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Epilepsy in Munster 2011

Dr Brian Sweeney Consultant Neurologist CUH

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Target population Munster 1.2 million Parts of Kilkenny and Wexford If Epilepsy prevalence is 0.65% c. 8000

people have epilepsy in this region 30-40% have drug resistance All need proper counselling and discussion

re diagnosis and its management

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Irish and UK data Up to 40 000 Irish people have epilepsy At least 2-3 seizures present to CUH Casualty

each day (Audit August/September 2004) UK

160 000 people will require hospital treatment 25 000 > 1 major seizure/month 60 000 > 1 minor seizure/month 20 000 patients have severe disabilities requiring

institutional care

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Epilepsy

Definition Classification Prevalence Pathogenesis Investigation Treatment Long term prognosis

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Definition

Recurring unprovoked seizures due to paroxysmal neuronal discharge

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Classification

Can be based on cause or mode of onset. Mode of Onset

Partial (Focal) onset Generalised Unclassifiable

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Partial Seizures Partial - onset in a focal region of cortex Simple partial - sensory, motor, autonomic or

psychic - without loss of consciousness Complex Partial - consciousness impaired Complex Partial with Secondary Generalisation -

evolving into a full-blown seizure Temporal, Frontal, Parietal or Occipital in origin

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Generalised Bilateral synchronous cortical spike and wave

discharge generated by thalamic slow calcium channels

Tonic-Clonic Typical Absence Atypical Absence Myoclonic Tonic Atonic

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Frequency of different types

1/3 generalised in onset 2/3 partial in onset, most commonly

temporal lobe attacks

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Status Epilepticus

Recurring seizures without recovery of consciousness in between

Convulsive status Absence status Complex partial status Epilepsia partialis continuans

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Secondary (‘Symptomatic’) Seizures

Seizures secondary to an acute metabolic, drug-induced or neurological condition

Patients usually not vulnerable in the long term if underlying cause is reversed.

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Incidence

Developed countries 50/100000/year (range 40-70)Underdeveloped countries - 100-190/year - only 6%of PWE in Pakistan or Phillipines on rx at any one timePatients may not be aware that they have epilepsy

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Prevalence

5-10/1000 persons Lifetime prevalence is 2-5% As the population ages there will be an

increased incidence and prevalence of epilepsy - at least 20% of new onset cases will be over 60

Febrile seizures prevalence - 5%

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Aetiology General Data 60-70% no clear cause

(‘Cryptogenic epilepsy) Cerebrovascular disease/Brain tumour/Alcohol-

induced/Post-traumatic With the advent of MRI increasing numbers of

structural lesions such as HS, Cortical dysplasia, Small foreign tissue lesions

Some patients may be reclassifed as having a generalised syndrome with analysis of EEG records

Recent NSE data - up to 60% of a community based MRI series have some structural lesion

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Pathogenesis Still not fully elucidated Discharges occur in the neocortex and limbic

structures such as the Amygdala and Hippocampus

Large 20-40mV discharges in a group of at least 1000-2000 neurones (‘minimum aggregate zone’

Giant EPSPs - glutamate dependent, voltage-sensitive calcium channels, voltage sensitive sodium channels

Excitatory neurones must be connected into a synaptic network

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Pathology Seizures complicate many brain diseases eg

Alzheimer disease Hippocampal Sclerosis Cortical dysplasia Lesion-associated - tumours/AVMs Inflammatory, Traumatic, Hypoxic-|schaemic

lesions Conditions and lesions secondary to seizures Dual pathology

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Investigation

Brain structural imaging -CT and MRI Functional imaging -fMRI/Ictal

SPECT/PET

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Hippocampal sclerosis

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Dysembryoblastic Neuroepithelial Tumour

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Left Temporal AVM

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Focal Cortical Dysplasia

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Investigation EEG - only 50% will have interictal abnormalities

- a normal EEG does not exclude Epilepsy! Some patients may never have any EEG findings

Sleep EEG Video-EEG - at least 70% of our recordings do

not have demonstrate attacks With sphenoidal leads Cortical monitoring - Depth electrodes

Therapeutic trial

EEG – 3/s spike and wave

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Bloods/Cardiovascular

FBC/U+E/Calcium/Magnesium/Glucose Toxicology ECG/Holter/ECHO/Syncope studies

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Differential Diagnosis Cardiovascular Metabolic Psychogenic - ‘Non-Epileptic Attack

