EpilepsyPost graduate medicine Jan 2002

What is epilepsy Occurance of two or more unprovoked seizures is

called epilepsy Epileptic seizures are behavioral changes resulting

from paroxysmal, excessive discharges from brain Single or occasional epileptic seizures or febrile fits

should not be classified as epilepsy Not all jerks , shakes and episodic behaviors are

seizures Tics, tremors, dystonias and sustained clonus in a

stroke pt may mimic epilepsy

Non epileptic paroxysmal dissorders that can mimic epilepsy Syncope

Reflex(vasovagal, carotid sinus, glossopharyngeal, cough)

cardiac output Decreased LV filling

(hypovolumia, orthostatic hypotensio, PE)

Cardiac arrhythmias Migraine (classic, basillar and

confusional) Cerebrovascular event (TIA) Periodic paralysis Sleep dissorders

GI disorders (Reflux, motility disorders)

Movement disorders Tics Tourette’s synd Non epileptic myoclonus Parox. Choreoathetosis

Psychiatric disorders Panic Somatization Dissociation

Conversion (non epileptic psychogenic fits)

Drug toxicity et subs abuse Breath holding spells

Non epileptic psychogenic seizure How to differentiate

Cannot reliably differrentiate Gradual onset Stopping & restarting Out of phase clonic movements of extremities Vocalization in the middle of the seizure Pelvic thrusting and lack of whole body rigidity

But frontal lobe cpx seizures may be misdiagnosed (rocking, kicking, bicycling, pelvic thrusting, genital manipulat ion and cursing)

Aetiology Unknown in 2/3rd

Head injury Stroke Brain tumor Cortical dysplasia Infection eg:neurocysticercosis Alcohol related

Diagnostic workup Firist diagnose seizure Then determine

Seizure type Syndromic classification Etiology Likelyhood of recurrence Is treatment needed

Diagnostic workup History taking Physical examination Neurological examination Diagnostic testing

Establishing the diagnosis Is a paroxysmal event with impairement of

awareness Diagnosis is clinical Eye witness is very essential There is no substitute for detailed Hx

Circumstance of the episode Patterns of occurance Preceding symptoms that may localise or suggest other

conditions Timing, pattern and tempo of evolution of symptoms Reported behaviour before, during and after the

event

History- before the event

Unusual stress (eg, severe emotional trauma)Sleep deprivationRecent illnessUnusual stimuli (eg, flickering lights)Use of medications and drugsActivity immediately before event (eg, change in posture, exercise)

History during the event Symptoms at onset (eg, aura)

Temporal mode of onset: gradual versus suddenDuration: brief (ictal phase <5 min) versus prolongedStereotypy: duration and features of episodes nearly identical versus frequently changingTime of day: related to sleep or occuring on awakening

History during the event Ability to talk and respond appropriately

Ability to comprehendAbility to recall events during the seizureAbnormal movements of the eyes, mouth, face, head, arms, and legsBowel or bladder incontinenceBodily injury

History after the event Confusion

LethargyAbnormal speechFocal weakness or sensory loss (ie, Todd's paralysis)Headache, muscle soreness, or physical injury

Episode is more likely to be syncopal if Is precipitated by anxiety or pain (eg, venipuncture) Occurs after the patient assumes an upright position Occurs only when the patient is standing or sitting Is associated with facial pallor and diaphoresis Is not associated with sustained tonic or clonic

movements, bladder incontinence, or biting of the tongue or cheek

Is not followed by postictal confusion, lethargy, muscle soreness, and headache

Is followed by a relatively rapid return to baseline

Past medical history Prolonged febrile fit Meningitis Encephalitis Head injury Cancer Stroke In diabetic pts hypo/hyperglycemia Hyponatremia, hypocalcemia, hypo

parathyroidism and hypothyroidism can cause fits

Drug history Theophyllin INAH Phenothiazine Clozapine Radiocontrast dye Alkylating agents Beta lactam antibiotics Others : lignocain, general anesthetics,

Tricyclics, SSRI, Acyclovir, beta blockers, decongestants, ectasy(MDMA)

Physical examination Examine the patient for injuries from the seizure or

fall. Check oxygen saturation and auscultate the chest for

possible aspiration. Measure heart rhythm and rate, blood pressure, and

orthostatic changes for assessment of syncope. Auscultate for carotid murmurs or carotid bruits and

sources of embolic stroke. Check for rapid pulses, which are often present after

seizure and may help in evaluation of psychogenic seizures.

