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About 1 % of children will have at least one afebrile seizure by age 14 yrs
As you all know, the brain has an electrical discharge which consists of 4 brain waves:
1.
2.
3.
4.
Beta
Alpha
Theta
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 regionsexcitatory 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
-Failure of Na + -K + pump secondary to
adenosine triphosphate
-Excess of excitatory neurotransmitter
-Excess of excitatory neurotransmitter
Deficit of inhibitory neurotransmitter
Disorder
Hypoxemia, ischemia, and hypoglycemia
Neonatal Seizures
Classification
Clinical
Subtle
Tonic
Electroencephalographic
Clonic
Myoclonic
Epileptic
NonEpileptic
Subtle Seizure:
Eye deviation
Apnea
Tonic:
Primarily in Preterm
Clonic:
Primarily in term
Focal or multifocal
Myoclonic :
Rare
JITTERINESS
SEIZURE
Predominant movement
4 times)
Tremor
(extension=flexion)
Autonomic changes
In the absence of other etiologies, family history of seizures may suggest poor
prognosis. (the doctor said poor but in the slides its good)
Search for history that supports TORCH infections TORCH infections may cause
meningitis, encephalitis, etc which could result in a brain insult.
Delivery history
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)
Malformation
Hypoglycemia
Hypocalcemia
Meningitis
Stroke
Trauma
Hemorrhage
Hypoxia-ischemia
1970
1987
20
Incidence (%)
40
60
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?
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. )
Initial Dose
Route
Phenobarbital 20mg/kg
lV, lM, PO
Phenytoin
20 mg/kg
lV, PO
Fosphenytoin
20 mg/kg
lV, lM
Lorazepam
lV
Diazepam
0.25 mg/kg
lV
Lorazepam
What are the determinants of the duration of the anticonvulsant therapy for neonatal
seizures?
Guidelines:
If a baby in the neonatal period is on Phenobarbital and the seizures stop, we evaluate
him:
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 some epilepsy syndromes that occur during infancy and childhood
Seizure Classification
Partial
Generalized
Simple
Complex
No change in
consciousness
Consciousness is
impaired or lost
Diffuse onset
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:
Generalized Seizures:
Myoclonic seizures
Tonic seizures
Absence seizures
Tonic-clonic seizures
Atonic seizures
Syncope
Breath-holding spells
Cataplexy
Behavioral staring
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
Seizure type(s)
Natural history
Response to AEDs
Etiology
Infantile Spasms
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)
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)
Clinically, A Triad:
LGS is one of the worst syndromes that could occur in adults and one of the most difficult to
treat.
Treatment:
Surgery
Prognosis:
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)
Seizures: 3 types:
1. Myoclonic
2. GTC (Generalized Tonic-Clonic)
3. Absence (in 15-40 %)
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)
Prognosis:
Idiopathic/Genetic
Hippocampal sclerosis (we talked about this when discussing febrile seizures)
Toxic disorders
Metabolic disorders
Prenatal/perinatal injury
Trauma
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 wont 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)
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)>
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:
Theyve been present for around a century and a half so we have old preparations
(conventional) and newer (since the 1990s) preparations.
Some examples of the new preparations:
-
Phenobarbital
Advantages
IV formulation
Once daily dosing if needed (because it has a long half life - 96 hours)
Cognitive concerns
Phenytoin
Advantages
IV formulation
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
Carbamazepine:
Advantages
Relatively inexpensive
Disadvantages
Double vision
Advantages
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
Lamotrigine:
Can be used to treat any type of convulsions.
Disadvantages
It is also one of the AED which could INCREASE the frequency of seizures
Levetiracetam:
Advantages
Disadvantages
Oxcarbazepine:
Topiramate:
Advantages
Migraine prevention
Disadvantages
Weight loss
Renal stones
Zonisamide:
It has limited use in pediatrics and not available here in Jordan.
Treatment of Pediatric Epilepsy:
Seizure type
Epilepsy syndrome
Myoclonic
Partial Onset
Tonic-Clonic
Atonic,Tonic
Partial
Simple Complex
Partial
Generalized
Valproate
Myoclonic
Partial Onset
Tonic-Clonic
Atonic,Tonic
Partial
Simple Complex
Partial
Generalized
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>
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)
Cost