Diseases of Central ervous ystem

6.5 eizures, pilepsy and onepileptic vents

S
E
N
E
Rekha Mittal

Provoked or cute ymptomatic eizure

Definitions and erminology

A
S
S
T
Provoked or acute symptomatic seizures are seizures
eizure occurring during the course of an acute illness, e.g.
S
A seizure is the clinical manifestation of an abnormal meningitis or head injury.
excessive paroxysmal electrical discharge from the brain.
pileptogenesis

N
This electrical discharge is conducted to the body and

E
produces a seizure. It could manifest in many different ways Epileptogenesis is the sequence of events that converts
(Table 6.5.1). normal neuronal networks into hyperexcitable epileptogenic
The type of seizure depends on the following: networks.

• The area of the brain producing the discharge

S
• The type of discharge pidemiology

E
• The age of the patient In India, prevalence rates for epilepsy are 5.59 per 1,000
Thus there are many different kinds of seizures: populations. Males and females are equally affected and

these rates are the same in different geographical areas.
pilepsy
E
Epilepsy is recurrent seizure for which there is no immediate tiology
E
precipitating cause. Etiology is multifactorial, and almost any insult to the brain
can result in seizures. Epilepsy can result from brain injury
pileptic yndrome due to infections, infestations, hypoxic damage, birth injury,
E
S
Epileptic syndrome is a syndrome where epilepsy is a malformations of the brain, genetic or metabolic causes
prominent feature. (Table 6.5.2).

diopathic pilepsies
Pathophysiology
I
E
Idiopathic epilepsies (now known as genetic epilepsies)
The exact pathophysiology of epileptogenesis is still not
are epilepsies, which have no underlying cause except a
well understood. However, it is known that seizures are
genetic predisposition to epilepsy.
produced when there is an abnormality in the:
ymptomatic pilepsies • Neurotransmitters levels
S
E
Symptomatic epilepsies are epilepsies where the cause is • Ion channels or
known, e.g. structural malformations, postmeningitic sequelae • Receptors.
and posthypoxic ischemic encephalopathy. In India and In many of the genetic epilepsies, there are abnormalities

countries where cysticercosis is endemic, neurocysticercosis of the ion channels or receptors due to mutations, resulting in
is the most common cause of focal seizures in children. epilepsies. These abnormalities can result in hyperexcitability
of neurons, which thus have a tendency to seizures.
Cryptogenic pilepsies The other epilepsies result from neuronal damage because
E

Cryptogenic epilepsies are epilepsies, which are expected to of various insults like infections, trauma and vascular events.
have a cause, but despite investigations, no cause is found.
nvestigations
I
Table 6.5.1 Clinical manifestations during seizures nvestigation of eizure
 
I
S
•  Abnormal motor activity, which may be a tonic contraction or single The plan of investigations depends on suspected cause (see

or repetitive jerks
“management of acute seizures and status epilepticus”).
•  Impairment or loss of consciousness or awareness

•  Abnormal behavior
lectroencephalogram

•  Abnormal sensory phenomena, e.g. abnormal sensation in one part of
E

the body, visual phenomena, smell, taste An EEG is the most important test for investigating epilepsy.
•  Abnormal experience: Fear anger illusions or hallucination. Children It is a graphic recording of the electric activity of the brain.

often run to the parent when this occurs An EEG is normal not due to normal patterns, but because it
•  Autonomic symptoms has no abnormal patterns. 339

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Table 6.5.2 Etiology of seizures and epilepsy
c
Causes of seizures
Infections
  Viral encephalitis
d
  Pyogenic meningitis
  Tubercular meningitis
  Neurocysticercosis
Metabolic events
Table 6.5.3 Electroencephalogram: information and limitations
Causes of epilepsy Information
Sequelae of any of the acute causes   Epileptic versus nonepileptic attacks
of seizures   Seizure type and epilepsy syndrome (Figs 6.5.1 to 6.5.3)
Cerebral malformations   Photosensitivity
Metabolic diseases   Partial seizures: To identify the focus (Fig. 6.5.4)
Degenerative brain diseases   Identify etiology, e.g. SSPE (Fig. 6.5.5)
Neoplasms   Monitor progress: Only in some epilepsies, e.g. typical absence seizures,


  Hypoglycemia Genetic disorders West syndrome. In most cases clinical response should be the criterion
  Hypocalcemia for judging response to treatment. Routine EEGs during treatment are
  Hypomagnesemia not required
  Dyselectrolytemia   Withdrawal of drugs: EEG is not required. Only clinical seizure control


(hypernatremia/hyponatremia) should decide whether drug is to be stopped
Vascular events
T
Limitations
  Cerebrovascular accidents
  Normal EEG does not exclude epilepsy
Drug intoxication/side effects
  Must always be interpreted in the clinical context
Vascular events
  With the exception of 3Hz spike wave discharges and hypsarrhythmia
  Thrombosis

  Embolism
  Hemorrhage
Neoplasms
Hypoxia/anoxia especially during
delivery
Head trauma
Febrile seizures
It is important to remember that EEG can be normal in
cases of epilepsy, while abnormal EEG does not necessarily
mean an epileptic disorder. Fifteen percent of cases of
epilepsy have a normal EEG, while 10% of the normal
population has an abnormal EEG. Thus the EEG must be
interpreted in the clinical context (Table 6.5.3 and Figs 6.5.1
to 6.5.5).
Ictal recordings are preferable over interictal ones.
Special provocation procedures like sleep deprivation,
hyperventilation and photic stimulation can be used to
increase the yield of EEG.
Video EEG is an EEG recording where the EEG and
video recordings are done at the same time. It may help
to differentiate non-epileptic events (NEE) from seizures,
and also help in identification of the type of seizure
(Fig. 6.5.6).
euroimaging
N
Neuroimaging gives important information about the
etiology in cases of symptomatic epilepsies (Figs 6.5.7
and 6.5.8). MRI is preferred since small lesions like cortical
dysplasia cannot be picked up on CT scan. Generally
neuroimaging should be done in all cases except where
clinical features and EEG are suggestive of idiopathic
epilepsy.
Positron emission tomography and single photon
emission computed tomography are functional scans that
may be done to study the perfusion. They are used in pre-
epilepsy surgery workup in refractory epilepsy and help in
identifying epileptic foci.
340

