A PNPLA8 frameshift variant in Australian shepherd dogs with hereditary ataxia.

Hereditary ataxias are common among canine breeds with various molecular etiology. We identified a hereditary ataxia in young-adult Australian Shepherd dogs characterized by uncoordinated movements and spasticity, worsening progressively and leading to inability to walk. Pedigree analysis suggested an autosomal recessive transmission. By whole genome sequencing and variant filtering of an affected dog we identified a PNPLA8:c.1169_1170dupTT variant. This variant, located in PNPLA8 (Patatin Like Phospholipase Domain Containing 8), was predicted to induce a PNPLA8:p.(His391PhefsTer394) frameshift, leading to a premature stop codon in the protein. The truncated protein was predicted to lack the functional patatin catalytic domain of PNPLA8, a calcium-independent phospholipase. PNPLA8 is known to be essential for maintaining mitochondrial energy production through tailoring mitochondrial membrane lipid metabolism and composition. The Australian Shepherd ataxia shares molecular and clinical features with Weaver syndrome in cattle and the mitochondrial-related neurodegeneration associated with PNPLA8 loss-of-function variants in humans. By genotyping a cohort of 85 control Australian Shepherd dogs sampled in France, we found a 4.7% carrier frequency. The PNPLA8:c.[1169_1170dupTT] allele is easily detectable with a genetic test to avoid at-risk matings.

Otitis media and interna with or without polyps in cats: association between meningeal enhancement on postcontrast MRI, cerebrospinal fluid abnormalities, and clinician treatment choice and outcome.

OBJECTIVES: The aim of this study was to evaluate the association between meningeal enhancement (MgE) and cerebrospinal fluid (CSF) analysis results, their individual association with bacteriology results from affected ear samples and whether these test results influenced clinicians' therapeutic choice in cats with otitis media and interna (OMI). METHODS: This was a multicentre retrospective study carried out over an 8-year period. Cats diagnosed with OMI, with or without a nasopharyngeal polyp, leading to peripheral vestibular signs were included. Only cats for which MRI with postcontrast T1-weighted sequences and CSF analyses available were included. Cats with intra-axial MRI lesions or empyema were excluded. RESULTS: Fifty-eight cats met the inclusion criteria. MgE was reported in 26/58 cases, of which nine had an abnormal CSF result (increased total nucleated cell count [TNCC] or total protein); 32/58 cases had no MgE, of which 10 showed abnormal CSF results. There was no association between bacteriology results (external ear canal or bulla) and MgE or abnormal CSF results. CSF abnormalities were statistically significantly more common in acute cases (n = 16/37) than in chronic cases (n = 3/21; Fischer's test P = 0.04). Prednisolone was prescribed in 10/16 cases with increased TNCC. Among the 42 cases with normal TNCC, 15 received prednisolone and 13 received non-steroidal anti-inflammatory drugs. Various antimicrobial drugs were prescribed in 53/58 cats. Duration of antimicrobial treatment was similar, regardless of positive bacterial culture (5.58 vs 4.22 weeks), abnormal CSF (5.83 vs 4.76 weeks) or MgE (5.33 vs 4.90 weeks). CONCLUSIONS AND RELEVANCE: No association was found between the CSF and MgE results. Furthermore, no association was found between MgE, CSF or bacteriology findings. In addition, abnormal CSF results might lead the clinician to treat with corticosteroids, but they did not have any impact on duration of antimicrobial treatment. CSF abnormalities were seen significantly less frequently in chronic cases. The outcome tended to be poorer when MgE was detected on MRI.

Haematomyelia and myelomalacia following an inadvertent thoracic intraspinal injection in a cat.

CASE SUMMARY: A 4-month-old cat was presented with acute paraplegia after the referring veterinarian performed a subcutaneous injection (cefovecin and dexamethasone) in the caudodorsal thoracic area, during which the cat suddenly became uncooperative. A complete neurological examination performed 1 day after the injection revealed paraplegia without deep pain perception and reduced segmental spinal reflexes in the pelvic limbs. Findings were consistent with either an L4-S3 myelopathy or a T3-L3 myelopathy with subsequent spinal shock. MRI showed swelling of the spinal cord from T1 to L1 with heterogeneous T2-weighted intramedullary hyperintensity and no contrast enhancement. A centrally located intraspinal signal void was visible in T2*-weighted images. These changes were compatible with a suspected traumatic intraspinal injection. Despite intensive supportive care over 4 days, neurological status did not improve and the cat was euthanased. Gross pathology findings revealed severe intramedullary haemorrhage and myelomalacia in the T10-L1 spinal cord segments. Histopathology of the spinal cord after haematoxylin and eosin staining revealed a severe intramedullary space-occupying haemorrhage with focal malacia. A trajectory-like, optically empty cavity containing some eosinophilic droplets at the edges was detected. Although no further evidence of trauma was noted in the surrounding structures, the spinal cord changes were compatible with a perforating trauma. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report of thoracic intraspinal injection causing myelomalacia defined by an ante-mortem MRI and confirmed post mortem by histopathology. The traumatic myelopathy appeared to be most compatible with an intraspinal injection causing vascular rupture.

Neuronal current imaging: An experimental method to investigate electrical currents in dogs with idiopathic epilepsy.

BACKGROUND: The diagnosis of idiopathic epilepsy (IE) in dogs is based on exclusion of other potential causes of seizures. Recently, a novel magnetic resonance imaging (MRI) sequence that utilizes a variant of the rotary saturation approach has been suggested to detect weak transient magnetic field oscillations generated by neuronal currents in humans with epilepsy. HYPOTHESIS/OBJECTIVES: Effects on the magnetic field evoked by intrinsic epileptic activity can be detected by MRI in the canine brain. As proof-of-concept, the novel MRI sequence to detect neuronal currents was applied in dogs. ANIMALS: Twelve dogs with IE and 5 control dogs without a history of epileptic seizures were examined. METHODS: Prospective case-control study as proof-of-concept. All dogs underwent a clinical neurological examination, scalp electroencephalography, cerebrospinal fluid analysis, and MRI. The MRI examination included a spin-locking (SL) experiment applying a low-power on-resonance radiofrequency pulse in a predefined frequency domain in the range of oscillations generated by the epileptogenic tissue. RESULTS: In 11 of 12 dogs with IE, rotary saturation effects were detected by the MRI sequence. Four of 5 control dogs did not show rotary saturation effects. One control dog with a diagnosis of neuronal ceroid lipofuscinosis had SL-related effects, but did not have epileptic seizures clinically. CONCLUSIONS AND CLINICAL IMPORTANCE: The proposed MRI method detected neuronal currents in dogs with epileptic seizures and represents a potential new line of research to investigate neuronal currents possibly related to IE in dogs.