Early Childhood Onset Vanishing White Matter Disease with Multiple Cranial Nerve Enhancement: A New Consensus Criteria?

Abstract

Vanishing White Matter Disease (VWM), also known as Childhood Ataxia with Central Nervous System Hypomyelination (CACH), although a rare neurological condition, is a prevalent hereditary leukoencephalopathy with a characteristic phenotype of gradual neurologic deterioration with ataxia being a prominent feature. It is characterized by a wide range of onset, from antenatal and infantile periods to early childhood and later adulthood periods. The early childhood form is considered the prevailing form, characterized by a preceding phase of normal development until the second or 3rd year of life, followed by progressive neurologic deterioration, accentuated by certain stressors, such as infections or minor trauma. Diagnosis is achieved based on the clinical pretext combined with distinctive MRI brain features, confirmed by DNA analysis detection of elf2B mutation. Our case is a healthy 18-month-old male who after a preceding upper respiratory tract infection, developed an ataxic gait, encephalopathy, and recurrent generalized seizures. Physical assessment revealed signs of generalized spasticity and hyperreflexia. Neuroimaging revealed diffuse symmetric supratentorial and infratentorial diffuse white matter hypomyelination. Interestingly, there was notable enhancement of the 3rd and 5th cranial nerves. Differential diagnosis included acute demyelinating leukoencephalopathies; and neuromatobolic disorders with acute presentations (including leukodystrophies, hypomyelinating disorders, and mitochondrial encephalopathies). In the early course of his management, he received immunomodulatory therapy in the form of pulse steroids, intravenous immunoglobulins, and oral tapering course of steroids. He had limited response to these interventions. Whole exome sequencing yielded a homozygous mutation in EIF2B3, confirming the diagnosis of VWMD/CACH. The presence of enhancing cranial neuropathies represent an atypical phenotype reported in other case reports and should alert the physician to avoid unnecessary intervention with immunosuppressive therapies.