Head tilt with severe rolling not responding to meds for 3 weeks

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5bunniesin40years

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Hi everyone,

I apologize for jumping in to this forum to get rather than give help, but I've been desperately searching for answers for weeks now and think the next best option is to ask for help with my specific case.

Ruby, my dear, sweet 2.5 yo girl, went from wonderfully active one day to gravely ill the next morning. When she did not race downstairs for breakfast as usual on the morning of 12/12, we found her under the bed, uninterested in food placed before her. Upon close examination, her head was slightly tilted, her eyes were starting to roll, her balance was off and she didn't want to move. We took her straight to the exotics vet.

The vet suspected either ear infection or EC, but was leaning towards EC because she didn't see anything in the outer ears, and because we had brought her in during the summer for what we considered to be an unusual amount of thirst/peeing. At this summer appointment, her kidney function was fine, but we had an EC titer done and found her to be positive on the measurement that shows exposure, but not active infection. Given cost and uncertainty of whether a repeat test would give us diagnostic information at this point, we didn't push for another EC test at this first appointment. We did agree to start meds for EC and ear infection, and to hospitalize her for assisted feeding and fluids, because she had no interest in eating. That's when this nightmare began.

She has been in and out of hospitalization and on/off a number of meds, but isn't clinically responding to any of them, and while I'm questioning the choices made earlier in her treatment, I guess what I really need now is advice on what else to try and for how long. I have exhaustively googled all possible variations on the theme of "head tilt rabbit recovery" to look for slivers of hope, but while I'm pretty sure I've read most objective sources, I can find both happy endings and sad endings in forums such as these (I've even gotten pretty good at searching for one vs. the other, depending on my state of mind at the moment).

So, here is what we've tried:
Day 0 (12/12) -- Nystagmus, poor balance, slight head tilt. Start fenbendazole, start SMZ-TMP, start chinese herbal meds for dizziness
Day 2 (12/14) -- Nystagmus/balance worsens, head tilts t0 9 o'clock; do x-ray, see "possible" thickening of bullae (sp?). Switch meds from SMZ to Camphenicol, stay on fenbendazole, start meclizine
Day 4 (12/16) -- Improvement. Nystagmus slows, appetite better, slightly more alert, with head closer to 10 o'clock. Sent home with above meds, critical care
Day 6 (12/18) -- Ruby's head tilt's past 9 o-clock, starts mild rolling. Run out of meclizine mid-day, call for refill, told to wait it out until tech appt next day; circles cages with agitation and start rolling more throughout night
Day 7 (12/19) -- Downturn. Significant rolling, cannot be righted, brought to vet early on emergency. Try acupuncture, meclizine re-started, switch from Fenbendazole to Albendazole, re-hospitalized with assisted feeding and fluids; looks slightly better when we visit in afternoon
Day 8 (12/20) -- Improvement. Ruby "stabilizes," (i.e. resumes eating on her own, but still occasionally rolling with handling). We go out of town for previously planned visit to NY (we live in NC). More on this later. Ruby stays in care of vet in step down from hospitalization (boarding + meds, instead of full-on hospitalization + assisted feeding). Meds stay the same.
Day 9-10 (12/21-12/22): Ruby's head stays at 9 o'clock and rolls occasionally, but continues eating on her own.
Day 11 (12/23): Camphenicol runs out; authorize re-fill of Rx and inquire about adding something else, but since she is stable, vet doesn't think this is necessary.
Day 12 (12/24): Same as Day 9-11, we celebrate Christmas with cautious relief.
Day 13 (12/25): Downtown #2. Unbenknownst to us (clinic was closed to calls/visits on Christmas day, though techs were going in for feedings/treatments 3x/day and vet was in 1x/day), things go south, again. Ruby starts rolling uncontrollably, cannot eat on her own. We find out later that she does still has appetite, but physically cannot manage to eat more than a few nibbles because it triggers severe rolling.
Day 14 (12/26): Vet calls with bad news about downturn. Starts talking about quality of life, suggests we come see her to "discuss our options." We (my husband, 2 human kids and other bunny) are still in NY. I put my husband on a plane that night to see Ruby in person the next morning. I indicate to vet that I've read that recovery from head tilt can take awhile and we still want to fight for her. I ask about more meds. Vet agrees to acupuncture, thinks we should continue with Camphenicol and Albendazole, in addition to resuming hospitalization with syringe feeding and fluids. I know that Camphenicol is one of the best of ear infections, though I worry about blood count warnings for the Albendazole and wonder why we didn't get Fenbendazole its 28 day course before switching that one, given data. Vet calls at end of day to say Ruby looks a little more alert, and that severe rolling had abated slightly.
Day 15 (12/27): Husband visits Ruby in morning and again in afternoon before flying back to NY. While somewhat out of it in morning, she has moments of alertness and nibbling greens and hay and enough rabbity presence to convince husband that she still wants to fight. I am relieved and agree when I see his videos. Husband tells vet of my desire to add more antibiotics; she relents and adds back SMZ-TMP (!).
Day 16-17 (12/28-12/29): Severe rolling resumes. On-call vet (also happens to be clinic owner) (it's a weekend) tries a couple doses of Midazolam for the rolling, but it apparently has little effect. Ruby needs to by syringe fed because she cannot physically reach her food without severe rolling.
Day 18 (12/30): Ruby is "the same." I call vet and ask if there is anything else we can add to meds. I actually want to get off SMZ-TMP because I haven't read it being of any value, but I do not want to insult the main vet on her case who repeatedly prescribed it (different vet at clinic prescribed the camphenicol). From what I had read, penicillin could be a decent option, but vet is in euthenasia frame of mind at this point and suggests that the pain of penicillin injections would be cruel for animal already in considerable distress from uncontrollable rolling, but agrees to add in Baytril. So, add Baytril. I make decision to shorten our trip and return home to bring our baby girl back into our loving, if technically way less skilled at administering meds/feeding home. We drive 10 hours back.
Day 19 (12/31): Ruby is the same. We take her home, with lots of education from the tech on administering her many meds. She does seem a bit happier to be home, and with trial and error, we figure out a safe enclosure situation (old baby bumpers on a 2x2 x-pen square with rolled up towels along all sides and many layers of padding beneath). We struggle but manage meds and feeding. We notice that Ruby's meclizine had been backed down during her boarding/hospitalization and I decide to increase it back to 3x/day, to see if it helps the rolling.
Day 20 (1/1): Today. Even with extra meclizine, it seems that Ruby is rolling even more than yesterday, and the severity of the rolling is difficult for both us and for her. Even in her small, padded space, she can flip over and over in the same position 4-5 times before her exhausted body finds a position in which to rest. If I had to describe it better, the word "rolling" wouldn't be strong enough -- it's like she has this pressure within her to violently flip again and again until she is worn out. Holding her in place can help, but not all the time. She's gotten the longest breaks from this rolling today while we were holding her to give meds/food, which took about 1 to 1.5 hours each time. That said, she is hungry, she is still looking for food and I think attention in her moments between rolls, and she still tries to groom. But today she is standing less than yesterday, trying to do whatever she can to minimize the rolling, but mostly to no avail.

