CASE REPORT
Hydrocephalus in an Elderly Man with Systemic Lupus Erythematosus Wei-Sheng Chen,1 Tsai-Hung Wu,2 Chung-Tei Chou,1 Chang-Youh Tsai1* A 71-year-old man presented with quadriplegia, seizures, dysarthria, motor aphasia and urinary incontinence lasting for several years. The development of proteinuria and increased susceptibility to infections brought the physician’s attention to possible underlying autoimmune diseases. Laboratory investigations revealed evidence for systemic lupus erythematosus (SLE) and antiphospholipid syndrome. Imaging studies showed obstructive hydrocephalus. Several courses of methylprednisolone therapies followed by maintenance therapy with low-dose steroid, ventriculoperitoneal shunt, and antihypertensives improved the proteinuria and dysarthria but not the urinary incontinence or dementia. A thromboembolic event in the central nervous system secondary to phospholipid antibodies or lupus activity may represent a pathogenetic basis for hydrocephalus. When encountering a patient with hydrocephalus but without apparent predisposing factors, it is always important to include SLE as a differential diagnosis. [J Formos Med Assoc 2009;108(6):513–517] Key Words: antiphospholipid antibodies, hydrocephalus, neuropsychiatric systemic lupus erythematosus (NP-SLE), vasculitis
Case Report
Systemic lupus erythematosus (SLE) is an autoimmune disease that frequently involves the central nervous system (CNS). Approximately 60% of lupus patients may have neuropsychiatric (NP) presentations.1–3 Hydrocephalus as a manifestation of NP-SLE is rare, and has been reported only sporadically.4–7 Computed tomography (CT) and magnetic resonance imaging (MRI) provide diagnostic information and may increase its diagnostic rate. We report an elderly man who developing hydrocephalus after a stroke, which might have originated from SLE-related antiphospholipid antibodies and vasculitis.
The patient was a 71-year-old man when he came in for an immune profile check-up. At 55 years of age, an abrupt headache with a transient lapse of consciousness had occurred, and was followed by vertigo. There were also nausea, vomiting and fever (38°C). He was sent to our hospital where stiff neck with a Bruzinski sign was recognized. His consciousness was clear by then and the pupils were isocoric, responding to light promptly. There was no sensory deficit. The first CT scan failed to reveal a lesion, but the second CT scan showed
©2009 Elsevier & Formosan Medical Association .
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Divisions of 1Allergy, Immunology and Rheumatology, and 2Nephrology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan. Received: September 13, 2007 Revised: November 13, 2007 Accepted: January 15, 2008
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*Correspondence to: Dr Chang-Youh Tsai, Division of Allergy, Immunology and Rheumatology, Department of Medicine, Taipei Veterans General Hospital, 201 Shih-Pai Road, Section 2, Taipei 112, Taiwan. E-mail:
[email protected]
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mild enlargement of the lateral ventricles 26 days later. These symptoms were treated with hydralazine (50 mg 3 times daily), propranolol (40 mg 3 times daily), and some hypnotics. A subarachnoid hemorrhage, which is the commonest cause of hydrocephalus,8 was highly suspected. During the next year, he experienced chronic productive cough with purulent expectoration and intermittent low-grade fever. Transbronchial biopsy revealed chronic granulomatous inflammation with caseous necrosis and Langhan’s giant cell reactions, although sputum culture and acid-fast stain failed to demonstrate Mycobacterium tuberculosis. Chest radiography showed miliary lesions throughout the lungs. An 18-month antituberculosis treatment was thus given. At the age of 65, he developed a painful disability in the left hip. A nuclide scan and radiography revealed ischemic necrosis of the left femoral head, for which he underwent total hip replacement. At 66 years of age, sudden quadriparesis, high fever, shaking chills, slurred speech, drooling, and urinary incontinence occurred. CT revealed low-density lesions in the left external capsule, caudate nucleus and pons. The cerebrospinal fluid (CSF) was normal without pleocytosis and CSF acid-fast stain and tuberculosis culture were negative. Because of coughing and persistent fever, he underwent various tests for M. tuberculosis, Cryptococcus, Legionella, Salmonella, scrub typhus, and Lyme disease, all of which were negative. Serum antinuclear antibodies (ANA) were 1:320 (speckled); anti-dsDNA antibodies were elevated (139 IU/mL; normal, < 30 IU/mL); direct Coombs’ and venereal disease research laboratory (VDRL) tests were positive; and IgG anticardiolipin antibodies (aCL) were elevated on two occasions more than 6 weeks apart (59 IU/mL and 120 IU/mL; normal, < 15 IU/mL). Single photon emission CT and gallium-67 whole body scan revealed pericarditis and thyroiditis. He bore no risk for stroke such as hypertension, diabetes, hyperlipidemia or smoking. MRI showed lacunar infarctions in the left external capsule and caudate head, and generalized loss of brain tissue with enlargement of the cortical sulci and 514
Figure 1. Magnetic resonance imaging of the brain with gadolinium-DTPA enhancement at the age of 66 shows generalized atrophy of the brain tissue with enlargement of cortical sulci and marked dilatation of the lateral ventricles.
