Mapping of apparent susceptibility yields promising diagnostic separation of progressive supranuclear palsy from other causes of parkinsonism

Abstract

There is a need for methods that distinguish Parkinson’s disease (PD) from progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), which have similar characteristics in the early stages of the disease. In this prospective study, we evaluate mapping of apparent susceptibility based on susceptibility weighted imaging (SWI) for differential diagnosis. We included 134 patients with PD, 11 with PSP, 10 with MSA and 44 healthy controls. SWI data were processed into maps of apparent susceptibility. In PSP, apparent susceptibility was increased in the red nucleus compared to all other groups, and in globus pallidus, putamen, substantia nigra and the dentate nucleus compared to PD and controls. In MSA, putaminal susceptibility was increased compared to PD and controls. Including all studied regions and using discriminant analysis between PSP and PD, 100% sensitivity and 97% specificity was achieved, and 91% sensitivity and 90% specificity in separating PSP from MSA. Correlations between putaminal susceptibility and disease severity in PD could warrant further research into using susceptibility mapping for monitoring disease progression and in clinical trials. Our study indicates that susceptibility in deep nuclei could play a role in the diagnosis of atypical parkinsonism, especially in PSP.

Automated brainstem volumetry can aid in the diagnostics of parkinsonian disorders

“…In PD there is no visible changes on structural MRI sequences, and when it comes to PSP and MSA, structural changes are usually not discernible until advanced disease stages [4,5]. We have shown that by using susceptibility-based MRI techniques and post-processing algorithms, a high diagnostic separation of PSP from PD and MSA can be achieved [6,7]. Another T 2 *-related marker is the so-called "swallow tail sign" on susceptibility weighted imaging in parkinsonism [8,9].…”

Characterization and diagnostic potential of R2* in early-stage progressive supranuclear palsy variants

“…The distribution of iron-related magnetic resonance imaging (MRI) signal within the brain was shown to have unique patterns across different neurodegenerative pathologies and has been suggested as a promising biomarker to characterize degenerative parkinsonian disorders like Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) [1][2][3][4]. In cohorts of patients with early to moderately advanced disease of 4-6 years duration, the iron content of subcortical brain nuclei was shown to support the differential diagnosis of PD, multiple system atrophy (MSA), and PSP with high accuracy [5,6]. In particular, increased iron-related signal within the red nucleus (RN) was one of the most distinctive features of PSP compared to PD and MSA.…”

Susceptibility‐Weighted Imaging in Neurodegenerative Disorders: A Review

“…Of all the atypical Parkinson syndromes, PSP has the most prominent iron deposition within the deep brain nuclei, including the putamen, red nucleus, SN pars reticulata, and cerebellar dentate nucleus (Fig 8). 30 Elevated iron levels of the red nucleus and dentate nucleus on the affected side could distinguish PSP from PD 33 . Similar to PD, there is increased iron deposition in the basal ganglia, and loss of nigrosome 1, revealing an absent swallow‐tail sign.…”

“…However, compared to PD and MSA, there is increased iron deposition in the red nucleus, globus pallidus, and dentate nucleus, manifesting as an increased hypointense signal on SWI in these regions. Also, unlike MSA, where hypointensity is more prominent on the lower and inner putamen, in PSP, there is overall an even distribution of dark signal throughout the basal ganglia 33,34 . However, studies have had variable results given the heterogeneity of this neurodegenerative disorder, and currently, SWI still has not established itself as an absolute or reliable imaging marker for PSP.…”

“…Recently, the mapping of apparent susceptibility based on SWI has been used to differentiate between the healthy volunteers, and patients with PD, MSA, and PSP. This technique was able to differentiate PSP and PD with 100% sensitivity and 97% specificity and PSP from MSA with 91% sensitivity and 90% specificity 33 …”