NEUROLOGY CASE
CONFERENCE
Subsection D2
Rivera. Rivere. Robosa. Rodas. Rodriguez.
Rogelio. Roque. Ruanto. Sabalvaro. Salac.
Salazar, J. Salazar, R. Salcedo. Saldana. Sales.
Salonga. San Diego. San Pedro. Sanez. Sanidad.
Santos, E. Santos, J.
CASE 2.1
Case 2.1
A 10 year-old girl was brought by her mother for a
consult because of poor academic performance.
School teachers often observed her to be absent
minded described as recurrent but brief periods of
blank staring and inattention. This was accompanied
by eye blinking, reflex scratching of her head, lip
smacking and chewing movements which all lasts for a
few seconds. These would occur many times a day and
after each attack, the patient would resume his usual
activity.
Missing Data




First episode or onset of symptoms
Presence or absence of fever, loose bowel
movement, vomiting
Previous school performance
Family History
Salient Features



10 year old girl
Poor academic performance
Absent minded
 Recurrent,
brief periods of blank staring and inattention
 Accompanied by eye blinking, reflex scratching of her
head, lip smacking and chewing movements
 Occurs many times a day
Differential Diagnosis
Neonates
(<1month)
Infants and
Children
(>1 month<12yrs.)
Adolescents
12-18yrs.
Young
Adults
18-35yrs.
Differential Diagnosis
Infants and Children
(>1 month-<12yrs.)
Probable Cause
Type
Febrile seizure
Genetic disorders
(metanolic, degenerative,
primary epilepsy
syndromes)
CNS infection
Developmental disorders
Trauma
Idiopathic
Complex partial seizures
Generalized Seizures:
•Atonic Seizures
•Absence (petit mal)
Epilepsy Syndromes
•JME
•Lennox-Gastaut
•MTLE
TYPES
Ictal phase: sudden
behavioral arrest or
Complex Partial motionless stare
Automatisms:
Chewing, lip smacking,
swallowing, “picking”
movements of hands
Seconds – an hour
Impaired recollection
or motionless stare
Atonic
Briefly impaired
consciousness
Quick head drop or nodding
movement
1 to 2 seconds
No post-ictal confusion
Myoclonic seizures frequent in
the morning
Provoked by sleep deprivation
One-third have
absence seizures
JME
Bilateral myoclonic
seizures;single or
repetetive
Consciousness is
preserved
Lennox-Gastaut
•Multiple seizure types Associated with CNS disease,
•Impaired cognitive
devt. Abnormalities, perinatal
function
hypoxia/ischemia, trauma,
infection
Impaired cognitive
syndrome
Aura
Behavioral
arrest/stare
Complex automatisms
Unilateral posturing
Postictal disorientation,
memory loss dysphasia
Sudden, brief lapses
of consciousness,
“daydreaming”
No loss of postural control
Rapid blinking, chewing
movements.
Can occur hundred times a day
Lasts for seconds
No postictal confusion
Decline in school
performance
MTLE
Absence
(petit-mal)
Clinical Impression:
Absence Seizure
Absence Seizure
•
A type of generalized seizure,
lasting for several seconds to
minutes and may occur several
times a day.
•
Children with idiopathic generalized
epilepsies may present with a history
of staring spells, but infrequent
absence seizures may not be
diagnosed until a generalized tonicclonic seizure has occurred.
Reference: Segan, S. (2009). Absence Seizures. American Academy of Neurology and American Epilepsy Society.
Absence Seizure
•
Other symptoms, such as behavioral problems may be
the presenting complaint.
–
•
•
Although the brief attacks are unrecognized, the lapses of
awareness interfere with attention.
Decline in school performance may be an indication of
the onset or breakthrough of absence seizures.
In symptomatic generalized epilepsies, atypical absence
seizures often occur in the setting of developmental
delay or mental retardation.
Reference: Segan, S. (2009). Absence Seizures. American Academy of Neurology and American Epilepsy Society.
Absence Seizure

On clinical examination, typical absence seizures
appear as:

Brief staring spells
 Patients
have no warning phase, and if engaged in gross
motor activity, such as walking, they may stop and stand
motionless or they may continue to walk.
 Unresponsive
during the seizure
 Children
have no memory of what happened during the
attack; they are generally unaware that a seizure has
occurred.
Reference: Segan, S. (2009). Absence Seizures. American Academy of Neurology and American Epilepsy Society.
Pathophysiology
•
•
The pathophysiology of absence seizures is not fully
understood.
Abnormal oscillatory rhythms are believed to develop in
thalamocortical pathways.
–
–
–
This involves GABA-B–mediated inhibition alternating with
glutamate-mediated excitation.
GABA-B inhibition appears to be altered in absence seizures.
Enhanced burst firing in selected corticothalamic networks may
increase GABA-B receptor activation in the thalamus, leading
to generalized spike-wave activity.
Reference: Segan, S. (2009). Absence Seizures. American Academy of Neurology and American Epilepsy Society.
Absence Seizure vs Complex Partial Seizure
•
An absence seizures can sometimes be confused with a
complex partial seizure but each type has its own
distinctive features:
–
Absence seizures :
•
•
•
•
Never preceded by an aura
Are of briefer duration – seconds rather than minutes
Begin frequently and end abruptly
The absence attack is always associated with the strikingly
typical EEG abnormality of spike and slow wave discharges,
usually at a frequency of 3Hz which occur can occur interictally
and ictally and are often provoked by hyperventilation.
Absence Seizures
Absence Seizures

In childhood absence epilepsy, seizures are
frequent and brief, lasting just a few seconds
(pyknoleptic). Some children can have many such
seizures per day. In other epilepsies, particularly
those with an older age of onset, the seizures can
last several seconds to minutes and may occur only
a few times a day (nonpyknoleptic or spanioleptic
absence seizures).

The etiology of idiopathic epilepsies with agerelated onset is genetic. About 15-40% of patients
with these epilepsies have a family history of
epilepsy; overall concordance in monozygotic twins
is 74% with a 100% concordance during the peak
age of phenotypic expression. Family members
may have other forms of idiopathic or genetic
epilepsy (eg, febrile convulsions, generalized tonicclonic seizures.
Typical Absence Seizures
Sudden onset of impaired movements
 Staring episodes or "absence spells"
 Accompanied by other motor, behavioral
or autonomic phenomena
 May interfere with school function and
learning

Reference: Pediatric Epilepsy: Diagnosis and Therapy: John M. Pellock,Blaise F. D. Bourgeois
Atypical Absence Seizure




Less abrupt onset and cessation
More pronounced changes in tone and longer
duration
Usually begins before 5 years of age
Associated with other generalized seizure types
and mental retardation
Reference: Pediatric Epilepsy: Diagnosis and Therapy: John M. Pellock,Blaise F. D. Bourgeois
Diagnostic Work-up
Electroencephalography (EEG)


The only diagnostic test for absence seizures
Ambulatory EEG monitoring over 24 hours may be
useful to quantitate the number of seizures per day
and their most likely times of occurrence.
EEG: Typical Absence

