Encephalomalacia

Other phenolic compounds of commercial importance include the terpenoids, including mono, di, tri, and sesquiterpenes. While most of these are used as essential oils, fragrances, and flavors in various products, they are toxins in certain species. For example the sesquiterpene lactones of the Centaurea species cause an irreversible Parkinson s-like condition in horses called nigro-pallidal encephalomalacia. This is a lethal condition and the prognosis for recovery is grave in most cases, affected horses should be euthanized before reaching the terminal stages. 

In livestock and laboratory animals, a deficiency of vitamin E substances may cause degeneration of reproductive tissues, muscular dystrophy, encephalomalacia, and liver necrosis. Considerable research is required to fully determine supplementation of livestock diets unless typical symptoms of a deficiency appear. Symptoms have appeared where there are selenium deficiencies in the soil and where there are excessive levels of nitrates in the soil. White muscle 1 is the term used to describe a condition of muscular dystrophy in cattle. 

In growing chicks, a deficiency can result in (i) encephalomalacia or crazy chick disease (ii) exudative diathesis, an oedema caused by excessive capillary permeability or (iii) muscular dystrophy. Encephalomalacia occurs when the diet contains unsaturated fats that are susceptible to rancidity. Some antioxidants, in addition to vitamin E, are also effective against encephalomalacia. Exudative diathesis is prevented by dietary selenium, and muscular dystrophy is a complex disease influenced by vitamin E, selenium, and the... 

Vitamin E-deficiency diseases are well known among laboratory and farm animals and can be a considerable problem in animal husbandry. Thus, the vitamin was discovered because its absence from the diet causes pregnant female rats to resorb their foetuses [25], and male rats to suffer testicular degeneration [26]. In the rabbit muscular dystrophy occurs, and in sheep and cattle similar muscular degeneration also is the principle sign of vitamin E deficiency [27], In the chick given high levels of linoleic acid and no vitamin E an acute central nervous system lesion called encephalomalacia occurs... 

A baby was born missing its right ear and external auditory canal. At 20 months an MRI scan of the brain showed focal atrophy and encephalomalacia of the right parieto-occipital lobe. His mother had used topical tretinoin (Retin A 0.025%) on her face and a large surface of the back before conception and during the first 2-3 months of pregnancy. His father had used oral isotretinoin before conception. 

The bioactivity of E-vitamers is defined as their ability to prevent or reverse specific vitamin E deficiency symptoms, such as fetal resorption in rats and muscular dystrophy and encephalomalacia in chicken (Machlin, 1991). The bioactivities of different E-vitamers parallel their bioavailability, indicating that bioactivity is more a function of the amounts available in the body than the chemical activities of these vitamers. Because diets are reasonably abundant in E-vitamers, vitamin E deficiency is rare in humans and is almost limited to malnourished people, people with fat malabsorption or those with a defect in the hepatic tocopherol binding protein (Dutta-Roy et al., 1994). 

Characteristic lesions of vitamin E deficiency in animals include necrotizing myopathy (inaccurately referred to as nutritional muscular dystrophy), exudative diathesis, nutritional encephalomalacia, irreversible degeneration of testicular tissue, fetal death and resorption, hepatic necrosis, and anemia. Several of these conditions are directly related to peroxidation of unsaturated lipids in the absence of vitamin E, and others can be prevented by synthetic antioxidants or vitamin E. 

Anke et al. 1975). Due to the antagonistic effect of sulfur, the lambs developed a secondary copper deficiency that in turn led to an induced encephalomalacia folloiving depletion of hepatic copper stores. 

Due to the effect of sulfur on copper and selenium metabolism, and reports of polio-encephalomalacia in beef cattle at dietary sulfur dosages > 5 g kg the National Research Council recommends a maximal tolerable level of sulfur of 4 g kg feed DM, vhereas 2 g kg feed DM is regarded as the sulfur requirement for cattle (National Research Council 2001). 

Fig. 6.6 WaUerian degeneration. Coronal T2 weighted image shows encephalomalacia of the right frontal and temporal lobes and T2 high signal extending into the right cerebral peduncle (arrow) from WaUerian degeneration...

Fig. 6.7 Laminar necrosis. This sagittal noncontrast T1 weighted image shows gyiiform T1 high signal in a chronic left MCA infarct. Mild enlargement of the sulci is consistent with encephalomalacia...

Refined palm oil contains approximately 500 to 700ppm vitamin E, which is present as the RRR-a-tocopherol (30%) and tocotrienol (70%) isomers. In contrast, oils such as com, soybean, and sunflower are good sources of the tocopherols but contain no tocotrienols. Historically, vitamin E activity (one international unit, lU) has been defined as 1 mg of all rac-a-tocopheiyl acetate, whereas Img of all RRR-a-tocopherol equals 1.49 lU. In addition, vitamin E activity in foods is expressed as the a-tocopherol equivalent (a-TE), which is the activity of 1 mg of RRR-a-tocopherol. On this basis, conversion factors for each milligram of the different tocopherols and tocotrienols present in palm oil to a-TE have been calculated as follows a-tocopherol, 1.0 y-tocopherol, 0.5 5-tocopherol, 0.1 a-tocotrienol, 0.3 and P-tocotrienol, 0.05. The factors for y- and 5-tocotrienol are presently unknown." The conversion factors are based on the ability of each isomer to overcome specific vitamin E deficiency symptoms such as fetal resorption, muscular dystrophy, and encephalomalacia. Since these factors are based on rat fetal resorption assays, their relevance to humans... 

