epilepsy - PowerPoint

							   Epilepsy


   Morgan Feely
Consultant Physician
       Target Meeting

    Tong, November 2006
Epilepsy

 A person is said to have ‘epilepsy’ when they have
  exhibited a tendency to have recurring seizures

 It is not a single disease

 Manifest by underlying brain dysfunction from many
  known or unknown causes

 Single seizures should not be diagnosed as epilepsy

 A patient could be said to have ‘one of the epilepsies’ as
  there are a number of seizure types and causes.
Epidemiology



 Bimodal incidence

 440,000 active cases in UK

 Typical practice: 15 patients per 2000
                                       Age-specific prevalence of treated epilepsy per 1000 persons
                                                Source: Wallace, Shorvon, Tallis, Lancet
                   9.5
                     9
                   8.5
                    8
                   7.5
                     7
                   6.5
Prevalence/100 0




                     6
                   5.5
                    5
                   4.5
                     4
                   3.5
                    3
                   2.5
                     2
                   1.5
                     1
                   0.5
                    0
                         5-9   10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84   85+

                                                                         Age
                  Age-specific incidence of treated epilepsy per 100,000 persons
                (Source: Wallace, Shorvon, Tallis: The Lancet, 1998 Dec 19–26;352
                                          (9145):1952-3)


                    210
                    200
                    190
                    180
                    170
Incidence/100,000




                    160
                    150
                    140
                    130
                    120
                    110
                    100
                     90
                     80
                     70
                     60
                     50
                     40
                     30
                     20
                     10
                      0
                          5-9   10-14   15-19   20-24   25-29   30-34   35-39   40-44   45-49   50-54   55-59   60-64   65-69   70-74   75-79   80-84   85+




                                                                                        Age
                The epilepsies


Generalised epilepsies       Location related
(mostly idiopathic)          epilepsies
                             (mostly symptomatic)
 tonic-clonic (T-C)
 and/or absences             partial seizures
 and/or myoclonic            partial +/- secondary
  seizures                     (T-C) generalisation


Over 200 epilepsy syndromes described - mostly of
relevance to young people
Seizures across the ages
   Teens/early 20’s    Late 20’s – 50’s     Late 50’s – 80+
  JME                   Alcohol / drugs     Cerebrovascular
                                                disease
  Primary               Brain tumours         Dementias
  generalised (T-C)
                             SAH              Brain tumours

  Partial +/-             Head injury
  secondary T-C
                           Metabolic disorders eg low Na

                       Late presentation
                        of earlier types

           Continuation of childhood/earlier epilepsy
Making the diagnosis 1


                History
                History and / or
                Eye witness or…
First tonic-clonic seizure in an adult
    Clinical scenario

 You are asked to see a patient who collapsed and
  appeared to have a ‘fit’ within the last few days and is
  now back to normal

 What are the key issues?
   Seizure versus (convulsive) syncope
   Provocation (late nights and alcohol, drugs) ?
   Is there any evidence of previous unrecognised seizures
   What is the patient’s occupation / driving status?
Differences between seizures and syncope
 Seizures                                  Syncope

  Any posture (e.g. in bed at night)       Occurs standing (or sitting if elderly)
  Blue lips during attack                  Pale and clammy
  Stiffness and tonic-clonic movements     Brief jerking movements may occur
 coincide with loss of consciousness and   after loss of consciousness
 often last for several minutes
  Patient is rigid as falls to ground      Patient loses tone then falls to ground
  Urinary incontinence common              Urinary incontinence can occur
 Disorientated or headache afterwards
 Tongue biting and serious injuries are    Quick recovery
 common
 Seizures arising from secondary
 generalisation may be preceded by an       Tongue biting rarely; serious injuries
 aura or recognisable partial seizure      occur in 5% of cases

                                            Often preceded by feeling warm and
                                           light headed
Case 1
18 year old female law student attends your surgery after
suffering a ‘blackout’ following breakfast. Her housemate
had said to her she had a ‘grand mal convulsion’.

