Odds and SODs of equine motor neuron disease.
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Biomedical subjects
Publications and source records attributed to I G Mayhew.
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Over a period of 5 years on a central Kentucky Thoroughbred stud farm 132 foals were evaluated for the presence of cervical vertebral malformation (CVM). Lateral cervical vertebral radiographs were obtained on 70 standing foals. These radiographs were evaluated semi-quantitatively and scored numerically for the presence of stenosis of the vertebral canal, enlarged physeal growth plates, caudal extension of the dorsal border of the orifice of the vertebral canal, angular fixation, delayed ossification of bone and degenerative joint disease. From these scores a total CVM score was given for each set of radiographs. All foals were repeatedly examined for clinical signs of neurological disease. Foals with no clinical signs of CVM had maximal total CVM scores (mean +/- sd) of 5.7 +/- 2.8 and foals affected with CVM had maximal total CVM scores of 17.0 +/- 2.8. Determination of the total CVM score was non-invasive, inexpensive and a very accurate procedure for predicting and diagnosing the presence of CVM in Thoroughbred foals up to 1 year of age.
Each of seven mares was given an intravenous (IV) injection of 40% dimethyl sulfoxide (DMSO) at a dosage of 1 g/kg, over 35 min, immediately followed by a single IV injection of a trimethoprim (TMP) and sulfamethoxazole (SMZ) combination (SMZ 83%, TMP 17%) at a combined dosage of 44 mg/kg (7.48 mg/kg TMP; 36.52 mg/kg SMZ). Each horse served as its own control and was alternately treated with an identical dose of TMP-SMZ treatment alone at least seven days following or preceding the DMSO and TMP-SMZ treatment. Serum and cerebrospinal fluid (CSF) concentrations of TMP and SMZ were measured over a six hour period. Dimethyl sulfoxide treatment caused no significant difference in the mean serum concentration of SMZ or in the mean CSF concentrations of TMP or SMZ. The mean serum concentration of TMP was significantly (p less than 0.05) increased at the two, four and six hour sampling time in the mares receiving pretreatment with DMSO. The clearance of TMP was also significantly (p less than 0.05) decreased from 675 mL/h/kg to 327 mL/h/kg by DMSO administration. Concentrations of TMP and SMZ in the CSF in both treatment groups exceeded the minimum inhibitory concentrations for many common bacterial pathogens of equine origin. In addition, CSF concentration of TMP exceeded the serum concentrations required for 50% inhibition of dihydrofolate reductases of protozoan origin. Serum TMP and SMZ concentration were similar to those reported to be effective against Toxoplasma gondii in in vitro studies on the killing or inhibition of the organism.
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The clinical, bacteriologic and pathologic findings of three adult horses suffering from avian tuberculosis are presented. Chronic weight loss and hypoproteinemia were pertinent clinical abnormalities in all three horses. Gross pathologic lesions were characterized by chronic enterocolitis with mesenteric lymphadenopathy in two horses and hepatic granulomas in the third horse. The microscopic diagnoses were chronic, non-caseating granulomatous enterocolitis, and necrotizing, non-mineralizing granulomatous hepatitis, respectively. All three horses had granulomatous lymphadenitis of mesenteric lymph nodes with varying degrees of non-mineralizing, coagulation necrosis. Various serotypes of the Mycobacterium avium-intracellulare complex were isolated from selected tissues and feces.
The clinical and pathologic findings of and therapy for such protozoal diseases as equine protozoal myeloencephalitis, toxoplasmosis, sarcocystosis, pneumocytosis, cryptosporidiosis, giardiasis, besnoitiosis, and klossiellosis are discussed. Emphasis is placed on disorders that occur with greater frequency in North America and on emerging protozoal diseases affecting horses.
Familial occipitalization of the atlas with atlantalization of the axis was defined as a single congenital disease in Arabian horses following a clinical, radiologic, and morphologic study of 16 horses with congenital malformations of the occiput, atlas, and axis, and from a study of three reported cases. The constant morphologic features were interpreted as congenital atlantooccipital fusion, hypoplasia of the atlas and dens, malformation of the axis, and modification of the atlantoaxial joint. Atlantoaxial subluxation was also a frequent finding. The clinical syndromes shown by these horses were variable but were broadly classified into four groups. Neurologic signs varied from symmetric ataxia, with hypometria and tetraparesis to tetraplegia. These often progressive clinical signs were due to a progressive and focal compressive myelopathy of the proximal cervical spinal cord. Pedigree analysis demonstrated the familial nature of this occipitoatlantoaxial malformation seen in horses of only the Arabian breed.
The responses of apparently healthy newborn foals to neurologic testing differ significantly from those of adult horses. These responses and the diagnostic techniques pertinent to neurologic problems are reviewed as a basis for evaluation of the compromised neonatal foal. The more frequently encountered neurologic diseases are discussed in a problem-oriented format. These clinical problems include behavioral abnormalities, convulsions, changes in consciousness, blindness, ataxia without loss of strength, ataxia with weakness and paralysis, and the floppy foal.
