Non-Infectious Meningoencephalitis: MUE, Idiopathic Tremor Syndrome, and SRMA

Inflammatory diseases of the central nervous system can present in dramatically different ways—from seizures and vestibular signs to generalized tremors, fever, or severe cervical pain.

Among the more commonly encountered non-infectious meningoencephalitides in dogs are meningoencephalitis of unknown etiology (MUE), idiopathic tremor syndrome, and steroid-responsive meningitis-arteritis (SRMA).

Although their presentations, treatment approaches, and prognoses differ, these diseases share an important characteristic: they appear to be immune-mediated and behave clinically much like autoimmune diseases.

Understanding their typical presentations can help veterinarians recognize when inflammatory CNS disease should move higher on the differential list.

Understanding the Terminology

The terminology surrounding non-infectious meningoencephalitis can be complicated.

Historically, several terms have been used to describe inflammatory diseases of the canine central nervous system, including:

• GME – Granulomatous meningoencephalitis

• NME – Necrotizing meningoencephalitis

• NLE – Necrotizing leukoencephalitis

• MUE – Meningoencephalitis of unknown etiology

• SRMA – Steroid-responsive meningitis-arteritis

GME, NME, and NLE are histopathologic diagnoses, meaning definitive differentiation requires evaluation of brain tissue. Because brain biopsies are rarely performed in clinical patients, these conditions are now commonly grouped under the broader term MUE when non-infectious meningoencephalitis is suspected.

Two relatively common inflammatory conditions that fall outside the MUE umbrella are idiopathic tremor syndrome and SRMA.

What Causes These Diseases?

MUE, SRMA, and idiopathic tremor syndrome appear to be immune-mediated diseases without an identifiable trigger.

While an auto-antigen has not been established well enough to classify them as true autoimmune diseases, their clinical behavior and response to immunosuppressive treatment closely resemble autoimmune conditions.

Numerous infectious diseases have been investigated as possible underlying causes without identifying a definitive infectious trigger.

Importantly, there is currently no good evidence suggesting that vaccination or particular medications cause these conditions.

Meningoencephalitis of Unknown Etiology (MUE)

Which Dogs Are Most Commonly Affected?

Most dogs with MUE present between 6 months and 8 years of age, with no apparent sex predisposition.

Small and toy breeds account for the majority of cases. Genetic predispositions have been identified in Pugs and Maltese, while other commonly affected breeds include:
 

• Yorkshire Terriers

• Chihuahuas

• French Bulldogs

• Papillons

• Shih Tzus

• Toy Poodles

• Coton de Tulears

However, MUE is not exclusive to these patients. It has also been identified in medium and large breed dogs and can occasionally occur in older small-breed dogs.

Recognizing the Signs of MUE

Clinical presentation can vary considerably.

Some dogs develop severe neurologic signs acutely, while others experience waxing and waning abnormalities over weeks or even months.

Seizures and vestibular signs—including head tilt, nystagmus, and ataxia—are common.

Because MUE can affect essentially any area of the central nervous system, almost any neurologic deficit is possible. One particularly important clue is the presence of multifocal CNS disease.

For example, a young small-breed dog presenting simultaneously with seizures and vestibular abnormalities should immediately raise concern for MUE.

Some dogs may also demonstrate cervical pain associated with cervical meningitis.

Diagnosing MUE

Diagnostic testing outside the central nervous system is typically normal in patients with MUE.

Significant extracranial abnormalities that correlate with the patient's clinical presentation should therefore prompt consideration of other disease processes. A mild neutrophilia may be consistent with a stress response, for example, while moderate to severe neutrophilia would be less typical of MUE and should raise concern for other infectious or inflammatory conditions.

Diagnosis typically requires:

• MRI

• Cerebrospinal fluid analysis (spinal tap)

• Infectious disease testing when indicated

Together, these diagnostics help support a presumptive diagnosis while ruling out other potential causes of neurologic disease.

Treating MUE

Treatment generally begins with corticosteroids at an immunosuppressive dose, followed by a gradual taper over approximately three to six months.

There is some evidence suggesting that adding a second immunosuppressive medication early in treatment may improve outcomes, although there is no strong evidence demonstrating that one additional medication is superior to another.

Medication selection is often influenced by factors such as patient size, cost, and frequency of administration.

Many neurologists use prednisone combined with cytarabine because cytarabine crosses the blood-brain barrier and targets lymphocytes, one of the primary immune cell types identified in the CNS of patients with MUE.

