Neuromonitoring in Neonatal-Onset Epileptic Encephalopathies

Abstract

Considering the wide spectrum of etiologies of neonatal-onset epileptic encephalopathies (EE) and their unfavorable consequences for neurodevelopmental prognoses, neuromonitoring at-risk neonates is increasingly important. EEG is highly sensitive for early identification of electrographic seizures and abnormal background activity. Amplitude-integrated EEG (aEEG) is recommended as a useful bedside monitoring method but as a complementary tool because of methodical limitations. It is of special significance in monitoring neonates with acute symptomatic as well as structural, metabolic and genetic neonatal-onset EE, being at high risk of electrographic-only and prolonged seizures. EEG/aEEG monitoring is established as an adjunctive tool to confirm perinatal hypoxic-ischemic encephalopathy (HIE). In neonates with HIE undergoing therapeutic hypothermia, burst suppression pattern is associated with good outcomes in about 40% of the patients. The prognostic specificity of EEG/aEEG is lower compared to cMRI. As infants with HIE may develop seizures after cessation of hypothermia, recording for at least 24 h after the last seizure is recommended. Progress in the identification of genetic etiology of neonatal EE constantly increases. However, presently, no specific EEG changes indicative of a genetic variant have been characterized, except for individual variants associated with typical EEG patterns (e.g., KCNQ2, KCNT1). Long-term monitoring studies are necessary to define and classify electro-clinical patterns of neonatal-onset EE.

Keywords: electroencephalopgraphy; genetic epilepsy; metabolic epilepsy; neonatal brain; suppression burst.

Figure 1

Focal epileptic discharges (left central region) in a 12-h-old neonate with perinatal stroke in the MCA territory. Saw-tooth pattern (arrows) of the aEEG (C3, C4) point to repetitive electrographic seizure activity. (Calibration is given in the figure, low-pass 30 Hz, high-pass 0.5 Hz).

Figure 2

(A,B) EEG of a female term newborn with non-ketotic hyperglycinemia presenting apathy and hyperexcitability from day 1. First clinical seizures occurred at day 5. EEG at day 6 (A) and at day 9 (B) showed burst suppression with severe suppression (<4 μV) and intermittent high-voltage burst with diffuse spikes. (C,D) EEG and cMRI findings of a female neonate presenting myoclonic seizures, respiratory insufficiency, muscular hypotonia, hypoglycemia, and elevated CSF lactate and alanine levels. Interictal (C) and ictal EEG showed burst suppression during awake and asleep periods. (D) Brain MRI showed agenesis of corpus callosum and polymicrogyria. Heterozygous X-linked frameshift deletion in PDHα1 gene (skewed-X-chromosome inactivation) was detected. (Calibration is given in the figure, low-pass 30 Hz, high-pass 0.5 Hz).

Figure 3

(A) aEEG findings of normal background activity in relation to maturational age. (B,C) Pathological background suppression classified according to Hellström-Westas (46). (B) PCA 39 weeks (postnatal age of 2 h), continuous extremely low voltage (CLV) tracing. (C) PCA 39 weeks (postnatal age of 5 h) burst suppression. (Calibration is given in the figure, low-pass 30 Hz, high-pass 0.5 Hz).

Figure 4

Focal epileptic discharges with a normal (A,B) and suppressed background (C,D). (A,B) EEG in a 2-day-old term newborn presenting tonic seizures with opisthotonos and apnoea. Ictal EEG (A) showed focal epileptic discharges that were also present during interictal periods (B). A saw-tooth pattern of the aEEG (C3, C4) indicates repetitive subclinical electrographic seizure activity. BFNC caused by a heterozygous KCNQ2 mutation was diagnosed. Neurodevelopmental outcome was normal. (C,D) EEG in a 10-h-old term newborn with moderate perinatal HIE (Sarnat stage II) and therapeutic hypothermia. Multichannel EEG (C,D) shows prolonged focal epileptic discharges and severely suppressed background activity. Suppressed lower amplitudes (<5 μV) and saw-tooth pattern of the aEEG (C3, C4) are shown. (Calibration is given in the figure, low-pass 30 Hz, high-pass 0.5 Hz).

Figure 5

Limits of aEEG monitoring in detection of seizure activity. (A) Low-voltage and brief (<10–30 s) epileptic discharges in a preterm of 28 weeks postconceptual age (PCA) not detected by the time-compressed display. (B) Pseudosuppression of background due to artifacts of high-frequency oscillatory ventilation. (C,D) Physiological paroxysmal transients. (C) Sharp theta on the occipital area of prematures (STOP) in a preterm of 30 weeks PCA. (D) Frontal sharp theta transients and delta brushes in a term newborn. (Calibration is given in the figure, low-pass 30 Hz, high-pass 0.5 Hz).

Figure 6

EEG findings in a female newborn with KCNT1-associated epileptic encephalopathy. The girl presented orofacial myoclonic seizures, bulbus deviation, and apnoeic spells. Interictal (A) and ictal (B,C) EEG at the age of 5 weeks. (A) Diffuse slowing of the background and occipital epileptiform discharges. (B,C) Ictal EEG with diffuse slowing and rhythmic low voltage epileptiform discharges over the centro-temporal and occipital regions with alternating laterality. (Calibration is given in the figure, low-pass 30 Hz, high-pass 0.5 Hz).

Figure 7

EEG findings of a female neonate with seizure onset in the first day of life caused by a de novo duplication of the SCN gene cluster of chromosome 2q24. (A) Suppression burst during asleep and awake periods. (B,C) Ictal pattern was initial suppression followed by focal epileptic discharges and continuously suppressed background. (Calibration 100 μV/cm, low-pass 30 Hz, high-pass 0.5 Hz).

Figure 8

EEG findings of a male neonate with onset of apnoeic spells and focal seizures at the age of 4 weeks. A novel compound heterozygosity for two inherited frameshift mutations in the CACNA1A gene was identified. (A) Interictal EEG shows suppression burst during both awake and asleep states. (B) Ictal EEG pattern was 2–3 Hz monomorphic, high-voltage epileptic discharge activity. (Calibration 100 μV/cm, low-pass 30 Hz, high-pass 0.5 Hz).

Figure 9

EEG in a female newborn with GNAO1 mutation presenting multifocal tonic seizures and apathy from the 2nd week of life. (A) Interictal EEG at the age of 3 weeks with suppression burst. (B) Ictal EEG reveals monomorphic, high-amplitude epileptic discharges over the fronto-central regions and diffuse slowing (Calibration 100 μV/cm, low-pass 30 Hz, high-pass 0.5 Hz).

Figure 10

EEG findings in a female neonate with STXBP1-associated EE at the age of 4 weeks. (A) Interictal EEG showing diffuse slowing, and low-voltage fast activity and occipital spikes. (B) Ictal EEG reveals periodic patterns and suppression burst. (Calibration is given in the figure, low-pass 30 Hz, high-pass 0.5 Hz).