Polioencephalomalacia (PEN or CCN)

 

The Condition

Polioencephalomalacia (CCN or cerebrocortical necrosis) is one of the most common neurological diseases (Green and Morgan, 1994; Wiener et al., 1983). It is an acute disease of ruminants, characterised by dullness, head pressing, blindness, opisthotonos, nystagmus or strabismus and paddling movements of the limbs. Convulsions and death soon follow. It can occur in adults and lambs although rarely in lambs under 12 weeks (Sargison, 2004).

Pathologically, it is characterised by brain swelling and laminar necrosis of the cerebral cortex, resulting from interference with brain metabolism. This interference is associated with a deficiency of thiamine at cell level (Rammell and Hill, 1986).

Thiamine pyrophosphate is the active form of thiamine and is required for the decarboxylation of pyruvate during its conversion to acetyl co-enzyme A (Co-A). Glucose is the most important form of energy for the brain and is mostly used via the glycolytic sequence and the tricarboxylic acid cycle. Much of the energy produced is required to maintain membrane potentials in the brain via the adenosine triphophatase (Na-K-ATPase) ionic pump. Thus, in thiamine deficiency, membrane repolarization is impaired, the water and electrolyte balance is upset, and thiamine pyrophosphate is reduced. Pyruvate and lactate accumulate in the tissues (Qi and Huston, 1995).

Ruminants do not depend on dietary sources of the vitamin B complex, as these vitamins are readily synthesised by the rumen microbes. However, in polioencephalomalacia, increased thiaminase type 1 levels are found in the rumen liquor, and this enzyme not only rapidly destroys thiamine but also leads to the production of active antagonists, which further deplete the blood and tissues of thiamine.

It is commonly believed that this enzyme is produced in the rumen by certain bacteria, such as Clostridium sporogenes and Bacillus thiaminolyticus (Edwin et al., 1982). These organisms proliferate under conditions in which the production of volatile fatty acids is reduced; e.g. lush, low fibre forages and high concentrate diets. However, some forages, such as bracken rhizomes (Pteridium aquilinum) (see Bracken Fern Poisoning in the Merck Veterinary Manual) and Mexican fireweed (Kochia scoparia), have been implicated, as they contain thiaminase type 1. There is also evidence that treatment with certain anthelminthics (e.g. levamisole and thiabendazole) may predispose to polioencephalomalacia. Excess dietary sulphur (Low et al., 1996; Olkowski et al., 1992, Rousseaux et al., 1991) and copper (Sargison et al., 1994) have also been associated with polioencephalomalacia.

Most cases occur about 2 weeks after movement to lush pasture  although it can also occur after the resumption of feeding following sheltering from severe and prolonged rainfall that may have prevented normal grazing (such an occurrence is common in SE Scotland) (Sargison, 2004). A rapid change from an all-forage to high-concentrate diet can cause CCN. This results from a shift in the bacterial populations in the rumen which can produce thiaminase. The thiaminase breaks down thiamine producing an analog which inhibits the thiamine-dependent reactions of glycolysis and the tri-carboxcylic acid cycle (Brent and Bartley, 1984).

Other conditions of sheep that present with similar signs of CCN include enterotoxaemia in young lambs, abscess of the spinal cord associated with drenching gun injury, pregnancy toxaemia, tapeworm infection and listeriosis (Sargison, 2004). Most of these can be differentiated by veterinary examination.

 

Methods of Control and Prevention

Low fibre forages and high concentrate diets, producing low levels of volatile fatty acids in the rumen, have been implicated in the epidemiology of polioencephalomalacia. As at least 60% of the dry matter in the diet of organic sheep should consist of fresh or conserved green forage (Defra, 2006), the likelihood of these animals getting polioencephalomalacia is very low.

During an outbreak, sufficient roughage should be provided. If the problem can be associated with a high sulphur intake, all possible sources of sulphur, including water, should be analyzed and the total sulphur concentration of the consumed dry matter estimated. Dietary ingredients or water with high sulphur concentration should be avoided or very gradually introduced to improve the chances of successful adaptation (The Merck Veterinary Manual, 2006).

The use of ammonium sulphate as an acidity regulator in vitamin/mineral premixes is ill-advised, as this may cause polioencephalomalacia. The inclusion of sulphur as sulphates and flowers of sulphur as copper antagonists in sheep feed may cause sulphur toxicity and hence cases of polioencephalomalacia, and is also not recommended (Blowey and Packington, 1994).

