Gaps, Controversies, and Proposed Roadmap for Research in Normal Pressure Hydrocephalus

Abstract

A BS TRACT: Idiopathic normal pressure hydrocephalus is considered common but remains underinvestigated. There are no uniformly accepted diagnostic criteria and therapeutic guidelines. We summarize the accumulated evidence regarding the definition, pathophysiology, diagnosis, and treatment of idiopathic normal pressure hydrocephalus, highlighting the many gaps and controversies, including diagnostic challenges, the frequent association with neurodegeneration and vascular disease, and the many unknowns regarding patient selection and outcome predictors. A roadmap to fill these gaps and solve the controversies around this condition is also proposed. More evidence is required with respect to diagnostic criteria, the value of ancillary testing, prospective population-based studies and novel trial designs. Furthermore, a need exists to develop new advanced options in shunt technology.

Altered glymphatic system in idiopathic normal pressure hydrocephalus

“…with 17 years' experience in movement disorders. NPH was diagnosed according to the International Guidelines ( Supplementary Table 1) [4,5]. Patients who did not undergo 3T brain MRI including DTI and susceptibility-weighted imaging (SWI) necessary for DTI-ALPS analysis, who had history of vascular ischemia, and who were confirmed to have recent infarction on MRI, were excluded.…”

“…Clinical status was assessed using the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MOCA), and the Unified Parkinson's Disease Rating Scale part III (UPDRS-III). All patients underwent diagnostic CSF drainage (lumbar puncture of 50 cc) process within a month from the MRI acquisition [5,6]. Response to CSF drainage was assessed after 24 h using the 10-m timed walk test [7,8], wherein a gait speed improvement more than 20% was considered as a responder.…”

To Shunt or Not to Shunt Patients with Idiopathic Normal Pressure Hydrocephalus? A Reappraisal of an Old Question

“…These new results make it difficult to justify clinical equipoise and therefore the design of randomized placebo-controlled clinical trial as claimed by Saper [15] but should open new research lines dedicated to understanding the reasons why~20% of patients were non-responders. As remarked by Fasano et al in a proposed roadmap for research in NPH, "The time has come to start to effectively rethink NPH and determine the many molecular and biological disruptions behind a disorder that, for too long, has remained idiopathic" [23].…”

“…To improve the treatment of iNPH patients, good screening tests for early detection of potential candidates at the primary care level that might be referred early to neurologists are needed. As remarked by Fasano et al, the need to improve the screening tools and to reach consensus for a universally-accepted and validated NPH scale that covers all the domains of the syndrome exists [23]. A consensus is also needed on the neuroimaging criteria needed to move the screened patients to the category of possible iNPH and therefore refer them to a tertiary center for further evaluations.…”

“…These tests might provide additional relevant information for confirming iNPH or predicting the response to a shunt. In this context, we need reproducible biomarkers to detect/exclude concomitant neurodegenerative diseases that can influence a patient's response to a shunt (Alzheimer's disease, progressive supranuclear palsy, Lewy body dementia) [23].…”