2024
The genetic basis of hydrocephalus: genes, pathways, mechanisms, and global impact
Hale A, Boudreau H, Devulapalli R, Duy P, Atchley T, Dewan M, Goolam M, Fieggen G, Spader H, Smith A, Blount J, Johnston J, Rocque B, Rozzelle C, Chong Z, Strahle J, Schiff S, Kahle K. The genetic basis of hydrocephalus: genes, pathways, mechanisms, and global impact. Fluids And Barriers Of The CNS 2024, 21: 24. PMID: 38439105, PMCID: PMC10913327, DOI: 10.1186/s12987-024-00513-z.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidOverview of genesEtiology of HCPathogenesis of HCChoroid plexus cauterizationEndoscopic third ventriculostomyIncreased intracranial pressureGenetic architectureGenetic basisImpact of geneticsVentricular shuntSurgical treatmentThird ventriculostomyPhenotypic heterogeneityHeterogeneous diseasePharmacological treatmentGenetic syndromesMolecular pathogenesisIntracranial pressureHydrocephalusTherapeutic measuresGenesGeneticsBrain injuryPathway
2023
Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study
Morton S, Hehnly C, Burgoine K, Ssentongo P, Ericson J, Kumar M, Hagmann C, Fronterre C, Smith J, Movassagh M, Streck N, Bebell L, Bazira J, Kumbakumba E, Bajunirwe F, Mulondo R, Mbabazi-Kabachelor E, Nsubuga B, Natukwatsa D, Nalule E, Magombe J, Erickson T, Ngonzi J, Ochora M, Olupot-Olupot P, Onen J, Ssenyonga P, Mugamba J, Warf B, Kulkarni A, Lane J, Whalen A, Zhang L, Sheldon K, Meier F, Kiwanuka J, Broach J, Paulson J, Schiff S. Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study. The Lancet Microbe 2023, 4: e601-e611. PMID: 37348522, PMCID: PMC10529524, DOI: 10.1016/s2666-5247(23)00106-4.Peer-Reviewed Original ResearchConceptsMother-newborn pairsPostinfectious hydrocephalusCerebrospinal fluidNeonatal sepsisSpp infectionUgandan infantsMaternal bloodObservational case-control studyHospital OfficeInfant's cerebrospinal fluidBurden of morbidityCase-control studyRoute of infectionSubset of participantsMaternal feverCranial ultrasoundNeonatal infectionSepsis cohortOptimise treatmentTransplacental transmissionCord bloodObservational studyPlacental samplesSepsisHydrocephalus
2022
Type IV Pili Are a Critical Virulence Factor in Clinical Isolates of Paenibacillus thiaminolyticus
Hehnly C, Shi A, Ssentongo P, Zhang L, Isaacs A, Morton S, Streck N, Erdmann-Gilmore P, Tolstoy I, Townsend R, Limbrick D, Paulson J, Ericson J, Galperin M, Schiff S, Broach J. Type IV Pili Are a Critical Virulence Factor in Clinical Isolates of Paenibacillus thiaminolyticus. MBio 2022, 13: e02688-22. PMID: 36374038, PMCID: PMC9765702, DOI: 10.1128/mbio.02688-22.Peer-Reviewed Original ResearchConceptsPostinfectious hydrocephalusClinical isolatesVirulence factorsCritical virulence factorPotential virulence factorsPoor long-term outcomesPrevention of hydrocephalusLong-term outcomesBacterial pathogensDevastating sequelaeNeonatal sepsisMiddle-income countriesNeonatal infectionSurgical interventionReference strainsNovel bacterial pathogensAfrican cohortBeta-lactamase genesChildhood mortalityHydrocephalusTherapeutic targetInfectionVirulent strainDevastating diseaseWhole-genome sequencingCytomegalovirus infections in infants in Uganda: Newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus
Hehnly C, Ssentongo P, Bebell L, Burgoine K, Bazira J, Fronterre C, Kumbakumba E, Mulondo R, Mbabazi-Kabachelor E, Morton S, Ngonzi J, Ochora M, Olupot-Olupot P, Mugamba J, Onen J, Roberts D, Sheldon K, Sinnar S, Smith J, Ssenyonga P, Kiwanuka J, Paulson J, Meier F, Ericson J, Broach J, Schiff S. Cytomegalovirus infections in infants in Uganda: Newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus. International Journal Of Infectious Diseases 2022, 118: 24-33. PMID: 35150915, PMCID: PMC9058984, DOI: 10.1016/j.ijid.2022.02.005.Peer-Reviewed Original ResearchConceptsNewborn-mother pairsCMV prevalenceClinical sepsisCytomegalovirus infectionCerebrospinal fluidPrevalence of CMVQuantitative PCRCMV positivityPostinfectious hydrocephalusVaginal sheddingCMV infectionHIV seropositivityNeonatal ageMaternal ageMaternal vaginalRisk factorsMedical CenterLong-term consequencesMother pairsSepsisNeonatesInfantsPrevalenceHydrocephalusCMV
2021
Brain growth after surgical treatment for infant postinfectious hydrocephalus in Sub-Saharan Africa: 2-year results of a randomized trial.
