Progressive multifocal leukoencephalopathy associated with thymoma with immunodeficiency: a case report and literature review

Abstract

BackgroundThe development of progressive multifocal leukoencephalopathy (PML) is associated with severe cellular immunosuppression. Good’s syndrome (GS) is a rare immunodeficiency syndrome related to thymoma, with the development of humoral as well as cellular immunosuppression; however, there are few reports of PML due to GS. One report suggested that the neurological symptoms of PML related to thymoma may be improved by a reduction of immunosuppressive therapy for myasthenia gravis (MG). It is therefore necessary to identify the cause of immunodeficiency in patients with PML to enable an appropriate treatment strategy to be adopted.Case presentation:A 47-year-old Japanese woman was admitted with aphasia and gait difficulty. She had an invasive thymoma that had been treated with repeated chemotherapy, including cyclophosphamide. She had also previously been diagnosed with MG (Myasthenia Gravis Foundation of America clinical classification IIa), but her ptosis and limb weakness had completely recovered. On admission, neurological examination revealed motor aphasia and central facial weakness on the right side. Laboratory studies showed severe lymphopenia, decreased CD4+ and CD8+ T cell and CD19+ B cell counts, and reduced levels of all subclasses of immunoglobulins, suggesting GS. Serology for human immunodeficiency virus (HIV) infection was negative. Brain magnetic resonance imaging showed asymmetric multifocal white matter lesions without contrast enhancement. Cerebrospinal fluid real-time polymerase chain reaction for JC virus was positive, showing 6,283,000 copies/mL. We made a diagnosis of non-HIV-related PML complicated with GS and probable chemotherapy-induced immunodeficiency. She then received intravenous immunoglobulin therapy, mirtazapine, and mefloquine, but died of sepsis 46 days after admission.ConclusionsIt is necessary to consider the possibility of immunodeficiency due to GS in patients with PML related to thymoma. Neurologists should keep in mind the risk of PML in MG patients with thymoma, even if the MG symptoms are in remission, and should thus evaluate the immunological status of the patient accordingly.

The Use of Antimalarial Drugs against Viral Infection

“…In many cases, MQ was combined with mirtazapine, an antidepressant that, acting on the 5-HT2A serotonin receptor, is able to inhibit JCPyV entry into glial cells, preventing the diffusion of the infection in oligodendrocytes. The outcomes of this treatment are controversial, leading to the resolution of the infection, with a claimed effect of MQ and mirtazapine treatment [86,87,[89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105], and to the resolution of the infection probably due to other factors [96,[106][107][108][109] or to the death of the patient, which was not always directly related to the unsuccessful therapy [87,96,[110][111][112][113][114][115][116]. In one case, the suspension of the therapy was necessary due to the side effects [117].…”

Improving detection of JC virus by ultrafiltration of cerebrospinal fluid before polymerase chain reaction for the diagnosis of progressive multifocal leukoencephalopathy

“…In Japan, real-time PCR testing of CSF specimens for JCV DNA is routinely performed at the Department of Virology 1, NIID [9, 20–26]. For this study, CSF specimens were collected by lumbar puncture from 21 individuals.…”

“…Quantitative real-time PCR assay targeting the JCV large T gene was carried out, as described in the earlier reports [9, 20–26]. To confirm the detection of JCV genomic DNA, real-time PCR for the JCV viral protein 1 ( VP1 ) gene was conducted [9].…”

Progressive Multifocal Leukoencephalopathy Associated With Idiopathic CD8+ Lymphocytopenia

“…Also, there is laboratory evidence of PD-1 upregulation on T cells in PML patients, which led to the off-label use of this drug in PML patients where no other option was available. Although there are not to date any randomized controlled trials for this therapy in PML, there have been many case reports some of which had favourable outcomes ranging from stabilization to moderate improvement of symptoms [5][6][7].…”