A Leukoencephalomyelopathy of Rottweiler Dogs
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Vet. Pathol. 21: 274-280 ( I 984)
A Leukoencephalomyelopathy of Rottweiler Dogs
D. A. GAMBLE
and C. L. CHRISMAN
Department of Comparative and Experimental Pathology, Department of Medical Sciences, College of
Veterinary Medicine, University of Florida, Gainesville, FL
Abstract. Two adult rottweiler dogs were evaluated for slowly progressive ataxia and paresis of all four limbs of over seven
months duration. On neurologic examination,signs referable to a lesion in the cervical spinal cord affecting motor and sensory
white matter tracts were found. Both dogs were necropsied and were found to have demyelinating lesions in the spinal cord,
brain stem, and deep cerebellar white matter. Primary morphologic alterationswere intact naked axons and thinly myelinated
axons accompanied by reactive astrogliosis. The spinal cord lesions tended to have bilateral symmetry and were found in the
lateral funiculi and occasionally in the dorsal funiculi. The cause and pathogenesis of the lesion were not determined.
Several anatomic and clinical descriptions of central known etiology in the cervical spinal cord was made in both
nervous system, white matter disorders in the dog are dogs. Distemper virus-induced myelopathy was considered
found in the literature. A leukomyelopathy of Afghan the strongest differential diagnosis. The female was killed
painlessly shortly after evaluation. The male was treated for
hounds has been well characteri~ed.’.~.’.~. l o Globoid
two months with corticosteroidswith no improvement in his
cell leukodystrophy has been described in cairn and neurologic status and then was killed painlessly. Complete
West Highland white terriers.” Other leukomyelopa- necropsies were done on both dogs.
thies and leukoencephalopathies include disorders in
’
miniature poodles,”. I dalmatians: Jack Russell ter- Materials and Methods
r i e r ~ ,and
’ ~ fox A dysmyelinating disorder has Tissues were fixed in 10% neutral buffered formalin, proc-
been documented in the chow chow breed.’3.’4 German essed, embedded in paraffin, sectioned, and stained with
shepherd myelopathy involves, but is not restricted to, hematoxylin and eosin (HE). Selected sections of central
the spinal cord white matter.’.6 This report describes nervous system tissue were stained with luxol fast blue-pe-
riodic acid-Schiff(luxol fast blue-PAS)and Bodian silver stain.
the clinical signs and lesions in two rottweiler dogs with Cervical spinal cord tissue from the male was removed and
a leukoencephalomyelopathy. fixed in cold Trump’s fixative within fifteen minutes after
euthanasia. One millimeter transverse sections from C4 were
Case Histories fixed for one hour. Sections then were minced for further
Two rottweiler dogs, one four-year-old male and one three- fixation, processed, and embedded in epon-araldite. One mi-
year-old female, were presented for clinical evaluation of a crometer toluidine blue-stained sections and ultra-thin sec-
slowly progressive ataxia and quadriparesis of nine and seven tions for electron microscopy were prepared and stained with
months duration, respectively. The dogs had a common lead citrate and uranyl acetate and examined.
grandsire on their sires’ side, but were raised in different
households. Generalized limb weakness, hypermetria, espe- Results
ciaiiy of the forelimbs, and delayed proprioceptive position- Lesions were restricted to the central nervous system.
ing, primarily in the rear limbs, were found on neurologic
examination. All spinal reflexes were exaggerated. No neuro- Grossly, the transverse section of the cervical spinal
logic abnormalities referable to structures above the foramen cord had a dull white, opaque discoloration in the
magnum were detected. No evidence of ventral gray matter lateral funiculi and sometimes in the dorsal funiculi
or neuromuscular disease could be detected with electro- (fig. 1). The lesions extended into the pyramidal tracts
myography. Cerebrospinal fluid analysis, vertebral column of the myelencephalon. The distribution of the lesions
radiograms, and myelograms were normal. Complete blood varied slightly in the two dogs (figs. 2, 3). In the female,
counts and serum chemistry profiles also were normal. The
dogs had a current vaccination status for canine distemper, the lesions were found only in the cervical and cranial
infectious canine hepatitis, canine parvovirus, leptospirosis, thoracic spinal cord, the pyramidal tracts, and deep
and rabies. A clinical diagnosis of leukomyelopathy of un- cerebellar white matter. in the male, the same distri-
274
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Fig. 1: Transverse section of
spinal cord at Cx from female dog.
