A 4-year-old 45.3-kg (99.7-lb) castrated male Labrador Retriever that had undergone right and left tibial plateau leveling osteotomies (TPLOs) at 7 and 4.5 months prior to the evaluation, respectively, was evaluated. The right TPLO healed without complications. At the left TPLO site, infection with methicillin-resistant Staphylococcus pseudintermedius (susceptible to chloramphenicol and amikacin) and draining tracts developed. Treatment with chloramphenicol was initiated. The left implant was removed approximately 12 weeks after placement because of osteomyelitis at the TPLO site; 2 fractured screws remained embedded in the bone. Chloramphenicol treatment was continued because of persistent draining tracts owing to S pseudintermedius infection. Three months after starting chloramphenicol treatment, the dog developed neurologic signs.
What is the problem? Where is the lesion? What are the most probable causes of this problem? What is your plan to establish a diagnosis? Please turn the page.
Assessment Anatomic diagnosis
| Problem | Â |
|---|---|
| Left facial drooping and absent left palpebral reflex | Â |
| Right hind limb monoparesis | Â |
Likely location of 1 lesion
Given the combination of the cranial nerve abnormalities and right pelvic limb monoparesis, there was concern for a multifocal CNS lesion or peripheral neuropathy.
Etiologic diagnosis—The differential diagnoses for the dog's neurologic abnormalities were a peripheral neuropathy or multifocal CNS lesions. Possible causes for multifocal CNS lesions included inflammatory, infectious, immune-mediated, paraneoplastic, or degenerative disease or neoplasia. Possible causes for peripheral neuropathy included inflammatory, metabolic, or degenerative disease; toxin exposure; infectious disease (neosporosis, toxoplasmosis, or, less likely, bacterial infection); or neoplasia.
A CBC and serum biochemical analyses were recommended. Radiography of the thorax, lumbar portion of the vertebral column, pelvis, and stifle joints was recommended to rule out gross abnormalities of the vertebral column and the TPLO sites. Magnetic resonance imaging of the brain, thoracic spinal segments, and lumbar spinal segments was performed. Brain MRI sequences included sagittal and axial T2-weighted images; axial fluid attenuation inversion recovery, fast field echo (gradient echo), diffusion-weighted, and apparent diffusion coefficient map images; and pre- and postcontrast sagittal, coronal (dorsal), and axial T1- and T2-weighted images. For the thoracic spinal segment MRI sequences, sagittal T2-weighted images were obtained. For the lumbar spinal segment MRI sequences, sagittal and axial (L4-S3 vertebrae) T2-weighted images; sagittal STIR images; and pre- and postcontrast sagittal, axial (L4-S3 vertebrae), and dorsal T1-weighted images were obtained.
Collection of a CSF sample following MRI was recommended. Electromyography was also recommended to determine the functional capacity of the spinal cord segments, nerve roots, muscles, and peripheral nerves.
Diagnostic test findings—Results of a CBC were consistent with mild anemia (Hct, 32.3%; reference range, 37.3% to 61.7%), neutrophilia (12.3 × 103 neutrophils/μL; reference range, 2.95 × 103 neutrophils/μL to 11.64 × 103 neutrophils/μL), and monocytosis (1.15 × 103 monocytes/μL; reference range, 0.16 × 103 monocytes/μL to 1.12 × 103 monocytes/μL). Serum biochemical analyses revealed high concentrations of BUN (28 mg/dL; reference range, 7 to 27 mg/dL) and globulins (4.6 g/dL; reference range, 2.5 to 4.5 g/dL), and high activities of alkaline phosphatase (1,581 U/L; reference range, 23 to 212 U/L) and creatine kinase (674 U/L; reference range, 10 to 200 U/L).
Radiography of the thorax and lumbar portion of the vertebral column revealed no abnormalities. Radiographically, the right pelvic limb had a healed TPLO site with a static implant; the left pelvic limb had 2 fractured screws embedded in the proximal portion of the tibia. A new sagittal fracture through the left proximal tibial segment with displacement of the segment laterally was noted. There was evidence of persistent osteomyelitis at the left osteotomy site.
Results of the electromyographic examinationa were considered normal. A nerve conduction study was not performed. The MRIb appearances of the brain and thoracic and lumbar portions of the vertebral column were structurally normal. A small amount of fluid was evident in the right frontal sinus and nasal cavity, and it was hyperintense on T2-weighted and T1-weighted pre- and postcontrast images. There was no evidence of turbinate destruction, and the fluid was suspected to be mucus. A CSF sample was collected from the cerebellomedullary cistern for analysis, the results of which were unremarkable.
The testing performed did not provide a definitive diagnosis for the neurologic abnormalities. Infectious disease testing (for neosporosis and toxoplasmosis) was considered but not performed at the time of evaluation. In humans,1–4 chloramphenicol administration is known to cause peripheral neuropathies; given the dog's history, a tentative diagnosis of peripheral neuropathy attributable to chloramphenicol toxicosis was made.
Comments
For the dog of the present report, chloramphenicol administration was discontinued because of the tentative diagnosis of a chloramphenicol-induced peripheral neuropathy. Artificial tear lubrication every 6 to 8 hours was initiated in the left eye.
