- Email: [email protected]
Hepatic Encephalopathy in a Red-Tailed Boa (Boa Constrictor Imperator)
CASE REPORT HEPATIC ENCEPHALOPATHY IN A RED-TAILED BOA (BOA CONSTRICTOR IMPERATOR) Marco Di Giuseppe, DVM, PhD, GPCert (ExAP), Matteo Oliveri, DVM, PhD, Manuel Morici, DVM, PhD, Giacomo Rossi, DVM, PhD, Dip. ECZM (Wildlife Population Health), and Filippo Spadola, DVM, PhD
Abstract A 5-year-old female red-tailed boa (Boa constrictor imperator) was presented for abnormal neurologic behavior. Ultrasound examination revealed an enlarged liver, with rounded margins and hypoechoic areas. A complete snake virus polymerase chain reaction (PCR) profile was performed together with diagnostic blood testing. The snake virus PCR profile results were negative. Supportive treatment for the patient consisted of fluid therapy and nutritional support, supplemented with carnitine. Lactulose was administered orally every 24 hours. The snake died 3 weeks after the initial presentation. Histopathological examination of the liver showed extensive necrotic degeneration with hepatocytic centrilobular organization and cholestasis. Histopathology of the central nervous system (CNS) revealed a degenerative pattern of neurons, and a hyperplastic aspect of the microglial cells, morphologically similar to Alzheimer type II astrocytes. The postmortem examination results indicate that the neurological signs were a consequence of hepatic encephalopathy (HE). Reptiles with hepatic disease may show a wide variety of clinical signs. The last stage of liver diseases is often HE. Diagnostic procedures include hematology, serum/plasma biochemistry, echography, and biopsy. The prognosis for a patient that is presented with clinical signs of HE is guarded at best. Recommended treatment for reptile patients that are diagnosed with HE is fluid support and more specific hepatic therapeutic agents, including lactulose, silymarin, and carnitine. Copyright 2017 Elsevier Inc. All rights reserved. Key words: hepatopathy; neurology; neuronal degeneration; snakes
A
5-year-old female red-tailed boa (Boa constrictor imperator) was presented for abnormal neurologic behavior. The snake was part of a large snake collection, and the owner described the patient as having a prolonged period of anorexia (approximately 2 months). The boa had no history of previous medical issues. Physical examination revealed a marked alteration of the neurological status, including stargazing, absence of the righting reflex, stupor, and reluctance to move (Fig. 1). Palpation failed to reveal any intracoelomic masses. Fresh fecal stain and floatation were performed. Ultrasound examination revealed an enlarged liver, with rounded margins and hypoechogenic areas (Fig. 2). Owing to the high prevalence of virus–associated neurological syndromes in snakes, a complete snake virus polymerase chain reaction (PCR) profile (adenovirus, arenavirus, paramyxovirus/ferlavirus, and reovirus) was performed using a cloacal swab and blood samples. With a modified hemagglutination inhibition assay, serum antibodies against ophidian paramyxovirus were determined. To verify infection with arenavirus (inclusion body disease), the presence of inclusion bodies in red blood cells was examined in the blood smear (hematoxylin and eosin stain), and a biopsy of the esophageal tonsil was taken for histology.
From the Centro Veterinario per Animali Esotici, Palermo, Italy; the Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences Brno, Brno, Czech Republic; the Department of Veterinary Science, Veterinary Teaching Hospital, University of Messina, Messina, Italy; and the School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy. Address correspondence to: Manuel Morici, DVM, PhD, GPCert (ExAP), Department of Veterinary Science, Veterinary Teaching Hospital, University of Messina, Polo universitario SS Annunziata, 98168 Messina, Italy. E-mail: [email protected]. Ó 2017 Elsevier Inc. All rights reserved. 1557-5063/17/2101-$30.00 http://dx.doi.org/10.1053/j.jepm.2017.01.029
9 6
Journal of Exotic Pet Medicine 26 (2017), pp 96–100
TABLE. Hematology and serum biochemistry panel results in the Boa constrictor imperator affected with hepatic encephalopathy
FIGURE 1. Clinical examination of the boa constrictor. The animal showed significant abnormalities of its neurological status, including stargazing, absence of the righting reflex, stupor, and reluctance to move.
