Inconsistent primary motor cortex glucose hypometabolism in primary lateral sclerosis

Primary lateral sclerosis (PLS) is a rare neurodegenerative disorder and a model for upper motor neuron degeneration, which is believed to begin in the primary motor cortex. However, clinical observation suggests that not all PLS cases show primary motor cortex glucose hypometabolism on 2-deoxy-2-[¹⁸F]fluoro-D-glucose positron emission tomography (FDG-PET). We aimed to assess the reliability of FDG-PET in identifying motor cortex hypometabolism over disease course in a sample of patients with PLS.

Baseline FDG-PET data from nine consecutive PLS patients were analyzed. At least one follow up assessment was available for five patients. We extracted the average FDG-PET signal in the primary motor cortex and other motor regions and calculated the covariate-corrected z scores based on data of healthy controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.

Among the nine patients evaluated, only four demonstrated glucose hypometabolism in the primary motor cortex across available baseline and follow up assessments. Glucose metabolism of motor regions declined over time in some patients, whereas others maintained stable levels despite a worsening in symptom severity.

Primary motor cortex hypometabolism in PLS patients is less consistent than previously reported, and the absence of this hypometabolic sign should not be considered as irrefutable evidence against PLS in the diagnostic process. The findings of our study underline the heterogeneity of PLS, indicating that more precise diagnostic tools would be beneficial to confirm a PLS diagnosis at an earlier stage.