A4.5-year-old neutered male domestic ferret (Mustela putorius furo) was examined because of a 15-day history of anorexia, generalized weakness, and exercise intolerance. The animal lived indoors and was fed a commercially available dry diet formulated for ferrets. Routine vaccinationa had been performed a few days prior to the onset of clinical signs. On initial examination, the ferret was bright, alert, and in good body condition. Results of physical and neurologic examinations were unremarkable. When the animal was allowed to walk freely around the examination room, it initially displayed a normal gait and normal exploratory behavior. After a few seconds, however, generalized weakness became evident and rapidly progressed to nonambulatory tetraparesis. The ferret remained in sternal recumbency and was reluctant to move. Cervical ventroflexion was also observed, and the ferret was unable to maintain a normal head carriage. On repeated neurologic examination, hopping and muscle tone were decreased in all limbs. Withdrawal reflexes were mildly decreased in all limbs. Patellar reflexes were normal bilaterally, and mental status and results of cranial nerve examination were normal. There was no evidence of pain during palpation of the vertebral column or on flexion and extension of the head and neck. Results of hematologic testing, serum biochemical analyses, and abdominal and thoracic radiography were unremarkable, and a neuromuscular disorder was suspected.
General anesthesia was induced and maintained through administration of isoflurane by mask, and electrophysiologic assessment was performed with a portable electrodiagnostic machine.b Body temperature was maintained at > 37°C (98.6°F) during the examination. Electromyography was performed with an intramuscular, concentric needle electrode and sub-dermal, monopolar ground electrode. Electromyography revealed normal insertional activity and normal resting activity in all tested muscles. The distal and proximal compound muscle action potentials for the right sciatic-tibial nerve were recorded and were not reduced, compared with published values1 (26.5 and 16.6 mV, respectively; mean ± SD reference values, 10.79 ± 2.75 mV and 13.02 ± 3.41 mV, respectively). The motor nerve conduction velocity was calculated for this nerve and was found to be slightly decreased, compared with published values1 (53 m/s; mean ± SD reference value, 63.25 ± 7.56 m/s). This finding was considered to be clinically unimportant because of the relatively small number of individuals on which the reference value was based.1 Supramaximal repetitive nerve stimulation induced decrements in amplitude and area of compound muscle action potentials of 45% and 41% (mean ± SD reference values,1 0.3 ± 3.83% and 0.1 ± 3.51%, respectively, at 2 Hz; Figure 1). Findings were consistent with a presumptive diagnosis of MG. To further investigate, a single dose of neostigmine methylsulfate (0.04 mg/kg [0.018 mg/lb], IV) was administered once the ferret had recovered from general anesthesia. The clinical status of the animal improved markedly after the drug was administered, with effects lasting approximately 4 to 6 hours, as reported by the ferret's owner. Serologic testing for AChR antibodies was performed at the Comparative Neuromuscular Laboratory of the University of California–San Diego. The result was strongly positive (1.4 nmol/L; previously published value for healthy ferrets,2 < 0.06 nmol/L). On the basis of these results, a diagnosis of acquired MG was made, and treatment was started with pyridostigminec (1 mg/kg [0.45 mg/lb], PO, q 12 h) and prednisoloned (0.8 mg/kg [0.36 mg/lb], PO, q 12 h).
Two weeks later, the ferret was reexamined. No clinical improvement had been noted by the owners since the onset of treatment. However, the treatment was well tolerated, and only a few episodes of mild diarrhea had been observed. The animal also had had continuous mild body tremors since the onset of treatment. Clinical and neurologic examinations revealed persistent marked exercise intolerance, and the owners were advised to administer pyridostigmine and prednisolone 3 times daily, rather than twice daily. Esomeprazolee (1.5 mg/kg [0.68 mg/lb], PO, q 24 h) was added to the treatment regimen because of adverse gastrointestinal effects.
Approximately 2 months after treatment had been initiated, the owners observed the first signs of improvement. The ferret was able to leave its cage and walk around following administration of pyridostigmine; however, the effect of the drug lasted only approximately 30 minutes. Treatment was maintained unchanged.
