A Simplified Callosal Angle Measure Best Differentiates Idiopathic-Normal Pressure Hydrocephalus from Neurodegenerative Dementia

Background: Idiopathic normal-pressure hydrocephalus (iNPH) can resemble or occur in combination with other brain disorders frequently present in the elderly such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Objective: To study the accuracy of a simplified callosal angle measure in differentiating iNPH from DLB and AD using conventional brain MRI. Methods: 76 patients (24 iNPH, 30 DLB, 22 AD) and 40 healthy controls served as discovering cohort. The callosal angle measure was obtained on standard coronal brain MRI images crossing the corpus callosum midpoint. 41 patients (21 iNPH and 20 DLB/AD) were used as independent validation cohort. A set of other conventional MRI markers of iNPH was also evaluated. Results: iNPH showed a significantly decreased mean callosal angle value compared to both disease groups and controls (iNPH = 109 +/- 9; DLB = 136.9 +/- 8.2; AD = 135.4 +/- 11.3; Controls = 138.5 +/- 5.2; p < 0.00001). Using a cut off angle of 123, derived by the mean -3SD of the control group, an accuracy of 96% (sensitivity 100%, specificity 95.4%) was obtained. By ROC analysis, the area under the curve was 0.99 (95% CI: 0.97-1). The measure was consistent (intra-rater: r = 0.94) and reproducible (inter-rater: r = 0.89). In the validation cohort, this cut off angle value discriminated iNPH from DLB/AD with 97.5% accuracy. None of the conventional MRI signs reached the same accuracy. Conclusions: This simplified callosal angle measure represents an accurate, reproducible, and easy marker of iNPH.