Radiological Changes in the Spinal Cord and Brain of Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)

Abstract

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive neurological disorder and shares many radiological and clinical features with other more prevalent myelopathies. Here, we quantified spinal cord and brain volumes in adults with HAM/TSP in comparison with healthy volunteers (HVs) and individuals diagnosed with relapsing-remitting or progressive multiple sclerosis (RRMS or P-MS). Clinical disability and MRI were assessed in 24 HVs, 43 HAM/TSP subjects, and 46 MS subjects. Spinal cord cross-sectional area (SCCSA) and brain tissue volumes were measured and compared. HAM/TSP subjects had significantly lower SCCSA corresponding to cervical levels 2 and 3 (C2-3) (54.0 ± 8 mm²), cervical levels 4 and 5 (C4-5) (57.8 ± 8 mm²), and thoracic levels 4 to 9 (T4-9) (22.7 ± 4 mm²) and significantly elevated brain white matter hyperintensity (WMH) fraction (0.004 ± 0.008) compared to the HVs (C2-3: 69.4 ± 8 mm², C4-5: 75.1 ± 9 mm², T4-9: 34.1 ± 4 mm²; all p < 0.0001; and WMH: 0.0005 ± 0.0007; p < 0.001). In the HAM/TSP subjects, SCCSA at all levels but not WMH showed a significant correlation with clinical disability scores. WMH in HAM/TSP subjects, therefore, may not be related to clinical disability. SCCSA in our limited RRMS cohort was higher than the HAM/TSP cohort (C2-3: 67.6 ± 8 mm², C4-5: 72.7 ± 9 mm², T4-9: 33.4 ± 5 mm²; all p < 0.0001) and WMH was lower than in P-MS subjects (p = 0.0067). Principal component analysis suggested that SCCSA and WMH may be used to differentiate HAM/TSP from MS. Understanding these differences msay help establish early diagnostic criteria for HAM/TSP patients.

Keywords: HTLV-1-associated myelopathy; central nervous system atrophy; magnetic resonance imaging; spinal cord atrophy; white matter hyperintensities.

Figure 1

Global spinal cord atrophy. (A) Representative mid-sagittal T1-weighted MR images of the cervical (upper row) and thoracolumbar (lower low) from healthy volunteers (HVs), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), relapsing–remitting multiple sclerosis (RRMS), and progressive multiple sclerosis (P-MS). Group-averaged spinal cord cross-sectional areas (SCCSA) from (B) C2–3, (C) C4–5, and (D) T4–9 showing significantly lower values in the HAM/TSP subjects at all regions of the cord. ** p < 0.01; **** p < 0.0001.

Figure 2

Brain volumes. (A) FLAIR image (top row) and brain segmentation results overlaid on FLAIR images showing segmented (bottom row) grey matter (brown), white matter (beige), cerebrospinal fluid (CSF, green), and white matter hyperintensities or lesions (teal) from a representative participant in each diagnosis group. Group-averaged analysis of (B) grey matter, (C) white matter, (D) CSF, and (E) lesion or white matter hyperintensity volumes expressed as a fraction of total intracranial volume and adjusted for age showing differences only in the WMH volumes. ** p < 0.01; **** p < 0.0001.

Figure 3

Correlation of radiological and clinical scores. (A) Plots showing a statistically significant correlation (partial Pearson’s) between Scripps neurologic rating scale (SNRS) and spinal cord cross-sectional area (SCCSA) at all cord levels (in columns) for HAM/TSP (top row) and RRMS (bottom row) subjects with disability increasing with reducing SCCSA. (B) SCCSA showed a significant correlation only in the C4–5 region in the P-MS group (left). Brain white matter hyperintensity (or lesion) volumes were significantly correlated with a clinical disability only in the relapsing–remitting multiple sclerosis group (correlation with EDSS shown on the right).

Figure 4

Principal component analysis. Principal components 1 (dominated by SCCSA) and 3 (dominated by median WMH volume from individuals) derived from brain and spine radiological variables show the ability to separate the diagnosis groups.