September Case of the Month - Intermittent Low Grade Colic

History: “Samson” Donovan, a 10-year-old Oldenberg gelding, presented on 8/24/12 for intermittent low-grade colic consisting mostly of parking out from discomfort, with no decline in condition or performance as a low-level dressage horse.  The owners report that he has also been gassy.  Physical examination and rectal exam were within normal limits and results of a sand flotation test are pending.  His colic episodes generally self-resolve or resolve with the aid of 5cc of Banamine.  He was recently started on the Succeed Digestive Conditioning Program and he is insured.

Labwork analysis:

1.      CBC/chemistry panel: Bloodwork was unremarkable, with insignificant changes in Cl and GGT.

2.      Fecal egg count: Fecal egg count was negative for parasites.

3.      Fecal occult blood: Fecal occult blood was negative for blood.

Diagnosis: Chronic colic, open.

Common causes of chronic intermittent colic include gastric ulceration, sand impaction, and enterolithiasis. 

Gastric ulcers are prevalent in horses, with statistics ranging from 58% of showhorses and 70% of Thoroughbred broodmares to 86% of racehorses.  Due to vague clinical signs and large variation in treatment dosage and duration using GastroGard, the gold standard method of diagnosis remains gastroscopy.  Alternative methods include the Succeed fecal blood test (limited in accuracy), urine sucrose, and blood sucrose.  The procedure for urine sucrose concentration for detecting gastric ulcers is documented in the paper: Evaluation of urine sucrose concentration for detection of gastric ulcers in horses.  O'Conner MS et al. Am J Vet Res. 2004 Jan;65(1):31-9.  In this study, horses were fed 1kg concentrate (Purina Horsechow 100) and intubated with 454g sucrose (10% solution in water).  Urine sucrose was collected 2h and 4h following the intubation.  Sucrose concentration is higher in horses with gastric ulceration, with a sensitivity of 83% and specificity of 90% using a cut-off of 0.7mg/ml.  The procedure for blood glucose can be found in the paper: Sucrose concentration in blood: a new method for assessment of gastric permeability in horses with gastric ulceration.  Hewetson M, Cohen ND, Love S, Buddington RK, Holmes W, Innocent GT, Roussel AJ.  J Vet Intern Med. 2006 Mar-Apr;20(2):388-94.  In this procedure, horses are withheld from feed for 20h, intubated with 250g sucrose, and serum sucrose was significantly elevated 45min later in horses with moderate to severe gastric ulceration. 

The definitive diagnosis for sand impaction and enterolithiasis is through abdominal radiography.   If the sand flotation that was performed by the owner is negative, the test can be improved by administering psyllium (Sand Clear instructions are 5oz daily for 7 days) and performing the sand flotation during and after the treatment.  Psyllium may also have some GI benefits of aiding in mucosal repair.

Recommendation:

1.      Diagnostics: I would recommend doing additional diagnostics, including gastroscopy.  If the gastroscopy is not possible, urine/blood sucrose or empirical treatment (take note GastroGard takes 3-5 days to take effect) can be used to indicate the presence of gastric ulcers.  If he is negative for ulcers, you may wish to consider referral for abdominal radiographs and/or a trial with psyllium and repeated fecal sand flotation.

2.      Treatment: For discomfort due to bloating, you may wish to consider administration of a proven prebiotic such as Saccharomyces boulardii (10 billion organisms PO BID).  All other treatments could be pursued based on the results of additional diagnostics.

Jean-Yin Tan, DVM, DACVIM (Large Animal Internal Medicine)

Cool Abstracts

The prevalence of hypocobalaminaemia in cats with spontaneous hyperthyroidism

Novel gastroretentive controlled-release drug delivery system for amoxicillin therapy in veterinary medicine

Influence of blood collection technique on platelet function and coagulation variables in dogs

Evaluation of orally administered famciclovir in cats experimentally infected with feline herpesvirus type-1

Effects of isoflurane anesthesia on cerebrovascular autoregulation in horses

In Print - Jean-Yin Tan, DVM, DACVIM (Large Animal)

Can Vet J. 2010 Sep;51(9):993-9.

Suspected systemic calcinosis and calciphylaxis in 5 horses.

Tan JY, Valberg SJ, Sebastian MM, Davis GD, Kelly JR, Goehring LS, Harland MM, Kuebelbeck KL, Waldridge BM, Newton JC, Reimer JM.

