Activation of Cerebral X-linked Adrenoleukodystrophy After Head Trauma

Abstract

A 21-year-old man with X-linked adrenoleukodystrophy (X-ALD) suffered a traumatic brain injury after a motor vehicle accident. He had been diagnosed with X-ALD after developing adrenal insufficiency ten years prior, but had no known neurologic involvement. Head magnetic resonance imaging (MRI) at the time of his motor vehicle accident revealed bilateral, frontalpredominant cerebral microbleeds, with no white matter abnormalities (Figure 1). After a 1-month hospital admission, he was transferred to rehabilitation, and during 2 months there, he reattained independence of activities of daily living. Unfortunately, he then suffered an acute neurocognitive decline, with inattention, disorientation, apathy, and impaired memory. Motor, sensory, and coordination testing was otherwise grossly unremarkable. Repeat gadolinium-enhanced MRI of the head showed interval Figure 1: Magnetic resonance imaging of the head at time of head injury. Axial MPGR images (A, B) show bilateral, predominantly frontal scattered hypointensities, consistent with traumatic microbleeds. Axial T2-weighted images (C, D) show no evidence of cerebral X-linked adrenoleukodystrophy, with normal-appearing white matter.

Modeling and rescue of defective blood–brain barrier function of induced brain microvascular endothelial cells from childhood cerebral adrenoleukodystrophy patients

“…MRI observation of gadolinium enhancement in the brain remains the only method to detect this progression [ 17 – 21 ]. Infections or head trauma have been described as initiators of the conversion from AMN to ccALD, but typically no extrinsic factor can be identified [ 22 – 24 ]. Current treatment for ccALD includes hematopoietic cell transplant (HCT), but this must be performed at the earliest stages of the disease [ 12 , 14 , 25 , 26 ].…”

Pathophysiology of X-Linked Adrenoleukodystrophy: Updates on Molecular Mechanisms

“…They also reported that the use of selective agonist of CB2r improved metabolic disturbances by rescuing GSK-3β-NRF2 axis and improved oxidative stress by induction of NRF2 antioxidant pathway [ 53 ]. Trauma or injury to the head triggers or activate symptoms in otherwise asymptomatic or arrested X-ALD patients [ 54 ]. It is possible that head trauma causes inflammatory response and thus followed by mitochondrial dysfunction, oxidative stress, and disruption of the BBB initiating the cerebral inflammatory demyelination and appearance of symptoms [ 55 ].…”