The incidence of progressive multifocal leukoencephalopathy (PML) in people living with HIV (PLWH) is 2%-4%. Currently, there is no effective therapeutic strategy for the treatment of PML in PLWH, resulting in a mortality of up to 50%. This study aimed to identify risk factors of death and prognostic markers in people living with HIV with PML.
A retrospective cohort study of AIDS-related PML individuals was conducted from January 1, 2015, to October 1, 2022, in Shanghai, China. PLWH who were diagnosed with PML for the first time were included. Kaplan-Meier curve and Cox regression were used to analyze the survival and its predictors. Levels of inflammatory markers and immune checkpoint inhibitors in blood and cerebrospinal fluid (CSF) were measured in the prestored samples using bead-based multiplex assay Indolamine 2,3-dioxygenase was determined using ELISA.
Twenty of 71 subjects had initiated antiretroviral therapy (ART) before PML onset and no patients discontinued ART during this period. In total, 34 patients (47.9%) had opportunistic infections (OIs), the median CD4+ T cell count was 73.0 (33.0-149.0) cells/μL. The estimated probability of survival at six months was 78% (95% confidential intervals [CIs]:0.63-0.85). OIs, low CD4+ T cell count were associated with lower estimated six-month survival (hazard ratio 8.01, 95% CIs: 1.80-35.00, P=0.006 and 5.01, 95% CIs:1.57-16.03, p=0.007). Indolamine 2,3-dioxygenase activity in CSF of non-survivors group were higher than survivors group (p<0.05).
The survival rate of AIDS-related PML in the modern ART era was higher than the survival rate a decade ago. Low CD4+T cell count, OIs, were all associated with death of individuals with AIDS-related PML. The role of IDO in AIDS-related PML warrant further investigation.

The aim of this study is to analyze the clinical characteristics and outcomes of Chinese patients with progressive multifocal leukoencephalopathy (PML) who were treated with programmed cell death protein 1 (PD1) blockade therapies. We retrospectively analyzed patients who were admitted to our hospital between October 1, 2020, and October 1, 2022, diagnosed with PML and treated with PD1 blockade therapies. Four patients with PML who were treated with PD1 blockade therapies were identified. All patients were male, and their ages ranged from 19 to 54 years old. One patient (Case 2) exhibited mild pleocytosis, while three patients (Cases 2-4) had markedly reduced T lymphocyte cell counts prior to treatment. The time interval between symptom onset and treatment initiation ranged from six to 54 weeks. All patients received pembrolizumab treatment, with a total of two to four doses administered. Three patients who responded to pembrolizumab treatment showed clinical improvement starting around 8 weeks after the initiation of therapy. Although one patient did not show clinical improvement, they ultimately survived until the last follow-up. None of the patients in this study exhibited immune-related adverse events or immune reconstitution inflammatory syndrome. PD1 blockade appears to be a promising novel therapeutic option for PML; additional prospective studies are necessary to confirm its efficacy.

UNASSIGNED: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the brain caused by reactivation of the JC virus, which can lead to a lytic infection of oligodendrocytes. We report a patient with HIV who developed PML.
UNASSIGNED: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the brain caused by reactivation of the John Cunningham virus (JCV), which can lead to a lytic infection of oligodendrocytes. Herein, we report the case of a patient with HIV who developed PML that presented as a progressive disturbance of consciousness and movement. The patient\'s clinical symptoms progressively deteriorated, and positive JC viral DNA in his cerebrospinal fluid (CSF) helped us diagnose him with PML. Magnetic resonance imaging (MRI) showed multiple asymmetric subcortical and deep white-matter lesions. Although we administered immunoreconstructive therapy, the patient\'s condition gradually worsened. Therefore, we suggest that PML should be considered if such lesions are found in MRIs of HIV patients.

