History
A 13-year-old 6.5-kg (14.3-lb) neutered male domestic shorthair cat was evaluated because of a peracute onset of tetraplegia. Within hours of being observed walking normally, the cat was found unable to stand. The cat had no prior medical problems. The cat was kept indoors, and its vaccination status was current.
Clinical and Gross Findings
Physical examination revealed no abnormalities with the exception of a grade 3/6 systolic heart murmur. There was no evidence of chronic kidney disease or hyperthyroidism. On neurologic examination, the cat was mentally normal but tetraplegic; overall examination findings were consistent with a lesion affecting the C1-C5 spinal cord segments. Systolic blood pressure measured via Doppler ultrasonography was 170 mm Hg. The cat was anesthetized, and MRIa revealed a focal, well-delineated, T2-weighted hyperintense spinal cord lesion located on the midline in the ventral region of the spinal cord parenchyma within the C2 vertebral foramen. The owner elected euthanasia and allowed postmortem evaluation only of the cervical portion of the spinal cord. No gross abnormalities were observed in the epidural space of the cervical vertebral column. The cervical spinal cord from the C1-C8 spinal cord segments was normal with the exception of a 1.5-cm-long, enlarged segment of the ventral spinal artery (VSA) that extended from 5 mm cranial at the level of the C2 spinal nerve to 5 mm cranial at the level of the C3 spinal nerve (Figure 1) The spinal cord was preserved in neutral-buffered 10% formalin prior to transverse sectioning that revealed a loss of the distinction between the ventral gray matter and the ventral funiculus at the level of the enlarged VSA. Cranial to the C3 spinal nerve, the VSA appeared enlarged.
Photographs of the cervical portion of the spinal cord removed at necropsy from a cat that was evaluated because of a peracute onset of tetraplegia. A—On the ventral aspect of the formalin-fixed gross specimen of the spinal cord between the C2 spinal nerve (white arrowhead) and the C3 spinal nerve (open arrowhead), an enlarged ventral spinal artery (VSA) is visible as a dark brown linear structure that is deep to the dura mater and courses along the ventral midline of the spinal cord. Bar = 4 mm. B—On a transverse section through the C2 spinal cord segment, the enlarged VSA is evident just to the left of the ventral median fissure (arrowhead). The lumen of the VSA is not visible. In comparison with the dorsal funiculus, the ventral funiculus is pale and there is less distinction between ventrally located gray matter and the adjacent white matter (arrow). Bar = 4 mm.
Citation: Journal of the American Veterinary Medical Association 257, 1; 10.2460/javma.257.1.53
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Histopathologic and Microbiological Findings
At the level of the C2 spinal cord segment, there was a focal, well-demarcated area of rarefaction and cavitation of the spinal cord parenchyma primarily on the midline in the ventral funiculus but also extending into the ventral portion of the gray matter bilaterally. In 1 transverse section of the C2 spinal cord segment, rarefaction of the white matter extended dorsally along the lateral aspect of the gray matter and also was present in the ventromedial aspect of the dorsal funiculus. At the margins of the lesion, there were numerous eosinophilic swollen axons (spheroids). Vessels within and immediately surrounding the area of rarefaction and cavitation had hypertrophied endothelial cells (reactive endothelia). A few neurons within the area of rarefaction were shrunken, eosinophilic, and devoid of Nissl substance and contained eosinophilic, pyknotic nuclei consistent with ischemic cell changes.
The VSA at the level of the C2 spinal cord segment had marked thickening of the tunica media characterized by homogeneously eosinophilic material (hyaline degeneration [Figure 2]). With application of periodic acid-Schiff stain, the hyaline material stained deep magenta (Figure 3) Within the hyaline degeneration, there were concentric rings of spindle-shaped cells and hemorrhage. The thickening resulted in stenosis of the lumen of the VSA. A perivascular mixed inflammation consisting of lymphocytes, plasma cells, and macrophages surrounded the affected portion of the VSA.
