Transcranial Ultrasound Assessment of Cerebral Pulsatility in Shunt Decision-making for Suspected Idiopathic Normal Pressure Hydrocephalus: a Prospective Cohort Study

Official title

Contribution of Cerebral Pulsatility Assessment by Transcranial Ultrasound to the Decision-making for Cerebrospinal Fluid Shunting in Patients With Suspected Idiopathic Normal Pressure Hydrocephalus: a Prospective Cohort Study

Overview

This will be a single-center, prospective, analytical cohort study. All included patients will undergo transcranial ultrasound (TPI) with measurement of cerebral pulsatility parameters prior to subtractive lumbar puncture during hospitalization in the neurosurgery department, followed by a second ultrasound assessment either at one year after surgery for operated patients, or at one year after the initial ultrasound assessment for non-operated patients. This ultrasound evaluation will be integrated into the routine work-up, which is already systematically performed in cases of suspected idiopathic normal pressure hydrocephalus (iNPH). The neurosurgical team's decision to perform cerebrospinal fluid (CSF) shunting will be made blinded to the ultrasound measurements and based solely on the standard clinical protocol. The primary objective of the study is to demonstrate that the mean amplitude of cerebral pulsatility (MeanBTP) prior to subtractive lumbar puncture is significantly higher in patients who show clinical improvement 12 months after CSF shunting compared with those who do not, with a type I error risk (alpha) of 0.05."

Detailed description

This will be a prospective, single-center cohort study including patients with suspected idiopathic normal pressure hydrocephalus (iNPH). Eligibility will require fulfillment of inclusion criteria and confirmation of non-opposition after written informed consent procedures.

All patients will undergo transcranial pulse imaging (TPI) with measurement of cerebral pulsatility parameters prior to subtractive lumbar puncture during hospitalization. Operated patients will have a second TPI assessment at 12 months post-surgery, while non-operated patients will undergo repeat TPI 12 months after baseline. Ultrasound assessments will be integrated into the standard hydrocephalus work-up.

The decision to perform cerebrospinal fluid (CSF) shunting will be made by the neurosurgical team blinded to ultrasound findings and based solely on standard clinical and radiological criteria. Baseline clinical (demographics, vascular risk factors, cognitive/gait/urinary symptoms, neurological history) and radiological variables (ventricular volume, Evans index, callosal angle, DESH, Radscale) will be collected.

During hospitalization, gait and cognitive function will be evaluated before and 48 hours after lumbar puncture. TPI will provide two indices of cerebral pulsatility: mean brain tissue pulsatility (MeanBTP) and maximal brain tissue pulsatility (MaxBTP), expressed as peak amplitude, peak amplitude mean, and root mean square.

Follow-up will include standardized clinical and radiological assessments. Non-operated patients will be evaluated at 12 months. Operated patients will be seen at 2 months and 12 months postoperatively, with documentation of complications, shunt valve settings, ventricular volume changes, and subdural collections.

Statistical analyses will be performed using STATA v11 (StataCorp, USA). Continuous variables will be expressed as means ± SD or medians; categorical variables as percentages. Normality will be assessed with the Kolmogorov-Smirnov test, and variance equality with F-test. Comparisons will use Student's t-test, chi-square, or Fisher's exact test as appropriate. Cox proportional hazards regression will be applied for multivariable analysis. P \< 0.05 will be considered significant.

The primary objective will be to demonstrate that the mean amplitude of cerebral pulsatility (MeanBTP) measured prior to subtractive lumbar puncture will be significantly higher in patients who show clinical improvement 12 months after cerebrospinal fluid (CSF) shunting compared with those who do not, with a type I error risk (alpha) of 0.05.

The secondary objectives will be to correlate cerebral pulsatility (measured by transcranial pulse imaging, TPI) with functional indices of iNPH and CSF shunting outcomes, including: speech therapy evaluation, physiotherapy-based gait assessment, global neurological disability, ventricular volume, and shunt valve opening pressure.

