Neonatal and Febrile Seizures

Neonatal and Febrile Seizures
Prepared by Philip J. Holt, M.D. for the:
6th Annual Georgia Epilepsy Symposium November 3, 2001

Conditions with Seizures Outside the Epilepsy Classifications
  • Single Seizure
  • Neonatal Seizures
  • Febrile Seizures
  • Status Epilepticus
Neonatal & Febrile Seizures
  • Common Pediatric Occurrences
  • Medically Controversial
  • Evolution of Understanding
  • Life long Implications
Neonatal Seizures: Definition & Diagnosis
  • Seizures that occur in the 1st month of life
  • Premature Infants up to 44 weeks gestation
  • Incidence 1.5 to 3.5 per 1000 live births
  • Any abnormal, repetitive, and stereotypical behavior is suspect for seizures
  • All, repetitive, and stereotypical behaviors are suspect for non-seizure
Types of Neonatal Seizures
  • Subtle or Fragmentary Seizures
  • Tonic Seizures
  • Multifocal Clonic Seizures
  • Focal Clonic Seizures
  • Myoclonic Seizures
Subtle or Fragmentary Seizures: Motor Automatisms
  • Repetitive facial movements
  • Rhythmic eye movements
  • Sustained eye deviation or fixation of gaze
  • Chewing movements
  • Rowing or Peddling Movements
Tonic Seizures
  • Sustained flexion or extension of Axial or appendicular muscle groups
  • Decerebrate posturing
  • Dystonic posturing
  • Focal tonic head or eye turning
  • Variable response to AED Rx
  • Low correlation to EEG
Multifocal & Focal Clonic Seizures
  • Rhythmic movements of muscle groups
  • Rapid twitch followed by a slow relaxation
  • May involve face, tongue, limbs, diaphragm
  • Focal clonic seizures can be caused by focal or generalized CNS insults
  • Generalized clonic seizures preceded by focal clonic seizures
Myoclonic Seizures
  • Rapid isolated jerks of single extremity, multifocal, or generalized
  • Lacks the slow phase of clonic seizures
  • Need EEG confirmation to exclude segmental release myoclonus
  • Myoclonus is also a symptom of encephalopathy in preterm and term infants
  • Occurs in sleep in healthy infants
Non-Seizure Symptoms that Mimic Seizures
  • Jitteriness
    • Rapid symmetric to-and-fro motion
    • Stopped by holding or changing position of the extremity
    • Tremulousness
    • slow rhythmic movements
    • occur awake and asleep
    • normal and abnormal infants
  • Shuddering or "Quaking"
EEG in Neonatal Seizures
  • Frequently have abnormal backgrounds
  • Seizure discharges have evolution of frequency, voltage & field
  • EEG monitoring show seizures last 10 seconds to >30 minutes and recur on average every 5 to 8 minutes
  • Periodic Lateralized Epileptiform Discharges (PLEDs)
  • Electroclinical disassociation: Clinical seizure activity does not always correspond to the seizure discharges on EEG
Etiology of Neonatal Seizures
  • Hypoxic-ischemic Encephalopathy
  • Structural: Hemorrhage, malformation, tumor
  • Metabolic: glucose, electrolytes, Ca++, AAs
  • Infection: bacterial, TORCH, herpes
  • Drugs: exposure or withdrawal
  • Inheritable Dz: Incontinentia pigmenti, Zellweger’s, Neurocutaneous dz, Pyridoxine Dependency, Five Day Fits
Asphyxia (HIE)
  • Intrauterine, delivery and postnatal causes
  • PO2 < 40 mm Hg & pH < 7.0
  • Low 10, 15, or 20 minute APGAR score
  • Neonatal Encephalopathy
    • Seizures
    • Abnormal arousal: hyper-alert or obtunded
    • Abnormal tone: hypertonia or hypotonia
    • Feeding or respiratory difficulties
Neonatal Stroke
  • Often unremarkable L&D with normal APGARS
  • Routine first 12 to 48+ hours
  • Focal seizures
  • Focal hemorrhage on CT
  • Coagulation defect or Inflammatory reaction is likely cause
  • Hemiparesis, partial seizures and normal IQ
Treatment of Neonatal Seizures
  • Treat the underlying condition (glucose, Ca++, Na+, anti-infectives)
  • Phenobarbital 20 mg/kg loading dose
  • Phenobarbital 10-20 mg/kg repeatedly
  • Phenytoin 20 mg/kg or Fosphenytoin 20mg/kg P.E.
