Equine - Neuromuscular Dz

Question 1

What toxin(s) does Clostridium botulinum produce?

Answer 1

Botulinum neurotoxin (BoNT/A, BoNT/B etc.)
BoNT mosaic toxins (BoNT/CD and BoNT/DC)

Question 2

List the antigenic types of C. botulinum and which types have been reported to cause disease in large animals.

Answer 2

C. botulinum type A, B, C1, C2, D, E, F, G;

Types A, B, C1 and D.

Question 3

What type of bacteria are C. tetani and C. botulinum?

Answer 3

Gram positive, anaerobic, spore-forming bacilli.

Question 4

List the three types of C. botulinum infection and the antigenic type commonly implicated in each.

Answer 4

1) Forage botulism: ingestion of pre-formed toxin i.e. pasture/forage/silage/haylage contaminated with soil (A&B) or animal carcasses (C&D); phosphorus deficient cattle chewing on bones with some muscle attached (D).
2) Toxicoinfectious botulism: colonisation of GIT by C. botulinum in neonates, toxins prod in GIT & absorbed (B).
3) Wound botulism: C. botulinum colonises wound and multiplies under anaerobic conditions and prod toxins.

Question 5

Which antigenic type of C. botulinum is most frequently associated with botulism outbreaks in horses in the USA?

Answer 5

Type B (>85% cases).

Question 6

Describe the mechanism of action of BoNT.

Answer 6

BoNT accessory proteins facilitate absorption across intestinal epic cells –> blood stream –> presynaptic cholinergic nerve terminal esp somatic neuromuscular endplate –> internalised into cytosol –> inactivates the SNARE complex –> vesicles do not undergo exocytosis –> acetylcholine not released at the NMJ –> flaccid paralysis.

Question 7

List the two types of Stringhalt reported in horses and how they can be distinguished on clinical examination.

Answer 7

1. Australian Stringhalt - BILATERAL hindlimb disease.

2. Classical Stringhalt - UNILATERAL hindlimb disease.

Question 8

List the plants reported to cause Australian Stringhalt by their scientific and common names.

Answer 8

1. Hypochaeris radicata (false dandelion, flatweed, cat’s ear, castear).
2. Taraxacum officinale (dandelion)
3. Marva parviflora (mallow).
4. Lathyrus odoratus (sweet pea) NB experimental infection.

Question 9

What is the characteristic gait abnormality observed in cases of Stringhalt?
What factors can exacerbate this gait abnormality?

Answer 9

Sudden, exaggerated flexion of one or both pelvic limbs during the swing phase of locomotion. Varies from slightly excessive flexion to violent movements during which the fetlock or toe will contact the abdomen, thorax and occasionally the elbow.
Backing, sharp turns, going downhill, sudden stops, transition for halt to walk, cold weather, excitement.

Question 10

Describe clinical signs which may be seen in cases of Australian Stringhalt in addition to bilateral hindlimb hyperflexion.

Answer 10

• Mild to severe muscle atrophy of the hindlimbs.
• Laryngeal paralysis (‘roaring’), stridor or change in voice.
• Bilateral knuckling over on the forelimbs (generalised weakness; ‘atypical stringhalt’).
• Generalised muscle atrophy and marked weight loss despite a good appetite.

Question 11

Describe the proposed pathophysiology of Classical Stringhalt.

Answer 11

Trauma to the proximal dorsal metatarsus, may be months before Stringhalt is observed; additional proposed risk factors: foot conditions, articular lesions of the hock or stifle; likely cumulative result of interference with limb reflexes, mechanical effects of adhesions involving digital extensors of the pelvic limb, painful conditions of the hock or distal limb.

Question 12

Describe the pathophysiology of Australian Stringhalt.

Answer 12

Ingestion of toxic weed –> distal neuropathy involving myelinated axons of the peripheral nervous system –> progressive degeneration of axons incl alpha motor neurons to skeletal muscle, 1A and 1B sensory neutrons from muscle spindles and Golgi tendon organs and gamma efferents to muscle spindles.

Question 13

Name the three nerves most commonly affected in cases of Australian and Stringhalt and the most common signalment of affected patients.

