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This randomized, double-blinded, cross-over study aim to evaluate the effects of shunt treatment in idiopathic normal pressure hydrocephalus (iNPH) by measuring cerebral ventricular volume and clinical symptoms at different shunt opening pressures. Further, proteins in the cerebrospinal fluid (CSF) will be compared before and after shunt surgery.
The participants are evaluated before surgery and one month, two months, three months and three months plus one day after surgery. At each evaluation point a MRI of the brain with volumetric sequences is performed and clinical data is collected (Walking speed and steps for Time up and go, 10m walking and 3m walking backwards. Mini Mental State Examination, balance, gait, self rating of incontinence, Epworth Sleepiness Scale).
At surgery, all patients are given a ventriculoperitoneal (VP) shunt (Strata ® ) with an opening pressure setting of 1.5. After the first evaluation, one month postoperatively, participants are randomized to either a higher (2.5) or a lower (1.0) opening pressure, ratio 1:1. The opening pressure setting is blinded both for patients and the clinician during the subsequent clinical evaluations. At two months, the opening pressure is crossed over to the alternative setting (2.5 or 1.0). At three months, all participants receive the lowest shunt opening pressure (0.5) with the final evaluation the next day.
Semiautomatic measurement of the lateral as well as the third cerebral ventricles will be performed using the MRI scans and volumetric software: SyMRI (SyntheticMR AB, Linköping, Sweden)
CSF is collected at three times for each participant, from the lumbar spine pre- and 3 months postoperatively and intracranially during surgery. Further, intracranial CSF is taken through the Rickham Reservoir at the 3 months postoperative evaluation. After CSF from the participants has been collected, a single batch mass spectrometry will be performed with all the samples simultaneously.
Sample size was determined to achieve 80% power for a two tailed paired t-test for a mean change in ventricular volume of 8ml, estimated from postoperative change in ventricular volume in a previous study.
Hypotheses:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High initial | Experimental | At the one month follow-up, the shunt is adjusted into a high opening pressure (2.5), which is crossed over to 1.0 at the two months follow-up. At the three months follow-up the opening pressure is set at 0.5 until the next day. |
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| Low initial | Experimental | At the one month follow-up, the shunt is adjusted into a low opening pressure (1.0), which is crossed over to 2.5 at the two months follow-up. At the three months follow-up the opening pressure is set at 0.5 until the next day. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ventriculoperitoneal shunt opening pressure setting | Other | The ventriculoperitoneal shunt (Strata®) opening pressure can be changed using a magnetic tool. The possible settings are 0.5, 1.0, 1.5, 2.0, 2.5 with a higher setting number corresponding to a higher opening pressure and less drainage through the shunt. All settings are used in routine clinical practice. |
| Measure | Description | Time Frame |
|---|---|---|
| Ventricular volume at different shunt settings (mL) | Change in ventricular volume (ml) measured by MRI | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Time of "Timed Up and Go" test at different shunt settings | Change in total walking time (sec) on "Timed Up and Go". | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Time of 10m walking test at different shunt settings | Change in total walking time (sec) on 10m walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Measure | Description | Time Frame |
|---|---|---|
| Ventricular versus lumbar cerebrospinal fluid composition determined by mass spectrometry | Change in CSF composition from ventricular versus lumbar collection sites. Quantified with mass spectrometry and statistically compared on a protein by protein basis. | Cerebrospinal fluid is collected during diagnostic procedures before surgery, during surgery and three months and one day after surgery. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Katarina Laurell, MD, PhD | Uppsala University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Neurology Clinic, Östersund Hospital | Östersund | Jämtland County | 83183 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37976516 | Derived | Liden S, Farahmand D, Laurell K. Volumetric effect of shunt adjustments in normal pressure hydrocephalus: a randomized, double-blind trial. J Neurosurg. 2023 Nov 17;140(5):1493-1500. doi: 10.3171/2023.9.JNS23668. Print 2024 May 1. |
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| ID | Term |
|---|---|
| D006850 | Hydrocephalus, Normal Pressure |
| ID | Term |
|---|---|
| D006849 | Hydrocephalus |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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Randomized, double blinded crossover design.
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Shunt setting at the two months and three months follow up.
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| Change in CSF composition after surgery determined by mass spectrometry | Change in CSF composition before versus after surgery. Quantified with mass spectrometry and statistically compared on a protein by protein basis. | Cerebrospinal fluid is collected during diagnostic procedures before surgery, during surgery and three months and one day after surgery. |
| Number of steps of "Timed Up and Go" test at different shunt settings | Change in number of steps on "Timed Up and Go" test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Number of steps of "Timed Up and Go" test at different time points regardless of shunt setting | Change in number of steps on "Timed Up and Go" test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Number of steps on 10m walking test at different shunt settings | Change in number of steps on 10m walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Number of steps on 10m walking test at different time points regardless of shunt setting | Change in number of steps on 10m walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Time of 3m backwards walking test at different shunt settings | Change in total walking time (sec) on 3m backwards walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Time of 3m backwards walking test at different time points regardless of shunt setting | Change in total walking time (sec) on 3m backwards walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Number of steps on 3m backwards walking test at different shunt settings | Change in number of steps on 3m backwards walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Number of steps on 3m backwards walking test at different time points regardless of shunt setting | Change in number of steps on 3m backwards walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Mini Mental State Examination at different shunt settings | Change in Mini Mental State Examination results. (min 0, max 30, higher is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Mini Mental State Examination at different time points regardless of shunt setting | Change in Mini Mental State Examination results. (min 0, max 30, higher is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Epworth sleepiness scale at different time points regardless of shunt setting | Change in Epworth sleepiness scale rating. (min 0, max 24, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Epworth sleepiness scale at different shunt settings | Change in Epworth sleepiness scale rating. (min 0, max 24, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Continence scale at different time points regardless of shunt setting | Change in continence scale rating. (min 1, max 6, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Continence scale at different shunt settings. | Change in continence scale rating. (min 1, max 6, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Balance scale at different shunt settings. | Change in Balance scale rating. (min 1, max 7, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Balance scale at different time points regardless of shunt setting | Change in Balance scale rating. (min 1, max 7, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Modified rankin scale at different time points regardless of shunt setting | Change in Modified rankin scale rating. (min 0, max 6, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Modified rankin scale at different shunt settings. | Change in Modified rankin scale rating. (min 0, max 6, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Gray matter volume at different time points regardless of shunt setting | Change in whole brain grey matter volume measured by MRI (mL). | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Gray matter volume at different shunt settings. | Change in whole brain grey matter volume measured by MRI (mL). | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| White matter volume at different time points regardless of shunt setting | Change in whole brain white matter volume measured by MRI (mL). | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| White matter volume at different shunt settings. | Change in whole brain white matter volume measured by MRI (mL). | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Time of "Timed Up and Go" test at different time points regardless of shunt setting | Change in total walking time (sec) on "Timed Up and Go". | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Time of 10m walking test at different time points regardless of shunt setting | Change in total walking time (sec) on 10m walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |
| Ventricular volume at different time points regardless of shunt setting (mL) | Change in ventricular volume (mL) measured by MRI | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. |