Epilepsy and seizureSpecialty Clerkship

Student SeminarGroup B2

Chan Ying Ting, PurdySiu Lok Man, Joanne

Lee Wai Yip, Jacky

OUTLINE

1. Prevalence and genetics

2. Etiology

3. Terminology

4. Classification of seizure

5. Epilepsy syndromes

6. Case studies

7. General management of seizures

PREVALENCE IN CHILDHOOD

75% with onset before age of 20 yearsPrevalence: 4.1/1000 in children up to 11 years old(National

Child Development study,1983); 4.71/1000 in children up to 19 years old(Oklaho

ma study,1989)Incidence: 49/100,000 population

Offspring risk for epilepsy to age 20 General population:1% Mother with epilepsy: 6% Father with epilepsy: 2.4%

Sibling risk for epilepsy to age 20 General population: 1% Proband with epilepsy: 3% Proband with 1 parent affected: 8%

ETIOLOGY

Febrile Febrile convulsion Convulsion with fever Intracranial infection

Non-febrile Metabolic disturbance Trauma Poisons / toxins / recreational drugs Cerebral dysgenesis / malformation Cerebral damage / cerebral tumor Neurocutaneous syndromes

TERMINOLOGY

Seizure—transient involuntary alteration of consciousness, behavior, motor activity, sensation and/or autonomic function due to abnormal discharge of cortical neurons; an episodic event, may have provoking factors, e.g. anoxia, alcohol, drugs

Convulsion– seizure with prominent alteration of motor activity Epilepsy—a disorder with recurrent seizures(2 or more),

unprovoked by a specific event such as fever, trauma, infection, or chemical change, stereotypic

Aura—a component of seizure which occurs before consciousness is lost and for which memory is retained afterwards; it localizes attack to the point of origin in the CNS

Automatisms--coordinated adapted involuntary motor activity occurring during the state of clouding of consciousness; usually followed by amnesia of the event

Tonic seizure: excessive motor outflow, giving rise to a tetanic state of the muscles involved.

Atonic seizure: muscle tone drops to a very low values resulting in a sudden fall of the body

Clonic seizure: a tonic seizure with periodic interruptions

Tonic-clonic seizure: starts as a generalized tonic seizure and then interrupted during clonic phase and ending in complete relaxation.

Myoclonic seizure: short involuntary contraction of one or more muscles (local or generalized)

CLASSIFICATION OF SEIZURE

Seizures

Partial Generalized

Simple Complex Partial with secondary generalization

Absence seizuresMyoclonic seizuresClonic seizuresTonic seizuresTonic-clonic seizuresAtonic seizures

* ILAE classification of seizures 1981

Partial vs Generalized

Partial: if only one hemisphere is involved

Simple—no impairment of consciousness, features depend on the region of the brain that is affected

Complex—consciousness impaired, may have automatisms e.g. chewing, wandering off, dressing, undressing

Generalized: most or both hemispheres are involved, loss of consciousness

Primary VS secondary

Simple Partial Seizures

Preserved consciousness (“aura”)Symptoms related to involved brain region

sa Frontal lobe: movement, thought, speech Temporal lobe: memory, speech, smell, taste, a

bdominal sensations Parietal lobe: body sensations Occipital lobe: vision

Complex Partial Seizures

Altered consciousness Unresponsive or less responsive, staring Impaired memory after seizure

-Automatisms: hand and mouth movements (lip smacking, grabbing)

Hypermotor: wild flailing movements (frontal)

Generalized Seizures

Most have abnormal, unnatural movements Tonic (stiffening) Clonic (repetitive jerking) Tonic-clonic (“grand mal”) Atonic (limp) Myoclonic (irregular jerking, may retain awareness) Atonic (falling suddenly)

Absence (“petit mal”): staring, may blink, arrest of activity

EPILEPSY SYNDROMES

Genetic causes: Familial neonatal convulsions

Benign familial convulsions of infancy

Benign partial seizures of infancy

Febrile seizures

Epilepsy syndromes:(1) Infantile spasms(West syndrome)

(2) Lennox-Gastaut syndrome

(3) Absence epilepsies

(4) Juvenile myoclonic epilepsy

(5) Benign rolandic epilepsy

Seizures Age (years)

Clinical Manifestations Development

Primary generalized epilepsy

Any Generalized tonic-clonic without fever

Usually normal

Childhood absence epilepsy

3-12 Blank stare with change of facial expression.

