Acute necrotizing encephalopathy: A comparison between influenza and non‐influenza cases

Abstract

The aim of this study was to clarify the difference between influenza and non-influenza cases in clinical symptoms, laboratory and neuroimaging findings, and outcome in children with ANE. We retrospectively studied 22 children with ANE. Eleven of them had virological proof of influenza infection and the other 11 were judged as non-influenza infection. There was no significant difference between influenza and non-influenza cases in sex, antipyretics use and neurological symptoms. Although laboratory data were not different between the two groups, brainstem lesions were relatively more frequent in influenza cases than in non-influenza cases. Outcome was not different between the two groups. The results of our study suggest that the pathogenesis of acute necrotizing encephalopathy will not be dependent on infectious agents. Key words acute necrotizing encephalopathy, influenza.ANE is a distinct subtype of acute encephalopathy described by . The most prominent feature of ANE is multiple, symmetric brain lesions in both thalami. CT or MRI sometimes reveal lesions in other brain regions including cerebral white matter, internal capsule, putamen, brainstem and cerebellum. The neurological outcome of ANE has been reported to be very poor. The majority of patients with ANE die or survive with moderate or severe neurological sequelae (1).The onset of ANE is triggered by acute febrile diseases, mostly viral infection, among which influenza is the most common prodromal illness (1, 4). However, there have been no reports on differences in clinical symptoms, laboratory and neuroimaging findings, and outcome according to the prodromal illness. We conducted a retrospective study in order to establish whether there are differences in these respects between influenza and non-influenza cases in patients with ANE. List of Abbreviations:ANE, acute necrotizing encephalopathy; IL-6, interleukin-6; CSF, cerebrospinal fluid; CT, computed tomography; MRI, magnetic resonance imaging; TNF-α, tumor necrosis factor-α. PATIENTS AND METHODWe recruited 22 children with ANE who had been admitted to 17 hospitals between 1998 and 2005. This cohort was derived from a previous report, whereas the purpose of the present study is quite different (5). The diagnosis of ANE was made on the basis of neuroradiological findings according to the criteria proposed by Mizuguchi et al. (1,2). In this study, we included patients with acute encephalopathy who had multiple focal lesions which were symmetrically distributed in both thalami and other brain regions such as the putamina, cerebral and cerebellar white matter, and brainstem tegmentum (1, 2, 6). CT was the initial neuroimaging performed in 21 patients and MRI in 1. Abnormal findings consistent with ANE were found in the first CT/MRI in all patients. We excluded patients with marked metabolic derangement such as elevated lactate, pyruvate, amino acids, or organic acids levels.

Acute Necrotizing Encephalopathy in 3 Brothers

“…13,17,18 Although brainstem lesions appear more commonly in influenza-related cases, documentation of influenza does not seem to predict outcome. 19 In our series, patient 2 was documented to have an acute infection with influenza A, but we were unable to determine a pathogen for the upper respiratory infection symptoms in his brothers. This is not surprising, because in the seminal case series, only 24% of cases had documentation of influenza infection.…”

A severity score for acute necrotizing encephalopathy

“…The first group comprised 41 children with ANE who had been admitted to 17 hospitals. (Supplementary Table 1) This cohort was derived from our previous report examining the relation between outcome and treatment [5,10,16]. The data were collected from the hospitals all over Japan, where the two senior authors (AO and MM) are collaborating for clinical studies on acute encephalopathy.…”

“…The exact etiology is not understood, although some studies have reported increased levels of cytokines such as interleukin-6 and tumor necrosis factor-a in patients with ANE and have postulated that a "cytokine storm" may be involved in the pathogenesis of this disease [4][5][6][7][8][9]. Neurological outcome of ANE is very poor and the mortality and morbidity rates are high [5,10].…”

Neurological complications of pandemic influenza A H1N1 2009 infection: European case series and review

“…More recently, the epidemic influenza A (H3N2) strain was associated with a surge in cases of encephalitis/encephalopathy in Japan [18,28,46], Europe [40] and America [25]. The spectrum of neurological conditions arising from neurovirulent strains of influenza includes seizures [4,25,40], acute necrotising encephalopathy (ANE) [30,40,42,44], Reye's syndrome [3], transverse myelitis [21], acute disseminated encephalomyelitis [21], Guillain-Barre syndrome [9,21], mutism [29] and movement disorders [37].…”