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.

Neutrophil-Lymphocyte Ratio in MUE

Meningoencephalomyelitis of unknown etiology (MUE) is a challenging antemortem diagnosis. MUE is the term used when we diagnosed inflammatory, non-infectious disease in the CNS. In the old days, we would have called this GME, NME or NLE, depending on the breed. However, those three inflammatory conditions cannot be distinguished on clinical picture, diagnostic testing, or treatment response, alone. Histopathology is needed to determine if a patient has GME, NME, and NLE. Without a brain biopsy, or post mortem sample, we cannot call it GME, NME or NLE. Several years ago, the term MUE started getting tossed around as an antemortem term for inflammatory brain disease, without a biopsy.

To diagnose MUE, a patient must have:
1) a neurologic examination with deficits identified (or a history of seizures) and
2) have a MRI with classical changes and
3) and CSF tap with a lymphocytic or monocytic pleocytosis and/or elevated protein level and
4) negative geographically specific infectious disease panel. If the pet meets these criteria, they can be diagnosed with MUE. 

MUE does not show up in routine blood work. Inflammatory leukograms are rare, elevated body temperature is not typically reported and pets are not systemically, clinically ill. However, some immune mediated diseases (such as MS) have garnered attention for a neutrophil to lymphocyte ratio present on routine CBC. 

A recent study out of Korea evaluated the ratio of neutrophils to lymphocytes in a standard CBC to see if we could predict a diagnosis of MUE. As it turns out, you can divide the neutrophil count by the lymphocyte count, and get a significantly higher number in dogs with MUE than healthy dogs. Furthermore, the ratio was significantly higher than dogs with idiopathic epilepsy but NOT different than dogs with brain tumors. The neutrophil-lymphocyte ratio was higher in dogs with MUE than all other forebrain diseases (hydrocephalus, idiopathic epilepsy, and brain tumors) but not always significantly so. 

What does this mean for us?

Unfortunately, nothing...yet. This is an interesting concept and a step towards a much needed tool for diagnosing MUE without invasive diagnostic testing. Performing a CBC, and calculating the ratio, is both simple and readily available in most (all?) veterinary practices today. However, if the ratio is high, it does not mean the pet has MUE. It may support a diagnosis of forebrain disease (which you already know from your neuro exam) and may support structural brain disease (i.e. not idiopathic epilepsy). Very importantly - this study did not find a significant difference between dogs with brain tumors and those with MUE. Sadly, brain tumors and MUE are often our top differentials for pets with forebrain disease so this ratio does not (yet) give us another non-invasive tool to differentiate between these two diseases. 
I enjoyed reading this study and learning about inflammatory markers for humans with MS (the human counterpart to MUE) and how this neutrophil-lymphocyte ratio could be used in the future for pets. If you'd like to read more, please see the link at the bottom of the page. 

Thanks for reading! I hope you have a wonderful week and look forward to working with you soon!

If you haven't heard yet, please note that I am moving my office. Please try to remit any outstanding invoices by August 30th. If you need my new invoicing address please email me, or watch for a note in the mail. 

Reference: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.16512

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!