De novo automatisms,e.g. rubbing face or hands

Perseverative automatisms

Normal

Benign rolandic epilepsy

2-12 Focal seizure with motor and/or sensory manifestations in oropharyngeal region

Normal

Infantile spasm 3m-3yrs

Clusters of flexion or extension spasms, loss of visual/social interaction. Atypical spasms like head nodding, shoulder shrugging, eye rolling, facial grimace

Usually abnormal

Lennox-Gastaut syndrome

2-5yrs Atypical absences, atonic seizures, tonic seizures, sometimes GTC and partial seizures.

May evolve from infantile spasms.

Developmental delay at onset common but progressive deterioration may occur.

(1)Infantile spasms (West syndrome)

Onset: between 4 and 6 months of age ‘salaam spasms’ Flexor spasms last 1-2 s and are often multiple, occurrin

g in bursts of 20-30 spasms, frequently on waking Infants will have developmental delay and later learning

disability or epilepsy. Treatment: vigabatrin or corticosteroids.

(2)Lennox-Gastaut Syndrome

Affects children of 2-5 years old Multiple presentation of seizures Later, neuro-developmental arrest or regression and beh

aviour disorder Treatment: Sodium valproate Poor prognosis

(3)Childhood Absence Epilepsy Onset at 3-12 years

Peak at 6-7 years

Second peak at 11-12 years

Females more than males

Family history in 15-44% Rarely associated with developmental

problems. Can be induced by hyperventilation.

Treatment: Sodium valproate Good prognosis with 95% remission in adolesce

nce.

Risk of generalized TC seizures is 30-40%(incre

ased risk if begin after the age of 8 years)

(4)Juvenile Myoclonic Epilepsy (JME)

Autosomal dominance with variable penetrance

A common cause of tonic-clonic seizures in teenagers a

nd young adults(myoclonus paricularly in morning)

Myoclonic seizures precede tonic-clonic seizures by 2-3

years; tonic-clonic seizures typically occur when patient r

eaches 10-17 years

Prognosis excellent but requires lifelong treatment

(5)Benign Rolandic Epilepsy

Most common partial epilepsy

Onset 2-12 years

M:F 1.5:1

Usually occuring in sleep-wake transition states

10-13% have a single seizure

20% have frequent seizures 65% nocturnal

15% nocturnal or diurnal

10-20% waking state only

Typical presentation:

On waking, fully conscious, mouth to one side, salivating an

d focal twitching of one side of the face

Duration 1-2 mins;

Child may recall a sensation of numbness, pins and needle

s or “electricity” in the tongue, gums or cheeks;

- Remains conscious but aphasic post-ictally

- Secondary generalization may be seen

- Remits spontaneously in adolescence; no sequelae

- No medication if infrequent seizures.

CASE STUDIES

History

M/9Normal development until 9 years oldEncephalitis at age 9 with coma and 2

generalized seizuresP/E: stupor, ?visual hallucinations, ataxiaCT and MRI normalMedullobastoma discovered at age 11,

died at age 16

Complex partial seizure evolving into secondary generalized seizure

Seizure started as complex partial motor seizure because there is impaired consciousness

Classical Jacksonian march is observed but it’s not a Jacksonian seizure since it’s not a simple partial seizure

Then evolves into a generalized tonic-clonic seizure

History

M/20 Caesarian section, anoxia, hemiconvulsions at

birth, normal development Seizure onset again at 9 years old CT atrophic parieto-occipital zone; MRI large

right parieto-occipital lesion probably due to birth trauma

Tx: carbamazepine, clobazam, vigabatrin, clorzepate, lamotrigine

Lives independently with a job

Complex partial seizure with automatisms Aura (secs-mins): unresponsive, dreamy (may

also have hallucinations, affect changes, déjà vu)

Automatism (occur in 90%): turning head to left, lip smacking (basically any continuation of an activity that was going on when the seizure occurred)

Alterations of mood, memory, perception (hence complex partial)

Posticteral drowsiness: confused and disoriented for minutes afterwards

History

F/28Previously healthy, no neurologically

relevant diseases or family historyAge of onset 7MRI shows slight dilatation of R lateral

ventricle; discrete hyperintense signals in frontal lobes

SPECT: low-flow area in L temporal and frontal lobes and R temporal lobe

Simple then complex seizure with secondary generalization

Starts off as simple partial seizure with autonomic involving ie. epigastric rising sensation

Although she is unable to speak, she raises as left hand as if to signal that she can understand

This is followed by a complex partial seizure as there is automatism (hand-rubbing and lip smacking) and unresponsiveness

Finally there is a tonic-clonic generalized seizure

History

F/8Previously health, no neurologically

relevant diseases, remote family history of epilepsy

P/E normal, neruoimaging not doneFrequent daily spells with LOC since 8interictal EEG: generalized regular 3Hz

spike with some polyspikes; normal background activity

Absence seizure - typical

Onset in childhoodChild stops activity, stares, blink/roll eyes,

unresponsive Usually lasts 5-10 secs but may occur

hundreds of times/dayUsually there is an additional feature like

automatism, mild clonus, or change in tone (eg. drop attacks)

