What Is Your Neurologic Diagnosis?

Charlotte B. Pfund VCA Animal Specialty Group-San Diego, San Diego, CA

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 DVM
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Vanessa Biegen VCA Animal Specialty Group-San Diego, San Diego, CA

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 DVM, DACVIM
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Thomas H. Boyer Pet Hospital of Penasquitos, San Diego, CA

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Jonathan Hayles Boneyard Veterinary Imaging Inc, San Diego, CA

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 DVM, MS, DACVR

Introduction

A 12-year-old 5.66-kg male green iguana (Iguana iguana) was referred with a history of left hind limb monoparesis and recurrent squamous cell carcinoma of the right hind limb femoral pores. A right hind limb mass had been first noticed 11 months earlier, and the referring veterinarian had surgically removed it twice, with the most recent surgery having been performed 1.5 months earlier. For both procedures, anesthesia had been induced with alfaxalone (10 mg/kg, IM) and maintained with isoflurane, and enrofloxacin (11 mg/kg, SC) had been administered. Histologic examination of removed tissues indicated that the mass was a squamous cell carcinoma, and bacterial culture indicated that it was secondarily infected with Enterococcus faecalis and a methicillin-resistant strain of Staphylococcus haemolyticus. Each time, the tumor had been incompletely excised, with neoplastic cells extending to multiple margins. After the second surgery, the patient had monoparesis of the left hind limb with knuckling and an inability to push off with the foot. At the time of presentation, the patient was receiving meloxicam (0.2 mg/kg, PO, q 24 h) for analgesia.

Assessment

Anatomic diagnosis

Pain sensation of the left hind limb was intact medially (femoral nerve) but absent laterally (tibial and peroneal branches of the sciatic nerve), suggesting a lesion involving the tibial and peroneal branches of the sciatic nerve. The absent withdrawal reflex at the level of the hock joint and the left hind limb monoparesis with intact motor activity in the hip and stifle regions but absent distally were both suggestive of a lesion involving the common peroneal nerve.

Likely location of a single lesion

Findings were suggestive of midsciatic nerve dysfunction (most likely, common peroneal and tibial nerve dysfunction) with preservation of more proximal sciatic nerve function.

Etiologic diagnosis

Important differential diagnoses for a sudden onset of monoparesis localizing to branches of the sciatic nerve included iatrogenic injury (IM or SC injection), neoplasia (metastasis of the squamous cell carcinoma or a primary tumor of the nerve such as a peripheral nerve sheath tumor), neuritis (immune-mediated or infectious), paraneoplastic disease, and degenerative disease. An anesthetic-related vascular event was considered unlikely because results of the neurologic examination were consistent with a peripheral neurolocalization rather than a central myelopathy.

Diagnostic Plan

The diagnostic plan included a serum biochemical profile, whole-body radiography with focused imaging of the pelvis, and CT of the pelvis and pelvic limbs with the iguana anesthetized (Figure 1).

Figure 1
Figure 1
Figure 1

Coronal (A) and axial (B) postcontrast (iohexol) CT images of the pelvic limbs of a 12-year-old green iguana (Iguana iguana) with a peracute onset of left hind limb monoparesis. Images are displayed in a soft tissue algorithm. A heterogeneously contrast-enhancing, soft tissue–attenuating mass is seen dissecting between the caudal thigh muscles in the midportion of the left thigh (black arrows). Additionally, a large, heterogeneously contrast-enhancing, soft tissue–attenuating mass of the proximocaudal aspect of the right thigh, consistent with recurrent squamous cell carcinoma (white arrows), can be seen.

Citation: Journal of the American Veterinary Medical Association 260, 9; 10.2460/javma.21.01.0013

Diagnostic Test Findings

Results of the serum biochemical panel were unremarkable. Radiography revealed normal osseous structures other than mild spondylosis of the thoracic and cranial tail vertebrae. No fractures or lytic changes to the bones were seen, making ongoing local invasion of osseous structures less likely. Irregularity of the musculature in the caudal aspect of the right hind limb consistent with previous surgical excision of the mass and subsequent healing was also noted.

For CT, the patient was anesthetized with propofol (10 mg/kg, IV); an endotracheal tube was placed, and anesthesia was maintained with isoflurane. Transverse CT images (0.5-mm slice thickness) were obtained before and after administration of contrast medium (iohexol; 640 mg/kg, IV), and sagittal and dorsal reconstructions were prepared.

