CPT-3 in Normal Pressure Hydrocephalus

Neuropsychometric Testing With Conner's Continual Performance Test -3 in Normal Pressure Hydrocephalus

The study will collect prospective cohort data of individuals that are undergoing routine clinical care for suspected idiopathic Normal Pressure Hydrocephalus (NPH). The administration of the Conner's Continual Performance Test - version 3 (CPT-3), an automated 14-minute computerized measure of reaction-time and sustained attention, will be added to the current neurocognitive screen being used (i.e., the Montreal Cognitive Assessment, MoCA) along with gait assessment. Patients will undergo pre-tap testing on the morning of their large volume Lumbar Puncture (CSF-TT). These patients will receive post-tap CPT-3 and MoCA testing one-to-three hours post-tap, and again at 2-3 days post-CSF-TT, during the follow-up appointment in clinic.

The standard NPH quantitative assessment methods of MoCA and gait evaluation will continue to be collected. For those patients that ultimately undergo ventricular shunt placement, the CPT-3 will be administered at their post-operative follow-up appointment (~3 months post-operation). The results of CPT-3 will not factor into consideration for shunt candidacy.

Study Overview

• Status: Terminated
• Conditions: Normal Pressure Hydrocephalus
• Intervention / Treatment: Diagnostic test: Conner's Continuous Performance Test-3

Detailed Description

Normal pressure hydrocephalus (NPH) is a syndrome involving the clinical triad of gait disturbance, urinary incontinence, and cognitive dysfunction, in the context of ventricular enlargement out of proportion to parenchymal atrophy with normal intracranial pressure.

In the 1980's, a protocol for quantitative measurement of symptom response to large volume CSF tap (40-50ml) was developed, as a method for evaluating suitability for undergoing ventricular shunting surgery. A 2016 systematic review of the literature noted heterogeneous findings within the eight prospective cohort studies that were included in analysis, but concluded that there appeared to be support for the CSF-TT as a rule-in screen for response to shunt placement.

Unfortunately, no extant literature has analyzed the independent predictive power of a clinically significant reaction time improvement in response to CSF-TT (widely defined across the literature as 5% improvement) to subsequent response to ventricular shunting. This frustrates an a priori power analysis. However, a rough estimate was calculated based on data presented within one of the aforementioned reviewed studies that identified an improvement in reaction time in response to CSF-TT, as well as an improvement in reaction time to subsequent shunting.

The authors reported that 17 of 68 (25%) of the patients were labeled as positive-responders to CSF-TT, defined as meeting at least 2 of the following criteria: 1) 5% improvement in reaction time, 2) 5% improvement in gait (time or steps), 3) 25% improvement on visuospatial recall task, 4) 25% improvement on visuospatial recognition task. Of those 17 positive responders, 16 (94%) met the same positive-response criteria, post-shunting. If we use a 50% response rate as a proportion null hypothesis, this gives us a z-statistic = 3.63, or f2 = 3.71. G*Power analysis, for a 4-predictor regression (i.e., the aforementioned indicators used), estimates a necessary sample size of 16. The primary limitation of this approach is that it is unclear which of the 2+ positive response criteria were met. However, review of the pre- versus post-shunting data suggests reaction time was significantly improved (p<0.001; Cohen's d = 0.399), suggesting it is reasonable to infer the domain was favorably impacted by the temporary effects of a CSF-TT.

Patients will undergo pre-tap testing on the morning of their CSF-TT. The administration of the Conners Continual Performance Test - version 3 (CPT-3), an automated 14-minute computerized measure of reaction-time and sustained attention, will be added to the current neurocognitive screen being used (i.e., the Montreal Cognitive Assessment, MoCA). The current CSF-TT protocol's quantitative methods for measuring urinary incontinence and gait will continue to be collected. These patients will receive post-tap CPT-3 and MoCA testing one-to-three hours post-tap, and again at 2-3 days post-CSF-TT, during the follow-up appointment with Neurosurgery. For those that undergo ventricular shunt placement, the CPT-3 will be administered at their post-operative follow-up appointment (~3 months post-operation).

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

• Study Contact: Name: James E Eaton, MD; Phone Number: 6105854494; Email: james.e.eaton@vanderbilt.edu
• Study Contact Backup: Name: Leah Acosta, MD; Email: lealani.mae.acosta@vanderbilt.edu

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

The study population will be adult patients with a clinical concern for Normal Pressure Hydrocephalus. They will be adults with cognitive impairment with at least one of the following: ventriculomegaly out of proportion to sulcal atrophy on imaging, urinary incontinence and problems with gait (magnetic gait or "apraxic gait").

Description

Inclusion Criteria:

• patients being referred for CSF tap test as part of routine clinical assessment of idiopathic Normal Pressure Hydrocephalus by their medical provider
• adults older than 18 years old

Exclusion Criteria:

• premorbid neurodegenerative disease (e.g. Alzheimer's Disease, Frontotemproal Dementia, Parkinson's Disease)
• serious acquired brain injury such as moderate to severe traumatic brain injury, large ischemic strokes
• seizure disorders
• serious neuropsychiatric disease (e.g. schizophrenia, bipolar disorder, major depressive disorder, active alcohol or drug abuse)
• untreated vitamin deficiencies (B12, Wernicke-Korsakoff Syndrome)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Attention and Responsiveness	5% Improvement in T-scores of patients after large volume lumbar puncture	1-3 hours after lumbar puncture, 2-3 days after lumbar puncture

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Attention and Responsiveness after Ventricular Peritoneal Shunt Placement	Patients that have VPS placed will be reassessed and again will be looking for improvement in T-scores.	Approximately 3-6 months after VPS placement

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: James E Eaton, MD, Resident Physician

Publications and helpful links

General Publications

• Kahlon B, Sundbarg G, Rehncrona S. Comparison between the lumbar infusion and CSF tap tests to predict outcome after shunt surgery in suspected normal pressure hydrocephalus. J Neurol Neurosurg Psychiatry. 2002 Dec;73(6):721-6. doi: 10.1136/jnnp.73.6.721.
• Hakim S, Adams RD. The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure. Observations on cerebrospinal fluid hydrodynamics. J Neurol Sci. 1965 Jul-Aug;2(4):307-27. doi: 10.1016/0022-510x(65)90016-x. No abstract available.
• Wikkelso C, Andersson H, Blomstrand C, Lindqvist G. The clinical effect of lumbar puncture in normal pressure hydrocephalus. J Neurol Neurosurg Psychiatry. 1982 Jan;45(1):64-9. doi: 10.1136/jnnp.45.1.64.
• Mihalj M, Dolic K, Kolic K, Ledenko V. CSF tap test - Obsolete or appropriate test for predicting shunt responsiveness? A systemic review. J Neurol Sci. 2016 Mar 15;362:78-84. doi: 10.1016/j.jns.2016.01.028. Epub 2016 Jan 22.

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2019
• Primary Completion (Actual): June 1, 2023
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: April 28, 2018
• First Submitted That Met QC Criteria: April 28, 2018
• First Posted (Actual): May 11, 2018

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hydrocephalus; Hydrocephalus, Normal Pressure
• Other Study ID Numbers: VR52393

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No