Acute Encephalopathy Research Articles

Acute Flaccid Paralysis, Seizures, and Encephalopathy in a Pediatric Patient With Influenza A and Coronavirus Disease 2019 Infection

Acute Flaccid Paralysis, Seizures, and Encephalopathy in a Pediatric Patient With Influenza A and Coronavirus Disease 2019 Infection

Chapter 24 - Toxic leukoencephalopathies

Toxic-metabolic encephalopathies are a group of disorders in which an exogenous or endogenous substance leads to transient or permanent neuronal damage. It is an important cause of potentially reversible acute encephalopathy syndrome. The signs and symptoms of toxic encephalopathies may be relatively nonspecific, and toxicologic tests are not always widely available. Imaging plays a key role in determining the most probable diagnosis, pointing to the next steps of investigation, and providing prognostic information. In this chapter, we review the main acquired toxic-metabolic leukoencephalopathies, commenting on their pathophysiology, imaging patterns, and rationale for an adequate diagnosis in detail.

A RARE CAUSE OF ENCEPHALOPATHY IN CHILDREN: PRES SYNDROME

Background: Major clinical symptoms of posterior reversible encephalopathy syndrome include headache, mental status changes, visual disturbances, seizures, especially in the posterior cerebral region, and radiographic findings of vasogenic edema, especially in the posterior cerebellar region. Case Report: We present our 6-year-old patient with chronic renal failure. admitted to our pediatric emergency department with an acute hypertensive crisis. Generalized tonic-clonic seizures and mental status changes were accompanied in the follow-up of the patient whose GCS was 11; With symptomatic treatment, regression in both clinical complaints and imaging findings of our patient is consistent with Posterior reversible encephalopathy syndrome (PRES). Conclusion: It is imperative to consider PRES syndrome as a differential diagnosis when pediatric patients exhibit symptoms of acute encephalopathy. It is crucial to emphasize the critical nature of early diagnosis and treatment, as well as the potential for complete recovery without sequelae.

Psychiatric Manifestations Caused by Mycoplasma pneumoniae Encephalitis Mimicking Autoimmune Encephalitis

AbstractA significant etiological factor for upper respiratory tract infections and community-acquired pneumonia is Mycoplasma pneumoniae. The incidence of extrapulmonary neurological problems in infected patients has been shown to range from 0.1 to 7%, often manifesting within a timeframe of 2 to 14 days following the onset of respiratory symptoms. Acute disseminated encephalomyelitis, Guillain–Barré syndrome, and transverse myelitis are among the immune-mediated illnesses encompassed under the syndrome. A 3-year-old male child exhibited symptoms of acute encephalopathy and behavioral disruption subsequent to an infection caused by M. pneumoniae. He presented with irritability, sleep disturbance, slurred speech, increased appetite, episodes of unresponsiveness, moving in circles, staring, and laughing episodes lasting for up to 15 to 30 minutes over a week. He lost his previous toilet training. Abnormal jerks were noted while awake and asleep. Symptoms were preceded by exposure to vague febrile illness 3 weeks prior to presentation. The patient's brain magnetic resonance imaging was normal. Electroencephalography showed a slow background with no epileptiform discharges. Cerebrospinal fluid analysis and polymerase chain reaction for viruses were negative. The workup for autoimmune encephalitis was negative. Mycoplasma serology IgM was detected. Marked improvement was noted after methylprednisolone pulse therapy, intravenous immunoglobulin, valproic acid, and azithromycin. In conclusion, our report serves as a reminder that M. pneumoniae infection is a possible cause of encephalopathy and behavioral disturbance in children. Early recognition and promotion of immunomodulatory and antimicrobial treatment can prevent the affected child from experiencing different levels of long-lasting impairments in cognitive, physical, or visual abilities.

