Ceroid-Lipofuscinosis in a Cocker Spaniel Dog - Veterinary Pathology

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Ceroid-Lipofuscinosis in a Cocker Spaniel Dog
L. Minatel, S. C. Underwood and J. C. Carfagnini
Vet Pathol 2000 37: 488
DOI: 10.1354/vp.37-5-488
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Vet Pathol 37:488–490 (2000)
Ceroid-Lipofuscinosis in a Cocker Spaniel Dog
L. MINATEL, S.C.UNDERWOOD, AND J. C. CARFAGNINI
Abstract. A neurodegenerative storage disease identified as ceroid-lipofuscinosis by light, fluorescence, and
electron microscopic examinations was diagnosed in a 4-year-old female Cocker Spaniel dog with progressive
ataxia and proprioceptive deficits. Stored pigment was found within neurons of the brain and spinal cord and
in smooth muscle cells of the urinary bladder and small muscular arteries. The microscopic findings resembled
those found in six other cases of generalized ceroid-lipofuscinosis in this breed. However, the brown discoloration
of the intestines, which was the major gross lesion observed in those cases, was not found. This is the
first report of the disease in Argentina.
Key words:
microscopy.
Brown bowel syndrome; ceroid-lipofuscinosis; Cocker Spaniel dogs; electron microscopy; light
Ceroid-lipofuscinoses are a complex group of inherited
neurodegenerative storage diseases that occur in humans and
animals and are characterized by the progressive accumulation
of a pigment similar to lipofuscin and ceroid within
neurons and other cells of the body. In humans, there are
four forms of the disease: infantile, late infantile, juvenile
(Batten’s disease), and adult (Kuff’s disease). 8 A comparable
spread was found in animals, especially in the dog. 8
Ceroid-lipofuscinosis has been reported in several breeds
of dogs, including English Setters, 4 Border Collies, 9 Cocker
Spaniels, 2,5 Dachshunds, 10 Salukis, 1 and Chihuahuas. 7 Similar
disease has been studied in Siamese cats, South Hampshire
and Rambouillet sheep, Devon cattle, Nubian goats, and primates.
8
Although the stored pigment has similar staining and fluorescent
properties similar to those of ceroid and lipofuscin,
the major constituent of this pigment is a lipid-binding protein
that is a component (subunit c) of mitochondrial ATP
synthase. 3 Studies on the ovine, bovine, canine, and human
(late infantile and juvenile diseases) pigments have shown
storage of subunit c. Patients with the infantile form of ceroid-lipofuscinosis
and Miniature Schnauzer dogs store a different
protein, identified as sphingolipid activator protein (or
saposins). 6 There are two families of ceroid-lipofuscinoses:
Those characterized by storage of subunit c and those in
which saposins accumulate. 6 Here, we describe ceroid-lipofuscinosis
in an adult Cocker Spaniel dog. This is the first
reported case of ceroid-lipofuscinosis in Argentina.
A 4-year-old female Cocker Spaniel dog was presented to
the referring veterinarian with progressive difficulty in walking.
The clinical examinations showed no abnormalities except
the gait. Neurologic examinations revealed hypermetric
ataxia and proprioceptive deficits in all four limbs. The dog
was euthanatized because of the progressive nature of the
disease and the lack of response to treatments, and the body
was submitted to the Department of Pathology at the Buenos
Aires Faculty of Veterinary Science for postmortem examination.
At necropsy, no significant gross abnormalities were
found, except a mild cystitis. The brain and spinal cord and
samples of urinary bladder were fixed in 10% formaldehyde
neutral solution. Representative blocks were processed for
paraffin embedment, sectioned at 5 m, and stained with
hematoxylin and eosin (HE). The following special stains
were applied to paraffin-embedded sections: periodic acid–
Schiff (PAS), Sudan black B, luxol fast blue, and thionine.
Unstained frozen sections of the spinal cord were examined
with fluorescence microscopy. Small formalin-fixed blocks
from the spinal cord were postfixed in 2% osmium tetroxide
in phosphate buffer and processed for electron microscopic
examination.