Findings in typical absence seizures include the
following:
 Background
activity is normal.
 In
syndromes with frequent absence seizures, such as
childhood absence epilepsy, a routine awake recording is
often pathognomonic.
 In syndromes with less frequent absence seizures (juvenile
absence epilepsy or juvenile myoclonic epilepsy), an
awake recording may be normal; a sleep or sleepdeprived recording may be needed.
 Typical
absence seizures have generalized 3-Hz spikeand-wave complexes.
EEG: Typical Absence
EEG: Typical Absence





The onset and ending of these seizures are abrupt; no
postictal EEG slowing is noted.
Hyperventilation often provokes these seizures and should
be a routine part of all EEGs in children.
EEG video monitoring demonstrates that clinical seizure
manifestations may lag behind the start of ictal EEG activity;
bursts lasting less than 3 seconds are usually clinically silent.
During the absence seizure, rhythmic eye blinks and mild
clonic jerks may be present. As a seizure progresses,
automatisms may be seen.
Clinical and EEG features may vary considerably in different
children.
EEG: Atypical Absence

Findings in atypical absence seizures include the
following:
 Background
activity is often abnormal, reflecting the
diffuse or multifocal underlying encephalopathy of
symptomatic generalized epilepsy.
 Seizures are characterized by slow spike-and-wave
paroxysms, classically 2.5 Hz.
EEG: Atypical Absence
EEG: Atypical Absence
•
The onset may be difficult to discern, and postictal EEG
slowing may be noted.
•
The clinical correlation of generalized spike-and-wave
complexes with clinical seizures is not as clear-cut as in
typical absence seizures.
•
EEG-video monitoring can show a more varied alteration of
consciousness than in typical absence seizures. If the
patient has underlying mental retardation, discerning
changes in mental status also may be more difficult in
atypical absence.
•
Changes in postural tone, most noticeably head nods, are
common.
Laboratory Studies

Laboratory tests for:
 Metabolic
abnormalities
 Toxic or drug ingestion
 Blood levels of electrolytes, glucose, calcium,
magnesium
 Hepatic or renal disease

If a clear history of the episodic nature of the
attacks is obtained, then the EEG can be diagnostic
and laboratory tests may not be necessary.
Imaging Studies

Neuroimaging is not indicated if the typical clinical
pattern is present.



Neuroimaging findings are normal in idiopathic epilepsies by
definition.
Often ordered if a child presents with a generalized
tonic-clonic seizure, to rule out significant structural
causes of seizures.
If imaging is performed, MRI is preferred to CT
scanning. MRI is more sensitive for certain anatomic
abnormalities.
Treatment
Treatment
DEPENDS on the underlying cause
 Metabolic
: correction
 Structural abnormality: seizure control +
consider surgery
Tumor
Vascular
 Idiopathic : seizure control
Treatment
Diagnosis and Classification of seizure disorder
Choose Anti-epileptic drug of choice
Main Goal: Adequate seizure control
Monitoring of response
(seizure-free) and side effects
Therapeutic Monitoring
Drug Interactions
Principles of Treatment









Individualized treatment
Selection of specific drug for initial therapy is based on specific
clinical seizure type.
Monotherapy is preferred.
Dose is increased gradually.
Enough time for steady state to be reached must be allowed.
Prompt substitution when serious adverse reaction develops.
If poor seizure control-gradually withdraw first drug while replacing
with second drug of choice for seizure type (should not be stopped
abruptly).
Treatment failures may be due to poor compliance or misdiagnosis.
Continue treatment to achieve minimum seizure-free period of 3-5
years.
References: Katzung Basic and Clinical Pharmacology, 9th ed. The Treatment of Epilepsy, 3rd ed.
Absence Seizures
•
•
•
•
Ethosuximide is the drug
of choice for typical
absence seizure
Valproic Acid is the drug
of choice for atypical
absence seizure.
Used only when treatment
tolerance or failure
appear with Ethosuximide
Wide spectrum AED
Anti Epileptic Drug
Glutamate
Antagonist
Phenobarbital
GABA
agonist
Na channel Ca channel
blocker
blocker
*
Phenytoin
*
Carbamazepine
*
Valproic Acid
*
*
*
*
*
*
Gabapentin
Topiramate
*
*
Oxcarbazepine
*
Ethosuximide
Lamotrigine
*
*
*
Ethosuximide







Primary indication: First-line or adjunctive therapy of generalized absence
seizures
Mechanisms of action: Inhibition of neuronal T-type calcium channels in the
thalamus (Type III AED)
Usual preparations: Capsules: 250 mg; syrup: 250 mg/5 mL
Usual dosages: Initial: 250 mg (adults); 10–15 mg/kg/day (children)
Maintenance: 750–1500 mg/day (adults); 15–40 mg/kg/day (children)
Dosing frequency: 2–3 times/day
Significant drug interactions:
 Ethosuximide levels are reduced by co-medication with carbamazepine,
phenytoin, phenobarbital and rifampicin.
 Valproic acid may exert synergistic effects with ethosuximide in
patients refractory to either drug given alone, and may have variable
and inconsistent effects on ethosuximide levels. Serum valproic acid levels
may be decreased by ethosuximide. Ethosuximide levels are increased by
isoniazid.
References: Katzung Basic and Clinical Pharmacology, 9th ed. The Treatment of Epilepsy, 3rd ed.
Ethosuximide




Serum level monitoring: usually optimized based on clinical
and EEG response.
Main advantages: Well-established treatment for absence
epilepsy without the risk of hepatic toxicity carried by valproic
acid
Main disadvantages: Adverse effects common. Unlike valproic
acid, ethosuximide does not protect against generalized tonic–
clonic seizures
Common/important adverse effects: Gastrointestinal symptoms,
drowsiness, ataxia, diplopia, headache, dizziness, hiccoughs,
sedation, behavioural disturbances, acute psychotic reactions,
extrapyramidal symptoms, blood dyscrasias, rash, lupus-like
syndrome, other severe idiosyncratic reactions.
References: Katzung Basic and Clinical Pharmacology, 9th ed. The Treatment of Epilepsy, 3rd ed.
Valproic Acid






Primary indications: First line for atypical absence seizures. First-line
therapy of idiopathic generalized epilepsies. First-line or adjunctive therapy
of cryptogenic or symptomatic generalized epilepsies. Valuable but not
generally first-line therapy for partialseizures
Mechanisms of action: Increases brain GABA activity by increasing activity
of glutamic acid decarboxylase, inhibition of GABA transaminase, inhibition
of succinic semialdehyde dehydrogenase
Usual dosages: Initial: 400–500 mg/day (adults); 15 mg/kg/day
(children)
Maintenance: 500–2500 mg/day (adults); 20–40 mg/day (children under
20 kg); 20–30 mg/kg/day (children over 20 kg)
Dosing frequency: 2-3 times a day
Serum level monitoring: Dosage usually can be adjusted on the basis of
clinical response, but monitoring serum valproic acid levels may be useful in
selected cases.
References: Katzung Basic and Clinical Pharmacology, 9th ed. The Treatment of Epilepsy, 3rd ed.
Valproic Acid




