Seizures and Epilepsy

Seizures and Epilepsy

Let’s begin by discussing general points about Seizures and Epilepsy:

• Incidence of epilepsy: 40 /100,000 children / yr

• About 1 % of children will have at least one afebrile seizure by age 14 yrs

• 0.4 %-0.8 % (4/1000- 8/1000) will have epilepsy by age 11 yrs

• Epilepsy is the most common neurologic problem in childhood

Now how can we differentiate between seizures and epilepsy?

• A seizure is a sudden, involuntary, time-limited alteration in neurologic function

(movement, behavior) secondary to abnormal discharge of neurons in the CNS

• Epilepsy is a chronic condition characterized by 2 or more unprovoked seizures.

Therefore we have recurrent seizures. In some textbooks it is stated as 2 attacks of

unprovoked seizures and in others it is stated as 3 or more attacks of unprovoked

seizures.

Epilepsy is considered as a clinical diagnosis. Therefore when someone has 2-3

attacks of unprovoked seizures (not precipitated by fever, hypocalcaemia,

hypoglycemia, etc) this person is diagnosed as having epilepsy. Seizures provoked by

the above factors are simply called secondary seizures and NOT epilepsy. Thus

epilepsy is now said to be idiopathic or gene-related.

As you all know, the brain has an electrical discharge which consists of 4 brain waves:

1. Beta

2. Alpha

3. Theta

4. Delta

Of course these electrical frequencies vary according to level of alertness, whether one is

asleep, etc. They can be recorded by an EEG (Electroencephalograph) or a video EEG. The

video EEG is a very important and reliable modality for diagnosis because there can be

conditions which mimic seizures. For example, the video EEG is connected to a little boy. If

he moved his arm suddenly and there was no change in the EEG then this is not considered

a seizure.

Neonatal Seizures

As you know the neonatal period limited to :

- First 28 days for term infants

- 44 weeks gestational age for pre-term infants.

A stereotypic, paroxysmal spell of altered neurologic function (behavior, motor, and/or

autonomic function) occuring during this period is called a neonatal seizure.

The incidence – 1-5: 1000 live births

Neonatal seizures differ from seizures that occur in older children and from epilepsy.

What is the cause of this difference?

It is due to their immature CNS which cannot sustain a synchronized, well orchestrated

generalized seizure. This is because the CNS requires 2 to 3 years to obtain complete

myelination thus many nerve fibers are still uncovered.

What is the anatomical difference in neonates?

1. Dendritic and axonal ramifications are still in process

2. Synaptogenesis is not complete

3. Deficient myelination in cortical efferent systems

What is the physiological difference in neonates?

1. In limbic and neocortical regions—excitatory synapses develop before inhibitory

synapses (therefore any stimulation of neurons could cause abnormal electrical

discharge)

2. Immature hippocampal and cortical neurons more susceptible to seizure activity

than mature neurons

3. Deficient development of substantia nigra system for inhibition of seizures

4. Impaired propagation of electrical seizures, whether synchronous or asynchronous,

as recorded by EEG.

Probable Mechanisms of Some Neonatal Seizures

Probable Mechanism Disorder

-Failure of Na + -K + pump secondary to

� adenosine triphosphate

-Excess of excitatory neurotransmitter

Hypoxemia, ischemia, and hypoglycemia

-Excess of excitatory neurotransmitter Hypoxemia, ischemia and hypoglycemia

Pyridoxine dependency

Deficit of inhibitory neurotransmitter Pyridoxine dependency

(i.e., relative excess of excitatory

neurotransmitter)

Membrane alteration— � Na +

Permeability

Now let’s talk about each one separately:

Subtle Seizure:

� More in preterm than in term

� Eye deviation

� Blinking, fixed stare

� Repetitive mouth and tongue movements

� Apnea

� Pedaling and tonic posturing of limbs

Tonic:

� Primarily in Preterm

� May be focal or generalized

� Sustained extension of the upper an

Clinical

Subtle Tonic

(i.e., relative excess of excitatory

Na +

Permeability

Hypocalcemia and hypomagnesemia

Now let’s talk about each one separately:

More in preterm than in term

Repetitive mouth and tongue movements

Pedaling and tonic posturing of limbs

May be focal or generalized

Sustained extension of the upper and lower limbs (mimics decerebrate posturing)

