GME in Dogs and Cats

Granulomatous Meningoencephalitis (GME) in Dogs and Cats

Granulomatous meningoencephalitis (GME) is an inflammatory disease that acts in many ways like cancer and that little is known about the causes. It can be very hard to diagnose as it is almost impossible to biopsy the central nervous system.

The general process of inflammation involves the infiltration of normal tissues by cells of the immune system. The immune system is made up of several types of cells which go to the area where they are called and release destructive biochemicals with the goal of obliterating an area of invasion by infectious organisms or of dead or diseased tissues.

What does GME involve?

Granulomatous inflammation involves inappropriate infiltration by mononuclear cells. These cells normally engulf and destroy debris. In GME, these cells form cuffs around the blood vessels of the brain and spinal cord (mostly in the white matter). The cuffs join at adjacent vessels forming actual masses/nodules.

We do not know where the cells of infiltration come from in GME. They may come from the circulation or come from local proliferation of cells already present. Current understanding is that GME is an immune mediated disease that seems to involve a type of immune cell called T-lymphocytes which send out inappropriate signals and starting this entire cascade of brain blood vessel circulation.

Originally the term reticulosis was used to refer to infiltrative diseases of the nervous system including GME, cancerous cell infiltrations and other diseases. There was a great deal of confusion and overlap of terminology and the expression reticulosis is no longer used. GME is complicated enough without including other conditions in its umbrella. GME is not a cancerous process and it is distinct from other inflammatory brain diseases. Unfortunately, obtaining a definitive diagnosis requires analysis of a piece of brain tissue, and since this is not likely to occur in a living patient, the term meningoencephalitis of unknown etiology (MUE) is often used to include all the inflammatory brain conditions.

The Clinical Signs with GME

The classical patient is a young to middle-aged small breed dog though any dog of any breed can be affected. What sort of neurologic signs are seen depend on which area of the nervous system is involved. Seizures, neck pain, unsteady gait, walking in circles, head tilt blindness, listlessness, facial abnormalities, and weakness can be seen. Symptoms can come on acutely or be more chronic.

Breeds felt to have a genetic predisposition to GME are Chihuahua, Dachshund, Maltese, and Miniature Poodle.

Types of GME

There are three types of GME:

Disseminated or multifocal (involving many locations in the nervous system)
Focal (limited to one location in the nervous system)
Ocular (involving the optic nerve/eye)

A patient may have more than one type. The disseminated form is the most common.

The focal type of GME typically has a slower onset (3-6 months) while the disseminated form is more rapid (2- 6 months). The disseminated form has a larger variety of signs within the same patient since many areas of the brain are involved at the same time. Dogs with the disseminated form have a poor prognosis with median survival times (without treatment) ranging from eight days to 30 days from the time of prognosis is better for the focal form. Regardless of the form, GME is not curable and life-long medication is necessary. The ocular form most commonly shows up as sudden, generally permanent blindness. It can affect one or both eyes but is not of a life-threatening nature.

Diagnosis of MUO

For patients with brain-related symptoms a basic blood panel, urinalysis, and a physical exam are the foundations of an evaluation. They can determine what medication can be used, and what other systems must be considered. After this a spinal tap and MRI will be needed to aid in diagnosis of the different brain issues.

Sampling of the cerebrospinal fluid (spinal tap) enables evaluation of cells in the CSF fluid. Cancer cells may be found as can be infectious organisms or the inflammatory cells typical of GME. General Anaesthesia is required to tap fluid from the nervous system and the procedure is not entirely without risk. There is a very small chance of sudden death from CSF sampling. It is important to rule out infection as the immune-suppression needed to treat GME would be disastrous in the case of an infection.

Conditions that might present similarly include:

Cancer
Fungal encephalitis (such as caused by Cryptococcus neoformans)
Parasitic encephalitis (such as toxoplasmosis)
Viral encephalitis (including canine distemper and rabies) though further spinal fluid testing is generally more revealing.

MRI (magnetic resonance imaging) is extremely useful for the diagnosis of GME in most cases but not always. MRI allows us to visualise the structure of the brain and spinal cord.

The only way to confirm GME with 100% certainty is by biopsy. As brain surgery in an unwell patient is very dangerous we would normally not perform this so definitive diagnosis is only on post-mortem.

Treatment of GME

Immune-suppression with corticosteroids (such as prednisolone) remains the corner stone of treatment for GME. Once the disease is controlled, you can begin to gradually drop the steroid dose until you reach the minimum dose required to control the disease. This process can take several months and relapses are common. Response to prednisolone is variable and results are much better if additional medications are added.

Cytosine arabinoside, a chemotherapy agent, can be added to prednisolone for a much better response. Monitoring is required with a medication this it can cause bone marrow suppression.

Cyclosporine is an immunomodulator somewhat different from the chemotherapy agents described above. It can be combined with prednisolone to treat GME without the bone marrow suppression side effects.

A new drug called leflunomide has been released to treat immune-mediated diseases of a type that includes GME. This is a relatively expensive treatment, which has limited use but it remains as a possible alternative to corticosteroid use for dogs that do not tolerate corticosteroid side effects.

If seizures have been a manifestation of GME, either disseminated or focal, medication will be used to control the seizures.

Ophthalmic GME also uses oral corticosteroids for therapy but may also employ topical ones. If glaucoma results from GME, then therapy for it is necessary. Again, therapy for this result of GME is addressed in a standard way; no specific GME glaucoma therapy is needed.

Prognosis with GME

GME has a poor prognosis. Most studies offer the generalizations that dogs with multifocal disease typically have a short survival (e.g., up to six weeks after diagnosis) and dogs with focal disease usually have a longer survival (e.g., three to six months). There are single case reports of dogs responding for longer periods. However, large prospective studies monitoring clinical responses to the newer treatment modalities are lacking and are greatly needed to allow an accurate prognosis to be given. Whilst the disease does carry a guarded prognosis, some individuals will respond to treatment for a considerable period of time.

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