Normal pressure hydrocephalus (NPH), a disease that exerts pressure on the brain due to an accumulation of cerebrospinal fluid, can lead to distressing side effects, including cognitive dysfunction, gait disturbance, and urinary incontinence.
But, because the standard of care for this disease is invasive and post-operative complications can be severe, patients — the majority of whom are over the age of 65 — are often counseled by their doctors not to undergo treatment.
A minimally invasive intervention could change this pattern of undertreatment, and that’s why CereVasc’s eShunt System is sparking interest across the field of neurosurgery.
We became aware of this technology, a concept that was developed by two neurosurgeons at Tufts Medical Center — Carl Heilman, MD, and Adel Malek, MD — about a decade ago and were immediately intrigued, as it represented the first potential major innovation in NPH treatment for decades. By this point, minimally invasive procedures had been successful in replacing open surgeries across many other specialties, most notably cardiology, and we wondered if this approach could transform the treatment of NPH, as well.
As CereVasc has moved through the process of developing the eShunt System and studying its performance in ongoing clinical studies, our team has become more and more encouraged by its potential to improve the standard of care for NPH and transform the neurological disease state paradigm. Due to the severity of NPH and its negative impact on a patient’s quality of life, it’s crucial that neurosurgeons remain informed about novel strategies that could introduce practice-changing improvements to treatment.
An Underdiagnosed Disease
NPH arises when the normal circulation of cerebrospinal fluid, or its eventual absorption into the blood, is interrupted. It is a progressive, life-threatening form of communicating hydrocephalus that is one potential cause of dementia.1
NPH affects more than 8 million people worldwide, including up to 3% of adults over age 65 in the United States, Japan and Europe.2,3 Most cases are described as idiopathic, as they have no apparent cause. The balance, which can develop in people of any age, are labeled secondary NPH and arise from head injuries or brain conditions such as tumors, bleeding or infection.1
Unfortunately, less than 20% of patients with NPH are correctly diagnosed,1 and many of them are deemed poor candidates for surgical intervention due to age, frailty and the high complication rate associated with the standard of care, the ventriculo-peritoneal (VP) shunt. This is a true dilemma, as there are no medications indicated for this disease and, without treatment, patients experience cascading decline.
Across the 60 years since this approach was introduced, studies have consistently demonstrated a failure rate of 40% to 50% within the first two years after placement due to issues such as infection, catheter obstruction and over-drainage.4 When that happens, either the shunt components or the entire shunt system must be surgically replaced.
Yet, in initial studies, the eShunt System has demonstrated a failure rate of just 2% — a promising finding that CereVasc will explore further in longer-term trials.
So far, the rate of infection with the eShunt System is virtually zero, while about 10% of those who undergo traditional shunting experience post-operative infection.4,5 Patients with this complication are admitted to the intensive care unit and are usually hospitalized for at least two weeks on intravenous antibiotics before undergoing a second invasive surgery to replace the initial shunt — all at a cost of about $50,000.
In addition, because the eShunt System is minimally invasive, we expect it to be appropriate for a much broader population of people with NPH. Take, for example, an 80-year-old man with NPH who also has cardiovascular disease that is being treated with stents and dual anti-platelet therapy. While this patient would be a very poor candidate for conventional shunt surgery, he would be eligible for our endovascular procedure, as it does not increase bleeding risk and would enable the continuation of anti-platelet therapy.
The eShunt System Versus Conventional Treatment
So, what are the differences between conventional therapy and the eShunt System?
Standard neurosurgery involves drilling a burr hole in the skull and passing a catheter down through the white matter of the brain to the lateral ventricle, where cerebrospinal fluid is produced, attaching a valve behind the patient’s ear, and then passing a second catheter subcutaneously across the patient’s chest and into the abdomen, so that fluid will flow down until it’s reabsorbed in the peritoneum.
With the eShunt system, no burr holes in the skull are required, nor is threading a catheter through any brain tissue. Instead, this new approach uses a temporarily inserted delivery system to move a catheter through a femoral vein in the groin to the base of the brain, where the eShunt Implant is permanently implanted. The implant is designed to drain cerebrospinal fluid from the intracranial subarachnoid space into the veins, mimicking its natural path in healthy individuals.
The eShunt System could also prevent some of the complications associated with conventional shunting and potentially improve the post operative burden on patients, their caregivers and the healthcare system.
A major potential complication with the standard of care, especially in the elderly, is that simple changes in a patient’s body position can accelerate the flow rate of cerebrospinal fluid through the catheter system, resulting in over-drainage of the fluid. Symptoms of over-drainage range from positional headache to subdural hematoma, which can necessitate another surgical procedure to evacuate the collected blood.
