Normal Pressure Hydrocephalus
Conditions
Keywords
hydrocephalus, activity monitors, gait impairment, shunt surgery, protokinetic, normal pressure hydrocephalus, shunt-responsiveness, white matter tractography, diffusion tensor imaging, neurodegenerative, NPH
Brief summary
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.
Detailed description
This single-centre observational cohort study will follow 50 patients diagnosed with symptomatic Normal Pressure Hydrocephalus (NPH) (idiopathic or late presenting congenital hydrocephalus and not secondary hydrocephalus) through their clinical journey, from initial assessment to post-CSF shunt surgery or a time when surgery is decided against. Separate groups of 50 asymptomatic individuals with chronic hydrocephalus and non-hydrocephalus individuals will act as controls. Participants will undergo comprehensive clinical assessments including gait, cognitive and urinary evaluations, quality of life measures, serum and CSF degenerative biomarker analysis, diffusion-weighted Magnetic Resonance Imaging (MRI) and optional brain and skin biopsies. Data collection will focus on capturing changes in clinical presentation and imaging findings before and after shunting. REDCap will be utilised as the primary tool for data storage. Primary outcome measures assess pre and post-shunting imaging changes in shunt-responders and non-responders. Shunt response will be defined as 10% improvement in gait speed. Secondary outcomes evaluate the relationship between biomarkers and clinical outcomes. Longitudinal data will help identify factors distinguishing responders from non-responders, with descriptive and inferential statistics used.
Interventions
PROCEDUREVentriculoperitoneal Shunt (VP)
VP 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.
PROCEDUREBrain and Skin Biopsy
Brain and skin biopsy's may be taken during the VP shunt to assist in histological analysis for neurodegenerative changes.
DIAGNOSTIC_TESTMRI Brain
MRI brain with diffusion imagining will be performed before and after shunt surgery.
Sponsors
Imperial College London
Medical Research Council
Michael J. Fox Foundation for Parkinson's Research
University College, London
University of Edinburgh
King's College London
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Group 1 (communicating hydrocephalus): Inclusion Criteria: * Adult patients \>60 * With gait apraxia * With or without cognitive impairment * Urinary dysfunction * Communicating Hydrocephalus
Exclusion criteria
* 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 * Clear alternative explanation for symptoms (e.g. Parkinson's disease with limb rigidity, peripheral neuropathy with sensory ataxia, cervical myelopathy). * Too frail for shunt surgery * Medically unstable (e.g. active angina, respiratory disease, recurrent delirium, active epilepsy). * Unable to tolerate MRI brain imaging * Unable to have a lumbar puncture * Immobile * Unable to attend the hospital for study visits Group 2 (asymptomatic and non-hydrocepahlus dementia and healthy controls): Inclusion Criteria (Any of the following): * Healthy Carers * Members of the Public * Staff of Imperial College/ICHT * Non-NPH Dementias (including Alzheimer's disease or vascular dementia) * Asymptomatic Hydrocephalus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| White Matter Pathway Diffusion Metrics | Perioperative | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurodegenerative Biomarkers and CSF-shunt responsiveness | Perioperative | 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 | From enrolment, at periprocedural and up to 27 weeks | The serum biomarkers will measure a-beta (pg/ml), G-FAB (pg/ml), NfL (pg/ml) and p-tau217 (pg/ml). |
| Sleep Monitoring | From enrolment and through study completion, an average of 1 year | 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 | From enrolment and through study completion, an average of 1 year | 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. |
| Tinetti Performance Oriented Mobility Assessment Score (balance) | From enrolment, at periprocedural and up to 27 weeks | Total scores range from 0 to 16, with higher scores indicating better outcomes of balance performance. |
| Tinetti Performance Oriented Mobility Assessment Score (Gait) | From enrolment, at periprocedural and up to 27 weeks | Total scores range from 0 to 12, with higher scores indicating better outcomes of gait performance. |
| International Consultation on Incontinence Questionnaire for Urinary Incontinence Short Form (ICIQ UI SF) | From enrolment, at periprocedural and up to 27 weeks. | The assessment measures the frequency and severity of urinary incontinence. The total scores range from 0-21. Higher scores indicate worse bladder symptoms. |
| International Consultation on Incontinence Questionnaire for Bowels (ICIQ-B) | From enrolment, at periprocedural and up to 27 weeks. | The assessment measures the pattern and control of bowel incontinence. The total scores for bowel pattern ranges from 1-21 and bowel control ranges from 0-28. Higher scores indicate worse bowel symptoms. |
| International Consultation of Incontinence Questionnaire for Sexual Function | From enrolment, at periprocedural and up to 27 weeks. | The assessment measures the severity and bother of sexual function. The scores for sexual function range from 1-5 and are assessed on an individual basis. Higher scores indicate worse sexual function. |
| International Consultation of Incontinence Questionnaire for Quality of Life | From enrolment, at periprocedural and up to 27 weeks. | The assessment measures the quality of life bladder, bowels and sexual function has on the individual. The scores suggest how much they bother the participant and it ranges from 0-10. Higher bother scores indicate lower quality of life. |
| Overactive Bladder Symptoms (OAB) | From enrolment, at periprocedural, and up to 27 weeks. | The total score ranges from 0 to 15, with higher scores indicating worse bladder severity symptoms. |
| Kubo scale | From enrolment, at periprocedural and up to 27 weeks. | Assesses gait disturbance, cognitive impairment and urinary disturbance. Total scores range from 0 to 12, with higher scores indicating better outcomes. |
| Patient Health Questionnaire-9 (PHQ-9) | From enrolment, at periprocedural and up to 27 weeks. | Assesses the severity of depression. Total score ranges from 0 to 27, with higher scores indicating more severe depressive symptoms. |
| Generalised Anxiety Disorder-7 (GAD-7) | From enrolment, at periprocedural and up to 27 weeks. | Assesses the severity of anxiety symptoms. Total scores range from 0 to 21, with higher scores indicating more severe anxiety. |
| Sintonen 15D | From enrolment, at periprocedural and up to 27 weeks. | Overall score adds 15 metrics of quality of life. Total scores range from 75-15 with lower scores indicating better quality of life. |
| PSP QoL | From enrolment, at periprocedural and up to 27 weeks. | Overall score adds 45 metrics of quality of life using a Likert scale to score from 0-5. Total scores range from 0-225 with lower scores indicating better quality of life. |
| Rockwood Clinical Frailty Scale Score | From enrolment, at periprocedural and up to 27 weeks. | Frailty rating score in older adults. Total scores range from 1 to 9 with higher indicating greater frailty. |
| Addenbrooke's Cognitive Examination ||| (ACE-|||) | From enrolment, at periprocedural and up to 27 weeks. | Total score evaluates cognitive functions including memory, language, visuospatial, attention and language. Total scores range from 0 to 100, with higher scores indicating better cognitive function. |
| Cognitron Cognitive Assessment Platform | From enrolment, at periprocedural and up to 27 weeks. | Includes a total score of a collection of cognitive tests to assess various cognitive domains in those with NPH pre and post surgery. There are specific domain specific scores. |
| PKMAS Gait Analysis Software | From enrolment, at periprocedural and up to 27 weeks. | Objective gait metric data is taken from the Protokinetics gait mat to analyse gait parameters of those with NPH. These metrics include, all aspects of gait (e.g. foot length, gait velocity, stride length) |
Countries
United Kingdom
Contacts
CONTACTChris Carswell
CONTACTHarvey G Burns
Outcome results
None listed