Diagnosis Of Progressive Multifocal Leukoencephalopathy Research Articles

Progressive multifocal leukoencephalopathy as the presenting feature in a patient with occult low-count monoclonal B-cell lymphocytosis.

Low Count Monoclonal B-Cell Lymphocytosis (LC-MBL) is a relatively poorly understood entity which has been suggested to be very common in asymptomatic adults and possibly related to infectious complications despite not progressing to CLL. We describe the first case of Progressive Multifocal Leukoencephalopathy (PML) presenting in a 72-year-old man with LC-MBL but no other immunocompromising conditions. A diagnosis of PML was confirmed with classic MRI findings in association with a high CSF John Cunningham polyomavirus (JCV) viral load (4.09' 105 copies/mL). An extensive search for underlying immunocompromising conditions only demonstrated LC-MBL representing approximately 4% of total leukocytes (0.2' 109/L). This is the first report of PML in association with LC-MBL. Careful review of peripheral blood flow cytometry results is necessary to identify this disorder. Further study of the epidemiology and infectious complications of LC-MBL are warranted.

18F-THK5351 Positron Emission Tomography Clearly Depicted Progressive Multifocal Leukoencephalopathy After Mantle Cell Lymphoma Treatment.

An 84-year-old Japanese woman presented with left hemiplegia 8 months after completing chemotherapy for mantle cell lymphoma. Brain magnetic resonance imaging (MRI) revealed a hyperintense lesion extending from the right parietal lobe to the left parietal lobe. Compared with these MRI results, 18F-THK5351 PET revealed more extensive accumulation. A brain biopsy showed progressive multifocal leukoencephalopathy (PML). Immunohistochemistry and John Cunningham virus (JCV) DNA-polymerase chain reaction indicated JCV infection. Therefore, a diagnosis of PML was made. 18F-THK5351 PET, indicative of activated astrocytes, clearly depicted PML lesions composed of reactive and atypical astrocytes. 18F-THK5351 PET may capture fresh progressive PML lesions better than MRI.

Progressive Multifocal Leukoencephalopathy in Systemic Lupus Erythematosus: A Consequence of Patient-Intrinsic or -Extrinsic Factors?

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system (CNS) caused by reactivation of the polyomavirus JC (JCV) typically in immunocompromised individuals. The risk of PML among rheumatic diseases may be higher for systemic lupus erythematosus (SLE), without, however, a clear association with the type and intensity of background therapy. We present the development and outcome of PML in a 32-year-old female lupus patient under mild immunosuppressive treatment, yet with marked B-cell lymphopenia in the peripheral blood and bone marrow (<1% of total lymphocytes). Despite treatment with the immune checkpoint inhibitor pembrolizumab, the patient showed progressive neurological and brain imaging deterioration and eventually died 15 months after PML diagnosis. To unveil possible underlying genetic liabilities, whole exome sequencing was performed which identified deleterious variants in GATA2 and CDH7 genes, which both have been linked to defective T- and/or B-lymphocyte production. These findings reiterate the possible role of disease-/patient-intrinsic factors, rather than that of drug-induced immunosuppression, in driving immune dysregulation and susceptibility to PML in certain patients with SLE.

No Association Between HLA-B*57:01 and Prevalence and/or Outcome of Progressive Multifocal Leukoencephalopathy in a French Nationwide Human Immunodeficiency Virus Cohort.

Among 34,351 patients living with human immunodeficiency virus with available HLA-B*57:01 included in the Dat'AIDS cohort, 194 patients (0.56%) had a history of progressive multifocal leukoencephalopathy (PML) and 1,746 (5.08%) were carriers of HLA-B*57:01. The frequency of HLA-B*57:01 was similar among patients with history of PML compared with patients without a history of PML (6.19% [95% confidence interval, CI 2.8%-9.6%] vs. 5.08% [95% CI 4.8%-5.3%]; p = .48). Among patients with PML, clinical and biological characteristics at PML diagnosis and the PML outcome were not different according to HLA-B*57:01 status.

Progressive multifocal leukoencephalopathy without overt immunosuppression.

