What Is Your Neurologic Diagnosis?

Stacey M. MeekerDepartment of Comparative Medicine, College of Medicine, University of Washington, Seattle, WA 98195.

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Piper M. TreutingDepartment of Comparative Medicine, College of Medicine, University of Washington, Seattle, WA 98195.

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Lillian Maggio-PriceDepartment of Comparative Medicine, College of Medicine, University of Washington, Seattle, WA 98195.

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Jessica M. SnyderDepartment of Comparative Medicine, College of Medicine, University of Washington, Seattle, WA 98195.

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A pet 3-year-old spayed female Sprague Dawley rat was evaluated because of bilateral progressive, seemingly nonpainful hind limb paresis of 6 weeks' duration. The rat had been adopted from a university at 6 months of age and had previously been used in nutritional studies; however, no other experimental manipulations had been performed. The rat was mentally alert and responsive; it had a body condition score of 4 on a scale from 1 to 5 and overt signs of pain were not elicited during palpation of the cervical or thoracolumbar region of the vertebral column. Other abnormalities detected during a general physical examination included a 1.5-cm-diameter firm, smooth, freely movable subcutaneous mass over the left ventral aspect of the thorax and a small amount of discolored brown-tinged urine that was voided during the examination.

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

ProblemRule out location
Bilateral hind limb paresis with absent pelvic limb proprioception and postural responses and intact pelvic limb reflexesMyelopathy in the region of T3 through L2
Decreased patellar response bilaterallyFemoral nerve lesion (or L2-L5 myelopathy in rodents) but response difficult to elicit in an aged rodent

Likely location of 1 lesion

Myelopathy in the region of T3 through L2

Etiologic diagnosis—Differential diagnoses for spontaneous, progressive paraparesis in a rodent include neoplasia, spontaneous radiculoneuropathy, infectious disease (bacterial or viral myelitis [albeit uncommon]), or intervertebral disk disease (albeit uncommon). Given the progressive nature of the clinical signs and the fact that the rat was caged when not directly supervised, trauma and vascular disease (ie, fibrocartilaginous emboli) were considered unlikely. On the basis of the age of the rat as well as the gradual onset and progressive nature of the clinical signs, the most likely differential diagnoses were neoplasia (eg, lymphoma) and spontaneous radiculoneuropathy. Suggested diagnostic testing included a CBC and serum biochemical analysis (to assess general health), radiography (to rule out boney changes consistent with neoplasia or infection) or MRI of the vertebral column (to rule out structural spinal cord disease), and evaluation of a CSF sample (to evaluate for infectious, inflammatory, or neoplastic diseases). However, owing to the rat's advanced age as well as the progressive worsening of its condition, euthanasia (by means of barbituate solution overdose administered via intraperitoneal injection) was elected and a necropsy was performed.

Diagnostic test findings—Results of the serum biochemical analysis were unremarkable. The CBC revealed mild to moderate neutropenia, indicative of neoplasia, immune-mediated disease, or sepsis (the latter considered less likely given the rat's clinical signs). On gross examination at necropsy, there was abundant brown to gray and friable tissue surrounding the descending aorta and ventral surface of the vertebral column extending from T4 through T12. Sections through this mass and through the thoracic and lumbar portions of the vertebral column and spinal cord were evaluated histologically. There was bilaterally symmetric severe radiculoneuropathy characterized by dilated myelin sheaths, axonal atrophy, and abundant cholesterol clefts affecting the ventral nerve roots and white matter. The gray matter was unaffected. There were multifocal moderate to severe degenerative changes of the intervertebral disks, vertebrae, and articular facets characterized by degeneration of the fibrocartilage, bone reversal lines, and irregular new bone formation (osteoarthritis). Histologic examination of the brown friable tissue revealed multifocal clusters and lobules of brown adipose tissue extending along the epaxial muscles and ventral aspect of the vertebral bodies. Although the brown fat appeared well differentiated and did not invade into the vertebral canal, the distribution was expanded beyond that typically observed in an animal of this age and was considered consistent with a benign hibernoma.1

Comments

Spontaneous radiculoneuropathy in aged rats has been reported2–6 and is characterized by variably severe demyelination of the ventral spinal nerve roots that leads to progressive hind limb paresis, as observed in the rat of this report. In rats, this condition predominantly develops in aged individuals and has been reported to affect as many as 80% to 100% of rats > 2 years of age.2–6 Although it has been suggested that progressive nephropathy, obesity, and decreased activity might have a role in exacerbating radiculoneuropathy, the etiopathogenesis of the disease is still unknown.3 Spontaneous radiculoneuropathy is a progressive degenerative condition, and treatment is focused on supportive care and husbandry changes.