There is no doubt that as dietary agents tocopherol and Factor 3/selenium arc different, independent entities (Schwarz, 1960). In principle, one must separate clearly three groups of diseases those caused purely by vitamin E deficiency, which are not influenced by Factor 3/selenium even in large excess (resorption sterility in rats, encephalomalacia in chicks) those... 

In 11)31, Pappenheimer and Goettsch published the first description of a newly discovered disease, which was called nutritional encephaloTnalaeia. Although the diet recommended by Pappenheimer and Goettsch for producing encephalomalacia in chicks contained some 20% lard and about 2 % cod liver oil, it was sometime later that the role of the dietary fats was evaluated. The composition of this diet is shown in Table I. 

Apparently damage of the capillaries in the affected areas is the primary cause of the exudation. If the development of exudate was merely a consequence of lowered colloid osmotic pressure in the plasma, the exudate fluid would be much lower in protein content. In encephalomalacia the albumin globulin ratio of the plasma remains normal after the onset of the disease. 

Though this diet sometimes also produced encephalomalacia, the exudative diathesis was the predominant symptom. On the contrary, diet No. 108 of Pappenheimer and Goettsch almost never produced exudative diathesis. (According to present knowledge, this must have been due, at least in part, to a higher content of selenium in diet 108.)... 

The fat components of these diets were essential for the development of the symptoms. When the fats were eliminated, encephalomalacia never appeared and exudative diathesis was very rare. Furthermore, the symptoms did not appear when the cod liver oil in diet 182 was made thoroughly rancid either before it was added to the diet, or after the mixed diet was left to stand in shallow trays at 50°C for 1 week, whereupon the iodine value dropped to 62 (Dam, 1943). 

We also found that selenium prevented exudative diathesis produced by a diet with 30 % casein and 10 % cod liver oil, but not encephalomalacia produced with the same diet or with a diet containing 30 % of lard (Dam et al., 1957b). 

Encephalomalacia occurred only in a few cases when Torula yeast diets that furnished about the same amount of linoleic acid as the casein diets with 30% lard were fed. When selenium was added to the Torula yeast diets, the chicks lived longer and a few more cases of encephalomalacia appeared. 

A systematic investigation showed that many yeasts counteract the development of encephalomalacia when used to supply protein instead of casein in diets containing 30% lard. The factor responsible for this effect has not been identified. In cooperation with Professor M. L. Scott, we have considered the possibility that ubichromenols in yeast may be the factors that counteract encephalomalacia, but the matter has not been definitively settled. 

The nature of fats capable of producing encephalomalacia in diets with casein as the protein source have been investigated further. In diets containing 30 % of lard, such as those frequently used in our studies, the principal polyunsaturated fatty acid is linoleic (about 1.5% of the diet) accompanied by some linolenic and still less arachidonic acid. 

When samples of the ethyl esters of linoleic and linolenic acids were tested at the 1.6 % level in a vitamin E-free diet with low selenium content, both these fatty acids produced exudative diathesis and gave rise to formation of peroxides in the affected fat tissue, but only linoleic acid produced encephalomalacia. This experiment has been repeated many times with diets containing added selenium so that the exudative diathesis was suppressed. In these cases encephalomalacia was the only symptom it occurred only with linoleic acid, not with linolenic acid. The samples of linolenate tested contained a certain amount of trans-isomers it is not known whether the presence of these isomers played a role in preventii encephalomalacia. It is clear, however, that whereas the acceleration of exudative diathesis is related to polyunsaturation of the dietary fatty acids, the production of encephalomalacia is a more complicated matter depending on the structure of the polyunsaturated fatty acid (Dam et aL., 1958b). 

In later experiments. Dam and S0ndergaard (1962) found that ethyl arachidonate was a much more active encephalomalacia-producing agent than linoleic acid when fed at the 1.5% level. This had previously been expected (Dam et al., 1958b Machlin and Gordon, 1960) from indirect evidence. 

Speculating further on the possible mode of action of linoleic acid, one might assume that the encephalomalacia-producing effect is mediated via... 

The hypothesis that autoxidation occurring in the brain is the cause of encephalomalacia seems obvious, but meets the following difficulties (1) as already mentioned, peroxides have never been detected in the brain of chicks with encephalomalacia (2) the brain of chicks is extremely low in vitamin E, even when this vitamin is supplied through the diet. 

Unpublished results from our laboratory have shown that the brains of chicks raised for 5 weeks on an encephalomalacia-producing diet containing 30% lard, and on the same diet supplemented with 10 mg % dl-a- and 10 mg % d-a-tocopheryl acetate, respectively, contained 1.5, 1.9, and 2.2 Mg of tocopherol per gram of tissue, whereas the corresponding figures for liver were 1.0, 14.7, and 21.2 Mg/gm. 

Apparently, more elaborate experimentation is required in order to elucidate the mode of action of arachidonic and linoleic acids in the development of encephalomalacia, and the problem may have to be considered from new points of view. 

---