Progressive multifocal leukoencephalopathy (PML) is a central nervous system disease caused by the human polyomavirus 2 that usually occurs in a setting of immunodeficiency. PML without overt immunosuppression is considered a rare occurrence but has been described in multiple previous case reports and series. Its prevalence, overall frequency, and prognosis are largely unknown. This is a single-center retrospective review of all University of Florida cases with the ICD10 PML diagnosis code (A81.2). PML without overt immunosuppression was defined as absence of human immunodeficiency virus (HIV) infection, hematological malignancy, immunomodulatory/-suppressive medications, autoimmune conditions with a propensity for PML (sarcoidosis, systemic lupus erythematosus). Cases that did not fulfill criteria for clinically or histologically definite PML were excluded. Of 52 patients with the ICD10 code A 81.2, 17 fulfilled definite diagnostic criteria for PML. Overt immunosuppression was identified in 15/17 (88.2%) cases (10/17 (58.8%): human immunodeficiency virus; 5/17 (29.4%): immunomodulatory/-suppressive medication). Two/seventeen (11.8%) cases were consistent with PML without overt immunosuppression. Possible contributing factors were a preceding dog bite and mild hypogammaglobulinemia M (39 mg/dL) in case 1 and significant alcohol use without evidence for liver disease in case 2. Both cases were fatal within 6 (case 1) and 2 (case 2) months. The results suggest that PML without overt immunosuppression may be more common than previously described. Therefore, PML should be considered even in the absence of overt immunosuppression if clinical and radiographic findings are suggestive of the diagnosis.

Serum Neurofilaments are a reliable biomarker to early detect PML in Multiple Sclerosis patients.

The earliest detection of progressive multifocal leukoencephalopathy (PML) is crucial in Natalizumab (NTZ)-treated Multiple Sclerosis (MS) patients. This study aims to assess serum Neurofilaments (sNFL) ability to early detect PML in longitudinal patients' follow-up. NFL were retrospectively measured in four PML cases occurred at the Regional Referring Center for MS (CRESM, Italy), in samples collected since one year before PML diagnosis, at PML diagnosis, during PML and in post-PML follow-up. sNFL levels were interpreted according to previously defined reference values. Clinical examination and EDSS were performed at each NTZ infusion. Routinary MRI was undertaken every six months; after PML diagnosis, MRI was performed according to clinical evaluation. sNFL were also measured in 45 NTZ-treated patients experiencing NEDA-3 status for at least 12 months. Patients showed different PML onsets and manifestations: in 3 patients routinary brain MRI revealed radiological signs of PML preceding different clinical manifestations, while in one patient brain MRI was performed after the clinical onset. PML diagnosis was defined at the time of the first detection of JCV DNA in cerebrospinal fluid. The following different PML phases were considered: 1. Basal (up to 4 months before PML diagnosis): sNFL values were in the normal range in all patients' samples, except for one (median 9.1 pg/ml, range 6.2-15.1 pg/ml) 2. Pre-PML (within 3 months before PML diagnosis): sNFL were elevated in all available samples (median 19.50 pg/ml, range 15.50-33.80 pg/ml). 3. PML diagnosis: sNFL were elevated in all patients (median 59.20 pg/ml, range 11.1-101.50 pg/ml). 4. PML/IRIS: during this phase, sNFL levels reached their peak (median 96.35 pg/ml, range 20.5-272.9) in all patients. 5. Post-PML (recovery phase, starting from the first MRI without enhancement, up to the end of follow-up): sNFL levels showed a decrease (median 12.80 pg/ml, range 9.30-30.60); however, based on reference values, sNFL were still elevated in 2 out of 4 patients at the end of their follow-up (622 and 887 days after PML diagnosis). sNFL were always elevated when MRI scan suggested a suspicious of PML. In NEDA-3 patients, sNFL levels were in the normal range in all patients' samples (median 4.7 pg/ml, range 1.4-8.6 pg/ml). Elevated sNFL were observed not only at PML diagnosis, but also in pre-PML phase. At PML recovery, sNFL weren't normalized in all patients' samples, suggesting ongoing neuronal degeneration. sNFL represent a reliable biomarker and should be introduced in clinical practice as an additional/alternative parameter to MRI to early detect and monitor PML.

