Article
Clinical Neurology
Markus Kinner, Christian Prehn, Ruth Schneider, Christoph Schroeder, Eva Kolb, Ralf Gold, Robert Hoepner, Andew Chan
Summary: This study evaluated the neuropsychological disease course of NTZ-PML patients and found that working memory and visuospatial abilities are core deficits. NTZ-PML patients performed worse in neuropsychological examinations compared to controls, especially affecting visuospatial ability and working memory during different disease stages.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Clinical Neurology
Christoph Mahler, Adrian-Minh Schumacher, Marcus Unterrainer, Lena Kaiser, Thomas Hollbacher, Simon Lindner, Joachim Havla, Birgit Ertl-Wagner, Maximilian Patzig, Klaus Seelos, Julia Neitzel, Matthias Maurer, Markus Krumbholz, Imke Metz, Wolfgang Bruck, Christine Stadelmann, Doron Merkler, Achim Gass, Vladimir Milenkovic, Peter Bartenstein, Nathalie L. Albert, Tania Kuempfel, Martin Kerschensteiner
Summary: The study evaluated the use of TSPO PET imaging to monitor CNS inflammation in natalizumab-associated PML lesions and distinguish them from multiple sclerosis lesions, showing potential for longitudinal monitoring of disease activity and differentiation of MS activity from PML progression.
Article
Clinical Neurology
Alyssa A. Toorop, Zoe Y. G. van Lierop, Eva E. M. Strijbis, Charlotte E. Teunissen, Axel Petzold, Mike P. Wattjes, Frederik Barkhof, Brigit A. de Jong, Zoe L. E. van Kempen, Joep Killestein
Summary: Two patients with relapsing-remitting MS developed carryover PML after switching from natalizumab to ocrelizumab. Despite mild immune reconstitution inflammatory syndrome (IRIS) and increasing NfL levels, PML-IRIS lesions stabilized after treatment and both patients continued therapy with ocrelizumab.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2021)
Article
Biochemistry & Molecular Biology
Roberto De Masi, Stefania Orlando, Silvia Armenise, Pantaleo Spagnolo, Ruggero Capra, Maria Carmela Costa
Summary: This case report investigates a Natalizumab-associated Progressive Multifocal Leukoencephalopathy (PML) with cerebellar localization and wakefulness disturbances. The study shows that awakening and clinical improvement occurred dramatically with the onset of immune reconstitution inflammatory syndrome (IRIS), which was mild in nature and colocalized with the PML lesion. MRI analysis revealed an increase in white matter volume and a decrease in grey matter during IRIS, while the cerebrospinal fluid volume consistently increased throughout the duration of PML. The brain parenchymal fraction decreased as expected, but the total brain volume remained stable. Neurodegeneration, supported by IRIS and humoral factors derived from the PML lesion, is believed to be the main cause of steady disability in Natalizumab-associated PML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Tobias Moser, Georg Zimmermann, Anna Baumgartner, Thomas Berger, Gabriel Bsteh, Franziska Di Pauli, Christian Enzinger, Elisabeth Fertl, Thomas Heller, Stefan Koppi, Paulus S. Rommer, Georg Safoschnik, Thomas Seifert-Held, Robert Stepansky, Johann Sellner
Summary: This study analyzed the course of multiple sclerosis (MS) patients in Austria after progressive multifocal leukoencephalopathy (PML) recovery and the long-term outcome of NAT-associated PML (NAT-PML). The study found that the number of NAT-PML cases is decreasing over time, and while many patients accumulated severe persistent neurological deficits after PML recovery, there was rare inflammatory MS-related disease activity.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Eli Hatchwell, Edward B. B. Smith, Shapour Jalilzadeh, Christopher D. D. Bruno, Yassine Taoufik, Houria Hendel-Chavez, Roland Liblau, David Brassat, Guillaume Martin-Blondel, Heinz Wiendl, Nicholas Schwab, Irene Cortese, Maria Chiara Monaco, Luisa Imberti, Ruggero Capra, Jorge R. R. Oksenberg, Jacques Gasnault, Bruno Stankoff, Todd A. A. Richmond, David M. M. Rancour, Igor J. J. Koralnik, Barbara A. A. Hanson, Eugene O. O. Major, Christina R. R. Chow, Peggy S. S. Eis
Summary: PML is a rare and dangerous brain disease caused by JC virus infection, with immunosuppressed patients being more susceptible. Research has identified four genetic variants in immune system genes that are associated with PML risk.
