Anticardiolipin antibodies‐associated stroke in primary CMV infection

Sirs, Etiological investigations for ischaemic stroke of young adults are negative in less than half of cases. In the absence of a personal history of thrombosis or obstetrical loss, anticardiolipin antibodies (aCLs) screening is controversial [1]. aCLs have been described in human immunodeficiency virus (HIV), hepatitis B, hepatitis C and cytomegalovirus (CMV) primary infection [2,3]. Recent studies highlight the risk for venous or arterial thrombosis in primary CMV infection, both in immunocompromised or immunocompetent patients [4]. We present a case of a healthy young male admitted for an ischaemic stroke revealing a primary CMV infection associated with positive screening for aCLs. A 30-year-old right-handed man was admitted in our stroke unit because of sudden right hemiparesis. He had no history of prior venous, arterial or known family history of thromboembolism, and denied smoking. One hour before admission, he presented a sudden right hemiparesis and non-fluent aphasia. His neurological status worsened thereafter with a somnolence. The patient had a right hemiparesis with Babinski’s sign, global aphasia, central facial paralysis and right-sided homonymous hemianopsia. The initial National Institutes of Health Stroke Scale (NIHSS) was 24. Brain magnetic resonance imaging (MRI) showed a hypersignal on diffusion but not in Flair sequences, proving a recent left middle cerebral artery (MCA) ischaemic stroke, and evidences a persistent thrombus in M2 (left MCA). Thrombolysis was started 4 h after the onset of stroke, leading to mild neurological improvement 24 h later (NIHSS = 17). At 24 h, MRI showed a complete recanalization of M2 with left MCA ischaemic stroke on Flair sequence. MR angiography at day 2 showed no sign of cervical arteries dissection. Electrocardiogram was normal. Transesophageal echocardiography revealed an isolated patent foramen ovale. Deep vein thrombosis was excluded. Toxic analysis was negative. Fever and adenopathy were noticed. Lab tests showed mononucleosis-like syndrome with atypical hyperbasophilic lymphocytes 9000/mm. Aspartate amino transferase and alanine amino transferase were 71 and 152 UI/l, respectively (N < 35 and 45), C-reactive protein 30 mg/l (N < 5), polyclonal hypergammaglobulinemia. Blood and urine cultures remained sterile, and chest X-ray was normal. Serological IgM and IgG ELISA tests for CMV were 3.5 UI/l and 107 UI/l, respectively (N < 7 and 10). Screening for HIV, hepatitis A, B and C, and Epstein–Barr virus was negative. The search for aCLs showed aCL-IgM 68.9 UMPL/ml (N < 7), aCL-IgG 12.7 UGPL/ml (N < 10), and anti-b2 glycoprotein 1 antibodies [IgM > 10 lg/ml (0.8–1), IgG 0.92 lg/ml (0.65– 0.9)]. There was no evidence for lupus anticoagulant and inherited thrombophilia. Screening for antinuclear antibodies, rheumatoid factor and cryoglobulin was negative. Anticoagulation with fluindione was initiated. At 12 months, the patient had mild aphasia; NIHSS was 2 and Rankin 1. Fluindione withdrawal was decided following two consecutive negative aCL tests (Table 1). To our knowledge, this is the first case of a stroke associated with ‘transitory antiphospholipid syndrome (APS)’ secondary to primary CMV infection. Recent criteria for APS-associated clinical events characterized by vascular venous or arterial thrombosis, were stroke [5] and/or pregnancy morbidity with biological immunological markers including circulating aCLs [6]. To confirm APS, positive aCLs tests need to be repeated 12 weeks apart [6]. Thus, a diagnosis of definite APS could not be retained in our patient as he had negative titer at 6 months (Table 1). The presence of IgM aCLs was highly suspicious of a transient serological phenomenon [7]. In the present case, we consider that ischaemic stroke could be linked to CMV infection through transient induction of aCLs. Firstly, the simultaneous occurrence of both clinical and biological findings is suggestive of this association, rather than incidental aCLs findings. Secondly, thrombosis has been described in 6.7% of primary CMV infection, including two intra-cranial venous thrombosis [4], as well as some cases of APS associated with CMV infection along with thrombotic events [2,8]. In such cases thrombosis was located in mesenteric, femoropopliteal and iliac veins, but digital arteries thrombosis, pulmonary embolism and transient ischaemic attack have also been reported [9]. Moreover, a mice model of APS has demonstrated a molecular mimicry with CMV-derived peptides in induction of aCLs associated with thrombosis. In this model, IgM aCLs appeared with the onset of infection, followed by IgG aCLs a second time.