Epilepsy: Factsheet 27/11/2007

- Epilepsy is the continuing tendency to have seizures: this propensity can arise from many
aetiologies. Thus epilepsy is considered a symptom of underlying brain disorder.
- Affects 0.5% of the population

Epileptic seizure = synchronous, paroxysmal and excessive discharge of neurones in cerebral

cortex, causing a clinically discernable event.
Clinical manifestations depend on region of cortex affected.
Frequently – sudden onset and cease spontaneously
-Brief, lasting seconds to minutes.
Seizures are usually followed by post-ictal drowsiness and confusion

Mechanisms
Spread of electrical activity between neurones is normally restricted – synchronous discharge
produces normal EEG.
Seizure: large groups of neurones are activated repetitively, unrestrictedly and
hypersynchronously.
This produces high voltage, spike-and-wave EEG activity (hallmark!)
Seizures are facilitated by lack of neuronal inhibition  hence one anticonvulsant strategy is
to increase GABA levels in the brain and spinal cord.

Aetiology

Trauma perinatal insults (contusion and haemorrhage) fetal anoxia

depressed skull fracture/ penetrating brain injury
Cerebrovascular disease (15%) AVM, Cavernoma, Vasculitis , Post stroke
Cerebral tumours (6%) 1y, particularly slow growing (e.g. meningioma, oligodendrocytoma)
Alcohol-related (6%) Withdrawal: 5-15% chronic alcoholic have seizures 1
Drugs Recreational – cocaine, amphetamines2; Therapeutic - isoniazid
Infection Acute bacterial meningitis, encephalitis, abscess, prion (CJD), AIDS
Degenerative Alzheimer’s disease, multiple sclerosis
Genetic (<2%) 30% epileptic pts have 1st degree relatives w/ epilepsy.
Metabolic abnormalities Hypoglycaemia, hypocalcaemia, hypoxia, mitochondrial disease

Classification
1. Generalised seizure types
a. Absence – typical (3Hz spike and wave) or atypical
b. Myoclonic
c. Tonic – stiffening of body not followed by jerking
d. Clonic
e. Tonic-clonic
f. Atonic (Akinetic) seizures -rare: sudden loss of tone  pt falls to ground

2. Partial seizure types

a. Simple partial – e.g. Jacksonian march (consciousness preserved)
b. Complex partial (loss of consciousness)
c. Secondarily generalised

3. Unclassifiable Seizure Types

1
Alcohol-induced hypoglycaemia may provoke seizures
2
Phenothiazines, monoamine oxidase inhibitors, TCAs, propofol  provoke if low seizure threshold
Generalised Seizures

Tonic Clonic (grand mal)

o patient has vague warning (prodrome) of malaise
o Initial TONIC phase – body becomes rigid, patient utters cry and falls
o Tongue usually bitten
o Next CLONIC phase – generalised convulsion, 4 limbs rhythmic jerking
o Followed by muscle relaxation, drowsiness and confusion
o Incontinence can occur at end of clonic phase
o Abrupt, isolated muscle jerking

Absence seizures (petit mal)

o Occur almost exclusively in childhood/adolescence
o Each attack accompanied by 3Hz spike and wave EEG
o Child appears suddenly blank and pales slightly for a few seconds
o May be precipitated by hyperventilation
o Eyelids twitch; a few muscle jerks may occur
o Children w/ AS tend to develop GTCS in adulthood
o Clinically similar absence attacks also caused by partial seizures of temporal lobes

Partial Seizures

A partial (focal) seizure = localised epileptic activity. This activity either remains focal or
spreads to involve both hemispheres (generalised seizure).
Most common sites are temporal lobes (60-70%), frontal lobes (30%)

FRONTAL: Jacksonian/focal motor seizures

o Simple partial seizures originating in motor cortex
o Clonic Jerking movements begin in hand and spread to involve contiguous muscle
groups contralateral to epileptic focus.
o If frontal lesion, conjugate gaze and head deviate away from focus
o Weakness of convulsing limbs several hours afterwards = Todd’s paralysis

TEMPORAL: can be complex or simple partial seizures

o Commonly derive from hippocampus  Hippocampal sclerosis
o Structural lesion in temporal cortex e.g. glioma, angioma
o Feelings of unreality (jamais vu) or undue familiarity (déjà vu)
o Vertigo, visual hallucinations

Can get other types of partial seizures e.g.

o Autonomic disturbances: flushing, sweating, piloerection, hyperventilation
o Frotnal cortex: strange smells
o Parietal cortex: sensory disturbances
o Occipital cortex: crude visual shapes
o Auditory cortex: strange sounds.
Diagnosis
Collateral Hx from witness is crucial
Examine onset, setting and stages of attacks
Neurological Examination to exclude differential diagnosis¨- e.g. hemiparesis /papilloedema
in tumour.
FBC (e.g. serum Ca2+)and EEG should be carried out
Imaging: CT/MRI

Treatment

One general measure is to avoid precipitating factors e.g. alcohol, lack of sleep, lights

Emergency
o Ensure patient comes to as little harm as possible
o Airway should be maintained during attack and post-ictal coma
o Prolonged seizure – rectal or i.v. diazepam
o If hypoglycaemia – give i.v. glucose

Status Epilepticus
o Seizure or series of seizures lasting > 30 minutes without regaining consciousness

GENERAL: Secure airway and resuscitate: Oxygen, BP, routine bloods

MEDICATION:
o Exclude hypoglycaemia and treat if present -> i.v. glucose
o Immediate i.v. lorazepam or diazepam (or rectally)
o If alcohol abuse suspected  give i.v. thiamine
o Anticonvulsants: lorazepam, i.v. fosphenytoin  Phenobarbital if necessary!
o If nothing else works  thiopental or i.v. propofol general anaesthesia!

