Acute Spinal Subdural Hematoma in a Patient with Active Systemic Lupus Erythematosus: a Case Report and Literature Review

□ CASE REPORT □

Acute Spinal Subdural Hematoma in a Patient with Active Systemic Lupus Erythematosus: A Case Report and Literature Review

Koji Akita 1, Taishi Wada 1, Shunpei Horii 1, Mitsuyo Matsumoto 2, Takeshi Adachi 1, Fumihiko Kimura 2 and Kenji Itoh 2

Abstract

We herein describe a case of acute spinal subdural hematoma (SSDH) during the administration of high- dose corticosteroids and intravenous heparin for the treatment of active lupus nephritis. After SSDH was promptly diagnosed using magnetic resonance imaging (MRI), the patient recovered well with conservative treatment involving the discontinuation of heparin sodium. Although SSDH is a rare complication, it should be considered as a cause of neurological manifestations in patients with active systemic lupus erythematosus.

Key words: MRI, spinal subdural hematoma, systemic lupus erythematosus

(Intern Med 53: 887-890, 2014) (DOI: 10.2169/internalmedicine.53.1624)

In addition, we provide a review of the literature. Introduction Case Report Complications involving the spinal cord are rare in patients with systemic lupus erythematosus (SLE) (1). Trans- A 30-year-old woman presented to our hospital with gen- verse myelitis, a demyelinating syndrome resulting from the eral fatigue, digital swelling and dyspnea on exertion lasting high disease activity of SLE, is the most frequent spinal for three months. A hematological examination revealed complication and has been suggested to have a strong asso- pancytopenia (red blood cell count, 314×104/mm3; hemoglo- ciation with the presence of anti-phospholipid antibodies (1). bin level, 8.5 g/dL; hematocrit, 26.3%; white blood cell However, symptoms that are similar to transverse myelitis count, 2,900/mm3; platelet count, 11.8×104/mm3). A urinaly- may be mimicked in cases of space occupying spinal cord sis revealed protein 2+ and occult blood 2+. Blood chemis- lesions, such as abscesses, hematomas and neoplasms. In- try and serological tests showed an elevated creatinine level trathecal bleeding should be considered as a differential di- of 1.09 mg/dL, a C-reactive protein level of 1.1 mg/dL, a agnosis in such cases. decreased C3 level of 32 mg/dL, a C4 level of 4 mg/dL, an Acute spinal subdural hematoma (SSDH) is an exceed- elevated antinuclear antibody (ANA) level of ×81,920 (pe- ingly uncommon and potentially life-threatening condition. ripheral pattern) and an anti-double-stranded (ds) DNA anti- SSDH usually occurs as a result of trauma or an accident on body level of >400 IU/mL. A chest X-ray scan indicated lumber puncture and rarely occurs spontaneously in cases of cardiomegaly (cardiothoracic ratio: 60%), and echocar- hematological disorders, vascular malformations, tumors or diography revealed a medium amount of pericardial effu- anticoagulant use (2, 3). sion. Although a prolonged activated partial thromboplastin We herein describe a case of SSDH that occurred during time (aPTT) of 41 seconds and an elevated D dimer value the administration of high-dose corticosteroids and intrave- of 3.7 ng/dL were observed, other coagulation parameters, nous (IV) heparin for the treatment of active lupus nephritis. including the levels of protein S, protein C and anti-

１Division of Cardiology, Department of Internal Medicine, National Defense Medical College, Japan and ２Division of Hematology and Rheuma- tology, Department of Internal Medicine, National Defense Medical College, Japan Received for publication August 22, 2013; Accepted for publication October 24, 2013 Correspondence to Dr. Kenji Itoh, [email protected]

