Specialty Spotlight: Meningoencephalitis of Unknown Origin

Specialty Spotlight: Meningoencephalitis of Unknown Origin
Laura Krzykowski, DVM, DACVIM (Neurology)

There are a variety of infectious and autoimmune diseases that can lead to encephalopathy in our canine patients. In this region of the country, we see autoimmune disease far more commonly than infectious diseases.  The subtypes of autoimmune encephalitis are named according to the type and distribution of inflammation seen on histopathology (Granulomatous Meningoencephalitis, Necrotizing Meningoencephalitis, Necrotizing Leukoencephalitis). Clinically, MRI and spinal tap results can overlap between these categories, and their treatment is similar, so they are often grouped together into the broad term “Meningoencephalitis of Unknown Origin” (MUO).

While dogs of any age, breed, or sex can develop MUO, young to middle-aged female dogs of small breeds (poodle, terrier, Pug, Chihuahua, Maltese, French Bulldog) are predisposed. Clinical signs consist of multifocal CNS dysfunction with an acute onset and rapid progression, though some patients with focal disease can have a slower progression. MRI can be normal, but typically shows multifocal areas of hyperintensity and contrast-enhancement with patchy margins. CSF analysis shows a predominantly mononuclear inflammation. Infectious disease testing is typically performed on CSF as well to rule-out infectious etiologies.

Overall prognosis for MUO is guarded, though survival improves with early, aggressive immunosuppression. I typically discuss prognosis with clients in groups of three: 1/3 of patients respond very positively to therapy and can be weaned off medication, 1/3 can have residual neurologic deficits or experience relapses which require life-long medication, and 1/3 can worsen despite therapy. I try to taper medications over a period of 4-6 months; if dogs have relapses during or after their taper, then life-long therapy is often warranted. If possible, I avoid future vaccinations in patients with MUO to decrease risk of relapse.

Glucocorticoids are a mainstay of therapy (i.e. prednisone 1 mg/kg q 12 hours).  I find that steroid therapy alone often leads to a higher chance of relapse and that the steroid doses required can yield unacceptable side effects. The most common immunosuppressive drugs that I use in combination with prednisone are cytarabine, cyclosporine, and mycophenolate.

Cytarabine (Cytosar) is a synthetic nucleoside analog that halts DNA replication during the S phase. Cytarabine can be administered as a CRI (variable doses used, between 200-400 mg/m2 over 12-24 hours) or as SQ injections (50 mg/m2 q 12 hours for 2 days). Doses are repeated every 3 weeks initially, then spaced out over time. A recent paper demonstrated that dogs treated with a CRI after diagnosis had higher survival rates compared to those treated with the SQ protocol (90% survival at 3 months compared to 44%). [Lowrie et al, Effect of a constant rate infusion of cytosine arabinoside on mortality in dogs with meningoencephalitis of unknown origin, Vet Journal 2016]. Myelosuppression is rare, but reported when using recommended doses; a CBC should be performed 1 week after the first dose and prior to subsequent doses.

Cyclosporine inhibits T cell function; the dose most commonly used for MUO is 5 mg/kg q 12 hours. Mycophenolate mofetil inhibits B and T cell function; the dose most commonly used is 10 mg/kg q 12 hours. I periodically check CBC and chemistry panels with both drugs to monitor for liver side effects or myelosuppression (rare). Azathioprine is another commonly used drug for MUO; I personally use this drug less frequently as I see a higher side effect profile compared to the drugs listed above.

Certainly, not every client is able to pursue referral and advanced imaging.  In cases with compatible history, breed, and clinical signs, encephalitis is often the top differential. I typically recommend full bloodwork (CBC, chemistry panel, T4) to rule out any metabolic disease which could cause an encephalopathy, as well as broad-spectrum infectious disease testing (a Fever of Unknown Origin Panel through Idexx covers the most common neurologic pathogens). While waiting for infectious disease results, I will treat the patient with steroids (prednisone 1 mg/kg/day) and antibiotics (clindamycin 10 mg/kg q 12, doxycycline 5 mg/kg q 12). If infectious disease testing is negative, steroids can be increased to immunosuppressive levels and if needed, an oral immunosuppressive drug could be added. I always discuss with clients that there is some risk to this treatment path, as not all infections can be excluded without advanced testing (such as bacterial meningitis).

Feel free to contact myself or Dr. Bishop if you have any questions about a suspected encephalitis case or a patient with rapidly progressive neurologic signs requiring referral.

-Laura Krzykowski, DVM, DACVIM (Neurology)