Computed tomography revealed a heterogeneously contrast-enhancing, soft tissue–attenuating mass dissecting between the caudal thigh muscles in the midportion of the left thigh. Differential diagnoses consisted of neoplasia (eg, a metastatic lesion of the primary right thigh tumor or a novel neoplastic lesion such as a peripheral nerve sheath tumor or vascular tumor), abscess (sterile or infectious), granuloma (sterile or infectious), injection site reaction, and hematoma. Invasion or compression of the left sciatic nerve by the mass was considered the most likely cause of the neurologic deficits in this limb. Although electromyography has been reported to be a useful tool to assess the extent of peripheral nerve injuries,1 it was not performed in this case.

Another pertinent finding was a large, heterogeneously contrast-enhancing, soft tissue–attenuating mass of the proximocaudal aspect of the right thigh, consistent with recurrent squamous cell carcinoma. Subtle mass invasion into the adjacent thigh musculature was possible.

Detection of the soft tissue mass in the left caudal thigh musculature prompted fine-needle aspiration. The mass was easily palpable, as it was harder than the surrounding tissues. Cytologic examination of 6 aspirate specimens showed primarily RBCs, macrophages, ghost nuclei, and a few multinucleate giant cells; no bacteria were seen. Findings were consistent with a sterile granuloma, with an injection site reaction suspected primarily on the basis of the peracute onset of signs after a reported injection.2 Other possible differential diagnoses included a foreign body reaction, cutaneous xanthoma, immune-mediated disease, and idiopathic causes.3,4

Treatment

Treatment of the patient proved to be difficult because both hind limbs were affected, although by different disease processes. To effectively excise the squamous cell carcinoma of the right hind limb, margins of 2 cm would have been necessary. This would have included all of the caudal thigh muscles and a portion of the femur and was not considered practical. A more reasonable approach would have been amputation of the right hind limb; however, the neurologic deficits in the left hind limb prevented consideration of this option.

The recommendation for the patient, therefore, was radiation therapy to treat the squamous cell carcinoma of the right hind limb and, ideally, preserve the limb while the left hind limb was monitored for neurologic improvement. The owner followed up with a veterinary oncologist who specialized in radiation therapy but ended up not following through with treatment because of a decline in the patient’s condition. The squamous cell carcinoma had grown from 4.4 X 2.5 cm to 6 X 6 cm in 2 months.

Comments

Peripheral nerves convey signals with the use of axons, and non-neuronal cells and connective tissues that surround the axons provide a complex connective tissue structure that is important in understanding and classifying nerve injuries. Myelinated nerves have axons encased with Schwann cells to improve conduction velocity. Individual axons are encased in endoneurium, the deepest structural layer. This is surrounded by perineurium, which bundles axons to form fascicles. The outermost layer is the epineurium.

Various types of nerve injuries can be differentiated as neurapraxia, axonotmesis, and neurotmesis (classification after Seddon) or classified as grades I through V (classification after Sunderland). Depending on the severity of the injury and the specific parts of the nerve that are affected, the prognosis for return of function varies greatly. Neurapraxia (grade I) is defined by focal segmental demyelination without damage to the axons themselves or the connective tissues. It typically occurs as a result of mild compression or traction of the nerve. Axonotmesis (grades II through IV) involves direct damage to the axons in addition to focal demyelination, with continuity of the nerve’s connective tissues maintained. Neurotmesis (grade V) is the most severe form of injury and indicates complete transaction of the axons and connective tissue layers, resulting in complete discontinuity of the nerve.5

During recovery from peripheral nerve injuries, the return of motor and sensory function can be graded with the Medical Research Council grading system from M0 to M5 (for motor function) and S0 to S4 (for sensory function), with higher grades representing better function. General prognostic indicators in human medicine are age of the patient (with young patients generally having a better prognosis) and early surgical repair.6 In a study7 involving human patients, 63.6% had a partial or complete recovery after sustaining a postinjection sciatic nerve injury. The most common causes of postinjection sciatic nerve injury were analgesic and antimicrobial injections, and the onset of signs was immediate in 90.9% of cases.7 Although peripheral nerve injuries can be managed nonsurgically with medications, electrical stimulation, and phytochemicals,8 the outcome of iatrogenic sciatic nerve injury after IM injection has been described as poor without surgical intervention.1 Monitoring for regeneration of peripheral nerve function can be done by frequently assessing sensibility, pain, and motor function; physiotherapy has been described to aid in recovery.9