Abstract

Five horses were presented with signs of myopathy along with systemic malaise, hyperfibrinogenemia, hyperphosphatemia, and an elevated calcium phosphorus product (Ca*P). Postmortem findings were consistent with systemic calcinosis, a syndrome of calcium deposition in the tissue of organs including lungs, kidneys, muscle, and heart that has not been previously described in horses.

An Update on EPM: The Latest in Diagnostics and Treatment

Jean-Yin Tan, DVM, DACVIM Large Animal Internal Medicine

Diagnostics

“My horse has been just a little off, Doc. I don’t really want to pay for a full-blown lameness or neuro exam or anything. Would you mind just taking a blood test for EPM while you’re here?”

If you’re a general equine practitioner, you’ve likely been asked a question like this in the middle of a routine vaccine visit, by a horse owner who’s been dabbling in reading a few of the latest horse publications and learning some catch phrases from her friends. Since you were hoping to just quickly knock off a few vaccines while on your way to 5 more lengthy calls that you have to cram into your afternoon, chances are you’ve been tempted to just pull the blood sample. After all, a full neurologic exam would take a lot of time and money, and that’s not what the owner wants to do, right?

It might be time to educate your client. The first rule of interpreting any diagnostic tests for EPM is that a clinical diagnosis of EPM must be made. In the absence of detectable neurologic deficits and elimination of other differential diagnoses, confirmation of exposure to Sarcocystis neurona via any number of diagnostic tests can mean very little.

Western Blot. Sensitivity is 80% and specificity 38% for testing of the serum of neurologic horses. That means it can be used to rule out EPM, but the low specificity means a large number of false positives, making the test inappropriate for diagnosing EPM. Cross-reaction may also occur with nonpathogenic Sarcocystis fayeri, which uses the horse as a natural intermediate host.

IFAT. The indirect immunofluorescent antibody test is a quantitative serologic test for EPM which provides actual titers and a likelihood ratio of the disease. Although sensitivity (83% for serum) is similar to that of the Western blot, specificity (97% for serum) is higher using the IFAT. Serum and CSF results have a moderately strong correlation. Furthermore, blood contamination of up to 104 RBCs/l does not affect CSF test results. The IFAT can also be used to detect EPM attributed to Neospora hughesii. There is however, cross-reaction with S. fayeri.

SAG-1 ELISA. The latest test is an ELISA that detects a specific surface antigen SAG-1 found on S. neurona merozoites. Although the low sensitivity and specificity (68% and 71% respectively) and geographical variation in presence of the surface antigen inhibits the commercially available SAG-1 ELISA from being a reliable diagnostic test, there is some potential for a more reliable SAG-2 ELISA in the future, especially given the lack of cross-reactivity with S. fayeri and N. hughesi.

So, what should I do? The Western Blot, IFAT, and SAG-1 ELISA are all different ways of detecting anti-S. neurona antibodies in serum or CSF. Currently, the IFAT offers the highest sensitivity and specificity. It is important, however, to take into consideration that cross-reaction with S. fayeri and vaccination can affect results.

CLICK TO SEE THE FULL CHART


Treatment
“Doc, I read in a horse magazine about a medication called toltrazuril? Do you think we should try that on my horse? I think it’s supposed to work real well on EPM.”

It’s busy season and you haven’t had much of a chance to sit down, let alone read the latest in journals on equine neurologic disease. If you’ve never heard of toltrazuril, don’t panic. I’ve put together a brief synopsis of drugs used for EPM below.

Antiprotozoals. FDA approved options are: sulfadiazine/pyrimethamine, ponazuril, nitazoxanide, and diclazuril. In the studies cited, successful treatment is defined as improvement in neurological grade by at least 1 level or CSF testing becoming negative on Western blot.

Sulfadiazine/pyrimethamine (ReBalance). At 20mg/kg sulfadiazine and 1mg/kg pyrimethamine orally daily for 90 days, 62% of affected horses have successful outcomes. However, adverse effects from folic acid deficiency include bone marrow suppression (12%), GI disturbance, decreased spermatogenesis in stallions, and congenital defects in foals when used in pregnant mares.


Ponazuril (Marquis). At 5mg/kg orally daily for 28 days, this antiprotozoal drug is responsible for the successful treatment of 60% of horses and at double-dose, 65% of affected horses. There were no adverse effects in a study of 101 horses. However, possible side effects listed by the manufacturer include blisters, hives, diarrhea, colic, and a seizure.

