Symptomatic spinal epidural lipomatosis (SEL) is very rare and frequently associated to chronic exogenous steroid use, obesity and Cushing syndrome. The idiopathic cases where no identifiable association with SEL are found constitute only 17% of all cases. The usual clinical manifestations of this entity consist of dorsal or lumbar pain with paresthesias and weakness in lower limbs, but acute symptoms of myelopathy are exceptional. We report a case of acute paraparesis and urinary retention caused by thoracic SEL in a 55-year-old male who did not have any recognized predisposing factor for this condition. Urgent surgical decompression was performed in order to relieve the symptoms. Slow but progressive improvement was assessed after surgery. We consider this case to be exceptional due to the needing to perform an urgent decompressive laminectomy to treat a rapidly progressive myelopathy caused by idiopathic SEL.
Epidural lipomatosis; Paraparesis; Spinal cord compression; Surgical decompression; Myelopathy
Abnormal fat deposition in the epidural space or spinal epidural lipomatosis (SEL) due to corticosteroid treatment or obesity may cause obstruction to cerebrospinal fluid flow. Little is known about SEL in patients with hematologic malignancies who require frequent lumbar punctures and corticosteroid treatment that places them at risk.
Patients and methods
Records and radiologic images of patients with SEL and leukemia or non Hodgkin lymphoma (NHL) treated at a single institution from 1999–2009 were reviewed. Risk factors were compared with 405 control patients with leukemia.
Fourteen patients with leukemia or NHL were diagnosed with SEL. The majority of patients underwent diagnostic imaging after unsuccessful lumbar punctures within one month of their primary diagnosis. Prior to SEL diagnosis, all patients received systemic and/or intrathecal corticosteroids. SEL diagnosis led to modification of intrathecal administration in 8 patients, including Ommaya reservoir placement in 4 patients. All patients completed protocol-specified chemotherapy without neurologic symptoms or surgical intervention. Risk factors for developing SEL include older age and high body mass index.
Investigation for SEL in leukemia or lymphoma patients with difficult lumbar punctures is warranted. Placement of an Ommaya reservoir may facilitate safe CNS-directed therapy in severely affected patients.
spinal epidural lipomatosis; lumbar canal obstruction; difficult lumbar puncture; leukemia; lymphoma
Spinal epidural lipomatosis (SEL) is a rare but well-recognized condition. In general, the onset of its symptoms is insidious and the disease progresses slowly. We report two cases of rapid progression of SEL with no history of steroid intake in non-obese individuals after epidural steroid injection. These SEL patients developed neurologic symptoms after less than 5 months; these symptoms were confirmed to be due to SEL by serial MR images. After the debulking of the epidural fat, their symptoms improved.
Spinal epidural lipomatosis; Epidural steroid injection
Epidural lipomatosis is a rare entity to cause spinal cord compression and neurological deficits. This is usually associated with excess of steroids in the body either because of endogenous source as in Cushings disease or exogenous intake as in some diseases like systemic lupus erythematosus, in some endocrinopathies or in morbid obesity. But in some cases no cause has been found. Such idiopathic cases of spinal epidural lipomatosis have also been reported. Here, we report a case of idiopathic spinal epidural lipomatosis with relapsing and remitting paraparesis which is quite unusual. Treatment depends upon neurological status of the patient. We operated the patient as he had significant neurological compromise and he improved significantly.
Idiopathic cord compression; myelopathy; paraparesis; spinal epidural lipomatosis
The authors report a case of a thoracic epidural spinal lipomatosis causing severe neurological deficits along the review of pertinent literature. The patient is a 56-year-old woman who presented with acute onset of severe paraparesis; she was investigated with cervical and thoracic MRI and then surgically managed because of an intraspinal mass compressing the cord. The operation consisted in the excision of the mass confirmed to be a fibrolipoma by pathological analysis. The patient attained complete neurological recovery and at 18 months follow-up she reported a generalised well-being. Thoracic lipomas are rare lesions that presenting mostly with back pain; however, in rare instances they may cause progressive and/or abrupt neurological dysfunction. Appropriate imaging can help in the diagnosis and management of such cases.
