Axonal Injury and Overall Tissue Loss Are Not Related in Primary Progressive Multiple Sclerosis
Bibliographic record
Abstract
BACKGROUND: There is an increasing body of evidence that magnetic resonance imaging-occult tissue damage is an important component of primary progressive multiple sclerosis (PPMS) pathology. Proton magnetic resonance spectroscopy (1H-MRS) can be used to measure in vivo whole-brain N-acetylaspartate (WBNAA) concentrations, the decrease of whose levels is considered a marker of neuronal-axonal injury. OBJECTIVES: To study WBNAA 1H-MRS as a tool to provide information about irreversible brain damage in PPMS and to investigate the relationship between WBNAA and other magnetic resonance imaging measures of MS disease burden, including brain atrophy. METHODS: The following magnetic resonance pulse sequences of the brain were obtained from 32 patients with PPMS and 16 age-matched healthy subjects: (1) dual-echo turbo spin-echo; (2) T1-weighted spin-echo; and (3) 1H-MRS to measure WBNAA concentration. Brain total lesion volumes were measured. Normalized brain volumes were calculated using a fully automated technique. Absolute WBNAA amounts were calculated using a phantom replacement method and were then corrected for individual subjects' brain size. RESULTS: Levels of WBNAA concentrations and normalized brain volumes were significantly lower in patients with PPMS (mean values, 10.2 mm and 1500.0 mL, respectively) than in healthy controls (mean values, 12.9 mm and 1585.2 mL). Both WBNAA concentrations and normalized brain volumes were included as independent factors in the final model of a multivariable analysis predicting the subjects' condition. No significant correlations were found between WBNAA values and normalized brain volumes, WBNAA and T2-weighted or T1-weighted lesion volumes. CONCLUSIONS: Axonal-neuronal damage in the brain of patients with PPMS seems to occur, at least partially, independently of the burden of magnetic resonance imaging-visible lesions. Whole-brain N-acetylaspartate values and normalized brain volumes were unrelated in this cohort, thereby suggesting that 1H-MRS and atrophy assessment may provide in vivo complementary information about the actual extent of brain damage in PPMS.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".