Significant drug interactions : Enzyme-inducing drugs and imipenem
antibiotics reduce serum valproic acid levels. Felbamate, stiripentol, isoniazid
and other drugs may increase valproic acid levels. Valproic acid inhibits the
metabolism of a number of drugs, most notably phenobarbital, lamotrigine
and rufinamide. Valproic acid displaces phenytoin from plasma protein
binding sites and may inhibit phenytoin metabolism at the same time
Common/important adverse effects: Tremor, sedation, asthenia,
encephalopathy, extrapyramidal symptoms, nausea, vomiting,
hyperammonemia, weight gain, polycystic ovary syndrome, hair loss, platelet
and coagulation disorders, liver toxicity, pancreatitis, teratogenic effects
(including spina bifida)
Main advantages: Unsurpassed efficacy in most generalized epilepsy
syndromes. Broad spectrum efficacy in different seizure types
Main disadvantages: Weight gain, severe liver toxicity (particularly in
children), teratogenicity
References: Katzung Basic and Clinical Pharmacology, 9th ed. The Treatment of Epilepsy, 3rd ed.
Other Modalities

Surgical Management
–

Surgical excision of epileptic foci in simple and
complex partial epilepsies that have not responded
to intensive and prolonged medical therapy may be
beneficial for some.
Regulation of Physical and Mental Activity
–
–
–
Precipitating factors need to be modified and
stressed to the patient.
Moderate amount of physical exercise can also be
advised.
Psychosocial difficulties need to be identified and
addressed early.
Reference: The Treatment of Epilepsy, 3rd ed.
Other Modalities

Ketogenic Diet
–
–

biochemical alteration both in the blood and in the
brain
possible GABA-mimetic effects of ketosis given the
structural similarities of GABA, -hydroybutyrate and
acetoacetate
Vagal Nerve Stimulation
–
vagal stimulation produces its effects are unclear and it
is done through attachment of electrodes to the vagus
nerve at the left carotid bifurcation
Reference: The Treatment of Epilepsy, 3rd ed.
Management
American Academy of Neurology Guidelines on CESSATION
OF TREATMENT

Stopping the treatment may be considered when:
The patient has been seizure-free for 2 to 5 years.
 The patient has a single type of seizure.
 The patient has no abnormalities on neurologic examination
and has a normal IQ.
 The patient’s electroencephalogram (EEG) has become
normal.

CASE 2.2
CASE 2.2
A 17 year-old male had an excellent antiepileptic
drug control of his generalized tonic-clonic seizures
for the past 3 years. Work up done showed an
abnormal EEG patterns consistent with generalized
type of seizures and a normal cranial CT scan.
Missing Data




Initial presentation of the patient when diagnosis was
established
Family history
History of trauma, loss of consciousness, severe headache
Precipitating factors


Prodromal symptoms



Fever, stress, fatigue, sleep deprivation, drug abuse, alcohol
Mood changes, sleep disturbances, lightheadedness, anxiety,
irritability, difficulty concentrating
Compliance to anti-epileptic medications
Frequency, duration and presentation of the patient during
the recent attack
Salient Features





17 year-old
Male
3 year history of generalized tonic-clonic seizurescontrolled
Abnormal EEG patterns consistent with generalized
type of seizures
Normal cranial CT scan
Clinical Impression:
Generalized Tonic Clonic
Seizures, controlled
Generalized Seizures

Paroxysmal discharges occurring in both hemispheres
• Generalized
tonic clonic
Reference: Rohkamm, Color Atlas of Neurology © 2004 Thieme
• Myoclonic
• Tonic or Atonic
• Absence
Generalized Seizures
CAUSES
Genetic
Acquired
• Predisposition
• Hereditary diseases
associated with epilepsies:
• Tuberous sclerosis,
• Sturge–Weber syndrome
• Mitochondrial
encephalopathies
• Sphingolipidoses
• Focal – possibly with secondary
generalization
• Bilateral
• Diffuse – primary generalized
epilepsies
• The causes include
developmental disorders,
pyridoxine deficiency,
hippocampal sclerosis, brain
tumors, head trauma,
cerebrovascular disturbances,
alcohol, drug abuse, medications,
and CNS infections.
Reference: Rohkamm, Color Atlas of Neurology © 2004 Thieme
Feature
Tonic-clonic Seizure
Absence Seizure
Myoclonic Seizure
Consciousness
Impaired
Impaired
Unaffected
Duration
1–3 minutes
A few (≤30) seconds
1–5 seconds
Symptoms and
signs
Initial cry (occasionally);
falls (loss of muscle
tone); respiratory arrest;
cyanosis; tonic, then
clonic seizures; muscle
relaxation followed by
deep sleep. Tongue
biting, urinary
and fecal incontinence
Brief absence, vacant
gaze and blinking
followed by immediate
return of mental clarity;
automatisms (lip
smacking, chewing,
fiddling, fumbling) may
occur
Sudden, bilaterally
synchronous jerks in
arms and legs; often
occur in series
Age group
Any age
Children and
adolescents
Children and
adolescents
Ictal EEG
Often obscured by
muscle artifacts
Reference: Rohkamm, Color Atlas of Neurology © 2004 Thieme
Polyspike waves,
Bilateral regular 3 (2–
spike waves, or sharp
4) Hz spike waves
and slow waves
Absence
Reference: Rohkamm, Color Atlas of Neurology © 2004 Thieme
Myoclonic
Generalized Tonic-Clonic Seizure




A seizure involving the entire body. It
is also called a grand mal seizure.
Usually involves muscle rigidity,
violent muscle contractions, and loss
of consciousness
They may occur in people of any
age, as a single episode, or as part
of a repeated, chronic condition
(epilepsy).
Internationally, as in the United
States, only a small proportion of
seizures are generalized tonic-clonic
seizures (20-25%).
Generalized Tonic-Clonic Seizure

Pathophysiology
 Thought
to be initiated by 3 different mechanisms:
 Abnormal
response of hyperexcitable cortex to initially
normal thalamic input
 Primary subcortical trigger
 Abnormal cortical innervation from subcortical structures
A
seizure results from a paroxysmal high-voltage
electrical discharge of susceptible neurons within an
epileptogenic focus. These neurons are known to be
hyperexcitable and, for unknown reasons, remain in a
state of partial depolarization.
Generalized Tonic-Clonic Seizure

Pathophysiology
 GABA-ergic
and hyperpolarized neurons surrounding
the epileptogenic focus inhibit the epileptogenic
neurons.
 At times, when the epileptogenic neurons overcome the
surrounding inhibitory influence, the seizure discharge
spreads to neighboring cortical structures and then to
subcortical and brainstem structures.
Generalized Tonic-Clonic Seizure

Pathophysiology

Brainstem structures involved:






Lateral geniculate body – produces a generalized tonic-clonic
seizure when kindled in the cat
Ascending pathways through the mamillary bodies and anterior
thalamus
Substantia nigra – includes a nigrotectal GABA-ergic projection and
locus ceruleus
Phases: Tonic, Clonic, Post-ictal
Tonic Phase - spread of excitability to subcortical, thalamic,
brainstem, and spinal cord structures
Clonic phase – discontinuous bursts of electrical activity brought
about by the interruption of the tonic phase by an inhibitory
impulse which starts from the thalamus
Generalized Tonic-Clonic Seizure
Tonic & Clonic Phases
Post-ictal Phase
• Loss of consciousness or fainting – 30
sec to 5 mins.
• General muscle contraction and rigidity
(tonic phase) – 15-20 sec.
• Violent rhythmic muscle contraction and
relaxation (clonic phase) – 1-2 mins.
• Biting the cheek/tongue, clenched
teeth/jaw
• Incontinence
• Stopped breathing or difficulty
breathing during seizure
• Cyanosis
• Normal breathing
• Sleepiness – 1 hr or longer
• Loss of memory (amnesia)
regarding events surrounding the
seizure episode
• Headache
• Drowsiness
• Confusion, temporary and mild
• Weakness for up to 24 - 48 hours
following seizure (Todd's
paralysis)
Initial Diagnostic Evaluation







CBC
Blood chemistries
Liver and thyroid function tests
EEG
Imaging study of the brain, preferably MRI
Video/EEG or prolonged EEG monitoring
Other forms: cardiac stress tests, Holter monitor, tilttable testing, sleep studies
EEG
Initial Phase
• Movement artifacts
obscure the EEG
tracing.
• (+) repetitive spikes or
spike-wave discharges
lasting a few seconds,
followed by an
approximately 10-s
period of 10-Hz
spikes.
Clonic Phase
• Spikes become mixed
with slow waves
• Then, EEG slowly
assumes a polyspikeand-wave pattern.
Post-ictal Phase
• Nearly flat for a
variable time
• Brain waves then
gradually resume their
pre-seizure pattern.
Treatment
Choices of Antiepileptic Drugs by Type of
Adult Seizure Disorders
SEIZURE TYPE
INITIAL CHOICE
SECOND LINE
Tonic-clonic
Carbamazepine,
valproate,
phenytoin
Lamotrigine,
oxcarbazepine
Myoclonic
Valproate
Topiramate,
levetiracetam,
zonisamide
Partial
Carbamazepine,
phenytoin
Valproate, lamotrigine,
oxcarbazepine,
levetiracetam
Absence
Valproate
Ethosuximide, lamotrigine
Unclassifiable
Valproate
Lamotrigine
Reference: Adams and Victor’s Principles of Neurology, 9th Edition.
General Principles of Treatment





The use of antiepileptic drugs is the most important
factor of treatment.
Establish the diagnosis and rule out underlying
pathology.
Classify seizure type, using EEG and clinical criteria.
Because of the long half-lives of phenytoin,
phenobarbital, and ethosuximide, these drugs need be
taken only once daily.
Valproate and carbamazepine have shorter half-lives,
and their administration should be spaced during the
day.
Reference: Adams and Victor’s Principles of Neurology, 9th Edition.
General Principles of Treatment




Serum-protein binding characteristics of antiepileptic drugs
and the interactions among these drugs and between
antiepileptic and other drugs should be considered.
Initially, only one drug should be used and the dosage
increased until sustained therapeutic levels have been
attained.
If the first drug does not control seizures, a different one
should be tried, but frequent shifting of drugs is not
advisable.
In changing medication, the dosage of the new drug should
be increased gradually to an optimum level while the
dosage of the old drug is gradually decreased; the sudden
withdrawal of a drug may lead to an increase in seizure
frequency or status epilepticus.
Reference: Adams and Victor’s Principles of Neurology, 9th Edition.
General Principles of Treatment


Phenytoin, carbamazepine, and valproate are
representative of antiepileptic drugs and are more
or less equally effective in the treatment of both
generalized and partial seizures.
Phenytoin and carbamazepine act by blocking
sodium channels, thus preventing abnormal neuronal
firing and seizure spread.
Reference: Adams and Victor’s Principles of Neurology, 9th Edition.
Phenytoin







Pediatric Dosage: 4-7 mg/kg
Adult Dosage: 300-400 mg/day
Oral, IM or IV
Idiosyncratic phenytoin hypersensitivity: rash, fever,
lymphadenopathy, eosinophilia and other blood
dyscrasias, and polyarteritis
Overdose: ataxia, diplopia, stupor, hirsutism,
hypertrophy of gums, coarsening of facial features
Chronic use may be associated with peripheral
neuropathy, some form of cerebellar degeneration.
Phenytoin should not be used with: disulfiram,
chloramphenicol, sulfamethizole, phenylbutazone, or
cyclosphosphamide
Reference: Adams and Victor’s Principles of Neurology, 9th Edition.
Carbamazepine





Pediatric Dosage: 20-30 mg/kg
Adult Dosage: 600-1200 mg/day
This drug causes same effects with phenytoin, but to
a slightly lesser degree.
Mild leukopenia is common; pancytopenia,
hyponatremia, diabetes insipidus are rare.
Oxcarbazepine, a more recently introduced
analogue or carbamazepine, has fewer side effects,
especially marrow toxicity.
Reference: Adams and Victor’s Principles of Neurology, 9th Edition.
Valproate





Pediatric Dosage: 30-60 mg/kg
Adult Dosage: 1000-3000 mg/day
All preparations are hepatotoxic.
There has been evidence of weight gain during the
first months of therapy with valproate.
Menstrual irregularities and PCOS may appear in
young women taking the drug.
Reference: Adams and Victor’s Principles of Neurology, 9th Edition.
Phenobarbital





Pediatric Dosage: 3-5 mg/kg
Adult Dosage: 90-200 mg/day
Still highly effective, but has many toxic effects:
drowsiness, mental dullness, nystagmus, staggering
Phenobarbital and primidone may provoke
behavioral problems in retarded children.
It is still used to advantage as an adjunctive
anticonvulsant and as a primary therapy in infantile
seizures.
Reference: Adams and Victor’s Principles of Neurology, 9th Edition.
Lamotrigine






Pediatric Dosage: 0.5 mg/kg
Adult Dosage: 300-500 mg/day
Lamotrigine closely resembles phenytoin in its antiseizure
activity but has different features relating to toxicity.
It selectively blocks the slow sodium channels, thereby
preventing the release of the excitatory
neurotransmitters glutamate and aspartate.
It is effective as a first-line and adjunctive drug for
generalized and focal seizures.
It does not provoke weight gain and ovarian problems.
Reference: Adams and Victor’s Principles of Neurology, 9th Edition.
Discontinuation of Anticonvulsants



Withdrawal of anticonvulsant drugs may be undertaken in
patients who have been free of seizures for a prolonged
period.
If the EEG tracing is abnormal by way of showing
paroxysmal activity, it is generally better to continue
treatment.
Callaghan et al.



In patients who had been seizure-free during 2 years of treatment
with a single drug, 1/3 relapsed after discontinuation of the drug.
This relapse rate was much the same in adults and children and
whether the drug was reduced over a period of weeks or months.
Relapse rate was lower in patients with absence and generalized
onset seizures than in patients with complex partial seizures and
secondary generalization.
Reference: Adams and Victor’s Principles of Neurology, 9th Edition.
Discontinuation of Anticonvulsants

Specchio et al.
 After
2 years on a single anticonvulsant during which no
seizures had occurred, the rate of relapse was 40% 2.5
years later and 50% at 5 years after discontinuation.
 This compared to a seizure recurrence rate of 20% for
patients remaining on medication.

