section name header

Basics ⬇

Outline

BASICS

Definition!!navigator!!

An acquired neurodegenerative disease primarily affecting somatic motor neurons.

Pathophysiology!!navigator!!

The cause of EMND is unproven, although there is a strong association between the disease and vitamin E deficiency. Lower motor neuron cell bodies in the spinal cord and brainstem degenerate, presumably from oxidative damage. The oxidative damage is likely a result of an imbalance in pro-oxidants and antioxidants and the disease is associated with a low vitamin E status. Early dysfunctional changes in the motor neuron cells may be associated with mitochondrial damage, followed by disintegration of the nucleus and neurofibrillary accumulation. Dead motor neurons may eventually be removed by glial cells. Clinical signs only become apparent when approximately 30% of the motor neurons become dysfunctional. Ventral horn motor neurons that supply postural muscles (those muscles with predominantly type 1 fibers) are preferentially affected; this is believed to occur because of the higher oxidative activity of predominant type 1 muscle and its corresponding parent motor neuron. The oxidative disease causes lipopigment (ceroid) accumulation in the endothelium of spinal cord capillaries, neurons, and RPE. The RPE ceroid can generally be seen on fundoscopic examination as brown streaks. Excessive lipopigment may also, on occasion, be found in the liver of affected horses.

Systems Affected!!navigator!!

  • Neuromuscular—motor neuron cell dysfunction causing neurogenic muscular atrophy and weakness
  • Ophthalmic—lipopigment accumulation in the RPE causes electroretinographic abnormalities; vision is likely affected
  • Gastrointestinal—a functional abnormality in carbohydrate absorption occurs in severely affected horses and may be related to a mitochondrial dysfunction in the enterocyte. There are rarely abnormal light microscopic changes

Genetics!!navigator!!

There is no known genetic basis to the disease. Although SOD activity is abnormally low in red blood cells and nervous tissue, this is believed to be a result of excessive oxidative stress. Abnormal polymorphisms in the SOD gene in affected horses versus controls have not been found.

Incidence/Prevalence!!navigator!!

Affects approximately 1 horse per 10 000 per year in the northeastern USA (between 1990 and 1996).

Geographic Distribution!!navigator!!

EMND is seen worldwide but is most common in those geographic areas less likely to have alfalfa hay, e.g. northeastern USA and Canada, and lack of pasture (urban areas). Clusters may occur on certain premises.

Signalment!!navigator!!

Environment. Most horses have a history of being kept without pasture and leafy green hay for at least 1 year; however, increasingly horses in Europe are presented with EMND even though they have had access to grass (those tested, however, are still low in vitamin E).

  • Breed predilection—all breeds of horses and ponies may be affected
  • Age—mean age is 12 years; range 2–25 years. Rarely, and in younger horses, EMND is diagnosed along with equine degenerative myeloencephalopathy
  • No gender predisposition

Signs!!navigator!!

Historical Findings

In many but not all cases there is a history of lack of access to grass.

Physical Examination Findings

Findings vary depending upon the stage/duration of the disorder and are due to neuromuscular weakness. EMND cases do not have proprioceptive deficits, i.e. they are not ataxic. Signs are best summarized by dividing into subacute and chronic forms.

Subacute Form

Horses develop an acute onset of trembling, fasciculations, lying down more than normal, frequent shifting of weight in the pelvic limbs, and abnormal sweating. Head carriage may be abnormally low. Horses may appear less comfortable when standing than walking. Appetite and gait are usually not noticeably affected. The owners may mention that the horses had been losing weight (loss of muscle mass) for 1 month prior to the trembling, etc.

Chronic Form

The trembling and fasciculations subside and the horse stabilizes but with varying degrees of muscle atrophy. With fibrosis of postural muscles the pelvic limbs have a shortened cranial phase of the stride reminiscent of fibrotic myopathy. In some cases, the atrophy is so severe that the horse looks emaciated. In other cases, there is noticeable improvement in muscle mass and/or fat deposition. The tail-head is frequently in an abnormally high resting position.

Risk Factors!!navigator!!

Low access to vitamin E or increased exposure to putative oxidant.

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

  • Finding evidence of neurogenic atrophy in a muscle biopsy of the sacrocaudalis dorsalis medialis muscle (tail-head muscle) is a sensitive and specific test for EMND. Rarely, very early cases many not show neurogenic atrophy but have a moth-eaten appearance on staining for mitochondria when frozen muscle biopsies are stained with NADH-Tr
  • Degeneration of the myelinated fibers of the spinal accessory nerve also has high specificity and sensitivity for the diagnosis of EMND

Differential Diagnosis!!navigator!!

