Clinical and pathological aspects of canine necrotizing meningoencephalitis

A meningoencefalite necrosante canina (MNC) é uma doença inflamatória idiopática que afeta principalmente os hemisférios cerebrais de cães de raças pequenas. A sintomatologia apresentada pelos animais é progressiva, sendo as crises convulsivas o principal sinal clínico. A etiologia da MNC ainda é pouco conhecida, sendo possivelmente multifatorial e influenciada por fatores genéticos e ambientais. Até o momento, os tratamentos têm sido paliativos, com uso de anti-inflamatórios corticoides em dosagens imunossupressoras e anticonvulsivos. Nesta revisão são descritos seis casos recentes de MNC no Brasil, ocorridos nas raças pug (dois casos), Yorkshire (dois casos) e maltês (dois casos). Deste total, três casos foram provenientes da Faculdade de Medicina Veterinária e Zootecnia - Universidade de São Paulo - SP e três do Laboratório de Patologia Veterinária - Universidade Federal de Santa Maria - RSThe canine necrotizing meningoencephalitis complex (CNM) is an inflammatory disease characterized by multifocal nonsuppurative idiopathic meningoencephalitis, which mainly affects the cerebral hemispheres of small and miniatute breed dogs. This paper presents clinical and pathological data regarding cases registered in Brazil, compared with cases in literature. The disease has been reported in pug, maltese, papillon, Shih tzu, chihuahua and pekingese dogs. More recent reports describe the occurrence of CNM in greyhound, West Highland white terrier and French bulldog. In Brazil, there have been cases of this disease in pug, maltese and Yorkshire dogs (Figure 3). Although the etiology of CNM is much still unknown; it is most likely a multifactorial disease, influenced by genetic and environmental factors. The viral etiology of meningoencephalitis was suggested by some authors in the first case reports. However, several studies have shown negative results to testing (PCR and serological tests) for viruses such as canine distemper, as well as protozoa and agents of dirofilariasis, ehrlichiosis and borreliosis in the cases presented. Still, etiologic agents are not discarded as possible factors triggering a secondary autoimmune response to a prior exposition. An epidemiological study with 60 affected pug dogs indicated higher frequency (though not statistically significant) in females (40 affected individuals). This evidence is supported by the fact that autoimmune encephalitis tend to affect more females than males in different species. The most likely pathogenesis of CNM is the autoimmune hypothesis reinforced by signs of autoantibodies against astrocytic glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF) of dogs affected by this disease. Determination of autoantibodies in CSF or serum of affected dogs has provided relevant data on the etiology of the disease, besides assisting diagnosis. The autoimmune hypothesis is also supported by the occurrence of glomerulonephritis in recent cases, with the presence of autoantibodies and its complexes in serum. The symptoms onset in cases of CNM is variable, and dog owners often fail to perceive the neurological signs of the disease, which are rather subtle in the beginning. With Chihuahuas, clinical service was sought after a period of time that varied from 5 days to 2.5 years. With pugs, clinical signs may appear from one to six months before death. Seizures are the most consistent clinical manifestations in CNM, and the neurological syndrome develops progressively. Other clinical signs include nystagmus, ataxia, head tilt, ipsilateral circling, incoordination, paralysis, changes in behavior and consciousness, depression and coma. Neurological examination may reveal changes / loss / decrease of sight, but in most cases the pupillary reflexes remain unalterared. Computerized tomography, magnetic resonance imaging and ultrasound examinations may provide evidence of tissue lesion, cystic areas, malacia and dilation of ventricles. Examination of CSF may indicate important changes such as increased protein, red blood cells or presence of occult blood and predominantly mononuclear pleocytosis. Definitive diagnosis, nevertheless, is still based on histopathological examinations done through brain biopsy or post-mortem. Alterations occur primarily in the cerebral hemispheres, but there may be morphological differences and varying location according to the dog's breed. Macroscopic alterations in CNM are relatively common, and were observed in most cases in São Paulo and Santa Maria, with lateral ventricular dilatation (4 / 6) (Figure 4), areas of change in color, and malacia in the cerebral cortex (5 / 6) (Figure 5). Kidney alterations may occur, such as proliferative membranous glomerulonephritis, characterized by a diffuse lesion in the cortical area, with thickening of Bowman's capsule, lymphoplasmacytic interstitial infiltrates and proteinaceous cylinders, as described in West Highland white terrier breeds 10 and pugs dogs. Prognosis for dogs affected by CNM is unfavorable. To present date, patients have received palliative care, with the use of steroidal anti-inflammatories such as prednisone, employed in immunosuppressive dosages, associated to anticonvulsants. This treatment may help extend the survival period, which has varied from less than 60 days to four months. Reports of combined treatment with prednisone and cyclosporine suggest greater efficacy in the treatment of clinical signs and increased survival periods, exceeding 300 days. Anticonvulsant drugs and steroid therapy usually show little eficacy. The study of neurological disorders in small animals has gained increased attention from veterinary practitioners in the past years. The information exchange among professionals (breeders, practitioners and pathologists) is of vital importance and will certainly prompt reporting of CNM cases. At present, the disease is probably under diagnosed in Brazil, since the definitive diagnosis still depends on histopathological examinations, usually post-mortem. The occurrence of seizures in affected animals is the symptom that usually leads them to the veterinary clinic. Thus, when CNM is considered for diagnosis, it is usually late. Practitioners are advised to inform the owners of predisposed breeds so that they are aware of the more subtle neurological symptoms of the disease, as listed in figures 1 and 2. They should also consider CNM as a possibility in differential diagnosesLa meningoencefalitis necrosante canina (MNC) es una enfermedad inflamatoria idiopática que afecta los hemisferios cerebrales de perros de razas pequeñas. Crisis convulsivas son la señal clínica más característica de un proceso progresivo que puede durar días o años. La etiología de este complejo no es conocida mas se cree que factores genéticos y ambientales puedan estar implicados. La terapia usada actualmente es paliativa y se usan corticosteroides inmunosupresores y anticonvulsivos. En esta revisión son descritos seis casos de MNC en Brasil, en las razas Pug (dos casos), Yorkshire (dos casos) y Maltés (dos casos). Tres casos fueron procedentes de la Faculdade de Medicina Veterinária e Zootecnia de la Universidade de São Paulo, SP, y tres del Laboratório de Patologia Veterinária de la Universidade Federal de Santa Maria, R