Neuronal ceroid-lipofuscinosis in longhaired Chihuahuas: clinical, pathologic, and MRI findings

Neuronal ceroid-lipofuscinosis (NCL) is a rare group of inherited neurodegenerative lysosomal storage diseases characterized histopathologically by the abnormal accumulation of ceroid- or lipofuscin-like lipopigments in neurons and other cells throughout the body. The present article describes the clinical, pathologic, and magnetic resonance imaging (MRI) findings of the NCL in three longhaired Chihuahuas between 16 mo and 24 mo of age. Clinical signs, including visual defects and behavioral abnormalities, started between 16 mo and 18 mo of age. Cranial MRI findings in all the dogs were characterized by diffuse severe dilation of the cerebral sulci, dilated fissures of diencephalons, midbrain, and cerebellum, and lateral ventricular enlargement, suggesting atrophy of the forebrain. As the most unusual feature, diffuse meningeal thickening was observed over the entire cerebrum, which was strongly enhanced on contrast T1-weighted images. The dogs' conditions progressed until they each died subsequent to continued neurologic deterioration between 23 mo and 24 mo of age. Histopathologically, there was severe to moderate neuronal cell loss with diffuse astrogliosis throughout the brain. The remaining neuronal cells showed intracytoplasmic accumulation of pale to slightly yellow lipopigments mimicking ceroid or lipofuscin. The thickened meninges consisted of the proliferation of connective tissues with abundant collagen fibers and mild infiltration of inflammatory cells suggesting neuroimmune hyperactivity. Although the etiology of this neuroimmune hyperactivity is not currently known, MRI findings such as meningeal thickening may be a useful diagnostic marker of this variant form of canine NCL.