It is generally recommended that IM injections in iguanas and lizards be given in the triceps musculature of the forelimbs. Owing to the renal-portal system in these animals, injections in the hind limb musculature are metabolized differently and can potentially be dangerous.10

Injection reactions after IM or SC injection in reptiles have been described previously.11,12 Administering enrofloxacin IM or SC has been reported to cause pain, inflammation, and necrosis at the injection site.11,12 The necrosis is caused by the high pH (10) of the drug, and dilution is ineffective for practical applications. Experimental IM injection of 2.27% enrofloxacin in striped bass is associated with severe hemorrhage, necrosis, and inflammation.13

Findings for the iguana of the present report should serve as a reminder for clinicians to carefully administer medications and consider injection reactions as a differential diagnosis for local neurologic signs. Our findings also illustrate that neurologic examination of nonmammalian species is possible and that a thorough neurologic examination can accurately identify the location of a lesion.

References

  • 1.

    Forterre F, Tomek A, Rytz U, Brunnberg L, Jaggy A, Spreng D. Iatrogenic sciatic nerve injury in eighteen dogs and nine cats (1997–2006). Vet Surg. 2007;36(5):464471. doi:10.1111/j.1532-950X.2007.00293.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Wiedmeyer CE, Fangman TJ, Schwartz K, Payne B. Fine-needle aspiration and cytology as an antemortem method for evaluating injection-site lesions. J Swine Health Prod. 2014;22(5):244247.

    • Search Google Scholar
    • Export Citation
  • 3.

    Santoro D, Prisco M, Ciaramella P. Cutaneous sterile granulomas/pyogranulomas, leishmaniasis and mycobacterial infections. J Small Anim Pract. 2008;49(11):552561. doi:10.1111/j.1748-5827.2008.00638.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Garner MM, Lung NP, Murray S. Xanthomatosis in geckos: five cases. J Zoo Wildl Med. 1999;30(3):443447.

  • 5.

    Menorca RM, Fussell TS, Elfar JC. Nerve physiology: mechanisms of injury and recovery. Hand Clin. 2013;29(3):317330. doi:10.1016/j.hcl.2013.04.002

  • 6.

    Lee SK, Wolfe SW. Peripheral nerve injury and repair. J Am Acad Orthop Surg. 2000;8(4):243252.

  • 7.

    Maqbool W, Sheikh S, Ahmed A. Clinical, electrophysiological, and prognostic study of postinjection sciatic nerve injury: an avoidable cause of loss of limb in the peripheral medical service. Ann Indian Acad Neurol. 2009;12(2):116119. doi:10.4103/0972-2327.53081

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Hussain G, Wang J, Rasul A, et al. Current status of therapeutic approaches against peripheral nerve injuries: a detailed story from injury to recovery. Int J Biol Sci. 2020;16(1):116134. doi:10.7150/ijbs.35653

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Rayner MLD, Brown HL, Wilcox M, Phillips JB, Quick TJ. Quantifying regeneration in patients following peripheral nerve injury. J Plast Reconstr Aesthet Surg. 2020;73(2):201208. doi:10.1016/j.bjps.2019.10.007

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Prezant RM, Jarchow JL. Indications and applications of clinical techniques in the green iguana. Semin Avian Exot Pet Med. 1997;6(2):6374. doi:10.1016/S1055-937X(97)80013-8

    • Search Google Scholar
    • Export Citation
  • 11.

    Fitzgerald KT, Martinez-Silvestre A. Toxicology. In: Divers SJ, Stahl SJ, eds. Mader’s Reptile and Amphibian Medicine and Surgery. 3rd ed. Elsevier; 2019:980.

    • Search Google Scholar
    • Export Citation
  • 12.

    Perry SM, Mitchell MA. Antibiotic therapy. In: Divers SJ, Stahl SJ, eds. Mader’s Reptile and Amphibian Medicine and Surgery. 3rd ed. Elsevier; 2019:1153.

    • Search Google Scholar
    • Export Citation
  • 13.

