What is idiopathic in normal pressure hydrocephalus?

Introduction: Normal pressure hydrocephalus (NPH) can be caused by acquired events - e.g. subarachnoid hemorrhage, meningitis, or trauma - or can be "idiopathic" (iNPH) when no clear cause is identifiable. The entity and nosology of iNPH has received renewed attention and has recently gone through scrutiny and academic debate.

Evidence Acquisition: Authors searched PubMed using the following keywords: "adult hydrocephalus," "alfa synuclein," "Alzheimer's disease," "beta-amyloid," "cerebrospinal fluid," "cilia," "CSF," "genes," "hydrocephalus," "idiopathic," "Lewy Body Dementia," "phosphorylated tau," "shunt responsiveness".

Evidence Synthesis: During the past decades several studies have reshaped our view of iNPH, examples are the identification of monogenic forms of iNPH caused by genes involved in the structure and function of cilia or the discovery of the glymphatic system. This review will discuss the causes of iNPH and particularly the relationship with neurodegeneration in terms of: 1) coincidental association; 2) iNPH predisposing to neurodegeneration, 3. neurodegeneration predisposing to iNPH, and 4. independent processes (genetic and environmental) predisposing to both. Based on the gathered evidence, a unified model is then presented, characterized by three sequential events: impairment of CSF dynamic, occurrence of reversible signs, occurrence of irreversible signs.

Conclusions: Almost 70 years after its description, a growing literature on its basic mechanisms is clarifying that iNPH is a syndrome with pathogenetic mechanisms arising from different causes. The paradigm shift has been recognizing that iNPH is not just a CSF disorder but rather a brain disorder expressing with ventriculomegaly. Finally, the better understanding of what causes iNPH support the proposal of changing its name into "Hakim's disease."