Publications by authors named "Dik A"

Background: Autoimmune encephalitis (AIE) is a disabling inflammatory condition of the brain deemed to be due to a dysregulated immune response. Viral infections and malignancies together with certain genetic polymorphisms are thought to contribute to the pathogenesis of AIE, yet the exact mechanisms remain insufficiently understood. Diagnosis of AIE currently relies on clinical consensus criteria.

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Background: Immune dysregulation is a hallmark of autoimmune diseases of the central nervous system (CNS), characterized by an excessive immune response, and primary CNS tumors (pCNS-tumors) showing a highly immunosuppressive parenchymal microenvironment.

Methods: Aiming to provide novel insights into the pathogenesis of CNS autoimmunity and cerebral tumor immunity, we analyzed the peripheral blood (PB) and cerebrospinal fluid (CSF) of 81 autoimmune limbic encephalitis (ALE), 148 relapsing-remitting multiple sclerosis (RRMS), 33 IDH-wildtype glioma, 9 primary diffuse large B cell lymphoma of the CNS (CNS-DLBCL), and 110 controls by flow cytometry (FC). Additionally, an in-depth immunophenotyping of the PB from an independent cohort of 20 RRMS and 18 IDH-wildtype glioblastoma patients compared to 19 controls was performed by FC combined with unsupervised computational approaches.

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Autoimmune limbic encephalitis (ALE) represents a heterogeneous disease associated with antibodies targeting extracellular (ALE) epitopes, intracellular (ALE) epitopes, anti-glutamic acid decarboxylase65 ALE (ALE), and ALE without detectable antibodies (ALE). Combining analysis of cellular parameters, investigated by flow cytometry, and soluble parameters in the blood and cerebrospinal fluid (CSF) from a large cohort of 148 ALE patients (33 ALE, 12 ALE, 28 ALE-GAD65, 37 ALE) in comparison to paradigmatic examples for neuro-inflammatory (51 relapsing remitting MS patients (RRMS)), and neuro-degenerative (34 Alzheimer's disease patients (AD)) diseases revealed discrete immune signatures in ALE subgroups. Identification of ALE-subtype specific markers facilitated classification of rare ALE-associated tumors, which may prompt further diagnostic efforts in clinical practice.

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Article Synopsis
  • IgG4 auto-antibodies targeting Caspr2 are linked to various neurological symptoms, but the exact mechanisms of how they cause neuronal dysfunction are not fully understood.
  • The study identifies two distinct biosignatures related to clinical phenotypes: limbic encephalitis (LE) and peripheral nerve hyperexcitability, with specific immune features associated with each condition.
  • Findings suggest that the presence of IgG1 antibodies and their pro-inflammatory effects are crucial for the development of LE, indicating that therapies targeting these pathways could improve patient outcomes.
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Epilepsy is one of the most common neurological disorders in the world. Common epileptic drugs generally affect ion channels or neurotransmitters and prevent the emergence of seizures. However, up to a third of the patients suffer from drug-resistant epilepsy, and there is an urgent need to develop new therapeutic strategies that go beyond acute antiepileptic (antiseizure) therapies towards therapeutics that also might have effects on chronic epilepsy comorbidities such as cognitive decline and depression.

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Article Synopsis
  • - Autoimmune limbic encephalitis (ALE) is characterized by new seizures, memory issues, and changes in behavior and cognition, primarily affecting the mesial temporal lobe.
  • - CD8 T cells are important in cases without detectable autoantibodies, but identifying these patients is challenging, highlighting the need for better imaging techniques.
  • - The use of [F]DPA-714-PET-MRI to visualize microglia activation in the hippocampus and amygdala shows promise for assessing innate immunity in patients with CD8 T cell-mediated ALE, and findings were supported by results in a mouse model.
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Autoimmune Encephalitis (AE) spans a group of non-infectious inflammatory conditions of the central nervous system due to an imbalanced immune response. Aiming to elucidate the pathophysiological mechanisms of AE, we applied an unsupervised proteomic approach to analyze the cerebrospinal fluid (CSF) protein profile of AE patients with autoantibodies against N-methyl-d-aspartate receptor (NMDAR) (n = 9), leucine-rich glioma-inactivated protein 1 (LGI1) (n = 9), or glutamate decarboxylase 65 (GAD65) (n = 8) compared to 9 patients with relapsing-remitting multiple sclerosis as inflammatory controls, and 10 patients with somatic symptom disorder as non-inflammatory controls. We found a dysregulation of the complement system, a disbalance between pro-inflammatory and anti-inflammatory proteins on the one hand, and dysregulation of proteins involved in synaptic transmission, synaptogenesis, brain connectivity, and neurodegeneration on the other hand to a different extent in all AE subtypes compared to non-inflammatory controls.