FRONTIERS IN NEUROLOGY
(2022)
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)
Review
Clinical Neurology
Shitiz Sriwastava, Durgesh Chaudhary, Samiksha Srivastava, Katherine Beard, Xue Bai, Sijin Wen, Syed Hassan Khalid, Robert P. Lisak
Summary: The incidence of PML in MS patients treated with S1PR modulators like fingolimod appears to be extremely low. Risk of PML increases with longer duration of treatment with S1PR modulators, and older age at the time of PML diagnosis is associated with worse prognosis.
JOURNAL OF NEUROLOGY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Manel Alleg, Morgane Solis, Seyyid Baloglu, Francois Cotton, Philippe Kerschen, Bertrand Bourre, Guido Ahle, Jean-Pierre Pruvo, Xavier Leclerc, Patrick Vermersch, Caroline Papeix, Elisabeth Maillart, Caroline Houillier, Cecile Molucon Chabrot, Beatrice Claise, Sandra Malak, Guillaume Martin-Blondel, Fabrice Bonneville, Alexis Caulier, Jean-Pierre Marolleau, Jerome Tamburini Bonnefoy, Philippe Agape, Celine Kennel, Xavier Roussel, Adrien Chauchet, Jerome De Seze, Samira Fafi-Kremer, Stephane Kremer
Summary: The study compared brain MRI findings in PML associated with rituximab, natalizumab treatments, and HIV infection. Different imaging features were observed in the three types of PML, with natalizumab-associated PML showing more inflammatory signs and cortex involvement, while rituximab and HIV-associated PML exhibited milder contrast enhancement and punctuate appearance. The differences in MRI findings may be related to varying levels of immunosuppression in the different patient groups.
EUROPEAN RADIOLOGY
(2021)
Article
Medicine, General & Internal
Viviana Lo Buono, Giangaetano D'Aleo, Simona Cammaroto, Maria Cristina De Cola, Francesca Palmese, Chiara Smorto, Silvia Marino, Giuseppe Venuti, Edoardo Sessa, Carmela Rifici, Francesco Corallo
Summary: This study reports a case of PML related to natalizumab and describes the longitudinal course of the disease, documenting the progressive deterioration of the patient's cognitive functioning. The findings expand the range of treatment-related complications associated with natalizumab and provide evidence for the early diagnosis of PML.
MEDICINA-LITHUANIA
(2022)
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
Arpan Patel, James Sul, Marc L. Gordon, Jared Steinklein, Shayna Sanguinetti, Bidyut Pramanik, Dushyant Purohit, Vahram Haroutunian, Alex Williamson, Igor Koralnik, Asaff Harel
Summary: This case report highlights the first occurrence of PML with ocrelizumab monotherapy in a patient with progressive multiple sclerosis without prior immunomodulation. The patient presented with progressive visual disturbance and confusion, ultimately confirmed to have PML through autopsy.
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
Darius Hausler, Katja Akgun, Lidia Stork, Hans Lassmann, Tjalf Ziemssen, Wolfgang Bruck, Imke Metz
Summary: Natalizumab is an effective drug for treating multiple sclerosis, but there are still inflammatory infiltrates and immune cell accumulation in the central nervous system during treatment; although the number of some immune cells increases, there is no significant correlation with clinical disability, and the pathogenic mechanism and clinical significance of these immune cells remain unclear.
