Transcript PPT - UPIQ

“Improving Care and Collaboration for Children with
Neurologic and Behavioral Conditions”
Webinar #2
Seizures
February 22, 2017
1:00pm -2:00pm
Betsy Ostrander, MD
Assistant Professor Pediatric Neurology
Director of Fetal & Neonatal Neurology
[email protected]
Disclosures
• Funding from: nothing to disclose
• Institutional support from: nothing to disclose
CME Credit
Accreditation: This activity has been planned and implemented
in accordance with the essential areas and policies of the
Accreditation Council for Continuing Medical Education through the
joint providership of Primary Children’s Hospital, the Department of
Pediatrics at the University of Utah School of Medicine, and UPIQ.
Primary Children’s Hospital is accredited by the ACCME to provide
continuing medical education for physicians.
AMA Credit: Primary Children’s Hospital Designates this live
activity for a maximum of 8 AMA PRA Category
• 1 Credit(s)™. Physicians should only claim the credit that
commensurate with the extent of their participation in the
activity.
Disclaimer
Most of the information today is based on clinical
practice of myself and my colleagues, based on
evidence when available, but also gleaning from the
“art” of neurology.
Objectives
• Identify differential diagnosis for fist time seizure
• Describe the characteristics of syncope versus
seizure
• Identify the appropriate neurodiagnostic for
evaluating patient with first time seizure.
• Know when and how to refer a patient to neurology
clinic.
Clinical problem:
“New onset seizure”
• Child presenting to ED or physician with a first (non-febrile)
paroxysmal event (TLOC= temporary loss of consciousness)
• Rarely witnessed by medical personnel
• Typically described by others
• 30,000 to 40,000 children/yr in US
• Although since this refers to “new onset (epileptic) seizures the
rate may be much higher
Most of what we will discuss does not apply to children
presenting with many seizures over a period of time (i.e.,
absence seizures or infantile spasms)
Key questions to address
• Was it a seizure and how do we figure that out?
• Is it going to happen again?
• What are the risk factors for recurrence?
• Does it matter if it was status epilepticus?
• Will my child die from a seizure?
• Should we treat and why?
• What do we treat with?
• When can we stop these toxic substances?
Question 1
• Was it a seizure and how do we figure that out?
• Is it going to happen again?
• What are the risk factors for recurrence?
• Does it matter if it was status epilepticus?
• Will my child die from a seizure?
• Should we treat and why?
• What do we treat with?
• When can we stop these toxic substances?
Was it a seizure?
• Epileptic seizure
• Paroxysmal, synchronous firing of a group of neurons
• Up to 30% or more of first onset paroxysmal events
may be misdiagnosed as epileptic1
1. Perrig and Jallon: Epilepsia 49(Supp 1):2-7, 2008
DDx of spells
• Stereotypies 1. Self-stimulation 2. mannerisms
• Syncope
• Infantile (“Breath-holding spells”)
• older
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GER/Sandifer syndrome
Acute dystonic reactions/drug reactions
Other movement disorders (tics, hemiballismus, myoclonus)
Migraine variants
Night terrors (and other parasomnias)
Hyperexplexia
Vertebrobasilar insufficiency (rare in children)
Cataplexy (Narcolepsy)
“Non-epileptic paroxysmal events” (PC for “pseudoseizures”)
• psychogenic seizures
• malingering
Evaluation of the Paroxysmal event:
How do we figure this out?
• Guess what: the History and PE are key!
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•
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•
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Reliability and veracity of history?
Was this really the first event?!
Elicit detailed circumstances of the event
A neurologist may be better at this1
Tongue biting
• Laboratory studies
• Electrolytes, Ca++, glucose, toxicology -- optional
• EEG -- recommended
• Imaging -- optional
1. Deacon et al., Neurology 61:1686, 2003.
Most common ddx: syncope
• Breath-holding spells
• Pallid infantile syncope
• Cyanotic infantile syncope
• Standard “vasovagal” (neurocardiogenic) syncope
• Hair-grooming syncope
• Earring-changing syncope
• “Convulsive syncope”
• “Anoxic epileptic seizures”
• Same as above but with a long (presumably epileptic) seizure
provoked by brain hypoperfusion
Syncope: the key is in the history!
• Provoking circumstances: pain, stress, emotion, blood-guts-gore, church, hair-grooming,
position of the patient; is patient held upright?
• Prodromal symptoms: subjective sense of:
• Dizzy/light-headed, hot/flushed, visual disturbance (dimming of vision), sense
of impending collapse, +/- nausea, mild GI distress (not ascending), heart
racing, tingling, weak etc..