Neurological examination Purpose is to identify focal or diffuse cerebral

dysfunction Certain features will suggest focus of fit

Aphasia – frontal lobe, temporal or parietal Right or left hemiparesis – contralateral motor cortex Sensory deficit – parietal lobe dysfunction

Should be observed for Fluency of language Facial asymetry Gaze preference Pupilary asymetry (Herniation of brain)

Extensor plantar for some time - normal

Diagnostic testing All pts should have

FBC Ca, SE Glucose LFT ECG – important to detect prolonged QT

(Morning generalised tonic clonic seizure)

Diagnostic testing Toxicity screening and alcohol level in

appropriate pts Lumbar puncture infection or fever

present, HIV or malignancy

Diagnostic testing -EEG Role misunderstood Detection of abnormality does not

equate epilepsy Absence of inter ictal abnormality does

not exclude epilepsy Only 1/3rd of epileptics show

abnormalities Ictal EEG could also be normal

Diagnostic testing -EEG EEG is diagnostic in certain conditions

Generalised 3Hz spike and wave activity-- 1ry generalised epilepsy

Ictal recordings are not routinely done except in incidental situations

EEG telemetry Ambualtory or video telemetry if

diagnosis remains in doubt Presurgical

Intracranial amytal testing to test memory and language function

Intracranial EEG to localise the focus

Imaging studies Immediately after fit CT scan– bleeding or

structural lesions MRI is the Ix of choice – sensitive & specific

for evaluation of structural lesions and brain parenchyma Mesial temporal sclerosis – hippocampus Dysplasia – cortical architectural abnormalities Better if could be done for all partial seizures Reveals abnormality in

30% with generalised epilepsy 70% with focal epilepsy

Detailed investigations Few pts will need

Hypoglycemia – early morning fits ECHO Ambulatory ECG Urinary catecholamines Porphyrins

Implications of diagnosis May loose job Life restricted Mental trauma Driving licence Marriage

So all differential diagnosis should be carefully considered

Classification Generalised

Arise from both sides of the brain simultaneously

Partial or focal Occurs within one or more restricted

regions of the brain and effect of a localised physiologic or structural abnormality of brain (Eg: tumor, dysplasia, stroke, trauma)

Classification Generalised

seizures Absence Atonic Myoclonic Clonic Tonic Tonic clonic (Grand

mal)

Partial Simple partial

consciousness not affected

Complex partialconsciousness

impaired Partial with 2ry

generalizationcan be tonic clonic,

tonic or clonic

When to treat Once diagnosed decide wether to treat or not Recurrece

After a single tonic clonic fit 15-60% After 2 fits – 85%

Probability of recurrence increases if Family history + Spike and wave pattern in EEG Hx of prior neurological insult Todd’s paralysis Status epilepticus Acute symp fit (occuring after brain insult)

First fit - to treat or not What is the risk of treating and non

treating What is the risk of recurrence Occupation- heavy vehicle drivers – yes In children – initial fit during sleep – no

need to treat Patients preference

Management - aim Prevent fits without causing adverse

effects Optimise patients quality of life Fits could be life threatening Pts with epilepsy are at risk of sudden

unexpected death (1/200/yr in refractory epilepsy)

Management - Principles Rx is usually not given after a single

unprovoked seizure, unless recurrence risk high

Avoid precipitating factors Identify underlying conditions and Rx Treatment strategies should be

explained to the pt

Management – Principles (Drugs) Choice – pts individual circumstance, syndrome and

side effect profile Low dose – slowly increase over weeks, minimising

side effects and promoting compliance If 1st line drug fails, add another 1st line drug while

gradually withdrawing the 1st drug If unsuccessful add 2nd line drug Vigabatrin and barbiturates should not be combined Refer refractory cases for evaluation for surgery

Monotherapy vs polytherapy 47% fit free with one drug 14% fit free with addition 2nd or 3rd drug If 2nd drug fails refer for evaluation of

surgery If not willing for surgery – consider

polytherapy

.

