Download Module 1 - Introduction to Epilepsy Basic Principles

Epilepsy
Prof. Magdy Dahab
August 26th, 2009
Prof. Magdy Dahab
Epilepsy
What Is Epilepsy?
 A syndrome of recurring episodes of
electrical activity of the central nervous
system called seizures.
 Seizures may vary from mild and
unnoticeable to full-scale convulsive
seizures.
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Some Common Symptoms of Epilepsy
 Uncontrollable movements of the body
 Disorientation
-Confusion
 Sudden fear
 Loss of consciousness
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What Causes Epilepsy?
 In over 70% of cases, no cause for epilepsy
has been identified.
 The other 30% can result from many other
possibilities.
 Head injuries
 Lack of oxygen during birth
 Genetic conditions
 Lead poisoning
 Severe Infections (Meningitis and Encephalitis)
 Problems during development of the brain
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Seizures
 “Provoked”
 Metabolic disorders
 Hypoglycemia
 Electolyte imbalance
 Withdrawal from massive amounts of alcohol or sedatives
 Massive sleep deprivation
 High fever
 Hypoxia
 Substance abuse
 Excessive use of stimulants
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Seizures
 “Unprovoked”
 Birth trauma
 Anoxia
 Brain tumors
 Infectious diseases in the mother
 Parasitic infections
 Genetic
 Vascular diseases affecting the brain’s blood vessels
 Neurotransmitter GABA (gamma-amino butyric acid) imbalance
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Epilepsy
 1-2% of people with epilepsy will have a diagnosable
genetic etiology for their seizure occurrence
 The general incidence of epilepsy is between 1% and
4%
 Two major type so seizures: Generalized and Partial
 Generalized – uncontolled discharge of neurons on BOTH
sides of brain. Seizure starts in one area and spreads across
the brain.
 Partial – abnormal electrical activity involving only a small
part of the brain - although sometimes a partial seizure can
spread to the whole brain
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Generalized Seizures

Tonic-clonic seizures


Absence seizures


Loss of muscle tone – causes person to fall down
Myoclonic seizures


Non-convulsive. Person may be unaware of surroundings and stare off.
Lasts only 5-30 seconds
Atonic seizures


“grand mal” – massive discharge of neurons on both cerebral hemispheres.
Body becomes rigid and jerks. “Tonic-clonic” means “stiffness-violent”
“grand mal” means “great sickness”
Involves motor cortex and causes twitching or jerking of certain body parts.
Status epilepticus

Frequent, long-lasting electrical activity with no regaining of consciousness
between attacks. Very dangerous and requires immediate medical attention.
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Partial seizures
 Simple partial seizures
 “Jacksonian” or “focal” seizures.
 Short seizures with no loss of consciousness
 People may see, hear or smell something odd & their body
may jerk.
 Complex partial seizures
 “Psychomotor” seizures
 A seizure with a change, but no loss, in consciousness.
 People may hear or see things or have a memory resurface.
Déjà vu may occur.
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Diagnosis
 Diagnosis requires a thorough evaluation of
patients medical history describing seizure
characteristics and frequency.
 People suffering from epilepsy
-brain waves have a characteristically
abnormal rhythm.
 Another way epilepsy is diagnosed is through
an electroencephalograph (EEG).
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Overview of Epileptic Syndromes
Focal Seizures
 60% 0f Epilepsy
 Focal Cortical
Disturbance
 Their origin usually
determines the clinical
picture
 Focal Spikes on eeg
Primary Generalised
Seizures
 Origin unclear either
sleep spindles or
hypersynchrony
 Commence bilaterally
 Spike and wave
 No aura
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Cerebral
cortex
regions
Functional Areas of the Brain
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Example of Primary Generalised Epilepsy
 Childhood
absence
seizure
Easy Kent Coastal PCT
Complex partial seizures
Epilepsy;
Commonsense
Logical
Disabling
Easy Kent Coastal PCT
Examples of Focal Seizures
Focal motor seizure
that becomes
secondarily
generalised.
Likely focus in right
frontal lobe
Easy Kent Coastal PCT
Cellular Electrophysiology
Membrane Potential
The Na+ / K+ Pump
http://www.biologymad.com/NervousSystem/nerveimpulses.htm
Easy Kent Coastal PCT
Cellular Electrophysiology
 Selectively Permeable
Membrane - Channels
 Depolarising Shift
 Epileptic Focus
Easy Kent Coastal PCT
Easy Kent Coastal PCT
Principles of Epidemiology
 Incidence Rate= new cases per year [n per
100,000 per year]
 For epilepsy is around 50 per 100,000
 Point Prevalence = All cases with active
epilepsy at a point in time [n per 1000].
 For epilepsy is 4-6 per 1000
 Active Epilepsy = to have had a seizure or
treatment in the last 5 yrs
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Conditions that may look like a seizure
 Syncope
 “Psychogenic” seizures
 Breath-holding spells
 Paroxysmal REM sleep behavior
 Panic attacks
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International classification of epilepsies
 Originally established in 1989 – currently under
revision
 Current system comprises two major categories:
 Localization-related syndromes
 Idiopathic
 Symptomatic
 Generalized-onset syndromes





