Early onset West syndrome with cerebral hypomyelination and reduced cerebral white matter

Area of Science:

• Neuroscience
• Developmental Biology
• Pediatric Neurology

Background:

• West syndrome, a form of early infantile epileptic encephalopathy, presents significant diagnostic challenges due to unknown etiologies in many cases.
• Despite extensive investigations, the precise causes of numerous pre-, peri-, and postnatal damages leading to West syndrome remain elusive.
• Understanding the underlying pathophysiology is crucial for timely diagnosis and intervention in affected infants.

Observation:

• Four infants presented with early-onset epileptic encephalopathy characterized by severe hypomyelination and reduced cerebral white matter volume.
• Clinical manifestations included impaired visual attention, acquired microcephaly, spastic tetraplegia, profound psychomotor delay, and infantile spasms.
• Magnetic Resonance Imaging (MRI) revealed striking cerebral hypomyelination, white matter volume reduction, and cortical atrophy, with serial scans showing absent myelination in three patients.

Findings:

• Electroencephalography (EEG) showed suppression-burst patterns in one patient and hypsarrhythmia in the other three.
• Notably, despite intractable seizures, none of the patients exhibited neurological development deterioration.
• The observed constellation of symptoms and MRI findings mimicked, but were ultimately incompatible with, 3-phosphoglycerate dehydrogenase deficiency and PEHO-like syndrome.

Implications:

• The findings suggest a potentially new clinical entity associated with early-onset West syndrome, characterized by severe hypomyelination and specific neurological deficits.
• This identification could lead to improved diagnostic approaches and targeted research for this specific subgroup of infants.
• Further research is warranted to elucidate the genetic or etiological basis of this newly described condition, aiding in better patient management and prognosis.