Novel eShunt System improves gait and cognition in normal pressure hydrocephalus patients

Introduction Normal pressure hydrocephalus (NPH) is a condition of excess cerebrospinal fluid (CSF) in the brain, associated with a symptom triad of impaired gait, cognition, and urinary incontinence. Standard of care treatment for NPH is surgical placement of a ventriculoperitoneal (VP) shunt, performed through a burr hole in the skull, catheter passage through brain parenchyma, and subcutaneous catheter tunneling for placement in the peritoneum. The eShunt System is a novel, endovascular cerebrospinal fluid (CSF) shunting approach for the treatment of normal pressure hydrocephalus (NPH), performed using transvenous, transfemoral catheter access. We conducted a prospective, multicenter, single‐arm trial to study the safety and effectiveness of the eShunt System to treat patients with NPH. The trial has completed enrollment and follow‐up through the primary endpoint, assessed at 90‐day follow‐up. Methods NPH triad symptoms of gait, cognition, and urinary dysfunction were assessed at baseline and 90‐days to evaluate the degree of improvement after eShunt Implant placement. The Timed Up & Go (TUG) test assessed patient gait, measuring duration to rise from a chair, walk 3 meters around a marker, and return to sitting; the Montreal Cognitive Assessment (MoCA) assessed patient cognition; and the Neurogenic Bladder Symptom Score (NBSS)[1] assessed patient urinary dysfunction. Study inclusion criteria were > 20% TUG improvement after screening lumbar CSF withdrawal, an opening pressure > 8 cmH 2 O, and candidate anatomy on brain MRI and CT. Results Sixty‐six subjects (21 female; mean 75.4 +/‐ 5.0 years) were treated with sixty‐four completing 90‐day follow‐up. Sixty‐one out of sixty‐four (95.3%) patients met the efficacy endpoint of improvement in any one of the three NPH symptoms relative to baseline. Matched pair analysis demonstrated statistically significant mean improvements for each symptom assessment with decreased TUG time (37.2%; p<0.0001; n=63), improved MoCA score (+2.3 points; p<0.0001; n=61) and improved NBSS score (‐2.1 points; p=0.0017; n=61). Mean TUG improvement surpassed the established minimal clinically important difference of >16.5%. There were no instances of hemorrhage, over‐drainage, infection or device‐related serious adverse events (SAE). Two procedure‐related SAEs occurred (3.0%), one sigmoid sinus thrombosis and one femoral artery pseudoaneurysm, resolving without surgical intervention. Conclusion In this cohort of sixty‐six (66) patients, treatment of NPH using the eShunt System was safe and effective resulting in clinically meaningful improvements in gait, cognition, and urinary symptoms through 90 days. A low incidence of SAEs, without any observations of cerebral hemorrhage, overdrainage or infection support minimally‐invasive endovascular shunting as a promising alternative to conventional VP shunt surgery for the treatment of NPH. A randomized controlled trial comparing the eShunt System to a VP shunt control arm is ongoing and will provide further longer term safety and efficacy data. [1] Welk, B., et al. (2014). The validity and reliability of the neurogenic bladder symptom score. The Journal of Urology, 192(2), 452‐457. NBSS ©2013 Dr. Blayne Welk, All rights reserved. NBSS contact information and permission to use: https://www.nbrg.org/research/nbss/”