Granulomatous meningoencephalomyelitis is a commonly diagnosed idiopathic inflammatory disease of the central nervous system
(CNS) in dogs. Incidence of GME reportedly ranges from 5 to 25% of all CNS disorders in dogs. Granulomatous meningoencephalomyelitis
has a progressive clinical course and often is fatal. Although the cause of GME is unknown, infectious, autoimmune, and neoplastic
causes have been proposed. Current literature supports evidence for a delayed-type T-cell mediated hypersensitivity of an
organ-specific autoimmune disease process. Meningoencephalomyelitis of unknown etiology (MUE) has been termed to categorize
a group of diseases that include granulomatous meningoencephalomyelitis (GME), necrotizing meningoencephalitis (NME), necrotizing
leukoencephalitis (NLE), or infectious meningoencephalitis for which the cause has not been identified. The MUEs may represent
a spectrum of CNS inflammatory diseases with similar pathogeneses.
Prevalence of GME is higher in female dogs in some studies; however both sexes can be affected. Granulomatous meningoencephalomyelitis
is frequently diagnosed in young to middle-aged, toy breed dogs with a mean age of 5 years.
Classification of GME consists of three clinical forms: multifocal (disseminated), focal, and ocular. Multifocal GME is characterized
by acute onset and rapid progression of neurologic dysfunction. Dogs with focal GME tend to have more insidious or slower
progression of neurologic signs. Affected dogs can have neurologic signs reflecting disease of a focal area of the CNS. The
forebrain is commonly involved in focal GME. Forebrain signs include seizure, behavioral change, visual deficits, and postural
deficits. Seizure is the most common clinical manifestation of forebrain disease. Brain stem signs include cranial nerve deficits,
central vestibular dysfunction, and gait deficits. The focal form also may primarily involve the cerebellum and cause dysmetria
and intention tremors. Spinal cord involvement produces mild to severe gait deficits leading to paresis or paralysis. Disseminated
or multifocal involvement of the nervous system leads to signs of at least two areas of the CNS: forebrain, brain stem, cerebellum,
spinal cord, and meninges. Dogs with multifocal GME will commonly manifest forebrain and brainstem signs. The ocular form
alone is not as common, but often is concurrent with the multifocal form. The ocular form can present with acute onset of
blindness, dilated pupils, and absent pupillary light reflex. Acute optic neuritis is recognized by a swollen optic disk with
poorly defined margins. Chronic signs of optic neuritis are recognized by atrophy of the optic nerve and sunken optic disks.
Fundoscopic examination can reveal retinal detachment and hemorrhage. Dogs with ocular GME can subsequently develop CNS involvement.
Definitive diagnosis of GME is based upon histology of CNS tissue obtained by biopsy or necropsy. Neuropathologic lesions
consist of perivascular infiltrates of mononuclear cells in the white matter and meninges of the brain and spinal cord. A
presumptive diagnosis of GME is based on signalment, brain imaging, CSF analysis, and excluding other excluding regional causes
of infectious encephalitides. The combined diagnostic approach with advanced brain imaging and cerebrospinal fluid analysis
is informative for a presumptive antemortem diagnosis of GME. Cerebrospinal fluid analysis is characterized by a predominantly
mononuclear pleocytosis with variable presence of neutrophils. Advance brain imaging results may be normal, or show solitary
or multiple heterogeneous contrast-enhancing lesions.
GME patients typically require lifelong immunosuppressive therapy. Combination therapy of glucocorticoids and other immunosuppressive
agents will potentially allow for reduction or elimination of glucocorticoid treatment. Megavoltage irradiation of GME lesions
has shown efficacy in some dogs with clinical signs suggesting focal involvement. Side effects include mucositis, keratitis,
brain necrosis (early effect), and bone necrosis (late effect). Radiation treatment is costly and requires general anesthesia.
Immunosuppressive doses of glucocorticoids have been the mainstay of treatment for GME; however, clinical response has been
variable and neurologic signs often recur. Immunosuppressive doses of prednisone, 1 to 2 mg/kg PO bid are initiated for 2
to 4 weeks and the dose is gradually reduced or tapered every 4 weeks when clinical signs stabilize or improve. The ultimate
goal is alternate-day therapy at the lowest dose as clinical signs stabilize. Animals often respond initially, but relapses
are common. Treatment is not curative, and life-long therapy is often required. High-dose corticosteroid therapy leads to
undesirable side effects such as gastric ulceration, hepatic dysfunction, and iatrogenic hyperadrenocorticism. Previously
reported median survival times in dogs administered glucocorticoids with focal and multifocal GME were 114 and 8 days respectively.
Dogs with focal forebrain dysfunction had the longest survival times.
A goal of using other immunomodulatory therapies is to allow discontinuation or reduction in glucocorticoid dose. Immunomodulatory
therapies that have shown clinical usefulness for GME include leflunomide, procarbazine, cytosine arabinoside and cyclosporine.
Limited numbers of dogs have restricted abilities to statistically evaluate outcomes in earlier studies of cytosine arabinoside,
procarbazine, cyclosporine and leflunomide. Another major limitation of recent studies is lack of histopathologic confirmation
of GME patients. All drugs have potential risks for myelosuppression.