EEG is a poor guide to seizure control
Abbreviations: SSPE, Subacute sclerosing panencephalitis; EEG, Electroen­
cephalogram
ther nvestigations
O
I
Other investigations depend on suspected etiology in case
of symptomatic epilepsies. These include metabolic and
genetic tests.
atural History
N
In any given population with epilepsy, 30% may undergo
remission without treatment. This emerges from studies of
epilepsy in poor countries where no treatment has been
given for epilepsy because of financial constraints. Of those
who are treated, 60–70% undergoes remission, while the
remaining has intractable seizures.
Classification of eizures and
S
pileptic yndromes
E
S
It is very important to identify the syndrome wherever
possible, for starting correct treatment and prognostication,
and to identify etiology and genetics. In the past, there
existed confusion between epilepsies and seizure types.
Many of the epilepsies were classified and described by the
names of the persons who first described them. There was
no uniformity in the classification and descriptions used in
different parts of the world.
The International League Against Epilepsy (ILAE)
described a classification of seizures in 1981, and epilepsies
and epileptic syndromes in 1989, which has been modified
in 2006. Table 6.5.4 shows classification of seizures.
Classification of pilepsies and pileptic yndromes
E
E
S
The ILAE proposed a classification of epilepsies and
epileptic syndromes in 1989. Earlier the epilepsies were
classified as localization related epilepsies, generalized

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S
Figure 6.5.1 Hypsarrhythmia, a high voltage chaotic electroencephalogram pattern which changes, characteristic of infantile spasms
 
341
Figure 6.5.2 Polyspike wave discharges suggestive of myoclonic seizures
 
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d
T
Figure 6.5.3 3/sec spike wave discharges suggestive of typical absence seizures
 
342
Figure 6.5.4 Epileptic focus—right frontal region
 
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 Diseases of Central ervous ystem
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S
Figure 6.5.5 Periodic complexes seen in subacute sclerosing pan encephalitis
 
-
Figure 6.5.6 Video electroencephalogram. Simultaneous electroencephalogram and video recording
 
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d
T
Figure 6.5.7 Structural malformation of central nervous system: agenesis Figure 6.5.8 Neurocysticercosis
 
 
of corpus callosum

Table 6.5.4 Classification of seizures

 
Generalized: The epileptic discharge involves both cerebral hemispheres at the same time
•  Generalized tonic clonic seizures (earlier known as grand mal seizures): t starts with a tonic phase characterized by a generalized stiffening of the whole

-
i
body, followed by rhythmic to and fro contractions of extremities. There may be a tongue bit in the tonic phase, with urinary or stool incontinence,
and froting during the clonic phase
•  Tonic seizures: There is sudden but sustained contraction of various muscle groups or the whole body. They may result in a drop attack if the patient is

standing. There are often underlying other neurological abnormalities, and other types of seizures
•  Atonic seizures: There is sudden loss of muscle tone of head and neck, trunk or limbs. Drop attack may result. These are also often associated with

underlying other neurological abnormalities and other types of seizure may occur
•  Clonic seizures: There are rhythmic jerking contractions and relaxation of various muscle groups

•  Myoclonic seizures: Sudden contraction of a muscle or muscle group. They can be single, or occur in clusters. They may be simply myoclonic, or

myoclonic atonic or myoclonic tonic
•  Absence seizures: There is a short period of alteration of consciousness:

  –  Typical absence: Start and end abruptly. There is no fall, and after the brief period of alteration consciousness (few seconds only), the child resumes

activity as if nothing has happened
  –  Atypical absence: Onset is gradual, the patient has alteration of consciousness for a variable duration (may be minutes) and ending is also

gradual. Postural changes can occur and they are often associated with other seizure types and neurological abnormalities and mental
retardation
  –  Absence with special features: Eyelid myoclonus, myoclonic absence

Focal or partial: The epileptic discharge starts in a focus of the brain in one hemisphere (focal or localization related seizures)
•  Without impairment of consciousness/responsiveness
•  Simple partial seizures (SPS)
•  With impairment of consciousness/responsiveness
•  Complex partial seizures (CPS)
•  Secondarily generalized seizures: both SPS and CPS may evolve to generalized seizures (which is a convulsive seizure):
  The seizure may start as a SPS and evolve to CPS. An AURA may often be the SPS before the CPS supervenes
Associated motor movements (repetitive semipurposive movements like fiddling with clothes, rubbing, walking, repeating a word or phrase) called automatisms
 

may occur during the period of impaired consciousness
The terms simple and complex have now been removed as it is often difficult to assess impairment of consciousness especially in children, and they may simply
 

be called focal seizures, and seizures may simply be described as focal seizures or focal motor seizures if there is a focal motor involvement
Focal, generalized or unclear: Epileptic spasms

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 Diseases of Central ervous ystem
Table 6.5.5 Information required for classifying as an epileptic able 6.5.6 Genetic and developmental epilepsy syndromes

 
T
 
syndrome by age of onset (according to International League Against
•  Seizure type (s) (seizure semiology plus electroencephalogram pattern) Epilepsy)
•  Age of onset Neonatal period
•  Developmental status •  Benign familial neonatal seizures
•  Etiology •  Early myoclonic encephalopathy
•  Anatomy •  Early infantile epileptic encephalopathy (Ohtahara syndrome)
•  Precipitating factors Infancy
•  Prognosis (occasionally) •  Migrating partial seizures of infancy
•  West syndrome
•  Myoclonic epilepsy of infancy
•  Benign infantile seizures
epilepsies and unknown whether localization related •  Dravet syndrome

N
or generalized. Typically, to classify an epilepsy into an •  Myoclonic epilepsy in nonprogressive disorders
epileptic syndrome, some information is required (Table Childhood
6.5.5), which may or may not be available. Practically, •  Early onset benign childhood occipital epilepsy (Panayiotopoulos


it is best to use the age-wise approach in classifying the type)
epilepsies (Table 6.5.6). •  Epilepsy with myoclonic astatic seizures

