Bailey was indeed a very special part of our family and knowing that he received such excellent care from such a wonderful group of people has made this difficult time for us more bearable.
Signalment: 9-year-old male neutered domestic shorthair cat
History: Presented to the Emergency Service as a transfer from his primary veterinarian for further evaluation of abdominal distention. The patient’s abdomen had become distended over the past several days. He was still acting normally with no vomiting, diarrhea, or change in appetite or labored breathing. He is indoors only. He was adopted as a kitten, only animal in the household, no travel history, and up to date on vaccinations.
Physical Exam Findings: Markedly distended, tense, abdomen with palpable fluid wave. Remainder of exam within normal limits.
Initial treatments: Abdominocentesis was preformed and 1325mls of milky white fluid was removed without complication.
Diagnostic Evaluation: A CBC performed at RDVM prior to referral showed neutropenia (0.07 k/ul, RR: 2.5-15 k/ul) and thrombocytopenia (clumping?), chemistry was normal with a low normal albumin (2.6, RR: 2.3-3.9 g/dl). Thoracic radiographs were normal. He was Felv/FIV neg. Abdominal Ultrasound showed a moderate volume of echogenic effusion. The mesentery and omentum were thickened and hyperechoic. Echocardiogram showed no cardiac disease. Abdominal Fluid analysis was consistent with chylous effusion, nucleated cells were predominantly small mature lymphocytes, with triglycerides >3200 and TP 6.1.
Assessment: Possible causes for chyloabdomen included neoplasia such as lymphosarcoma or other cancer, lymphangiectasia, FIP, or cardiac disease, but the later had been excluded based on normal echocardiogram and FIP was considered less likely given age and lack of exposure.
Plan: He was started on Rutin (250 mg PO q8 hours) with a plan to follow up with internal medicine.
Follow-up exam with Internal Medicine: Since discharge from the ER, the patient’s appetite had been slightly decreased since starting the Rutin and it was decreased to twice daily. Otherwise doing well.
On recheck exam, the patient had a palpable abdominal fluid wave and had muscle wasting along his spine. He had gained weight (0.4 kg since discharge). A brief ultrasound showed a moderate amount of echogenic effusion, no pleural effusion was noted. There was not enough peritoneal effusion to do an abdominocentesis. An FIP PCR on the abdominal effusion was discussed. An abdominal exploratory was recommended for a more definitive diagnosis.
Abdominal Exploratory Findings: The omentum was very friable. The mesentery was diffusely friable and dark in color. A dark red mass was noted at the ileocolic junction. There were numerous small nodules on the surface of the intestines, the majority on the jejunum but also present on the deudenum, ileum, and large intestines. There was peritoneal effusion in the abdominal cavity. The right lobes of the liver contained a large amount of what appeared to be fibrin and the lobes were rounded.
The surgical findings were discussed with the owners. They opted for humane euthanasia due to concern for quality of life, and amount and severity of widespread disease on exploratory.
Histopathology findings: The ileocecocolic mass, jejunal and liver biopsy were submitted for histopathology.
Moderately differentiated serosal hemangiosarcoma, intestines; Mild lymphoplasmocytic portal hepatitis.
Chylous effusion are predominantly composed of chyle, the lymphatic fluid that flows thru the lacteals of the small intestines and the thoracic duct. The effusion has a characteristic milky white appearance. Underlying causes for chylous effusion include cardiac disease, mediastinal masses, heartworm disease, trauma, granulomas, congenital thorax duct abnormality, biliary cirrhosis, Vitamin E deficiency and diffuse lymphatic disease such as lymphangiectasia or lymphosarcoma (Borku et. Al 2005). Unlike chylothorax, chyloabdomen is uncommon in cats. There are various causes of chylous abdominal effusion in cats such as trauma, lymphoma, chronic pancreatitis, feline infectious peritonitis (FIP), cancer. In one study, seven out of nine cats with chyloabdominal had intra-abdominal neoplasia. Hemangiosarcoma (3 cats), paraganglioma (1 cat) lymphoma (2 cats, small intestinal), lymphangiosarcoma (1 cat, abdominal wall). Unfortunately, four of the cats had unresectable tumors. Survival times varied depending on location and type of neoplasia ranging from euthanasia at the time of surgery, 5 cats were euthanized within 3 months of surgery, one cat with lymphoma lived for 14 months after surgery and also received chemotherapy. Of the two cats with non-neoplastic disease, one had severe biliary cirrhosis and the other had vitamin E deficiency (Gores BR et al 1994). There have also been several case reports of cats with chylous abdominal effusion with FIP, one cat had chylous effusion in the thorax and abdomen (Boreu et al 2005).
