Article
Clinical Neurology
Giulia Berzero, Sabrina Basso, Luca Stoppini, Andrea Palermo, Anna Pichiecchio, Matteo Paoletti, Federica Lucev, Simonetta Gerevini, Andrea Rossi, Elisa Vegezzi, Luca Diamanti, Paola Bini, Matteo Gastaldi, Serena Delbue, Cesare Perotti, Elena Seminari, Maura Faraci, Mario Luppi, Fausto Baldanti, Marco Zecca, Enrico Marchioni, Patrizia Comoli
Summary: The study found that using JCPyV-specific T cell therapy to treat hematological patients with PML is safe and effective, with no treatment-related adverse events observed. Some patients experienced an increase in JCPyV-specific lymphocytes and a decrease in JCPyV viral load in cerebrospinal fluid. Six out of 9 patients achieved PML control, with 5 alive and in good clinical condition at their last follow-up.
ANNALS OF NEUROLOGY
(2021)
Article
Clinical Neurology
Gautier Breville, Igor J. Koralnik, Patrice H. Lalive
Summary: Isolated brainstem lesions at disease onset are extremely rare in PML cases, with most patients experiencing initial clinical worsening. However, some patients may achieve full or partial recovery despite the reserved prognosis due to the vital structures in the brainstem.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Clinical Neurology
Xiang Wang, Jinxiu Chen, Jing Gong, Ying Wu, Xiang-hao Liu
Summary: This case presents a rare occurrence of progressive multifocal leukoencephalopathy (PML) caused by JC virus infection in a previously healthy and immunocompetent patient. The patient showed disease stabilization after receiving a combination treatment, which may contribute to our understanding of virus infections during the coronavirus epidemic.
Article
Medicine, General & Internal
Varun Jain, Hannah Branstetter, Srikar Savaram, Matthew Vasquez, Gabriel Swords, Sina Aghili-Mehrizi, John Rees, Marie Rivera-Zengotita, Mayra Montalvo, Miguel Chuquilin, Addie Patterson, Torge Rempe
Summary: This study is a retrospective review of all PML cases at the University of Florida. 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.
Article
Clinical Neurology
Marine Joly, Cecile Conte, Charles Cazanave, Vincent Le Moing, Pierre Tattevin, Pierre Delobel, Agnes Sommet, Guillaume Martin-Blondel
Summary: This study examined the epidemiology and prognosis of progressive multifocal leukoencephalopathy using a large cohort of patients in France. The findings revealed a stable incidence rate of the disease in France, with HIV infection being the main predisposing condition. Male patients had a higher risk of mortality compared to females, and patients with solid neoplasms had the worst prognosis.
Article
Immunology
Anni Honkimaa, Joni Suppula, Olli Tynninen, Mika Saarela, Hanna Liimatainen, Pia Laine, Petri Auvinen, Eeva Auvinen
Summary: Progressive multifocal leukoencephalopathy (PML) is a severe neurological condition caused by reactivation of JC polyomavirus (JCPyV) in immunosuppression. Asymptomatic JCPyV persists in peripheral tissues. Upon reactivation, neurotropic rearrangements may emerge, and the virus gains access to the brain. To assess the mechanisms of PML pathogenesis, brain tissue material from PML patients was collected for small RNA sequencing. Upregulation of 8 microRNAs (miRNAs) in PML brain was validated using quantitative microRNA polymerase chain reaction (PCR). Bioinformatics tools were utilized to identify major associations of the upregulated miRNAs: neuroinflammation and blood-brain barrier disruption. The results indicate involvement of human miRNA regulation in PML pathogenesis.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Neurosciences
Chia-Yu Chiu, Eva Amenta, Violeta Chavez, Yuriko Fukuta, Rodrigo Hasbun
Summary: The diagnosis of PML is based on clinical, radiographic, and laboratory findings, but a negative JCPyV PCR in the CSF does not always rule out JCPyV-related PML. This review examines the characteristics of biopsy-proven PML in patients with undetectable JCPyV CSF PCR and suggests alternative approaches in this scenario.