A 68-year-old male presented with rapidly progressive paraplegia. MR images of the thoracic spine were interpreted as being consistent with an abscess within an epidural lipomatosis compressing the spinal cord. Laminectomy was performed, and a large amount of pus was drained from the epidural lipomatosis, from which Staphylococcus aureus was isolated. This is the first reported case of an abscess involving an epidural lipomatosis.
Epidural lipomatosis; Spinal abscess; Magnetic resonance imaging
Spinal epidural lipomatosis is a rare complication of chronic corticosteroid treatment. We report a new pediatric case and an analysis of this and 19 pediatric cases identified in the international literature. The youngest of these combined 20 patients was 5 years old when lipomatosis was diagnosed. Lipomatosis manifested after a mean of 1.3 (+/- 1.5) years (SD) (median, 0.8 years; range, 3 weeks - 6.5 years) of corticosteroid treatment. The corticosteroid dose at the time of presentation of the lipomatosis ranged widely, between 5 and 80 mg of prednisone/day. Back pain was the most common presenting symptom. Imaging revealed that lipomatosis almost always involved the thoracic spine, extending into the lumbosacral region in a subset of patients. Predominantly lumbosacral involvement was documented in only two cases. Although a neurological deficit at presentation was documented in about half of the cases, surgical decompression was not performed in the cases reported after 1996. Instead, reducing the corticosteroid dose (sometimes combined with dietary restriction to mobilize fat) sufficed to induce remission. In summary, pediatric spinal epidural lipomatosis remains a potentially serious untoward effect of corticosteroid treatment, which, if recognized in a timely manner, can have a good outcome with conservative treatment.
Case report: To report a case of epidural lipomatosis in a patient with abnormal adipose tissue distribution, glucose intolerance and mixed hyperlipidemia. A 63-year-old male patient presented with low back pain radiating to the left calf on standing and walking (walking distance <100 m). He weighed 97.5 kg, was 1.73 m tall (BMI 32.6 kg/m2) and had a waist circumference of 113 cm. He had a glucose intolerance after a 75-g glucose oral load test. CT-Myelography revealed voluminous epidural lipomatosis around L4–L5 and L5–S1. Low calorie diet and reduction in alcohol intake achieved a weight loss of 17.5 kg in 7 months (80 kg, BMI 25.8 kg/m2, waist circumference 94 cm) and dramatic improvement in low back pain, walking distance (>500 m) and reduction of lipomatosis on CT-scan. Our case suggests a relationship between central obesity phenotype and epidural lipomatosis. Specific insulin resistance treatment might be proposed for these patients if this hypothesis is confirmed in further studies.
Lipomatosis; Epidural; Obesity; Hyperinsulinism
Complications after lumbar anaesthesia and epidural blood patch have been described in patients with congenital small spinal canal and increased epidural fat or epidural lipomatosis. These conditions, whether occurring separately or in combination, require magnetic resonance imaging for diagnosis and grading, but their clinical significance is still unclear.
A 35-year-old Caucasian woman who was undergoing a Caesarean section developed a longstanding L4-L5 unilateral neuropathy after the administration of spinal anaesthesia. There were several attempts to correctly position the needle, one of which resulted in paraesthesia. A magnetic resonance image revealed that the patient's bony spinal canal was congenitally small and had excess epidural fat. The cross-sectional area of the dural sac was then reduced, which left practically no free cerebrospinal fluid space.
The combination of epidural lipomatosis of varying degrees and congenital small spinal canal has not been previously discussed with spinal anaesthesia. Due to the low cerebrospinal fluid content of the small dural sac, the cauda equina becomes a firm system with a very limited possibility for the nerve roots to move away from the puncture needle when it is inserted into the dural sac. This constitutes risks of technical difficulties and neuropathies with spinal anaesthesia.
Mediastinal widening is a common finding on chest radiograph, and can be caused by numerous conditions. Most of these diseases have grave prognosis if accompanied by chest pain, and require immediate attention. However, mediastinal lipomatosis is a very benign condition caused by deposition of adipose tissue in the mediastinum.
We present a case of a morbidly obese female patient who presented to emergency department with a fall. She had mediastinal widening on chest radiograph, and borderline low voltage on electrocardiogram. On computed tomography, mediastinal lipomatosis was evident.
Obesity is a major epidemic in United States, and can lead to deposition of fat in the chest. Mediastinal lipomatosis is very benign condition, which rarely causes grave consequences.