BACKGROUND: JC virus (JCV) is common among healthy individuals and remains latent but may be reactivated under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy (PML). Here, we present a rare case of PML caused by JC virus infection in a previously healthy and immunocompetent patient.
METHODS: A 67-year-old female without any disease history was admitted after presenting with rapidly progressive dementia. The preoperative diagnosis was progressive multifocal leukoencephalopathy, and corticosteroid treatment did not improve the symptoms. Brain lesions were surgically sampled, and JCV infection was confirmed by high-throughput DNA gene detection. This patient received a combined treatment of mirtazapine, mefloquine, and traditional Chinese herbs, and had stabilization of the disease on followed-up.
CONCLUSIONS: Although it is a rare, this case demonstrates that JC virus infection within the brain occurs in apparently healthy people. This case may increase our understanding of virus infection when facing the coronavirus epidemic in recent years, considering that similar medications were used.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating lytic brain infection caused by the John Cunningham virus (JCV). JCV manifests primarily in patients with innate immunodeficiency or taking immunomodulatory medications. In this case study, we report a PML patient with comorbid mediastinal teratoma and mild lymphopenia.
METHODS: A 73-year-old female presented with a 3-month history of progressive hemiplegia, hemianopsia, and cognitive impairment. She was diagnosed as PML by cerebrospinal fluid metagenomics sequencing and brain biopsy. Extensive immunological tests did not reveal an apparent immunodeficiency, but further work-up revealed that the PML was most likely the first presentation of mediastinal teratoma and the mild lymphopenia. Mirtazapine and immunoglobulin were started, the patient\'s condition was relatively stable and approved to be discharged from hospital. But unfortunately, she died of the lung infection 10 months after first presentation.
CONCLUSIONS: This case confirms that mediastinal teratoma may induce the lymphopenia and trigger PML, delayed or incorrect diagnosis may worsen the course of the disease and result in poor prognosis.

Good\'s syndrome (GS) is an immunodeficiency characterized by thymoma, hypogammaglobulinemia, and impaired T-cell function. Progressive multifocal encephalopathy (PML), an infection caused by JC virus (JCV), usually occurs in patients infected with human immunodeficiency virus (HIV), or in patients on treatment with immunosuppressive or immunomodulatory drugs. There were few reports of PML due to GS, especially with the comorbidity of peripheral neuropathy. We describe a case of an uncommon presentation of PML and peripheral neuropathy in a male who presented with blurred vision, cognitive changes, limb weakness, and numbness over a 4-month period due to GS. To the best of our knowledge, this is the first report of PML and peripheral neuropathy due to GS. This case aims to highlight that it is necessary to consider the possibility of PML due to GS in patients with thymoma and intracranial lesions, and we should focus not only on opportunistic infections of the central nervous system, such as PML, but also on peripheral neuropathy.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by JC virus (JCV) and is difficult to diagnose. We report on a male HIV-positive patient with PML finally diagnosed by 3 times lumbar punctures and 2 times brain biopsies. Negative results of JCV-PCR in cerebrospinal fluid (CSF) do not rule out the diagnosis of PML when clinical manifestations and neuroimaging features suspected PML. It is necessary to obtain new CSF and make repeat tests and even perform brain biopsy.

Metagenomic next-generation sequencing (mNGS) is a novel approach to identify pathogens undetected by conventional methods. Herein, we report a case in which mNGS was used to identify JC virus from the cerebrospinal fluid sample of an HIV positive patient with progressive multifocal leukoencephalopathy (PML).

We performed a cross-sectional study in 123 Chinese multiple sclerosis patients residing in Hong Kong to evaluate their anti-John Cunningham virus status using STRATIFY JCV DxSelect assays. Anti-John Cunningham virus antibody was present in 98/123 (80%) subjects, among which 75/98 (77%) had an anti-John Cunningham virus index ≥1.5. Anti-John Cunningham virus antibody seropositivity was not correlated with age, disease duration, Expanded Disability Status Scale scores, types of multiple sclerosis (relapsing vs progressive), or disease-modifying treatments used. We found a very high seroprevalence and index of anti-John Cunningham virus antibodies in Chinese multiple sclerosis patients, which may impact the risk assessment and recommendation of disease-modifying treatments in this population.

Human JC and BK polyomaviruses (JCV/BKV) can establish a latent infection without any clinical symptoms in healthy individuals. In immunocompromised hosts infection or reactivation of JCV and BKV can cause lethal progressive multifocal leukoencephalopathy (PML) and hemorrhagic cystitis, respectively. Vaccination with JCV/BKV derived antigen epitope peptides or adoptive transfer of virus-specific T cells would constitute an elegant approach to clear virus-infected cells. Furthermore, donor leukocyte infusion (DLI) is another therapeutic approach which could be helpful for patients with JCV/BKV infections.So far, only few immunodominant T cell epitopes of JCV and BKV have been described and therefore is a fervent need for the definition of novel epitopes. In this study, we identified novel T cell epitopes by screening libraries of overlapping peptides derived from the major capsid protein VP1 of JCV. Virus like particles (VLPs) were used to confirm naturally processing. Two human leucocyte antigen (HLA)-A*02-restricted epitopes were characterized by fine mapping with overlapping peptides and nonamer peptide sequences were identified. Cytokine release profile of the epitope-specific T cells was analyzed by enzyme-linked immunospot (ELISPOT) assays and by flow cytometry. We demonstrated that T cell responses were of polyfunctional nature with the potential of epitope-specific killing and cross-reactivity between JCV and BKV. These novel epitopes might constitute a new potential tool to design effective diagnostic and therapeutic approaches against both polyomaviruses.