Introduction

• Cause: dominantly inherited lower motor neurone disease.
• Three clinical pictures, accelerated, intermediate and chronic.
• Homozygotes show the accelerated disease, heterozygotes the intermediate or chronic phenotypes.
• Signs: begin before the puppy reaches maturity and progress.
• Progressive weakness with muscle atrophy.
• Treatment: none.
• Prognosis: accelerated and intermediate forms progress until the puppy is unable to walk.

Pathogenesis

Etiology

• Inherited by an autosomal dominant trait.
• Dogs that are homozygous for the trait develop clinical signs between 6 and 8 weeks of age and rapidly progress (accelerated disease) with death ensuing by 4 to 5 months of age.
• Heterozygotes for the trait are divided into intermediate and chronic forms phenotypically.

Pathophysiology

• Premature degeneration of the cell bodies of motor neurones.
• Impaired slow-axonal transport of cytoskeletal proteins, neurofilament proteins and tubulin → build up of material in axons → axonal swelling.
• Altered levels of choline acetyltransferase activity.
• Possible alteration in spinal cord glutamate activity.

• Premature degeneration and death of neuronal cell populations in the spinal cord and brain stem → interruption of nerve impulses to skeletal muscle → decreased or absent reflexes, muscle tone, and voluntary movement → progressive muscle atrophy (seen as prominent thinness and loss of bodyweight).
• Although there are some indicators of oxidative stress (changes in vitamin E and serum copper levels), these are more likely to be an effect of the disease than a cause.

Timecourse

• Accelerated disease has a course of about 2 months.
• Intermediate disease has a course of 1-2.5 years.
• Chronic disease has a protracted course of several years.

Diagnosis

Treatment

Prevention

Outcomes