Hemangiosarcoma (HSA) in cats is also uncommon and accounts for less than 2% (visceral and non-visceral HSA) of feline malignancy. The frequency of feline visceral HSA was estimated to be 0.04%. HSA typically has a poor to guarded prognosis since it is highly metastatic. One study, reports 77% of cats had multifocal disease at the time of diagnosis (Culp et al. 2008). Chemotherapy with doxorubicin and vincristine have been used in select cases.
Submitted by: Sarah Muhrer, DVM
1. Borku MK, Ural K, Karakurum MC, et al: Chylous pleural and peritoneal effusion in a cat with feline immunodeficiency virus; diagnosis by lipoprotein electrophoresis. Revue Med.Vet 12: 612-614, 2005.http://www.revmedvet.com/2005/RMV156_612_614.pdf2.x/full
2. Culp WN, Drobatz KJ, Glassman, MM et al: Feline visceral hemangiosarcom: Journal of Veterinary Internal Medicine 22: 148-152, 2008 http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2008.002
3. Gores BR, Berg J, Carpenter JL et al:Chylous ascites in cats: nine cases (1978-1993): Journal of the American Veterinary Medical Association 8: 1161-1164, 1994. https://www.researchgate.net/publication/15307805_Chylous_ascites_in_cats_Nine_cases_1978-1993
4. Savary KC, Sellon RK, and Law JM: Chylous abdominal effusion in a cat with feline infectious peritonitis. Journal of the American Animal Hospital Association 37: 35-40, 2001. www.jaaha.org/doi/pdf/10.5326/15473317-37-1-35
Alfaxalone is a neurosteroid anesthetic agent used clinically to induce general anesthesia in a variety of species including dogs and cats. Although alfaxalone is classified as a steroid, it has not been shown to have glucocorticoid or mineralocorticoid activity. Like many other intravenous hypnotic agents, including propofol, etomidate, and thiopental, alfaxalone produces it’s sedative effect through interaction with the GABAA receptor. Older formulations of the drug (e.g. Saffan®) caused histamine release and other adverse reactions due to the use of a castor oil surfactant (Cremophor EL) to solubilize the alfaxalone. New formulations solubilized in 2-hydroxypropyl beta-cyclodextrin (Alfaxan®) do not have that effect and have been approved in the US for intravenous use in dogs and cats. Alfaxan® comes as a clear, preservative- free 1% solution (10 mg/ml) and is currently scheduled as a class IV controlled substance.
Alfaxalone produces smooth, rapid induction of anesthesia, excellent muscle relaxation, and a short duration of anesthesia (6 – 10 min after 2 mg/kg in unpremedicated dogs), clinically similar to propofol. In dogs, cardiovascular function is generally well maintained after an induction dose of 2 mg/kg given over 1 minute. A dose-dependent decrease in arterial blood pressure and transient increase in heart rate have been noted in dogs and tachycardia may be pronounced in some dogs. The most common side effect is dose–related respiratory depression, although this seems to be less pronounced than that seen with propofol (mean duration of apnea being 30 seconds after a dose of 2 mg/kg alfaxalone). However, decreases in PaO2 can also occur, possibly due to changes in ventilation/perfusion matching, and supplemental oxygen should be provided.
Alfaxalone has minimal cumulative effect due to it’s rapid metabolism and may be given by continuous rate infusion (4-6 mg/kg/hr), Recovery is generally uneventful. In contrast to propofol, alfaxalone is metabolized by the liver and this should be taken into account when using the drug in patient’s with severely impaired liver function.
