Transcript Pediatric Epilepsy: An Overview and Update on Treatment Options Mitzi Payne, MD Pediatric Neurology Marshall University.

Pediatric Epilepsy: An
Overview and Update on
Treatment Options
Mitzi Payne, MD
Pediatric Neurology
Marshall University
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Approach to a patient with “spells”
Paroxysmal events
Obtain thorough history:
– Before event
– Description of event
– After the event
Do descriptions vary event to event?
Are the events epileptic?
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If the “spells” appear to be
epileptic…
What type of epileptic seizures?
What is the cause of the seizure?
Is there a syndrome associated with the
seizure type?
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“Fits, faints, and funny turns”1
• Differential Diagnosis of “spells”
Syncope
Migraine
Sleep disorders
Pseudoseizures (nonepileptic seizures)
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Helpful tools for diagnosis
Accurate history and description of events
Ask family member to “act out” event
Ask family to videotape event
Provoking factors
Electroencephalogram
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Some important points
Classification(s)
– seizure type an ictal event believed to represent a
unique pathophysiological mechanism and anatomic
substrate
– epilepsy syndrome a complex of signs and symptoms
that define a unique epilepsy condition
Etiological categories of syndromes
– idiopathic no underlying structural brain disease,
presumed genetic
– symptomatic seizures are the result of lesional or
metabolic disease of the brain
– probably symptomatic (cryptogenic) believed
symptomatic but no etiology established
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Seizures: focal vs. generalized
Generalized seizure
– a seizure whose initial semiology indicates, or is
consistent with, more than minimal involvement of
both hemispheres
Focal seizure (partial, localization-related)
– a seizure whose initial semiology indicates, or is
consistent with, initial activation of only part of one
cerebral hemisphere
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Generalized seizure types
Myoclonic
Sudden, <100 ms involuntary contraction of muscle(s)
or muscle groups
Clonic
Repetitive, rhythmic myoclonus at 2-3 Hz
Tonic
Sustained muscle contraction for seconds to minutes
Generalized
tonic-clonic
Bilateral symmetrical tonic contraction, then bilateral
clonic contractions
Atonic
Sudden, brief, 1–2 s decrease in tone without
preceding myoclonic or tonic event
Astatic
Loss of posture (=drop) due to atonic, myoclonic, or
tonic event
Spasm
Axial contraction, may be asymmetric
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Generalized epilepsies
Idiopathic
generalized
epilepsies
Benign myoclonic epilepsy in infancy
Epilepsy with myoclonic-astatic seizures
Epilepsy with myoclonic absence seizures
Childhood absence epilepsy
IGE with variable phenotypes
Juvenile absence, JME, epilepsy with GTC only
Generalized epilepsies with febrile seizures plus
Epileptic
encephalopathies
Syndromes of infancy
Early myoclonic encephalopathy; Ohtahara,
Dravet, West syndromes
Lennox-Gastaut syndrome
Landau-Kleffner syndrome
Epilepsy with continuous spike waves in SW sleep
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Focal seizure types
Focal
sensory
Focal
motor
with elementary sensory symptoms
with experiential sensory symptoms
with elementary clonic motor signs
with symmetric tonic motor signs
with automatisms
Secondarily generalized seizures
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EEG Activating Procedures:
Hyperventilation
Deep and regular respirations at a rate of
20 / minute for 2 to 4 minutes
Drop in plasma CO2 by 4-7 ml%
Normal response (and best seen in
children) is high amplitude slow activity
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EEG Activating Procedures:
Hyperventilation
Hyperventilation may induce diffuse sharp
waves or spike-wave complexes
Patients with generalized epilepsies are most
likely to have these findings
Actual seizures can be induced by
hyperventilation
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–
–
–
Absence (petit mal)
Absence (petit mal)
Absence (petit mal)
Temporal lobe seizures
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EEG Activating Procedures:
Intermittent Photic Stimulation
Strobe light flashes (1-30 Hz)
Photic driving
Rhythmic activity over the posterior head regions
Photomyoclonic response
Repetitive muscle spikes over the anterior regions of the
head
Photoconvulsive (-paroxysmal) response
Generalized spike and wave complexes
15-20 Hz
May have jerking or impairment of consciousness
Photosensitive epilepsies
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EEG Activating Procedures
Somatosensory stimulation
Electrical stimulation of peripheral nerves
Epileptiform discharges in contralateral
hemisphere
Reenactment of a trigger
Visual stimulation of geometric patterns
Auditory stimulation
Reading
Hypoglycemia
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Common Childhood Epilepsy
Syndromes
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Infantile spasms
West syndrome
Onset ages 3-12 months
Brief axial contractions
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–
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–
usually bilateral, may be asymmetrical
typically flexor, may be extensor
usually in clusters, less likely random
typically on awakening, or when drowsy
EEG shows hypsarrhythmia
– multifocal spikes
– high voltage, chaotic background
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Flexor spasm
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Infantile spasms
• “Symptomatic” cases
– congenital infections
– CNS malformations
– metabolic disorders
– genetic syndromes
– tuberous sclerosis
– perinatal asphyxia
– postnatal trauma
– acquired infections
– immunizations
Often “cryptogenic”
