Treatment Timing, EEG, Neuroimaging, and Outcomes After Acute Necrotizing Encephalopathy in Children

Appavu, Brian; Foldes, Stephen T.; Fox, Jordana; Shetty, Sheetal; Oh, Ann; Bassal, Frederick; Marku, Iris; Mangum, Tara; Boerwinkle, Varina L.; Neilson, Derek; Kruer, Michael C.

doi:10.1177/0883073820984063

Cited by 4 publications

(11 citation statements)

References 30 publications

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“…Yamamoto et al ( 5 ) conducted a retrospective cohort study and found that age, CSF protein levels, and brainstem lesions were significantly associated with the prognosis of ANE, while the levels of AST, ALT, LDH and CK, and treatment modality were not significantly associated with ANE prognosis. In another small-size study, Appavu et al ( 16 ) showed that age, CSF proteins, specific MRI lesion location, and EEG epileptiform discharge were not obviously correlated with ANE prognosis. Although similar to other studies, the present study showed elevated serum levels of PCT, AST, ALT, LDH, CK-MB, and CSF protein in most pediatric patients, but we could not determine the relationship between these indicators with the prognosis of ANE.…”

Section: Discussionmentioning

confidence: 98%

Clinical evaluation of acute necrotizing encephalopathy in children

Fan

Huang

et al. 2022

Front. Pediatr.

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ObjectiveAcute necrotizing encephalopathy (ANE) is a rare but severe encephalopathy and is associated with a high morbidity and mortality. We aimed to analyze and compare the clinical features and predictive indicators of pediatric ANE.Materials and methodsThis retrospective study included children with ANE diagnosed at Guangzhou Women and Children’s Medical Center between November 2018 and January 2020. Pediatric patients’ information, including clinical characteristics, laboratory tests, neuroelectrophysiology and brain magnetic resonance imaging (MRI) findings, MRI score, brainstem auditory evoked potential (BAEP) grades, ANE severity scores (ANE-SS), and modified Rankin scale (mRS), were collected.ResultsTwelve ANE patients were included. Among them, one patient (8.3%) died from brainstem dysfunction, one (8.3%) recovered and 10 (83.3%) experienced neurological sequelae. All patients had an initial viral infection and neurological symptoms such as acute disturbance of consciousness (ADOC) or seizure, and the interval from onset of the disease to neurological manifestations was 3 (1.25–3) days. MRI score-I ranged from 1 to 3 (1.8 ± 0.7), MRI score-II ranged from 1 to 4 (2.5 ± 1.1). ANE-SS varied from 1 to 6 (3.9 ± 1.3). The scores of mRS were from 0 to 6 (2.9 ± 1.7). Higher MRI score were associated with worse outcomes, while the BAEP grade and ANE-SS score were not significantly associated with mRS.ConclusionANE is a severe encephalopathy syndrome with rapid progression, resulting in serious neurological sequelae. Compared with BAEP grade and ANE-SS, brain MRI shows more comprehensive advantages in predicting the prognosis of ANE patients. More in-depth research and better indicators are still needed to support the evaluation and treatment of ANE.

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Section: Discussionmentioning

confidence: 98%

Clinical evaluation of acute necrotizing encephalopathy in children

Fan

Huang

et al. 2022

Front. Pediatr.

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“…Although the efficacy of intravenous dexamethasone and pulse methylprednisolone therapy has not been systematically compared, a clear correlation was established between better prognoses and early steroid therapy (within 24 h) in ANE in patients without brainstem lesions [ 11 , 23 ]. Early immunomodulatory therapy is associated with fair outcomes in patients with ANE, as indicated by Appavu et al [ 26 ]. Okumura et al reported that, in 12 patients with ANE without brainstem lesions, 58% had no or mild neurologic sequelae after receiving early steroid therapy [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Early High-Dose Methylprednisolone Therapy Is Associated with Better Outcomes in Children with Acute Necrotizing Encephalopathy

et al. 2022

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Background: The neurologic outcomes of acute necrotizing encephalopathy (ANE) are very poor, with a mortality rate of up to 40% and fewer than 10% of patients surviving without neurologic deficits. Steroid and immunoglobulin treatments have been the most commonly used options for ANE, but their therapeutic efficacy is still controversial. Method: We retrospectively reviewed the medical records of 26 children diagnosed with ANE. We also divided these patients into two groups: 21 patients with brainstem involvement and 8 patients without brainstem involvement. Pulse steroid therapy (methylprednisolone at 30 mg/kg/day for 3 days) and intravenous immunoglobulin (2 g/kg for 2–5 days) were administered to treat ANE. Results: The overall mortality rate was 42.3%, and patients who did not survive had significantly higher initial lactate and serum ferritin levels, as well as higher rates of inotropic agent use with brainstem involvement. There were no significant differences in the outcomes of pulse steroid therapy or pulse steroid plus immunoglobulin between survivors and non-survivors. When analyzing the time between symptom onset and usage of pulse steroid therapy, pulse steroid therapy used within 24 h after the onset of ANE resulted in significantly better outcomes (p = 0.039). In patients with brainstem involvement, the outcome was not correlated with pulse steroid therapy, early pulse steroid therapy, or pulse steroid therapy combined with immunoglobulin. All patients without brainstem involvement received “early pulse methylprednisolone” therapy, and 87.5% (7/8) of these patients had a good neurologic outcome. Conclusion: Pulse steroid therapy (methylprednisolone at 30 mg/kg/day for 3 days) administered within 24 h after the onset of ANE may be correlated with a good prognosis. Further studies are needed to establish a consensus guideline for this fulminant disease.

