GRANULOMATOUS meningoencephalomyelitis, or GME, is an inflammatory condition affecting the brain and/or spinal cord. It is not uncommon and is important to consider in any animal presenting with deranged CNS function.
Treatment is sometimes difficult and unsuccessful but can also be rewarding, with some affected animals surviving for many years beyond diagnosis.
This article will consider the typical features of the condition, highlighting some of the treatments being adopted by neurologists around the world, and will touch on some of the controversies that might confuse the unwary reader.
The disease
Three forms of GME are recognised: a focal form, in which a single granulomatous lesion behaves as a space occupying mass; an optic form, in which only the optic nerves appear to be affected; and a multifocal form, in which lesions are scattered throughout the CNS.
The last of these is the most common and can present in a variety of ways according to the region of the nervous system affected.
Onset can be acute or chronic and abnormalities can range from blindness with no other abnormalities, to coma; focal spinal cord disease is also possible. Most commonly, the brainstem is affected – in particular the caudal brainstem and cerebellum, leading to disruption of the vestibular nuclei and clinical signs of central vestibular disease.
Other cranial nerve nuclei might also be affected in brainstem disease and damage to motor and sensory fibre tracts running between the limbs and higher centres can cause tetraparesis of varying severity.
Signalment
Certain breeds seem to be at risk for GME. Those most commonly identified with the condition include Toy Poodles, West Highland White Terriers, Dachshunds, Maltese Terriers and Chihuahuas. Other, predominantly smaller, breeds are also affected and a small but significant number are larger breeds, such that signalment should not be used to exclude the diagnosis.
Females are approximately 1.5 times more likely to suffer and the commonest age range at presentation is between four and eight years, confirming most clinicians’ observations that the condition is most prevalent in middle-aged females.
Diagnosis
A range of differential diagnoses should be considered in an animal suspected of having GME. The key diagnostic findings that suggest GME are advanced neuro-imaging (usually MRI – Figure 1) and CSF analysis indicative of inflammation, with no evidence of infectious diseases; multifocal neurological deficits also support the diagnosis.
Infectious diseases must be considered in an animal suspected of having GME, particularly since the treatment for the condition centres on immunosuppression, which could be catastrophic in an animal with infection.
Bacterial infection is a very rare cause of meningoencephalitis in companion animals and typically triggers a neutrophil response in the CSF. Other infectious diseases include protozoal diseases such as Toxoplasma and Neospora, viral diseases such as canine distemper and various tick-borne diseases such as Borrelia and Anaplasma.
All are rare causes of neurological disease in companion animals and diagnostic testing should be directed towards those diseases that are plausible; for example, an animal with no history of exposure to ticks and no evidence of disease elsewhere in the body is very unlikely to have Borrelia or Anaplasma.
The complete history and clinical presentation therefore must be considered in order to reach a diagnosis.
Treatment
The focus of treatment is suppression of the immune response, with high doses of corticosteroids forming the foundation of most regimes. In recent years, a number of other drugs have been employed to augment immunosuppression, including azathioprine, procarbazine, cyclosporine, vincristine, cyclophosphamide and cytosine arabinoside.
Though anecdotal reports of treatment using these drugs abound, there remains no convincing evidence that any one is better than the others, or even than corticosteroids alone.
An animal with a diagnosis of GME that fails to respond to corticosteroids would likely benefit from a specialist opinion.
Controversies in diagnosis
GME, as with many diseases, tends not to follow the typical presentation described in textbooks: diagnosis can be problematic and several diseases may be mistaken for GME, in particular neoplasia, which can mimic the focal form of the disease.
This has prompted some centres abroad to pursue brain biopsy to obtain a definitive diagnosis. This technique is not currently practised in the UK and might seem irrelevant to many practitioners; however, its use has prompted changes in terminology, which might confuse casual readers of the literature.
When an animal is described as “having GME” without having biopsy confirmation, what is meant is that it probably has GME, i.e. various diagnostic tests support this diagnosis and there is no evidence for any other disease.
Because some clinicians now perform brain biopsies, there is an emerging argument that dogs with a clinical diagnosis of GME (or probable GME) should be described differently from those that have a confirmed histological diagnosis.
New terms have therefore appeared in the veterinary literature, such as “Multifocal Encephalomyelitis of Unknown Etiology, or Origin” (MUE and MUO). These are increasingly used in published clinical studies and are, strictly speaking, correct.
The drive for new terminology comes from the need to distinguish clinical trials involving animals that definitely have GME from those that do not – and that might therefore have a different condition.
This distinction is potentially useful, since it should make different trials more straightforward to compare and might also help us to evolve better approaches to treatment.
However, there are negative points: if future studies focus only on confirmed GME, the number of animals that can be enrolled in studies is likely to drop significantly, partly because very few centres worldwide practise this technique but also because a sizeable number of patients with GME are not amenable to biopsy.
This group includes animals with no identifiable lesion on MRI and those with brainstem disease, in which the risks of biopsy outweigh the potential benefits. Advances in treatment might therefore be hampered rather than helped.
Conclusion
Does the evolution in terminology for inflammatory brain diseases really matter for most practitioners? Arguably not, since treatment is similar irrespective of whether or not there is histological confirmation of the diagnosis.
However, clinicians need to be aware that GME and MUE/MUO are similar in many respects, overlapping to a large extent (Figure 2), and that recently published studies showing apparently better survival times with newer treatments cannot readily be compared with older studies in which GME was confirmed.
To complicate matters, current terms seem destined to change further: for example, MUE is not a useful acronym for the UK, since “etiology” is spelt differently here from the USA, whereas MUE/MUO has not yet been accepted in the latter.
What is needed is a consensus on the naming of this condition that can be applied universally; until then, confusion seems destined to persist.