887 Intern Med 53: 887-890, 2014 DOI: 10.2169/internalmedicine.53.1624 thrombin III, were within the normal ranges. Anti- cardiolipin (CL) antibodies and lupus anticoagulant were later proven to be negative. The patient was diagnosed with SLE, fulfilling the 1982 American College of Rheumatology (ACR) criteria, with non-erosive arthritis, pericarditis, a renal disorder, a hematological disorder and the presence of anti-ds DNA antibodies with positive ANA. The SLE disease activity index (SLEDAI) score was 23, indicating a very high disease activity. The administration of intravenous pulse methylprednis- olone (1,000 mg/day for three days) followed by oral prednisolone (60 mg daily) was started to treat the lupus nephritis and pericarditis. Considering for the possibility of antiphospholipid antibody syndrome (APS), as indicated by the Figure 1. A contrast-enhanced computed tomography scan prolonged aPTT, and high-dose corticosteroid-induced accel- obtained 30 minutes after the onset of symptoms shows a small erated coagulability, IV heparin sodium (15,000 units/day) lesion with high signal density on the left side of the spinal cord was also administered. at the seventh thoracic vertebral level. On the ninth day of treatment, the patient presented with sudden back and chest pain and, a few hours later, experi- enced a headache and stiffness in her neck. A physical examination revealed tachycardia and a high blood pressure of Discussion 220/146 mmHg; however, no apparent objective neurological findings were detected. Blood examinations, electrocardi- We herein reported a case of acute SSDH that occurred ography, echocardiography and contrast-enhanced computed during the administration of high-dose corticosteroids and tomography (CE-CT) did not demonstrate any signs of acute heparin sodium infusion in a patient with SLE. coronary syndrome, aortic dissection, pulmonary embolism Spinal involvement is a very rare manifestation of SLE; or intracranial bleeding. However, a small lesion of in- however, this condition is intractable and often refractory, creased signal density was observed in the spinal cord at the resulting in neurological sequelae. A prompt diagnosis and seventh thoracic vertebral level on a CE-CT scan (Fig. 1). appropriate treatment are required. The possibility of the prodromal stage of transverse myelitis Transverse myelitis, a demyelinating syndrome that re- due to the activity of SLE and intrathecal bleeding were sults from the high disease activity of SLE, is the most fre- considered as differential diagnoses. An MRI scan of the quent spinal complication (1); however, similar symptoms spine revealed a small, round lesion with a highly intense may be mimicked by space-occupying spinal cord lesions. signal on T2-weighted images and an isointense signal on Intrathecal bleeding should be considered as a differential T1-weighted images; the lesion appeared to compress the diagnosis. Only nine reports of intrathecal bleeding during spinal cord at the seventh thoracic vertebral level (Fig. 2). the clinical course of SLE have been published in the litera- These results were consistent with the findings of the acute ture (4-12) (Table). In these cases, the bleeding sites covered phase of SSDH (2, 3). No signs of transverse myelitis were a wide range of the spine. Of the nine reported cases, hema- observed (1). Bloody cerebrospinal fluid was noted on a spi- tomas were observed in the thoracic spine in three cases and nal tap. A coagulation test showed a prolonged aPTT of 53 in the cervical spine in four cases. No unique spinal bleed- seconds induced by the administration of heparin sodium. ing sites associated with SLE were noted among the small Conservative management comprised discontinuation of number of examples. Interestingly, six of the nine reported the heparin sodium infusion. Blood pressure control and cases involved hemorrhagic events when the patients exhib- pain relief were also included because the patient did not ited a high level of disease activity of SLE (4, 6, 7, 9-11). exhibit any motor, sensory or autonomic nervous disorders. Vasculitis at the bleeding site was pathologically docu- Her back pain and headache were palliated within six days mented in three of the six active cases (4, 10, 11). On the after onset. She recovered well with no neurological se- other hand, Satoh described the a case of a patient who de- quelae. An MRI scan performed 26 days after onset indi- veloped a spinal epidural hematoma when the SLE disease cated that the hematoma had almost completely regressed. A activity was low and stable, without vasculitis or vascular contrast-enhanced MRI scan did not show any signs of vas- malformation at the site of bleeding (12). cular malformation or tumor-like structures at the site of In the present case, the hematoma appeared on the ninth bleeding. day of the initial treatment for lupus nephritis and pericarditis. The serum compliment value and the CRP level had re- turned to normal, whereas the anti-ds DNA antibody level was still high. The SLEDAI score at the onset of bleeding

888 Intern Med 53: 887-890, 2014 DOI: 10.2169/internalmedicine.53.1624

Figure 2. A sagittal magnetic resonance imaging scan of the spinal cord on the day after onset shows a small, round lesion at the seventh thoracic vertebral level with an isointense signal on a T1- weighted image (a) and a highly intense signal on a T2-weighted image (b). An axial T2-weighted image of the spinal cord demonstrating a highly intense signal and round lesion compressing the spinal cord at the seventh thoracic vertebral level (c).