Schiff S, Kulkarni A, Mbabazi-Kabachelor E, Mugamba J, Ssenyonga P, Donnelly R, Levenbach J, Monga V, Peterson M, Cherukuri V, Warf B. Brain growth after surgical treatment for infant postinfectious hydrocephalus in Sub-Saharan Africa: 2-year results of a randomized trial. Journal Of Neurosurgery Pediatrics 2021, 28: 326-334. PMID: 34243157, PMCID: PMC8742836, DOI: 10.3171/2021.2.peds20949.Peer-Reviewed Original ResearchPostinfectious hydrocephalusSurgical treatmentBrain volumeBrain growthBSID-III cognitive scoresMajor public health burdenSurgical treatment armSuccessful surgical treatmentBrain volume lossBrain volume changesEndoscopic third ventriculostomyFraction of patientsPublic health burdenChoroid plexus cauterizationBSID-III scoresNormal brain volumePostinfectious etiologySingle centerSub-Saharan AfricaTreatment armsThird ventriculostomyInfection preventionHealth burdenCT scanHydrocephalusImmune activation during Paenibacillus brain infection in African infants with frequent cytomegalovirus co-infection
Isaacs A, Morton S, Movassagh M, Zhang Q, Hehnly C, Zhang L, Morales D, Sinnar S, Ericson J, Mbabazi-Kabachelor E, Ssenyonga P, Onen J, Mulondo R, Hornig M, Warf B, Broach J, Townsend R, Limbrick D, Paulson J, Schiff S. Immune activation during Paenibacillus brain infection in African infants with frequent cytomegalovirus co-infection. IScience 2021, 24: 102351. PMID: 33912816, PMCID: PMC8065213, DOI: 10.1016/j.isci.2021.102351.Peer-Reviewed Original ResearchNeonatal sepsisBrain infectionImmune activationInnate immune system responseRisk of hydrocephalusDominant bacterial pathogenHost immune responsePlatelet-activating factorImmune system responseOxidative stress reactionSecondary sequelaeAdjunctive treatmentImmune response networkNeutrophil activityIL-12Hydrocephalic infantsAfrican infantsIL-13IL-4JAK/STAT pathwayAntigen-presenting complexImmune responseHydrocephalusPotential targetNeuroinflammation
2020
Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus
Jin SC, Dong W, Kundishora AJ, Panchagnula S, Moreno-De-Luca A, Furey CG, Allocco AA, Walker RL, Nelson-Williams C, Smith H, Dunbar A, Conine S, Lu Q, Zeng X, Sierant MC, Knight JR, Sullivan W, Duy PQ, DeSpenza T, Reeves BC, Karimy JK, Marlier A, Castaldi C, Tikhonova IR, Li B, Peña HP, Broach JR, Kabachelor EM, Ssenyonga P, Hehnly C, Ge L, Keren B, Timberlake AT, Goto J, Mangano FT, Johnston JM, Butler WE, Warf BC, Smith ER, Schiff SJ, Limbrick DD, Heuer G, Jackson EM, Iskandar BJ, Mane S, Haider S, Guclu B, Bayri Y, Sahin Y, Duncan CC, Apuzzo MLJ, DiLuna ML, Hoffman EJ, Sestan N, Ment LR, Alper SL, Bilguvar K, Geschwind DH, Günel M, Lifton RP, Kahle KT. Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus. Nature Medicine 2020, 26: 1754-1765. PMID: 33077954, PMCID: PMC7871900, DOI: 10.1038/s41591-020-1090-2.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusPoor neurodevelopmental outcomesPost-surgical patientsCerebrospinal fluid accumulationNeural stem cell biologyGenetic disruptionWhole-exome sequencingPrimary pathomechanismEarly brain developmentNeurodevelopmental outcomesHigh morbidityCSF diversionMutation burdenFluid accumulationBrain ventriclesCH casesBrain developmentDe novo mutationsPatientsExome sequencingCSF dynamicsDisease mechanismsHydrocephalusNovo mutationsCell typesPoisson Kalman filter for disease surveillance
Ebeigbe D, Berry T, Schiff S, Sauer T. Poisson Kalman filter for disease surveillance. Physical Review Research 2020, 2: 043028. DOI: 10.1103/physrevresearch.2.043028.Peer-Reviewed Original ResearchPaenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants
Paulson J, Williams B, Hehnly C, Mishra N, Sinnar S, Zhang L, Ssentongo P, Mbabazi-Kabachelor E, Wijetunge D, von Bredow B, Mulondo R, Kiwanuka J, Bajunirwe F, Bazira J, Bebell L, Burgoine K, Couto-Rodriguez M, Ericson J, Erickson T, Ferrari M, Gladstone M, Guo C, Haran M, Hornig M, Isaacs A, Kaaya B, Kangere S, Kulkarni A, Kumbakumba E, Li X, Limbrick D, Magombe J, Morton S, Mugamba J, Ng J, Olupot-Olupot P, Onen J, Peterson M, Roy F, Sheldon K, Townsend R, Weeks A, Whalen A, Quackenbush J, Ssenyonga P, Galperin M, Almeida M, Atkins H, Warf B, Lipkin W, Broach J, Schiff S. Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants. Science Translational Medicine 2020, 12 PMID: 32998967, PMCID: PMC7774825, DOI: 10.1126/scitranslmed.aba0565.Peer-Reviewed Original ResearchConceptsPostinfectious hydrocephalusCSF samplesPIH casesPotential causative organismsCerebrospinal fluid accumulationCytomegalovirus coinfectionUgandan infantsNeonatal sepsisSurgical palliationNeonatal infectionInfant casesOptimal treatmentInfant cohortCommon causeCausative organismPediatric hydrocephalusFluid accumulationHydrocephalusAnaerobic bacterial isolatesControl casesInfectionFacultative anaerobic bacterial isolatesInfantsParasitic DNADiseaseComplete Genome Sequences of the Human Pathogen Paenibacillus thiaminolyticus Mbale and Type Strain P. thiaminolyticus NRRL B-4156
Hehnly C, Zhang L, Paulson J, Almeida M, von Bredow B, Wijetunge D, Galperin M, Sheldon K, Schiff S, Broach J. Complete Genome Sequences of the Human Pathogen Paenibacillus thiaminolyticus Mbale and Type Strain P. thiaminolyticus NRRL B-4156. Microbiology Resource Announcements 2020, 9: 10.1128/mra.00181-20. PMID: 32273361, PMCID: PMC7380522, DOI: 10.1128/mra.00181-20.Peer-Reviewed Original ResearchInflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets
Karimy JK, Reeves BC, Damisah E, Duy PQ, Antwi P, David W, Wang K, Schiff SJ, Limbrick DD, Alper SL, Warf BC, Nedergaard M, Simard JM, Kahle KT. Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets. Nature Reviews Neurology 2020, 16: 285-296. PMID: 32152460, PMCID: PMC7375440, DOI: 10.1038/s41582-020-0321-y.Peer-Reviewed Original ResearchConceptsPosthaemorrhagic hydrocephalusPostinfectious hydrocephalusNeurosurgical disordersPathogenic mechanismsToll-like receptor 4Pathogenesis of hydrocephalusImportant protective responseEpendymal denudationCommon neurosurgical disorderSustained inflammationInflammatory mediatorsNeuroinflammatory conditionsImmune cellsReceptor 4Therapeutic approachesReparative inflammationCerebrospinal fluidCSF pathwaysHydrocephalusTherapeutic targetInflammationTherapeutic interventionsBrain ventriclesProtective responsePhysical irritants
2014
Volumetric brain analysis in neurosurgery: Part 2. Brain and CSF volumes discriminate neurocognitive outcomes in hydrocephalus.
Mandell J, Kulkarni A, Warf B, Schiff S. Volumetric brain analysis in neurosurgery: Part 2. Brain and CSF volumes discriminate neurocognitive outcomes in hydrocephalus. Journal Of Neurosurgery Pediatrics 2014, 15: 125-32. PMID: 25431901, DOI: 10.3171/2014.9.peds12427.Peer-Reviewed Original ResearchConceptsFrontal-occipital horn ratioNeurocognitive outcomesBrain volumeCSF volumeFluid volumePediatric patientsBrain developmentEvaluation of hydrocephalusGoal of treatmentSmaller brain volumesLower cognitive outcomesPoor neurocognitive outcomesNormal brain developmentLarge fluid volumesHealthy brain developmentVolumetric brain analysisSurgical treatmentVentricular sizeHydrocephalic patientsCT scanHydrocephalusPatientsBayley ScalesBrain growthFine motor
2012
Rainfall drives hydrocephalus in East Africa.
Schiff S, Ranjeva S, Sauer T, Warf B. Rainfall drives hydrocephalus in East Africa. Journal Of Neurosurgery Pediatrics 2012, 10: 161-7. PMID: 22768966, DOI: 10.3171/2012.5.peds11557.Peer-Reviewed Original Research
2011
Association of bacteria with hydrocephalus in Ugandan infants.
Li L, Padhi A, