Analysis of Intracerebroventricular (ICV) Device Function and Integrity under Long-Term ICV-ERT in CLN2 Patients

Background: Intracerebroventricular (ICV) application methods enable the administration of therapeutics directly into the central nervous system via an ICV port system. Since several years, this mode of administration is also used for intracerebroventricular enzyme replacement therapy (ICV-ERT) in CLN2 disease, the first approved treatment for NCL diseases. This is the first treatment where a recombinant lysosomal enzyme, cerliponase alfa, is administered into the lateral cerebral. Unlike in treating brain tumours or infections, ICV application in CLN2 disease does not require a bolus injection but a 4-hour-long infusion every 2 weeks. Both long infusion time and recurrent administration of the enzyme significantly increase the risk for device-related adverse events.

Methods: Since the start of the first phase 1/2 trial on cerliponase alfa in 2013, we have treated and followed up 58 CLN2 patients at our center. To understand the effect of long-term ICV-ERTs on device integrity and function, we performed a series of systematic analyses of each device which was explanted due to device-related problems. These analyses comprised microbiological testing, high-resolution photo documentation of device membrane integrity, and histologic analyses.

Results: We encountered the following device-related problems in 58 patients with more than 4,000 punctures in total: device infections (n = 14), CSF leakages (n = 11), and mechanical tube blockage (n = 1).

Conclusion: Our results document the change of device function and integrity over time under ICV-ERT and are important in order to decide when and if prophylactic device exchange should be considered in this long-term treatment.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
28 October 2021