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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
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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
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
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
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
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