Chapter 39: Neonatal Seizures

I. Intensive and convalescent care

1. Definition

   1. A clinical seizure is defined as a paroxysmal alteration of neurologic function (behavioral, motor and/or autonomic).

   2. An electrographic seizure is defined as a repetitive discharge that evolves in time and space. In practical terms, it is a seizure detected only by electroencephalogram (EEG) without clinical correlate.

   3. An electroclinical seizure is an event with concomitant clinical and electrographic seizures.

2. Incidence

   1. The incidence of seizures in the term neonate ranges between 1 and 3/1000 live births.

   2. Higher incidence is observed among neonates with low gestational age and low birthweight—up to 57.5/1000 for infants <1500 g and 20.4/1000 for infants <28 weeks.

   3. The neonatal period has the highest incidence of seizures across the life span.

3. Pathophysiology

   1. The immature brain is highly excitable.

      1. The balance between excitation and inhibition favors excitation.

      2. The neurotransmitter receptors are developmentally regulated with lower expression of inhibitory receptors (some γ-aminobutyric-acid or GABA receptors) and higher expression of excitatory receptors (glutamate receptors) compared to adulthood.

      3. GABA_A receptor activation in the immature brain can cause depolarization instead of hyperpolarization because the chloride gradient is reversed in the immature brain.

      4. Developmental regulation of ion channels and neuropeptides may also contribute to neuroexcitation.

   2. The neonatal brain is a unique environment that likely explains, at least in part, the refractoriness to common antiepileptic medications.

   3. Etiology

      See Table 39-1.

   4. Etiology based on seizure onset

      1. First 6 hours after birth

         • NKH, sulfite oxidase/molybdenum cofactor deficiency, B6/PLP dependent seizures, cortical dysplasia, trauma, local anesthetic toxicity

      2. After first 6 hours

         • HIE, cortical dysplasias, vascular, trauma, infectious, metabolic, toxic

4. Risk factors

   1. Family history of neonatal seizures

      1. Benign familial neonatal seizures (BFN): KCNQ1, KCNQ2, KCNQ3 (Note: Some mutations can be associated with a malignant course, and not benign as previously thought.)

      2. Sodium channelopathies: SCN1A, SCN2A

      3. Metabolic disorders

   2. Problems with pregnancy

      1. Fever and/or rash during pregnancy

         • Congenital infection (SCRATCHES: syphilis, CMV, rubella, AIDS, toxoplasmosis, chicken pox, HSV, enterovirus)

         • Chorioamnionitis

      2. History of vaginal bleeding

         • Abruption, previa

      3. Hiccups/increased fetal movement

         • NKH (nonketotic hyperglycinemia), B6/PLP (vitamin B₆/pyridoxal-5-phosphate) dependent seizures, cortical dysplasia

      4. Substance abuse

         • Cocaine

      5. HELLP syndrome

         • Fatty acid oxidation disorders

   3. Problems with delivery

      1. Fetal heart rate abnormalities, prolapsed cord, placenta abruption, previa

         • Hypoxic-ischemic encephalopathy (HIE)

      2. No maternal pain relieve, pupillary abnormalities, cardiac arrhythmia

         • Local anesthetic toxicity

      3. Precipitous delivery, vacuum, breech

         • Subdural, subarachnoid and intraparenchymal hemorrhages, stroke

      4. No vitamin K administration at birth

         • Hemorrhagic disease of the newborn

      5. Maternal fever and abnormal amniotic fluid

         • Chorioamnionitis

      6. Premature delivery/extremely low birthweight infants

         • Higher risk of intraventricular hemorrhage (IVH), sepsis, and meningitis

5. Clinical presentation

   1. Clinical assessment of a suspected seizure (paroxysmal alteration of neurologic function) should include

      1. Mental status: Most seizures course with altered mental status.

      2. Spontaneous character of the event: Seizures are characteristically unprovoked and should not respond to restrain, change in position or stimulation.

      3. Vital signs: Most seizures occur with tachycardia.

   2. Clinical seizures types

      1. Subtle seizures

         • Paroxysmal alterations in neonatal behavior and motor or autonomic function (tachycardia, blood pressure elevation, apnea, cutaneous vasomotor phenomena, pupillary change, salivation, or drooling) that are not clearly tonic, clonic, or myoclonic.

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