CASE REPORTS
Paraplegia Due to Intramedullary Hemorrhage After Mitral Valve Repair Satoshi Numata, MD, PhD, Takaaki Samura, MD, Yasushi Tsutsumi, MD, and Hirokazu Ohashi, MD, PhD Department of Cardiovascular Surgery, Fukui Cardiovascular Center, Fukui, Japan
We report the case of a patient who developed paraplegia after mitral valve repair and maze procedure. The first day after surgery, marked weakness of both lower extremities was noted. Neurologic examination showed almost complete loss of sensory and motor function below the level of the first thoracic vertebrae. Magnetic resonance imaging showed intramedullary hemorrhage ranging from the C7 to Th2 segments. Preoperative anticoagulation therapy and general heparinization during heart surgery may cause this rare complication. (Ann Thorac Surg 2015;99:302–3) Ó 2015 by The Society of Thoracic Surgeons
FEATURE ARTICLES
S
pinal cord infarction resulting in paraplegia after cardiac surgery has been reported after coronary artery surgery [1-4]. In our patient, the intramedullary hemorrhage which caused the paraplegia may have been the result of preoperative anticoagulation therapy, as opposed to the more common causes of such hemorrhage which are trauma, vascular malformation, or bleeding diastheses [5]. A 77-year-old male was admitted to our hospital for dyspnea on effort and chest discomfort. He had a history of acute traumatic subdural hematoma which, was medically treated 3 months before admission. Other than that, he did not have any particular medical history such as hypertension, dyslipidemia, and diabetes. On admission, an electrocardiogram showed atrial fibrillation and heart rate was 91 beats per minute. Transthoracic echocardiography revealed severe mitral valve regurgitation due to prolapse of the P2 to P3 portion of the posterior leaflet with torn chordae. There was no thrombus at the left atrial appendage. Left ventricular dimension was 53 mm in diastole and 30 mm in systole. Coronary angiography showed no significant stenosis of coronary arteries. Computed tomography of the chest showed no severe atherosclerotic changes at the ascending and the descending aortae. This patient took warfarin sodium (Coumadin) preoperatively and international normalized ratio of prothrombin time (PT-INR) has been
approximately 2.0. Coumadin was discontinued 4 days before surgery. This patient underwent mitral valve repair and maze procedure electively. The chest was opened through a median sternotomy. Cardiopulmonary bypass was maintained by the ascending aortic and bicaval cannulation. Cardioplegic solution was given antegradely and retrogradely after cross clamping the ascending aorta. The mitral valve was repaired with a triangular resection and suture of the prolapsed posterior leaflet, and 30-mm ring annuloplasty. Perfusion pressure during cardiopulmonary bypass was maintained steadily. Coming off bypass was uneventful and chest was closed routinely. He was sent to the intensive care unit with stable circulation. The patient’s conscious level was recovered and movement of upper extremities was noted soon after surgery. On the morning after, the patient could be extubated; however, marked weakness of both lower extremities was noted. Neurologic examination showed almost complete loss of sensory and motor function below the level of the first thoracic vertebrae. On postoperative day 1 the patient underwent spinal drainage. Cerebrospinal fluid was drained with gravity whenever cerebrospinal fluid pressure exceeded 10 mm Hg. Continuous fentanyl infusion, which was routinely used for pain control after sternotomy, was discontinued and continuous naloxone infusion was started. However, neurologic symptoms did not improve at all. Computed tomographic image showed there was no aortic dissection and aneurysmal changes at the thoracic aorta. An Adamkiewicz artery arose from the right L1 lumber artery. The T2 weighted MRI showed hyposignal foci in the lateral areas of the spinal cord, ranging from the C7 to Th2 segments, suggesting intramedullary hemorrhage (Fig 1). The patient was sent to another hospital for further
Accepted for publication April 4, 2014. Address correspondence to Dr Numata, Department of Cardiovascular Surgery, Fukui Cardiovascular Center, 2-228 Shinpo Fukui Japan 9100833; e-mail: [email protected].
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
Fig 1. The T2 weighted magnetic resonance image showed hyposignal foci in the spinal cord, ranging from the C7 to Th2 segments. 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.03.050
Ann Thorac Surg 2015;99:303–5
rehabilitation. During follow-up at outpatient clinic, his symptom did not change.