To summarize health,
Day 0: Head tilt, dizzyness, nystagmus
Day 4: Improvement
Day 7: Downturn -- rolling begins
Day 8: Improvement
Day 13: Downturn #2 -- rolling intensifies
Day 20: Slight downturn, downward trajectory, or just down spirits?

And to summarize meds:
Day 0: Fenbendazole, SMZ-TMP, chinese herbal for dizziness
Day 2: Stop SMZ-TMP, start Camphenicol, start Meclizine
Day 6: Run out of meclizine, hell breaks loose
Day 7: Re-start meclizine, stop fenbendazole, start albendazole
Day 11: Refill Camphenicol (day 9)
Day 15: Add back SMZ-TMP, try Medazolam
Day 18: Add Baytril



So. Is there anything else we can try? Has anyone had rolling go on this long and still recover? I love this girl so much.

Sorry this is so long. There is so much more to tell about sweet Ruby and the impact she has had on our lives in her short half a year as part of our family, but today I am looking for advice.

Thanks in advance,
Melissa
(Mom to 5 bunnies over 40 years, starting with my childhood rabbit from pet store when I didn't know any better, then my first pair of rescues in my younger adulthood and now Ruby is the other half of my second pair; though I am technically 41, we adopted Ruby last May, when I was still 40)
 

JBun

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I think at this point I would be inclined to try the antibiotic zithromax(azithromycin). There are several accounts of it successfully treating head tilt caused by an ear infection in rabbits, when it seemed like there wasn't much hope. If I was in your situation I would want to give it a try, even over pen g injections, and it is given orally. If you google 'head tilt in rabbits and zithromax' it will bring up info on it's use and some personal accounts of it helping rabbits with head tilt. This first link has one account of a rabbit being successfully treated with it. Though do be aware, that though usually tolerated, there are some accounts of rabbits reacting badly to zithromax. So that is something to take into account. But to me, at this stage it would be worth the risk.
https://onthewonk.co.uk/headtilt-experiences/siouxsie/
https://onthewonk.co.uk/headtilt-experiences/lara-detailed-diary/
https://onthewonk.co.uk/headtilt-help/does-my-rabbit-have-headtilt/
https://wabbitwiki.com/wiki/Head_tilt

But antibiotics won't be effective if the head tilt isn't being caused by an infection. It it's EC or another cause, then antibiotics aren't going to help.

