Transcript Epilepsy and seizure - University of Hong Kong

Epilepsy and seizure
Specialty Clerkship
Student Seminar
Group B2
Chan Ying Ting, Purdy
Siu Lok Man, Joanne
Lee Wai Yip, Jacky
OUTLINE
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Prevalence and genetics
Etiology
Terminology
Classification of seizure
Epilepsy syndromes
Case studies
General management of seizures
PREVALENCE IN CHILDHOOD
75% with onset before age of 20 years
Prevalence:
 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(Oklahoma 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
Simple
Complex
Generalized
Partial with
secondary
generalization
* ILAE classification of seizures 1981
Absence seizures
Myoclonic seizures
Clonic seizures
Tonic seizures
Tonic-clonic seizures
Atonic seizures
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
regionsa
Frontal lobe: movement, thought, speech
Temporal lobe: memory, speech, smell, taste,
abdominal 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
Clinical Manifestations
(years)
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
3m3yrs
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,
occurring 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
behaviour 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
adolescence.
 Risk of generalized TC seizures is 3040%(increased 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
and young adults(myoclonus paricularly in morning)
 Myoclonic seizures precede tonic-clonic seizures by 2-3
years; tonic-clonic seizures typically occur when patient
reaches 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
and focal twitching of one side of the face
 Duration 1-2 mins;
 Child may recall a sensation of numbness, pins and
needles 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/9
Normal development until 9 years old
Encephalitis at age 9 with coma and 2
generalized seizures
P/E: stupor, ?visual hallucinations, ataxia
CT and MRI normal
Medullobastoma 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 tonicclonic 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/28
Previously healthy, no neurologically
relevant diseases or family history
Age of onset 7
MRI 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/8
Previously health, no neurologically
relevant diseases, remote family history of
epilepsy
P/E normal, neruoimaging not done
Frequent daily spells with LOC since 8
interictal EEG: generalized regular 3Hz
spike with some polyspikes; normal
background activity
Absence seizure - typical
Onset in childhood
Child stops activity, stares, blink/roll eyes,
unresponsive
Usually lasts 5-10 secs but may occur
hundreds of times/day
Usually there is an additional feature like
automatism, mild clonus, or change in
tone (eg. drop attacks)
May be induced by hyperventilation
History
M/17
Newphew of father and son of the
newphew both have epilepsy
Onset 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/6
Good past health and no family history
P/E: hypotonic muscles
CT showed mild diffuse cerebral atrophy
Refractory 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/14
Good past health, no family history
Onset at 2 years 9 months
One month before onset, he had severe
measles
Refractory 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/7
Normal pregnancy and delivery and no
family history
P/E: marked ataxia, severe MR, dull,
protruded tongue, hypertonia, hyperreflexia, 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/4
Premature birth with injury
Febrile convulsions in paternal cousin
P/E: sever MR
CT 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 screening
Pediatric history
Past health
Drug history
Birth history
Immunization history
Developmental history
Social history
Known history of epilepsy
currently on medication
Possible 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 /
kernig’s sign / papilloedema  CNS infection?
Rash / focal signs of infection  source of febrile illness
 Epilepsy
Dysmorphism / head circumference
Skin features (adenoma sebaceum / shagreen patch /
multiple cafe-au-lait spots / nevus flammeus)
Neurological examination  any focal neurological
deficits
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 side
Do not restrain- protect child from injury
Stay with child
Do not put objects in mouth
Loosen tight clothes
Principles of drug treatment
in epilepsy
1. A balance between seizure control and drug side-effects.
2. Presence of 2 or more seizures, should consider drug therapy,
especially 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
seizure 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 drug
Generalized tonic-clonic
Sodium valproate
Myoclonic
Sodium valproate
Absence
Sodium valproate
Partial, complex partial or Sodium valproate
partial secondarily
Carbamazepine
generalized
Infantile spasm
Vigabatrin
Corticosteroid
Lennox Gastaut
Sodium valproate
syndrome
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,
blurred vision), ataxia [rare: lupus-like syndrome,
aplastic anemia, liver toxicity]
Phenobarbital
Dosage is age-dependent
Maintenance dose: 2-6 mg/kg/day
S/E: sedation in teenagers(but tolerance
usually 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,
nystagmus,ataxia
 Serious –pancytopenia, Steven-Johnson syndrome
 Others--lymphadenopathy
Vigabatrin
Licensed in UK in 1989
For treatment of refractory partial seizures
and infantile spasm
Paediatric dose: 40-80mg/kg/day
S/E: transient sedation and dizziness,
behavioral and emotional changes
Drug 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 monitoring
1. 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 97110;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.
Thank you!