epilepsy

Epilepsy

Prof Akram M Al-Mahdawi CABM,MRCP,FRCP,FACP,FAAN


‘Sacred illness’ ‘Sacred illness’: 600 BCHippocrates 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 syncope
Syncope
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

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%
10%
20%

Clinical features associated with localization

Simple partial seizures
No loss of consciousnessSymptoms depend on area of brain involved:MotorSensoryAutonomicPsychosensoryIt 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 lobeA common seizure type in adulthoodCan be introduced by a simplex partial psychosensory seizure:olfactory hallucinationdйjа vu, jamais vufeeling of alienationLoss of consciousness: stare, ‘going blank’Automatisms:oral automatismsfiddling 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 stateTransient abnormalities associated with seizures-Spikes (< 70 m sec)-Sharp waves (~70 – 200 msec)-Spike-wave complexesMay 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?PregnancyDriver’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

AEDs

Old Primidon Phenobarbital Phenytoin Clobazam Clonazepam Ethosuximid Valproate Carbamazepine
New Lamotrigine Oxcarbazepine Topiramate Gabapentin Vigabatrin Levatiracetam Zonisamide Tiagabin

Mechanism of action of AEDs

Inhibition 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 interactions

Enzyme 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
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Guidelines for anticonvulsant therapy 
Start with one first-line drug Start 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 levelsFalse diagnosis: the patient doesn’t have epilepsy‘Pseudoseizures’ → precise description of seizure, EEG / video monitoringInadequate selection of AEDTrue inefficacy of AED → AED switchOther AED on monotherapyAED 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 interaction with 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 once Stage of Established status(SZ continue after 30 min) 1-Phenobarbit infusion 10mg/kg at 100 mg/min 2-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/hrThiopental 100-250mg given once 20 sec—-----3-5mg/kg/hrMidazolam 0.1-0.3 mg/kg—NOT exceeding 4mg/min slowly IV infusion----0.05-0.4 mg/kg/hrSZ control—300mg/day phenytoin or 400-1200 mg/day by nasogastric tubeWhen seizure control for 12 hr ,then the anaesthetic drugs withdrawn slowly over 12 hrs,if recure again 12 hrs