Article
Immunology
Pilar Santiago-Setien, Cristina Barquin-Rego, Paula Hernandez-Martinez, Maria Ezquerra-Marigomez, Marta Torres-Barquin, Cristina Menendez-Garcia, Fernando Uriarte, Yesica Jimenez-Lopez, Mercedes Misiego, Jose Ramon Sanchez de la Torre, Sonia Setien, Manuel Delgado-Alvarado, Javier Riancho
Summary: This study aimed to assess the long-term safety and effectiveness of switching from natalizumab to ocrelizumab in multiple sclerosis (MS) patients at high risk of progressive multifocal leukoencephalopathy (PML). The results showed no significant differences in relapse rate, radiological activity, or disability progression between patients who switched to ocrelizumab and those who continued with natalizumab. However, a slightly higher proportion of patients in the ocrelizumab-switcher group maintained a no evidence of disease activity (NEDA-3) status at week 96.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Clinical Neurology
E. Carreon Guarnizo, R. Hernandez Clares, T. Castillo Trivino, V Meca Lallana, V Arocas Casan, F. Iniesta Martinez, J. Olascoaga Urtaza, J. E. Meca Lallana
Summary: This study analyzed the effectiveness and safety of tocilizumab in patients with NMOSD who had previously failed immunosuppressant treatment, and the results showed that tocilizumab was safe and effective in clinical practice.
Article
Behavioral Sciences
Francisco Carlos Perez-Miralles, Daniel Prefasi, Antonio Garcia-Merino, Jose Ramon Ara, Guillermo Izquierdo, Virginia Meca-Lallana, Francisco Gascon-Gimenez, Maria Luisa Martinez-Gines, Lluis Ramio-Torrenta, Lucienne Costa-Frossard, Oscar Fernandez, Sara Moreno-Garcia, Jorge Maurino, Joan Carreres-Polo, Bonaventura Casanova
Summary: The study found that changes in white and gray matter volumes of specific brain regions can predict disability progression and cognitive performance of PPMS patients after one year.
BRAIN AND BEHAVIOR
(2021)
Article
Clinical Neurology
Jose Fernandez-Velasco, Jens Kuhle, Enric Monreal, Virginia Meca-Lallana, Jose Meca-Lallana, Guillermo Izquierdo, Francisco Gascon-Gimenez, Susana Sainz de la Maza, Paulette E. Walo-Delgado, Aleksandra Maceski, Eulalia Rodriguez-Martin, Ernesto Roldan, Noelia Villarrubia, Albert Saiz, Yolanda Blanco, Pedro Sanchez, Ester Carreon-Guarnizo, Yolanda Aladro, Luis Brieva, Cristina Iniguez, Ines Gonzalez-Suarez, Luis A. Rodriguez de Antonio, Jaime Masjuan, Lucienne Costa-Frossard, Luisa M. Villar
Summary: Ocrelizumab induced changes in immune cell distribution in patients with primary progressive MS, reducing inflammatory cells and leading to a decrease in sNfL levels.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2021)
Article
Clinical Neurology
Virginia Meca-Lallana, Francisco Gascon-Gimenez, Ricardo C. Ginestal-Lopez, Yolanda Higueras, Nieves Tellez-Lara, Joan Carreres-Polo, Sara Eichau-Madueno, Jesus Romero-Imbroda, Angela Vidal-Jordana, Francisco Perez-Miralles
Summary: Cognitive impairment is common in patients with MS, affecting their quality of life and work. Early detection and appropriate follow-up are important. Recommendations for cognitive evaluation methods and frequency are provided for all MS patients.
NEUROLOGICAL SCIENCES
(2021)
Article
Clinical Neurology
Irene Moreno-Torres, Virginia Meca Lallana, Lucienne Costa-Frossard, Celia Oreja-Guevara, Clara Aguirre, Elda Maria Alba Suarez, Mayra Gomez Moreno, Laura Borrega Canelo, Julia Sabin Munoz, Yolanda Aladro, Alba Carcamo, Elena Rodriguez Garcia, Juan Pablo Cuello, Enric Monreal, Susana Sainz de la Maza, Fernando Perez Parra, Francisco Valenzuela Rojas, Carlos Lopez de Silanes de Miguel, Ignacio Casanova, Maria Luisa Martinez Gines, Rosario Blasco, Aida Orviz Garcia, Luisa Maria Villar-Guimerans, Guillermo Fernandez-Dono, Victor Elvira, Carmen Santiuste, Mercedes Espino, Jose Manuel Garcia Dominguez
Summary: This study found that patients with multiple sclerosis do not have a higher risk of SARS-CoV-2 infection or severe COVID-19 outcomes compared to the general population, but they do have higher hospitalization rates. In the study, males with MS had higher incidence rates and risk of hospitalization than females.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Multidisciplinary Sciences
Jose E. Meca-Lallana, Jorge Maurino, Francisco Perez-Miralles, Lucia Forero, Maria Sepulveda, Carmen Calles, Maria L. Martinez-Gines, Ines Gonzalez-Suarez, Sabas Boyero, Lucia Romero-Pinel, Angel P. Sempere, Virginia Meca-Lallana, Luis Querol, Lucienne Costa-Frossard, Daniel Prefasi, Rocio Gomez-Ballesteros, Javier Ballesteros
Summary: The study aimed to assess the psychometric properties of the SymptoMScreen (SyMS) in patients with Neuromyelitis Optica Spectrum Disorder (NMOSD). Results showed that the SyMS demonstrated strong internal reliability, behaved as a unidimensional scale, and had overall medium scalability. Fatigue and body pain were identified as the domains with the highest scalability coefficients.
