Acute necrotizing encephalopathy in adult patients with influenza: a case report and review of the literature.

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.

Acute hemorrhagic leukoencephalitis in a COVID-19 patient-a case report with literature review.

PURPOSE: Acute hemorrhagic leukoencephalitis (AHLE) is a rare and severe form of acute disseminated encephalomyelitis (ADEM). Only a few reports of AHLE in coronavirus disease 2019 (COVID-19) patients have been described to date. We report a case of COVID-19-related AHLE along with a literature review describing salient clinical and imaging characteristics. METHODS: A literature search was performed on Medline (2020-present), PubMed, Cochrane Library, CINAHL, and Google scholar on 28 January 2021 for all articles published using MeSH terms "COVID-19" or "SARS-CoV-2" with "Acute hemorrhagic leukoencephalitis" or "Acute hemorrhagic encephalitis." Relevant case reports and case series describing clinical and imaging features of AHLE associated with SARS-CoV-2 infection were included, data compiled, and critically reviewed. RESULTS: Acute onset encephalopathy and rapidly deteriorating neurological status is the common clinical presentation in AHLE. CSF analysis reveals elevated proteins and lymphocytic pleocytosis. Typical neuroimaging features include multifocal, variable-sized, poorly defined cerebral white matter lesions with cortical sparing. Involvement of the brainstem, cerebellar peduncles, and deep grey matter can also occur, although rarely. Lesions are hyperintense on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) images, hypointense on T1W images, and show microhemorrhages, variable diffusion restriction, and post-contrast enhancement. Extensive microhemorrhages, brainstem involvement, and gross hemorrhage often portend a poor prognosis. CONCLUSION: Heightened awareness about the clinical and imaging presentation of COVID-19-related AHLE can positively alter the outcome in a select few by enabling early diagnosis and aggressive management.

[Influenza A-associated acute necrotizing encephalopathy]. / Encefalopatía necrotizante aguda asociada a influenza A.

INTRODUCTION: Acute necrotizing encephalopathy of childhood (ANEC) is a rare disease characterized by alteration of consciousness and multiple symmetric brain lesions mainly involving the thalamus. It presents a high mortality rate and severe sequelae. OBJECTIVE: To describe a school-age patient with influenza A-related ANEC with favorable evolution. CLINICAL CASE: Six-year-old boy with 3 days history of upper respiratory symptoms and fever (39 °C). One day previous to admission, he presented altered state of consciousness. A lumbar puncture was performed, showing a mild increase of protein level in CSF. MRI showed bilateral foci of symmetric restricted signal in the thalamus, mammillary bodies, periaqueductal gray, ventral tegmentum, hippocampus, and in both external capsules, which was compatible with ANEC. The patient received empirical treatment with methylprednisolone and oseltamivir. Subsequently, a positive result was received for influenza. Considering diagnosis and severity of illness, it was decided to administer immunoglobulin. The patient got better slowly but favorably. At discharge, he still was mildly bradypsychic with decreased visual acuity, spontaneous speech and walking with assistance. At 6 months of follow-up, the patient presented normal speech and gait, with persistent visual impairment in the right eye. CONCLUSIONS: Our patient presented ANEC, whose timely diagnosis and management were associated with a favorable neurological evolution in the long term. Although ANEC is an infrequent pathology, it has very high morbidity and mortality rates, so it is very important to have a high degree of suspicion in order to request a targeted imaging study, search for related infectious causes, and start proper treatment.

Acute necrotizing encephalopathy infected with the SARS-CoV-2 in children: Case series and literature review of clinical outcomes with the use of Tocilizumab.

BACKGROUND AND 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). CONCLUSION: 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 hemorrhagic leukoencephalopathy associated with influenza A (H1N1) virus.