Comment
References 1. Thomas NJ, Harvey AT. Paraplegia after bypass operations: relationship to severe hypertension and vascular disease. J Thorac Cardiovasc Surg 1999;114:834–6. 2. Miranda M, Hossne NA Jr, de Viela AT, Buffolo E. Paraplegia after off-pump coronary artery bypass grafting. Ann Thorac Surg 2014;97:326–7. 3. Saxena P, Abu Hasan FA, Merry C. Spinal cord ischemia following coronary artery bypass surgery. J Card Surg 2012;27: 45–6. 4. Pelletier MP, Ai-Khaldi AA, Berry GJ, Morin JF. Paraplegia after routine cardiac surgery: a rare complication. J Card Surg 2002;17:410–2. 5. Kreppel D, Antoniadis G, Seeling W. Spinal hematoma: a literature survey with meta-analysis of 613 patients. Neurosurg Rev 2003;26:1–49. Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
303
Novel TGFBR2 and Known Missense SMAD3 Mutations: Two Case Reports of Thoracic Aortic Aneurysms Paola Panesi, MS, Ilenia Foffa, MS, PhD, Saverio Sabina, MS, Lamia Ait Ali, MD, PhD, and Maria Grazia Andreassi, MS, PhD IFC-CNR Institute of Clinical Physiology, Pisa; and Fondazione CNR/Regione Toscana G. Monasterio, Massa, Italy
We report the clinical presentation and genetic screening of 2 patients with thoracic aortic aneurysms. A novel TGFBR2 mutation in the 5’untranslated region (c.-59C>T) was identified in a 31-year-old man with a Stanford type A aortic dissection. Bioinformatics tools showed that c.-59C>T variant was predicted to affect exonic splicing enhancer, as validated by quantitative realtime RT-PCR, revealing a sixfold increase of TGFBR2 mRNA in aneurysmal aortic tissue collected during surgery. A previously described missense mutation, p.E239K, in the SMAD3 gene was identified in a 60-yearold man who presented with diffuse vasculopathy. These findings suggest that the features of aneurysmal disease extending beyond the ascending aorta may help to target SMAD3 genetic screening and that alterations in the core splicing machinery can contribute to aneurysmal disease. (Ann Thorac Surg 2015;99:303–5) Ó 2015 by The Society of Thoracic Surgeons
T
horacic aortic aneurysm (TAA) is a major disease affecting the aorta, typically asymptomatic, leading to an acute aortic dissection with life-threatening complications including sudden catastrophic death [1]. Recent evidence highlighted a dysregulation of transforming growth factor-beta (TGF-b) signaling in ascending TAA [1]. Accordingly, mutations in the genes that encode the TGF-b receptors (TGFBR1 and TGFBR2) have been identified as a cause of familial thoracic aortic aneurysms and dissections (TAAD) [2]. Exome sequencing of the SMAD3 gene in families with multiple members with TAA and acute aortic dissections identified mutations in 2% of familial cases of TAA, in particular in families having diffuse vasculopathy extending beyond the ascending aorta [3]. We report 2 unrelated patients with familial TAA, 1 associated with a novel TGFBR2 mutation and 1 with a previously reported SMAD3 missense mutation, discussing implications for management and treatment as well as new research perspectives. This study was conducted with informed
Accepted for publication Feb 11, 2014. Address correspondence to Dr Foffa, CNR Institute of Clinical Physiology, via Aurelia Sud, Massa 54100, Italy; e-mail: [email protected].
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.02.068
FEATURE ARTICLES
Paraplegia after cardiac surgery is a rare complication. There are some articles reporting spinal cord infarction after coronary artery surgery [1–4]. In those cases, highly likely mechanism of spinal cord infarction could be microembolization of atherosclerotic plaque or cholesterol emboli from the aorta. In our case, the patient did not have a history of hypertension, hyperlipidemia, diabetes, or peripheral vascular diseases. Before manipulating cardiopulmonary bypass, epiaortic echography was performed, which showed there was no particular atherosclerotic plaque at the ascending aorta. Therefore, we might suggest atherosclerotic disease did not influence paraplegia significantly in this patient. The MRI revealed that the cause of paraplegia of this patient was intramedullary hemorrhage. There seems to be a difference on the cause of paraplegia between reported cases (infarction) and our case (hemorrhage). Intramedullary hemorrhage is commonly caused by trauma, vascular malformation, or bleeding diatheses [5]. This patient took Coumadin before surgery for atrial fibrillation and discontinued 4 days before surgery. The PT-INR on admission was 2.4. Three days before surgery, the patient complained of left-sided back pain. Electrocardiogram, chest X-ray, brain computed tomography, and blood data did not show any significant changes. Pain was controlled by conventional analgesia. Retrospectively thinking, the patient might be complicated with small intramedullary hemorrhage due to preoperative anticoagulation therapy, when he complained of back pain preoperatively. It may be presumed that during cardiac surgery with general heparinization, the size of hemorrhage increased. Consequently, the hemorrhage caused paraplegia after surgery. We might suggest that the patient should have been examined with MRI, which was the only one modality for diagnosing intramedullary hemorrhage. This report suggests that intramedullary hemorrhage may occur with usual oral anticoagulation therapy and after cardiac surgery.
