Noninvasive measures of brain edema predict outcome in pediatric cerebral malaria

Samuel D Kampondeni, Gretchen L Birbeck, Karl B Seydel, Nicholas A Beare, Simon J Glover, Colleen A Hammond, Cowles A Chilingulo, Terrie E Taylor, Michael J Potchen, Samuel D Kampondeni, Gretchen L Birbeck, Karl B Seydel, Nicholas A Beare, Simon J Glover, Colleen A Hammond, Cowles A Chilingulo, Terrie E Taylor, Michael J Potchen

Abstract

Background: Increased brain volume (BV) and subsequent herniation are strongly associated with death in pediatric cerebral malaria (PCM), a leading killer of children in developing countries. Accurate noninvasive measures of BV are needed for optimal clinical trial design. Our objectives were to examine the performance of six different magnetic resonance imaging (MRI) BV quantification measures for predicting mortality in PCM and to review the advantages and disadvantages of each method.

Methods: Receiver operator characteristics were generated from BV measures of MRIs of children admitted to an ongoing research project with PCM between 2009 and 2014. Fatal cases were matched to the next available survivor. A total of 78 MRIs of children aged 5 months to 13 years (mean 4.0 years), of which 45% were males, were included.

Results: Areas under the curve (AUC) with 95% confidence interval on measures from the initial MRIs were: Radiologist-derived score = 0.69 (0.58-0.79; P = 0.0037); prepontine cistern anteroposterior (AP) dimension = 0.70 (0.56-0.78; P = 0.0133); SamKam ratio [Rt. parietal lobe height/(prepontine AP dimension + fourth ventricle AP dimension)] = 0.74 (0.63-0.83; P = 0.0002); and global cerebrospinal fluid (CSF) space ascertained by ClearCanvas = 0.67 (0.55-0.77; P = 0.0137). For patients with serial MRIs (n = 37), the day 2 global CSF space AUC was 0.87 (0.71-0.96; P < 0.001) and the recovery factor (CSF volume day 2/CSF volume day 1) was 0.91 (0.76-0.98; P < 0.0001). Poor prognosis is associated with radiologist score of ≥7; prepontine cistern dimension ≤3 mm; cisternal CSF volume ≤7.5 ml; SamKam ratio ≥6.5; and recovery factor ≤0.75.

Conclusion: All noninvasive measures of BV performed well in predicting death and providing a proxy measure for brain volume. Initial MRI assessment may inform future clinical trials for subject selection, risk adjustment, or stratification. Measures of temporal change may be used to stage PCM.

Keywords: Brain herniation; brain volume; intracranial pressure; noninvasive measures; pediatric cerebral malaria; receiver operator characteristic.

Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Images for radiologist-derived BV 1-8 score, L-R:Top row (BV 1,2,3), Middle row (BV4,5,6), Bottom row (BV 7,8,8)
Figure 2
Figure 2
SamKam ratio
Figure 3
Figure 3
Cranial cisternal CSF quantification method
Figure 4
Figure 4
ROCs for all six MRI brain edema evaluation methods
Figure 5
Figure 5
Staging of PCM
Figure 6
Figure 6
Poor prognosis: Mid-sagittal T1 flair image showing severe brain edema in a child who succumbed to CM: radiologist BV score = 8; prepontine cistern dimension = 0; Cisternal CSF volume = 0.41 ml; SamKam ratio = 35; and RF = 0.026
Figure 7
Figure 7
Earlier oedema resolution detection by staging than global image assessment. Axial T2 images done on subsequent days showing severe oedema in two children. Top row:Child died (BV scores 8; 8; RF= 0.026). Bottom row: Child survived (BV scores 8; 8; RF=2.4)

