What Is Your Neurologic Diagnosis? - AVMA Journals

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What Is Your Neurologic Diagnosis? A

n 11-year-old 6-kg (13.2-lb) neutered male Yorkshire Terrier was evaluated for thoracolumbar hyperesthesia and sudden-onset ambulatory paraparesis. A week prior, the referring veterinarian identified signs of thoracolumbar discomfort during a routine physical examination and NSAID treatment was instituted. At the referral examination, clinical signs had progressed to bilateral hind limb ataxia and hyperesthe-

sia with vocalization. Historically, the dog had chronic diabetes mellitus and had undergone bilateral cataract phacoemulsification surgery. Current treatments included insulina (2.17 U/kg [0.99 U/lb], SC, q 12 h). Physical examination revealed a pendulous abdomen with cranial abdominal organomegaly, bilaterally weak femoral pulses, and symmetric mild ventral abdominal alopecia. A neurologic examination was performed.

Neurologic examination Observation Alert X Normal X Normal Para X

Mental Posture Gait Paresis Other

Depressed Head tilt Ataxia X Tetra

Disoriented Tremor Pelvic limbs X Hemi

Stupor Falling All 4 Mono

Coma Circling

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

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

Spinal reflexes Quadriceps Extensor carpi Flexion Crossed extensor Perineal

LF

RF

NE 2

NE 2

2 NE NE NE

2 NE NE NE

LF

RF

2 2 2

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

LR

RR

1 NE 0 NE

1 NE 0 NE

LR

RR

3

3

1 2 2

1 2 2

2 2 2

L

R

2 2 2 2 2 2 2

2 2 2 2 2 2 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

All findings were considered normal.

Sensation (Locate and describe abnormal) Hyperesthesia 3 Over T13 and L1 vertebrae Superficial pain 2 Cutaneous reflex 2 Deep pain NE Owing to intact motor function

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 246, No. 12, June 15, 2015

Vet Med Today: What Is Your Neurologic Diagnosis?

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Assessment Anatomic diagnosis Rule out location

Problem Ambulatory paraparesis and ataxia with bilaterally decreased postural reactions, withdrawal deficits, and sudden-onset thoracolumbar hyperesthesia (T13-L1 region of the vertebral column)

Focal or diffuse spinal cord lesion within the T3-L3 region of the vertebral column, L6-S2 spinal cord segments, or sciatic nerve

Weak femoral pulses

Cardiovascular (hypotension) or thromboembolic vascular disease

Likely location of one lesion Considering the combination of signs, a lesion within the T3-L3 spinal cord segments was suspected. However, this did not explain the dog’s weak pulses and weak withdrawal reflex; thus, cardiovascular or thromboembolic disease was not definitively excluded.

Etiologic diagnosis—Differential diagnoses considered for the dog of the present report were intervertebral disk disease with disk extrusion or protrusion, neoplasia, or infectious or inflammatory myelitis. On the basis of the dog’s signalment, fibrocartilaginous embolic myelopathy and diskospondylitis were considered less likely. Weak femoral pulses and hind limb withdrawal responses were consistent with vascular occlusion cranial to the femoral arteries, underlying cardiovascular disease, or hypotension. Diagnostic testing included a minimum database, CBC, serum biochemical analysis, and urinalysis (to evaluate for infection or inflammation and ascertain general status) with survey radiography of the thorax and abdomen (to assess for vertebral abnormalities and neoplasia). Echocardiography was performed (to rule out a cardiogenic cause of weakness). Hyperesthesia of the thoracolumbar region, bilateral femoral hyperreflexia, and bilaterally reduced withdrawal prompted an MRI examination of the T13S1 region of the vertebral column. Diagnostic test findings—The CBC results revealed mild neutrophilia (12,348 neutrophils/µL; reference range, 3,000 to 11,500 neutrophils/µL) with a normal leukocyte count (14.7 X 103 cells/µL; reference range, 7 X 103 cells/µL to 22 X 103 cells/µL), and high plasma protein concentration (9 mg/dL; reference range, 6 to 8 mg/dL). Serum biochemical analyses revealed hyperglycemia (348 mg/dL; reference range, 75 to 125 mg/dL), high concentrations of BUN (39 mg/ dL; reference range, 8 to 24 mg/dL) and total protein (8.5 g/dL; reference range, 5.5 to 8 g/dL), hyperglobulinemia (5.7 g/dL; reference range, 2.1 to 4.3 g/dL), hypercholesterolemia (577 mg/dL; reference range, 140 to 360 mg/dL), mildly high activities of alanine aminotransferase (95 U/L; reference range, 10 to 90 U/L) and alkaline phosphatase (227 U/L; reference range, 11 to 140 U/L), and severely high creatine kinase activity (1,666 U/L; reference range, 50 to 300 U/L). Moderate proteinuria with a normal urine specific gravity (1.039; reference range, 1.035 to 1.045) was detected by urinalysis. All clinicopathologic findings (results of the CBC, serum biochemical analysis, and urinalysis) with the exception of high creatine kinase activity were 1294