The fresh fecal stain and flotation failed to reveal any possible parasite that would have caused the clinical signs (Acanthoamoeba spp.). Both the PCR profile and hemagglutination inhibition assay tested negative. The plasma biochemistries and complete blood count (Table) revealed increased concentrations of creatine kinase (170 U/L), phosphorous (8.8 mg/dL), and sodium (4170 mmol/L). No inclusion bodies were present in the blood smear. Histology of the esophageal tonsil showed no signs of basophilic intracytoplasmic inclusions attributable to arenavirus. Supportive treatment consisted in fluid therapy (20 mL/kg of reptile solution) and nutritional support (2 mL/kg orally, Oxbow Carnivore Care; Oxbow Animal Health, Murdock, NE USA) supplemented with carnitine (Rossovet, Pfizer Italia, Italy) and lactulose (0.5 mL/kg orally, every 24 hours; Laevolac, Roche, Switzerland). Unfortunately, the snake died 3 weeks after its initial presentation. Necropsy revealed an enlarged and pale liver (Fig. 3). Histopathology of the liver showed extensive necrotic degeneration with hepatocytic centrilobular organization and cholestasis (Fig. 4). No abnormalities were found in the lungs. The esophageal tonsil was slightly reactive. No other macroscopic pathological alterations were noticed. Histopathology of the
Parameters
Values
Units
AST Bile acids (BA) CK UA GLU Caþþ PHOS TP ALB GLOB Kþ Naþ WBC HCT RBC
9 o35 170 4.1 62 15.6 8.8 9.6 2.0 7.6 0.0 4170 2.4 20 0.55
U/L Umol/L U/L mg/dL mg/dL mg/dL mg/dL g/dL g/dL g/dL mmol/L mmol/L 103/μL % 106/μL
References 5 to 35 53 to 138 1.2 to 5.8 10 to 60 10 to 22 2.6 to 4.9 4.6 to 8.0 1.9 to 5.3 2.2 to 6.9 3.0 to 5.7 130 to 152 0.88 to 22.5 10 to 45 0.16 to 2.1
ALB, albumin; AST, aspartate aminotransferase; BA, bile acids; CK, creatine kinase; GLU, glucose; GLOB, globulins; HCT, hematocrit; PHOS, phosphorus; RBC, red blood cell; TP, total protein; UA, urinalysis; WBC, white blood cell.
central nervous system (CNS) revealed a degenerative pattern of neurons, and a hyperplastic (or binucleated) aspect of the microglial cells, morphologically similar to Alzheimer type II astrocytes (Fig. 5).1 DISCUSSION In snakes, neurological abnormalities may be caused by several disease conditions, including exposure to toxins, trauma, neoplasia, meningitis (viral, bacterial, or mycotic), osteomyelitis, thiamine deficiency, and hepatic dysfunction.2-12 Viral diseases involving the CNS are frequently diagnosed in snakes. Inclusion body disease (arenavirus) is a common condition in ophidian medicine.13 Inclusion body disease is characterized by nonsuppurative meningoencephalitis and
FIGURE 2. Boa constrictor. Ultrasound examination showing enlarged liver, with rounded margins and hypoechogenic areas. Giuseppe et al./Journal of Exotic Pet Medicine 26 (2017), pp 96–100
9 7
FIGURE 3. Boa constrictor. An enlarged and pale liver was noted at the time of necropsy.
