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Tremorgenic Mycotoxicosis in Dogs

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Tremorgenic Mycotoxicosis in Dogs 3 CE Credits Tremorgenic Mycotoxicosis in Dogs Andrew K. Barker, DVM Chase Stahl, BS Steve M. Ensley, DVM, PhD Nick D. Jeffery, BVSc, PhD, DECVS, DECVN Iowa State University Abstract: Ingestion of tremorgenic mycotoxins formed in spoiled food can cause an acute tremor syndrome, the severity of which can range from mild to life-threatening. Swift recognition of the likely cause is required for accurate prognostication and rapid institution of appropriate therapy, which leads to complete resolution in most cases. Clinical Signs 19687). Experimental intoxication of mice and rats produced dose- Tremorgenic mycotoxicosis in dogs typically presents as an acute dependent signs, including tremors, behavioral changes, seizures, onset of generalized tremors, sometimes of sufficient severity to and death. Examination of different isolates of P. crustosum found resemble a seizure; animals occasionally present in status epilepticus.1 that 100% produced penitrem A in addition to roquefortine.8 Such cases usually present as emergencies. Affected animals may Roquefortine is mainly produced by Penicillium roqueforti (the also salivate, pant excessively, be pyrexic (body temperature may same species used in making Roquefort cheese) but may also be exceed 107°F [41.7°C]), and show mydriasis, nystagmus, and hyper- produced by several other types of Penicillium fungi, including P. sensitivity to noise and touch.2–5 The time to onset of convulsions or crustosum.6 tremors after ingestion varies from ~30 minutes to several hours.1,4 Nonneurologic signs can include vomiting, diarrhea, flatulence, and Mode of Action tachycardia,4 and severely affected animals may be recumbent and The mode of action of the tremorgenic mycotoxins is variable unable or unwilling to raise their head. At presentation, it can be and not fully understood, although access to the brain across the difficult to elicit an accurate history from owners, but, occasionally, blood-brain barrier is facilitated by their lipophilia.6 Rats injected access to garbage or other sources of decaying food is known. Access with penitrem A show marked increases in the release of glutamate, to rotten material is significant because there are few reports of GABA, and aspartate at cerebrocortical synapses.9 A similar inter- tremorgenic mycotoxicosis, despite the ubiquity of mycotoxin- ference with neurotransmission within the cerebellum is thought to producing molds in the environment. cause the characteristic tremor.4 Penitrem A also increases gastric smooth muscle activity in vitro,10 probably through sensitizing it to Etiology acetylcholine, and similar effects may also occur within the central Ingestion of a variety of moldy foods, including grains, walnuts, nervous system. almonds, and peanuts, as well as nonspecific garbage, has been In one study, focal tremors developed within 7 to 10 minutes of associated with tremorgenic mycotoxicosis.2 Dogs are more intraperitoneal injection of penitrem A in rats11 and changes were commonly affected than other species of domestic animals, detected only within the cerebellum at necropsy. Initial changes were probably because of their tendency to scavenge6; intoxication of seen as ischemic changes several dogs within the same household has also been reported.5 in Purkinje cells. Animals The most common sources of tremorgenic mycotoxins are that were not euthanized Key Points fungi of the genus Penicillium,7,8 which are found in decomposing returned to near-normal • The propensity of dogs to ingest food and vegetable matter. Many tremorgenic compounds are behavior within 1 week.11 rotting material exposes them to the known, including penitrems, thomitrems, aflatrem, cyclopiazonic Areas of necrosis within risk of tremorgenic mycotoxicosis. acid, and roquefortine. It is believed that different tremorgenic the cerebellar granule cell mycotoxins produce clinical signs of varying severity, but con- layer and vacuolization of • Rotting foodstuffs often consist of sumption of more than one toxin is common in clinical cases.3 the molecular layer have many different potential fungal The major tremorgens in domestic dogs are penitrem A and also been reported.12 growth substrates and may contain roquefortine, with Penicillium crustosum contamination the most The minimum oral toxic a variety of fungal toxins. commonly identified source (first reported by Wilson et al in dose of penitrem A, aflatrem, Vetlearn.com | February 2013 | Compendium: Continuing Education for Veterinarians® E1 ©Copyright 2013 Vetstreet Inc. This document is for internal purposes only. Reprinting or posting on an external website without written permission from Vetlearn is a violation of copyright laws. Tremorgenic Mycotoxicosis