The midbrain to pons ratio: a simple and specific MRI sign of progressive supranuclear palsy

Abstract

Objectives: MRI-based measurements used to diagnose progressive supranuclear palsy (PSP) typically lack pathologic verification and are not easy to use routinely. We aimed to develop in histologically proven disease a simple measure of the midbrain and pons on sagittal MRI to identify PSP.

Methods: Measurements of the midbrain and pontine base on midsagittal T1-weighted MRI were performed in confirmed PSP (n = 12), Parkinson disease (n = 2), and multiple system atrophy (MSA) (n = 7), and in controls (n = 8). Using receiver operating characteristic curve analysis, cutoff values were applied to a clinically diagnosed cohort of 62 subjects that included PSP (n = 21), Parkinson disease (n = 10), MSA (n = 10), and controls (n = 21).

Results: The mean midbrain measurement of 8.1 mm was reduced in PSP (p < 0.001) with reduction in the midbrain to pons ratio (PSP smaller than MSA; p < 0.001). In controls, the mean midbrain ratio was approximately two-thirds of the pontine base, in PSP it was <52%, and in MSA the ratio was greater than two-thirds. A midbrain measurement of <9.35 mm and ratio of 0.52 had 100% specificity for PSP. In the clinically defined group, 19 of 21 PSP cases (90.5%) had a midbrain measurement of <9.35 mm.

Conclusions: We have developed a simple and reliable measurement in pathologically confirmed disease based on the topography of atrophy in PSP with high sensitivity and specificity that may be a useful tool in the clinic.

Figure 1. Flow diagram in the pathologically confirmed group (A) and application of cutoff values to the clinically defined group (B)

MSA = multiple system atrophy; PD = Parkinson disease; PSP = progressive supranuclear palsy; ROC = receiver operating characteristic.

Figure 2. Measuring the anterior-posterior distance of the pons and midbrain

(A) Midsagittal T1 image on conventional MRI. (B) Elliptical regions of interest were placed over the pons and the midbrain in the midsagittal slice. Two lines were drawn to define the major axes of the ellipses, corresponding to oblique superior-inferior axes (thin white lines). The maximal measurement perpendicular to the major axis was taken (thick white lines). In all cases, the posterior border of the pons was clearly identifiable and did not include the pontine tegmentum; the midbrain measurement did not include the collicular plate and was chosen to maximize the chance of detecting atrophy of this region in progressive supranuclear palsy as exhibited by the concave appearance in the midsagittal plane.

Figure 3. Scatterplots of the midbrain and pons measurements showing both pathologically confirmed and clinically diagnosed groups, and receiver operating characteristic curve analysis in the pathologically confirmed group comparing PSP and MSA

MSA = multiple system atrophy; PD = Parkinson disease; PSP = progressive supranuclear palsy.