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Neurology: motor neuron disease

ISSN 2398-2977


Introduction

  • Sporadic, neurodegenerative disease causing weakness and muscle atrophy (first described in 1990).
  • Incidence: most prevalent in North America, but has been shown to account for up to 15% of neurology admissions in the UK.
  • Cause: unclear, oxidative damage to motor neurons, associated with vitamin E/selenium deficiency.
  • Diagnosis: tailhead (sacrocaudalis dorsalis medialis) muscle biopsy or EMG.
  • Treatment: none proven, vitamin E therapy used.
  • Prognosis: approximately one third of cases will deteriorate rapidly and require euthanasia, one third remain stable with obvious signs of disease and cannot be ridden, and one third improve in response to therapy.

Presenting signs

Active phase of disease
  • Normal appetite.
  • Trembling.
  • Weight shifting when standing.
  • Raised tail head.
  • Paresis.
  • Abnormal positioning of limbs.
  • Muscle atrophy.
  • Lack of pasture access.
  • Feeding ration rich in grain and poor quality grass/hay.
  • Frequent and excessive periods of recumbency.
Arrested phase
  • Weight loss.
  • Abnormally low head carriage.
  • Exercise intolerance.

Geographic incidence

  • North eastern region of North America - 1 per 100,000 horses/year.
  • South America.
  • Japan.
  • Europe.

Age predisposition

  • 2-23 (~9) years.
  • The risk of disease increases with age peaking at approximately 15 years.

Breed/Species predisposition

Cost considerations

  • Loss of animal.
  • Treatment and investigation.

Pathogenesis

Etiology

  • Non-inflammatory neuronal degeneration and neuronal loss at all levels of the spinal cord, including the brainstem.
  • The ventral horn grey matter, ie the lower motor neurons, is particularly targeted.
  • Denervation of the muscle results in atrophy of the type I and II fibers abut EMND predominantly affects type I fibers. At least 30% of motor axons must be destroyed before there is clinical evidence of atrophy. Postural muscles are most severely affected because of their high percentage of type I fibers.
  • Motor neurons are particularly susceptible to oxidative stress due to their very long axons and resulting in high energy requirements.
  • The etiopathogenesis of EMND is not fully understood but it is thought that neurons undergo free radical damage. The histopathologic identification of lipopigments deposition in the capillaries of the spinal cord is suggestive of oxidative injury.

Predisposing factors

General
  • Restricted pasture access, for at least 1 year typical, however EMND has recently been described in horses kept at pasture.
  • Affected horses have been found to have consistently low plasma Vitamin E concentrations.
  • Inflammatory bowel disease and/or liver disease has been found in as many as 5% of horses with EMND as have abnormal glucose absorption tests these horses could potentially therefore have abnormal absorption or metabolism of Vitamin E. 
  • Ration rich in grain/poor-medium quality grass hay or straw/no alfalfa.

Specific

  • Motor neurons with high oxidative activity, ie those supplying type I muscle fibers.
  • Lack of dietary antioxidants.
  • Periods of oxidative stress - short-term neurotoxin exposure - increased consumption of intrinsically produced, free radical reducing enzymes.

Pathophysiology

  • Degeneration of somatic motor neurons in ventral horns of spinal cord and selected brainstem nuclei.
  • Death of motor neurons is accompanied by degenerative axonal changes in ventral roots/peripheral nerves   →   neurogenic muscle atrophy.
  • Type I muscle fibers appear most affected.
  • Cervicothoracic and lumbosacral intumescences of spinal cord are most severely affected.
  • >30% need to be dysfunctional   →   acute onset of clinical disease.
  • Subclinical cases exist.
  • Scattered muscle fiber necrosis and lipopigment accumulation in capillaries of spinal cord and retina are characteristic of lipid peroxidation and vitamin E deficiency.

Timecourse

  • Unclear.

Epidemiology

  • No evidence of contagion.

Diagnosis

Presenting problems

  • Loss of muscle mass/muscle wastage.
  • Weight loss.
  • Weakness.
  • Poor performance.

Client history

  • Limited pasture access in most cases.
  • Ration rich in grain/low quality hay/straw.
  • Acute onset of signs (active phase) or chronic signs (arrested phase).

Clinical signs

Active phase
  • Trembling - muscle tremors and fasciculations.
  • Excessive periods of recumbency.
  • Abnormal limb positioning - weight onto rear legs and hold all 4 limbs closer together than normal.
  • Weakness without ataxia.
  • Appetite remains normal - normal gut motility.
  • Malabsorption of nutrients from the gut suggests that absorptive function of the gut is abnormal   →   abnormal function. 
  • Symmetrical muscle atrophy, especially in triceps   Forelimb: triceps muscle atrophy  , scapula, quadriceps, lumbar   Back: muscle atrophy 02 - lumbar  , sacral and neck muscles.
  • Stabilization in 2-8 weeks to arrested form.
  • Symmetrical buckling of forelimbs while standing.
  • Abnormally low head carriage.
  • Sweating.
  • Elevation of tailhead.
  • Cranial nerve deficits.
  • Persistent recumbency, respiratory distress.

Arrested phase

  • Failure to gain weight despite normal appetite.
  • Exercise intolerance.
  • Excessive recumbency.
  • Tailhead elevation.
  • Abnormal gait - stumbling, stringhalt-like in several limbs   Hindlimb: hyperflexion - stringhalt  .