Nitazoxanide (Navigator). Although no longer commercially available, this antiparasitic drug used at 50mg/kg orally daily for 28 days has been found to successfully treat 57% of horses. However, fatal enterocolitis, fever, anorexia, lethargy are noted side effects and affect up to 31% of horses.

Diclazuril. This FDA-approved but unmarketed antiprotozoal drug has been used as pellets at 1mg/kg orally daily for 28 days with a 67% success rate. Adverse reactions that may not necessarily be correlated with the drug include laminitis or decline in neurologic status.

Toltrazuril (Baycox 5%). An anti-coccidial drug used in other species, this drug is being reviewed by the FDA for use in horses for EPM. At 5mg/kg orally daily for 10 days, it has been found in limited studies to achieve excellent absorption into CSF with no adverse effects.

Antiinflammatories. Nonsteroidal antiinflammatory drugs can help decrease initial worsening of signs during treatment associated with inflammatory response to the parasite. Corticosteroids are not recommended but single doses may help curb inflammation and allow antiprotozoal drugs to work. Many veterinarians use DMSO as well. There have been no clinical trials to support or refute the use of Vitamin E and thiamine supplementation.

Immunostimulants. Some veterinarians have advocated the use of immunomodulation with drugs such as Prioponibacterium acnes, mycobacterial cell wall extracts, levamisole, and alpha-interferon. These could potentially affect T cell-mediated immunity and stimulate macrophages. However, without further investigation, theoretical immunopathologic effects on the CNS should also be considered.

What do I do if the horse relapses? It is theorized that 10% of horses relapse within 3 years of discontinuation of therapy. Treatment options include longer duration of therapy (off-label doubling of the standard period of treatment), using higher doses of ponazuril, combining ponazuril with sulfadiazine/pyrimethamine, using twice-weekly continuous therapy with sulfadiazine/pyrimethamine, and possibly using anthelmintic levamisole as an immunostimulant.

So…What should I treat with? Currently the only commercially available antiprotozoal with the least reported adverse effects is ponazuril. However, look for other options such as diclazuril or toltrazuril appearing on the market in the future. Although conservative use of antiinflammatories is widely accepted, the efficacy of treatments such as DMSO, thiamine, Vitamin E, and immunostimulants has not been specifically investigated but can be used at your discretion.

UPDATE
The new SAG-2 and SAG-4,3 assays for EPM which are now available. These have possible advantages over the previous available assays because:

-These surface antigens are those most commonly expressed by S. neurona strains
-Quantitative test

-Provide serum/CSF ratios

The disadvantage is that both CSF and blood samples need to be submitted to provide accurate information.

References
1. Daft B, Barr, BC, Gardner, IA, et al. Sensitivity and specificity of western blot testing of cerebrospinal fluid and serum for diagnosis of equine protozoal myeloencephalitis in horses with and without neurologic abnormalities. J Am Vet Med Assoc 2002;221:1007-1013.

2. Duarte P, Daft, BM, Conrad, PA, Packham, AE, Gardner, AE. Comparison of a serum indirect fluorescent antibody test with two Western blot tests for the diagnosis of equine protozoal myeloencephalitis. J Vet Diagn Invest 2003;15:8-13.

3. Duarte P, Daft, BM, Conrad, PA, et al. Evaluation and comparison of an indirect fluorescent antibody test for detection of antibodies to Sarcocystis neurona, using serum and cerebrospinal fluid of naturally and experimentally infected, and vaccinated horses. J Parasitol 2004;90:379-386.

4. Dubey J, Lindsay, DS, Saville, WJA, et al. A review of Sarcocystis neurona and equine protozoal myeloencephalitis (EPM). Vet Parasit 2001;95:89-131.

5. Furr M, McKenzie, H, Saville, WJA, et al. Prophylactic administration of ponazuril reduces clinical signs and delays seroconversion in horses challenged with Sarcocystis neurona. J Paristol 2006;92:637-643.

6. Granstrom D, Howe, D, Bentz, B, et al. Current treatments for equine protozoal myeloencephalitis. Equine Disease Quarterly 2007;16.

7. Hoane J, Morrow, JK, Saville WJ, et al. Enzyme-linked immunosorbent assays for detection of equine antibodies specific to Sarcocystis neurona surface antigens. Clin Diagn Lab Immunol 2005;12:1050-1056.

8. Johnson A. Evidence-based review of diagnosis and treatment of Sarcocystis neurona infection (Equine Protozoal Myeloencephalitis). AAEP 2009.