• no definite cause
established but child is
delayed
Rarely “idiopathic”
• no cause established and
child is normal
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Infantile spasms
Short term treatment to stop spasms, improve
EEG
– ACTH effective, dose not established
oral steroids not proven effective
– Vigabatrin, especially in tuberous sclerosis
not available in US,
potential retinal toxicity
Data insufficient to show early treatment or
any treatment changes long term outcome
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West Syndrome
Infantile Spasms
Hypsarrhythmia on EEG
Developmental regression that begins
concurrently with the onset of spasms
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Prognosis of West Syndrome2
Series of 150 patients with West
Syndrome between 1954 and 1970
– Idiopathic (n = 44)
– Symptomatic (n = 106)
Outcomes measured by school type or
residence (home or hospital)
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Outcome
Idiopathic cases:
– Normal school 37%
– Death 6%
– Other seizure types 43%
– Neurologic abnormality 31%
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Outcome
Symptomatic cases:
– Normal school - none
– Death 37%
– Other seizure types 59%
– Neurological abnormality 65%
– Large number progress to develop Lennox
Gastaut Syndrome
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Rolandic epilepsy
Onset ages 2-12 yrs, peak 5-10 yrs
Characteristic seizures
Infrequent simple partial seizures
– tingling in mouth, on face, speech arrest
– rare GTCS in sleep
Resolve by puberty
Characteristic EEG
– high voltage centrotemporal spikes
– usually bilateral
Imaging normal
Considered an idiopathic focal epilepsy
– some evidence for genetic basis
Treatment
– may not be necessary
– may respond to many drugs
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Centrotemporal spikes in Benign
Rolandic Epilepsy
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Presentation of “staring spells”
• Complex partial seizures
• Absence seizures
• Behavior staring
Complex Partial Seizures
• Commonly temporal lobe focus
• Begins in one area, then spreads enough
to impair consciousness, but not to evoke
a generalized tonic-clonic seizure
• Staring is often part of the initial spread
• Also can see automatisms…
Automatisms
•
•
•
•
Coordinated involuntary movements
Consciousness impaired
Patient does not recall activity
Simple
– Lip smacking, chewing, uttering sounds,
picking, tapping, walking straight or in circles
• Complex (behavior involved)
– Undressing, chewing inedible objects,
wandering, aggression
Complex Partial Seizure
Complex Partial Seizure
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Complex Partial Seizure
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Treatment of complex partial
seizures
• Use medications for focal onset seizures
– Levetiracetam (Keppra)
– Oxcarbamazepine (Trileptal)
– Carbamazepine (Tegretol/ Carbatrol)
– Lamotrigine (Lamictal)
– Topiramate (Topamax)
– Zonisimide (Zonegran)
– Phenobarbital
– Valproic Acid (Depakote)
– Lacosamide (Vimpat)
Absence epilepsy
Childhood absence
(petit mal) epilepsy
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•
•
•
Peak onset age 4-6 years
Many seizures daily
Seizures last seconds
70+% have associated automatisms
– eyelid flutter
– simple vocalizations
– picking movements
• Typical EEG with 3 Hz spike wave
• Majority resolve by adolescence
slightly irregular
3 per second spike wave ▼
Absence Seizure
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Absence Seizure
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Absence Seizure
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Pathophysiology of Absence
Seizures
• Generalized discharges occur from
abnormal oscillatory rhythm in
thalamocortical circuits
• High density of T-type calcium channels in
thalamus, thought to be involved
Treating absence seizures
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•
•
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Ethosuximide (Zarontin)
Valproic Acid (Depakote)
Lamotrigine (Lamictal)
Levetiracetam (Keppra)
Absence v. Complex Partial Sz
• Absence
• < 30 sec
• Non-convulsive status
epilepticus
• Frequent (100’s a day)
• Sudden onset, sudden
termination
• No post-ictal state
• Hyperventilation a trigger
• EEG: 3-4 Hz spike and
wave
• Rare interictal
abnormalities
Complex Partial
• > 1 minute
• Rare non-convulsive
epilepticus
• Occur ≤ daily
• Frequent simple, complex
automatisms
• Evolve to other sz
manifestations
• Post-ictal state
• EEG: Interictal focal
abnormalities
Behavioral Staring
• Most commonly seen in children with
ADD, PDD, MR
• Occurs when “bored” or over-stimulated
• Does not typically make the patient fall or
stop an activity abruptly
• Can be stopped with close contact /
stimulation
• Also can be seen in children with epilepsy!
Evaluation of a
1st unprovoked seizure
Good evidence recommends EEG
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Generalized burst
EEG can help diagnose the event
EEG can identify a specific syndrome
EEG can help with prognosis
timing of EEG not determined
immediate EEG may show abnormality or post
ictal slowing
Benign focal spike
– abnormal EEG best predictor of recurrence in
neurologically normal children
– abnormal neuro exam also strong predictor of
recurrence
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Evaluation of a
1st unprovoked seizure
• Insufficient evidence for routine labs, LP, imaging
– consider emergent imaging
if postictal focal deficit, or not at baseline in several hours
– consider nonurgent MRI
with significant neuro abnormalities of unknown etiology
a seizure of focal onset
in children under 1 year of age
– consider LP
in the very young child (<6 months)
in the patient who fails to return to baseline
in any patient with meningeal signs
if increased ICP suspected, image before LP
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How likely is
a 2nd seizure?
