Title : Longitudinal neuropsychiatric manifestations in vanishing white matter disease: A pediatric case report
Abstract:
Background: Vanishing White Matter disease (VWM) is a rare inherited leukodystrophy characterized by progressive neurological deterioration. While motor and cognitive decline are well described, psychiatric and behavioral manifestations throughout development remain under-recognized and poorly characterized.
Case Presentation: The report is the longitudinal clinical course of a male patient with genetically confirmed Vanishing White Matter disease, followed from early childhood through late adolescence, with a focus on neuropsychiatric manifestations. At seven years of age, the patient initiated follow-up with psychology and pediatric neurology due to attention difficulties and poor academic performance, leading to a diagnosis of attention-deficit/hyperactivity disorder (ADHD). A longstanding pattern of social withdrawal was also reported.
At nine years of age, the patient experienced afebrile seizures, prompting neurological investigation. After recurrent hospitalizations and diagnostic workup, VWM was confirmed through genetic testing between late 2017 and early 2018. Following diagnostic disclosure, the patient exhibited a significant reduction in mood and increased irritability lasting approximately six months, with milder persistence until around twelve years of age. No structured psychological follow-up occurred after diagnosis.
Neurological progression included dysphagia requiring enteral feeding, prolonged hospitalizations for refractory seizures, and loss of independent ambulation by eleven years of age, resulting in wheelchair dependence. Despite severe neurological decline, psychiatric and behavioral symptoms remained relatively stable from early adolescence until approximately sixteen years of age, with preserved affective regulation and positive interpersonal interactions with caregivers and educators.
During late adolescence (ages 16–17), the patient developed sleep–wake cycle disturbance, cognitive and interactional decline, weight loss related to gastroparesis, and worsening seizure control, culminating in prolonged intensive care admission. A vagus nerve stimulation (VNS) device was implanted in December 2025 for seizure management. The patient later developed severe infectious complications and was transitioned to palliative care, passing away in January 2026.
Throughout all developmental stages, the caregiver denied the presence of psychotic symptoms, dissociative phenomena, disinhibition, self-injurious behavior, heteroaggression, or suicidal ideation.
Conclusion: This case highlights a distinct longitudinal trajectory of neuropsychiatric manifestations in VWM, with early psychiatric symptoms preceding neurological diagnosis, transient emotional deterioration following diagnostic disclosure, prolonged psychiatric stability despite progressive neurological impairment, and late cognitive–behavioral decline near end of life. These findings underscore the importance of systematic psychiatric monitoring and integrated neuropsychiatric care in pediatric leukodystrophies.
