Pathogenesis of idiopathic Normal Pressure Hydrocephalus: A review of knowledge

•Physiopathology of iNPH combines vascular, hemodynamic and metabolic aspects.•CSF disturbances are most probably the origin of disease.•Cerebral dyshomeostasis, hypometabolism and neurotoxicity can explain Hakim’s triad.•Neurodegeneration is rather a consequence than a pathogenetic factor in iNPH. Idiopathic Normal Pressure Hydrocephalus (iNPH) is a frequent neuropsychiatric entity. Clinically it is characterised by Hakim’s triad: Dementia, gait disturbance and urinary incontinence. While its symptomatology is typical, the etiology and thereby physiopathology of iNPH still remain enigmatic. This review summarizes and synthesizes different etiologic conceptions and physiopathologic aspects of iNPH. A research of literature via the PubMed/MEDLINE and the Cochrane database was conducted. Only English language articles clearly outlining a reasonable concept of physiopathology were included. Most authors advocate that iNPH is a result of chronically altered cerebrospinal fluid (CSF) dynamics, i.e. deranged CSF production, kinetics and reabsorption. In addition, there are vascular, metabolo-neurodegenerative and hereditary factors. Neuroinflammation does not seem to play a significant role in the etiology of iNPH. All in all, iNPH seems to combine several pathogenetic factors leading to a self-reinforcing vicious circle. The majority of studies hint at CSF disturbances on grounds of altered hemodynamics.