Neuronal vacuolation and spongiform lesions in young Rottweiler dogs

Vacuolização neuronal e lesões espongiformes em cães Rottweiler jovens

Abstract

Descreve-se a ocorrência de vacuolização neuronal e lesões espongiformes no sistema nervoso central (SNC) de dois cães jovens da raça Rottweiler, um macho e uma fêmea, pertencentes à mesma ninhada de oito filhotes. Os sinais clínicos e neurológicos apareceram aos três meses de idade e foram progressivos, tornando-se graves e compreendendo ataxia inicial dos membros pélvicos, com evolução para ataxia generalizada, reações proprioceptivas diminuídas, hiperreflexia, estrabismo posicional, disfagia e tosse ao se alimentar. Exame neuropatológico revelou lesões apenas no SNC, consistindo em vacuolização neuronal intracitoplasmática e vacuolização de neurópilo em várias regiões do cérebro e da medula espinal, principalmente no tronco encefálico. Os vacúolos eram únicos ou múltiplos, pequenos, de 1 a 2mim, ou grandes, quase do tamanho do corpo celular. Em geral, as lesões foram semelhantes àquelas vistas nas encefalopatias espongiformes transmissíveis. Enfermidade aparentemente idêntica foi relatada muito recentemente na Europa e nos Estados Unidos e, ao que tudo indica, tem origem familiar.

Cão; Rottweiler; vacuolização neuronal; lesão espongiforme

Dog; Rottweiler; neuronal vacuolation; spongiform lesion

Cão; Rottweiler; vacuolização neuronal; lesão espongiforme

(Comunicação)

Neuronal vacuolation and spongiform lesions in young Rottweiler dogs

(Vacuolização neuronal e lesões espongiformes em cães Rottweiler jovens)

L.S. Jardim¹, J.P. Andrade-Neto², A.C. Alessi^1*

¹Departamento de Patologia Veterinária, Faculdade de Ciências Agrárias e Veterinárias - UNESP

Rodovia Carlos Tonani, km 5

14870-000 - Jaboticabal – SP, Brasil.

²Clínica Alto da Lapa, São Paulo

Recebido para publicação em 9 de setembro de 1998.

E-mail: [e-mail]

Neuronal vacuolation and spongiform lesions are important features of the histopathology of transmissible spongiform encephalopathies (TSE), used as diagnostic in the majority of cases (Wells & McGill, 1992). However, vacuoles may occur in neuronal soma sporadically in clinically normal cattle, sheep and cats, as well as in dogs although rare, are sometimes interpreted as incidental (Pumarola et al., 1995). Hamir et al. (1997) reported neuronal vacuolation in two raccoons, but without clinical correlation. The first reports about an apparently new disease involving neuronal vacuolation in Rottweiler dogs were published by Kortz et al. (1997) and Van Den Ingh et al. (1998). This disease occurred in young Rottweiler dogs from Europe and USA and was characterized by intracytoplasmic neuronal vacuolation and mild spongiform lesions resembling spongiform encephalopathy. The authors differentiated this TSE-like disease from the familial progressive lower motor neuron disease (Shell et al. 1987), leucoencephalomyelopathy (Gamble & Chrisman, 1984) and neuroaxonal dystrophy (Cork et al., 1983).

This communication describes the occurrence of a disease in two young Rottweiler from one litter similar to that described by Kortz et al. (1997) and Van Den Ingh et al. (1998). The pathology comprised mainly to neuronal vacuolation and spongiform lesions limited to the brain and spinal cord which were strikingly similar to TSE.

Two young Rottweiler dogs, one male and one female, from the same litter of 8 puppies, were affected. The two dogs were brought initially to the Alto da Lapa Clinic – São Paulo, SP, with progressive neurological signs. The owners reported that the neurological signs appeared at the age of three months. The initial reported signs included pelvic limbs weakness and ataxia for two months. The physical examination, routine blood and cerebrospinal fluid evaluation of the male dog were unremarkable. On the other hand, neurological examination revealed generalized ataxia with the pelvic limbs being weaker than the thoracic ones. Slowed proprioceptive placing reactions were detected in the pelvic and right thoracic limbs; the spinal reflexes were exaggerated and position strabismus was detected in cranial nerves examination. This dog had no improvement with corticosteroid therapy for one month. The owner reported that this dog developed disphagy and cough when food was ingested.

