NEUROSCIENCE

1.3b Seizures and the Epilepsies in Infants, Children, and Adolescents

Mel Michael G. Villaluz, MD|| August 25, 2021

OUTLINE
I. Status Epilepticus IV. Anti-Seizure Medication
II. Sudden Death in Epilepsy V. SE Management Goals
III. Approach to Seizure
a. Evaluation after 1st
seizure
b. EEG
c. Neuroimaging
procedure
d. Major issues in Epilepsy
management
e. Management of
Epilepsy
LEGEND Figure 2. SE Pathophysiology (see appendix for bigger picture)
Remember Lecturer Book Previous Presentation Why do we need to time this event? because majority is mediated by
Trans mechanisms. For example, for the first 10 min there is usually an
     inhibition failure of GABA responsive post synaptic potential that is why
there is continuing abnormal propagation of electrical cavity. But beyond
LECTURE OBJECTIVES 60 min/1hr, the excessive excitation shows pure unresponsiveness to
your GABA inhibitory pathway, these are usually manifesting by the
• Discuss the definition of seizures vs. epilepsy
pathophysiology underlying the prolonged seizures. Usually after 1 hr,
• What is the pathophysiology of seizures?
you will already have a homeostatic failure, or you will go into a
• Classification of Seizure types (Video Presentation) decompensation.
• Classification of Epilepsies Depending on these stages, you can actually time the status
• Discuss special conditions – febrile seizures, neonatal seizures epilepticus according to clinical stages upon their presentation, such as
• Discuss Status Epilepticus Acute Seizures for the first 5 min. Between 5 min to 30 min that’s Early
• Management of Seizures, Epilepsy and Status Epilepticus or Impending SE. If your patient is still unresponsive between 30min –
1hr you call that Established SE. For beyond 1hr, you call that
I. STATUS EPILEPTICUS Refractory SE or Drug-resistant SE.
• Seizures so frequent or so prolonged as to create a fixed and lasting
condition. (Mortality: 20- 30%)
• one of the most common neurological emergencies
• A continuous, generalized tonic-clonic seizure lasting more than 30
minutes or absence of lucid intervals in between seizures
• Most seizures last for 3 to 5 minutes and occasionally up to 10
minutes. If seizure persists more than 10 minutes, therapeutic
intervention must be initiated
• The classical definition of established SE requires that seizures
(continuous or intermittent without return to baseline mental status)
last for a minimum of 30 minutes.

Pathophysiology
• A condition resulting either from the failure of the mechanisms
responsible for seizure termination or from the initiation of
mechanisms, which lead to abnormally, prolonged seizures (after
time point, t1). meaning pumalpak yung inhibitory pathways niya
• It is a condition, which can have long-term consequences (after time
point t2), including neuronal death, neuronal injury, and alteration of
neuronal networks, depending on the type and duration of seizures.
Figure 3. SE Pathophysiology (see appendix for bigger picture)
This is a graphical representation on what happens in the first stages
of your SE. First, the compensating phase on the first 30mins. After
30mins there is rapid decompensation in the body.
 For example, in the first 30 min you can see elevated BP, increased
lactate, and increased glucose supply in the brain. After 30 min there is
rapid decrease causing hypotension, hypoglycemia, and showing
respiratory compromise and hypothermia which can contribute to death.

Classification

Figure 1. SE Pathophysiology
Depending on the seizure type, t1 is different depending on the
seizure type. For tonic clonic seizures the first where you initiate
treatment is at 5 min, then you have to control the seizures by 30mins
and that is your t2. In contrast to be a focal status with impairment of
awareness the time limit is moved to 10 min and the seizure should be
stopped within 60mins after initiation of treatment. Absence status Figure 4. SE Classification
epilepticus has a rate between 10 to 15 min, you have to remember that There is another way to look at SE. Either it can be Nonconvulsive
absence status epilepticus occurs for few seconds only, and there is no or Convulsive SE.
time limit, no t2 assignment for absence status epilepticus.

