Polioencephalomalacia (PEM) is a histological description of a neurological disease in ruminants that is a result of various aetiologies, including high sulphur intake, altered thiamine status, salt poisoning/water deprivation and lead poisoning (Smith, 2009).
The property is situated the Central Tablelands of N.S.W. The area has experienced multiple years of drought up until 2010-2011 with good rainfall and pasture growth.
In April of 2011 a mob of 1200, 4 -5 year old Merino ewes, experienced significant losses including 20 deaths and 40 ewes showing CNS signs. The pasture they were grazing consisted of unimproved clover and phalaris. There is no supplementary feeding. When losses continued despite vaccination, the district veterinarian was contacted. PEM was suspected based on the presenting clinical signs; blindness, ataxia and recumbency. The cause of the PEM was hypothesised to be a plant toxin and therefore the sheep were moved to the adjoining paddock. The remaining clinically affected sheep were treated with 10 mg/kg i.m of thiamine (Nature Vet 100 mL, Thiamine Hydrochloride 125 mg/mL). Fifty percent of cases required two doses 24 hours apart for recovery. The owner reported a good clinical response to the treatment in most cases except for those that were severely affected.
Post-mortems were performed on a recently dead sheep and another displaying severe clinical signs. The brains were removed and no gross abnormalities were apparent. There were no abnormalities on gross inspection in other any organs.
In light of the isolated incident, nutrition and signalment of the animals involved it a toxic plant was suspected. A local agronomist was contacted to identify any weeds or plants within the paddock that could be implicated with PEM, in particular Nardoo fern, Bracken and Rock fern, which contain high levels of thiaminase I enzyme. These plants were not found. The only weed that was identified as significant to the case was Chenopodium murale (Green Fat Hen). It was clear on inspection that the weed was abundant particularly around the camp and the sheep had been nibbling the tops of the plant. The plant was also in seed at the time. According to the agronomist Chenopodium spp are not usually grazed as they are unpalatable and have a fishy odour. This plant had not been identified by the farmer previously. Chenopodium spp have been linked to high sulphur intake PEM in sheep as they accumulate sulphate in high concentrations (Kahn, 2011 and Burgess, 2008).
The histopathology results of the brain were focal mild lymphoid perivascular infiltrations in the brain stem. A focal area of fluorescence was seen under UV light. Further sectioning of the cortex revealed a laminar, acute, cortical, neuronal necrosis confirming polioencephalomalacia. These brains were submitted for the Transmissible Spongiform Encephalopathy (TSE) scheme to exclude TSE. Submission was based on the absence of any gross pathology in other organs and the presenting neurological signs. The TSE result was negative. The histopathology along with the response to thiamine confirmed the diagnosis of PEM.
The sheep were removed from that particular paddock but losses of at least one per day occurred for the next six weeks. The farmer reported a 75% response to treatment including those that required a second dose. To prevent any more losses in the mob it was advised to prophylactically mass treat the remainder with a one off intramuscular injection of thiamine at 10 mg/kg. The cost of the dose is $0.75 -1.00/dose (5 mL dose of Vitamin B1). The prophylactic treatment with vitamin B1 is not expected to have serious side effects when administered at the therapeutic dose. However since it is water soluble with a short half-life, it is questionable whether a spike in thiamine would prevent or eliminate the causal agent (Burgess, 2008).
The producer was contacted again 7 weeks after the original insult to check the progress of the case. The farmer was willing to follow the advice of mass treatment with vitamin B1; however, there was a delay in the supply. In the meantime, animals appeared to recover without treatment, as there were no more losses identified for three consecutive days.
It is suspected that the cause of the PEM was due to high sulphur intake from the Chenopodium spp. The continued losses 6 weeks following removal from the pasture may be a result of the delayed effect of the high sulphur intake. PEM because of sulphur toxicity has been reported to cause clinical signs from a few hours to 32 days following exposure (Aitken, 2007 & Kahn, 201 1). It has been shown in cattle that undergo a transition to a high sulphur intake, that ruminal sulphide concentrations peak 1 -4 weeks after the change (Burgess, 2008). PEM peaks when ruminal sulphide is the highest. An alternate hypothesis is that it takes the rumen some time to break down the plant, especially the seeds that may contain high concentrations of sulphur. The only means of confirming PEM is by histological analysis although the response to thiamine treatment was an indicator of the disease. A blood test for thiamine is available, however at $88.00 sample, was considered impractical for monitoring the disease.
The mass treatment of the remaining animals is advisable as a preventative of any more losses (Aitken, 2007). This was successful in a case of sulphur toxicity in lambs according to Aitken (2007) whereby the mob received a single i.m injection of vitamin B I at 20 mg/kg. It has been shown that thiamine is effective at reducing symptoms, even those cases with high sulphur intake PEM, possibly by increasing the energy availability to the brain (Drewnoski, 2010).
Polioencephalomalacia can be induced by high dietary sulphur or by altered thiamine status
1. High sulphur intake
High sulphur sources include lucerne, molasses-urea supplements, plants such as Kochia (Kochia scoparia) and Chenopodium spp, turnips, rape mustard, oil seed meals, by-products of com, sugar cane, sugar beet and within the water in some areas (Kahn 2011 & Burgess, 2008). Excess sulphur may decrease the levels of thiamine either directly or via thiaminase production. The sulphite ion is a strong nucleophile and it readily binds to thiamine and may cause secondary deficits in vitamin B1. Alternatively it is hypothesised that high sulphur intake results in the production of excessive ruminal sulphide due to ruminal microbial reduction of ingested sulphur. The hydrogen sulphide gas accumulates and on eructation the gas is inhaled (refer to Figure I). High concentrations of hydrogen sulphide have been associated with energy deprivation to the central nervous system (CNS) through interference with cellular energy metabolism (Kahn 2011). This may be due to inhibition of cytochrome C, an enzyme of the electron transport chain that is involved in the production of adenosine triphophate (Drewnoski, 2010). The alternate may be a result of oxidative injury possibly via inhibition of superoxide dismutase and glutathione peroxidise (Drewnoski, 2010 & Burgess, 2008).
2.Altered thiamine status
i. Acute dietary deficiency of thiamine: This is usually only prevalent in pre-ruminants .e. young animals with an underdeveloped rumen (Burgess, 2008).
ii. Thiaminases; can be produced by gut bacteria or ingested as preformed plant products. They can either destroy thiamine or form anti-metabolites that interfere with thiamine function (Kahn, 201 1). Thiaminase I is produced by Bacillus thiaminolyticus and Clostridium sporogenes. High amounts of thiaminase I enzyme is found in Nardoo fern (Mars ilea drummondii), Rockfern (Cheilanthes sieberi) and Bracken fern (Pteridium aquilinum). Anthelmintics such as levamisole or thiabendazole can act as co-substrates for thiaminase I (Burgess, 2008). Thiaminase II is produced by B aneurinolyticus, which proliferates under high grain intake and catalyses the cleavage of thiamine (Kahn, 2011).
iii. Thiamine analogs; competitively inhibit glycolytic reactions. Bacteria, plants (bracken) and drugs such as amprolium, pyrithiamine and oxythiamine (Burgess, 2008) can produce them.