Idiopathic with age-related onset
Idiopathic &/or symptomatic
Symptomatic
Nonspecific etiology
Specific syndromes
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Complex partial seizures
 stare into space/engage in automatisms, such
as grimacing, gesturing, chewing, lip
smacking
 last 3 minutes or less
 post-ictal: somnolence, confusion, headache
for up to several hours
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Generalized tonic-clonic seizure
 No aura
 tonic phase x 10-20 seconds:
 sudden LOC, loss of posture, arms flex, eyes
deviate upward
 extension of back, neck, arms, legs
 involuntary crying out
 ends with tremors which merge c clonic
phase
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Generalized tonic-clonic seizure
 Clonic phase x 90 seconds:
 brief, violent, generalized flexor contractions
alternating with progressively longer muscle
relaxation
 cyanosis
 cheek or tongue biting, salivation
 loss of bowel, bladder control
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Generalized tonic-clonic seizure
 Post ictal phase x minutes to hours
 headache
 mild confusion
 sore muscles
 may sleep and feel refreshed
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Evaluation of single seizure

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


History of event
Medical History
Family History
Social History
Physical Examination
Neurological Examination
Laboratory Evaluation
 EEG
 MRI
 Routine lab work
Epilepsy
Prof. Magdy Dahab
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Treatment and Prognosis
 Antiepileptic (anticonvulsant) medications









Carbamazepine (Tegretol)
Clobazam (Frisium)
Clonazepam (Rivotril)
Diazepam (Valium)
Divalproex sodium (Depakote)
Ethosuximide (Zarontin)
Phenobarbital (many different names)
Phenytoin (Dilantin)
Valproic Acid (Depakene)
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Special topics in the Management of Epilepsy
1. Woman and Epilepsy
Pregnancy and epilepsy.
1. Pre-conceptual Care


ensure pregnancies are planned [high dose oestrogen pills if
necessary, 4 packs of COC consecutively with 4 day pill free
interval, Depo-provera every 10 weeks not 12.]
Discuss modification of AED to reduce number and total dose
Advise oral folic acid 5mg daily when intending pregnancy
Belfast Register ….www.epilepsyandpregnancy.com
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Special Topics in the Management of Epilepsy
Ante-Natal Care




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Continue 5mg Folic acid until at least 12 weeks
Adjust AED if necessary on medical grounds
Monitoring of plasma levels is not usually necessary [SIGN
guidelines]
Offer serum screening at 16weeks and anomaly scan at 18-22
weeks
Prescribe oral vit K 20mg a day from 36weeks in on enzyme
inducing AED
Prolonged seizures can be controlled by IV Diazepam [ rectally
is OK if IV access not possible]
Belfast Register ….www.epilepsyandpregnancy.com
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Special Topics in the Management of Epilepsy
Intra-Partum Care





Continue usual AED regime during labour
Control seizures with i.v. diazepam
Early decision for LSCS if seizures uncontrolled
Offer same range of analgesics as available to
other mothers
Give infant vitamin K 1mg IM at birth
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Special Topics in the Management of Epilepsy
Post Partum Care

