Page 789 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

748 SECTION | XI Bacterial and Cyanobacterial Toxins

VetBooks.ir system and the myenteric and submucosal plexuses of the horse sera, gut contents, viscera, wounds, tissues or food-
stuffs (the gold standard test); (2) detection of C. botuli-
enteric nervous system. The clinical syndromes are
num spores or toxin in suspect foodstuffs in association
described as acute, subacute and chronic depending on
the duration of the disease (typically the duration of sur- with clinical signs; and (3) ELISA detection of serum
vival after initial diagnosis). The syndrome almost always antitoxin antibodies in unvaccinated horses with clinical
includes dullness, anorexia, dysphagia and tachycardia. signs. However, a definitive diagnosis is usually difficult
The cranial nerves (and their CNS nuclei) involved in pre- to achieve. There are no gross or pathognomonic histolog-
hension and mastication (cranial nerves V, VII, IX, X, ical lesions associated with classical botulism, and serum
and XII) often become involved. Ptosis (due to denerva- toxin levels in the horse are often too low to be detected
tion of sympathetic axons innervating Mu ¨ller’s superior by the mouse bioassay. Due to the sensitivity of horses,
tarsal muscle) and patchy sweating (due to sympathetic the mouse bioassay is most useful in early, peracute
denervation with chemical hypersensitivity of the sweat equine botulism, when higher concentrations of toxin may
gland and/or vasodilatation and subsequent increased be present in the bloodstream. Greater diagnostic success
sudiferous adrenaline arriving at the sweat glands and or may be achieved through detection of botulinum toxin in
elevated baseline plasma adrenalin) may occur. In acute food using the mouse bioassay rather than detection
cases, mild to moderate abdominal pain and large within affected animals (Galey, 2001). Anaerobic fecal or
volumes of nasogastric reflux are common. Weight loss tissue culture enrichment can be used to enhance bacterial
and progressive myasthenia (base-narrow stance, leaning spore numbers and toxin levels for greater detection.
back against walls, weight shifting of the limbs) are com- However, because spores may be present in the feces of
mon findings in the chronic disease. The pathophysiologi- healthy horses, direct detection of systemically absorbed
cal basis for the effects on muscles is uncertain. Overt botulinum toxin within the animal is a more reliable find-
botulism-like flaccid paralysis does not occur and, unlike ing. Following a positive result from the mouse bioassay,
botulism cases, affected horses to not spend progressively the serotype can be identified using the mouse neutraliza-
longer periods of time in recumbency and triceps/quadri- tion test.
ceps fasciculations persist during periods of recumbency. The key diagnostic histological finding in EGS is neu-
Generalized small intestinal distention and colon/cecal ronal degeneration (extensive chromatolysis, with loss of
impactions are common findings and reflect intestinal Nissl substance; eccentricity or pyknosis of the nuclei;
dysmotility due to enteric nervous system damage. neuronal swelling and vacuolation; accumulation of intra-
A tentative diagnosis of classical botulism can be made cytoplasmic eosinophilic spheroids and axonal dystrophy;
following a neurological examination and repeat neurologi- cell death followed by neuronophagia; and an apparent
cal examinations are useful for monitoring disease progres- increase in capsule/satellite cells). The neuronal damage
sion. Routine clinical pathology examinations are usually is most prominent in the prevertebral and paravertebral
negative but can be useful for differential diagnosis pur- ganglia of the autonomic nervous system and in enteric
poses. Typically normal laboratory values in the presence neurons (myenteric and submucous plexuses). However,
of neurological deficits support a diagnosis of botulism. there is usually extensive neurological damage throughout
Important differential diagnoses include: equine protozoal the autonomic nervous system. The exact pathogenesis of
myeloencephalitis, equine viral encephalitis (alphaviruses: the neuronal damage is unknown. There is evidence of
eastern and western equine encephalitis, mdariaga virus, elevated galanin, extensive cytoskeletal disruption with
highland virus, Venezuelan equine encephalitis, everglades loss of the Golgi apparatus, apoptosis, accumulation of
virus, Ross River virus, Semliki Forrest virus, Una virus; noradrenalin and/or enzymes involved in noradrenaline
flaviviruses: Japanese encephalitis, Murray Valley enceph- synthesis (tyrosine hydroxylase and dopamine-β-hydoxy-
alitis, Kunjin virus, St. Louis encephalitis, Usutu, West lase), reduction in glutamate immunostaining, and an
Nile virus, Louping ill, Powassan, tickborn encephalitis), abnormal distribution of enzymes involved in glutamate
equine herpes virus-1, rabies, guttural pouch mycosis, and metabolism (glutamate dehydrogenase and glutamine
listeriosis; other toxicoses such as leukoencephalomalacia synthase) and increased synaptophysin. Damage to the
(moldy corn poisoning), ionophore poisoning (monesin, CNS nuclei associated with cranial nerves III, V, VI,
salinomycin, and narasin), yellow star thistle poisoning, VIII, XII, X as well as the accessory cuneate nucleus, the
yew poisoning, white snake root poisoning, and organo- red nucleus, the reticular formation, spinal cord lower
chlorine poisoning; metabolic disorders such as equine motor neurons and spinal cord intermediolateral horn
motor neuron disease, azoturia, eclampsia, hypocalcemia, neurons.
hyperkalemic periodic paralysis, and white muscle disease, Once botulism is suspected, the patient should be con-
and pharyngeal ulceration. fined to prevent exertion. Polyvalent antiserum (antitoxin)
A tentative diagnosis of classical equine botulism can should be given as soon as possible; the recommended
be confirmed by: (1) mouse bioassay detection of toxin in dose for an adult horse is 70,000 IU and for foals it is