Spinal Cord Infarct in a Calf after Aortic Catheter Implantation (2011)

An 8-week-old healthy female German-Holstein calf weighing 60 kg underwent aortic catheterization to facilitate arterial access for continuous monitoring of blood pressure and serial arterial blood sampling as part of a research project. Aortic puncture was carried out under ultrasonographic guidance on the nonsedated, standing animal between the left transverse processes of the 3rd (L3) and 4th (L4) lumbar vertebrae on the lateral border of the longissimus lumborum muscle.1 A 120 mm hypodermic needlea was percutaneously directed into the vessel and a sterile 45-cm-long polyethylene catheterb was introduced by a modified Seldinger technique.1 Finally, the needle was withdrawn, leaving 15 cm of the catheter in the lumen of the abdominal aorta. The catheter was connected to a Luer-lock adapterc and a 3-way stopcock. In contrast to Offinger et al,1 the catheter and the stopcock were kept in medical ethanol and flushed with saline before use. Approximately 2 minutes after the catheter was successfully implanted in the aorta and irrigated with heparinizedd (10,000 IU heparin/L) 0.9% sterile saline, the calf's hind limbs suddenly collapsed; the calf could not regain an upright position and remained in sternal recumbency. Repeated efforts to assist the calf into a standing position failed, because its pelvic limbs could not support the weight. However, if lifted and supported under the trunk, the calf could hop on its thoracic limbs. On clinical examination, the animal was bright, alert, and responsive, had a normal appetite, and could maintain sternal recumbency. Both pelvic limbs were flexed at the hip joint and the stifle joint was hyperextended. Heart and respiratory rates, as well as body temperature, were within physiological limits. Cardiac and pulmonary auscultation identified no abnormalities. Although consciousness, examination of the cranial nerves, forelimb postural reactions, and forelimb spinal reflexes appeared normal, severe paraparesis with hyperextensive posture of both stifle joints and hyperflexion of the hip joints was noted. The tone of the quadriceps muscles was normal whereas the tone of the remaining hind limb muscles was severely decreased. Both hind legs were warm and femoral pulses were palpable. Neurological examination2 of the pelvic limbs identified bilateral decreased patellar and absent tibialis cranialis and withdrawal reflexes. On exerting pressure on the medial areas of the pelvic limb with hemostats, superficial and deep pain perception was present. However, application of the same noxious stimuli to the caudal and lateral areas of the distal extremities caused no pain reaction. The perineal reflex also was absent, tail and anus were atonic and analgesic, and the bladder was distended and had to be expressed manually. Hematology and serum biochemistry results, including serum creatine kinase activity, were within normal limits in the calf. Neuroanatomically, the absence of superficial and deep pain sensation in the area innervated by the sciatic and the pudendal nerves, along with normal reflexes in the area innervated by the saphenous nerves, suggested a lower motor neuron (LMN) spinal cord lesion localized between L6 and the sacral spinal cord segments. The decreased patellar reflex was considered to be a result of the hyperextension of the limbs and, together with pain on the medial side of the leg, indicated that the segments L4 and L5 and the femoral and saphenous nerves were intact. Destruction of the L6, S1, and S2 segments prevented stimulation of α-motoneurons of the sciatic nerves. Therefore, no active flexion of the stifle, tarsus, or digits occurred, although passive flexion was possible. Bladder paralysis occurred as a result of the lesion of the sacral segments. At this point, the tentative diagnosis was an acute vascular accident (thromboembolism or fibrocartilagenous or air embolism) involving the spinal cord, causing ischemic myelopathy and consequentially paraplegia. Antithrombotic and antiphlogistic therapy was instituted by daily administration of heparind (100 IU/kg IV) and carprofene (1.4 mg/kg SC) for 5 and 3 days, respectively. Additionally, a single epidural injection of 8 mg dexamethasonef combined with 1,200,000 IU benzylpenicilling was administered. The injection volume was expanded to a final volume of 20 mL with sterile isotonic saline to allow for cranial diffusion to the lesion, which was suspected to be in the lumbar region. The water-soluble penicillin was included to treat possible bacterial infections and the dexamethasone to decrease spinal cord swelling. Enrofloxacinh (2.5 mg/kg IV) was applied as standard procedure after aortic catheterization. The next day, magnetic resonance