7-year-old, Thoroughbred cross mare (Equus caballus).The horse presented with a sudden onset of anorexia, dysphagia and severe colic with no discernible gut sounds. Tachycardia (80 beats per minute), dehydration, patchy sweating and muscle tremors were also noted. On rectal examination the mucosa was dry and tacky and the content was dry with mucosal casts. Euthanasia was elected.

Gross Description:  

At necropsy, the stomach was distended with green fluid. Multiple linear red erosions were noted in the distal third of the esophagus. The small intestine was dilated with green fluid and gas, with pale red mucosal and serosal surfaces. The large and small colons were filled with large dry balls of fecal material coated with a black viscous substance (blood). There was multifocal reddening of the colonic mucosa.

Histopathologic Description:

Many neurons in the coeliaco-mesenteric ganglion have a swollen, hypereosinophilic, finely vacuolated cell body with significant reduction in or absence of Nissl granules and either a pyknotic nucleus or absence of nuclear detail. Others have a deeply eosinophilic, rounded cell body with absence of Nissl substance and a paracentral or peripheral pyknotic nucleus. Smaller numbers of neurons show margination of the Nissl granules with central deeply eosinophilic cytoplasm (central chromatolysis). There are numerous perineuronal axonal spheroids of various sizes. Many neurons contain small amounts of clumped, granular golden-brown pigment (lipofuscin).

Morphologic Diagnosis:  

Coeliaco-mesenteric ganglion: Neuronal degeneration and necrosis, acute, multifocal, severe.


Equine dysautonomia; grass sickness

Contributor Comment:  

These gross and histological lesions are considered diagnostic for equine dysautonomia, or grass sickness, a disease that largely occurs in horses at pasture (of a wide variety of breeds) in the United Kingdom, western parts of continental Europe, and South America. The risk is highest for young horses (2 to 7 years of age). The greatest number of cases in the UK occurs in the spring. A similar syndrome has been described in cats in the same areas, in a few dogs, and in wild hares. Acute, subacute or chronic cases may be seen with typical clinical signs in horses including muscle tremors, abnormal sweating patterns, dysphagia, reflux of gastric contents, distended small intestinal loops, absence of gut sounds and absence of or abnormal (dry) feces. Megaesophagus occurs in more than 90% of feline and canine cases. Many horses die or are euthanized within the first two weeks but small numbers of animals have survived long-term. Chronic cases present with a more insidious onset of clinical signs.

In acute cases, which are more common, at post-mortem examination there is typically distension of the stomach, and there may be evidence of gastro-esophageal reflux, i.e. distal esophageal ulceration. The large colon is usually filled with firm fecal balls that have a black coating of blood products. Histological lesions are classically described as being found in postganglionic sympathetic and parasympathetic neurons; typically at post-mortem the coeliacomesenteric and cranial cervical ganglia are sampled in addition to intestinal tract specimens. Normal neuronal numbers in these sites have been published.(6) Lesions are also found in parasympathetic terminal cardiac ganglia and have been associated with a functional reduction in cardiac autonomic control.(5) Cytoplasmic vacuolation, chromatolysis and necrosis of neurons is noted, and numbers of neurons are reduced significantly.(1) More chromatolytic neurons are noted in acute than in chronic cases. However, lesions have also been reported in general somatic efferent and general visceral efferent lower motor neurons in the brainstem and spinal cord including chromatolysis of lower motor neurons of the general visceral efferent nucleus of cranial nerves III and X, and the general somatic efferent nuclei of cranial nerves III, V, VII and XII.(2) For antemortem diagnosis it is typical to submit a full-thickness biopsy specimen from the ileum as pathology in the intestinal tract is seen most consistently and severely in that segment, particularly in the submucosal plexuses.(1)

The cause is not known, but the most popular current theory being, with some circumstantial evidence, that this is a form of botulism (Clostridium botulinum type C).(4)

JPC Diagnosis:  

Ganglion, celiaco-mesenteric (per contributor): Neuronal degeneration and necrosis, acute, diffuse, with satellite cell hypertrophy and proliferation, and minimal multifocal lymphocytic ganglioneuritis.