Type of epilepsy

First-line agents Second-line agents

Partial Carbamazepine, oxcarbazepine (Trileptal), phenytoin (Dilantin)

Divalproex sodium (Depakote), felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), tiagabine HCl (Gabitril Filmtabs), topiramate (Topamax), valproate (Depakene, Depacon), zonisamide (Zonegran)

Init ial treatment for partial and general ized epilepsies

Init ial treatment for part ial and generalized epilepsies

Generalized First line 2nd line

•Absence seizures

Ethosuximide (Zarontin), valproate

Lamotrigine, levetiracetam

•Idiopathic Lamotrigine, valproate Topiramate, zonisamide

•Symptomatic Lamotrigine, topiramate, valproate, zonisamide

Barbiturates, benzodiazepines

Seccond line drugs All of the newer AEDs, including

felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, tiagabine, and zonisamide, have demonstrated efficacy when used as adjunctive therapy in patients with poorly controlled seizures of partial onset

Seccond line drugs

Lamotrigine Could be used as 1st line

Gabapentin Safe, tolerable Monotherapy in liver disease, cutaneous

allergies, porphyria, immune deficiencies, elderly

Drug interactions

No interactionGabapentin (Neurontin)Levetiracetam (Keppra)

InducersCarbamazepinePhenobarbital (Bellatal, Luminal Sodium, Solfoton)Phenytoin (Dilantin)Primidone (Mysoline)

Drug interactions Inhibitors

Felbamate (Felbatol)Valproate (Depakene, Depacon)

Affected by enzyme-inducing drugsCarbamazepineFelbamateLamotrigine (Lamictal)Oxcarbazepine (Trileptal)PhenobarbitalPhenytoinPrimidoneTiagabine HCl (Gabitril Filmtabs)Topiramate (Topamax)ValproateZonisamide (Zonegran)

Healthcare issues for patients with epilepsy

Coping with the diagnosisObserving and recording seizuresIdentifying potential triggers and high-risk timesMaintaining personal safetyHandling seizure emergenciesManaging adverse drug effectsUnderstanding the nonmedical options for seizure management

Issues in social relationships and community living for patients with epilepsy

Personal adjustment to epilepsySexuality issuesEducation and employmentRecreational opportunitiesDisclosure of epilepsy to employersStigma and discriminationIndependent livingTransportationRespite care

Healthcare issues for patients with epilepsy

Managing concomitant illnessUnderstanding the relationship between seizures and hormonal statesPracticing family planningManaging pregnancy and menopauseMaintaining bone health

Withdrawl of treatment

>70% on Rx enter prolonged long term remission

Even untreated 50% undergo remission Why withdrawl

Side effects Social restrictions cost

Assess the patient Do a follow up EEG Counsel pt and family

Withdrawl of treatment Pts fit free for >2yrs to be considered 2/3rd are fit free Recurrences occur

50% within 6/12 Majority within 1 year

Surgical treatment Is not a recent development If refractory refer to specialist epilepsy

clinic for evaluation Prolonged video telemetry is the gold

standard for assesment of seizure before surgery

Fit free >60%

Presurgical evaluation for epilepsy Routine electroencephalography (EEG)

Video-EEG monitoringMagnetic resonance imagingPositron emission tomography*Single-photon emission computed tomography*Neuropsychological evaluationIntracarotid amobarbital test (ie, Wada's test)

Epilepsy in women Cong malformation with drugs 4-6% (2x

normal population) >90% with epilepsy have normal

pregnancy and deliver normal children Most will need drug Rx, because

benefits outweighs risks Number of drugs proportional to risk of

teratogenecity

Epilepsy in women All females in childbearing age should

be on folic acid Congenital abnormalities (with all)

Minor dysmorphic anomalies Hyperptelorism Epicanthal folds Distal digital hypoplasia

Valproate: 2% risk of spina bifida So avoid in females unless clearly indicated

Epilepsy in women Contraceptive failure

Barbiturates carbamezipine Phenytoin Topiramate

No effects on contraception Gabapentin Lamotrigine Valproate