Defining the Clinicoradiologic Syndrome of SARS-CoV-2 Acute Necrotizing Encephalopathy: A Systematic Review and 3 New Pediatric Cases

BACKGROUND AND OBJECTIVES: We characterize clinical and neuroimaging features of SARS-CoV-2-related acute necrotizing encephalopathy (ANE). METHODS: Systematic review of English language publications in PubMed and reference lists between January 1, 2020, and June 30, 2023, in accordance with PRISMA guidelines. Patients with SARS-CoV-2 infection who fulfilled diagnostic criteria for sporadic and genetic ANE were included. RESULTS: From 899 articles, 20 cases (17 single case reports and 3 additional cases) were curated for review (50% female; 8 were children). Associated COVID-19 illnesses were febrile upper respiratory tract infections in children while adults had pneumonia (45.6%) and myocarditis (8.2%). Children had early neurologic deterioration (median day 2 in children vs day 4 in adults), seizures (5 (62.5%) children vs 3 of 9 (33.3%) adults), and motor abnormalities (6 of 7 (85.7%) children vs 3 of 7 (42.9%) adults). Eight of 12 (66.7%) adults and 4 (50.0%) children had high-risk ANE scores. Five (62.5%) children and 12 (66.7%) adults had brain lesions bilaterally and symmetrically in the putamina, external capsules, insula cortex, or medial temporal lobes, in addition to typical thalamic lesions of ANE. Hypotension was only seen in adults (30%). Hematologic derangements were common: lymphopenia (66.7%), coagulopathy (60.0%), or elevated D-dimers (100%), C-reactive protein (91.7%), and ferritin (62.5%). A pathogenic heterozygous c/.1754 C>T variant in RANBP2 was present in 2 children: one known to have this before SARS-CoV-2 infection, and a patient tested because the SARS-CoV-2 infection was the second encephalopathic illness. Three other children with no prior encephalopathy or family history of encephalopathy were negative for this variant. Fifteen (75%) received immunotherapy (with IV methylprednisolone, immunoglobulins, tocilizumab, or plasma exchange): 6 (40.0%) with monotherapy and 9 (60.0%) had combination therapy. Deaths were in 8 of 17 with data (47.1%): a 2-month-old male infant and 7 adults (87.5%) of median age 56 years (33-70 years), 4 of whom did not receive immunotherapy. DISCUSSION: Children and adults with SARS-CoV-2 ANE have similar clinical features and neuroimaging characteristics. Mortality is high, predominantly in patients not receiving immunotherapy and at the extremes of age.

Severe and rare neurological manifestations following COVID-19 infection in children: A Malaysian tertiary centre experience.

INTRODUCTION: Since the emergence of COVID-19, we have experienced potent variants and sub-variants of the virus with non-specific neurological manifestations. We observed a surge of the Omicron variant of COVID-19 patients with neurological manifestations where less cases of multisystem inflammatory syndrome in children (MIS-C) were reported. This article describes our experience of children with severe and rare neurological manifestations following COVID-19 infection. METHODS: This is a retrospective observational case series of patients under 18 years old who fulfilled the WHO COVID-19 case definition and were referred to our paediatric neurology unit at Hospital Tunku Azizah Kuala Lumpur. Their demographic data, neurological symptoms, laboratory and supporting investigations, neuroimaging, treatment and outcomes were collected and analysed. RESULTS: There were eleven patients with neurological manifestations who fulfilled the WHO COVID-19 case definition. Nine patients presented with seizures and/or encephalopathy, one patient with eye opsoclonus and another patient with persistent limbs myokymia. Based on the history, clinical, electrophysiological and radiological findings, two of them had febrile infection-related epilepsy syndrome, two had acute disseminated encephalomyelitis, two had acute necrotising encephalopathy of childhood, one each had hemiconvulsion-hemiplegia-epilepsy syndrome, acute encephalopathy with bilateral striatal necrosis, hemi-acute encephalopathy with biphasic seizures and reduced diffusion, infection-associated opsoclonus and myokymia. CONCLUSIONS: This case series highlighted a wide spectrum of neurological manifestations of COVID-19 infection. Early recognition and prompt investigations are important to provide appropriate interventions. It is essential that these investigations should take place in a timely fashion and COVID-19 quarantine period should not hinder the confirmation of various presenting clinical syndromes.

