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Epilepsy
Prof Akram M Al-Mahdawi
CABM,MRCP,FRCP,FACP,FAAN
‘Sacred illness’• ‘Sacred illness’: 600 BC• Hippocrates 400 BC: It is thus with regard to the disease called
sacred: it appears to me to be in no way more divine nor more sacred than other diseases [...].The brain is the cause of this affliction [...].
Alexander the Great Julius Caesar Napoleon F. Dostoyevsky
Definition
Epilepsy: Chronic brain disorder of various etiologies characterized by recurrent unprovoked seizures.
Epileptic Sz: Discrete epileptic event due to transient, hyper-synchronous , abnormal neuronal behavior.
Epileptic Syndromes: Grouping of similar epileptic patterns according to sz type, EEG, age of onset, familial episodes, prognosis, other clinical signs.
Event that may mimic seizures
Physiological event Syncope TIA TGA Sleep disorder Dizziness/vertigo
Psychiatric-based events Panic/anxiety Conversion Dissociative Hyperventilation Acute psychosis malingering
Events features favoring epileptic seizures Aura Brief duration(1-2 min) Postical confusion Amnesia for the event Events arising from sleep Self injury Eye open at the onset of the event
Epileptic seizure versus syncopeSyncope Tonic-clonic seizure
Position Upright Any
Facial colour Paleness Cyanosis
Onset Gradual; introduced by dizziness, blurring of vision
Sudden; can start by ‘aura’ (simplex partial seizure)
Twitchings Rarely (‘convulsive syncope’) Always
Enuresis Rarely Often
Tongue bite No Often
Duration 10-20 seconds Few minutes
Postictal confusion No Yes
Perspiration Pronounced Not typical
Epilepsy: Etiology Vs. Age of Onset
0 10 20 30 40 50 60 70 80 90
Perinatal injury
Metabolic defect
cong. Malformation
Infection
Genetic Epilepsy
Pstnatal Trauma
Brain Tumor
Vascular dis.
Trigger factors for seizures
Sleep deprivation Alcohol (particularly withdrawal) Recreational drug misuse Physical and mental exhaustion Flickering lights, including TV and computer screens infections and metabolic disturbances Uncommonly: loud noises, music, reading, hot baths
Localization of Partial Seizure Focus
70%70% 10%10%
20%20%
Clinical features associated with localization
Temporal lobe-Déjà vu,epigastic aura,fear/fright,formed visual images.
Frontal lobe-muscle/motor activity,forced eye deviation,speech arrest.
Parietal lobe-parasthesias,sensory phenomenon Occipital-flashes,colors
Simple partial seizures No loss of consciousness Symptoms depend on area
of brain involved: Motor Sensory Autonomic Psychosensory
It can be the introductory phase of a complex partial or generalised tonic-clonic seizure (‘aura’)
Complex partial seizures Origin is most often in the temporal lobe A common seizure type in adulthood Can be introduced by a simplex partial psychosensory
seizure: olfactory hallucination déjà vu, jamais vu feeling of alienation
Loss of consciousness: stare, ‘going blank’ Automatisms:
oral automatisms fiddling with the hands
Temporal lobe epilepsy Most common epilepsy in adulthood;
can be heralded by a few seizures in childhood, but typical age of onset is 20-22 years
Seizure types: olfactory hallucination (simplex
partial) psychosensory seizures (simplex
partial) complex partial generalised tonic-clonic
Febrile convulsions in childhood Hippocampal sclerosis Often refractory to therapy
Benign centrotemporal epilepsy Age of onset: 3-15 years Seizure types: facial, oro-bucco-
pharyngeal motor and sensory simplex partial seizures; speech arrest
Nocturnal seizures Mild disease. Normal neurological and mental EEG- centrotemporal spike
waves Spontaneous remission by
puberty
West syndrome Age of onset: 3-5 months Seizure types: infantile spasms Causes: inborn metabolic, storage
diseases, perinatal hipoxic brain damage Cryptogenic in 40-50% Neurological symptoms, mental
retardation; bad prognosis; can transform into Lennox-Gastaut syndrome
EEG: hypsarrhythmia R:corticotropin,steroid,vigabatrin Prognosis: often poor but depend on
etiology
Lennox-Gastaut syndrome Age of onset:2-8 years 3-10 of childhood epilepsy Seizure types: atonic, axial tonic,
myoclonic, atypical absence, tonic-clonic
30%of WS syndrome will have LGS Causes: same as in West syndrome;
can develop from West syndrome Neurological symptoms, mental
retardation Unfavourable prognosis (refractory
seizure,mental handicap{80%}. Ketogenic diet,1st line AEDs
{valproate,lamotrigine,topiramate
Generalised tonic-clonic seizure(grand mal)
The most common seizure
Course: Cry, loss of consciousness, fall Tonic phase- generalised muscle
contraction, apnoe Clonic phase- rhythmic
contraction of muscles, tongue bite, foaming, enuresis
Terminal sleep and gradual regaining of consciousness (transient confusion)
10-25 yrs ,65 controlled with AEDs but relapse
Juvenile myoclonic seizure
Sudden, quick, arrhythmic muscle contraction, twitch of a limb; no loss of consciousness
EEG: generalised polyspike and wave activity