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Amyotrophic lateral sclerosis (ALS) affects the life of the family caregiver as well as the patient. This study aimed to determine the care burden and related factors among family caregivers of Turkish ALS patients. This descriptive study was conducted with 108 ALS patients and their informal caregivers through face-to-face interviews at home.

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Article Synopsis
  • Autoimmune neurological syndromes (AINS) associated with anti-GAD65 autoantibodies lead to various neurological symptoms, including seizures and cerebellitis, and also have a connection to autoimmune diabetes.
  • A genome-wide association study (GWAS) in a German cohort revealed 16 significant genetic loci linked to susceptibility to AINS, with a notable variant in the HLA class I region.
  • Over 40% of identified genetic variants affect the expression of genes in immune and neural cells, emphasizing the relationship between immune response and neurological function through specific pathways.
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Objective: Autoimmune limbic encephalitis (ALE) is characterized by memory impairment, psychiatric symptoms, and epileptic seizures. Though, the neuropsychological profile of ALE is not yet well defined. However, there is some evidence that neuropsychological impairments might exceed those related to the limbic system and that different autoantibodies (AABs) are associated with distinguishable pattern of neuropsychological impairments.

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Objective: Direct pathogenic effects of autoantibodies to the 65 kDa isoform of glutamic acid decarboxylase (GAD65) in autoimmune limbic encephalitis (LE) have been questioned due to its intracellular localization. We therefore hypothesized a pathogenic role for T cells.

Methods: We assessed magnet resonance imaging, neuropsychological and peripheral blood, and CSF flow cytometry data of 10 patients with long-standing GAD65-LE compared to controls in a cross-sectional manner.

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Autoimmune limbic encephalitis (ALE) is the most common type of autoimmune encephalitis (AIE). Subacute memory disturbance, temporal lobe seizures, and psychiatric symptoms are clinical hallmarks of the disease. However, little is known on the factors contributing to cognitive functioning in ALE.

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Objective: Limbic encephalitis (LE) comprises a spectrum of inflammatory changes in affected brain structures including the presence of autoantibodies and lymphoid cells. However, the potential of distinct lymphocyte subsets alone to elicit key clinicopathological sequelae of LE potentially inducing temporal lobe epilepsy (TLE) with chronic spontaneous seizures and hippocampal sclerosis (HS) is unresolved.

Methods: Here, we scrutinized pathogenic consequences emerging from CD8 T cells targeting hippocampal neurons by recombinant adeno-associated virus-mediated expression of the model-autoantigen ovalbumin (OVA) in CA1 neurons of OT-I/RAG1 mice (termed "OVA-CD8 LE model").

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Background: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by inflammatory and neurodegenerative processes. Despite demyelination being a hallmark of the disease, how it relates to neurodegeneration has still not been completely unraveled, and research is still ongoing into how these processes can be tracked non-invasively. Magnetic resonance imaging (MRI) derived brain network characteristics, which closely mirror disease processes and relate to functional impairment, recently became important variables for characterizing immune-mediated neurodegeneration; however, their histopathological basis remains unclear.

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Objective: The aim of this study was to adapt the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ), developed for the evaluation of quality of life in amyotrophic lateral sclerosis (ALS) patients, into the Turkish society.