  • Colic is often considered because of the propensity of the horses to stand for only brief periods during the subacute form. The normal appetite and fecal production should serve to rule out an abdominal disorder
  • Laminitis is another consideration because of the almost constant shifting of weight in the subacute form. The ease of motion and even desire to walk as seen in EMND is contradictory to the diagnosis of laminitis
  • Other neuromuscular disorders such as botulism and myositis/myopathy may have similarities to EMND. The normal appetite, elevated tail-head, and lack of cranial nerve dysfunction should separate EMND from botulism. Chronic myopathies, e.g. polysaccharide storage myopathy, may appear very similar to EMND, and a muscle biopsy may be required to delineate between the two. EMND causes symmetric muscle weakness and atrophy without ataxia and elevation of muscle enzymes (in the subacute cases) as opposed to equine protozoal myeloencephalitis
  • The severe muscle wasting with a normal appetite in the chronic form may look similar to intestinal malabsorption syndrome. Plasma albumin is low in most infiltrative bowel syndromes but is normal in EMND

CBC/Biochemistry/Urinalysis!!navigator!!

The CBC is generally within normal range. The most common abnormal biochemical finding is a moderate elevation in muscle enzymes in the subacute case. A few horses may have elevated liver enzymes. The urinalysis is normal in most cases, although some may have myoglobinuria. CBC, biochemistry, and urinalysis are all normal in the chronic cases.

Other Laboratory Tests!!navigator!!

  • In the subacute cases, plasma or serum vitamin E (alpha tocopherol) is abnormally low (mean 0.56 μg/mL). Serum ferritin and lipid peroxidases are often abnormally high
  • In chronic cases, alpha tocopherol values may have returned to normal
  • Fundoscopic examination frequently reveals brown streaking of the retina. This is specific for vitamin E deficiency and only supportive for EMND
  • Glucose malabsorption is generally present in subacute cases, but is only supportive for EMND

Pathologic Findings!!navigator!!

  • An abnormal paleness of some muscles (e.g. vastus intermedius) containing most type 1 fibers may be observed. Body fat stores are variable
  • Microscopically, central nervous system lesions are confined to the spinal cord ventral horn cells, and cranial nerves nuclei V, VII, VIII, IX, X, XI, and XII. Degeneration of corresponding motor nerves and neurogenic muscle atrophy is found
  • There is lipofuscinosis of the retinal pigment epithelial layer and spinal cord endothelium in all cases and of the liver in a few cases
  • There are no light microscopic lesions in the intestine in 90% of cases, but ultrastructural changes may be seen

Treatment ⬆ ⬇

Outline

TREATMENT

Horses with EMND can be treated either on the farm or in the hospital. Transporting can worsen the clinical signs.

Activity!!navigator!!

The affected horse should not have free movement restricted but should not be exercised and/or ridden.

Diet!!navigator!!

Leafy green hay or grass with additional vitamin E (2000–7000 units/day) should be provided.

Client Education!!navigator!!

Regular access to grass for all horses if this is deficient.

Medications ⬆ ⬇

MEDICATIONS

Oral vitamin E supplements.

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

With the subacute form, improvement in clinical signs often corresponds to return of serum muscle enzymes to normal values. Vitamin E concentrations should be monitored to determine that levels return to normal. It should be kept in mind, however, that neurons that have been lost will never be replaced, and an increase in weight is likely to be due to fat deposition rather than muscle hypertrophy.

Prevention/Avoidance!!navigator!!

All other horses kept under similar conditions should be supplemented with vitamin E.

Expected Course and Prognosis!!navigator!!

  • Of horses subacutely affected with EMND approximately 40% will stabilize within 3–8 weeks and regain some loss of muscle mass. Other horses will have progressive deterioration in clinical signs or no improvement, in spite of vitamin E treatment
  • Horses with the chronic and more stabilized form may have several years of quality life but not performance. Their life expectancy would be shorter than normal and another acute onset of clinical signs may occur years later (similar to the human postpolio paresis). Horses diagnosed with EMND should not be ridden as they can be unsafe and moderate to severe exercise will likely shorten their life expectancy

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Abbreviations!!navigator!!

  • EMND = equine motor neuron disease
  • NADH-Tr = nicotinamide adenine dinucleotide tetrazolium reductase
  • RPE = retinal pigment epithelium
  • SOD = superoxide dismutase

Suggested Reading ⬆ ⬇

Bedford HE, Valberg SJ, Firshman AM, et al. Histopathologic findings in the sacrocaudalis dorsalis medialis muscle of horses with vitamin E-responsive muscle atrophy and weakness. J Am Vet Med Assoc 2013;242:1127–1137.

Finno CJ, Miller AD, Sisó S, et al. Concurrent equine degenerative myeloencephalopathy and equine motor neuron disease in three young horses. J Vet Intern Med 2016;30:1344–1350.

Ledwith A, McGowan CM. Muscle biopsy: a routine diagnostic procedure. Equine Vet Educ 2004;16:62–67.

McGorum BC, Mayhew IG, Amory H, et al. Horses on pasture may be affected by equine motor neuron disease. Equine Vet J 2006;38:47–51.

Author(s) ⬆

Author: Caroline N. Hahn

Consulting Editor: Caroline N. Hahn