Table. Reported Cases of Intrathecal Bleeding during the Clinical Course of SLE

Age Sex Type of bleeding Type of lupus Status of lupus APS Anticoagulant use Ref. No. 24 F SSDH nephritis active No No 9 50 F SSAH nephritis, vasculitis at the site active N/A No 11 39 F SEDH nephritis active Yes No 6 47 F SEDH arthritis not active No No 12 44 F SEDH nephritis, pleuritis, pericarditis active No No 7 29 F N/A N/A N/A Yas warfarin 8 20 F SEDH nephritis, vesculitis at the site active No No 10 52 F SSAH vasculitis at the site active No No 4 32 F SEDH nephritis N/A N/A N/A 5 30 F SSDH nephritis, pericarditis active No heparin sodium Present case SSDH: spinal subdural hematoma, SSAH: spinal subarachnoid hemorrhage, SEDH: spinal epidural hematoma, APS: anti-phospholipid antibody syndrome, N/A: not addressed was 18. Although it had decreased from a score of 23 at the of major bleeding events during IV heparin therapy is re- initiation of treatment for SLE, it continued to indicate a ported to be rather low, ranging from 0% to 7%, and is even high disease activity. There is a possibility that local vasculi- lower when the appropriate dose of heparin is determined tis caused by the SLE activity led to small vascular rupture. based on the aPTT (3, 13). However, although the risk of Thrombosis in the spinal vessels can trigger local vasculi- heparin-induced bleeding increases with the concomitant use tis, resulting in the formation of a hematoma. The possibil- of aspirin or thrombolytic agents (13), the present patient ity of APS was considered due to the patient’s prolonged did not use any additional anticoagulants or aspirin. The in- aPTT and slightly elevated D dimer level on admission. fusion of heparin sodium in the present case may have been However, other coagulation parameters were normal, and an adverse factor; however, it is unlikely to be the sole tests for both anti-CL antibodies and lupus anticoagulant cause of the SSDH. Regarding SLE, anticoagulant therapy is were negative. The patient also had no history of thrombo- usually administered in cases complicated with APS. Bleed- sis. Moreover, she was receiving heparin sodium infusion at ing complications have been reported in a few patients with the time of the event. Only two of the nine reported cases SLE and APS (8, 14), whereas no bleeding risk factors or were complicated with APS, and no relationships between unique bleeding sites associated with SLE have been re- thrombosis and bleeding events were found (Table and ref. ported. 6, 8). It is unlikely that the formation of thrombi contributed Most patients with SSDH exhibit neurological disorders to the bleeding event in the present case. that require emergent decompression of the spinal cord to The administration of anticoagulants, including heparin prevent irreversible neurological damage (2, 3). Even if sodium, can be counted as a risk factor for spontaneous prompt surgical evacuation of the hematoma is applied, the SSDH. The incidence of anticoagulant therapy-associated outcomes are rather unsuccessful in patients with moderate spontaneous SSDH is reported to range from 8.7% to 17.7% to severe neurological deficits (2, 3). The present patient did of all SSDH cases (2, 3). In contrast, the overall incidence not display any neurological disorders, other than severe

