Minimally Invasive Approach Could Change Standard of Care for Normal Pressure Hydrocephalus

Until now, people with normal pressure hydrocephalus (NPH) have regularly faced a consequential decision about the care of their condition: the most common treatment for this accumulation of excess cerebrospinal fluid (CSF) in the brain is a sixty-year-old open neurosurgical procedure that is prone to complications and carries with it significant potential risks for this patient population.

A form of communicating hydrocephalus that primarily affects people over age 65, NPH can lead to urinary incontinence, gait disturbance, and cognitive dysfunction, contributing to lower quality of life and in some cases leads to death.¹ 

Unfortunately, NPH is diagnosed in fewer than 20 percent of cases due to insufficient and complex diagnostic criteria and its similarity to other forms of dementia. Equally disconcerting is that many of those diagnosed have comorbidities that make them poor candidates for the existing standard of care treatment: open brain surgery to place a ventriculo-peritoneal (VP) shunt.^2,3

That’s why single-arm studies of a minimally invasive treatment for NPH have stimulated interest among neurosurgeons, people living with NPH, and their caregivers. The eShunt System, which implants a CSF shunt endovascularly, has the potential to make treatment an option to more patients with NPH—with fewer complications. Additional studies suggest that the Implant could have additional practice-changing applications, such as the delivery of gene therapy to the central nervous system.

Having secured Breakthrough Device Designation for the treatment of NPH from the U.S. Food and Drug Administration (FDA); and now in a Pivotal trial in the United States, this approach has the potential to positively impact patient safety and outcomes.

The promise of minimally invasive surgery

To place a VP shunt, a neurosurgeon must drill a burr hole in a patient’s skull to access the CSF containing area of the brain with a catheter. They then connect a series of longer fluid-draining catheters extending from the brain, tunneled under the skin across the chest and abdomen, ending in an incision into the peritoneal cavity to drain excess CSF that is thought to be causing the clinical symptoms of NPH.   

Unfortunately, this method is associated with a consistent single digit percent post-operative infection rate and a 40 percent to 50 percent likelihood of complications within two years of placement that may require complete replacement of the CSF brain to abdomen catheter system.^4-6

As the name implies, a minimally invasive alternative does not require any burr holes to be drilled into the skull or rely upon long indwelling catheters to drain excess CSF. Instead, through a temporarily inserted delivery system threaded up through the femoral vein in the groin, the surgeon permanently places a 3-cm long device at the base of the patient’s brain, where it allows the drainage of CSF into the venous outflow at the base of the brain.

Studies suggest that this approach can shorten post-operative hospital stays, decrease shunt infection risk to virtually zero, and significantly reduce complications and failure rates. In addition, the eShunt System may limit doctor’s appointments after surgery due to its unique design that self-regulates the rate of CSF drainage, avoiding the common complication of over-drainage of CSF. These combined benefits can reduce the post-operative burden on patients, their caregivers, and the healthcare system.

Practice-changing implications

There are additional potential applications for this minimally invasive system on the horizon.

While we have focused on adult patients with NPH so far, there is also a significant unmet need in the pediatric population, and we plan to expand our clinical studies in the future to include children with hydrocephalus who need to undergo shunt treatment.

In addition, we recently published a study demonstrating that we were able to safely and widely distribute an investigational gene therapy for Tay Sachs disease to the brain and spinal cord in a sheep model, leveraging the eShunt System delivery location. As there are a variety of gene therapies in the works, it’s likely that many drug developers will be interested in this route of administration.⁷

Finally, we plan to evaluate the treatment of a number of other forms of hydrocephalus which occur frequently in pediatric patients, in patients diagnosed with idiopathic intracranial hypertension, which can cause vision loss in patients who are predominantly women who are obese; and of childbearing age and in patients who develop hydrocephalus as a result of head and/or brain trauma. We will pursue a variety of clinical studies in patients with these conditions who would also benefit from a potentially more effective treatment option than what is available to them today.⁸

All these applications have something in common—the potential to move treatment away from open surgery and toward minimally invasive techniques. It’s a trend that has improved quality of life for patients across a host of disease states, and we’re optimistic that our technology will help make that difference for patients in the NPH community and beyond.^9,10

The eShunt System is an investigational device, and its safety and effectiveness have not been established. This device is limited by Federal law to investigational use only. Any potential applications mentioned are currently under research and are not approved by the FDA.

References:

1. Cleveland Clinic. Normal Pressure Hydrocephalus (NPH). Reviewed October 30, 2022. Accessed November 20, 2024. https://my.clevelandclinic.org/health/diseases/15849-normal-pressure-hydrocephalus-nph. 
2. Yale Medicine. Normal Pressure Hydrocephalus. Published 2024. Accessed November 20, 2024. https://tinyurl.com/4f9thsck.
3. Patel S, Ditamo M, Mangal R, Gould M, Ganti L. Normal Pressure Hydrocephalus. Cureus. 2023;15(2):e35131. doi: 10.7759/cureus.35131.
4. 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.
5. Bangash M, Moshref R, Alfiky MM. Is the Ventriculo-Peritoneal Shunt Failure Predictable? A Novel Approach. Open Access J Neurol Neurosurg. 2022;16(4). DOI: 10.19080/OAJNN.2022.16.555944.
6. McAllister et al., Opportunities for Hydrocephalus Research: Pathways to Better Outcomes J Neurosurg 123:1427-38, 2015.
7. Benatti HR, Anagnostakou V, Taghian T, et al. A minimally invasive endovascular approach to the cerebellopontine angle cistern enables broad CNS biodistribution of scAAV9-CB-GFP. Mol Ther. Published online August 26, 2024. https://doi.org/10.1016/j.ymthe.2024.08.024.
8. Cleveland Clinic. Idiopathic Intracranial Hypertension. Published 2024. Accessed November 20, 2024. https://my.clevelandclinic.org/health/diseases/21968-idiopathic-intracranial-hypertension.
9. Huang L-c, Chen D-z, Chen L-w, Xu Q-c, Zheng Z-h, Dai X-f. Health-related quality of life following minimally invasive totally endoscopic mitral valve surgery. Journal of Cardiothoracic Surgery. 2020;15(194). https://cardiothoracicsurgery.biomedcentral.com/articles/10.1186/s13019-020-01242-8.
10. Claessens J, Rottiers R, Vandenbrande J, et al. Quality of life in patients undergoing minimally invasive cardiac surgery: a systematic review. Indian J Cardiovasc Surg. 2023;39(4):367-380. doi: 10.1007/s12055-023-01501-y.