Background: Immune-mediated mechanisms substantially contribute to the Rasmussen encephalitis (RE) pathology, but for unknown reasons, immunotherapy is generally ineffective in patients who have already developed intractable epilepsy; overall laboratory data regarding the effect of immunotherapy on patients with RE are limited. We analyzed multiple samples from seven differently treated children with RE and evaluated the effects of immunotherapies on neuroinflammation. Immunotherapy was introduced to all patients at the time of intractable epilepsy and they all had to undergo hemispherothomy.
Methods: Immunohistochemistry, flow cytometry, Luminex multiplex bead and enzyme-linked immunosorbent assay techniques were combined to determine: 1) inflammatory changes and lymphocyte subpopulations in 45 brain tissues; 2) lymphocyte subpopulations and the levels of 12 chemokines/cytokines in 24 cerebrospinal fluid (CSF) samples and 30 blood samples; and 3) the dynamics of these parameters in four RE patients from whom multiple samples were collected.
Results: Sustained T cell-targeted therapy with cyclophosphamide, natalizumab, alemtuzumab, and intrathecal methotrexate (ITMTX), but not with azathioprine, substantially reduced inflammation in brain tissues. Despite the therapy, the distributions of CD8 T cells and the levels of C-X-C motif ligand (CXCL) 10, CXCL13, and B cell activating factor (BAFF) in patients' CSF remained increased compared to controls. A therapeutic approach combining alemtuzumab and ITMTX was the most effective in producing simultaneous reductions in histopathological inflammatory findings and in the numbers of activated CD8 T cells in the brain tissue, as well as in the overall CD8 T cell population and chemokine/cytokine production in the CSF.
Conclusions: We provide evidence that various T cell-targeted immunotherapies reduced inflammation in the brains of RE patients. The observation that intractable epilepsy persisted in all of the patients suggests a relative independence of seizure activity on the presence of T cells in the brain later in the disease course. Thus, new therapeutic targets must be identified. CXCL10, CXCL13 and BAFF levels were substantially increased in CSF from all patients and their significance in RE pathology remains to be addressed.
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http://dx.doi.org/10.1186/s12883-020-01932-9 | DOI Listing |
Clin Neurophysiol
January 2025
Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address:
Objective: Sleep-related hypermotor epilepsy (SHE) is a relatively uncommon epilepsy syndrome, characterized by seizures closely related to the sleep cycle. This study aims to explore interictal electroencephalographic (EEG) characteristics in SHE.
Methods: We compared EEG data from 20 patients with SHE, 20 patients with focal epilepsy (FE), and 14 healthy controls, carefully matched for age, sex, education level, epilepsy duration, and drug-resistant epilepsy.
Int J Mol Sci
January 2025
Department of Neuropediatrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 13353 Berlin, Germany.
Epilepsy affects 50 million people worldwide and is drug-resistant in approximately one-third of cases. Even when a structural lesion is identified as the epileptogenic focus, understanding the underlying genetic causes is crucial to guide both counseling and treatment decisions. Both somatic and germline DNA variants may contribute to the lesion itself and/or influence the severity of symptoms.
View Article and Find Full Text PDFMedicina (Kaunas)
January 2025
Department of Neurosurgery, University of Medicine and Pharmacy "Carol Davila", 030147 Bucharest, Romania.
: The Index of Response to Stimulation (IRES) is a new index that we introduce in this study to grade the effectiveness of vagus nerve stimulation in the treatment of drug-resistant epilepsy. We assessed 76 patients at 6, 12, and 18 months after VNS evaluating improvement with the IRES in four key dimensions: seizure duration decrease, seizure intensity decrease, improvement in quality of life, and seizure frequency decrease. This scale goes from 0, meaning no improvement, to 8, meaning maximal improvement, making the scale a really good measure of clinical utility.
View Article and Find Full Text PDFNeurophysiol Clin
January 2025
Neuroscience Service, High Complexity El Cruce, "Nestor Kirchner" Hospital, ENYS. UNAJ. CONICET, Florencio Varela, Provincia de Buenos Aires, Argentina.
Objectives: The aim of this study is to describe a population of patients with drug resistant epilepsy who underwent stereoelectroencephalography (SEEG) for epilepsy presurgical evaluation in a high complexity public hospital in Argentina.
Methods: We included patients from 2014 to 2023. We conducted a retrospective study of patients with drug-resistant epilepsy admitted to the Video-EEG unit.
Epilepsy Behav
January 2025
Division of Child Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address:
Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy marked by drug-resistant seizures and profound cognitive and behavioral impairments, with nearly 95% of individuals affected by moderate to severe intellectual disability. This review comprehensively explores the cognitive and behavioral impacts of current treatment options for LGS, including antiseizure medications (ASMs), neuromodulation strategies, the ketogenic diet, and surgical interventions. Given the limited availability of LGS-specific data for several ASMs, the evidence base is supplemented with findings from general epilepsy populations and individuals with epilepsy and intellectual disabilities.
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