Resting-state functional magnetic resonance imaging for idiopathic normal pressure hydrocephalus

• Abnormal characteristic static and dynamic functional network connectivity in idiopathic normal pressure hydrocephalus
• Resting-state functional-MRI in iNPH: can default mode and motor networks changes improve patient selection and outcome? Preliminary report
• Reduced default mode network connectivity relative to white matter integrity is associated with poor cognitive outcomes in patients with idiopathic normal pressure hydrocephalus
• Dynamic functional networks in idiopathic normal pressure hydrocephalus: Alterations and reversibility by CSF tap test
• Default mode network connectivity in patients with idiopathic normal pressure hydrocephalus
• Global cerebral hypoperfusion in preclinical stage of idiopathic normal pressure hydrocephalus

Resting-state functional magnetic resonance imaging (rs-fMRI) has demonstrated functional connectivity alterations in inter-hemispheric, frontal, occipital, default-mode (DMN) and motor network (MN) circuits.

Fabbro et al. reported the experience in a cohort of idiopathic normal pressure hydrocephalus patients that underwent cerebrospinal fluid dynamics evaluation and rs-fMRI. The study aimed to identify functional circuits related to iNPH and explore the relationship between DMN and MN recordings and clinical modifications before and after infusion and tap test, trying to understand idiopathic normal pressure hydrocephalus pathophysiology and to predict the best responders to ventriculoperitoneal shunt (VPS) implant.

They prospectively collected data regarding clinical assessment, neuroradiological findings, lumbar infusion and tap test of thirty-two iNPH patients who underwent VPS implant. Rs-fMRI was performed using MELODIC-ICA both before and after the tap test. Rs-fMRI data of thirty healthy subjects were also recorded.

At the baseline, reduced z-DMN and z-MN scores were recorded in the iNPH cohort compared with controls. Higher z-scores were recorded in more impaired patients. Both z-scores significantly improved after the tap test except in subjects with a low resistance to outflow value and without a significant clinical improvement after the test. A statistically significant difference in mean MN connectivity scores for tap test responders and non-responders was demonstrated both before (p = 0.0236) and after the test (p = 0.00137). A statistically significant main effect of the tap test on DMN connectivity after CSF subtraction was recorded (p = 0.038).

The results suggest the presence of a partially reversible plasticity functional mechanism in DMN and MN. Low values compensate for the initial stages of the disease, while higher values of z-DMN were recorded in older patients with a longer duration of symptoms, suggesting an exhausted plasticity compensation. The standardization of this technique could play a role as a non-invasive biomarker in iNPH disease, suggesting the right time for surgery. Trial Registration Prot. IRB 090/2021 ¹⁾

Patients with reduced DMN connectivity relative to the severity of brain white matter disruption have severe memory deficits at baseline and poorer cognitive outcomes after shunt placement. However, further larger-scale studies are needed to confirm these findings ²⁾.