imaging (MRI)i was carried out. The calf was premedicated with 0.1 mg/kg 2% xylazinej IM and 2.0 mg/kg ketaminek IV. Anesthesia was maintained with inhalant isofluranel and oxygen after intubation. MRI examination was performed about 48 hours after the onset of clinical signs with the calf in dorsal recumbency. T2-weighted images in sagittal (TR: 4,700 ms, TE 112 ms, slice thickness 3 mm) and transverse planes (TR: 3,458 ms, TE 96 ms, slice thickness 3 mm) from the lumbar vertebral column to the sacrum disclosed an intramedullary hyperintense signal abnormality beginning at vertebral body L4. This lesion occurred mainly in the gray matter with right lateralization. The spinal cord segments caudal to vertebral body L5 showed severe hyperintensity of both the gray and white matter. Additional signal changes (T2 weighted, hyperintense) were identified in the area of the right-sided paralumbar muscles adjacent to the 5th and 6th lumbar vertebrae. On sagittal and transverse T1-weighted images (TR: 330 ms, TE 12 ms, slice thickness 3 mm) the described intramedullary lesion was normointense, whereas the muscular abnormality had a mildly hypointense signal. After administration of contrast mediumm (0.2 mmol/kg IV) no pathological enhancement of the spinal cord was observed, but physiological enhancement of the described paraspinal muscle and the body of the 5th lumbar vertebra was absent. Gradient-echo MRIs (TR: 880 ms, TE 26 ms, slice thickness 3 mm) in the transverse plane showed hyperintensity of the altered spinal cord parenchyma, whereas the described paraspinal musculature showed a nonhomogeneous hyperintense signal with multifocal hypointense areas indicating necrosis within this muscle group (Fig 1). Altogether, MRI findings supported the clinical differential diagnosis and indicated marked focal ischemic necrosis, especially of the gray matter in the caudal lumbar and cranial sacral segments of the spinal cord. Magnetic resonance tomography: T2-weighted images in transverse planes (TR: 3,458 ms, TE 96 ms, slice thickness 3 mm) at vertebral body L5. “x” labels an intramedullary hyperintense signal abnormality in the gray matter with a right lateralization. “o” labels hyperintense signal changes in the area of the right sided paralumbar muscles; R, right sided. Despite intense physical therapy and continuation of antiphlogistic and antithrombotic medication as described previously, the calf's ability to stand did not improve. In consideration of the poor prognosis and animal welfare, the calf was euthanized and submitted for postmortem examination. Pathological examination showed a mild to moderate, focal subacute hematoma with necrosis, mineralization, resorptive lymphohistiocytic inflammation, hemosiderosis, and granulationtissue formation within the muscular and retroperitoneal tissues along the puncture channel and focally surrounding the abdominal aorta. On the left side of the abdominal aorta, at the level of the 4th lumbar vertebral body, a punctural lesion of <1 mm in diameter was observed. A small arterial thrombus was firmly attached to the inner surface of the contralateral vessel wall on an area of approximately 5 mm in diameter and protruded 1–2 mm into the lumen. Microscopic examination of the arterial thrombus displayed ongoing organization characterized by infiltrating macrophages occasionally containing intracytoplasmic brown granular pigment (hemosiderin), capillary sprouts, and fibroblasts. Gross examination of the spinal cord revealed locally extensive bilateral malacia and focal hemorrhage of the gray matter extending from the 4th lumbar spinal nerve root to the caudal end of the sacral spinal cord (Fig 2). Microscopically, sections of the affected spinal cord segment contained extensive bilateral malacia of gray matter and adjacent white matter characterized by necrotic neurons and glial cells, disintegration of neuropil, myelin sheaths, and axons, as well as a peripheral zone of intercellular edema, multifocal perivascular hemorrhages, and infiltrating macrophages and fewer lymphocytes. Many macrophages (microglia) displayed were enlarged and had foamy cytoplasm (gitter cells) indicative of phagocytotic activity. The arteria spinalis ventralis and multiple other small- to medium-sized arterial vessels (Aa. sulcocomissurales, Aa. radicularis dorsalis; multiple rami marginales within the white matter) ranging from the area of the 4th lumbar spinal nerve root to the caudal end of the sacral cord displayed multifocal partial to total occlusion of the vessel lumina by fibrin-rich thrombi, displaying multifocal attachment to the vessel walls with endothelial necrosis and loss, whereas they exhibited no contact to the vessel walls in other areas. These thrombi displayed signs of organization characterized by