Microscopic examination of slides stained with HE revealed
storage of yellow-brown granules in the cytoplasm of
some neurons of the brain and spinal cord. The amount of
stored pigment varied in different anatomic areas. Deposits
were most pronounced in neurons of the spinal cord (both
dorsal and ventral horn) and basal bodies of the cerebellum
(Fig. 1) but were less evident in neurons of the cerebral
cortex and brain stem and in Purkinje cells. The most affected
neurons were swollen, and their nuclei and Nissl bodies
were displaced to the periphery; others looked normal
except for small amounts of stored material. The aggregations
of granules were commonly at one pole of the neuronal
body, often near the axon hillock (Fig. 2). Neuronal necrosis
with astrocytosis and aggregation of gitter cells were found
in basal bodies of the cerebellum and spinal cord, but loss
was not a common feature. The pigment was also evident in
the cytoplasm of glial cells. Similar but fewer yellow-brown
granules were found in the cytoplasm of the smooth muscle
cells of the urinary bladder (Fig. 3) and in the wall of small
muscular arteries.
The stored granules stained magenta with PAS, black with
Sudan black B, blue with luxol fast blue, and green with
thionine. Fluorescence microscopic examination showed
masses of yellow-green autofluorescent cytoplasmic granules.
Electron microscopic examination of affected neurons revealed
a variable number of cytosomes containing some
granular and amorphous but mostly membranous material
(Fig. 4).
The light microscopic findings, autofluorescence, and appearance
of the inclusions on electron microscopy corre-
488
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Vet Pathol 37:5, 2000 Brief Communications and Case Reports
489
Fig. 1. Cerebellum; dog. Neurons of the basal bodies contain stored pigment in the cytoplasm. Sudan black. Bar
100 m.
Fig. 2. Cerebellum; dog. Heavy aggregation of granular material at one pole of a neuron. Sudan black. Bar 16.5 m.
Fig. 3. Urinary bladder; dog. Mild accumulation of granular material in the cytoplasm of smooth muscle cells (arrows).
PAS, Mayer’s hematoxylin counterstain. Bar 25 m.
Fig. 4. Electron micrograph. Spinal cord; dog. Laminated membranous material of neuronal cytosomes. Bar 0.2 m.
spond closely with previous descriptions of ceroid-lipofuscinosis.
Six cases of this disease have been reported in Cocker
Spaniel dogs. 2,5 All of them had the same feature: a generalized
storage of a lipofuscinlike pigment, with a heavy
accumulation in smooth muscle. Moreover, all cases had the
same gross lesion, yellow-brown discoloration of the intestines.
These characteristics defined a clinical entity in Cocker
Spaniel dogs named brown bowel syndrome. 2 In the present
however, stored material was found within smooth muscle
cells of the urinary bladder and small muscular arteries, but
the major gross lesion of this syndrome was not found. Intestines
of this dog were not available for pathologic study.
There are three possible reasons for the lack of this characteristic
gross lesion: 1) the amount of pigment stored in
smooth muscle cells of the intestine was not enough to give
the viscera a yellow-brown discoloration, 2) the severity of
neurologic signs precipitated euthanasia before appreciable
amounts of pigment could accumulate in smooth muscle
cells, and 3) discoloration of the intestines was so mild that
the lesion was missed. The small amount of pigment found
in smooth muscle cells of the urinary bladder support the
first explanation.
Blindness and behavioral changes were reported in Cocker
Spaniel dogs with ceroid-lipofuscinosis. 2,5 None of these
signs were noticed in the present case.
The microscopic findings in this dog are in accord with
those found in the other six Cocker Spaniel dogs with generalized
ceroid-lipofuscinosis. However, because brown
bowel was not found, gross discoloration of the intestines
should not be expected in all cases.
Acknowledgement
We thank Dr. Daniel H. Farfallini, Buenos Aires, Argentina,
for submitting the case.
References
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in two Saluki dogs. J Comp Pathol 92:375–380,
1982
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490 Brief Communications and Case Reports
Vet Pathol 37:5, 2000
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Request reprints from Dr. L. Minatel, Department of Pathology,
Faculty of Veterinary Science, University of Buenos
Aires, Av. San Martin 5285, (1417) Capital Federal (Argentina).
E-mail: lminatel@ciudad.com.ar.
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