• LOC
• Brief (seconds to < 1 min), crumples vs. falls like a log
• Brief “seizures” often associated (20-30%) or even more1
• Seconds, various motor components (often tonic only, or fragmentary), +/incontinence, rare tongue biting (tip not side of tongue)
• Rapid recovery
• Within seconds to minutes– can talk and oriented to themselves
• Minimal/modest post-ictal effects
• May be tired but lucid (normal cognitive processing)
1. Lempert et al., Ann Neurol 36:233,1994
Typical opisthotonic
posture seen in the “tonic”
phase of breathholding
spells (infantile syncope).
Said to be more common in
the pallid group.
From: Lombroso et al.
Pediatrics 39(4):563, 1967
Lombroso et al. Pediatrics 39(4):563, 1967. 1.8 yr old boy with typical cyanotic infantile
syncope. (Note: mild bradycardia).
Lombroso et al., Pediatrics 39(4):563, 1967. 2.6 yr old boy with typical pallid infantile
syncope. Note 12 secs of asystole
Lombroso… Pediatrics 39(4):563, 1967. Another child with prior pallid infantile syncope
and relatively long persistence of such spells. Here at 7.2 yoa.
16.6 year old girl with
episodes of losing
consciousness associated
with various brief tonic or
clonic components.
Typical vasovagal spell
induced by venipuncture and
watching the blood come
out!
Ocular compression did not
induce a spell. Venipuncture
while watching produces
typical spell with bradycardia
and unrepsonsiveness.
Lombroso et al. Pediatrics
39(4):563, 1967.
Example of an “Anoxic Epileptic Seizure”:
typical breathholding spell induced by ocular
compression followed by “epileptic”
convulsion.
Each panel ~ 20 sec. Top panel: ocular
compression induces nearly immediate
asystole, then isoelectric EEG.
Middle panel, tonic seizure, followed by
onset of rhythmic clonus
Bottom panel, rhythmic spike-wave
corresponding to rhythmic clonic jerking;
frequency slows as seizure subsides.
Horrocks et al., Arch Dis Child 90:1283, 2005
Acute seizure recorded during routine EEG in a 3 year old with single non-febrile seizure
the week before. Child was sleep deprived. No other epileptiform features were seen
Continuation of the seizure. Note: each gen. S-W discharge corresponds to gen. clonic
movements. Notice how the frequency of these declines as seizure dissipates.
Table: Syncopal vs. Epileptic LOC
Provoking factors
Prodromal symptoms
FHx
Physical findings
Incontinence
Convulsive movements
Duration of LOC
Recovery
Postictal phase
Syncope
Usual: fright, emotion, pain,
site of blood, standing, etc…
Dizziness, lightheaded;
dimming of vision; nausea; GI
discomfort; feeling weak;
impending collapse;
diaphoresis; palpitations
+ for fainting and BHS
Pallor, diaphoresis
Flaccidity
Uncommon
Brief, erratic, myoclonic; brief
tonic; rare T-C (?partic. if held
upright)
< 30 sec
Quick. (< 1 min) Rapid return
of lucidity
Absent or brief/mild
May be tired but mild
Epileptic Seizure
Rare (e.g., stimulus evoked
seizures)
None, or:
Aura: e.g., “rising epigastric
sensation”, brief , ineffable;
fear; vertigo
+/- for epilepsy
Cyanosis, tongue biting
Convulsive seizure
Common
Epileptic cry, tonicclonic
> 30 sec – 2 minutes
Slow (> several min);
disoriented
Usually pronounced: > 15 min,
confusion, disorientation,
exhaustion and sleep
After the History…
• Examination:
• Tongue biting
• Look for findings that suggest “remote symptomatic” etiology
• Evidence based recommendations are:
• Electrolytes, calcium, glucose, toxicology – (Level C) “option”
• EEG – Recommended (Level A)
• Within 24 hours may be better than later
• Sleep deprived EEG if later
• Imaging (Level C)
• Evidence in fact does not support “routine” imaging (see subsq slide)
• MRI is the preferred modality (Level A)
• Not needed in children with definite idiopathic epilepsy (e.g., BRE)
BRE = Benign Rolandic Epilepsy (Epilepsy with Centro-temporal spikes)
Tongue Biting
• 106 prospective, monitored patients with seizures
• 63 had generalized convulsive type events
• 34 of these were epileptic
• 8 had lateral tongue laceration
• 29 had only non-epileptic events
• None had tongue laceration
• 45 retrospective patients with syncope
• 1 had tip of tongue laceration
• Lateral Tongue biting:
• Sensitivity: 24%
• Specificity: 100%
Benbadis et al. Arch Int Med 155:2346, 1995.
