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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
Epilepsy in Munster 2011
  • Dr Brian Sweeney
  • Consultant Neurologist
  • CUH

1

target population
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
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
Epilepsy
  • Definition
  • Classification
  • Prevalence
  • Pathogenesis
  • Investigation
  • Treatment
  • Long term prognosis

4

definition
Definition
  • Recurring unprovoked seizures due to paroxysmal neuronal discharge

5

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

6

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

9

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

10

secondary symptomatic seizures
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
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
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
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
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
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
Investigation
  • Brain structural imaging -CT and MRI
  • Functional imaging -fMRI/Ictal SPECT/PET

17

investigation1
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
Bloods/Cardiovascular
  • FBC/U+E/Calcium/Magnesium/Glucose
  • Toxicology
  • ECG/Holter/ECHO/Syncope studies

24

differential diagnosis
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
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
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
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
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 therapy1
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
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 choice1
Drug Choice?
  • Broad Spectrum - work in all types
    • Valproate
    • Lamotrigine
    • Topiramate
    • Levetiracetam
    • Zonisamide
    • Phenobarbitone
    • Benzodiazepines

33

drug choice2
Drug Choice?
  • Narrow spectrum
    • Partial-onset
      • Carbamazepine
      • Phenytoin
      • Vigabatrin
      • Gabapentin
      • Tiagabine
      • Oxcarbazepine
      • Pre-Gabalin

Absence attacks - Ethosuximide

34

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

35

combination treatment polypharmacy
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
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
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
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
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
Other options…
  • Vagus nerve stimulation
  • Deep brain stimulation
  • Seizure detection and immediate response drug delivery systems
  • Gamma knife

42

prognosis1
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