What Is Your Neurologic Diagnosis? - AVMA Journals

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What Is Your Neurologic Diagnosis?

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9-year-old 42-kg (92.4-lb) neutered male Golden Retriever was referred to the University of Georgia because of chronic, progressive ambulatory paraparesis of 3 weeks’ duration. At the onset, the dog appeared to be in pain and had difficulty standing up on the pelvic limbs. The referring veterinarian treated the dog with meloxicam (0.8 mg/kg [0.36 mg/lb], PO, q 12 h). One week later, the dog began scuffing the dorsum of the foot of the right

pelvic limb. Administration of meloxicam was discontinued, and the dog was treated with prednisone (1.0 mg/kg [0.45 mg/lb], PO, q 12 h), with the dosage reduced by 50% every 5 days. Despite treatment, the pelvic limb weakness progressed to involve the left pelvic limb. Twenty-four hours prior to the referral evaluation, the dog’s condition deteriorated rapidly; although ambulatory, the dog was severely paraparetic.

Neurologic examination Observation Mental Posture Gait Paresis Other

Alert X Normal Normal Pelvic limbs X

Postural reactions

Depressed Head tilt Ataxia X Tetra

Disoriented Tremor Pelvic limbs X Hemi

Stupor Falling X All 4 Mono

Coma Circling

Key: 4 = exaggerated, clonus; 3 = exaggerated; 2 = normal; 1 = diminished; 0 = none; NE = not evaluated

Wheelbarrow Hopping Ext postural thrust Proprioceptive pos Hemistand/walk Placing–tactile Placing–visual

Spinal reflexes Quadriceps Extensor carpi Flexion Crossed extensor Perineal

LF NE 2

RF NE 2

2 NE NE NE

2 NE NE NE

LF

RF

NE 2 NE

NE 2 NE

Cranial nerves

II, VII–Vision menace II, III–Pupils resting Stim L Stim R II–Fundus III, IV, VI–Strabismus, resting III, IV, VI, VIII–Strabismus, position

L

R

2 2 2 2 2 2 2

2 2 2 2 2 2 2

LR

RR

0 NE 0 NE

0 NE 0 NE

LR 2

RR 3

2 NE 2

2 NE 2

VIII–Nystagmus, resting VIII–Nystagmus, change V–Sensation VII–Facial mm V, VII–Palpebral flex IX, X–Gag XII–Tongue

L

R

2 2 2 2 2 2 2

2 2 2 2 2 2 2

Comments CN

Sensation (Locate and describe abnormal) Hyperesthesia

3

Palpation over the L2-L3 vertebral articulation and over the lumbosacral articulation elicited signs of pain

Superficial pain NE Cutaneous reflex Deep pain

2 N

Not assessed because of the presence of voluntary motor ability

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.

JAVMA • Vol 251 • No. 8 • October 15, 2017

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Assessment Anatomic diagnosis Rule out location

Problem Paraparesis

Focal or diffuse lesion in the T3-L3 spinal cord segments (ie, T3-L3 myelopathy) or in the L4-S1 spinal cord segments (lower motor neurons [LMNs]), L4-S1 nerve roots, L4-S1 spinal nerves, femoral or sciatic nerves, neuromuscular junctions of the femoral and sciatic nerves, or muscles of the pelvic limbs (ie, upper motor neuron [UMN] vs LMN weakness)

General proprioceptive ataxia

Focal or diffuse lesion causing T3-L3 myelopathy

Postural reaction deficits in the pelvic limbs

Focal or diffuse lesion causing T3-L3 myelopathy or lesion in the L4-S1 spinal cord segments (LMNs), L4-S1 nerve roots, L4-S1 spinal nerves, femoral or sciatic nerves, neuromuscular junctions of the femoral and sciatic nerves, or muscles of the pelvic limbs (ie, UMN vs LMN lesion)

Normal spinal reflexes with increased muscle tone

Focal or diffuse lesion causing T3-L3 myelopathy

Focal area of hyperesthesia

Focal lesion involving the meninges, nerve roots, spinal nerves, vertebrae, or epaxial musculature at the site of hyperesthesia

Likely location of 1 lesion Focal or diffuse lesion affecting the T3-L3 spinal cord segments resulting in myelopathy. The focal area of hyperesthesia suggests a focal lesion.