S
•  Benign childhood epilepsy with centrotemporal spikes
•  Late onset childhood occipital epilepsy (Gastaut type)
Differential Diagnosis of eizures and •  Epilepsy with myoclonic absences
S
pilepsies •  Lennox Gastaut syndrome

-
E
•  Epileptic encephalopathy with continuous spike and wave during
he onepileptic vents 
-
-
sleep including Landau Kleffner syndrome
T
N
E
-
•  Childhood absence epilepsy
Nonepileptic events are events, which resemble seizures
Adolescence
but are not the result of abnormal electrical discharges.
•  Juvenile absence epilepsy
They are also known as nonepileptic attack disorder, •  Juvenile myoclonic epilepsy
epilepsy imitators, epilepsy mimickers and pseudoseizures. •  Epilepsy with generalized tonic clonic seizures only
These can also produce recurrent episodes of motor

-
•  Progressive myoclonus epilepsies

movement or apparent changes of consciousness or Relation with age less specific
behavior that are also seen in children with epilepsy. Also •  Autosomal dominant nocturnal frontal lobe
-
disorders that mimic seizures are more likely to occur in •  Familial temporal lobe epilepsies
children who have epilepsy, associated with abnormal EEG •  Autosomal dominant partial epilepsy with auditory features
or to be relieved by antiepileptic drugs (AED) making their •  Generalized epilepsies with febrile seizures plus
diagnosis more difficult. •  Familial focal epilepsy with variable foci
•  Reflex epilepsies
Incidence   –  Idiopathic photosensitive occipital lobe     
 
  –  Visual sensitive epilepsies
Twenty to thirty percent of all patients reporting to epilepsy
 
  –  Primary reading epilepsy
 
clinics are found to have NEE. As many as 30% of patients   –  Startle epilepsy
 
with NEE have real seizures as well. Nonepileptic events and Seizure disorders that are not traditionally given the diagnosis of epilepsy:
epilepsies both present at all ages and in many different •  Benign neonatal seizures
forms. Therefore many conditions can mimic epilepsy at •  Febrile seizures
different stages of a child’s life.

Types
pproach to Differentiation of onepileptic
A
N
Nonepileptic events can be divided into two groups: vents from eizures
E
S
1. Physiological : These are various physiological History and Clinical Examination

NEE
phenomena, which resemble seizures on observation or
History and clinical examination can give clues to the correct
when described by parents.
diagnosis. A description of event, especially an eyewitness
2. Psychogenic : These are seen mostly in children account is very important in obtaining a correct diagnosis.

NEE
more than 5 years of age and are either conversion A review of home videos is often the most important aid to
reactions or malingering. diagnosis. The event should typically be suggestive of some

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 type of seizure. Developmental delay and neurological
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c
deficits are more likely to be associated with true seizures,
but may also be associated with NEEs.
Age-Based Approach
d
Consider the types of seizures in a particular age group, and
if the event does not match the type of seizures occurring in
that age group, one should review the NEE in that age group
(Table 6.5.7). For example, myoclonic jerks during sleep
in a neonate may be confused with myoclonic seizures;
leading to forceful crying. They occur in children 6 months to
2 years of age and disappear by 6 years age. Males are more
commonly affected than females in a ratio of 3:1. Family
history may be present in one-fourth of the cases.
Pathophysiology: The spell is actually a reflex rather than
a behavior problem as was thought earlier. They are of two
types:
1. Cyanotic (more common): There is forceful expiration

during crying, a respiratory pause (breath holding)
daydreaming in a school going child may be confused with resulting in hypoxia and cyanosis.
complex partial seizures. 2. Pallid: Vagal stimulation following a painful stimulus or

Attempts to Observe the Event
T
This is possible if the event occurs at a particular time or is
precipitated by something, e.g. breath holding spells: try to
make the child cry. If psychogenic seizures are suspected,
the event may be induced by suggestions.
Ancillary Testing: Electroencephalogram/Video
Electroencephalogram
Ancillary testing is done when there is doubt about the
diagnosis of NEE despite history and clinical observation of
the patient.
Sometimes true seizures and NEEs may coexist making
differentiation between the two very difficult.
Common onepileptic vents
N
E
Breath Holding Spells
Breath holding spells are stereotypic events that occur in
response to a painful stimulus or an adverse emotional event
during pause in respiration during expiration, results in
cardiac asystole, hypoxia and pallor.
Clinical presentation: The child holds his/her breath
following a sudden painful stimulus and becomes pale
or becomes cyanosed after a prolonged expiration while
crying. He/she then loses consciousness for a brief period,
usually less than a minute. There may be stiffening of
the whole body, followed by a few clonic jerks making
the event appear like a seizure. He/she gradually regains
consciousness with return of normal color, and may remain
drowsy or sleep for sometime. The attack may occur many
times in a day.
anagement: Is as follows:
M
• Counseling regarding the benign nature of the condition
is a must to alleviate anxiety
• Diverting the child’s attention at the onset of crying can
abort an attack

