Brief resolved unexplained events: a new diagnosis, with implications for evaluation and management.

Brief resolved unexplained events (BRUE) are concerning episodes of short duration (typically < 1 min) characterized by a change in breathing, consciousness, muscle tone (hyper- or hypotonia), and/or skin color (cyanosis or pallor). The episodes occur in a normal-appearing infant in the first year of life, self-resolve, and have no readily identifiable explanation for the cause of the event. Previously called apparent life-threatening events (ALTE), the term BRUE was first defined by the American Academy of Pediatrics (AAP) in 2016. The criteria for BRUE carry greater specificity compared to that of ALTE and additionally are indicative of a diagnosis of exclusion. While most patients with BRUE will have a benign clinical course, important etiologies, including airway, cardiac, gastrointestinal, genetic, infectious, neurologic, and traumatic conditions (including nonaccidental), must be carefully considered. A BRUE is classified as either lower- or higher-risk based on patient age, corrected gestational age, event duration, number of events, and performance of cardiopulmonary resuscitation at the scene. The AAP clinical practice guideline provides recommendations for the management of lower-risk BRUEs, advocating against routine admission, blood testing, and imaging for infants with these events, though a short period of observation and/or an electrocardiogram may be advisable. While guidance exists for higher-risk BRUE, more data are required to better identify proportions and risk factors for serious outcomes among these patients. Conclusion: BRUE is a diagnosis with greater specificity relative to prior definitions and is now a diagnosis of exclusion. Additional research is needed, particularly in the evaluation of higher-risk events. Recent data suggest that the AAP guidelines for the management of lower-risk infants can be safely implemented.This review article summarizes the history, definitional changes, current guideline recommendations, and future research needs for BRUE. What is Known: • BRUE, first described in 2016, is a diagnosis used to describe a well-appearing infant who presents with change in breathing, consciousness, muscle tone (hyper- or hypotonia), and/or skin color (cyanosis or pallor). • BRUE can be divided into higher- and lower-risk events. Guidelines have been published for lower-risk events, with expert recommendations for higher-risk BRUE. What is New: • BRUE carries a low rate of serious diagnoses (< 5%), with the most common representing seizures and airway abnormalities. • Prior BRUE events are associated with serious diagnoses and episode recurrence.

Achondroplasia is associated with increased occurrence of apparent life-threatening events.

AIM: To assess the clinical picture underlying apparent life-threatening events (ALTEs) occurring in infants with achondroplasia and provide guidance for evaluation after an event. METHODS: A population of 477 individuals with achondroplasia was retrospectively reviewed, and information regarding possible ALTEs was recorded in a REDCap database. RESULTS: ALTEs occurred in the first year of life in 18 of 477 individuals (3.8%). Most (14/18, 78%) occurred in the first 6 months of life and presented as episodes of apnoea and/or seizures. Of affected infants, 8/18 (44%) had more than one episode. Many of the initial ALTEs arose while infants were in car seats (11/18, 61%). Assessment following ALTEs most often demonstrated either craniocervical junction concerns and/or seizures, with 12/18 (67%) patients undergoing cervicomedullary decompression and 5/18 (28%) starting on anti-epileptic medications after the event. CONCLUSION: Although this study is limited in size and was retrospective, it shows that infants with achondroplasia appear to be at high risk for ALTEs. Evaluation after an event should include neuroimaging of the foramen magnum, inpatient hospital observation including respiratory monitoring and electroencephalography, and a car seat challenge.

Brief resolved unexplained events vs. child maltreatment: a review of clinical overlap and evaluation.

Within their first year, a number of infants present for medical evaluation because of unexplained changes in color, tone, breathing, or level of responsiveness. This broad collection of symptoms has an accordingly large differential diagnosis that includes both brief resolved unexplained event (BRUE) and child maltreatment. The overlap between clinical presentation for BRUE and maltreatment can present a diagnostic challenge - especially given the significant consequences for infants and families for diagnostic error at that juncture. In this review, we provide overviews of the presenting features and findings in cases of BRUE and child maltreatment with a focus on areas of overlap and differentiation.

Risk of Death in Infants Who Have Experienced a Brief Resolved Unexplained Event: A Meta-Analysis.

