UM

Examination
Generally less helpful unless
Focal neurological deficits Stigmata of underlying systemic disease Cardiac findings other causes of a blackout

Witnessing an attack!

Goh KJ, Neurology, UM

Goh KJ, Neurology, UM

Goh KJ, Neurology, UM

Seizure
Precipitant Prodrome Onset Duration Convulsions Incontinence Biting tongue Breathing Post ictal confusion Recovery Self injury Rare (flashing lights, HV)

Syncope
Common (upright posture, blood)

Psychogenic episode
Common (emotional factors) Uncommon Gradual Prolonged (may be hours) Atypical movements Uncommon Rare HV Rare Variable Uncommon

Common (epileptic Common aura) Sudden 1-3 Minutes Gradual 1-3 Seconds

Common (if Common (may convulsive seizures) have brief jerks) Common Common Quiet Common, sleeps Slow Common Uncommon Uncommon Apnoea Rare Rapid
Goh KJ, Neurology, UM

Rare

Epilepsy
Introduction
Terminology Classification

Diagnosis
History and physical examination Laboratory investigations

Prognosis
Remission of seizures Mortality
Goh KJ, Neurology, UM

Epilepsy
Introduction
Terminology Classification

Diagnosis
History and physical examination Laboratory investigations

Prognosis
Remission of seizures Mortality
Goh KJ, Neurology, UM

Laboratory investigations
Mandatory blood investigations
FBC BUSE, creatinine LFT Calcium, Magnesium

ECG CSF examination

If underlying infective, inflammatory or neoplastic process suspected
Goh KJ, Neurology, UM

EEG
Provide a simple and inexpensive way of demonstrating the abnormal cortical excitability that underlie epilepsy Low sensitivity 25-56%, moderate specificity 2578-98% 78EEG can be normal in epilepsy; abnormal EEG does not indicate patient has epilepsy

Goh KJ, Neurology, UM

EEG - indications
Diagnosis of paroxysmal neurological events Making a syndromic diagnosis
Focal vs. generalised seizure disorders Typical findings suggest certain syndromes e.g. absence, benign rolandic, myoclonic epilepsies Photosensitivity

Workup for epilepsy surgery Diagnosis and monitoring of status epilepticus

Goh KJ, Neurology, UM

Interictal epileptiform discharges

Spikes or sharp waves Seen in 0.5% of healthy adults Yield of first EEG 50%. May improve with
Repeat EEG recordings Sleep and activating procedures hyperventilation and photic stimulation Prolonged recording and timing of EEG after seizure
Goh KJ, Neurology, UM

Goh KJ, Neurology, UM

Goh KJ, Neurology, UM

Goh KJ, Neurology, UM

Goh KJ, Neurology, UM

Brain imaging
Indicated if a focal seizure is suspected MRI is imaging modality of choice
Mesial temporal sclerosis Cortical dysplasias Cavernomas Benign tumours e.g. dysembryoplastic neuroepithelial tumours (DNET) gangliogliomas

Goh KJ, Neurology, UM

Goh KJ, Neurology, UM

Goh KJ, Neurology, UM

DNET

Goh KJ, Neurology, UM http://www.bic.mni.mcgill.ca/~andrea/research.html

Neurocysticerocosis
Goh KJ, Neurology, UM

Problems with epilepsy

Continued seizures with loss of self independence Cognitive and behavioural disorders Medication side effects Progressive neurological deficits Status epilepticus Sudden unexplained death in epilepsy (SUDEP)
Goh KJ, Neurology, UM

Treatment of epilepsy
Patient education
Avoid precipitating factors Avoid potential for injuries

Lifestyle modification
Occupation Driving

Medical therapy NonNon-medical therapy

Goh KJ, Neurology, UM

Drug therapy for epilepsy

Decision to begin therapy depend upon
risk of seizure recurrence e.g. risk is high in partial onset seizures and those with abnormal EEG or neuroimaging diagnosis of epilepsy syndrome (if possible) patients age and occupation

Immediate AED treatment after first seizure reduces the occurrence of seizures in the next two years but does not affect long-term remission rates* long-

* Marson A, et al. Lancet 2005 Goh KJ, Neurology, UM

Drug therapy for epilepsy

Anti epileptic medication (AED)
Standard (old) AEDs Second generation (new) AEDs

Goh KJ, Neurology, UM

Standard AEDs
Phenobarbitone (PB) Primidone (PRM) Phenytoin (PHT) Ethosuximide (ESM)* Carbamazepine (CBZ) Sodium Valproate (VPA)
* Not available in Malaysia
Goh KJ, Neurology, UM

New AEDs
Oxcarbazepine Lamotrigine Topiramate Gabapentin Levetiracetam
* Not available in Malaysia
Goh KJ, Neurology, UM

Tiagabine* Tiagabine* Zonisamide Pregabalin Vigabatrin* Vigabatrin* Felbamate* Felbamate*