attributed to dehydration and endocrinopathy. High creatine kinase activity raised the suspicion of myopathy and an ischemic event. Results of thoracoabdominal imaging were consistent with endocrine system– related hepatomegaly and results of echocardiography were consistent with mild mitral and tricuspid valve regurgitation attributable to endocardiosis. Pre- and postcontrast enhanced MRI of the T3-S1 region of the vertebral column was performed (Figure 1). Image sequences included T1-weighted (T1-W), T2-weighted (T2-W), T1-fluid attenuated inversion recovery, T1-W fast spoiled gradient echo, short tau inversion recovery (STIR), 3-D reconstructable MR myelography, and 2-D time of flight (TOF) MR angiography in multiple planes. Magnetic resonance myelography revealed multifocal desiccated intervertebral disks throughout the vertebral column with mild to moderate areas of com-

Figure 1—Sagittal contrast-enhanced TI-weighted fast spoiled gradient echo fat saturated (A) and T2-weighted (B) images of the lumbar vertebral column, MR myelogram (C) of the C4-S3 region of the vertebral column, and transverse 3-D reconstructed MR myelogram of the L4 and L5 region of the vertebral column (D) of a dog with thoracolumbar hyperesthesia and sudden-onset ambulatory paraparesis. In panels A and B, notice the large, ovoid, hypointense lesion within the aorta and ventral to the L4-L7 region of the vertebral column. In panels C and D, MR myelography clearly reveals multifocal intervertebral disk protrusions (loss of the ventral and, to a lesser degree, the dorsal subarachnoid columns). Notice the poorly defined area of T2-weighted hyperintensity (indicative of edema, fluid stasis, or proteinaceous fluid) in the region of the aorta, just ventral to the L4 vertebral body. JAVMA, Vol 246, No. 12, June 15, 2015

pressive myelopathy at the T12-13 and L7-S1 intervertebral disk spaces. A non-enhancing, heterogeneous, ovoid (3.8 cm in length), sharply marginated luminal structure (compared with the surrounding gray matter, the structure was iso- to hyperintense on T2-W images, hyperintense on STIR images, and hypointense on T1-W images) was present in the abdominal portion of the descending aorta caudal to the renal arteries. Time of flight angiography of the abdominal aorta revealed abrupt termination of flow extending from the level of the L4 vertebra into the left external iliac artery. Findings of abdominal ultrasonography with color flow Doppler evaluation agreed with MRI findings, in that an echogenic thrombus was detected in the distal portion of the aorta and extended into the left external iliac artery. Markedly reduced blood flow was evident, as was bilateral adrenomegaly. On the basis of the combined findings, a diagnosis of aortic thromboembolic disease (ATE) and hind limb ischemia was made. Other findings included chronic intervertebral disk disease and subclinical mitral and tricuspid valve endocardiosis. Adrenomegaly, thromboembolic disease, and biochemical abnormalities prompted evaluation for hyperadrenocorticism. Results of an ACTH stimulation test on the ninth day following initial examination were consistent with hyperadrenocorticism (prestimulation cortisol concentration, 5.6 µg/µL [reference range, 0 to 9.9 µg/µL]; poststimulation cortisol concentration, 29.9 µg/µL [reference range, 5.5 to 20 µg/dL]). Pituitary-dependent hyperadrenocorticism was considered most likely given the lack of MRI and ultrasonographic evidence of macroscopic adrenal gland tumors. Comments In dogs, aortic thrombosis and thromboembolism are uncommon and have an underlying pathogenesis that is different from ATE in cats. Cats with aortic thrombosis and thromboembolism generally have cardiac disease with predispositions for left atrial blood turbulence, thrombus formation, and subsequent (usual) embolization to the aortic bifurcation.1 In dogs with ATE, focal thrombosis of the distal portion of the aorta is often seen as a result of underlying prothrombotic disease (eg, protein-losing nephropathy, endocrinopathy, cardiac disease) or paraneoplastic causes.1–3 Clinical signs in affected dogs include hind limb weakness or paresis, proprioceptive deficits, weak (or absent) femoral pulses, altered hind limb reflexes, cold extremities, and chronic hyperesthesia exacerbated by physical activity.1–3 Laboratory abnormalities include high serum creatine kinase activity and plasma D-dimer concentration with variable clotting profiles.1–3 Treatment of dogs with ATE includes administration of tissue plasminogen activator, streptokinase, warfarin sodium, heparin sodium, dalteparin sodium, aspirin, or clopidogrel bisulphate, and thrombectomy. Response to treatment varies, and prognosis depends on the underlying cause and initial improvement with treatment.1,3 In most dogs, morbidity is not associated with the initial thromboembolic event. A median diseaseJAVMA, Vol 246, No. 12, June 15, 2015

