Subarachnoid Spinal Hemorrhage in a Case of Systemic Lupus Erythematosus Edward P. Fody, MD; Martin G. Netsky, MD; Robert E. Mrak, MD \s=b\ A 50-year-old woman with an 18-year history of systemic lupus erythematosus (SLE) died after an exacerbation of the illness, characterized by deteriorating mentation and right hemiplegia. Necropsy spinal subarachnoid hemorrhage resulting from aneurysmal dilation and rupture of the posterior spinal artery, which was involved by vasculitis. The left parietal lobe and internal capsule revealed massive contained recent infarcts. To our knowledge, this is the first reported case of SLE with spinal subarachnoid hemorrhage revealed by necropsy. {Arch Neurol 37:173:174, 1980) lupus erythematosus (SLE) ÇJystemic ^ produces vasculitis in many or¬ gans, but involvement of the neuraxis by frank arteritis is uncommon, even in patients with profound neurologic symptoms.1 We describe a patient with long-standing SLE who died with a clinically undiagnosed neuro¬ logic illness. Necropsy showed a mas¬ sive spinal subarachnoid hemorrhage secondary to aneurysmal dilation and rupture of the posterior spinal artery. Arteritis was the cause of the rupture. REPORT OF A CASE A 50-year-old woman complained of several days of swelling in feet, ankles, and arms, exertional chest pain, dyspnea, and constant frontal headache. The patient had first been seen in 1959 because of intermit¬ tent pain and swelling in joints of the upper extremities. A cell preparation was positive for lupus erythematosus. The patient's condition improved after treat- Accepted for publication March 10, 1979. From the Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tenn. Read in part before the 67th annual meeting of the International Academy of Pathology, United States-Canadian Division, Atlanta, March 7, 1978. ment with aspirin and hydroxychloroquine sulfate. She did well for the next 15 years except for progressive arthritis of the hands, necessitating reconstructive surgery. In August 1975, the serum reaction for antinuclear antibody was 4 + and a 24-hour urine specimen contained 2 g of protein. A renal biopsy analyzed by light and electron microscopy revealed "glomerulonephritis, immune-complex mediated and diffuse, with endothelial, epithelial, and mesangial deposits consistent with lupus nephritis." At this time, serum complement level was 0, and anti-DNA antibody level was 100 units (normal, <30 units). The patient was given prednisone (40 mg/day) and azathioprine (50 mg/day), and her condition , improved. The final admission was in December 1976. She now had a mild erythematous rash involving the face, palms, and neck, and dependent pitting edema. The find¬ ings on neurologic examination were normal. The urine reaction for protein was 3 + Protein concentration in the CSF was 31 mg/dL, glucose level was 55 mg/dL, and there were 30 RBCs and no WBCs per high-power field. Stained specimens and cultures were negative for bacteria. On the second day of hospitalization, the patient had a temperature of 39 °C and nuchal rigidity. Lumbar puncture was refused. Her mental capacities deterio¬ rated steadily. A lumbar puncture per¬ formed on the seventh day revealed an opening pressure of 114 mm H_,0, glucose level of 10 mg/dL, protein concentration of 200 mg/dL, and 84,000 RBCs and 3,500 WBCs per high-power field. Computerized tomogram of the head was normal. Cere¬ . bral angiogram showed generalized vascu¬ lar spasm; a malformation of blood vessels was not identified. Cephalosporin, gentamicin, and chloramphenicol therapy was started. On the tenth day of hospitaliza¬ tion, the patient responded only to pain. A right flaccid hemiplegia was noted. Sensa¬ tion was thought to be intact, and Babinski's sign was not present. She died on the 12th day of hospitalization. NECROPSY FINDINGS The spinal cord contained a large adher¬ Reprint requests to Department of Pathology, Vanderbilt University School of Medicine, 21st ent blood clot dorsally, covering much of the thoracic region and extending to the cervical and lumbar levels, but not includ¬ Netsky). ing the site of lumbar puncture. Vascular and Garland Streets, Nashville, TN 37232 (Dr Downloaded From: http://archneur.jamanetwork.com/ by a University of Pittsburgh User on 06/02/2015 lesions were not noted macroscopically. The hemorrhage ended abruptly at the foramen magnum. The brain was severely edematous. A recent ischemie infarct in the left cerebral hemisphere involved the white and gray matter in the parietal region, extending into the posterior part of the internal capsule.J Other gross lesions were * not noted in the CNS. Multiple sections of the spinal cord around the zone of hemorrhage were exam¬ ined microscopically. The following meth¬ ods were used: hematoxylin-eosin, Luxol Fast blue, Verhoeff's elastic tissue stain, PAS, and Masson's trichrome stain. A diffuse subarachnoid hemorrhage was present around the dorsal portion of the spinal cord. Large amounts of hemosiderin were noted throughout the areas of hemor¬ rhage. Several thrombosed degenerating vessels were identified in the position of the posterior spinal artery. One bulging vessel in the midthoracic region was inflamed and almost completely destroyed. Adjacent to and within the wall of this vessel were masses of degenerating cells containing mainly polymorphonuclear leu¬ kocytes. The vascular nature of this struc¬ ture was confirmed by the presence of elastic membranes and smooth muscle cells within the wall (Figure). The spinal cord was intact and was not demyelinated. Sections of the cerebral cortex in the region of the infarct showed edema, nuclear pyknosis in neurons, irregular cytoplasm, and focal mild hemorrhages. A section from the left visual cortex revealed a thrombus in one meningeal vessel. Addi¬ tional vascular or perivascular inflamma¬ tion was not found within the CNS. Renal findings included interstitial nephritis and glomerular changes similar to those seen in the previous biopsy. Noted also were inactive granulomatous disease of the lungs, bilateral adrenal cortical atro¬ phy, multiple small hepatic angiomas, and cholelithiasis. An acute vasculitis with endothelial proliferation and thrombosis was present in the gallbladder and vagi¬ na. COMMENT Neurologic problems are common in of SLE, affecting up to 75% of patients.' The symptoms include sei¬ zures, cranial nerve disorders, paraly¬ sis, peripheral neuropathy, and men¬ tal changes; the difficulties may wax cases spinal subarachnoid hemorrhage also may produce this finding. In our patient, SLE caused a vasculitis of a spinal artery with secondary aneurysm formation, rupture, and hemorrhage. Such an event is rare in the CNS, although it has occurred in the brain in cases of polyarteritis nodosa, poststreptococcal glomerulonephritis, and SLE, and in the spinal cord in instances of polyarteritis no¬ Evidence of infection was dosa. absent in our case, hence we assume that the vasculitis was mediated immunologically. We believe this is the first reported case of SLE with spinal subarachnoid hemorrhage re¬ vealed by necropsy. A nonfatal case has been reported from Japan.11 '-,; Ronald J. Gregory took the photomicrograph. Nonproprietary Name and Trademark of Drug Azathioprine—Im u ran. References Portion of wall of aneurysm revealing disrupted internal elastic membrane (arrow) and necrotic smooth muscle cells at site of aneurysmal rupture. Some degenerated leukocytes are scattered through this section. (Verhoeff's elastic tissue, 125). and wane during the course of the disease. In one large series involving 249 fatal cases of SLE, the primary cause of death was CNS damage in 13%.:i Peng et al stated that 11 of 30 deaths in patients with SLE were related to neurologic involvement.4 By contrast, examination of the brain at necropsy in cases of SLE is often disappointing. Acute necrotizing ar¬ teritis may occur in the brain, but is uncommon. Perivascular infiltrates of lymphocytes are more frequent. Symptomatic involvement of the spinal cord in SLE usually results from transverse myelopathy. In a comprehensive review of this entity, Andrianakos et al'' found the compli¬ Other causes of spontaneous suba¬ rachnoid hemorrhage of the cord include angioma and telangiectasis, solitary aneurysm, coarctation of the aorta, mycotic aneurysm of a spinal artery, various tumors (ependymoma, schwannoma, neurofibroma, glioblastoma multiforme, meningeal sarco¬ ma), and anticoagulant therapy."1" In addition, various infections and blood dyscrasias are said to produce spinal subarachnoid hemorrhage, although specific cases have not been docu¬ mented.11 Spinal angioma is the most common spontaneous spinal subarach¬ noid hemorrhage, occuring in 13%." cause of rachnoid hemorrhages were not re¬ Women are affected more than men; signs and symptoms are usually related to irritation of the meninges. The mortality is 15%, and rebleeding is common. The CSF findings in our patient are similar to those previously reported in cases of involvement of the cord by A fatal subarachnoid hemorrhage in the cranium occurred in one instance of SLE, but this complication has not been encountered in the spinal cord.1 It has been suggested that decreased CSF glucose level is charac¬ teristically associated with SLEinduced transverse myelopathy, but cation to be fatal in 13 of 26 cases. Necropsy findings in the spinal cord differed, but included thromboses of small blood vessels, myelomalacia and necrosis, perivascular infiltrates, ar¬ teritis, and subdural hematoma. Suba¬ ported. SLE, producing transverse myelopa- thy.' Downloaded From: http://archneur.jamanetwork.com/ by a University of Pittsburgh User on 06/02/2015 1. Johnson RT, Richardson EP: The neurological manifestations of systemic lupus erythematosus: A clinical-pathological study of 24 cases and review of the literature. Medicine 47:337-369, 1968. 2. Englander RN, Netsky MG, Adelman LS: Location of human pyramidal tract: Anatomic evidence. Neurology 25:823-826, 1975. 3. Dubois EL, Wierzchoweicki M, Cox MB, et al: Duration and death in systemic lupus erythematosus: An analysis of 249 cases. JAMA 227:1399-1402, 1974. 4. Feng PH, Cheah PS, Lee YK: Mortality in systemic lupus erythematosus: A 10-year review. Br Med J 4:772-774, 1973. 5. Andrianakos AA, Duffy J, Suzuki M, et al: Transverse myelopathy in systemic lupus erythematosus. Ann Intern Med 83:616-624, 1975. 6. Aminoff MS: Spinal Subarachnoid Hemorrhage and Haematomyelia in Spinal Angiomas. Oxford, Basil Blackwell & Mott Ltd, 1976. 7. Grollmus J: Spinal subarachnoid hemorrhage with schwannoma. Acta Neurochir 31:253\x=req-\ 256, 1975. 8. Shuangshoti S, Dharmmoponpilas J: Supratentarial glioblastoma multiforme with infratentorial ependymoma with repeated hemorrhages. J Med Assoc Thai 61:489-496, 1978. 9. Garcia CA, Dulcey S, Dulcey J: Ruptured aneurysm of the spinal artery of Adamkiewicz during pregnancy. Neurology 29:394-398, 1979. 10. Henson RA, Croft PB: Spontaneous spinal subarachnoid haemorrhage. Q J Med 25:53-66, 1956. 11. Wilson SAK, Bruce AN: Neurology, ed 2. Baltimore, Williams & Wilkins Co, 1955, pp 1528\x=req-\ 1536. 12. Bruetsch WL: Periarteritis nodosa, in Minckler J (ed): Pathology of the Nervous System. New York, McGraw-Hill, 1971, chap 110. 13. DeBeukelaer MM, Young GF: Subarachnoid hemorrhage complicating acute poststreptococcal glomerulonephritis. Arch Neurol 35:473\x=req-\ 474, 1978. 14. Matsumoto Y, Ishihara J, Ozika K, et al: A case of systemic lupus erythematosus with subarachnoideal bleeding. J Jpn Soc Intern Med 65:1045-1049, 1976.