Discriminating among degenerative parkinsonisms using advanced 123 I-ioflupane SPECT analyses

Abstract

123I-ioflupane single photon emission computed tomography (SPECT) is a sensitive and well established imaging tool in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS), yet a discrimination between PD and APS has been considered inconsistent at least based on visual inspection or simple region of interest analyses. We here reappraise this issue by applying advanced image analysis techniques to separate PD from the various APS.This study included 392 consecutive patients with degenerative parkinsonism undergoing 123I-ioflupane SPECT at our institution over the last decade: 306 PD, 24 multiple system atrophy (MSA), 32 progressive supranuclear palsy (PSP) and 30 corticobasal degeneration (CBD) patients. Data analysis included voxel-wise univariate statistical parametric mapping and multivariate pattern recognition using linear discriminant classifiers.MSA and PSP showed less ioflupane uptake in the head of caudate nucleus relative to PD and CBD, yet there was no difference between MSA and PSP. CBD had higher uptake in both putamen relative to PD, MSA and PSP. Classification was significant for PD versus APS (AUC 0.69, p < 0.05) and between APS subtypes (MSA vs CBD AUC 0.80, p < 0.05; MSA vs PSP AUC 0.69 p < 0.05; CBD vs PSP AUC 0.69 p < 0.05).Both striatal and extra-striatal regions contain classification information, yet the combination of both regions does not significantly improve classification accuracy.PD, MSA, PSP and CBD have distinct patterns of dopaminergic depletion on 123I-ioflupane SPECT. The high specificity of 84–90% for PD versus APS indicates that the classifier is particularly useful for confirming APS cases.

Analysis of Extrastriatal 123I-FP-CIT Binding Contributes to the Differential Diagnosis of Parkinsonian Diseases

“…Several previous studies have demonstrated lower overall striatal DAT binding in PSP and MSA-P than PD, with relative sparing of the caudate nucleus in PD (4,8,9,14). Already in early disease stages, patients initially diagnosed with PD that later converted to MSA or PSP have lower DAT binding in the caudate nucleus than patients in whom a diagnosis of PD is maintained (4).…”

“…Literature on the role of extrastriatal SERT in the differential diagnosis of PD, MSA, and PSP is scarce. Nevertheless, higher SERT binding has been observed in the midbrain and pons of PD patients relative to MSA-P and PSP patients (10,20), and whole brain analysis has been reported to be informative before (14). In the hypothalamus, SERT has been shown to be ubiquitously present in controls in a postmortem human brain study (30).…”

“…However, to differentiate between PD, MSA-P, and PSP using DAT imaging by 123 I-FP-CIT SPECT remains a challenge. Although some studies have demonstrated lower striatal DAT binding in MSA-P and PSP patients than in PD patients, findings have so far been inconsistent (4,(6)(7)(8)(9)(10)(11)(12)(13)(14). Moreover, at the individual level there is a clear overlap in binding ratios between MSA-P, PSP, and PD patients, which precludes a role for striatal DAT imaging with 123 I-FP-CIT SPECT to differentiate between degenerative parkinsonian diseases in daily clinical practice.…”

Parkinson Hastalığı ve Atipik Parkinson Sendromlarının Ayırıcı Tanısı

“…Other supportive evidence to support a diagnosis of PD 6 . UK PDS criterion is met, when bradykinesia is associated with one of the symptoms of rigidity, 4-6 Hz resting tremor or postural instability 17 .…”

“…APS has rapid and poor prognosis and in most cases, a duration of less than 10 years results in death 16 . Poor prognosis is typically due to the, fact that there has been less success with pharmacologic treatment and therapeutic options for APS is limited compared to PD 17 .…”