Quantitative FLAIR MRI in Amyotrophic Lateral Sclerosis

Abstract

Rationale and objectives: T2-weighted magnetic resonance imaging (MRI) hyperintensity assessed visually in the corticospinal tract (CST) lacks sensitivity for a diagnosis of amyotrophic lateral sclerosis (ALS). We sought to explore a quantitative approach to fluid-attenuated inversion recovery (FLAIR) MRI intensity across a range of ALS phenotypes.

Materials and methods: Thirty-three classical ALS patients, 10 with a flail arm presentation, and six with primary lateral sclerosis underwent MRI at 3 Tesla. Comparisons of quantitative FLAIR intensity in the CST and corpus callosum were made between 21 healthy controls and within patient phenotypic subgroups, some of whom were studied longitudinally.

Results: Mean FLAIR intensity was greater in patient groups. The cerebral peduncle intensity provided the strongest subgroup classification. FLAIR intensity increased longitudinally. The rate of change of FLAIR within CST correlated with rate of decline in executive function and ALS functional rating score.

Conclusions: FLAIR MRI encodes quantifiable information of potential diagnostic, stratification, and monitoring value.

Keywords: Amyotrophic lateral sclerosis; biomarker; motor neuron disease; neuroimaging; phenotype; prognosis.

Figure 1

Quantitative corticospinal tract and corpus callosum FLAIR intensity in controls, ALS (including flail arm), and PLS. *P ≤ 0.05; **P ≤ 0.01. ALS, amyotrophic lateral sclerosis; FLAIR, fluid-attenuated inversion recovery; PLS, primary lateral sclerosis.

Figure 2

FLAIR intensity in controls vs patients (including all ALS, flail arm, and PLS patients) stratified according to disease duration. All comparisons by independent samples t testing, two tailed. *P ≤ 0.05; **P ≤ 0.01; ALS, amyotrophic lateral sclerosis; FLAIR, fluid-attenuated inversion recovery; NS, nonsignificant; PLS, primary lateral sclerosis.

Figure 3

Regression analysis of rate of change of CST FLAIR intensity over time vs rate of decline of ALSFRS (R² = 0.198, P = 0.05) and vs rate of change in trail making test, B − A score (R² = 0.458, P = 0.03). x axis: rate of change of clinical score per month of disease; y axis: rate of change of MRI intensity per month of disease × 10⁻³. Left panel: A single outlier with a very high rate of ALSFRS-R decline >2 points per month was excluded. Right panel: Only 10 patients were able to complete the TMT on their second visit, hence the smaller dataset. ALSFRS-R, revised Amyotrophic Lateral Sclerosis Functional Rating Scale; CST, corticospinal tract; FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging; TMT, Trail Making Test.