Download Neonatal Seizures

Neonatal Seizures
Priscilla Joe, MD
Children’s Hospital & Research Center at Oakland
Pathophysiology
• Abnormal synchronous depolarization from
large group of neurons
• Excessive excitatory amino acid release
(glutamate)
• Lack of inhibitory systems (GABA)
• Depolarization results from Na influx into
cells; repolarization from outflux of K+
• Disruption of Na/K ATP pump
Basic Mechanisms of Seizures
• Abnormal energy production (hypoxemia,
hypoglycemia)
• Alteration in neuronal membrane
(hypocalcemia, hypomagnesemia)
• Relative excess of excitatory versus
inhibitory neurotransmitters (GABA)
Biochemical Changes with Seizures
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↓ ATP
↓ phosphocreatine
Pyruvate converted to lactate
↓ brain glucose
Increased production of pyruvate from ADP
Incidence
• Higher in neonates than any other age group
• Most frequent in the first 10 days of life
Do Prolonged Seizures Harm the
Developing Brain?
• Animal studies:
– Persistent neonatal seizures in rats induce neuronal
death and changes in hippocampus
• Chronic seizures in adults associated with memory
impairment and poor psychosocial outcome
• Permanent reduction in seizure threshold
associated with significant deficits in learning and
memory
Causes of Neonatal Seizures
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HIE (32%)
Intracranial hemorrhage (17%)
CNS infection (14%)
Infarction (7%)
Metabolic disorders (6%)
Inborn errors (3%)
Unknown (10%)
Drug withdrawal (1%)
Adverse Effects of Seizures
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Cell division and migration
Formation and expression of receptors
Synaptogenesis and apotosis
Long term effects: seizure threshold,
learning, and cognition
Ferriero D. N Engl J Med 2004;351:1985-1995
Subtle Seizures
• More common in premature infants
• Most frequently observed type of seizure
• Clinical manifestations: Bicycling
movements, lip smacking, apnea, and eye
movements or staring, unresponsiveness
• Typically have no electrographic correlate,
are likely primarily subcortical
Clonic Seizures
• Focal or multifocal, rhythmic movements
with slow return movement
• May be associated with generalized or focal
brain abnormality
• Most commonly associated with
electrographic seizures
Tonic Seizures
• Sustained flexion or extension of one
extremity or the whole body
• Extensive neocortical damage with
uninhibited subcortically generated
movements
• May or may not have electrographic
correlate
Myoclonic Seizures
• Rapid, isolated jerks which lacks the slow
return phase of clonic movements
• Typically not associated with electrographic
correlate
• Myoclonic movements may be normal in
preterm or term infants
Nonepileptic movements
• Benign sleep myoclonus
• Tremulousness or jitteriness
• Stimulus evoked myoclonus from metabolic
encephalopathies, CNS malformation
Benign Sleep Myoclonus
• Onset 1st week of life
• Synchronous jerks of upper and lower extremities
during sleep
• No EEG correlate
• Provoked by benzodiazepines
• Ceases upon arousal
• Resolves by 2 months
• Good prognosis
Jitteriness vs. Seizures
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No ocular phenomena
Stimulus sensitive
Tremor
Movements cease with passive flexion
Hypoxic Ischemic Encephalopathy
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Seizures begin within 24-72 hours after birth
Accounts for 50-60% of all neonatal seizures
Most asphyxia occurs before or during birth
Arterial cord pH < 7.0, base deficit < -10
60% develop seizures within 1st 12 hours
Recent stress: hypotonia and unresponsiveness
Longer standing dysfunction: hypertonia with
cortical thumbing, joint contractures or conversely
hypotonia with encephalopathy
Meningitis/ Encephalitis
• Accounts for 5-10% of all neonatal seizures
• TORCH, enterovirus, parvovirus
