11-month-old, male castrated, dachshund, canine, (Canis familiaris)This dog was presented to the North Carolina
State University College of Veterinary Medicine
Neurology Service for a 3-month history of stumbling and
falling which had progressed to severe vestibular ataxia,
nystagmus, and possible seizure activity. This dog had
been treated previously with antibiotics and there was no
The necropsy was limited to the
head only.Â Bilaterally, the meninges of the caudal part
of the temporal, parietal lobe and the occipital lobe
were fluctuant and markedly thickened, up to 6 mm.
Serosanginous fluid and dark red soft clots were found
within the subdural space (subdural hematoma).Â On the
cut surface, the arachnoid space was markedly dilated due
to marked cerebral atrophy which was most prominent
in the left occipital lobe.Â The lateral ventricles were
asymmetrical with the left lateral ventricle smaller than
the right lateral ventricle (Fig.Â 3-1).Â The third ventricle
was slightly enlarged ventrodorsally and the interthalamic
adhesion was moderately thinned.
in the cerebral cortical gray matter, approximately
60% of the neurons contain abundant, eosinophilic to
amphophilic, granular to globular, cytoplasmic pigment,
which occasionally displaces the nuclei peripherally
(Fig.Â 3-4).Â The cytoplasmic pigment stains positively
with the PAS reaction and Sudan black and more
obviously, but less frequently, with LFB stain (Fig.Â 3-5).
Moderate numbers of neurons are shrunken, rounded or
angular, and hypereosinophilic, with hyperchromatic or
pyknotic nuclei, interpreted as neuronal degeneration and
necrosis.Â The dura and arachnoid mater are markedly
thickened up to 5 times normal by fibroblasts, moderate
multifocal angiogenesis and additional connective tissue
matrix.Â Multifocally, there is a moderate amount of
subarachnoid hemorrhage.Â Under U.V.Â illumination the
pigment is autofluorescent.Â Ultrastructurally, the neurons
have intracytoplasmic storage bodies which consist of
curvilinear forms (Figs.Â 3-5, 3-6).
Other sections examined: Cerebellum: There is moderate depletion of Purkinje cells and marked depletion of granular cells accompanied by marked narrowing of the granular layer and the molecular layer of the cerebellar cortex.Â Purkinje cells also contain eosinophilic cytoplasmic pigment which stains with PAS and LFB.
Eye: Bilaterally, there is mild depletion of the ganglion cells in the retina.Â There are a few ganglion cells with intracytoplasmic granules which stain with LFB.Â There is multifocal detachment of the retina with mild hypertrophy and hyperplasia of the pigmented epithelium (tombstone change).
moderate, neuronal degeneration and necrosis and
abundant neuronal intracytoplasmic granular pigment
with cerebral atrophy
Moderate ventricular asymmetry is present with the right lateral ventricle being somewhat larger than the left.Â The third ventricle is also enlarged.Â There is a large accumulation of fluid peripheral to the cerebral cortex (extra-axial) most apparent from the level of the optic chiasm caudally (Fig.Â 3-2).Â This fluid accumulation does not suppress on the FLAIR sequence as does the fluid within the ventricles and is slightly T1 hyperintense relative to fluid within the ventricles.Â The interthalamic adhesion is noticeably small and asymmetrical.Â The cerebellum has an irregular margin and the folia within the cerebellum have increased conspicuity.Â Post contrast medium administration, there is florid enhancement of the meninges surrounding the cerebral cortex and falx.Â There is no abnormal parenchymal enhancement.Â There is no evidence of increased intracranial pressure.
