Archana A Patel1, Ali Jannati2, Sameer C Dhamne3, Monica Sapuwa4, Elizabeth Kalanga4, Maitreyi Mazumdar5, Gretchen L Birbeck6, Alexander Rotenberg2. 1. Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: archana.patel@childrens.harvard.edu. 2. Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 3. Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 4. Blantyre Malaria Project, Queen Elizabeth Central Hospital, Blantyre, Malawi. 5. Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 6. Blantyre Malaria Project, Queen Elizabeth Central Hospital, Blantyre, Malawi; Epilepsy Division, Department of Neurology, University of Rochester, Rochester, NY, USA.
Abstract
OBJECTIVE: Cerebral malaria (CM) affects 500,000 million children annually, 10% whom develop epilepsy within two years. Acute identification of biomarkers for post-CM epilepsy would allow for follow-up of the highest risk populations in resource-limited regions. We investigated the utility of electroencephalogram (EEG) and clinical metrics obtained during acute CM infection for predicting epilepsy. METHODS: We analyzed 70 EEGs recorded within 24 h of admission for CM hospitalization obtained during the Blantyre Malaria Project Epilepsy Study (2005-2007), a prospective cohort study of pediatric CM survivors. While all studies underwent spectral analyses for comparisons of mean power band frequencies, a subset of EEGs from the 10 subjects who developed epilepsy and 10 age- and sex-matched controls underwent conventional visual analysis. Findings were tested for relationships to epilepsy outcomes. RESULTS: Ten of the 70 subjects developed epilepsy. There were no significant differences between groups that were analyzed via visual EEG review; however, spectral EEG analyses revealed a significantly higher gamma-delta power ratio in CM survivors who developed epilepsy (0.23 ± 0.10) than in those who did not (0.16 ± 0.06), p = 0.003. Excluding potential confounders, multivariable logistic-regression analyses found relative gamma power (p = 0.003) and maximum temperature during admission (p = 0.03) significant and independent predictors of post-CM epilepsy, with area under receiver operating characteristics (AUROC) curve of 0.854. CONCLUSIONS: We found that clinical and EEG metrics acquired during acute CM presentation confer risk of post-CM epilepsy. Further studies are required to investigate the utility of gamma activity as a potential biomarker of epileptogenesis and study this process over time. Additionally, resource limitations currently prevent follow-up of all CM cases to surveil for epilepsy, and identification of acute biomarkers in this population would offer the opportunity to allocate resources more efficiently.
OBJECTIVE:Cerebral malaria (CM) affects 500,000 million children annually, 10% whom develop epilepsy within two years. Acute identification of biomarkers for post-CM epilepsy would allow for follow-up of the highest risk populations in resource-limited regions. We investigated the utility of electroencephalogram (EEG) and clinical metrics obtained during acute CM infection for predicting epilepsy. METHODS: We analyzed 70 EEGs recorded within 24 h of admission for CM hospitalization obtained during the Blantyre Malaria Project Epilepsy Study (2005-2007), a prospective cohort study of pediatric CM survivors. While all studies underwent spectral analyses for comparisons of mean power band frequencies, a subset of EEGs from the 10 subjects who developed epilepsy and 10 age- and sex-matched controls underwent conventional visual analysis. Findings were tested for relationships to epilepsy outcomes. RESULTS: Ten of the 70 subjects developed epilepsy. There were no significant differences between groups that were analyzed via visual EEG review; however, spectral EEG analyses revealed a significantly higher gamma-delta power ratio in CM survivors who developed epilepsy (0.23 ± 0.10) than in those who did not (0.16 ± 0.06), p = 0.003. Excluding potential confounders, multivariable logistic-regression analyses found relative gamma power (p = 0.003) and maximum temperature during admission (p = 0.03) significant and independent predictors of post-CM epilepsy, with area under receiver operating characteristics (AUROC) curve of 0.854. CONCLUSIONS: We found that clinical and EEG metrics acquired during acute CM presentation confer risk of post-CM epilepsy. Further studies are required to investigate the utility of gamma activity as a potential biomarker of epileptogenesis and study this process over time. Additionally, resource limitations currently prevent follow-up of all CM cases to surveil for epilepsy, and identification of acute biomarkers in this population would offer the opportunity to allocate resources more efficiently.
Authors: Karl B Seydel; Samuel D Kampondeni; Clarissa Valim; Michael J Potchen; Danny A Milner; Francis W Muwalo; Gretchen L Birbeck; William G Bradley; Lindsay L Fox; Simon J Glover; Colleen A Hammond; Robert S Heyderman; Cowles A Chilingulo; Malcolm E Molyneux; Terrie E Taylor Journal: N Engl J Med Date: 2015-03-19 Impact factor: 91.245
Authors: C R Newton; T Chokwe; J A Schellenberg; P A Winstanley; D Forster; N Peshu; F J Kirkham; K Marsh Journal: Trans R Soc Trop Med Hyg Date: 1997 Mar-Apr Impact factor: 2.184
Authors: Mustafa Q Hameed; Tsung-Hsun Hsieh; Leon Morales-Quezada; Henry H C Lee; Ugur Damar; Paul C MacMullin; Takao K Hensch; Alexander Rotenberg Journal: Cereb Cortex Date: 2019-12-17 Impact factor: 5.357
Authors: Alexander Andrews; Tesfaye Zelleke; Rima Izem; Jiaxiang Gai; Dana Harrar; Jessica Mvula; Douglas G Postels Journal: Pediatr Neurol Date: 2021-10-19 Impact factor: 3.372
Authors: Archana A Patel; Gretchen L Birbeck; Maitreyi Mazumdar; Suzanna Mwanza; Rosemary Nyirongo; Dixon Berejena; Joseph Kasolo; Tina Mwale; Violet Nambeye; Kafula Lisa Nkole; Nfwama Kawatu; Bo Zhang; Alexander Rotenberg Journal: BMJ Open Date: 2022-07-18 Impact factor: 3.006