EQUINE VETERINARY EDUCATION Equine vet. Educ. (2006) 18 (3) 126-129

Clinical Commentary
Equine motor neuron disease
Department of Equine Sciences, Faculty of Veterinary Medicine, Utrect University, Yalelaan 12, The Netherlands.

Equine motor neuron disease (EMND) is typically characterised by clinical signs such as rapidly progressive muscle atrophy, weight loss despite good to very good appetite, an increased time spent lying down, trembling, sweating, shifting the weight while standing, typical base-narrow stance of the legs, tucked-up abdomen and a somewhat stiff rather than ataxic gait (Cummings et al. 1990; Divers et al. 1994). The severity of signs varies among cases and the progression over time is not the same for all horses. In general, horses that become increasingly recumbent or are lying down for the majority of the time are subjected to euthanasia for humane reasons (Syrjä et al. 2006; van der Kolk 2005). In some horses the clinical situation will stabilise over time (Swagemakers et al. 2005). Definitive diagnosis is possible only after post mortem examination of the central nervous system, since the lesion is located in the lower motor neuron system in the ventral grey matter of the spinal cord (Valentine et al. 1994), and therefore EMND cannot be confirmed in horses that are still alive. A tentative clinical diagnosis is based on a combination of clinical signs, blood biochemistry, oral glucose uptake test (oGTT), i.v. glucose tolerance test (ivGTT), euglycaemic and hyperglycaemic clamps, histopathological examination of muscle biopsy and electromyography (EMG) (Palencia et al. 2005; Polack et al. 2000; Wijnberg 2002; van der Kolk et al. 2005). Abnormalities in the blood include a slight elevation of muscle enzyme activities and altered antioxidant status (Mohammed et al. 1994; de la Rua Domenech et al. 1997a,b). Oral glucose uptake tests performed in horses with EMND are abnormal in many (47–75%) patients (Divers et al. 1994; Benders et al. 2001, 2005). Benders et al. (2005) and van der Kolk et al. (2005) determined that in 75% of the patients the oGTT was abnormal and, in addition, the ivGTT showed a decrease in peak in 83% of horses. Hyperglycaemic glucose clamp results showed a 2.1–4.5-fold increase in glucose metabolism (van der Kolk et al. 2005; Swagemakers et al. 2005). Euglycaemic glucose clamp results indicated a 5.6-fold increased insulin sensitivity in one horse (van der Kolk et al. 2005). Based on these results, the daily caloric intake of a horse could be doubled. A high-level showjumper that showed a 2.6fold increase in glucose metabolism upon first examination was fed ad libitum good quality roughage, 8–10 kg concentrates (pellets) and had access to pasture. This resulted in stabilisation

and improvement of the clinical situation after 3 months (Swagemakers et al. 2005). A second measurement after 3 months showed a decline in glucose metabolism to 1.7 times normal, and the horse was competing at a low level of event. As well as finding changes in glucose metabolism, examining muscle biopsies and EMG may also result in finding abnormalities to support a tentative clinical diagnosis of EMND. EMG includes evaluation of insertional activity, pathological spontaneous activity and quantitative motor unit action potential analysis. Insertional activity and pathological spontaneous activity have been evaluated previously under general anaesthesia (Podell et al. 1995; Kyles et al. 2001) and also in the standing horse (Wijnberg 2002, 2003a–c, 2004; Wijnberg 2003; Ciminaghi et al. 2004). The advantage of performing EMG in the standing animal is that anaesthesia and recovery in already compromised animals can be avoided. The passive stay mechanisms present in the horse allow evaluation of insertional activity and presence of abnormal pathological activity without interference in muscle activity; in addition, pathological spontaneous activity can be induced by muscle contraction. Even in the splenius muscle, moments without muscle activity can be found. Motor unit action potentials (MUPs) are necessary for quantitative MUP analysis and can be induced by provoking controlled muscle activity. Measurement of the characteristics of these potentials enables determination of the presence of generalised neuropathy (Daube 1991; Stålberg et al. 1996; Wijnberg et al. 2003b, 2004; Benders et al. 2005; Wijnberg 2005). Pathological spontaneous activity can be found in elderly horses (Wijnberg et al. 2003a), also at risk of EMND (de la Rua Domenech et al. 1995), or in cases of myopathy (Wijnberg et al. 2003c), and evaluation of these alone can therefore lead to false positive results. The clinical picture, combined with the results of the quantitative MUP analysis indicating generalised neuropathy, assists in determining ante mortem evidence supporting the tentative diagnosis of EMND. Data on quantitative EMG analysis in horses suffering from EMND have been published previously (Benders et al. 2005). In a study by Wijnberg (2002), data on histopathological examination, muscle histopathology and morphometry of the lateral vastus muscle were compared with results from quantitative MUP analysis (Tables 1 and 2). This study included 7 Dutch Warmblood horses with clinical signs of