OBJECTIVE: To estimate an upper bound on the risk of death after a brief resolved unexplained event (BRUE), a sudden alteration in an infant's breathing, color, tone, or responsiveness, previously labeled "apparent life-threatening event" (ALTE). STUDY DESIGN: The meta-analysis incorporated observational studies of patients with ALTE that included data on in-hospital and post-discharge deaths with at least 1 week of follow-up after hospital discharge. Pertinent studies were identified from a published review of the literature from 1970 through 2014 and a supplementary PubMed query through February 2017. RESULTS: The 12 included studies (n = 3005) reported 12 deaths, of which 8 occurred within 4 months of the event. Applying a Poisson-normal random effects model to the 8 proximate deaths using a 4-month time horizon yielded a post-ALTE mortality rate of about 1 in 800, which constitutes an upper bound on the risk of death after a BRUE. CONCLUSIONS: This risk is about the same as the baseline risk of death during the first year of life. The meta-analysis therefore supports the return-home approach advocated in a recently published clinical practice guideline-not routine hospitalization-for BRUE patients who have been evaluated in the emergency department and determined to be at lower risk.

Independent risk factors for recurrence of apparent life-threatening events in infants.

The risk factors for recurrent apparent life-threatening event (ALTE) are unclear although the risk of recurrent ALTE is an important consideration for the management of ALTE patients. This study aimed to identify the risk factors for recurrent ALTE. We conducted a secondary analysis of the data from a single center retrospective cohort study in Japan conducted from March 2002 to January 2012, which included children diagnosed with ALTE at a pediatric emergency department (ED) in Tokyo. Among 112 ALTE patients, 18 (16%) had recurrences and 94 (84%) did not. Symptoms of respiratory tract infection (RTI) were more frequent in the recurrent group than in the non-recurrent group (44 vs. 14% p = 0.0055), and the proportion of patients triaged as level 1 was larger in the recurrent group than in the non-recurrent group (31 vs. 7%, p = 0.0312). Pallor was observed more frequently in the recurrent group than in the non-recurrent group (100 vs. 76%, p = 0.0216). Multivariate analysis demonstrated that the independent risk factors of recurrent ALTE were respiratory tract infection symptoms (OR, 5.02; 95% CI, 1.48-16.98). CONCLUSION: ALTE patients who had RTI symptoms at the ED visit for first ALTE should be admitted for close observation of potential recurrences. What is Known: • Approximately 10% of ALTE patients experienced recurrence of ALTE episodes. • The risk of recurrent ALTE is one of the major consideration for the management of ALTE patients at the ED because these patients have higher rates of serious underlying diseases which require interventions. What is New: • Respiratory infection symptoms at ED presentation can be independent risk factors for recurrent ALTE.

Incidence of apparent life-threatening events and post-neonatal risk factors.

AIM: Even though a standard clinical definition for an apparent life-threatening event (ALTE) was established more than two decades ago, the specific International Classification of Disease (ICD) code was firstly included only in 2012. This study estimated the incidence of ALTEs in Northern Italy, together with features and risk factors. METHODS: We used the Lombardy Region Hospital Discharge Records (HDR) database to estimate the cumulative incidence for ALTE during 2002-2006 and drew up a risk profile by comparing cases with and without ALTE who were followed in infancy. RESULTS: There were 246 infants registered in the HDR with ALTE putative diagnostic codes, suggesting a cumulative incidence of 4.1 per 1000 live births in the study area. Of the 148 cases with clinical co-morbidities, 31% had gastroesophageal reflux and 7% had acute respiratory infections. We analysed follow-up data from 15 ALTE cases and 1619 healthy infants and found that the significant risk factors were gastroesophageal reflux and a family history of sudden death. CONCLUSION: We established the regional incidence of ALTE and found risk factors in infants considered healthy in the first week of life and without pathological perinatal conditions. The systematic use of the specific ALTE ICD code (R68.13, ICD-10-CM) and common knowledge about ALTE diagnostic guidelines are clearly needed.

B12 deficiency is common in infants and is accompanied by serious neurological symptoms.