Table 6.5.7 Nonepileptic events at different ages

 
Neonates—2 years Early childhood Late childhood and adolescence
Abnormal movements Abnormal movements Abnormal movements
During sleep During sleep Psychogenic “seizures”
Benign neonatal sleep myoclonus Sleep myoclonus Loss of consciousness/awareness/
Sleep myoclonus When awake tone
When awake Chorea Psychogenic “seizures”
Masturbation Tics Syncope
Jitteriness Paroxysmal choreoathetosis Narcolepsy/cataplexy
clonus Others
Stereotypies Abnormal behavior Fears and phobia
Myoclonic movements During sleep
Spasmus nutans Sleepwalking
Opsoclonus Night terrors
Abnormal breathing Nightmares
phenomena Confusional arousals
Recurrent apneic attacks When awake
Breath holding spells Panic/rage attacks
Delirium
Loss of consciousness/awareness
Daydreaming
Others
Benign paroxysmal vertigo
Migraine
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• Some children have low hemoglobin levels, therefore
iron therapy may help in decreasing the frequency of
attacks
• In case of severe multiple attacks, piracetam in doses of
50 mg/kg/day in three divided doses may be given, and
can significantly decrease the frequency of attacks.
Benign Neonatal Sleep Myoclonus
This is a myoclonus that is sometimes seen in neonates at
age of 1–2 weeks, up to 6 months of age. It comprises of
repetitive jerking or myoclonic movements of the different
body parts, and occurs only during sleep. Awakening the
baby terminates the attacks. The baby remains neurologically
normal. They may be mistaken for seizures and put on AEDs
to which there is no response. EEG and video EEG are normal.
reatment: Treatment is not required. Parents should be
T
counseled about the benign nature of the condition.
Syncope
Syncope is a transient loss of consciousness, resulting
in loss of tone and a fall, from which the patient makes a
spontaneous recovery. Presyncope is the period just before
consciousness is lost. It consists of a lightheaded feeling,
weakness and unsteadiness. It may result in a drop attack.
Twenty percent of children suffer from one or more attacks
of syncope before the age of 15 years, but most of the
syncopal attacks are benign in children.
Syncope can be differentiated from seizures by taking a
detailed history. If there is a doubt, then the tilt table test can
be done, which involves putting the patient in 70° position
after strapping to a table, and checking vital parameters
and symptoms of syncope in that position. Cardiac syncope
should be suspected if the syncope occurs during exercise
or when lying down.
If the child has vasovagal syncope, the child should avoid
situations that precipitate the attack. During an attack, the
clothes should be loosened and the patient should be made
to lie down for some time. No attempt should be made to
give mouth to mouth respiration.
Psychogenic Seizures
Psychogenic seizures are events that resemble seizures and
occur due to emotional or psychological reasons. There
is no accompanying epileptiform discharge in the brain.
They are usually a conversion reaction, but may be a form
of malingering as well. Twenty to thirty percent of children
attending epilepsy units may have psychogenic seizures.
They are seen only after the age of 5 years.
Psychogenic seizures are mainly of two types:
1. Unresponsiveness with no motor activity
2. Unresponsiveness with varying degrees of motor
activity, ranging from just shivering to thrashing around
violently.
Diseases of Central ervous ystem
Table 6.5.8 Features of psychogenic nonepileptic events
•  May be precipitated by an emotional event
•  All episodes may not be similar
•  No history of injury despite fall
•  Memory of events during the episode may be present sometimes
•  Thrashing movements are side to side rather than flexion extension,

and appear to vary with time
•  Waxing and waning of movements
•  Screwing up the eyes when attempts are made to examine then, and

uprolling of eyes on attempts to passively open the eyes
•  When hand is raised up it falls on the side rather than on the face

•  There is usually no frothing, but saliva may trickle out from the

mouth. Voluntary tongue bite may occur
N
•  No urinary incontinence; but may occur occasionally

•  Patient appears to periodically be focused and interact with

surroundings
•  Attack terminates with a particular action, e.g. sprinkling water on the

face holding legs together or rubbing hands
S
•  Duration: Variable but is often prolonged

•  Patient may start crying before, during or after the attack. Sometimes,

tears may just flow.
Both forms may be difficult to differentiate from true
epilepsy, just on the basis of history alone. It is important
to try to observe an episode to discern whether it is a true
seizure or a psychogenic one. A video EEG is required if
any doubt remains about the existence of seizures. Some
clues to psychogenic seizures are given in Table 6.5.8. Once
diagnosed, children should undergo neuropsychological
testing and counseling. Most children/parents would opt
for discontinuing the drugs. A trial of placebo may be
given.
Sometimes true seizures coexist with psychogenic
seizures when it becomes extremely difficult to differentiate
true from psychogenic seizures, leading to either under
­
treatment or overtreatment.
Certain ypes of eizures and
T
S
pileptic yndromes
E
S
cute eizures and tatus pilepticus
A
S
S
E
Most seizures terminate spontaneously without treatment
or after administration of a fast acting anticonvulsant
drug. Status epilepticus (SE) means that seizures continue
for a prolonged period. The International League Against
Epilepsy defines SE as seizures that continue for more than
30 minutes or recurrent seizures for more than 30 minutes
without recovery of consciousness in between the attacks.
• Practical definition: Any patient who is brought with
seizures to the hospital or whose seizures last for more
than 5 minutes is to be treated as SE
• efractory : If seizures fail to respond to appropriate
R
SE
first and second line drug treatment and persist for
more than 60 minutes.
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Table 6.5.10 Diagnostic evaluation of status epilepticus
c
 
Overall incidence is 50 patients per 100,000 population per All cases
year. Status epilepticus in children is most likely in those less •  Blood biochemistry: Glucose and electrolytes, and other metabolic


than 3 years of age. Seventy percent of children less than 1 parameters
d
year with epilepsy may have SE. •  Blood gases assessment
Associated fever
Classification of Status Epilepticus •  Blood counts
•  Cerebral spinal fluid exam
• ccording to seizure type: For example, generalized •  Urine examination
A
tonic clonic, partial, absence •  Necessary cultures
• ccording to the clinical presentation: Studies on case to case basis
A
– Convulsive status: When the seizures have a •  Electroencephalogram
–
predominant motor component, e.g. GTCS, clonic, •  Neuroimaging
tonic, myoclonic, epilepsia partialis continua, •  Drug levels
T
seizures in one half of the body
– Nonconvulsive status: Absence, complex partial SE,
–
continuous spike waves during slow wave sleep.
out a diagnostic evaluation (Table 6.5.10) and treat the
Pathophysiology underlying condition. A suggested management protocol
is shown in Table 6.5.11.
Convulsive SE can be life-threatening and also cause permanent
neuronal damage after 1.5–2 hours of seizure activity due to Follow-Up Advice
excessive glutamate production leading to excessive neuronal
depolarization, rise in intracellular sodium and calcium, cerebral All parents must be taught home management of seizures
edema and finally cell damage and death. Systemic changes with a benzodiazepine (nasal/buccal midazolam, rectal
include hypoxia, hypotension and hyperpyrexia. Metabolic diazepam or sublingual lorazepam). The child should be
derangements like acidosis, hypoglycemia and hyperkalemia put on long-term anticonvulsants if he is found to have EEG
can result in cardiac, respiratory and renal failure. abnormality, abnormal neuroimaging or is far from medical
facility, parents are not educated or confident about home
Etiology management of seizures.
Etiology of status is essentially the same as that of seizures
Prognosis
and epilepsy (Table 6.5.1). However, certain factors can
precipitate seizures and SE in a person with epilepsy • Mortality is 1–2% in developed countries. Improvement
(Table 6.5.9). in prognosis of convulsive SE is due to more effective
and prompt treatment
Management • orbidity: ong-term complications include epilepsy,
M
l
The success of treatment of SE depends on how quickly focal neurological deficit, post-status encephalopathy
the seizure is brought under control. The principles of and mental retardation. Recurrence of SE can occur in
management are well defined, but the protocols vary. What up to 13% cases.
is important is that every medical care facility must have a
very clear protocol or drill in the management of SE. One ebrile eizures
F
S
does not have to wait for 30 minutes to set into motion Definition
the treatment protocol for SE. Goals of management are
to stop the seizure activity as soon as possible and prevent These are seizures, which occur between 3 months to 5
brain damage and systemic complications, and at the years of age, associated with fever but without evidence of
same time to support airway-breathing-circulation, carry intracranial infection or defined cause for the seizure, and
without any history of seizures earlier.