Acute subdural hematoma in an infant with a biphasic clinical course and late reduced diffusion

Background: Bright tree appearance (BTA) is a characteristic finding on diffusion-weighted magnetic resonance (MR) imaging with transient high intensity in the white matter. BTA is characteristic of infants with acute encephalopathy with biphasic seizures, but it has also been reported in head trauma cases. In this report, we describe an infant case of traumatic brain injury that demonstrated a biphasic clinical course and late reduced diffusion (TBIRD). Case Description: A 5-month-old boy suffered from head trauma and developed coma and seizures. Computed tomography scans revealed acute subdural hematoma on the right side. He underwent an emergency operation to remove the hematoma but subsequently had seizure clusters for three days. Diffusion-weighted MR imaging revealed BTA in the right cerebral hemisphere. He was treated with antiepileptic agents and fully recovered to pre-injury condition, and MR imaging no further revealed any BTA 20 days after head trauma. He developed no complications at the 10-month postoperative follow-up. Conclusion: We reported a case of TBIRD following head trauma in the infant. The pathogenesis remains unclear, but we consider the possibility of biphasic seizures in infant head trauma cases, and we should appropriately administer the anticonvulsants and carefully check for MR imaging.

Recurrent exercise-induced acute kidney injury associated with hypouricemia: a case report and literature review

BackgroundHereditary renal hypouricemia (RHUC) is a heterogenous disorder characterized by defective uric acid (UA) reabsorption resulting in hypouricemia and increased fractional excretion of UA. RHUC is an important cause of exercise-induced acute kidney injury (EIAKI), nephrolithiasis and posterior reversible encephalopathy syndrome (PRES). We present here an unusual case of a patient with RHUC who presented with recurrent EIAKI and had two heterozygous mutations in the SLC2A9 gene.Case presentationA 43-year old man was admitted to our clinic because of bilateral loin pain, nausea and sleeplessness for 3 days after strenuous exercise. The laboratory results revealed increased levels of blood urea nitrogen (BUN) (15 mmol/l) and serum creatinine (Scr) (450 μmol/l), while the UA level was extremely low at 0.54 mg/dl, and his fractional excretion of urate (FE-UA) was 108%. The patient had an episode of acute kidney injury after playing soccer approximately 20 years ago, and on routine physical examination, his UA was less than 0.50 mg/dl. In view of the marked hypouricemia and high FE-UA, a diagnosis of RHUC was suspected, which led us to perform mutational screening of the SLC22A12 and SLC2A9 genes. DNA sequencing revealed no mutation in SLC22A12 gene, but two heterozygous mutations in the SLC2A9 gene.ConclusionsThis is a rare report of a patient with RHUC2 due to the mutation of SLC2A9. And this unique symptom of EIAKI and decreased or normal serum concentrations of UA warrant more attention as an early cue of RHUC.

Unbound Bilirubin and Acute Bilirubin Encephalopathy in Infants Born Late Preterm and Term with Significant Hyperbilirubinemia

To compare the association of unbound bilirubin (UB), total serum bilirubin (TSB), and bilirubin:albumin molar ratio (BAMR) with acute bilirubin encephalopathy (ABE), as assessed by bilirubin-induced neurologic dysfunction (BIND) score, in infants with significant hyperbilirubinemia (TSB ≥20mg/dL or underwent exchange transfusion). In this prospective cohort study, infants ≥34weeks of gestational age with significant hyperbilirubinemia during the first 2 postnatal weeks were eligible, unless they had craniofacial malformations, chromosomal disorders, TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus and herpes simplex) infections, surgery, or a family history of congenital deafness. TSB, serum albumin, and UB were measured at hospital admission using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Infants were evaluated on admission for ABE using a standardized neurologic examination and assigned a BIND score by trained physicians. Infants with a total BIND score of 0 were deemed to not have ABE, whereas those with a score ≥1 were deemed to have ABE. A total of 151 infants were studied, among whom 37 (24.5%) had ABE. Of these, 19 had mild ABE (BIND score 1-3) and 18 had moderate-to-severe ABE (BIND score 4-9). On logistic regression, UB, but not TSB or BAMR, was associated with ABE (aOR 1.64; 95% CI 1.17-2.3). On ordered logistic regression, UB, but not TSB or BAMR, was associated with severity of ABE (aOR 1.76; 95% CI 1.28-2.4). Our findings of the association between UB and ABE indicate that BIND scoring may be useful for evaluation of ABE in infants ≥34weeksof gestational age.

