Head trauma can initiate the onset of adreno-leukodystrophy
Abstract
X-linked adreno-leukodystrophy and its adult variant, adrenomyeloneuropathy, are caused by mutations in ABCD1 that encodes a peroxisomal membrane protein of unknown physiological significance. In spite of identical mutations, they can have markedly divergent neurological and neuropathologic characteristics. Adreno-leukodystrophy classically presents in normal boys with mild neuropsychiatric features, which progress to frank neurological signs, the vegetative state and death in approximately three years. Adrenomyeloneuropathy typically affects young men with spastic paraparesis and sensory ataxia that can progress over decades. The neuropathologic correlate for adreno-leukodystrophy is severe inflammatory demyelination of posterior cerebral white matter, while a chronic distal axonopathy of spinal cord and peripheral nerve occurs in adrenomyeloneuropathy. Consequently, both modifier genes and environmental factors have been implicated in their pathogeneses. We report five cases of adreno-leukodystrophy whose onsets were initiated by moderate to severe head trauma, two of whom were conversions from adrenomyeloneuropathy. Their clinical courses were rapidly incapacitating, short (i.e., weeks to a few years) and fatal due to marked cerebral inflammatory demyelination. These cases, in concert with several previous reports, indicate that head trauma is one environmental factor that can have a profoundly deleterious effect on those genetically at risk for, or with milder clinical phenotypes of, this disease. Avoidance of potential head trauma and a rapid response to episodes of moderate to severe head trauma in this patient population seem prudent.
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Anecdotal cases of head trauma precipitating cALD with inflammatory demyelination beginning at the contusion site have been reported.
“Anecdotical cases of head trauma precipitating cALD have been reported with inflammatory demyelination beginning at the site of the contusion [43,44,45,46].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [45]
Traumatic brain injury has been implicated in a few anecdotal but striking observations of cALD occurrence following head trauma.
“It has been implicated in a few anecdotical but striking observations of cALD occurrence following a head trauma [43,45,46].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [45]
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“This is also supported by the development of different clinical phenotypes in monozygotic twins [135,136] and the observation that moderate head trauma can initiate cerebral demyelination in AMN patients [137,138].”
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- Authors
- Raymond, G. V., Seidman, R., Monteith, T. S., Kolodny, E., Sathe, S., Mahmood, A., & Powers, J. M.
- Affiliations
- Kennedy Krieger Institute (US)
- Stony Brook University Hospital (US)
- University of California, San Francisco (US)
- NYU Langone Health (US)
- The University of Texas Medical Branch at Galveston (US)
- University of Rochester Medicine (US)
- Corresponding author
- Powers, James M.
- Venue
- Journal of the Neurological Sciences
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 290
- Issue
- 1-2
- Pages
- 70-74
- ISSN
- 0022-510X (ISSN-L)
- OpenAlex
- W2153279033
- Cited by
- 90
- References
- 1
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 12 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 7 · 2016: 5 · 2015: 10 · 2014: 5 · 2013: 6 · 2012: 5
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of the Neurological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- adrenomyeloneuropathy, ABCD1 mutations, peroxisomal membrane proteins, head trauma, environmental triggers, inflammatory demyelination, white matter demyelination, genetic modifiers, disease onset
- MeSH terms
- Adolescent, Adrenoleukodystrophy, Adult, Brain, Brain Injuries, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Myelin Sheath, Nerve Fibers, Myelinated, Retrospective Studies, Spinal Cord, Time Factors, Tomography, X-Ray Computed, Causality, Fatal Outcome, Disease Progression, Persistent Vegetative State, Genetic Predisposition to Disease, Lipid Metabolism, Young Adult
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