The neurological complications of influenza affect mainly the pediatric Asian population. In the category of influenza-associated encephalopathy, acute necrotizing encephalopathy (ANE) is a rapidly progressive and fulminant brain disorder associated with significant neurological sequelae and mortality. To date, only a few adult cases of influenza-associated ANE have been reported. We describe a 44-year-old woman who presented with rapid progression of consciousness impairment and recurrent generalized convulsions. Influenza was diagnosed three days prior to presentation, and infection with influenza A (H3N2) pdm09 was subsequently confirmed. A diagnosis of ANE was made based on the presence of characteristic brain MRI findings, the exclusion of central nervous system infection, and an elevated serum interleukin-6 level. Pulse steroid therapy followed by tocilizumab was initiated, which led to clinical stabilization and improvement. Genetic testing revealed that the patient carried heterozygous human leukocyte antigen DQB1 03:03 and DRB1 09:01 genotypes. An analysis of the adult cases of influenza-associated ANE in the literature and the present case revealed a wide range of ages (22-71 years), a short interval (median 3 days) between the clinical onset of influenza and ANE, and a high overall mortality rate (32%). The thalamus was the most frequent (91%) location of the lesions. Our report highlights the importance of identifying this devastating but treatable neurological complication of influenza in adults, especially those of Asian descent. As a cytokine storm is the most accepted pathogenic mechanism for ANE, cytokine-directed therapies may be promising treatments for which further investigation is warranted.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes acute necrotizing encephalopathy (ANE), which has a high mortality rate and severe sequelae. This study aimed to identify ANE early and evaluate the usefulness of tocilizumab in ANE treatment.
METHODS: We retrospectively included eight paeefediatric ANE cases infected with SARS-CoV-2 at Xi\'an Children\'s Hospital, China, from December 1, 2022 to May 1, 2023. A literature search was performed using the PUBMED, SPRING, SCOPUS, and EMBASE databases. This study included eleven patients. Clinical characteristics, laboratory test results, imaging features, and treatment options were analysed.
RESULTS: Eight of the 19 cases (42 %) died, one (5 %) recovered, and nine (47 %) improved with residual neurological dysfunction. Eighteen patients presented with fever, with 56 % having ≥40 °C. Twelve patients (63 %) presented with dysfunction consciousness. Eight (42 %) patients experienced frequent convulsions. All eight patients in our hospital had elevated procalcitonin levels (mean: 21.32 ng/mL, range: 0.10-89.40 ng/mL). Alanine aminotransferase levels were elevated (mean: 632.81 U/L, range: 13.00-2251.00 U/L) in six patients. Seven patients showed elevated uric acid levels(mean: 396.50 μmol/L, range: 157.00-660.00 μmol/L). Brain imaging indicated that all the patients had symmetrical injuries to the bilateral thalami, accompanied by symmetrical injuries in the cerebrum, cerebellum, basal ganglia, and brain stem. Compared with the classical treatment (n = 9), the combination with tocilizumab (n = 6) showed a statistically difference in mortality (p = 0.028 < 0.05).
CONCLUSIONS: The typical clinical manifestations of ANE in children with SARS-CoV-2 infection are acute onset with high fever, frequent convulsions and rapidly worsening disturbance of consciousness. Tocilizumab treatment could reduces mortality in ANE.

Acute necrotizing encephalopathy (ANE) is a rare immune-mediated complication of a viral infection commonly involving the bilateral thalamus and has been reported mainly in children. Here, we describe the MRI findings of coronavirus disease 2019 (COVID-19)-associated ANE in two pediatric patients, including a 7-year-old girl with fever and mental change, and a 6-year-old girl with fever and generalized seizures. Brain MRI revealed symmetrical T2 fluid attenuated inversion recovery high-signal intensity lesions in the bilateral thalamus with central hemorrhage. In one patient, the thalamic lesions showed a trilaminar pattern on the apparent diffusion coefficient map. This report emphasizes the importance of creating awareness regarding these findings in patients with COVID-19, particularly in children with severe neurological symptoms. Furthermore, it provides a literature review of several documented cases of COVID-19 presenting with bilateral thalamic hemorrhagic necrosis, suggesting a diagnosis of ANE.
급성 괴사성 뇌병증은 바이러스 감염의 드문 면역 매개 합병증이다. 일반적으로 양쪽 시상을 침범하며, 주로 어린이에서 보고된다. 저자들은 소아에서 발생한 코로나바이러스감염증과 관련된 급성 괴사성 뇌병증 2건을 보고하고자 한다. 7세 여아는 발열과 의식변화, 6세 여아는 발열과 전신성 간질로 내원하였다. 뇌 MRI에서 두 환자 모두 양쪽 시상에 중심부 출혈을 동반한 대칭적인 액체감쇠역전회 고신호강도 병변이 보였고, 한 환자에서는 겉보기확산계수에서 시상에 층상 병변이 보였다. 저자들은 이 보고를 통해 급성 괴사성 뇌병증의 특징적인 뇌 MRI 영상 소견을 인지함으로써 심각한 신경학적 증상을 나타내는 코로나바이러스감염증 환자의 경우 특히 소아에서 영상 소견을 바탕으로 한 빠른 진단이 필요함을 강조하고자 한다. 또한, 급성 괴사성 뇌병증을 시사하는 양측 시상의 출혈성 괴사로 나타났던 코로나바이러스 감염 증례에 대한 문헌을 검토하고자 한다.

UNASSIGNED: Acute Necrotizing Encephalopathy (ANE), is a kind of severe Central Nervous System Disease. The commonest pathogen is the influenza virus. The pathogenesis of ANE is bound up to genetic susceptibility and cytokine storm. Interleukin-6 (IL-6) is deemed as the core function in cytokine storm of ANE and that plays a significant role in evaluating the severity of Influenza-Related ANE. Tocilizumab, an IL-6 antagonist, is known to be safe and effective in the treatment of ANE when used early and has an essential role in improving prognosis and preventing disability.
UNASSIGNED: This case reports a 2 year 10 month old boy who developed ANE after being infected with influenza A virus (H1N1-2019). After treatment with Tocilizumab, the child\'s consciousness was clear, no convulsions occurred, the movement of limbs was improved, and the lesions of encephalopathy were significantly reduced.
UNASSIGNED: The early use of Tocilizumab is safe and effective for the treatment of ANE caused by influenza virus.

Acute necrotizing encephalopathy (ANE) is a rare neurological complication related to COVID-19. Here we present a case series of six Chinese cases with ANE associated with COVID-19 and review all reported cases in the literature. A total of six cases with ANE related to COVID-19 were enrolled in this study. Clinical manifestations, neuroimaging data, treatment and outcomes of these patients were analyzed. A literature review was performed in Pubmed and Embase and 25 cases with clinical and neuroimaging data were collected and analyzed. Among our six cases, the age of onset ranged from 15 to 56 years, with a male-to-female ratio of nearly 1:1. All patients presented with reduced consciousness. Elevated interleukin 6 in serum and/or cerebrospinal fluid (CSF) was detected in four patients. Two patients improved clinically after intravenous methylprednisolone and intravenous immunoglobulin (IVIG). Based on the literature review, the majority of cases were from Europe and the United States (60%). Two age peaks at 10-20 years (20%) and 50-60 years (28%) were observed. Two cases were found with a heterozygous Thr585Met mutation. The mortality of ANE caused by COVID-19 was 42%. The use of IVIG in combination with other immunotherapies was related to better outcome (P = 0.041) and both two patients who received Tocilizumab survived. This is the first Chinese case series about ANE associated with COVID-19. Elevated serum and CSF interlukin-6 were found in certain cases. The mortality and morbidity rates remained high although prompt immunotherapy could improve the outcomes.