A follow-up examination was performed 10 months after the onset of treatment. At that time, the owner reported better exercise tolerance, and physical examination revealed a marked improvement in the ferret's clinical status. The ferret was able to walk around the examination room without evident weakness, and only mild generalized tremors persisted. Follow-up serologic testing for AChR antibodies was performed, and the titer (0.08 nmol/L) was substantially lower, compared with the initial value. In view of the clinical improvement and decreased AChR antibody titer, the prednisolone dosage was tapered over the next 4 months, followed by discontinuation of pyridostigmine administration. No clinical signs of relapse were observed, and a follow-up AChR antibody titer measured after treatment was discontinued (0.01 nmol/L) was low. Thirty months after initial examination, the ferret was reportedly healthy and not receiving any medications.
No third-party funding or support was received in connection with this study or the writing or publication of the manuscript. The authors declare that there were no conflicts of interest.
Canigen CHPPi, Virbac, Carros Cedex, France.
Nicolet Viking Quest, Natus Medical Inc, San Carlos, Calif.
Mestinon, Meda Pharma GmbH, Wangen-Bruttisellen, Switzerland.
Microsolone, Merial, Lyon, France.
Inexium, AstraZeneca, Courbevoie, France.
Shelton GD, Joseph R, Richter K, et al. Acquired myasthenia gravis in hyperthyroid cats on Tapazole therapy (abstr), in Proceedings. 15th Annu Meet Am Coll Vet Intern Med. J Vet Intern Med 1997;11:120.
1. Bianchi E, Callegari D, Ravera M, et al. Electrodiagnostic examination of the tibial nerve in clinically normal ferrets. Vet Med Int 2010;2010:756321.
2. Couturier J, Huynh M, Boussarie D, et al. Autoimmune myasthenia gravis in a ferret. J Am Vet Med Assoc 2009;235:1462–1466.
3. Shelton GD. Myasthenia gravis and disorders of neuromuscular transmission. Vet Clin North Am Small Anim Pract 2002;32:189–206.
5. Hague DW, Humphries HD, Mitchell MA, et al. Risk factors and outcomes in cats with acquired myasthenia gravis (2001–2012). J Vet Intern Med 2015;29:1307–1312.
6. Dewey CW, Bailey CS, Shelton GD, et al. Clinical forms of acquired myasthenia gravis in dogs: 25 cases (1988–1995). J Vet Intern Med 1997;11:50–57.
7. Lewis RM, Picut CA. Neuromuscular disorders. In: Lewis RM, Preut CA, eds. Veterinary clinical immunology: from classroom to clinics. Philadelphia: Lea & Febiger, 1989;104–120.
10. Taylor SM. Selected disorders of muscle and the neuromuscular junction. Vet Clin North Am Small Anim Pract 2000;30:59–75.
11. Bell ET, Mansfield CS, James FE. Immune-mediated myasthenia gravis in a methimazole-treated cat. J Small Anim Pract 2012;53:661–663.
12. Shelton GD, Lindstrom JM. Spontaneous remission in canine myasthenia gravis: implications for assessing human MG therapies. Neurology 2001;57:2139–2141.
13. Dewey CW, Shelton GD, Bailey CS, et al. Neuromuscular dysfunction in five dogs with acquired myasthenia gravis and presumptive hypothyroidism. Prog Vet Neurol 1995;6:117–123.
15. Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol 2015;14:1023–1036.
16. Aronsohn MG, Schunk KL, Carpenter JL, et al. Clinical and pathologic features of thymoma in 15 dogs. J Am Vet Med Assoc 1984;184:1355–1362.
17. Klebanow ER. Thymoma and acquired myasthenia gravis in the dog: a case report and review of 13 additional cases. J Am Anim Hosp Assoc 1992;28:63–69.
18. Sims MH, McLean RA. Use of repetitive nerve stimulation to assess neuromuscular function in dogs. A test protocol for suspected myasthenia gravis. Prog Vet Neurol 1990;1:311–319.
19. Shelton GD. Treatment of autoimmune myasthenia gravis. In: Bonagura JD, Twedt DC, eds. Kirk's current veterinary therapy XIV. St Louis: Elsevier/Saunders, 2009;1108–1111.
20. Skeie GO, Apostolski S, Evoli A, et al. Guidelines for treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol 2010;17:893–902.
21. Shelton GD. Routine and specialized laboratory testing for the diagnosis of neuromuscular diseases in dogs and cats. Vet Clin Pathol 2010;39:278–295.