Cardiovascular causes of tracheobronchial compression: a decade experience in a Paediatric Congenital Heart Centre.

BACKGROUND: Vascular compression of the airway often complicates CHD management. This study evaluated the use of CT in determining cardiovascular causes, clinical manifestations, and outcome of tracheobronchial compression among children with CHD. METHODS: A retrospective review of clinical records of all patients with CT scan evidence of tracheobronchial compression from January 2007 to December 2017 at National Heart Institute. Cardiovascular causes of tracheobronchial compression were divided into three groups; group I: vascular ring/pulmonary artery sling, II: abnormally enlarged or malposition cardiovascular structure due to CHD, III: post-CHD surgery. RESULTS: Vascular tracheobronchial compression was found in 81 out of 810 (10%) patients who underwent CT scan. Group I lesions were the leading causes of vascular tracheobronchial compression (55.5%), followed by group II (34.6%) and group III (9.9%). The median age of diagnosis in groups I, II, and III were 16.8 months, 3 months, and 15.6 months, respectively. Half of group I patients are manifested with stridor and one-third with recurrent chest infections. Persistent respiratory symptoms, lung atelectasis, or prolonged respiratory support requirement were clues in groups II and III. Higher morbidity and mortality in younger infants with severe obstructive airway symptoms, associated airway abnormalities, and underlying complex cyanotic CHD. CONCLUSIONS: Vascular ring/pulmonary artery sling and abnormally enlarged or malposition cardiovascular structure were the leading causes of cardiovascular airway compression. A high index of suspicion is needed for early detection due to its non-specific presentation. The outcome often depends on the severity of airway obstruction and complexity of cardiac lesions.

A Malaysian Medical Non-Governmental Organization's (NGO) Experience in the Emergency Response for COVID-19, Using the Whole-of-Society Collaborative Concept.

Non-governmental organizations (NGOs) are one of the important players during a pandemic, including the Islamic Medical Association of Malaysia (IMAM) Response and Relief Team (IMARET). During the coronavirus disease (COVID-19) pandemic, IMARET played a key role in assisting health relief efforts in Malaysia. We are sharing this experience as a medical NGO's response to the pandemic. This report presents data from the March 18 to June 10, 2020, retrieved from IMARET's database with approval from the Executive Committee and the IMARET COVID-19 Task Force. We report that IMARET's task force consists of 30 people, mostly medical doctors. Supplies distributed included personal protective equipment with other medical equipment, such as portable ultrasounds and ventilators. IMARET engaged with 33 collaborators and 92 partners and funders. There were 135 volunteers with the majority being medical volunteers. IMARET raised more than RM $3 million (US $740 000) garnering support from over 40 000 donors in 85 days. In conclusion, NGOs play a significant role that effectively enhance and complement the consolidated works by the authorities and public in the effort to overcome COVID-19 challenges.

Paediatric scurvy: frequently misdiagnosed.

Paediatric scurvy is uncommon in the modern age but cases have been reported in children with neurodevelopmental issues and restricted dietary habits. The broad clinical picture is frequently overlooked as primarily other systemic diseases are considered first leading to extensive investigations and delay in diagnosis. A 4-year-old boy with autism and bilateral lower limb pain and refusal to walk is reported. His restricted diet and radiographic findings were highly suggestive of scurvy which was confirmed by the extremely low levels of ascorbic acid. Treatment with ascorbic acid replenishment and maintenance resulted in remarkable improvement. This case highlights the importance of a high index of suspicion in at-risk children so as to avoid unnecessary invasive investigations and procedures.

The effectiveness of a Malaysian House Officer (HO) preparatory course for medical graduates on self-perceived confidence and readiness: A quasi-experimental study.

