As discussed last week, a neurodisability score (NDS) has been proposed for use in dogs with meningitis of unknown origin (MUO). The goal is to help grade the clinical signs more objectively and, hopefully, prognosticate more accurately. The score was developed by Drs. Goncalves et al (https://doi.org/10.1111/jvim.16717) from the UK and published in 2023.
A retrospective evaluation of medical records was performed to identify common clinical signs at presentation. Subsequently these signs were grouped in to the following categories for prospective use: seizure activity, ambulatory status, posture and cerebral, cerebellar, brainstem and visual signs. For the prospective part, the score was tested on 31 dogs diagnosed with MUO. Table 2 of the published article has an outline of the scoring system which I would suggest you look at if you have time. As an example, under the “ambulatory status” section the options are “normal, mild paresis or ataxia but ambulatory without falling, moderate/severe paresis or ataxia with frequent falling, and nonambulatory”. Each of these options is given a numeric score from 0 (least severe) to 3 (most severe). As the categories are worked through, points will be accrued based on their neurologic exam. The maximal score is 21, indicating he most severe disease. According to the article, the mean score at presentation was 8 +/- 2.85 points. All of the things that you imagine would affect this score such as concurrent disease, treatment prior to referral, and evaluator skill must be considered here (which the authors did consider, for the most part). In the end, they found a significant difference in dogs that survived to discharge (median 8; range 3-14) and those that did not (median 12.3; range 8-13). You can see as well as I can that there is marked overlap between the ranges which makes it difficult in a clinical patient to draw conclusions. Furthermore, the study did not evaluate validity (did the test measure what it was supposed to be measuring) and did not find an association at a specific cut-off value related to long-term outcome. The study presented in last weeks TidBit Tuesday suggested a cut off value of 7 would be used to predict death by 6 months for dogs with MUO. I’m ecstatic that this work is being done but caution you to use it with care. Euthanizing a pet simply based on this score feels inappropriate at this time. Predicting a poorer possible outcome at 6 months and relaying this information to a client would be an appropriate use of the NDS. It IS encouraging that we may have a universally available tool for ALL VETS (i.e. not a specialty tool like an MRI, or a neurofilament in CSF) that we can use to talk about MUO in objective terms. As with most of the TidBit Tuesdays there will be much more to come on this topic over time so stay tuned!
Thanks for reading! Changes to my schedule are once again upon us as the summer sets in. My schedule varies WEEKLY so please reach out if you have a case that needs to be seen but cannot find a suitable time on the schedule; I may have more flexibility than what is listed, so please ask. I will be closed at the end of June for a few days for a family wedding, and mid-July for the Dane County Fair but otherwise anticipate high availability for you this summer. Enjoy the beautiful spring weather and the delicious smells of blooming things this week!
The Prognosis Meningoencephalitis of Unknown Origin
Meningoencephalitis of unknown origin (MUO) is a frequent diagnosis for dogs with multifocal neurologic signs. The name should tip you off that we’re still figuring out this interesting disease amd do not know the underlying cause yet. It is thought to be immune mediated, and therefore treatment often includes an immunosuppressive dose of steroids +/- an additional immunosuppressive such as cytarabine, azathioprine or cyclosporine. Despite decades of awareness of this disease we are still working out the prognostic indicators. Back in my academic days, a resident of mine and I tried to sort out this question by evaluating brain MRI results, with little success. A recent study took another crack at the elusive prognostic indicators and published their findings in JVIM (Goncalves R, et al. JVIM 2024).
Materials and Methods
447 dogs were included in this retrospective study from 2 institutions. Did you see that giant number of included cases?? Go vet med, go! Anyhoo, the authors included dogs with signs of inflammation (brain MRI, spinal tap) and because it was a retrospective study, there were a number of different treatment protocols included. Perhaps this creates too much variability to carefully evaluate outcome or prognosis. I might argue that there is no other way to accrue a large number of cases of MUO. A neuro disability score (NDS) was assigned to these patients (score developed by the author and several others and published in 2023). Survival was reported.
Results
I’m going to list some of the key results below but if you wish to learn more about the results, please refer to the article. It is well written and comprehensive.
Median age at presentation was 48 months
The majority of breeds represented were small breeds, but a few Labs, spaniels, and larger dogs were also included.
The season of diagnosis was equal across all 4 seasons
Common presenting complaints were proprioceptive deficits (77%), ataxia (65%), obtunded mentation (62%), seizures (32%).
The most common neuroanatomic lesion localization was multifocal (43%), followed by forebrain (29%)
Median follow-up time was 11 months. 82% of dogs survived to discharge and 63% were alive at 6 months.
A significant difference in survival was noted for dogs WITH a NDS compared to those without and a score of greater than 7 resulted in a sensitivity of 61% and specificity of 67% for predicting death at 6 months after diagnosis.
Relapse occurred in 50% of dogs that survived to discharge
Of those that relapsed, incomplete resolution of neurologic disease during the 6 month follow-up period, a higher NDS and neurologic signs >7 days duration before intervention were statistically associated with relapse.
What should we do with this information?