Copper-zinc superoxide dismutase (SOD) deficiency.14 ± 0. 2006) and low antioxidant concentration in the blood or altered antioxidant status can also be seen in cases of equine degenerative myelopathy (EDM). 1992.b. 1997a. However. 2002. Williams et al.16 mg/l. However. 2005). age and physical condition of the horse. although accumulation of copper induces oxidative stress by radical formation. The reference values described in the literature for vitamin E are highly variable. Blythe et al. 2004). In man. The most commonly cited hypothesis of the aetiology of EMND is that of a vitamin E deficiency. 1996.5 ± 0. 1987. McGorum et al. Why ventral motor neurons alone are affected is unclear. reference values should be established in each laboratory. (1989) described laboratory measurement variations for vitamin E as being relatively low (2. In a study by Maylin et al. Wijnberg 127 lower motor neuron disease and these were compared with age-matched healthy control horses.9 ± 1. 2003. nutrition. Concentrations of copper in the spinal cord of diseased horses were found to be significantly higher than in controls. 2005).9%) and between (83%) animals was large. Because of the similarity of motor neuron lesions to amyotrophic lateral sclerosis (ALS) described in man. abnormal iron deposits are associated with degenerative processes such as ALS and Alzheimer’s or Parkinson’s disease (Oba et al. William et al. A comparable mechanism has also been suggested for EDM (Dill et al. 2003. The increased glucose metabolism found in horses with EMND might induce an enhanced need for vitamin E (van der Kolk et al. 1991. it is better to measure multiple samples before determining vitamin E status. McGorum et al. In a recent study in our institute (unpublished data) we found a significantly lower (P<0. 1990). During this process. As other authors have remarked (Cummings et al. It appeared that quantitative EMG performed in the conscious horse and muscle morphometry were superior to histopathology to determine evidence of neuropathy. the role of metals in oxidative stress has been extensively studied (Carrì et al. selenium and GSHpx activity might give a better picture of antioxidant status. Mattson 2004). van der Kolk et al. but ranged widely from 1. A correlation coefficient of 0. resulting in damage to cell membranes and leakage of lysosomal hydrolytic enzymes. breed. 2004). The GSHpx activity has been seen to return to baseline 12–18 h after recovery from exercise (Frankiewietz-Josko et al.d. and reference values are highly variable. 2005). whereas variation within (14. Syrjä et al. The low vitamin E concentration found in most horses with EMND is a nonspecific finding. 2004). The majority of information on reference values for antioxidants is given for vitamin E.d. responsible for 10% of cases in man of the familial form of ALS (Deng et al. and concentrations vary greatly between horses and even within a horse (Craig et al. The vitamin E concentration was interpreted as normal. 1994. These radicals induce lipid peroxidation. According to Blythe et al. resulting in oxidative damage of the nervous tissue (Divers et al. 1994. In the same way. Adequate concentrations of trace elements such as copper.1%). A recent survey on EMND in several European countries found no evidence of a common trigger in the environment that might induce oxidative stress (McGorum et al.5 mg/l (2. GSHpx catalyses reduced gluthatione donation of an electron in order to reduce hydroperoxides (Williams et al. mean ± s. 2000).5 mmol/l]) in 14 young (age 1. 2003) and equine research has also been performed in this area (de la RuaDomenech et al. 2005). 1996. (1992). Ludvíková et al. has not been detected in the horse (de la Rua Domenech et al. Valentine et al.1 mg/l [4. 2000). de la Rua-Domenech et al. 1989. GSHpx activity probably reflects a response to oxidative processes.88 mg/l (Williams et al. blood concentration was 5. 