Answer 13

1. Recurrent laryngeal nerves.
2. Peroneal branch of the sciatic nerve.
3. Tibital branch of the sciatic nerve.
   Tall adult horse > young horses, shorter horses and ponies as LONG nerves affected (has been reported in Shetlands).

Question 14

List the typical findings on electromyography in cases of Stringhalt.

Answer 14

• Increased insertion activity of affected muscle.
• Abnormal spontaneous activity e.g. fibrillation potentials, positive sharp waves, in affected muscles.
• Slowed nerve condition velocity in peroneal nerves.

Question 15

List the typical gross and histologic pathology findings in long-standing cases of stringhalt.

Answer 15

• Atrophy of muscles of the pelvic limbs and the larynx.
• Peripheral nerves: demyelination, perineurial fibrosis, accumulation of myelin debris (lesions worst distally).
• +/- evidence of nerve regeneration: regenerating nerve clusters, onion bulbs, Schwann cell proliferation.

Question 16

List two medications with reported success in treatment of Stringhalt and their mechanisms of action.

Answer 16

1. Phenytoin (10-15mg/kg PO q12-24h): inhibits voltage-gated Na channels.
2. Mephenesin: inhibits polysynaptic reflexes in the spinal cord (limited success).

Question 17

Describe surgical therapy for treatment of Stringhalt and the prognosis for return to function.

Answer 17

Lateral digital extensor myotenectomy: surgical removal of the distal muscle belly and tension of insertion of the lateral digital extensor; 50-85% success rate.

Question 18

What is the prognosis for recovery from Stringhalt?

Answer 18

• Few reports re Classical Stringhalt - presumed to persist in majority (1 resolved, 2/4 improved in one case study).
• Australian Stringhalt: many cases resolve after removal from weeds; some die (recumbency; unable to walk to feed/water); some have persistent CSx; recovery takes on average 6-12mo (3d-3yr).

Question 19

Identify ticks capable of causing tick paralysis, the countries in which they are located and the domestic animal species affected.

Answer 19

1. Ixodes holocyclus - Australia - cats, dogs, foals, horses, calves, sheep, pigs.
2. Dermancentor spp - USA - dogs, humans, cattle, camelids.
3. Ixodes rubicundus & Rhipicephalus evertsi - Africa - small ruminants.

Question 20

Outline the pathophysiology of tick paralysis.

Answer 20

Neurotoxin in saliva of female tick –> inoculated into affected animal when tick feeds –> inhibits release of acetylcholine from nerve terminals at the NMJ.

Question 21

Describe the clinical signs of tick paralysis.

Answer 21

Progressive generalised flaccid paralysis –> recumbency and death (respiratory paralysis) over hours to day. Early signs include ataxia, paraparesis, change in voice.

Question 22

Describe the treatment of tick paralysis.

Answer 22

1. Identify and REMOVE ticks!!! (Px good for Dermancentor if removed before animal is moribund) –> tick search x3, clip, spray with fipronil.
2. Administer hyperimmune serum - 0.5ml/kg horses (NB canine product; potential for anaphylaxis).
3. Supportive care: NPO (dysphagic!), sternal, oxygenation, +/- IVF, deep bedding, stand and turn frequently.

Question 23

What is the alternate name for Atypical Myopathy (AM) and in what countries does it occur?

Answer 23

Atypical myopathy (Europe); seasonal pasture myopathy (US).
Largely UK and Northern Europe; isolated cases reported in USA, Australia, Falkland Islands.
N.B. mal seco = clinically and pathologically identical disease in South America (mainly Chile).

Question 24

What is the causative agent of AM and where does it originate from?

Answer 24

Hypoglycin A (toxic metabolite = methylenecyclopropyl acetic acid; MCPA).
Seeds of Acer negundo (box elder) and Acer pseudoplantanus (sycamore maple) trees.

Question 25

List risk factors for development of AM.

Answer 25

• Presence of box elder or sycamore maple trees.
• Young adults: peak incidence 2-7yo.
  {- Dec risk if previous hx of contact/co-grazing with an EGS horse (+ inc risk young age = acquired immunity?)}
• Previous occurrence of cases on the premises, increased soil nitrogen content, pasture disturbance (e.g. construction) and an increased number of horses
• Grazing at pasture.
• Recent movement to a new premises (esp first 2wk).
• Change of feed type or quantity during the 14 days prior to disease and the use of an ivermectin
  anthelmintic at the ultimate and penultimate treatments.
• Cooler, drier weather and irregular ground frosts.

