Necrotizing Meningoencephalitis (NME) in Cats and Dogs: Update on Long-Term Management
Necrotizing meningoencephalitis (NME) is an idiopathic, breed specific, unique inflammation disorder of brain in small breed dogs diagnosed more frequently in young adult animals, from six months to seven years of age. The disease primarily affecting the cerebral hemispheres has been described in Pug, Maltese, and Yorkshire terrier. Even though the cause of this disease is unknown, a certain autoantibody against a canine brain tissue was detected in the cerebrospinal fluid (CSF) and serum, indicating an autoimmune pathology in NME.
The most common clinical signs of NME patients include seizure episode, circling, vestibule-cerebellar signs, but variations exist by the multifocal intracranial inflammation including ultimate death. CSF analysis reveals monocytic pleocytosis and total CSF protein elevation. Brain magnetic resonance imaging (MRI) examination finds focal or multifocal intracranial lesions showing hyposignal intensities on T1-weighted images and hypersignal intensities on T2-weighted images. Histologically, NME has characteristics of nonsuppurative inflammation of the brain with extensive necrosis and is similar to granulomatous meningoencephalitis (GME) on the basis of the dense aggregations of inflammatory cells, around blood vessels, especially lymphocytes, reticulohistocytes and macrophages (perivascular cuffing). However, the microcavitations, the necrosis and the extensive sclerosis are different features from GME.
Administration of immunosuppressive doses of glucocorticoids is the traditional primary treatment in NME in dogs. However, response is variable and clinical signs often recur quickly with tapering dosage. Adverse effects such as polyuria-polydipsia, polyphagia, weight gain, hepatotoxicity, iatrogenic hyperadrenocorticism and lethargy are frequently seen during long-term therapy. Glucocorticoids given at immunosuppressive doses, which may help reduce inflammatory and immune reactions during initial stage of the disease but many dogs require sustained therapy to avoid relapse. Prognosis is poor and long-term therapy causes many complications.
Recent reports suggested that the cyclosporine is the effective therapeutic options for NME in dogs. We compared the long-term effects of cyclosporine plus prednisolone therapy with sole prednisolone therapy in management in dogs with NME.
Cyclosporine, cyclic oligopeptides, which is able to block the transcription of cytokine genes in activated T cells is nor nephrotoxic or hepatotoxic in dogs unless extremely high blood concentrations (over 3,000 ng/ml) are maintained. No major adverse effects were associated with long-term cyclosporine administration, except for mild dermatologic changes and transient lymphopenia. Because combination therapy of cyclosporine can reduce prednisolone dosage of treatment, the major side effects of prednisolone were more diminished than those of high dose prednisolone therapy. When combination therapy was used, steroid could improved clinical signs initially, and prolonged effect until cyclosporine exert its effect. Combination treatment of prednisolone with cyclosporine is more effective in survival time than administration of only prednisolone in NME cases.
Another combination therapy consists of azathioprine and prednisolone was reported to be a safe and effective treatment for canine meningoencephalitis.
In addition, several immunomodulatory drugs including cytosine arabinoside (CA), procarbazine, lomustine (CCNU), leflunomide, and mycophenolate mofetil (MMF) have been reported as adjunctive therapy combined with glucocorticoids.
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