Background

Abdominal ultrasound examinations (AUS) are commonly performed before advanced neurodiagnostics to screen for diseases that might affect diagnostic plans and prognosis.

Objectives

Describe the type and frequency of abnormalities found by AUS in dogs presenting with a neurological condition, identify risk factors associated with abnormalities, and evaluate treatment decisions based on findings.

Animals

Seven hundred and fifty-nine hospitalized dogs.

Methods

Retrospective study. Medical records of dogs presented from 2007 to 2009 for neurologic disease were searched for signalment, neuroanatomic localization, and AUS findings. Whether dogs had advanced neurodiagnostics and treatment was analyzed.

Results

Fifty-eight percent of dogs had abnormal findings on AUS. Probability of abnormalities increased with age (P < 0.001). Nondachshund breeds had higher probability of abnormal AUS than dachshunds (odds ratio [OR] = 1.87). Eleven percent of dogs did not have advanced neurodiagnostics and in 1.3%, this was because of abnormal AUS. Dogs with ultrasonographic abnormalities were less likely than dogs without to have advanced neurodiagnostics (OR = 0.3 [95% confidence interval [CI]: 0.17, 0.52]), however, the probability of performing advanced diagnostics was high regardless of normal (OR = 0.95 [95% CI: 0.92, 0.97]) or abnormal (OR = 0.85 [95% CI: 0.81, 0.88]) AUS. Treatment was more often pursued in small dogs and less often in dogs with brain disease.

Conclusions and clinical importance

Findings from screening AUS had a small negative effect on the likelihood of pursuing advanced neurodiagnostics. Although it should be included in the extracranial diagnostic workup in dogs with significant history or physical examination abnormalities, AUS is considered a low-yield diagnostic test in young dogs and dachshunds.

Background

Reports of motor polyneuropathies in young cats are scarce. Further, in-depth electrophysiologic evaluation to confirm a motor polyneuropathy in young cats of various breeds other than 2 Bengal cats is lacking.

Hypothesis/objectives

To confirm a motor polyneuropathy in young cats of various breeds.

Animals

Five young cats with heterogenous chronic or relapsing episodes of weakness.

Methods

Retrospective case series. Cats were presented for evaluation of generalized neuromuscular disease and underwent electrophysiologic examination including electromyography, nerve conduction, and repetitive nerve stimulation. Minimum database and muscle and nerve biopsy analyses were carried out. Descriptive statistics were performed.

Results

Disease onset was at 3 months to 1 year of age and in 5 breeds. The most common clinical sign (5 of 5 cats) was weakness. Additional neurologic deficits consisted of palmigrade and plantigrade posture (4/4), low carriage of the head and tail (4/4), and variable segmental reflex deficits (5/5). Motor nerve conduction studies were abnormal for the ulnar (4/4), peroneal (5/5), and tibial (2/2) nerves (increased latencies, reduced amplitudes, slow velocities). A marked decrement was observed on repetitive nerve stimulation of the peroneal nerve in 3 cats for which autoimmune myasthenia gravis was ruled out. All sensory nerve conduction studies were normal. Histologic evaluation of muscle and nerve biopsies supported heterogenous alterations consistent with motor polyneuropathy with distal nerve fiber loss.

Conclusions and clinical importance

Heterogenous motor polyneuropathies should be considered in young cats of any breed and sex that are presented with relapsing or progressive generalized neuromuscular disease.

Background

In children, frequent congenital malformations with concomitant agenesis of the corpus callosum are diagnosed by neuroimaging in association with other cerebral malformations, including interhemispheric cysts and ventriculomegaly. Similar studies providing full characterization of brain defects by in vivo magnetic resonance imaging (MRI), and correlations with the pertinent anatomic pathologic examinations are absent in veterinary medicine.

Hypothesis/objectives

Congenital brain defects underlie the neurologic signs observed in Toyger cats selectively bred for a short ear phenotype.

Animals

Using proper pedigree analysis and genetic evaluations, 20 related Oriental-derived crossbred Toyger cats were evaluated. Seven clinically healthy (carrier) cats and 13 clinically affected cats that had neurologic signs, short ear phenotype and concomitant complex brain anomalies were studied.

Methods

Complete physical and neurologic examinations and MRI were performed in all clinically healthy and affected cats. Postmortem and histopathologic examinations were performed in 8 affected cats and 5 healthy cats.

Results

Neurologic and MRI investigations confirmed 13 clinically affected cats with structural brain abnormalities. Ventriculomegaly with frequent concomitant supratentorial interhemispheric, communicating ventricular type-1b cysts and multiple midline and callosal malformations were detected in all cats displaying neurologic signs. Genetic analysis confirmed autosomal recessive mode of inheritance with no chromosomal abnormalities.

Conclusions and clinical importance

Neuroanatomic dissections and histopathology were helpful for evaluation of abnormalities in midline brain structures, and for the full characterization of cysts. However, MRI was more sensitive for detection of small cysts. In this feline model, MRI diagnosis had extremely good correlation with pathologic abnormalities noted in the subset of animals that were examined by both modalities.

Purpose

Spontaneously occurring glioma in pet dogs is increasingly recognized as a valuable translational model for human glioblastoma. Canine high-grade glioma and human glioblastomas share many molecular similarities, including the accumulation of immunosuppressive regulatory T cells (Tregs) that inhibit anti-tumor immune responses. Identifying in dog mechanisms responsible for Treg recruitment may afford to target the cellular population driving immunosuppression, the results providing a rationale for translational clinical studies in human patients. Our group has previously identified C-C motif chemokine 2 (CCL2) as a glioma-derived T-reg chemoattractant acting on chemokine receptor 4 (CCR4) in a murine orthotopic glioma model. Recently, we demonstrated a robust increase of CCL2 in the brain tissue of canine patients bearing high-grade glioma.

Methods

We performed a series of in vitro experiments using canine Tregs and patient-derived canine glioma cell lines (GSC 1110, GSC 0514, J3T-Bg, G06A) to interrogate the CCL2-CCR4 signaling axis in the canine.

Results

We established a flow cytometry gating strategy for identifying and isolating FOXP3⁺ Tregs in dogs. The canine CD4 + CD25^high T-cell population was highly enriched in FOXP3 and CCR4 expression, indicating they are bona fide Tregs. Canine Treg migration was enhanced by CCL2 or by glioma cell line-derived supernatant. Blockade of the CCL2-CCR4 axis significantly reduced migration of canine Tregs. CCL2 mRNA was expressed in all glioma cell lines, and expression increased when exposed to Tregs but not CD4 + helper T-cells.

Conclusion

Our study validates CCL2-CCR4 as a bi-directional Treg-glioma immunosuppressive and tumor-promoting axis in canine high-grade glioma.