July 2025
In this VETgirl online veterinary continuing education blog, Dr. Missy Carpentier, DACVIM (Neurology) details the inflammatory diseases of the central nervous system with a focus on meningoencephalomyelitis of unknown origin (MUO) and other non-infections inflammatory CNS diseases. Diagnosing inflammatory CNS disease cannot be based solely on the neurologic exam and blood work. It often requires advanced diagnostics such as MRI and CSF. Inflammatory disease of the nervous system is more prevalent than many realize, and it is important to include this disease as a differential for your neurologic patients.

Inflammatory Disease of the Nervous System

By Missy Carpentier, DVM, DACVIM (Neurology) with Minnesota Veterinary Neurology, Columbus, MN

Inflammatory disease of the central nervous system is a term used to describe several different conditions that cause inflammation of the CNS, specifically meningitis, encephalitis and myelitis. Inflammatory disease of the CNS can have both infectious and non-infectious etiologies, with non-infectious inflammatory CNS disease most common. Specific histologic subtypes of non-infectious inflammatory disease cannot be identified on antemortem tests and therefore it has led to the term meningoencephalomyelitis of unknown origin (MUO). This is what we call an umbrella term which includes several different subtypes of idiopathic encephalitis’ that include: granulomatous meningoencephalomyelitis (GME), necrotizing leukoencephalitis (NLE), and necrotizing meningoencephalitis (NME). Steroid responsive meningitis arteritis (SRMA), eosinophilic meningoencephalitis, and idiopathic tremor syndrome are part of the non-infectious category, but with distinct findings they are considered outside of the MUO category. This summary is focused on the MUOs and other non-infectious inflammatory CNS diseases. There is some information on infectious inflammatory disease in the diagnosis section as it is important that you rule out infectious causes prior to immunosuppressing your patients.

SIGNALMENT AND CLINICAL SIGNS

** IF THE PATIENT FITS INTO A PURSE YOU NEED TO HAVE INFLAMMATORY CNS DISEASE ON YOUR LIST OF DIFFERENTIALS. **

Although inflammatory CNS disease can affect any dog or cat, small, female dogs between 3-7 years of age are most commonly affected by all subtypes of MUO. Specific breeds that are over-represented include Pugs, Yorkshire Terriers, Maltese, and French Bulldogs. Specific breeds that fit outside of the purse category are those affected with SRMA, which are commonly your young, large breed dogs (think of the B’s – Boxer, Bernese Mountain Dog, Beagle, Border Collie, and then others include Weimaraner, Novia Scotia Duck Tolling Retriever, Whippet, and Springers).

The neurologic signs of inflammatory CNS disease are quite variable, and often are associated with the specific part of the CNS that is affected. Some of the most common clinical signs include lethargy, behavioral changes, seizures, circling, vestibular signs, spinal hyperesthesia, and paresis. Most of these patients have a multifocal neurolocalization. It is common for these patients to also have systemic signs of disease, including vomiting, diarrhea, or inappetence. Being febrile is NOT common with most inflammatory CNS cases, except for SRMA.

DIAGNOSIS

There are several CNS diseases that can present in the same manner as inflammatory CNS disease. Because of the overlap, the diagnosis of inflammatory CNS disease cannot be based solely on the neurologic exam and blood work. Further testing, including MRI and cerebrospinal fluid analysis (CSF analysis) are extremely important diagnostic tests when inflammatory CNS disease is suspected. The MRI reinforces the suspicion of inflammatory disease and can rule out other causes of neurologic disease, while the CSF can help confirm if inflammation is present, as well as the type of inflammation. The CSF can also be used to evaluate for certain infectious organisms or perform further infectious disease testing. Once the MRI and CSF supports the diagnosis of inflammatory disease, the next step is to rule out infectious etiologies prior to immunosuppressing the patients (in severe cases, this may not be an option, and immunosuppression may need to be started immediately following the MRI and CSF if it is highly likely that we are dealing with a non-infectious case).

MRI AND CSF

MRI is the recommended cross sectional imaging tool when evaluating for inflammatory CNS disease. The most common findings on MRI include T2W and FLAIR hyperintense lesions, T1W isointense to hypointense lesions, and variable contrast enhancement throughout the brain and meninges. It is important to recognize that 25% of inflammatory CNS disease cases can have a normal MRI, therefore a normal brain MRI does not completely rule out inflammatory CNS disease. Following the MRI, a spinal tap is routinely performed unless there are contraindications to so do (such as brain herniation, evidence of elevations in intracranial pressure, or severe Chiari malformation).