AIM: Adverse neurological symptoms have been linked to vitamin B12 deficiency in infants. This explorative study described the clinical presentation associated with vitamin B12 deficiency in this age group. METHODS: The study comprised infants who were born between 2004 and 2012 and were tested for vitamin B12 levels after they were admitted to a hospital with neurological symptoms at less than one year of age. Vitamin B12 deficiency was defined as low cobalamin in serum and/or increased homocysteine and/or increased methylmalonate. It was diagnosed according to the applicable International Classification of Diseases, 10th revision, and recorded as vitamin B12 deficiency in the medical records. All information was retrieved from medical records and compared to symptomatic infants with normal levels. RESULTS: Of the 121 infants tested, 35 had vitamin B12 deficiency and 86 had normal levels. Vitamin B12 deficiency was diagnosed at an average age of 1.7 months and was more common among boys. Seizures and apparent life-threatening events were the most common symptoms among infants with B12 deficiency compared to infants with normal levels. CONCLUSION: Vitamin B12 deficiency was more common in infants than we expected and presented with severe symptoms, such as seizures and apparent life-threatening events.

Real Time Apnoea Monitoring of Children Using the Microsoft Kinect Sensor: A Pilot Study.

The objective of this study was to design a non-invasive system for the observation of respiratory rates and detection of apnoea using analysis of real time image sequences captured in any given sleep position and under any light conditions (even in dark environments). A Microsoft Kinect sensor was used to visualize the variations in the thorax and abdomen from the respiratory rhythm. These variations were magnified, analyzed and detected at a distance of 2.5 m from the subject. A modified motion magnification system and frame subtraction technique were used to identify breathing movements by detecting rapid motion areas in the magnified frame sequences. The experimental results on a set of video data from five subjects (3 h for each subject) showed that our monitoring system can accurately measure respiratory rate and therefore detect apnoea in infants and young children. The proposed system is feasible, accurate, safe and low computational complexity, making it an efficient alternative for non-contact home sleep monitoring systems and advancing health care applications.

Syncope is a frequently under-diagnosed condition in infants and toddlers and has similar features to those seen in adolescents and adults.

AIM: Vagal syncope may not be readily recognised by the caregivers of younger children, often leading to extensive diagnostic evaluation. Our aim was to determine the characteristics of syncope in younger children and to assess whether this age group was more prone to undergoing extensive diagnostic work-ups and receiving wrong aetiological diagnoses. METHODS: We collected clinical data on children up to six years of age, referred to our paediatric neurology clinic between 2007 and 2014 following one or more episodes of sudden loss of consciousness. RESULTS: A family history of syncope was present in 59.5% of the 37 children, and a trigger for syncope was identified in 30 children. Most of the episodes were short, with witnesses reporting an immediate or quick recovery. Most of the children underwent diagnostic procedures, particularly an electroencephalogram, and all the results were normal. Epilepsy did not develop in any of these cases. Syncope recurred in 22 patients during a two-year follow-up. CONCLUSION: Vagal syncope had similar features in toddlers and young children to those seen in adolescents and adults. Its diagnosis should be considered following loss of consciousness due to an identifiable trigger and rapidly regaining consciousness to avoid unnecessary diagnostic procedures and hospitalisation.

Updated Swedish advice on reducing the risk of sudden infant death syndrome.

UNLABELLED: This article reviews updated advice and factual material from the Swedish National Board of Health and Welfare on reducing the risk of sudden infant death syndrome. Issues covered by the guidance for parents and healthcare professionals include sleeping positions, smoking, breastfeeding, bed sharing and using pacifiers. CONCLUSION: The guidelines conclude that infants under three months of age are safest sleeping in their own cot and that a pacifier can be used when they are going to sleep.

Metabolic disease in 10 patients with sudden unexpected death in infancy or acute life-threatening events.

In order to determine the associations between sudden unexpected death in infancy (SUDI) or acute life-threatening events (ALTE) and inborn errors of metabolism, particularly organic acidemia and fatty acid oxidation disorders, we evaluated clinical features in patients with SUDI or ALTE. The subjects were infants between the ages of 7 days and 3 years who developed SUDI or ALTE between January 2004 and December 2013. They were then diagnosed as having inborn errors of metabolism on gas chromatography-mass spectrometry (GC/MS) and/or tandem mass spectrometry (MS/MS). The age distribution, onset forms, and clinical findings were evaluated during the acute phase. Inborn errors of metabolism were detected in three of 196 patients with SUDI, and in seven of 167 patients with ALTE. Of these 10 patients, nine had a history of poor feeding and somnolence during the neonatal period, and symptoms of infection such as cough, fever or vomiting during infancy. Routine laboratory tests during an acute phase indicated hyperammonemia, liver dysfunction, increased blood creatine kinase, acidosis, positive ketone bodies in urine or blood, or hypoglycemia. When SUDI or ALTE are encountered in the emergency unit, it is essential that a detailed medical history is taken, particularly with regard to the neonatal period, and that specific abnormalities are investigated on routine laboratory tests. Moreover, samples such as urine, serum, and filter paper blood specimens should be collected for GC/MS and/or MS/MS of organic acids and acylcarnitines, to identify inborn metabolic disorders.

