Neurological Symptoms and Cause of Death Among Young Children in Low- and Middle-Income Countries
Authors: Ajanovic Sara , Madewell Zachary J. , El Arifeen Shams , Gurley Emily S. , Hossain Mohammad Zahid , Islam Kazi Munisul , Rahman Afruna , Assefa Nega , Madrid Lola , Abdulahi Mohammednur , Igunza Kitiezo Aggrey , Murila Florence , Revathi Gunturu , Christopher Mugah , Sow Samba O. , Kotloff Karen L. , Tapia Milagritos D. , Traor Cheik Bougadari , Mandomando Inacio , Xerinda Elisio , Varo Rosauro , Kincardett Milton , Ogbuanu Ikechukwu U. , Nwajiobi-Princewill Phillip , Swarray-Deen Alim , Luke Ronita , Madhi Shabir A. , Mahtab Sana , Dangor Ziyaad , du Toit Jeanie , Akelo Victor , Mutevedzi Portia , Tippett Barr Beth A. , Blau Dianna M. , Whitney Cynthia G. , Bassat Quique ,   Child Health and Mortality Prevention Surveillance (CHAMPS) Consortium, Solomon Fatima , Sorour Gillian , Lombaard Hennie , Wadula Jeannette , Petersen Karen , Hale Martin , P. Govender Nelesh , J. Swart Peter , G. Lala Sanjay , Velaphi Sithembiso , Chawana Richard , Adam Yasmin , Wise Amy , Myburgh Nellie , Bari Sanwarul , Parveen Shahana , Kamal Mohammed , Uddin Ahmed A.S.M. Nawshad , Hoque Mahbubul , Tasnim Saria , Islam Ferdousi , Ariuman Farida , Mosiur Rahman Mohammad , Begum Ferdousi , Zaman K. Zaman , Rahman Mustafizur , Ahmed Dilruba , Sabrina Flora Meerjady , Shirin Tahmina , Rahman Mahbubur , Oundo Joseph , Ibrahim Alexander M. , Temesgen Fikremelekot , Gure Tadesse , Alemu Addisu , Mulatu Yeshi Melisachew , Abayneh Gizaw Mahlet , MS Orlien Stian , Ali Solomon , Aggrey Igunza Kitiezo , Otieno Peter , Nyamthimba Onyango Peter , Agaya Janet , Oliech Richard , Akinyi Were Joyce , Gethi Dickson , Aol George , Misore Thomas , Owuor Harun , Muga Christopher , Oluoch Bernard , Ochola Christine , M. Tennant Sharon , L. Greene Carol , Mehta Ashka , Johnson J. Kristie , Gaume Brigitte , Mamby Keita Adama , Koka Rima , D. Fairchild Karen , Kone Diakaridia , Sidibe Diakaridia , Sanogo Doh , Onwuchekwa Uma U. , Kourouma Nana , Sissoko Seydou , Bougadari Traore Cheick , Juma Jane , Diarra Kounandji , Traore Awa , Diarra Tiéman , Chawla Kiranpreet , Nhampossa Tacilta , Manhique Zara , Mocumbi Sibone , Menéndez Clara , Munguambe Khátia , Nhacolo Ariel , Maixenchs Maria , Moseray Andrew , Bintu Tarawally Fatmata , Seppeh Martin , Mash Ronald , Ojulong Julius , Duduyemi Babatunde , Bunn James , Swaray-Deen Alim , Bangura Joseph , Jambai Amara , Mannah Margaret , Ita Okokon , Chukwuegbo Cornell , Sannoh Sulaiman , Nwajiobi Princewill , Kowuor Dickens , Kaluma Erick , Balogun Oluseyi , Jo Cain Carrie , Samura Solomon , Pratt Samuel , Moses Francis , Sesay Tom , Squire James , Kamanda Sesay Joseph , Kaykay Osman , Halu Binyam , Legesse Hailemariam , Smart Francis , Kenneh Sartie , Ameh Soter , Ritter Jana , Wilson Tais , Winchell Jonas , Witherbee Jakob , Garel Mischka , T. Salzberg Navit , P. Koplan Jeffrey , Han Lee Kyu , Martines Roosecelis , Warang Shamta , Diaz Maureen , Waller Jessica , Nair Shailesh , Liu Lucy , Liu Courtney Bursuc , LaHatte Kristin , Raymer Sarah , Blevins John , Argeseanu Solveig , Vyas Kurt , Bhandari Manu 
Published: September 2024

ImportanceThe emergence of acute neurological symptoms in children necessitates immediate intervention. Although low- and middle-income countries (LMICs) bear the highest burden of neurological diseases, there is a scarcity of diagnostic and therapeutic resources. Therefore, current understanding of the etiology of neurological emergencies in LMICs relies mainly on clinical diagnoses and verbal autopsies.ObjectiveTo characterize the association of premortem neurological symptoms and their management with postmortem-confirmed cause of death among children aged younger than 5 years in LMICs and to identify current gaps and improve strategies to enhance child survival.Design, Setting, and ParticipantsThis cross-sectional study was conducted between December 3, 2016, and July 22, 2022, at the 7 participating sites in the Child Health and Mortality Prevention Surveillance (CHAMPS) network (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa). Minimally invasive tissue sampling was performed at the CHAMPS sites with specimens from deceased children aged younger than 5 years. This study included deceased children who underwent a premortem neurological evaluation and had a postmortem-confirmed cause of death. Data analysis was performed between July 22, 2022, and January 15, 2023.Main Outcomes and MeasuresDescriptive analysis was performed using neurological evaluations from premortem clinical records and from postmortem determination of cause of death (based on histopathology, microbiological testing, clinical records, and verbal autopsies).ResultsOf the 2127 deaths of children codified during the study period, 1330 (62.5%) had neurological evaluations recorded and were included in this analysis. The 1330 children had a median age of 11 (IQR, 2-324) days; 745 (56.0%) were male and 727 (54.7%) presented with neurological symptoms during illness before death. The most common postmortem-confirmed neurological diagnoses related to death were hypoxic events (308 [23.2%]), meningoencephalitis (135 [10.2%]), and cerebral malaria (68 [5.1%]). There were 12 neonates with overlapping hypoxic events and meningoencephalitis, but there were no patients with overlapping meningoencephalitis and cerebral malaria. Neurological symptoms were similar among diagnoses, and no combination of symptoms was accurate in differentiating them without complementary tools. However, only 25 children (18.5%) with meningitis had a lumbar puncture performed before death. Nearly 90% of deaths (442 of 511 [86.5%]) with neurological diagnoses in the chain of events leading to death were considered preventable.Conclusions and RelevanceIn this cross-sectional study of children aged younger than 5 years, neurological symptoms were frequent before death. However, clinical phenotypes were insufficient to differentiate the most common underlying neurological diagnoses. The low rate of lumbar punctures performed was especially worrying, suggesting a challenge in quality of care of children presenting with neurological symptoms. Improved diagnostic management of neurological emergencies is necessary to ultimately reduce mortality in this vulnerable population.