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Imaging Findings and Clinical Perspectives of Acute Necrotising Hong Kong J Radiol. 2020;23:285-8 | https://doi.org/10.12809/hkjr2017177 CASE REPORT Imaging Findings and Clinical Perspectives of Acute Necrotising Encephalopathy: Report of Two Cases HL Wong, HY Lau, JCW Siu Department of Radiology, Tuen Mun Hospital, Tuen Mun, Hong Kong INTRODUCTION contrast magnetic resonance imaging (MRI) revealed First coined by Mizuguchi1 in 1997, acute necrotising symmetrical T2 and fluid attenuated inversion recovery encephalopathy (ANE) is a severe, uncommon type of hyperintensities with restricted diffusion over bilateral encephalopathy with distinctive imaging and clinical thalami, white matter, and brain stem (Figure 1a-c). features and a global distribution. Despite ongoing Bilateral thalami were markedly swollen with central studies, the exact pathogenesis of ANE is yet to be hypo-enhancement (Figure 1d). Features were suggestive determined and is still classified as an idiopathic disorder. of ANE. It is hypothesised that the disease is an immune response to a prior, mostly viral, infection. With two illustrative The patient was started on intravenous pulse steroid cases, we showcase the current understanding of the but his neurological condition deteriorated rapidly. A pathogenesis, clinical and radiological presentation of follow-up computed tomography (CT) scan of the brain the disease as well as the latest treatment strategies. showed diffuse cerebral oedema with effacement of bilateral cerebral sulci and cisterns. Evidence of coning CASE 1 was also observed. An urgent bilateral craniotomy and A 2-year-old boy with good past health developed fever decompression were performed. Despite the surgical and upper respiratory symptoms for 1 day. His symptoms management, the patient’s condition remained poor. deteriorated overnight and he developed generalised Neurologically, the patient showed minimal brain seizure. He was then urgently admitted to the Accident stem response and scored 4 (E1V1M2) in the Glasgow and Emergency Department where the seizure was Coma Scale. On day 5 after admission, the patient aborted with anticonvulsant therapy. He was transferred succumbed. to the paediatric intensive care unit for further care. CASE 2 A nasopharyngeal swab for rapid antigen test was A 6-year-old boy with good past health presented with positive for influenza A. Despite empirical treatment high fever, upper respiratory symptoms and transient with vancomycin, rocephin, acyclovir, and oseltamivir, episodes of confusion. An urgent CT scan of the brain the patient developed breakthrough seizure. An urgent performed on admission revealed no abnormality. A Correspondence: Dr HL Wong, Department of Radiology, Tuen Mun Hospital, Tuen Mun, Hong Kong Email: [email protected] Submitted: 2 Dec 2019; Accepted: 10 Dec 2019 Contributors: JCWS designed the study. HLW acquired and analysed the data, and drafted the manuscript. JCWS and HYL critically revised the manuscript for important intellectual content. Conflicts of Interest: All authors have disclosed no conflicts of interest. Funding/Support: This case report received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Ethics Approval: The patients were treated in accordance with the tenets of the Declaration of Helsinki. The patients provided written informed consent for all treatments and procedures. © 2020 Hong Kong College of Radiologists. CC BY-NC-ND 4.0 285 Acute Necrotising Encephalopathy in Hong Kong (a) (b) (c) (d) Figure 1. A 2-year-old boy with acute necrotising encephalopathy. T2-weighted axial image showing abnormal hyperintensities at (a) bilateral cerebral white matter, (b) bilateral thalami, and (c) brain stem. (d) T1-weighted axial post-contrast image showing bilateral thalamic symmetrical hypoenhancing lesions. (a) (b) (c) (d) Figure 2. A 6-year-old boy with acute necrotising encephalopathy. T2-weighted axial image showing hyperintensities and swelling at (a) bilateral cerebral white matter, (b) bilateral thalami, and (c) brain stem. (d) T1-weighted inversion recovery sagittal image showing significant swelling at the thalamus and brainstem with kinking of the cervicomedullary junction. rapid antigen test on nasopharyngeal swab was positive DISCUSSION for influenza A. Pathogenesis and Aetiology of Acute Necrotising Encephalopathy The patient’s level of consciousness deteriorated rapidly: The most widely accepted cause of ANE is Glasgow Coma Scale score dropped from 15 to 4 over 7 hypercytokinaemia.2 Patients with ANE mount hours. MRI performed 12 hours after admission revealed an exaggerated immune response to infection by bilateral symmetrical T2 hyperintensities in the thalamus releasing a high level of cytokines. There is evidence and brain stem (Figure 2a and b). Associated