Inherited polyneuropathy in Leonberger dogs: A mixed or intermediate form of Charcot‐Marie‐Tooth disease?

Abstract

A spontaneous distal, symmetrical polyneuropathy in related Leonberger dogs with onset between 1 to 9 years of age was characterized clinically, electrophysiologically, histologically, and morphometrically. Exercise intolerance and weakness was associated with a high-steppage pelvic-limb gait, a loss or change in the pitch of the bark, and dyspnea. Neurological examination revealed marked atrophy of the distal limb muscles, depressed spinal and cranial nerve reflexes, and weak or absent movement of the laryngeal and pharyngeal muscles. Electrophysiological evaluation was consistent with denervation and was characterized by loss or marked attenuation of compound muscle action potentials and slowed motor nerve conduction velocity. Muscle biopsy specimens showed neurogenic atrophy. Chronic nerve fiber loss associated with decreased myelinated fiber density and a shift of the axonal size-frequency distribution toward smaller fibers was the predominant finding in peripheral nerve specimens. Pedigree analysis of a large multigenerational family, including nine sibships with at least one affected individual, suggested X-linked inheritance. Mutational and linkage analysis of this family may aid in identification of the chromosomal loci and gene responsible for this inherited axonal neuropathy. Further characterization of this inherited axonal neuropathy may establish the Leonberger dog as a spontaneous animal model of inherited axonal neuropathy and possibly lead to the discovery of a new gene or genes associated with axonal variants.

Antemortem Diagnosis of a Distal Axonopathy Causing Severe Stringhalt in a Horse

“…1,8,12,15 A distal axonopathy has been described in Leonberger dogs, in which a high-stepping pelvic limb gait with atrophy of distal limb muscles and laryngeal weakness are found. 16 The horse of this case report showed no obvious clinical signs of laryngeal neuropathy, but endoscopy to eliminate this possibility was not performed.…”

Electroneurography of the ulnar nerve in dogs

“…Motor nerve conduction velocity (MNCV) testing is valuable in the detection of neuromuscular diseases: inherited and acquired polyneuropathies (Shelton et al 2003;Gabriel et al 2006;Vanhaesebrouck et al 2008), general weakness (Jeffery et al 2006), botulism (Uriarte et al 2010), neuromuscular junction disorders (Meriggioli and Sanders 2005), polyradiculoneuritis (Hirschvogel et al 2012), cauda equina syndrome (Sekiguchi et al 2008), or peripheral nerves tumours (Le Chevoir 2012). Conduction velocity is defined as the speed at which an action potential propagates along a nerve.…”

Tetraparesis, Hemiparesis, and Ataxia

“…Neurogenic muscle atrophy is rapid and severe, occurring within 1 to 2 weeks from onset of clinical signs, and can progress to joint contracture in chronic cases. 357 This represents a compensatory response to allow the carpi or tarsi to "flip" forward for limb placement. As an aside, muscle atrophy is a clinical feature for wallerian degeneration and axonal degeneration but not for pure myelinopathies (axons still remain intact).…”