Imaging in X-Linked Adrenoleukodystrophy

Abstract

Magnetic resonance imaging (MRI) is the gold standard for the detection of cerebral lesions in X-linked adrenoleukodystrophy (ALD). ALD is one of the most common peroxisomal disorders and is characterized by a defect in degradation of very long chain fatty acids (VLCFA), resulting in accumulation of VLCFA in plasma and tissues. The clinical spectrum of ALD is wide and includes adrenocortical insufficiency, a slowly progressive myelopathy in adulthood, and cerebral demyelination in a subset of male patients. Cerebral demyelination (cerebral ALD) can be treated with hematopoietic cell transplantation (HCT) but only in an early (pre- or early symptomatic) stage and therefore active MRI surveillance is recommended for male patients, both pediatric and adult. Although structural MRI of the brain can detect the presence and extent of cerebral lesions, it does not predict if and when cerebral demyelination will occur. There is a great need for imaging techniques that predict onset of cerebral ALD before lesions appear. Also, imaging markers for severity of myelopathy as surrogate outcome measure in clinical trials would facilitate drug development. New quantitative MRI techniques are promising in that respect. This review focuses on structural and quantitative imaging techniques—including magnetic resonance spectroscopy, diffusion tensor imaging, MR perfusion imaging, magnetization transfer (MT) imaging, neurite orientation dispersion and density imaging (NODDI), and myelin water fraction imaging—used in ALD and their role in clinical practice and research opportunities for the future.

ABCD1 Gene Mutations: Mechanisms and Management of Adrenomyeloneuropathy

“…68 Lesions may also be seen along the corticospinal, visual, and/or auditory tracts. 69,70 As MRI of the brain enables early detection of cerebral ALD, the progression of which may be prevented with hematopoietic stem cell transplantation, 13,68 it is recommended that brain MRI be repeated every 6 months until the age of 12 and annually thereafter in those with X-ALD. 4,71 Spinal cord imaging is not currently used routinely in the monitoring of persons with X-ALD.…”

“…4,71 Spinal cord imaging is not currently used routinely in the monitoring of persons with X-ALD. 68 However, imaging of the spinal cord may be performed to rule out other potential causes of their neurological signs and symptoms, such as multiple sclerosis or cord compression. The finding of spinal cord atrophy, while also present in other neurodegenerative disorders, is a common finding in X-ALD patients, in whom the reduction in spinal cord cross-sectional area is most pronounced at the thoracic levels.…”

Reversible Dementia With Bilateral White Matter Changes Caused by Dural Arteriovenous Fistula

“…Genetic diseases, such as X-linked adrenoleukodystrophy and mitochondrial disorders could be the cause. Van de Stadt et al 9 suggest X-linked adrenoleukodystrophy should be considered in males if confluent white matter changes were observed. Patients with mitochondrial disease can present with cognitive dysfunction, and those with mitochondrial neurogastrointestinal encephalopathy and mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) can present with diffuse white matter changes on MRI 10 .…”

Microstructural Changes in Normal-Appearing White Matter in Pediatric X-Linked Adrenoleukodystrophy: A Diffusion Tensor Imaging Study

“…8 9 Magnetic resonance imaging (MRI) is recommended for all X-ALD patients for early detection of brain involvement, as it has been shown to detect cerebral lesions before the onset of clinical symptoms. 10 11 12…”

“…8,9 Magnetic resonance imaging (MRI) is recommended for all X-ALD patients for early detection of brain involvement, as it has been shown to detect cerebral lesions before the onset of clinical symptoms. [10][11][12] Diffusion tensor imaging (DTI) is an advanced MRI technique that provides quantitative diffusion data of water molecules in tissue. DTI detects both the magnitude and directionality of diffusion restriction and gives data about tissue microstructure.…”