OBJECTIVE: Acute necrotizing encephalopathy (ANE) is a rare neurological disorder that is often associated with viral infections. Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a few COVID-19-associated ANE cases have been reported. Since very little is known about ANE, the present study aimed to determine the clinical, biochemical, and radiological characteristics of affected patients.
METHODS: A search was conducted on PubMed, Scopus, Embase, and Web of Science databases for articles published up to August 30, 2022 using relevant keywords. Case reports and series in the English language that reported ANE in adult patients with COVID-19 confirmed by reverse transcription polymerase chain reaction were included in this study. Data on the demographic, clinical, laboratory, and radiological characteristics of patients were extracted and analyzed using the SPSS software (version 26).
RESULTS: The study included 30 patients (18 males) with COVID-19 and ANE who were aged 49.87±18.68 years (mean±standard deviation). Fever was the most-prevalent symptom at presentation (66.7%). Elevated C-reactive protein was observed in the laboratory assessments of 13 patients. Computed tomography and magnetic resonance imaging were the most-common radiological modalities used for brain assessments. The most commonly prescribed medications were methylprednisolone (30%) and remdesivir (26.7%). Sixteen patients died prior to discharge.
CONCLUSIONS: The diagnosis of COVID-19-associated ANE requires a thorough knowledge of the disease. Since the clinical presentations of ANE are neither sensitive nor specific, further laboratory and brain radiological evaluations will be needed to confirm the diagnosis. The suspicion of ANE should be raised among patients with COVID-19 who present with progressive neurological symptoms.

Human herpesvirus type 6 (HHV-6) is a DNA virus considered a member of the Herpesviridae family. HHV-6 is acquired early in life, when it may cause roseola infantum and nonspecific febrile illnesses which is usually a self-limiting disease before the age of two. Primary HHV-6 encephalitis and acute necrotizing encephalopathy (ANE) are rare diseases to occur in immunocompetent children. We describe an unusual case of HHV-6 encephalitis with mixed features of acute necrotizing encephalopathy and acute disseminated encephalomyelitis and contextualize it with a review of the literature on HHV-6 encephalitis in immunocompetent children. Although the incidence of primary HHV-6 encephalitis is rare in immunocompetent children, HHV-6 encephalitis associated with acute necrotizing encephalopathy is a devastating disease, highly fatal and neurologically damaging disease. Therefore, early testing and diagnosis are crucial as well as effective management of encephalitis with antiviral therapy is highly recommended.

Damage associated with lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH) to the central nervous system (CNS) is not uncommon. However, the combination with brain damage resembling acute necrotizing encephalopathy (ANE) is rarely reported. Herein, we introduce the diagnosis and treatment of a case of ANE associated with LA-HLH in our hospital and review the relevant literature. After treatment, the child was discharged with only dysarthria and decreased sucking ability. The child is now discharged from the hospital for 6 months with regular follow-up. There were no disease recurrence signs. LA-HLH and ANE were related to cytokine storm. Therefore, early steroid application is essential for treating these diseases.

BACKGROUND: Acute necrotising encephalopathy (ANE) is a rapidly progressive encephalopathy associated with acute viral illness. A missense mutation in nuclear pore gene RANBP2 has been identified as a major cause of familial and recurrent ANE, which is now termed as ANE1. First presentation of ANE can mimic an acute disseminated encephalomyelitis (ADEM), although ANE presents in a slightly younger age group. Identification of this disorder at radiological study is the most important determinant of the outcome. ANE1 is inherited as autosomal dominant, but shows incomplete penetrance.
METHODS: We report two female children who presented with atypical clinical presentation (afebrile) and atypical radiological presentation (lack of bilateral thalamic involvement), not fitting into the original diagnostic criteria for ANE1. Both received steroid therapy for a presumed diagnosis of ADEM and made good clinical recovery. We also reviewed the available literature on ANE1, including the clinical profile, MRI brain descriptions, CSF characteristics and common mutations.
RESULTS: A total of 59 patients are reported in patients with ANE1 were identified, the incidence of ANE was higher in younger age group (<4 yrs) as compared to ADEM 5.3 yrs (3.6-7). Male and female were equally affected. High CSF protein (>0.45 g/l) was reported in 44/47 (94%) in absence CSF pleocytosis (Cells > 5 × 10(6)/L). Neuroimaging findings showed multifocal involvement across different studies, and bilateral thalamic involvement was seen in 77% of patients.
CONCLUSIONS: Based on the literature review of ANE1 with RANBP2 mutation, we propose a threshold for RANBP2 mutation testing.