MND is a fatal neurodegenerative condition showing a highly heterogenous clinical progression. Neuroimaging provides reliable quantitative measures of upper motor neuron damage and extra-motor involvement, with important prognostic implications.

To assess the predictive value of multimodal brain magnetic resonance imaging (MRI) on survival in a large cohort of patients with motor neuron disease (MND), in combination with clinical and cognitive features.

Two hundred patients with MND were followed-up for a median time of 4.13 years. At baseline, subjects underwent neurologic examination, cognitive assessment, and brain MRI. Grey matter (GM) volumes of cortical and subcortical structures and diffusion tensor (DT) MRI metrics of white matter (WM) tracts were obtained. A multivariable Royston-Parmar survival model was created using clinical and cognitive variables. The increase of survival prediction accuracy provided by the inclusion of MRI variables was assessed.

The multivariable clinical model included predominant upper (PUMN) or lower motor neuron (PLMN) presentations and diagnostic delay as significant prognostic predictors, reaching an area under the ROC curve (AUC) of survival prediction at 4 years of 0.79. The combined clinical and MRI model including GM volumes of selected fronto-temporal regions and DT MRI metrics of the corticospinal and extra-motor tracts reached an AUC of 0.89. Considering amyotrophic lateral sclerosis (ALS) patients only, the multivariable clinical model including diagnostic delay and semantic fluency scores provided an AUC of 0.62, whereas the combined clinical and MRI model reached an AUC of 0.77.

Our study demonstrated that brain MRI measures of structural damage of the motor and extra-motor systems, when combined with clinical and cognitive features, are useful predictors of survival in patients with MND, particularly when a diagnosis of ALS is made.