Neonatal Seizures

Classification

Clonic Myoclonic

Electroencephalographic

Epileptic

Hypocalcemia and hypomagnesemia

d lower limbs (mimics decerebrate posturing)

Electroencephalographic

EpilepticNon-

Epileptic

� Sustained flexion of upper with extension of lower limbs (mimics decorticate

posturing)

� Signals severe ICH (intracranial hemorrhage) in preterm infants

Clonic:

� Primarily in term

� Focal or multifocal

� Clonic limb movements(synchronous or asynchronous, localized or often with no

anatomic order of progression)

� Consciousness may be preserved

� Signals focal cerebral injury

Myoclonic :

� Rare

� Focal, multifocal or generalized

� Lightning-like jerks of extremities (upper limbs > lower limbs)

Note: It is very important to differentiate between jitterness and seizures:

CLINICAL FEATURE JITTERINESS SEIZURE

Abnormality of gaze or eye O +

movement

Movements are stimulus + O

sensitive (if you irritate the

child or put him under stress,

jitterness will increase but

seizure will not)

Predominant movement Tremor Clonic jerking <unequal>

(extension=flexion) (extends arm once, flexes 3-

4 times)

Movements cease with passive + O

flexion (stops shaking when you

touch the limb)

Autonomic changes O +

Etiology of Neonatal Seizures:

Importance of knowing the etiology:

• It is critical to recognize neonatal seizures, and to determine their etiology, as

sometimes the underlying cause is treatable and at others it can be due to a brain

insult, and of course the prognosis depends on the underlying cause.

For example, a baby has hypoglycemia as he was born to a diabetic mother, this

patient will have a good prognosis if discovered early before acquiring a brain insult.

However, if the seizure was due to infection, hemorrhage or malformation, the

prognosis will be bad. Thus we can recognize the importance of knowing the

etiology.

• Seizures are usually related to significant illness, sometimes requiring specific

therapy

• Neonatal seizures may interfere with important supportive measures, such as

alimentation and assisted respirations for associated disorders. For example, a

neonate may have apnea as the presenting symptom of a seizure (subtle seizure). If

you do not deal with the apnea the neonate may develop anoxia hence brain anoxia

hence brain damage.

• Experimental data give some reason for concern that under certain circumstances

the seizure per se may be a cause of brain injury.

What helps us in determining the etiology?

� Clinical history provides important clue

� Family history may suggest genetic syndrome

� In the absence of other etiologies, family history of seizures may suggest poor

prognosis. (the doctor said poor but in the slides it’s good)

� Pregnancy history is important

� Search for history that supports TORCH infections – TORCH infections may cause

meningitis, encephalitis, etc which could result in a brain insult.

� History of fetal distress, preeclampsia or maternal infections

� Delivery history

� Type of delivery and antecedent events

� Apgar scores are extremely important, especially the 5 minute and 10 minute scores

(which are important for the neonate).

The 1 minute score is important for the physician not the neonate. This is because if

an infant has a 1 minute APGAR score below 3, this means that the baby is severely

distressed, thus the physician must perform CPR, intubation, etc. However, the 1

minute score does NOT reflect the prognosis.

The 5 and 10 minute score however, if they are below 7, we will be worried that the

child may develop HIE (hypoxic ischemic encephalopathy) if it is associated with

abnormal manifestations of the CNS. However sometimes the APGAR score can be

misleading. If the baby has a low APGAR score yet was not in need of resuscitation,

then we must look for other causes of the seizure besides HIE.

HIE is a terminology used in the term infant to describe the clinical manifestation of

brain injury starting immediately or up to 48 hours after asphyxia(critical reduction in

oxygen delivery to the fetus antenatally, during labour or delivery)

� Postnatal history (metabolic disturbances, sepsis)

� Neonatal seizures in infants without uneventful antenatal history and delivery may

result from postnatal cause

� Tremors may be secondary to drug withdrawal or hypocalcemia

� Temperature and blood pressure instability may suggest infection (sepsis)

Comparison of prominent etiologic diagnoses of seizures in the newborn period. (Data

modified from Mizrahi and Kellaway, 1987; Rose and Lombroso, 1970)

0 20 40 60

Hypoxia-ischemiaHemorrhage

TraumaStroke

MeningitisHypocalcemiaHypoglycemiaMalformation

Incidence (%)

19701987

As we can see from observing the chart above, the largest number of cases is due to

Hypoxia-ischemia (approximately half of all cases).