JOURNAL OF NEUROVIROLOGY
(2023)
Review
Clinical Neurology
Nora Moehn, Lea Grote-Levi, Franziska Hopfner, Britta Eiz-Vesper, Britta Maecker-Kolhoff, Clemens Warnke, Kurt-Wolfram Suehs, Mike P. Wattjes, Guenter U. Hoeglinger, Thomas Skripuletz
Summary: Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral disease of the brain caused by human polyomavirus 2. It affects patients with compromised immune systems and currently has no effective treatment. The primary therapeutic strategy focuses on reconstituting the immune system, with recent studies showing promising effects with anti-PD-1 antibodies and allogeneic virus-specific T cells.
JOURNAL OF NEUROLOGY
(2022)
Article
Immunology
Anne-Sophie L'honneur, Juliana Pipoli Da Fonseca, Thomas Cokelaer, Flore Rozenberg
Summary: Intrahost deep sequencing of JC polyomavirus whole genome in patients with progressive multifocal leukoencephalopathy reveals compartment-specific and opposite patterns of genome variations in brain and urine. Neurotropic quasispecies stem from initial deletions in noncoding control region, evolve rapidly, and acquire mutations in capsid. Long-read deep sequencing shed light on emergence of neurotropic JCV populations in PML.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Virology
Nyater Ngouth, Maria Chiara Monaco, Lorenzo Walker, Sydney Corey, Ijeoma Ikpeama, Gary Fahle, Irene Cortese, Sanchita Das, Steven Jacobson
Summary: This study compares the droplet digital PCR (ddPCR) assay with the gold standard quantitative PCR (qPCR) for the quantification of JC viral loads in clinical samples. The results show a strong correlation between ddPCR and qPCR, with ddPCR demonstrating increased sensitivity. Additionally, a novel triplex ddPCR method for detecting JC viral DNA sequences is described.
Review
Clinical Neurology
Irene Cortese, Daniel S. Reich, Avindra Nath
Summary: The Review provides an overview of progressive multifocal leukoencephalopathy and diseases caused by JC virus, discussing emerging immunotherapeutic approaches for increased survival. It highlights the need to reassess PML pathophysiology and clinical course, and the challenges of reversing underlying immunosuppression in the absence of antiviral therapies. Emerging treatments show promise but caution is advised to manage potential complications such as immune reconstitution inflammatory syndrome and long-term neurological effects.
NATURE REVIEWS NEUROLOGY
(2021)
Review
Infectious Diseases
Adam S. Nelson, Niveditha Yalamarthi, Michelle K. Yong, Emily Blyth
Summary: In recent clinical trials, adoptive immunotherapy with BK and JC virus-specific T-cells (VST) has shown good clinical success in treating BK viremia and haemorrhagic cystitis post-haemopoietic stem cell transplant (HSCT). However, there have been some cases of immune mediated renal allograft loss in renal transplant recipients. VST have also shown promise in treating JC virus PML, with some patients experiencing clearance of the virus and clinical improvement. Further evaluation and standardization of dosing and outcome measures are needed for optimal use of VST in these conditions.
CURRENT OPINION IN INFECTIOUS DISEASES
(2021)
Article
Neurosciences
Nicole Becker, Aditi Sharma, Matthew Gosse, Brooke Kubat, Kyle S. Conway
Summary: This study presents a comprehensive description of the neuropathology in a 24-year-old female patient with compound heterozygous variants in the NDUFV1 gene and progressive cavitating leukoencephalopathy. The autopsy neuropathology showed extensive white matter involvement with regions of active demyelination, while muscle biopsy demonstrated histologic abnormalities and mitochondrial abnormalities. These findings support the link between mitochondrial abnormalities and demyelinating processes in the central nervous system.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Clinical Neurology
Jennifer Meylor, Daniel Crespo Artunduaga, Michael Mendoza, Sam I. Hooshmand, Ahmed Z. Obeidat
Summary: Progressive multifocal leukoencephalopathy (PML) is a central nervous system infection caused by human polyomavirus 2, usually affecting immunocompromised patients. However, this report presents two cases of PML in older individuals with chronic kidney disease (CKD). CKD can lead to immune system dysfunction and potentially increase the risk of PML.
NEUROLOGICAL SCIENCES
(2023)
Article
Clinical Neurology
Takashi Nagahori, Wataru Shiraishi, Masafumi Nishikawa, Ayano Matsuyoshi, Takenori Ogura, Yui Yamada, Kenta Takahashi, Tadaki Suzuki, Kazuo Nakamichi, Tetsuya Hashimoto, Taketo Hatano
Summary: A 58-year-old Japanese woman with untreated sarcoidosis and HTLV-1 infection presented with aphasia. Neurosarcoidosis was suspected, and she was treated with steroids and infliximab. However, she developed PML, which was the first reported case associated with HTLV-1 infection and sarcoidosis.