Progressive multifocal leukoencephalopathy in multiple myeloma: a case report of a patient with SARS-CoV-2 infection and an updated systematic literature review.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by a reactivation of the human polyomavirus 2 (HPyV-2, previously known as JCV) in immunosuppressed individuals. Few cases of PML have been described in multiple myeloma (MM) patients. We described a case of PML in a patient with MM with fatal worsening that occurred during SARS-CoV-2 infection. We also performed a literature review to update the 16 cases series of MM patients with PML already collected until April 2020. A 79-year-old female patient with refractory IgA lambda MM in Pomalidomide- Cyclophosphamide-Dexamethasone regimen developed gradual lower limbs and left arm paresis along with a decreased consciousness 3.5 years after the MM diagnosis. Symptoms developed shortly after the recognition of hypogammaglobulinemia. After SARS-CoV-2 infection, her neurological status quickly worsened until she deceased. MRI features and JCV-positive PCR on CSF confirmed the PML diagnosis. Our literature review adds sixteen clinical cases of PML in MM published between May 2020 and March 2023 to the 16 cases already collected in the previously published review by Koutsavlis. PML has been increasingly described in MM patients. It remains questionable if the HPyV-2 reactivation is determined by the severity of MM itself, by the effect of drugs or by a combination of both. SARS-CoV-2 infection may have a role in worsening PML in affected patients.

A wolf in sheep’s clothing: when a stroke is not a stroke, and how comprehensive speech and language therapy assessment and intervention can help to set the alarm

A 70-year-old male patient, who was diagnosed with human immunodeficiency virus (HIV) in 2001 and did not undergo antiretroviral therapy, was admitted two months after the onset of left cortical-subcortical ischemic stroke, with involvement of the corona radiata and the left thalamus. As a consequence of this vascular event, he suffered aphasia, severe dysarthria, dysphagia, and right hemiparesis. The patient took part in a rehabilitation program at a rehabilitation centre for neurological diseases with a specialised interdisciplinary rehabilitation team. He underwent speech therapy intervention with a frequency of 2-3 hours per day. Despite the intensity of the program, there was a decline in his clinical and functional status during hospitalisation, with decreased capacity to swallow and communicate (either because of the exacerbation of the aphasia, or due to the worsening of dysarthria and apraxic features). Due to this global deterioration, additional imaging, as well as serological and aetiological examination was performed, which led to a diagnosis of progressive multifocal leukoencephalopathy in the context of HIV1 infection. Antiretroviral therapy was administered to reverse the symptoms. This case illustrates the relevance of clinical disclosure for the establishment of appropriate functional prognoses and discharge planning. It also shows that the initial clinical features can be misleading and can lead to concealment of the real aetiology, as well as delays in appropriate treatment, especially in multipathology patients.

Epileptic seizures associated with progressive multifocal leukoencephalopathy in HIV-infected patients in Korea.

We investigated the incidence and risk factors of seizures related to progressive multifocal leukoencephalopathy (PML) in Korean patients infected with HIV. Of the 34 patients, 14 (41.2%) developed epileptic seizures during a median follow-up of 82months. The median time from PML diagnosis to seizure onset was 44 months, ranging from 0 to 133 months. Patients with PML who developed seizures more commonly had cognitive impairment and multiple or diffuse lesions on brain MRI. These findings highlight the increased seizure risk among HIV-infected patients with PML at any stage of the disease, particularly in cases with extensive involvement.