Spontaneously occurring spinal epidural hematomas are uncommon clinical findings, and the chronic form is the rarest and its most frequent location is the lumbar spine. Pure radicular involvement is far less frequent than myelopathy. We report a case of progressive radiculopathy in a 52-year-old man with spontaneously occurring cervical epidural hematoma (SCEH). The patient had left hand weakness and numbness for 4 months. MRI scan showed small space-occupying lesion around left 8th cervical nerve root. After surgery we confirmed chronic organizing epidural hematoma. To the best of our knowledge, this is the second reported case in the worldwide literature of pure radiculopathy in a patient with chronic SCEH.
Spontaneous epidural hematoma; Radiculopathy; Chronic
We intend to report the largest series of spinal epidural cavernomas (SEC), discuss their clinical features, imaging characteristics, surgical findings, outcome analysis and compare them with similar reports in the literature.
Among the cases of spinal tumors treated surgically by the authors, there have been nine cases of SEC’s. All the data were collected prospectively and the cases have been followed after surgery up to the time of this analysis.
There were six female and three male patients with the ages ranging between 13 and 74 years. The lesions were located in the thoracic spine (4 cases), lumbar spine (4 cases) and one at the sacral level. Clinical presentations included acute spinal pain and paraparesis in two, low back pain and radiculopathy in five, and slowly progressive myelopathy in the other two cases. The lesion was iso-intense with the spinal cord in T1W images and hyperintense in T2W images and showed strong homogeneous enhancement after contrast medium injection in most of our cases. In the presence of hemorrhage inside the lesion, it was hyperintense in both T1W and T2W MR sequences as in our case 6. In the single case presenting with acute hemorrhage, epidural hematoma was the only finding, our case 1. Complete surgical removal was achieved in all our cases, and confirmed by postoperative MRI.
SEC is hard to be differentiated from other epidural spinal lesions before intervention but should be considered in the list of differential diagnosis regarding its favorable outcome.
Cavernous angioma; Magnetic resonance imaging; Spinal epidural cavernoma; Spinal epidural lesion
Neurological deficits following epidural or spinal anesthesia are extremely rare. Transient paraplegia following epidural anesthesia in a patient with thoracic disc herniation has been presented. A 44-year-old woman developed paraplegia during the operation for vascular surgery of her legs under epidural anesthesia. Epidural hematoma or spinal cord ischemia was ruled out by magnetic resonance imaging of the thoracic and lumbar spine in which protruded disc at T11-12 level compressing the spinal cord has been verified. Patient responded well to steroid treatment and rehabilitation interventions. Physicians should be aware of preceding disc protrusions, which may have detrimental effects on spinal cord perfusion, as a cause of persistent or transient paraplegia before epidural anesthesia procedure. MRI is a valuable imaging option to rule out epidural anesthesia complications and coexisting pathologies like disc herniations.
Vertebral haemangiomas are recognized to be one of the commonest benign tumours of the vertebral column, occurring mostly in the thoracic spine. The vast majority of these are asymptomatic. Infrequently, these can turn symptomatic and cause neurological deficit (cord compression) through any of four reported mechanisms: (1) epidural extension; (2) expansion of the involved vertebra(e) causing spinal canal stenosis; (3) spontaneous epidural haemorrhage; (4) pathological burst fracture. Thoracic haemangiomas have been reported to be more likely to produce cord compression than lumbar haemangiomas.
A forty-nine year old male with acute onset spinal cord compression from a pathological fracture in a first lumbar vertebral haemangioma. An MRI delineated the haemangioma and extent of bleeding that caused the cord compression. These were confirmed during surgery and the haematoma was evacuated. The spine was instrumented from T12 to L2, and a cement vertebroplasty was performed intra-operatively. Written consent for publication was obtained from the patient.
The junctional location of the first lumbar vertebra, and the structural weakness from normal bone being replaced by the haemangioma, probably caused it to fracture under axial loading. This pathological fracture caused bleeding from the vascularized bone, resulting in cord compression.