Article
Engineering, Biomedical
Akira Matsushima, Yoichi Maruyama, Noriaki Mizukami, Mikio Tetsuya, Minoru Hashimoto, Kunihiro Yoshida
Summary: A wearable curara (R) robot was validated in a single-arm study for people with degenerative cerebellar ataxia, showing rehabilitative effects on gait function comparable to therapist-assisted training.
BIOMEDICAL ENGINEERING ONLINE
(2021)
Article
Cell Biology
Mieko Doi, Keisuke Ishizawa, Kei Ikeda, Kazuo Nakamichi, Yoshihiko Nakazato, Toshimasa Yamamoto, Atsushi Sasaki
Summary: This article presents a case of progressive multifocal leukoencephalopathy in an immunocompromised female patient, discussing the utility of cytology and histology, specifically focusing on JC polyomavirus-infected oligodendrocytes and astrocytes.
Article
Medicine, General & Internal
Yu Hashimoto, Takumi Tashiro, Ryosuke Ogawa, Kazuo Nakamichi, Masayuki Saijo, Takahisa Tateishi
Summary: A 79-year-old man developed progressive multifocal leukoencephalopathy during ofatumumab therapy for refractory chronic lymphocytic leukemia, and unfortunately passed away despite treatment.
Article
Microbiology
Nor Azila Muhammad Azami, Meng Ling Moi, Yasushi Ami, Yuriko Suzaki, Satoshi Taniguchi, Shigeru Tajima, Masayuki Saijo, Tomohiko Takasaki, Ichiro Kurane, Chang-Kweng Lim
Summary: This study characterized the viral kinetics and antibody response induced by DENV type 2 Asian I and Asian/American genotypes in marmosets, revealing differences in viremia duration and levels as well as their impact on neutralizing antibody titers and ADE activity. These findings highlight the importance of genotype-specific neutralizing antibodies in vaccine development.
Article
Clinical Neurology
Kento Seko, Yuto Uchida, Takashi Kanamori, Keita Sakurai, Toshihiko Usami, Tomoyuki Kuno, Koji Takada, Kazuo Nakamichi, Noriyuki Matsukawa
Summary: Progressive multifocal leukoencephalopathy associated with a therapeutic regimen of daratumumab, lenalidomide, and dexamethasone for multiple myeloma is described. The patient developed cognitive dysfunction and was diagnosed with the disease based on positive polymerase chain reaction test. Symptoms improved after cessation of treatment.
NEUROLOGY AND CLINICAL NEUROSCIENCE
(2022)
Review
Hematology
Taro Edahiro, Noriyasu Fukushima, Tatsuya Otani, Masahiro Nakamori, Kazuo Nakamichi, Ren Chishaki, Keita Fujino, Tatsuji Mino, Tetsumi Yoshida, Sayaka Sugihara, Masatoshi Nishizawa, Tatsuo Ichinohe
Summary: Progressive multifocal leukoencephalopathy (PML) is a rare neurological disease caused by the reactivation of latent John Cunningham polyomavirus. Hematological disorders associated with immunomodulatory monoclonal antibodies and hematopoietic stem cell transplantation (HSCT) are risk factors for PML. The use of the novel immunomodulatory agent blinatumomab may increase the risk of developing PML.
ACTA HAEMATOLOGICA
(2022)
Article
Virology
Yuki Takamatsu, Tomoki Yoshikawa, Takeshi Kurosu, Shuetsu Fukushi, Noriyo Nagata, Masayuki Shimojima, Hideki Ebihara, Masayuki Saijo, Takeshi Noda
Summary: This study identified the localization of VP30 on the surface of ruffled nucleocapsids and revealed its role in nucleocapsid assembly. Phosphorylation of VP30 facilitates its association with nucleocapsid-like structures but does not affect nucleocapsid transport characteristics and virus-like particle budding efficiency.