CASE REPORT PANESI ET AL MUTATIONS IN THORACIC AORTIC ANEURYSMS
Paraplegia Due to Intramedullary Hemorrhage After Mitral Valve Repair Satoshi Numata, MD, PhD, Takaaki Samura, MD, Yasushi Tsutsumi, MD, and Hirokazu Ohashi, MD, PhD Department of Cardiovascular Surgery, Fukui Cardiovascular Center, Fukui, Japan
We report the case of a patient who developed paraplegia after mitral valve repair and maze procedure. The first day after surgery, marked weakness of both lower extremities was noted. Neurologic examination showed almost complete loss of sensory and motor function below the level of the first thoracic vertebrae. Magnetic resonance imaging showed intramedullary hemorrhage ranging from the C7 to Th2 segments. Preoperative anticoagulation therapy and general heparinization during heart surgery may cause this rare complication. (Ann Thorac Surg 2015;99:302–3) Ó 2015 by The Society of Thoracic Surgeons
FEATURE ARTICLES
S
pinal cord infarction resulting in paraplegia after cardiac surgery has been reported after coronary artery surgery [1-4]. In our patient, the intramedullary hemorrhage which caused the paraplegia may have been the result of preoperative anticoagulation therapy, as opposed to the more common causes of such hemorrhage which are trauma, vascular malformation, or bleeding diastheses [5]. A 77-year-old male was admitted to our hospital for dyspnea on effort and chest discomfort. He had a history of acute traumatic subdural hematoma which, was medically treated 3 months before admission. Other than that, he did not have any particular medical history such as hypertension, dyslipidemia, and diabetes. On admission, an electrocardiogram showed atrial fibrillation and heart rate was 91 beats per minute. Transthoracic echocardiography revealed severe mitral valve regurgitation due to prolapse of the P2 to P3 portion of the posterior leaflet with torn chordae. There was no thrombus at the left atrial appendage. Left ventricular dimension was 53 mm in diastole and 30 mm in systole. Coronary angiography showed no significant stenosis of coronary arteries. Computed tomography of the chest showed no severe atherosclerotic changes at the ascending and the descending aortae. This patient took warfarin sodium (Coumadin) preoperatively and international normalized ratio of prothrombin time (PT-INR) has been
approximately 2.0. Coumadin was discontinued 4 days before surgery. This patient underwent mitral valve repair and maze procedure electively. The chest was opened through a median sternotomy. Cardiopulmonary bypass was maintained by the ascending aortic and bicaval cannulation. Cardioplegic solution was given antegradely and retrogradely after cross clamping the ascending aorta. The mitral valve was repaired with a triangular resection and suture of the prolapsed posterior leaflet, and 30-mm ring annuloplasty. Perfusion pressure during cardiopulmonary bypass was maintained steadily. Coming off bypass was uneventful and chest was closed routinely. He was sent to the intensive care unit with stable circulation. The patient’s conscious level was recovered and movement of upper extremities was noted soon after surgery. On the morning after, the patient could be extubated; however, marked weakness of both lower extremities was noted. Neurologic examination showed almost complete loss of sensory and motor function below the level of the first thoracic vertebrae. On postoperative day 1 the patient underwent spinal drainage. Cerebrospinal fluid was drained with gravity whenever cerebrospinal fluid pressure exceeded 10 mm Hg. Continuous fentanyl infusion, which was routinely used for pain control after sternotomy, was discontinued and continuous naloxone infusion was started. However, neurologic symptoms did not improve at all. Computed tomographic image showed there was no aortic dissection and aneurysmal changes at the thoracic aorta. An Adamkiewicz artery arose from the right L1 lumber artery. The T2 weighted MRI showed hyposignal foci in the lateral areas of the spinal cord, ranging from the C7 to Th2 segments, suggesting intramedullary hemorrhage (Fig 1). The patient was sent to another hospital for further
Accepted for publication April 4, 2014. Address correspondence to Dr Numata, Department of Cardiovascular Surgery, Fukui Cardiovascular Center, 2-228 Shinpo Fukui Japan 9100833; e-mail: [email protected].
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
Fig 1. The T2 weighted magnetic resonance image showed hyposignal foci in the spinal cord, ranging from the C7 to Th2 segments. 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.03.050
Ann Thorac Surg 2015;99:303–5
rehabilitation. During follow-up at outpatient clinic, his symptom did not change.