The eShunt System appears to circumvent that problem, as we’ve treated 70 patients so far without any evidence of over-drainage. Freedom from this side effect would represent a major treatment advance for patients with NPH, and CereVasc intends to continue to investigate this issue in clinical studies.
There’s an easy explanation for the difference in side effects between the two treatment strategies.
In the conventional approach, patients are implanted with a valve mechanism that is meant to regulate pressure between the ventricles of the brain and the abdomen, dynamics that are not naturally related. When patients develop symptoms of over-drainage, doctors can adjust the valve mechanism using an external magnet. Of course, this can lead to serial doctor’s appointments and hospital admissions.
On the other hand, the eShunt System is designed with a self-adjusting valve that responds to the differential pressure between the subarachnoid space and the venous outflow, acting in a natural way to adjust positional flow rate without a doctor’s intervention.
Developing the eShunt System
Over the past year, CereVasc has achieved some major milestones in advancing the eShunt System toward regulatory review.
- In August, the technology received Breakthrough Device Designation from the U.S. Food and Drug Administration (FDA) as a potential treatment for NPH. In addition to enabling priority review, the designation allows us to have enhanced communication with the FDA during the clinical trial and premarket review processes.
- In September, we announced the 50th patient enrolled in the pilot studies (NCT05232838 and NCT05250505) of the eShunt System in the U.S. and Argentina.
- In May, we received Investigational Device Exemption approval from the U.S. Food and Drug Administration (FDA) to initiate the STRIDE pivotal study that will compare the safety and effectiveness of the eShunt System against that of conventional treatment. Since then, we have kicked off enrollment at the trial’s initial site and expect to ramp it up this winter. Our goal is to complete enrollment in 2025, with data readout and FDA submission occurring in the third quarter of 2026.
Democratizing NPH Treatment
In many ways, the eShunt System is representative of a trend happening across medicine; treatment is migrating away from open surgery, with its high complication rates and long recovery times, and toward minimally invasive procedures, which offer the potential for improved safety and convenience.
This is not only advantageous for patients, but for neurosurgeons, many of whom dislike the conventional shunting procedure for NPH because of its invasiveness, failure rate and association with costly and time-consuming follow-up care.
While a small subset of neurosurgeons focus primarily on shunt procedures and can manage the conventional approach with a low rate of failure, we believe that the eShunt System will democratize treatment for NPH by enabling a wider array of physicians to offer therapy — and with a much more consistent rate of success.
That kind of improvement is crucial, as some symptoms of NPH, such as cognitive decline, are irreversible, making early intervention in as many cases as possible the optimal path.1 I look forward to sharing future findings about the potential for a minimally invasive treatment for NPH, and I encourage neurosurgeons to embrace these possibly life-changing improvements as they become available.
References:
- Yale Medicine. Normal Pressure Hydrocephalus. Published in 2024. Accessed November 20, 2024. https://tinyurl.com/4f9thsck.
- Das JM, Biagioni MC. Normal Pressure Hydrocephalus. StatPearls. Updated June 26, 2023. Accessed November 20, 2024. https://www.ncbi.nlm.nih.gov/books/NBK542247/.
- Cleveland Clinic. Normal Pressure Hydrocephalus (NPH). Reviewed October 30, 2022. Accessed October 23, 2024. https://my.clevelandclinic.org/health/diseases/15849-normal-pressure-hydrocephalus-nph.
- McAllister JP, Williams MA, Walker ML. An update on research priorities in hydrocephalus: overview of the third National Institutes of Health-sponsored symposium “Opportunities for Hydrocephalus Research: Pathways to Better Outcomes.” J Neurosurg. 2015;123(6):1427-38. doi: 10.3171/2014.12.JNS132352.
- Paff M, Alexandru-Abrams D, Muhonen M, Loudon W. Ventriculoperitoneal shunt complications: A review. Interdiscip. Neurosurg. 2018;13:66-70. https://doi.org/10.1016/j.inat.2018.04.004.
Editor’s Note: Daniel Levangie is an experienced executive with senior operating experience in the field of medical devices and in vitro diagnostics. He is President and Chief Executive Officer of CereVasc, Inc., and Co-Founder and Managing Partner of ATON Partners, LLC, a Boston-based private investment and management consulting firm. Before that, Mr. Levangie most recently served as Chief Executive Officer of Dune Medical Devices and Co-Founder and Managing Partner of Constitution Medical Investors (CMI), Inc., a Boston-based private investment and product development firm that was acquired by Roche Diagnostics Corporation in July 2013. A graduate of the College of Pharmacy of Northeastern University in Boston, he is a member of the Board of Directors of Exact Sciences, Inc., and Renalytix, Inc.