GM2 Gangliosidosis (B Variant) in Two Japanese Chins: Clinical, Magnetic Resonance Imaging and Pathological Characteristics

Abstract

A 15-month-old, male neutered Japanese Chin dog was presented for evaluation of blindness and an abnormal gait first observed at 11 months of age. On presentation, the dog was periodically obtunded and had cerebellar ataxia with spastic, hypermetric postural reactions. The dog had an absent menace response and ventro-lateral strabismus in both eyes.A magnetic resonance imaging (MRI) examination was performed with a 3.0 T MRI unit a and a receiveonly quadrature knee coil, and consisted of turbo spin echo sequences with T2-weighting (T2W), and fluid attenuation inversion recovery T2-and T1-weighting (T2W FLAIR & T1W FLAIR) and gradient echo sequences (FSPGR, fast spoiled gradient echo; fast imaging employing steady state acquisition, FIESTA). The T1W FLAIR images were acquired before and after the IV administration of gadolinium-based MRI contrast (Magnevist, b 0.1 mmol/kg). The distinction between gray and white matter regions of the cerebrum and cerebellum was diminished to absent on T2W images (Fig 1). Bilaterally, small regions of more normal-appearing corona radiata were identified in the frontal lobes and rostral internal capsule. In the cranial cervical spinal cord, gray matter was indistinguishable from white matter. On the precontrast T1W FLAIR images, cerebral white matter was hyperintense to gray matter and had ill-defined margins. The cerebral sulci may have been mildly widened for the age of the patient, but the interthalamic adhesion and cerebellar folia were of the appropriate proportions (Fig 1). In addition, the lateral and third ventricles were subjectively dilated. Specifically, a focal enlargement of the caudodorsal aspect of the 3rd ventricle was noted, adjacent to a very small more caudal fluid accumulation, sometimes referred to as a supracollicular intra-arachnoid diverticulum. No abnormal enhancement was observed on postcontrast images. Spectroscopy c was performed in the cerebellar white matter, by a point resolved spectroscopy (PRESS) pulse sequence (Fig 2) and showed a decrease in the N-acetylaspartate (NAA) peak and NAA/creatine (NAA/Cr) ratio in the cerebellar white matter, compared with the normal dog cerebellum. The choline/Cr (Cho/Cr) and the Ch/NAA ratios were higher in the affected dog.The owner elected for euthanasia, and a necropsy was performed. Formalin and fresh frozen samples were collected. Using hematoxylin and eosin staining, the gray matter of the cerebrum and spinal cord was diffusely pale. Approximately 95% of the neurons throughout the cerebrum and dorsal and ventral horn of the spinal cord were up to 4 times larger than normal. These neurons contained abundant finely granular, foamy cytoplasm, which often displaced the nucleus and the Nissl substance to the periphery (Fig 3). Occasional swollen neurons contained dark basophilic nuclei consistent with neuronal degeneration. Many glial cells contained variably vacuolated cytoplasm. Primarily within the white matter of the spinal cord, axons were swollen with dilated myelin sheaths. Fragmented axons were replaced by eo...

Magnetic Resonance Findings of the Corpus Callosum in Canine and Feline Lysosomal Storage Diseases

“…Therefore, this finding may be a specific marker for suspecting canine GM2 gangliosidosis variant 0. Furthermore, the MRI findings in another type of GM2 gangliosidosis (B variant; Tay-Sachs disease) in 2 Japanese Chins were just reported [16]. The initial clinical signs of this type of GM2 gangliosidosis seem to begin at 11–16 months, and thus are classified as late juvenile- or early adult-onset.…”

Two‐Year Follow‐Up Magnetic Resonance Imaging and Spectroscopy Findings and Cerebrospinal Fluid Analysis of a Dog with Sandhoff's Disease

“…N-acetylaspartate is a marker for intact neuroaxonal tissue 20 and decreased NAA/Cr implies neuroaxonal damage in humans with SD 18,21,22 and decreased NAA and NAA/Cr have been described in a dog with GM2 B variant. 6 Increased Cho and Cho/Cr were thought to be associated with demyelination in a human SD patient. 21 In our MRS protocol using a long TE (136 ms), it was difficult to differentiate metabolites that had a peak at approximately 3.5-3.6 ppm because the spectra of Gly and Ins overlap.…”

“…Compared with our previous report of MRS in healthy dogs, there was a pattern of decreased NAA/Cr and increased Cho/Cr, Gly‐Ins/Cr, and Lac‐Ala/Cr ratios (Gly‐Ins/Cr and Lac‐Ala/Cr ratio increased at later stage). N‐acetylaspartate is a marker for intact neuroaxonal tissue and decreased NAA/Cr implies neuroaxonal damage in humans with SD and decreased NAA and NAA/Cr have been described in a dog with GM2 B variant . Increased Cho and Cho/Cr were thought to be associated with demyelination in a human SD patient .…”

“…These abnormal accumulations lead to delayed myelin formation, and swelling and destruction of neurons, axons, and myelin in the central nervous system, resulting in severe neurologic dysfunction . Although GM2 gangliosidoses are thought to affect gray matter primarily, myelin deficiency has been recognized in both the cat and dog . As a corollary of these pathological changes, abnormal signal intensity of the cerebral white matter (WM) on magnetic resonance imaging (MRI) has been documented in humans and domestic animals with GM2 gangliosidoses…”

“…4 Although GM2 gangliosidoses are thought to affect gray matter primarily, myelin deficiency has been recognized in both the cat and dog. 1,[5][6][7] As a corollary of these pathological changes, abnormal signal intensity of the cerebral white matter (WM) on magnetic resonance imaging (MRI) has been documented in humans and domestic animals with GM2 gangliosidoses 1,5,6,8,9 Sandhoff's disease (SD) is 1 of 3 main variants of GM2 gangliosidoses-gangliosidosis variant 0, caused by deleterious mutations of the HEXB gene encoding the b-subunit that is a common component of the lysosomal acid b-hexosaminidase A and B. 10 In dogs, clinical features and MRI findings in SD have been reported in a Golden Retriever, a family of Toy Poodles, in a mixed-breed dog and, recently, in Shiba-Inu dogs.…”