Anatomically standardized 99mTc-ECD brain perfusion SPECT allows accurate differentiation between Multi- System Atrophy and Idiopathic Parkinson’s disease

Introduction : The clinical differentiation between typical idiopathic parkinson disease (IPD) and atypical parkinsonian disorders such as multiple system atrophy (MSA) is complicated by the presence of signs and symptoms common to both forms. The goal of this study was to re-evaluate the contribution of brain perfusion SPECT with anatomical standardisation and automated analysis and in the differentiation of IPD and MSA. This was performed by discriminant analysis in comparison to a large set of ageand gender-matched healthy volunteers. Patient and Methods : Tc-ethyl cysteine dimer (ECD) SPECT was performed on 140 subjects : 81 IPD patients (age 62.6 ± 10.2 y ; disease duration 11.0 ± 6.4 y ; 50 M/31F), 15 MSA patients (61.5 ± 9.2 y ; disease duration 3.0 ± 2.2 y ; 9M/6F) and 44 ageen gender-matched healthy volunteers (age 59.2 ± 11.9 y ; 27M/17F). Patients were matched for symptom severity (Hoehn and Yahr stage). Automated predefined volume-of-interest analysis was carried out after anatomical standardisation. Stepwise discriminant analysis with cross-validation using the leave-one-out method was used to determine the subgroup of variables giving the highest accuracy for this differential diagnosis. Results : Between MSA and IPD, the only regions with highly significant uptake differences after Bonferroni correction were the putamen voxel of interest (VOI). Comparing MSA versus normals and IPD, with putamen VOI values as discriminating variables, cross-validated performance showed correct classification of MSA patients with a sensitivity of 73.3% and a specificity of 84%, accuracy 83.6%. Additional input from right caudate head, left prefrontal and left mesial temporal cortex allowed 100% discrimination also after cross-validation. Discriminating between the IPD group and healthy volunteers was accurate in 94% of the cases after cross-validation, with a 91.4% sensitivity and specificity of 100%. The three-group classification (MSA, IPD and healthy volunteers), resulted in an overall accuracy of 86% posthoc, with 98% of normals, 78% IPI) and 93% of MSA correctly classified. These values were slightly lower after crossvalidation : 96% for healthy volunteers, 77% for IPD and 67% for MSA (67%). Conclusion : Using a large set of ageand gender-matched healthy volunteer data and anatomical standardisation, it is possible to differentiate between idiopathic Parkinson’s disease and multiple system atrophy in clinically relevant circumstances with high discriminating power.