May be induced by hyperventilation

History

M/17Newphew of father and son of the

newphew both have epilepsyOnset of seizure at age 15, treated with

carbamazepine but still has daily convulsions

Myoclonic – juvenile myoclonic epilepsy

Sudden, brief, generalized muscle contractions Most common type is the juvenile myoclonic

epilepsy (Janz syndrome) which occurs after puberty and doesn’t remit with age

Also occurs in degenerative and metabolic disease

Another type is themyoclonic absence type

History

M/6Good past health and no family historyP/E: hypotonic musclesCT showed mild diffuse cerebral atrophyRefractory to all available antiepileptic

drugs

Generalized clonic seizure

Clonic seizure is quite rare, even in this caes there is a very short tonic start

Differentiate from myoclonic seizures by the sustained rhythmical nature of the jerks

History

M/14Good past health, no family historyOnset at 2 years 9 monthsOne month before onset, he had severe

measlesRefractory to all available antiepileptic

drugs

Generalized tonic seizure

This particular case is unusual in that despite the tonic bending posture, the boy keeps on walking without falling

History

M/7Normal pregnancy and delivery and no

family historyP/E: marked ataxia, severe MR, dull,

protruded tongue, hypertonia, hyper-reflexia, spontaneous mild jerks of limbs

CT showed central and peripheral cerebral atrophy

Generalized tonic-clonic seizure

Many generalized tonic-clonic seizure have more than one tonic and clonic phase

Tonic phase: contraction of muscles – flexion/extension of limbs, twitching of eyelids, respiratory muscles in spasm (cyanosis), LOC

Clonic phase: violent jerking of face and limbs, tongue biting, incontinence

In this case there is a pronounced tonic stretching of the limbs follow by a clonic phase

History

M/4Premature birth with injury Febrile convulsions in paternal cousinP/E: sever MRCT showed moderate diffuse cerebral

atrophy

Generalized Atonic seizure

Many seizures in this type of children are a mixture of atonic, tonic, and myoclonic elements

Differentiation depends on analysis by combine EEG and EMG to see which element is more predominate

GENERAL MANAGEMENT OF SEIZURES

Aim

To confirm it is a genuine seizure attack Etiology of the seizure attack

Epilepsy + classification Convulsion with a febrile illness

Simple febrile convulsion CNS infection

Severity of the attack / any associated injury Management plan Prognosis

Is it a genuine seizure attack?

Symptoms before onset of seizure (prodrome) Aura (sensation / motor) Behavioural change (mood / behaviour)

Presence of prodrome strongly suggest partial onset seizures

Symptoms during the seizure Loss of consciousness?

Temporal relationship with other symptoms LOC right from the beginning? Secondary generalization?

Other symptoms Vocal symptoms Motor symptoms Respiration Autonomic symptoms

Symptoms following seizure Amnesia of the event Confusion / lethargy / sleepiness Headache or muscle ache Transient focal weakness (Todd’s paresis) Nausea or vomiting

The child is febrile Simple febrile convulsion?

Check for the criteria CNS infection?

Ask more on associated symptoms of meningitis / encephalitis

Epilepsy? Any provoking factors

Trauma Toxin / drug / alcohol consumptions Flashes / sleep deprivation / physical exhaustion

Causes Previous CNS insult / developmental milestones Preceding neurological deficits Intracranial SOL / increased ICP Associated symptoms of neurocutaneous syndrome Family history

Systemic screeningPediatric history

Past health Drug history Birth history Immunization history Developmental history Social history

Known history of epilepsycurrently on medicationPossible causes of breakthrough seizure

Poor drug compliance Sleep deprivation Infection / fever Recent change of drug regimen

Physical examination

Febrile General condition / vital signs septic? Anterior fontonelle pressure / GCS / neck stiffness / kern

ig’s sign / papilloedema CNS infection? Rash / focal signs of infection source of febrile illness

Epilepsy Dysmorphism / head circumference Skin features (adenoma sebaceum / shagreen patch / m

ultiple cafe-au-lait spots / nevus flammeus) Neurological examination any focal neurological defic

its

Investigations

Blood test Sepsis Metabolic derangement

Urine toxicology screening (optional) EEG

Standard investigations for first unprovoked seizure LP (optional)

Only if suspect CNS infectionDrug level (if known history of epilepsy on medication)

Imaging (CT / MRI) MRI is a better choice if available Those with

Significant cognitive or motor impairment of unknown etiology

Unexplained neurological abnormalities Partial onset seizure Suspicious EEG abnormalities Children under 1 year of age