Conference Comment:  

During the conference, participants reviewed the key diagnostic features of this perplexing entity, as expertly synthesized in the contributors comments. This condition highlights the importance of carefully considering the clinical history and presenting signs when collecting tissues at necropsy; an elevated index of suspicion for grass sickness should prompt the astute diagnostician to examine the celiaco-mesenteric ganglion. The conference moderator reminded participants to be cautious when evaluating autonomic ganglia microscopically, specifically to avoid misinterpreting the hypertrophic and hyperplastic satellite cells as lymphocytes. In this case, there is minimal lymphocytic ganglioneuritis, which is not always present in horses with grass sickness; more prominent are the numerous proliferating satellite cells, which can sometimes be mistaken for lymphocytes.

Conference participants based a discussion of chromatolysis on the example provided here. Chromatolysis is a histologically appreciable change in the soma resulting from dispersal of Nissl granules, which are composed of rough endoplasmic reticulum; chromatolysis may be classified as central or peripheral based on its location within the soma and is best demonstrated with special stains, such as cresyl violet. Cells undergoing central chromatolysis are usually swollen with a distinctly eccentric nucleus, while peripheral chromatolysis is more commonly associated with cell shrinkange. Chromatolysis is always considered to be a lesion; however, correctly identifying and interpreting it is predicated on knowing the normal distribution of Nissl granules at a given location.(3) In the autonomic ganglia, for instance, Nissl granules are normally concentrated at the periphery of the soma, so chromatolysis results in intense central eosinophilia, often with multiple fine clear vacuoles at the periphery of the soma, as is superbly demonstrated in this case.(7) Chromatolysis is a nonspecific reaction that essentially represents a metabolic adaptation to change. For instance, in cases of axonal injury, chromatolysis is evidence of the anabolic response required for regeneration, and has in this context been referred to as the axon reaction. When axonal regeneration is complete, the chromatolytic soma may pass through a densely basophilic phase before returning to normal. Alternatively, chromatolysis may precede cell death, the likelihood of which increases with increasing proximity of the axonal lesion to the cell body. Chromatolysis is also a characteristic feature of numerous motor neurodegenerative conditions and perinatal copper deficiency in sheep and goats.(3)

The dysautonomias of horses, cats, dogs, and hares share not only compelling epidemiological and geographical commonalities, but also a similar distribution of central neuropathology, lending further credence to the suggestion of a common etiology.(2)


1. Doxey DL, Milne EM, Woodman MP, Gilmour JS, Chisholm HK: Small intestine and small colon neuropathy in equine dysautonomia (grass sickness). Vet Res Commun 19:529-543, 1995
2. Hahn CN, Mayhew IG, de Lahunta A: Central neuropathology of equine grass sickness. Acta Neuropathol 102:153-159, 2001
3. Maxie MG, Youssef S: Nervous system. In: Jubb, Kennedy, and Palmers Pathology of Domestic Animals, ed. Maxie MG, 5th ed., vol. 3, p. 444. Elsevier Saunders, Philadelphia, PA, 2007
4. Newton JR, Hedderson EJ, Adams VJ, McGorum BC, Proudman CJ, Wood JLN: An epidemiological study of risk factors associated with the recurrence of grass sickness (dysautonomia) on previously affected premises. Equine Vet J 36:105-112, 2004
5. Perkins JD, Bowen IM, Else RW, Marr CM, Mayhew IG: Functional and histopathological evidence of cardiac parasympathetic dysautonomia in equine grass sickness. Vet Rec 146:246-250, 2000
6. Pogson DM, Doxey DL, Gilmour JS, Milne EM, Chisholm HK: Autonomic neurone degeneration in equine dysautonomia (grass sickness). J Comp Path 107:271-283, 1992
7. Summers BA, Cummings JF, De Lahunta A: Veterinary Neuropathology, pp. 433-434. Mosby, St. Louis, MO, 1995

Click the slide to view.

2-1. Esophagus

2-2. Colon

2-3. Celiaco-mesenteric ganglion (per contributor)

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