Pathogenesis of encephalopathy and delirium: neocortical neuronal membrane potential and action potential firing are changed by coronavirus-associated cytokines

Introduction: Encephalopathy and delirium are common following coronavirus infection [1], and the associated neuroinflammation often results in long-term behavioral and cognitive impairment. Neurovirulent cytokines (NVC) are strongly implicated in the pathogenesis of coronavirus encephalopathy [2]. We hypothesized that characterizing the abnormal signaling in NVC exposed neurons will enable us to identify targets to treat encephalopathy and prevent its downstream effects. Method(s): We incubated primary mouse neocortical cultures in NVC known to be increased in coronavirus encephalopathy (TNF-alpha, IL-1beta, IL-6, IL-12 and IL-15). Using whole-cell patch clamp methods, we tested how neuronal function was impacted by 22-28-h exposure to NVC. Result(s): We found that NVC depolarized the resting membrane potential (RMP), reduced the firing threshold of neocortical neurons, and increased baseline spontaneous action potential (AP) firing. NVC altered the sensitivity (or input-output properties) of single neurons to changes in their microenvironment. Specifically, decreasing external Ca2+ and Mg2+ from physiological to low (1.1-0.2 mM) levels increased evoked AP firing in control, but not following exposure to NVC. AP firing threshold and spontaneous firing rates returned to control levels 1 h after NVC wash-out. However, the RMP and attenuated sensitivity of evoked APs to changes in the microenvironment remained persistently abnormal suggesting two distinct mechanisms were at play. Interestingly, hyperpolarizing the RMP reversed this altered response. Conclusion(s): Sustained exposure to NVC reversibly depolarizes neocortical neuronal RMP, altering excitability and the ability of neurons to respond to microenvironment changes. By characterizing the pathogenesis of the underlying changes in neuronal function in our model of coronavirus encephalopathy we will identify intervenable drug targets.

Early switch from cladribine to alemtuzumab in highly-active relapsing-remitting multiple sclerosis: A case report

Background Management of patients with multiple sclerosis (MS) and evidence of disease activity during treatment with cladribine tablets represents a challenging point. Objectives To report a patient with highly active multiple sclerosis (HAMS) who has been early switched from cladribine to alemtuzumab owing to tumultuous clinical and radiological activity Methods A single retrospective case report. Results. Treatment with alemtuzumab has led to a complete suppression of disease activity without any evidence of infections or acquired autoimmune diseases. Conclusion Our report suggests that an early switch from cladribine to alemtuzumab, may be safe and efficacious in selected HAMS cases.Copyright © 2022 The Authors

Audiological evaluation of the cochlear nerve with brainstem evoked response audiometry in patients with COVID-19.

PURPOSE: In this clinical study, it was aimed to prospectively evaluate the cochlear nerve with brainstem evoked response audiometry (BERA) in terms of audiological ailments in patients with COVID-19. Although the relationship of COVID-19 with tinnitus and hearing loss has been investigated since the day this infectious respiratory disease emerged, its relationship with BERA has not been fully demonstrated from a neurological perspective. METHODS: It was carried out on a group of patients who had COVID-19 in the last 6 months between February and August 2021 in Diyarbakir Gazi Yasargil Training and Research Hospital. Patients between the ages of 18-50, who applied to the otorhinolaryngology and neurology clinic and had COVID-19 in the last 6 months, were selected. The COVID-19 group of our study consisted of 30 patients, 18 males and 12 females, who had had COVID-19 disease in the last 6 months, and 30 healthy individuals, 16 males and 14 females, as the control group. RESULTS: In patients with COVID-19, the evaluation of the destruction of the cochlear nerve with BERA showed that there was a statistically significant prolongation in I-III and I-V interpeaks at 70, 80 and 90 db nhl. CONCLUSIONS: Statistically significant prolongation of especially I-III and I-V Interpeaks in BERA showed that COVID-19 has the potential to cause neuropathy. We believe that the BERA test should be considered in the neurological evaluation of cochlear nerve damage in patients with COVID-19 as a differential diagnosis.

Monitoring of Auditory Function in Newborns of Women Infected by SARS-CoV-2 during Pregnancy.