in Dogs Box 1. Common Etiologies of Tremors in Dogs Primary neurologic disorders Toxin ingestion • Amphetamines/pseudoephedrine • Steroid-responsive tremor syndrome • Tremorgenic mycotoxins • Paintballs (“little white shaker syndrome”) • Metaldehyde • Ethylene glycol • Episodic tremors (idiopathic) • Organophosphates/carbamates • Heavy metals (aluminum, lead) • Cerebellar disease • Strychnine • Xanthines (e.g., caffeine, theophylline, • Ivermectin • Congenital action-related tremors theobromine) Iatrogenic Endocrine/metabolic disorders • Bromethalin • Blood transfusion reactions • Hypoglycemia • Macadamia nuts Infectious diseases • Hypocalcemia/eclampsia • Marijuana • Distemper • Hepatic encephalopathy • Cocaine • Rabies or roquefortine has not been determined; however, since the conditions can be differentiated from acute toxicoses based on amount of the compounds ingested cannot be quantified in practice, history, clinical progression of the disease, and routine blood it is not possible to determine if a dog has ingested a toxic dose. tests. For instance, hypoglycemia and hypocalcemia are easily recognized during routine investigation of emergency patients, Differential Diagnosis and while eclampsia can cause acute tremors,15 the signalment Tremors are a nonspecific clinical sign; the Cornell University (pregnancy or lactation) should aid recognition. Idiopathic Veterinary Consultant Web site (www.vet.cornell.edu/consultant/ tremor syndrome (previously called little white shaker syndrome) consult.asp) lists almost 200 different causes of tremors in dogs. is the most prominent diagnostic differential for a small-breed Some of the more common causes are listed in BOX 1. Therefore, dog with acute-onset tremors and no other significant clinical a detailed history and typical additional clinical signs (e.g., vomiting, signs. Although most common in young members of small, white seizures) associated with mycotoxin ingestion may be helpful in breeds, idiopathic tremor syndrome can occur in many dog breeds. rapid identification of the etiology (FIGURE 1). Importantly, affected animals have normal neurologic and physical In view of the acute onset of nonspecific signs and history of these examination findings apart from the tremors, which can be acute patients, toxicosis is often suspected. Common toxins resulting in onset but frequently become progressively severe over a period in tremors, seizures, and similar neurologic signs include metal- of days, which aids in differential diagnosis. In addition, tremors dehyde (slug bait), organophosphates and carbamates, strych- usually occur only when the animal is stimulated and affected nine, xanthines, and bromethalin. Strychnine toxicosis cannot always Suspected mycotoxin ingestion be differentiated from tremor- genic mycotoxicosis based on clinical signs,13 although it is Seizure No seizure generally associated with tetanic Administer anticonvulsant spasms rather than tremor, and No tremors exposure is relatively rare. Similar Tremors No response Induce emesis Administer muscle relaxant considerations apply in ruling out Administer second (methocarbamol) exposure to bromethalin (ro- anticonvulsant denticide), xanthines (caffeine, theophylline, theobromine), and No response Adequate control Inadequate control 14 Induce general anesthesia Repeat methocarbamol macadamia nuts. administration In dogs in which a nontoxic etiology of tremors merits con- sideration, the differential diag- nosis includes idiopathic tremor Monitor for changes in status Provide supportive care syndromes, hypoglycemia, hypo- calcemia, eclampsia, and cere- Figure 1. Diagnostic tree for acute tremors in dogs, based on initial assessment and emergency/cage-side tests. bellar disorders. Many of these Figure 1. Diagnostic tree for acute tremors in dogs, based on initial assessment and emergency/cage-side tests. Vetlearn.com | February 2013 | Compendium: Continuing Education for Veterinarians® E2 Tremorgenic Mycotoxicosis in Dogs mycotoxicosis. Known ingestion Primary neurologic disorder of, or possible access to, moldy Results of blood tests normal Toxin ingestion food, garbage, or compost is highly suggestive. Hepatic encephalopathy Definitive diagnosis is made by Tremors alone analysis of vomitus or stomach Hypoglycemia contents, blood, urine, or the (rule out primary vs. Results of blood tests insulinoma) suspected contaminated material. abnormal (suspect metabolic cause) Hypocalcemia Analytic methods include iden- (rule out primary vs. tification of the mold through Acute-onset tremors eclampsia) culture of the organism or detec- Other 1,4,17 tion of the toxins themselves, Congenital although the presence of mold Neoplasia does not necessarily mean my- Cerebellar signs Idiopathic tremor cotoxin will be present. Liquid Other Other neurologic signs chromatography–mass
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