Occurs in genetic (idiopathic) epilepsies
90% remit with AEDs but relapse if AEDs withdrawn
R-Na valproate.Levetiracetam
Absence
Cognitive dysfunction with a sudden onset and end, lasting 5-10 seconds
Stare, expressionless face; arrest of ongoing activity; generally no motor phenomena
Occurs in genetic (idiopathic) epilepsies, mostly in children
CAE-4-8 yrs,frequent brief absence,3/sec spike and wave,R-ethosuximide,Na valproate.levetiracetam.40% develop GTCS,80 remit in adulthood
JAE.10-15 yrs, less frequent abcence,polyspike and wwave.R Na valproate,levetiracetam.80% develop GTCs,80% seizyre free in adulthood
Diagnostic steps History EEG
Negative EEG does not exclude epilepsy Positive EEG without clinical signs does not prove
epilepsy EEG after sleep withdrawal or during sleep Long-term EEG / video monitoring CT, MRI
EEG Abnormalities
•Background abnormalities
-Significant asymmetries and/or degree of slowing inappropriate for clinical state
•Transient abnormalities associated with seizures
-Spikes (< 70 m sec)
-Sharp waves (~70 – 200 msec)
-Spike-wave complexes
•May be focal, lateralized or generalized
Indications for brain imaging in epilepsy
Epilepsy starting after the age of 20 years Seizures having focal features clinically EEG showing a focal seizure source Control of seizures difficult or deteriorating
How to administer first aid for seizures
Move person away from danger (fire, water, machinery, furniture) After convulsions cease, turn into 'recovery' position (semi-prone) Ensure airway is clear, but do NOT insert anything in mouth (tongue-biting occurs at
seizure onset and cannot be prevented by observers) If convulsions continue for more than 5 minutes or recur without person regaining
consciousness, summon urgent medical attention Do not leave person alone until fully recovered (drowsiness and confusion can persist for
up to 1 hour
First Seizure
•Whether to treat first seizure is controversial
•Increased risk of relapse
1-Abnormal imaging 2-Abnormal EEG 3-Family history of epilepsy
•Currently, most patients are not treated for the first seizure unless there is an increased risk for relapse
Medical treatment of epilepsy When do we start antiepileptic medication
(AED)? Which AED to choose? When and how do we switch AEDs? When is polytherapy needed? When can AEDs be discontinued? Pregnancy Driver’s licence
Therapeutic principles Aim: maximal seizure control, minimal side
effects Monotherapy Usually gradual introduction of AED Assessment of AED effect (seizure frequency)
After AED has reached steady state Depends on the average time interval of seizures
before treatment
AEDsOld
Primidon Phenobarbital Phenytoin Clobazam Clonazepam Ethosuximid Valproate Carbamazepine
New Lamotrigine Oxcarbazepine Topiramate Gabapentin Vigabatrin Levatiracetam Zonisamide Tiagabin
Mechanism of action of AEDsInhibition of voltage gated Na, Ca channels
Na: phenytoin, carbamazepine, oxcarbazepine, lamotrigine, topiramate, felbamate, zonisamide
Ca: ethosuximid, valproate? lamotrigine, topiramate, zonisamide
Potentiaton of GABA mediated inhibition
phenobarbital, benzodiazepins, vigabatrin, tiagabine, topiramate, valproate, gabapentin, felbamate
Decrease of glutamate mediated excitation
felbamate, topiramate
Pharmacology of AEDs I.Hepatic metabolism valproate, carbamazepine,
oxcarbazepine, lamotrigine, topiramate, clobazam, clonazepam, phenobarbital, primidon, phenytoin, ethosuximid, felbamate, tiagabin
No metabolism gabapentin, vigabatrin
topiramate, levatiracetam
Hepatic enzyme induction carbamazepine, phenytoin, phenobarbital, primidon (oxcarbazepine)
Hepatic enzyme inhibition valproate
Drug interactionsEnzyme inductors
carbamazepine, phenytoinphenobarbital, primidon
Increase of metabolism / decrease of efficacy
valproate, lamotrigine, topiramate, carbamazepine
oral contraception
oral anticoagulation
Enzyme inhibitors
valproate
Decrease of metabolism / increase in efficacy - toxicity
lamotrigine, carbamazepine, phenytoin
Does not cause interaction
lamotrigine, gabapentin, topiramate, vigabatrin
Guidelines for anticonvulsant therapy
Start with one first-line drugStart at a low dose; gradually increase dose until effective control of seizures is achieved
or side-effects develop (drug levels may be helpful) Optimize compliance (use minimum number of doses per day) If first drug fails (seizures continue or side-effects develop), start second first-line drug
whilst gradually withdrawing first If second drug fails (seizures continue or side-effects develop), start second-line drug in
combination with preferred first-line drug at maximum tolerated dose (beware interactions)
If this combination fails (seizures continue or side-effects develop), replace second-line drug with alternative second-line drug
If this combination fails, check compliance and reconsider diagnosis (is there an occult structural or metabolic lesion or are seizures truly epileptic?)