A longer seizure-free period is associated with a
lesser rate of relapse.
Reference: Adams and Victor’s Principles of Neurology, 9th Edition.
Prognosis


With treatment, seizures are eliminated in one-third
of patients with epileptic seizures, and frequency of
seizures is reduced by > 50% in another one-third.
About 60% of patients whose seizures are wellcontrolled by drugs can eventually stop the drugs
and remain seizure-free.
Sudden unexplained death in epilepsy (SUDEP) is a
rare complication of unknown cause.
Reference: http://www.merck.com/mmpe/sec16/ch214/ch214a.html
CASE 2.3
CASE 2.3
An 11 month-old male infant was rushed to the hospital
because of first-onset and single episode of generalized
seizure.
The infant was noted to be coughing with nasal catarrh for the
last 5 days. Hours before the seizure episode, his temperature
was taken to be 38.9C. Perinatal and postnatal histories were
unremarkable.
The father admitted to be having the same episodes when he
was still around 5 years old during the height of his fever.
Neurological examination was normal.
Salient Features
11 months
old
Male
Recent URI
Spike in
body temp
38.9 °C
(+)Family
history
Normal
Neuro Exam
Missing Data



Duration of the seizure episode
If there are other accompanying symptoms such as
vomiting, loss of consciousness, urinating or soiling
himself.
Recent vaccination (DTP or MMR)
Clinical Impression:
Febrile Seizure
Differential Diagnosis
DIFFERENTIAL DIAGNOSIS
1.
2.
3.
Meningitis
Encephalitis
Epilepsy
MENINGITIS


An inflammation of the
membranes (meninges) and
cerebrospinal fluid surrounding
the brain and spinal cord,
usually due to the spread of an
infection.
The swelling associated with
meningitis often triggers the
"hallmark" symptoms of this
condition, including headache,
fever and a stiff neck.
MENINGITIS
•
Most cases of meningitis are caused by a viral
infection, but bacterial and fungal infections also
can lead to meningitis.
–
•
Bacterial infections are the most damaging, identifying
the source of the infection is an important part of
developing a treatment plan.
Depending on the cause of the infection, meningitis
can resolve on its own in a couple of weeks — or it
can be a life-threatening emergency.
Acute Bacterial Meningitis
 Usually
occurs when bacteria enter the bloodstream
and migrate to the brain and spinal cord.
 Can directly invade the meninges, as a result of an ear
or sinus infection or a skull fracture.
Acute Bacterial Meningitis
–
Streptococcus pneumoniae
•
–
Most common cause of bacterial meningitis in infants and
young children in the United States.
Neisseria meningitidis
•
•
•
Another leading cause of bacterial meningitis.
It commonly occurs when bacteria from an upper respiratory
infection enter your bloodstream.
Highly contagious and may cause local epidemics in college
dormitories and boarding schools and on military bases.
Acute Bacterial Meningitis
–
Haemophilus influenzae
•
•
Before the 1990s, Haemophilus influenzae type b (Hib) bacterium was the
leading cause of bacterial meningitis.
Hib vaccines —routine childhood immunization
–
•
–
Greatly reduced the number of cases of this type of meningitis
It tends to follow an upper respiratory infection, ear infection (otitis media) or
sinusitis.
Listeria monocytogenes
•
These bacteria can be found almost anywhere — in soil, in dust and in foods
that have become contaminated
–
•
Most healthy people exposed to listeria don't become ill
–
•
Soft cheeses, hot dogs and luncheon meats
Pregnant women, newborns and older adults tend to be more susceptible.
Listeria can cross the placental barrier, and infections in late pregnancy may
cause a baby to be stillborn or die shortly after birth.
MENINGITIS
•
Viral meningitis
–
–
–
–
•
Usually mild and often clears on its own within two weeks
A group of common viruses known as enteroviruses are responsible for
about 90 percent of viral meningitis in the United States
Most common signs and symptoms: Rash, sore throat, joint aches and
headache
“Worst headache I've ever had”
Chronic meningitis
–
–
–
–
Ongoing (chronic) forms of meningitis occur when slow-growing
organisms invade the membranes and fluid surrounding the brain
Although acute meningitis strikes suddenly, chronic meningitis develops
over four weeks or more
Signs and symptoms: Headaches, fever, vomiting and mental cloudiness
Rare
MENINGITIS
•
Fungal meningitis
–
–
Relatively uncommon
Cryptococcal meningitis
•
–
•
Fungal form of the disease that affects people with immune
deficiencies, such as AIDS
Life-threatening if not treated with an antifungal medication
Other Causes
–
Meningitis can also result from noninfectious causes, such as
drug allergies, some types of cancer and inflammatory
diseases such as lupus.
Reference: Harrison’s Principles of Internal Medicine, 17th Edition.
CASE
MENINGITIS
• II month old male infant
• First onset and single episode of
generalized seizure
• coughing with nasal catarrh for the
last 5 days
• T = 38.9C
• Perinatal and postnatal histories
were unremarkable
• The father admitted to be having the
same episodes when he was still
around 5 years old during the height
of his fever
• Neurological examination was
normal
• History of infection
• Classic triad of fever, headache, and
nuchal rigidity
• (+) Kernig's sign and Brudzinski's
sign
• Decreased level of consciousness
occurs in >75% of patients and can
vary from lethargy to coma
• Nausea, vomiting, and photophobia
are also common complaints
• Seizures
• Raised ICP
• Reduced level of consciousness,
papilledema, dilated poorly
reactive pupils
ENCEPHALITIS
•
“Inflammation of the brain," it usually refers to brain
inflammation resulting from a viral infection.
–
Primary encephalitis
•
–
Secondary encephalitis
•
•
Involves direct viral infection of the brain and spinal cord
A viral infection first occurs elsewhere in the body and then travels
to the brain
In contrast to viral meningitis, where the infectious
process and associated inflammatory response are
limited largely to the meninges, in encephalitis the brain
parenchyma is also involved.
ENCEPHALITIS
•
It can be caused by:
–
Bacterial infection
•
•
–
A complication of a current infectious disease
•
–
Syphilis (secondary encephalitis)
Parasitic or protozoal infestations
•
•
–
Spreads directly to the brain (primary encephalitis)
Bacterial meningitis
Can also cause encephalitis in people with compromised immune
systems
Such as toxoplasmosis, malaria, or primary amoebic
meningoencephalitis
Lyme disease and/or Bartonella henselae may also cause
encephalitis
CASE
ENCEPHALITIS
• II month old male infant
• First onset and single episode of
generalized seizure
• Coughing with nasal catarrh for the
last 5 days
• T = 38.9C
• Perinatal and postnatal histories were
unremarkable
• The father admitted to be having the
same episodes when he was still
around 5 years old during the height
of his fever
• Neurological examination was
normal.
• History of infection
• Fever, headache and nuchal rigidity
• (+) Kernig’s and Brudzinski’s sign
• Photophobia and seizures
• Altered level of consciousness
• Evidence of either focal or diffuse
neurologic signs and symptoms
• Focal findings are aphasia, ataxia,
upper or lower motor neuron
patterns of weakness, involuntary
movements and cranial nerve
deficits
• Hallucinations, agitation, personality
change, behavioral disorders, and, at
times, a frankly psychotic state
EPILEPSY