Question 26

List potential gross pathologic findings on post-mortem of a horse affected by EGS.

Answer 26

• Multiple abnormalities related to GI dysfunction e.g.:
  * Acute cases: stomach/SI fluid distension,
  reflux oesophagitis.
  * Subacute: firm, corrugated impactions of the
  large colon and caecum, the outer surface of
  which often shows a characteristic black coating.
  * Subacute and chronic: mucus-coated hard
  faeces in the small colon and rectum.
• Poor body condition: dysphagia, anorexia, cachexia.
• Marked, bilateral rhinitis sicca in some chronic cases.

Question 27

Describe the typical lesions identified on histologic examination of nerves in EGS cases.

Answer 27

• Findings are indicative of neuronal degeneration.
• Extensive chromatolysis, with loss of Nissl substance, eccentricity or pyknosis of the nuclei, neuronal swelling and vacuolation, accumulation of intracytoplasmic eosinophilic spheroids and axonal dystrophy.

Question 28

In which organs is neuronal loss/damage observed in EGS? In addition to decreased numbers of neurons, what else is present in decreased numbers?

Answer 28

• Stomach, duodenum, jejunum, ileum, caecum, large colon, small colon and, more variably, the rectum.
• Acute: widespread; greatest in ileum.
• Chronic: less extensive in jejunum and small colon.
• Interstitial cells of Cajal dec in ileum and pelvic flexure.

Question 29

Describe the location of affected neurons in EGS.

Answer 29

• Lesions are most evident in the prevertebral and paravertebral ganglia of the ANS and ENS; somatic motor neurons also affected.
• ANS: ciliary ganglion, cranial cervical ganglion, caudal cervical ganglion, stellate ganglion, thoracic and abdominal sympathetic trunk, coeliaco-mesenteric or coeliac/cranial mesenteric ganglion, the caudal mesenteric ganglion and the parasympathetic terminal cardiac ganglion.
• ENS: myenteric and submucous plexuses.
• CNS: CN III, V, VI, VII, VIII, X, XII, spinal cord lower
  motor neurons and spinal cord intermediolateral horn neurons.

Question 30

List the clinical signs of EGS.

Answer 30

• All forms: dullness, anorexia, dysphagia, tachycardia, ptosis, patchy sweating, muscle fasiculations.
• Acute: colic, large volumes NGT reflux.
• Subacute: colic, no/small volume NGT reflux, impactions.
• Chronic: weight loss, ‘tucked up’ appearance, progressive myasthenia (base narrow stance, leaning against walls, weight shifting), rhinitis sicca.

Question 31

The prognosis is very poor for recovery from EGS and treatment consists only of supportive care until some normal GI/muscle function is regained. List the criteria used to select appropriate candidates for treatment.

Answer 31

Criteria:

1. Willingness to attempt to drink and swallow food.
2. Retention of some ability to drink and swallow food.
3. Absence of continuous, moderate to severe colic signs.

Question 32

Describe the clinical signs of botulism in horses.

Answer 32

Dysphagia (poor tongue tone, milk/feed in nostrils or trachea, persistent DDSP), lethargy, weakness, mydriasis and sluggish PLRs, increased time spent recumbent and hypometric gait –> recumbency and dyspnoea.

Question 33

What is the common name for (USA) endemic toxicoinfectious botulism of foals and what antigenic type causes it?

Answer 33

Shaker Foal Syndrome.

C. botulinum type B.

Question 34

What are the principles of treatment of a horse or foal with botulism?