severe neurological signs (e.g., stargazing, incoordination, and ataxia).14,15 The snake patient infected with ophidian paramyxovirus is usually presented with pneumonia and respiratory clinical signs. However, Jacobson et al.16,17 and Orós et al.18 associated paramyxovirus with neurological dysfunction in rattlesnakes. Reovirus has been isolated from the brain of a Crotalus viridis showing abnormal neurologic signs, however, no histologic lesions were identified in the CNS of that snake.19 Oliveri and Cermakova diagnosed reovirus in a Morelia viridis that was presented with severe polyneuropathy, stupor, and ataxia (personal communication). Adenovirus infection has been reported in snakes.20-25 Raymond et al.26 reported foci of gliosis within the CNS, and several glial and endothelial cells contained intranuclear adenovirus-like inclusion bodies in infected snakes. Acanthamoeba spp. have also been correlated with neurological disease in snakes.27 However, none of the disease conditions listed above were identified in the snake described in this
FIGURE 4. Boa constrictor (histopathology of the liver). Extensive necrotic degeneration was observed with hepatocytic centrilobular organization and cholestasis. Note the presence of areas of swollen hepatocytes and foci of chronic inflammation (big arrow). Areas of melanomacrophages concentration are also evident (small arrowhead). H&E, scale bar ¼ 500 μm. H&E, hematoxylin and eosin.
9 8
FIGURE 5. Boa constrictor. Histopathology of the central nervous system revealed a degenerative pattern of neurons, and a hyperplastic (or binucleated) aspect of the microglial cells, morphologically similar to Alzheimer type II astrocytes, clinical conditions seen in liver encephalopathy. H&E, scale bar ¼ 150 μm. H&E, hematoxylin and eosin.
report. As previously stated, the histopathology results of the red-tailed boa showed extensive necrotic degeneration of the liver, with hepatocytic centrilobular organization and cholestasis (Fig. 4), and a degenerative pattern of neurons together with a hyperplastic (or binucleated) aspect of the microglial cells, morphologically similar to Alzheimer type II astrocytes (Fig. 5). The postmortem examination results indicate that the neurological signs were a consequence of hepatic encephalopathy (HE). Reptiles with hepatic disease may show a wide variety of clinical signs. Lethargy, chronic anorexia, weight loss, and gastrointestinal and neurological signs are common. The last stage of liver disease often results in HE. Clinical signs of HE are extremely variable (e.g., circling, weakness, ataxia, ptyalism, seizures, and coma). The pathophysiology of HE is not completely known. Hazell and Butterworth28 proposed a synergistic effect involving liver failure and ammonia detoxification, increased cerebral inflammatory proteins, impaired brain perfusion with development of astrocytes swelling, and neuronal edema. Chen et al.29 propose an alteration of CNS functions during HE due to dendritic morphology remodeling of cortical and hippocampal pyramidal neurons. Reduction of the dendritic spine density causes an increase of the motor evoked potential threshold and a prolonged central motor conduction time. Hematology of the HE affected patient often shows anemia, heterophilia and monocytosis. Biochemistries frequently reveal high values of aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, alanine
Giuseppe et al./Journal of Exotic Pet Medicine 26 (2017), pp 96–100
