Clues to the pathophysiology of recurrent laryngeal neuropathy

Descriptions of equine recurrent laryngeal neuropathy (RLN) were first made by Bouley, and Dupuy in the 1820s. Atrophy of equine laryngeal intrinsic muscles was commonly identified at necropsy in horses that ‘roared’. The pathophysiology remains enigmatic, as does the aetiology: genetic, acquired and environmental factors have each been proposed. In summary, RLN can be described as a distal axonopathy of (predominantly) the left recurrent laryngeal nerve with secondary neurogenic muscle atrophy of intrinsic laryngeal muscles. The consequence is a reduced size of the rima glottis, which becomes relevant at exercise and manifests as poor performance due to reduced PaO2. Certain issues currently remain unresolved – (1) actual disease prevalence; (2) polyneuropathy vs mononeuropathy; (3) selective involvement of specific motor units. These elements will be discussed.

Estimates of RLN prevalence in horses vary widely. Historically, horses were diagnosed on the basis of the sound of their inspiratory stridor made at exercise. More advanced techniques, in particular exercising laryngoscopy, laryngeal computed tomography and ultrasound reveal that these earlier methods underestimated disease prevalence. Indeed, when examined histologically, it is hard to find a normal horse. This has profound implications for the search for the genetic cause and for genetic modifiers.

Histopathological changes within the distal nerves of horses with RLN reveal collapsed myelin sheaths, increased relative myelin sheath thickness, regenerating Schwann cell membrane clusters and ‘onion-bulb’ formations indicative of demyelination and remyelination. More specific indicators of a primary axonopathy are the central axon fragments commonly seen within myelin digesting chambers, accumulation of axoplasmic organelles and margination of microtubules. Such defects are seen in human neuropathies with suspected axonal transport defects.

It is conceivable that RLN might have both an acquired and genetic basis: indeed, RLN has long been proposed to be related to stretch-induced trauma of the nerve as it passes around the aorta in the thorax perhaps similar to the induced neuropathy that occurs in humans with hereditary neuropathy with liability to pressure palsies associated with a mutation in peripheral myelin protein (PMP)-22. A combination of both a genetic and acquired component would seem to be necessary, since similar axonopathies are not known to be present in other athletic quadrupeds.