Implications of perivascular spaces in amyotrophic lateral sclerosis: clinical significance and structural correlation

Perivascular space dysfunction may potentially contribute to the development and progression of amyotrophic lateral sclerosis (ALS). This study investigated the clinical relevance of perivascular space dysfunction in ALS. Two perivascular space parameters were quantified in patients with ALS: (1) the enlarged perivascular space (ePVS) score and (2) the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. These parameters were analyzed in relation to the clinical, structural, and prognostic features of ALS. The study included 55 patients with ALS (33 men; mean age, 61.38 ± 10.95 years). The DTI-ALPS index was marked reduced in the patients as compared to age- and gender-matched controls, and there were no differences in ePVS scores between the two groups. ePVS total score was positively correlated with the ALS progression, as measured by the monthly change in revised ALS functional rating scale (ALSFRS-R). ePVS basal ganglia regional score was inversely correlated with muscle strength. Additionally, both ePVS score and DTI-ALPS index were associated with regional gray matter volumes of the superior frontal gyrus and middle frontal gyrus, and DTI-ALPS index was associated with diffusion parameters of the corticostriatal and corticothalamic tracts. This study underscores the importance of perivascular space dysfunction in ALS according to the ePVS and a reduced DTI-ALPS index, which were respectively associated with disease progression, neurological deficits including reduced muscle strengths, and cortical and subcortical structural changes.