Rostral lesion shift and tract-specific degeneration drive functional heterogeneity in degenerative cervical myelopathy
7 affiliations
- 1Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK USA
- 2Division of Pain Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Palo Alto, CA USA
- 3Department of Radiology, Northwestern University, Chicago, IL USA
- 4Department of Orthopedic Surgery, Stanford University School of Medicine, Palo Alto, CA USA
- 5Department of Neurosurgery, Stanford University School of Medicine, Palo Alto, CA USA
- 6Department of Physical Medicine and Rehabilitation, University of Texas Southwestern Medical Center, Dallas, TX USA
- 7Department of Physical Medicine and Rehabilitation Physical Therapy Program, University of Colorado School of Medicine, Aurora, CO USA
Abstract
Background: Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord impairment worldwide, yet conventional magnetic resonance imaging metrics of canal stenosis fail to explain the remarkable heterogeneity in patient outcomes.
Methods: We applied automated deep-learning segmentation to map the topography of intramedullary lesions in 73 patients and determine their tract-specific functional impact. Functional measures included the modified Japanese Orthopaedic Association score, comprising upper- and lower-body motor dysfunction, sensory function, and sphincter function domains; the Nine-Hole Peg Test for dexterity; and the Standing Balance Test.
Results: Here we show presence of T2-hyperintense lesions in 45% of the cohort, defining a biologically distinct phenotype associated with greater neurological disability. Spatially, lesion density peaked at C4, rostral to the site of maximal compression (C5), implicating venous congestion and ascending degeneration as key pathophysiological drivers. Multivariate modeling revealed that balance impairment represents a systems-level failure, predicted independently by combined damage to the dorsal columns (P = 0.032) and lateral reticulospinal tract (P = 0.011). In contrast, dexterity deficits were not attributable to any single tract, suggesting reliance on global cord integrity. Importantly, we found that unlike in traumatic spinal cord injury, residual tissue bridges (spared tissue) did not universally predict function; they conferred protective benefit for balance (P = 0.044) only when reticulospinal tract integrity was accounted for.
Conclusions: These findings establish tract-specific lesion profiling as a mechanistic biomarker, shifting the clinical framework from measuring global compression to characterizing biological vulnerability.
Related
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BibTeX
@article{muhammad2026rostral,
title = {{Rostral lesion shift and tract-specific degeneration drive functional heterogeneity in degenerative cervical myelopathy}},
author = {Fauziyya Muhammad and Dario Pfyffer and Nicholas Dobson and Todd Parrish and Serena S. Hu and John Ratliff and Nathaniel D. Stetson and Yasin Dhaher and Andrew C Smith and Kenneth A. Weber and Zachary A. Smith},
journal = {Communications Medicine},
year = {2026},
month = jul,
doi = {10.1038/s43856-026-01764-7},
url = {https://doi.org/10.1038/s43856-026-01764-7},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Rostral lesion shift and tract-specific degeneration drive functional heterogeneity in degenerative cervical myelopathy
AU - Fauziyya Muhammad
AU - Dario Pfyffer
AU - Nicholas Dobson
AU - Todd Parrish
AU - Serena S. Hu
AU - John Ratliff
AU - Nathaniel D. Stetson
AU - Yasin Dhaher
AU - Andrew C Smith
AU - Kenneth A. Weber
AU - Zachary A. Smith
PY - 2026
DA - 2026/07/05
JO - Communications Medicine
DO - 10.1038/s43856-026-01764-7
UR - https://doi.org/10.1038/s43856-026-01764-7
AB - Background: Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord impairment worldwide, yet conventional magnetic resonance imaging metrics of canal stenosis fail to explain the remarkable heterogeneity in patient outcomes. Methods: We applied automated deep-learning segmentation to map the topography of intramedullary lesions in 73 patients and determine their tract-specific functional impact. Functional measures included the modified Japanese Orthopaedic Association score, comprising upper- and lower-body motor dysfunction, sensory function, and sphincter function domains; the Nine-Hole Peg Test for dexterity; and the Standing Balance Test. Results: Here we show presence of T2-hyperintense lesions in 45% of the cohort, defining a biologically distinct phenotype associated with greater neurological disability. Spatially, lesion density peaked at C4, rostral to the site of maximal compression (C5), implicating venous congestion and ascending degeneration as key pathophysiological drivers. Multivariate modeling revealed that balance impairment represents a systems-level failure, predicted independently by combined damage to the dorsal columns (P = 0.032) and lateral reticulospinal tract (P = 0.011). In contrast, dexterity deficits were not attributable to any single tract, suggesting reliance on global cord integrity. Importantly, we found that unlike in traumatic spinal cord injury, residual tissue bridges (spared tissue) did not universally predict function; they conferred protective benefit for balance (P = 0.044) only when reticulospinal tract integrity was accounted for. Conclusions: These findings establish tract-specific lesion profiling as a mechanistic biomarker, shifting the clinical framework from measuring global compression to characterizing biological vulnerability.
SN - 2730-664X
ER -