Luke A. Massey, MRCP Hans R. Jäger, MD, FRCR Dominic C. Paviour, PhD Sean S. O’Sullivan, PhD, MRCPI Helen Ling, BScMed, BMBS, MSc David R. Williams, PhD Constantinos Kallis, PhD Janice Holton, PhD, FRCPath Tamas Revesz, MD, FRCPath David J. Burn, MD, FRCP Tarek Yousry, Dr med Habil, FRCR Andrew J. Lees, MD, FRCP Nick C. Fox, MD, FRCP Caroline Micallef, MD, FRCR Correspondence to Dr. Luke A. Massey: l.massey@ion.ucl.ac.uk 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) typi- cally lack pathologic verification and are not easy to use routinely. We aimed to develop in histolog- ically 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 5 12), Parkinson disease (n 5 2), and multiple system atrophy (MSA) (n 5 7), and in controls (n 5 8). Using receiver operating characteristic curve analysis, cutoff values were applied to a clinically diagnosed cohort of 62 subjects that included PSP (n 5 21), Parkinson disease (n 5 10), MSA (n 5 10), and controls (n 5 21). Results: The mean midbrain measurement of 8.1 mm was reduced in PSP (p , 0.001) with reduc- tion 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. Neurology â 2013;80:1856–1861 GLOSSARY MSA 5 multiple system atrophy; PD 5 Parkinson disease; PSP 5 progressive supranuclear palsy. Neurodegenerative diseases presenting with parkinsonism including idiopathic Parkinson dis- ease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA) can be dif- ficult to differentiate clinically particularly early in the disease course. 1 Characteristic midbrain atrophy in PSP and pontine atrophy in MSA can be assessed on MRI 2 ; however, many magnetic resonance–based measurements proposed as diagnostic for PSP or MSA lack pathologic verifi- cation and are often not easy to apply routinely. 3–9 Our hypothesis was that simple measurements of the midbrain and pons (or their ratio) on midsagittal MRI would identify confirmed PSP and MSA. METHODS Standard protocol approvals, registrations, and patient consents. A pathologically confirmed cohort of PSP, PD, and MSA subjects (table 1) was selected from the Queen Square Brain Bank at UCL Institute of Neurology; brains were donated following ethically approved protocols under license from the Human Tissue Authority. A cohort of PSP, PD, MSA, and healthy subjects was prospectively recruited at the National Hospital for Neurology and Neurosurgery, as part of an ethically approved study with written informed consent. Participants and protocols. In the pathologically confirmed group, the diagnosis was determined using standard neuropathologic criteria. 10 In the clinically diagnosed group, participants fulfilled operational criteria 11–13 and were assessed with clinimetric scales including Hoehn and Yahr, 14 the Unified Parkinson’s Disease Rating Scale, 15 Folstein Mini-Mental State Examination, 16 the Frontal From the Sara Koe PSP Research Centre (L.A.M., D.C.P., S.S.O., H.L., J.H., T.R., A.J.L.), Rita Lila Weston Institute for Neurology Studies and Queen Square Brain Bank, Department of Molecular Neurosciences, UCL Institute of Neurology, London, UK; Department of Brain Repair and Rehabilitation (H.R.J., T.Y., C.M.), UCL Institute of Neurology and Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London; Dementia Research Centre (N.C.F.), UCL Institute of Neurology, London; Van Cleef Roet Centre for Nervous Diseases (D.R.W.), Monash University, Melbourne, Australia; Forensic Psychiatry Research Unit (C.K.), Queen Mary, University of London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. 1856 © 2013 American Academy of Neurology