Table 6.5.9 Precipitating factors of seizures/status epilepticus in Epidemiology

chronic neurological disorders
Febrile illness
Inadequate antiepileptic drugs (substandard brands/different
compositions)
Sudden discontinuation of antiepileptic drugs
Sleep deprivation/fatigue/emotional upset
Central nervous system stimulants like theophylline
Two to four percent of all children below the age of 5 years
suffer from febrile seizures (FS). Incidence is equal in both
sexes. Twenty-five to forty percent children with FS have a
family history of FS. Any infection that causes fever can cause
FS. In view of the high incidence of family history, children
with FS are said to have a genetic predisposition to FS.

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Type of Seizures in Febrile Seizures Types of Febrile Seizures

Diseases of Central ervous ystem

Febrile seizures are generalized tonic, clonic or tonic-clonic
seizures, occasionally hypotonic, but never myoclonic. If
focal seizures occur they may be unilateral, and may be
followed by Todd’s paralysis suggesting a focal origin of the
seizures.
Febrile seizures are of two types (Table 6.5.12).
Investigations
• EEG is not required for the diagnosis or management
of FS, whether simple or complex, even when they

Table 6.5.11 Suggested protocol for management of status epilepticus or any patient presenting with acute seizures
 
Time Action
0–5 minutes Observe
Initial observation and management •  Seizure activity; diagnose SE, assess patients condition
Airway

N
•  Suction secretions
•  Administer oxygen
•  Insert nasal airway
Breathing
•  Intubate and provide ventilator support if required (this may done at any time throughout the

management process)

S
Circulation
•  Start intervenous line, draw samples for blood sugar and biochemistry. Glucose may be estimated by a
glucometer.
  Start two lines if possible
•  If hypoglycemic or glycemic status unknown: IV glucose 2 ml/kg—6 months 25% glucose, less than 6

months 10% glucose
Monitoring
•  Vital signs monitoring especially pulse oximetry
5–15 minutes • Continue maintaining airway breathing circulation monitoring
Stabilization, monitoring and ABC • Drug administration
support IV line established: No IV access:
•  Lorazepam 0.1mg/kg (max 5 mg) at 2 mg/min •  Diazepam rectally 0.5 mg/kg
Drug administration OR •  Midazolam intranasal /buccal 0.2–0.4 mg/kg,

•  Midazolam at 2 mg/min 0.1–0.2 mg/kg intramuscular – 0.1–0.2 mg/kg.
Start first line drug: OR •  Lorazepam sublingual 0.1 mg/kg
Any benzodiazepine. •  Diazepam 0.2 mg/kg (max – 10 mg) at 5 mg/min Repeat twice if seizures do not stop in 5 minutes

(Rapid onset of action but short acting ) Dose can be repeated twice if seizures do not stop Followed by
after 5 minutes •  Fosphenytoin IM—20 mg/kg phenytoin

equivalent (PE). Divide in half and give two
separate injections for more rapid action
15–35 minutes No response, seizures recur or initial seizures more than 10 minutes:
Monitoring and ABC support Phenytoin (PHT)
20 mg/kg@ 1 mg/kg min IV infusion (solution only in saline as PHT is incompatible with dextrose or calcium)
Drug administration OR
Fosphenytoin (FOS)
Second line drug 20 mg/kg of PE @ 3 mg/kg/min (150 mg/min)
(solution in dextrose or saline)
Phenytoin/fosphenytoin (1.5 mg of FOS = 1 mg of PHT)
(Slower onset of action but longer acting)
35–60 minutes •  Continue maintaining airway breathing circulation monitoring
(Established SE) •  Repeat phenytoin/fosphenytoin
  5 mg/kg 2 doses to max dose of 30 mg/kg
Monitoring and ABC Support •  Start third agent—phenobarbitone/midazolam infusion
  –  Phenobarbitone 20 mg/kg @ 2 mg/kg/min IV
Shift to ICU     OR
 
  –  Midazolam drip—0.2 mg/kg bolus, followed by infusion of 0.2–2 mg/kg/hour
iv
Drug administration     OR
 
  –  Valproate injection—20 mg/kg bolus over 5 minutes, then maintain at 5 mg/kg/hour for 6 hours
Repeat second line drug in smaller dose •  PLUS 
•  Give mannitol
Start third line drug Mannitol infusion to reduce cerebral edema if there are sign of raised intracranial pressure—
5 mL/kg over 10 minutes in all patients if seizures persist for more than 30 minutes 349
Contd...