surface reendothelization, hyaline change of the fibrin, formation of internal clefts, and sinusoid spaces filled by erythrocytes and encased necrotic white blood cells (Fig 3). A detailed examination of the affected spinal cord area using serial histologic sections with an interval of approximately 6 mm revealed no embolized exogenous particles, skin, or soft tissue within the vessels. Furthermore, no mucopolysaccarides or chondroid materials were detected by alcian blue special staining. Spinal cord. Bovine. Transversal section of the lumbar spinal cord reveals a focally extensive bilateral ischemic malacia of the gray matter (stars) surrounded by a rim of edema and hemorrhage in the adjacent white matter (arrows). Furthermore a thrombembolus is present within the arteria spinalis ventralis (arrowhead). Df, dorsal funiculus of the white matter; dh, dorsal horn of the gray matter; dr, dorsal spinal nerve root; lf, lateral funiculus of the white matter; vh, ventral horn of the gray matter; vr, ventral spinal nerve root. Arteria spinalis ventralis. Bovine. Light microscopy of a thrombembolus displaying signs of organization characterized by surface reendothelization (arrows), hyaline change of the fibrin (stars), and encased necrotic white blood cells. Tm, tunica media; vl, remaining vessel lumen. HE. Bar = 100 μm. There was a moderate focal ischemic necrosis with mineralization, resorptive inflammation, and granulation tissue formation in the right-sided paralumbar musculature, medial to the tuber coxae, possibly representing a second focus of a primarily arterial thrombotic lesion. Additionally, the urinary bladder displayed mild dilatation and mild multifocal subacute lymphoplasmacytic cystitis. The latter changes were interpreted as a consequence of a neurological impairment of bladder function as a sequela of the myelomalacia. The final pathological diagnosis was subacute arterial thromboembolism of the lumbar and sacral spinal cord with ischemic myelomalacia most likely originating from an arterial thrombus within the lumbar aorta contralateral to the arterial puncture site. This diagnosis was supported by the findings on MRI of an ischemic myelopathy of the caudal lumbar and sacral spinal cord segments. The majority of spinal cord gray matter is supplied by the ventral spinal artery and, because it has the highest area of vascularity, is most susceptible to ischemia. Ischemic myelopathy as a result of acute spinal cord infarction caused by fibrocartilagineous emboli has been described in several large animal species, including pigs,3 sheep,4 a calf,5 and horses.6,7 Aortic thrombosis and subsequent embolization has been identified as another major cause of spinal cord ischemia. In cats and humans, the formation of arterial thrombi is strongly associated with underlying cardiovascular and thromboembolic diseases8 or abdominal aortic operation.9 In calves and horses, the origin of occluding thrombi is less clear.10,11 In the few described cases, predisposing factors associated with the formation of thromboemboli were identified to be valvular endocarditis, bacterial endotoxin,12 immune complexes,13 disruption of laminar blood flow,14 injury to vascular endothelium, and alteration in the coagulability of the blood.15 However, the clinical and postmortem examination provided no evidence of such causes of ischemic myelopathy, and the chronology of events appears highly indicative of a direct causal relationship to the catheterization. Application of a recently published classification system for forensic histological age determination of thromboses and embolism in fatal human pulmonary thromboembolism16 suggested that both the aortic arterial thrombus and the spinal cord thromboemboli were 1–7 weeks old. This stage of the process is characterized by infiltrating endothelial sprouts, fibroblasts, and macrophages containing hemosiderin, coalescing ribbons of fibrin with entrapped necrotic white blood cells, and reendothelization of the thrombus surface (phase II; 2nd–8th week). These alterations are in accordance with the 7-day period between catheterization and necropsy of the calf. Trauma to the vascular endothelium at insertion, caused by the needle, the catheter tip, or the guide wire exposes luminal blood to collagen and tissue factors and may have stimulated thrombus formation by the activation of platelets and the coagulation cascade. This could have been further exacerbated by alterations in normal blood flow15 caused by the indwelling catheter. In a murine model, by real time in vivo imaging, thrombus formation was demonstrated 15–20 seconds after laser-induced endothelial injury.17 In hamsters, thrombi were detected 8 ± 1.1 minutes after trauma to the carotid artery caused by crushing the exposed vessel with a