© Therese Rodin
The most common variant of non-viral induced encephalitis in Pugs is often called Pug dog encephalitis (PDE) but sometimes also necrotizing meningoencephalitis (NME). Since not only Pugs suffer from the disease, the latter is more accurate.
Description: Granulomatous meningoencephalitis (GME), necrotizing meningoencephalitis (NME) and necrotizing leukoencephalitis (NLE) are inflammatory diseases of the dog’s brain. All three diseases appear to be autoimmune reactions. It is often difficult to diagnose exactly which of the diseases the dog has; it is possible to say with greater certainty only in autopsy (Talarico and Schatzenberg 2010: 138). Pugs are mainly affected by NME but can also be affected by GME and NLE, as well as what the researchers call MUE, “meningoencephalitis of unknown etiology” (Levine et al. 2008: 962; Talarico and Schatzenberg 2010: 139, 142, 145; see also Park et al., 2012: 683 for NME and NLE in Pugs.) Levine et al. studied 74 Pugs that had died of non-viral encephalitis, of which 81% had NME, while the other 19 percent had one of the other forms of non-viral encephalitis. In another population of 16 Pugs who died due to non-viral encephalitis, 69% were diagnosed with NME and the remaining had another type of non-viral initiated encephalitis (Levine et al. 2008: 964).
In the case of NME and Pugs, it has been shown that an increased risk of illness is connected to a specific genetics. Greer et al. have found three specific areas on chromosome 12 that recur in Pugs with NME. (Chromosome 12 contains gene clusters linked to the immune system.) Greer et al. investigated a population of 35 Pugs who had fallen ill in NME and a control group of 38 Pugs that had not fallen ill. Among the Pugs that were ill, the researchers to a greater extent identified three gene variants (alleles) of three specific genes on chromosome 12. 21 of the 35 affected dogs were homozygous for the three alleles and 11 of the affected were heterozygous for these alleles. (Three of the sick dogs did not have these alleles.) Among the 38 Pugs that had not fallen ill, four were homozygous for these alleles and 11 were heterozygous (Greer et al. 2010: 112, Table 3, 115). (23 of the healthy Pugs did not have these alleles.)
Since so many of the NME-affected Pugs were homozygous with these alleles, one must expect a higher risk for the homozygous dogs. There were also quite a few of the sick Pugs that were heterozygous and therefore our interpretation is that the study suggests that one must expect that even carriers have an increased risk of falling ill, compared to the Pugs that do not have this gene set. Because not everyone who has these alleles gets ill, it is likely that other genes as well as the environmental impact are important for the disease to break out (Greer et al. 2010: 114).
There has been a development in Pugs with an increased homozygotization of alleles linked to NME, which the researchers partly argue is caused by a loss of genetic diversity and a general increased homozygosity which is often a result of “a strong male founder effect”. They write that 87% of all Pugs go back to a single male and in addition there are three other males, each found in 4% of the remaining population. They further write:
Pure breeding has been a contributing factor in the appearance of many deleterious traits and was recognized early on as a potential factor in the increasing occurrence of a wide range of autoimmune disorders of dogs. (Greer et al. 2010: 115).
In Levine et al:s study, the mean age of disease outbreaks in Pugs with NME was 27.5 months, i.e. 2 years and 3½ months, with a range from 4 to 113 months, i.e. from 4 months to 9 years (2008: 964). In another study, the debut was established somewhere between six months and seven years with a mean age of 29 months. Disease onset was most common in young dogs (Talarico and Schatzenberg 2010: 143). The other encephalites usually appear slightly later than NME. E.g. GME according to one study (which included several breeds) had its onset between 6 months and 12 years with 4 years and 7 months as an average age for disease onset (ibid. 139; Levine et al. 2008: 965).
It is more common for bitches to fall ill than males in all the encephalites mentioned. In the case of NME, but not the other encephalites, those dogs that have become more likely to have a lower body weight than the control group (Levine et al. 2008: 963, 965).
The prognosis for Pugs that are affected by any of the non-viral encephalites is poor and if the dog does not get under treatment, it usually dies within a few days or a few weeks. Common symptoms are seizures, depression, circling and effects on the visual cortex, visual impairments and ultimately death (Talarico and Schatzenberg 2010: 143). In Levine et al:s study, Pugs with NME survived on average 93 days and those with one of the other non-viral initiated encephalites on average 112 days (2008: 964).
As for survival, Levine et al. write that their data could be skewed in the way that only Pugs that died of the disease were included in the study. It may be that the Pugs that were hardest struck with the illness were included and that therefore the survival time cannot be generalized to all Pugs with non-viral encephalitis (Levine et al. 2008: 966).
Goal: The goal is that no Pug will experience this disease. (Read a personal story about our Mimmi and PDE/NME here on the website.)
Strategy: The risk of falling ill in a non-viral encephalitis can currently only be tested for PDE/NME. Not all dogs who are homozygous with the gene marker develop the disease, and there are fewer heterozygous who develop it. Because it is so serious, we still advocate that all dogs that are intended for breeding should undergo the gene test for PDE/NME. If a Pug is at-risk (homozygous) or carrier (heterozygous) and is older than the usual onset age for the disease, about 3–4 years, and has qualities that are considered to add something to the breed, that Pug can be combined with one that is does not have the gene marker for PDE/NME. Since also heterozygous dogs have a higher risk of developing the disease than those who do not have this gene set, the goal is that these genes should not remain in the Pug population in the long term.
Since genes are often inherited in clusters, so-called haplotypes, the removal of carriers of the NME-related genes means a loss of many other genes. The Pug is already depleted in terms of genetic diversity and as long as no new genes are supplied (from other breeds) ther genetic variety gets even lower since genes are constantly lost. The less the genetic variation is, the more genetic diseases are likely to arise, so the removal of something that you do not want may lead to new problematic situations being created. Despite this, our strategy is that this gene set should eventually be gone. The only long-term cure for reduced genetic variation and homozygosity is to carry out crossbreeding. (See more about this below under “Genetic diversity”.)
Designations of free, carriers and at-risk:
Sources and further reading:
Greer, K. A. et al. 2010. “Necrotizing meningoencephalitis of Pug Dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis”. Tissue Antigens: Immune Response Genetics 76, 110–118.
Levine, J. M. et al. 2008. “Epidemiology of Necrotizing Meningoencephalitis in Pug Dogs”. Journal of Veterinary Internal Medicine 22, 961–968.
Park, E. S. et al. 2012. ”Comprehensive Immunohistochemical Studies on Canine Necrotizing Meningoencephalitis (NME), Necrotizing Leukoencephalitis (NLE), and Granulomatous Meningoencephalomyelitis (GME)”. Veterinary Pathology 49, 682–692.
Talarico, Lauren R. and Scott J. Schatzenberg 2010. ”Idiopathic granulomatous and necrotising inflammatory disorders of the canine central nervous system: a review and future perspectives”. Journal of Small Animal Practice 51, 138–149.
Chapters in Strategies for the breeding of Healthy Pugs
- Hips, Elbows and Patella
- Hemivertebrae and other vertebral anomalies
- Spinal Arachnoid Diverticulum (SAD)
- Pug Myelopathy (PM)
- Degenerative Myelopathy (DM)
- PDE/NME and other non-viral induced encephalitides
- Brachycephalic Obstructive Airway Syndrom (BOAS)
- Dentition and mouth health in the Pug
- Eyes (Brachycephalic Ocular Syndrome)
- Mating and Fertility
- Genetic diversity