Idiopathic Normal Pressure Hydrocephalus
Conditions
Keywords
Cognition, CSF biomarkers, CSF tap test, Gait assessment
Brief summary
Idiopathic normal pressure hydrocephalus (iNPH) is a neurological condition that can cause walking difficulties, cognitive impairment, and urinary incontinence. Although iNPH can be treated with cerebrospinal fluid (CSF) shunt surgery, diagnosis is often challenging because its symptoms and brain imaging findings may overlap with those of other neurodegenerative disorders, such as Alzheimer's disease or vascular parkinsonism. As a result, some patients may experience delayed diagnosis or may not be referred for potentially beneficial surgical treatment. This observational study aims to evaluate whether combining different types of clinical information can improve the diagnosis of iNPH and help identify patients who are more likely to benefit from surgery. The study integrates cognitive testing, motor performance assessment, CSF biomarker analysis, and brain magnetic resonance imaging. Patients aged over 60 years with suspected iNPH who are evaluated within a standardized diagnostic care pathway will be included. Cognitive and motor performance will be assessed before and after a cerebrospinal fluid tap test, which is part of routine clinical practice. Results will be compared between patients who receive a confirmed diagnosis of iNPH and undergo CSF shunt surgery and patients who receive an alternative diagnosis and do not undergo surgical treatment. The results of this study may help improve diagnostic accuracy, reduce false-negative test results, and support better clinical decision-making in patients with suspected idiopathic normal pressure hydrocephalus.
Detailed description
This is an observational, non-interventional cohort study designed to assess the diagnostic and prognostic value of a multimodal approach in patients with suspected idiopathic normal pressure hydrocephalus (iNPH). The study includes patients aged over 60 years who are referred to a standardized diagnostic, therapeutic, and care pathway for suspected iNPH at a tertiary referral center. All data are collected as part of routine clinical practice after informed consent. Clinical data collection includes demographic and medical information, standardized neuropsychological assessments, motor performance tests, cerebrospinal fluid (CSF) analysis, and brain magnetic resonance imaging. Cognitive and motor assessments are performed before and after the CSF tap test, which is routinely used to support diagnostic and therapeutic decision-making in iNPH. The exposed cohort consists of patients with confirmed iNPH who undergo CSF shunt surgery, while the non-exposed cohort includes patients who receive an alternative diagnosis and are managed without surgical intervention. The two groups will be compared with respect to changes in cognitive and motor performance, CSF biomarker profiles, and neuroimaging parameters. Secondary analyses will explore associations between changes in cognitive and motor outcomes, CSF biomarkers, neuroimaging features, and surgical outcomes, including clinical response at 6 months following surgery when available within the study timeframe. The study combines prospectively collected data with retrospectively available clinical data to provide a comprehensive characterization of patients with suspected iNPH and to support improved diagnostic accuracy and surgical candidate selection.
Interventions
None listed
Sponsors
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
60 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Age 60 years or older. * Patients with suspected idiopathic normal pressure hydrocephalus referred to the institutional diagnostic, therapeutic, and care pathway. * Ability to provide written informed consent.
Exclusion criteria
* Refusal or inability to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montreal Cognitive Assessment (MoCA) total score after CSF tap test | Baseline and 72 hours post-CSF tap test | Difference in MoCA total score between baseline (pre-CSF tap test) and 72 hours after CSF tap test in patients with suspected iNPH. Higher scores indicate better cognitive performance (range 0-30). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Simple Visual Reaction Time After CSF Tap Test | Baseline and 72 hours post-CSF tap test | Difference in mean reaction time (milliseconds) between baseline and 72 hours after CSF tap test. Lower values indicate better performance. |
| Change in Go/No-Go Test Accuracy After CSF Tap Test | Baseline and 72 hours post-CSF tap test | Difference in response accuracy (%) between baseline and 72 hours after CSF tap test. Higher percentages indicate better inhibitory control and executive function. |
| Change in Timed Up and Go (TUG) Test Score After CSF Tap Test | Baseline and 72 hours post-CSF tap test | Difference in time required to complete the Timed Up and Go test (seconds) between baseline and 72 hours after CSF tap test. Lower times indicate better mobility performance. |
| Change in Short Physical Performance Battery (SPPB) Score After CSF Tap Test | Baseline and 72 hours post-CSF tap test | Difference in SPPB total score (range 0-12) between baseline and 72 hours after CSF tap test. Higher scores indicate better lower-extremity function. |
| Change in Tinetti Performance-Oriented Mobility Assessment Score After CSF Tap Test | Difference in total Tinetti score (range 0-28) between baseline and 72 hours after CSF tap test. Higher scores indicate better gait and balance performance. | Difference in total Tinetti score (range 0-28) between baseline and 72 hours after CSF tap test. Higher scores indicate better gait and balance performance. |
| Cerebrospinal Fluid Biomarker Profile Differences Between Surgical and Non-Surgical Patients | Baseline (at diagnostic lumbar puncture) | Comparison of CSF biomarker concentrations measured at diagnostic lumbar puncture, including Aβ42, Aβ40, total tau, phosphorylated tau, Aβ42/Aβ40 ratio, p-tau/Aβ42 ratio, and aquaporin-4. Analyses will evaluate differences between patients undergoing CSF shunt surgery and those receiving an alternative diagnosis without surgery. |
| Association Between Multimodal Markers and Six-Month Surgical Outcome | Baseline through 6 months post-surgery | Correlation between pre- to post-tap-test changes in cognitive and motor measures, CSF biomarkers, neuroimaging parameters, and clinical response at 6 months following CSF shunt surgery. |
Countries
Italy
Contacts
CONTACTAndrea Arighi, MD
CONTACTFrancesca Mameli, PsyD
Outcome results
None listed