Anticonvulsant drugs:
o Indicated when a firm clinical diagnosis of epilepsy is made – substantial risk of
recurrence
o Monotherapy w/ established anticonvulsant is best
o Dose is increased until control is achieved or tolerance exceeded
o Second drug added if control is not achieved

Drug Type of epilepsy Side effects

Carbamazepine Partial, 2y gen, GTCS Rashes,
Blood dyscrasias -leucopaenia
Phenytoin Partial, 2y gen, GTCS Rashes, SLE , lymphadenopathy,
Blood dyscrasias
Sodium valproate3 Partial, 2y gen, GTCS, Anorexia, hair loss, liver damage
Absence
Ethosuxamide Absence
Gabapentin Partial, 2y gen, GTCS (?)
Lamotrigine Partial, 2y gen, GTCS, Toxic epidermal necrolysis
Myoclonic
Vigabatrin (Infantile spasm) Partial, 2y gen, GTCS (?) Retinal damage, psychological

3
Valproate does not reduce efficacy of contraceptives (inhibits GABA transaminase)
Tiagabine Partial, 2y gen
Notes from Dr Mifsud tutorial

Complex Partial Seizures

Complex partial seizure does not necessarily imply loss of consciousness – more accurate to
say ALTERED level of consciousness
e.g. patient might not fall to the floor – to a witness a CPS may look rather like an
absence seizure

Most CPS originate in the temporal lobe

Focal Symptoms
o Visual images (same one over and over)
o Speech (altered awareness)
o Olfactory (foul rubber burning)
o Dysmnestic: Déjà vu and jamais vu, recall of former lives
o Affective : fear, anger, depression, dreamy states

A typical account from a witness may be of the patient staring and not being able to respond
to questions/ functions of daily life (e.g. brushing hair, making tea).

Reactive automatisms before the seizure e.g. blinking, smacking lips, pulling at buttons
Individual may not remember what had happened during the aura or the seizure
Treat with CARBAMAZEPINE – to find out if seizures are fully controlled afterwards, the best
thing to ask is “ do you still experience auras” – because in this case the auras ARE the
seizures.

Juvenile Myoclonic Epilepsy

Begins at 8-18 years of age –family history is common

Present with triad of absences, morning Myoclonus and GS.
Absences
Seizures consist of unilateral or bilateral myoclonic jerks
usually affecting the upper limbs
Tonic clonic seizures and absences may occur also.
Seizures occur in the morning, precipitated by alcohol
EEG shows irregular spike and wave, and high frequency spikes
Seizures respond well to VALPROATE
Generalised Seizures
Some drugs make myoclonus worse : Carbamazepine, Morning Myoclonus
vigabatrin, barbituates

ABSENCE SEIZURES COMPLEX PARTIAL SEIZURES

No aura Aura
Shorter duration Longer duration
No post-ictal phase Post-ictal phase common

Absences seizures

Primary generalised seizures - begin at 7-11 years

Natural course is to grow out of them although a small proportion of children go on to
develop GTCS
Diagnosing Epilepsy

When diagnosing epilepsy: think is this generalised o focal?

ONSET matters because this is a guide fo treatment e.g. Carbamazepine can make 1y
generalised seizures WORSE!
If you think seizures are of focal onset:
o Carbamazepine – side effects of dizziness and diplopia
o Levitiracetam (Kepra)
o Lamotrigine
o Valproate (Epilim)
o Gabapentin (pain)
o Vigabatrin – not used due to risk of severe visual defects (only in West syndrome)

NB. Levitiracetam can be used for both focal onset and 1y generalised seizures
o Efficacious at low doses
o May cause behavioural disturbances
Gabapentin –not useful
Pregabalin – efficacious at low doses (used in refractory epilepsy)

If seizures are 1y generalised:

o give phenytoin 300mg/day – risk of rashes, blood dyscrasias and lymphadenopathy
o Phenytoin has complex pharmacokinetics
o As for any drug: 5 half-lives to reach steady state
o Each half life for phenytoin is 24 hours (hence measuring blood levels after 24 hours
is useless – must check after 5 days)
o Aesthetic side effects of phenytoin: gum hypertrophy, acne, hirsutism

Toxicity:
o Nausea/vomiting
o Dizziness and ataxia (balance totally off)
o Nystagmus
o Drowsiness
o Diplopia

NB. Can get liver damage sue to drug interactions e.g. with antibiotics (so always check the
BNF before prescribing drugs)

Scenario: 22 year old man brought into A/E: 4 fits in one day and still has not woken up
o Secure airway, intubate and give oxygen
o Monitor routine bloods and BP
o Secure venous access – many anticonvulsants cause phlebitis so choose large vein
o U&Es – check glucose, calcium, sodium + DRUGS: alcohol, cocaine, amphetamines
o Give glucose/thiamine to treat any underlying hypoglycaemia/ nutritional deficiency
o Imaging to check for head injury
o Check temperature for febrile convulsions -encephalitis/meningitis