Etiologic diagnosis—The primary differential diagnoses for the dog of the present report included intervertebral disk herniation, neoplasia (vertebral neoplasm [osteosarcoma, fibrosarcoma, nerve sheath neoplasm, round cell neoplasm, or metastatic neoplasia]), meningomyelitis (infectious or noninfectious), diskospondylitis with secondary empyema or vertebral instability, or trauma. The diagnostic plan included a CBC, serum biochemical profile, urinalysis, and 3-view thoracic radiography (to evaluate for evidence of infection, inflammation, or metastatic neoplasia or identify a primary neoplasm), radiography collimated to image the vertebral column (to evaluate for a primary or metastatic vertebral neoplasm, diskospondylitis with secondary vertebral instability, and traumatic injury), and MRI of the vertebral column caudal to the T1 vertebra (to identify a structural cause for the myelopathy [ie, primary or metastatic neoplasm, intervertebral disk herniation, meningomyelitis, diskospondylitis with its sequelae, and traumatic injury]). Consideration of CSF sample analysis would be dependent on the MRI findings. Diagnostic test findings—Results of the CBC, serum biochemical profile, urinalysis, and radiography of the thorax and vertebral column were considered normal. With a 3.0-T MRI unit,a multiplanar T1- and T2-weighted images of the thoracolumbar vertebral column were obtained. Following IV administration of a contrast agent, additional T1-weighted images were obtained with the Dixon technique for fat suppression. The T2-weighted MRI images revealed multifocal hyperintense areas within the thoracic and lumbar spinal cord (Figure 1). In some areas of hyperintensity, there were round to ovoid areas that were isointense, compared with normal areas of the 898

spinal cord. These isointense areas were contiguous with spinal nerve roots, which were subjectively enlarged. There was also attenuation of the subarachnoid space, suggestive of expansion or swelling of the spinal cord. Following IV contrast agent administration, multifocal intramedullary, round to ovoid contrast-enhancing areas that had broad attachment to the meninges were evident on T1-weighted images acquired with fat suppression. Additionally, the meninges overlying the thoracic and lumbar spinal cord were enhanced as were the spinal nerve roots. The MRI findings were consistent with a neoplastic, infectious (granulomatous), or noninfectious inflammatory process. Given the severity of the dog’s clinical signs, the owner elected euthanasia (by means of IV injection of pentobarbital solution) and allowed postmortem examination to be performed. Microscopically, within the thoracic and lumbar spinal cord, there was a multifocal, multinodular, unencapsulated, relatively well-demarcated, densely cellular neoplasm that had infiltrated, expanded, effaced, and compressed the meninges, spinal nerve roots, and spinal cord parenchyma. The neoplasm was arranged in dense sheets and bundles to streams and was supported by a fine fibrovascular stroma. Neoplastic cells had marked pleomorphism and ranged from round to spindloid, with variably distinct cell borders and scant to abundant pale, eosinophilic cytoplasm. Nuclei were oval and elongated to round or reniform with clumped chromatin and 1 or 2 nucleoli. Anisocytosis and anisokaryosis were marked. Large, atypical nuclei and frequent multinucleated cells were seen. Multinucleated neoplastic cells frequently contained phagocytosed debris. The mitotic rate was 15 mitotic figures/10 hpfs (400X). Within the perilesional spinal cord white matter,