Disorder’ aka Pseudoseizures

Up to 1/3 of referrals to an Epilepsy Centre (Walton, Liverpool) were found to have alternative causes for episodes

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Counselling/Treatment - General principles Generally not if only one episode (but maybe if

+ve EEG/Structural brain lesion/Elderly/Severe episode)

‘Oligo-Epilepsy’ Treatment for at least 2 years Try to keep to once or twice per day Inform patient about side effects and the

possibility of treatment failure Lifestyle issues – alcohol/drugs

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General Principles Cannot drive until 12 months seizure-free Exceptions:

Sleep attacks only for > 2 years May resume driving in 6 months if seizure

related to medication change or surgery work-up

Simple partial seizures without disturbance of consciousness or motor control

All must be certified by a neurologist

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Women with Epilepsy

Inform re potential interactions of the specific drug with OCP

Inform re teratogenic risk Potential changes in Pharmacology in

pregnancy Folic Acid 5mg/day Vitamin K supplementation

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Drug therapy Bromide - Sir Charles Locock - May 11 1857 to

Royal Medical and Chirurgical Society Barbituric acid - Saint Barbara’s Day 1864. AE

properties recognised by Hauptmann - 1912 Phenytoin - Putnam and Merritt using Phenyl

ring containing compounds provided by Parke-Davis - 1938

Trimethadione - 1944 - succeeded by Ethosuximide

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Drug therapy

Carbamazepine - synthesised by Geigy chemists in 1953

Valproic acid - organic solvent synthesised 1881. AE properties recognised in France 1961 and first marketed in 1967

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Drug GABA-mediated

Blockade voltage gated Na channels

Blockade voltage gated Na channels

Unknown

PBZ Yes

PHT Yes

CBZ Yes

VALP Yes Yes Yes

ETH Yes

BENZ Yes

VIGA Yes

LAM Yes

GAB Yes

PRE-G Yes

LEV Yes

TOP Yes Yes Yes

OXC Yes

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Drug Choice?

Age/Gender Need rapid onset of action? OCP/Pregnancy Prior drug history Efficacy vs Side Effects Status Epilepticus - drug has to be soluble

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Drug Choice?

Broad Spectrum - work in all types Valproate Lamotrigine Topiramate Levetiracetam Zonisamide Phenobarbitone Benzodiazepines

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Drug Choice? Narrow spectrum

Partial-onset• Carbamazepine• Phenytoin• Vigabatrin• Gabapentin• Tiagabine• Oxcarbazepine• Pre-Gabalin

Absence attacks - Ethosuximide

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Most commonly used by me!

Carbamazepine Valproate Lamotrigine

Levetiracetam Phenytoin Topiramate

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Combination Treatment/Polypharmacy

May help some patients Increased risk of interactions

In our QOL study of 90 consecutive patients most important discriminator was seizure freedom and not number of drugs taken

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Prognosis 60-70% should expect to be seizure-free without

major side effects In these patients the choice of drug may not

matter that much - they might respond any drug they try

However relapse rates as high as 40% if drugs are withdrawn even after good long term control

Major socio-economic effects if seizures relapse Put pros and cons to patient and give them your

assessment of their individual risk

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Drug-resistance Seizures refractory for more than 2 years of

trying more than 3-4 AEDs 30-40% of patients - pharmacogenomics an

increasing area of interest

Reassess diagnosis and other factors like compliance or lifestyle problems

Video-EEG Repeat imaging

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If focal onset…. Surgery may be an option High quality MRI Video-EEG - catch at least 2-3 attacks to ensure

consistent seizure focus Neuropsychology Psychiatry review If there is congruence between MRI and EEG

findings surgical resection is possible At least 3000 Irish patients might be suitable for

such surgery

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Surgery Best results with clear Temporal origin

50% become seizure free 20% significantly improved <1% risk of adverse outcome 10% risk of psychiatric problems

Frontal <50% chance of good outcome Occipital/Parietal - greater risk of surgery causing

deficit

Ictal PET Scan

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Other options…

Vagus nerve stimulation Deep brain stimulation Seizure detection and immediate response

drug delivery systems Gamma knife

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Prognosis Generally good However SMR x 3 times controls Due to cause of epilepsy/accidents Sudden Unexpected Death in Epilepsy (SUDEP)

Young adults/Early age on onset/Generalised Tonic-Clonic seizures/High seizure frequency/Polypharmacy/Poor compliance