aminotransferase, and lactate dehydrogenase, but none of these analytes are truly liver-specific enzymes in reptiles. Bile acids may eventually prove to be a promising hepatic marker.30 Diagnostic imaging techniques are also clinically useful to detect changes in size or appearance of the liver. An endoscopically obtained tissue biopsy sample is considered as a useful diagnostic tool to diagnose liver disease.31 Prognosis of the patient exhibiting clinical signs of HE is guarded at best. Recommended treatment for snakes that are diagnosed with HE involves fluid administration (avoidance of solutions that contain lactate), along with more specific hepatic therapeutic agents. Carnitine (250 mL/kg orally) is a derivate of the amino acid lysine, which is involved in the transport of the acetyl coenzyme A through the cellular membrane of the hepatocyte.31,32 Lactulose is commonly used in treating hyperammonemia, which is believed to be one of the underlying causes of HE. Lactulose (0.5 mL/kg orally) is fermented by the gut flora into metabolites that acidify the colon. An acidic environment turns freely diffusible ammonia (NH3) into ammonium (NHþ 4 ), which can no longer be absorbed.33-35 Silymarin (milk thistle) has a long history of use in the treatment of liver disease, predominantly in controlling inflammation and limiting uptake of toxins. In the human patient, silymarin exerts membrane stabilizing and antioxidant activity and promotes hepatocyte regeneration; furthermore, it reduces the inflammatory reaction and inhibits fibrogenesis in the liver.36 The use of silymarin to treat HE in reptiles appears to be promising. REFERENCES 1. Diemer NH, Klinken L: Astrocyte mitoses and Alzheimer type I and II astrocytes in anoxic encephalopathy. Neuropathol Appl Neurobiol 2:313-321, 1976 2. Craig LE, Wolf JC, Ramsay EC: Spinal cord glioma in a ridge-nosed rattlesnake (Crotalus willardi). J Zoo Wild Med 36:313-315, 2005 3. Done L: Neurological disorders, in Mader D (ed): Reptile Medicine and Surgery. St. Louis, MO, Elsevier/Saunders, pp 852-857, 2006 4. Gyimesi SS, Garner MM: Pituitary adenoma in a Dumeril's ground boa, Acrantophis dumerili. J Herpetol Med Surg 17: 16-18, 2007 5. Cole GA, Rao DB, Steinberg H: Suspected vitamin E and selenium deficiency in a veiled chameleon (Chameleo calyptratus). J Herpetol Med Surg 18:113-116, 2008 6. Anderson ET, Troan BV, Stringer EM: Cerebral xanthoma in a long-nosed snake (Rhinocheilus lecontei). J Herpetol Med Surg 20:58-60, 2010 7. Wyneken J: Reptilian neurology: anatomy and function. Vet Clin North Am Exot Anim Pract 10:837-853, 2007
8. Kummrow MS, Berkvens CN, Paré JA, et al: Cerebral xanthomatosis in three green water dragons (Physignathus cocincinus). J Zoo Wild Med 41:128-132, 2010 9. Stenglein MD, Sanders C, Kistler AL: Identification, characterization, and in vitro culture of highly divergent arenaviruses from boa constrictors and annulated tree boas: candidate etiological agents for snake inclusion body disease. mBio 3(4):e00180, http://x.d.org/10.1128/mBio.00180-12 10. Ariel E: Viruses in reptiles. Vet Res 42:100, 2011 11. Hepojoki J, Salmenperä P, Sironen T, et al: Arenavirus coinfections are common in snakes with boid inclusion body disease. J Virol 89:8657-8660, 2015 12. McNamara TS, Cook RA, Behler JL, et al: Cryptococcosis in a common anaconda (Eunectes murinus). J Zoo Wildl Med 25:128-132, 1994 13. Schaeffer DO, Waters RM: Neuroanatomy and neurological diseases of reptiles. Semin Avian Exot Pet Med 5: 165-171, 1996 14. Schumacher J, Jacobson ER, Homer BL, et al: Inclusion body disease in boid snakes. J Zoo Wildl Med 25: 511-524, 1994 15. Chang L, Jacobson ER: Inclusion body disease, a worldwide infectious disease of boid snakes: a review. J. Exotic Pet Med 19:216-225, 2010 16. Jacobson E, Gaskin JM, Simpson CF, et al: Paramyxo-like virus infection in a rock rattlesnake. J Am Vet Med Assoc 177:796-799, 1980 17. Jacobson E, Gaskin JM, Page D, et al: Illness associated with paramyxo-like virus infection in a zoologie collection of snakes. J Am Vet Med Assoc 179:1227-1230, 1981 18. Orós J, Sicilia J, Torrent A, et al: Immunohistochemical detection of ophidian paramyxovirus in snakes in the Canary Islands. Vet Rec 149:21-23, 2001 19. Vieler E, Baumgärtner W, Herbst W, et al: Characterization of a reovirus isolate from a rattle snake, Crotalus viridis, with neurological dysfunction. Arch Virol 138:341-344, 1994 20. Heldstab A, Bestetti G: Virus associated gastrointestinal diseases in snakes. J Zoo Anim Med 15:118-128, 1984 21. Jacobson ER, Gaskin JM, Gardiner CH: Adenovirus-like infection in a boa constrictor. J Am Vet Med Assoc 187: 1226-1227, 1985 22. Davison AJ, Wright KM, Harrach