Cerebral lesions in hematological malignancies: a case report

Background Progressive multifocal leukoencephalopathy is a rare central nervous system disease, resulting from reactivation of latent John Cunningham virus. Monoclonal antibodies have recently become a relevant risk factor for developing progressive multifocal leukoencephalopathy. Case summary We report the case of a 62-year-old Caucasian man who was admitted to our department in June 2020 because of right homonymous hemianopia. Magnetic resonance imaging findings were first interpreted as an intracranial relapsed lymphoma, so brain biopsy was performed, but no neoplastic cell was found. Histological sample only showed a large number of macrophages. The patient came back to our attention because of the worsening of neurological symptoms. A second magnetic resonance imaging showed widespread lesions suggestive of a demyelinating process. John Cunningham virus DNA was detected by polymerase chain reaction assay of the cerebrospinal fluid (over 9 million units/μL). The patient was treated supportively, but the outcome was poor. Discussion A multidisciplinary assessment should be performed for differential diagnosis of cerebral lesions in hematologic malignancies. Progressive multifocal leukoencephalopathy should be suspected in cases of subacute neurological symptoms and imaging findings consistent with it, especially if the patient received immunosuppressive or immunomodulatory drugs.

Changes in John Cunningham virus index in Multiple Sclerosis patients treated with different disease-modifying therapies

Background: Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic infection caused by John Cunningham virus (JCV) reactivation, potentially associated to natalizumab (NTZ) treatment for Multiple Sclerosis (MS). The anti-JCV antibodies titre (JCV index) increases during NTZ treatment; however, the effects of other disease modifying therapies (DMTs) on JCV index have not been fully explored. Objective: to evaluate changes in JCV index during treatment with several DMTs. Methods: This longitudinal study evaluated JCV index before starting DMT (T0) and on DMT (T1). Results: A total of 260 (65.4% females, mean age 43±11.3 ) were enrolled: 68 (26.2%) treated with fingolimod (FTY), 65 (25%), rituximab or ocrelizumab (RTX/OCR), 37 (14.2%), dimethyl-fumarate (DMF), 29 (11.2%), cladribine (CLD), 23 (8.8%), teriflunomide (TFM), 20 (7.7%), interferon or glatiramer acetate (IFN/GA), and 18 (6.9%) alemtuzumab (ALM). At T1, the percentage of patients with JCV index '0.90 was significantly increased in the ALM group (16.7% versus 66.7%, p=0.05), the percentage of patients with JCV index >1.51 was significantly reduced in RTX/OCR group (51.6% versus 37.5%, p=0.04). In the FTY group, a significant reduction in percentage of patients with JCV index '0.90 was also found (23.5% versus 1.4%, p=0.0006). The mean JCV index was reduced in RTX/OCR and ALM groups, while a significant increase was observed in the FTY group. Conclusion: DMTs with a T and/or B depleting mechanism of action induced a significant reduction of the JCV index. These results may suggest new possible sequencing strategies potentially maximizing disease control, while reducing PML risk.

A Case of John Cunningham Virus Induced Rhombencephalitis after Rituximab Therapy for Idiopathic Thrombocytopenic Purpura

Background. John Cunningham virus (JCV) is known to cause progressive multifocal leukoencephalopathy (PML) in immuno-compromised patients due to lytic infection of oligodendrocytes and astrocytes. Rarely, it may also present as granule cell neuronopathy (GCN), leading to degeneration of cerebellar granule cell neurons. It is described in patients with underlying conditions or medication contributing to immune compromise. Case Presentation. A 73-year-old man presented with ataxia and difficulty in speech which began 3 months after initiation of treatment for idiopathic thrombocytopenic purpura with rituximab. Neurological examination was significant for torsional nystagmus, motor aphasia, right-sided dysmetria, and dysdiadochokinesia with gait ataxia. Magnetic resonance imaging (MRI) showed right cerebellar lesion and cerebrospinal fluid (CSF) polymerase chain reaction (PCR) was positive for JC virus. Conclusion. The diagnosis of JC virus-related cerebellar disease can be missed, due to the subacute to chronic onset and challenges in detection. Clinicians should have a high degree of suspicion for development of these symptoms, even a few months after initiation of immune-modulatory therapy because the progression and outcomes can be disastrous.

Epstein-Barr virus, human cytomegalovirus, human herpesvirus 6 and 7, human adenovirus, John Cunningham virus, and BK virus are not associated with gliomas in humans

Introduction: The literature points to several viruses associated with brain carcinogenesis, including gliomas. Aim: The aim of this study was to assess the presence of several viruses in gliomas and plasma from patients with brain tumor and the possible association of viral positivity with the clinical course. Material and methods: The study group consisted of 37 patients with gliomas who were subjected to surgery. Mean patient age was 54.59 (SD 15.85) years. The presence of viral DNA was assessed using real-time polymerase chain reaction. Results and discussion: We did not confirm any BK virus, John Cunningham virus, or human adenovirus-positive gliomas. The percentage of patients with gliomas positive for Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus (HHV) 6 and 7 was 18.9%, 8.1%, 2.7%, and 10.8%, respectively. We did not confirm the co-occurrence of glioma and plasma viral positivity. Fisher’s test did not reveal the influence of viral infection on the risk of death. We did not detect any differences regarding sex, WHO classification of gliomas, or the functional impairment evaluated by the Karnofsky scale index at admission to the hospital in the group of patients positive or negative for EBV, CMV, or HHV6. Conclusions: We cannot confirm an association of the investigated viruses with gliomas.

Trafficking of JC virus-like particles across the blood–brain barrier

John Cunningham virus-like particles (JC VLPs) are able to cross the blood-brain barrier in vitro and in vivo.

The effect of tonsillectomy on John Cunningham virus serological status in multiple sclerosis patients: A retrospective case–control study

Tonsils are believed to be the initial site of the John Cunningham virus (JCV) infection. The long-term effect of childhood tonsillectomy on JCV status in multiple sclerosis (MS) patients has not been investigated. In this retrospective case–control study, we analyzed data of 144 JCV seropositive cases and 82 JCV seronegative controls from three outpatient MS clinics in the United States. Early tonsillectomy (before the age of 8) was reported among 8 (5.56%) JCV seropositive subjects and 19 (23.17%) controls. Early tonsillectomy was associated with JCV negative status (adjusted odds ratio = 5.39, 95% confidence interval = 2.13–13.62, p < 0.001) independent of age and gender.

Risiken progressiver multifokaler Leukenzephalopathie

Progressive multifokale Leukenzephalopathie (PML) ist eine Erkrankung des zentralen Nervensystems. Sie wird durch den sogenannten John Cunningham Virus (JCV) ausgelöst. Natalizumab, ein Medikament, das bei Multipler Sklerose (MS) eingesetzt wird, erhöht das Risiko für PML. Im Rahmen dieser Studie untersuchten die Autoren, inwiefern risikominimierende Maßnahmen die Inzidenz von PML bei Natalizumab-Patienten beeinflussen.