Progressive Multifocal Leukoencephalopathy Secondary to Possible Covert Administration of Osimertinib, a Case Report. (P13-10.004)

<h3>Objective:</h3> to report a case of rapidly progressive multifocal leukoencephalopathy with unclear cause, possibly secondary to covert administration of Osimertinib. <h3>Background:</h3> Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that was first reported in 1958. It is caused by reactivation of the John Cunningham (JC) virus. Drug-induced PML is increasingly reported in the era of molecular anti-neoplastic targeted therapy. Osimertinib, a tyrosine kinase inhibitor (TKI) was described in one case report to be associated with rapidly progressive PML, we believe our case to be the second. <h3>Design/Methods:</h3> Case report, N/A <h3>Results:</h3> 47-year-old-male with pulmonary sarcoidosis presented with worsening confusion and jerking episodes for nine months. Examination was significant for pseudobulbar affect, left sided weakness, and hyperreflexia. MRI brain showed multiple hyperintense FLAIR lesions in the subcortical white matter without enhancement. MRI cervical, thoracic, and lumbar spine was unremarkable. CT chest abdomen and pelvis was negative for malignancy but showed findings consistent with pulmonary sarcoidosis. CSF showed normal cell count and protein. CSF viral studies, bacterial studies, fungal studies, N-methyl-D-Aspartate Receptor Ab IgG CSF, NMO IgG, CSF were negative. He was found to have low total CD4 count of 118. Blood tests for infectious (including HIV), autoimmune, and paraneoplastic causes were unremarkable. He was noted to have. Brain biopsy confirmed the diagnosis of PML. There was reported concern about covert administration of Osimertinib which was available at home. The patient’s course was complicated by sepsis and he passed away after a month of hospitalization. <h3>Conclusions:</h3> This case demonstrates a challenging presentation of PML in an originally supposed immunocompetent patient. Inhibition of tyrosine kinase-dependent pathways can potentially aid in the replication of JC virus. Holding immunosuppressive therapy remains the mainstay for management for non-HIV related PML. Early recognition of this fatal etiology and its subcategory would help guide clinical management. <b>Disclosure:</b> Dr. Centofanti has nothing to disclose. Dr. Alkhoujah has nothing to disclose. Dr. Bishja has nothing to disclose.

Nationwide Laboratory Surveillance of Progressive Multifocal Leukoencephalopathy in Japan: Fiscal Years 2011-2020.

Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular immunity. PML is a non-reportable disease with a few exceptions, making national surveillance difficult. In Japan, polymerase chain reaction (PCR) testing for JCV in the cerebrospinal fluid (CSF) is performed at the National Institute of Infectious Diseases to support PML diagnosis. To clarify the overall profile of PML in Japan, patient data provided at the time of CSF-JCV testing over 10 years (FY2011-2020) were analyzed. PCR testing for 1537 new suspected PML cases was conducted, and 288 (18.7%) patients tested positive for CSF-JCV. An analysis of the clinical information on all individuals tested revealed characteristics of PML cases, including the geographic distribution, age and sex patterns, and CSF-JCV-positivity rates among the study subjects for each type of underlying condition. During the last five years of the study period, a surveillance system utilizing ultrasensitive PCR testing and widespread clinical attention to PML led to the detection of CSF-JCV in the earlier stages of the disease. The results of this study will provide valuable information not only for PML diagnosis, but also for the treatment of PML-predisposing conditions.

Sequence analysis of the non-coding control region of John Cunningham virus isolates from patients with multiple sclerosis treated with natalizumab

Introduction. The John Cunningham virus (JCPyV) causes a fatal demyelinating disease of the central nervous system known as progressive multifocal leukoencephalopathy (PML). In healthy people, the JCPyV non-coding control region (NCCR) is not rearranged, while NCCRs in immunocompromised patients are characterized by frequent rearrangements and can be associated with PML development. Therefore, patients treated with natalizumab, which decreases the migration of leukocytes and monocytes through the blood-brain barrier to inflammatory foci, are at increased risk of developing PML.&#x0D; The purpose of the study was to analyze NCCR sequences of JCPyV isolates from patients with multiple sclerosis (MS) treated with natalizumab.&#x0D; Materials and methods. A total of 26 blood plasma samples and 8 cerebrospinal fluid samples were analyzed using nested PCR to study the JCPyV NCCR structure in Russian MS patients treated with natalizumab. The NCCRs present in the samples were cloned and sequenced by Sanger sequencing. All the JCPyV NCCR sequences were compared with the archetype sequence and mapped. The NCCR sequences were also examined for presence of putative transcription factor binding sites.&#x0D; Results. A total of 48 NCCR sequences were found. The analysis showed that up to 55% of NCCRs were identified as rearranged NCCRs, while the other were archetype-like NCCRs. All the sequences can be divided into 6 types with one dominant rearrangement pattern. This rearranged NCCR was also found in a patient with the confirmed PML diagnosis and a poor prognosis. All the rearranged NCCRs were characterized by the presence of additional transcription factor binding sites.&#x0D; Conclusion. The study has helped identify previously unknown NCCR patterns typical of MS patients treated with natalizumab in Russia, thus confirming the need for the further research on NCCR rearrangements in MS patients undergoing natalizumab treatment to gain better understanding of the origin of neurovirulent JCPyV variants.