EEG
• Recommended– Level A
• Yield may be higher if within 24 hours
• But non-specific abnormalities more common
• Epileptiform EEG increases the risk for recurrence
• From ~40% to 70%
• More on this later
Imaging–
recommendations are ambiguous
• Practice parameter: Evaluating 1st non-feb sz in children, (Neurol 55:616,
2000)
• “There is insufficient evidence to support a recommendation at the level of
standard or guideline for the use of routine neuroimaging”
• If neuroimaging is obtained MRI preferred (Level A or B)
• Reassessment: Neuroimaging in the emerg. patient presenting with a sz
(Neurology 69:1772, 2007)
• “An emergency CT may be considered in children with a first seizure” (Level C)–
i.e, an option
• “An emergency CT should be considered in patients …[with] abnormal
neurological exam., predisposing history or focal seizure onset” (Level B) [this
recommendation not specific to children]
Imaging – General guidelines
• IN ED setting: CT brain if:
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•
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Young sick kid (< 2yoa)
Status
Focal features (Hx/exam)
Acute illness/”not returning to baseline”
• In outpatient setting/patient not “sick”
• MRI is the preferred modality
• MRI may not be needed if clinical history/EEG support
definitive type of idiopathic epilepsy
Question 2
• Was it a seizure and how do we figure that out?
• Is it going to happen again?
• What are the risk factors for recurrence?
• Does it matter if it was status epilepticus?
• Will my child die from a seizure?
• Should we treat and why?
• What do we treat with?
• When can we stop these toxic substances?
Recurrence risk for single unprovoked
seizure (in child)
• data is stronger; remarkable consensus
• Cluster of seizures in < 24hrs often considered
equal to single seizure
• Excellent epidemiological data exists
• multiple countries
• many studies are population based
• Overall risk of recurrence is ~ 40%
From Shinnar et al., Pediatrics 98:216, 1996
Timing of recurrence
• Mean time to recurrence
• Median time to recurrence
11.3 mos
5.7 mos
• Within first month
• Within 6 months
• Within 2 years
21%
53%
88%
Question 3
• Was it a seizure and how do we figure that out?
• Is it going to happen again?
• What are the risk factors for recurrence?
• Does it matter if it was status epilepticus?
• Will my child die from a seizure?
• Should we treat and why?
• What do we treat with?
• When can we stop these toxic substances?
Risk Factors for recurrence
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Family history of epilepsy
Previous febrile seizures
Hx of cognitive impairment/developmental delay
Focal seizure/Todd’s paralysis
Focal abnormality on examination
Etiology (i.e., remote symptomatic vs cryptogenic)
Epileptiform EEG (focal or generalized)
• Most of these increase risk of recurrence to > 50%
Note: status epilepticus is probably not among the independent risk factors
From Shinnar et al., Pediatrics 98:216, 1996
Other less strong risk factors
• Occurrence during the sleep state
• Increased risk if occurs during sleep
• Age of occurrence
• For cryptogenic group:
• Age less than 3: lower risk
• For “remote symptomatic” group
• Age less than 3: higher risk
Status Epilepticus
• Does not influence recurrence risk (independently
of etiology)
• However, of the children presenting with status:
• 21% had recurrences consisting of status
• Compared with 2% of those not presenting with status
Specific comments on EEG
• the EEG provides more than a binary result
• Some abnormalities are “non-specific”
• Focal or posterior slowing
• Specific epileptiform patterns
• when combined with history, age of onset etc…
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Help define epilepsy syndrome
Very helpful in defining recurrence risk
Very helpful in prognosis
Influence decision re: imaging
Example of posterior slow waves, R > L. Such a finding may be “nonspecific” (in this case
child also had epileptiform discharges)
Insert EEG with epileptiform discharge in 1st seizure
9 year old girl with single unprovoked seizure and abnormal first EEG: single, somewhat
subtle, gen S-W in early sleep (the only finding).