    Scott G, Law M, Christiansen EF, Lewbart GA, Harms CA. Evaluation of localized inflammatory reactions secondary to intramuscular injections of Enrofloxacin in striped bass (Morone saxatilis). J Zoo Wildl Med. 2020;51(1):4652. doi:10.1638/2019-0096

    • PubMed
    • Search Google Scholar
    • Export Citation

Contributor Notes

Corresponding author: Dr. Pfund (pfund.charlotte@gmail.com)

In collaboration with the American College of Veterinary Internal Medicine

  • Figure 1

    Coronal (A) and axial (B) postcontrast (iohexol) CT images of the pelvic limbs of a 12-year-old green iguana (Iguana iguana) with a peracute onset of left hind limb monoparesis. Images are displayed in a soft tissue algorithm. A heterogeneously contrast-enhancing, soft tissue–attenuating mass is seen dissecting between the caudal thigh muscles in the midportion of the left thigh (black arrows). Additionally, a large, heterogeneously contrast-enhancing, soft tissue–attenuating mass of the proximocaudal aspect of the right thigh, consistent with recurrent squamous cell carcinoma (white arrows), can be seen.

  • 1.

    Forterre F, Tomek A, Rytz U, Brunnberg L, Jaggy A, Spreng D. Iatrogenic sciatic nerve injury in eighteen dogs and nine cats (1997–2006). Vet Surg. 2007;36(5):464471. doi:10.1111/j.1532-950X.2007.00293.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Wiedmeyer CE, Fangman TJ, Schwartz K, Payne B. Fine-needle aspiration and cytology as an antemortem method for evaluating injection-site lesions. J Swine Health Prod. 2014;22(5):244247.

    • Search Google Scholar
    • Export Citation
  • 3.

    Santoro D, Prisco M, Ciaramella P. Cutaneous sterile granulomas/pyogranulomas, leishmaniasis and mycobacterial infections. J Small Anim Pract. 2008;49(11):552561. doi:10.1111/j.1748-5827.2008.00638.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Garner MM, Lung NP, Murray S. Xanthomatosis in geckos: five cases. J Zoo Wildl Med. 1999;30(3):443447.

  • 5.

    Menorca RM, Fussell TS, Elfar JC. Nerve physiology: mechanisms of injury and recovery. Hand Clin. 2013;29(3):317330. doi:10.1016/j.hcl.2013.04.002

  • 6.

    Lee SK, Wolfe SW. Peripheral nerve injury and repair. J Am Acad Orthop Surg. 2000;8(4):243252.

  • 7.

    Maqbool W, Sheikh S, Ahmed A. Clinical, electrophysiological, and prognostic study of postinjection sciatic nerve injury: an avoidable cause of loss of limb in the peripheral medical service. Ann Indian Acad Neurol. 2009;12(2):116119. doi:10.4103/0972-2327.53081

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Hussain G, Wang J, Rasul A, et al. Current status of therapeutic approaches against peripheral nerve injuries: a detailed story from injury to recovery. Int J Biol Sci. 2020;16(1):116134. doi:10.7150/ijbs.35653

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Rayner MLD, Brown HL, Wilcox M, Phillips JB, Quick TJ. Quantifying regeneration in patients following peripheral nerve injury. J Plast Reconstr Aesthet Surg. 2020;73(2):201208. doi:10.1016/j.bjps.2019.10.007

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Prezant RM, Jarchow JL. Indications and applications of clinical techniques in the green iguana. Semin Avian Exot Pet Med. 1997;6(2):6374. doi:10.1016/S1055-937X(97)80013-8

    • Search Google Scholar
    • Export Citation
  • 11.

    Fitzgerald KT, Martinez-Silvestre A. Toxicology. In: Divers SJ, Stahl SJ, eds. Mader’s Reptile and Amphibian Medicine and Surgery. 3rd ed. Elsevier; 2019:980.

    • Search Google Scholar
    • Export Citation
  • 12.

    Perry SM, Mitchell MA. Antibiotic therapy. In: Divers SJ, Stahl SJ, eds. Mader’s Reptile and Amphibian Medicine and Surgery. 3rd ed. Elsevier; 2019:1153.

    • Search Google Scholar
    • Export Citation
  • 13.

    Scott G, Law M, Christiansen EF, Lewbart GA, Harms CA. Evaluation of localized inflammatory reactions secondary to intramuscular injections of Enrofloxacin in striped bass (Morone saxatilis). J Zoo Wildl Med. 2020;51(1):4652. doi:10.1638/2019-0096

    • PubMed
    • Search Google Scholar
    • Export Citation

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