Dull, white discoloration of dor-
solateral aspect of lateral funiculi.
bution was found but lesions extended caudally as far white matter was replaced by a light blue pallor. A
as L,. The smaller lesions (figs. 2, 3) and bilaterally narrow rim of normal white matter always was seen
symmetrical focal lesions in the deep cerebellar white between the edge of the lesion and the pial surface (fig.
matter could be detected only microscopically. A tend- 4, “e”). A sharp line of demarcation between normal
ency for symmetry was seen but unilateral and asym- peripheral white matter and the lesion was characteris-
metrical lesions were encountered. tic. Rarefaction and microcavitation occurred in the
Microscopically, the lesions were characterized by a center of the larger lesions (fig. 4,“c”). By comparing
loss of myelin staining. With HE-stained sections, the approximate serial sections stained with HE and Bodian
normally intense eosinophilia of the white matter was stains, axons could be seen coursing through both the
lost. The neuropile had a fine fibrillar appearing mesh- rarefied center and the edge of the lesion (figs. 5-8).
work dotted with numerous oligodendrocyte nuclei. Reactive astrocytes were numerous in many areas. A
With luxol fast blue-PAS, the deep blue staining of the few swollen degenerating axons were seen occasionally.
Fig. 2: Distribution of lesions CI
in male dog. Upper left drawing
represents the medulla oblong-
ata.
Fig. 3: Distribution of lesions
in female dog. Top drawing rep
resents the medulla oblongata.
c3x4
Downloaded from vet.sagepub.com by guest on May 23, 2015276 Gamble and Chrisman
Fig. 4 Macroscopic view of transverse section of spinal cord at C4from male dog. Both lateral funiculi and dorsal funiculus
have striking staining pallor. Center of lesion (c) has rarefiedappearance. Edge (e) demarcated sharply from normal peripheral
white matter. Luxol fast blue-PAS.
The vessels permeating the lesions were prominent and occurred, then wallerian degeneration would be seen
cuffed by mononuclear phagocytes. With toluidine below the lesion in the motor tracts and above the
blue-stained 1-pm sections, axons surrounded by thin lesions in the sensory tracts of the spinal cord. This was
myelin sheaths could be found (fig. 9). Many axons had not seen. The Bodian stain clearly demonstrated axons
distorted, irregular profiles, some with slightly increased coursing through even the rarefied regions of spinal
diameters. Axonal spheroids were found in the acces- cord. Axons could be found in 1-pm toluidine blue-
sory cuneate nucleus, nucleus gracilis, nucleus cunea- stained sections as well as by electron microscopy.
tus, and the nucleus of the dorsospinocerebellar tract Ultrastructurally, thinly myelinated axons were
of the male dog only. Few axonal spheroids were seen found throughout the lesions. Axons with diminished
and they were not associated with detectable neuronal myelin sheaths but without evidence of active break-
loss. down can be interpreted as evidence of remyelina-
Ultrastructurally, thinly myelinated axons separated tion*17.20 The rarefied appearance of the central zone of
by broad astroglial processes were found (figs. 10, 11). the larger cord lesions probably is a result of interstitial
Astrocyte cytoplasm and intercellular spaces were vac- and intracellularedema. This was seen ultrastructurally
uolated. The abundant astrocyte processes, as well as as empty intracellular vacuoles in astrocyte processes
the interstitial and intracellular vacuolation, contrib- and a vacuolated appearance of intercellular spaces.
uted to the splaying of the axons. Again, axon profiles Perivascular mononuclear phagocytes containing my-
were distorted and irregular. Minimal disorientation of elin breakdown fragments which appear as multilami-
the neurofilamentswas seen. An occasional naked axon nated membranous structures indicate the process was
was found. Mononuclear phagocytes, in perivascular active. However, no unequivocal evidence of active
spaces, contained multilaminated membranous struc- myelin destruction characterized by splitting of the
tures within vacuoles. lamellae was seen. The finding of irregular axonal con-
tours is difficult to interpret. Perhaps demyelinated
Discussion axons exposed to encroaching astrocyte processes and
Interpretation of the morphologic changes suggests other axons is responsible for distorting the axolemma.
the primary lesion is demyelination. An important Some of the irregularity may be a result of the method
concept in distinguishing demyelination from second- of fixation. Perhaps the distorted contour indicates a
ary degeneration is the lack of neuronal fiber degener- primary axon abnormality. In canine neuroaxonal dys-
ation above and below the lesion. If axon damage trophy, distension of the axons results in attenuation of
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Figs. 5, 6: Approximate serial, longitudinal sections of cervical spinal cord from edge of lesion (area “e” in fig. 4). Fig. 5:
Lesion well demarcated from normal white matter (arrows). HE. Fig. 6: Axons coursing through both normal and abnormal
regions. Bodian.
