GME Article

GME, or granulomatous meningoencephalomyelitis, is a common neurologic disease in dogs, yet its cause is unknown and no cure exists.

An inflammatory condition of the nervous tissue, it usually involves the brain, but can also affect the spinal cord and its covering, called the “meninges.”

“This condition is also part of the class of CNS inflammatory diseases known as meningoencephalomyelitis of unknown etiology (MUE). It is difficult to distinguish GME from other breed-specific inflammatory disorders and infectious diseases,” says Joan R. Coates, D.V.M., M.S., DACVIM, a professor of neurology and neurosurgery at the University of Missouri College of Veterinary Medicine in Columbia. It’s more common in smaller dog breeds, particularly Toys, Poodles and the smaller Terriers, and strikes at a median age of 5. However, no statistics exist as to how many dogs are diagnosed each year with GME.

While there may be an as-yet unproven, underlying genetic predisposition, it’s also thought that infectious agents may underlie GME. Despite the development of different types of tests, researchers have been unable to find a “consistent underlying infectious cause,” Coates says. However, infectious diseases of the brain can look like GME. “So it’s very important to rule out other infectious causes like viral, tick-borne diseases and fungal diseases.”

Regardless of its cause, dogs are best served by an early and accurate diagnosis so that treatment can be most effective and limit the neurologic effects that accompany it. If your regular veterinarian suspects or diagnoses GME, Coates recommends an evaluation by a board-certified neurologist or internist, particularly one who has experience with it. Titering for infectious diseases is also important, she says, because the drugs used to treat GME will accentuate an infectious disease.

In addition to being either focused in the brain or the spinal cord, GME takes three forms: multifocal or disseminated, focal and ocular.

Coates explains that with multifocal GME, a dog typically has one, two, or more neurologic signs, such as loss of balance, seizures, depression, a “dull” mental state, neck pain and the inability to do its normal tasks, such as herding, showing or agility.

In the focal form, the inflammation is located in a particular area of the brain, and a dog usually has just one “neurologic abnormality,” Coates says.

Multifocal and ocular diseases “tend to be very acute and very rapidly progress,” Coates says, while the focal type is more chronic and progresses less rapidly.

“It’s an art to diagnose and determine the extent of GME,” she says. “The important thing is getting an accurate presumptive diagnosis. We always do a CBC and chemistry profile because this disease can mimic an infectious disease too. Preferably, we’ll do an MRI of the brain. The distribution of GME tends to be within the white matter of the brain. Once we get the MRI, that’s going to tell us where the lesions are, and even in a case where we have signs of a focal disease, it’s not unusual to see other lesions on the MRI.” Coates also does a spinal fluid analysis, which usually shows an elevated white blood cell count and elevated protein concentration.

When it comes to therapy for GME, “we really want to reduce that inflammatory response with immunosuppressive therapy and try to get the disease into remission,” Coates says. Corticoteroids, such as prednisone, are administered along with other types of immunosuppressants. “It has been shown that if you combine immunosuppressive therapies the treatment protocol may be more effective,” she says. “Oftentimes we combine the prednisone with cyclosporine or cytosine arabinoside.” The drugs must be able to cross the blood-brain barrier, which keeps blood and brain fluids separate, to be effective in reducing inflammation. “There have been other immunosuppressive therapies studied, but an evidence-based approach study is still needed to determine drug efficacy,” she says.

During the course of these therapeutic approaches, it is important to carefully monitor the blood cell counts and for side effects on other organ systems such as liver and kidney, Coates says.

In addition to reducing inflammation, the neurological effects also must be treated. For example, if a dog has seizures, anticonvulsant drugs will be administered.

more updates on GME/NME studies:

GAINESVILLE, Fla. — By analyzing the genes of bacteria, University of Florida researchers have moved a step closer to pinpointing how two brain disorders common in small-breed dogs occur.

The researchers found that the bacteria, known as Mycoplasma canis, invade dog’s cells and suppress their immune system responses.

“This could explain how the bacteria are able to enter the brain in certain circumstances,” said lead investigator Daniel Brown, Ph.D., an associate professor of infectious diseases at the UF College of Veterinary Medicine. “If our theory is correct, it is possible that antibiotic therapy aimed at the mycoplasma could be beneficial if the condition is diagnosed early enough.”

The findings, which appear in the August issue of the Journal of Bacteriology, were also presented at the annualmeeting of the International Organization for Mycoplasmology in France.

The researchers studied two common brain syndromes called granulomatous meningoencephalomyelitis, orGME, and necrotizing meningoencephalitis, or NME, which occur primarily in small toy-breed dogs such as pugs,Malteses, Yorkshire terriers, Chihuahuas and Pomeranians. The diseases affect the central nervous system,causing brain damage and symptoms such as seizures, decreased alertness and difficulty maintaining balance. There is no cure, but drugs can control the brain inflammation by suppressing the immune system.

No clear data exist on how widespread the disorders are.

“Although reliable information on new and existing cases is pretty scarce or nonexistent, inflammatory central nervous system disease is certainly one of the most common problems we deal with as veterinary neurologists,” said Christopher Mariani, D.V.M., Ph.D., an assistant professor of neurology at North Carolina State University’s College of Veterinary Medicine. Mariana was not involved in the UF study.

The syndromes previously were thought to be caused by a virus or by an attack of the body’s own immune system. But University of Georgia researchers Renee Barber, D.V.M., and Scott Schatzberg, D.V.M., Ph.D., and colleagues, including Brown, reported earlier this year that whereas viruses were absent from the brain tissues of dogs with the diseases, the bacterium Mycoplasma canis was unexpectedly common. Interestingly, the researchers also found traces of the bacteria in some dogs that did not have the disease.

The bacteria would not have been detectd by the methods used previously to search for a presumed viral agent.

In the new study, Brown and colleagues examined five strains of Mycoplasma canis isolated from three different parts of the body — the brain, the genital tract and the throat.
They found no difference between the genetic makeup of the bacteria from brain tissue and that of the bacteria from other sites.

What they did find was evidence that the bacteria don’t just sit on the surfaces of cells, but actually penetrate inside cells. That may be what enables entry into the bloodstream and eventually, to the brain, the researchers said

“This finding is tantalizing, because it may offer an explanation as to why scientists have never been able to specify a viral, autoimmune or other cause of GME and NME,” Brown said.

In addition, different strains of bacteria were not equally efficient at suppressing the dogs’ immune responses.

The researchers are continuing to analyze the effects of bacterial infection on immune system cells known as macrophages to determine how the bacteria could breach the blood-brain barrier. Later, they will extend their studies to examining how the bacteria interact with different types of brain cells.

“The study is intriguing, but more work needs to be completed to determine the significance of these bacteria as a possible cause of GME and NME,” said Karen Vernau, D.V.M., an associate clinical professor and chief of neurology/neurosurgery at the University of California, Davis’ College of Veterinary Medicine, who was not involved in the study.