TRANS Polloso, Tobias, Toscano TRANSHEAD Torres 1 OF 3

1.3b Seizures and Epilepsies in Infants, Children, and Adolescents LONG EXAM 1

Nonconvulsive SE is usually presenting with behavioral ▪ Seizure triggers

manifestations such as clouding of awareness, unresponsiveness and ▪ Home videos (helpful)
even… (hindi na clear yung audio sa part na ‘to).
 The Convulsive SE is the most common that you will encounter in Physical Examination
your clinical practice, meaning this is a tonic-clonic seizure of continuous • Anthropometrics
activity. → Head Circumference
• Physical findings
Stages → Facial features
→ Skin lesions
→ Ophthalmologic exam
• Neurologic exam
→ Focal deficits
→ Muscle tone
→ Sensory testing
→ Limb asymmetry

B. Electroencephalography
• Should be performed in all cases of a first unprovoked nonfebrile
seizure to help predict the risk of seizure recurrence
→ A normal EEG does not exclude epilepsy
→ Not all abnormal EEGs mean epilepsy

C. Neuroimaging Procedure
• Indications:
→ Focal seizures
→ Postictal focal deficits
→ Patient's status is not returning to baseline
→ Trauma preceding the seizure
→ Patients with a high-risk medical history
Figure 5. SE Stages • CT Scan vs. MRI
In the emergency room you divide it according to stages. → CT scan
Early phases – first 10min, here you start initiating treatment. ▪ Trauma (bleed)
Established SE – 10 – 30min ▪ Mass
 Refractory SE – if patient goes between 30 - 60min ▪ Increased ICP
Super-refractory SE – still seizing >24hrs despite treatment → MRI with contrast
▪ Preferred imaging (nonemergency)
SIXTH LECTURE OBJECTIVE
Discuss Status Epilepticus D. Major Issues in Epilepsy Management

II. SUDDEN DEATH IN EPILEPSY

• Most common epilepsy-related cause of mortality
• ~17% of deaths in patients with epilepsy

Proposed Mechanisms
• Cardiogenic Model
→ Seizure induced cardiac arrhythmia
→ Cardiocerebral channelopathies
→ Mutations in SCN1A, SNC8A, ATP1A3, and KCNQ1
→ more common in genetic epilepsy
Figure 6. Issues in Epilepsy Management
• Mixed respiratory/cardiogenic models
Major issues in epilepsy management are that you always want to
→ Seizure-induced dysautonomia seizure after 30mins achieve seizure control to improve quality of life. Usually we have to
→ High adenosine during seizure → cardiorespiratory collapse → balance the seizure control depending on what treatment modality you
depression in the brainstem → dysautonomia → finally death want based on the etiology, comorbidities, emotional factors,
socioeconomic factors, current anti-seizure medication regimen
Risk Factors recommended, and the ability to deal with complex instructions or
• Polytherapy with more than three ASMs situations is important.
• Male gender
• Young age at epilepsy onset E. Management of Epilepsy
• Developmental delay • WHEN TO INITIATE ANTI-SEIZURE MEDICATION?
• Poor AED compliance → Diagnosis of epilepsy has been established.
• Nocturnal seizures → After 1st unprovoked seizure
• Poorly controlled tonic-clonic seizures (especially if > 3 per year)
• High frequency of seizures (especially if > 50 per year) Generalized
• Having epilepsy for > 30 year in adults • EEG with GSW discharges
• Family History
III. Approach to SE → Sibling with epilepsy
A. Evaluation after 1st Seizure Focal
• Particular abnormalities on brain MRI
History • Abnormal neurological examination
• Seizure type • Nocturnal seizure
→ Onset • Todd’s phenomenon (presence or absence of paralysis) after the
▪ Level of awareness seizure

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• IV. Anti-Seizure Medication Mechanism of Action

Figure 7. Choosing the Right Anti-seizure Medication


Figure 11. MoA of Different ASM (see appendix for bigger picture)
You have to know where the MOA of different medications. Majority
is affecting the presynaptic neuron. For example, levetiracetam acts on
a protein. Others act on voltage-gated sodium channel thereby inhibiting
the release of excitatory neurotransmitters. Some acts on inhibitory
synapse or excitatory synapse.

