Conference 10 - 2015 Case: 04 20151202

Signalment:

Bovine, Charolais (Bos taurus), male, 3 years oldThis three-yearold, charolais bull was presented for a two-month history of chronic posterior paresia. Clinical examination showed right hock stiffness with right leg mobility reduction.

Gross Description:

No lesions were observed on macroscopic examination

Histopathologic Description:

Brain, cerebellum: Multifocally in the white matter can be found numerous 20-100 μm diameter eosinophilic, acellular, granular to fibrillar, round to ovoid-shaped plaques, haphazardly distributed. The rest of the white matter contains multifocal, intra- and intercellular, optically empty, vacuolation (spongiosis). A mild, non-suppurative, inflammatory reaction can be found within and around the pathological areas, characterized by discrete lymphocytic perivascular cuffing and mild gliosis with increased number of oligodendrocytes and hyperacidophilic astrocytes (reactive astrocytes).

Kluver and Barerra stains showed the material was bright blue (consistent with myelin). No PAS positive material was observed.

Morphologic Diagnosis:

Brain, cerebellum, white matter, eosinophilic plaques, multifocal, severe with mild spongiosis and discrete gliosis in a Charolais bull, characteristic of progressive ataxia of Charolais cattle.

Lab Results:

No biochemical abnormalities ante mortem were found. Cerebrospinal fluid cytological examination was normal.

Condition:

Oligodendroglial dysmyelinogenesis

Contributor Comment:

Progressive ataxia is a condition seen in purebred and crossbred Charolais cattle. It is a genetic disease suspected to be of autosomal recessive transmission.(2,6) The chromosomic locus containing the gene coding the basic myelin protein is likely to be involved in this condition.(1) However studies are still ongoing to identify the causal mutation. It is a slowly progressive disease affecting Charolais cattle from 6 months to two years or more. Clinically, the animal will generally present a progressive hindlimb stiffness evolving into incoordination and dysuria. All other neurological functions are not thought to be affected.(2,6) The pathogenesis of the disease is an oligodendroglial dysmyelinogenesis. It is thought that the defect of production and maintenance of myelin sheaths in white matter, leading to widening of the node of Ranvier and subsequent poor saltatory nerve impulse conduction causing the nervous symptoms observed.

Ultrastructurally, the disease is characterized by hypertrophic and hyperplastic oligodendrocytes emitting numerous and disorganized small processes around the node of Ranvier, leading to myelin sheaths malformation in the white matter. The histological examination displays haphazard, multifocal, pale, eosinophilic, granular to fibrillar, 20-100 μm plaques which are pathognomonic for this disease, along with mild oligodendroglial hyperplasia, discrete astrocytosis, lymphocytic infiltration and cuffing.(2,4,5,6)

JPC Diagnosis:

Cerebrum and cerebellum, white matter: Dysmyelinogenesis, multi-focal, moderate, with fibrillary plaques and oligodendroglial hypertrophy.

Conference Comment:

The conference description was very similar to the contributors description above. Participants discussed the appearance of the fibrillary plaques as having a distinctive structure, often forming columns in certain regions of the section, and being absent of nuclei. The formation and origin of the plaques was discussed as originating from processes of hypertrophied oligodendrocytes, and not from the accumulation of abnormal myelin. This is a unique entity in that there are few known genetic diseases which affect oligodendrocytes. There is some slide variation, but lesion characteristics appear similar in all sections.

This condition is reported in both sexes of Charolais cattle, and has also been reported in three-quarter crossbred as well as purebred animals. Gross lesions are absent, but the microscopic lesions are unique and distinctive. Axons are found to traverse the plaques with mostly normal myelin and no sign of degradation or phagocytosis of the myelin. Evidence of axonal degeneration, when found, is mild. As mentioned above, ultrastructural examination suggests the abnormality lies within the paranodal region of axons. Younger plaques are characterized by axons wrapped with hypertrophied oligodendrocyte processes, in a thin myelin sheath, near the nodes of Ranvier. In older plaques the axons may be demyelinated and surrounded by more abundant oligoden-drocyte processes. The defect lies in the inability of oligodendrocytes to maintain the paranodal myelin structure with resultant oligodendrocyte hypertrophy.(2)

There are two types of oligodendrocytes within the CNS, interfascicular oligodendrocytes and satellite cells. The interfascicular oligodendrocytes are respon-sible for myelination of axons and normally they appear as small cells with hyperchromatic nuclei; special staining techniques, such as myelin basic protein, are normally required to visualize their processes. The nuclei of oligodendrocytes are often seen aligned in rows parallel to myelinated axons, where they maintain the internodal segments of the myelin sheath.(7)

References:

1. Duchesne A, Eggen A. Radiation hybrid mapping of genes and newly identified microsatellites in candidate regions for bovine arthrogryposis-palatoschisis and progressive ataxia based on comparative data from man, mouse and rat. J Anim Breed Genet. 2005;122(Suppl.1):28-35.

2. Maxie MG, Youssef S. The nervous system. In: Maxie MG ed. Jubb, Kennedy and Palmers Pathology of Domestic Animals. 5th ed. Vol 1. Edinburgh, UK: Saunders Elsevier; 2007:381-385.

3. Morrison JP, Schatzberg SJ, De Lahunta A, Ross JT, Bookbinder P, Summers BA. Oligodendroglial dysplasia in two Bullmastiff dogs. Vet Pathol. 2006 ;43:29-35.

4. Parodi AL. Progressive ataxia in cattle study of histologic lesions. Recueil de Medecine Veterinaire de l'Ecole d'Alfort. 1981 ; 339-345. (in French)

5. Patton CS. Progressive ataxia in Charolais cattle. Vet Pathol. 1977;14:535-537.

6. Vandevelde M, Higgins R, Oevermann A . Veterinary Neuropathology: Essentials of Theory and Practice. Chichester, UK: Wiley-Blackwell; 2012:176-177.

7. Zachary JF. Nervous System. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, MO: Mosby Elsevier; 2012:777-778.