clamp. The formed thrombi gradually embolized and disintegrated 15 ± 2.1 minutes after traumatization.18 Because the onset of neurological signs in this calf was within minutes of the puncture, the detachment of thromobemboli must have occurred very shortly after the procedure. Therefore, even taking into account interspecies variances in hemostasis, it appears unlikely that a thromboembolus originating from endothelial damage contralaterally to the puncture site disintegrated that rapidly and led to infarction of the spinal vessels. Cutaneous, SC, or muscular material accumulated in the lumen of the hypodermic needle may have been introduced into the abdominal aorta while threading the catheter into the vessel. Emboli may have travelled with the aortic bloodstream into arterial branches supplying the vertebrae. Skin tissue emboli originating from needle punctures19,20 or catheter fragment emboli have been reported in studies in humans.21 Although the temporal sequence would support these explanations, skin tissue or a polyethylene fragment would have been detected macroscopically or histologically. Also, it appears unlikely that these emboli would cause multiple arterial emboli. Moreover, because of the high pressure in the abdominal aorta, we would expect tissue accumulated within the needle to be flushed out by the strong retrograde blood flow after entering the aorta. Thus, we suspect the risk of introducing tissue into the aorta was rather low. The 3-way stopcock and catheter were immersed in ethanol before use. The multiple thrombi in the vessels of the spinal cord may have formed from remnants of ethanol within the lumen of the stopcock despite irrigating with saline before connection to the catheter. After the catheter was inserted and connected to the stopcock, irrigating may have caused these remnants to enter the aortic blood stream, or depending on the location of the catheter's tip, directly into spinal vessels. Because of the sclerosing properties and local toxic effects related to its protein denaturant and hydroscopic properties, ethanol is widely used as an embolizing agent for large area tissue destruction.22 Therapeutic transcatheter arterial embolization is an established procedure to treat neoplasms and arteriovenous malformations in a variety of tissues. Major complications described in transcatheter arterial embolization are spinal cord infarction and distal embolization of particles into the aorta and its branches.23 To achieve renal infarction in dogs, 0.2 mL/kg body weight of pure ethanol was injected into the renal artery.24 It appears unlikely that remnants of alcohol within the introduced catheter played a role in the pathogenesis of the thromboembolus because the catheter was irrigated with saline before insertion as well as by the retrograde aortic blood directly after insertion. Another cause of embolization may have been small air bubbles introduced into the vessel on irrigating the catheter. In arterial vessels, cerebral air emboli because of a patent foramen ovale originating from central venous catheters and resulting in neurologic manifestations have been described in humans.25 Special attention, however, was paid on removal of possible air bubbles within the used syringe before irrigating with heparinized saline. Thus, it appears unlikely that air bubbles were introduced into the aorta. Furthermore, during catheterization, the high blood pressure within the abdominal aorta immediately forced blood out of the catheter thus resulting in an immediate retrograde blood flow, which would not allow for air bubbles to be introduced. The etiology of the multiple thromboembolic arterial infarct of the spinal cord in the calf of this report is not definitely proven, but it appears highly likely that the embolism was caused by ethanol. Thus, in order to reduce the risk of thromboembolism after catheterization of vessels, catheter material should not be stored in ethanol or thorough irrigation before use must be carried out. aTSK-Supra Cannula, length 120 mm, OD 2 mm, TSK, Tochigi, Japan bPolyethylene tube, AD 1.27 mm, Kleinfeld Labortechnik, Gehrden, Germany cTeflon, AD 1.5 mm, Walter Veterinär Instrumente e. K., Baruth/Mark, Germany dHeparin-calcium 25000-ratiopharm, Ratiopharm GmbH, Ulm, Germany eRimadyl Cattle, Pfizer Pharma GmbH, Karlsruhe, Germany fDexamethason-Injektionslösung, CP-Pharma, Burgdorf, Germany gPenicillin-G-Natrium, Bela-Pharm, Vechta, Germany hBayer Vital GmbH, Leverkusen, Germany iMagnetom Impact Plus, 1.0 T, Siemens, Erlangen, Germany jRompun, Bayer Vital GmbH kKetamin 10%, Selectavet GmbH, Weyarn-Holzolling, Germany lIsofluran-Baxter, Baxter Deutschland GmbH, Unterschleißheim, Germany m Gadolinium-dimeglumine (GdDTPA), Magnevist, Schering Deutschland GmbH, Berlin, Germany