In cats, clinically relevant doses of 2 – 5 mg/kg IV given over 1 minute in unpremedicated cats also cause dose-dependent cardiopulmonary depression. The decrease in arterial blood pressure is related to a decrease in systemic vascular resistance, with minimal changes in heart rate or cardiac output. A dose-dependent decrease in respiratory rate is the most common side effect. A decrease in PaO2 unrelated to changes in ventilation has been noted and supplemental oxygen should be provided. Occasional excitement in the recovery period has been reported in cats.
Alfaxalone is commonly used for short-term sedation or induction of anesthesia. As with most anesthetic drugs, alfaxalone may be given in combination with other sedative or anesthetic agents including opioids (butorphanol, methadone, hydromorphone, oxymorphone), benzodiazepines (midazolam, diazepam), and/ or alpha-2 agonists and the dose should be adjusted accordingly (1-2mg/kg (dogs); 2-4 mg/kg (cats) with the alfaxalone titrated to effect). In smaller patients, the alfaxalone may be diluted 1:1with sterile saline to allow more accurate dosing.
Although not approved for intramuscular use in the US, alfaxalone is clinically effective when given by this route and may be especially helpful in handling fractious or stressed cats (1-2 mg/kg when given in combination with an opioid and benzodiazepine) to allow physical examination and i.v. catheter placement. The volumes of drug required in larger dogs somewhat limits its usefulness in those patients. Alfaxalone does not provide analgesia when given alone, but may act synergistically with other analgesic agents, such as opioids. Recent reports comparing Apgar scores after Caesarian section in dogs, show improvement in scores in puppies after alfaxalone induction relative to propofol induction. In addition, alfaxalone has proved an effective anesthetic in other species including iguanas, turtles, rabbits and marmosets.
Submitted by: Sandra Z Perkowski, VMD, PhD, Dipl ACVAA
Bertelsen MF, Sauer CD. Alfaxalone anaesthesia in the green iguana (Iguana iguana). Vet Anaesth Analg 2011;38(5):461-466
Grint NJ, Smith HE, Senior JM. Clinical evaluation of alfaxalone in cyclodextrin for the induction of anesthesia in rabbits. Vet Rec 2008;163(13):395-396.
Grubb TL, Greene SA, Perez TE. Cardiovascular and respiratory effects, and quality of anesthesia produced by alfaxalone administered intramuscularly to cats sedated with dexmedetomidine and hydromorphone. J Feline Med Surg 2013;15(10):858-865.
Muir W, Lerche P, Wiese A, Nelson L, Pasloske K, Whittem T. Cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in dogs. Vet Anaesth Analg 2008;35(6):451-462.
Muir W, Lerche P, Wiese A, Nelson L, Pasloske K, Whittem T. The cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in cats. Vet Anesth Analg 2009: 36,42-54.
Doebeli A, Michel E, Bettschart R, Harnack S, Reichter IM. Apgar score after induction of anesthesia for canine cesarean section with alfaxalone versus propofol. Theriogenology 2013: 80(8): 850-854.
Tamura J, Ishizuka T, Fukui S, et al. The pharmacological effects of the anesthetic alfaxalone after intramuscular administration to dogs. J Vet Med Sci. 2015;77(3):289-296.
Whittem T, Pasloske KS, Heit MC, Ranasinghe MG. The pharmacokinetics and pharmacodynamics of alfaxalone in cats after single and multiple intravenous administration of Alfaxan at clinical and supraclinical doses. J Vet Pharmacol Ther 2008;31(6):571-579.
The use of intralipid therapy has been gaining traction as a treatment option for an ever expanding range of toxicities. While it has not quite become the standard of care, it has been viable for patients in the veterinary field and has been reported as case studies in the human field.