Vertebral haemangioma; Pathological fracture; Spinal cord compression; Vertebroplasty; Paralysis; Paraparesis
Spinal epidural hematoma (SEH) represents the most frequent entity of acute or chronic spinal bleeding. Based upon pathogenesis, SEH can be classified as idiopathic, spontaneous, and secondary. The idiopathic forms are considered not to be attributed to any specific risk factors. Spontaneous SEH, accounting for 0.3–0.9% of all spinal epidural space occupying lesions, instead is associated with risk factors (such as substantial soft trauma or coagulation abnormalities). The chronic form, as our literature review revealed, is the rarest and its most frequent location is the lumbar spine. The pathophysiology of spontaneous and idiopathic SEH is still under debate: There are only a few reports in literature of chronically evolving SEH with progressively increasing pain and neurological impairment. Magnetic resonance imaging may be inconclusive for differential diagnosis. Here, we present two cases of lumbar chronic SEH with slow, progressive, and persistent lumbar radicular impairment. The first patient reported a minor trauma with slight back contusion and thus was classified as spontaneous SEH. In the second case not even a minor trauma was involved, so we considered it to be idiopathic SEH. In both cases preoperative blood and coagulation tests were normal and we did not find any other or co-factors in the patients’ clinical histories. MR imaging showed uncertain spinal canal obstructing lesions at L3 and L4 level in both cases. Surgical treatment allowed a correct diagnosis and resulted in full clinical and neuroradiological recovery after 1 year follow-up. Our aim is to discuss pathogenesis, clinical and radiological features, differential diagnosis and treatment options, on the background of relevant literature review.
Spontaneous; Idiopathic; Chronic; Hematoma; Epidural; Spinal
Case report and literature review.
Report the highly unusual presentation of thoracic spine chordoma in an 89-year-old and review existing literature as it impacts treatment in the elderly.
Summary of background data
Chordomas are infrequent tumors of the spine that commonly present during mid-adulthood at the spheno-occipital or sacrococcygeal junctions. The mobile spine is affected in 10–15% of cases but chordomas are extremely rare in the thoracic spine. Chordoma rarely enters the differential diagnosis of spinal tumors in elderly patients, for whom metastases and multiple myeloma are by far the most common.
A case report is detailed of an 89-year-old male presenting with incapacitating pain and early signs of thoracic myelopathy. A lytic, expanding lesion of the T10 vertebral body with epidural spinal cord compression was identified. In the absence of evidence of other primary tumor, a CT-guided needle biopsy revealed chordoma. A literature review of reported thoracic spine chordomas was also performed.
An intralesional posterolateral resection and reconstruction was performed with good results and no recurrence at 13 months’ follow-up. 30 reports of thoracic spine chordomas were identified in the literature since 1902. Mean age of presentation at 35.7 years is earlier than for most chordomas. The oldest previously reported patient was 68-year-old. Neurological impairment at presentation is rare with the usual presenting symptom being pain. Response to radiation and chemotherapy is limited. 5-year survival rates range from 50 to 60%.
Chordoma is a highly uncommon epidural neoplasm of the thoracic spine and is vanishingly rare in elderly patients. This report documents the oldest reported patient with thoracic spine chordoma at 89-year-old. Their locally aggressive behavior typically prompts consideration of aggressive surgical resection. When tailored to the individual patient, such procedures are feasible without excessive morbidity even in elderly patients.
Chordoma; Spine; Vertebrae, thoracic; Corpectomy
Ischiofemoral impingement syndrome is known as one of the causes of hip pain due to impingement of ischium and femur, and usually correlated with trauma or operation. We report a rare case of ischiofemoral impingement syndrome that has no history of trauma or surgery. A 48-year-old female patient was referred for 2 months history of the left hip pain, radiating to lower extremity with a hip snapping sensation. She had no history of trauma or surgery at or around the hip joint and femur. The magnetic resonance imaging (MRI) of the lumbar spine showed no abnormality, except diffuse bulging disc without cord compression at the lumbosacral area. Electrophysiologic study was normal, and there were no neurologic abnormalities compatible with the lumbosacral radiculopathy or spinal stenosis. Hip MRI revealed quadratus femoris muscle edema with concurrent narrowing of the ischiofemoral space. The distance of ischiofemoral space and quadratus femoris space were narrow. It was compatible with ischiofemoral impingement syndrome. After treatment with nonsteroidal anti-inflammatory drugs, physical therapy, and exercise program, the patient's pain was relieved and the snapping was improved. To our knowledge, this is the first reported case of a nontraumatic, noniatrogenic ischiofemoral impingement syndrome, and also the first case to be treated by a nonsurgical method in the Republic of Korea.
