Cerebrospinal fluid (CSF) is a protein-poor fluid that is an ultrafiltrate of blood produced in the choroid plexus in the brain. This all-important fluid provides a way to remove waste, cushioning, and a nutrient source in some situations. As with most things, you can have too much of a good thing. In diseases like hydrocephalus, syringomyelia or hydromyelia there is excess CSF in parts of the nervous system which can result in clinical abnormalities. These abnormalities may include seizures, behavior changes, pain, phantom scratching, difficulty with ambulation and blindness. Studies have determined that omeprazole, a proton pump inhibitor, can decrease CSF production when administered IV or intrathecal (in the ventricle). As a result, many neurologists, me included, prescribe omeprazole for dogs with hydrocephalus or Syringohydromyelia. Our goal is to improve clinical signs through a reduction in CSF production.
In 2016, a group from Belgium (The Veterinary Journal 209 (2016) 119–124)) evaluated oral administration of omeprazole in a group of clinically normal research beagles to determine if CSF production was reduced. A few notable points here – 1) these were clinically normal beagles and therefore were expected to have normal CNS anatomy and 2) this was an indirect measure of CSF production via the albumin quotient calculation. The albumin quotient, which is a common way to indirectly measure CSF production, is calculated by dividing CSF albumin by the serum albumin. As CSF production goes down, the quotient should go up. No statistical difference in the albumin quotient was noted after 14 days of omeprazole administration, however a slight overall increase in the quotient was noted. Why did this happen when it was previously shown to reduce CSF production via IV or intrathecal administration? We have a few options here…
Oral absorption does not have as great of an effect compared to IV or intrathecal. A 0.2 mg/kg IV dose given to rabbits showed a whopping 25% reduction in CSF production. We typically recommend 1mg/kg PO. Perhaps we should be giving more? The PO study did not measure omeprazole concentrations in the CSF, so it is unknown how much transferred after oral dosing.
Chronic administration may result in a lesser response over time (the other studies were single dose studies) OR we needed more exposure to affect a response. Subjectively, clients do not report an immediate improvement on omeprazole therefore perhaps exposure longer than 14 days was needed.
Normal beagles are, well, normal. Animals with hydrocephalus or Syringohydromyelia may have different CSF production mechanisms (upregulated? Down regulated?) which could result in a more profound shift when exposed to omeprazole.
What is the take-away message? Based on this study, omeprazole has fallen out of favor with many neurologists. However, I continue to recommend this medication because the IV/intrathecal study was fairly convincing, and I think I have seen remarkable clinical response in some patients. Notice the modifiers to that sentence! “I think” and “some patients.” Here’s the thing though…adverse effects are rare with omeprazole, so I also don’t think there is a big downside to trying it. I continue to have clients report a favorable response to phantom scratching events (times/day and/or severity) as well as cognitive function. Seizures and gait deficits tend to respond less, in my experience. I do, however, tell clients about the results of the PO study so that they are (hopefully) realistic in their expectations. Nonetheless, it continues to be part of my armament when treating excess-fluid-diseases in the CNS. Why subject an animal to steroids if omeprazole will work?
I hope you are enjoying your start to January and look forward to working with you soon!