Veterinary literature has reviewed intravenous lipid emulsion therapy (ILE) [1,2] and published case reports or studies are available noting efficacy in toxicities including macrocyclic lactones [3,4], baclofen , beta-blockers, calcium channel blockers , NSAID [7,8], bromethalin , lidocaine , permethrin toxicity [11,12], tricyclic antidepressants (13). Intravenous lipid emulsion (ILE) in human literature has been reported as a therapy for local anesthetic [14,15] calcium channel blocker [16,17], psychotropic medication  , glyphosatesurfactant herbicide toxicities and even cocaine overdosage . Original work performed by Weinberg noted a response in rats with bupivicaine induced systole with lipid emulsion . How exactly ILE works is not certain but two theories are considered. The “lipid sink” theory is most commonly considered the primary mode of action. In this theory, the formation of a lipid compartment within the intravascular space can serve as a “sink” into which the lipophilic drug will be drawn into. The drug is then excreted/metabolized. Determination of a drug’s lipophilicity may be noted by its log P value. A value >1 indicates lipophilic compound which may move into the temporary lipid phase and be less distributed throughout the body. The formulation of ILE utilized may play a role and supports the “lipid-sink” theory based on one study . This theory has been supported in two case reports that followed plasma ropivacaine  and serum verapamil concentrations . An alternate theory is that the lipid provides an energy source for the cardiac myocytes by increasing the availability of FFA. The increase of FFA may also aid in increasing the activation of voltage-gated calcium channels in the myocardium, increasing cytosolic calcium channels This mechanism may be most important in cases of calcium-channel blockade [23,24].
There has not been an absolute protocol established for administration of intralipid therapy. A commonly utilized protocol includes an IV bolus of 20% ILE (1.5 mL/kg) followed by a continuous rate infusion of 0.25 mL/kg/min for 30–60 minutes. IntraLipid 20% (Baxter) is the most commonly referred to solution. It is composed 20% Soybean Oil, 1.2% Egg Yolk Phospholipids, 2.25% Glycerin, and Water for Injection. It may be infused through a peripheral intravenous catheter (350 mOsmol/kg water) without the use of a filter. The solution must be handled aseptically. Complications of ILE therapy may include fever, hyperlipemia, thrombocytopenia, hemolysis, prolonged coagulation times, seizures or anaphylactoid reactions to the soybean component. In one cat corneal lipidosis was suspected following treatment for ivermectin toxicity . The ph of Intralipid may vary from 6-9 pending where it is is in its shelflife which should be taken into account in the individual patient. While the log P value predicts the lipophilicity of a drug, other factors such as distribution, patient pH, intravascular volume and oxygenation status affect response to ILE. Restoration of intravascular volume and oxygenation should be corrected prior to initiating ILE treatment.
Submitted by: William Pullin, DVM, DACVIM
1. Fernandez, AL, Lee JA, Rahilly L, et al. Use of intravenous lipid emulsion as an antidote in veterinary toxicology. J Vet Emerg Crit Care 2011 Aug;21(4):309-20. doi: 10.1111/j. 1476-4431.2011.00657.x
2. Gwaltney-Brant S, Meadows I. Use of intravenous lipid emulsions for treating certain poisoning cases in small animals. Vet Clie North Am Small Animal Pract. 2012 Mar;42(2): 251-62, vi. doi:10.1016/j.cvsm.2011.12.001
3. Clarke DL, Lee JA, Murphy LA, Reineke EL. Use of intravenous lipid emulsion to treat ivermectin toxicosis in a Border Collie. J Am Vet Med Assoc. 2011 Nov 15;239(10):1328-33. doi: 10.2460/javma.239.10.1328
6. Maton BL, Simonds EE, Lee JA, et al. Use of high-dose insulin therapy and intravenous lipid emulsion to treat severe, refractory diltiazem overdose in a dog. J Vet Emerg Care. 2013 May/June ;23(3):321-7. don 10.1111/vec.12053