References

    1. Beare NA, Lewallen S, Taylor TE, Molyneux ME. Redefining cerebral malaria by including malaria retinopathy. Future Microbiol. 2011;6:349–55.
    1. Brinker T, Stopa E, Morrison J, Klinge P. A new look at cerebrospinal fluid circulation. Fluids Barriers CNS. 2014;11:10.
    1. Brott T, Marler JR, Olinger CP, Adams HP, Jr, Tomsick T, Barsan WG. Measurements of acute cerebral infarction: Lesion size by computed tomography. Stroke. 1989;20:871–5.
    1. Chesnut RM, Temkin N, Carney N, Dikmen S, Rondina C, Videtta W, et al. A trial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med. 2012;367:2471–81.
    1. Kampondeni SD, Chilingulo C, Seydel KB, Potchen MJ, Bradley WG, Latourette M, editors. Vol. 87. Atlanta, GA: American Society of Tropical Medicine and Hygiene; 2012. MRI Measure (SamKam) Predicts Outcome in Pediatric Cerebral Malaria (Abstract No: 1427) p. 433.
    1. Khan MN, Shallwani H, Khan MU, Shamim MS. Noninvasive monitoring intracranial pressure-A review of available modalities. Surg Neurol Int. 2017;8:51.
    1. Lewallen S, Bronzan RN, Beare NA, Harding SP, Molyneux ME, Taylor TE. Using malarial retinopathy to improve the classification of children with cerebral malaria. Trans R Soc Trop Med Hyg. 2008;102:1089–94.
    1. Marsh K, Forster D, Waruiru C, Mwangi I, Winstanley M, Marsh V, et al. Indicators of life-threatening malaria in African children. N Engl J Med. 1995;332:1399–404.
    1. Milner DA, Jr, Whitten RO, Kamiza S, Carr R, Liomba G, Dzamalala C. The systemic pathology of cerebral malaria in African children. Front Cell Infect Microbiol. 2014;4:104.
    1. Newton CR, Crawley J, Sowumni A, Waruiru C, Mwangi I, English M, et al. Intracranial hypertension in Africans with cerebral malaria. Arch Dis Child. 1997;76:219–26.
    1. Newton CR, Kirkham FJ, Winstanley PA, Pasvol G, Peshu N, Warrell DA, et al. Intracranial pressure in African children with cerebral malaria. Lancet. 1991;337:573–6.
    1. Newton CR, Peshu N, Kendall B, Kirkham FJ, Sowunmi A, Waruiru C, et al. Brain swelling and ischaemia in Kenyans with cerebral malaria. Arch Dis Child. 1994;70:281–7.
    1. Potchen MJ, Kampondeni SD, Ibrahim K, Bonner J, Seydel KB, Taylor TE, et al. NeuroInterp: A method for facilitating neuroimaging research on cerebral malaria. Neurology. 2013;81:585–8.
    1. Potchen MJ, Kampondeni SD, Seydel KB, Birbeck GL, Hammond CA, Bradley WG, et al. Acute brain MRI findings in 120 Malawian children with cerebral malaria: New insights into an ancient disease. AJNR Am J Neuroradiol. 2012;33:1740–6.
    1. Seydel KB, Kampondeni SD, Valim C, Potchen MJ, Milner DA, Muwalo FW, et al. Brain swelling and death in children with cerebral malaria. N Engl J Med. 2015;372:1126–37.
    1. Smith M. Monitoring intracranial pressure in traumatic brain injury. Anesth Analg. 2008;106:240–8.
    1. Taylor TE. Caring for children with cerebral malaria: Insights gleaned from 20 years on a research ward in Malawi. Trans R Soc Trop Med Hyg. 2009;103(Suppl 1):S6–10.
    1. Taylor TE, Fu WJ, Carr RA, Whitten RO, Mueller JS, Fosiko NG, et al. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med. 2004;10:143–5.
    1. Tucker B, Aston J, Dines M, Caraman E, Yacyshyn M, McCarthy M, et al. Early Brain Edema is a Predictor of In-Hospital Mortality in Traumatic Brain Injury. J Emerg Med. 2017;53:18–29.
    1. van der Worp HB, Claus SP, Bar PR, Ramos LM, Algra A, van Gijn J, et al. Reproducibility of measurements of cerebral infarct volume on CT scans. Stroke. 2001;32:424–30.
    1. WHO. World Malaria Report. 2017. [last accessed on 2018 Feb 1]. Available from:

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