 Seizure versus syncope
   features to support syncope or convulsive syncope…WITNESS / TELEPHONE

 Provocation
   Studying for exams, started drinking at university, no illicit drugs

 Is there any evidence of previous unrecognised seizures
   Since the age of 16 occasionally ‘daydreams’, jerks in the morning, cup of tea

 What is the patient’s occupation / driving status
   Student, drives a car, NB. OCP
Diagnosis: JME
Case 2

42 year old businessman attends surgery following a
generalised seizure. On record he has a heavy alcohol
consumption (>50 units per week), but has recently cut
down.

 Seizure versus syncope
   No clear witness account, any eye witnesses?
 Provocation
   Alcohol (ab)use and cut down
 Is there any evidence of previous unrecognised seizures
   ‘Has had a fit before’ after binge drinking
 What is the patient’s occupation / driving status
   Driver. DVLA issues. Provoked seizure?
Case 3

42 year old businessman attends surgery with his wife who
is concerned he is behaving oddly at times, repeatedly
saying things over and over. On record he has a heavy
alcohol consumption (>50 units per week)

 Seizure versus syncope
   History from wife ‘Golf-traps! Golf-traps!’ , detached : complex partial seizure(s)
 Provocation
   Alcohol use, but not in keeping with focal seizure
 Is there any evidence of previous unrecognised seizures
   No
 What is the patient’s occupation / driving status
   Driver. Urgent investigations
Diagnosis:
Glioblastoma
Case 4

A 69 year old male attends with seven attacks of speech
disturbance lasting 3 minutes over the last 4 months. He
has been investigated previously for TIA / stroke.

 Seizure versus syncope
   No evidence of syncope. Recurrent stereotypical focal neurology. Clean stroke tests.

 Provocation
   No evidence. Not situational. Without warning.

 Is there evidence of unrecognised seizures?
   No

 What is the patient’s occupation / driving status?
   Driver. DVLA issues
Case 5

You are asked to see a 73 year old lady in her RH. She had a
previous Left hemi-paresis. The staff think that she has ‘had
another stroke.’

 Seizure versus syncope?
   Speak to RH witness. ‘Vacant’ at onset with ‘jerking movements’ of left upper limb.

 Provocation
   Recently started antidepressant for low mood, recent UTI and ‘antibiotics’

 Is their evidence of unrecognised seizures?
   RH staff say she occasionally ‘switches off’ and ‘stares into space’. Recurrent ‘strokes’

 Occupation / driving status
   Less relevant, ‘lifestyle issues’. Avoid unnecessary tests?
Making the diagnosis 2
Making the diagnosis 3
Management
Management
Starting AED treatment in newly diagnosed epilepsy


AIMS                        PRINCIPALS

 Prevention of seizures     Appropriate drug for
                              patient’s seizure(s)
 Minimal side effects
                             Appropriate drug for
 Optimise QOL                individual patient

                             Through trial and error
 Antiepileptic drug development

AEDS                                                                          More
20
                                                             Levetiracetam
                                                                               Oxcarbazepine
                                                                  Tiagabine
15                                                                             Fosphenytoin
                                                             Topiramate
                                                                              Gabapentin
                                                             Felbamate
                                                                          Lamotrigine
10                                                          Zonisamide
                                          Sodium valproate                Vigabatrin
                                                                   Carbamazepine
                                             Ethosuximide       Benzodiazepines
5
                            Phenobarbital               Primidone
           Bromide
                                            Phenytoin
0
    1840     1860    1880   1900     1920      1940     1960      1980        2000
                                   Year
Choice of drug

  Seizure type

  Women of childbearing age

  Pregnancy

  Breastfeeding

  Children

  Elderly

  Learning disability
 Treatment options by seizure type
GENERALISED-ONSET SEIZURES                  PARTIAL-ONSET SEIZURES
Absence myoclonic tonic / atonic primary T-C simple  complex-partial