Progressive Multifocal Leukoencephalopathy in a Patient with Multifocal Neurological Manifestations Caused by Solitary Brainstem Involvement.

A Japanese man in his 60s on medication for chronic lymphocytic leukemia presented with progressive, multifocal neurological manifestations. Magnetic resonance imaging showed a small, solitary region of brainstem involvement. Sensitive real-time polymerase chain reaction testing detected a small amount of JC virus (JCV) DNA (170 copies/mL) with pathogenic mutation in cerebrospinal fluid. We diagnosed the patient with progressive multifocal leukoencephalopathy (PML). The small PML lesion may have caused multifocal neurological symptoms because of its focal brainstem involvement. This case contributes to knowledge regarding the diagnosis and treatment of brainstem PML in the context of hematologic malignancies and other underlying diseases.

Undetectable JC virus CSF PCR in patients with JC virus-induced progressive multifocal leukoencephalopathy.

The diagnosis of progressive multifocal leukoencephalopathy (PML) is based on a combination of clinical, radiographic, and laboratory findings. However, negative JC polyomavirus (JCPyV) PCR in CSF does not always rule out JCPyV-related PML. In this narrative review, we sought to examine the characteristic of biopsy-proven PML in patients with undetectable JCPyV CSF PCR and provide alternative approaches in this scenario.

Differential diagnosis of immune reconstitution inflammatory syndrome and progressive multifocal leukoencephalopathy after natalizumab withdrawal

The appearance of new foci on MRI, the increase in neurological deficits, including the appearance of cognitive disorders and disturbances in the level of consciousness in patients with multiple sclerosis during the «washing period» when transferring from natalizumab (NZ) to another drug, may be due to both progressive multifocal leukoencephalopathy (PML) and exacerbation of the disease in the absence of therapy. Discontinuation of NS is fraught not only with a resumption, but with an increase in disease activity, the development of an immune reconstitution inflammatory syndrome (IRIS) due to the opening of the blood-brain barrier. Often, the processes of differential diagnosis of IRIS and natalizumab-associated PML are complex and require the use of additional methods of examination and monitoring of the dynamics of the patient's condition. However, the severity of the condition and the severity of the consequences caused by incorrect therapeutic tactics significantly reduce the time for diagnosis and require an immediate decision. The difficulties of differential diagnosis of IRIS and PML are reflected in the clinical case.

Progressive Multifocal Leukoencephalopathy Associated With Sarcoidosis: A Multi-Center Case Series

Objective We aim to describe the clinical, laboratory, and radiographic features that characterize patients with progressive multifocal leukoencephalopathy (PML) in the context of sarcoidosis (S-PML). Background Sarcoidosis has been associated with CD4+, CD8+, and CD19+ lymphopenia, T-cell anergy, and increased infection risk. S-PML has been reported in approximately 60 cases. PML is often mistaken for neurosarcoidosis, leading to harmful administration of high-dose steroids. Preliminary evidence suggests that experimental therapies such as interleukins 2 and 7, checkpoint inhibitors, polyomavirus-specific T-cell therapy, and infliximab may offer promise for treatment. To ensure optimal outcome, it is crucial to identify S-PML accurately and with minimal delay. Design/Methods Data and imaging for patients were collected retrospectively from the electronic medical record from Mass General-Brigham network hospitals, National Institutes of Health, Mayo Clinic, Columbia University Irving Medical Center, University of California San Francisco, University of Michigan, and Beth Israel Deaconess Medical Center. Results Twenty-five patients with definite S-PML were identified. Median age at diagnosis of sarcoidosis was 54 years, and median time between sarcoidosis and PML diagnosis was 12 months. Sarcoidosis was isolated to lung in 14/25 patients; 10/25 had multisystem involvement; one patient had isolated dermatologic sarcoidosis. Of all patients, 16/25 patients had never received immunosuppressive medications prior to neurological symptom onset. Median serum lymphocyte count at time of PML diagnosis was 430 cells/uL (range: 50-1490). On MRI, 8/25 patients had infratentorial lesions only, while 8/25 had both infratentorial and supratentorial lesions, and 6/25 showed contrast enhancement. Seven/twenty-five patients progressed to death. Conclusions This study characterizes the clinical, laboratory, and imaging features of S-PML patients from seven major US medical centers. These data will be used to identify risk factors for development of PML in the context of sarcoidosis and to investigate any biomarkers that might aid in accurate and timely diagnosis.