9. MacKay R. Equine essentials - equine protozoal myeloencephalitis: Managing relapses. Veterinary Technician 2008;29.

10. Reed S, Saville, WJ, Schneider, RK. Neurologic disease: Current topics in-depth. AAEP 2003.

11. Saville W, Dubey, JP, Oglesbee, MJ, et al. Experimental infection of ponies with Sarcocystis fayeri and differentiation from Sarcocystis neurona infections in horses. J Parasitol 2004;90:1487-1491.

Meet Dr. Jean-Yin Tan

Dr. Tan graduated from Cornell University in 2005. She went on to complete an internship at Mid-Atlantic Equine Medical Center in NJ and a large animal internal medicine residency at the University of Minnesota. She spent a year at UC Davis completing an Equine Primary Care fellowship and is now working in New Jersey. Dr. Tan has publications in journals including the American Journal of Veterinary Research and the Canadian Veterinary Journal and has spoken at various local conferences as well as ACVIM Forum. Her interests include neonatology, respiratory disease, and gastroenterology. She has experience with all large animals as well as horses!

Cool Recent Abstracts

SMALL ANIMAL

Intracranial Arachnoid Cysts in Dogs

from Compendium by Curtis W. Dewey - Veterinary Answers Consultant, Peter V. Scrivani, Ursula Krotscheck, Sofia Cerda-Gonzalez, Kerry Smith Bailey, Dominic J. Marino

Intracranial arachnoid cyst (IAC) is an infrequently reported developmental disorder seen primarily in small-breed dogs. It usually occurs in the caudal fossa, in the region of the quadrigeminal cistern. Although still considered uncommon, IAC is being recognized more frequently in veterinary medicine, coinciding with the increased availability of magnetic resonance imaging. In this article, clinical information from previously reported cases of canine IAC is combined with additional case information from our hospitals. Similar to IAC in people, it is thought that canine IAC is often an incidental finding. When IAC is responsible for neurologic disease in dogs, generalized seizures and cerebellovestibular dysfunction are the most common clinical presentations. Medical therapy of IAC focuses on management of increased intracranial pressure and seizures, if the latter are part of the clinical complaints. Surgical therapy of IAC involves either cyst fenestration or shunting the excess fluid to the peritoneal cavity.


Peripheral Nucleated Red Blood Cells as a Prognostic Indicator in Heatstroke in Dogs

from JVIM by I. Aroch, G. Segev, E. Loeb, Y. Bruchim

Heatstroke in dogs is often fatal and is associated with a high prevalence of secondary complications. Peripheral nucleated red blood cells (NRBC) occur in dogs with heatstroke, but their association with complications and the outcome is unclear. Peripheral NRBC are common in dogs with heatstroke and have prognostic significance. Forty client-owned dogs with naturally occurring heatstroke. Prospective, observational study. Dogs were followed from presentation to discharge or death. Serum biochemistry and coagulation tests were performed at presentation. CBC and evaluation of peripheral blood smears were performed at presentation and every 12 hours. The relative and the absolute NRBC numbers were calculated. Presence of NRBC was observed in 36/40 (90%) of the dogs at presentation. Median relative and absolute NRBC were 24 cells/100 leukocytes (range 0[ndash]124) and 1.48 × 103/[mu]L (range 0.0[ndash]19.6 × 103/[mu]L), respectively. Both were significantly higher in nonsurvivors (22) versus survivors (18) and in dogs with secondary renal failure and DIC versus those without these complications. Receiver operator curve analysis of relative NRBC at presentation as a predictor of death had an area under curve of 0.92. A cut-off point of 18 NRBC/100 leukocytes corresponded to a sensitivity and specificity of 91 and 88% for death. Relative and absolute numbers of peripheral NRBC are clinically useful, correlate with the secondary complications, and are sensitive and specific markers of death in dogs with heatstroke, although they should never be used as a sole prognostic indicator nor should they replace clinical assessment.