Classified as a disorder of at least two unprovoked
recurrent seizures.
More common in young and old, plateau at 2nd – 4th
decades of life
In children (0-14 years old)
congenital> trauma=infection>CVA=tumor
EPILEPSY

Genetic Predispostion
 The
direct result of a known or presumed genetic defect
in which seizures are the core symptom of the disorder.
 Examples
include childhood absence epilepsy, autosomal
dominant nocturnal frontal lobe epilepsy, and Dravet
syndrome.
EPILEPSY

Epileptic Seizures
 No
sexual predisposition, may occur at any age.
 Loss of consciousness is common.
 Onset is usually abrupt and may have a short aura.
 Vocalization is present during automatism.
Dravet’s Syndrome






Severe myoclonic epilepsy of infancy (SMEI)
Generalized epilepsy syndrome
Onset is in the first year of life.
Peaks at about 5 months of age with febrile
hemiclonic or generalized status epilepticus.
Boys are twice as often affected as girls.
Prognosis is poor.



Most cases are sporadic.
Family history of epilepsy and febrile convulsions is
present in around 25 percent of the cases.
Known causative genes are the sodium channel α
subunit genes SCN1A and SCN2A, an associated β
subunit SCN1B, and a GABAA receptor γ subunit
gene, GABRG2.
Pathophysiology
Seizure
Generation
Synaptic Level
Cellular Level
Na+ channels
Increase Influx of
Na+
Increase intracellular
Na+ and water
Increase Tissue
excitability
Cations
K+ channels
GABA
Glutamate
Ca2+
channels
Decrease
intracellular K+
Decreased
Increased
Cell
hyperexcitability
Firing of thalamic and
cortical neurons
Hyperexcitable state
CASE
DRAVET’S SYNDROME
• II month old male infant
• First onset and single episode
of generalized seizure
• Coughing with nasal catarrh for
the last 5 days
• T = 38.9C
• Perinatal and postnatal
histories were unremarkable.
• The father admitted to be
having the same episodes when
he was still around 5 years old
during the height of his fever.
• Neurological examination was
normal.
• Onset is in the 1st year of life.
• Peaks at about 5 months of
age with febrile hemiclonic or
generalized status epilepticus
• Boys are twice as often
affected as girls.
• (+)Family History
Febrile Seizures
Febrile Seizure

Most common type of seizure that occurs during childhood that is
associated with a febrile illness not caused by an infection of the central
nervous system (CNS), without previous neonatal seizures or a previous
unprovoked seizure, and not meeting the criteria for other acute
symptomatic seizures (International League Against Epilepsy).

Rare before 9 months and after 5 years of age

The peak age of onset is 14-18 months.

A strong family history of febrile convulsions in siblings and parents
suggests a genetic predisposition.
 In a child with febrile seizure, the risk of febrile seizure is 10% for
the sibling and almost 50% for the sibling if a parent has febrile
seizures as well.
References: Nelson’s Pediatrics 18th ed. and eMedicine.medscape.com
Febrile Seizure





Febrile seizures are not associated with reduction in later
intellectual performance, and most children with febrile
seizures have only a slightly greater risk of later epilepsy than
the general population.
Usually it takes the form of a single, generalized motor seizure
occurring as the temperature rises or reaches its peak.
Seldom does the seizure last longer than a few minutes.
By the time an EEG can be obtained, there is usually no
abnormality.
Recovery is complete.
References: Nelson’s Pediatrics 18th ed. and eMedicine.medscape.com
Risk Factors







Family history of febrile seizures
High temperature
Parental report of developmental delay
Neonatal discharge at an age greater than 28 days
(suggesting perinatal illness requiring hospitalization)
Daycare attendance
Presence of 2 of these risk factors increases the
probability of a first febrile seizure to about 30%.
Maternal alcohol intake and smoking during
pregnancy has a 2-fold increased risk.
References: Nelson’s Pediatrics 18th ed. and eMedicine.medscape.com
Types of Febrile Seizure


Simple
 Associated with a core temperature that increases rapidly to
≥39°C.
 It is initially generalized and tonic-clonic in nature.
 Lasts a few seconds and rarely <15 mins.
 Followed by a brief postictal period of drowsiness.
 Occurs only once in 24 hrs.
Complex
 Duration is >15 mins.
 Focal seizure activity or focal findings are present during the
postictal period.
 Repeated convulsions occur within 24 hrs.
References: Nelson’s Pediatrics 18th ed. and eMedicine.medscape.com
Recurrent Seizures
•
•
•
Approximately 30–50% of children have recurrent seizures with later
episodes of fever and a small minority has numerous recurrent febrile
seizures.
Risk factors for recurrent febrile seizures include the following:
– Young age at time of first febrile seizure <12 mos.
– Relatively low fever at time of first seizure
– Family history of a febrile seizure in a first-degree relative
– Brief duration between fever onset and initial seizure
– Multiple initial febrile seizures during same episode
Patients with all 4 risk factors have greater than 70% chance of
recurrence. Patients with no risk factors have less than a 20% chance of
recurrence.
References: Nelson’s Pediatrics 18th ed. and eMedicine.medscape.com
Pathophysiology
•
•
•
•
Febrile seizures occur in young children at a time in their development when the seizure
threshold is low.
This is a time when young children are susceptible to frequent childhood infections such as
upper respiratory infection, otitis media, viral syndrome, and they respond with comparably
higher temperatures.
Animal studies suggest a possible role of endogenous pyrogens, such as interleukin 1beta,
that, by increasing neuronal excitability, may link fever and seizure activity.
Preliminary studies in children appear to support the hypothesis.
References: Nelson’s Pediatrics 18th ed. and eMedicine.medscape.com
Febrile Seizures
History
•
•
•
•
•
The type of seizure (generalized or focal) and its duration should be
described to help differentiate between simple and complex febrile
seizures.
Focus on the history of fever, duration of fever, and potential exposures
to illness.
A history of the cause of fever (eg, viral illnesses, gastroenteritis) should
be elucidated.
Recent antibiotic use is particularly important because partially
treated meningitis must be considered.
A history of seizures, neurologic problems, developmental delay, or
other potential causes of seizure (eg, trauma, ingestion) should be
sought.
Febrile Seizures
Physical Examination


The underlying cause for the fever should be sought.
A careful physical examination often reveals otitis media, pharyngitis, or a viral
exanthem.

Serial evaluations of the patient's neurologic status are essential.