Encourage breast feeding
 Offer advice for safe settings for feeding,
bathing etc.
 Review AED and contraceptive regimens
 Encourage pre-conceptive care for future
pregnancies
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Special topics in the Management of Epilepsy
Catamenial seizures- “the clustering of epileptic
seizures in relation to the menstrual cycle”
 Seizure control is worse in anovulatory cycles
 Oestrogen- inhibits GABA, potentiates glutaminergic
transmission, increases neuronal metabolism and
discharge rates and promotes kindling.
 Progesterone- its metabolites are barbiturate like
ligands at GABA receptor, reduces neuronal
transmission and discharge rate, suppresses kindling
and inhibits epileptic discharges
 Seizures likely when oestrogen/progesterone ratio is
highest
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Sexual dysfunction in epilepsy
Hypo sexuality –
 surveys suggest 22-67% reduction in sexual interest
Erectile Dysfunction –
 occurs in 57%[ Toone et al 1989], up to 83% in TLE
Sexual Functioning in Males [1989]
 Previous SI 56% [compared to 98% controls]
 S.I. in the previous month 43% [compared to 91% in
controls]
 Previous erectile dysfunction 57% [compared to 18%
controls]
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Social Aspects of Epilepsy
o Occupational – Unemployment, poor jobseeking skills, Non competitive, unskilled manual
employment as a result of disadvantaged
education, pressure of keeping current job
o Social – Social isolation as a result of no driving
licence, unable to drink alcohol, stigma
o Tiredness
o Over protective parents
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Employment
Disability Discrimination Act 1995 & 1996
Disability is defined as; “a physical or mental impairment
which has a substantial and long term adverse effect
upon one’s ability to carry out normal day to day
activities.”
Substantial is more than minor and long term is longer than
12 months
Exclusions; Hay fever, tendency to set fires or steal, physical
or sexual abuses of others
Disability Discrimination Help Line Tel: 0345 622644
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Driving
Collapse at the wheel





CVA 8%
Heart 9%
Diabetes 17%
Blackout 22%
Epilepsy 38%
Others 7%
Group1 Driving Licence- Must be 1 yr seizure free with a
medical review before restarting or only nocturnal
seizures for 3 yrs
Group 2- Withdrawn for 10 yrs and can be re-issued if 10yrs
seizure freedom and has not taken AD during the time or
does not have a continuing liability to epileptic seizures
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Driving
AED Withdrawal
Risk of developing seizure increases by 40% so
advise patients not to drive during withdrawal
and for 6 months afterwards
Confidentiality
 If patients continues to drive inform patient not to
 If continues to drive advise if continues will inform
DVLA [copy of warning letter to patient and GP]
 If still continues advise will inform DVLA and do so
[occurs very exceptionally]
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Overview of established Anti Epileptic Drugs
Carbamazepine