From Shinnar et al., Pediatrics 98:216, 1996
Example. 1: Benign Rolandic Epilepsy
(BECTS)
• Sleep-related partial sz with 2e generaliztn
• Shortly after sleep onset or before awakening
• Rare diurnal seizures (usually simple partial)
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•
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•
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Often + FHx
Onset 5-8 years of age
No pre-morbid neurological problems
EEG: uni- or bilateral centro-temporal spikes
Prognosis:
• Very good for seizure control (CBZ, OXC)
• Very good for cognitive outcome
• Excellent for remission (>95%)
Example. 2: Idiopathic generalized
epilepsy (IGE)
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•
•
•
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Gen tonic-clonic seizures +/- absence
Often + FHx
Onset variable (peak 5-10 years)
No pre-morbid neurological problems
EEG: generalized 3/sec spike-wave discharges; less regular gen
S-W discharges in sleep
• Prognosis:
• Very good for seizure control (VPA, LTG)
• Very good for cognitive outcome
• Quite good for remission (~70%)
7 yr old; recent generalized tonic-clonic seizure
Same 7 yr old; generalized discharges in sleep
Example 3: Juvenile Myoclonic
Epilepsy
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•
•
•
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Gen tonic-clonic seizures, myoclonic and absence
Often + FHx
Onset variable (peak >12 years of age)
No pre-morbid neurological problems
EEG: generalized “fast” 4-5/sec spike-wave discharges; less
regular gen S-W discharges in sleep; photosensitivity
• Prognosis:
• Quite good for seizure control (VPA, LTG)
• Very good for cognitive outcome
• Very poor for remission (<10%)
Insert JME EEG here
EEG demonstrating generalized spike and wave discharges occurring at somewhat
irregular but faster frequency (~4-5 cps).
Example 4: Mesial temporal sclerosis
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Classic complex-partial seizures (with temporal lobe semiology)
Sometimes history of prolonged febrile seizure (febrile status)
FHx usually negative
Onset variable
Associated neurobehavioral problems & psychiatric/mood disorders
EEG: focal temporal lobe spikes and polymorphic slow waves; but interictal
EEG may be normal
• Prognosis:
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•
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Poor for seizure control with AEDs (CBZ, OXC)
Marginal for behavioral outcome and quality of life
Very poor for spontaneous remission
Potential to do well with surgical resection (epilepsy surgery)
15 year old girl with new onset typical complex-partial seizures. (MRI nl, but similar
patterns would be seen in MTS)
Question 4
• Was it a seizure and how do we figure that out?
• Is it going to happen again?
• What are the risk factors for recurrence?
• Does it matter if it was status epilepticus?
• Will my child die from a seizure?
• Should we treat and why?
• What do we treat with?
• When can we stop these toxic substances?
Mortality in childhood epilepsy
• Mortality risk depends on associated neurologic
disability (not on seizures as such)
• Overall mortality rate
• 5-8 X that of non-epileptic population
• In otherwise neurologically normal epileptic
children:
• Equal to that of non-epileptic children
• In neurologically seriously affected children
• Rate is > 25 X that of gen population
SUDEP
sudden unexpected death in epilepsy
• Extremely rare in children but~10 % of all epilepsy
related deaths and 50% of deaths in refractory
epilepsy
• Nova Scotia cohort
• 1/692 pts followed for up to 20 yrs
• = 1/9009 person-years
• Dutch cohort
• 0/472 pts followed for at least 5 years
• RF: refractory epilepsy, GTC, poor compliance, multiple
medications
• Mechanism: cardiac arrhythmia, central apnea, cerebral &
autonomic nervous system dysfunction
Question 5
• Was it a seizure and how do we figure that out?
• Is it going to happen again?
• What are the risk factors for recurrence?
• Does it matter if it was status epilepticus?
• Will my child die from a seizure?
• Should we treat and why?
• What do we treat with?
• When can we stop these toxic substances?
Treatment after the 1st non-febrile
seizure?
• Controversial (all the articles say so) but…
• Almost always the answer is: NO
• Nowadays, most families prefer not to anyhow
• Reduces risk for 2nd seizure (abs 30-60%)
• Consider Rx: if parent absolutely terrified and risk
factors suggest higher risk of recurrence
• Consider Rx: if first episode was status epilepticus
(opinion)
Not treating after the first seizure
• Allows better clarification of events
• Allows event frequency to be determined
• Avoids unnecessary side effects of Rx
• Does NOT increase risk of developing epilepsy
• Does NOT change prognosis
• Does NOT increase risk of intractable epilepsy
• Does NOT make future seizures harder to control
• Does NOT (significantly) increase risk of death
Question 6
• Was it a seizure and how do we figure that out?
• Is it going to happen again?
• What are the risk factors for recurrence?
• Does it matter if it was status epilepticus?
• Will my child die from a seizure?
• Should we treat and why?
• What do we treat with?
• When can we stop these toxic substances?