Spontaneous radiculoneuropathy is considered to involve expansion of the myelin sheath with the most severe demyelination of the ventral spinal nerve roots occurring at the lumbosacral level but with possible extension into the thoracolumbar spinal cord.5 In the case described in the present report, sections of the thoracolumbar vertebral column and spinal cord were evaluated because of the abnormal appearance of the ventral aspect of the vertebral bodies and periaortic sheath noted during gross examination. Interestingly, the changes in the nerve roots of the thoracolumbar portion of the spinal cord were similar to those in the lumbosacral nerve roots, suggesting that the degenerative changes may have been present throughout the rat's spinal cord.

The gray to brown and friable mass in the region of the ventral aspect of the vertebral body and aorta was histologically characterized by well-differentiated clusters of brown fat. These changes were consistent with benign hibernoma, and most likely represented an incidental finding unrelated to the radiculoneuropathy. Though hibernomas are uncommon, they have been reported as a spontaneous neoplasm in many mammals, including aged rats,7,8 and originate from brown adipose tissue. Although commonly described as a rare lesion (incidence in rats, < 0.1%8,9), a prevalence of up to 3.5% in Sprague Dawley rats > 1 year of age has been reported.8 Brown adipose tissue is important in thermogenesis, and stores can be found throughout the thorax, abdomen, and subcutaneous spaces of most neonates.8,10 Although brown adipose stores decrease with age in most species, deposits in rodents can persist throughout life.8,10,11 In rats, most hibernomas develop in the thoracic cavity with predilection for the periaortic and ventral vertebral region likely because of the persistent stores of brown adipose tissue at these sites.8 There have been case reports12,13 of hibernomas resulting in posterior paresis in rats either as a result of impingement of the spinal cord or invasion into the vertebral canal. However, in the case described in the present report, there was no evidence of invasion into or compression of the spinal cord; thus, the hibernoma was considered an incidental finding.

The findings in this geriatric rat with progressive hind limb paralysis were indicative of spontaneous radiculoneuropathy. Given the frequency of spontaneous radiculoneuropathy determined in previous surveys of geriatric laboratory rats in experimental studies,2–4 this is an important differential diagnosis and consideration for aged pet rats with progressive myelopathy at the T3 through L2 or L3 through S2 regions. In addition, although likely an incidental finding in the case described in the present report, hibernomas may cause hind limb paresis as well and should also be considered as a differential diagnosis in such cases.

Acknowledgments

Supported by the University of Washington Department of Comparative Medicine for post-doctoral training in laboratory animal medicine and pathology.

Presented in poster form at the 2014 National Meeting for the American Association for Laboratory Animal Sciences, San Antonio, Tex, October 2014.

Submitted to the Joint Pathology Conference (JPC) Wednesday Slide Conference teaching series.

References

  • 1. Elwell MR, Stedham MA, Kovatch RM. Skin and subcutis. In: Boorman GA, ed. Pathology of the Fischer rat: reference and atlas. San Diego: Academic Press, 1990; 273274.

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  • 2. Krinke G, Suter J, Hess R. Radicular myelinopathy in aging rats. Vet Pathol 1981; 18: 335341.

  • 3. Krinke G. Spinal radiculoneuropathy in aging rats: demyelination secondary to neuronal dwindling? Acta Neuropathol 1983; 59: 6369.

  • 4. Mitsumori K, Maita K, Shirasu Y. An ultrastructural study of spinal nerve roots and dorsal root ganglia in aging rats with spontaneous radiculoneuropathy. Vet Pathol 1981; 18: 714726.

    • Crossref
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  • 5. King W, Russell S. Metabolic, traumatic, and miscellaneous diseases. In: Suckow MA, Weisbroth SH, Franklin CL, eds. The laboratory rat. 2nd ed. Waltham, Mass: Elsevier, 2006;533534.

