Broader Epstein-Barr virus-specific T-cell receptor repertoire in patients with multiple sclerosis

Introduction: Epstein-Barr virus (EBV) infection precedes signs of multiple sclerosis (MS) pathology and cross-reactive antibodies might link EBV infection mechanistically to CNS autoimmunity. Objective(s): As an altered immune reaction against EBV antigens in T cells of MS patients has been suggested, we queried deep, peripheral blood T-cell receptor beta chain (TCRbeta) repertoires of 1395 MS patients, 887 controls, and 35 monozygotic, MS-discordant twin pairs for multimerconfirmed, viral antigen-specific TCRbeta sequences. Aim(s): Quantification of HLA-matched EBV-specific, CMV-specific, Influenza A virus-specific, and SARS-CoV-2-specific TCRbeta sequences in MS patients, controls, and COVID-19 patients. Result(s): We detected higher numbers of MHC-I restricted EBVspecific TCRbeta sequences in MS patients, and validated this with independent cohorts and sequencing methods. Genetic as well as early environmental factors could be excluded by validation in diseased siblings of monozygotic twin pairs discordant for MS. Therapeutic blockade of VLA-4-mediated T-cell extravasation amplified this observation, while interferon beta treatment and B-cell depletion did not modulate occurrence of EBV-specific T cells. EBV-specific CD8+ T cells were characterized as effectormemory cells in peripheral blood and cerebrospinal fluid of healthy controls. In MS patients, the cerebrospinal fluid also contained EBV-specific central-memory CD8+ T cells, suggesting recent priming. Conclusion(s): MS is not only preceded by EBV infection, but also associated with a broader EBV-specific TCR repertoire, which would be consistent with an ongoing anti-EBV immune reaction in MS patients.

Prediction of abdominal CT body composition parameters by thoracic measurements as a new approach to detect sarcopenia in a COVID-19 cohort.

As most COVID-19 patients only receive thoracic CT scans, but body composition, which is relevant to detect sarcopenia, is determined in abdominal scans, this study aimed to investigate the relationship between thoracic and abdominal CT body composition parameters in a cohort of COVID-19 patients. This retrospective study included n = 46 SARS-CoV-2-positive patients who received CT scans of the thorax and abdomen due to severe disease progression. The subcutaneous fat area (SF), the skeletal muscle area (SMA), and the muscle radiodensity attenuation (MRA) were measured at the level of the twelfth thoracic (T12) and the third lumbar (L3) vertebra. Necessity of invasive mechanical ventilation (IMV), length of stay, or time to death (TTD) were noted. For statistics correlation, multivariable linear, logistic, and Cox regression analyses were employed. Correlation was excellent for the SF (r = 0.96) between T12 and L3, and good for the respective SMA (r = 0.80) and MRA (r = 0.82) values. With adjustment (adj.) for sex, age, and body-mass-index the variability of SF (adj. r2 = 0.93; adj. mean difference = 1.24 [95% confidence interval (95% CI) 1.02-1.45]), of the SMA (adj. r2 = 0.76; 2.59 [95% CI 1.92-3.26]), and of the MRA (adj. r2 = 0.67; 0.67 [95% CI 0.45-0.88]) at L3 was well explained by the respective values at T12. There was no relevant influence of the SF, MRA, or SMA on the clinical outcome. If only thoracic CT scans are available, CT body composition values at T12 can be used to predict abdominal fat and muscle parameters, by which sarcopenia and obesity can be assessed.

Randomized Controlled Trial of Closed-Loop Allostatic Neurotechnology to Improve Sensory Function and Pain Management After Traumatic Brain Injury

Persistent symptoms after mild traumatic brain injury (mTBI), including chronic pain and sensory disturbance, may be related to alterations at the level of neural oscillations. Studies in mTBI patients show disturbed sleep as a core component of symptoms. The purpose of this study is to evaluate a noninvasive, closed-loop, acoustic stimulation neurotechnology (HIRREM-SOP called Cereset Research, using non-invasive BrainEcho technology) as a novel treatment to enable both physiological and clinical recovery from mTBI, through auto-calibration of neural oscillations. The study is conducted as a single blind study at two sites USUHS/Walter Reed and WAMC. The hypothesis is that usage of Cereset Research neurotechnology (ten sessions, 90 minutes each), will entail greater reduction in persistent symptoms of mTBI, at three months, than exposure to non-specific random tones that are delivered in a comparable way. The participant enrollment has begun at both USUHS/Walter Reed and WAMC. Both sites progressed nicely until March of 2020 when COVID forced a complete shutdown of research interventions. IRB permissions were granted for the sites to do follow-up visits remotely, but no new clients were allowed to be enrolled or begin the intervention process. COVID restrictions have recently been lifted so the sites can again begin to advertise and enroll new participants. COVID caused this study to be delayed at least 4 to 6 months.

Exploratory study of acoustic neuromodulation improves pain, autonomic function, and symptoms of insomnia, stress, and anxiety in individuals with chronic pain

Objective: Evaluate the impact of Cereset Research™ (CR), on pain, autonomic function, insomnia, stress, and anxiety for those with chronic pain. Background: Chronic pain is a worldwide crisis causing negative health outcomes, and risk for psychological disorders. Effective non-drug, noninvasive, cost-effective, durable modalities are lacking. CR is a noninvasive, closed-loop, acoustic neuromodulation technology, echoing brainwaves in real time as auditory tones. Design/Methods: 19 adults (10 females, median age 48) with chronic pain (median 5 years), and insomnia (ISI, of ≥8 points for ≥1 month), stress (PSS of ≥14), or anxiety (GAD-7 of ≥5), enrolled in this exploratory trial. Subjects received 6-12, sixty-minute sessions of tones linked to brainwaves plus continued current care. Data was collected at baseline (V1), 0-21 days (V2) after intervention, 4-7 weeks after V2 (V3), and 4-7 weeks after V3 (V4). HRV (SDNN and rMSSD) was obtained as primary outcome based on 10-minute BP and HR recordings using a continuous non-invasive blood pressure system, with change in ISI, PSS, GAD-7, CES-D, PCL-C, and MPQ as secondary outcomes. We report interim results for symptom and HRV outcomes across visits. Results: 19 subjects completed V1-V2 measures. Due to COVID-19, V1-V4=10. Median change V1 to V4 ISI:-6.5 (p=0.001);PSS score:-5.5 (p<0.01);GAD-7:-6 (p<0.01), CES-D:-7 (p<0.01);and PCL-C:-8 (p<0.01);MPQ:-8.5 (p=0.52). Mean (median) SDNN and rMSSD significantly increased by 45.7 % (30.9%) and 89.1% (47.1%) respectively from V1 to V2. SDNN improved from V1 to V4 36.6% (39.0%), p=0.02. Conclusions: Interim results suggest significant, durable reductions in self-reported scores for insomnia, anxiety, depression, post-traumatic stress, and pain in those with chronic pain. In this small cohort, many reductions were clinically meaningful and there were also trends for improved HRV. Further evaluation is needed for this scalable, non-drug intervention.