There's a facebook group called help for head tilt hoppers where you might be able to find support and further info to help your bun. It might also be worth asking your vet to consult with a rabbit specialist on treatment options.
https://www.facebook.com/groups/HelpforHeadTiltHoppers/
http://www.disabledrabbits.com/head-tilt.html
https://www.facebook.com/groups/201759429869484/
 

5bunniesin40years

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Thanks so much for your responses! If it is ear infection, I had read about azithromycin on several sites but hadn't looked into it systematically, so it is very helpful to see these links. I do wonder what the vet would think about adding a *fourth* antibiotic (camphenicol, SMZ-TMP, Baytril and Azithromycin) -- they were iffy about adding the third, and I really wanted to say they could discontinue SMZ-TMP because I read it wasn't helpful, but I was concerned that the prescribing vet for SMZ, i.e. the primary vet on our case, would not take well to my suggestion, and I need her to be on our side. They might suggest I discontinue the camphenicol because we've been on it for 20 days and it just ran out, but from what I've read, that has the best chance of working on an ear infection, though it admittedly has had no noticeable affect thus far, and I would like to give it at least 30 days before quitting. Has anybody been on 4 antibiotics at once? Ideally we would be on the three preferred abx, i.e. camphenicol, Baytril and azithromycin. I'm trying to prepare for my call in to the vet. I am hoping to get another Rx without subjecting Ruby to the stress of transport (it's only about 15-20 minutes to the vet, but the whole experience is traumatic with an uncontrollably rolling rabbit). I ostensibly have to call about the camphenicol, but will use the opportunity to ask for azithromycin.

If it is EC, I have read about ivermectin on Barbi Brown's bunnies website, but I've seen some warnings in other forums about it crossing the blood brain barrier being a *bad* thing for rabbits. At this point, however, I'd be willing to try new options. Does anyone have experience switching from albendazole (or any of the "zoles") to ivermectin? I would think that you wouldn't want to do both at the same time, but you would also want to give albendazole time to work. Also, do the 21 and 28 day milestones in parasitic treatment (i.e. the days you are supposed to disinfect like crazy) correspond to any clinical changes?

My vet didn't spend a lot of time trying to distinguish between ear infection and EC, other than the x-ray of the ear bones. I think her earlier peeing issues and the positive exposure titer are making them lean towards EC, and possibly also making them more grim because we have had no response to the antiparasitics thus far. So, I get the sense that the abx changes have been to humor me, more than because they think it will help. We never discussed central vs. peripheral signs, though I've done some reading online and don't think Ruby is a clear case either way. They noted "positional" nystagmus in her vet notes, but from what I can see, it is intermittent, and while a bit hard to tell with the head angle, I do think her nystagmus has been pretty much horizontal, or at most, at a bit of an angle (her head tilts to the right, so, looking at her up(left) eye, it rolls from right to left (or, perhaps, bottom right corner to upper left corner), and then flicks back). She has not shown any clear hind limb weakness or incontinence.

Also, I realized I forgot to mention a few things about our meds:
--When we started the third antibiotic, the vet added a daily dose of benebac. Thus far, no GI issues, and in general, she has not had gut issues since we adopted her last May. (My other little guy, different story -- we are well versed in stasis.)
--Ruby has been on meloxicam (NSAID) since day 0.
--Ruby was on reglan for the first 3 days because of her unwillingness to eat, but it was stopped once she regained sufficient appetite.
--I asked about steroids on day 0, but the vet said no

And finally, an update on condition:
We are getting her meds and feedings in, though it is taking two people about 1.5 hours each time (x3 per day). The violent rolling episodes continue. With the energy of her latest CC feeding, she is trying to groom herself and dig her towels in between rolling, and will eagerly nibble her favorite herbs as best as possible, but she really is rolling 75% of the time that she tries to move, and it frustrates her. She still tries to to her rabbity things, but it's incredibly difficult.

Thanks again, and I hope you don't mind my additional questions! Off to call vet, hoping for more meds!
 