B: DNA sequence of frog adenovirus. J Gen Virol 81:2431-2439, 2000 23. Ramis A, Fernández-Bellon H, Majó N, et al: Adenovirus hepatitis in a boa constrictor (Boa constrictor). J Vet Diagn Invest 12:573, 2000 24. Farkas SL, Benkő M, Elo P, et al: Genomic and phylogenetic analyses of an adenovirus isolated from a corn snake (Elaphe guttata) imply a common origin with members of the proposed new genus Atadenovirus. J Gen Virol 83: 2403-2410, 2002 25. Latney LV, Wellehan J: Selected emerging infectious diseases of squamata. Vet Clin North Am Exot Anim Pract 16: 319-338, 2013 26. Raymond JT, Lamm M, Nordhausen R, et al: Degenerative encephalopathy in a coastal mountain kingsnake (Lampropeltis zonata multifasciata) due to adenoviral-like infection. J Wildl Dis 39:431-436, 2003 27. Scheller P, Pantchev N (eds): Parasitology in Snakes, Lizards and Chelonians. Frankfurt am Main, Germany, Edition Chimaira, 2008 28. Hazell AS, Butterworth RF: Hepatic encephalopathy: an update of pathophysiologic mechanisms. Proc Soc Exp Biol Med 222:99-112, 1999
Giuseppe et al./Journal of Exotic Pet Medicine 26 (2017), pp 96–100
9 9
29. Chen JR, Wang BN, Tseng GF, et al: Morphological changes of cortical pyramidal neurons in hepatic encephalopathy. BMC Neurosci 15:15, 2014 30. Campbell TW: Clinical pathology, in Mader D, Divers SJ (eds): Current Therapy in Reptile Medicine and Surgery. St. Louis, MO, Elsevier/Saunders, pp 70-92, 2014 31. Divers SJ, Cooper JE: Reptile hepatic lipidosis. Semin Avian Exot Pet Med 9(3):153-164, 2000 32. Seddon NR: in Stryer L (ed): Biochemistry. New York, WH Freeman, pp 1136, 1988
1 0 0
33. Shukla S, Shukla A, Mehboob S, et al: Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy. Aliment Pharmacol Ther 33:662-671, 2011 34. Stahl SJ: Medical management of bearded dragons. Proc North Am Exotic Anim Pract 6:789-792, 2003 35. Jepson L (ed): Exotic Animal Medicine: A Quick Reference Guide. (ed 1). Philadelphia, PA, Elsevier/Saunders, 2009 36. Féher J, Lengyel G: Silymarin in the prevention and treatment of liver diseases and primary liver cancer. Curr Pharm Biotechnol 13:210-217, 2012
Giuseppe et al./Journal of Exotic Pet Medicine 26 (2017), pp 96–100
Abstract A 5-year-old female red-tailed boa (Boa constrictor imperator) was presented for abnormal neurologic behavior. Ultrasound examination revealed an enlarged liver, with rounded margins and hypoechoic areas. A complete snake virus polymerase chain reaction (PCR) profile was performed together with diagnostic blood testing. The snake virus PCR profile results were negative. Supportive treatment for the patient consisted of fluid therapy and nutritional support, supplemented with carnitine. Lactulose was administered orally every 24 hours. The snake died 3 weeks after the initial presentation. Histopathological examination of the liver showed extensive necrotic degeneration with hepatocytic centrilobular organization and cholestasis. Histopathology of the central nervous system (CNS) revealed a degenerative pattern of neurons, and a hyperplastic aspect of the microglial cells, morphologically similar to Alzheimer type II astrocytes. The postmortem examination results indicate that the neurological signs were a consequence of hepatic encephalopathy (HE). Reptiles with hepatic disease may show a wide variety of clinical signs. The last stage of liver diseases is often HE. Diagnostic procedures include hematology, serum/plasma biochemistry, echography, and biopsy. The prognosis for a patient that is presented with clinical signs of HE is guarded at best. Recommended treatment for reptile patients that are diagnosed with HE is fluid support and more specific hepatic therapeutic agents, including lactulose, silymarin, and carnitine. Copyright 2017 Elsevier Inc. All rights reserved. Key words: hepatopathy; neurology; neuronal degeneration; snakes
A