The neuronal ceroid
lipofuscinoses (NCLs) are inherited lysosomal storage
diseases characterized by progressive neuropathy and
accumulation of autofluorescent lipopigment in neurons
and other cells.3 NCLs have been described in human
beings, cattle, sheep, goats, cats and in several breeds of
dogs.1,4 Human NCLs are classified into several forms
based on the age of clinical onset, causative gene and
ultrastructure of the accumulating lysosomal storage
bodies.3 The causative mutations in dogs have been
reported in English setters (a missense mutation in CLN
8), border collies (a nonsense mutation in CLN5), bulldogs
(a missense mutation in CTSD) and juvenile dachshund
(a frame shift mutation in canine TPP1: the ortholog of
human CLN2).Â The canine TPP1 gene encodes a lysosomal
enzyme called tripeptidyl 1 peptidase 1 and is known as the
causative gene of infantile neuronal ceroid lipofuscinosis
in humans and when mutated leads to accumulation of
curvilinear-appearing cytosomes in neurons as well.3
The major accumulating protein in this breed is unknown, but subunit C of mitochondrial ATP is reported in English setters, border collies and Tibetan terriers, and sphingolipid activator proteins A and D have been identified in some types of human NCLs.1,3,4 The cerebral and cerebellar cortex atrophy with cytoplasmic eosinophilic pigmen, which stained with PAS and LFB stain in neurons, is consistent with ceroid lipofuscinosis.Â The autofluorescence and ultrastructure of the accumulating pigment in this dog are very similar to the previous reports of juvenile ceroid lipofuscinosis in this breed.Â The dilated subdural space is considered to be secondary to the cerebral cortical atrophy.
Cerebrum: Neuronal degeneration,
necrosis and loss, extensive, with gliosis, cerebral atrophy,
meningeal fibrosis, subdural hemorrhage, and eosinophilic
neuronal cytoplasmic bodies
also known as Batten disease, has been
reported in several domestic species and was recently
reported in a Vietnamese pot-bellied pig.2 The mode
of inheritance is thought to be autosomal recessive for
this type of storage disease.5 Although accumulation of
intracytoplasmic storage material can be found in many
organs, the most prominent pathologic manifestations
of these diseases are seen in the retina, cerebral cortex,
Gross lesions can vary from being nearly imperceptible to marked cerebral atrophy.Â The earlier the onset of the disease the more severe the brain atrophy.4 Ultrastructurally, ceroid-lipofuscinosis can take on many different structural forms including curvilinear bodies, fingerprint bodies, and laminated stacks of membranes.5 Areas of cerebral atrophy often appear to have a brown tinge.5 The subdural hematoma in the present case is suspected to have resulted from trauma associated with motor disturbances.
Veterinary research into affected sheep resulted in a major contribution to understanding the human and animal ceroid lipofuscinoses by demonstrating that the stored material is predominantly protein (subunit C of mitochondrial ATP synthase) rather than lipid, as had been believed.Â Further research showed that in some forms of the disease, sphingolipid activator proteins are accumulated.Â Thus, ceroid lipofuscinosis is actually a misnomer.
1.Â Awano T, Katz LM, Brein PD, Sohar I, Lobel P, Coates
RJ, Johnson CG, Giger U and Jonson SG: A frame shift
mutation in canine TPP1 (the ortholog of human CLN2) in
a juvenile Dachshund with neuronal Ceroid lipofuscinosis.
Mol Genet Metab 89:254260, 2006
2.Â Cesta MF, Mozzachil K, Little PB, Olby NJ, Sills RC, Brown TT: Neuronal ceroid lipofuscinosis in a Vietnamese pot-bellied pig (Sus scrofa).Â Vet Pathol 43:556-560, 2006
3.Â Haltia M: The neuronal ceroid-lipofusinoses: From past to present, review.Â Biochamica et Biophysica 1762:850-856, 2006
4.Â Jolly DR, Palmer ND, Studdert PV, Sutton HR, Kelly RW, Koppang N, Dahme G, Hartley JW, Patterson SJ and Riis CR: Canine ceroid-lipofusinoses: A review and classification.Â J Small Anim Prac 35:299-306, 1994
5.Â Maxie MG, Youssef S: Nervous system.Â In: Jubb, Kennedy and Palmers Pathology of Domestic Animals, vol.Â 1 ed.Â Maxie MG, 5th ed., pp.329-330.Â Elsevier, Philadelphia, PA, 2007