Photomicrographs of transverse sections through the C2 spinal cord segment from the cat in Figure 1. A—Ventral to the ventral portion of the gray matter, there is rarefaction and cavitation of the ventral funiculus (arrow). The box denotes the region in panel B. Within the box, notice that the VSA is enlarged and has a thickened wall that results in stenosis of the lumen. H&E stain; bar = 1 mm. B—The wall of the VSA is replaced by hyaline material. Within the hyaline material are spindle-shaped cells and areas of hemorrhage. Perivascular inflammation surrounds the VSA. Vacuolation of the white matter is present (asterisk). H&E stain; bar = 200 μm. C—Section of the spinal cord just caudal to the section in panel A. In addition to the ventral funiculus, there is rarefaction of the ventromedial region of the ventral gray matter as well as in the ventral aspect of the dorsal funiculus (arrowhead). The box denotes the region in panel D. Within the box, the tunica media of the VSA is thickened by hyaline material and concentric rings of spindle-shaped cells. H&E stain; bar = 1 mm. D—Compared with panel B, the VSA lumen and the tunica intima are visible in this view. There also is more marked perivascular inflammation (arrow). H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 257, 1; 10.2460/javma.257.1.53
Photomicrograph of the VSA in the section in panel D of Figure 2. Periodic acid-Schiff staining imparts a deeply magenta color to the hyaline material within the tunica media. Periodic acid-Schiff stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 257, 1; 10.2460/javma.257.1.53
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: ischemic infarction involving the ventral funiculus and ventral aspect of the gray matter of the C2 spinal cord segment and hyaline arteriolopathy of the VSA in a cat.
Comments
Arteriosclerosis is a general term for stiffening of arteries and has been subclassified as atherosclerosis, Mönckeberg medial calcific sclerosis, and arteriolosclerosis.1 Atherosclerosis is characterized by enlargement of the tunica intima of arteries by various lipids, connective tissues, inflammatory cells, and a variety of extracellular material.2 Mönckeberg medial calcific sclerosis is characterized by calcification of the tunica media and internal elastic lamina of medium to large arteries.3 Arteriolosclerosis is characterized by thickening of the tunica media of arteries by either hyaline material or as a result of hyperplasia and hypertrophy of spindle-shaped cells (myointimal cells) within the tunica media.1 Hyaline material likely represents the accumulation of serum proteins in the subendothelial space; as in the case described in the present report, hyaline material has a glassy, homogeneously eosinophilic appearance that stains magenta with application of periodic acid-Schiff stain.4 In people, arteriolosclerosis is often observed in patients with hypertension or diabetes mellitus.5 In addition to hyaline and hyperplastic arteriolosclerosis, fibrinoid necrosis of the small arterioles may be associated with hypertension.5 Arteriolosclerosis in a cat without evidence of hypertension or diabetes mellitus has been reported.6 In cats with experimentally induced hypertensive encephalopathy, vascular lesions including both hyaline and hyperplastic arteriolosclerosis develop in the leptomeningeal vasculature, often overlying ischemic regions in the CNS parenchyma.7 In the cat of the present report, the lesion within the VSA was most consistent with hyaline arteriolosclerosis and was likely the proximate cause of ischemic infarction of the spinal cord. Although an exhaustive attempt to document hypertension in this cat was not undertaken, given the single, mildly high systemic blood pressure measurement and lack of common predisposing causes (ie, chronic kidney disease or hyperthyroidism), it was likely that the cat did not have sustained hypertension. Unfortunately, the heart and its potential causal role were not investigated.
The blood supply to the spinal cord is provided segmentally at each intervertebral foramen along the length of the vertebral column. In the cervical region of the vertebral column, paired spinal branches arise from the vertebral arteries to supply the cervical portion of the spinal cord.8 Each spinal branch divides into a dorsal and ventral branch. The ventral branch courses ventrally to join the VSA. In the thoracic region of the vertebral column, paired spinal branches arise from the dorsal intercostal arteries at each intervertebral articulation to supply the thoracic spinal cord. The dorsal intercostal arteries in the cranial, mid, and caudal thoracic portions of the vertebral column arise from the costocervical artery, thoracic vertebral artery, and aorta itself, respectively.8 In the lumbar region of the vertebral column, paired spinal branches arise from the lumbar arteries that extend directly from the aorta and supply the lumbar and sacral portions of the spinal cord.8 At the level of the first cervical vertebra, the paired vertebral arteries each enter their respective lateral vertebral foramen, penetrate the dura mater and arachnoid layer, and divide into a cranial and caudal branch, which unite with fellow branches from the contralateral side.9 The joined cranial branches form the basilar artery, whereas the joined caudal branches form the cranial end of the VSA, which runs the length of the spinal cord just ventral to the ventral median fissure.9 Variations exist in which the cranial end of the vertebral artery enters the vertebral canal to form the VSA at a more caudal location. Similarly, paired spinal branches penetrate the dura matter and arachnoid at each intervertebral foramen and divide into a small dorsal and a larger ventral branch, which course with their respective spinal nerve roots.8 On reaching the surface of the spinal cord, the dorsal branches divide to create the paired dorsal lateral arteries, whereas the ventral branches join the VSA. The spinal branch with the largest diameter is typically at the level of L4 in cats.9 The dorsal and ventral divisions of the spinal branches also give off branches that form a network of arteries that cover the surface of the spinal cord.