5-year-old female red-tailed boa (Boa constrictor imperator) was presented for abnormal neurologic behavior. The snake was part of a large snake collection, and the owner described the patient as having a prolonged period of anorexia (approximately 2 months). The boa had no history of previous medical issues. Physical examination revealed a marked alteration of the neurological status, including stargazing, absence of the righting reflex, stupor, and reluctance to move (Fig. 1). Palpation failed to reveal any intracoelomic masses. Fresh fecal stain and floatation were performed. Ultrasound examination revealed an enlarged liver, with rounded margins and hypoechogenic areas (Fig. 2). Owing to the high prevalence of virus–associated neurological syndromes in snakes, a complete snake virus polymerase chain reaction (PCR) profile (adenovirus, arenavirus, paramyxovirus/ferlavirus, and reovirus) was performed using a cloacal swab and blood samples. With a modified hemagglutination inhibition assay, serum antibodies against ophidian paramyxovirus were determined. To verify infection with arenavirus (inclusion body disease), the presence of inclusion bodies in red blood cells was examined in the blood smear (hematoxylin and eosin stain), and a biopsy of the esophageal tonsil was taken for histology.
From the Centro Veterinario per Animali Esotici, Palermo, Italy; the Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences Brno, Brno, Czech Republic; the Department of Veterinary Science, Veterinary Teaching Hospital, University of Messina, Messina, Italy; and the School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy. Address correspondence to: Manuel Morici, DVM, PhD, GPCert (ExAP), Department of Veterinary Science, Veterinary Teaching Hospital, University of Messina, Polo universitario SS Annunziata, 98168 Messina, Italy. E-mail: [email protected]. Ó 2017 Elsevier Inc. All rights reserved. 1557-5063/17/2101-$30.00 http://dx.doi.org/10.1053/j.jepm.2017.01.029
9 6
Journal of Exotic Pet Medicine 26 (2017), pp 96–100
TABLE. Hematology and serum biochemistry panel results in the Boa constrictor imperator affected with hepatic encephalopathy
FIGURE 1. Clinical examination of the boa constrictor. The animal showed significant abnormalities of its neurological status, including stargazing, absence of the righting reflex, stupor, and reluctance to move.
The fresh fecal stain and flotation failed to reveal any possible parasite that would have caused the clinical signs (Acanthoamoeba spp.). Both the PCR profile and hemagglutination inhibition assay tested negative. The plasma biochemistries and complete blood count (Table) revealed increased concentrations of creatine kinase (170 U/L), phosphorous (8.8 mg/dL), and sodium (4170 mmol/L). No inclusion bodies were present in the blood smear. Histology of the esophageal tonsil showed no signs of basophilic intracytoplasmic inclusions attributable to arenavirus. Supportive treatment consisted in fluid therapy (20 mL/kg of reptile solution) and nutritional support (2 mL/kg orally, Oxbow Carnivore Care; Oxbow Animal Health, Murdock, NE USA) supplemented with carnitine (Rossovet, Pfizer Italia, Italy) and lactulose (0.5 mL/kg orally, every 24 hours; Laevolac, Roche, Switzerland). Unfortunately, the snake died 3 weeks after its initial presentation. Necropsy revealed an enlarged and pale liver (Fig. 3). Histopathology of the liver showed extensive necrotic degeneration with hepatocytic centrilobular organization and cholestasis (Fig. 4). No abnormalities were found in the lungs. The esophageal tonsil was slightly reactive. No other macroscopic pathological alterations were noticed. Histopathology of the
Parameters
Values
Units
AST Bile acids (BA) CK UA GLU Caþþ PHOS TP ALB GLOB Kþ Naþ WBC HCT RBC
9 o35 170 4.1 62 15.6 8.8 9.6 2.0 7.6 0.0 4170 2.4 20 0.55
U/L Umol/L U/L mg/dL mg/dL mg/dL mg/dL g/dL g/dL g/dL mmol/L mmol/L 103/μL % 106/μL
References 5 to 35 53 to 138 1.2 to 5.8 10 to 60 10 to 22 2.6 to 4.9 4.6 to 8.0 1.9 to 5.3 2.2 to 6.9 3.0 to 5.7 130 to 152 0.88 to 22.5 10 to 45 0.16 to 2.1
ALB, albumin; AST, aspartate aminotransferase; BA, bile acids; CK, creatine kinase; GLU, glucose; GLOB, globulins; HCT, hematocrit; PHOS, phosphorus; RBC, red blood cell; TP, total protein; UA, urinalysis; WBC, white blood cell.