Check for meningeal signs as well as for signs of trauma or toxic ingestion.
CASE
• II month old male infant
• First onset and single episode of
generalized seizure
• Coughing with nasal catarrh for the
last 5 days
• T = 38.9C
• Perinatal and postnatal histories
were unremarkable.
• The father admitted to be having
the same episodes when he was
still around 5 years old during the
height of his fever.
• Neurological examination was
normal.
FEBRILE SEIZURES
• History of infection
• Ages of 3 months and 5 years
• Twice more common in boys than
girls
• Fever and seizures
Management
Diagnostics


To determine the cause of the fever
To rule out meningitis or encephalitis
Lumbar Puncture with CSF examination

Cerebrospinal fluid
(CSF) is essential in
confirming the diagnosis
of meningitis,
encephalitis, and
subarachnoid
hemorrhage.
Lumbar Puncture with CSF Examination

Contraindications:
 Elevated
ICP owing to a suspected mass lesion of the
brain or spinal cord
 Symptoms and signs of pending cerebral herniation in
a child with probable meningitis
 Critical illness
 Skin infection at the site of the LP
 Thrombocytopenia
Lumbar Puncture with CSF examination
Normal
WBC
Protein
0-5
lymphocyte
15-45
High
neutrophil
Acute
→
bacterial
(after 5 days)
lymphocytes
Others
Low
Turbid
N or slight
increase
Viral
TB
High
Sugar
50-75
>50% of
blood
sugar
High
lymphocytes
High
Clear
Clear
Low <40
Xanthochromic
EEG



Not recommended after an initial simple febrile
seizure in children with a normal neurologic
examination.
Typically does not identify specific abnormalities or
help predict recurrent seizures.
Consideration of EEG if febrile seizures are complex
or recurrent.
Reference: http://www.merck.com/mmpe/sec19/ch283/ch283c.html
Treatment
Treatment for Nasal Catarrh
•
•
•
Pseudoephedrine/Dextromethorphan can be
given for the cough and decongesting the
airways of the infant.
It works by constricting blood vessels and
reducing swelling in the nasal passages,
which helps you to breathe more easily. The
cough suppressant works in the brain to help
decrease the cough reflex.
However, you should not use decongestants
for more than 5-7 days at a time. This is
because they can only provide short-term
relief for catarrh, and using them for any
longer can make your symptoms worse.
Medical Treatment

Treatment of infants
with seizures is
different than
treatment for adults.
Unless a specific cause
is found, most infant
with first-time seizures
will not be placed on
medications.
Medical Treatment
•
Phenobarbital
- Enhances the inhibitory
actions of gammaaminobutyric acid (GABA)
on neurons.
- Decreases the occurrence
of subsequent febrile
seizures.
- Oral Dosage (as
recommended by the
American Academy of
Pediatrics): 1 to 3 mg/kg.
Medical Treatment
Benzodiazepine
•
Centrally acting muscle relaxant.
•
Gel, rectal 2.5 mg (pediatric)
•
•
•
Anticonvulsant properties may be in
part or entirely due to binding to
voltage-dependent sodium channels.
It can reduce the risk of subsequent
febrile seizures.
Because it is given intermittently, this
therapy probably has the fewest
adverse effects. If preventing
subsequent febrile seizures is
essential, this would be the treatment
of choice.
Medical Treatment
•
Paracetamol
(Acetaminophen)
- Inhibits prostaglandins in
CNS, but lacks antiinflammatory effects in
periphery; reduces fever
through direct action on
hypothalamic heat-regulating
center.
-15 mg/kg; taken once
every 4 hours, up to 4 times
per day if needed
Prevention
Prevention
•
•
•
Most seizures cannot be
prevented.
There are some exceptions,
but these are very difficult
to control, such as head
trauma and infections
during pregnancy.
Children who are known to
have febrile seizures should
have their fevers well
controlled when sick.
Prevention


The best way to
prevent fevers is to
reduce the infant's
exposure to infectious
diseases.
Hand-washing is the
single most important
prevention measure
for people of all ages.
Prevention
If another seizure ensues:
• The initial efforts should be directed
first at protecting the infant from
additionally injuring himself.
• Lie down the infant.
• Remove glasses or other harmful
objects in the area.
• Do not try to put anything in mouth. In
doing so, it may injure the infant.
• Immediately check if the infant is
breathing. Call a doctor or proceed to
the nearest hospital.
CASE 2.4
Case 2.4
A 30 year-old female patient has been
maintained on phenytoin 100 mg TID for the
past 5 years with good control of her
idiopathic generalized seizure. She is 3 months
pregnant when she visited your clinic.
Missing Data
(+) / (-)
•
Frequency and Severity
 Associated
•
with:
Subtherapeutic anticonvulsant levels
•
•
•
•
Nausea and vomiting leads to missed doses.
Expanded intravascular volume lowers serum drug levels.
Hepatic, plasma and placental enzymes increase drug
metabolism.
Increased glomerular filtration hastens drug clearance.
Missing Data
(+) / (-)
•
Frequency and Severity
 Associated
•
with:
Lower seizure threshold
• “Exhaustion from sleep deprivation”
Missing Data
•
•
•
(+) / (-) Diabetes
(+) / (-) Hypertension
(+) / (-) Intake of folic acid
Salient Features
3o year old
female
1st trimester of
pregnancy
Phenytoin
100mg TID for
the past 5 years
Clinical Impression:
Idiopathic Generalized Seizure
Disorder
Generalized Tonic Clonic Seizure
•
Prodromal symptoms
–
–
–
Occurring hours or days before a seizure.
Mood changes, sleep disturbances, lightheadedness,
anxiety, irritability, difficulty concentrating and, rarely, an
ecstatic feeling, abdominal pain, facial pallor, or
headache. Most patients lose consciousness without any
premonitory symptoms.
Patients with generalized tonic-clonic seizures do not have
auras. An aura represents a simple partial seizure.
Generalized Tonic Clonic Seizure
•
The patient may have completely nonfocal findings on
neurologic examination when not having seizures.
Seizures typically are divided into tonic, clonic, and
postictal phases.
–
Tonic phase
•
The tonic phase begins with flexion of the trunk and elevation and
abduction of the elbows. Subsequent extension of the back and
neck is followed by extension of arms and legs. This can be
accompanied by apnea, which is secondary to laryngeal spasm.
Generalized Tonic Clonic Seizure
 Autonomic
signs are common during this phase and include
increase in pulse rate and blood pressure, profuse sweating, and
tracheobronchial hypersecretion.
 Although urinary bladder pressure rises, voiding does not occur
because of sphincter muscle contraction.
 This stage lasts for 10-20 seconds.
Generalized Tonic Clonic Seizure
–
Clonic phase
•
•
•
•
The tonic stage gives way to clonic convulsive movements, in which
the tonic muscles relax intermittently, lasting for a variable period
of time.
A generalized tremor occurs at a rate of 8 tremors per second,
which may slow down to about 4 tremors per second. Each spasm
is accompanied by pupillary contraction and dilation. Some
patients may have tongue or cheek bites.
The atonic periods gradually become longer until the last spasm.
Voiding may occur at the end of the clonic phase as sphincter
muscles relax. The atonic period lasts about 30 seconds. The patient
continues to be apneic during this phase.
The convulsion, including tonic and clonic phases, lasts for 1-2
minutes.
Generalized Tonic Clonic Seizure
–
Postictal state
•
•
•
A variable period of unconsciousness during which the
patient becomes quiet and breathing resumes.
The patient gradually awakens, often after a period of
stupor or sleep, and often is confused, with some
automatic behavior.
Headache and muscular pain are common. The patient
does not recall the seizure itself.
Generalized Tonic Clonic Seizure
•
Most generalized epilepsies are idiopathic, but a
definite genetic locus has been found for some of
these generalized types of epilepsy.
History
•
•
Unusual sensations suggesting an aura
Seizure manifestations
SUBTYPE
MANIFESTATIONS
Absence seizure
Brief staring spells with arrest of
activity, often w/ eye fluttering,
which just last a few seconds
Myoclonic seizure
Very brief isolated body jerks
that tend to occur in the morning
Generalized tonic-clonic
seizure
Convulsions of the whole body
lasting 1-2 minutes
History
•
Ask about the first and any subsequent seizures.
•
•
•
•
•
•
•
Duration
Frequency
Sequential evolution
Longest & shortest interval between seizures
Aura
Postictal state
Precipitating factors
History
•
Risk factors
•
•
•
•
•
•
Rare triggers
•
•
•
•
Prior head trauma or CNS infection
Drug use or withdrawal
Alcohol withdrawal
Non-adherence to anticonvulsants
Family history of seizures or neurologic disorders
Repetitive sounds
Flashing lights
Touching certain parts of the body
Sleep deprivation
•
Can lower the seizure threshold
Physical Examination

