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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


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