Comparison of qPCR with ddPCR for the Quantification of JC Polyomavirus in CSF from Patients with Progressive Multifocal Leukoencephalopathy.

Background: Lytic infection of oligodendrocytes by the human JC polyomavirus (JCPyV) results in the demyelinating disease called progressive multifocal leukoencephalopathy (PML). The detection of viral DNA in the cerebrospinal fluid (CSF) by PCR is an important diagnostic tool and, in conjunction with defined radiological and clinical features, can provide diagnosis of definite PML, avoiding the need for brain biopsy. The main aim of this study is to compare the droplet digital PCR (ddPCR) assay with the gold standard quantitative PCR (qPCR) for the quantification of JC viral loads in clinical samples. Methods: A total of 62 CSF samples from 31 patients with PML were analyzed to compare the qPCR gold standard technique with ddPCR to detect conserved viral DNA sequences in the JCPyV genome. As part of the validation process, ddPCR results were compared to qPCR data obtained in 42 different laboratories around the world. In addition, the characterization of a novel triplex ddPCR to detect viral DNA sequence from both prototype and archetype variants and a cellular housekeeping reference gene is described. Triplex ddPCR was used to analyze the serum from six PML patients and from three additional cohorts, including 20 healthy controls (HC), 20 patients with multiple sclerosis (MS) who had never been treated with natalizumab (no-NTZ-treated), and 14 patients with MS who were being treated with natalizumab (NTZ-treated); three from this last group seroconverted during the course of treatment with natalizumab. Results: JCPyV DNA was detected only by ddPCR for 5 of the 62 CSF samples (8%), while remaining undetected by qPCR. For nine CSF samples (15%), JCPyV DNA was at the lower limit of quantification for qPCR, set at <250 copies/mL, and therefore no relative quantitation could be determined. By contrast, exact copies of JCPyV for each of these samples were quantified by ddPCR. No differences were observed between qPCR and ddPCR when five standardized plasma samples were analyzed for JCPyV in 42 laboratories in the United States and Europe. JCPyV-DNA was undetected in all the sera from HC and MS cohorts tested by triplex ddPCR, while serum samples from six patients with PML tested positive for JCPyV. Conclusion: This study shows strong correlation between ddPCR and qPCR with increased sensitivity of the ddPCR assay. Further work will be needed to determine whether multiplex ddPCR can be useful to determine PML risk in natalizumab-treated MS patients.

Single-center experience on progressive multifocal leukoencephalopathy (PML) cases, neuroimaging relevance, and management at West Virginia University (WVU).

