gms | German Medical Science

VZV reactivation is common following kidney transplantation but it rarely causes disease of the CNS. We report two cases of VZV CNS infection in kidney transplanted patients.

Patient 1: A 64-year-old woman developed left sciatica, three weeks after her kidney transplantation, followed 2 weeks later by delirium, fever, and generalized zoster rash predominant in the left leg. Cerebrospinal fluid (CSF) analysis showed mild pleocytosis, with VZV DNA. Brain MRI was normal. A 3-week course of intravenous acyclovir was started and mycophenolate mofetil was discontinued. After 12 days of treatment, she became markedly confused. Brain CT and CT angiography revealed nonaneurysmal bilateral sylvian subarachnoid haemorrhage. Acute hydrocephalus was treated by external ventricular drainage. Mental status improved gradually over the following 2 months, but the patient kept left leg weakness.

Patient 2: A 32-year-old man presented with right-sided zoster ophthalmicus with kerato-uveitis in the month of return to dialysis after transplant failure. Brain CT scan was normal. Immunosuppressive treatment was decreased and intravenous acyclovir was initiated for 7 days, followed by valacyclovir for 10 days. Five weeks after resolution of shingles, he developed right 3rd and 6th cranial nerve palsy. Brain MRI revealed inflammation of the right orbital apex and an asymptomatic right lenticulostriate infarct. Intravenous acyclovir was resumed. One week later, he developed an acute left-sided sensorimotor deficit with sensory neglect. Brain MRI showed additional acute infarcts in the right carotid territory, and catheter angiography identified multifocal stenosis with branch occlusions in the right middle and posterior cerebral and left pericallosal arteries. CSF analysis found pleocytosis and increased protein levels, but no VZV DNA (anti-VZV immunoglobulin dosage not available). Despite full-dose antiviral therapy and tapering of immunosuppressant agents, asymptomatic brain infarcts recurred over 2 weeks, and progression of the vasculopathy was documented, affecting bilateral vessels of different sizes. Clinical and radiological stabilization was finally achieved with discontinuation of immunosuppressant agents and allograft nephrectomy. Eight years later, he remains with right-eye keratitis and left-sided deficit.

These cases emphasize the protean CNS manifestations of VZV vasculopathy. Intracranial arteries of any size can be affected, with progressive multifocal stenoses, ectasia and pseudoaneurysm, causing combinations of headaches, facial or radicular pain, brain or subarachnoid hemorrhage, as well as brain, cranial nerve or nerve root ischemia. Timely diagnosis of VZV vasculopathy is important because mortality is high without treatment (up to 25%), especially in immunocompromised individuals. VZV vasculopathy may be difficult to recognize because clinical manifestations and brain imaging abnormalities are variable and non-specific. Temporal association of zoster rash with neurological symptoms is helpful in the diagnosis. However a prolonged prodrome or the absence of rash in the setting of pain may delay the recognition of VZV infection. VZV vasculopathy is confirmed by documentation of anti-VZV immunoglobulins, VZV DNA, or both in the CSF. Prompt initiation of high-dose intravenous acyclovir together with reduction of immunosuppression may improve outcomes.