7. Herring JM, McMichael MA, Corsi R, Wurlod V. Intravenous lipid emulsion therapy in three cases of canine naproxen overdose. J Vet Emerg Crit Care (San Antonio). 2015 Sep-Oct; 25(5):672-8. doi: 10.1111/vec.12307
11. Peacock R, Hosgood G, Swindells KL, Smart L. Randomized, controlled clinical trial of intravenous lipid emulsion as an adjunctive treatment for permethrin toxicosis in cats. J Vet Emerg Crit Care. 2015 Sep-Oct;25(5):597-605. doi: 10.1111/vec.12322
12. Seitz MA, Burkitt-Creedon JM. Persistent gross lipemia and suspected corneal lipidosis following intravenous lipid therapy in a cat with permethrin toxicosis.J Vet Emerg Crit Care 2016 Nov-Dec;26(6):804-8
13. Cave G, Harvey M, Shaw T, et al. Comparison of intravenous lipid emulsion, bicarbonate, and tailored liposomes in rabbit clomipramine toxicity. Acad Emerg Med. 2013 Oct;20(10): 1076-9. doi 10.111/acem.12224
14. Litz RJ, Roessel T, Heller AR, Stehr SN. Reversal of central nervous system and cardiac toxicity after local anesthetic intoxication by lipid emulsion injection. Anesth Analg. 2008;106:1575–1577. doi: 10.1213/ane.0b013e3181683dd7
15. Mizutani K, Oda Y, Sato H. Successful treatment of ropivacaine-induced central nervous system toxicity by use of lipid emulsion: effect on total and unbound plasma fractions. J Anesth. 2011 Jun;25(3):442-5
16. Young AC, Velez LI, Kleinschmidt KC. Intravenous fat emulsion therapy for intentional sustained-release verapamil overdose. Resuscitation. 2009;80:591–593. doi: 10.1016/ j.resuscitation.2009.01.023
17. French D Armenian P, Ryan W, et al. Serum verapamil concentrations before and after Intralipid therapy during treatment of overdose. Clin Toxicol (Phila). 2011 Apr;49(4):340-4. doi 10.3109/15563650.2011.572556
18. Nair F, Paul FK, Protopapas M. Management of near fatal mixed tricyclic antidepressant and selective serotonin reuptake inhibitor overdose with Intralipid 20% emulsion. Aneasth Intensive Care. 2013 Mar;41(2):264-5
19. Han SK, Jeong J, Yeom S, Ryu J, Park S. Use of a lipid emulsion in a patient with refractory hypotension caused by glyphosate-surfactant herbicide. Clin Toxicol (Phila) 2010;48(6):566– 568. doi: 10.3109/15563650.2010.496730
21. (Weinberg GL, VadeBoncouer T, Ramaraju GA, et al. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivicaine-induced asystole in rats. Anesthesiology 1998; 88(4): 1071-1075.)
Treatment of a well-differentiated hepatocellular carcinoma with CyberKnife stereotactic radiation therapy
The patient, an 11-year-old FS Golden Retriever, presented to a referral hospital where she was diagnosed with a low grade hepatocellular carcinoma (HCC). The only clinical sign present was an increase in ALT of 137 (reference range ALP 0-120) and ALP of 427 (reference range 0-140) which was found on routine bloodwork. An ultrasound revealed a 13 x 8 cm isoechoic mass occupying the right medial and portions of the right lateral liver lobes. The mass was mostly solid but with an approximately 5 x 6 cm hypoechoic region which appeared cavitated. Tru-cut biopsies were obtained of the mass and histopathology confirmed low grade HCC. Thoracic radiographs were free of metastatic disease. Due to the location and size of the mass within the liver, surgical resection was not deemed a reasonable treatment option. Other pertinent medical history included complete resection of a low grade mammary carcinoma nine months prior to diagnosis with HCC.
The patient was referred to a second specialty hospital for stereotactic radiation therapy in the form of CyberKnife. This type of radiation therapy is the delivery of a highly conformal dose of radiation therapy to a target with steep dose gradients resulting in a very low dose of radiation being delivered to surrounding normal tissue. This form of therapy relies on highly accurate target localization and precise delivery of radiation. The accuracy associated with this type of RT results in the ability to deliver a higher dose of radiation more rapidly with less normal tissue toxicity.