The female dog was brought to the same private clinic twenty days after the male dog with the same history and clinical signs: ataxia of all limbs with more evidence in the pelvic ones, progressing to a dysfunction of the cranial nerves and no improvement with corticosteroid therapy. Neurological examination revealed ataxia of all limbs, increased response on myotatic reflexes, slowed proprioceptive placing reactions and altered postural reactions, more evident on the pelvic limbs (Fig. 1); cranial nerves examination revealed bilateral position strabismus, head left tilt, disphagy, regurgitation of food, abnormal vocalization, cough and inspiratory dyspnea.

The male dog was killed at the age of six months after a period of serious deterioration of the clinical condition. Necropsy was undertaken and CNS and other organs were collected, immersed in 10% phosphate buffered formalin solution. This material was sent to the Department of Veterinary Pathology (DPVE) of the University of São Paulo State, Jaboticabal – SP, Brazil, for histopathological analysis. The female dog was killed at eight months of age when clinical signs were serious. Euthanasia, complete necropsy and microscopic evaluation of this animal were performed at the DPVE. Parts of the CNS, peripheral nerves, intestines, gall bladder, liver, kidneys and other organs were collected and immersion-fixed in 10% phosphate buffered formalin. Parts of these organs were frozen for further studies, for rabies virus search and for frozen sections. Samples selected from the formalin-fixed organs were routinely embedded in paraffin, sectioned at 5mm and stained with hematoxylin and eosin (HE) or by the Laphan method. Some selected samples were embedded in histo-resin, sectioned at 2mm and stained with toluidin blue. Frozen sections of the CNS were stained with Sudan IV. Other paraffin sections were utilized for PAP immunohistochemical technique employing primary antibodies to the glial fibrillary acidic protein (GFAP – Dako Corp.).

Gross examination confirmed in the female dog the presence of megaesophagus, but there were no other relevant macroscopic alterations in both animals. Microscopically the more conspicuous lesions were observed at the CNS, including intracytoplasmic neuronal vacuolation and some vacuolation of the neuropil in several regions of the brain and spinal cord. In the peripheral nervous system no lesion were observed.

The vacuoles were unique or multiple, small as 1-2mm or as large as the whole neuron body (Fig. 2-5). Sometimes, the vacuoles were "lobulated", slightly divided by bridges of delicate membrane like formation (Fig. 4). The nuclei was generally in the original position or sometimes it was dislocated to the periphery (Fig. 2). The female dog, that lived a longer period of time with the disease, presented mainly single large vacuoles, instead of multiple (Fig. 3). All the vacuoles were empty at the paraffin, histo-resin and frozen sections. Neuronal vacuolation was present in large amounts bilaterally at the lateral vestibular nucleus (Fig. 2, 3, 4) accompanying spongiform lesions in the neuropil. In lesser amounts neuronal vacuolation was present at the nucleus of spinal tract of trigeminal nerve, fastigial nucleus, reticular formation, hypoglossal motor nucleus, nucleus of oculomotor nerve, central gray substance, lateral cuneate nucleus, olivary nucleus, thalamic nucleus (Fig. 5) and at the dorsal and ventral horn of the spinal cord. Vacuolated neurons in the cortex gray matter were rarely seen. Some Purkinge cells appeared also vacuolated. Necrosis of neurons was also present in the areas where vacuolation was intense. Other alterations were a mild axonal necrosis and swelling in the spinal cord white matter, evidenciated by the special staining. No pigments of any type were detected. The assay for the presence of distemper and rabies virus (direct immunofluorescence) was negative. Immunohistochemistry for GFAP revealed only normal astrocytes present also in the regions where vacuolation was intense.

These aspects point out to the occurrence of a similar disease reported firstly by Kortz et al. (1997) and Van Den Ingh et al. (1998) in Rottweiler dogs, but different from the neurologic syndromes that affect young or adult dogs – the well know progressive lower motor neuron disease (Shell et al., 1987), the leucoencephalomyelopathy (Gamble & Chrisman, 1984) and the neuroaxonal dystrophy (Cork et al., 1983). Several clinical signs presented by the Rottweiler dogs examined in this study were similar to those reported by Kortz et al. (1997) and Van den Ingh et al. (1998). Ataxia and progressive neurologic deterioration was common to all the animals. Laryngeal/pharyngeal dysfunction was also observed in both studies, but in this, it was also observed one case of megaesophagus. The neuropathological findings were also very similar, but in this study, the female dog presented more prominent vacuoles than the male and the dogs examined by Kortz et al. (1997) and Van Den Ingh et al. (1998). This fact could be attributed to the longer evolution period of the disease of the female dog. But, in general, the morphology, location and size of the vacuoles were apparently identical in both studies.