free period of 24.2 months is reported in a study1,3 of dogs with ATE that were treated with oral administration of warfarin. The dog of this report was treated with enoxaparin sodium (1 mg/kg [0.45 mg/lb], SC, q 6 h), clopidogrel (1 mg/kg, PO, q 24 h), and aspirin (1 mg/ kg, PO, q 24 h). The dog was maintained on the previous dosage of insulin. Chronic intervertebral disk disease was conservatively managed with cage rest. The dog’s paraparesis gradually improved. Marked bilateral proprioceptive placing deficits persisted 119 days after the initial referral evaluation. Medical management continued with the addition of trilostane (1.5 mg/kg [0.68 mg/lb], PO, q 12 h) to manage hyperadrenocorticism and the hypercoagulable state, which was attributed to the loss of antithrombin III. Serial ultrasonographic assessments revealed gradual reduction of thrombus size (decreased to 0.5 cm in length by day 119) with adequate blood flow around the thrombus. The case described in the present report exemplifies a clinical situation in which nonneurologic disease affects neurologic function and highlights the importance of inclusion of the aorta within the field of view on MRI images of the vertebral column of paraparetic dogs for accurate diagnosis. The dog of this report had multiple disease entities known to cause hypercoagulability.4–6 Vessel thrombi should be considered as a differential diagnosis in dogs with hind limb weakness and neurologic deficits. a. Humulin-N, Lilly USA LLC, Indianapolis, Ind.

References 1. 2. 3. 4. 5. 6.

Winter RL, Sedaca CD, Adams A, et al. Aortic thrombosis in dogs: presentation, therapy, and outcome in 26 cases. J Vet Cardiol 2012;14:333–342. Van Winkle TJ, Hackner SG, Liu SM. Clinical and pathological features of aortic thromboembolism in 36 dogs. J Vet Emerg Crit Care (San Antonio) 1993;3:13–21. Boswood A, Lamb CR, White RN. Aortic and iliac thrombosis in six dogs. J Small Anim Pract 2000;41:109–114. Rose L, Dunn ME, Bedard C. Effect of canine hyperadrenocorticism on coagulation parameters. J Vet Intern Med 2013;27:207–211. Pace SL, Creevy KE, Krimer PM, et al. Assessment of coagulation and potential biochemical markers for hypercoagulability in canine hyperadrenocorticism. J Vet Intern Med 2013;27:1113–1120. Alzahrani SH, Ajjan RA. Coagulation and fibrinolysis in diabetes. Diab Vasc Dis Res 2010;7:260–273.

This report was submitted by Elizabeth C. Hiebert, DVM; Jennifer M. Gambino, DVM; Kyle D. Hutcheson, DVM; and Gabriel A. Garcia, DVM; from the Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762. The authors declare that no conflicts of interest or sources of funding exist. Address correspondence to Dr. Hiebert ([email protected]).

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.


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