Idiopathic normal pressure hydrocephalus: A sulcal morphometry approach to brain phenotype and clinical response

Idiopathic normal pressure hydrocephalus (iNPH), the leading cause of reversible dementia in older adults, is characterized by urinary incontinence, gait impairment, cognitive decline, and ventriculomegaly. Neuroradiological features rely on visual assessment, including sulcal characteristics. This study applies automatic sulcal-based morphometry to characterize the sulcal phenotype in iNPH and to distinguish responders from non-responders. We analyzed the sulcal morphology in 32 iNPH patients and 41 healthy controls. Patients were categorized as responders (Resp) or non-responders (nResp) based on gait improvement following a cerebrospinal fluid tap test. A generalized linear model identified the iNPH sulcal phenotype, and a Support Vector Machine (SVM) classifier was applied to distinguish iNPH patients from controls, as well as Resp from nResp. We found that sulcal depth and widening were the key descriptors of the iNPH brain phenotype. Eight core sulci contributed the most, including compressed central, superior frontal, and frontal intraparietal bilateral sulci, and flattened left calcarine and posterior lateral fissures. An SVM classifier trained on these features effectively differentiated iNPH patients from controls (AUC: 0.933) but had limited accuracy for Resp vs. nResp (AUC: 0.556). Post-hoc analyses showed smaller superior frontal sulcal opening in nResp than in Resp. This study identified an iNPH neuroradiological phenotype based on sulcal morphology, emphasizing depth and opening as key markers. SVM classifiers trained on different sulci features performed well in differentiating healthy controls from iNPH patients but was less effective for Resp vs. nResp. Future research should investigate more advanced anatomical landmarks in iNPH.