ventricular system (Figure 1). A high signal on T2-weighted imaging in periventricular white matter indicated demyelination. Chest radiography demonstrated mild left pleural effusion. Echocardiography showed concentric left ventricular hypertrophy, and a mild posterior and lateral pericardial effusion. Based on these manifestations, including elevated anti-dsDNA level, positive ANA, autoimmune hemolytic anemia, and pericarditis, the patient was diagnosed as having SLE and was treated with daily oral prednisolone (15 mg/day). This was almost 10 years after the first episode of stroke. Pretibial pitting edema and bilateral knee arthritis appeared several months before the admission at the age of 68. Renal biopsy revealed a thickened glomerular basement membrane with electron-dense deposits on its outer surface, diffuse global effacement of the visceral epithelial foot processes with segmental microvillous transformation, and segmental dilatation of the capillary lumens. Sialoscintigraphy revealed moderate xerostomia (grade III). Gallium-67 scan showed increased uptake in the renal parenchyma and lymphadenopathy in the pulmonary hilar region. The ANA titer increased markedly to > 1:2560 (speckled). Anti-dsDNA antibodies were 55 IU/mL J Formos Med Assoc | 2009 • Vol 108 • No 6
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(normal, < 30 IU/mL), C3/C4 was 104/28 mg/dL (normal, 72–105/18–30 mg/dL); immunoglobulin levels were normal (IgG, 1560 mg/dL [normal, 751–1560]; IgA, 281 mg/dL [normal, 82–453]; IgM, 116 mg/dL [normal, 46–304]); and C-reactive protein was 7.03 mg/dL (normal, < 0.5 mg/dL). Plasma aldosterone was 33.22 pg/mL (normal, 7–30 pg/mL). Autoantibodies to SS-A/Ro, SS-B/La, mitochondrion and smooth muscle were negative. There were variable anemia (7.9–12.2 g/dL) and leukopenia (< 3500/mm3 on several occasions). Daily urine protein excretion was 1.2 g. The hands showed symmetrical juxta-articular osteoporosis in the metacarpophalangeal and proximal interphalangeal joints. Another MRI showed a 1-cm sized protruding aneurysm in the distal segment of the right vertebral artery and hydrocephalus. Monthly methylprednisolone (1 g/day for 3 doses) had an effect on improving slurred speech and proteinuria. The other supplementary oral medications included hydroxychloroquine 200 mg twice a day, dipyridamole 25 mg thrice a day, and pentoxifylline 400 mg twice a day. At 69 years of age, a new episode of generalized convulsion, vomiting, and consciousness deterioration occurred. Coma scale went to E4V3M5 and gait was unstable. Electroencephalography showed diffuse background slowing. Electrolyte imbalance (Na, 120 mg/dL [normal, 128–142 mg/dL]) and serum osmolality 259 mosm/kg (normal, 285– 295 mosm/kg) suggested inappropriate secretion of antidiuretic hormone. 99mTc-DTPA cisternography showed non-communicating hydrocephalus (Figure 2). The patient underwent an operation to establish a ventriculoperitoneal shunt. Thereafter, his condition stabilized. He remains on oral methylprednisolone 4 mg/day and antihypertensives. Urinary tract infections occur frequently because of long-standing urinary catheterization.