Emergency imaging in those with post-ictal focal deficit not resolving / not returning to baseline within several hours after seizure

Seizure Precautions

Turn child on sideDo not restrain- protect child from injuryStay with childDo not put objects in mouthLoosen tight clothes

Principles of drug treatment in epilepsy1. A balance between seizure control and drug side-effects.2. Presence of 2 or more seizures, should consider drug therapy, espe

cially those with short fit interval(usu. <1 year).3. Absence seizure and myoclonic seizure, once diagnosed should be

treated with drugs.4. Start with lowest dose monotherapy and titrate upwards until seizur

e control is attained or side effects are experienced.5. Choice of drugs depends on type of seizures or epileptic syndromes,

age of patient and potential drug adverse effects.6. If polypharmacy has to be used, beware of drug interactions.7. In case of well controlled epilepsy, regular clinical supervision is the

only essential measure.

Type of Epilepsy First line drugGeneralized tonic-clonic Sodium valproate

Myoclonic Sodium valproate

Absence Sodium valproate

Partial, complex partial or partial secondarily generalized

Sodium valproate

Carbamazepine

Infantile spasm Vigabatrin

Corticosteroid

Lennox Gastaut syndrome

Sodium valproate

Sodium valproate(Epilim)

Started at 15-20mg/kg/day in divided doses(max. daily dose: 60mg/kg/day)

S/E: sedation, drowsiness, increased appetite and weight, idiosyncratic liver failure

Drug interactions: serum levels decrease with carbamazepine, phenobarbital and phenytoin

Carbamazepine(Tegretol)

Mainly for treatment of partial seizures with and without secondary generalization.

Three and sometimes four dose per day are better tolerated than twice daily dosing regimens.

Maintenance dose: 10-30mg/kg/day.(Adult dose 600-2400mg/day)

Therapeutic serum level: 8-12mcg/ml S/E: visual disturbance (recurrent diplopia, blurre

d vision), ataxia [rare: lupus-like syndrome, aplastic anemia, liver toxicity]

Phenobarbital

Dosage is age-dependentMaintenance dose: 2-6 mg/kg/dayS/E: sedation in teenagers(but tolerance u

sually develops), irritability in children(up to 1/3 of cases), hyperactivity, sleep disorders and cognitive abnormalities

Drug interactions: Induces P450

Phenytoin (Dilantin)

Absorption incomplete and erratic in neonates and young children.

Half-life in infants is usually long and variable Maintenance dose: 4-8mg/kg/day Serum therapeutic level: 10-20mcg/ml Side-effects: Cosmetic—gum hypertrophy, hirsutism Toxic level—behavioral change, nausea, emesis, nystag

mus,ataxia Serious –pancytopenia, Steven-Johnson syndrome Others--lymphadenopathy

Vigabatrin

Licensed in UK in 1989For treatment of refractory partial seizures

and infantile spasmPaediatric dose: 40-80mg/kg/dayS/E: transient sedation and dizziness, beh

avioral and emotional changesDrug interactions: Not significant

Newer anti-epileptic drugs-S/E

Gabapentin— rare: insomnia Lamotrigine—skin rash(3-15%)Topiramate—anorexia, renal calculi

Main indications for therapeutic drug monitoring1. To verify patient’s compliance

2. Presence of “breakthrough seizures” in previously well-controlled cases

3. Persistent seizures despite therapy

4. Suspicion of side effects

5. When several anticonvulsants are being used

6. Use of drugs with narrow therapeutic window

7. Very young age when blood levels fluctuates

Discontinuation of drug treatment

1. Duration of treatment varies with different types of seizures and age of onset

2. In most epileptic syndromes, a normal EEG is not a prerequisite for discontinuation of treatment.

3. Epileptic syndroms of lesional origin and those synfromes known to be refractory to treatment should be treated for long periods(more than 5 years).

4. Termination of treatment can be considered after a seizure free period of 2 to 4 years.

5. Gradual withdrawal over a period of 3 to 6 months is advised.

Reference(s)

Video Atlas of Epileptic Seizures and CD-Rom. Commission on Classification and Terminology of ILAE: 1981.

Manual of Child Neurology. The Hong Kong Society of Child Neurology & Developmental Paediatrics. (1st edition). Pages 97-110;117-134.

Manual for Paediatric Interns and Residents. HKU Department of Paediatrics and Adolescent Medicine. (3rd Edition September 2003).Pages 80-83.

Illustrated Textbook of Paediatrics. Tom Lissauer and Graham Clayden. (2nd Edition). Mosby. Chapter 25:365-384.

Clinical Guideline on Management of Febrile Convulsion. Hong Kong Journal of Paediatrics(new series) 2002;7:143-151.

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