Relationships between Low Serum Cobalamin Concentrations and Methlymalonic Acidemia in Cats

from JVIM by C. G. Ruaux, J. M. Steiner, D. A. Williams

Serum cobalamin concentrations below reference range are a common consequence of gastrointestinal disease in cats. Serum cobalamin [le] 100 ng/L is associated with methylmalonic acidemia. To determine the prevalence of cobalamin deficiency, defined by elevated serum methylmalonic acid (MMA), in cats with serum cobalamin [le] 290 ng/L, and the optimum serum cobalamin concentration to predict cobalamin deficiency in cats. Residual serum samples (n = 206) from cats with serum cobalamin [le] 290 ng/L. Retrospective, observational study. Serum cobalamin and folate were measured with automated assays. Serum MMA was determined by gas chromatography-mass spectrometry. Cobalamin deficiency was defined as serum MMA > 867 nmol/L. Sensitivity and specificity of serum cobalamin concentrations [le]290 ng/L for detecting MMA > 867 nmol/L were analyzed using a receiver-operator characteristic curve. There was a negative correlation between serum cobalamin and MMA concentrations (Spearman's r=[minus]0.74, P < 0.0001). The prevalence of MMA [ge] 867 nmol/L in cats with serum cobalamin [le] 290 ng/L was 68.4%. Serum cobalamin [le] 160 ng/L had a 74% sensitivity and 80% specificity for detecting MMA > 867 nmol/L. No significant difference in serum folate concentrations was detected between affected and unaffected cats. Elevated MMA concentrations, suggesting cobalamin deficiency, are common in cats with serum cobalamin [le] 290 ng/L. Cobalamin deficiency is clinically significant, and supplementation with parenteral cobalamin is recommended for cats with gastrointestinal disease and low serum cobalamin concentrations.

For more on MMA in human beings, click here.


Small Mammals
Single- and multiple-dose pharmacokinetics of marbofloxacin after oral administration to rabbits

From AJVR by James W. Carpenter, MS, DVM; Christal G. Pollock, DVM (VETERINARY ANSWERS CONSULTANT); David E. Koch, MS; Robert P. Hunter, PhD

Objective—To determine the pharmacokinetics of marbofloxacin after oral administration every 24 hours to rabbits during a 10-day period.

Animals—8 healthy 9-month-old female New Zealand White rabbits.

Procedures—Marbofloxacin (5 mg/kg) was administered orally every 24 hours to 8 rabbits for 10 days. The first day of administration was designated as day 1. Blood samples were obtained at 0, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours on days 1 and 10 of marbofloxacin administration. Plasma marbofloxacin concentrations were quantitated by use of a validated liquid chromatography–mass spectrometry assay. Pharmacokinetic analysis of marbofloxacin was analyzed via noncompartmental methods.

Results—After oral administration, mean ± SD area under the curve was 10.50 ± 2.00 μg·h/mL and 10.90 ± 2.45 μg·h/mL, maximum plasma concentration was 1.73 ± 0.35 μg/mL and 2.56 ± 0.71 μg/mL, and harmonic mean terminal half-life was 8.0 hours and 3.9 hours for days 0 and 10, respectively.

Conclusions and Clinical Relevance—Marbofloxacin administered orally every 24 hours for 10 days appeared to be absorbed well and tolerated by rabbits. Administration of marbofloxacin at a dosage of 5 mg/kg, PO, every 24 hours is recommended for rabbits to control infections attributable to susceptible bacteria.


EQUINE
Risk Factors for Equine Postoperative Ileus and Effectiveness of Prophylactic Lidocaine

from JVIM by S. Torfs, C. Delesalle, J. Dewulf, L. Devisscher, P. Deprez
Postoperative ileus (POI) is a frequent and often fatal complication of colic surgery. Reliably effective treatments are not available. To determine risk factors and protective factors associated with POI, and to assess the effect of lidocaine IV on short-term survival. One hundred and twenty-six horses that underwent small intestinal colic surgery and that survived for at least 24 hours postoperatively. Retrospective cross-sectional study. The association of 31 pre-, intra-, and postoperative variables with POI and the association of lidocaine treatment with short-term survival were investigated. Associations were evaluated with univariable logistic regression models, followed by multivariable analysis. Significant associations of high heart rate (odds ratio [OR] = 1.05, 95% confidence interval [CI] 1.03[ndash]1.08), the presence of more than 8 L of reflux at admission (OR = 3.02, 95% CI 1.13[ndash]8.02) and the performance of a small intestinal resection (OR = 2.46, 95% CI 1.15[ndash]5.27) with an increased probability of POI were demonstrated. Prophylactic lidocaine treatment was significantly associated with a reduced incidence of POI (OR = 0.25, 95% CI 0.11[ndash]0.56). Lidocaine treatment was also significantly associated with enhanced short-term survival (OR = 0.30, 95% CI 0.09[ndash]0.98). The variables associated with an increased risk of POI can be useful in identifying horses at risk of POI and in providing a more accurate prognosis. The results are supportive for lidocaine IV as an effective prokinetic treatment after small intestinal colic surgery.