The second is metabolic, specifically hypocalcaemia

Then we have infection, trauma, hemorrhage, etc

Now if an infant is suspected or found to have neonatal seizure, what laboratory tests must

be done to rule out the above causes one by one, bringing us closer to the correct etiology?

� Complete blood count, differential, platelet count

� urinalysis

� Blood glucose , Ca, Mg

� Blood oxygen and acid-base analysis (pH)

� Blood, CSF and other bacterial cultures

� CSF analysis (to rule out meningitis)

� EEG

� Ultrasound (this can be performed on any infant with open fontanelles to see if

there is Ivh – Intraventricular hemorrhage)

� CT or MRI

� Serum immunoglobulins, TORCH antibody titers, and viral cultures (if we suspect any

infection)

� Blood and urine metabolic studies (bilirubin, ammonia, lactate, FeCl³, reducing

substance.) – if we suspect a metabolic cause like hypoglycemia, hypocalcemia

� Blood and urine toxic screen

� Blood and urine amino and organic acid screen (as urea cycle defects as well as

organic acidemia may present with convulsions)

Treatment

Identify the underlying cause and treat accordingly:

Hypoglycemia - D10 solution

Hypocalcemia - Calcium gluconate

Hypomagnesemia- Magnesium sulfate

Meningitis- initiation of antibiotics

Pyridoxine deficiency- Pyridoxine (if you give the baby whatever was deficient, and you treat

him with phenobarbitone, and there was no improvement, this should give you a hint that

this seizure could be caused by pyridoxine deficiency. When you start giving this baby

pyridoxine, you will notice on the EEG that the icteric activity will disappear and the seizures

will cease. )

Why do we treat patients with neonatal seizures?

� To minimize brain damage

� Some controversy exists about when to start anticonvulsants

� If seizure is prolonged (longer than 3 minutes), frequent or associated with

cardiorespiratory disturbance, we must give anticonvulsants.

Drug Therapy for Neonatal Seizures

Standard Therapy

AED Initial Dose Route

Phenobarbital 20mg/kg lV, lM, PO

Phenytoin 20 mg/kg lV, PO

Fosphenytoin 20 mg/kg lV, lM

Lorazepam 0.05 to 0.1 mg/kg lV

Diazepam 0.25 mg/kg lV

AED= antiepileptic drug; IV= intravenous; IM= intramuscular; PO= oral

Regarding the doses, just know that the initial dose for the first three medications is 20

mg/kg which is different from the maintenance dose.

Notes about the table:

� Fosphenytoin is just a newer version of Phenytoin

� Lorazepam preferred over diazepam, however it is not available in Jordan.

� Since Phenobarbital is given IV, IM and orally it can be used for the acute phase and

for maintenance; however Lorazepam and Diazepam can only be used for the acute

phase.

� So for a baby with neonatal seizures not caused by metabolic disturbances, it is

preferable to give only these two medications – Diazepam and Phenobarbital.

Acute therapy of neonatal seizures:

When an infant is seizing, the first thing you do is take a dipstick and the samples you

need then:

� If with hypoglycemia – give glucose

� If no hypoglycemia- Phenobarbital:20mg/kg IV loading dose

If necessary : additional phenobarbital: 5 mg/kg IV to a max of 20 mg/kg (consider

omission of this additional Phenobarbital if the baby is asphyxiated)

� Phenytoin: not given nowadays due to extensive side effects

� Lorazepam

What are the determinants of the duration of the anticonvulsant therapy for neonatal

seizures?

� Neonatal neurological examination

� Cause of neonatal seizure

� Electroencephalogram

Guidelines:

If a baby in the neonatal period is on Phenobarbital and the seizures stop, we evaluate

him:

� If neonatal neurological examination becomes normal discontinue therapy

� If neonatal neurological examination is persistently abnormal, consider etiology

and obtain EEG

� In most such cases- Continue phenobarbital

- Discontinue phenytoin

- Reevaluate in 1 month

One month after discharge

� If neurological examination has become normal, discontinue phenobarbital

� If neurological examination is persistently abnormal, obtain EEG

� If there is seizure activity on EEG we continue Phenobarbital for another month

� If there is no seizure activity on EEG, discontinue phenobarbital

This usually goes on for 6 months.