Discussion Hydrocephalus in SLE is rare, much less hydrocephalus in SLE in an elderly male. Absence of J Formos Med Assoc | 2009 • Vol 108 • No 6
arthritis or skin lesions led the first neurologist to ignore the underlying autoimmune disease. However, evidence for SLE with antiphospholipid syndrome was solid. Fulfilling the criteria for SLE,9,10 he had anemia/leukopenia, arthritis, thromboembolism in CNS, aCL, anti-dsDNA antibodies, serositis, and glomerulonephritis. Circumferential evidence included avascular necrosis of the femoral head, which occurred before glucocorticoid therapy, thyroiditis, and xerostomia. Normal pressure hydrocephalus is a setting of symptoms associated with ventricular dilation and normal intracranial pressure. Although it is rarely encountered in SLE, a number of authors have proposed possible pathogenic mechanisms for its occurrence.11–13 Kaplan et al have reported pseudotumor cerebri associated with cerebral venous thrombosis as a possible cause of obstructive hydrocephalus.12 Borenstein and Jacobs have proposed a CNS inflammation leading to aqueductal stenosis.5 Our patient had several episodes of cerebral hemorrhage including a subarachnoid and a pons hemorrhage. There might have been other episodes of minor thromboembolic events because lacunar infarctions were also demonstrated in at least one MRI evaluation. With the presence of IgG anticardiolipin antibodies, the possibility of an antiphospholipid antibodyrelated or vasculitis-related cerebrovascular accident, resulting in obstructive hydrocephalus, could not be excluded, although communicating hydrocephalus secondary to antiphospholipid syndrome has been previously reported.11 SLE per se occurs less frequently in the elderly. Hydrocephalus in elderly male SLE patients is even more unusual. Uhl et al reported an elderly woman with normal pressure hydrocephalus who presented with gait disturbance, dementia and urinary incontinence,4 much like our patient. However, our patient was more distinctive in that various autoimmune symptoms, as well as immune incompetence, were present consecutively. These included stroke, tuberculous infection, avascular necrosis of the femoral head, kerato-conjunctivitis sicca, arthritis, serositis and renal disease. It was unclear when the serology appeared in the chronological 515
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Figure 2. TC99m DTPA cisternography shows delayed ascending of the radiotracer to the basal cisterns 3 hours after lumbar intrathecal injection and persistent ventricular reflux from 3 to 24 hours after lumbar puncture. At 24 hours, most of the radioactivity was still in the ventricles and basal cistern rather than in the vertex. ANT = anterior; RLAT = right lateral; LLAT = left lateral.
course of the disease because the possibility of autoimmune disease was ignored at the beginning. Another interesting point was antiphospholipid syndrome. Although we did not unequivocally demonstrate uncorrectable prolongation of the prothrombin time or partial thromboplastin time, as well as the presence of lupus anticoagulant, the repeated thromboembolic phenomenon or CNS hemorrhage and the detection of IgG anticardiolipin antibodies on two occasions suggested that phospholipid antibodies played an important role in these particular neurologic manifestations. Ayoub and colleagues reported a young woman with a bleeding tendency, lupus 516
anticoagulant, anticardiolipin antibodies, antibodies against coagulation factor and hydrocephalus.14 However, she did not present with frank neurologic symptoms like our patient. With regard to the treatment effect of the steroid, the patient seemed only to have selective symptoms responding to methylprednisolone. These included slurred speech and glomerulonephritis. Since the thrombotic complications were irreversible, the transient effect on dysarthria was likely to have originated from the relieving of the local brain edema by the steroid. Because the glomerular involvement was mild, proteinuria never recurred after methylprednisolone pulse J Formos Med Assoc | 2009 • Vol 108 • No 6
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therapy. On the other hand, hydroxychloroquine played little role in the control of systemic autoimmune symptoms in this particular patient. In conclusion, elderly patients with SLE may present with repeated cerebral thrombosis or hemorrhage associated with obstructive hydrocephalus, particularly when antiphospholipid antibodies are present. Physicians should keep autoimmune diseases in mind when making the differential diagnosis of neurological diseases.
Acknowledgments This work was partly supported by grants from the National Science Council (NSC95-2314B075-097) and Taipei Veterans General Hospital (V96-C1-030), Taiwan.
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4. Uhl MD, Werner BE, Romano TJ, et al. Normal pressure hydrocephalus in a patient with systemic lupus erythematosus. J Rheumatol 1990;17:1689–91. 5. Borenstein DG, Jacobs RP. Aqueductal stenosis: a possible late sequela of central nervous system inflammation in systemic lupus. South Med J 1982;75:475–7. 6. Kitching GB, Thompson JR, Hasso AN, et al. Angiographic demonstration of lupus cerebral phlebitis with communicating hydrocephalus. Neuroradiology 1977;14:59–63. 7. You HY, Wang SR. Normal pressure hydrocephalus in a patient with systemic lupus erythematosus: a case report. J Chin Med Assoc 1998;61:551–5. 8. Black PMCL. Hydrocephalus and vasospasm after subarachnoid hemorrhage from ruptured intracranial aneurysm. Neurosurgery 1986;18:12–6. 9. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271–7. 10. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725. 11. Mortifee PRS, Bebb RA, Stein H. Hydrocephalus in SLE with APS. J Rheumatol 1992;19:1299–302. 12. Kaplan RE, Springate JE, Feld LG, et al. Pseudotumor cerebri associated with cerebral venous sinus thrombosis, internal jugular vein thrombosis, and systemic lupus erythematosus. J Pediatr 1985;107:266–8. 13. Chan DQ. Neurologic, ophthalmic, and neuropsychiatric manifestations of pediatric systemic lupus erythematosus. Optometr Vision Sci 2000;77:388–94. 14. Ayoub O, Aljurf M, Al Nounou R, Chaudhri NA. Systemic lupus erythematosus presenting with haemorrhagic manifestation. Clin Lab Haematol 1999;21:413–6.
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