Novel non-invasive method for measuring intracranial pressure for drug delivery and other neurologic disorders.
Authors: Kumthekar Priya , Schwartz Margaret , Nagpal Seema , Glitza Isabella Claudia , Forsyth Peter A. J. , Gormley William , Patel Rajan , Glicksman Marcie , Sonabend Adam M. 
Published: June 2024

2031

Background: Leptomeningeal carcinomatosis (LC) represents an area of largely unmet clinical need, and intrathecal (IT) drug delivery is often used as treatment (tx). In addition, LC can lead to hydrocephalus, sometimes also during IT treatment . Intracranial pressure (ICP) changes might occur during IT administration, and could have serious clinical consequences, including neurological damage and tracking ICP changes might be beneficial. EnClear Therapies has developed a novel way of externally monitoring ICP through attachment via a minimally invasive intrathecal catheter. In addition, the device allows for easy sampling of CSF, and could aid in tracking of biomarkers longitudinally. Here, we describe this new sensor device and provide data on its use in non-human primates. Methods: The EnClear device utilizes a pressure sensor that easily attaches via a Luer lock to any IT catheter, such as an Ommaya placed intraventriclular and/or lumbar intrathecal. The associated software continually displays the pressure waveform data from the sensor on a monitor with the subject’s pressure, respiration and heart rate. To test the sensitivity of the system, ICP response to a bolus drug infusion of 2 ml was measured before, during, and after infusion, in 7 non-human primates as change in pressure (ΔP) following volume (ΔV) administration, known as intracranial elastance or compliance (ΔP/ΔV). Results: When ICP was measured at both intraventricular and lumbar IT locations, there were good concordance between the two sites in each subject (0.88 correlation coefficient). Transient elevation of ICP during drug delivery in non-human primates was evident, climbing to as high as 20-40 mmHg. Of note, the ICP was variable between subjects with identical infusion volume. Intracranial elastance was calculated for each subject during infusions and resulted in a range of 12 to 36 mmHg; a 3-fold difference in elastance was measured between subjects. Conclusions: In 7 healthy non-human primates, the EnClear ICP measurement device has demonstrated that changes to cranial volume and pressure response can be measured with external sensors with reliable correlation between the two measurement locations. While pressure was consistent between locations, intersubject variability was seen despite identical drug and volume administration. Use of the pressure waveforms from EnClear’s device can be used to enable clinicians to understand individual patient brain elastance and leverage this knowledge for personalized drug delivery. Intersubject variability further supports the need for ICP monitoring and this platform provides a less invasive manner to do this. An upcoming clinical study in patients with LC is planned to compare EnClear’s new device directly to the standard of care, the implanted Camino ICP monitor. The applications go beyond LC, and will benefit patient care for other CNS disorders.