central nervous system (CNS) revealed a degenerative pattern of neurons, and a hyperplastic (or binucleated) aspect of the microglial cells, morphologically similar to Alzheimer type II astrocytes (Fig. 5).1 DISCUSSION In snakes, neurological abnormalities may be caused by several disease conditions, including exposure to toxins, trauma, neoplasia, meningitis (viral, bacterial, or mycotic), osteomyelitis, thiamine deficiency, and hepatic dysfunction.2-12 Viral diseases involving the CNS are frequently diagnosed in snakes. Inclusion body disease (arenavirus) is a common condition in ophidian medicine.13 Inclusion body disease is characterized by nonsuppurative meningoencephalitis and
FIGURE 2. Boa constrictor. Ultrasound examination showing enlarged liver, with rounded margins and hypoechogenic areas. Giuseppe et al./Journal of Exotic Pet Medicine 26 (2017), pp 96–100
9 7
FIGURE 3. Boa constrictor. An enlarged and pale liver was noted at the time of necropsy.
severe neurological signs (e.g., stargazing, incoordination, and ataxia).14,15 The snake patient infected with ophidian paramyxovirus is usually presented with pneumonia and respiratory clinical signs. However, Jacobson et al.16,17 and Orós et al.18 associated paramyxovirus with neurological dysfunction in rattlesnakes. Reovirus has been isolated from the brain of a Crotalus viridis showing abnormal neurologic signs, however, no histologic lesions were identified in the CNS of that snake.19 Oliveri and Cermakova diagnosed reovirus in a Morelia viridis that was presented with severe polyneuropathy, stupor, and ataxia (personal communication). Adenovirus infection has been reported in snakes.20-25 Raymond et al.26 reported foci of gliosis within the CNS, and several glial and endothelial cells contained intranuclear adenovirus-like inclusion bodies in infected snakes. Acanthamoeba spp. have also been correlated with neurological disease in snakes.27 However, none of the disease conditions listed above were identified in the snake described in this
FIGURE 4. Boa constrictor (histopathology of the liver). Extensive necrotic degeneration was observed with hepatocytic centrilobular organization and cholestasis. Note the presence of areas of swollen hepatocytes and foci of chronic inflammation (big arrow). Areas of melanomacrophages concentration are also evident (small arrowhead). H&E, scale bar ¼ 500 μm. H&E, hematoxylin and eosin.
9 8
FIGURE 5. Boa constrictor. Histopathology of the central nervous system revealed a degenerative pattern of neurons, and a hyperplastic (or binucleated) aspect of the microglial cells, morphologically similar to Alzheimer type II astrocytes, clinical conditions seen in liver encephalopathy. H&E, scale bar ¼ 150 μm. H&E, hematoxylin and eosin.