1997a.75–12. 2000. many authors suggest that the disease resembles ALS. (1980). Reference values found in the literature for selenium vary from 50–250 µg/l (Valentine et al. The question remains as to whether the low vitamin E is the cause or perhaps the result of increased oxidative damage due to an as yet unidentified cause.4–22 mmol/l). iron. for GSHPx this is more difficult to establish due to variation in the units used.0–9. nonworking and growing Standardbred horses . Antioxidant status depends on nutrition. (1991) and Craig et al. 1989.001) vitamin E concentration (mean ± s. McGorum 2003. the horse had been supplemented with 300 mg vitamin E. The iron accumulation determined in the horse with EMND described in the preceding report (Syrjä et al. Reference values for Standardbreds were lower than described for Thoroughbreds. de la Rua. 1996). D. in ALS abnormalities of the pyramidal system are also present (Brown 2001). The activity has been seen to increase during exercise as a result of utilisation of reduced gluthatione during the radicalscavenging process. a variant of motor neuron disease in which spinal motor neuron degeneration is present without pyramidal involvement. 2003. it is not low in all horses with EMND (van der Kolk et al. time of year. and method and duration of storage of the sample. 1993). 2005. myopathy and grass sickness (Mayhew et al. 1990. 1. 2004). The concentration of vitamin E depends on age. McGorum et al. and those fed commercial feed had a concentration of 15. Wijnberg 2002. 2005b). In endurance horses on a normal diet supplemented with 5000 iu/day vitamin E. 2005a). 2003). Craig et al. 1994).5 years). and in winter lower concentrations were measured than in summer. Polack et al. van der Kolk et al. Ideally. Combining blood concentrations of vitamin E. ranging from 1. suggesting that in horses with EMND the higher concentrations of copper reflect a higher activity of SOD as a result of more radical formation (Polack et al. it seems more correct to compare EMND with progressive spinal atrophy (PSMA) in man.7 mg/l. as described below (Marlin 1980. 2002. 2006) may have been induced or contributed to oxidative stress.I. iron can catalyse the formation of highly reactive hydroxyl radicals from hydrogen. health and physical activity of a horse as well as time of year. 2005). zinc and selenium are necessary for antioxidant enzymes such as SOD and glutathione peroxidase (GSHpx) (Banerjee et al. activity. but these are generally absent in EMND (Valentine et al. Banerjee et al.Domenech et al. 1989). horses that were fed locally-produced feed had a mean blood selenium concentration of 7.6 mg/l.94 was found between GSHpx activity and selenium concentration. with some information available for GSHpx and selenium (Ludvíková et al. In man. Craig et al.

128 Equine motor neuron disease (Group A) compared with that of 4. Divers.5 kg straw and 2–4 kg standard pellets with a daily commercial supplement containing 500–600 mg vitamin E and 0. Summers. Acta vet. Mohammed. and van der Kolk. J. 26. A.. antioxidants and oxidative stress are the subjects of many ongoing veterinary studies. The factors described above should be taken into account when determining antioxidant status in horses. Hung W. A. 0. P. J. (2001) Electromyography under caudal epidural anaesthesia as and aid to the diagnosis of equine motor neuron disease. Braunwald. The Standardbreds had an unknown feed history other than grazing at pasture. C. S.C. A..H. (1992) Variability of α-tocopherol values associated with procurement. Rowe. 74. Results of these investigations should help in resolving the aetiology of diseases such as EMND. Am. D. 307-312. J.X.. Fauci. K. M. 154. B. Barrington. B. Pavlata. A. 166-168. H..A. Jameson and . L.O. H. K. References Banerjee. Ludvíková.G. 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