Case Series of Canine Myasthenia Gravis: A Classification Approach With Consideration of Seronegative Dogs

Abstract

Background: Myasthenia gravis (MG) is categorized into several subgroups, including seronegative MG. Seronegative human patients are well documented, but seronegative dogs remain clinically uncharacterized and their prevalence unknown.

Objectives: This study aims to evaluate the clinical presentation, diagnosis, treatment, and outcome of canine MG subgroups.

Animals: One hundred sixty-seven owner-owned dogs diagnosed with MG from three referral centers.

Methods: Retrospective case series. We classified myasthenic dogs into subgroups, adhering to human guidelines.

Results: We classified 167 dogs into four subgroups: acetylcholine receptor (AChR) antibody-positive generalized (49.7%, n = 83/167), focal (19.2%, n = 32/167) and thymoma-associated MG (9%, n = 15/167) and seronegative MG (22.2%, n = 37/167). Dogs with thymoma-associated MG were older (median 102 months; Interquartile Range (IQR) 96-120; p < 0.001) and seronegative dogs were younger (median 30 months; IQR 11.5-66; p = 0.017), compared to the generalized subgroup (median 67 months; IQR 36-96). Seronegative dogs presented less frequently with megaesophagus, compared to the generalized subgroup (63.8% vs. 85.7%; Odds Ratio 3.4; 95% confidence intervals (C.I.) 1.4-8.9; p = 0.025). Myasthenic dogs' survival time was significantly reduced when thymoma (Hazard Ratio (H.R.) 3.7; 95% C.I. 1.4-9.9; p = 0.028) or esophageal weakness (H.R. 3.8; 95% C.I. 2.0-7.0; p < 0.001) was present. Conversely, a higher likelihood of remission was achieved when esophageal weakness was absent (H.R. 3.8; 95% C.I. 1.4-10.0; p = 0.007).

Conclusion and clinical importance: Dogs with seronegative MG are more common than previously reported. Myasthenic subgroups differ in presentation and outcome, with esophageal weakness key to survival and remission. Diagnostic tests for seronegative dogs and effective treatments for esophageal weakness in myasthenic dogs are urgently needed.

Keywords: acetylcholine receptor; antibody test; autoimmune; junctionopathy.

Chart 1

Classification of myasthenia gravis of 167 dogs of 3 centres.

FIGURE 1

Signalment. (A) Breed distribution. Breeds less than 2% were categorized within ‘other breeds’. (B) Age of onset of clinical signs was analyzed for the 4 myasthenic subgroups. (C) Duration of clinical signs prior to presentation was analyzed for the 4 myasthenic subgroups.

FIGURE 2

Severity scores of generalized (A) and bulbar weakness (B) were analyzed for the 4 myasthenic subgroups based on human MGFA scores (for interpretation of the scores, see methods).

FIGURE 3

AChR antibody titers were analyzed for the 4 myasthenic subgroups.

FIGURE 4

Survival curves and their 95% confidence intervals. (A) Survival time of the 4 myasthenia subgroups. Confidence intervals were omitted for clarity of the graph. (B) Dogs with esophageal weakness had shorter lifespans compared to dogs without esophageal weakness (p < 0.001). (C) Remission time. Dogs without esophageal weakness had a higher chance of remission from myasthenia (p = 0.005).

FIGURE 5

Severity scores of generalized (A) and bulbar weakness (B) were analyzed over time based on human MGFA scores (marginal means and 95% confidence intervals, linear mixed model). Three time points were examined: The initial presentation, discharge, and the first recheck. Generalized weakness significantly improved between the initial presentation and the first recheck (p = 0.012).