On recheck examination 5 days later, the dog had normal cranial nerve functions. The dog's condition had improved but it still required sling assistance to stand and walk. The dog was ambulatory on 3 limbs and continued to be non–weight bearing in the left pelvic limb secondary to severe orthopedic disease. For the right pelvic limb, proprioception was normal and motor function was strong. For the left pelvic limb, proprioception was difficult to assess, and motor function was weak because of the presence of orthopedic disease. The draining tract on the medial aspect of the left stifle region had developed a 4-cm-long, ovoid, moist, red swelling since discontinuation of chloramphenicol treatment.
Amputation of the left pelvic limb or treatment of the TPLO site infection with amikacin was discussed with the owners as continued treatment options. The owners elected to pursue treatment of the infection. Administration of amikacin (15 mg/kg [6.8 mg/lb], SC, q 24 h) for 7 days was initiated. Resolution of the draining tract on the medial aspect of the left stifle region was noted, and an additional 7-day course of amikacin treatment (at the same dosage) was undertaken. The draining tract had completely resolved at a recheck examination 1 week after the second course of amikacin was complete. During this treatment course, the dog's neuropathy continued to improve and it was able to bear weight on the right pelvic limb although severe muscle atrophy was apparent; muscle atrophy in the left pelvic limb was more severe. The dog still required sling assistance to stand and walk, and it had also developed mild fecal incontinence. The fecal incontinence was suspected to be related to the peripheral neuropathy.
Three weeks after initial evaluation of the neurologic clinical signs, the owners took the dog to a rehabilitation center to start physical therapy. The dog underwent acupuncture and a photobiomodulation (laser) regimen. Given that the draining tract had resolved, underwater treadmill exercise was initiated. The dog responded well to physical therapy and was able to stand and move without assistance within 1 month. Although it was still weak in the left pelvic limb, the dog's motor function had improved. On follow-up examination 3 months after the start of physical therapy, the dog was ambulatory and its activity level had returned to normal. The left pelvic limb continued to have minor deficits, and mild intermittent fecal incontinence was still present. At the dog's annual examination 4 months after the follow-up visit (a total of 8 months after development of neurologic clinical signs), it had continued mild ataxia and intermittent fecal incontinence. Whether the left pelvic limb deficits were attributable to severe orthopedic disease or neurologic disease could not be determined conclusively.
Anecdotal evidence and 1 retrospective study5 have implicated chloramphenicol administration as a cause of pelvic limb weakness in dogs. In that study,5 14 of 39 (36%) dogs evaluated had evidence of pelvic limb weakness. Of the 14 dogs that developed pelvic limb weakness, 6 (42%) had resolution of clinical signs once chloramphenicol administration was discontinued or the course of treatment was completed.5 In the dogs that developed pelvic limb weakness, weight was found to be a significant factor, unlike dogs that developed gastrointestinal adverse effects (vomiting, drooling, anorexia, gagging, diarrhea, or any combination of these signs) or no adverse effects. Dogs that developed pelvic limb weakness had a mean body weight of 35.4 kg (77.9 lb). The dog of the present report weighed 45.3 kg and its chloramphenicol dosage was based on that weight.
Optic neuritis with accompanying peripheral neuropathy is a known adverse effect of chloramphenicol administration in people.6 The cause of the neuropathy is unknown, and treatment of affected humans includes discontinuation of the chloramphenicol treatment and administration of large doses of vitamins B12 and B6.6 The dog of the present report did not receive vitamins B12 and B6. It is possible that administration of vitamins B12 and B6 may be a valid treatment option for veterinary patients with chloramphenicol-induced peripheral neuropathy.
Chloramphenicol administration is increasing in popularity because of the increasing number of multidrug-resistant bacterial infections7 encountered in veterinary medicine. The case described in the present report is of clinical importance because chloramphenicol-induced peripheral neuropathy in dogs has not been previously reported, to the author's knowledge. Awareness of this possible chloramphenicol-related adverse effect may affect antimicrobial selection for dogs that weigh ≥ 35 kg (77 lb) and have infections with chloramphenicol-susceptible organisms.
Acknowledgments
The author thanks Drs. Karyn Maxworthy and Adam Moeser for performing the medical workup and providing editorial input.
Footnotes
Neuropack MEB-9102 EP/EMG Measuring System, Nihon Kohden, Irvine, Calif.
1.5-T MRI Gyroscan Compact Plus, Koninklijke Philips, Netherlands.
References
1. Godel V, Nemert P, Lazar M. Chloramphenicol optic neuropathy. Arch Ophthalmol 1980;98:1417–1421.
2. Cocke JG Jr. Chloramphenicol optic neuritis. Am J Dis Child 1967;114:424–426.
3. Cocke JG Jr, Brown RE, Geppert LJ. Optic neuritis with prolonged use of chloramphenicol. J Pediatr 1966;68:27–31.
4. Lasky MA, Pincus MH. Bilateral optic neuritis following chloramphenicol therapy. JAMA 1953;151:1403–1404.
5. Short J, Zabel S, Cook C, et al. Adverse events associated with chloramphenicol use in dogs: a retrospective study (2007–2013). Vet Rec 2014;175:537.
6. Wiest DB, Cochran JB, Tecklenburg FW. Chloramphenicol toxicity revisited: a 12 year old patient with a brain abscess. J Pediatr Pharmacol Ther 2012;17:182–188.
7. Bryan J, Frank LA, Rohrbach BW. Treatment outcome of dogs with methicillin-resistant and methicillin-susceptible Staphylococcus pseudintermedius pyoderma. Vet Dermatol 2012;23:361–368.