Ischiofemoral; Impingement; Impingement syndrome
Staphylococcal enterotoxins (SEs) are a common causative agent of food poisoning. Recently, many new SE-like (SEl) toxins have been reported, although the role of SEls in food poisoning remains unclear. In this study, the emetic potentials of SElK, SElL, SElM, SElN, SElO, SElP, and SElQ were assessed using a monkey-feeding assay. All the SEls that were tested induced emetic reactions in monkeys at a dose of 100 μg/kg, although the numbers of affected monkeys were significantly smaller than the numbers that were affected after consuming SEA or SEB. This result suggests that these new SEs may play some role in staphylococcal food poisoning.
A 55-year-old obese man (body mass index, 31.6 kg/m2) presented radiating pain and motor weakness in the left leg. Magnetic resonance imaging showed an epidural mass posterior to the L5 vertebral body, which was isosignal to subcutaneous fat and it asymmetrically compressed the left side of the cauda equina and the exiting left L5 nerve root on the axial T1 weighted images. Severe arthritis of the left facet joint and edema of the bone marrow regarding the left pedicle were also found. As far as we know, there have been no reports concerning a solitary epidural lipoma combined with ipsilateral facet arthorsis causing lumbar radiculopathy. Solitary epidural lipoma with ipsilateral facet arthritis causing lumbar radiculopathy was removed after the failure of conservative treatment. After decompression, the neurologic deficit was relieved. At a 2 year follow-up, motor weakness had completely recovered and the patient was satisfied with the result. We recommend that a solitary epidural lipoma causing neurologic deficit should be excised at the time of diagnosis.
Solitary epidural lipoma; Posterior facet; Ipsilateral arthritis; Lumbar radiculopathy
Study Design Case report.
Objective Merkel cell carcinoma (MCC), an uncommon cutaneous neuroendocrine malignancy, is a rare cause of spinal metastasis, with only five cases previously reported. We report a rare case of MCC metastatic to the spine in an immunocompromised patient.
Methods A 55-year-old male with previously resected MCC, immunocompromised due to cardiac transplant, presented with sharp mid-thoracic back pain radiating around the trunk to the midline. Computed tomography of the thoracic spine showed a dorsal epidural mass from T6 to T8 with compression of the spinal cord. Laminectomy and subtotal tumor resection were performed, and pathology confirmed Merkel cell tumor through immunohistochemistry staining positive for cytokeratin 20 and negative for thyroid transcription factor-1.
Results Further treatment with radiation therapy was initiated, and the patient did well for 4 months after surgery, but returned with a lesion in the cervical spine. He then opted for hospice care.
Conclusions With an increasing number of immunocompromised patients presenting with back pain, MCC should be considered in the differential diagnosis of spinal metastatic disease.
carcinoma; Merkel cell; spinal cord compression; thoracic; metastasis; immunocompromised patient
Intervertebral disk herniation is relatively common. Migration usually occurs in the ventral epidural space; rarely, disks migrate to the dorsal epidural space due to the natural anatomical barriers of the thecal sac.
A 49-year-old man presented with 1 week of severe back pain with bilateral radiculopathy to the lateral aspect of his lower extremities and weakness of the ankle dorsiflexors and toe extensors. Lumbar spine magnetic resonance imaging with gadolinium revealed a peripheral enhancing dorsal epidural lesion with severe compression of the thecal sac. Initial differential diagnosis included spontaneous hematoma, synovial cyst, and epidural abscess. Posterior lumbar decompression was performed; intraoperatively, the lesion was identified as a large herniated disk fragment.
Dorsal migration of a herniated intervertebral disk is rare and may be difficult to definitively diagnose preoperatively. Dorsal disk migration may present in a variety of clinical scenarios and, as in this case, may mimic other epidural lesions on magnetic resonance imaging.
Vertebral disk, herniation; Back pain, radiculopathy; Abscess, epidural; Hematoma, epidural; Laminectomy; Decompression, lumbar
Adiposis dolorosa (AD) is a syndrome of obese and non-obese individuals whose hallmark is lipomatosis: unencapsulated painful fatty masses in subcutaneous fat. Lipomatosis may contain excess collagen and multi-nucleated giant (MNG) cells. Case reports suggest metabolic defects in AD.