At each spinal cord segment, 2 to 4 perforating branches leave the VSA to course dorsally in the ventral median fissure and penetrate the spinal cord.9,10 These perforating branches provide for the blood supply to the lateral and ventral aspects of the gray matter.9,10 The superficial white matter is supplied by the network of arteries that cover the surface of the spinal cord circumferentially.9,10
Interruption of the blood supply to the spinal cord results in ischemic myelopathy. Although common in dogs, fibrocartilaginous embolic myelopathy in cats is uncommonly reported.11 Likewise, ischemic myelopathy in which there is necrosis of the ventrally located gray matter of the lumbar portion of the spinal cord in the absence of vertebral fractures or luxations infrequently develops in cats following motor vehicle-induced trauma; in such cases, an underlying ischemic mechanism is suggested, and the lesion is termed traumatic ischemic poliomyelomalacia.12 Ischemic myelopathy in the cranial cervical portion of the spinal cord, related to hyaline arteriolosclerosis of the VSA, in older cats has been described.13 Cats with ischemic myelopathies affecting the cervical portion of the spinal cord range in age from 8 to 18 years,13–16 and signs consist of a peracute onset of tetraparesis that ranges from ambulatory tetraparesis to tetraplegia, often with flexion of the neck. Affected cats do not have signs of pain. Comorbidities include hypertension, hypertrophic cardiomyopathy, and chronic kidney disease.15 With supportive treatment, affected cats may regain the ability to ambulate and may ultimately return to normal function within weeks to months of the onset of tetraparesis.13,15 Relapse, either as a recurrence of tetraparesis or paresis related to different anatomic localization in the spinal cord, may occur.15 As for the cat of the present report, MRI of the cervical portion of the spinal cord of affected cats typically reveals a focal, elliptical, T2-weighted hyperintense lesion in the ventral aspect of the spinal cord that does not display contrast enhancement.15 The lesion affects the area of spinal cord supplied by the penetrating branches of the VSA. Grossly, aneurysmal dilation of the VSA may be observed13; microscopic findings include vacuolation of the white matter of the ventral funiculus and ischemic necrosis of the neurons of the ventral and lateral aspects of the gray matter.13 Marked thickening of the vascular wall of the VSA by hyaline degeneration is observed in the cranial cervical portion of the spinal cord.13 In some affected cats, similar vascular changes also are observed in the basilar and meningeal arteries.13 Perivascular mixed inflammation surrounding affected vessels also may be present.13
In the cat of the present report, ischemic myelopathy was identified in the C2 spinal cord segment in the vascular territory supplied by the penetrating branches of the VSA. At the level of the C2 spinal cord, the VSA was markedly thickened as a result of hyaline arteriolosclerosis.
It is interesting to note that this focal ischemic myelopathy secondary to underlying vascular pathological changes in the VSA in cats predictably occurs in the cranial cervical portion of the spinal cord. This location may be predisposed to ischemia as a result of vascular anatomic features. Both the VSA and the ventral spinal branches are notably smaller at the level of C2 than at other regions of the cervical, thoracic, and lumbar portions of the spinal cord.9 Although the smaller diameter of the ventral spinal branches and VSA at the level of the C2 spinal cord segment may represent an at-risk region for ischemia, it remains to be determined why pronounced vascular change seems to concentrate specifically in the vasculature of the cranial cervical portion of the spinal cord in cats.
The cat of the present report had a focal ischemic myelopathy that affected the ventral gray column and the ventral funiculus at the level of C2, which implicated the VSA. Hyaline arteriolosclerosis was observed in the VSA. On the basis of a single arterial blood pressure measurement, the cat did not appear to have hypertension, but serial blood pressure monitoring was not performed. In cats with arteriolosclerosis of the VSA, attention should be focused on evaluation of the vasculature in other organs and on identification of predisposing causes of systemic hypertension.
Footnotes
1.5-T Brivo MR 355 Inspire, General Electric Medical Healthcare, Milwaukee, Wis.
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