Article
Clinical Neurology
Georgina Arrambide, Miguel Angel Llaneza-Gonzalez, Lucienne Costa-Frossard Franca, Virginia Meca-Lallana, Eva Fernandez-Diaz, Irene Moreno-Torres, Jose Manuel Garcia-Dominguez, Gloria Ortega-Suero, Lucia Ayuso-Peralta, Mayra Gomez-Moreno, Javier J. Sotoca-Fernandez, Ana Belen Caminero-Rodriguez, Luis A. Rodriguez de Antonio, Marcial Corujo-Suarez, Maria A. Otano-Martinez, Francisco Carlos Perez-Miralles, Virginia Reyes-Garrido, Teresa Ayuso-Blanco, Jose Jesus Balseiro-Gomez, Mercedes Munoz-Pasadas, Inmaculada Perez-Molina, Carmen Arnal-Garcia, Angela Domingo-Santos, Cristina Guijarro-Castro, Cristina Iniguez-Martinez, Nieves Tellez Lara, Fernando Castellanos-Pinedo, Tamara Castillo-Trivino, Debora Maria Cerdan-Santacruz, Angel Perez-Sempere, Berta Sebastian Torres, Amaya Alvarez de Arcaya, Eva Costa-Arpin, Eduardo Duran-Ferreras, Marta Fragoso-Martinez, Montserrat Gonzalez-Platas, Lamberto Landete Pascual, Jorge Millan-Pascual, Celia Oreja-Guevara, Jose E. Meca-Lallana
Summary: This study aimed to understand the characteristics of COVID-19 in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state. The results showed that older individuals with comorbidities, progressive disease course, and higher disability in MS patients were more likely to experience severe and fatal outcomes with COVID-19. The study did not find a critical role of MS therapy in the course of COVID-19.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2021)
Article
Multidisciplinary Sciences
J. E. Meca-Lallana, C. Oreja-Guevara, D. Munoz, J. Olascoaga, A. Pato, L. Ramio-Torrenta, V. Meca-Lallana, M. A. Hernandez, M. E. Marzo, J. C. Alvarez- Cermeno, A. Rodriguez-Antigueedad, X. Montalban, O. Fernandez
Summary: In Spain, patients with multiple sclerosis treated with fingolimod showed significant reduction in the annualized relapse rate and stable EDSS scores after 4 years of treatment. The percentage of patients without T1 Gd+ lesions and free from new/enlarged T2 lesions also increased progressively. Adverse events were mild in severity, with a positive benefit-risk balance observed.
Article
Medicine, General & Internal
Yolanda Higueras, Elisa Salas, Virginia Meca-Lallana, Pedro Carrascal Rueda, Ofir Rodriguez De la Fuente, Rosana Cabello-Moruno, Jorge Maurino, Miguel Angel Ruiz Diaz
Summary: The study found that patients with multiple sclerosis often search for disease-related information on the internet, but their most trusted sources of information are neurologists and nurses. Younger patients and those with higher cognitive levels tend to use various search resources.
