What Is Your Neurologic Diagnosis?

Kyu-duk Yeon 1Department of Veterinary Emergency Medicine, Konkuk Veterinary Medical Teaching Hospital, Konkuk University, Seoul 05029, Republic of Korea.

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Jung-Hyun Kim 2Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.

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Hyun-Jung Han 1Department of Veterinary Emergency Medicine, Konkuk Veterinary Medical Teaching Hospital, Konkuk University, Seoul 05029, Republic of Korea.

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A15-year-old 8.0-kg (17.6-lb) sexually intact female mixed-breed dog was presented because of a peracute onset of unilateral imbalance and head tilt and 1 episode of grand mal seizure. Medical history of the dog indicated an absence of previous health problems. At the hospital, the dog was unable to stand and maintained sternal or lateral recumbency. On physical examination, the dog's mucous membranes were pale with normal capillary refill time; its rectal temperature was 38.1°C (100.6°F), respiratory rate was 18 breaths/min, and heart rate (with bounding pulses) was 130 beats/min. Systolic arterial blood pressure measured with the Doppler method was 160 mm Hg. A large palpable mass was detected predominantly in the upper portion of the abdomen. On neurologic examination of the dog, postural reactions were delayed or absent bilaterally. Increased muscle tone was noted in all 4 limbs.

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
Head tilt to the right and head and body turn to the leftCranial nerve VIII (right side), flocculonodular and rostral node of cerebellum (left side), or vestibular nuclei of the brainstem
Upper motor neuron tetraparesisBrainstem, cerebellum, prosencephalon (cerebral cortex or thalamus), or cervical region of the spinal cord (C1-T2 segments)
Seizure historyProsencephalon (cerebral cortex or thalamus)

Likely location of 1 lesion

Diffuse lesions affecting the prosencephalon and a left-sided lesion of the cerebellum were preferentially considered.

Etiologic diagnosis—Central vestibular and pros-encephalic signs can be induced by vascular disorders, primary or metastatic neoplasia, infectious or inflammatory disease processes, metabolic disease, and degenerative disease. For the dog of the present report, the history of peracute onset of neurologic signs and presence of a palpable mass in the abdomen were suggestive of intracranial tumor metastasis or a vascular disorder of a paraneoplastic syndrome. A CBC, serum biochemical analysis, coagulation profile, and thoracic and abdominal radiography were planned as the initial diagnostic approach, followed by additional diagnostic testing with MRI of the dog's head to assess for intracranial disease and thoracoabdominal CT to evaluate the abdominal mass and potential metastasis.

Diagnostic test findings—The CBC revealed that the dog had microcytic, normochromic anemia (Hct, 21.8%; reference interval, 37% to 61%), mild leukocytosis (19,450 WBCs/μL; reference interval 5,050 to 16,760 WBCs/μL), neutrophilia (16,550 neutrophils/μL; reference interval, 2,950 to 11,640 neutrophils/μL), and thrombocytopenia (63,000 platelets/μL; reference interval, 148,000 to 484,000 platelets/μL). Serum biochemical findings included high creatine kinase activity (1,065 U/L; reference interval, 10 to 200 U/L), high aspartate aminotransferase activity (78 U/L; reference interval, 0 to 50 U/L), and high globulin concentration (4.8 g/dL; reference interval, 2.5 to 4.5 g/dL). A coagulation profile revealed severely high D-dimer concentration (16.5 mg/dL; reference interval, 0 to 0.3 mg/dL) and delayed activated partial thromboplastin time (105 seconds; reference range, 72 to 102 seconds); the prothrombin time was within the reference interval (15 seconds; reference interval, 11 to 17 seconds). Radiography revealed a mass effect at the center of the abdomen.

Magnetic resonance imaging of the dog's head was performed with a 1.5-T MRI unit.a Images were acquired with the following sequences: dorsal, sagittal, and transverse T2-weighted images; sagittal and transverse T1-weighted images; transverse FLAIR images; transverse and dorsal postcontrast T1-weighted images; transverse diffusion-weighted images; and transverse apparent diffusion coefficient images.

A focal, clearly demarcated, T2-weighted hyperintense, T1-weighted isointense lesion was found in the region of the left rostral cerebellar hemisphere (Figure 1). On FLAIR images, the appearance of the lesion was similar to that on the T2-weighted images. On the T1-weighted images obtained after administration of contrast agent, a mild degree of peripheral contrast enhancement was observed around the lesion. The lesion appeared hyperintense on the diffusion-weighted images and hypointense on the apparent diffusion coefficient map; these findings were consistent with focal ischemia resulting from acute infarction.1 The T2-weighted hyperintense region included major anatomic structures on the left side, namely the cerebellar cortex, cerebellar white matter, flocculus nucleus, fastigial nucleus, dentate nucleus, and rostral vestibular nucleus. The hyperintense region was confined to the supply area of the right rostral cerebellar artery (RCeA).2