Complications of Neonatal Seizures:

� Cerebral palsy

� Hydrocephalus

� Epilepsy

� Spasticity (severe)

� Feeding difficulties

By this we finish the first half of this lecture, and now we will begin with the second half:

Epilepsy in Childhood

Objectives:

• Review the international classification of seizures.

• Review some epilepsy syndromes that occur during infancy and childhood

• Discuss the evaluation process of seizures in children

• Discuss the medications used to treat pediatric seizures

• Discuss alternative therapies for intractable epilepsy

What are the steps in evaluation of pediatric epilepsy?

Steps in evaluation:

1. Is the spell a seizure event?

2. What is the differential diagnosis?

3. Is it epilepsy (does it fit the clinical diagnosis of epilepsy)?

4. Is it part of an epilepsy syndrome?

5. What tests are needed?

6. What is the therapy?

International Classification of Seizure Types:

Partial Seizures: arise from specific foci (an area in part of one hemisphere is affected).

Partial seizures can become generalized.

Generalized Seizure: from the beginning both hemispheres are affected thus it has a diffuse

onset.

Partial Seizures:

– Simple Partial Seizures

• With motor signs

• with somatosensory or special sensory symptoms

• With autonomic symptoms

• With psychic symptoms

– Complex Partial sz (CPS)

• Simple partial + i

• Consciousness impaired at onset

– CPS evolving to secondary generalized

Partial

Simple

No change in consciousness

International Classification of Seizure Types:


Partial seizures can become generalized.


Simple Partial Seizures

With motor signs

with somatosensory or special sensory symptoms

autonomic symptoms

With psychic symptoms

Complex Partial sz (CPS)

Simple partial + impaired consciousness

Consciousness impaired at onset

secondary generalized

Seizure Classification

Partial

Complex

Consciousness is impaired or lost

Generalized

Diffuse onset



Generalized Seizures:

– Myoclonic seizures

– Tonic seizures

– Absence seizures

– Tonic-clonic seizures

– Atonic seizures

Conditions that mimic childhood epilepsy:

• Syncope

• Breath-holding spells

• Cataplexy

• Behavioral staring

• Movement disorders ( e.g. tics)

• Parasomnias( night terrors, sleep walking,..)

• Migraine (hemiplegic migraine)

Familial hemiplegic migraine (FHM) is an autosomal dominant classical migraine

subtype that typically includes hemiparesis (weakness of half the body) during the

aura phase. It can be accompanied by other symptoms, such as ataxia, coma and

epileptic seizures. - Wikipedia

• Benign myoclonus (movement without any abnormalities in the EEG)

• Gastro esophageal reflux disease (if it is accompanied by vomiting, the infant can

develop torticollis while vomiting which can be confused with a seizure)

Epileptic Syndrome

• An epileptic syndrome consists of a complex of signs and symptoms that occur

together in a child with epilepsy more often than would be expected by chance

• An epileptic syndrome is defined by:

– Seizure type(s)

– Natural history

http://en.wikipedia.org/wiki/Autosomal_dominant

http://en.wikipedia.org/wiki/Migraine

http://en.wikipedia.org/wiki/Hemiparesis

http://en.wikipedia.org/wiki/Aura_(symptom)

http://en.wikipedia.org/wiki/Aura_(symptom)

http://en.wikipedia.org/wiki/Ataxia

http://en.wikipedia.org/wiki/Coma

http://en.wikipedia.org/wiki/Seizure

– EEG(ictal and inter ictal)

– Response to AEDs

– Etiology

Now let’s talk about a few Epileptic Syndromes:

Infantile Spasms

• Peak onset : 4-6 mo ( 90 % before 12 mo)

• Clinically characterized by spasms, which are mostly a mix between flexion and

extension (it is sometimes called “salam attack” as it mimics the Indian salute/salam.

When putting arms together like the Indian salute, your forearm will be flexed and

your hand will be extended)

• Spasms occur in clusters (can occur up to 20-30 times)

• West syndrome = infantile spasms +mental retardation + hypsarhythmia

Hypsarhythmia – abnormal EEG with characteristic wave patterns as if each limb has

its own electrical impulse.