Diagnostic investigation

Biochemistry
  • Low plasma Vitamin E (alpha-tocopherol): <1 microg/ml in >90% of cases.
  • Low tissue alpha-tocopherol in muscle, peripheral nerve and spinal cord.
  • Low plasma glutathione peroxidase. 
  • Evidence of malabsorption caused by infiltrative bowel disease and chronic liver disease   Liver disease: overview  .

Histopathology

  • Sacrocaudalis dorsalis medialis muscle shows angular atrophy of the muscle fibers.
  • Ventral branch of spinal accessory nerve.
Other
  • Electromyography:
    • Widespread denervation responses - positive sharp waves or fibrillation responses if performed under general anesthesia or epidural block.
  • Ophthalmic examination  Eye: examination - direct ophthalmoscopy - close  : abnormal pigment deposition in non-tapetal area of retina.
  • CSF analysis  CSF: collection  : increased CSF protein concentration   CSF: protein  .
  • Glucose absorption test   : glucose absorption test abnormal in 30% of cases.

Confirmation of diagnosis

Discriminatory diagnostic features

  • History and clinical signs, especially in active disease.

Definitive diagnostic features

  • Tissue biopsy and histopathology.

Gross autopsy findings

  • Muscle atrophy.

Histopathology findings

  • Motor neurons appear smaller and chromatolytic or necrotic with neuronophagia during the active phase.
  • Arrested form - focal aggregates of glial cells most evident in ventral horns.
  • Type I muscle fiber atrophy with scattered fiber necrosis.
  • Extensive deposition of lipopigment in spinal cord capillaries and within retinal pigment epithelial layer of eye.

Differential diagnosis

Treatment

Standard treatment


All OfVitamin E   Vitamin E  supplementation 5000-7000 iu PO SID.
AndPrednisolone   Prednisolone  0.5 mg/kg PO BID, reducing daily.
AndSupportive therapy.

Monitoring

  • Occasionally horses progress rapidly to persistent recumbency, respiratory distress and require euthanasia   Euthanasia  .
  • Most horses stabilize in 2-8 weeks to arrested form.
  • Further acute flare-ups may occur 1-6 years after initial episode   →   euthanasia   Euthanasia  .

Subsequent management

Treatment

  • Euthanasia   Euthanasia  is often necessary either in acute recumbent cases or chronic failure to gain weight.
  • Can develop gait abnormalities, ie 'spastic gait'   Neurology: stringhalt   due to fibrosis of type I predominant postural muscles.

Prevention

Prophylaxis

  • Access to pasture.
  • High quality green forage (decrease grain) in diet.
  • Vitamin E supplementation   Vitamin E  3000 iu/day.

Outcomes

Prognosis

  • Poor.
  • Acute active disease - generally persists for 2-8 weeks followed by decrease in signs in >70% of cases.
  • Return of some muscle mass in following months but remain disfigured and unsafe to ride.
  • Recurrence can occur 1-6 years later and   →   euthanasia requested   Euthanasia  .
  • 30% show minimal improvement in first year and require euthanasia   Euthanasia  .
  • A few cases become recumbent in acute phase and require euthanasia   Euthanasia  .

Expected response to treatment

  • Improvement in clinical signs.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Bedford H E et al (2013) Histopathologic findings in the sacrocaudalis dorsalis medialis muscle of horses with vitamin E-responsive muscle atrophy and weakness. JAVMA 242 (8), 1127-1137 PubMed.
  • McGowan C M, McGowan T W & Patterson-Kane J C (2009) Prevalence of equine polysaccharide storage myopathy and other myopathies in two equine populations in the United Kingdom. Vet J 180 (3), 330-336 PubMed.
  • Syrja P et al (2006) Equine motor neuron disease (EMND) in a horse without vitamin E deficiency: a sequela of iron excess? Equine Vet Educ 18 (3), 122-126 VetMedResource.
  • Wijnberg I D (2006) Equine motor neuron disease. Equine Vet Educ 18 (3), 126-129 VetMedResource
  • McGorum B C et al (2006) Horses on pasture may be affected by equine motor neuron disease. Equine Vet J 38 (1), 47-51 PubMed.
  • Benders N A, Wijnberg I D & Van der Kolk J H (2001) Equine motor neuron disease: a review based on a case report. Tijdschr Diergeneeskd 126 (11), 376-380 PubMed.
  • Kyles K W J (2001) Electromyography under caudal epidural anaesthesia as an aid to diagnosis of equine motor neuron disease. Vet Rec 148 (17), 536-538 PubMed.
  • Verhulst D, Barnett K C & Mayhew I G (2001) Equine motor neuron disease and retinal degeneration. Equine Vet Educ 13, 59-61 VetMedResource.
  • Divers T J, deLahunta A, Hintz H F, Riis R C, Hackson C A & Mohammed H O (2001) Equine motor neuron disease. Equine Vet Educ 13, 63-67 VetMedResource.
  • Valentine B A, Divers T J, Murphy D J & Todhunter P G (1998) Muscle biopsy diagnosis of equine motor neuron disease and equine polysaccharide storage myopathy. Equine Vet Educ 10, 42-50 VetMedResource.
  • Divers T J, Mohammed H O & Cimmings J F (1997) Equine motor neuron disease. Vet Clin North Am Equine Pract 13 (1), 97-105 PubMed.
  • Divers T J et al (1994) Equine Motor Neuron Disease - Findings in 28 horses and proposal of a pathophysiological mechanism for the disease. Equine Vet J 26 (5), 409-415 PubMed.

Other sources of information

  • Divers T J, Mohammed H O, Hintz H F & De Lahunta A (2003) Equine Motor Neuron Disease: A Reivew of Clinical and Experimental Studies. In: Proc 49th AAEP Convention. pp 230-232.