Relationship between the Clinical Characteristics and Intervention Scores of Infants with Apparent Life-threatening Events.

We investigated the clinical presentations, diagnostic and therapeutic modalities, and prognosis from follow-up of infants with apparent life-threatening events (ALTE). In addition, the relationship between the clinical characteristics of patients and significant intervention scores was analyzed. We enrolled patients younger than 12 months who were diagnosed with ALTE from January 2005 to December 2012. There were 29 ALTE infants with a peak incidence of age younger than 1 month (48.3%). The most common symptoms for ALTE diagnosis were apnea (69.0%) and color change (58.6%). Eleven patients appeared normal upon arrival at hospital but 2 patients required cardiopulmonary resuscitation during the initial ALTE. The most common ALTE cause was respiratory disease, including respiratory infection and upper airway anomalies (44.8%). There were 20 cases of repeat ALTE and 2 cases of death during hospitalization. Four patients (15.4%) experienced recurrence of ALTE after discharge and 4 patients (15.4%) showed developmental abnormalities during the follow-up period. The patients with ALTE during sleep had lower significant intervention scores (P=0.015) compared to patients with ALTE during wakefulness and patients with previous respiratory symptoms had higher significant intervention scores (P=0.013) than those without previous respiratory symptoms. Although not statistically significant, there was a weak positive correlation between the patient's total ALTE criteria and total significant intervention score (Fig. 2, r=0.330, P=0.080). We recommend that all ALTE infants undergo inpatient observation and evaluations with at least 24 hr of cardiorespiratory monitoring, and should follow up at least within a month after discharge.

Transient renal dysfunction with reversible splenial lesion.

We report the case of a 6-month-old boy with transient renal dysfunction who had an intensified signal in the splenium of the corpus callosum on magnetic resonance imaging. He presented to hospital with fever and sudden disturbance of consciousness. Cerebrospinal fluid analysis did not show pleocytosis. The mild consciousness disturbance disappeared after 30 min, but the splenial signal persisted even after 8 days. Further, renal glucosuria, increased excretion of select amino acids, and abnormal fractional excretion of electrolytes were observed, indicating renal tubular dysfunction. The abnormal urinary findings spontaneously resolved by day 9 of hospitalization. The splenial lesion took 21 days to normalize. There were no signs of neurological complications 2 months later. This case suggests the possibility of renal involvement in splenial lesions.

Outcomes for the apparent life-threatening event infant.

Aim: To examine the outcome for apparent life-threatening event infants and the determining factors for that outcome. Methods: A retrospective review of 903 infants (0-12 months of age) presenting to the pediatric wards at Christchurch Hospital between 1985 and 1996 with events characterized by some combination of apnoea, change in color, and muscle tone. Events, resulting in 1088 admissions, were classified from medical record review according to the severity and underlying conditions, with risk factors and long-term outcomes examined. Results: The severity of events was reduced with implementing sudden infant death syndrome recommendations regarding the risk of prone sleeping. There were no sudden infant death syndrome deaths on home apnoea monitoring. Five apparent life-threatening event infants, not referred for home apnoea monitoring, subsequently died of sudden infant death syndrome. Two infants died and one suffered significant hypoxic insult when apnoea monitoring was interrupted under the age of 4 months. Asthma and neurodevelopmental conditions appeared to be over-represented subsequently in the apparent life-threatening event group. Conclusion: Identifying apparent life-threatening event infants at risk of sudden infant death syndrome lacked specificity. The use of apnoea home monitoring appeared protective in this cohort, but safe sleeping practices remained central for reducing sudden infant death syndrome risk.

Intussusception Initially Diagnosed as a Brief Resolved Unexplained Event (BRUE).

