Idiopathic Normal Pressure Hydrocephalus (iNPH) is a progressive condition of the elderly that results in severe disability. iNPH can dramatically respond to Cerebral spinal fluid(CSF)-shunting where excess ventricular fluid is diverted from the brain. Not all patients with iNPH respond to CSF-shunting however. The reasons for this are uncertain.
Aim 1: To understand if specific nerve pathways (white matter tracts) that are near ventricles are damaged in patients that respond to shunting as opposed to those that do not.
Aim 2: Can we explain shunt non-responsiveness by screening for dementia like illnesses (neurodegeneration) using a large array of methods.
Aim 3: To understand whether wearable activity and bed sleep monitors are palatable in a NPH population and to understand if these metrics relate to quality of life.
Aim 4: To see whether self-administered digital cognitive assessments can measure improvements pre and post surgery.
Adult patients >60
With gait apraxia
With or without cognitive impairment
Urinary dysfunction
Asymptomatic hydrocephalus
High pressure-hydrocephalus
Serious head injury within 5 years of presentation or a clear secondary cause (e.g. brain infection)
History of childhood gait disturbance
Patients with hydrocephalus, neurodegenerative disease and healthy controls will be recruited by Dr Chris Carswell at Imperial College Hospital NHS Trust.
Cohort
Prospective
Ventriculoperitoneal Shunt (VP)
Procedure/SurgeryVP Shunt surgery involves surgical insertion of a catheter (tube) to divert brain fluid from the cerebral ventricles to the abdominal peritoneum. This will be performed in Group 1 patients as clinically indicated.
Brain and Skin Biopsy
Procedure/SurgeryBrain and skin biopsy's may be taken during the VP shunt to assist in histological analysis for neurodegenerative changes.
MRI Brain
Diagnostic testMRI brain with diffusion imagining will be performed before and after shunt surgery.
White Matter Pathway Diffusion Metrics
Change from baseline in diffusion tensor imaging (DTI) metrics of white matter pathways (e.g. FA, AD, RD) before and after shunt surgery. The following tracts will be studied: corpus collosum, internal capsule, corona radiata and anterior thalamic radiation.
Neurodegenerative Biomarkers and CSF-shunt responsiveness
Composite degenerative index (plasma abeta, GFAP, Ptau217, NfL, CSF synuclein RT QuIC and brain and skin histology) will be generated and compared between CSF shunt-responsive and CSF non-responsive groups.
Serum Neurodegenerative Biomarkers
The serum biomarkers will measure a-beta (pg/ml), G-FAB (pg/ml), NfL (pg/ml) and p-tau217 (pg/ml).
Sleep Monitoring
The Withings' Sleep mats are devices designed to track sleep patterns. Participants will be offered under mattress sleep monitors capable of showing time spent in bed and analyse sleep cycles.
Activity Monitoring
The Withings' Activity Monitors are devices designed to track physical activity and heart rate. Participants will be offered wrist activity monitors which capture data on steps taken, calories burned and overall movement throughout the day, providing insights into daily activity levels.
Click on the lead sponsor to view all of their trials.
Imperial College London
Lead sponsor
Medical Research Council
Collaborator
Michael J. Fox Foundation for Parkinson's Research
Collaborator
University College, London
Collaborator
University of Edinburgh
Collaborator
King's College London
Collaborator