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Partial Epilepsy – Not for Absence or Myoclonic
Jerks
Start at 100-200mg a day increase slowly
S/E- diplopia, nausea, headache, dizziness
Idiosyncratic reactions possible [up to 10%]
Monitoring needed- increase ‘Chrono’ dose
Beware of interactions
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Overview of established
Anti Epileptic Drugs
Clobazam
 Used intermittently
 Extra cover for catamenial seizures, stressfull
events , clusters of attacks
 Dose- 10mg [SLS] once or twice a day for 3
days
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Overview of established
Anti Epileptic Drugs
Clonazepam
 Limited role due to tolerance, sedation and
withdrawal seizures
 Usually reserved for refractory seizures
especially Myoclonic jerks
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Overview of established
Anti Epileptic Drugs
Ethosuximide
 Indication – Absence seizures [hence
paediatric field usually]
 Introduce slowly 500mg daily increasing to 12 g a day
 Side Effects – GI and CNS
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Overview of established
Anti Epileptic Drugs
Gabapentin
 Add on therapy for partial seizures only
 Dose starts at 300mg a day and increases to
1800-2400 mg a day with t.d.s dosing
 No interactions[ not metabolised]
 Side effects – well tolerated occas.
drowsiness, dizziness, diploplia, ataxia and
headaches
 ? Efficacy
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Overview of established
Anti Epileptic Drugs
Lamotrigine
 Broad spectrum and first line [ less
teratogenic than VPA]
 Dosing – slow to minimise side effects usually
25mg a day increasing every 2 weeks, b.d.
dosing. Max dose around 400mg a day.
 Interactions – VPA , CBZ and PHT
 Idiosyncratic reactions in up to 5%
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Overview of established
Anti Epileptic Drugs
Piracetam
 Need a wheelbarrow !
 Indications – refractory myoclonus
 Dose – 7.2g in t.d.s. dosage, increasing
weekly to 12-24 g/day!!
 No known interactions
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Overview of established
Anti Epileptic Drugs
Phenytoin
 Was considered first line for partial seizures
 Poor side effect profile- rash , liver toxicity.
blood dyscrasias, cosmetic changes,
neurotoxicity etc
 Dosing difficulties – saturation kinetics
 Many interactions
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Overview of established
Anti Epileptic Drugs
Phenobarbitone [and Mysoline]
 World-wide best seller for partial seizures
 Side –effects largely unacceptable- effects on
cognition, mood and behaviour. Also arthritic
changes, dupytrons contracture, frozen
shoulder
 Interactions- accelerates metabolism of many
lipid soluble drugs
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Overview of established
Anti Epileptic Drugs
Sodium Valproate
 Broad Spectrum and Powerful [ no-longer
first line in women]
 Dose – 300- 500mg a day, usually bd dosage
 Side effects- tremor, wt. gain, POS, possible
hepatotoxicity, blood dyscrasias and
pancreatitus
 Interactions- can inhibit liver enzymes
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Overview of established
Anti Epileptic Drugs
Vigabatrin
 Tertiary Care Initiation
 Peripheral field loss [permanent in up to 40%]
 Used for very resistant cases or in infantile
spasms
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Overview of the Newer
Anti Epileptic Drugs
Topiramate
 Second line – Broad Spectrum [5 mechanisms of
action]
 Dose starts at 25mg a day -2 in 3 tolerate it
slowly increased to 200-400mg a day
 Side effects- Irritability, drowsiness, headaches,
dizziness, cognitive slowing, speech
impairment, weight loss and paraesthesia.
 Beware of kidney stones [occurs in 4 %]
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Overview of the Newer
Anti Epileptic Drugs
Oxcarbazepine- analogue of CBZ
 Indications – same as CBZ, may worsen
absence and myoclonic epilepsy.
 Dose – start at 300mg a day and increase to
900 – 2400mg a day as needed
 Side effects – hyponatraemia, headaches,
occas. rashes and teratogenicity
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Overview of the Newer
Anti Epileptic Drugs
Levetiracetam – Piracetam derivative
 Licensed as second line for refractory partial
epilepsy but is broad spectrum
 Dose- start at 125mg [half a tab] a day and build up
to max of 3,000mg if needed
 Side effects – no known idiosyncratic reactions may
cause somnolence, irritability [initially]
 Interactions – Nil definite ?? CBZ and PHT
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STATUS EPILEPTICUS
Definition
 Most epileptic seizures stop with minutes
 Continuous seizures >10 mins
 Does not recover between recurrent seizure
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Type
 Generalized
 Generalized tonic-clonic, absence,
myoclonic ,tonic,atonic,akinetic,clonic
 Partial onset
 Simple
 complex
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Treatment of protocol
 0 min: hx of recent seizures,impaired
cons,observe 10 mins,start EEG as soon as
possible
 5 mins:iv set normal saline or dextrose
solution
 10 mins:lorazepam 0.1 mg/kg iv push
(<2mg/min)

Epilepsy problem solving in clinical practice-Dieter Schmidt and Steven C
Schachter
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Treatment protocol
 25 mins : phenytoin 20 mg/kg slow iv push
(<50 mg/min) or fosphenytoin iv push fast 150
mg/min,monitor BP,ECG during infusion
 If continuing: another 5 mg/kg phenytoin,can
give twice,to a maximun dose of 30 mg/kg
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Treatment of protocol
 60 mins:phenobarbital 20 mg/kg iv push
 Support respiration,on endo
 Phenobarbital 5~15 mg/kg
 Phenobarbital 0.5~5 mg/kg/hr for maintain
 Continuous infusion of propofol or
midazolam
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Thank You
www.magdydahab.com
Prof. Magdy Dahab
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