The immunohistochemistry did not reveal astrocytosis or astrogliosis, even in the regions where the neuronal and neuropil lesions were prominent. On the contrary, Kortz et al. (1997) observed mild fibrillary astrocytosis. This study differed also on the aspect that no lesions were found in the peripheral nervous system.

In conclusion, the clinical and neuropathological aspects of the disease affecting the two dogs from the same litter of eight pups reported here suggest that it is the same disease reported by Kortz et al. (1997) and Van Den Ingh et al. (1998) and has a clear similarity with TSE, when analyzed by optic microscopy. The etiology remains obscure, but the ratio of affected/normal pups suggests genetic determination. Suspicion of BSE or scrapie is not plausible considering the short incubation period and that these diseases are not yet diagnosed in Brazil

Keywords: Dog, Rottweiler, neuronal vacuolation, spongiform lesion

ACKNOWLEDGEMENTS

To Fapesp and CNPq for financial support and to the technicians Maria Ines Y. Campos and Francisca A. Ardisson.

RESUMO

Descreve-se a ocorrência de vacuolização neuronal e lesões espongiformes no sistema nervoso central (SNC) de dois cães jovens da raça Rottweiler, um macho e uma fêmea, pertencentes à mesma ninhada de oito filhotes. Os sinais clínicos e neurológicos apareceram aos três meses de idade e foram progressivos, tornando-se graves e compreendendo ataxia inicial dos membros pélvicos, com evolução para ataxia generalizada, reações proprioceptivas diminuídas, hiperreflexia, estrabismo posicional, disfagia e tosse ao se alimentar. Exame neuropatológico revelou lesões apenas no SNC, consistindo em vacuolização neuronal intracitoplasmática e vacuolização de neurópilo em várias regiões do cérebro e da medula espinal, principalmente no tronco encefálico. Os vacúolos eram únicos ou múltiplos, pequenos, de 1 a 2mm, ou grandes, quase do tamanho do corpo celular. Em geral, as lesões foram semelhantes àquelas vistas nas encefalopatias espongiformes transmissíveis. Enfermidade aparentemente idêntica foi relatada muito recentemente na Europa e nos Estados Unidos e, ao que tudo indica, tem origem familiar.

Palavras-Chave: Cão, Rottweiler, vacuolização neuronal, lesão espongiforme

• CORK, L.C., TRONCOSO, J.C., PRICE D.L. et al. Canine neuroaxonal dystrophy. J. Neuropathol. Exp. Neurol., v.42, p.286-296, 1983.
• GAMBLE, D.A., CHRISMAN, C.L. A leucoencephalopathy in Rottweiler dogs. Vet. Pathol., v.21, p.274-280, 1984.
• HAMIR, A.N., HEIDEL, J.R., PICTON, R. et al. Neuronal vacuolation in Raccoons (Procyon lotor). Vet. Pathol., v.34, p.250-252, 1997.
• KORTZ, G.D., MEIER, W.A., HIGGINS, R.J. et al. Neuronal vacuolation and spinocerebellar degeneration in young Rottweiler dogs. Vet. Pathol., v.34, 296-302, 1997.
• PUMAROLA, M., JUANOLA, B., FATZER, R. Neuronal vacuoles in the canine brain. Schweiz. Arch. Tierheilkd., v.137, p.62-64, 1995.
• SHELL, L.G., JORTNER, B.S., LEIB, M.S. Familial motor neuron disease in Rottweiler dogs: neuropathologic studies. Vet. Pathol., v.24, p.135-139, 1987.
• VAN DEN INGH, T.S.G.A.M., MANDIGERS, P.J.J., VAN NES, J.J. A neuronal vacuolar disorder in young rottweiler dogs. Vet. Rec, v.142, p.245-247, 1998.
• WELLS, G.A.H., McGILL, I.S. Recently described scrapie-like encephalopathies of animals: case definitions. Res. Vet. Sci., v.53, p.1-10, 1992.

Publication Dates

• Publication in this collection
  05 Apr 2001
• Date of issue
  Oct 1999

History

• Received
  09 Sept 1998