Dravet Syndrome: Diagnosis History Seizure Evolution

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Dravet Syndrome Diagnosis History Seizure
Evolution
Linda Laux, MD Pediatric Epileptologist Lurie
Childrens Epilepsy Center Northwestern
University Feinberg School of Medicine
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DISCLOSURES

• Salary support from Dravet Syndrome Foundation
  for Predictive Factors for Long-TermCognitive
  Outcome in Dravet Syndrome

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Dravet Syndrome (DS)

• Epilepsy syndrome with intractable seizures and
  cognitive/motor/behavior concerns that is highly
  associated with a sodium channel receptor
  mutation
• Clinical diagnosis of DS
• Seizure onset lt 12 months of age
• Prior to seizure onset unremarkable PMHx, normal
  development, normal neuroimaging
• Seizures
• Pleomorphic seizure types
• Generalized (GTC, myoclonic, atypical absence)
• Focal (alternating unilateral hemiconvulsions,
  other)
• Developmental issues (slowing/plateau/regression)
• Co-morbidity Ataxia/gait abnormalities,
  behavioral issues

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Historical Overview

• Charlotte Dravet recognized the clinical
  constellation of this epilepsy syndrome Dravet,
  Vie Medicale 1978
• Studying children with Lennox-Gastaut syndrome
• Group of children were different
• Initial normal development, history
• Seizure onset in the first year of life, often as
  febrile convulsions
• Primarily clonic and myoclonic seizures
• Seizures treatment resistant
• Cognitive, behavior problems
• No brain lesions
• New syndrome Severe Myoclonic Epilepsy of
  Infancy (SMEI)
• Publications
• 1978 Les epilepsies graves de lenfant
• 1982 Advances in Epileptology the XIIIth
  Epilepsy International Symposium

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Historical Overview

• Severe Myoclonic Epilepsy in Infancy Variants
• Severe Myoclonic Epilepsy Borderline (borderland)
  SMEB
• Intractable Childhood Epilepsy with GTC seizures
  ICE-GTC
• Identification of high association with SCN1A
  mutation
• Identification of SCN1A mutation with epilepsy
  (GEFS) Escayg, Nat Genet. 2000
• Association of SCN1A mutation with Dravet
  syndrome Claes, Am J Hum Genetic 2001
• Seven patients with de novo SCN1A mutations (no
  mutations in 184 control chromosomes
• SMEI not the best name
• Children not severe in infancy
• Not all the children have myoclonic seizures.
• Dravet syndrome
• Dravet Syndrome Spectrum

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Dravet Syndrome The First Seizure

• Seizure onset
• Less than one year of age mean 6 month
• Seizure semiology (description)
• Convulsive seizure (clonic gtgt tonic clonic)
• Generalized, unilateral (hemiconvulsions)
• Less likely complex partial, myoclonic
• May be prolonged (status epilepticus)
• Seizure Trigger fever, vaccinations
• Normal development, examination
• Normal MRI and EEG
• Typical initial diagnosis (Complex) febrile
  seizures
• No medication begun (/- Diastat)

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Dravet Syndrome The First Year

• Seizures
• Semiology
• Convulsive seizure (clonic gtgt tonic clonic)
• Generalized
• Alternating unilateral clonic seizures
  (hemiconvulsions)
• Less frequent complex partial, myoclonic
• Duration prolonged
• Frequency Not frequent
• Triggers fever (low), vaccinations,
  hyperthermia, abrupt change in temperature
• Normal development (majority)

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Dravet Syndrome Childhood

• Very active seizure phase
• Seizures more varied
• Seizure frequency markedly increases
• Multiple medication/treatment trials
• Seizures initially still prolonged
• Less prolonged seizures (status epilepticus) over
  time
• With active seizure phase, developmental,
  cognitive, motor, behavioral concerns develop
  (1-5 years)
• EEG becomes abnormal
• Background slowing
• Generalized and multifocal interictal
  spikes/sharps

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Interictal EEG
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Dravet Syndrome Varied Seizure Types

