Epilepsy in Munster 2011 Dr Brian Sweeney Consultant Neurologist CUH 1

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 2

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 3

Epilepsy Definition Classification Prevalence Pathogenesis Investigation Treatment Long term prognosis 4

Definition Recurring unprovoked seizures due to paroxysmal neuronal discharge 5

Classification Can be based on cause or mode of onset. Mode of Onset Partial (Focal) onset Generalised Unclassifiable 6

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 7

Generalised Bilateral synchronous cortical spike and wave discharge generated by thalamic slow calcium channels Tonic-Clonic Typical Absence Atypical Absence Myoclonic Tonic Atonic 8

Frequency of different types 1/3 generalised in onset 2/3 partial in onset, most commonly temporal lobe attacks 9

Status Epilepticus Recurring seizures without recovery of consciousness in between Convulsive status Absence status Complex partial status Epilepsia partialis continuans 10

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. 11

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 time Patients may not be aware that they have epilepsy 12

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% 13

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 14

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 15

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 16

Investigation Brain structural imaging -CT and MRI Functional imaging -fMRI/Ictal SPECT/PET 17

Hippocampal sclerosis 18

Dysembryoblastic Neuroepithelial Tumour 19

Left Temporal AVM 20

Focal Cortical Dysplasia 21

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 22

EEG – 3/s spike and wave

Bloods/Cardiovascular FBC/U+E/Calcium/Magnesium/Glucose Toxicology ECG/Holter/ECHO/Syncope studies 24

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 25

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 26

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 27

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 28

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 29

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 30

Blockade voltage gated Na channels Unknown Drug GABA-mediated Blockade voltage gated Na channels Unknown PBZ Yes PHT CBZ VALP ETH BENZ VIGA LAM GAB PRE-G LEV TOP OXC 31

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 32

Drug Choice? Broad Spectrum - work in all types Valproate Lamotrigine Topiramate Levetiracetam Zonisamide Phenobarbitone Benzodiazepines 33

Drug Choice? Narrow spectrum Partial-onset Carbamazepine Phenytoin Vigabatrin Gabapentin Tiagabine Oxcarbazepine Pre-Gabalin Absence attacks - Ethosuximide 34

Most commonly used by me! Carbamazepine Valproate Lamotrigine Levetiracetam Phenytoin Topiramate 35

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 36

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 37

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 38

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 39

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 40

Ictal PET Scan

Other options… Vagus nerve stimulation Deep brain stimulation Seizure detection and immediate response drug delivery systems Gamma knife 42

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 43