Clinical Profiles and Patterns of Neurodegeneration in Amyotrophic Lateral Sclerosis: A Cluster-Based Approach Based on MR Imaging Metrics.

BACKGROUND AND PURPOSE

The previous studies described phenotype-associated imaging findings in amyotrophic lateral sclerosis (ALS) with a prior categorization of patients based on clinical characteristics. We investigated the natural segregation of patients through a radiologic cluster-based approach without a priori patient categorization using 3 well-known prognostic MR imaging biomarkers in ALS, namely bilateral precentral and paracentral gyrus cortical thickness and medulla oblongata volume. We aimed to identify clinical/prognostic features that are cluster-associated.

MATERIALS AND METHODS

Bilateral precentral and paracentral gyri and medulla oblongata volume were calculated using FreeSurfer in 90 patients with amyotrophic lateral sclerosis and 25 healthy controls. A 2-step cluster analysis was performed using precentral and paracentral gyri (averaged pair-wise) and medulla oblongata volume.

RESULTS

We identified 3 radiologic clusters: 28 (31%) patients belonged to "cluster-1"; 51 (57%), to "cluster 2"; and 11 (12%), to "cluster 3." Patients in cluster 1 showed statistically significant cortical thinning of the analyzed cortical areas and lower medulla oblongata volume compared with subjects in cluster 2 and cluster 3, respectively. Patients in cluster 3 exhibited significant cortical thinning of both paracentral and precentral gyri versus those in cluster 2, and this latter cluster showed lower medulla oblongata volume than cluster 3. Patients in cluster 1 were characterized by older age, higher female prevalence, greater disease severity, higher progression rate, and lower survival compared with patients in clusters 2 and 3.

CONCLUSIONS

Patients with amyotrophic lateral sclerosis spontaneously segregate according to age and sex-specific patterns of neurodegeneration. Some patients with amyotrophic lateral sclerosis showed an early higher impairment of cortical motor neurons with relative sparing of bulbar motor neurons (cluster 3), while others expressed an opposite pattern (cluster 2). Moreover, 31% of patients showed an early simultaneous impairment of cortical and bulbar motor neurons (cluster 1), and they were characterized by higher disease severity and lower survival.