Prior to treatment with radiation, the patient underwent ultrasound-guided fiducial marker placement in the solid portions of the tumor to allow accurate localization of the tumor during the radiation treatments and a planning CT scan in order to define the tumor and surrounding healthy tissue such as the GI tract, lungs, spinal cord and kidneys. The patient received 3 treatments of CyberKnife stereotactic radiation therapy for a total dose of 30 Gy within a one week time period. Due to motion of the tumor with each phase of respiration, tracking was used in the form of Synchrony cameras which can track the motion of the tumor in “real time” and continuously deliver radiation as the tumor moves. The patient did well for each of her treatments and was discharged from the hospital successfully.
Three months after treatment, the patient had a repeat abdominal ultrasound performed which revealed that the tumor had decreased in size to 5 x 5 cm. Bloodwork at that time revealed an ALT of 242 (reference range 18-121 U/L) with all other values being within normal limits. Another repeat ultrasound was performed in 6 months after treatment which revealed that the tumor had further decreased in size to 3.7 x 4.1 x 4.1 cm. Bloodwork at this point showed that ALT had decreased to 180 (reference range 18-121 U/L). All other values were within normal limits.
In human medicine, stereotactic radiation therapy is becoming more routinely used for non-resectable HCC. Doses of 30-60 Gy are typically used over 3-6 treatments. 1-4 In these cases, other options for treatment include arterial chemoembolization or conformal fractionated external beam radiation therapy. The latter treatment modality has been limited in the past due to the risk of radiation-induced liver disease (RILD). RILD is a sub-acute form of liver injury due to radiation damage to normal, healthy liver tissue surrounding the tumor. It typically occurs 4-8 weeks after completion of RT but has been described in humans as late as 7 months after radiation. Clinical signs of classical RILD include fatigue, abdominal pain, hepatomegaly, ascites and elevation of alkaline phosphatase out of proportion to other liver enzymes. A second form of RILD (non-classical) include jaundice and markedly elevated serum transaminase. 5 In the patient being currently described, the decision to use a radiation dose at the low end of typical human doses was due to the proximity of the mass to the stomach and our attempt to avoid normal tissue toxicity. A moderate elevation in ALT was noted after therapy, which may have correlated with a low grade RILD, however, other abnormal clinical signs associated with typical RILD were not observed.
In veterinary medicine, to the author’s knowledge, there are no studies evaluating the use of stereotactic radiation therapy to treat HCC, however, one study exists which evaluates a more traditional form of radiation therapy in the form of 3D conformal external beam radiation therapy. This modality is capable of delivering equivalent doses of radiation, however, the precision and accuracy of stereotactic radiotherapy is lacking, resulting in a greater possibility of RILD due to the inclusion of larger amounts of normal tissue in the radiation field. However, in the aforementioned study, only 1 of 6 dogs included in the study developed RILD. Individual fraction sizes ranged from 6-10 Gy with the total dose administered being 18-42 Gy over several weeks. Five of 6 dogs had an objective response and median follow-up time was 534 days.6
The tumor tracking capability of CyberKnife Synchrony cameras has been shown in human medicine to significantly reduce the volume of normal liver tissue included in the radiation field, while maintaining high precision in tumor localization, conformity and tumor coverage. This may be especially useful in patients with preexisting liver disease or poor liver function in which they are at a higher risk for developing RILD. 1
This case report demonstrates the successful treatment of a dog with non-resectable low grade HCC with stereotactic radiation therapy. Consideration can be given in the future to dose escalation in which a higher dose of radiation can be given over 3 doses, or more doses can be added to the treatment protocol for a higher cumulative dose.