If, however, cases do occur, in-contact animals should be supplemented with thiamine until normal rumen fermentation is re-established. Although dietary supplementation of thiamine at 3-10 mg/kg feed has been recommended for prevention, the efficacy of this approach has not been carefully evaluated (The Merck Veterinary Manual, 2006). Oral treatment with the less water soluble thiamine derivatives, such as thiamine propyl disulphide or thiamine tetrafurfuryldisulphide, is the best option, as these do not get destroyed by thiaminase and are readily absorbed from the gut (Barlow, 1991).

 

Methods of Treatment

If the disease is observed at an early stage, high levels of thiamine HCl (10 mg/kg BW iv) should be administered every three to four hours until the animal has recovered. Although Vitamin B1 injection would be the best option (Thomas, 1986), these are not currently available in the UK and therefore the best option would be a multi-vitamin injection (Sargison, 2004). If there is no improvement after two days the animals should be euthanased.

For most recent information on different sector body requirements on withdrawal periods for livestock products following medicinal use please see

Withdrawal of Products following medication.

 

Good Practice based on Current Knowledge

 

References

Barlow, R. M. (1991): Polioencephalomalacia. In: Diseases of Sheep.  2nd edition. Ed.W. B. Martin and I. D. Aitken. pp. 181-183. Blackwell Scientific Publications, Oxford.

Blowey, R. Packington, A. (1994): Polioencephalomalacia associated with ingestion of ammonium sulphate.Veterinary Record 134: 24, 636.

Brent, B.E. and E.E. Bartley (1984) Thiamin and niacin in the rumen. J. Anim. Sci. 59:813.

Defra (2006) The Compendium of UK Organic Standards

Edwin, E. E. Jackman, R. Jones, P. (1982): Some properties of thiaminases associated with cerebrocortical necrosis. Journal of Agricultural Science, UK 99: 2, 271-275.

Green, L. E. Morgan, K. L. (1994): Risk factors associated with postpartum deaths in early born, housed lambs in southwest England. Preventive Veterinary Medicine 21: 1, 19-27.

Jeffrey, M. Duff, J. P. Higgins, R. J. Simpson, V. R. Jackman, R. Jones, T. O. Mechie, S. C. Livesey, C. T. (1994): Polioencephalomalacia associated with the ingestion of ammonium sulphate by sheep and cattle. Veterinary Record 134: 14, 343-348.

 Low, J. C. Scott, P. R. Howie, F. Lewis, M. FitzSimons, J. Spence, J. A. (1996): Sulphur-induced polioencephalomalacia in lambs. Veterinary Record 138: 14, 327-329.

Olkowski, A. A. Gooneratne, S. R. Rousseaux, C. G. Christensen, D. A. (1992): Role of thiamine status in sulphur induced polioencephalomalacia in sheep. Research in Veterinary Science 52: 1, 78-85.

Qi, K. Huston, J. E. (1995): A review of thiamin requirement and deficiency of sheep and goats. Sheep & Goat Research Journal 11: 1, 25-30.

Rammell, C. G. Hill, J. H. (1986): A review of thiamine deficiency and its diagnosis, especially in ruminants. New Zealand Veterinary Journal 34: 12, 202-204.

Rousseaux, C. G. Olkowski, A. A. Chauvet, A. Gooneratne, S. R. Christenson, D. A. (1991): Ovine polioencephalomalacia associated with dietary sulphur intake.  Journal of Veterinary Medicine - Series A 38: 3, 229-239.

Sargison, N. D. Scott, P. R. Penny, C. D. Pirie, R. S. (1994): Polioencephalomalacia associated with chronic copper poisoning in a Suffolk ram lamb. Veterinary Record 135: 23, 556-557.

Sargison, N (2004) NADIS Sheep Focus: Polioencephalomalacia (CCN or cerebrocortical necrosis). www.nadis.org.uk

The Merck Veterinary Manual (2006) Polioencephalomalacia: Introduction. www.merckvetmanual.com

The Henston Large Animal and Equine Veterinary Vade Mecum (1998): 10th edition. Henston Veterinary Publications.  Veterinary Business Development Ltd. Peterborough, UK

Thomas, K. W. (1986): Oral treatment of polioencephalomalacia and subclinical thiamine deficiency with thiamine propyl disulphide and thiamine hydrochloride. Journal of Veterinary Pharmacology & Therapeutics 9: 4, 402-411.

Wiener, G. Woolliams, C. Macleod, N. S. M. (1983): The effects of breed, breeding system and other factors on lamb mortality. 1. Causes of death and effects on the incidence of losses. Journal of Agricultural Science, UK 100: 3, 539-551.