METHODS: Systematic review of English language publications in PubMed and reference lists between January 1, 2020, and June 30, 2023, in accordance with PRISMA guidelines. Patients with SARS-CoV-2 infection who fulfilled diagnostic criteria for sporadic and genetic ANE were included.
RESULTS: From 899 articles, 20 cases (17 single case reports and 3 additional cases) were curated for review (50% female; 8 were children). Associated COVID-19 illnesses were febrile upper respiratory tract infections in children while adults had pneumonia (45.6%) and myocarditis (8.2%). Children had early neurologic deterioration (median day 2 in children vs day 4 in adults), seizures (5 (62.5%) children vs 3 of 9 (33.3%) adults), and motor abnormalities (6 of 7 (85.7%) children vs 3 of 7 (42.9%) adults). Eight of 12 (66.7%) adults and 4 (50.0%) children had high-risk ANE scores. Five (62.5%) children and 12 (66.7%) adults had brain lesions bilaterally and symmetrically in the putamina, external capsules, insula cortex, or medial temporal lobes, in addition to typical thalamic lesions of ANE. Hypotension was only seen in adults (30%). Hematologic derangements were common: lymphopenia (66.7%), coagulopathy (60.0%), or elevated D-dimers (100%), C-reactive protein (91.7%), and ferritin (62.5%). A pathogenic heterozygous c/.1754 C>T variant in RANBP2 was present in 2 children: one known to have this before SARS-CoV-2 infection, and a patient tested because the SARS-CoV-2 infection was the second encephalopathic illness. Three other children with no prior encephalopathy or family history of encephalopathy were negative for this variant. Fifteen (75%) received immunotherapy (with IV methylprednisolone, immunoglobulins, tocilizumab, or plasma exchange): 6 (40.0%) with monotherapy and 9 (60.0%) had combination therapy. Deaths were in 8 of 17 with data (47.1%): a 2-month-old male infant and 7 adults (87.5%) of median age 56 years (33-70 years), 4 of whom did not receive immunotherapy.
DISCUSSION: Children and adults with SARS-CoV-2 ANE have similar clinical features and neuroimaging characteristics. Mortality is high, predominantly in patients not receiving immunotherapy and at the extremes of age.
METHOD: The draft definitions were based on existing criteria, standardized, and discussed by a panel of international experts using nominal group technique over 18 months to achieve consensus. All criteria use the same format: (1) presence of infection/fever; (2) clinical features including encephalopathy; (3) neuroradiological features on magnetic resonance imaging; (4) exclusion of other causes.
RESULTS: We first highlighted differences between ITES and infectious and autoimmune encephalitis, which is the most important differential diagnosis. Consensus was achieved to define five specific ITESs: acute encephalopathy with biphasic seizures and late reduced diffusion; acute necrotizing encephalopathy; mild encephalopathy with a reversible splenial lesion; acute fulminant cerebral oedema; and acute shock with encephalopathy and multiorgan failure. Two further conditions that are currently classified as epilepsy syndromes but have similar features to ITES, namely febrile infection-related epilepsy syndrome and hemiconvulsion-hemiplegia-epilepsy syndrome, are also discussed.
INTERPRETATION: The consensus definition is expected to improve awareness of this disease concept, provide diagnostic framework, and facilitate future international research and clinical trials.
RESULTS: The decline in breastfeeding in the Philippines in the mid-twentieth Century associated with intensive BMS marketing via health systems and consumer advertising. As regulations tightened, the industry more aggressively promoted CMFs for older infants and young children, thereby 'marketing around' the Milk Code. It established front groups to implement political strategies intended to weaken the country's breastfeeding policy framework while also fostering a favourable image. This included lobbying government officials and international organizations, emphasising its economic importance and threats to foreign investment and trade, direct litigation against the government, messaging that framed marketing in terms of women's choice and empowerment, and forging partnerships. A resurgence in breastfeeding from the mid-1980s onwards reflected strengthening political commitment for a national breastfeeding policy framework and Milk Code, resulting in-turn, from collective actions by breastfeeding coalitions, advocates and mothers.
CONCLUSION: The Philippines illustrates the continuing battle for worldwide Code implementation, and in particular, how the baby food industry uses and adapts its market and political practices to promote and sustain CMF markets. Our results demonstrate that this industry's political practices require much greater scrutiny. Furthermore, that mobilizing breastfeeding coalitions, advocacy groups and mothers is crucial to continually strengthen and protect national breastfeeding policy frameworks and Code implementation.