1. Gated Volumetric-Modulated Arc Therapy vs. Tumor-Tracking CyberKnife Radiotherapy as Stereotactic Body Radiotherapy for Hepatocellular Carcinoma: A Dosimetric Comparison Study Focused on the Impact of Respiratory Motion Managements. Yoon K, Kwak J, Cho B, Park JH, Yoon SM, Lee SW, Kim JH. PLoS One. 2016 Nov 22;11(11):e0166927. doi: 10.1371/journal.pone.0166927https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119818/
2.Stereotactic body radiotherapy for primary hepatic malignancies – Report of a phase I/II institutional study. Weiner AA, Olsen J, Ma D, Dyk P, DeWees T, Myerson RJ, Parikh P. Radiother Oncol. 2016 Oct;121(1):79-85. doi: 10.1016/j.radonc.2016.07.020. http://www.thegreenjournal.com/article/S0167-8140(16)31236-1/abstract
3. Stereotactic Body Radiotherapy for Hepatocellular Carcinoma. McPartlin AJ, Dawson LA. Cancer J. 2016 Jul-Aug;22(4):296-301. doi: 10.1097/PPO.0000000000000201. http://journals.lww.com/journalppo/Abstract/2016/07000/Stereotactic_Body_Radiotherapy_for_Hepatocellula r.10.aspx
4.Stereotactic Body Radiotherapy for Hepatocellular Carcinoma Resulting in a Durable Relapse-Free Survival: A Case Report Monitoring Editor: Alexander Muacevic and John R Adler Samual Francis,1 Ned Williams,1 Christopher J Anker,2 Akram Shaaban,3Robin Kim,4 Dennis Shrieve,1 and Jonathan Tward1Cureus. 2016 Oct; 8(10): e841. Published online 2016 Oct 24. doi: 10.7759/cureus.841 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120964/
5. Radiation induced liver disease: A clinical update R. Bensona, R. Madana, , , R. Kilambib, S. Chandera Journal of the Egytial National Cancer Institute. 2016 March 28 (1) 7-11 http://www.sciencedirect.com/science/article/pii/S1110036215000849
6.Three-dimensional conformal radiation therapy for inoperable massive hepatocellular carcinoma in six dogs. J Small Anim Pract. July 2015;56(7):441-5. T Mori 1, Y Ito 1, M Kawabe 1, R Iwasaki 1, H Sakai 2, M Murakami 1, K Maruo 1http://onlinelibrary.wiley.com/doi/10.1111/jsap.12352/abstract
SRMA, also known as corticosteroid responsive (aseptic) meningitis is an auto-immune disease that targets the leptomeninges and associated vessels. The exact cause is unknown. Studies have suggested a Th2-mediated response with elevated Immunoglobulin A (IgA) levels in the CSF and serum. Elevated IL-8 levels have been noted in the CSF which is associated with invasion of neutrophils into the leptomeninges.
SRMA is mostly seen in medium to large breed dogs with the Boxer, Bernese Mountain Dog, Beagle, Golden Retrievers, German Shorthaired Pointers and Nova Scotia Duck Tolling Retriever possibly being predisposed. In the Beagle, SRMA was been previously labeled as ‘Beagle Pain Syndrome’. Although these breeds seem to be overrepresented with SRMA, it can affect almost any breed of dog. SMRA typically occurs in dogs less than 2 years of age.
Classically, dogs with SRMA present with fever and severe spinal pain. A majority of patients will have neck pain. Dogs will often experience severe allodynia (pain from a non-painful stimulus) and/or severe anticipation of pain. When walking, dogs will typically have a short, choppy gait. Frequently, no specific neurologic deficits will be noted (i.e. proprioceptive / reflex deficits). Extreme lethargy and decreased appetite may also be noted.
The diagnosis of SRMA is made by a combination of imaging studies and a cerebral spinal fluid (CSF) analysis. MRI of the most painful region is often recommended to rule out other causes of spinal pain such as a herniated disc, vertebral malformations, and other causes of myelitis (i.e. infectious). MRI is a non-invasive test, but does require general anesthesia to keep the dog still and comfortable during the procedure. If no structural cause for the spinal pain is found the next step is to perform a CSF analysis. The total nucleated cell count (TNCC), protein level and cytology of the spinal fluid will be evaluated. Classically you will see a marked neutrophilic pleocytosis and elevated protein levels.
