An interesting case: Neuronal Ceroid Lipofuscinosis by Melanie Dobromylskyj

Two 9 month old littermates, one male neutered and one female neutered, both of whom were rescued as kittens, presented with neurological signs including marked ataxia, intermittent seizures, tremors, “rearing up like meerkats” and “falling over backwards”. The onset of symptoms was within two days of each other, and the symptoms were progressive although one progressed quite quickly and the other more slowly.

No obvious toxins were identified in their environment, including lead. There was no pyrexia, and no haematological or biochemical changes were found. Trial treatments included thiamine, clindamycin and Keppra, but there was no clinical response.

Due to the progressive nature of the disease and lack of response to therapy, the owner opted for euthanasia. Samples of both brains were submitted to Finn Pathologists. There were no apparent gross changes visible on assessment. Sections were taken for histological assessment, including pituitary gland, cerebrum, midbrain, hindbrain and cerebellum.

Within many of the neurons within the cerebellum, hippocampus and sometimes elsewhere within the grey matter of the cerebrum, there was an accumulation of material within the cytoplasm; this material was deeply eosinophilic to sometimes red, with a slightly glassy appearance and often formed variably-sized, circular bodies with fairly distinct borders. There was also a decrease in Purkinje cells within the cerebellum, associated with a proliferation of cells resembling astrocytes. There was also some white matter degeneration noted within the cerebellum.

High power view (400x), HE-stained section through the hippocampus. The green arrows indicate the accumulated material within the cytoplasm of neurons.

At this stage the favoured diagnosis was of some form of storage disease; these are thought to be due to congenital defects, which lead to a fault in the normal degradation and processing pathways of certain materials. This material then tends to accumulate within various cell types, including the neurons – which is when they lead to clinical signs. Depending on the specific enzyme defect, the accumulated material can consist of glycolipids, carbohydrates, proteins, etc. The young age at onset and these two genetically similar cats being affected would also be consistent with a storage disease, and particularly in the absence of any other possible causes.

Special stains were used to try and further determine the precise nature of the material within the cytoplasm of these neurons, including Periodic Acid Schiff (PAS) for glycogen (negative) and Luxol Fast Blue (negative). However, when viewed under fluorescence (using a special microscope at the Royal Veterinary College), the material demonstrated auto fluorescence (green). This would be consistent with lipofuscin and in this case lead to a presumptive diagnosis of a ceroid-lipofuscinosis type of storage disease.

When viewed under fluorescence at 200x magnification, the accumulated material demonstrates auto fluorescence (green). Courtesy of Prof. Simon Priestnall, Royal Veterinary College

A case report was published in JFMS Open Reports in 2018 of a case of neuronal ceroid lipofuscinosis in a cat (White et al.) – this case was a 2 year old male Domestic Short Hair cat presenting with a two week history of altered mentation, blindness and focal epileptic seizures:

“The neuronal ceroid lipofuscinoses represent a heterogeneous group of genetically determined neurodegenerative lysosomal storage diseases. The disease is characterised by abnormal accumulation of autofluorescent lipopigments within the neuronal and extraneural tissue. Neuronal ceroid lipofuscinosis has been described in several domestic species, including dogs, cats, cattle, sheep, goats, monkeys and mice.”

References and Further Reading:

White C., Mortier J., Verin R., et al. MRI findings of neuroal ceroid lipofuscinosis in a cat. J Feline Med Surg Open Reports 2018.

Weissenbeck H. and Rossel C. Neuronal ceroid-lipofuscinosis in a domestic cat: clinical, morphological and immunohistochemical findings. J Comp Pathol 1997; 117: 17–24.

Kuwamura M., Nakagawa M., Nabe M., et al. Neuronal ceroid-lipofuscinosis in a Japanese domestic shorthair cat. J Vet Med Sci 2009: 71: 665–667.

Furusawa Y., Mizukami K., Yabuki A., et al. Mutational analysis of the feline CLN3 gene and an ultrastructural evaluation of lysosomal storage material in a cat with neuronal ceroid lipofuscinosis: an investigation into the molecular basis of the disease. Vet J 2012; 194: 425–428.

Chalkley M.D., Armien A.G., Gilliam D.H., et al. Characterization of neuronal ceroid-lipofuscinosis in 3 cats. Vet Pathol 2014; 51: 796–804.

 Please could we also thank:

  • The Axiom client who submitted the case and gave permission for its use on the website and for teaching purposes – Pete Coleshaw from Jaffa Vets.
  • Simon Priestnall at the RVC for his help with the fluorescence microscopy and opinions.
  • Mark Wessels and Nick Woodger who also gave their opinions on the case (this is something seen in farm animal species more than cats, so they both were very helpful in this instance!!).

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