Magnetic resonance imaging-based volumetry differentiates progressive supranuclear palsy from corticobasal degeneration Klaus Gro ¨schel, a,b Till-Karsten Hauser, a,b Andreas Luft, a,b Nicholas Patronas, c Johannes Dichgans, a,b Irene Litvan, d and Jo ¨rg B. Schulz a,b, * a Neurodegeneration Laboratory, Department of General Neurology, University of Tu ¨bingen, Tu ¨bingen, Germany b Hertie Institute for Clinical Brain Research, University of Tu ¨bingen, Tu ¨bingen, Germany c National Institutes of Health, Bethesda, MD, USA d Department of Neurology, University of Louisville School of Medicine, Louisville, KY, USA Received 8 July 2003; revised 8 September 2003; accepted 29 September 2003 Because there are no biological markers for the clinical diagnosis of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), we established a mathematical model based on three-dimen- sional magnetic resonance (MR) imaging to differentiate between these parkinsonian disorders. Using MR imaging-based volumetry we studied the pattern of atrophic changes in patients with probable, possible or definite PSP (n = 33) or CBD (n = 18). Patients were compared with 22 controls with similar age. To establish a mathematical model that would allow for differentiation of PSP, CBD and controls we performed a discriminant analysis. We found a significant reduction in average brain, brainstem, midbrain and frontal gray matter volumes in patients with PSP, whereas patients with CBD showed atrophy of parietal cortex and corpus callosum. With the exception of reduced midbrain volumes in PSP, the measured volumes of anatomical structures showed an extensive overlap with the normal range on an individual basis. Using only post mortem confirmed cases of PSP (n = 8) and CBD (n = 7) as well as all controls, the volumes of midbrain, parietal white matter, temporal gray matter, brainstem, frontal white matter and pons were identified to separate best between groups and were used to construct a model with two canonical variables. This model allowed to correctly predict the diagnosis in 95% of controls as well as in 76% of all PSP and 83% of all CBD patients. Similar results were obtained only when patients with a possible and probable diagnosis of PSP and CBD, who were not involved in the development of the discriminant analysis, were classified. 3D-MR imaging-based volumetry may help to differentiate PSP from CBD ante mortem. D 2003 Elsevier Inc. All rights reserved. Keywords: Progressive supranuclear palsy; Corticobasal degeneration; Volumetric MRI Introduction Progressive supranuclear palsy (PSP) and corticobasal degen- eration (CBD) are relatively rare sporadic degenerative parkinso- nian disorders that in contrast to idiopathic Parkinson’s disease (PD) respond poorly to levodopa therapy. In the absence of biological markers for their ante mortem diagnosis, clinical diag- nosis currently relies upon the presence and progression of clinical features. Although clinical diagnostic criteria exist, their similar age at symptom onset (around age 60), and occasional overlapping features lead at early disease stages to confuse one with each other or with other parkinsonian disorders including multiple system atrophy and PD. Recent epidemiologic studies have established PSP as the most frequent cause of atypical parkinsonism with a prevalence of 5 – 6.4 per 100,000 (Bower et al., 1997; Schrag et al., 1999). Clinically, PSP is characterized by poorly levodopa-responsive parkinsonism, vertical supranuclear gaze palsy, early postural instability, axial dystonia, gait disturbances, and frontolimbic dementia (Litvan et al., 1996a, 1999). Despite an increasing number of publications there are still no data available on the incidence and prevalence of CBD. The classical clinical presentation of CBD includes lateralized extrapy- ramidal features such as parkinsonism, focal myoclonus or dysto- nia, and lateralized cognitive features such as unilateral ideomotor apraxia, aphasia, sensory hemineglect and alien limb syndrome (Rebeiz et al., 1968). Recently, a CBD dementia presentation associated with bilateral parkinsonism and pyramidal signs has also been recognized, but its diagnosis pre mortem is challenging (Bergeron et al., 1998; Grimes et al., 1999; Litvan et al., 1999). Neuropathologically, both diseases are tauopathies. PSP shows prominent subcortical neurofibrillary degeneration. Although there are lesions in the basal ganglia and brainstem in CBD as well, the most severe changes are found in focal cortical areas and cerebral white matter. Microscopically, PSP is characterized by the presence of tufted astrocytes, whereas in CBD ballooned neurons and astrocytic plaques are characteristic. Despite their distinctive clinical and pathological phenotypes these disorders share molecular and genetic similarities (accumu- 1053-8119/$ - see front matter D 2003 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2003.09.070 * Corresponding author. Department of Neurology, University of Tu ¨bingen, Hoppe-Seyler-Strasse 3, D-72076 Tu ¨bingen, Germany. Fax: +49-7071-29-5260. E-mail address: joerg.b.schulz@uni-tuebingen.de (J.B. Schulz). Available online on ScienceDirect (www.sciencedirect.com.) www.elsevier.com/locate/ynimg NeuroImage 21 (2004) 714 – 724