New insights into the treatment of meningoencephalomyelitis of unknown origin since 2009: A review of 671 cases

Abstract

“Meningoencephalomyelitis of unknown origin” (MUO)—a collective term for a group of clinically-indistinguishable (but pathologically distinct) autoimmune diseases of the CNS—has become increasingly commonly recognized throughout the world. In the 1960s−1980s the focus was primarily on the pathological description of these conditions and, largely anecdotally, their response to glucocorticoids. The subsequent availability of magnetic resonance imaging for companion animals led to a focus on imaging characteristics and response of MUO to various immunosuppressive medications. Previous reviews have not found clear evidence of superiority of any specific treatment regimen. Here, we review outcomes in a further 671 dogs treated with various combinations of glucocorticoids and immunosuppressive drugs and reported since 2009, aiming to determine whether recommendations can be drawn from the material published during more recent decades. We observe that: (i) there is more complete information on outcome of MUO-affected dogs solely receiving glucocorticoids and these reports provide evidence to undermine the dogma that MUO inevitably requires treatment with glucocorticoids plus an immunosuppressive drug; (ii) there is far more information on the pharmacokinetics of cytarabine delivered by a variety of routes, revealing that previous dosing and duration of administration in dogs with MUO may not have been optimal; and, (iii) there is a large number of cases that could be available for entry into multi-institutional randomized controlled trials. Finally, we suggest new research avenues that might aid future clinical trials in MUO through improved understanding of etiological triggers and individual patterns of immune response, such as the impact of the gut microbiome, the potential of CSF flow cytometry, and the establishment of robust clinical scores for evaluation of treatment success.

Prognosis in meningoencephalitis of unknown origin in dogs: Risk factors associated with survival, clinical relapse, and long‐term disability

“…Nonetheless, despite the long study period, there is still no clear evidence of superiority of any specific treatment regimen with multicenter randomized controlled trials required to determine the superiority of a specific treatment. 23 We showed that pugs, the presence of seizures and paresis at the time of presentation, and a higher NDS score were associated with an increased risk of death at 6 months after diagnosis in dogs with MUO.…”

“…The presence of motor symptoms at onset of disease has been associated with unfavorable outcome in patients with multiple sclerosis (MS) [18][19][20][21][22] and several similarities between MS and MUO have been suggested recently. [23][24][25] It has been suggested that motor symptoms reflect either more extensive or more persistent functional effects or lesions. 26 Interestingly, no association was found between specific neurolocalizations (such as brainstem) and survival.…”

“…Immunosuppression by use of corticosteroids remains the cornerstone of MUO treatment 23 . Several other medications have been used, generally with corticosteroids, including cytosine arabinoside, cyclosporine, lomustine, azathioprine, procarbazine, leflunomide, and mycophenolate mofetil 1 .…”

Suspected pregnancy‐associated meningoencephalitis of unknown origin in a dog

“…5 Prednisolone in combination with other immunosuppressive medication has been reported to improve survival times, 3,27 although there is conflicting evidence to support this and more recent reviews have indicated favourable outcomes with glucocorticoids alone. 28 In our patient, prednisolone therapy was initiated early in the course of treatment; however, due to deterioration of the clinical signs, a second immunosuppressive drug (cytarabine) was administered. Different protocols have been described for cytarabine treatment.…”

Usefulness of neurological assessment scales in prognosis of meningoencephalitis of unknown origin in Yorkshire Terriers

“…Therefore, the knowledge gained is not easily applicable for clinical use, and need for establishment of robust clinical scores for evaluation of treatment has been suggested. [12]. Several established scales have been used to describe the neurological status of dogs, however its usefulness in prognostication was not been compared so far.…”