Progressive multifocal leukoencephalopathy (PML) is an increasingly common and rapidly fatal demyelinating infection of central nervous system caused by the highly prevalent John Cunningham (JC)virus in immunocompromised individuals belonging to all age groups and genders. Human immunodeficiency virus (HIV) is the most common predisposing factor among other immunodeficient conditions leading to reactivation and multiple neurological symptoms. It has varied findings on magnetic resonance imaging (MRI) and diagnosis is confirmed by positive JC virus in cerebrospinal fluid (CSF). We report 12 confirmed cases of PML from a single academic center. We comprehensively described clinical presentations, risk factors, CSF and neuroimaging findings, treatment and outcome for these cases of PML, a rare disease. The cases were almost equivalently distributed among young and old age groups and both genders. Positive JC virus on CSF was present in the majority of cases along with mild to severe reduction in lymphocyte counts. Significant MRI changes were present in all cases ranging from T2 hypertense signals to white matter lesions in various regions. Treatment with the reversion of immune-modulators, optimization of antiviral therapy (ART), plasmapheresis (PLEX), IVIG, Mirtazapine, oral steroids, and others was started as soon as the diagnosis was made in the majority of the cases. However, PML is a rapidly fatal illness and hence, survival was only seen in 4 cases in our study. The objective of this article is to highlight the importance of early diagnosis of PML with CSF findings and neuroimaging, early reversion of immunosuppressive medications, and careful monitoring and treatment of HIV cases with goals to reduce mortality, long-term morbidity, and deficits.

JC polyomavirus DNA detection in clinical practice.

There are limited data about the use and clinical value of JC polyomavirus (JCPyV) DNA detection in various clinical indications. We reviewed the clinical records of 410 patients from whom cerebrospinal fluid (CSF), plasma, urine, or tissue samples had been collected for JCPyV DNA polymerase chain reaction (PCR) between 2012 and 2018. JCPyV DNA was analyzed in 224 plasma, 190 CSF-, 32 urine and 10 tissue samples. 240 patients had a history of hematopoietic stem cell or solid organ transplantation, 159 had nephrological disease, 90 had hematologic malignancies, 58 had neurological disease, 37 had infectious disease and 23 had AIDS/HIV as underlying disease. Six patients had no underlying disease. The main reasons to take CSF or plasma samples were neurological symptoms of unknown etiology. Most urine samples were taken to monitor kidney transplantation patients. JCPyV DNA PCR contributed to the diagnosis of progressive multifocal leukoencephalopathy in eight patients (2.0%), of which seven had hematologic malignancy as an underlying disease. JCPyV PCR is most informative among immunosuppressed patients with neurologic symptoms. CSF and brain biopsy are useful when there is clinical suspicion of PML, whereas plasma samples are not useful. The value of plasma samples is a matter of dispute in the screening of JCPyV-associated nephropathy, as BK polyomavirus is the causative agent in most polyomavirus-associated nephropathy cases. JCPyV detection is valuable in case the patient has past, current or planned treatment with immunosuppressive drugs.

Progressive multifocal leukoencephalopathy in patients with immunovirological control and at least 6 months of combination antiretroviral therapy.

: Progressive multifocal leukoencephalopathy (PML) has rarely been reported in people with HIV (PWH) with long-term HIV immune-virological control. We describe the clinical and biological characteristics of patients with confirmed PML among PWH with a CD4+ cell count more than 200 cells/μl and an undetectable HIV RNA viral load after at least 6 months of combined antiretroviral therapy (cART) at the time of PML diagnosis, in the large French multicenter Dat'AIDS cohort. : Among 571 diagnoses of PML reported in the Dat'AIDS cohort between 2000 and 2019, 10 cases (1.75%) occurred in PWH with a CD4+ cell count greater than 200 cells/μl and an undetectable HIV RNA viral load after at least 6 months of cART. Median CD4+ cell count at PML diagnosis was 395 cells/μl (IQR 310-477). The median duration between the last detectable HIV viral load and the PML diagnosis was 41.1 months (IQR 8.2-67.4). Only one patient treated with rituximab-based chemotherapy for a large B-cell lymphoma had an established risk factor for PML. Among the nine other patients with no apparent severe immunodeficiency, multiple factors of impaired immunity could have led to the development of PML: hepatitis C virus (HCV) co-infection (n = 6), cirrhosis (n = 4), HHV-8 co-infection (n = 3) with Kaposi's sarcoma (n = 2) in association with Castleman's disease (n = 1) and indolent IgA multiple myeloma (n = 1). : This study highlights that factors other than low CD4+ cell count and high HIV viral load may be associated with the occurrence of PML. Further studies are warranted to investigate in greater detail the immunologic characteristics of PWH with immune-virological control who develop PML.