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 Contd...
extbook of Pe iatri s
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After 60 minutes (Refractory stage) More than 60 minute
Monitoring and ABC support •  Continue maintaining airway breathing circulation monitoring (Ventilator support is required at this stage)
ICU care •  Continuous EEG monitoring if available
d
EEG monitoring •  Continuous infusion of midazolam in increasing doses till seizure control
OR
Drug administration: Induce coma Pentobarbital: loading dose: 20 mg/kg over 1 hour followed by a maintenance infusion of 0.25–5 mg/kg/hour
OR
Thiopentone: loading dose: 5–10 mg/kg over 2–5 minutes, maintenance 2–10 mg/kg/hour
OR
Propofol: loading dose 1–3 mg/kg, maintenance 2–10 mg/kg/hour
Remember
•  In children most SE is symptomatic, hence investigation thoroughly to find etiology.
T
•  LP should not be done in a convulsing patient.
•  There is no place of oral administration of drugs in acute seizures; where IV access is a problem rectal/buccal/nasal routes should be used.
•  Most children can be managed successfully with BZP/PHT.
•  Fosphenytoin is preferred if cost is not an issue. (Cost of Fosphenytoin is 3 times cost of phenytoin; 10 kg child—cost of phenytoin loading approx Rs

25, cost of Fosphenytoin—Rs 75.)
•  Start the next drug/s only after full loading doses of PHT/PB have been given.
•  Give the full loading dose in one dose as this is more effective, rather than suboptimal doses many times.
•  For hypotension, inotropes may be required.
•  Choice of drug depends on cost and availability, as well as the ICU and monitoring facilities. It is better to give valproate rather than phenobarbitone

and midazolam rather than pentobarbitone if ventilation facility is not available.
•  After seizure control: Discontinue drug infusion at 12 hours. If seizures recur reinstate drug and try weaning off at 12 hourly intervals.
•  Continue maintenance doses of PHT and phenobarbitone 12–24 hours after loading dose administration.
•  End point of treatment: n EEG—no electrographic seizures or burst suppression pattern; if no EEG monitoring is available—clinical seizure control.
o
•  Prognosis depends on how fast the seizures are controlled.
Abbreviations: SE, Status epilepticus; EEG, Electroencephalogram; BZP, Benzodiazepines

Table 6.5.12 Types of febrile seizures • isk of epilepsy: Overall risk of epilepsy following FS
R
is 2–5%. Preventing FS does not decrease the risk of
 
Simple Complex
•  Less than 15 minutes duration •  More than 15 minutes duration epilepsy
• isk of mesial temporal sclerosis ( ): There is


  and   and/or
R
MTS
•  No focal features s/o focal •  Focal features present including a strong association between the development of


origin of seizure Todd’s paralysis refractory temporal lobe epilepsy/MTS and complex
•  Only one attack in one febrile   and/or FS (especially prolonged or focal.) However, it remains

episode of fever •  More than one attack in one unclear whether the prolonged FS is the cause of MTS,

febrile episode or whether a pre-existing MTS predisposes the child to
have prolonged FS.
are recurrent. An abnormal EEG does not change the Mental and Neurological Development
management of FS, and is therefore not recommended
as part of the assessment of a child with FS. Mental and neurological development remains normal if it
• Neuroimaging is not required in simple FS but may be was normal before onset of FS.
done in:
Mortality
– Micro/macrocephaly, neurocutaneous syndrome or
–
pre-existing neurological deficit Mortality is not increased in children with FS as compared
– Persistent postictal neurological deficit after the FS to the normal population.
–
– Recurrent complex FS.
West yndrome
–
S
Management This is an epileptic syndrome with three essential features:
Management of attack of first FS and subsequent long-term 1. Characteristic seizures called infantile spasms: The

management of FS is shown in Flow chart 6.5.1. child has a sudden spasm of the body in which the head,
neck or trunk undergoes a contraction, resulting in
Risks Following FS either flexion (flexor spasms), but sometimes extension
• isk of recurrence: Thirty-five percent of all children (extensor spasms) or flexion of one part and extension
R
will have recurrence after the first FS. Management/ of the other (mixed spasms). The severity of the spasms
350 prevention of recurrences is shown in Figure 6.5.9 can be very mild when parents may notice only a mild

vip.persianss.ir
 Flow chart 6.5.1 Algorithm for management of febrile seizures

Diseases of Central ervous ystem

 
N
S
Source: Reproduced from Indian Journal of Pediatrics Special Supplement on Epilepsy 2007
 
vibration to severe resulting in complete folding over Pathophysiology
the body. They occur in clusters, and each cluster has It is postulated that the hypsarrhythmia and spasms
many jerks. They are maximum on getting up from sleep originate from the brainstem.
or when falling asleep (infantile spasms may be used
synonymously with West syndrome by many people). Investigations
2. Electroencephalogram findings of hypsarrhythmia,
• Electroencephalogram has diagnostic findings in this

which is a high voltage completely chaotic EEG, which
changes every second with spikes from multiple foci. syndrome
3. Developmental regression with onset of seizures. In • euroimaging: MRI is the imaging modality of choice.
N
It may show CNS malformation or evidence of an earlier

many cases developmental delay pre-exists.
CNS insult
Onset is most common around 3–4 months of age, • Biochemical investigations to look for inborn errors of

and they may remit with treatment or spontaneously by metabolism.
around 2 years age, or they may remain uncontrolled and
evolve into other syndromes (Lennox-Gastaut syndrome) Treatment
or seizure types (tonic, atonic, atypical absences or
myoclonic). Following options are available:
• teroids: ACTH or prednisolone
S
Etiology • igabatrin: Especially in infantile spasms due to
V
Almost any CNS insult can result in infantile spasms. tuberous sclerosis or symptomatic infantile spasms
Tuberous sclerosis is often associated with infantile • ther anticonvulsant drugs: Valproate, benzodiaze
O
­
spasms. pines, topiramate or levetiracetam 351