Medical Therapy
AEDs are the mainstay of therapy in epilepsy Choice of AED depend on efficacy as well as safety (risk of adverse effects) Clinical efficacy is determined from clinical experience and therapeutic trial data Adverse effects are determined from clinical trials but importantly, also from long-term longclinical observations/experience
Goh KJ, Neurology, UM

Problems in AED choice

Few Class I data on standard AEDs Many trials of newer AEDs have been for registration purposes and may not answer appropriate clinical questions Fewer studies on monotherapy i.e. in new onset epilepsies Few comparative studies between AEDs especially the new AEDs
Goh KJ, Neurology, UM

Considerations in AED choice

Partial epilepsy versus generalised epilepsy Monotherapy in new onset epilepsy or add-on addtherapy in refractory epilepsy

Goh KJ, Neurology, UM

* McCorry D, Chadwick D, Marson A. Lancet Neurology 2004; 3: 729-35 729Goh KJ, Neurology, UM

* McCorry D, Chadwick D, Marson A. Lancet Neurology 2004; 3: 729-35

Goh KJ, Neurology, UM

Drug monitoring
Monitoring should be clinical primarily Drug level monitoring should to document compliance or to confirm clinical toxicity Drug levels are not routinely available for the newer AEDs

Goh KJ, Neurology, UM

Stopping treatment
No definitive guide Generally for two or more years of seizure freedom Will have to be individualised

Goh KJ, Neurology, UM

Special situations

Women Elderly Children

Goh KJ, Neurology, UM

Epilepsy
Introduction
Terminology Classification

Diagnosis
History and physical examination Laboratory investigations

Prognosis
Remission of seizures Mortality
Goh KJ, Neurology, UM

Epilepsy
Introduction
Terminology Classification

Diagnosis
History and physical examination Laboratory investigations

Prognosis
Remission of seizures Mortality
Goh KJ, Neurology, UM

Prognosis
Two aspects
Seizure remission Mortality

Seizure remission
Treated epilepsy Untreated epilepsy true natural history

Goh KJ, Neurology, UM

Seizure remission
Seizure remission rates range from 58 to 80%

Kwan P, Sander JW. JNNP. 2004 JNNP.

Goh KJ, Neurology, UM

Seizure remission
Seizure remission rates range from 58 to 80%

Kwan P, Sander JW. JNNP. 2004 JNNP.

Goh KJ, Neurology, UM

Seizure remission
Refractory seizures about 30% of epileptics never achieve seizure remission Factors that predict refractory seizures
Frequent seizures before therapy and Poor response to first antiepileptic drug therapy Underlying aetiology: idiopathic vs. symptomatic/cryptogenic

Two distinct populations of patients

Kwan P, Brodie MJ. NEJMGoh KJ, Neurology, UM MJ. Epilep Res. 2004 NEJM. 2000; Brodie .

Brodie MJ. Epilepsia. 2005

Goh KJ, Neurology, UM

Seizure remission
Does untreated epilepsy spontaneously remit? Evidence from developing countries
31% had spontaneous remission in population based study in Ecuador Prevalence of epilepsy similar in countries with large treatment gap Smaller studies in developed countries
Placencia M, Sander JM, Roman M et al. JNNP 1994
Goh KJ, Neurology, UM

Kwan P, Sander JW. JNNP. 2004

Goh KJ, Neurology, UM

Refractory epilepsy
Replace with new AED or add-on? addIf add-on, choice AED combination no clear addevidence for any particular combination Considerations
Side effects Drug interaction Different modes of action

Goh KJ, Neurology, UM

Non medical therapy

Epilepsy surgery Vagus nerve stimulation (VNS) Others e.g. ketogenic diet

Goh KJ, Neurology, UM

Mortality
Increased risk of premature death in epilepsy Causes due to underlying cause e.g. trauma, stroke, tumour , encephalitis or SeizureSeizure-related
SUDEP Status epilepticus Accidents during seizure Treatment related deaths Suicide
Goh KJ, Neurology, UM

Mohanraj R, Norrie J, Stephen LJ et al. Lancet Neurol. 2006

Goh KJ, Neurology, UM

Mohanraj R, Norrie J, Stephen LJ et al. Lancet Neurol. 2006

Goh KJ, Neurology, UM

Mortality
Excess mortality was related to seizure control
Patients with uncontrolled and chronic epilepsy . Newly diagnosed patients who were seizure free at follow up had no increased mortality Survival was reduced in patients with symptomatic/cryptogenic epilepsy compared to idiopathic epilepsy

Seizure related deaths were more likely in the chronic epilepsy group
Mohanraj R, Norrie J, Stephen LJ, et al. Lancet Neurol. 2006
Goh KJ, Neurology, UM

Learning points
Differentiate between epileptic seizure (symptoms) and epilepsy (diagnosis). Diagnosis of epilepsy is primarily clinical with adjunctive investigations Investigations may help in classifying the epilepsy (focal vs. generalised) and determine the cause (if any) About 1/3 of patients will never achieve seizure remission and there is an excess in mortality in chronic symptomatic epilepsy
Goh KJ, Neurology, UM

Goh KJ, Neurology, UM