  • Pyridoxine 50 mg
Outcome of Neonatal Seizures
  • Influence by etiology comorbid CNS insult
  • 15% to 40% mortality (higher mortality in series with EEG confirmed seizures)
  • 65% neurologic sequelae in survivors
  • Epilepsy in 15% to 30% by age 7 years
  • Infantile spasms in the first year of life
  • Normal EEG, development, & HC have low risk of seizure recurrence
Febrile Seizures
  • Seizure with fever from 6 months to 5 years of age without CNS infection
  • Neurologically normal children
  • Simple Febrile Seizure: <15 minutes, generalized, occurs once in 24 hours
  • Complex Febrile Seizure:>15 minutes, focal, multiple times in 24 hours
  • Cause: Genetics
Work-up of Febrile Seizures
  • Evaluate source of fever
  • If prolonged or repeated consider short term therapy
  • Educate family
  • Estimate risk of recurrence
  • EEG of no value and should not be done
Risk of Recurrence of Febrile Sz
  • Less than 1 year of age: 50%
  • Greater than 1 year: 20% to 33%
  • Short length of fever before seizure
  • Low grade fever
    • Raises question: Was it really a Febrile Seizure or an unprovoked seizure with a low grade, transient post-ictal temperature elevation?
Treatment of Febrile Seizures Before February 8, 1990
  • Phenobarbital debated after first seizure
  • Phenobarbital usually prescribed after 2nd FS
  • 30% to 50% behavior effect accepted
  • Valproic Acid more effective than PB but not used because of toxicity
  • Studies with phenytoin and carbamazepine showed no ability to prevent FS
Treatment of Febrile Seizures After February 8, 1990
Farwell et. al. Phenobarbital for febrile seizures: Effects on intelligence and seizure recurrence.
NEJM 322:364-9, 1990.
  • Just Do Nothing
  • Anti-pyretics of no value and possible risk
  • Diazepam prn tried with illness
Diazepam for Febrile Seizures
  • Oral diazepam at dose of 0.33 mg/kg q 8 hr during febrile illness
  • Rosman et al. NEJM 329:79-84, 1993.
  • Unknown if oral lorazepam is better
  • Lorazepam v. diazepam v Placebo Status Epilepticus. NEJM 345:631-7,2001.
  • Rectal diazepam approved for seizure clusters, used for recurrent and prolonged febrile seizures.
    Diastat® dose based on age and weight.
Outcome for Febrile Seizures:
  • Nelson: NCPP data : Simple febrile seizures, 2-4% develop epilepsy by age 7
  • Annegars et al. NEJM. 316:493-8, 1987
    • 687 Children with FS followed to age 25
    • Risk of Epilepsy recurrent Simple FS = 2.5%
    • Risk increased with number of Complex FS Criteria: 1=7%, 2=17-22%, 3=49%
Febrile Status Epilepticus
Shinnar, Pelock, Berg et. al. Short-term outcomes of children with febrile status epilepticus. Epilepsia. 42(1): 47-53, 2001.
  • Neurologically abnormal 20% vs 5%
  • Neonatal Seizures 3% vs 0%
  • Family History of Epilepsy 11% vs 5%
  • Lower Family Hx of FS 15% vs 27%
Febrile Seizures and TLE
Maher J. McLachlan RS. Febrile convulsions. Is seizure duration the most important predictor of temporal lobe epilepsy
  • Brain. 118:1521-8, 1995.
  • 6 families with 59 individual with FS, 8 with TLE
  • 1 of 213 family members with TLE
  • No difference in no. Sz, max. Sz/day, age onset
  • Mean Duration individuals with TLE=100 minutes vs. No-TLE=9 m (P<0.02)
Hippocampal Sclerosis Revisited
Fisher PD, Sperber EF, Moshé SL. Brain & Development 20:563-573, 1998. (review)
  • Retrospective Clin/MRI Studies link FS-MTS
  • Prospective Studies do not link FS-MTS
  • Adult animal models with induced HS and SZ
  • Normal developing animal models SZ no HS
  • Abnormal animal models SZ with HS
  • Pre-existing pathology + FS relationship to HS
Febrile Seizures and IQ
  • Farwell, NEJM 1990: Non-PB Rx group was more normal than the PB Rx group.
  • Verity, Greenwood, Golding, Long-Term Intellectual and Behavioral Outcomes of Children with Febrile Convulsions NEJM 338:1723-1728 1998.
    • Population based study to age 10
    • FS no difference than non-FS patients
    • Special Ed: FS <1 yr.=7.5%, >1 yr.=1.5%
Febrile Seizures References:
  • Baumann, Duffner, Treatment of Children with Simple Febrile Seizures Pediatr Neurol 23:11-17, 2000.
  • Knudsen FU. Febrile Seizures: treatment and prognosis. Epilepsia. 41:2-9, 2000.
  • Neurodiagnostic Evaluation of the Child with a First Simple Febrile Seizure, Pediatrics 97:769-75,1996.
  • Practice Parameter: Long Term Treatment of the Child with Simple Febrile Seizures. Pediatrics 103:1307-1309, 1999.
  • Academy of Pediatrics Policy Statements: