Brain growth after surgical treatment for infant postinfectious hydrocephalus in Sub-Saharan Africa: 2-year results of a randomized trial

View More View Less
  • 1 Center for Neural Engineering;
  • | 2 Departments of Neurosurgery,
  • | 3 Engineering Science and Mechanics, and
  • | 4 Physics, The Pennsylvania State University, State College, Pennsylvania;
  • | 5 Departments of Neurosurgery and
  • | 6 Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada;
  • | 7 CURE Children’s Hospital of Uganda, Mbale, Uganda; and
  • | 8 Department of Neurosurgery, Boston Children’s Hospital, Boston, Massachusetts
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

OBJECTIVE

Hydrocephalus in infants, particularly that with a postinfectious etiology, is a major public health burden in Sub-Saharan Africa. The authors of this study aimed to determine whether surgical treatment of infant postinfectious hydrocephalus in Uganda results in sustained, long-term brain growth and improved cognitive outcome.

METHODS

The authors performed a trial at a single center in Mbale, Uganda, involving infants (age < 180 days old) with postinfectious hydrocephalus randomized to endoscopic third ventriculostomy plus choroid plexus cauterization (ETV+CPC; n = 51) or ventriculoperitoneal shunt (VPS; n = 49). After 2 years, they assessed developmental outcome with the Bayley Scales of Infant Development, Third Edition (BSID-III), and brain volume (raw and normalized for age and sex) with CT scans.

RESULTS

Eighty-nine infants were assessed for 2-year outcome. There were no significant differences between the two surgical treatment arms in terms of BSID-III cognitive score (p = 0.17) or brain volume (p = 0.36), so they were analyzed together. Raw brain volumes increased between baseline and 2 years (p < 0.001), but this increase occurred almost exclusively in the 1st year (p < 0.001). The fraction of patients with a normal brain volume increased from 15.2% at baseline to 50.0% at 1 year but then declined to 17.8% at 2 years. Substantial normalized brain volume loss was seen in 21.3% patients between baseline and year 2 and in 76.7% between years 1 and 2. The extent of brain growth in the 1st year was not associated with the extent of brain volume changes in the 2nd year. There were significant positive correlations between 2-year brain volume and all BSID-III scores and BSID-III changes from baseline.

CONCLUSIONS

In Sub-Saharan Africa, even after successful surgical treatment of infant postinfectious hydrocephalus, early posttreatment brain growth stagnates in the 2nd year. While the reasons for this finding are unclear, it further emphasizes the importance of primary infection prevention and mitigation strategies along with optimizing the child’s environment to maximize brain growth potential.

ABBREVIATIONS

BSID-III = Bayley Scales of Infant Development, Third Edition; CCHU = CURE Children’s Hospital of Uganda; ETV+CPC = endoscopic third ventriculostomy plus choroid plexus cauterization; VPS = ventriculoperitoneal shunt.

Illustration from Seaman et al. (pp 260–267). Copyright Jane Whitney. Published with permission.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Correspondence Benjamin C. Warf: Boston Children’s Hospital, Boston, MA. benjamin.warf@childrens.harvard.edu.

S.J.S., A.V.K., and B.C.W. contributed equally to this work.

INCLUDE WHEN CITING Published online July 9, 2021; DOI: 10.3171/2021.2.PEDS20949.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

  • 1

    Warf BC. Educate one to save a few. Educate a few to save many. World Neurosurg. 2013;79(2)(suppl):15.e1515.e18.

  • 2

    Dewan MC, Rattani A, Mekary R, et al. Global hydrocephalus epidemiology and incidence: systematic review and meta-analysis. J Neurosurg. 2018;130(4):115.

    • Search Google Scholar
    • Export Citation
  • 3

    Warf BC. Hydrocephalus in Uganda: the predominance of infectious origin and primary management with endoscopic third ventriculostomy. J Neurosurg. 2005;102(1)(suppl):115.

    • Search Google Scholar
    • Export Citation
  • 4

    Lepard JR, Dewan MC, Chen SH, et al. The CURE Protocol: evaluation and external validation of a new public health strategy for treating paediatric hydrocephalus in low-resource settings. BMJ Glob Health. 2020;5(2):e002100.

    • Search Google Scholar
    • Export Citation
  • 5

    Warf BC, Alkire BC, Bhai S, et al. Costs and benefits of neurosurgical intervention for infant hydrocephalus in sub-Saharan Africa. J Neurosurg Pediatr. 2011;8(5):509521.

    • Search Google Scholar
    • Export Citation
  • 6

    Warf BC. Comparison of 1-year outcomes for the Chhabra and Codman-Hakim Micro Precision shunt systems in Uganda: a prospective study in 195 children. J Neurosurg. 2005;102(4)(suppl):358362.

    • Search Google Scholar
    • Export Citation
  • 7

    Mbabazi-Kabachelor E, Shah M, Vaughan KA, et al. Infection risk for Bactiseal Universal Shunts versus Chhabra shunts in Ugandan infants: a randomized controlled trial. J Neurosurg Pediatr. 2019;23(3):397406.

    • Search Google Scholar
    • Export Citation
  • 8

    Warf BC. Comparison of endoscopic third ventriculostomy alone and combined with choroid plexus cauterization in infants younger than 1 year of age: a prospective study in 550 African children. J Neurosurg. 2005;103(6)(suppl):475481.

    • Search Google Scholar
    • Export Citation
  • 9

    Warf BC, Campbell JW. Combined endoscopic third ventriculostomy and choroid plexus cauterization as primary treatment of hydrocephalus for infants with myelomeningocele: long-term results of a prospective intent-to-treat study in 115 East African infants. J Neurosurg Pediatr. 2008;2(5):310316.

