Download Hippocampal sclerosis

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




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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
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Epilepsy
 Definition
 Classification
 Prevalence
 Pathogenesis
 Investigation
 Treatment
 Long
term prognosis
4
Definition
 Recurring
unprovoked seizures due to
paroxysmal neuronal discharge
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Classification
 Can
be based on cause or mode of onset.
 Mode of Onset
Partial (Focal) onset
 Generalised
 Unclassifiable

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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

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Generalised
Bilateral synchronous cortical spike and wave
discharge generated by thalamic slow calcium
channels
 Tonic-Clonic
 Typical Absence
 Atypical Absence
 Myoclonic
 Tonic
 Atonic

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Frequency of different types
 1/3
generalised in onset
 2/3 partial in onset, most commonly
temporal lobe attacks
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Status Epilepticus
 Recurring
seizures without recovery of
consciousness in between
 Convulsive status
 Absence status
 Complex partial status
 Epilepsia partialis continuans
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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.
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Incidence
Developed countries 50/100000/year
(range 40-70)
Underdeveloped countries - 100190/year - only 6%of PWE in Pakistan or
Phillipines on rx at any one time
Patients may not be aware that they have
epilepsy
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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/Alcoholinduced/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, voltagesensitive calcium channels, voltage sensitive
sodium channels
 Excitatory neurones must be connected into a
synaptic network

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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

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Investigation
 Brain
structural imaging -CT and MRI
 Functional imaging -fMRI/Ictal
SPECT/PET
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Hippocampal sclerosis
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Dysembryoblastic Neuroepithelial
Tumour
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Left Temporal AVM
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Focal Cortical Dysplasia
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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

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With sphenoidal leads
Cortical monitoring - Depth electrodes

Therapeutic trial

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EEG – 3/s spike and wave
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Bloods/Cardiovascular
 FBC/U+E/Calcium/Magnesium/Glucose
 Toxicology
 ECG/Holter/ECHO/Syncope
studies
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Differential Diagnosis
 Cardiovascular
 Metabolic
- ‘Non-Epileptic Attack
Disorder’ aka Pseudoseizures
 Psychogenic
 Up
to 1/3 of referrals to an Epilepsy Centre
(Walton, Liverpool) were found to have
alternative causes for episodes
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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

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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 workup
 Simple partial seizures without disturbance of
consciousness or motor control
 All must be certified by a neurologist

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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
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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 ParkeDavis - 1938
 Trimethadione - 1944 - succeeded by
Ethosuximide

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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
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Drug
GABAmediated
PBZ
Yes
Blockade
Blockade
Unknown
voltage gated voltage gated
Na channels Na channels
PHT
Yes
CBZ
Yes
VALP
Yes
Yes
ETH
Yes
Yes
BENZ
Yes
VIGA
Yes
LAM
Yes
GAB
Yes
PRE-G
Yes
LEV
TOP
OXC
Yes
Yes
Yes
Yes
Yes
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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
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Drug Choice?
 Broad
Spectrum - work in all types
Valproate
 Lamotrigine
 Topiramate
 Levetiracetam
 Zonisamide
 Phenobarbitone
 Benzodiazepines

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Drug Choice?

Narrow spectrum

Partial-onset
•
•
•
•
•
•
•
Carbamazepine
Phenytoin
Vigabatrin
Gabapentin
Tiagabine
Oxcarbazepine
Pre-Gabalin
Absence attacks - Ethosuximide
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Most commonly used by me!
 Carbamazepine
 Valproate
 Lamotrigine
 Levetiracetam
 Phenytoin
 Topiramate
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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

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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

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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

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Surgery

Best results with clear Temporal origin
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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
Ictal PET Scan
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Other options…
 Vagus
nerve stimulation
 Deep brain stimulation
 Seizure detection and immediate response
drug delivery systems
 Gamma knife
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Prognosis
Generally good
 However SMR x 3 times controls
 Due to cause of epilepsy/accidents
 Sudden Unexpected Death in Epilepsy (SUDEP)

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Young adults/Early age on onset/Generalised TonicClonic seizures/High seizure
frequency/Polypharmacy/Poor compliance
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