Figure 1—Sagittal plane MRI images of the lumbar vertebral column of a dog that was evaluated because of chronic, progressive ambulatory paraparesis of 3 weeks’ duration. Twenty-four hours prior to the referral evaluation, the dog’s condition deteriorated rapidly; although ambulatory, the dog was severely paraparetic. A—T2-weighted image. Notice the ill-defined hyperintensity throughout the spinal cord. The hyperintensity observed in the spinal cord within the T13 and L1 vertebrae is related to partial volume averaging, whereby some of the signal is created by the adjacent epidural fat. At the level of the L4 vertebra, there is an isointense region of spinal cord that is outlined by a hyperintense area giving the impression of a mass effect (arrow). B—T1-weighted image. Overall, there is minimal change in the intensity of the spinal cord except for an ill-defined, faintly hyperintense area of the spinal cord at the level of the L4 vertebra (arrow). C—Postcontrastadministration T1-weighted image. Following IV administration of a contrast agent, multiple well-defined, contrast-enhancing, round to ovoid intramedullary lesions that have broad attachments to the meninges are visible. D—Postcontrast-administration T1-weighted image with fat saturation. In this image, not only are the intramedullary lesions more easily seen, but also the contrast enhancement of the meninges along a length of the spinal cord in the field of view is more easily visualized.

there were multifocal areas of rarefaction that were frequently invaded by individualized neoplastic cells. Numerous swollen axons (spheroids), lipid-containing macrophages, and frequent lymphoplasmacytic perivascular cuffs also were observed. Similar neoplastic cells had also expanded into or effaced multifocal areas within the cerebral leptomeninges along with a focally extensive area of the brainstem parenchyma. Vascular invasion was not noted. The neoplastic cells had strong positive membranous immunoreactivity for CD18 and were not immunoreactive for CD11d. Neoplastic cells in organs outside of the CNS were not found. The gross and microscopic findings for the spinal cord and brain were consistent with primary, multifocal CNS histiocytic sarcoma.

Comments The case described in the present report was associated with neurologic findings consistent with a focal or diffuse lesion affecting the T3-L3 spinal cord segments. Signs included general proprioceptive ataxia and UMN-quality paraparesis (normal to increased spinal reflexes and increased muscular tone in the pelvic limbs). Moreover, the case highlighted the fact that neurologic deficits reflect the anatomic location of the lesion rather than provide an etiologic diagnosis. Although common disease processes (ie, intervertebral disk herniation) should be considered, a comprehensive differential diagnosis list should be constructed to devise a diagnostic plan and establish a definitive diagnosis. For the dog of this report, the diagnosis was primary CNS histiocytic sarcoma involving the spinal cord and brain. Histiocytic sarcoma is a neoplastic proliferation of dendritic or macrophage cell lineages. Histiocytic sarcoma can be a neoplasm that is localized to a single organ (either as a solitary mass or as multiple

masses within a single organ) or can be a disseminated disease (previously referred to as malignant histiocytosis) affecting multiple organs.1 With respect to the CNS, histiocytic sarcoma develops in the vertebrae and secondarily affects the spinal cord or develops solely in the CNS (primary histiocytic sarcoma).1 In the case of CNS histiocytic sarcomas, intracranial or spinal cord involvement may occur. Although there are too few reported cases of histiocytic sarcoma involving the CNS in dogs from which any breed predilection can be determined, middle-aged to older Labrador Retrievers, Golden Retrievers, Welch Pembroke Corgis, and Shetland Sheepdogs appear overrepresented.2–4 This is in contrast to the breeds that are commonly affected with histiocytic sarcomas that develop outside of the CNS, which include Bernese Mountain Dogs, Flat-Coated Retrievers, and Rottweilers.1 Typically, intracranial histiocytic sarcoma develops as an extraparenchymal mass affecting the cerebrum.2,3,5 Clinical signs often include seizures, abnormal mentation, and visual deficits.2,3 With primary spinal cord involvement, localized and disseminated forms have been reported.4,6,7 Intracranial histiocytic sarcomas often develop as intradural but extramedullary lesions or as intramedullary lesions.3 Affected dogs have variable degrees of paresis or paralysis as well as signs of pain. In general, MRI findings reflect the anatomic location of the neoplasm. In dogs with intracranial histiocytic sarcoma, MRI often reveals a well-demarcated, extraparenchymal mass that is of mixed intensity to hypointense on T2-weighted images, is hypointense on T1-weighed images, and has strong, homogeneous contrast enhancement.3,5 For spinal cord histiocytic sarcoma, MRI reveals either a single mass or multifocal masses with similar changes in intensity as observed in lesions involving the brain.3 Following administration of contrast agent, often there is strong contrast enhancement of


