Hakim's disease: an update on idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) increases with age but is still underdiagnosed and undertreated. In the last decade, iNPH research has expanded into understanding broader contributions to iNPH, the role of cerebrospinal fluid (CSF), and imaging biomarkers to aid early detection, help diagnosis and differentiation from iNPH mimics, and aid with outcome prediction.

We performed a literature search on the PubMed database. English language articles published between 2015-2024 were included. The strategies focused on iNPH and specific terms related to the topics of this review.

We first addressed the ambiguity of current classification terminology and reviewed the newly proposed classification system. This review has shown that prevalence is higher than previously reported. We have reviewed imaging and found numerous highly sensitive and specific imaging markers to aid diagnosis and differentiate from common mimics. CSF biomarkers have revealed that amyloid β and tau levels were lower in iNPH patients, which helped with differentiation from iNPH mimics, and that other emerging inflammatory markers need to be studied further. We also found numerous promising genetic markers in familial iNPH involved in cilial dysfunction, neuroinflammation, and neurodegeneration. Literature also reported the frequent presence of spinal stenosis, and studies reported better iNPH outcomes when these were addressed.

This has shown that there is a need for the development of a structured and standardized classification system, iNPH assessment protocol with standardized testing, and standardized biomarkers to aid diagnosis and treatment, and that this needs an interdisciplinary team approach.