Epilepsy treatment 101:
(assuming we opt to treat; child > 2 yo)
• Distinguish generalized epilepsies from partial epilepsies (Hx
(semiology) and EEG)
• If generalized:
• Valproic acid (VPA), lamotrigine (LTG) or topiramate (TPX)
• LTG for teenagers (partic young women)?
• If focal:
• oxcarbazepine or carbamazepine
• If uncertain (generalized semiology and normal EEG):
• VPA or LTG (particularly in children < 5 yo).
But, what about “new” AEDs
• Acc. to Evid Based Review 2004:
• All AEDs are equal in efficacy
• Other factors become critical:
•
•
•
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“track record” (i.e., experience with use)
Cost
Side effects
Insurance company hassles
New AEDs: general comments
• Cost: favors older agents
• Side effects: favors lamotrigene, levetiracetam and
oxcarbazepine
• Topiramate may be as bad as phenobarbital
• Experience/efficacy:
• Favors VPA, oxcarbazepine (+/- lamictal)
• Insurance coverage: favors older (generic) agents
Table: Serious and less serious adverse events associated with “new” AEDs
AED
Gabapentin (Neurontin)
Serious Adverse Events
None
Lamotrigene (Lamictal)
Rash (including S-J syndrome; inc risk
with concomitant VPA ),
hypersensitivity reactions (hepatic,
renal), DIC, arthritis, lupus-like
None
Levetiracetam (Keppra)
Oxcarbazepine (Trileptal)
Tiagabine (Gabitril)
Topiramate (Topamax)
Zonisamide (Zonegran)
Less-Serious Adverse Events
Weight gain, peripheral edema,
behavioral changes*
Tics*, insomnia (both very infrequent)
Irritability/hyperactivity, behavioral
problems
Hypersensitivity reactions (AHS), rash, Asthenia, sleepiness, dizzyness
hyponatremia
Stupor or spike-wave stupor
Weakness, tiredness, etc…
Nephrolithiasis, acute-glaucoma,
Weight loss, tiredness, mental slowing,
hypohydrosis*, metab acidosis
language dysfunction
Rash, nephrolithiasis, hypohydrosis*
Headache, tiredness, irritability,
photosensitivity, weight loss
*mostly in children. AHS, Anticonvulsant hypersensitivity syndrome. Other common side effects: basically all the AEDs may have
neurotoxic effects particularly at higher doses: tiredness, sleepiness, decreased attention span, decreased energy, dizziness etc. (All
newer brand name AEDs associated with MIs upon receiving pharmacy bill.)
Adapted from French et al. Neurol 62:1252, 2004
Question 7
• Was it a seizure and how do we figure that out?
• Is it going to happen again?
• What are the risk factors for recurrence?
• Does it matter if it was status epilepticus?
• Will my child die from a seizure?
• Should we treat and why?
• What do we treat with?
• When can we stop these toxic substances?
Discontinuation of AEDs
• In general, aim for 2 seizure-free years
• If this is achieved
• And the neurological examination is normal
• And a routine awake/asleep EEG is non-epileptiform
then, risk of recurrence after stopping AEDs is ~30%
Discontinuation of AEDs
• Abrupt discontinuation not optimal
• It does not reduce recurrence risk to extend
discontinuation phase longer than 4-6 weeks
• Hence, usually taper over 4-6 weeks
• Review precautions (swimming, bathing etc..):
• Apply these for at least 6 mos after discontinuation
Summary:
• In evaluating the “new-onset seizure”
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•
•
•
Paramount importance of history
Be aware of syncope as great mimic
Obtain EEG
Hold out for MRI unless clinically warranted to obtain CT
in ED setting
Summary:
• Risk of recurrence overall is 40%
• Risk factors for recurrence are:
• FHx of seizures
• Previous febrile seizures
• Anything that suggests underlying brain disease and
“remote symptomatic etiology”
• Epileptiform EEG
• Seizure during sleep
Summary:
• The risk of death from seizure (alone) is extremely
low
• Treatment with AED is rarely indicated after the
first event
• Drugs of choice (personal preference)
• Generalized  LEV (maybe VPA, LTG)
• Partial  oxcarbazepine
• Discontinue AED after 2 seizure-free years
• If EEG normal and neurological exam normal
Univ Utah/PCMC
Seizure Fast Track Clinic
• When to refer…
• First time seizure
• Do not need EEG nor imaging prior
• Uncertain semiology
• Not necessarily need to be seen by neurology...
• Breath holding spells, syncope
• 801 213 3599
Comments/Questions
Reminder: 3rd Team Lead Call, Tuesday, March 21rd @ 1:00pm