Figure 1—
Figure 1—

Magnetic resonance and CT images of a 15-year-old dog with peracute neurologic signs of unilateral imbalance and right head tilt and that had an episode of seizure. A—Left parasagittal T2-weighted image of the head. There is a sharply demarcated focal hyperintensity located in the rostral lobe of the cerebellum (arrow). B—Dorsal T2-weighted image at the level of the interthalamic adhesion. Notice a sharply demarcated triangular hyperintense lesion in the left cerebellar hemisphere (arrow). C—Contrast-enhanced CT image of the splenic mass. The mass is 115.51 × 114.71 mm (white dotted lines) with a distinct margin. It has a nonhomogeneous enhancement pattern and is hypoattenuated relative to areas of unaffected spleen. Free intra-abdominal fluid is present, likely hemoperitoneum caused by rupture of the splenic mass (asterisk). D—Transverse T2-weighted image at the level of the tympanic bulla. A sharply demarcated triangular hyperintense lesion involving the left-sided cerebellar cortex, left-sided cerebellar medulla, dentate nucleus, rostral vestibular nucleus, and cerebellar flocculus is present (arrowhead). E—Transverse T2-weighted diffusion-weighted image obtained at a level approximately corresponding to that of the image in panel D. Hyperintense lesions within the cerebellum may be attributable to the presence of restricted diffusion or the artifact of T2 shine-through (arrowhead). F—Transverse apparent diffusion coefficient map obtained at a level approximately corresponding to that of the image in panel D. The lesion appears hypointense, indicating restricted diffusion, and excludes T2 shine-through as a cause for the finding of hyperintensity on the diffusion-weighted image (arrowhead).

Citation: Journal of the American Veterinary Medical Association 257, 9; 10.2460/javma.257.9.911

Thoracoabdominal CT was performed to investigate the abdominal mass and assess for regional metastasis. Pre- and postcontrast images were acquired with a triphase 16-slice helical CT scanner.b A large splenic mass (115.51 × 76.32 × 114.71 mm) that occupied most of the abdominal cavity was identified. The mass had a cavitated appearance with a heterogeneous enhancement pattern in all phases. A large amount of free fluid adjacent to the splenic mass was observed, which was considered as suspected hemoperitoneum due to rupture of the splenic mass. The splenic lymph nodes and liver lymph nodes were enlarged with heterogeneous contrast enhancement. Multiple hypodense, wedge-shaped areas were found in both kidneys, which were consistent with segmental renal infarction.

On the basis of these findings, the diagnoses of cerebellar and renal infarction and ruptured splenic tumor were made for the dog of the present report. Emergency splenectomy was performed with transfusion of whole blood to address the risk of persistent bleeding from uncontrolled hemorrhage of the splenic tumor. Rupture of the splenic tumor and associated massive intra-abdominal hemorrhage were confirmed perioperatively. Samples of the mass underwent histologic examination, which revealed extramedullary hematopoiesis with multiple areas of thrombosis, necrosis, hemorrhage, and hematoma and the presence of erythroid precursors, plasma cells, and eosinophils. Thus, the mass was confirmed as a benign hematoma. After surgery, the dog was administered constant rate infusions of fentanyl and lidocaine (loading doses of 4 μg of fentanyl/kg [1.8 μg/lb] and 2 mg of lidocaine/kg [0.9 mg/lb], IV, followed by constant rate infusions of 4 μg of fentanyl/kg/h and 0.2 mg of lidocaine/kg/h [0.09 mg/lb/h]) for 24 hours; subsequently, analgesia was provided with a fentanyl patch (12 μg/h) and carprofen (2.2 mg/kg [1 mg/lb], SC, q 12 h). Low-molecular-weight heparin (150 U/kg [68.1 U/lb], SC, q 8 h) and clopidogrel (loading dose of 10 mg/kg [4.5 mg/lb], PO, followed by 4 mg/kg, PO, q 24 h) were administered for management of thrombosis. At 7 days after surgery, the dog's thrombocyte count and delayed activated partial thromboplastin time were restored to within reference intervals, and the D-dimer concentration (1.1 mg/dL) was considerably decreased but remained greater than the upper reference limit.

In a follow-up telephone interview at 4 weeks after surgery, the dog's owner reported that the dog had no clinical improvement and persistent vestibular signs. Euthanasia was performed at the owner's request 30 days following diagnosis, but the dog did not undergo necropsy.