The changes that will be present on the CSF are directly related to the status of the blood-brain-barrier and the meningeal involvement. Patients that have “deep” brain inflammatory lesions with minimal meningeal involvement can have normal CSF despite drastic findings on MRI. The most common CSF findings for non-infectious inflammatory disease include:

 

Once you have diagnosed inflammatory CNS disease, the next step is to rule out any infectious causes. The most common infectious disease etiologies that will be assessed based on each individual case includes:

  • Lyme disease, Ehrlichia, and Anaplasma (commonly assessed with a 4DX)
  • FELV/FIV
  • Cryptococcus Antigen Latex Agglutination
  • Toxoplasma IgM/IgG titers
  • Neospora – IFA
  • Aspergillus Antigen
  • Histoplasma Antigen
  • Blastomyces Antigen
  • Coccidioides Antigen
  • Canine distemper virus
  • Rabies

TREATMENT

The treatment protocol that is chosen will depend on the primary cause. In cases of infectious disease, treatment consists of the appropriate antibiotic or antifungal medication. While we are waiting for infectious disease testing results, most patients are started on clindamycin 12.5mg/kg PO BID and doxycycline 10mg/kg PO SID. If there is a high index of suspicion for fungal disease, then an -azole will be started. Even in cases of infectious inflammatory CNS disease, most patients will need steroids to provide an anti-inflammatory effect. Once you start treating the infection, there will be a large die off-of organisms leading to an immense inflammatory response that we need to control.

The goal of treating non-infectious inflammatory CNS disease is immunosuppression. This idea lies within the understanding that this is an autoimmune disease and therefore to induce remission we need to inhibit the inflammation and modulate lymphocytic function. The most common and often most needed medication is corticosteroids, and other immunomodulatory agents are added in based on response to treatment and severity of clinical signs. Other medications that need to be considered will include start of a long term anti-epileptic drug (if they present with seizures) and analgesics due to the hyperesthesia that is present with meningitis. Depending on the severity of signs, stabilization with oxygen supplementation, fluids to maintain cerebral perfusion, and osmotic therapy to reduce elevations in ICP may be necessary.

Any time steroids are needed the goal is to achieve disease remission and do our best to control the side effects associated with steroids. Often the steroids are started at an anti-inflammatory dose (0.5-1mg/kg/day) and increased to an immunosuppressive dose (2-4mg/kg/day) once we know infectious disease testing is negative AND if the patient isn’t doing well on the current prednisone dose, therefore indicating an increase is required. If the patient is doing well on just an anti-inflammatory dose, then the dose will not be increased. The majority of my MUO patients are most commonly treated using between 1-2mg/kg/day of steroids (it is not common that I need to go higher on my dose, but of course there are exceptions). Also, no patient needs to receive more than 40mg of prednisone a day. So, in large breed dogs, I never go above a TOTAL dose of 40mg/day, even if their weight says they should be getting more.

Most patients will need to be on steroids for a minimum of 8-12 months. The goal is to slowly taper these patients down on their dose of steroids and get them to an every other day dose, sometimes even a twice weekly dose, and then try and discontinue the steroids. Unfortunately, relapses are common, and some patients are never able to be discontinued off the prednisone.

Long term prednisone side effects can be hard on the owners and the patient, and that is one of the reasons that we will also add in a 2nd immunomodulatory agent in a “prednisone-sparing” effect.

Other reasons that we will add in a 2nd immunomodulatory agent include:

1) Severity of clinical signs

2) Lack of complete response to steroids

Other immunosuppressive/immunomodulatory agents that I commonly use include cytosine arabinoside (Cytosar), cyclosporine, and mycophenolate, but others that can also be used include leflunomide, procarbazine, lomustine, azathioprine, and COP (cyclophosphamide, vincristine, in addition to the prednisone). Selection of what 2nd agent to use is case dependent, but I will say that I have the most success with the addition of Cytosar intravenous infusions. These infusions are generally given at a dose of 200mg/m2 IV over 8 hours every 28 days to start, and the frequency is extended to 45 days based on how the patient is doing.

PROGNOSIS

Prognosis for these cases used to always be grave, however, with further understanding of the disease process’ and earlier diagnosis, these patients can do well. I give owners the rule of 3 for prognosis – I base it on how the patient is doing 3 days, 3 weeks and 3 months post treatment. It is important for owners to realize that these patients are never cured, our goal is to get them into remission. As such, relapses are always possible – even years after completing treatment. Because of this, and some of my worse relapses being post vaccines, I do not recommend vaccines for these patients both during and after treatment.

 

SUMMARY

Inflammatory disease of the nervous system is more prevalent than many realize, and it is important to include this disease as a differential for your neurologic patients.

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