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 response.

Gross Description:  

The necropsy was limited to the head only. 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). On the cut surface, the arachnoid space was markedly dilated due to marked cerebral atrophy which was most prominent in the left occipital lobe. The lateral ventricles were asymmetrical with the left lateral ventricle smaller than the right lateral ventricle (Fig. 3-1). The third ventricle was slightly enlarged ventrodorsally and the interthalamic adhesion was moderately thinned.

Histopathologic Description:

Cerebrum: Diffusely 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. 3-4). The cytoplasmic pigment stains positively with the PAS reaction and Sudan black and more obviously, but less frequently, with LFB stain (Fig. 3-5). Moderate numbers of neurons are shrunken, rounded or angular, and hypereosinophilic, with hyperchromatic or pyknotic nuclei, interpreted as neuronal degeneration and necrosis. The dura and arachnoid mater are markedly thickened up to 5 times normal by fibroblasts, moderate multifocal angiogenesis and additional connective tissue matrix. Multifocally, there is a moderate amount of subarachnoid hemorrhage. Under U.V. illumination the pigment is autofluorescent. Ultrastructurally, the neurons have intracytoplasmic storage bodies which consist of curvilinear forms (Figs. 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. 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. There are a few ganglion cells with intracytoplasmic granules which stain with LFB. There is multifocal detachment of the retina with mild hypertrophy and hyperplasia of the pigmented epithelium (tombstone change).

Morphologic Diagnosis:  

Diffuse, moderate, neuronal degeneration and necrosis and abundant neuronal intracytoplasmic granular pigment with cerebral atrophy

Lab Results:  

MRI findings
Moderate ventricular asymmetry is present with the right lateral ventricle being somewhat larger than the left. The third ventricle is also enlarged. 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. 3-2). 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. The interthalamic adhesion is noticeably small and asymmetrical. The cerebellum has an irregular margin and the folia within the cerebellum have increased conspicuity. Post contrast medium administration, there is florid enhancement of the meninges surrounding the cerebral cortex and falx. There is no abnormal parenchymal enhancement. There is no evidence of increased intracranial pressure.


Ceroid lipofuscinosis

Contributor Comment:  

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). 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. 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. The dilated subdural space is considered to be secondary to the cerebral cortical atrophy.

JPC Diagnosis:  

Cerebrum: Neuronal degeneration, necrosis and loss, extensive, with gliosis, cerebral atrophy, meningeal fibrosis, subdural hemorrhage, and eosinophilic neuronal cytoplasmic bodies

Conference Comment:  

Neuronal ceroidlipofuscinosis, 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, andcerebellum.5

Gross lesions can vary from being nearly imperceptible to marked cerebral atrophy. 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. Further research showed that in some forms of the disease, sphingolipid activator proteins are accumulated. Thus, ceroid lipofuscinosis is actually a misnomer.


1. 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. Cesta MF, Mozzachil K, Little PB, Olby NJ, Sills RC, Brown TT: Neuronal ceroid lipofuscinosis in a Vietnamese pot-bellied pig (Sus scrofa). Vet Pathol 43:556-560, 2006
3. Haltia M: The neuronal ceroid-lipofusinoses: From past to present, review. Biochamica et Biophysica 1762:850-856, 2006
4. 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. J Small Anim Prac 35:299-306, 1994
5. Maxie MG, Youssef S: Nervous system. In: Jubb, Kennedy and Palmers Pathology of Domestic Animals, vol. 1 ed. Maxie MG, 5th ed., pp.329-330. Elsevier, Philadelphia, PA, 2007

Click the slide to view.

3-1. Brain, dog

3-2. Cranium, dog. 

3-3. Cerebrum, dog.

3-4. Cerebrum, dog.

3-5. Neuron, dog.

3-6. Neuron, dog

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