Altered amygdala volumes and microstructure in focal epilepsy patients with tonic-clonic seizures, ictal, and post-convulsive central apnea.

OBJECTIVES: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death for patients with epilepsy; however, the pathophysiology remains unclear. Focal-to-bilateral tonic-clonic seizures (FBTCS) are a major risk factor, and centrally-mediated respiratory depression may increase the risk further. Here, we determined the volume and microstructure of the amygdala, a key structure that can trigger apnea in people with focal epilepsy, stratified by the presence or absence of FBTCS, ictal central apnea (ICA), and post-convulsive central apnea (PCCA). METHODS: Seventy-three patients with focal impaired awareness seizures without FBTC seizures (FBTCneg group) and 30 with FBTCS (FBTCpos group) recorded during video electroencephalography (VEEG) with respiratory monitoring were recruited prospectively during presurgical investigations. We acquired high-resolution T1-weighted anatomic and multi-shell diffusion images, and computed neurite orientation dispersion and density imaging (NODDI) metrics in all patients with epilepsy and 69 healthy controls. Amygdala volumetric and microstructure alterations were compared between three groups: healthy subjects, FBTCneg and FBTCpos groups. The FBTCpos group was further subdivided by the presence of ICA and PCCA, verified by VEEG. RESULTS: Bilateral amygdala volumes were significantly increased in the FBTCpos cohort compared to healthy controls and the FBTCneg group. Patients with recorded PCCA had the highest increase in bilateral amygdala volume of the FBTCpos cohort. Amygdala neurite density index (NDI) values were decreased significantly in both the FBTCneg and FBTCpos groups relative to healthy controls, with values in the FBTCpos group being the lowest of the two. The presence of PCCA was associated with significantly lower NDI values vs the non-apnea FBTCpos group (p = 0.004). SIGNIFICANCE: Individuals with FBTCpos and PCCA show significantly increased amygdala volumes and disrupted architecture bilaterally, with greater changes on the left side. The structural alterations reflected by NODDI and volume differences may be associated with inappropriate cardiorespiratory patterns mediated by the amygdala, particularly after FBTCS. Determination of amygdala volumetric and architectural changes may assist identification of individuals at risk.

Altered Amygdala Volumes and Microstructure in Focal Epilepsy Patients with Tonic-Clonic Seizures, Ictal and Post-Ictal Central Apnea.

Objectives: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death for patients with epilepsy; however, the pathophysiology remains unclear. Focal-to-bilateral tonic-clonic seizures (FBTCS) are a major risk factor, and centrally-mediated respiratory depression may increase the risk further. Here, we determined volume and microstructure of the amygdala, a key structure that can trigger apnea in people with focal epilepsy, stratified by presence or absence of FBTCS, ictal central apnea (ICA) and post-ictal central apnea (PICA). Methods: 73 patients with only-focal seizures and 30 with FBTCS recorded during video EEG (VEEG) with respiratory monitoring were recruited prospectively during presurgical investigations. We acquired high-resolution T1-weighted anatomical and multi-shell diffusion images, and computed neurite orientation dispersion and density imaging (NODDI) metrics in all epilepsy patients and 69 healthy controls. Amygdala volumetric and microstructure alterations were compared between healthy subjects, and patients with only-focal seizures or FBTCS The FBTCS group was further subdivided by presence of ICA and PICA, verified by VEEG. Results: Bilateral amygdala volumes were significantly increased in the FBTCS cohort compared to healthy controls and the focal cohort. Patients with recorded PICA had the highest increase in bilateral amygdala volume of the FBTCS cohort.Amygdala neurite density index (NDI) values were significantly decreased in both the focal and FBTCS groups relative to healthy controls, with values in the FBTCS group being the lowest of the two. The presence of PICA was associated with significantly lower NDI values vs the non-apnea FBTCS group (p=0.004). Significance: Individuals with FBTCS and PICA show significantly increased amygdala volumes and disrupted architecture bilaterally, with greater changes on the left side. The structural alterations reflected by NODDI and volume differences may be associated with inappropriate cardiorespiratory patterns mediated by the amygdala, particularly after FBTCS. Determination of amygdala volumetric and architectural changes may assist identification of individuals at risk.

Inappropriate Ventilatory Homeostatic Responses in Hospitalized COVID-19 Patients.

