Diagnostic Accuracy of Magnetic Resonance Imaging Measures of Brain Atrophy Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Degeneration

Abstract

Key Points Question Can widely available atrophy measures on magnetic resonance imaging (MRI) increase diagnostic accuracy of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD)? Findings In this diagnostic study of 326 participants, different methods for quantifying cerebral atrophy on MRI at first diagnosis were applied. The combination of cortical and subcortical measures of atrophy had excellent diagnostic accuracy for the differentiation between PSP, CBD, and other pathologies, even in the subgroup of participants who did not have a movement disorder at diagnosis. Meaning These findings suggest that structural MRI could be used to increase diagnostic certainty of underlying PSP and CBD in diverse clinically relevant scenarios.

Magnetic Resonance Planimetry in the Differential Diagnosis between Parkinson’s Disease and Progressive Supranuclear Palsy

“…The midbrain is generally more atrophic in PSP-RS than in CBS at a group level [ 71 ], while no differences were found between PSP-P and CBS in one study [ 70 ]. This overlap can be partially explained because the clinical diagnosis of CBS is associated with a bucket of different underlying pathologies, including CBD, Alzheimer’s disease, TDP-43 pathology but also PSP pathology in a significant number of cases [ 67 , 72 ], thus making the pathological confirmation absolutely needed in this context. Very recently, a large pathological study [ 67 ] demonstrated that MRPI yielded good performances (AUC of 0.83) in differentiating between pathologically confirmed PSP-RS and CBD (see below, paragraph 2.6).…”

“…This overlap can be partially explained because the clinical diagnosis of CBS is associated with a bucket of different underlying pathologies, including CBD, Alzheimer’s disease, TDP-43 pathology but also PSP pathology in a significant number of cases [ 67 , 72 ], thus making the pathological confirmation absolutely needed in this context. Very recently, a large pathological study [ 67 ] demonstrated that MRPI yielded good performances (AUC of 0.83) in differentiating between pathologically confirmed PSP-RS and CBD (see below, paragraph 2.6). Further pathological studies are warranted to investigate the role of planimetric biomarkers in distinguishing between PSP-P and CBD.…”

“…There is plenty of evidence in PSP for a mismatch between neuropathology and clinical presentation, which contributes to the suboptimal clinical diagnostic accuracy of parkinsonian syndromes. There are several reports of patients with a clinical PSP phenotype associated with non-PSP pathologies such as cortico-basal degeneration pathology (CBD) [ 67 , 72 , 73 , 77 , 78 , 79 ], globular glial tauopathies [ 73 , 78 ], TDP-43 pathology [ 79 , 80 ], and alpha-synucleinopathies [ 77 , 78 , 81 , 82 ]. On the other hand, patients with post-mortem PSP diagnosis can at times present in the early stages with parkinsonian syndromes resembling PD or MSA [ 73 , 82 , 83 ], cortico-basal syndrome [ 67 , 72 ], behavioral variant of fronto-temporal dementia [ 67 , 72 , 84 , 85 , 86 ], primary progressive aphasia [ 67 , 87 ], and rarely amnestic syndrome [ 67 ].…”

“…There are several reports of patients with a clinical PSP phenotype associated with non-PSP pathologies such as cortico-basal degeneration pathology (CBD) [ 67 , 72 , 73 , 77 , 78 , 79 ], globular glial tauopathies [ 73 , 78 ], TDP-43 pathology [ 79 , 80 ], and alpha-synucleinopathies [ 77 , 78 , 81 , 82 ]. On the other hand, patients with post-mortem PSP diagnosis can at times present in the early stages with parkinsonian syndromes resembling PD or MSA [ 73 , 82 , 83 ], cortico-basal syndrome [ 67 , 72 ], behavioral variant of fronto-temporal dementia [ 67 , 72 , 84 , 85 , 86 ], primary progressive aphasia [ 67 , 87 ], and rarely amnestic syndrome [ 67 ]. In this context of clinico-pathological heterogeneity, a biomarker associated with the underlying pathology would be of extreme value to guide the clinical diagnosis and also the selection of patients for clinical trials with new therapies directed to molecular targets.…”

Error in Article Information

“…In the Original Investigation titled “Diagnostic Accuracy of Magnetic Resonance Imaging Measures of Brain Atrophy Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Degeneration,” 1 published April 29, 2022, there was an error in the Article Information section. Funding/Support should have included grants R01AG038791 and U19AG063911 from the National Institutes of Health to Dr Boxer.…”