Evidence from multiple Class III studies
Recurrence ranged from 14%-65%
Most recurrences early (in 1st year)
Factors increasing recurrence risk
– abnormal EEG
– etiology
remote symptomatic seizure recurrence >50%
idiopathic seizure recurrence 30-50%
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Summary of evidence:
Treatment of 1st unprovoked seizure
Most children with a 1st seizure have few or no
recurrences
10% will have many seizures regardless of initial Rx
Rx after 1st vs. 2nd seizure does not affect long term
prognosis
Rx in adults and children leads to decreased recurrences
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Recommendations:
Treatment of a 1st Seizure
Anticonvulsant treatment after a 1st seizure must be
individualized
– treatment is not indicated for prevention of epilepsy
– treatment may be considered if risks of recurrent seizure out
weigh risks of Rx
Treatment must take into account patient and family
preferences
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Febrile seizures
The most common seizures in childhood
In US affect 2-4% of children < age 5 yrs
8% Japan, 14% Guam
1/3 have at least 1 recurrence
Risk factors for recurrence
first febrile seizure < 1 year of age
low degree of fever at first febrile seizure
family history of febrile seizures
brief duration between fever onset and febrile seizure
4 risk factors = 70% recurrence
No risk factors = 20% recurrence
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Febrile seizures
Simple
– generalized
– and <15 minutes duration
Complex
– focal
– or >15 minutes
– or recurrent within 24 hours
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Evaluation of the child
with simple febrile seizures
Lumbar puncture
– if meningeal signs
– in infants < 12 months
– with prior antibiotic Rx
Blood studies not needed routinely
Imaging not necessary
EEG not necessary in simple febrile seizures
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Treatment of the child
with simple febrile seizures
Effective in reducing recurrences but
with potential toxicities
– continuous phenobarbital or valproic acid
– intermittent diazepam
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Treatment options for
pharmacoresistant epilepsy
Ketogenic diet
Vagus nerve stimulation
Surgery
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Ketogenic diet
Very high fat, very low CHO,
minimum RDA protein
Vitamins, mineral supplements
necessary
Rigid compliance essential
Effective in 1/3-1/2 cases
breakfast
– all seizure types
– all ages, but easiest to maintain in
children
lunch
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Ketogenic diet formulations
Formulated in fat:CHO ratios
– generally between 4:1 and 3:1
– Atkins diet is about 2.2:1
Traditional diet
– uses 40% cream, fatty foods
MCT diet
– adds oils to “normal foods”
Tube feeding diet
– CHO-free formula + microlipids or
cooking oil
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Surgical treatment of epilepsy
Lobectomy
– anterior temporal lobectomy most frequent procedure
– 70% of selected patients become seizure-free
Extratemporal resection
– nature and extent of pathology determine results
Hemispherectomy, multilobar resections
– done in cases with extensive pathology
Corpus callosotomy
– rarely performed as sole procedure
Multiple subpial transections
– Palliative, done when focus is in “eloquent cortex”
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Epilepsy surgery evaluation
(for example)
Record seizures
MRI, MRA, SPECT, PET
Speech and memory tests
VideoEEG
– Wada test
– neuropsych testing
– fMRI
Electrocorticography,
intracranial monitoring
Brain mapping
SPECT
Intracranial
grid
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Vagus nerve stimulation (VNS)
FDA approved 1997
– adjunctive treatment
pharmacoresistant partialonset epilepsy
– ages 12 and older
Over 25,000 implanted
– 5,000 in children <12
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Vagus nerve stimulation
Mild electrical
pulses sent to
L vagus
Automatic,
intermittent stimulation
On-demand stimulation with
magnet
In-office programming
Compliance assured
Programming
Magnet activation
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VNS pulse generator and lead
>25,000 patients worldwide
Model 102 (June 2002)
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single pin lead
6.9 mm thick
weight 25 grams
6-11 year battery life
Outpatient implantation
– 1 hour surgery
– device test in OR, activated
later
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Seizure-response dogs
How do they do it?
Trained by several
organizations
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Diastat
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Rectal diazepam
- Given for seizures lasting longer than 5 minutes
- Diastat is a safe way to give rescue seizure medication in
the home or school environment
- Dose varies by age and weight
- If seizure continues 5 minutes after Diastat given, then
EMS should be contacted
- Some children have seizures that consistently are
prolonged; in the case Diastat may be prescribed to be
given at onset of seizure, instead of waiting 5 minutes.
- Not FDA approved in children less than 2 years of age
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Other Rescue Medication Options
- Nasal midazolam - children refractory to Diastat
- Oral lorazepam - seizure clusters
- Routine seizure medications are NOT given as rescue
medications
- If a child routinely requires rescue medications on a
consistent basis, then routine scheduled seizure
medications need to be changed
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Thank you!
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