Methods: This methodological study was conducted in 92 ALS patients registered in 2 chapters (Istanbul and Izmir) of Turkish ALS-Motor Neuron Diseases Association. The expert opinion and forward-backward translation methods were applied for the linguistic validity of the ALSAQ (long and short versions: ALSAQ-40 and ALSAQ-5, respectively).

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N-Methyl-D-aspartate (NMDA) receptors (NMDARs) are among the most important excitatory neurotransmitter receptors in the human brain. Autoantibodies to the human NMDAR cause the most frequent form of autoimmune encephalitis involving autoantibody-mediated receptor cross-linking and subsequent internalization of the antibody-receptor complex. This has been deemed to represent the predominant antibody effector mechanism depleting the NMDAR from the synaptic and extra-synaptic neuronal cell membrane.

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Article Synopsis
  • The study aimed to evaluate complications in ICU patients with autoimmune encephalitis (AE), their management, and factors affecting recovery outcomes.
  • It involved 120 patients across various hospitals, finding that many experienced severe issues like disorders of consciousness and sepsis, with mechanical ventilation being a major risk factor for poor recovery.
  • The findings suggest that common ICU complications are better predictors of outcomes than specific types of AE, highlighting the need for effective management and further research in this area.
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Erythropoietin (EPO) has been shown to improve cognitive function in mammals as well as in patients of psychiatric diseases by directly acting on the brain. In addition, EPO attenuates the synaptic transmission and enhances short- and long-term synaptic plasticity in hippocampus of mice, although there are still many discrepancies between different studies. It has been suggested that the divergences of different studies take root in different application schemata or in long-term trophic effects of EPO.

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Cellular and humoral immunity towards distinct onconeural antigens is the hallmark of paraneoplastic neurological diseases (PNDs). Stable formation of immunoglobulin (Ig) G antibodies to particular onconeural antigens occurs in the majority of cases, whereas persistent coexistence of antibodies specific for multiple onconeural antigens is a relatively rare phenomenon of certain malignant tumors like small cell lung cancer (SCLC). We here describe onconeural antigen spreading in a 70-year-old Caucasian male with PND due to SCLC.

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Temporal lobe epilepsy with amygdala enlargement (TLE-AE) is increasingly recognized as a distinct adult electroclinical syndrome. However, functional consequences of morphological alterations of the amygdala in TLE-AE are poorly understood. Here, two emotional stimulation designs were employed to investigate subjective emotional rating and skin conductance responses in a sample of treatment-naïve patients with suspected or confirmed autoimmune TLE-AE (n = 12) in comparison to a healthy control group (n = 16).

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Herpes simplex virus-1 has been identified as the trigger factor in certain cases of NMDA-receptor autoimmune encephalitis. We report on a 67-year-old female patient, who was severely affected by post-herpetic NMDA-receptor autoimmune encephalitis. Her symptoms did not improve under methylprednisolone pulse therapy and plasma exchange under acyclovir prophylaxis.

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Objective: To investigate the reproducibility of diffusion-weighted magnetic resonance imaging (DW-MRI) in assessing tumor response early in the course of neoadjuvant chemoradiotherapy in patients with operable esophageal cancer.

Methods: Eleven male patients (mean age 54.8 years) with newly diagnosed esophageal cancer underwent DW-MRI before and 10 days after start of chemoradiotherapy.

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The constant input of chemical fungicides against foliar diseases in glasshouse crops has instigated research on alternative control substances. Various salts have been mentioned in the literature and we have tested several bicarbonates, sulphates and phosphates against powdery mildew fungi in cucumber, tomato, sweet pepper and rose and against Bremia lactucae in lettuce. The experiments were run according to EPPO guidelines for efficacy in glasshouses of Applied Plant Research (PPO).

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The role of saprophytic phyllosphere yeasts in removing aphid honeydew and other nutrients from wheat leaves was evaluated in growth cabinet experiments at different temperatures and relative humidities. Population densities of both pink and white yeasts (Sporobolomyces roseus and Cryptococcus laurentii, respectively) increased between 12 and 24°C, if nutrients were supplied. White yeast numbers increased rapidly at a constant vapor pressure deficit (VPD) of 0.

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