Figure 8. Anti-seizure Medication (see appendix for bigger picture)

Only 33 is available in the country. 1st generation phenobarbital. 2nd
generation valproic acid and carbamazepine.

Figure 9. Summary of Evidence and Recommendations Epilepsy

Treatment Guidelines (ILAE, 2013) Figure 12. MoA, Principle Indication, and Major Limitations of Different
Example how to treat seizures in children. Based on the seizure type. ASM (see appendix for bigger picture)
 Focal seizures – Oxcarbazepine and carbamazepine. Oxcarbazepine Summary for MOA for each ASM. Important to know there are only
is better tolerated than carbamazepine. They are usually several ASM that have multiple mechanism of action, one of these is
interchangeable. valproic acid and topiramate.
 Generalized tonic-clonic seizure – Most DOC is carbamazepine or When we say adjunctive use, it means it cannot stand alone meaning
valproic acid. there should be a prior drug before utilizing these medications.
 Absence seizures – First DOC is valproic acid
Advantages and Disadvantages
Table 1. Ad and Disadvantages of ASM
Anti-seizure
Advantages Disadvantages
Medication
• Drug interaction
• Hypersensitivity
Carbamazepine • Unsurpassed
reactions
High risk for efficacy for focal
sedation
adverse events seizures
• Do not use for
GGE
• Works in focal
• Hyponatremia
seizures
• Does not work in
Oxcarbazepine • Possibly better
Figure 10. Recommendations for ASM in Primary Care GGE
tolerated in
Primary for primary caregiver depending on the seizure type • Drug interaction
children than

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CBZ → Identification and management of associated systemic

(Carbamazepine) complications.
• Less efficacious • The initial therapy for SE includes maintenance of adequate brain
than CBZ for oxygenation and cardiorespiratory function, identification and
focal seizure correction of seizure triggers such as hypoglycemia, electrolyte
• High imbalance, lowered drug levels, infection, and fever, and prevention
teratogenicity of systemic complications
Valproic Acid
among AEDs,
Usually DOC for • Unsurpassed
drug interaction Treatment
generalized onset efficacy in IGE
tonic-clonic seizures • Works in focal
Usually not • 1st line ASM for Status Epilepticus
and absence epilepsy
use for women → Benzodiazepines
>20yo or child ▪ Benzodiazepines are typically used as initial treatment for
seizure
bearing potential SE because of their wide availability, initial efficacy, and
because of high multiple routes of administration.
risk ▪ GABAa receptor agonist
teratogenicity. ▪ Increased chloride conductance and neuronal
• Liver failure hyperpolarization
• Low risk of drug • Psychiatric side ▪ Diazepam
interaction effects − Initial Dose
Levetiracetam • Low risk of • Only add-on use o 0.15 – 0.3mg / kg IV up to 10mg / dose, may repeat in 5
hypersensitivity in myoclonic minutes
reactions seizures − Administration Rates and Alternative Dosing
• Mood stabilizer Recommendations
• Drug interaction
• Works in focal o Up to 5 mg/min (IVP)
• Hypersensitivity
Lamotrigine seizures and o Peds: 2–5 years, 0.5 mg/kg (PR); 6–11 years, 0.3 mg/kg
reactions (PR); greater than 12 years, 0.2 mg/kg (PR)
absence
• Slow titration − Adverse Events
seizures
• Less well o Hypotension
tolerated than o Respiratory Depression
CBZ for focal − Considerations
• Works in focal seizures o Rapid redistribution (short duration)
seizures and in • Drug interaction o Active metabolite
Phenobarbital o IV contains propylene glycol
myoclonic • Hypersensitivity
seizures reactions ▪ Midazolam
• Sedation − Initial Dose
• Do not use for o 0.2 mg/kg IM/IV up to maximum of 10 mg
absence seizures − Administration Rates and Alternative Dosing
Recommendations
Gradual Discontinuance of ASM Criteria o Peds: 10 mg IM (>40 kg)
o 5 mg IM (13–40 kg)
• Seizure - free 2 to 5 years on ASM/s (mean 3-5 years)
o 0.2 mg/kg (intranasal)
• Single type of focal seizure or single type of generalized seizures
o 0.5 mg/kg (buccal)
• Normal neurologic examination / normal I.Q.
− Adverse Events
• Normal neuroimaging o Respiratory depression
• EEG normalized with treatment o Hypotension
− Considerations
Summary of Management o Active metabolite
o Renal elimination
o Rapid redistribution (short duration)
▪ Lorazepam* not available in PH
− Initial Dose
o 0.1 mg/kg IV up to 4 mg per dose, may repeat in 5–10
min
− Administration Rates and Alternative Dosing
Recommendations
o Up to 2 mg/min (IVP)
− Adverse Events
o Hypotension
o Respiratory depression
− Considerations
Management is based on seizure type determination. First DOC for o Dilute 1:1 with saline IV
focal seizure is carbamazepine. First DOC for generalized is valproic o Contains propylene glycol
acid. • 2nd line ASM Options used when unresponsive to 1st line drugs
→ Phenobarbital
• V. Status Epilepticus Management Goals ▪ Initial Dose
− 15-20 mg/kg IV, may give an additional 5–10 mg/kg
Management ▪ Adverse Events
• STOP the SEIZURE − Hypotension
→ Prompt administration of appropriately selected antiseizure − Respiratory depression
medications → Phenytoin sodium channel blocker
• WHAT is the CAUSE ▪ Initial Dose
→ Identification and management of any seizure precipitant(s) o 20 mg/kg IV, may give an additional 5–10 mg/kg
▪ Adverse Events
• MINIMIZE COMPLICATIONS
− Arrhythmias

