The recent discovery of neuronal cell-surface antibodies profoundly expanded the clinical spectrum of paraneoplastic neurological syndromes. Many of these syndromes are associated with impaired cognitive function, a clinical symptom that is of increasing concern in cancer patients. However, the frequency of these antibodies in cancer patients and their relation to clinical syndromes is currently unknown. Here, we investigated the prevalence of neuronal cell-surface antibodies and associated paraneoplastic neurological syndromes in 323 patients with different cancer types and in 105 controls. Cerebrospinal fluid and serum samples were analysed for a large panel of anti-neuronal antibodies and all patients were screened for cognitive deficits. Blood-brain barrier integrity was assessed using the age-normalized albumin cerebrospinal fluid/serum ratio. Anti-neuronal autoantibodies were observed in 24.5% of cancer patients (in contrast to 3.1% in neurological control patients without cancer and 2.5% in healthy controls) and were almost exclusively detected in serum. The majority of antibodies were directed against cell-surface antigens (75.9%), most frequently IgA/IgM isotypes targeting the N-methyl-D-aspartate (NMDA) receptor. Cognitive deficits and cerebellar syndromes were significantly more prevalent in antibody-positive in comparison with antibody-negative patients (21 vs. 7%, p = 2.7 × 10; 11 vs. 2%, p = 3.0 × 10). Antibody-positive patients with cognitive deficits had a significantly increased albumin cerebrospinal fluid/serum ratio in comparison with antibody-positive patients with other neurological deficits, indicating blood-brain barrier dysfunction (49.1 × 10 vs. 12.0 × 10; p = 0.036). Our results show that anti-neuronal antibodies have a high prevalence in a wide range of different tumour types and are associated with distinct neurological deficits. Specifically, the results suggest a so far undefined cognitive paraneoplastic syndrome in patients with antibodies targeting neuronal surface antigens and concurrent blood-brain barrier dysfunction. Anti-neuronal antibodies might thus serve as a biomarker for potentially treatment-responsive cognitive impairments in cancer patients.
Background: Antineuronal antibodies can be associated with both gastrointestinal (GI)
Background: Alcohol use disorder (AUD) belongs to the most burdensome clinical disorders worldwide. Current treatment approaches yield unsatisfactory long-term effects with relapse rates up to 85%. Craving for alcohol is a major predictor for relapse and can be intentionally induced via cue exposure in real life as well as in Virtual Reality (VR). The induction and habituation of craving via conditioned cues is used in Cue Exposure Therapy (CET), a long-known but rarely used strategy in Cognitive Behavioral Therapy (CBT) of AUD. VR scenarios with alcohol related cues offer several advantages over real life scenarios and are within the focus of current efforts to develop new treatment options. As a first step, we aim to analyze if the VR scenarios elicit a transient change in craving levels and if this is measurable via subjective and psychophysiological parameters. Methods: A single-arm clinical study will be conducted including n=60 patients with AUD. Data on severity of AUD and craving, comorbidities, demographics, side effects and the feeling of presence in VR will be assessed. Patients will use a head-mounted display (HMD) to immerse themselves into three different scenarios (neutral vs. target situations) while heart rate, heart rate variability, pupillometry and electrodermal activity will be measured continuously. Subjective craving levels will be assessed before, during and after the VR session. Discussion: Results of this study will yield insight into the induction of alcohol craving in VR cue exposure paradigms and its measurement via subjective and psychophysiological parameters. This might be an important step in the development of innovative therapeutic approaches in the treatment of patients with AUD. Trial registration: This study was approved by the Charité - Universitätsmedizin Berlin Institutional Review Board (EA1/190/22, 23.05.2023). It was registered on ClinicalTrials.gov (NCT05861843).
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