Midsagittal Midbrain Area and Midbrain-to-Pons-Ratio Cannot Distinguish Overlap Syndromes Between Amyotrophic Lateral...

When amyotrophic lateral sclerosis (ALS), a TDP-43 proteinopathy, and progressive supranuclear palsy (PSP), a tauopathy, are associated with frontotemporal dementia (ALS-FTD or PSP-FTD), clinical differentiation can be challenging. There are no established imaging biomarkers to differentiate ALS-FTD from PSP-FTD.

We evaluated the midsagittal midbrain area (MBA) and the midbrain-to-pons-(MB/P)-ratios in T1 MPRAGE MRI of 36 PSP cases (n = 14 PSP-FTD), 77 ALS cases (n = 10 ALS-FTD), and 72 healthy controls (HC).

In ALS, both parameters were indistinguishable from HC. Patients with ALS-FTD had low MBA-values and MB/P-ratios not significantly different from cases of PSP. While ROC-analyses provided an excellent diagnostic accuracy of both parameters for differentiating PSP from HC (AUC_MBA = 0.974) as well as PSP from ALS (AUC_MBA = 0.982), midbrain morphometry provided poor diagnostic accuracy for distinguishing ALS-FTD from PSP-FTD (AUC_MBA = 0,614).

The MBA and the MB/P-ratio are morphometric parameters that have proven reliable in atypical Parkinsonian syndromes. Both can distinguish between PSP and ALS in their typical clinical forms. However, they cannot differentiate between PSP-FTD and ALS-FTD.