Advances help in treatment of canine GME; prognosis poor
Granulomatous meningoencephalomyelitis (GME) is a relatively common nonsuppurative inflammation of the brain, spinal cord, and meninges. The etiology is unknown.
Neurological signs of GME may be multifocal or focal, according to the localization of the lesion(s) within the CNS.
Focal or multifocal abnormalities may be seen on MR or CT imaging. A definitive diagnosis of GME requires a histopathological examination of the lesion(s) via biopsy, though working diagnosis by exclusion of known infectious causes is often the practical reality.
Poor to grave prognosis Although corticosteroid therapy may delay the progression of the disease, GME has historically been considered to have a poor to grave prognosis.
However, radiation therapy is not helpful for diffuse GME. Financial considerations, multiple anesthesias, and side effects associated with radiation therapy make this type of treatment relatively less common.
Some hope In a recent conference, PA Cuddon and JR Coates (Proceedings, 20th ACVIM Forum, 319-321) describe new adjunctive and/or alternative therapies for GME that may be effective.
The authors evaluated the effects of cytosine arabinoside and procarbazine in dogs with GME. Cytosine arabinoside (Cytosar-U®) known as ara-C, acts on mitotically active cells by inserting into DNA molecules causing premature chain termination. Ara-C has the ability to cross the blood brain barrier and has immunosuppressive effects. The author study demonstrated that the high dose administration of ara-C is associated with cytotoxic concentrations within the CNS. They recommend a subcutaneous injection of ara-C at a dose of 50 mg/meters2 twice daily for two consecutive days (2003 cost ² $ 6 per 5 ml solution @ 20 mg/ml). This regimen is repeated initially every three weeks. Myelosuppression may occur.
A CBC should be performed 10-14 days after the first course of cytosine therapy, and then once every two to three months. For better therapeutic results, cytosine therapy is usually combined with prednisone (1 mg/kg orally, BID). Prednisone is reduced after the second round of cytosine injections. Cytosine has been occasionally used as a sole agent in some dogs with GME.
Procarbazine (Matulane®) is a monoamine oxidase inhibitor that alkylates DNA and affects RNA and protein synthesis. This substance also crosses the blood brain barrier and shows promise in the treatment of GME.
Due to the small size of dogs with GME, procarbazine should be compounded into a liquid. The authors recommend a 10 mg/ml oil based liquid (the expiration date is 30 days). Procarbazine is administered orally at a dose of 25 to 50 mg/meters2/day. Procarbazine can sometimes cause neurotoxicity, but myelosuppression (thrombocytopenia, leukopenia) seems to be the major limiting factor.
The CBC should be checked once a week for the first month, then monthly thereafter. After the first month of treatment, the authors suggest reducing the frequency of the dose to every other day. The use of these potent medications may also be considered to reduce side effects in dogs particularly sensitive to corticosteroid therapy.