PATIENT PREFERENCE AND ADHERENCE
(2022)
Article
Immunology
Jose Fernandez-Velasco, Enric Monreal, Jens Kuhle, Virginia Meca-Lallana, Jose Meca-Lallana, Guillermo Izquierdo, Celia Oreja-Guevara, Francisco Gascon-Gimenez, Susana Sainz de la Maza, Paulette E. Walo-Delgado, Paloma Lapuente-Suanzes, Aleksandra Maceski, Eulalia Rodriguez-Martin, Ernesto Roldan, Noelia Villarrubia, Albert Saiz, Yolanda Blanco, Carolina Diaz-Perez, Gabriel Valero-Lopez, Judit Diaz-Diaz, Yolanda Aladro, Luis Brieva, Cristina Iniguez, Ines Gonzalez-Suarez, Luis A. Rodriguez de Antonio, Jose M. Garcia-Dominguez, Julia Sabin, Sara Llufriu, Jaime Masjuan, Lucienne Costa-Frossard, Luisa M. Villar
Summary: This study aimed to investigate the role of inflammation in the response to ocrelizumab in patients with PPMS. The findings showed that over 60% of patients achieved no evidence of disease activity (NEDA) after one year of treatment, regardless of their baseline characteristics. The baseline inflammation influenced the predominant immunological pathways, with inflammatory B cells playing a pivotal role in Gd+ patients and inflammatory T and innate immune cells in Gd- patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Clinical Neurology
Jose E. Meca-Lallana, Rocio Gomez-Ballesteros, Francisco Perez-Miralles, Lucia Forero, Maria Sepulveda, Carmen Calles, Maria L. Martinez-Gines, Ines Gonzalez-Suarez, Sabas Boyero, Lucia Romero-Pinel, Angel P. Sempere, Virginia Meca-Lallana, Luis Querol, Lucienne Costa-Frossard, Daniel Prefasi, Jorge Maurino
Summary: This study aimed to describe the impact of NMOSD on HRQoL from the patients' perspective and its relationship with other disease factors. Fatigue, pain, and depressive symptoms were found to be frequent problems among patients with NMOSD, negatively impacting their quality of life. Assessment of patient-oriented outcomes may be useful for early interventions.
NEUROLOGY AND THERAPY
(2022)
Article
Clinical Neurology
Luis Brieva, Bonaventura Casanova Estruch, Juan Antonio Garcia Merino, Virginia Meca-Lallana, Jordi Rio, Alfredo Rodriguez-Antigueedad, Eduardo Aguera, Jose Ramon Ara, Adrian Ares Luque, Carmen Arnal Garcia, Yolanda Blanco, Tamara Castillo-Trivino, Lucienne Costa-Frossard, Montserrat Gonzalez Platas, Lamberto Landete Pascual, Miguel Llaneza-Gonzalez, Maria Luisa Martinez Gines, Jorge Matias-Guiu, Jose E. Meca-Lallana, Mar Mendibe Bilbao, Angel Perez Sempere, Lucia Romero-Pinel, Albert Saiz, Ester Moral
Summary: Experts reached a consensus on treatment switching approaches in relapsing multiple sclerosis (RMS) through a modified Delphi process, providing up-to-date guidance on disease modifying therapy sequencing for optimal patient management.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2022)
Article
Clinical Neurology
Virginia Meca-Lallana, Alfredo Rodriguez-Antigueedad, Miguel A. Llaneza, Jose E. Meca-Lallana
Summary: Nfl-PM shows potential in determining subclinical activity in MS and identifying populations at risk of developing the disease, but integration into healthcare practice faces obstacles such as the lack of normalized values and standardized protocols.
REVISTA DE NEUROLOGIA
(2021)
Article
Clinical Neurology
Lucienne Costa-Frossard, Jose M. Garcia-Dominguez, Irene Moreno-Torres, Jesus Fortun, Luisa M. Villar, Virginia Meca-Lallana
Summary: There is limited data on the safety and efficacy of SARS-CoV-2 vaccines in patients with multiple sclerosis, but evidence suggests that mRNA vaccines are as safe in these patients as in others. Some immunosuppressive therapies may reduce the effectiveness of these vaccines, and it is recommended to schedule vaccination before starting treatment if possible.
REVISTA DE NEUROLOGIA
(2021)