Hypsarrhythmia is abnormal interictal high amplitude waves and a background of

irregular spikes seen in electroencephalogram, mostly in infant diagnosed with

infantile spasms. - Wikipedia

• Treatment:

- Hormonal- ACTH, corticosteroids (if ACTH is not available) ,

- Anticonvulsants (the most effective for infantile spasms are the new AED

(Vigabatrin),

<Hormones and AED are used to treat idiopathic infantile spasm>

- Surgery (in symptomatic infantile spasm which has an underlying cause- we

perform surgery to remove the cause)

http://en.wikipedia.org/wiki/Interictal

http://en.wikipedia.org/wiki/Electroencephalogram

http://en.wikipedia.org/wiki/Infantile_spasms

http://en.wikipedia.org/wiki/Infantile_spasms

• Prognosis: overall poor

Lennox- Gastaut Syndrome:

• Age of onset:1-8 yrs ( 3-6 more common)

• Clinically, A Triad:

1. Multiple seizure types (tonic most common)

2. Cognitive/ motor impairment

3. Slow spike and wave on EEG

• Etiology: Usually symptomatic (surgery), could be idiopathic (medications)

– 30 % of patients with infantile spasms develop LGS.

LGS is one of the worst syndromes that could occur in adults and one of the most difficult to

treat.

• Treatment:

– AED (Valproate, benzodiazepines, lamotrigine. Topamax, Felbamate…)

– Nonpharmacologic (Ketogenic diet, Vagus nerve stimulator)

– Surgery

• Prognosis: Very poor

– Less than 15 % are seizure free

– Impaired cognition and cerebral palsy are common

Notice the “burst activity” on EEG which is characteristic of LGS

Benign Partial Epilepsy of Childhood with centro-temporal

spike (BECTS)

• Also called Benign Rolandic Epilepsy

• The most common focal epilepsy in childhood

• Represents 15 % of childhood epilepsy

• Onset: 3-13 years( peak 6-8 yrs)

• Typical seizures are nocturnal, partial with secondary generalization in a

neurologically and cognitively normal child (therefore called Benign)

• The typical partial seizure involves:

– Unilateral parasthesias of the tongue, lips, gums and cheeks

– Unilateral clonic or tonic activity of above

– Speech arrest and salivation

• EEG: Central-temporal spikes.

• Treatment: Almost every AED is effective

Gabapentin and Carbamazepine are preferred

• Prognosis:

– Has the best prognosis of all epilepsies!

– By mid teens the disorder resolves in almost all patients

Childhood Absence Epilepsy: (CAE)

• Onset: 4-10 years

• More common in females

• Normal neurologic and developmental status

• Multiple seizures daily (can reach 30-40)

• Seizures last 5-15 second

• EEG: Classical 3 Hz diffuse spike and wave discharges with normal background.

• The seizures and the discharges are activated by hyperventilation and flickering

lights. (can be used for diagnosis)

• Treatment: Ethosuximide, valproate, lamotrigine

Notice how there are 3 spikes in 1 second (3 Hz).

Juvenile Myoclonic Epilepsy: (JME)

• Onset: commonly 12-18 yrs (8-26 yrs)

• Seizures: 3 types:

1. Myoclonic

2. GTC (Generalized Tonic-Clonic)

3. Absence (in 15-40 %)

• Seizures frequently occur upon awakening

• Precipitating Factors:

– Lack of sleep

– Emotional stress

– Alcohol consumption

• Genetics: multiple loci: in the short and long arm in several locations 6p, 15q14,

8p,1p (the doctor did not read these locations)

• EEG : Background is normal. Generalized 4-6 Hz polyspike and slow wave complexes;

Some have 3-4 Hz spike and slow wave complexes. (therefore it can mimic the

absence seizure on the EEG)

• Treatment : Valproate, Lamotrigine,Topiramate

• Prognosis:

– Seizures are controlled in the majority of patients.

– JME is one form of epilepsy in which discontinuation of pharmacotherapy

cannot be recommended. In most books the recommendation for treatment

in general is 2-4 years but this cannot be applied to this syndrome because

when therapy is stopped, the seizures will return.

