Journal article
T2 Hyperintensities in Gracile Tracts of Cervical Spinal Cord in Giant Axonal Neuropathy ( GAN )
Muscle & nerve, Vol.72(5), pp.1152-1155
11/2025
DOI: 10.1002/mus.70004
PMCID: PMC12529028
PMID: 40878963
Abstract
Introduction/Aims
Giant axonal neuropathy (GAN) is a hereditary neurodegenerative disease due to the absence or loss of function of the gigaxonin gene. Pathologic findings in GAN are those of “dying-back” axonal degeneration, in which the distal axon degenerates but the more proximal axon and neuronal cell body remain intact. Aims of this study were to (1) document imaging abnormalities that may occur in the spinal cords of GAN patients; and (2) assess histologically the spinal cords of GAN rodent models.
Methods
A clinical trial of intrathecal (IT) scAAV9/JeT-GAN gene transfer provided a cohort of GAN patients for study. We examined spinal magnetic resonance imaging (MRI) studies from a subset of pretreatment GAN patients ages 6–14 years. For radiologic-pathologic correlation, we examined histologically spinal cords from GAN rodent models with pathological features of human GAN.
Results
Of 10 GAN-patient spinal MRIs, 7 showed cervical or diffuse cord atrophy. Five MRIs additionally showed hyperintense, T2-signal abnormalities bilaterally in the cervical gracile tracts. Microscopy of GAN-rodent spinal cords revealed many actively degenerating axons in the cervical gracile tracts but few degenerating axons elsewhere in the cord.
Discussion
The localization of spinal T-2 signal abnormalities to the cervical gracile tracts in GAN patients mirrors the localization of active dying-back axonal degeneration in GAN rodent models and suggests that these T2-signal abnormalities may be used as a surrogate marker of active axonal degeneration in the long tracts of the spinal cord in GAN and possibly other dying-back neurodegenerative diseases involving the spinal cord.
Details
- Title: Subtitle
- T2 Hyperintensities in Gracile Tracts of Cervical Spinal Cord in Giant Axonal Neuropathy ( GAN )
- Creators
- Diane Armao - University of North Carolina at Chapel HillThomas W. Bouldin - University of North Carolina at Chapel HillDiana X. Bharucha-Goebel - Children's NationalTerry S. Hartman - University of North Carolina at Chapel HillSteven J. Gray - The University of Texas Southwestern Medical CenterRachel M. Bailey - The University of Texas Southwestern Medical CenterDimah Saade - University of IowaJoshua J. Todd - National Institute of Neurological Disorders and StrokeMinal Jain - National Institutes of Health Clinical CenterMelissa Waite - National Institutes of Health Clinical CenterCarsten G. Bönnemann - National Institute of Neurological Disorders and StrokeJ. Keith Smith - University of North Carolina at Chapel Hill
- Resource Type
- Journal article
- Publication Details
- Muscle & nerve, Vol.72(5), pp.1152-1155
- DOI
- 10.1002/mus.70004
- PMID
- 40878963
- PMCID
- PMC12529028
- NLM abbreviation
- Muscle Nerve
- ISSN
- 0148-639X
- eISSN
- 1097-4598
- Publisher
- WILEY
- Grant note
- National Institute of Arthritis and Musculoskeletal and Skin Diseases: R01NS087175, F32 NS095515, 5T32AR056993 NIH/NINDSNational Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Child Neurology Society Philip R. Dodge Young Investigator AwardAmerican Society of Gene and Cell Therapy Career Development AwardPathology Services Core, Lineberger Comprehensive Cancer Center|UNC School of MedicineIntramural Research Program of the NIH
NIH/NINDS R01NS087175 and Hannah's Hope Fund (D.A.); NIH/NINDS R01NS087175 (S.J.G.); NIH/NINDS F32 NS095515 (R.M.B.); grant 5T32AR056993, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Child Neurology Society Philip R. Dodge Young Investigator Award, American Society of Gene and Cell Therapy Career Development Award (D.X.B.-G.). We thank Yuhui Hu, S.J.G. lab, UTSW, for her histologic technician skills. We are grateful for the support of the Pathology Services Core, Lineberger Comprehensive Cancer Center|UNC School of Medicine. The views, information or content, and conclusions presented do not necessarily represent the official position or policy of, nor should any official endorsement be inferred on the part of, the Clinical Center, the National Institutes of Health, or the Department of Health and Human Services. This research was supported by the Intramural Research Program of the NIH.
- Language
- English
- Electronic publication date
- 08/16/2025
- Date published
- 11/2025
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984948120402771
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