vip.persianss.ir
 • Pyridoxine should be tried early in all children in whom
extbook of Pe iatri s
c
a clear cause for spasms has not been identified
• Epilepsy surgery for focal cortical lesions should be
considered if the child has not shown a response to
three trials of different AEDs.
d
Childhood bsence pilepsy
A
E
This is idiopathic generalized epilepsy with a genetic basis.
Onset is at 4–8 years, girls are more affected than boys.
Seizures
These include typical absence seizures with sudden loss of
consciousness, associated with automatisms in the form of
T
lip smacking, eye blinking and hand picking. The seizure
terminates suddenly as child resumes activity as if nothing
happened. Many attacks occur every day. The attacks can
be precipitated by hyperventilation. Child is neurologically
normal.
Electroencephalogram
Electroencephalogram shows 3 Hz spike wave discharges
on a normal background. Hyperventilation precipitates 3
Hz discharges on EEG and the seizure clinically.
Treatment
Valproate and ethosuximide.
Prognosis
Response to treatment is very good. Seizures remit in most
children by 10–12 years of age. However, many children
may develop infrequent generalized tonic clonic seizures.
anagement of pilepsy
M
E
Drug herapy
T
Decision Making: Should Antiepileptic Drugs Be Started?
The most important consideration in management of
epilepsy is the possibility of recurrence of the seizure. Drug
treatment is considered only when recurrent seizures are
confirmed. The decision should be taken after counseling
the parents, especially after a first seizure.
Generalized tonic clonic seizures: Recur in only
around 40% cases; hence, first episode of generalized tonic
clonic seizure does not require treatment with long-term
AEDs. Exceptions to this rule include; the first episode was a
SE where the patient resides in a place, which is far off from
medical facility or parents are overanxious and unable to
administer home treatment of acute seizures.
Partial, absence, atonic and myoclonic seizures:
Because of high rates of recurrence of seizures, treatment is
indicated in these seizure types.
Choice of Antiepileptic Drugs
Choice of antiepileptic drugs has been described in
detail in Table 6.5.13 for details. The efficacy of the four
352
first line antiepileptic drugs (phenytoin, phenobarbital,
carbamazepine and valproate) in management of common
epileptic disorders including generalized tonic clonic as well
as focal seizures is nearly similar. The decision regarding
specific drug depends upon:
• The type of seizures and epileptic syndrome
• Side effects
• Cost and
• Lifestyle of the patient.
In our set up in view of low cost, ease of administration
and low side effects, phenytoin is the drug of choice.
Monotherapy should be the rule. Polytherapy should be
avoided because of drug interactions, and subsequent
alteration of drug efficacy.
Starting Antiepileptic Drugs
Start an AED in a small dose and build up gradually to an
optimal dose. It is best to calculate a target dose, and start
with one-third of that, and increase by one-third every
week till target dose is reached in case of drugs with short
half-lives like carbamazepine and valproate. Phenytoin
and phenobarbitone may be started with the full optimum
dose at the start. If seizures continue, increase gradually till
maximum tolerated dose is reached or seizure is controlled.
reating a relapse: Restart the same drug in the same
T
dose as was effective in controlling seizures earlier.
Changing Antiepileptic Drugs
Start the second drug in a small dose, and build it up to a
dose effective in controlling seizures. Taper off the second
drug as above.
Principles of Combination Therapy
• Use drugs with different mechanisms of action
• Drugs should have large therapeutic index
• Few side effects
• Keep in mind drug interactions: Combination may cause
increased toxicity or decreased efficacy.
Drug Level Monitoring
Drug levels may be estimated in certain specific situations
(Table 6.5.14), but this is not usually required. Drug
dosage should be decided by clinical control of seizure or
appearance of side effects. Drugs whose levels are useful
include phenytoin, carbamazepine, phenobarbitone and
valproate.
Follow-up
Parents should be instructed to maintain a seizure diary
(Flow chart 6.5.2) containing details of seizure type, duration
and frequency.
Initial follow-up should be:
• After 4 weeks
• If breakthrough seizures occur and
• If side effects occur.
Subsequent follow-up (if seizures are controlled): three
monthly.
vip.persianss.ir
  
Table 6.5.13 Drugs used in treating epilepsy
A. Conventional antiepileptic drugs
Drugs Indications Preparation Dose Side effects toxicity Remarks
Phenytoin Focal seizures Suspension 5–8 mg/kg/day Gum hypertrophy, Younger children require higher
GTCS 30 mg/5 mL Rash doses
-
125 mg/5 mL In two divided doses Steven Johnson syndrome
Toxicity Since it has a long half life, the drug
Tablets 100 mg Ataxia may be started with the target
Nystagmus dose
Blurring of vision
Make sure about which preparation
the patient is using because of wide
variation in the concentration in
different preparation

Avoid phenytoin in children if cost

is not a factor
Phenobarbitone Neonatal seizures Tablets 30 mg 3–5 mg/kg/day Sedation Younger children require higher
Status epilepticus Syrup 30 mg/5 mL Hyperkinetic behavior doses
-
Tonic clonic Single dose or two divided doses Dependence
Focal seizures Since it has a long half life, the drug
Clonic febrile seizures may be started with the target dose

Valproate Broad spectrum, effective against
any seizure type
Idiopathic generalized epilepsies—
Childhood absence epilepsy,
juvenile myoclonic epilepsy,
infantile spasms,
-
Lennox Gastaut syndrome
Carbamazepine Focal seizures
Generalized tonic clonic seizures
Tablets 200, 400 mg 20–40 mg/kg/day Hepatotoxicity Precaution in children less than 1
Syrup 200 mg/5 mL Doses up to 80 mg/kg/day may be Drowsiness year of age
used provided there are no side Lethargy
effects Weight gain,
Hyperammonemia
Three divided doses Teratogenicity
Sustained release preparation: Two
divided doses
Suspension: 100 mg/5 mL 10–30 mg/kg/day Rash Start with low dose
Tablets 200, 400, 600 mg Three divided doses Bone marrow depression
-
Sustained release tablets are also Steven Johnson syndrome Not to be used in absence and
available 200 mg, 500 mg myoclonic, atonic and atypical
absence seizures

The suspension is thick and settles

at the bottom, it needs to be
shaken thoroughly

Contd...