Answer 34

• Bind the toxin: trivalent BoNT anti-toxin (A, B, C) - 20,000IU/foal and 50,000IU/adult (one dose as 12d t1/2); 98% died w/out vs 96% foals and >70% adults survived with early anti-toxin tx.
• Eliminate the source of infection: removal of contaminated feed; lance, drain, debride, lavage wounds.
• Supportive care: deep bedding/turn/sling recumbent horses; keep head above level of heart several hours/day if standing (prevent oedema); nutrition (oral, NGT, PPN); urinary catheter BID/remove faeces if required.
• ABs only to tx known infection ONLY (penicillin/metro contradicted as > BoNT release) e.g. asp pneumonia, cystitis or in heavily instrumented foals.
• InO2 or ventilation of foals.

Question 35

In animals that survive, how long does it take the clinical signs of botulism to reverse?

Answer 35

• Recumbent animals: (death usually w/in 3d) recumbency resolves in 1-4 weeks; complete recovery weeks to months,
• Non-recumbent animals: dysphagia, limb weakness, sluggish PLRs recover in days to weeks.

Question 36

What vaccine is available to prevent against Botulism in horses and what is the recommended vaccine schedule?

Answer 36

• BoNT/B toxoid; highly effective vaccine (NB no BoNT/C or multivalent licensed in USA).
• Adults: 2 doses 4 weeks apart then annually.
• Broodmares: 4-6 weeks pre-foaling.
• Foals: 3 doses 4 weeks apart; usually commence at 2-3mo BUT maternal antibody doesn’t interfere with vacc, therefore high risk foals should commence at 2wo.

Question 37

Which two toxins are produced by Clostridium tetani?

Answer 37

Tetanolysin and tetanospasmin (TeNT).

Question 38

Describe the pathophysiology of tetanus.

Answer 38

Deep wound, injection site, post-foaling uterus (RFM), Sx site, umbilicus etc. contaminated with C. tetani –> growth of C. tetani spores in anaerobic environment –> elaboration of exotoxins –> neurologic deficits.

Question 39

Describe the actions of tetanolysin within the body.

Answer 39

Damages tissue, reduced redox potential, increases expansion of infection.

Question 40

Describe the actions of tetanospasmin within the body.

Answer 40

Diffuses from tissue to vascular system –> somatic NMJ and autonomic ganglia –> binds to nerve terminals –> internalised –> transported retrograde in axons –> CNS –> binds irreversibly to presynaptic inhibitory interneurons (‘Renshaw cells’) –> cleaves synaptobrevin (SNARE) –> inhibits release of glycine and GABA –> spastic paralysis.

Question 41

Describe possible post-mortem findings in a horse with tetanus.

Answer 41

• Gram stain of wound exudates –> gram +ve, spore-forming bacilli (30% cases).
• Gross pathology non-specfic e.g. secondary muscle damage, pulmonary congestion, atelectasis etc.
• IHC detection of TeNT antigen in spinal cord ventral or intermediate horn cells.

Question 42

List clinical signs of tetanus in the horse.

Answer 42

CSx develop 1-60d post inoculation; commence with head & neck, may remain localised/mild or –> death; include:

• Trismus, risus sardonicus, 3rd eyelid prolapse, lockjaw, neck stiffness.
• Rigid extension of limbs/back/neck (sawhorse stance).
• Stiff tail.
• +/- colic (bloat in ruminants).
• Tonic-clonic muscle spasms following stimuli.
• Dysphagia.
• Fluctuant HR/BP.
• Recumbency.
• Death: rest failure, aspiration, autonomic overactivity (cardiac dysrhythmias).

Question 43

What are the principles of treatment of a horse or foal with tetanus?

Answer 43

1. Neutralise unbound toxin: tetanus anti-toxin 20IU/kg/day for 5d; horses only: intrathecal admin (lumbosacral) 400-1000IU/kg.
2. Eliminate the infection: open, drain, debride, lavage wound; metronidazole > penicillin for 3-5d.
3. Provide muscle relaxation: pack ears, dim lights, minimal handling etc.; acepromazine, diazepam, midazolam, dantrolene, Mg (blocks neuromuscular transmission, interferes with catecholamine release, dec catecholamine receptor responsiveness, anticonvulsant).
4. Ensure good footing: non-slip floor, +++ padding, sling?
5. Maintain hydration and nutritional status.

Question 44

What is the prognosis for horses with tetanus?

Answer 44

68-75% fatality.

NB ~50% dairy cattle, >80% small ruminant.