– 90 % relapse after discontinuation of AED

Etiology of Epilepsy in Childhood: (Secondary Epilepsy)

• Idiopathic/Genetic

• CNS malformations, neurocutaneous disorders (eg. Neurofibromatosis)

• Hippocampal sclerosis (we talked about this when discussing febrile seizures)

• Vascular disease(AV malformation, Berry Aneurysm)

• CNS infection (meningitis, encephalitis, brain abscess)

• Toxic disorders

• Metabolic disorders

• CNS neoplasm(less than 1 %)

• Prenatal/perinatal injury

• Trauma

• Miscellaneous: demyelinating disorders, vasculitis

Epilepsy not due to the above causes is termed idiopathic or caused by genetic factors.

To diagnose epilepsy we need to do the following:

• Detailed History

• Physical Examination

• Supportive Investigations:

– EEG/ Video EEG (as we mentioned earlier the video EEG is better than the

EEG because the EEG records for 20-30 minutes and there won’t necessarily

be an abnormal electrical discharge within this time period. The video EEG is

especially useful if the history is not very informative and you are not sure

about the diagnosis, so you attach the video EEG which keeps recording for

24-48 hours and then you can analyze this EEG to make a diagnosis)

– Neuroimaging (CT scan, MRI)

– Metabolic work up (if we suspect infection)

– Lumbar puncture

Treatment:

• 1. Anticonvulsant medications

• 2. Nonpharmacologic treatments

– Ketogenic diet (we increase the fat in the diet so that more ketones are

formed and studies showed that this decreased the frequency of seizures)

– Vagus nerve stimulator (similar to the pacemaker which is put in the heart.

This device is attached to the vagus nerve sheath. Now any abnormal

impulses in the brain will be transferred to the cranial nerves. When an

abnormal impulse reaches the vagus nerve, the vagus nerve through various

mechanisms, will stop the impulse therefore aborting the seizure. This device

has been FDA approved and shown to decrease the frequency of seizures,

and it has even been done on several cases in Jordan.

<The Ketogenic diet and the Vagus nerve stimulator are only done under certain

indications – Cases which are resistant to Anticonvulsant Treatment (3 or more

drugs were used to control the seizure and there was no control)>

• 3. Epilepsy Surgery – if there is a clear focus we can remove it.

Also in certain extremely severe cases where the seizure manifests itself all the time,

we can do palliative surgery, for example temporal lobectomy. We could also cut the

corpus callosum in half so the right and left side will work independently therefore

we decrease the generalization of the seizure.

Let us talk briefly about the history of AED Therapy in the US:

They’ve been present for around a century and a half so we have old preparations

(conventional) and newer (since the 1990’s) preparations.

Some examples of the new preparations:

- Levetiracetam (trade name Keppra)

- Topiramate (Topamax)

- Lamotrigine (Lamictal)

- Gabapentin

- Vigabatrin

Now we will talk briefly about some important medications:

Phenobarbital

• Maintenance dose(mg/kg/day) 2-5(neonate); 3-7(child)

• Advantages

– IV formulation

– Can quickly load and bolus

– Once daily dosing if needed (because it has a long half life - 96 hours)

– Widely available and inexpensive

• Disadvantages (these are the most significant):

– Hyperactivity in younger children

– Cognitive concerns

Phenytoin

• Maintenance dose mg/kg/day 5-15 neonate/infant ; 3-7 child

• Advantages

– IV formulation

– Can quickly load and bolus

– Once daily dosing if needed

– Widely available and inexpensive

• Disadvantages (rarely used in pediatrics due to its severe side effects, mostly given

by neurological surgeons after brain surgery)

– Gum Hyperplasia

– Hirsutism

– Lymphadenopathy

– Hepatic failure

– Hypocalcaemia

– Possible hypersensitivity reaction

– Bone marrow suppression

Carbamazepine:

• Maintenance dose mg/kg/day 10-40

• Advantages

– Improved tolerability over phenobarbital and phenytoin

– Possible mood stabilization

– Sustained-release formulation (thus can be given once daily)

– Relatively inexpensive

• Disadvantages

– Rare idiosyncratic leukopenia and aplastic anemia (idiosyncratic – can be

induced by any dose – not dose related)


– Double vision

– Skin rash and hypersensitivity reactions(could cause Steven-Johnson

syndrome)

– One of AED which could INCREASE the frequency of seizures

Valproate: (most common AED in use, not to be given below 2 years)


• Advantages

– Broad spectrum (can be used to treat any convulsion)

• Disadvantages

– Alopecia

– Hepatotoxicity

– Weight gain


VALPROATE IS THE ONLY HEPATIC ENZYME INHIBITOR – therefore when you give any other

medication you must be careful because its toxicity will increase.