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S N
353
Diseases of Central ervous ystem
 T d c
extbook of Pe iatri s

354
Contd...

Nitrazepam Myoclonic seizures Tab 5 mg, 10 mg 0.5 mg/kg/day two divided doses Drowsiness
Hypotonia
Ataxia
Clonazepam Myoclonic seizures, atonic, tonic, Tabs 0.5 mg, 0.03–0.1 mg/kg/day Drowsiness
-
atypical absence 2 mg two three divided doses Hypotonia
Ataxia
-
Clobazam Add on drug for any seizure type Tabs 5 mg, 0.5 mg/kg/day one two divided Drowsiness
10 mg, 20 mg doses Hypotonia
Intermittent use in Febrile Ataxia less than other
seizures, or seizures due to known benzodiazepines
precipitating causes

B. Newer antiepileptic drugs

Oxcarbazepine Same as carbamazepine
Vigabatrin Monotherapy: Infantile spasms
especially those due to tuberous
sclerosis
Add on: Refractory focal seizures
Lamotrigene Broad spectrum, add on drug.
Multiple seizure types
Monotherapy: Refractory partial
seizures in children more than 12
years of age
Add on focal/generalized epilepsy
West syndrome, Broad spectrum
add on drug for epilepsy with
multiple types of seizures, e.g.
-
Lennox Gastaut syndrome
Tab 150 mg, 300 mg, 600 mg 8–10 mg/kg/day in two divided Fewer side effects like allergies and Drug level monitoring is not
doses bone marrow suppression required
Suspension Target maintenance – 30 mg /kg/
day
Maximum 50 mg/kg/day
Tab 500 mg Start with 40 mg/kg/day Visual field defects Not easily available/manufactured
Target maintenance dose 80–100 Blindness in India.
mg/kg/day
Max 120–150 mg/kg/day Perimetry/fundoscopy regularly to
check for visual complications
Tab 25 mg, 50 mg, 100 mg With valproate start with 0.15 mg/ Rash Use with care with valproate
kg/day Headache
Increase to 0.3 mg/kg/day Drowsiness Level is affected by other
Monotherapy 0.3 mg/kg/day antiepileptic drugs
Increase to 0.6 mg/kg/day
With enzyme inducing drug start
with 0.6 mg/kg/day increase to 1.2
mg/kg/day

Contd...

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 Contd...

Topiramate Monotherapy: Focal or generalized Tab 25 mg, 50 mg, 100 mg, 200 mg Start with 0.5 mg/kg/day Drowsiness Good drug with few drug
epilepsy Increase to 5 mg/kg/day Ataxia, interactions
Metabolic acidosis
Add on Focal/generalized epilepsy Max dose: Hyperammonemia especially with
West syndrome, Broad spectrum 8 mg/kg/day valproate
add on drug for epilepsy with
multiple types of seizures, e.g.
-
Lennox Gastaut syndrome
Levetiracetam Add on for myoclonic seizures Tab 250 mg, 500 mg, Start with 10 mg/kg/day Headache Safe drug for children
Focal seizures 750 mg Anorexia No drug interactions with other
Primary generalized seizures 20 mg/kg/day increase weekly Drowsiness antiepileptic drugs
Increase to 60 mg/kg/day Behavior problems
In two divided doses
Gabapentin Add on for refractory focal epilepsy Tab 100 mg, 300 mg, 400 mg,   Start with 10–15 mg/kg/day Headache Worsens myoclonus and absences
without generalization 600 mg Target dose less than 5 years 40 Anorexia
Neuralgias mg/kg/day Drowsiness
More than 5 years 30 mg/kg/day Behavior problems
Three divided doses

vip.persianss.ir
S N
355
Diseases of Central ervous ystem
 Flow chart 6.5.2 A sample seizure diary
extbook of Pe iatri s

 
c
ame of child Age Sex
N


Month Year
d


ypes of seizure: (in case the child has multiple types of seizures)
T
Type 1 Type 2 Type 3 Type 4



ntiepileptic drugs ( Ds)
A
AE
Name Dose Timing


Date Type of seizure Time of onset Time of control Precipitating factor Routine AED given Any AED given to Remarks
(in case any identified) Yes/No control acute seizure
T
Instructions:
A separate page has to be made every month.
Any skipping of doses/alteration of AED is to be recorded.
In case of multiple types of seizures, each seizure type should be assigned a number, and the number be noted.
Remarks: Anything unusual to be brought to the doctor’s notice.

(This diary should preferably be made in the language used locally)

Table 6.5.14 Indications for drug level monitoring Refer to Pediatric Neurologist

 
Uncontrolled seizures despite adequate doses of the correct antiepileptic • Children less than 2 years
drugs (through levels) • Uncontrolled seizures
Breakthrough seizures • Suspected syndromes
Antiepileptic drugs toxicity (peak levels) • Multiple seizure types.
In polytherapy
Change in antiepileptic drugs dose or regimen
Other systemic disease altering drug metabolism or excretion Counseling
To check compliance
xplain Disease
E
Indications for Hospitalization Parents should be informed about the nature of the disease
• Status epilepticus and chances of recurrence with and without treatment.
• To observe the seizure type Some epilepsies are inherently refractory to treatment, and
• Distinguish between seizure and NEE the poor outcome in such cases should be explained to the
• Serious adverse reactions parents at the outset.
• To check compliance.
ifestyle
Duration of Treatment
L
Patients should be advised to allow the child to continue
Duration of treatment is usually 18–24 months seizure free a normal lifestyle. School teachers should be informed
period. Increasing duration of AEDs therapy beyond 2 years about the nature of disease and should be specifically
does not decrease the risk of relapse. Certain other epilepsies
told not to be biased against these children. Some caution
may warrant earlier stopping, e.g. benign centrotemporal
is advocated in possibly dangerous circumstances like
epilepsy, acute symptomatic epilepsy due to inflammatory
cycling, swimming and activities near fire particularly in the
granulomas.
first year of remission.
Stopping Antiepileptic Drugs
Before tapering, the parents must be counseled about the Drug esistant pilepsy
risk of relapse after tapering.
R
E
• The drug must never be stopped abruptly; it must be Drug resistant epilepsy may be defined as failure of
tapered gradually over 4–12 weeks adequate trials of two tolerated and appropriately chosen
356 • If patient is on multiple drugs, taper one drug at a time, and used AED schedules (whether as monotherapy or in
wait for 1 month and then taper the next drug. combination) to achieve sustained seizure freedom.

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