Primary outcome measures

• Clinical improvement [Time frame: 12 months]

Secondary outcome measures (7)

• Mattis Dementia Rating Scale score (MDRS) [Time frame: 12 months]
• Wechsler Adult Intelligence Scale - 4th edition (WAIS-IV) [Time frame: 12 months]
• Get Up and Go test (s) [Time frame: 12 months]
• 10-meter walk test [Time frame: 12 months]
• Reduction in modified Rankin Scale score (≤ 1 point compared with baseline) at 12 months [Time frame: 12 months]
• Reduction in ventricular volume (total ventricular volume and third ventricular volume) at 12 months [Time frame: 12 months]
• Shunt valve opening pressure (mmH₂O) at 12 months [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Adult
• Suspected iNPH (= at least 1/3 of the triad symptoms + ventriculomegaly on brain imaging)
• Hospitalised at Tours University Hospital for 'hydrocephalus assessment'
• Patient who has provided written and signed consent

Non-inclusion criteria

• Individuals who objected to data processing
• Walking assessment by the physiotherapy team impossible AND cognitive assessment by the speech therapy team impossible

Exclusion criteria

• Patients already fitted with a CSF shunting system (VPS)
• Suspicion of obstructive hydrocephalus (aqueduct stenosis, tumour, etc.)
• Patients under legal protection (guardianship, curatorship, judicial protection).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 1 center

• university hospital, Tours — Tours

Publications

• Ternifi R, Cazals X, Desmidt T, Andersson F, Camus V, Cottier JP, Patat F, Remenieras JP. Ultrasound measurements of brain tissue pulsatility correlate with the volume of MRI white-matter hyperintensity. J Cereb Blood Flow Metab. 2014 Jun;34(6):942-4. doi: 10.1038/jcbfm.2014.58. Epub 2014 Apr 9. PMID 24714033
• Byram B, Trahey GE, Palmeri M. Bayesian speckle tracking. Part II: biased ultrasound displacement estimation. IEEE Trans Ultrason Ferroelectr Freq Control. 2013 Jan;60(1):144-57. doi: 10.1109/TUFFC.2013.2546. PMID 23287921
• LANGFITT TW, KASSELL NF, WEINSTEIN JD. CEREBRAL BLOOD FLOW WITH INTRACRANIAL HYPERTENSION. Neurology. 1965 Aug;15:761-73. doi: 10.1212/wnl.15.8.761. No abstract available. PMID 14315301
• Kucewicz JC, Dunmire B, Giardino ND, Leotta DF, Paun M, Dager SR, Beach KW. Tissue pulsatility imaging of cerebral vasoreactivity during hyperventilation. Ultrasound Med Biol. 2008 Aug;34(8):1200-8. doi: 10.1016/j.ultrasmedbio.2008.01.001. Epub 2008 Mar 12. PMID 18336991
• Kucewicz JC, Dunmire B, Leotta DF, Panagiotides H, Paun M, Beach KW. Functional tissue pulsatility imaging of the brain during visual stimulation. Ultrasound Med Biol. 2007 May;33(5):681-90. doi: 10.1016/j.ultrasmedbio.2006.11.008. PMID 17346872
• Biogeau J, Desmidt T, Dujardin PA, Ternifi R, Eudo C, Vierron E, Remenieras JP, Patat F, Camus V, Constans T. Ultrasound Tissue Pulsatility Imaging Suggests Impairment in Global Brain Pulsatility and Small Vessels in Elderly Patients with Orthostatic Hypotension. J Stroke Cerebrovasc Dis. 2017 Feb;26(2):246-251. doi: 10.1016/j.jstrokecerebrovasdis.2016.09.002. Epub 2016 Nov 25. PMID 27894887
• Desmidt T, Hachemi ME, Remenieras JP, Lecomte P, Ferreira-Maldent N, Patat F, Camus V. Ultrasound Brain Tissue Pulsatility is decreased in middle aged and elderly type 2 diabetic patients with depression. Psychiatry Res. 2011 Jul 30;193(1):63-4. doi: 10.1016/j.pscychresns.2011.01.002. Epub 2011 May 17. PMID 21592742
• Eide PK, Brean A. Intracranial pulse pressure amplitude levels determined during preoperative assessment of subjects with possible idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien). 2006 Nov;148(11):1151-6; discussion 1156. doi: 10.1007/s00701-006-0896-0. Epub 2006 Oct 16. PMID 17039303

Identifiers

NCT: NCT07285928 · DR250159 - HYDROPULSE

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