“MRI Findings in a Rottweiler with Leukoencephalomyelopathy”

Joseph S. Eagleson, DVM, DACVIM (Neurology)*, Marc Kent, DVM, DACVIM (Neurology), Simon R. Platt, BVM&S, DECVN,DACVIM (Neurology), Raquel R. Rech, DVM, DACVP, PhD, Elizabeth W. Howerth, DVM, DACVP, PhD

JAmAnimHosp Assoc 2013; 49:255–261

A 22 mo old male rottweiler presented with a 1 mo progressive history of general proprioceptive ataxia and upper motor neuron tetraparesis. Neurologic examination was consistent with a lesion affecting the first through fifth cervical spinal cord segments. MRI disclosed bilaterally symmetric hyperintensities on T2-weighted images in the crus cerebri and pyramidal tracts of the brain and the dorsal portion of the lateral funiculi of the cervical spinal cord. Fifty days after initial presentation, the dog was euthanized due to disease progression. Pathologic examination of the central nervous system (CNS) revealed a bilaterally symmetric chronic leukoencephalomyelopathy (LEM) consistent with previous reports of LEM in rottweilers. To the authors’ knowledge, this is the first report to describe the MRI characteristics of LEM in the rottweiler. The topography of the changes observed with MRI paralleled the pathologic changes, which were widespread loss of myelin, decreased axon numbers, and astroglial proliferation.

Conclusion:  MRI of the CNS of affected rottweilers may aid in establishing a presumptive antemortem diagnosis of LEM.

**Neuropath details: 

Severe loss of myelin and astrogliosis was found on pathology.  Further, microscopic investigation in the present case using immunohistochemistry (i.e.antibodies against MBP, neurofilament, and GFAP) and electron microscopy corroborated severe myelin loss, astrogliosis/astrocytosis, as well as demonstrating decreased numbers and degeneration of axons. In addition, minimal abortive attempts of oligodendroglial and Schwann cell remyelination were present ultrastructurally. Interestingly, Schwann cells have not be observed in the spinal cord in previously reported cases of LEM.  Schwann cell invasion into the spinal cord can occur in a variety of conditions, including primary myelin disorders as well as focal compressive and concussive processes. Although typically excluded from the CNS, Schwann cell invasion occurs at transition zones where the peripheral nervous system interfaces with the CNS, such as the dorsal and ventral root entry zones and near blood vessels.  Consistent with this, Schwann cells in the present case were observed near blood vessels

**The cause of LEM is unknown and thought to be hereditary in rottweilers.  The following have proved negative for inborn errors of metabolism:  b-galactosidase, b-hexosaminidase, b-hexosaminidase A, aryl sul-phatase A, acid phosphatase, b-glucuronidase, a-mannosidase, a-fucosidase, b-glucocerebrosidase, b-galactocerebrosidase, and sphingomyelinase.

FIGURE 1 Transverse plane T2-weighted MRI of the second cervical vertebral (A) and fourth cervical vertebral (B) spinal cord segments, the medulla oblongata (C) and corresponding gross spinal cord specimen from the fourth cervical vertebra (D) from of a 22 mo old male rottweiler with general proprioceptive ataxia and upper motor neuron tetraparesis.

There are bilaterally symmetrical, hyperintense lesions in the dorsolateral funiculi of the spinal cord (arrows in A and B). Images were acquired 50 days after initial presentation.A, B:Insets are from the MRI performed on initial presentation. In the caudal medulla oblongata, symmetrical hyper-intensities also are observed in the pyramids of the medulla oblongata (arrows in C). At the level of the fourth cervical vertebra, the hyperintensities corresponded to bilaterally symmetric opaque foci (arrows) on gross sections (D)

FIGURE 2 Transverse gross and microscopic sections of the spinal cord at the level of second cervical vertebra from the 22 mo old male rottweiler in Figure 1 reveal lesions involving the white matter.

A: Similar to Figure 1D, gross transverse section of the cervical spinal cord at the level of the second cervical vertebra, bilaterally symmetric white foci are also evident in the dorsal area of the lateral funiculi (arrows).

B:On a low power magnification of a transverse section of the cervical spinal cord, there are bilaterally symmetric areas of pallor in the lateral funiculi (arrows). Hematoxylin and eosin staining, bar¼2 mm.  Inset of B: A transverse section of the cervical spinal cord from banked tissue from an age matched control dog. Bar ¼ 2 mm. Note the uniform staining of the white matter.

C:The bi-laterally symmetric areas of pallor in the dorsal areas of the lateral funiculi indicate loss of myelin (arrows). Luxol fast blue staining, bar¼2 mm.  Inset of C: A transverse section of the cervical spinal cord from banked tissue from an age matched control dog. Note the uniform staining of the white matter. Bar¼2mm.

D:The loss of myelin is replaced by gliosis with numerous gemistocytic astrocytes (arrows). In the affected areas, vessels are prominent with hyper-trophy of the endothelial cells (arrowheads). Hematoxylin and eosin staining, original magnification3400, bar¼40 mm

FIGURE 3 Microscopic sections of the demyelinated area of dorsolateral lateral funiculus of the first cervical vertebral spinal cord segment from the affected rottweiler compared with the white matter of a similar area of the cervical spinal cord from banked tissue samples from an age matched control dog free of neurologic disease using a variety of immunohistochemical stains.

A: Immunohistochemical stain for myelin basic protein (MBP). In the bilaterally symmetric areas of pallor in the cervical spinal cord, there is severe myelin loss around axons with minimal punctuate positive remnants of myelin. MPB with fast red chromogen/hematoxylin counterstain, original magnification 31000.

B: For comparison, similar location of the cervical spinal cord from a normal dog stained for MBP with fast red chromogen/hematoxylin counterstain, original magnification 31000.

C:Immunohistochemical stain for neurofilament reveals decreased axon numbers. Di-aminobenzidine (DAB) chromogen/hematoxylin counterstain, original magnification31000.

D:For comparison, similar location of the cervical spinal cord from a normal dog stained for neurofilament as in panel C, original magnification31000.

E:Immunohistochemical stain for glial fibrillary acidic protein (GFAP). Myelin loss is replaced by astrocytosis and gemistocytic astrocytes. DAB chromagen/hematoxylin counterstain, original magnification31000.

F:For comparison, similar location of the cervical spinal cord from a normal dog stained for glial fibrillary acidic protein (GFAP) as in panel E. DAB chromagen/hematoxylin counterstain, original magnification31000. Bar¼15 mm

FIGURE 4 Electron micrographs from a demyelinated area of dorsolateral lateral funiculus of the first cervical vertebral spinal cord segment reveal axons that are few in number and scattered among oligodendroglial processes.

A: Those axons present are irregularly shaped (A) with wavy decompacted myelin sheaths (M). Lead cit-rate/uranyl acetate staining, bar ¼1mm.

B: Schwann cell remyelination is evident. Myelinated axons (A) are observed surrounded by Schwann cells (S) with basement membrane (arrow). Note the wavy, decompacted myelin (M) and adjacent hypertrophied astrocytic process (As).

Lead citrate/uranyl acetate staining, bar¼1mm