Risk factors for post-encephalopathic epilepsy in patients with acute encephalopathy with biphasic seizures and late reduced diffusion

BackgroundPost-encephalopathic epilepsy (PEE) is a serious complication of acute encephalopathy syndromes, and is more frequent in patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) than in children with acute encephalopathy. However, a risk factor analysis using laboratory findings in the acute phase of AESD has not yet been performed. Therefore, the present study examined risk factors of AESD-related PEE using laboratory parameters in the acute phase of AESD. MethodsWe retrospectively screened 27 pediatric patients with AESD for inclusion, and enrolled 20 (“the PEE group”, n = 6; “the non-PEE group”, n = 14) according to inclusion criteria. ResultsThe incidence of AESD-related PEE was 30 %, and the median duration from the onset of AESD to the development of PEE was 2.5 months (range, 1–32). The most common types of seizures were focal seizures, epileptic spasms, and startle seizures: 4 out of 6 patients (66.7 %) had intractable epilepsy. The median values of alanine aminotransferase (ALT) in the 1st and 2nd seizure phases of AESD and aspartate aminotransferase (AST) in the 2nd seizure phase were significantly higher in the PEE group than in the non-PEE group (p < 0.01). ConclusionsThis is the first study to report higher serum levels of ALT and AST at the onset of AESD as risk factors for AESD-related PEE. We also provided a detailed description on the clinical characteristics on AESD-related PEE, which are consistent with previous findings.

Acute necrotising encephalopathy of childhood – A narrative review

Acute encephalitis syndrome (AES) can pose challenges in diagnosis and management. Infection-associated acute encephalopathies (AEs) are increasingly being recognised and closely mimic AES. We provide an overview of various causes of AE and a detailed review of the clinical laboratory, including neuroradiologic features of acute necrotising encephalopathy (ANE) of childhood, its treatment, and outcome. A literature search was performed using the keywords’ Paediatric acute encephalopathy’ and ‘acute necrotising encephalopathy of childhood’ in PubMed and Google Scholar, and all relevant articles from 2001 to 2021 (including case reports) in the English language were reviewed. Relevant and major articles before 2001 were also reviewed. Infection-associated AEs remain under-recognised and pose a challenge in neurocritical care. Judicious use of neuroimaging and laboratory tests aids diagnosis of specific clinicoradiological AE syndromes. We need to suspect ANE if fever (esp. viral illness) is followed by the rapid deterioration in the sensorium associated with tone abnormalities or seizures. Neuroimaging typically shows symmetric lesions in the thalami, internal capsule or cerebellar white matter and tegmentum. While definite treatment guidelines are not available, several interventions have shown potential benefits in supporting patients with ANE. These include standard supportive care, immunotherapy, especially high-dose pulse methylprednisolone, therapeutic hypothermia initiated before 12 h to reduce cytokines, and anti-oedema measures. However, it is essential to note that outcomes in ANE can be highly variable, with a mortality rate of approximately 30% and only 10% experiencing intact survival. Predictors of poor outcome include age younger than one year, increased cerebrospinal fluid protein/transaminases, the presence of haemorrhage/cavitation/brainstem lesions on neuroimaging, and a high ANE severity score.

DeltaScan for the Assessment of Acute Encephalopathy and Delirium in ICU and non-ICU Patients, a Prospective Cross-Sectional Multicenter Validation Study

To measure the diagnostic accuracy of DeltaScan: a portable real-time brain state monitor for identifying delirium, a manifestation of acute encephalopathy (AE) detectable by polymorphic delta activity (PDA) in single-channel electroencephalograms (EEGs). Prospective cross-sectional study. Six Intensive Care Units (ICU's) and 17 non-ICU departments, including a psychiatric department across 10 Dutch hospitals. 494 patients, median age 75 (IQR:64-87), 53% male, 46% in ICUs, 29% delirious. DeltaScan recorded 4-minute EEGs, using an algorithm to select the first 96 seconds of artifact-free data for PDA detection. This algorithm was trained and calibrated on two independent datasets. Initial validation of the algorithm for AE involved comparing its output with an expert EEG panel's visual inspection. The primary objective was to assess DeltaScan's accuracy in identifying delirium against a delirium expert panel's consensus. DeltaScan had a 99% success rate, rejecting 6 of the 494 EEG's due to artifacts. Performance showed and an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.86 (95% CI: 0.83-0.90) for AE (sensitivity: 0.75, 95%CI=0.68-0.81, specificity: 0.87 95%CI=0.83-0.91. The AUC was 0.71 for delirium (95%CI=0.66-0.75, sensitivity: 0.61 95%CI=0.52-0.69, specificity: 72, 95%CI=0.67-0.77). Our validation aim was an NPV for delirium above 0.80 which proved to be 0.82 (95%CI: 0.77-0.86). Among 84 non-delirious psychiatric patients, DeltaScan differentiated delirium from other disorders with a 94% (95%CI: 87-98%) specificity. DeltaScan can diagnose AE at bedside and shows a clear relationship with clinical delirium. Further research is required to explore its role in predicting delirium-related outcomes.

Correlation between Persistent Serum Lactate Elevation and Brain Magnetic Resonance Imaging Abnormalities in Children with Status Epilepticus

Purpose: This study was conducted to evaluate the correlation between persistent serum lactate elevation and brain magnetic resonance imaging (MRI) in children with status epilepticus (SE). Methods: In this prospective analytical study, serum lactate levels were measured 24 hours after episodes of SE, and brain MRI was performed within 7 to 14 days after SE termination. MRI abnormalities were classified as acute encephalopathy (AE) grade I to III. The Kruskal-Wallis test was utilized for statistical analysis. Results: The study included 42 participants with SE, of whom 85.70% were boys, with a mean age of 4.94 years. Viral encephalitis was the most common diagnosis, accounting for 47.60% of cases. Elevated serum lactate levels were detected in 71.40% of patients, and approximately 47.60% exhibited abnormal MRI findings consistent with AE grade I. The median serum lactate levels for AE grades I, II, and III were 1.50, 3.10, and 0.78 mmol/L, respectively. Two patients died, and 66.70% experienced neurologic sequelae. A significant correlation (&lt;i&gt;P&lt;/i&gt;=0.021) was observed between persistent serum lactate elevation and abnormal brain MRI findings. Conclusion: In children with SE, AE grade I was the most common neuroimaging pattern observed, and persistently elevated serum lactate level was correlated with abnormal brain MRI findings.

Effect of esketamine pretreatment on acute sepsis-associated encephalopathy

PurposeEsketamine, the S(+) enantiomer of ketamine, exhibits good anesthetic efficacy and controllability; however, its potential clinical applications, particularly in sepsis-associated encephalopathy (SAE), remain underexplored. SAE involves the development of diffuse brain dysfunction after sepsis, leading to markedly increased sepsis-related disability and mortality. In this study, we investigated the effects of esketamine pretreatment on acute SAE. MethodsMice were randomly divided into four groups: control (C, n = 22), acute SAE (L, n = 22), esketamine pretreatment + acute SAE (EL, n = 22), and nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor (ML385) + esketamine pretreatment + acute SAE (N + EL, n = 22). Acute SAE was established using intraperitoneal (i.p.) injection of lipopolysaccharide (LPS; 10 mg/kg), while controls received equal amounts of saline. The EL group received daily i.p. injections of esketamine (10 mg/kg) for 5 consecutive days, followed by LPS on day 6. The N + EL group received i.p. injections of ML385 (30 mg/kg) 1 h before esketamine pretreatment. The remainder of treatment followed the same protocol as the EL group. Behavioral tests were performed 24 h post-LPS injection, and whole blood and brain tissues were collected for further analysis. ResultsEsketamine improved sepsis symptoms, 7-day survival, and spatial cognitive impairment, without altering locomotor activity. Moreover, esketamine reversed the LPS-induced increase in serum S100 calcium-binding protein β and neuron-specific enolase levels and reduced hippocampal neuroinflammation, oxidative stress, and neuronal apoptosis in the EL group. However, these neuroprotective effects of esketamine were reversed by ML385. ConclusionThe results of our study suggest that esketamine pretreatment mitigates acute SAE, highlighting the involvement of the Nrf2/heme oxygenase-1 pathway in mediating its neuroprotective effects.

Informal gold miners with mercury toxicity: Novel asymmetrical neurological presentations

Mercury is a highly toxic heavy metal that may cause neurological, respiratory, gastrointestinal and dermatological illnesses. Previously described neurological manifestations of mercury toxicity are symmetrical, and include a pancerebellar syndrome, generalised seizures and encephalopathy. Mercury is used in the gold mining process, and in artisanal or illicit gold mining, often without necessary protection. Here we describe the cases of two artisanal gold miners from western Johannesburg, South Africa, who presented with atypical neurological manifestations of mercury toxicity. Patient 1 presented with focal seizures, an asymmetrical cerebellar syndrome and an acute encephalopathy. Patient 2 had unilateral cerebellar ataxia. Both patients had toxic mercury levels, with no other cause identified for their symptoms. Patient 1 responded well to chelation therapy, but patient 2 refused admission and further medical treatment. The neurological manifestations of mercury toxicity are typically symmetrical, whereas our two patients presented with markedly asymmetrical features. It is important to maintain a high index of suspicion for mercury poisoning, even in patients with atypical and unilateral or asymmetrical presentations. A prompt diagnosis and the commencement of early chelation therapy have the potential to produce good outcomes.

Antenatal jaundice instruction and acute bilirubin encephalopathy in Nigeria

BackgroundAcute Bilirubin Encephalopathy (ABE) is common in Nigeria. Parents’ inability to recognize jaundice and delays in seeking care are significant barriers to its prevention.MethodsWe compared associations of (1) interactive antenatal maternal jaundice instruction with postnatal reinforcement, (2) standard postnatal instruction, and (3) no maternal instruction with the incidence of ABE among 647 jaundice admissions stratified for risk factors identified in initial descriptive analysis.ResultsEighty-three (83/647;12.8%) admissions developed ABE including eleven jaundice-related deaths. ABE was present at admission in 20/22 (90.9%) if mothers received no jaundice instruction and no antenatal care, 42/182 (23.1%) if received antenatal care but no instruction, 16/95 (16.8%) if received postnatal instruction only, and 4/337 (1.2%) if mothers received both antenatal and postnatal instruction (p < .001). ABE was highly associated with out-of-hospital delivery, number of antenatal clinic visits, and birth attendant, but these risks were mitigated by antenatal/postnatal instruction. Admission rates with bilirubin levels below treatment guidelines (12 mg/dL) were higher following instruction (30.7%) than with no instruction (14.4%). Limiting subjects to those meeting admission criteria increased ABE rates in all groups without altering conclusions.ConclusionInteractive antenatal instruction with postnatal reinforcement resulted in timely care seeking and a lower incidence of ABE.ImpactEmpowering mothers to participate in neonatal jaundice management is critical in low-income countries where jaundice monitoring and follow up are unreliable.Instructing mothers about jaundice in antenatal clinics with postnatal reinforcement is more effective than standard postpartum instruction in facilitating jaundice detection, timely care seeking, and lowering the incidence of acute bilirubin encephalopathy (ABE).Antenatal training also mitigates risks for ABE associated with out-of-hospital deliveries, limited antenatal care, and unskilled birth attendants.Impact: Adding structured jaundice instruction in antenatal clinics could greatly reduce bilirubin induced brain injury in countries where ABE is common.

Periodic Discharges in Critically Ill Children: Predictors and Outcome.

We aimed to identify clinical and EEG monitoring characteristics associated with generalized, lateralized, and bilateral-independent periodic discharges (GPDs, LPDs, and BIPDs) and to determine which patterns were associated with outcomes in critically ill children. We performed a prospective observational study of consecutive critically ill children undergoing continuous EEG monitoring, including standardized scoring of GPDs, LPDs, and BIPDs. We identified variables associated with GPDs, LPDs, and BIPDs and assessed whether each pattern was associated with hospital discharge outcomes including the Glasgow Outcome Scale-Extended Pediatric version (GOS-E-Peds), Pediatric Cerebral Performance Category (PCPC), and mortality. PDs occurred in 7% (91/1,399) of subjects. Multivariable logistic regression indicated that patients with coma (odds ratio [OR], 3.45; 95% confidence interval [CI]: 1.55, 7.68) and abnormal EEG background category (OR, 6.85; 95% CI: 3.37, 13.94) were at increased risk for GPDs. GPDs were associated with mortality (OR, 3.34; 95% CI: 1.24, 9.02) but not unfavorable GOS-E-Peds (OR, 1.93; 95% CI: 0.88, 4.23) or PCPC (OR, 1.64; 95% CI: 0.75, 3.58). Patients with acute nonstructural encephalopathy did not experience LPDs, and LPDs were not associated with mortality or unfavorable outcomes. BIPDs were associated with mortality (OR, 3.68; 95% CI: 1.14, 11.92), unfavorable GOS-E-Peds (OR, 5.00; 95% CI: 1.39, 18.00), and unfavorable PCPC (OR, 5.96; 95% CI: 1.65, 21.46). Patients with coma or more abnormal EEG background category had an increased risk for GPDs and BIPDs, and no patients with an acute nonstructural encephalopathy experienced LPDs. GPDs were associated with mortality and BIPDs were associated with mortality and unfavorable outcomes, but LPDs were not associated with unfavorable outcomes.

COVID-19 and Brain complications in adult and pediatric patients: A review on neuroimaging findings

In this review, we will discuss the neuroimaging findings of patients with COVID-19 from the outbreak (late December 2019) to the end of October 2021. PubMed, Scopus, Google Scholar, Science Direct, ProQuest, Web of Science and the World Health Organization database (January 01, 2020, to October 30, 2021) were searched for related published articles. In each of the databases, the appendix search strategies were performed and the below keywords were used: COVID-19”OR“coronavirus disease 2019” AND “brain MRI” OR “brain magnetic resonance imaging” OR “brain CT” OR “neuroimaging”. In total, neuroimaging findings of 1550 patients, with ages from 1-96 years, were analyzed. Most brain neuroimaging findings include hyperintensity, Cerebral venous thrombosis, intraventricular and subarachnoid hemorrhage, infarction, leukoencephalopathy, acute ischemic strokes and posterior reversible encephalopathy syndrome (PRES) in adult patients and severe encephalopathy, stroke, infarction, CNS infection/demyelination, neuritis or polyradiculitis, venous thrombosis, Guillain-Barré syndrome, and longitudinally extensive myelitis, and myositis in pediatric patients. Our findings showed that the most important complication of the coronavirus is not just respiratory complications, because although transiently, COVID-19-related brain complications are seen in pediatrics as well as adults, and families should pay more attention to health care.

Prophylactic Minocycline for Delirium in Critically Ill Patients: A Randomized Controlled Trial

BackgroundDelirium is a potentially severe form of acute encephalopathy. Minocycline has neuroprotective effects in animal models of neurological diseases; however, data from human studies remain scarce. Research QuestionDoes the neuroprotective effect of minocycline prevent delirium occurrence in critical ill patients? Study design and MethodsThis study was a randomized, placebo-controlled, double-blind trial conducted in four Intensive Care Units (ICUs). Patients aged 18 years or older were eligible and randomized to receive minocycline (100 mg twice a day) or placebo. The primary outcome was delirium incidence within 28 days or before ICU discharge. Secondary outcomes included days in delirium during ICU stay, delirium/coma free days, length of mechanical ventilation, ICU length of stay, ICU mortality, and hospital mortality. The kinetics of different inflammatory (interleukin-1β, interleukin-6, interleukin-10, and C-reactive protein) and brain-related biomarkers (brain-derived neurotrophic factor and S-100B) were used as exploratory outcomes. ResultsA total of 160 patients were randomized, but one patients on the placebo group died before treatment, thus 159 patients were analyzed (minocycline, n=84; placebo, n=75). After the COVID-19 pandemic it was decided to early stop patient inclusion. There was a small but significant decrease in delirium incidence (17 (20%) patients in the minocycline arm compared to 26 (35%) patients in the placebo arm, P=0.043). No other delirium-related outcomes were modified by minocycline treatment. Unexpectedly, there was a significant decrease in hospital mortality (39% vs. 23%, P=0.029). Among all analyzed biomarkers, only plasma levels of C-reactive protein decreased significantly after minocycline treatment (F=0.75, P=0.78 within time; F=4.09, P=0.045 group⋅time). InterpretationOur findings in this rather small study signals a possible positive effect of minocycline on delirium incidence. Further studies are needed to confirm the benefits of this drug as a preventive measure in critically ill patients. Clinical Trial RegistrationNCT04219735

Gender Disparities in Outcomes of Autoimmune Hemolytic Anemia Admissions: An Analysis of the National Inpatient Sample

Introduction Autoimmune hemolytic anemia (AIHA) is a condition characterized by the immune destruction of red blood cells, which can necessitate hospitalization in severe cases. The purpose of this study is to compare outcomes of AIHA hospitalizations between genders. Methods We utilized the International Classification of Diseases (ICD) codes to identify all hospitalizations with the primary diagnosis of AIHA in the National Inpatient Sample (NIS) from 2002 to 2019. We excluded all pediatric (age &amp;lt; 18 years) and elective hospitalizations. We described the baseline characteristics of both groups including demographics and comorbidities. We fitted multivariable logistic regression models to compare outcomes between males and females while adjusting for age, race, and comorbidities. Results A total of 60,529 met the inclusion and exclusion criteria. The majority of these were females (59.1% vs 40.1%, p &amp;lt; 0.001). Males were older (median age 67 vs. 66 years, p &amp;lt; 0.001) and had more white race (73.4% vs. 67.9%, p &amp;lt; 0.001). The distribution of associated comorbidities also differed different between both groups ( (Table 1). On adjusted analysis, males had higher in-hospital mortality rates. They also had higher rates of most secondary outcomes; including rates of circulatory shock, need for mechanical ventilation, bacterial pneumonia, acute myocardial infarction, deep vein thrombosis, hemorrhagic stroke, acute kidney injury, and requiring new hemodialysis. Females had higher rates of urinary tract infections. No significant differences were found in the rates of requiring blood transfusions, sepsis, acute heart failure, pulmonary embolism, ischemic stroke, encephalopathy, and gastrointestinal bleeding (Figure 1). Furthermore, male hospitalizations were associated with higher costs (median [IQR] of $11,400 [6,700-20,500] vs. $10,000 [6,000- 17,200]) despite similar length of stay (median [IQR] of 4 days [3-7] vs. 4 days [3-7]). Conclusion Male patients hospitalized with AIHA experience poorer in-hospital compared to females. More research is essential to understand the underlying causes for these disparities and to tailor management to improve outcomes for both male and female AIHA patients.

Anemia Outside the Box: Nonimmune Intramedullary Hemolytic Anemia Driven By Vitamin B12 Deficiency