BACKGROUND: Acute hemorrhagic leukoencephalopathy (AHLE) is a rare condition associated with H1N1. In this condition the infection triggers an autoimmune response which results in perivascular demyelination and hemorrhage in the brain parenchyma. METHODS: We report a case of a patient who developed brain edema and herniation as a result of AHLE. RESULTS: A 27-year-old presented to a community hospital with fever, dyspnea, and malaise and was found to have H1N1-associated pneumonia. Despite treatment he progressed to acute respiratory distress syndrome and required mechanical ventilation. Due to failure on conventional ventilation, he was transferred to our hospital and was placed on high-frequency oscillatory ventilation. He was showing improvement until day 6 of transfer to our hospital when he was suddenly noted to have a rise in his blood pressure followed by hypotension. The following morning he was noted to have non-reactive pupils and was declared brain dead. Autopsy of the brain was consistent with AHLE. CONCLUSIONS: This case emphasizes the importance of awareness of this disease. The non-specific signs and symptoms, and the use of sedatives, make diagnosis challenging in the early stages of this disease. If suspected early, appropriate imaging can aid in the diagnosis. Treatment with immunosuppressive agents and plasmapheresis may prevent rapid progression and death. This is the first published case of AHLE in association with H1N1 that has been confirmed pathologically.

Novel human reovirus isolated from children with acute necrotizing encephalopathy.

For many encephalitis cases, the cause remains unidentified. After 2 children (from the same family) received a diagnosis of acute necrotizing encephalopathy at Centre Hospitalier Universitaire (Tours, France), we attempted to identify the etiologic agent. Because clinical samples from the 2 patients were negative for all pathogens tested, urine and throat swab specimens were added to epithelial cells, and virus isolates detected were characterized by molecular analysis and electron microscopy. We identified a novel reovirus strain (serotype 2), MRV2Tou05, which seems to be closely related to porcine and human strains. A specific antibody response directed against this new reovirus strain was observed in convalescent-phase serum specimens from the patients, whereas no response was observed in 38 serum specimens from 38 healthy adults. This novel reovirus is a new etiologic agent of encephalitis.

Acute necrotizing encephalopathy associated with novel influenza A (H1N1) virus in Turkey.

Influenza-associated acute necrotizing encephalopathy has been well recognized but not yet been reported with novel influenza A in Turkey. We report a 6-year-old boy infected with novel influenza A who displayed the typically characteristic clinical features and neuroimaging findings of acute necrotizing encephalopathy. Physicians who care for children should be aware of acute necrotizing encephalopathy in any child presenting with acute mental status changes during influenza infection. We would like to remind of this entity, because early diagnosis and treatment may reduce mortality and morbidity.

Acute encephalopathy and encephalitis caused by influenza virus infection.

PURPOSE OF REVIEW: Influenza-associated acute encephalopathy/encephalitis (IAE) is an uncommon but serious complication with high mortality and neurological sequelae. This review discusses recent progress in IAE research for a better understanding of the disease features, populations, outcomes, diagnosis, and pathogenesis. RECENT FINDINGS: In recent years, many IAE cases were reported from many countries, including Japan, Canada, Australia, Austria, The Netherlands, United States, Sweden, and other countries and regions. During the novel influenza A/H1N1 pandemic, many IAE cases with A/H1N1 infection in children were reported, particularly in those hospitalized with influenza infection. Pathogenesis of IAE is not fully understood but may involve viral invasion of the CNS, proinflammatory cytokines, metabolic disorders, or genetic susceptibility. An autosomal dominant viral acute necrotizing encephalopathy (ANE) was recently found to have missense mutations in the gene Ran-binding 2 (RANBP2). Another recurrent ANE case following influenza A infection was also reported in a genetically predisposed family with an RANBP2 mutation. SUMMARY: Although IAE is uncommon, compared with the high incidence of influenza infection, it is severe. However, this complication is not duly recognized by health practitioners. Recent advances highlight the threat of this complication, which will help us to have a better understanding of IAE.