    • Search Google Scholar
    • Export Citation
  • 6. Witt CJ, Johnson LK. Diagnostic exercise: rear limb ataxia in a rat. Lab Anim Sci 1990; 40: 5289.

  • 7. Anagawa A, Okazaki Y, Murakami Y, et al. A case of spontaneous malignant hibernoma in a Crl:CD(SD)IGS rat. J Toxicol Pathol 2009; 22: 205208.

  • 8. Bruner RH, Novilla MN, Picut CA, et al. Spontaneous hibernomas in Sprague-Dawley rats. Toxicol Pathol 2009; 37: 547552.

  • 9. Carter RL. Tumours of the soft tissues. IARC Sci Publ 1973; 5: 151157.

  • 10. Hofstetter J, Suckow MA, Hickman DL. Morphophysiology. In: Suckow MA, Weisbroth SH, Franklin CL, eds. The laboratory rat. 2nd ed. Waltham, Mass: Elsevier, 2006;98.

    • Search Google Scholar
    • Export Citation
  • 11. Jerome C, Hoch B. Skeletal system. In: Treuting PM, Dintzis SM, Frevert CW, et al, eds. Comparative anatomy and histology: a mouse and human atlas. Waltham, Mass: Elsevier Academic Press, 2012;69.

    • Search Google Scholar
    • Export Citation
  • 12. Coleman GL. Four intrathoracic hibernomas in rats. Vet Pathol 1980; 17: 634637.

  • 13. Stefanski SA, Elwell MR, Yoshitomi K. Malignant hibernoma in a Fischer 344 rat. Lab Anim Sci 1987; 37: 347350.

Contributor Notes

Address correspondence to Dr. Meeker (sm45@uw.edu).
  • 1. Elwell MR, Stedham MA, Kovatch RM. Skin and subcutis. In: Boorman GA, ed. Pathology of the Fischer rat: reference and atlas. San Diego: Academic Press, 1990; 273274.

    • Search Google Scholar
    • Export Citation
  • 2. Krinke G, Suter J, Hess R. Radicular myelinopathy in aging rats. Vet Pathol 1981; 18: 335341.

  • 3. Krinke G. Spinal radiculoneuropathy in aging rats: demyelination secondary to neuronal dwindling? Acta Neuropathol 1983; 59: 6369.

  • 4. Mitsumori K, Maita K, Shirasu Y. An ultrastructural study of spinal nerve roots and dorsal root ganglia in aging rats with spontaneous radiculoneuropathy. Vet Pathol 1981; 18: 714726.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. King W, Russell S. Metabolic, traumatic, and miscellaneous diseases. In: Suckow MA, Weisbroth SH, Franklin CL, eds. The laboratory rat. 2nd ed. Waltham, Mass: Elsevier, 2006;533534.

    • Search Google Scholar
    • Export Citation
  • 6. Witt CJ, Johnson LK. Diagnostic exercise: rear limb ataxia in a rat. Lab Anim Sci 1990; 40: 5289.

  • 7. Anagawa A, Okazaki Y, Murakami Y, et al. A case of spontaneous malignant hibernoma in a Crl:CD(SD)IGS rat. J Toxicol Pathol 2009; 22: 205208.

  • 8. Bruner RH, Novilla MN, Picut CA, et al. Spontaneous hibernomas in Sprague-Dawley rats. Toxicol Pathol 2009; 37: 547552.

  • 9. Carter RL. Tumours of the soft tissues. IARC Sci Publ 1973; 5: 151157.

  • 10. Hofstetter J, Suckow MA, Hickman DL. Morphophysiology. In: Suckow MA, Weisbroth SH, Franklin CL, eds. The laboratory rat. 2nd ed. Waltham, Mass: Elsevier, 2006;98.

    • Search Google Scholar
    • Export Citation
  • 11. Jerome C, Hoch B. Skeletal system. In: Treuting PM, Dintzis SM, Frevert CW, et al, eds. Comparative anatomy and histology: a mouse and human atlas. Waltham, Mass: Elsevier Academic Press, 2012;69.

    • Search Google Scholar
    • Export Citation
  • 12. Coleman GL. Four intrathoracic hibernomas in rats. Vet Pathol 1980; 17: 634637.

  • 13. Stefanski SA, Elwell MR, Yoshitomi K. Malignant hibernoma in a Fischer 344 rat. Lab Anim Sci 1987; 37: 347350.

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