Factors Predicting Response to Shunting in Normal Pressure Hydrocephalus (NPH)

The research project is designed to determine which combination of tests will enable physicians to predict whether a patient with symptoms of normal pressure hydrocephalus (NPH) will improve with a shunt.

Study Overview

• Status: Terminated
• Conditions: Normal Pressure Hydrocephalus
• Intervention / Treatment: Device: Programmable Shunt Insertion (Codman, Medtronic); Behavioral: Assessments in physical therapy, occupational therapy, and speech therapy

Detailed Description

Normal pressure hydrocephalus (NPH) is a potentially reversible progressive neurological condition disproportionately affecting the elderly population. Given current controversies regarding its exact definition, accurate incidence and prevalence figures are elusive. NPH was first described forty years ago as a triad of symptoms consisting of gait difficulties, urinary incontinence, and memory problems in patients with enlarged ventricles in the absence of increased intracranial pressure (ICP). The cause of primary, or idiopathic NPH (INPH) remains elusive, while secondary NPH results from intracranial insults such as head trauma, meningitis, or intracranial hemorrhage. NPH can be successfully treated with cerebrospinal fluid (CSF) shunting. However, the accurate diagnosis and treatment of patients with NPH remains problematic, despite significant advances in brain imaging and ICP physiology.

Objectives - The primary aims of this study are:

1. to confirm the ability of external lumbar drainage to increase the success rate of selectively shunting patients with NPH compared to historical controls
2. to refine the diagnosis of NPH by determining whether the factors that change before and after lumbar drainage will predict failure to improve after shunting. A related aim is to assess the complications attributable to lumbar drainage.
3. to perform a preliminary evaluation of programmable shunt valves for NPH compared to historical controls using fixed-pressure valves. A related aim is to determine whether post-op objective analysis of gait, cognitive function and urinary symptoms will help refine the programmable shunt setting on an individual basis.

Secondary study aims include:

Investigating the pathophysiology of NPH by: 1) correlating cortical vein compliance measured by MRI flow quantification studies with CSF pressure waveform analysis; 2)assessing funduscopic changes before and during ELD; 3) performing and cross correlating CSF chemical analysis on screening positive and negative patients as well as screening-positive patients who are shunt responsive versus unresponsive.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • University of California, Irvine - Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Walking difficulties in both legs which has developed gradually, not explained by other conditions, either in combination with mental impairment and urinary incontinence
• Brain CT or MRI findings of enlarged ventricles compared to established standards (minimum Evans ratio of 0.30 as measured by reviewing films)
• Mental impairment must be mild to moderate, emerging with or after the walking difficulties
• Age > or = 18 years old
• MMSE (Mini-mental status exam): < or = 10
• Urinary incontinence

Exclusion Criteria:

• No or only minimal walking difficulties combined with severe dementia
• Severe medical problems with limited life expectancy (less than six months)
• Contraindications to surgery
• Lack of informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Comparison for patients of lumbar drain and shunt surgery; Subjective comparisons made for patients - before and after external lumbar drain, before and after shunt surgery. Device: Programmable Shunt Insertion (Codman Medtronic) Behavioral: Assessments in physical therapy, occupational therapy, and speech therapy Follow-up testing to be administered by trained physician assistant in the outpatient setting on an approximately monthly basis: 10m walk, timed up-and-go, mini-mental status exam, 9-hole grooved pegboard, motor visual perception test (MVPT), modified rankin score (MRS)

Device: Programmable Shunt Insertion (Codman, Medtronic); Medical Device - Shunt insertion surgery of adjustable valve and laparoscopic assistance for placement of peritoneal catheter. Patient will be brought to operating room suite where general anesthesia is induced. Patient will be placed with a small roll on shoulder, supine, on the operating room table. Patient's head will be turned with the parietal area uppermost in the field. Patient will be prepared and draped in the usual sterile fashion. Site prep includes parietooccipital area, side of neck, chest, and entire abdomen. Ventricular catheter placed and then attached to shunt valve. Catheter is then fitted over grooved blue burr hole guide. Excess catheter pulled down to pull valve into pocket on the skull. Sterile dressings applied.; Other Names: Codman Shunt; Medtronic Strata Valve; Behavioral: Assessments in physical therapy, occupational therapy, and speech therapy; Follow-up testing to be administered by trained Physician Assistant in the outpatient setting on an approximately monthly basis: 10m walk, timed up-and-go, Mini-Mental Status Exam, 9-hole Grooved Pegboard, Motor Visual Perception Test (MVPT), Modified Rankin Score (MRS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evans Ratio	A brain CT scan is obtained after the first week to ten days and the shunt is adjusted according to the patients signs and symptoms. Prior to any downward adjustment of the shunt valve (which allows more CSF drainage), a brain CT is obtained to look for subdural hematoma or effusion. If any type of subdural collection is found, the valve pressure is increased (to reduce CSF flow) until the collection resolves.	initial and follow-up visits

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Therapy, Occupational Therapy, and Speech Therapy	The evaluations for physical therapy, occupational therapy and speech therapy are performed along with external lumbar drainage (ELD) to assess NPH subjects.	30 min per clinic visit

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Investigators: Principal Investigator: Laura Pare, MD, FRCSC, UC Irvine

Publications and helpful links

Helpful Links

• UC, Irvine Medical Center - Dept of Neurosurgery's NPH webpage

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: January 3, 2008
• First Submitted That Met QC Criteria: February 12, 2008
• First Posted (Estimate): February 13, 2008

Study Record Updates

• Last Update Posted (Actual): January 12, 2021
• Last Update Submitted That Met QC Criteria: December 18, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Normal Pressure Hydrocephalus; NPH
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hydrocephalus; Hydrocephalus, Normal Pressure
• Other Study ID Numbers: HS 2005-4609; J&J Proposal #38973 (Other Identifier: J&J Proposal #38973); Award #032906 (Other Identifier: Award #032906)