Background: The clinical presentation of COVID-19 suggests altered breathing control - tachypnoea, relative lack of dyspnoea, and often a discrepancy between severity of clinical and radiological findings. Few studies characterize and analyse the contribution of breathing drivers and their ventilatory and perceptual responses. Aim: To establish the prevalence of inappropriate ventilatory and perceptual response in COVID-19, by characterizing the relationships between respiratory rate (RR), dyspnoea and arterial blood gas (ABG) in a cohort of COVID-19 patients at presentation to hospital, and their post-Covid respiratory sequelae at follow-up. Methods: We conducted a retrospective cohort study including consecutive adult patients admitted to hospital with confirmed COVID-19 between 1st March 2020 and 30th April 2020. In those with concurrent ABG, RR and documented dyspnoea status on presentation, we documented patient characteristics, disease severity, and outcomes at hospital and 6-week post-discharge. Results: Of 492 admissions, 194 patients met the inclusion criteria. Tachypnoea was present in 75% pronounced (RR>30) in 36%, and persisted during sleep. RR correlated with heart rate (HR) (r = 0.2674), temperature (r = 0.2824), CRP (r = 0.2561), Alveolar-arterial (A-a) gradient (r = 0.4189), and lower PaO2/FiO2 (PF) ratio (r = -0.3636). RR was not correlated with any neurological symptoms. Dyspnoea was correlated with RR (r = 0.2932), A-a gradient (r = 0.1723), and lower PF ratio (r = -0.1914), but not correlated with PaO2 (r = -0.1095), PaCO2 (r = -0.0598) or any recorded neurological symptom except for altered consciousness. Impaired ventilatory homeostatic control of pH/PaCO2 [tachypnoea (RR>20), hypocapnia (PaCO2 <4.6 kPa), and alkalosis (pH>7.45)] was observed in 29%. This group, of which 37% reported no dyspnoea, had more severe respiratory disease (A-a gradient 38.9 vs. 12.4 mmHg; PF ratio 120 vs. 238), and higher prevalence of anosmia (21 vs. 15%), dysgeusia (25 vs. 12%), headache (33 vs. 23%) and nausea (33 vs. 14%) with similar rates of new anxiety/depression (26 vs. 23%), but lower incidence of past neurological or psychiatric diagnoses (5 vs. 21%) compared to appropriate responders. Only 5% had hypoxia sufficiently severe to drive breathing (i.e. PaO2 <6.6 kPa). At 6 weeks post-discharge, 24% (8/34) showed a new breathing pattern disorder with no other neurological findings, nor previous respiratory, neurological, or psychiatric disorder diagnoses. Conclusions: Impaired homeostatic control of ventilation i.e., tachypnoea, despite hypocapnia to the point of alkalosis appears prevalent in patients admitted to hospital with COVID-19, a finding typically accompanying more severe disease. Tachypnoea prevalence was between 12 and 29%. Data suggest that excessive tachypnoea is driven by both peripheral and central mechanisms, but not hypoxia. Over a third of patients with impaired homeostatic ventilatory control did not experience dyspnoea despite tachypnoea. A subset of followed-up patients developed post-covid breathing pattern disorder.

Artificial Intelligence in Medicine: A Multinational Multi-Center Survey on the Medical and Dental Students' Perception.

Background: The emerging field of artificial intelligence (AI) will probably affect the practice for the next generation of doctors. However, the students' views on AI have not been largely investigated. Methods: An anonymous electronic survey on AI was designed for medical and dental students to explore: (1) sources of information about AI, (2) AI applications and concerns, (3) AI status as a topic in medicine, and (4) students' feelings and attitudes. The questionnaire was advertised on social media platforms in 2020. Security measures were employed to prevent fraudulent responses. Mann-Whitney U-test was employed for all comparisons. A sensitivity analysis was also performed by binarizing responses to express disagreement and agreement using the Chi-squared test. Results: Three thousand one hundred thirty-three respondents from 63 countries from all continents were included. Most respondents reported having at least a moderate understanding of the technologies underpinning AI and of their current application, with higher agreement associated with being male (p < 0.0001), tech-savvy (p < 0.0001), pre-clinical student (p < 0.006), and from a developed country (p < 0.04). Students perceive AI as a partner rather than a competitor (72.2%) with a higher agreement for medical students (p = 0.002). The belief that AI will revolutionize medicine and dentistry (83.9%) with greater agreement for students from a developed country (p = 0.0004) was noted. Most students agree that the AI developments will make medicine and dentistry more exciting (69.9%), that AI shall be part of the medical training (85.6%) and they are eager to incorporate AI in their future practice (99%). Conclusion: Currently, AI is a hot topic in medicine and dentistry. Students have a basic understanding of AI principles, a positive attitude toward AI and would like to have it incorporated into their training.

Acute disseminated encephalomyelitis (ADEM) associated with COVID-19.

A 53-year-old man admitted to the critical care secondary to respiratory failure due to COVID-19 developed agitation and global hypotonia. Brain MRI revealed bilateral hyperintense lesions throughout the brain and cerebrospinal fluid identified oligoclonal bands. Intravenous high-dose glucocorticoids were administered followed by an oral tapering dose and the patient clinically improved. Acute disseminated encephalomyelitis should be considered in patients with COVID-19 who present with altered mentation and polyfocal neurological deficits.

Real World Patterns of Antimicrobial Use and Microbiology Investigations in Patients with Sepsis outside the Critical Care Unit: Secondary Analysis of Three Nation-Wide Point Prevalence Studies.

Recent description of the microbiology of sepsis on the wards or information on the real-life antibiotic choices used in sepsis is lacking. There is growing concern of the indiscriminate use of antibiotics and omission of microbiological investigations in the management of septic patients. We performed a secondary analysis of three annual 24-h point-prevalence studies on the general wards across all Welsh acute hospitals in years 2016-2018. Data were collected on patient demographics, as well as radiological, laboratory and microbiological data within 48-h of the study. We screened 19,453 patients over the three 24 h study periods and recruited 1252 patients who fulfilled the entry criteria. 775 (64.9%) patients were treated with intravenous antibiotics. Only in 33.65% (421/1252) of all recruited patients did healthcare providers obtain blood cultures; in 25.64% (321/1252) urine cultures; in 8.63% (108/1252) sputum cultures; in 6.79% (85/1252) wound cultures; in 15.25% (191/1252) other cultures. Out of the recruited patients, 59.1% (740/1252) fulfilled SEPSIS-3 criteria. Patients with SEPSIS-3 criteria were significantly more likely to receive antibiotics than the non-septic cohort (p < 0.0001). In a multivariable regression analysis increase in SOFA score, increased number of SIRS criteria and the use of the official sepsis screening tool were associated with antibiotic administration, however obtaining microbiology cultures was not. Our study shows that antibiotics prescription practice is not accompanied by microbiological investigations. A significant proportion of sepsis patients are still at risk of not receiving appropriate antibiotics treatment and microbiological investigations; this may be improved by a more thorough implementation of sepsis screening tools.