Chronic meningitis and central nervous system vasculopathy related to Epstein Barr virus
An 11-year-old boy presented to us in December 2009 with fever, headache and seizures. In July 2008, he had headache with vomiting and photophobia. He was evaluated elsewhere and was found to have aneurysmal dilatation of intracranial segments of anterior, middle and posterior cerebral arteries on magnetic resonance imaging (MRI) and catheter angiogram of brain []. With the possibility of CNS angitis, he was treated with one pulse of intravenous Methylprednisolone and intravenous Cyclophosphamide, which was not continued further. He continued to have intermittent headache and fever. In November 2009, he had worsening of headache with seizures. He was admitted elsewhere and again received pulse intravenous Methylprednisolone and intravenous Cyclophosphamide, followed by a tapering course of oral steroids. In December 2009, he presented to us with headache, fever and recurrent right-side focal seizures with secondary generalisation. He was the first child of two siblings, born to nonconsanginous parents. There was no history of similar illness in the other sibling, with no other remarkable family history. MRI brain showed fusiform aneurysmal dilatations of arteries of anterior and posterior circulation with ectasia of the terminal internal carotid arteries (ICAs), proximal anterior cerebral arteries (ACAs), proximal middle cerebral arteries (MCAs) and their cortical branches. There was loss of flow void in right vertebral artery suggesting thrombosis. There was leptomeningeal enhancement [Figures –]. Cerebrospinal fluid (CSF) analysis showed 200 WBC/mm3 (100% lymphocytes), protein of 2.2 g/dL and sugar of 29 mg/dL. CSF cultures (bacterial and fungal) were negative. CSF multiplex polymerase chain reaction (PCR) was positive for EBV and negative for other viruses screened (herpes simplex 1 and 2, adeno, varicella and CMV viruses). Blood virus screening (HIV, hepatitis B and C viruses) was negative. Work up for lymphoproliferative disorder including screening for lymphadenopathy, CSF flow cytometry and bone marrow examination were negative. Quantitative immunoglobulin assay was normal (IgG – 1275 mg%, IgA – 201 mg% and IgE – 12.5 IU/ml). His peripheral blood lymphocyte subset analysis showed CD4+ T cells - 1091/μL and CD3+ T cells - 6060/μL. Positron emission tomography (PET) scan was unremarkable. The markers for systemic vasculitis were negative. Nerve conduction study and a muscle, nerve and skin biopsy were normal. During the hospital stay, he had worsening of headache; repeat MRI brain showed T2 hyperintensity in right caudate nuclei, bilateral frontal and hippocampal areas [Figure and ]. Repeat CSF analysis showed persistent lymphocytic pleocytosis, raised proteins, low sugars and EBV PCR positive status. He was discharged on oral anticoagulation and oxcarbamazepine. In June 2010, he had fever, pancytopenia and bone marrow aplasia, probably due to EBV-associated X-linked lymphoproliferative disorder (XLP). His peripheral blood lymphocyte subset analysis showed CD3+ T cells - 3888/μL, CD4+ T cells -756/μL, CD8+ T cells - 3074/μ L, CD19+ T cells - 108/μL and CD56+ T cells - 150/μL, suggestive of mild B cell deficiency. He was treated with antibiotics for respiratory infection and also growth factors. He continued to deteriorate and succumbed to sepsis within 2 weeks. A molecular diagnosis looking for mutation in the SH2D1A/DSHP/SLAM-associated protein (SAP) gene could not be done for the lack of availability of the test.