Comments

Ischemic stroke is caused by a thrombotic or thromboembolic event and results in infarction with loss of neurofunction of the related vascular region.2 In dogs, infarction appears to frequently occur in the cerebellum.2–6 Most cases of cerebellar stroke in dogs are associated with the area of the RCeA.2–6 In dogs, the RCeA arises from the caudal communicating artery and branches to the rostral aspect of the cerebellar hemisphere, vermis, and dorsolateral aspect of the brainstem.2 Ischemic infarcts affecting the territory of the RCeA result in peracute to acute, nonprogressive signs of neurologic deficits characterized by ataxia, head tilt, opisthotonos, nystagmus, strabismus, torticollis, decreased menace response, and postural and proprioceptive deficits.2–6 The dog of the present report had a territorial infarct in a rostral lobe of the cerebellum, indicative of thrombotic obstruction of the RCeA, and developed acute vestibular signs and postural deficits that were consistent with the lesion. The dog had also had a seizure episode, which is usually associated with a lesion in the prosencephalon area. However, there was no imaging evidence of structural disease affecting the prosencephalon or other possible causes of the seizure; hence, we primarily suspected idiopathic ischemic attack or transient ischemic attack as the cause of seizure. A transient ischemic attack is caused by transient and focal brain ischemia without any marked infarction detectable with MRI, and usually manifests as a short neurologic episode before the stroke event.2,7 In 2 studies, transient ischemic attacks occurred in 549 of 2,416 (23%) humans with ischemic stroke8 and in 5 of 23 (22%) dogs with cerebellar infarcts.2

Medical conditions commonly associated with ischemic stroke in dogs are hypertension (and its potential underlying causes), endocrine disease (hyperadrenocorticism, hypothyroidism, hyperthyroidism, and diabetes mellitus), kidney disease (especially protein-losing nephropathy), heart disease, and metastatic disease.3,5 In the dog of the present report, the splenic mass was a benign hematoma with low possibility of metastatic disease, and there was no evidence of diseases typically associated with ischemic stroke. We considered that hypercoagulability induced by rupture of the hematoma was the main cause of infarction, on the basis of reports9,10 describing the pathophysiology of hypercoagulability and coagulopathy after trauma in humans. Massive trauma-related tissue injury exacerbates thrombosis by inducing increased amounts of procoagulants in the systemic circulation and impairing endogenous anticoagulant activity, which eventually lead to generation of thrombin in the systemic circulation.9 Moreover, following blood-vessel damage, tissue factor, which is necessary for initiation of coagulation, is expressed by vascular adventitial cells such as adventitial fibroblasts, pericytes, and smooth muscle cells and could activate thrombosis.11 Similar to findings for humans with trauma-associated coagulopathy, mild to moderate trauma in small animals results in increased systemic thrombin generation and blood hypercoagulability, which can be balanced with catecholamine-induced release of tissue plasminogen activator and protein C pathway; in cases of severe trauma, this can progress to systemic anticoagulation and hyperfibrinolysis owing to consumptive coagulopathy, activation of the thrombomodulin-activated protein C pathway, and glycocalyx damage due to catecholamine surge.12 The damage of glycocalyx leads to release and systemic circulation of endogenous anticoagulants and profibrinolytic agents.12 We considered that pathophysiologic changes similar to those of trauma-associated coagulopathy had developed because of the ruptured hematoma in the dog of the present report. With regard to the dog's suspected hypercoagulability, the histologic findings of multiple areas of thrombosis, necrosis, and hemorrhage and the presence of inflammatory cells were indicative of massive tissue injury and damage to the blood vessels. Tissue injury and blood vessel damage are the main causes of hypercoagulability following trauma. Consumptive coagulopathy was considered because of the abnormal coagulation variables, such as thrombocytopenia, high D-dimer concentration, and delayed activated partial thromboplastin time; additionally, the presence of hyperfibrinolysis was considered but not confirmed because the dog did not undergo thromboelastography. Nevertheless, coagulopathy associated with rupture of a splenic hematoma may promote thrombus formation and lead to thrombosis at the level of the systemic circulation.

Dogs with cerebellar ischemic stroke have a good to excellent prognosis, and most affected dogs recover rapidly within the first week with supportive care alone.3 Clinicians should investigate potential underlying causes and administer treatment to limit the risk of recurrences.3 The dog of the present report had no clinical improvement at 4 weeks after splenectomy, despite excision of the ruptured hematoma (considered to be the underlying cause of thrombosis) and absence of postoperative coagulopathy. The poor outcome for this dog could have been a consequence of development of multiple thrombi that resulted in an extensive stroke-associated lesion. We suspected multiple thrombi because of the multiple areas of thrombosis in the splenic mass, infarction of another organ (the kidneys), and evidence of consumptive coagulopathy. In particular, these findings met 4 of the 6 diagnostic criteria for disseminated intravascular coagulation, namely a splenic tumor and its rupture as the underlying cause, prolongation of prothrombin time or activated partial thromboplastin time, thrombocytopenia, and high concentration of D-dimers.13,14

The dog of the present report had neurologic findings associated with cerebellar infarction concurrent with a ruptured splenic hematoma. Hypercoagulation and coagulopathy as a result of the ruptured hematoma were potential factors contributing to systemic thrombosis that led to cerebellar infarction. In contrast to the previously described cases of cerebellar infarction in dogs,2,5 prognosis for the dog of the present report was guarded despite removal of the potential underlying cause.

Acknowledgments

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT; 2020R1A2C101378711).

The authors declare that there were no conflicts of interest.

Footnotes

a.

1.5T Siemens Magnetom Essenza, Siemens Healthcare, Erlagen, Germany.

b.

SOMATOM go. Now, Siemens Healthcare, Erlagen, Germany.

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