Figs. 7,8: Approximate serial, longitudinal sections of cervical spinal cord from center of lesion (area “c” in fig. 4). Junction
of gray and white matter (arrows). Fig. 7: Neuropile has fine lacy appearance and distinct staining pallor. HE. Fig. 8: Axons
can be seen coursing through the lesion. Bodian.
Fig. 9: Transverse 1-rm section of cervical spinal cord corresponding to junction between areas “c” and “errin fig. 4. Axons
thinly myelinated (arrow); many have irregular contours; a few have increased diameters. Toluidine blue.
Fig. 10: Electronmicrograph (same area as fig. 9). Myelin sheaths diminished; axolemmal membranes irregular; slight
disarray of neurofilaments. Bar = 2 pm.
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Fig. 11: Electronmicrograph
(same area as fig. 9). Myelin sheaths
diminished; uncondensed oligoden-
drocyte cytoplasm still remains (ar-
rows)-indicative of remyelination.
Vacuolated spaces (v) within astro-
cyte processes. Bar = 1 pm.
the myelin sheaths.x Many of the demyelinated axons, erally symmetrical. Such symmetry and lesional distri-
however, did not have increased diameters or accu- bution is seen in subacute combined degeneration in
mulated membranous or subcellular structures seen in man and is a manifestation of vitamin Blzdeficiency.”
neuroaxonal dystrophy. Leukoencephalomalacia in horses is caused by a my-
The term leukoencephalomyelopathy denotes a dis- cotoxin of Fusarium moniliforme.-)6Bilateral symmet-
order affecting white matter in the brain and spinal rical necrosis of periventricular white matter often oc-
cord. It is purposefully vague with no inference as to curs.
the pathogenesis or histologic character of the lesion. A An infectious cause of demyelination in the dog is
question which should be answered is whether the exemplified by the canine distemper v i r u ~ . ’ The
~.~~
disorder is a demyelinating disease or a leukodystrophy. exact mechanism of demyelination is controversial.
A demyelinating disease is characterized by a process Whether myelin loss occurs by cytopathic effect of the
of disintegration of the myelin sheath without damage virus on the oligodendrocyte or whether immune-me-
to axons. I’ Leukodystrophies are regarded as inherited diated destruction of myelin occurs is debated.” In the
conditions in which myelin formation is defective and mouse, a neurotropic strain of the mouse hepatitis
cannot be maintained.” This question cannot be re- virus, type 4 (JHM strain) has a propensity to infect
solved, but since the dogs were related, a late-onset oligodendrocytes. A temperature sensitive mutant of
leukodystrophy should be considered. Leukodystro- this virus has caused recurrent demyelination of the
phies in the Afghan lo miniature poo- brain and spinal cord of BALB/c mice for as long as
’’
dies,". cairn and West Highland white terriers,’? and one year after experimental inoculation.’8
dalmatians4occur in young dogs-usually less than one A disease acting through vascular mechanisms is
year of age. Adult-onset leukodystrophieshave not been considered because of the distribution of the lesions.
described in the dog. The possibility of an acquired The lesions in the spinal cord were found at or near the
demyelinating disease also exists. These rottweiler dogs perfusion boundaries of the ventral and dorsal blood
may have been predisposed genetically to acquire the supplies.’x The dorsal spinal arteries are developed
disorder through toxic, metabolic, nutritional, vascular, poorly in the cervical region in the dog.” Vascular
or infectious mechanisms. mechanisms also would explain the segmental distri-
Toxic, metabolic, and nutritional mechanisms must bution better. Experimental vascular occlusion and
be considered because the lesions tended to be bilat- spinal cord compression with superimposed hypovo-
Downloaded from vet.sagepub.com by guest on May 23, 2015Leukoencephalom yelopathy 279
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common grandsire of the dogs with leukoencephalo- 13 GOODING, M.R.; WILSON, C.B.; HOFF,J.T.: Experimental
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NER,A.: Primary demyelination in experimental canine
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18 KNOBLER, R.L.; TUNISON, L.A.; LAMPERT, P.W.; OLD
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19 LAMPERT, P.W.: Autoimmune and virus induced demye-
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Request reprints from Dr. David A. Gamble, The New York Hospital-Come11 Medical Center, Dept. of Medicine, Div. of
Geriatrics and Gerontology, Room A453,525 East 68th St., New York, NY 10021 (USA).
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