Update on Neurological Manifestations of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2, the source of COVID-19, causes numerous clinical findings including respiratory and gastrointestinal findings. Evidence is now growing for increasing neurological symptoms. This is thought to be from direct in-situ effects in the olfactory bulb caused by the virus. Angiotensin-converting enzyme 2 receptors likely serve as a key receptor for cell entry for most coronaviridae as they are present in multiple organ tissues in the body, notably neurons, and in type 2 alveolar cells in the lung. Hematogenous spread to the nervous system has been described, with viral transmission along neuronal synapses in a retrograde fashion. The penetration of the virus to the central nervous system (CNS) allows for the resulting intracranial cytokine storm, which can result in a myriad of CNS complications. There have been reported cases of associated cerebrovascular accidents with large vessel occlusions, cerebral venous sinus thrombosis, posterior reversible encephalopathy syndrome, meningoencephalitis, acute necrotizing encephalopathy, epilepsy, and myasthenia gravis. Peripheral nervous system effects such as hyposmia, hypogeusia, ophthalmoparesis, Guillain-Barré syndrome, and motor peripheral neuropathy have also been reported. In this review, we update the clinical manifestations of COVID-19 concentrating on the neurological associations that have been described, including broad ranges in both central and peripheral nervous systems.

Adenovirus as a rare cause of acute necrotising encephalitis.

Adenovirus is a common cause of upper and lower respiratory tract infections. Rarely, neurological manifestations may occur, ranging from mild aseptic meningitis to potentially fatal acute necrotising encephalopathy (ANE). Very little is known in regards to the exact pathogenesis of ANE in association with adenovirus. This report describes the presentation of a previously healthy 14-month-old girl diagnosed with adenovirus-induced ANE. Herein, we highlight the clinicoradiological manifestation of this uncommon association with adenovirus in order to maintain a high index of suspicion for early diagnosis and a better outcome.

Influenza-Associated Acute Necrotizing Encephalopathy in Siblings.

Encephalopathy is an important complication associated with influenza, most frequently observed in young children, with a wide range of severity. The most severe category of influenza-associated encephalopathy (IAE) is acute necrotizing encephalopathy (ANE), characterized by high frequency of neurologic sequelae and fatal outcomes. We report two young siblings who developed fever and seizures with altered mental status. Influenza A(H1N1)pdm09 virus infection was identified in upper respiratory tract specimens from both patients, and neuroimaging revealed bilateral inflammatory lesions, consistent with acute necrotizing encephalopathy. Neither child had received influenza vaccination. Both children progressed to critical illness and required invasive mechanical ventilation. In addition to critical care management, both patients received high-dose corticosteroids, mannitol, anticonvulsants, and antiviral treatment of influenza. The older child recovered fully and was discharged 2 weeks after illness onset, but the younger sibling developed severe brainstem edema and cerebellar tonsillar herniation, and died on illness day 11. Both children tested positive for Ran Binding Protein 2 (RANBP2) gene mutations. RANBP2 is a genetic polymorphism associated with recurrent episodes of necrotizing encephalitis with respiratory viral infections. Annual influenza vaccination is especially important for ANE survivors, with or without RANBP2 mutations, their household contacts, and caregivers. During influenza season, close monitoring of any child with a history of neurological complications associated with respiratory illness is indicated, with prompt initiation of antiviral treatment with onset of acute respiratory illness, and influenza testing performed by molecular assay.

Acute necrotizing encephalopathy causing human bocavirus.

Acute necrotizing encephalopathy is characterized by multiple, symmetrical lesions involving the thalamus, brainstem, cerebellum, and white matter and develops secondarily to viral infections. Influenza viruses are the most common etiological agents. Here, we present the first case of acute necrotizing encephalopathy to develop secondarily to human bocavirus. A 3-year-old girl presented with fever and altered mental status. She had had a fever, cough, and rhinorrhea for five days. The patient was admitted to the intensive care unit with an initial diagnosis of encephalitis when vomiting, convulsions, and loss of consciousness developed. Signs of meningeal irritation were detected upon physical examination. There was a mild increase in proteins, but no cells, in the cerebrospinal fluid (CSF). Brain magnetic resonance imaging showed symmetrical, heterogeneous hyperintensities bilaterally in the caudate nuclei and putamen. Ammonium, lactate, tandem mass spectroscopy, and urine organic acid were normal. No bacteria were detected in the CSF cultures. Human bocavirus was detected in a nasopharyngeal aspirate using real-time PCR, while no influenza was detected. Oseltamivir, acyclovir, 3% hypertonic saline solution, and supportive care were used to treat the patient, who was discharged after two weeks. She began to walk and talk after one month of physical therapy and complete recovery was observed after six months. Human bocavirus is a recently identified virus that is mainly reported as a causative agent in respiratory tract infections. Here, we present a case of influenza-like acute necrotizing encephalopathy secondary to human bocavirus infection.