BACKGROUND: Gestational SARS-CoV-2 infection can impact maternal and neonatal health. The virus has also been reported to cause newborn sensorineural hearing loss, but its consequences for the auditory system are not fully understood. OBJECTIVE: The aim of this study was to evaluate the impact of maternal SARS-CoV-2 infection during pregnancy on newborn' hearing function during the first year of life. METHODS: An observational study was conducted from 1 November 2020 to 30 November 2021 at University Modena Hospital. All newborns whose mother had been infected by SARS-CoV-2 during pregnancy were enrolled and underwent audiological evaluation at birth and at 1 year of age. RESULTS: A total of 119 neonates were born from mothers infected by SARS-CoV-2 during pregnancy. At birth, five newborns (4.2%) presented an increased threshold of ABR (Auditory Brainstem Evoked Response), but the results were confirmed only in 1.6% of cases, when repeated 1 month later, while the ABR thresholds in all other children returned to normal limits. At the 1-year follow-up, no cases of moderate or severe hearing loss were observed, while concomitant disorders of the middle ear were frequently observed. CONCLUSIONS: Maternal SARS-CoV-2 infection, regardless of the trimester in which it was contracted, appears not to induce moderate or severe hearing loss in infants. It is important to clarify the possible effect of the virus on late-onset hearing loss and future research is needed.

Exploring the Effect of Silence on Auditory Network Regions in Young Female Adults who Experience Temporary Tinnitus on Exposure to Silence.

OBJECTIVES: To examine the differences in auditory evoked cortical responses that may underlie the tendency of some people to perceive tinnitus. The study hypothesis is that the mean ALR and P300 amplitudes in normal hearing adults who perceive temporary tinnitus after exposure to sustained silence will be larger than the mean ALR and P300 amplitudes in normal hearing adults who do not perceive temporary tinnitus after exposure to sustained silence. DESIGN: This was a prospective cross-sectional study. The approval for the study was obtained from the IRB and COVID ramp up committee of University of North Carolina Greensboro (UNCG). Participants completed comprehensive hearing screening and preand postsilence ALR and P300 recordings were obtained. After the first ALR/P300 recording participants were exposed to ten minutes of silence. Participants completed a Qualtrics questionnaire to report any tinnitus perception that emerged during silence exposure. Absolute N1, P2 and P300 waveform amplitudes and latencies were identified and were entered into an SPSS spreadsheet for data analysis. RESULTS: Thirty adult females with normal pure tone hearing thresholds and no history of persistent tinnitus were included in the study. The mean age of the participants was 22.5 ± 3.9 years. When exposed to silence, eight (26.7%) participants perceived temporary tinnitus. N1 and P300 waveforms were smaller in amplitude and faster in latency in the tinnitus perception group; however, the ALR and P300 waveform latencies and amplitudes did not statistically differ significantly between the participants who perceived temporary tinnitus in silence and those who did not (p>0.05). The difference in waveform morphology between the tinnitus perception group and the non-tinnitus perception group revealed a greater difference in P300 amplitude after exposure to silence. CONCLUSION: Differences in ALR and P300 latencies and amplitudes were observed between the tinnitus perception group and non-tinnitus perception group, with smaller P300 amplitudes appearing in the group perceiving tinnitus. While the results did not statistically significant, this pattern may reflect a mismatch between the neuronal response in the auditory cortex (N1 and P2 amplitudes and latencies) and the neuronal activity in the modulatory network regions (P300).

Bilateral diaphragmatic dysfunction: A cause of persistent dyspnea in patients with post-acute sequelae of SARS-CoV-2

Persistent shortness of breath is one of the most common concerns reported by patients with post-acute sequelae of SARS-CoV-2. Here, we present a case of bilateral diaphragmatic paralysis as a cause shortness of breath that developed after SARS-CoV-2 infection. A middle-aged gentleman with history of sleep apnea and body mass index 27.9 kg/m2 presented to our post-COVID clinic with 3 months of dyspnea and orthopnea after contracting SARS-CoV-2 in November 2020. During acute infection, he was hospitalized for hypoxemia, which improved with steroids and supplemental oxygen. At 3 months, he continued to report dyspnea and orthopnea. On examination, he had tachycardia and increased respiratory rate with paradoxical respiratory abdominal movement. Chest imaging showed elevated bilateral hemidiaphragms without any parenchymal lung disease. Pulmonary function test revealed severe ventilatory defect with restrictive lung disease. He was diagnosed with bilateral diaphragmatic dysfunction which was confirmed by absence of evoked potentials in diaphragm after phrenic nerve stimulation bilaterally. He was advised to use continuous positive airway pressure machine to assist with breathing at night. At his last follow-up (1-year post-infection), he was symptomatically improving without specific interventions.