Brief resolved unexplained event (BRUE) are transient and worrying episodes observed in infants and are characterized by changes in skin color, breathing, muscle tone, and/or responsiveness. We describe the case of a female infant who was initially diagnosed with BRUE but was later determined to have intussusception. She presented to our emergency department with a transient pallor and a single episode of vomiting that resolved before her visit. Physicians did not detect any abnormalities on physical or laboratory examinations, so she was diagnosed with BRUE and discharged to be re-evaluated the next day. After returning home, she vomited several times. The patient revisited our hospital the following day and was definitively diagnosed with intussusception using ultrasonography, which was successfully treated using fluoroscopy-guided hydrostatic reduction. This case was initially diagnosed as a BRUE; however, re-evaluation helped in identifying the proper diagnosis of intussusception. Physicians should exercise caution when diagnosing patients with BRUE. When the diagnostic criteria are not completely met, follow-up should be conducted, assuming that the patient has a potentially serious condition.

Neonatal respiratory inhibition.

OBJECTIVE: To present information on neonatal respiratory inhibition (NRI) to the medical staff caring for infants. METHODS: The author reviewed investigations of the above conditions. NRI is defined as severe hypoxemia accompanied by clinical manifestations of central cyanosis and a decrease in SpO2 to less than 70%. Neonatal respiratory inhibition consists of respiratory inhibition after crying (RIAC), feeding hypoxemia, and respiratory inhibition after gastroesophageal reflux (RIGER). The infants were monitored continuously via pulse oximetry from birth until discharge. To identify the details of NRI, we analyzed detailed notes taken by both parents and medical staff during monitoring using specific software designed to interpret pulse oximetry measurements. RESULTS: Among infants who weighed at least 2000 g and who were born at a gestational age of at least 36 weeks, NRI was observed in ∼50% of infants, including RIAC in ∼25%, feeding hypoxemia in 40%, and RIGER in 2 ∼ 4%, respectively. Among the infants with NRI, ∼40% experienced one or more episodes of prolonged cyanosis for at least 60 s. RIAC, feeding hypoxemia, and RIGER is significantly associated with each other. Among perinatal factors, NRI was related to maternal diabetes mellitus, twin pregnancy, asymmetric intrauterine growth restriction, threatened premature labor, cesarean section, shorter gestational periods, and abnormal ultrasound findings, including increased echogenicity in the ganglionic eminence (GE), a cyst in the GE, a subependymal cyst, and slight lateral ventricular enlargement. Almost all infants with RIAC and RIGER, even those with severe cases, recovered until discharge around day 5. Despite the provision of nursing guidance in feeding control, ∼60% of infants experienced feeding hypoxemia continuously. The more frequently the infants experienced feeding hypoxemia, the more severe the degree of feeding hypoxemia became. Breastfeeding reduced the frequency and degree of feeding hypoxemia compared to bottle feeding. Approximately 40% of infants with feeding hypoxemia required additional feeding control after being discharged. CONCLUSIONS: NRI is very common and occurs in many infants worldwide. The infants with NRI experienced repeated severe hypoxemia due to RIAC, feeding hypoxemia, and RIGER after birth. Breastfeeding and careful feeding control should be recommended to mothers of infants with repeated feeding hypoxemia. Spreading knowledge about NRI worldwide is very important.

Apparent Life-Threatening Event in an Infant with SARS-CoV-2 Infection.

The 2019 novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global outbreak of infection. In general, children with coronavirus disease-2019 have been reported to show milder respiratory symptoms than adult patients. Here, we have described a case of a SARS-CoV-2-infected infant who presented to our hospital with a severe episode of an apparent life-threatening event (ALTE). An 8-month-old, otherwise healthy female infant presented to our hospital because of a sudden cardiopulmonary arrest. Approximately 1 h before this episode, the patient showed no symptoms, except a worse humor than usual. On arrival at our hospital, the patient had severe acidosis, but there were no clear signs of inflammatory response. Chest computed tomography showed weak consolidations in the upper right lung and atelectasis in the lower left lung. No signs of congenital heart disease or cardiomyopathy were observed on echocardiography, and no significant arrhythmia was observed during the clinical course. However, SARS-CoV-2 RNA was detected by real-time reverse transcription polymerase chain reaction in tracheal aspirate and urine samples. Although the assessment of further similar cases is indispensable, this case suggests that SARS-CoV-2 infection may be an underlying factor in the pathophysiology of ALTE.

Diagnostic Evaluation Low Yield for Patients with a Lower-Risk Brief Resolved Unexplained Event.