Encefalopatía necrotizante aguda asociada a influenza A / Influenza A-associated acute necrotizing encephalopathy

INTRODUCCIÓN: La encefalopatía necrotizante aguda (ENA) es una patología rara, caracterizada por compromiso de conciencia y presencia de múltiples lesiones encefálicas simétricas localizadas principalmente en tá lamo. Se asocia a alta letalidad e importantes secuelas. OBJETIVO: Describir el caso de un paciente escolar con ENA asociada a influenza-A con evolución favorable. CASO CLÍNICO: Paciente de 6 años de edad, con historia de 3 días de evolución de síntomas respiratorios altos asociados a fiebre (39 °C). Veinticuatro horas previo a la consulta destacaba compromiso de conciencia cualicuantitativo. Se realizó punción lumbar con proteinorraquia leve. En resonancia magnética (RM) se identificó focos de restricción a la difusión bilaterales de distribución simétrica, talámicos, en cuerpos mamila res, periacueductales, de tegmento pontino, hipocampales y en ambas cápsulas externas, asociado a componente hemorrágico y edema vasogénico, sugerente de ENA. Recibió tratamiento empírico con metilprednisolona y oseltamivir. Posteriormente, se recibió resultado positivo para virus influenza- AH1. Dado diagnóstico, se decidió administrar inmunoglobulina, evolucionando lento pero favora blemente. Al alta levemente bradipsíquico, con disminución de agudeza visual, lenguaje espontáneo y marcha con apoyo. A los 6 meses de seguimiento presentaba lenguaje y marcha normales, persis tiendo alteración visual a derecha. CONCLUSIÓN: Nuestro paciente presentó una ENA cuyo diagnóstico y manejo oportunos se asociaron a una favorable evolución neurológica en el largo plazo. Si bien la ENA es una patología infrecuente, la morbimortalidad asociada es altísima, por lo que resulta de gran importancia tener un alto grado de sospecha, a fin de solicitar estudio imagenológico dirigido, buscar causas infecciosas relacionadas e iniciar un manejo oportuno.

INTRODUCTION: Acute necrotizing encephalopathy of childhood (ANEC) is a rare disease characterized by alteration of consciousness and multiple symmetric brain lesions mainly involving the thalamus. It presents a high mortality rate and severe sequelae. OBJECTIVE: To describe a school-age patient with influenza A-related ANEC with favorable evolution. CLINICAL CASE: Six-year-old boy with 3 days history of upper respiratory symptoms and fever (39 °C). One day previous to admission, he presented altered state of consciousness. A lumbar puncture was performed, showing a mild increase of protein level in CSF. MRI showed bilateral foci of symmetric restricted signal in the thalamus, mammillary bodies, periaqueductal gray, ventral tegmentum, hippocampus, and in both external capsules, which was compatible with ANEC. The patient received empirical treatment with methylprednisolone and oseltamivir. Subsequently, a positive result was received for influenza. Considering diagnosis and severity of illness, it was decided to administer immunoglobulin. The patient got better slowly but favorably. At discharge, he still was mildly bradypsychic with decreased visual acuity, spontaneous speech and walking with assistance. At 6 months of follow-up, the patient presented normal speech and gait, with persistent visual impairment in the right eye. CONCLUSIONS: Our patient presented ANEC, whose timely diagnosis and management were associated with a favorable neurological evolution in the long term. Although ANEC is an infrequent pathology, it has very high morbidity and mortality rates, so it is very important to have a high degree of suspicion in order to request a targeted imaging study, search for related infectious causes, and start proper treatment.