report. As previously stated, the histopathology results of the red-tailed boa showed extensive necrotic degeneration of the liver, with hepatocytic centrilobular organization and cholestasis (Fig. 4), and a degenerative pattern of neurons together with a hyperplastic (or binucleated) aspect of the microglial cells, morphologically similar to Alzheimer type II astrocytes (Fig. 5). The postmortem examination results indicate that the neurological signs were a consequence of hepatic encephalopathy (HE). Reptiles with hepatic disease may show a wide variety of clinical signs. Lethargy, chronic anorexia, weight loss, and gastrointestinal and neurological signs are common. The last stage of liver disease often results in HE. Clinical signs of HE are extremely variable (e.g., circling, weakness, ataxia, ptyalism, seizures, and coma). The pathophysiology of HE is not completely known. Hazell and Butterworth28 proposed a synergistic effect involving liver failure and ammonia detoxification, increased cerebral inflammatory proteins, impaired brain perfusion with development of astrocytes swelling, and neuronal edema. Chen et al.29 propose an alteration of CNS functions during HE due to dendritic morphology remodeling of cortical and hippocampal pyramidal neurons. Reduction of the dendritic spine density causes an increase of the motor evoked potential threshold and a prolonged central motor conduction time. Hematology of the HE affected patient often shows anemia, heterophilia and monocytosis. Biochemistries frequently reveal high values of aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, alanine
Giuseppe et al./Journal of Exotic Pet Medicine 26 (2017), pp 96–100
aminotransferase, and lactate dehydrogenase, but none of these analytes are truly liver-specific enzymes in reptiles. Bile acids may eventually prove to be a promising hepatic marker.30 Diagnostic imaging techniques are also clinically useful to detect changes in size or appearance of the liver. An endoscopically obtained tissue biopsy sample is considered as a useful diagnostic tool to diagnose liver disease.31 Prognosis of the patient exhibiting clinical signs of HE is guarded at best. Recommended treatment for snakes that are diagnosed with HE involves fluid administration (avoidance of solutions that contain lactate), along with more specific hepatic therapeutic agents. Carnitine (250 mL/kg orally) is a derivate of the amino acid lysine, which is involved in the transport of the acetyl coenzyme A through the cellular membrane of the hepatocyte.31,32 Lactulose is commonly used in treating hyperammonemia, which is believed to be one of the underlying causes of HE. Lactulose (0.5 mL/kg orally) is fermented by the gut flora into metabolites that acidify the colon. An acidic environment turns freely diffusible ammonia (NH3) into ammonium (NHþ 4 ), which can no longer be absorbed.33-35 Silymarin (milk thistle) has a long history of use in the treatment of liver disease, predominantly in controlling inflammation and limiting uptake of toxins. In the human patient, silymarin exerts membrane stabilizing and antioxidant activity and promotes hepatocyte regeneration; furthermore, it reduces the inflammatory reaction and inhibits fibrogenesis in the liver.36 The use of silymarin to treat HE in reptiles appears to be promising. REFERENCES 1. Diemer NH, Klinken L: Astrocyte mitoses and Alzheimer type I and II astrocytes in anoxic encephalopathy. Neuropathol Appl Neurobiol 2:313-321, 1976 2. Craig LE, Wolf JC, Ramsay EC: Spinal cord glioma in a ridge-nosed rattlesnake (Crotalus willardi). J Zoo Wild Med 36:313-315, 2005 3. Done L: Neurological disorders, in Mader D (ed): Reptile Medicine and Surgery. St. Louis, MO, Elsevier/Saunders, pp 852-857, 2006 4. Gyimesi SS, Garner MM: Pituitary adenoma in a Dumeril's ground boa, Acrantophis dumerili. J Herpetol Med Surg 17: 16-18, 2007 5. Cole GA, Rao DB, Steinberg H: Suspected vitamin E and selenium deficiency in a veiled chameleon (Chameleo calyptratus). J Herpetol Med Surg 18:113-116, 2008 6. Anderson ET, Troan BV, Stringer EM: Cerebral xanthoma in a long-nosed snake (Rhinocheilus lecontei). J Herpetol Med Surg 20:58-60, 2010 7. Wyneken J: Reptilian neurology: anatomy and function. Vet Clin North Am Exot Anim Pract 10:837-853, 2007
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