Other commonly used medications include:

• Cyclosporine

• Mycophenolate

• Leflunomide

• Azathioprine

What Is the Prognosis for MUE?

Prognosis is highly variable.

One of the most important predictors of long-term prognosis is the patient's initial response to treatment. Interestingly, the severity of neurologic disease at presentation does not necessarily correlate with long-term outcome.

Most patients respond well initially, although relapses are common and many dogs require lifelong treatment with at least one medication.

Generally, most dogs live one to three years before experiencing a significant relapse and succumbing to the disease. Less commonly, complications associated with chronic immunosuppression may affect outcome.

Some dogs, however, can be cured.

Idiopathic Tremor Syndrome

Idiopathic tremor syndrome—sometimes called immune-mediated cerebellitis or “little white shaker disease”—typically affects young to middle-aged small-breed dogs.

The hallmark presentation is the acute onset of relatively fine, generalized tremors.

Some patients may also develop erratic, uncoordinated eye movements known as opsoclonus. Because of the continuous muscular activity associated with severe tremors, affected dogs may become hyperthermic.

Diagnostic evaluation is generally similar to that performed for MUE.

Treating Idiopathic Tremor Syndrome

Treatment typically involves corticosteroids at an immunosuppressive dose followed by a gradual taper over three to six months.

Unlike many MUE patients, additional immunosuppressive medications are rarely necessary.

Injectable or oral benzodiazepines may also be beneficial initially to reduce severe tremors while waiting for corticosteroid therapy to take effect.

The prognosis is generally favorable. Most dogs can be controlled with corticosteroids alone, and many can ultimately be cured.

Steroid-Responsive Meningitis-Arteritis (SRMA)

SRMA has a very different clinical presentation.

Nearly all affected dogs present before two years of age, with the majority diagnosed before their first birthday.

SRMA is commonly associated with several of the “B” breeds, including:

• Boxers

• Bernese Mountain Dogs

• Beagles

However, the disease can occur in many medium- and large-breed dogs.

Recognizing SRMA

The classic presentation is relatively straightforward: acute onset fever and cervical pain in a young dog.

Unlike MUE, neurologic deficits are uncommon. Fever and cervical pain may be the only abnormalities identified, although mild proprioceptive deficits can occasionally occur.

An inflammatory leukogram may also be present because SRMA tends to affect patients systemically.

An Important Differential: Discospondylitis

SRMA represents one of the clinical situations in which cervical radiographs can be particularly valuable.

Discospondylitis is an important differential diagnosis for a young dog presenting with fever and cervical pain and should be considered before beginning immunosuppressive treatment.

MRI and cerebrospinal fluid analysis, with infectious disease testing when appropriate, are typically used to confirm the diagnosis. In some cases, cerebrospinal fluid analysis alone may be sufficient.

Treating SRMA

As with the other immune-mediated diseases discussed, treatment generally begins with corticosteroids at an immunosuppressive dose, followed by a gradual taper over three to six months.

Additional immunosuppressive medications or pain medications are rarely required.

The prognosis is generally favorable. Most dogs respond to corticosteroid therapy alone, and many can be cured.

Recognizing the Patterns

MUE, idiopathic tremor syndrome, and SRMA all represent non-infectious inflammatory diseases of the nervous system, but recognizing their characteristic presentations can help clinicians determine which disease process should rise to the top of the differential list.

A young to middle-aged small-breed dog with multifocal CNS disease, seizures, or vestibular signs may warrant investigation for MUE.

A young small-breed dog with acute generalized tremors may fit the presentation of idiopathic tremor syndrome.

And a young medium- or large-breed dog with acute fever and cervical pain but an otherwise relatively normal neurologic examination should raise suspicion for SRMA.

While advanced diagnostics are often necessary to reach a diagnosis, recognizing these patterns early can help veterinary teams guide the diagnostic process and begin appropriate treatment.

Refer a Patient to PASE Neurology

The Philadelphia Animal Specialty & Emergency (PASE) Neurology Department is available for scheduled appointments six days a week and for neurologic emergencies seven days a week.

Our Neurology team works closely with referring veterinarians to provide advanced neurologic evaluations, MRI and diagnostic testing, individualized treatment plans, and ongoing support for patients with complex neurologic conditions.

Philadelphia Animal Specialty & Emergency (PASE)
2100 Washington Ave.
Philadelphia, PA 19146
267-727-3738