                                               secondary generalisation


Ethosuxamide                                   CARBAMAZEPINE
                                               Phenytoin
                                               Vigabatrin
                                               Gabapentin
                                               Oxcarbazepine


                             VALPROATE
                             LAMOTRIGINE
                             Levetiracetam
                             Topiramate
                             Phenobarbital
                             Benzodiazepines
Initial (first line) treatment

Drugs for generalised seizures   Drugs for partial seizures (+/-
                                 secondary generalisation)

 Valproate (Epilim Chrono)       Carbemazepine (Tegretol
                                   Retard)
 Lamotrigine
                                  Lamotrigine
 [Topiramate]
                                  Valproate (Epilim Chrono)

                                  Levetiracetam

                                  [Topiramate ]
Sodium valproate (Epilim Chrono)



 Useful for location related    Can cause tiredness,
  and generalised epilepsy        tremor, weight gain,
                                  alopecia
 Can be brought up to
  therapeutic dose quickly       Teratogenic (spina bifida)

 Low(er) doses tolerated
  and possibly drug of
  choice for elderly patients
Carbamazepine (Tegratol)



 Good drug for partial seizures in young(er) adults

 Needs gradual build up to a therapeutic dose

 Enzyme-inducer, therefore interactions/oestoporisis

 Most specialists use MR (Tegretol Retard)
Lamotrigine (Lamictal)

   Broad spectrum
                               Needs to build up
                                slowly (months) to
   Good tolerability as        reduce AEs
    monotherapy

                               Rash common,
   Well tolerated by the       sometimes severe and
    elderly                     associated with Steven-
                                Johnson’s syndrome
   Synergistic effect with
    sodium valproate           Blood dyscrasias

   Least teratogenic
Newer second line agents - Levetiracetam
(Keppra)
   Relatively new but appears    Sedation common,
    well tolerated and             though tends to resolve
    efficacious

                                  Long-term experience
   Monotherapy licence
                                   still lacking

   Licensed for partial
    seizures +/- secondary
    generalisation (may be
    effective in other seizure
    types)

   Can be started at close to
    therapeutic range
Newer second line agents - Topiramate



 Potent anticonvulsant       Often not tolerated due to
  activity                     side effects: confusion,
                               word-finding difficulties,
 Useful for most forms of     weight loss
  epilepsy
                              Needs slow induction
When to start treatment


 What is the cause?

 What is the risk of recurrence?

 First Vs second seizure?

 What does the patient / carer think?
Poor control



• Concurrent pro-convulsant drugs   Alcohol
                                    prescription

• Lifestyle                         Sleep
                                    Stress

• Concordance / compliance          Why?
                                    ADR
                                    other drugs
                                    Social aspects
Treatment errors

• Incorrect / incomplete detection of seizure(s) resulting
  in inappropriate drug choice.

• Appropriate drug for the seizure(s), but not the
  patient.

• Wrong dose (high or low)

• Seizures are controlled, but intolerance / SE are a
  problem.

• The occurrence of a progressive neurological
  condition
Prognosis

• 70 – 80% prolonged remission

• Poor control    Structural lesion
                  EEG abnormality
                  Associated neuropsychiatric disorder

                  More than one drug ?
• SUDEP
AED withdrawal


• Seizure free (remission) > 3 (2?) years

• Overall risk of recurrence is 40%

• Most relapses occur within the first year off treatment

• Factors increasing relapse; syndrome, structural
  abnormality, severe epilepsy before remission, age.

• Discussion        risk versus continued therapy
                    DVLA – 6 month suspension
                    Leisure pursuits
                    Contraception / pregnancy etc
Service Level
Primary Care                        Secondary care
GMS                                 Establish diagnosis
Referral      First seizure         initiate treatment
              Poor control
              Special cases         Follow up
              AED withdrawal        Difficult control
Follow-up if stable                 Tertiary referral
Re-refer
                                    Neuro-oncology
                                    Obstetrics
                                    Elderly
                Epilepsy Nurse specialists