Gabapentin:


• Advantages

– Well tolerated

– Rapid escalation if needed

– Used for neuropathic pain

Lamotrigine:

Can be used to treat any type of convulsions.

• Disadvantages

– Skin rash (Steven-Johnson syndrome) which is the most worrisome side

effect.

– It is also one of the AED which could INCREASE the frequency of seizures

Levetiracetam:


• Advantages

– Rapid titration if needed

• Disadvantages

– Less data in children (not to be used before 4 years of age)

Oxcarbazepine:


Topiramate:

• Maintenance dose mg/kg/day 2-20 (infants); 2-10 (children)

• Advantages

– Broad spectrum (can be used for any type of seizure)

– Migraine prevention

• Disadvantages

– Weight loss

– Renal stones

Zonisamide:

It has limited use in pediatrics and not available here in Jordan.

Treatment of Pediatric Epilepsy:

• Goal: Seizure control without side effects

• Appropriate therapy requires accurate diagnosis:

– Seizure type

– Epilepsy syndrome

Treatment of Seizure Types: Traditional AED

Primary Generalized Partial Onset

Absence Myoclonic Tonic-Clonic Simple Complex

Secondary

Atonic,Tonic Partial Partial Generalized

Ethosuximide Benzodiazepines Carbamazepine, Phenytoin, Phenobarbital, Primidone

Valproate

Treatment of Seizure Types: 2005, New AED

Primary Generalized Partial Onset

Absence Myoclonic Tonic-Clonic Simple Complex

Secondary

Atonic,Tonic Partial Partial Generalized

Ethosuximide Benzodiazepines Carbamazepine, Phenytoin, Phenobarbital, Primidone,

Gabapentin, Oxcarbazepine, Tiagabine, Pregabalin

Valproate, Felbamate, Lamotrigine, Levetiracetam, Zonisamide, Topiramate

Why have we added these preparations in addition to Valproate? Because they have fewer

side effects and they are less toxic on the liver (recall that valproate is an enzyme inhibitor)

What are the factors that affect our choice of AED?

• Side effect profile (if a drug stopped the seizures yet caused idiosyncratic liver

failure, what did we gain?)

• Titration schedule (any AED should never be given as a full dose immediately)

For example, if the maximum dose of valproate is 60 mg we should never start with

this amount. We start with 5 mg, and every 4-5 days we increase another 5 mg until

the seizures become controlled. Then we follow up the patient to observe the

frequency of seizures and the side effects experienced due to the given medication.

<some newer preparations do not need such a slow increase in the dose as in the

conventional way>

• Other medications the patient is already on, we should know

– Drug-drug interaction

– Mechanism of action (we should not combine 2 medications that have the

same or similar mechanism of action. For example, if the drug the patient is

on is a Na inhibitor, we should look for a medication that acts on GABA or Ca

to increase efficacy)

• Overall clinical experience

• Physician’s personal experience

• Cost

Alternatives to Anticonvulsant treatment:

Medically intractable seizures (pharmacoresistant epilepsy)

It is estimated that 20-30 % of patients with epilepsy have medically intractable seizures

(which is actually a large percentage)

We have already mentioned the alternatives to anticonvulsant treatment earlier.

Done By:

Zeina Yanbeiy

If it is not truthful and not helpful, don't say it.

If it is truthful and not helpful, don't say it.

If it is not truthful and helpful, don't say it.

If it is truthful and helpful, wait for the right time. - Buddha

Do not believe in anything simply because you have heard it. Do not believe in anything simply because it

is spoken and rumored by many. Do not believe in anything merely on the authority of your teachers and

elders. Do not believe in traditions because they have been handed down for many generations. But after

observation and analysis, when you find that anything agrees with reason and is conducive to the good

and benefit of one and all, then accept it and live up to it. – Buddha

Wu hay a7la ta7iye la a7la C 10 wu shuraka2na C 9 ☺ wu be3tezir innu il mo7adara 25 saf7a!

Seizures and Epilepsy

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