• Convulsive and focal seizures
• Convulsive (clonic gtgt tonic clonic)
• Generalized, unilateral
• May have preserved consciousness with unilateral
• Focal seizures
• From any brain region
• Atypical convulsive seizures with both
  generalized and focal components
• Any variation stiffness (body turning), clonic
  jerks
• Asymmetric, asynchronous, focal
• EEG with generalized and focal features during
  the seizures
• In some literature falsely generalized,
  unstable seizures
• Triggers Fever, vaccinations, hyperthermia,
  abrupt change in temperature, excitement

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Dravet Syndrome
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Dravet Syndrome
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Dravet Syndrome
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DS Varied Seizure Types

• Nonconvulsive Seizures
• Atypical absence
• 5-20 seconds (but may be prolonged)
• Often with myoclonic jerks (head nods, eye
  blinks)
• Myoclonic seizures
• Quick muscle jerks
• Whole body, head drops, extremities
• Eyelid flutters /- EEG correlate
• Obtundation State
• Prolonged nonconvulsive seizure (atypical
  absence, myoclonic)
• Triggers photic stimulation, visual patterns,
  concentration, fine motor skills, tired,
  excitement

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Eyelid flutter
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Myoclonic seizure
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Myoclonic Seizure
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Myoclonic seizure
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Atypical absence seizure
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Dravet Syndrome Adolescent, Adults

• Stabilize
• Less frequent (although seizure control can
  worsen pre-teens/teenagers)
• Decreased incidence of prolonged seizures
• However, limited literature
• Adults
• Brief nocturnal convulsions most common seizure
  type Jansen, Neurology 2006, Akiyama, Epilepsia
  2010
• Refractory to medications/treatment
• Adults 16 seizure free gt 1 year (5/31 patients)
  Akiyama, Epilepsia 2010
• Adults 8 seizure free gt 1 year (5/64 patients)
  Tayayama, Epilepsia, 2014

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General characteristics seizures in Dravet
syndrome

• 1. Mixed seizure types
• Both generalized and focal seizures
• Generalized convulsions, myoclonic atypical
  absence
• Focal hemiconvulsions, other
• Seizures with both generalized and focal features
• Treatment
• Broad spectrum medication useful for generalized
  and focal seizures
• Although a child may have many different seizure
  types, may have a specific seizure type of
  concern to focus treatment.

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General characteristics seizures in Dravet
syndrome 2. Seizures are treatment resistant
Seizure Control Fewest seizures possible No
status epilepticus
Medications Limited adverse side effects
Maximize Cognitive Potential Maximize Quality of
Life
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General characteristics seizures in Dravet
Syndrome

• 3. Seizures prolonged especially when young
• Need specific acute seizure plan
• Convulsive versus nonconvulsive status
  epilepticus
• May be different for seizure clusters
• Acute seizure Plan
• Home
• Paramedics
• Emergency room
• Revisions to plan over time

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General characteristics seizures in Dravet
syndrome

• 4. Specific seizure triggers (avoidance)
• Vaccinations
• Do not recommend avoiding
• Fever
• Antipyretics, benzodiazepines
• Hyperthermia
• Use of cooling vest
• Abrupt change in temperature
• Excitement
• Visual Photic stimuli, visual patterns
• Sunglasses (Zeiss Z1F133)
• Unilateral eye patching

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Vaccinations in Dravet Syndrome

• De-Novo mutations of the sodium channel gene
  SCN1A in alleged vaccine encephalopathy a
  retrospective study Berkovic , Lancet 2006
• 14 patients with alleged vaccine encephalopathy
• SMEI 8/8 patients SCN1A mutations
• SMEB 3/4 patients SCN1A mutations
• Lennox-Gastaut 0/2 patients SCN1A mutations
• Effect of vaccination on onset and outcome of
  Dravet syndrome a retrospective study McIntosh,
  Lancet Neurology, 2010
• 40 patients with DS Vaccine proximate (n12),
  vaccine distant (n28)
• No difference in intellectual outcome, subsequent
  seizure type, or SCN1A mutation
• Early seizure onset in vaccine proximate group
  (7.8 weeks)

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Overview History, Diagnosis, Seizure Evolution
in Dravet Syndrome

• Friday
• Morning SCN1A mutation, genetics
• Afternoon Treatment
• Saturday
• Track 1 Research
• Clinical, SUDEP, Basic Science
• Track 2 Family Program
• Sunday Co-morbidities
• Cognitive, behavior, gait, sleep

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WELCOME!!
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Lurie Childrens Epilepsy Center