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“…While the exact pathogenesis is not fully understood, evidence suggests that ANE results from an exaggerated systemic inflammatory response characterized by extensive release of pro-inflammatory cytokines and natural killer cell activation ( 6 ). Brain involvement is thought to result from blood brain barrier disruption from both cytotoxic and vasogenic edema causing confusion, altered level of awareness, and potentially focal neurologic deficits or seizures ( 6 , 8 ). While most cases are sporadic, familial cases of ANE have been associated with a causative gene mutation ( RANBP2 ) ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

“…While most cases are sporadic, familial cases of ANE have been associated with a causative gene mutation ( RANBP2 ) ( 9 ). Brain magnetic resonance imaging (MRI) demonstrates symmetric T2 hyperintense lesions in the bilateral thalami along with the brainstem, periventricular white matter, and cerebellum; presence of brainstem lesions portend a worse prognosis ( 1 , 6 , 8 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

“…There are no standardized treatment guidelines for ANE; however, generally utilized treatment strategies combine immunosuppressive interventions and supportive/symptomatic management. The most frequently reported immunosuppressive therapy is high dose intravenous (IV) steroids [methylprednisolone, (MP) at least 30/mg/kg/day for at least 3 days] ( 8 , 10–14 ). Additionally, case reports and case series report the use of intravenous immune globulin (IVIG) ( 10 , 15 , 16 ), plasma exchange (PLEX) ( 10 , 16–19 ), and biologics such as tocilizumab (an IL-6 inhibitor) ( 8 , 11 , 19 , 20 ).…”

Section: Introductionmentioning

confidence: 99%

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Case report: Acute necrotizing encephalopathy: a report of a favorable outcome and systematic meta-analysis of outcomes with different immunosuppressive therapies

Fischell,

Kliot

et al. 2023

Front. Neurol.

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Acute Necrotizing Encephalopathy (ANE) is a condition characterized by symmetric, bilateral lesions affecting the thalamus and potentially other areas of the brain following an acute febrile illness. It manifests clinically as abrupt development of encephalopathy, or alteration in mental status that often includes development of seizures and progression to coma. Treatment strategies combine immunosuppressive therapies and supportive care with varying levels of recovery, however there are no universally accepted, data-driven, treatment algorithms for ANE. We first report a case of a previously healthy 10-year-old female with acute onset diplopia, visual hallucinations, lethargy, and seizures in the setting of subacute non-specific viral symptoms and found to have bilateral thalamic and brainstem lesions on MRI consistent with ANE. She was treated with a combination of immunomodulatory therapies and ultimately had a good outcome. Next, we present a meta-analysis of 10 articles with a total of 158 patients meeting clinical and radiographic criteria for ANE. Each article reported immunosuppressive treatments received, and associated morbidity or mortality outcome for each individual patient. Through our analysis, we confirm the effectiveness of high-dose, intravenous, methylprednisolone (HD-IV-MP) therapy implemented early in the disease course (initiation within 24 h of neurologic symptom onset). There was no significant difference between patients treated with and without intravenous immunoglobulin (IVIG). There was no benefit of combining IVIG with early HD-IV-MP. There is weak evidence suggesting a benefit of IL-6 inhibitor tocilizumab, especially when used in combination with early HD-IV-MP, though this analysis was limited by sample size. Finally, plasma exchange (PLEX) improved survival. We hope this meta-analysis will be useful for clinicians making treatment decisions for patients with this potentially devastating condition.

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Treatment Timing, EEG, Neuroimaging, and Outcomes After Acute Necrotizing Encephalopathy in Children

Cited by 4 publications

References 30 publications

Clinical evaluation of acute necrotizing encephalopathy in children

Clinical evaluation of acute necrotizing encephalopathy in children

Early High-Dose Methylprednisolone Therapy Is Associated with Better Outcomes in Children with Acute Necrotizing Encephalopathy

Case report: Acute necrotizing encephalopathy: a report of a favorable outcome and systematic meta-analysis of outcomes with different immunosuppressive therapies

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