The duration of anesthetic effect and the histopathologic changes resulting from a controlled freeze of the palmar and plantar digital nerves in the horse were evaluated. Two techniques were compared: (i) nerves were frozen by direct application of the cryoprobe after surgical exposure and (ii) nerves were frozen by percutaneous application of the cryoprobe to the overlying skin. Return of skin sensation and ability to detect a stimulus were used to determine return of nerve function. The duration of anesthetic effect was significantly (P less than 0.005) longer for nerves frozen after surgical exposure than for those frozen by the percutaneous technique (mean 156 days vs 47.5 days). At the termination of the study, horses were euthanatized and all nerves were examined histologically. Neuromas-in-continuity were observed in 10 of 28 frozen nerves. Classification was based on the involvement of the supporting fibrous connective tissues of the nerve, endoneurium, perineurium, and epineurium. The direct technique of freezing the nerve after surgical exposure was repeatable and could be used to provide temporary neurectomy in the horse. The percutaneous technique caused a temporary loss of pain perception, but could not be relied on to interrupt nerve function for longer than a few weeks.
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Behaviour and response to neurological testing of apparently healthy newborn foals differed significantly from the adult in several ways. Foals responded to external stimulation with exaggerated movements although they tended to sink into a relaxed state when restrained. They had a more angular head position and assumed a base wide stance. The menace reflex developed during the first two weeks post partum. In general, the foals' gait was choppy or dysmetric. In lateral recumbency the foals had increased extensor tone, hyperreflexive tendon reflexes, crossed extensor reflexes as well as recumbent extensor thrust reflexes in all four limbs.
Pharmacokinetic characteristics of the anticonvulsant phenobarbital were studied in seven pony and two Thoroughbred foals aged between four and 10 days. A single, 20 mg/kg bodyweight (bwt) dose of phenobarbital was given intravenously over 25 mins and the serum concentrations of the drug were measured using an EMIT AED assay (coefficient of variation 1.37 per cent at 30 micrograms/ml, n = 7). Phenobarbital elimination was found to follow first order kinetics. The mean (+/- sd) peak phenobarbital serum concentration was 18.6 +/- 2.1 micrograms/ml at 1 h after initiation of infusion with a mean (+/- se) half-life of 12.8 +/- 2.1 h. The mean (+/- se) volume of distribution was 0.86 +/- 0.026 litres/kg bwt and mean (+/- se) total body clearance was 0.0564 +/- 0.0065 litres/kg bwt/h. Sedation was noticed 15 to 20 mins after the beginning of infusion and lasted for up to 8 h. All foals could be aroused and could walk although they were ataxic for the first 1 to 2 h. A degree of delayed hyperexcitability occurred 3 to 8 h after infusion. In equine neonatal seizure disorders it is recommended to use a loading dose of 20 mg/kg bwt of phenobarbital, followed by maintenance doses of 9 mg/kg bwt at 8 h. With this regimen, average steady state serum phenobarbital concentrations should range between approximately 11.6 and 53 micrograms/ml. Phenobarbital serum concentrations should be monitored following the loading dose and 24 h after initiating the maintenance doses to check that levels remain within the suggested (human) therapeutic range of 15 to 40 micrograms/ml.
Arthrogryposis multiplex congenita was studied in a newborn thoroughbred foal. The syndrome affected only the left hind limb allowing the right hind limb to serve as a reference. There was a significant depletion of large motor neurons from the ventral horn of the spinal cord from L3 to S4 on the affected side. Hypoplasia of nerves, muscles, and bones was present in the affected limb. Histologically, hypoplasia and degeneration of myofibers and nerve bundles were seen. No cause of the syndrome, which corresponds to most human cases, was determined. Neuromuscular arthrogryposis was diagnosed because of the difficulty in distinguishing primary neuropathic from primary myopathic forms of the disease.
Six mares were given 5 IM injections (at 12-hour intervals between doses) of amikacin sulfate at a dosage of 7 mg/kg of body weight. Serum amikacin concentrations were measured serially throughout the study; synovial, peritoneal, endometrial, and urine concentrations were determined after the last injection. Amikacin concentrations of the CSF were measured serially in 3 of the 6 mares; 1 of the 3 mares had septic meningitis. Mean serum amikacin concentrations peaked at 1 to 2 hours after IM injection. The highest mean serum concentration was 19.2 micrograms/ml (1.5 hours after the 5th injection). The highest mean synovial concentration was 10.8 micrograms/ml at 2 hours after the 5th injection; the highest mean peritoneal concentration was 16.2 micrograms/ml at 3 hours after the 5th injection. The mean endometrial amikacin concentration was 2.5 micrograms/g (1.5 hours after the 5th injection). Amikacin reached a CSF concentration of 0.97 micrograms/ml in the mare with meningitis, but amikacin was not detected in CSF of healthy mares. Urine concentrations reached 1,458 micrograms/ml. Pharmacokinetic values were estimated after the 1st injection (elimination rate constant = 0.31/hour; half-life = 2.3 hours; apparent volume of distribution = 0.26 L/kg), and after the 5th injection (elimination rate constant = 0.28/hour; half-life = 2.6 hours; apparent volume of distribution = 0.30 L/kg); significant differences were not observed.