The take home message should be that we should perform a NDS on patients with suspected or confirmed MUO to help provide a prognosis AND that a more rapid referral may provide a better long-term outcome.
Stay tuned next week for a review of the NDS! Thanks for reading and I Hope you have a great rest of your week!
Predictive Signs for MUO
Meningoencephalitis of unknown origin (MUO) is a non-infectious, inflammatory brain disease common in dogs. The vast majority of dogs diagnosed with meningoencephalitis have MUE, not infectious meningitis. MUO includes granulomatous meningoencephalitis (GME) and the necrotizing encephalitides (NME,NLE) and is the term used to describe antemortem non-infectious, inflammatory CNS diseases in dogs and cats. Providing owners with a prognosis when diagnosed with MUO is extremely challenging. A recent study evaluated several prognostic factors on the early survival in dogs with MUO. (https://www.sciencedirect.com/science/article/abs/pii/S1090023322000995)
Key Points:
98 dogs with MUO were included. 30/98 died within 30 days of the diagnosis.
Adding cytosar to a glucocorticoid protocol did NOT alter the prognosis.
Obtundation at presentation was the ONLY factor statistically associated with poor prognosis. Dogs had a 6.6x higher odds of death in the first 7 days, 2.1x increased risk in the first 30 days when presenting with obtunded mentation.
What does this mean for your patients?
It means that we still have a long way to go when sorting out what MUO means, and how it affects dogs. It means that a dog with a severely elevated WBC on CSF, or with other abnormalities on neurologic examination do not necessarily have a poorer prognosis. If you are seeing a patient with multifocal CNS neuroanatomic lesion localization, be sure to evaluate the pet's level of mentation. Survival may be reduced if obtundation is present. Refer as soon as possible for a neurology consultation and/or work up, depending on client preferences.
References: Lawn RW, Harcourt-Brown TR. Risk factors for early death or euthanasia within 100 days of diagnosis in dogs with meningoencephalitis of unkonwn origin. Vet J 2022. vol. 287.
Short and sweet this week. This article was too good to pass up, so please excuse the short TidBit Tuesday this week.
Safe fast to those of you observing Yom Kippur, Happy Feast of St. Francis of Assisi day and Happy Cinnamon Roll day to the rest of you! (Yes, that is actually a THING on October 4th.
Neospora Meningoencephalitis vs Immune Mediated Meningoencephalitis
Immune mediated meningoencephalitis (aka meningitis of unknown origin: MUO) is very common and is a cause of intracranial disease for many pets. Infectious meningoencephalitis accounts for only about 2% of the cases seen through a referral center and is, therefore, in the minority. Infectious meningitis may be secondary to fungal infection, protozoal (Toxoplasma or Neospora), viral, bacterial or in southern states, some tick borne diseases. Neospora infection is one of the more common causes of infectious meningoencephalitis we see in Wisconsin (probably second only to fungal) and therefore one of the main differential diagnoses for a pet with meningoencephalitis. The current way to diagnose Neospora is via serum titer elevation, evidence of encysted protozoa on biopsy or necropsy, or PCR on serum or CSF. All of these tests take a variable amount of time, depending on the laboratory, so some researchers in the UK came up with another idea. (https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.16334)
Scientific Question: Can we differentiate between Protozoal meningoencephalitis and MUO using CK and AST values?
Rational: Protozoa (Toxoplasma and Neospora) are often found in muscle which would result in membrane disruption, thus elevating CK (and subsequently AST). Seizures, a common sign of MUO and protozoal meningoencephalitis, can also elevate CK so the researchers also aimed to evaluate the temporal relationship between seizures and CK elevation.
Methods: This was a retrospective study of 59 dogs diagnosed with MUO and 21 dogs diagnosed with Neospora (no dogs were diagnosed with Toxoplasma in this study).
Results: A significantly higher CK and AST value were identified in dogs with Neospora compared to those with MUO. Using a cutoff value of 458 U/L, there was a sensitivity of 95.24% and specificity of 96.61% for active Neospora meningoencephalitis and using a prevalence of 2.25% for active infection in the UK, there was a negative predictive value of 99%. This suggests that dogs with a CK less than 485 U/L are unlikely to have a diagnosis of Neospora infection associated with their intracranial signs. Twenty of 21 dogs with Neospora had CK higher than 485 U/L, and 2 dogs with MUO had CK > than 485 U/L in this study.
Things to remember: CK has a short half-life (22 hours) so if you test, do so within the acute phase of disease. CK and AST are not muscle specific and can be found in myocardium, intestine and AST in the liver also.
What do you do with this information? If you have a dog with suspected meningoencephalitis, consider running a CK and AST on initial blood work. If it is greater than 485 U/L, a Neospora titer should be performed.
Have a great week and thanks for reading!
Note about the holidays: I will be available for emergency cases on December 24, and 25th.
New Years Eve and Day, I will be spending time with my family building a colossal gingerbread house and stables. If I'm not baking, cutting and cooling gingerbread I will be making sticky frosting glue and won't be available for phone calls, texts or email. Thank you for your understanding!