The last 12 months has seen new interest in Acute Necrotizing Encephalopathy and also continuing studies & research.
We believe some of the gaps in the knowledge of ANE has been noted (in the medical community) in part due to the Covid-19 pandemic. We are seeing recognition of these gaps, particularly treatments and the lack thereof. With studies being done on the cytokine storm that occurs in some Covid patients we are very hopeful that this will transfer to be of benefit to ANE patients.
Currently our ANE community stands at 311 members with approximately 120 different families, some with multiple family members being genetic carriers and/or affected by ANE. We are also aware of many cases of ANE (news articles, case reports etc) that we have not been able to reach.
To this day patients are still told there are only 150-300 cases reported worldwide and of these around 59 genetic cases. This number is grossly underestimated and we would love to see a new collation of published ANE case reports completed. This year we shared an article from Egypt that had 30 ANE children admitted in 17 months at the one hospital (1).
Influenza numbers globally have been very low due to the various measures undertaken to limit the spread of Covid19. This however did not mean that our support group didn’t gain new members. Families that have only just found us or members with rarer or unknown triggers were welcomed.
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Alexander Palazzo and his team at the Palazzo lab in Toronto, Canada continue to research Ranbp2 (where the most common genetic variations for ANE are found). Unfortunately due to the worldwide pandemic some of this work has had to be put on hold. We were greatly disappointed that a planned workshop where ANE families could attend and provide specimens for Alex’s research was also postponed. Various speakers on different aspects of ANE were to present at the workshop. This was also to be an opportunity for many families to meet for the first time, learn about ANE and contribute to research. However, it was wonderful to see new articles with some exciting work from Alex and his team published (2). We congratulate them and thank them for this achievement and for their many, many hours of work.
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We are pleased to say that we have broadened our international contact base for physicians and researchers this year. They are either creating studies or research on different aspects of ANE or have expressed an interest in collaborating with us to further meet the needs and goals of ANE International as a Patient Advocacy Group focused on Education, Awareness and Support. We are excited for what the future may hold.
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It came as no surprise to our community that Covid-19/ANE associated case reports were published in the relatively early days of the pandemic. What did surprise us was that these were in adults. To date, in comparison to overall pandemic numbers Covid 19/ANE appears to be very rare. There have been even less reports in children.
To date and to the best of our knowledge none of these reports have mentioned genetic testing in the patients. We feel that this was a real missed opportunity, not only for further knowledge for our families but for ANE as a whole.
We questioned why the term “Acute Hemorrhagic Necrotizing Encephalopathy” was often used in reports of some of these adult Covid cases. Acute Necrotizing Encephalopathy is listed as its own entity on the Genetic and Rare Disease (Gard) website (3) and Infection Induced Acute Encephalopathy 3, IIAE3 (genetic ANE) listed as a subtype.
Under IIAE3 are other names that ANE is known as; here we find postinfectious acute necrotizing hemorrhagic encephalopathy alongside ANEC, ADANE, ANE1 among others. As an organisation promoting awareness we find this quite frustrating that other less known labels are being used.
However, the further study of Covid19 associated ANE may reveal differences in the disease with this trigger and why it seems to particularly affect adults. From the article – COVID-19–associated acute necrotising encephalopathy successfully treated with steroids and polyvalent immunoglobulin with unusual IgG targeting the cerebral fibre network (yes…that is quite a mouthful!) (4) we find the following comment in conclusion.
COVID-19-mediated ANE with IgG antibodies emerging from peripheral tissues and targeting the cerebral fibre network around basal ganglia is a possible new entity that should be further studied.
The following reference from the article, Acute Necrotizing Encephalopathy: A Disease Meriting Greater Recognition (5) notes differences between adult and child cases.
Among the observed differences between ANE in adults and children, the authors report higher white matter (89%) and cerebellar (100%) involvement, in addition to parenchymal hemorrhage (90%), in adults. Our previous study of pediatric ANE found cerebellar lesions in only 23% of affected children. The reason for the higher occurrence rate in adults than children is not considered in detail by the authors, but it may reflect differences in infectious agents, genetic background, immune response, and age-specific tissue vulnerability.
It remains to be seen if further research can elucidate on Covid19 associated ANE and adult versus child cases.
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To finish off we’d just like to say a huge thank you to all our ANE families. Our tribe. They are a truly wonderful group of people that even with cultural and language differences are always focused on lifting and supporting each other in so many different ways. They share their own lived experiences of ANE – the many types of grief, the milestones, joys and frustrations associated with such a devastating disease. Through all the unknowns that the pandemic has brought, the feeling of oneness, that we are not alone within our community is truly invaluable. To the many friends & family that support our members and the ANE community as a whole we thank you. We acknowledge the support of all who follow ANE International and continue to help us raise awareness. There are a whole lot of Us in #ANEandUs and for that we are truly grateful.
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(1). Ibrahim, R.S.M., Elzayat, W., Seif, H.M. et al. Multi-parametric magnetic resonance imaging in acute necrotizing encephalopathy of children: validity and prognostic value. Egypt J Radiol Nucl Med 51, 113 (2020). https://doi.org/10.1186/s43055-020-00214-1
(2) Qingtang Shen, Yifan E Wang, Alexander F Palazzo, et al Crosstalk between nucleocytoplasmic trafficking and the innate immune response to viral infection Journal of Biological Chemistry JBC Reviews/Articles in Press, 100856
Qingtang Shen, Yifan E. Wang, Mathew Truong, Kohila Mahadevan, Jingze J. Wu, Hui Zhang, Jiawei Li, Harrison W. Smith, Craig A. Smibert, Alexander F. Palazzo, et al RanBP2/Nup358 enhances miRNA activity by sumoylating Argonautes PLOS Genetics February 18, 2021
(3) https://rarediseases.info.nih.gov/diseases/13233/acute-necrotizing-encephalopathy
(4) Delamarre L, Gollion C, Grouteau G NeuroICU Research Group, et alCOVID-19–associated acute necrotising encephalopathy successfully treated with steroids and polyvalent immunoglobulin with unusual IgG targeting the cerebral fibre network Journal of Neurology, Neurosurgery & Psychiatry 2020;91:1004-1006.
(5) H Kikokoro, Acute Necrotizing Encephalopathy: A Disease Meriting Greater Recognition American Journal of Neuroradiology December 2020, 41 (12) 2255-2256;
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