If this combination fails, consider alternative, non-drug treatments (e.g. epilepsy surgery, vagal nerve stimulation)
Do not use more than two drugs in combination at any one time
Side effects of AEDs Allergy Central nervous system side effects
(dose dependent) drowsiness, headache dizziness, dysequilibrium cognitive dysfunction (memory)
Idiosynchratic reactions / chronic side effects bone marrow suppression hepatic failure rash weight gain, weight loss tremor polycystic ovary syndrome visual field defect
Summary of Serious and Non-serious Adverse Events of the Newer AEDs
AED Serious Adverse Events Nonserious Adverse Events
Gabapentin None Weight gain, peripheral edema, behavioral changes
Lamotrigine Rash, including Stevens Johnson and toxic epidermal necrolysis (increased risk for children, also more common with concomitant valproate use and reduced with slow titration); hypersensitivity reactions, including risk of hepatic and renal failure, DIC, and arthritis
Tics and insomnia
Levetiracetam None Irritability/behavior change
Oxcarbazepine Hyponatremia (more common in elderly), rash None
Topiramate Nephrolithiasis, open angle glaucoma, hypohidrosis (predominantly children)
Metabolic acidosis, weight loss, language dysfunction
Zonisamide Rash, renal calculi, hypohidrosis (predominantly children)
Irritability, photosensitivity, weight loss
Possible causes of AED inefficacy Inadequate dose → dose escalation Lack of compliance → measure blood AED levels False diagnosis: the patient doesn’t have epilepsy ‘Pseudoseizures’ → precise description of seizure, EEG
/ video monitoring Inadequate selection of AED True inefficacy of AED → AED switch
Other AED on monotherapy AED combination
Withdrawing anticonvulsant therapy
Withdrawal of medication may be considered after apatient has been seizure-free for more than 2 years. Childhood-onset epilepsy, particularly classical absenceseizures, carries the best prognosis for successful drug withdrawal. Other epilepsy syndromes, such as juvenile myoclonic epilepsy, have a marked tendency to recur after drug withdrawal.
Seizures that begin in adult life, particularly those with partial features, are also likely to recur, especially if there is an identified structural lesion.
Overall, the recurrence rate after drug withdrawal depends on the individual's epilepsy history.
Patients should be advised of the risks of recurrence, to allow them to decide whether or not they wish to withdraw.
If undertaken, withdrawal should be slowly, reducing dose gradually over weeks or months. Withdrawal may necessitate precautions around driving or occupation.
Discontinuation of AED Discontinuation of AED is not recommended:
Earlier unsuccessful AED withdrawal Earlier refractoriness to treatment Known brain lesion Juvenile myoclonic epilepsy
contraception
AEDs induce hepatic enzymes that metabolise synthetic hormones, increasing the risk of contraceptive failure. This is most marked with carbamazepine,
phenytoin and barbiturates, but clinically significanteffects can be seen with lamotrigine and topiramate.
If the AED cannot be changed, this can be overcome by giving higher-dose preparations of the oral contraceptive.
Sodium valproate and levetiracetam have no interactionwith hormonal contraception.
Risks of Congenital Abnormalities
Congenital malformations Most common: orofacial clefts, heart defects Less common: microcephaly, neural tube defects
Major malformations General population: 2% to 4% Newborns prenatally exposed to AEDs: 4% to 8% Multiple AEDs and higher doses may substantially increase malformation rate
Minor malformations
Epilepsy and breast feeding
Breast feeding is not contraindicated with women on AEDs.
Sleep deprivation can provoke seizures.
Epilepsy and driving
Driving is prohibited for one year after a seizure with loss of consciousness
Driving is permitted: 2-3 years of seizure free interval with patients on
AEDs 2-3 years of seizure free interval after withdrawal of
AEDs
AEDs and Bone Health
Status Epilepticus
1-10 mg IV Diazepam or 4 mg IV lorazepam bolus, can repeated onceStage of Established status(SZ continue after 30 Stage of Established status(SZ continue after 30
min)min)1-Phenobarbit infusion 10mg/kg at 100 mg/min2-phenytoin infusion 15mg/kg at 50mg/min or
Fosphenytoin 15mg/kg at 100mg/min.Can repeate another 5-10mg/kg of phyentoin
3-if SZ continue after 30-60min (refractory)
Propofol 2mg/kg----1-3 mg/kg/hr Thiopental 100-250mg given once 20
sec—-----3-5mg/kg/hr Midazolam 0.1-0.3 mg/kg—NOT exceeding 4mg/min
slowly IV infusion----0.05-0.4 mg/kg/hr SZ control—300mg/day phenytoin or 400-1200 mg/day
by nasogastric tube When seizure control for 12 hr ,then the anaesthetic drugs
withdrawn slowly over 12 hrs,if recure again 12 hrs