bilateral that the level of various inflammatory mediators, cerebral and cerebellar white matter hyperintensities including different interleukins (IL-6, IL-15, IL-1β, were also observed (Figure 2c). Features were suggestive IL-10), tumour necrosis factor-α as well as interferon-γ,2-4 of ANE. There was significant swelling at the thalamus is raised in the serum as well as the cerebrospinal fluid. and brain stem with kinking of the cervicomedullary This causes multiple system failure.1 junction (Figure 2d). Crowding of the foramen magnum was evident. Both environmental and host factors seem to play a role in a predisposition to ANE. A neurosurgical opinion was sought and the boy was deemed too ill to benefit from surgery. He remained A number of different infections are associated with comatose with no obvious return of any brainstem ANE and different pathogens have been reported, function despite all medical support. The patient was including viruses and bacteria.2,5 Influenza virus is the certified dead on day 12 after admission. most common culprit. 286 Hong Kong J Radiol. 2020;23:285-8 HL Wong, HY Lau, JCW Siu There have been some recurrent cases reported within the lesions will have a low T1 signal and high T2 signal. certain families, suggesting a genetic predisposition.5 There will also be fluid restriction on diffusion-weighted In recurrent cases, missense mutations in Ran-binding imaging and apparent diffusion coefficient.5 protein 2 were identified as the susceptibility alleles.5 As the disease progresses, imaging features change. Clinical Presentation of Acute Necrotising Oedema will subside and features of petechial Encephalopathy haemorrhage and necrosis may appear. On CT, this will In general, the clinical presentation of ANE can be appear as new heterogeneous hyperdense foci within the classified into three stages: the prodromal stage, the previously seen hypodensities.1,5 On MRI T1-weighted acute encephalopathy stage, and the recovery stage. image, there will be new hyperintensities within the pre-existing hypointense lesions, while on T2-weighted The presentation in the prodromal stage is highly image they will show up as a hypointense centre variable, due to the wide range of antecedent pathogens surrounded by a high signal rim.5 Susceptibility weight possible. Symptoms may include fever, upper respiratory images and T2* gradient echo imaging are more able symptoms, gastroenteritis, or skin rashes. Patients with to show the petechial haemorrhage that will appear as ANE may also present with more severe symptoms low signal foci with blooming artefact.5 The classically including shock, disseminated intravascular coagulation described ANE imaging features of concentric structures, and even multiple organ failure.5 tricolour pattern, or target-like appearance can be seen on apparent diffusion coefficient images. The centre As the disease progresses, the acute encephalopathy of the lesion shows high signal with a hypointense rim stage ensues during which neurological symptoms suggesting cytotoxic oedema. A further outer rim of will manifest rapidly. Seizures, an altered level of hyperintensity suggests vasogenic oedema.5,6 consciousness and focal neurological deficits may occur. The patient usually requires intensive care With specific imaging features of ANE and a rapid support. neurological decline, the imaging differential diagnoses of ANE are limited. Entities that need to be considered Although majority of the cases result in high morbidity include acute disseminated encephalomyelitis, Reye’s and mortality, milder forms with recovery have also syndrome and Leigh’s syndrome. Acute disseminated been reported.5 encephalomyelitis is associated with multiple bilateral brain lesions bilaterally. Nonetheless the lesions do Radiological Findings and Imaging not typically affect the brain symmetrically as in ANE. Differential Diagnoses of Acute Necrotising Although Reye’s syndrome and Leigh’s syndrome may Encephalopathy present with symmetrical brain lesions, both entities are Contrary to the highly non-specific clinical presentations, characterised by the presence of lactic acidosis. imaging features of ANE can usually help to narrow down the differential diagnosis.5 The list of differential In both of our cases, the later imaging features were diagnoses is limited when rapid neurological deterioration not well demonstrated due to the rapid clinical course. is taken into account. Unfortunately both patients succumbed before follow- up imaging was available. However, the typical early The typical imaging presentation of ANE is multiple imaging features of ANE were well demonstrated. symmetrical lesions with supra- and infra-tentorial brain involvement. The thalami, brain stem, cerebral white Diagnostic Criteria
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