INTRODUCTION: House Officer (HO) Preparatory Courses in Malaysia are designed to prepare medical graduates to work as a HO. The courses are designed to address the issues related to lack of confidence and readiness to work, which could lead to stress and HO dropping out of work. The modules focus on how to prepare medical graduates into the real-life working scenario. Hence, we determined the effectiveness of a HO Preparatory Course on the level of confidence and readiness to work among medical graduates. METHODOLOGY: A quasi-experimental study was conducted at three time-points (pre-intervention, post-intervention and one-month after working as a HO) on the level of confidence and readiness of medical graduates. The intervention was the Medicorp module, which included information and training needed for the HO such as common clinical cases in the wards, case referrals, experience sharing and hands on clinical training. We recruited eligible participants undergoing the course between April-November 2018. The adapted IMU Student Competency Survey was used to measure the confidence and readiness levels, which were scored from a Likert scale of 1-5. The higher score indicated higher levels of confidence or readiness. RESULTS: A total of 239 participants were recruited at baseline (90% response rate). They were mostly female (77.8%), Malays (79.1%), single (90.0%), graduated overseas (73.6%), in 2018 (65.3%). The mean (SE) confidence scores significantly increased from 2.18 (1.00) pre-course to 3.50 (0.75) immediately after course and 3.79 (0.92) after one-month of work (p <0.001, η2 = 0.710). The mean (SE) readiness scores at pre-course, immediately and one-month post work were 2.36 (1.03), 3.46(0.78) and 3.70(0.90), respectively (p< 0.001, η2 = 0.612). CONCLUSION: The HO Preparatory Course module was effective in increasing levels of confidence and readiness for medical graduates, most of whom are overseas graduates; namely Egypt, Russia and Indonesia.

Internal iliac artery thrombosis in a 2-month-old infant with incomplete Kawasaki disease.

We report a case of a 2-month-old infant with incomplete Kawasaki disease with multiple coronary and systemic arteries aneurysms complicated with internal iliac arteries thrombosis. The atypical clinical presentations and severity of systemic vascular involvements discuss the importance of high index of suspicions in younger infants and treatment options in such cases.

Quasi-experimental study on the effectiveness of a house officer preparatory course for medical graduates on self-perceived confidence and readiness: a study protocol.

INTRODUCTION: Being a house officer (HO) is said to be associated with high levels of stress, leading to mental health problems and sometimes to quitting the medical profession altogether. In Malaysia, the number of HOs completing training on time is slowly declining, with increasing annual dropout rates. Feeling incompetent is one of the contributors towards this growing problem. This study aimed to evaluate the effectiveness of a 3-day pre-HO intervention module in addressing participants' confidence, readiness and psychological well-being in preparation for their HO training. METHODS AND ANALYSIS: The pre-HO intervention is the 'Medicorp' module that includes clerkship, experience sharing, hands-on skills training, common clinical cases and introduction of the local healthcare system. This is a pre-post quasi-experimental study lasting 1 year, with three assessment time points-at pretraining, immediately after training and 1 month into the participants' HO-ship. The study is currently ongoing and involves 208 participants who attended the course in Malaysia. Participants with known psychiatric illness, working HOs and medical students are excluded. A pretested, self-administered questionnaire that includes baseline sociodemography, adaptation of the International Medical University (IMU) Student Competency Survey and the Depression Anxiety Stress Scale has been adopted, and 1 month follow-up will be conducted by telephone. Data will be analysed using SPSS V.24. The primary outcome is change in confidence level, while the secondary outcomes are changes in the readiness and psychological well-being of the participants. ETHICS AND DISSEMINATION: This study protocol has received ethics approval from Ethics Committee for Research Involving Human Subjects Universiti Putra Malaysia and the National Medical Research Registry Malaysia. Written informed consent has been obtained from each participant. Results will be disseminated through journals and conferences, especially those involved in medical education specifically looking into the training of medical doctors. TRIAL REGISTRATION NUMBER: NCT03510195.