Objective: Assess occurrence of the dendritic spine scaffolding protein Drebrin as a pathophysiologically relevant autoantibody target in patients with recurrent seizures and suspected encephalitis as leading symptoms.
Methods: Sera of 4 patients with adult onset epilepsy and suspected encephalitis of unresolved etiology and equivalent results in autoantibody screening were subjected to epitope identification. We combined a wide array of approaches, ranging from immunoblotting, immunoprecipitation, mass spectrometry, subcellular binding pattern analyses in primary neuronal cultures, and immunohistochemistry in brains of wild-type and Drebrin knockout mice to in vitro analyses of impaired synapse formation, morphology, and aberrant neuronal excitability by antibody exposure.
Results: In the serum of a patient with adult onset epilepsy and suspected encephalitis, a strong signal at ∼70kDa was detected by immunoblotting, for which mass spectrometry revealed Drebrin as the putative antigen. Three other patients whose sera also showed strong immunoreactivity around 70kDa on Western blotting were also anti-Drebrin-positive. Seizures, memory impairment, and increased protein content in cerebrospinal fluid occurred in anti-Drebrin-seropositive patients. Alterations in cerebral magnetic resonance imaging comprised amygdalohippocampal T2-signal increase and hippocampal sclerosis. Diagnostic biopsy revealed T-lymphocytic encephalitis in an anti-Drebrin-seropositive patient. Exposure of primary hippocampal neurons to anti-Drebrin autoantibodies resulted in aberrant synapse composition and Drebrin distribution as well as increased spike rates and the emergence of burst discharges reflecting network hyperexcitability.
Interpretation: Anti-Drebrin autoantibodies define a chronic syndrome of recurrent seizures and neuropsychiatric impairment as well as inflammation of limbic and occasionally cortical structures. Immunosuppressant therapies should be considered in this disorder. ANN NEUROL 2020;87:869-884.
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http://dx.doi.org/10.1002/ana.25720 | DOI Listing |
Eur J Paediatr Neurol
December 2024
Department of Brain & Neurosciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. Electronic address:
Objective: Early diagnosis and treatment of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) are crucial for a favorable prognosis. Detecting the causative autoantibodies can be challenging. Probable diagnostic criteria are useful in adults less so in children.
View Article and Find Full Text PDFEur J Clin Microbiol Infect Dis
December 2024
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.
Objectives: This study aimed to describe the clinical and epidemiologic characteristics of suspected cases of human mpox in one of the most affected health zones, Katako-Kombe, Sankuru Province, in the Democratic Republic of the Congo. Also, to identify key challenges to prevent and improve the health of the affected community.
Methods: Between January 26, 2023 and November 30, 2023, the DRC reported its highest incidence of mpox cases,with a total of 12,569 suspected cases in 156 health zones from 22 of the 26 country's provinces.
Lancet Neurol
January 2025
Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer/CaixaResearch Institute, Hospital Clínic de Barcelona, Barcelona, Spain; Pediatric Neuroimmunology Unit, Neurology Department, Sant Joan de Déu Children's Hospital, Barcelona, Spain; Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain; European Reference Networks-RITA. Electronic address:
Background: The usefulness of current diagnostic approaches in children with suspected autoimmune encephalitis is unknown. We aimed to assess the diagnosis of autoimmune encephalitis in clinical practice and to compare the performance of two international diagnostic algorithms (one intended for patients of any age [general], the other intended for paediatric patients), with particular emphasis on the evaluation of patients with probable antibody-negative autoimmune encephalitis because this diagnosis suggests that immunotherapy should be continued or escalated but is difficult to establish.
Methods: We did a prospective cohort study that included all patients (<18 years of age) with suspected autoimmune encephalitis recruited at 40 hospitals in Spain whose physicians provided clinical information every 6 months for 2 years or more.
J Craniofac Surg
December 2024
Department of Neurology, Jiaxing Second Hospital, Jiaxing, China.
Objective: This study aimed to evaluate the clinical utility of oligoclonal bands (OCB) in differentiating between immune and infectious diseases of the central nervous system (CNS).
Methods: The study enrolled patients hospitalized with suspected autoimmune or infectious CNS disorders between 2021 and 2023. Patients were categorized into diagnostic groups: multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), autoimmune encephalitis (AE), and viral encephalitis (VE).
Crit Rev Oncol Hematol
December 2024
Center for Clinical Investigation, INSERM U1434, Strasbourg University, 1 Avenue Molière, Strasbourg 67098, France; Neurology Department, Strasbourg University Hospitals, 1 Avenue Molière, Strasbourg 67098, France. Electronic address:
The ever-increasing use of immune checkpoint inhibitors (ICIs) has significantly improved cancer management, but at the cost of frequent immunologic side effects. Among them, neurologic immune-related adverse events (nirAEs) are less common but pose a challenge to clinicians due to their severity, heterogeneous nature and nonspecific clinical presentation, making diagnosis complex. The prognosis of these nirAEs, especially those related to the central nervous system (CNS), correlates with their rapid recognition and therapeutic management.
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