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− Hypotension 5. First DOC for absence seizure

− Purple glove syndrome a. Valproic acid
→ Valproate Sodium has multiple MOA, making this an b. Carbamazepine
excellent 2nd line for SE c. Levetiracetam
▪ Initial Dose d. Phenobarbital
− 20–40 mg/kg IV, may give an additional 20 mg/kg
▪ Adverse Events
− Hyperammonemia Answers: a, b, d, c, a
− Pancreatitis
− Thrombocytopenia IX. REFERENCES
→ Levetiracetam • Doc Villaluz lecture video
▪ Initial Dose
• Menkes, J. H., Sarnat, H. B., & Maria, B. L. (2006). Child
− 1,000–3,000 mg IV
− Peds: 20–60 mg/kg IV (40-60mg/kg/day) **
Neurology (7th ed.). Lippincott Williams & Wilkins.
▪ Adverse Events • Swaiman, K. F. (2018). Swaiman's Pediatric Neurology:
− None Principles and Practice (6th ed.). Elsevier.

The first-line drug is usually a benzodiazepine (most frequently

lorazepam). Sometimes it might be useful to try a second dose of
benzodiazepines. However, when seizures last 10 minutes or longer the
recommended treatment is fosphenytoin and for seizures of more than
15 to 30 minutes duration a second nonbenzodiazepine antiepileptic
drug should be administered. The most commonly used is phenobarbital
although other options include valproate or levetiracetam. When
seizures last more than 30 to 60 minutes and the patient has not
responded to prior medications SE can be considered refractory and
switch to continuous infusions of antiepileptic drugs or anesthetic
therapies is advised

SEVENTH OBJECTIVES
Management of Seizures, Epilepsy and Status Epilepticus

VIII. REVIEW QUESTIONS / QUIZ

1. the time beyond which the seizure should be considered as
“continuous seizure activity
a. t1
b. t2
c. t3
d. t4
2. the time beyond which there is a risk of long-term
consequences.
a. t1
b. t2
c. t3
d. t4
3. The following events happen after 30min of SE except:
a. Hypotension
b. Hyperthermia
c. Hypoglycemia
d. Alkalosis
4. First line treatment for SE
a. Phenytoin
b. Midazolam
c. Benzodiazepine
d. Phenobarbital

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APPENDIX

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