How do MRI lesions affect survival for MUE?

 
A study was published this week that looked at the survival times between dogs with and dogs without MRI lesions and diagnosed with meningoencephalomyelitis of unknown etiology (MUE). MUE is diagnosed if a dog has evidence of CNS inflammation (meningitis, encephalitis, myelitis or a combination of these) without evidence of infectious etiology. Signs can be focal or multifocal, and age is irrelevant. To make this diagnosis an MRI, CSF tap, and infectious disease testing are performed. There is a subset of dogs that are diagnosed with immune mediated CNS disease that do not show evidence of disease on MRI but have all of the other markers of MUE. The purpose of this paper was to determine if there is a difference in survival between the two groups of dogs.
Results
A total of 73 dogs with MUE were included in the study. This included 19 dogs with a normal MRI and 54 with an abnormal MRI. The survival time was >107 months in both groups with a significantly longer survival in the normal MRI group. Neither group reached median survival in Kaplan-Meier survival, however. Death was secondary to MUE in 1/19 dogs with a normal MRI, and 18/54 in dogs with an abnormal MRI.
Below is the breakdown comparison between the two groups:

• Remission – 68% of the normal MRI group; 53% of the abnormal MRI group.

• Death within 3 months due to disease – 5% in the normal MRI group and 13% in the abnormal MRI group.

No difference was found between dog groups regarding remission, disease-free interval, or relapse while on prednisone. The two groups received similar treatment protocol, for which corticosteroids were included in all dogs and a variation of additional immunosuppression. The total nucleated cell count (TNCC) was higher in the dogs with the abnormal MRI however this did not correlate with higher rates of death after multivariate analysis. The only significant factor associated with death was the presence of an abnormal MRI.

Why don’t they have lesions on MRI?

Perhaps we’re catching these cases early in the course of disease. This would stand to reason why they might have a lower death rate than those with more progressive disease at the time of diagnosis. Another option is that this is a different form of inflammatory brain disease. MUE is a “catch all” for inflammatory brain disease that isn’t infectious, or a specific form such as SRMA or EME. It likely includes all of the previously diagnosed cases of GME and NME.
Take away: If you have a dog with spinal pain, seizures, vestibular signs or multifocal CNS signs remember MUE! This disease can cause all of those signs, and a collection of other signs, in dogs. Early detection may = improved outcomes. So, if your patient is showing neurologic signs, please reach out to get a consult ASAP and to proceed with additional testing when able. We might just save their life!

Thanks for reading! I hope you are scratching out the very best that summer has to offer. I look forward to working with you soon!

Reference: Survival in dogs with meningoencephalomyelitis of unknown etiology with and without lesions detected by magnetic resonance imaging. Ostrager A, Bently, TR, Lewis MJ, Moore GE.
 

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!

Early detection of Pug Encephalitis

Pug encephalitis, termed necrotizing meningoencephalitis (NME), is a common cause of CNS inflammation in Pug, Maltese, Chihuahua, Shih Tzu and other small breed dogs. The typical presentation is a dog less than 4 years old with acute, progressive, multifocal CNS signs. (However, meningoencephalitis is the great pretender so it may present in ANY age, breed, sex, and with neurologic examination findings!) Many Pugs are reported to be resistant to immune suppression, however this is not a global truth. On histopathology, areas of necrosis are identified, along with infiltration of inflammatory cells which leads to the term necrotizing meningoencephalitis. Antemortem, a diagnosis cannot be rendered. MRI and CSF changes would lead a practitioner to a diagnosis of meningoencephalitis but without histopathology (biopsy or necropsy) the dog would be diagnosed with meningoencephalitis of unknown etiology (MUE). MUE includes the necrotizing meningoencephalitis and granulomatous meningoencpehalitis thus it is not a histopathologic diagnosis but a clinical one.

What if we could detect NME earlier?

Researchers recently published a study with this question in mind. They evaluated 36 pug dogs that were deemed clinical normally by their owners. Genetic studies were performed; 5 homozygous/high risk, 19 heterozygous/medium risk and 12 low genetic risk (previously published data about genetic link) dogs were included. They then performed 2, sequential neurologic examinations on these dogs at least 4-6 weeks apart. Dogs that were considered repeatably abnormal subsequently underwent MRI (spine, brain, or both) and had a CSF analysis performed.

Results of the study

Dogs considered low risk had 0 repeatable abnormalities on neurologic examination. Eight of the 36 "at risk" pugs had repeatable abnormalities. Abnormalities included back pain, menace deficits, ataxia and paw replacement deficits (1 or more). The only statistically significant finding was multifocal spinal pain. The 8 dogs underwent imaging and mild brain abnormalities were noted in all dogs with variable severity. CSF changes were noted in 3 of the 8 dogs.

What is the actionable result of this study?