    • Search Google Scholar
    • Export Citation
  • 10

    Warf BC, Stagno V, Mugamba J. Encephalocele in Uganda: ethnic distinctions in lesion location, endoscopic management of hydrocephalus, and survival in 110 consecutive children. J Neurosurg Pediatr. 2011;7(1):8893.

    • Search Google Scholar
    • Export Citation
  • 11

    Warf BC, Dewan M, Mugamba J. Management of Dandy-Walker complex-associated infant hydrocephalus by combined endoscopic third ventriculostomy and choroid plexus cauterization. J Neurosurg Pediatr. 2011;8(4):377383.

    • Search Google Scholar
    • Export Citation
  • 12

    Warf BC, Tracy S, Mugamba J. Long-term outcome for endoscopic third ventriculostomy alone or in combination with choroid plexus cauterization for congenital aqueductal stenosis in African infants. J Neurosurg Pediatr. 2012;10(2):108111.

    • Search Google Scholar
    • Export Citation
  • 13

    Warf BC. Congenital idiopathic hydrocephalus of infancy: the results of treatment by endoscopic third ventriculostomy with or without choroid plexus cauterization and suggestions for how it works. Childs Nerv Syst. 2013;29(6):935940.

    • Search Google Scholar
    • Export Citation
  • 14

    Kulkarni AV, Schiff SJ, Mbabazi-Kabachelor E, et al. Endoscopic treatment versus shunting for infant hydrocephalus in Uganda. N Engl. J Med. 2017;377(25):24562464.

    • Search Google Scholar
    • Export Citation
  • 15

    Peterson M, Warf BC, Schiff SJ. Normative human brain volume growth. J Neurosurg Pediatr. 2018;21(5):478485.

  • 16

    Warf BC. Combined Endoscopic Third Ventriculostomy and Choroid Plexus Cauterization (ETV/CPC) for Hydrocephalus in Infants and Children with Special Emphasis on the Developing World. 2nd ed. Endo-Press;2015.

    • Search Google Scholar
    • Export Citation
  • 17

    Warf B, Ondoma S, Kulkarni A, et al. Neurocognitive outcome and ventricular volume in children with myelomeningocele treated for hydrocephalus in Uganda. J Neurosurg Pediatr. 2009;4(6):564570.

    • Search Google Scholar
    • Export Citation
  • 18

    Lane JD, Mugamba J, Ssenyonga P, Warf BC. Effectiveness of the Bactiseal Universal Shunt for reducing shunt infection in a sub-Saharan African context: a retrospective cohort study in 160 Ugandan children. J Neurosurg Pediatr. 2014;13(2):140144.

    • Search Google Scholar
    • Export Citation
  • 19

    Marano PJ, Stone SSD, Mugamba J, et al. Reopening of an obstructed third ventriculostomy: long-term success and factors affecting outcome in 215 infants. J Neurosurg Pediatr. 2015;15(4):399405.

    • Search Google Scholar
    • Export Citation
  • 20

    Peterson MR, Cherukuri V, Paulson JN, et al. : Normal childhood brain growth and a universal sex and anthropomorphic relationship to cerebrospinal fluid. J Neurosurg Pediatr.In press.

    • Search Google Scholar
    • Export Citation
  • 21

    Warf BC, Dagi AR, Kaaya BN, Schiff SJ. Five-year survival and outcome of treatment for postinfectious hydrocephalus in Ugandan infants. J Neurosurg Pediatr. 2011;8(5):502508.

    • Search Google Scholar
    • Export Citation
  • 22

    El-Dib M, Limbrick DD Jr, Inder T, et al. Management of post-hemorrhagic ventricular dilatation in the infant born preterm. J Pediatr. 2020;226:P16P27.E3.

    • Search Google Scholar
    • Export Citation
  • 23

    Karimy JK, Reeves BC, Kahle KT. Targeting TLR4-dependent inflammation in post-hemorrhagic brain injury. Expert Opin Ther Targets. 2020;24(6):525533.

    • Search Google Scholar
    • Export Citation
  • 24

    Kahle KT, Kulkarni AV, Limbrick DD Jr, Warf BC. Hydrocephalus in children. Lancet. 2016;387(10020):788799.

  • 25

    McAllister JP II. Pathophysiology of congenital and neonatal hydrocephalus. Semin Fetal Neonatal Med. 2012;17(5):285294.

  • 26

    de Graaf-Peters VB, Hadders-Algra M. Ontogeny of the human central nervous system: what is happening when?. Early Hum Dev. 2006;82(4):257266.

    • Search Google Scholar
    • Export Citation
  • 27

    Paulson JN, Williams BL, Hehnly C, et al. Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants. Sci Transl Med. 2020;12(563):eaba0565.

    • Search Google Scholar
    • Export Citation
  • 28

    Sheth KN, Mazurek MH, Yuen MM, et al. Assessment of brain injury using portable, low-field magnetic resonance imaging at the bedside of critically ill patients. JAMA Neurol. 2020;78(1):4147.

    • Search Google Scholar
    • Export Citation
  • 29

    O’Reilly T, Teeuwisse WM, de Gans D, et al. In vivo 3D brain and extremity MRI at 50 mT using a permanent magnet Halbach array. Magn Reson Med. 2021;85(1):.

    • Search Google Scholar
    • Export Citation
  • 30

    Cherukuri V, Ssenyonga P, Warf B, et al. Learning based segmentation of CT brain images: application to post-operative hydrocephalic scans. IEEE Trans Biomed Eng. 2018;65(8):.

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 70 70 70
Full Text Views 20 20 20
PDF Downloads 30 30 30
EPUB Downloads 0 0 0