Abstract
Progressive multifocal leukoencephalopathy (PML) is a subacute brain infection by the opportunistic John Cunningham (JC) virus. Herein, we describe seven patients with PML, lymphopenia, and sarcoidosis, in three of whom PML was the first manifestation of sarcoidosis. At onset, the clinical picture comprised rapidly progressive spastic hemi- or limb pareses as well as disturbances of vision, speech, and orientation. Cerebral magnetic resonance imaging showed T2-hyperintense, confluent, mainly supratentorial lesions. Four patients developed punctate contrast enhancement as a radiological sign of an immune reconstitution inflammatory syndrome (IRIS), three of them having a fatal course. In the cerebrospinal fluid, the initial JC virus load (8–25,787 copies/ml) did not correlate with interindividual severity; however, virus load corresponded to clinical dynamics. Brain biopsies (n = 2), performed 2 months after symptom onset, showed spotted demyelination and microglial activation. All patients had lymphopenia in the range of 270–1150/µl.To control JC virus, three patients received a combination of mirtazapine and mefloquine, another two patients additionally took cidofovir. One patient was treated with cidofovir only, and one patient had a combined regimen with mirtazapine, mefloquine, cidofovir, intravenous interleukin 2, and JC capsid vaccination. To treat sarcoidosis, the four previously untreated patients received prednisolone. Three patients had taken immunosuppressants prior to PML onset, which were subsequently stopped as a potential accelerator of opportunistic infections. After 6–54 months of follow up, three patients reached an incomplete recovery, one patient progressed, but survived so far, and two patients died. One further patient was additionally diagnosed with lung cancer, which he died from after 24 months. We conclude that the combination of PML and sarcoidosis is a diagnostic and therapeutic challenge. PML can occur as the first sign of sarcoidosis without preceding immunosuppressive treatment. The development of IRIS might be an indicator of poor outcome.
Highlights
Progressive multifocal leukoencephalopathy (PML) is a diffuse infectious disease of the central nervous system (CNS) with a disabling and potentially lethal course.[1,2] The opportunistic John Cunningham (JC) virus lingers in kidneys or lymphatic tissues in about 65–90% of the healthy population.[3]
When being diagnosed with PML, no underlying malignancy was known, and a positron emission tomography–computed tomography (PET-CT) revealed only bilateral roundish compactions in the apical lower lobes, which were evaluated as unspecific infiltrations possibly related to sarcoidosis at that time
Immunosuppression is the common cause of PML enabling the ubiquitously lingering JC virus to infect the CNS
Summary
Progressive multifocal leukoencephalopathy (PML) is a diffuse infectious disease of the central nervous system (CNS) with a disabling and potentially lethal course.[1,2] The opportunistic John Cunningham (JC) virus lingers in kidneys or lymphatic tissues in about 65–90% of the healthy population.[3] First described in 1958 in a patient, Gisa Ellrichmann Ralf Gold Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. Rastislav Pjontek Department of Diagnostic and Interventional Neuroradiology, Medical Faculty of the RWTH Aachen University, Aachen, Germany. Carsten Lukas Department of Radiology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. Jens Panse Department of Oncology, Hematology and Stem Cell Transplantation, Medical Faculty of the RWTH Aachen University, Aachen, Germany. Schulz Department of Neurology, Medical Faculty of the RWTH Aachen University, Aachen, Germany
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