Comment
References 1. Thomas NJ, Harvey AT. Paraplegia after bypass operations: relationship to severe hypertension and vascular disease. J Thorac Cardiovasc Surg 1999;114:834–6. 2. Miranda M, Hossne NA Jr, de Viela AT, Buffolo E. Paraplegia after off-pump coronary artery bypass grafting. Ann Thorac Surg 2014;97:326–7. 3. Saxena P, Abu Hasan FA, Merry C. Spinal cord ischemia following coronary artery bypass surgery. J Card Surg 2012;27: 45–6. 4. Pelletier MP, Ai-Khaldi AA, Berry GJ, Morin JF. Paraplegia after routine cardiac surgery: a rare complication. J Card Surg 2002;17:410–2. 5. Kreppel D, Antoniadis G, Seeling W. Spinal hematoma: a literature survey with meta-analysis of 613 patients. Neurosurg Rev 2003;26:1–49. Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
303
Novel TGFBR2 and Known Missense SMAD3 Mutations: Two Case Reports of Thoracic Aortic Aneurysms Paola Panesi, MS, Ilenia Foffa, MS, PhD, Saverio Sabina, MS, Lamia Ait Ali, MD, PhD, and Maria Grazia Andreassi, MS, PhD IFC-CNR Institute of Clinical Physiology, Pisa; and Fondazione CNR/Regione Toscana G. Monasterio, Massa, Italy
We report the clinical presentation and genetic screening of 2 patients with thoracic aortic aneurysms. A novel TGFBR2 mutation in the 5’untranslated region (c.-59C>T) was identified in a 31-year-old man with a Stanford type A aortic dissection. Bioinformatics tools showed that c.-59C>T variant was predicted to affect exonic splicing enhancer, as validated by quantitative realtime RT-PCR, revealing a sixfold increase of TGFBR2 mRNA in aneurysmal aortic tissue collected during surgery. A previously described missense mutation, p.E239K, in the SMAD3 gene was identified in a 60-yearold man who presented with diffuse vasculopathy. These findings suggest that the features of aneurysmal disease extending beyond the ascending aorta may help to target SMAD3 genetic screening and that alterations in the core splicing machinery can contribute to aneurysmal disease. (Ann Thorac Surg 2015;99:303–5) Ó 2015 by The Society of Thoracic Surgeons
T
horacic aortic aneurysm (TAA) is a major disease affecting the aorta, typically asymptomatic, leading to an acute aortic dissection with life-threatening complications including sudden catastrophic death [1]. Recent evidence highlighted a dysregulation of transforming growth factor-beta (TGF-b) signaling in ascending TAA [1]. Accordingly, mutations in the genes that encode the TGF-b receptors (TGFBR1 and TGFBR2) have been identified as a cause of familial thoracic aortic aneurysms and dissections (TAAD) [2]. Exome sequencing of the SMAD3 gene in families with multiple members with TAA and acute aortic dissections identified mutations in 2% of familial cases of TAA, in particular in families having diffuse vasculopathy extending beyond the ascending aorta [3]. We report 2 unrelated patients with familial TAA, 1 associated with a novel TGFBR2 mutation and 1 with a previously reported SMAD3 missense mutation, discussing implications for management and treatment as well as new research perspectives. This study was conducted with informed
Accepted for publication Feb 11, 2014. Address correspondence to Dr Foffa, CNR Institute of Clinical Physiology, via Aurelia Sud, Massa 54100, Italy; e-mail: [email protected].
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.02.068
FEATURE ARTICLES
Paraplegia after cardiac surgery is a rare complication. There are some articles reporting spinal cord infarction after coronary artery surgery [1–4]. In those cases, highly likely mechanism of spinal cord infarction could be microembolization of atherosclerotic plaque or cholesterol emboli from the aorta. In our case, the patient did not have a history of hypertension, hyperlipidemia, diabetes, or peripheral vascular diseases. Before manipulating cardiopulmonary bypass, epiaortic echography was performed, which showed there was no particular atherosclerotic plaque at the ascending aorta. Therefore, we might suggest atherosclerotic disease did not influence paraplegia significantly in this patient. The MRI revealed that the cause of paraplegia of this patient was intramedullary hemorrhage. There seems to be a difference on the cause of paraplegia between reported cases (infarction) and our case (hemorrhage). Intramedullary hemorrhage is commonly caused by trauma, vascular malformation, or bleeding diatheses [5]. This patient took Coumadin before surgery for atrial fibrillation and discontinued 4 days before surgery. The PT-INR on admission was 2.4. Three days before surgery, the patient complained of left-sided back pain. Electrocardiogram, chest X-ray, brain computed tomography, and blood data did not show any significant changes. Pain was controlled by conventional analgesia. Retrospectively thinking, the patient might be complicated with small intramedullary hemorrhage due to preoperative anticoagulation therapy, when he complained of back pain preoperatively. It may be presumed that during cardiac surgery with general heparinization, the size of hemorrhage increased. Consequently, the hemorrhage caused paraplegia after surgery. We might suggest that the patient should have been examined with MRI, which was the only one modality for diagnosing intramedullary hemorrhage. This report suggests that intramedullary hemorrhage may occur with usual oral anticoagulation therapy and after cardiac surgery.
CASE REPORT PANESI ET AL MUTATIONS IN THORACIC AORTIC ANEURYSMS
