1. Epilepsy in Munster 2011
Dr Brian Sweeney
Consultant Neurologist
CUH 1

2. Target population Munster 1.2 million Parts of Kilkenny and Wexford
If Epilepsy prevalence is 0.65% c people have epilepsy in this region
30-40% have drug resistance
All need proper counselling and discussion re diagnosis and its management 2

3. 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
people will require hospital treatment
> 1 major seizure/month
> 1 minor seizure/month
patients have severe disabilities requiring institutional care 3

4. Epilepsy Definition Classification Prevalence Pathogenesis
Investigation
Treatment
Long term prognosis 4

5. Definition
Recurring unprovoked seizures due to paroxysmal neuronal discharge 5

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

7. 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

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

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

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

11. 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

12. Incidence Developed countries 50/100000/year (range 40-70)
Underdeveloped countries /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

13. 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

14. 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

15. 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 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

16. 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

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

18. Hippocampal sclerosis18

19. Dysembryoblastic Neuroepithelial Tumour19

20. Left Temporal AVM 20

21. Focal Cortical Dysplasia21

22. 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

23. EEG – 3/s spike and wave

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

25. 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

26. 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

27. 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

28. 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

29. Drug therapy
Bromide - Sir Charles Locock - May to Royal Medical and Chirurgical Society
Barbituric acid - Saint Barbara’s Day AE properties recognised by Hauptmann
Phenytoin - Putnam and Merritt using Phenyl ring containing compounds provided by Parke- Davis
Trimethadione succeeded by Ethosuximide 29

30. Drug therapy Carbamazepine - synthesised by Geigy chemists in 1953
Valproic acid - organic solvent synthesised AE properties recognised in France 1961 and first marketed in 1967 30

31. 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

32. 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

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

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

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

36. 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

37. 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

38. 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

39. 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

40. 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

41. Ictal PET Scan

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

43. 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