In contrast to patients with an apparent life-threatening event (ALTE), the American Academy of Pediatrics recommends very limited evaluation for patients categorized as lower-risk brief resolved unexplained event (BRUE). This retrospective review aims to explore potential missed diagnostic opportunities for patients with a lower-risk BRUE (n = 10) through comparison with a subset of patients with ALTE (n = 72). None of the patients with a lower-risk BRUE had laboratory, imaging or ancillary studies that were diagnostic. Among patients with ALTE, 5 had laboratory and 3 had imaging studies that were diagnostic. None of the patients with a lower-risk BRUE had recurrent events during hospitalization or a serious underlying diagnosis identified within the 90 day follow-up period. As recommended by the AAP, patients with a lower-risk BRUE do not need diagnostic evaluation and can be discharged home with outpatient follow-up.

A Common 3'UTR Variant of the PHOX2B Gene Is Associated With Infant Life-Threatening and Sudden Death Events in the Italian Population.

Heterozygous mutations in the Paired like homeobox 2b (PHOX2B) gene are causative of congenital central hypoventilation syndrome (CCHS), a rare monogenic disorder belonging to the family of neurocristopathies and due to a defective development of the autonomic nervous system. Most patients manifest sudden symptoms within 1 year of birth, mainly represented by central apnea and cyanosis episodes. The sudden appearance of hypoxic manifestations in CCHS and their occurrence during sleep resemble two other unexplained perinatal disorders, apparent life-threatening event (ALTE) and sudden and unexpected infant death (SUID), among which the vast majority is represented by sudden infant death syndrome (SIDS). Differently from CCHS, characterized by Mendelian autosomal dominant inheritance, ALTE and SIDS are complex traits, where common genetic variants, together with external factors, may exert an additive effect with symptoms likely manifesting only over a "threshold." Given the similarities observed among the three abovementioned perinatal disorders, in this work, we have analyzed the frequency of PHOX2B common variants in two groups of Italian idiopathic ALTE (IALTE) and SUIDs/SIDS patients. Here, we report that the c*161G>A (rs114290493) SNP of the 3'UTR PHOX2B (i) became overrepresented in the two sets of patients compared to population matched healthy controls, and (ii) associated with decreased PHOX2B gene expression, likely mediated by miR-204, a microRNA already known to bind the 3'UTR of the PHOX2B gene. Overall, these results suggest that, at least in the Italian population, the SNP c*161G>A (rs114290493) does contribute, presumably in association with others mutations or polymorphisms, to confer susceptibility to sudden unexplained perinatal life-threatening or fatal disorders by increasing the effect of miR-204 in inducing PHOX2B expression down-regulation. However, these are preliminary observations that need to be confirmed on larger cohorts to achieve a clinical relevance.

Cytotoxic lesions of the corpus callosum in children: Etiology, clinical and radiological features, and prognosis.

OBJECTIVES: Cytotoxic lesions of the corpus callosum (CLOCCs) are secondary lesions associated with entities like infection manifested by restricted diffusion on diffusion-weighted cranial magnetic resonance imaging. Our objectives are to evaluate the clinic-radiological spectrum of pediatric patients with cytotoxic lesions of the corpus callosum (CC). METHODS: Children (0-18 years) admitted between February 2017 and May 2020 with splenial lesions showing diffusion restriction on MRI, either isolated or within involvement of other parts of the brain, were included retrospectively. The primary lesions of the CC (e.g. acute disseminated encephalomyelitis, acute ischemic infarction, and glioblastoma multiforme) were excluded. CLOCCs were divided into infection-associated, metabolic disorder-associated, and trauma-associated lesions, as well as CLOCCs involving other entities. Data were collected from the medical databases. RESULTS: Forty-one patients were determined to have CLOCCs. Twenty-five (61%) were infection-associated, nine (22%) were trauma-associated, and three (7%) were metabolic disorder-associated cases, including 2 inherited disorders of metabolism. There were four (10%) patients with other entities, three with epilepsy, and one had an apparent life-threatening event. Six patients had a known etiology among the infection-associated group; one had multisystem inflammatory syndrome caused by COVID-19 and one had been infected by COVID-19 without any complications. All the infection-associated patients with isolated splenial lesions recovered totally, although six patients required intensive care hospitalization. Four trauma-associated patients had sequela lesions. CONCLUSIONS: CLOCCs are associated with a spectrum of diseases, including the new coronavirus, COVID-19 infection. Infection-associated CLOCCs has the best prognosis, although severe cases may occur. Sequelae are possible based on the etiology.