The evolution of neurophysiological features in holoprosencephaly

Area of Science:

• Neuroscience
• Developmental Biology
• Clinical Neurology

Background:

• Semilobar holoprosencephaly is a severe congenital brain malformation.
• Understanding the neurophysiological development in affected infants is crucial for prognosis and management.

Purpose of the Study:

• To describe the longitudinal evolution of electroencephalography (EEG), visual and auditory evoked responses (VERs and AERs), and sleep patterns in three infants with semilobar holoprosencephaly.

Main Methods:

• Case series study involving three infants diagnosed with semilobar holoprosencephaly.
• Longitudinal monitoring of EEG, VERs, AERs, and sleep architecture from the neonatal period.
• Detailed analysis of EEG characteristics, including rhythmic activity, epileptic discharges, and ictal patterns.

Main Results:

• Neonatal EEGs showed prominent rhythmic alpha-theta activity, which evolved into non-specific slow dysrhythmia and later epileptic discharges (spikes, hypsarrhythmia).
• Evoked responses (VERs and AERs) were abnormal and showed progressive decline in amplitude, with VERs eventually abolished in two cases.
• Sleep disturbances were significant, with absent sleep cycles in the neonatal period and lack of circadian rhythm development in two cases, likely due to frequent seizures.

Conclusions:

• Semilobar holoprosencephaly is associated with significant and evolving neurophysiological abnormalities, including progressive EEG deterioration and severe evoked response deficits.
• Sleep development is profoundly affected, with frequent seizures disrupting normal sleep architecture and circadian rhythms.
• These findings underscore the widespread impact of holoprosencephaly on brain development and function.