JBun

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Ivermectin doesn't treat EC, regardless of what some sites claim. It's impossible due to the type of parasite that EC is(it's actually fungal) and ivermectin's action on parasites(affects the cns of only certain kinds of parasites). The cases where ivermectin appears to affect head tilt positively, would mean that there was either an underlying case of ear mites contributing to the head tilt issue(in which case the ivermectin cleared up the ear mites), or it's just a coincidence that the rabbit improved at the same time as ivermectin was administered. Ear mites is almost never the primary cause of head tilt, particularly in severe cases. I would only ever use ivermectin with caution when head tilt is involved, if it was a mild case and I suspected ear mites as the cause, or in a more severe case if there was a secondary case of ear mites contributing.

With what antibiotics to give, some antibiotics can't be given concurrently, but I'm not sure which ones can or can't from the list of ones you are giving. And with what antibiotics to continue with, my opinion is that there isn't much cause to continue with an antibiotic if it hasn't shown to cause any improvement over 2-3 weeks. It would likely mean the bacteria involved is not sensitive to that particular antibiotic, so no use in continuing to use it(or could also mean infection isn't the cause of the head tilt). There's just no reason I can see, to continue putting out the money and administering an antibiotic that isn't proving effective at all.

If baytril and azithromycin can be given concurrently, I would stick with those two. Though with the baytril I would make sure it's being dosed once a day at the higher recommended dosage, as opposed to what most vets do by dosing twice a day at a lower dose. Reason is that baytril works best off peak serum concentration. If your vet is having you do twice a day dosing, here is some info on the recommended once a day dosing. With the azithromycin, I would just phone them, say the sulfa and chloramphenicol haven't proved effective and that I would like to give azithromycin a try, and ask when to come pick up the new med. If you need to have documented evidence of it's success in treating head tilt in rabbits to convince the vet, make sure to have that ready to email to them. Best to find actual scientific studies to send them as opposed to personal stories.
https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/enrofloxacin
http://wildpro.twycrosszoo.org/S/00dis/Bacterial/Staphylococcosis.htm (this is about a staph infection, but under treatment it has the info and reference for once a day dosing for baytril)

I think the day 21 and 28 cleaning have to do with the EC life cycle, but I haven't read up on it enough to say how exactly.

Horizontal nystagmus usually points more to an ear infection, though not definitive.

What meloxicam dosage is being given (mg per kg of body weight)? Sometimes less experienced vets(with rabbits) dose this far below what rabbits need to be effective. With how severe things sound for your rabbit, it might be advisable to revisit the topic of steroids again. It's not usually advised in rabbits except as a last ditch effort when things are so severe that something drastic needs to be attempted. But it may be that you are at that point.

If you believe EC is the cause of this and want to concentrate on that treatment, usual dosage for fenbendazole is 20mg/kg once a day, but I have read of some vets prescribing 40mg/kg, however I don't have any references to support that dosage rate. With the possible risks of using albendazole that I have read of, I personally wouldn't chose to use it. Fenbendazole is the one most often used for treating EC, as it is the one that was used in the study on EC and rabbits. Fenbendazole is available otc as the goat dewormer Safeguard, liquid suspension. I don't recommend using the paste as it's intended for very large animals, which makes accurate dosing very difficult, risking possible OD. I would only use paste if it is the panacur manufactured for use specifically for rabbits.. I've used the Safeguard goat dewormer for my rabbits in the past. So if you suspect EC, it might be worth trying to find info on the higher dosage rate and discussing it with your vet.
 

5bunniesin40years

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Thanks again for your response, JBun. I wish I'd had the patience to wait for your tips before calling the vet, but I was anxious not to miss a dose of the abx we had just run out of (chloramphenicol). So, I called the vet, but as per usual (i.e. other than when my bunny was in emergency care), had to relay a message about the request for a change in meds to the doctor via the front desk, which did not facilitate my ability to make a convincing argument, nor to have an actual conversation about pros and cons. So when I arrived to pick up my refill, the front desk relayed back to me that the doctor was adamant about us giving the three abx we are on a longer time to work before making any additional changes. From what I've read, I'm not against this "give it time" approach in general for treatment of an ear infection, given how stubborn they can be, and I did doubt that any vet would approve four concurrent abx therapies, but I would much prefer to be on a better combination of drugs that have been shown to be specifically helpful for this type of infection, especially for difficult cases that are not responding to the standard treatment approach. I am disappointed that I did not leave with a new drug, but I guess I can see the logic, for the moment.