Question 45

What vaccine(s) is/are available to prevent against Botulism in horses and what is the recommended vaccine schedule?

Answer 45

Tetanus toxoid (TT):
- Adults: 2 doses 4 weeks apart then annually; repeat if wounded or undergoing Sx >6mo after last booster.
- Broodmares: 4-6 weeks pre-foaling.
- Foals: 4-6mo, 2nd dose 4wk later, 3rd dose 10-12mo.
Tetanus anti-toxin (TAT):
- Give to wounded, un-vaccinated horses (+TT) or foals (TAT only)

Question 46

Which antibiotic should be avoided in horses with botulism and why?

Answer 46

Aminoglycosides, as they may potentiate the neuromuscular blockade caused by BoNT.

Question 47

What is Equine Motor Neuron Disease (EMND?)

Answer 47

An acquired neurodegenerative disorder of the ventral horns of the grey matter of the spinal cord and selected brainstem nuclei of adult horses resulting in skeletal muscle weakness and atrophy.

Question 48

What is the aetiology of EMND?

Answer 48

Vitamin E deficiency (+/- selenium deficiency).

Question 49

What age of horse is most at risk for EMND?

Answer 49

Reported cases: mean 9yo (2-27); highest risk 16yo.

NB CSx develop after at least 18 months of being on a Vitamin E deficient diet.

Question 50

List the risk factors associated with development of EMND.

Answer 50

• Use of pelleted feed.
• Frequent supplementation with vitamin/mineral supplements lacking Vitamin E/selenium.
• Lack of absorption of Vitamin E despite appropriate diet i.e. GI or hepatic disease.
• Unknown if low vitamin E diet is the only nutritional or management factor responsible for influencing development of EMND.

Question 51

Describe the pathophysiology of EMND.

Answer 51

Hypovitaminosis E –> systemic oxidative stress –> cellular damage.
Evidence: dominant involvement of oxidatively active type I myofibres in atrophied skeletal muscles, abundant deposits of ceroid lipofuscin in retinal pigmented epithelium and the endothelium of spinal cord capillaries.

Question 52

What are the clinical signs of EMND?

Answer 52

CSx reflect denervation of skeletal muscle: muscle weakness,+/- muscle wasting, trembling of anti-gravity muscles, sweating, ‘horse on ball’ stance, shifting weight, difficulty standing still, hypometric gait but not ataxic, neck low, tail head elevated.
40% cases horizontal band of pigment above the optic disc at the tapetal-nontapetal junction.

Question 53

How do you diagnose EMND ante-mortem?

Answer 53

• Typical CSx, age >2yo, diet low in green forage and high in carbohydrates.
• Serum: low vitamin E, mild to mod inc CK and AST.
• Muscle biopsy: sacrocaudalis dorsalis tailhead muscle –> neurogenic muscle atrophy characterised by variable numbers of atrophied angular fibres (type I predominate); 90% sensitivity, low specificity.
• Nerve biopsy: 5cm section of ventral branch of spinal accessory n as it courses over the sternocephalicus m –> mild to severe Wallerian degeneration of axons and Schwann cell proliferation; PPV 75%, NPV 90%.

Question 54

List post-mortem examination findings in horses with EMND.

Answer 54

Widespread degeneration and loss of somatic motor neurons in the ventral horns of the spinal cord accompanied by degnerative axonal changes in the ventral roots and peripheral nerves.
All brainstem CN somatic motor nuclei, except III, IV and VI are involved.
Minimal to no lesions in autonomic nervous system.

Question 55

What is the recommended treatment for EMND?

Answer 55

Vitamin E (at least 10IU/kg/da); natural (RRR-alpha-tocopherol) has higher bioavailability than synthetic (all-rac-alpha-tocopherol or dl-alpha-tocopherol).
Good quality grass and alfalfa hay (rich in vitamin E).
High quality and quantity pasture, hay and concentrates due to higher caloric requirements.

Question 56

List the three potential outcomes for horses with EMND

Answer 56

• 40% of cases progressive deteriorate and are euthanised.
• 40% improve markedly; look normal on PE but may ‘recrudesce’ with intensive training or competition.
• 20% stabilise with permanent muscle wasting and emaciaton.