Bovine spastic syndrome in Holstein cattle: exploring potential pathophysiological mechanisms

Abstract Background Bovine spastic syndrome (BSS) is an adult-onset neuromuscular disorder characterized by progressive hindlimb spasticity and episodic muscle contractions, with clinical similarities to human hereditary spastic paraplegias. Although it has been assumed that BSS is a neuromuscular disorder, there is limited knowledge of the pathophysiological mechanisms of this disorder and no comprehensive pathophysiological studies have been published. The aims of our study were (1) to describe the clinical features of spastic syndrome in two affected Holstein cows, (2) to perform an in-depth immunohistochemical and ultrastructural evaluation of muscle tissue and, (3) to perform genetic testing through PCR-based variant screening. Results On clinical examination, the animals exhibited stimulus-induced unilateral spasticity, spastic contractions, kyphosis and tremor. In addition, one case showed dermatologic lesions. SERCA1 and RyR1 immunohistochemistry showed normal expression and preserved sarcoplasmic reticulum architecture in BSS-affected cows, indicating intact excitation-contraction coupling machinery. Electron microscopy of the muscle revealed normal ultrastructure in one case and marked glycogen accumulation and myofibrillar disorganization in the other. Genetic analysis revealed the absence of the TOR3A : p.Phe111Leu variant previously associated with spastic syndrome in Holstein, supporting the hypothesis of genetic heterogeneity. Conclusions This study advances the clinicopathological characterization of BSS in Holstein cattle by providing previously unreported histopathological, ultrastructural, and immunohistochemical data. Combined clinical and molecular findings highlighted variability between cases, potentially indicating distinct pathophysiological pathways. The absence of known BSS-associated genetic variants, together with parallels to human and animal neuromuscular disease models, points to potential genetic heterogeneity, although the small sample size precludes definitive conclusions. These exploratory data emphasize the importance of further genomic and functional research to better understand the molecular basis of BSS.