Review of theories into the pathogenesis of normal pressure hydrocephalus

Normal pressure hydrocephalus (NPH) represents a unique form of hydrocephalus characterised by the paradox of ventriculomegaly without significant elevations in intracranial pressure, with the clinical triad of gait instability, cognitive impairment, and urinary incontinence. A myriad of neurobiological correlates have been implicated in its pathophysiology. We review the literature to provide an up-to-date, narrative review of the proposed mechanisms underlying the pathophysiology of NPH, proposing a holistic framework through which to understand the condition. We conducted a narrative review of the literature on NPH, assessing the various mechanisms underlying its pathophysiology and clinical presentation. NPH represents a unique form of hydrocephalus manifesting as a disorder of the cerebral vasculature, characterised by arteriosclerosis and reduced intracranial elastance. There are multiple mechanisms underlying its pathophysiology, which include windkessel impairment causing redistribution of intracranial pulsatility from the subarachnoid space to the ventricles, reductions in cerebral blood flow, impaired glymphatic clearance, reduced blood-brain barrier integrity and alterations in venous haemodynamics. Moreover, NPH shares similar clinical features and pathological mechanisms as other neurodegenerative conditions such as Alzheimer's disease and vascular dementia. The severity of each respective mechanism of pathophysiology can lead a patient to develop one condition versus another. Analysing NPH as a disorder of the cerebral vasculature, glymphatics, and most of all, the distribution of intracranial pulsatility, provides a novel framework through which to understand and manage this condition, one which requires further investigation.