April 2017



Signalment (JPC #2136869): 6-month-old Wapiti (elk)


HISTORY: This animal had incoordination for two weeks before being found in recumbency, depressed, and with evidence of diarrhea.


HISTOPATHOLOGIC DESCRIPTION: Cerebellum: Multifocally, there is marked spongiosis in the Purkinje cell layer.  Approximately 30% of Purkinje cells have several small or one large clear cytoplasmic vacuole with swollen cytoplasm and dispersion of Nissl substance (chromatolysis and degeneration) or are rarely shrunken with hypereosinophilic cytoplasm with pyknosis or karyolysis (necrosis). Often Purkinje cells have swollen axons (“torpedoes”) that extend into the granular layer, and swollen dendrites that extend into the molecular layer. Multifocally there is Purkinje cell loss with occasional replacement by large round clear spaces in the Purkinje cell layer (“empty baskets”). Purkinje cells are occasionally disorganized and located in the internal granular layer (ectopic Purkinje cells). There is a slight decrease in the number of granular cells with mild thinning of the granular cell layer. There is scattered spongiosis in the underlying cerebellar white matter.


MORPHOLOGIC DIAGNOSIS: Cerebellum, Purkinje cells: Vacuolar degeneration, necrosis, and loss, multifocal, with torpedoes and ectopia, Wapiti (Cervus elaphus mannitobensis), cervid.


ETIOLOGIC DIAGNOSIS:  Neuronal mycotoxicosis


CAUSE:  Tremorgenic mycotoxin (lolitrems produced by Neotyphodium (Acremonium) lolii)


CONDITION Perennial ryegrass staggers



(Perennial ryegrass staggers):

·       Perennial ryegrass staggers is caused by ingestion of lolitrems produced by endophytic fungus Neotyphodium (previously known as Acremonium) lolii that grows on perennial ryegrass (Lolium perenne)

·       Reported in sheep, cattle, goats, horses, red deer, fallow deer, and wapiti

·       Primarily in New Zealand and Australia; less often in US and Europe

·       The toxins are collectively known as tremorgens; four tremorgenic neurotoxins have beenidentified:  Lolitrem A, B, C, & D (lolitrem B is the most common)

·       Disease commonly occurs in dry periods (June-September in Northern hemisphere; December-June in Southern hemisphere)

·       Low mortality; usually complete recovery within a few weeks after removal from pasture

·       Endophyte growth of Neotyphodium has been shown to protect the plant against insect attack, disease, root predation by nematodes, and drought stress

(Annual ryegrass staggers):

·       Annual ryegrass staggers is caused by corynetoxin which is elaborated by seedheads of annual ryegrass (Lolium rigidium) infected with the nematode Anguina agrostis

·       Nematode larvae infect the seedhead and form a gall as the plant sprouts;  the nematode carries Rathayibacter toxicus (Clavibacter toxicus) which grows within the gall and produces a yellow slime that contains the toxin corynetoxin; corynetoxin is closely related to tunicamycin antibiotics

·       Toxin accumulates due to lack of rumenal breakdown

·       Peak toxin levels occur as the plant dries in late summer

·       Morbidity and mortality rates vary but may reach 100%



(Perennial ryegrass staggers):

·       Lolitrem binds and inhibits GABA receptors of the internuncial neurons primarily a functional neurological derangement, perhaps of neurotransmission

(Annual rye-grass staggers):

·       Corynetoxin, a glycolipid, blocks N-glycosylation of glycoproteins which compromises cell membrane integrity

·       Corynetoxin causes microvascular damage and alters the blood-brain cerebrospinal (CSF) barrier which leads to neuronal injury



·       Same for both diseases

·       Ataxia, stiff gait, nystagmus, head tremors, opisthotonos, intention tremors, seizures

·       Head/neck swaying and base-wide stance

·       Signs are less severe at rest and worse when excited

·       Falling and convulsions

·       Resolution of clinical signs on removal from pasture

·       Chronic exposure to toxin may induce persistent clinical signs



·       None for perennial ryegrass staggers

·       Annual ryegrass staggers – hemorrhages in cerebellum, liver, lungs, and spleen; multifocal greenish hue to cerebellum and cerebrum (rare)



(Perennial rye-grass staggers)

·       Fusiform enlargement of dendrites and axons ("torpedoes") in the granular and Purkinje cell layers of the cerebellum 

·       Vacuolar degeneration and loss of Purkinje cells

(Annual rye-grass staggers)

·       Disrupted vascular integrity and protein leakage (edema)

·       Neuropil degeneration

·       Perivascular edema that reacts with PAS

·       Gemistocytosis and necrobiosis of oligodendroglia

·       Patch loss of Purkinje cells and scattered small foci of malacia



·       Axonal lesions are best demonstrated by the use of silver staining techniques (Holmes method)

·       Microscopic identification of Neotyphodium on the perennial ryegrass

·       Corynetoxin can be extracted with boiling alcohol



·       Other tremorgenic syndromes:

·       Penicillium crustosum, Aspergillus clavatus, Claviceps paspali (ergot of Paspalum):  No “torpedoes” reported in these tremorgenic neuromycotoxicosis


·       Other conditions with “torpedoes”:

·       Abiotrophy – mild gliosis and decreased granular layer neurons may be present

·       Bovine viral diarrhea virus (pestivirus) – cerebellar folia atrophy, mild astrocytosis

·       GM2 gangliosidosis – neurons swollen with abundant granular to foamy cytoplasm that displaces the nucleus



·       Cattle, sheep, goats, horses, deer can be affected

·       Dogs: Tremorgenic mycotoxicosis may result from penitrem A or roquefortine (produced by Penicillium) associated with moldy cream cheese and hamburger buns

·       Horses: Tremorgenic mycotoxicosis may result from the consumption of dallis grass

·       Diagnosed in alpacas in the UK



  1. Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:309,322.
  2. Riet-Correa F, Rivero R, Odriozola E, Adrien Mde L, Medeiros RM, Schild AL. Mycotoxicoses of ruminants and horses. J Vet Diagn Invest. 2013;25(6):692-708.
  3. Summers BA, Cummings JF, de Lahunta A. Veterinary Neuropathology. St. Louis, MO: Mosby Elsevier; 1995:261-263.

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