889 Intern Med 53: 887-890, 2014 DOI: 10.2169/internalmedicine.53.1624 back and chest pain, despite the administration of spinal 1-49, 2003. compression at the site of the hematoma, and recovered well 4. Tang SC, Lee CF, Lee CW, Jeng JS. Systemic lupus erythematosus flare up manifestation as cerebral and spinal subarachnoid with conservative treatment. The administration of steroids, hemorrhage. Lupus 20: 1211-1213, 2011. with or without surgical evacuation, has resulted in a good 5. Chang MO, Koh ES, Kim MJ, Chang YS, Chung S. Spontaneous neurological recovery in some SSDH case reports (15, 16). spinal epidural hematoma. QJM 105: 705-706, 2012. The size of the hematoma in reported lupus patients with 6. Mohazab HR, Langer B, Spigos D. Spinal epidural hematoma in a good neurological improvement remained within three verte- patient with lupus coagulopathy: MR findings. AJR Am J Roent- brae and was rather smaller than that observed in patients genol 160: 853-854, 1993. 7. Goker B, Block JA. Spinal epidural hematoma complicating active with worse outcomes. Tang reported a case of cerebral and systemic lupus erythematosus. Arthritis Rheum 42: 577-578, 1999. spinal subarachnoid hemorrhage in a patient with active lu- 8. Castellino G, Cuadrado MJ, Godfrey T, Khamashta MA, Hughes pus (4). Despite having a massive spinal hemorrhage, the GR. Characteristics of patients with antiphospholipid syndrome patient recovered well under prompt aggressive immune with major bleeding after oral anticoagulant treatment. Ann therapy and ventricular drainage. In the present case, the Rheum Dis 60: 527-530, 2001. 9. Weil MH. Disseminated lupus erythematosus with massive hemor- size of the hematoma was rather small and remained within rhagic manifestations and paraplegia. J Lancet 75: 358-360, 1955. the width of one vertebra; therefore, the spinal cord damage 10. Romero-Vargas S, Ruiz-Sandoval JL, Barges-Coll J, et al. Patho- may not be irreversibly serious. Furthermore, she received logical demonstration of cervical spinal cord inflammatory vascu- high-dose corticosteroid treatment for lupus nephritis and litis in a patient with spontaneous spinal epidural haematoma as- pericarditis at the onset of the spinal hematoma. We surmise sociated with systemic lupus erythematosus. Neuropathol Appl Neurobiol 36: 568-570, 2010. that the administration of high-dose prednisolone relieves 11. Fody EP, Netsky MG, Mrak RE. Subarachnoid spinal hemorrhage spinal cord damage. in a case of systemic lupus erythematosus. Arch Neurol 37: 173- In conclusion, acute SSDH is a neurological emergency 174, 1980. that is primarily followed by the development of severe neu- 12. Satoh S, Hirakata M, Kameda H, et al. A case of systemic lupus rological disorders. Although SSDH is a rare complication, erythematosus associated with spinal epidural hematoma. Nihon Rinsho Meneki Gakkai Kaishi 21: 166-171, 1998 (in Japanese, it should be considered a possible cause of neurological Abstract in English). manifestations in patients with active SLE. 13. Levine MN, Raskob G, Landefeld S, Kearon C. Hemorrhagic complications of anticoagulant treatment. Chest 119 (1 Suppl): The authors state that they have no Conflict of Interest (COI). 108S-121S, 2001. 14. al-Sayegh FA, Ensworth S, Huang S, Stein HB, Klinkhoff AV. Hemorrhagic complications of long-term anticoagulant therapy in References 7 patients with systemic lupus erythematosus and antiphospholipid syndrome. J Rheumatol 24: 1716-1718, 1997. 1. Kovacs B, Lafferty TL, Brent LH, DeHoratius RJ. Transverse 15. Omori N, Takada E, Narai H, Tanaka T, Abe K, Manabe Y. Spon- myelopathy in systemic lupus erythematosus: an analysis of 14 taneous cervical epidural hematoma treated by the combination of cases and review of the literature. Ann Rheum Dis 59: 120-124, surgical evacuation and steroid pulse therapy. Intern Med 47: 437- 2000. 440, 2008. 2. Domenicucci M, Ramieri A, Ciappetta P, Delfini R. Nontraumatic 16. Al B, Yildirim C, Zengin S, Genc S, Erkutlu I, Mete A. Acute acute spinal subdural hematoma: report of five cases and review spontaneous spinal subdural haematoma presenting as paraplegia of the literature. J Neurosurg 91 (1 Suppl): 65-73, 1999. and complete recovery with non-operative treatment. BMJ Case 3. Kreppel D, Antoniadis G, Seeling W. Spinal hematoma: a litera- Rep 2009: 2009. ture survey with meta-analysis of 613 patients. Neurosurg Rev 26:

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