The take away here is that the MRI was more sensitive to detecting "pre clinical" NME than CSF analysis. Is this actually "pre clinical" if the dogs had repeatable neurologic examination abnormalities? I argue perhaps not, perhaps they were "undetected" by clients rather than preclinical. That said, we don't subject dogs to annual neurologic exams without reason so perhaps this is a reasonable way to conduct the study. (Maybe we should??) I always ask myself: what I would do with the information gained when I suggest a test or procedure? In this case, would I treat this dog with "pre clinical" MRI changes or would we wait to see if this develops into progressive disease? I don't know the answer to this question and they didn't pursue treatment in this study so I don't have an objective answer for you. For me, these types of studies will help us help dogs considered genetic "at risk" for NME. Perhaps we identify treatment earlier? Perhaps we find out that there is a specific environmental trigger? Perhaps you learned that there is a genetic "risk" for pugs. Have a pug patient or pet that you think should be genetic tested? Here is the link: http://www.vgl.ucdavis.edu/services/dog.php

The big question is - at risk does NOT equate to disease - so what do we do with the information??

Thanks for reading today. I really enjoyed reading this study and hope you enjoyed my summary.

Have a great week and keep those consults rolling. My kids will be in and out of different camps this summer so my schedule will be changing week-by-week. As always, please reach out if you cannot find a suitable time for your patient using the online scheduler and I will do my best to find timely spot!

Meningitis...Encephalitis...?

Canine Meningitis...Encephalitis...Meningoencephalitis... oh bother...

Canine Meningitis...Encephalitis...Meningoencephalitis... oh bother...

Canine meningoencephalitis is a general term, used to collectively describe inflammation in the brain and meninges of dogs. Although infectious meningoencephalitis can occur, the majority of dogs have a non-infectious, inflammatory disease.

Remember the term GME? Well, that is only ONE type of non-infectious inflammatory meningoencephalitis! Note: to call it GME we need histopathology. Not surprisingly, many clients do not opt for brain biopsies so we cannot confirm if it is GME, or NME or NLE or another histologic subtype of inflammatory brain disease antemortem. That won't do!

IF I CANNOT CALL IT GME IN A LIVE PATIENT, WHAT DO I CALL IT?

We call the collection of non-infectious, inflammatory brain diseases Meningoencephalitis of Unknown Etiology (MUE). Or, if you're British it's MUA (aetiology). Or, sometimes its called MUO (origin). Shoot, we're back to alphabet soup again. 😒 When we settle on a term, I'll let you know, but for now the literature typically refers to non-infectious, inflammatory brain disease as MUE. (Not GME)

CLINICAL SIGNS
* Any age, breed or body condition. (cats too!)
* Chronic or acute progression of signs (I've diagnosed it in dogs with clinical signs for 6 months, and those with a 24 hour history of signs).
* Multifocal or focal neuroanatomic lesion localization.
* Unless the dog has SRMA (one form of non-infectious inflammatory brain disease), fever is NOT a common clinical sign.

DIAGNOSIS
MUE is a clinical diagnosis which must be supported by diagnostic investigation. Without diagnostic investigation the word presumptive is recommended, or simply include MUE in the listed differential diagnoses in the medical record.

* Magnetic resonance imaging (MRI) focused to the area of neuroanatomic lesion localization
* Cerebrospinal fluid (CSF) analysis
* Negative geographically specific infectious disease testing
We cannot diagnose MUE with blood work, or on neurologic examination alone. (Sorry)

Extra tidbit - GME is not caused by vaccination or population density according to a recently completed study!*

TREATMENT
Standard treatment is immunosuppressive glucocorticoid therapy (1 mg/kg twice daily prednisone or prednisone equivalent dose) because of the ease of administration for owners, good penetration through the blood brain barrier and comparatively low cost. A slow taper over months is recommended, however some animals require medication for life. If glucocorticoid therapy is intolerable to dog or owner, other protocols could be considered.

PROGNOSIS
Survival to 3 months is the most reliable predictor of long-term survival.

What do I tell clients? Start treatment, and repeat a CSF tap at 1 month. If the pet is doing well, CSF tap is normal or normalizing, keep going. If all is going well by 3 months, consider repeating another CSF tap and continue to monitor life-long for relapse of clinical signs. The prognosis is based on the old saying, " if the dog is doing well, it's likely to do well." Sigh...just a sign that we have a lot more work to do sorting out this disease.

As a small business, I sincerely appreciate your business and your willingness to continue to support mobile neurology. I am the only mobile veterinary neurologist in Wisconsin and Illinois and, I appreciate your support!

Stay Safe, and Happy December Everyone!

*Barnes Heller HL, Granick M, Pinkerton M, Keuler NS. Case-control study of risk factors for granulomatous meningoencephalomyelitis in dogs. JAVMA 2019:254(7):7-10.