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

Major histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune-mediated myositis (IMM) of humans and dogs and in dysferlin-deficient muscular dystrophy.

Hypothesis/objectives

To determine if sarcolemmal MHC is expressed in active IMM in horses, if MHC expression is associated with lymphocytic subtype, and if dysferlin is expressed in IMM.

Animals

Twenty-one IMM horses of Quarter Horse-related breeds, 3 healthy and 6 disease controls (3 pasture myopathy, 3 amylase-resistant polysaccharide storage myopathy [PSSM]).

Methods

Immunohistochemical staining for MHC I, II, and CD4+, CD8+, CD20+ lymphocytes was performed on archived muscle of IMM and control horses. Scores were given for MHC I, II, and lymphocytic subtypes. Immunofluorescent staining for dysferlin, dystrophin, and a-sarcoglycan was performed.

Results

Sarcolemmal MHC I and II expression was detected in 17/21 and 15/21 of IMM horses, respectively, and in specific fibers of PSSM horses, but not healthy or pasture myopathy controls. The CD4+, CD8+, and CD20+ cells were present in 20/21 IMM muscles with CD4+ predominance in 10/21 and CD8+ predominance in 6/21 of IMM horses. Dysferlin, dystrophin, and a-sarcoglycan staining were similar in IMM and control muscles.

Conclusions and clinical importance

Deficiencies of dysferlin, dystrophin, and a-sarcoglycan are not associated with IMM. Sarcolemmal MHC I and II expression in a proportion of myofibers of IMM horses in conjunction with lymphocytic infiltration supports an immune-mediated etiology for IMM. The MHC expression also occured in specific myofibers in PSSM horses in the absence of lymphocytic infiltrates.

Canine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative disorder of the CNS white matter currently described in Rottweiler and Leonberger dogs. Genome-wide association study (GWAS) allowed us to map LEMP in a Leonberger cohort to dog chromosome 18. Subsequent whole genome re-sequencing of a Leonberger case enabled the identification of a single private homozygous non-synonymous missense variant located in the highly conserved metallo-beta-lactamase domain of the N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD) gene, encoding an enzyme of the endocannabinoid system. We then sequenced this gene in LEMP-affected Rottweilers and identified a different frameshift variant, which is predicted to replace the C-terminal metallo-beta-lactamase domain of the wild type protein. Haplotype analysis of SNP array genotypes revealed that the frameshift variant was present in diverse haplotypes in Rottweilers, and also in Great Danes, indicating an old origin of this second NAPEPLD variant. The identification of different NAPEPLD variants in dog breeds affected by leukoencephalopathies with heterogeneous pathological features, implicates the NAPEPLD enzyme as important in myelin homeostasis, and suggests a novel candidate gene for myelination disorders in people.