OOD 27.6.4: Toxin-induced neurological disease

Question 1

Cause and pathogenesis of tetanus

Answer 1

Cause:Clostridium tetani exotoxin (tetanospasmin)
* This bacterium is ubiquitous in soil and ruminant faeces but toxin only produced in specific circumstances and anaerobic environment
* Spores are long-lived and resistant to most disinfection
* Tetanospasmin inhibits Renshaw neurones and this is irreversible
* Horses are particularly sensitive
* Infection generally associated with dirty wounds

Question 2

Incubation and mortality of tetanus

Answer 2

• Incubation: 7-21 days
• Mortality: 70%

Question 3

Clinical signs of tetanus

Answer 3

• Prolapsed nictitating membrane
• Tight facial expression (Risus sardonicus)
• Limp spasticity (“sawhorse” stance)
• Fixed extended neck
• Tight jaw (trismus)
• Laryngeal spasm (stridor), drooling
• Dysphagia
• Elevated tail head
• Recumbency
• Dyspnoea
• Hyperthermia
• Profuse sweating and tachy/bradycardia (autonomic storms)

Question 4

Treatment of tetanus

Answer 4

• Tetanus antitoxin slow IV >10,000 IU needed
• Muscle relaxants e.g. Dantrolene, methocarbamol, acepromazine
• Magnesium sulphate: blocks neuromuscular transmission, catecholamine release, antagonises Ca
• Supportive care: IV fluids and dextrose, quiet environment, thick bedding

Question 5

What to do if you find a suspicious wound and are worried about tetanus?

Answer 5

• Open, clean, debride
• Provide antibiotics: in humans trials, metronidazole performed better compared to penicillin
• (Penicillin = drug of choice in ruminants / anything that may enter the food chain)

Question 6

Prevention of tetanus

Answer 6

• Vaccination of pregnant mares 4 weeks before delivery
• Vaccinate foals at 4-6 months, then 4 weeks later, then at 12 months. Then give biannually.
• If mare not vaccinated, provide TAT at birth and vaccinate foals at 1-3 months with 3 doses 4 weeks apart, then at 12 months, then biannually.

Question 7

Causative agent of Botulism

Answer 7

• Causative agent: Clostridium botulinum exotoxin (Botulism neurotoxin)
• Toxins A&B are found in contaminated forage, soil, wounds, injections etc.
• Toxin C is found in carcasses on forage

Question 8

Pathogenesis of botulism

Answer 8

• Ingestion of preformed toxins in spoiled feedstuffs, or entry of spores to body via contaminated wounds, or umbilicus
• Horses are very sensitive; most common form is Type B (“foal shaker syndrome”)
• Toxin (BoNT) inhibits acetylcholine release
• The toxin crosses the GIT but not the BBB

Question 9

Incubation and half life of botulism

Answer 9

• Incubation: 3-7 days
• Half-life: 12 days

Question 10

Clinical signs of botulism

Answer 10

• Mydriasis
• Slow PLR
• Tongue hypotonia
• Dysphagia
• Weakness
• Muscle tremors
• Recumbency

Question 11

What is the feed challenge test, when would you use it and what is a normal result?

Answer 11

Feed challenge test: give 8 oz of grain in a shallow pan. A normal horse should be able to eat it in less than 2 mins.

Could use if suspicious of tongue hypotonia / dysphagia e.g. in botulism

Question 12

Diagnosis of botulism

Answer 12

• Toxin is only found in 30-40% cases
• Can check faecal / GI fluid / liver samples and send for PCR ± bioassays

Question 13

Treatment of botulism

Answer 13

• Time-critical: 70% survival if early treatment
• Serum antitoxin: 500ml-1L - only works on unbound toxin
• Nutritional support: e.g. NGT but care due to decreased motility, or parenteral nutrition
• Support recumbency: with deep bedding, head elevation, slings, padded helmets

Question 14

Prevention of botulism

Answer 14

Vaccination in endemic areas

Question 15

What is stringhalt and what are the possible causes?

Answer 15

Stringhalt: disorders characterised by sudden and exaggerated flexion of the pelvic limbs during the swing phase of locomotion.
* Classical stringhalt: unilateral and possibly due to trauma of extensor muscles, OA of hock
* Pasture-associated stringhalt: bilateral and associated with ingestion of plant neurotoxin at pasture

Question 16

Epidemiology and pathogenesis of pasture-associated stringhalt

Answer 16

• Outbreaks seen in horses at pasture
• Occurs due to ingestion of plant neurotoxin (Hypochoeris radicata, false daffofil) which leads to demyelination of long nerves
• There is long nerve axonopathy and muscle atrophy within 2 weeks
• Particularly seen in peroneal, tibial nerves, recurrent laryngeal nerve, and atrophy in the gaskin and thigh

Question 17

Clinical signs of stringhalt

Answer 17

• During forward walking: flexing limb snaps forwards and upwards in an adducted and sagittal plane
• Muscle atrophy within 2 weeks

Question 18

Diagnosis of stringhalt

Answer 18

• Determine whether toxic or mechanical: use nerve blocks, intra-articular blocks; see if unilateral or bilateral; see if multiple horses affected

Question 19

Treatment of stringhalt

Answer 19

• Mechanical: OA treatment, splinting of the lateral digital flexor
• Toxic: phenytoin PO BID

Question 20

Prognosis for stringhalt

Answer 20

• Mechanical: 50% recovered
• Toxic: 50% fully recovered within 12 months

Question 21

Epidemiology and pathogenesis of rye-grass staggers

Answer 21

• Initial signs occur 5-10 days after consumption
• Ingestion of tremorgenic mycotoxins (secondary diterpenoid metabolites produced by endophyte fungi affecting perennial rye-grass, paspalum, bermude grass)
• Initial signs are seen 5-10 days after consumption

Question 22

Clinical signs of rye-grass staggers

Answer 22

• Coarse muscle tremors esp in thoracic limbs and muzzle (cerebellar damage)
• Jerky hindlimb movement
• Wide-based stance
• Exaggerated truncal sway
• Abortion in pregnant mares

Question 23

Treatment of rye-grass staggers

Answer 23

• Remove from pasture - should see resolution within 2 weeks
• Reduce handling and keep in quiet environment
• Provide water and feed: IV if necessary over first 48hrs
• Remove infested pasture via mowing and burning