Usually present by day 3 of life, except for HSV
which may present in 2nd week of life
• GBS, listeria, E coli, strep pneumoniae
Presents at end of 1st week to 3 months of age
Intracranial Hemorrhage
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Accounts for 10% of all seizures
Grade IV IVH/PVH
Subarachnoid/subdural hemorrhage
Cerebral infarction (ischemia, dehydration,
infection, polycythemia)
Cerebral Infarction
• Most frequently involves middle cerebral
artery
• Focal, clonic seizures common
• At risk for spastic hemiparesis
• Venous sinus thrombosis may cause
hemorrhage stroke
• ECMO
Etiologies: CNS malformations
• Lissencephaly, pachygyria, linear sebaceous
nevus syndrome, polymicrogyria
• Present with seizures at a later age
Etiologies: Metabolic
• Hypoglycemia, hypocalcemia, hypomagnesemia,
hyper/hyponatremia
• Inborn errors of metabolism (>72hrs of age):
Aminoacidopathies, urea cycle disorders,
biotinidase deficiency, mitochondrial disorders,
beta oxidation disorders, glucose transporter
deficiency, peroxisomal disorders
Epileptic syndromes-benign
• Benign familial neonatal seizures
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Autosomal dominant
Inter-ictal exam is normal
Long term outcome is good
Unusual tonic-clonic pattern
• Benign idiopathic neonatal seizures
– Term, normal birth
– Normal inter-ictal state, EEG
– Clonic, occur day 5, may be Zn deficiency
Epileptic syndromes-malignant
• Neonatal Myoclonic encephalopathy
– Fragmentary partial seizures, massive
myoclonus
– Metabolic disorders, abnormal EEG
– Poor prognosis
• Ohtahara syndrome
– 10d -3 mo
– Numerous brief Tonic seizures
– Dysgenesis is cause, prognosis very poor
Metabolic Evaluation
• Blood: glucose, lytes, BUN, creatinine,
lactate, pyruvate, ammonia, biotinidase,
quantitative amino acids, very long chain
fatty acids
• Urine: quantitative amino acids
• CSF: cell count, glucose, protein, pyruvate,
lactate, quantitative amino acids, HSV PCR
EEG
• Scalp recordings measure discharges that
spread to the surface
• Discharges from frontal or temporal regions
may not spread to the surface
• More common in the newborn
Clinical Seizures Without EEG
Correlate
• May represent uninhibited brainstem
reflexes
• Discharges from deep cerebral structures
and brainstem may not reach the cortical
surface
Treatment
• More difficult to suppress than in older
children
• Treatment is worthwhile because seizures:
– May cause hemodynamic or respiratory
compromise
– Disrupt cerebral autoregulation
– May result in cerebral energy failure and
further injury
Treatment
• Stabilize vital signs and treat underlying
hypotension
• Correct transient metabolic disturbances
• Phenobarbital is first line agent
• Lorazepam
• Phenytoin
Prognosis based on etiology
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Hypoxia-ischemia
Meningitis
Hypoglycemia
Early Hypocalcemia
• Subarachnoid hemorrhage
• Late Hypocalcemia
50% normal outcome
Almost all are normal
Prognosis based on etiology
• Cerebral dysgenesis has grave prognosis,
almost none are normal
• Prematurity and seizures associated with
high risk of death or very poor outcome
Prognosis based on type
• Subtle
• Clonic
• Generalized Tonic
• Myoclonic
Depends on cause,
other seizure types
Better prognosis
Poor
Poor
Prognosis by EEG
• Severe inter-ictal EEG background
associated with adverse outcome
• Normal EEG background at presentation
associated with good outcome
• Ictal features less reliable
– Better outcome when clinical and EEG seizures
correlate
– Increased number and frequency may relate to
worse outcome
Conclusions
• Neonatal seizures are often subtle
• Close examination and characterization
important for prognosis and evaluation
• Treatment usually successful in stopping
seizures, but risk of neuro-developmental
abnormalities remains high
• Prevention of causes remains a priority