(1) To determine whether women with AD have altered relative resting energy expenditure (REE per total body mass) compared with controls; and (2) to quantitate lipomatosis-associated collagen, MNGs and tissue and blood cytokines that may influence REE.
A total of 10 women with AD were compared with age, body mass index, fat and weight-matched control women. Adipose tissue was obtained from five women with AD and five controls and evaluated for collagen and macrophages/MNGs. Fat mass and fat-free mass were identified by dual X-ray absorptiometry. REE was by determined indirect calorimetry and related to mass. Adipokines and cytokines were evaluated in blood and tissue.
Relative REE (REE per total body mass) was lower in women with AD compared with controls (P=0.007). Only lipomatosis (group) and total body mass were significant predictors of REE in forward stepwise regression (P<0.0001). Adipose interleukin (IL)-6 levels were elevated (P=0.03) and connective tissue was increased fourfold in lipomatosis compared with control tissue (P<0.0001). There was no difference in adipose tissue macrophages between groups; 30% of women with AD had MNG cells. Anti-inflammatory IL-13 levels were elevated (P=0.03), and cytokines important in the recruitment of monocytes, Fraktalkine (P=0.04) and macrophage inflammatory protein-1β (P=0.009), were significantly lower in the blood of women with AD compared with controls.
The lower relative REE in women with AD compared with controls was associated with increased connective (non-metabolic) tissue in the lipomatosis, and inflammation, although underlying metabolic defects may be important as well. Understanding the pathophysiology and metabolism of lipomatosis in AD may contribute to a better understanding of metabolism in non-lipomatosis obesity.
adiposis dolorosa; resting energy expenditure; IL-6; Dercum's disease; lipomatosis
Selenoprotein S (SelS) is an important endoplasmic reticulum and plasma membrane-located selenoprotein implicated in inflammatory responses and insulin resistance. However, the effects of SelS on endothelial cells (ECs) have not been reported. In the present study, the role of SelS in oxidative stress and the underlying mechanism were investigated in human ECs.
A SelS over-expression plasmid (pc-SelS) and a SelS-siRNA plasmid were transfected into human umbilical vein endothelial cells (American Type Culture Collection, USA). The cells were divided into four groups: control, SelS over-expression (transfected with pc-SelS), vector control, and SelS knockdown (transfected with siRNA-SelS). After treating the cells with H2O2, the effects of oxidative stress and the expression of caveolin-1 (Cav-1) and protein kinase Cα (PKCα) were investigated.
Following treatment with H2O2, over-expression of SelS significantly increased cell viability and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) production and Cav-1 gene and protein expression. However, no effects on PKCα were observed. In contrast, knockdown of SelS significantly decreased cell viability, SOD activity, and PKCα gene and protein expression, and increased MDA production and Cav-1 gene and protein expression.
SelS protects ECs from oxidative stress by inhibiting the expression of Cav-1 and PKCα.
Endothelial cell dysfunction; Oxidation; Selenoprotein S; Caveolin-1; Protein kinase Cα
Spondylotic change of the spine is common in the cervical and lumbar regions and may present with compression of the spinal cord and nerve roots. Myelopathy due to degenerative disease in the thoracic spine is exceptional. Only a few cases have been reported in the literature and these reports have described disease in the lower four thoracic segments. We report a case of paraparesis caused by degenerative disease in the upper thoracic spine which has not previously been described.
Many studies have reported spontaneous spinal epidural hematoma (SSEH). Although most cases are idiopathic, several are associated with thrombolytic therapy or anticoagulants. We report a case of SSEH coincident with acute myocardial infarction (AMI), which caused serious neurological deficits. A 56 year old man presented with chest pain accompanied with back and neck pain, which was regarded as an atypical symptom of AMI. He was treated with nitroglycerin, aspirin, low molecular weight heparin, and clopidogrel. A spinal magnetic resonance image taken after paraplegia developed 3 days after the initial symptoms revealed an epidural hematoma at the cervical and thoracolumbar spine. Despite emergent decompressive surgery, paraplegia has not improved 7 months after surgery. A SSEH should be considered when patients complain of abrupt, strong, and non-traumatic back and neck pain, particularly if they have no spinal pain history.
Acute myocardial infarction; Hematoma, epidural, spinal; Paraplegia; Thrombolytic therapy; Anticoagulants