JOURNAL OF VIROLOGY
(2022)
Article
Clinical Neurology
Takashi Nagahori, Wataru Shiraishi, Masafumi Nishikawa, Ayano Matsuyoshi, Takenori Ogura, Yui Yamada, Kenta Takahashi, Tadaki Suzuki, Kazuo Nakamichi, Tetsuya Hashimoto, Taketo Hatano
Summary: A 58-year-old Japanese woman with untreated sarcoidosis and HTLV-1 infection presented with aphasia. Neurosarcoidosis was suspected, and she was treated with steroids and infliximab. However, she developed PML, which was the first reported case associated with HTLV-1 infection and sarcoidosis.
Article
Medicine, General & Internal
Akito Funatsu, Kazuo Nakamichi, Midori Araki, Tetsuya Fukumoto, Hideki Mine
Summary: A Japanese man in his 60s with chronic lymphocytic leukemia developed progressive multifocal neurological symptoms. The MRI showed a small solitary brainstem lesion. PCR testing detected a small amount of JC virus DNA in his cerebrospinal fluid, confirming a diagnosis of progressive multifocal leukoencephalopathy (PML). This case contributes to knowledge about brainstem PML in patients with hematologic malignancies and other underlying diseases.
Article
Clinical Neurology
Kosuke Okamoto, Akitoshi Takeda, Hiroyuki Hatsuta, Terunori Sano, Masaki Takao, Masahiko Ohsawa, Yukio Miki, Kazuo Nakamichi, Yoshiaki Itoh
Summary: This article reports a case of PML in a patient who developed bilateral visual disturbance and progressive aphasia after 16 months of treatment for follicular lymphoma. The MRI revealed white matter lesions with massive iron deposition. Autopsy findings confirmed the presence of abundant iron-laden macrophages and reactive astrocytes in the juxtacortical regions adjacent to the white matter lesions. This is the first reported case of PML after lymphoma with confirmed iron deposition.
Article
Virology
Kazuo Nakamichi, Yoshiharu Miura, Toshio Shimokawa, Kenta Takahashi, Tadaki Suzuki, Nobuaki Funata, Masafumi Harada, Koichiro Mori, Nobuo Sanjo, Motohiro Yukitake, Kazuya Takahashi, Tsuyoshi Hamaguchi, Shoko Izaki, Satoru Oji, Jin Nakahara, Ryusuke Ae, Koki Kosami, Souichi Nukuzuma, Yosikazu Nakamura, Kyoichi Nomura, Shuji Kishida, Hidehiro Mizusawa, Masahito Yamada, Masaki Takao, Hideki Ebihara, Masayuki Saijo
Summary: A 10-year study was conducted in Japan to analyze the profile of PML and the characteristics of patients with CSF-JCV positivity. The study found that ultrasensitive PCR testing and increased clinical attention led to the early detection of CSF-JCV in the last five years of the study period. The results provide valuable information for PML diagnosis and treatment.
Article
Multidisciplinary Sciences
Atsuhiro Matsuno, Akira Matsushima, Masashi Saito, Kazumi Sakurai, Katsuyuki Kobayashi, Yoshiki Sekijima
Summary: LSVT-BIG therapy has a positive effect on gait function, specifically improving gait speed and stride length. This improvement is likely related to the enlargement of flexion and extension angles and range of motion in the hip joint.
Article
Clinical Neurology
Takayoshi Akimoto, Makoto Hara, Satoshi Hirose, Kazuo Nakamichi, Hideto Nakajima
Summary: This article reports a case of a 58-year-old woman with a history of systemic lupus erythematosus who presented with progressive gait disturbances. MRI and CSF examination revealed punctate lesions and rapidly progressive cerebellar syndrome. Further testing detected the presence of progressive multifocal leukoencephalopathy. Treatment led to stabilization of the patient's condition.
NEUROLOGY INTERNATIONAL
(2023)
Article
Rheumatology
Mita Sakuraba, Shinji Watanabe, Yasuhiro Nishiyama, Kenta Takahashi, Kazuo Nakamichi, Mikito Suzuki, Takashi Nawata, Kota Komai, Takahisa Gono, Mitsuhiro Takeno, Tadaki Suzuki, Kazumi Kimura, Masataka Kuwana
Summary: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection caused by JC virus (JCV) reactivation, typically presenting with bilateral subcortical lesions on MRI. However, our case suggested that PML can initially manifest as a solitary infratentorial lesion in immunocompromised patients, eventually progressing to multifocal invasion of the cerebral white matter.
MODERN RHEUMATOLOGY CASE REPORTS
(2021)