So, we remain on Chloramphenicol (Day 21), SMZ-TMP (Day 7 (well, + 2, because started in first week then stopped, and then re-started last Friday when I first asked for a new abx, though my husband was the one who approved the specific choice at the time because he was the one present; had I been there, I would asked for something else) and Baytril (Day 4). If Ruby's condition doesn't change, I will call in again when SMZ-TMP hits day 10 or 14 and use some of the strategies you suggested to ask directly for azithromycin, including the presentation of scientific data (my husband and I are both science PhDs -- it shouldn't be that hard!) -- if I can speak directly to the vet, that is. In the meantime, I will look into the once daily dosing for Baytril, because we are currently on twice daily dosing, but by my quick calculations, it looks like the concentration is already pretty high for 2x/day (2.1 ml per dose (bottle is 20mg/ml) = 40.2 mg per dose for a 2250g (approx, around time of Rx) rabbit = 18(ish) mg/kg per dose?).

I just checked on her meloxicam, and she is prescribed 0.6ml of a 4mg/ml bottle, 1x per day = 2.4 mg per day, and for her weight (2.25 kg), a dose of 1(ish) mg/kg per day -- this seems close to the higher amounts permitted for rabbits these days.

I really don't have a strong lean for infection vs. EC with the information I have from the signs that have been observed; if we had more diagnostics, e.g. brain CT or repeat titers on the EC (though we decided against this cost bc we already knew she was positive for exposure), or maybe a repeat x-ray of the ear (though I've never seen that done; I just know that I've read that you might not see a thickening earlier in the infection disease process) or something in the ear that could be reached for purposes of culture (it was implied to me that the outer ear looked clear but since the inner ear was out of reach, a culture would not be possible, and now that we are in abx and don't want to stop, a culture would be useless), maybe, but given her symptoms, I really don't have a sneaking suspicion either way. And from what I've read, despite a lot of ambiguity and controversy over the years, having one isn't necessarily better or worse than the other as a primary cause of the head tilt (if EC can ever be the primary cause, according to one of the sources I had read), from a prognosis standpoint if treated with the most aggressive therapy currently available.

Thanks for the additional information about ivermectin; there does seem to be a lot of controversy about its use for these purposes, but I hadn't delved deep enough to figure out what side I landed on. I expressed my concerns about albendazole (after it had been prescribed and started and after I had a chance to read up on it) after she was on it for about 10 days and asked if bloodwork would be a good idea to see if it was having any negative effects on her blood counts; the vet agreed to bloodwork but also stated that they had switched to it because it was just a "stronger version of fenbendazole" that doesn't need to be metabolized by the liver first and thus was prescribed when Ruby took her first downturn at the 1 week point to act more directly on the parasite, and that concerns about it on the internet were not well founded. The bloodwork came back fine, save for some elevated immunoglobulins (generally elevated in an inflammatory state), so I let it be, but I do wonder if we could "step down" back to a higher dose of fenbendazole (they gave me the rest of her bottle since I had paid for it) to reduce serious side effect risk for the full course without messing up the mechanism of the drugs action on the EC life cycle. I do wish we had just stayed on the one drug for 28 days, and instead had switched up the abx at that 1 week point!

So, while I continue to keep my fingers crossed (for the night; I might be banging on the vet's door again tomorrow) about slowly but steadily fighting infection (of either variety) with the drugs already on board, do you have any suggestions for meds or strategies to reduce the rolling itself? This is probably the most distressing symptom I have ever witnessed in a rabbit, and I hate not being able to help her. Ruby has been on meclizine since Day 3 and I honestly don't think it helps much because I cannot imagine the rolling being any worse, though she did take her first downturn after we ran out of our first Rx of meclizine. The sedative (midazolam) did not seem to have any effect either, nor has the chinese herbal medicine (Di ta ten) she was prescribed. That is, I don't see any improvement shortly after dosing. As for strategies, I have found that touching her body on the opposite side from her tilt makes her lean towards my touch, and thus can sometime avert an imminent rolling episode, but this isn't always successful (nor can I always have my hand on her). I've read about PT, but I figure that is something that you dont' do until your rabbit is clearly on the road to recovery by obvious response to medication in the fighting of infection, and I don't think we've hit that point. So, I've been doing things like leaving the light on at night, creating towel "tracks" for support (that last all of a minute before she flips and messing everything up) within her small enclosure and the hand support thing described above, but any additional tips are welcome.

Finally, thanks for the recommendation of the facebook site -- I don't use facebook for social media purposes anymore, but I appreciate the value of having access to very specfic communities, e.g. the rabbit head tilt community -- I plan to watch a couple of their videos for tips on how to medicate rabbits with a tilt, because that angle and the rolling present significant obstacles.

It's time for another nightly vigil with my sweet girl a few feet from my bed...I keep hoping that the next day is the day things turn around...
 
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