It is important to note that a neutrophilic pleocytosis not 100% specific for SMRA and common infectious diseases should be ruled out with serum or CSF titers. The infectious disease testing submitted should be determined based on geographical location and specific exposure risks. Frequently tested organisms include Rickettsial diseases, Toxoplasma, Neospora, Cryptococcus, and Distemper virus. Approximately 46% of dogs with SRMA will have a concurrent immune-mediated polyarthritis. The clinical signs (i.e. short and choppy gait) can look very similar therefore the clinician needs to pay special attention to palpation of the joints in dogs with suspected SRMA. Frequently if polyarthritis is suspected, arthrocentesis can be performed after the MRI while the dog is still under anesthesia.
To help aid in the diagnosis of SRMA a C-Reactive Protein (CRP) can be measured. CRP is an acute-phase protein that is produced by the liver in response to inflammation in the body. A dog with SRMA will frequently have a high CRP level. This test is also useful to monitor how a patient is responding to treatment and to identify if they are relapsing.
Corticosteroids are the cornerstone of treatment of SRMA. Typically prednisone is started with a high initial dose (2-4 mg/kg/day) and then tapered slowly over several months. Common side effects of corticosteroids may include increased eating and drinking, behavior changes, gastrointestinal upset, and weight gain. The vast majority of dogs with SRMA will become clinically normal very rapidly; often in as little as 1 or 2 days. Occasionally, dogs with more advanced disease will require additional immuno-modulating medications. Cyclosporine, azathioprine, and mycophenolate are examples of other medications that have been used in conjunction with corticosteroids to help control the disease.
Treatment typically lasts for at least 6 months depending on the patient’s response. Because clinical remission is often rapid, tapering the prednisone too quickly is a common mistake that can trigger a relapse. Many dogs can be weaned off corticosteroids completely if done slowly (~6 months). Ideally a normal CRP should be obtained before attempting to taper medications. Ultimately a repeat CSF analysis may be needed to confirm a relapse. Should a relapse occur the initial corticosteroid dose should be restarted and then taper more slowly than the first attempt. Some dogs may require a low dose of corticosteroids life-long.
SRMA typically has an excellent prognosis. Usually after 24-48 hours of starting corticosteroids the dog is improving if not yet normal. The lack of a rapid positive response to the steroids should indicate to the clinician that SRMA may not be the cause of the clinical signs or the patient has a more severe variation of SMRA.
- Bathen-Noethen A, Carlson R, Menzel D, Mischke R, Tipold A. Concentrations of acute-phase proteins in dogs with steroid responsive meningitis-arteritis. J Vet Intern Med [Internet]. 2008;22(5):1149–56. http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2008.0164.x/full
- Dewey CW, da Costa RC. Practical Guide to Canine and Feline Neurology. 3rd ed. 2016.
- Lowrie M, Penderis J, Eckersall PD, McLaughlin M, Mellor D, Anderson TJ. The role of acute phase proteins in diagnosis and management of steroid-responsive meningitis arteritis in dogs. Vet J [Internet]. 2009 Oct;182(1):125–30. http://www.sciencedirect.com/science/article/pii/S1090023308001615
- Lowrie M, Penderis J, McLaughlin M, Eckersall PD, Anderson TJ. Steroid responsive meningitis-arteritis: a prospective study of potential disease markers, prednisolone treatment, and long-term outcome in 20 dogs (2006-2008). J Vet Intern Med [Internet]. 2009;23(4):862–70. http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2009.0337.x/full
- Tipold A, Schatzberg SJ. An update on steroid responsive meningitis-arteritis. J Small Anim Pract [Internet]. 2010 Mar [cited 2013 Dec 11];51(3):150–4. http://onlinelibrary.wiley.com/doi/10.1111/j.1748-5827.2009.00848.x/full
- Webb A., Taylor SM, Muir GD. Steroid-responsive meningitis-arteritis in dogs with noninfectious, nonerosive, idiopathic, immune-mediated polyarthritis. J Vet Intern Med. http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2002.tb02368.x/abstract