Introduction: Vitamin B12 and folate deficiencies are common etiologies of macrocytic anemia, mostly encountered with chronic alcohol use, and uncommon for healthy individuals with unremarkable medical history. The pathogenesis of the resulting anemia is described by two possible mechanisms: either ineffective erythropoiesis, driven by vitamin B12 deficiency, or more rarely, via nonimmune intramedullary hemolysis. We present a very rare case of severe vitamin B12 deficiency leading to nonimmune intramedullary hemolysis and highlight the diagnostic evaluation and tailored management. Case Presentation: A 49-year-old female with history of depression, chronic alcohol use and chronic nitrous oxide inhalation, presented with lethargy, hypotension and fevers with visual hallucinations, and was subsequently admitted for acute encephalopathy. Findings on physical examination included diminished proprioception and diminished sensation to fine touch, pinprick and vibration of the lower extremities with distal hyperreflexia of the patellar and Achilles tendon reflexes bilaterally. Lab work was notable for leukopenia and macrocytic anemia with a significant drop in hemoglobin to 9.6 from a baseline of 13.2 within 5 months and MCV of 103. Extensive investigation of encephalopathy was undertaken, of which we note infectious workup, prompted by the septic presentation, which showed Staphylococcus aureus bacteremia. On the other hand, the patient's anemia was concurrently investigated. Hemolysis workup was positive (LDH 394 U/L; direct bilirubin 1.6 mg/dL; haptoglobin&amp;lt;8 mg/dL; reticulocyte count 6.1%); however, schistocytes were low on peripheral smear (Figures 1 and 2). As such, nonimmune intramedullary hemolysis was suspected. Further anemia workup revealed severe vitamin B12 deficiency (75 ng/L), consistent with the physical exam findings, but normal folate levels. Of note, methylmalonic acid levels and homocysteine were also elevated (respectively 4.39 nmol/mL, and 142 umol/L). The constellation of the clinical presentation and all the laboratory findings confirmed a nonimmune intramedullary hemolytic process, elicited by vitamin B12 deficiency. This deficiency was thought to be multifactorial, mainly caused by chronic alcohol abuse, in addition to persistent nitrous oxide use. It was also suggested that hemolysis could be a consequence of drug-induced carboxyhemoglobinemia (level was 9.4%), whereby carboxyhemoglobin can form during the binding and release of nitric oxide from hemoglobin. Treatment was focused on replacing vitamin B12 with 1000 mcg daily intramuscular injections for 7 days, then weekly thereafter for 4 weeks, followed by monthly injections. Improvement of hemoglobin to 11.1 with improvement of neurologic exam findings were noted prior to discharge. Conclusion: Nonimmune hemolytic anemia must be included in the differential diagnosis when evaluating patients with anemia concurrent with vitamin B12 deficiency, mostly encountered with chronic alcohol use. Vitamin B12 supplementation remains the key treatment to correct this rare, but serious outcome of vitamin B12 deficiency.

409. Unvaccinated Adolescents Bear the Majority of Disease Burden of Severe COVID-19 Among Those Admitted to the Intensive Care Unit (ICU)

Abstract Background COVID-19 vaccination is one of the most important public health tools to prevent severe COVID-19. Methods COVID-19 vaccine (Pfizer-BioNTech) first received the U.S. Food and Drug Administration (FDA) Emergency use authorization (EUA) for individuals 16 years of age and older on 12/11/2020 and for 12-15 years of age on 5/10/2021. We evaluated clinical and epidemiologic characteristics of critically ill adolescents with COVID-19 admitted to the intensive care unit (ICU) at our tertiary-care centers in Northwestern Iowa (encompassing Sioux City and Sergeant Bluff locations) during the 1-year post-vaccination approval period from June 1, 2021- May 31, 2022. Adolescence was defined as age-group 12-21 years per WHO definition. Results Twenty-one adolescents were admitted to the ICU with a median age of 16 years (IQR 12-20 years) and male: female ratio of 1:1.3. The majority (77%) were admitted with COVID-19 related pneumonia and 10 developed hypoxemic respiratory failure; 19 of 21 (90%) adolescent patients admitted to the ICU during this period were unvaccinated and all adolescents developing respiratory failure (10/10, 100%) were unvaccinated. Majority of patients with respiratory failure (70%) required mechanical ventilation (MV). Seventy % of patients with respiratory failure were obese (BMI of &amp;gt;30); 40% of patients had two or more pre-existing comorbidities; those with BMI &amp;gt;40 were 4.3 times more likely to develop respiratory failure (p&amp;lt; 0.0001). Inflammatory markers were 5-20 times higher among patients with respiratory failure (p&amp;lt; 0.05); 60% of those with respiratory failure developed complications including ARDS, acute renal injury and cerebral anoxic encephalopathy. All with respiratory failure required parenteral steroids. Mean duration of ICU stay was significantly longer for patients with respiratory failure [14.6 (±1.7) days versus 7.5 (± 2.6) days, p&amp;lt; 0.0001)]. None of the patients died. After hospital discharge, 30% patients reported post COVID-19 fatigue at 3-month follow up. Conclusion Our results showed that all of the critically ill adolescent patients with COVID-19 associated hypoxemic respiratory failure were unvaccinated and majority developed complications. These results further emphasize importance of COVID-19 vaccination efforts for adolescents. Disclosures All Authors: No reported disclosures