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the meninges over an extensive length of the spinal cord in MRI images.3,8 Alternatively, histiocytic sarcoma may result in a diffuse intramedullary hyperintensity in the spinal cord on T2-weighted images.8 Analysis of a CSF sample from affected dogs may reveal neoplastic histiocytes6; however, neoplastic cells are not observed in CSF samples in most cases.3 Ultimately, a definitive diagnosis is made on the basis of microscopic identification of neoplastic cells with histiocytic features along with their reactions with specialized immunohistochemical stains.1 For dogs with histiocytic sarcoma involving the CNS, limited survival data exist to determine optimal treatment and define prognostic information. In 19 dogs with localized and disseminated histiocytic sarcoma involving the CNS (brain, spinal cord, or both) treated with various combinations of surgery, radiation, and chemotherapy, the median survival time was 3 days (range, 1 to 92 days).3 In a case report,9 a dog undergoing craniectomy for removal of a histiocytic sarcoma survived 9 months after surgery. The prognosis for dogs with histiocytic sarcoma involving the CNS is grave. Study of additional cases of dogs with histiocytic sarcoma involving the CNS may help yield information that may lead to improved therapeutic approaches and enhance survival times in affected animals.

3.0-T MRI, Siemens Skyra MRI, Erlangen, Germany.

References 1. 2.

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4. 5.

6. 7. 8. 9.

Mariani CL, Jennings MK, Olby NJ, et al. Histiocytic sarcoma with central nervous system involvement in dogs: 19 cases (2006–2012). J Vet Intern Med 2015;29:607–613. Ide T, Uchida K, Kagawa Y, et al. Pathological and immunohistochemical features of subdural histiocytic sarcomas in 15 dogs. J Vet Diagn Invest 2011;23:127–132. Ishikawa C, Ito D, Kitagawa M, et al. Comparison of conventional magnetic resonance imaging and nonenhanced three dimensional time-of-flight magnetic resonance angiography findings between dogs with meningioma and dogs with intracranial histiocytic sarcoma: 19 cases (2010–2014). J Am Vet Med Assoc 2016;248:1139–1147. Tzipory L, Vernau KM, Sturges BK, et al. Antemortem diagnosis of localized central nervous system histiocytic sarcoma in 2 dogs. J Vet Intern Med 2009;23:369–374. Uchida K, Morozumi M, Yamaguchi R, et al. Diffuse leptomeningeal malignant histiocytosis in the brain and spinal cord of a Tibetan Terrier. Vet Pathol 2001;38:219–222. Taylor A, Eichelberger B, Hodo C, et al. Imaging diagnosis— spinal cord histiocytic sarcoma in a dog. Vet Radiol Ultrasound 2015;56:E17–E20. Tamura S, Tamura Y, Nakamoto Y, et al. MR imaging of histiocytic sarcoma of the canine brain. Vet Radiol Ultrasound 2009;50:178–181.

This report was submitted by Marc Kent, DVM; Shannon Kirejczyk, DVM; Sophie A. Aschenbroich, DVM; Renee M. Barber, DVM, PhD; and Simon R. Platt, BVM&S; from the Departments of Small Animal Medicine and Surgery (Kent, Barber, Platt) and Pathology (Kirejczyk, Aschenbroich), College of Veterinary Medicine, University of Georgia, Athens, GA 30602. Address correspondence to Dr. Kent ([email protected]).

Footnotes a

3.

Moore PF. A review of histiocytic diseases of dogs and cats. Vet Pathol 2014;51:167–184. Thongtharb A, Uchida K, Chambers JK, et al. Histological and immunohistochemical studies on primary intracranial canine histiocytic sarcomas. J Vet Med Sci 2016;78:593–599.

This feature is published in coordination with the American College of Veterinary Internal Medicine on behalf of the specialty of neurology. Contributors to this feature should contact Dr. Helen L. Simons (800-2482862, ext 6692) for case submission forms. Submissions will be sent to Dr. Karen Kline, DVM, DACVIM, for her review, except when Dr. Kline is an author.
