Final diagnosis: Granulomatous
meningoencephalomyelitis
History: A reportedly 3-year-old, spayed
female rat terrier dog was submitted to the ADDL for necropsy. This dog
originally presented to the referring veterinarian with a history of ataxia and
pelvic limb paraparesis. Clinical signs progressed over the next two weeks
with the development of tetraparesis, hyperesthesia, loss of anal tone, and
hemorrhagic diarrhea. Lower motor neuron reflexes were present in the pelvic
and thoracic limbs. Following treatment, clinical signs improved slightly over
the next five days with the recurrence of anal tone, increased alertness, and
increased mobility in the forelimbs; however, clinical signs subsequently
worsened the following week-end resulting in death.
Gross findings: On gross examination, the spinal
cord was soft and swollen, filling the vertebral canal. No other significant
lesions were observed in the brain or other body systems.
Histologic findings: Along the entire length of the
spinal cord, the meninges were markedly expanded by a pleomorphic inflammatory
infiltrate, predominantly consisting of macrophages and lymphocytes with fewer
plasma cells and neutrophils. Epitheloid macrophages were often arranged in
concentric layers forming granulomas which were often oriented around small
vessels. Inflammatory cells extended from the meninges into the white, and
sometimes, grey, matter, effacing and rarefying the neuropil. There was marked
lymphocytic perivascular inflammation which was predominantly in the white
matter.
In the cerebrum, macrophages,
lymphocytes, and plasma cells expanded the meninges, occasionally extending
into and effacing adjacent neuropil. Foci of predominantly perivascular
necrosis and granulomatous inflammation, consisting of epitheloid macrophages,
lymphocytes, and fewer neutrophils and plasma cells, were scattered throughout
the cerebrum, primarily in the white matter. Similar foci of necrosis and
inflammation were present in the pons and ventral cerebellum. Special stains,
including Gram, periodic acid-Schiff (PAS), and Giemsa stains were performed on
sections of spinal cord in order to identify potential infectious agents;
however, no organisms were identified.
Discussion: Granulomatous
meningo-encephalomyelitis (GME) is an inflammatory disease of unknown etiology,
characterized by predominantly perivascular, granulomatous inflammation in the
meninges and white matter of the central nervous system. Lesions may be focal,
multifocal, or disseminated, affecting the cerebrum, cerebellum, brainstem,
spinal cord, or optic tracts. Granulomatous meningoencephalomyelitis occurs in
many breeds of dog and can occur both in males and females; however, small
breed dogs, poodles, terriers, and female dogs have been shown to have an
increased incidence of disease. The age of onset is usually between one and
nine years; however, animals may be affected at any age. Affected animals
usually present with an acute onset of disease, which progresses over days to
months. The clinical presentation is variable, reflecting the distribution of
lesions, but may include intermittent fever, lethargy, depression, convulsions,
head tilt, circling, cervical pain, hyperesthesia, conscious proprioceptive
deficits, paresis, or paralysis.
Clinical diagnosis of GME is based
on clinical signs and cerebral spinal fluid analysis, which is characterized by
pleocytosis, increased protein, and normal to increased pressure in the absence
of infectious agents. A definitive diagnosis of GME is based on characteristic
histopathologic lesions. Including primarily perivascular granulamatous
inflammation in meninges and white matter with no associated infectious
agents. Immunosuppressive therapy, primarily consisting of corticosteroids,
has been the principle treatment modality for GME and, in some cases, can
result in long term improvement of clinical signs; however, GME is a
continuously progressive disease, often resulting in recurrence and progression
of clinical signs, especially when immunosuppressive therapy is discontinued.
Radiation therapy has also been used with some success, particularly in the
presence of focal disease. In general, due to its progressive nature, GME is
associated with a poor prognosis. However, in one study, animals with focal
disease had longer median survival times as compared to those with multifocal
disease. Currently, the cause of granulomatous meningoencephalomyelitis is
unknown, and GME has not been associated with any infectious agents. Based on
the predominance of CD3+ T-cells and MCH II+ macrophages, one study has
proposed that GME may be a T-cell mediated autoimmune disorder; however,
additional studies have not been performed to support or refute this
hypothesis. |