A bitten tongue, incontinence (eg., urine or
feces in clothing), or, in patients who have lost
consciousness, prolonged confusion, suggest
seizure.
Physical examination rarely indicates the
cause when seizures are idiopathic but may
provide clues when seizures are
symptomatic.

Intellectual functions,
neurologic exam and
imaging (MRI) are
normal.

Diagnostic evaluation must determine whether
the event was a seizure vs. pseudoseizure or
syncope.
EEG
•
•
•
The only definitive test to confirm
the diagnosis.
Represents a recurrent, sudden,
excessive discharge of cortical
neurons.
When abnormal, it’s very
characteristic:
• Interictal symmetric bursts of 4to 7-Hz epileptiform activity
• Interictal spike-and-wave
abnormalities without any clinical
seizure activity
EEG of the Subtypes of Generalized Seizure
SUBTYPE
Absence seizure
Myoclonic seizure
Generalized tonic-clonic
seizure
EEG CHANGES
Very characteristic
pattern wave complexes
Bilateral polyspike and
wave abnormality at a
rate of 4- to 6-Hz
Can show either of the
above patterns or
generalized spikes
Seizure and Pregnancy
Seizure and Pregnancy
•
•
•
A woman with a seizure disorder can
carry a pregnancy safely.
Seizures can harm the developing
fetus by reducing the blood supply to
the placenta.
For most pregnant women who have
epilepsy, seizures remain the same. For
a few, seizures become less frequent.
For others — particularly women who
have poorly controlled epilepsy —
pregnancy increases the number of
seizures.
Complications
•
•
•
•
•
•
•
Severe morning sickness
Anemia
Vaginal bleeding during and
after pregnancy
Abruptio placenta
Pre-eclampsia
Premature baby
LBW baby
Complications


The occurrence of seizures in the first trimester poses
the greatest risk of congenital malformation and
developmental delay in the offspring.
For babies whose mothers take seizure medication,
the risk of birth defects is 4 to 8 percent —
compared with 2 to 3 percent for all babies.

An antifolate effect on blood and interference
with vitamin K metabolism have been reported,
for which reason pregnant women taking
phenytoin should be given vitamin K before
delivery and the newborn infant should receive
vitamin K as well to prevent bleeding.

The obstetrician and neurologist should work
together prior to conception and throughout the
pregnancy to closely monitor seizures and
contributing factors (eg., sleep deprivation and
medication compliance).
AEDs & Pregnancy
Phenytoin
•
Fetal hydantoin syndrome
–
•
craniofacial anomalies, distal digital hypoplasia,
epicanthal folds, hypertelorism, low-set ears, and
developmental delay
Mothers who received phenytoin monotherapy
during pregnancy demonstrated slightly delayed
locomotor development.
Phenobarbital

Fetal hydantoin syndrome and fetal alcohol
syndrome
Valproic Acid


Syndrome of specific craniofacial abnormalities and
long, thin digits with hyperconvex nails
Neural tube defects
Carbamazepine


Craniofacial abnormalities and hypoplastic nails
Neural tube defects and cardiac abnormalities
Trimethadione


Epicanthal folds, low-set ears, microcephaly, short
stature, and irregular teeth
Rarely used in the treatment of epilepsy and should
certainly be discontinued during pregnancy
Prevention and Treatment
Phenytoin: Fetal Hydantoin Syndrome
A 30 year-old female patient has been maintained on phenytoin 100 mg TID
for the past 5 years with good control of her idiopathic generalized seizure.
She is 3 months pregnant when she visited your clinic.

Because exposure to multiple
antiepileptic drugs (AEDs)
seems to be more teratogenic
than monotherapy, patients
are advised to switch to a
single AED prior to conception
and taper to the lowest
possible dose.

Supplemental folate has been shown to
decrease neural tube defects in patients
without epilepsy and decrease other
congenital anomalies in women with epilepsy.
4 mg of folic acid should be taken daily
starting two to three months prior to
pregnancy and be continued through the
first trimester.
A fetal echocardiogram should be performed
at 19 to 20 weeks’ gestation with careful
attention to cardiac anomalies.
 Because of the increased risk neural tube
defects, a maternal serum AFP and
acetylcholinesterase screening test should be
offered.

Preconceptual Management of Women With
Epilepsy






Attempt to decrease pharmacotherapy to
monotherapy.
Taper dosages of AEDs to the lowest possible dose.
In women who have not had a seizure for 2-5 years,
attempt complete withdrawal of pharmacotherapy.
Establish the level of total and free AEDs necessary
for achieving good clinical control.
Consider preconceptual genetic counseling.
Supplement the diet with folate at 4 mg/d.
Management of Women With Epilepsy
During Pregnancy
Check total and free levels of AEDs monthly.
 Consider early genetic counseling.
 Check maternal MSAFP levels and perform a
level II fetal survey and ultrasonography at
19-20 weeks' gestation.
 Consider amniocentesis for alpha-fetoprotein
and acetylcholinesterase.

Gabapentin, lamotrigine, felbamate,
topiramate, and oxcarbazepine




These newer anticonvulsants have not been studied extensively
in pregnancy, though the use of pregnancy registries for AEDs
are providing larger sample sizes.
The benefits and risks between congenital anomalies and
seizure control needs to be considered when preparing the
women with epilepsy for pregnancy.
The new anticonvulsants generally have a better
pharmokinetic profile and are not metabolized to known
teratogens.
All of these anticonvulsants are considered US Food and Drug
Administration pregnancy category C. Of note, they are still
known to both cross the placenta and into breast milk.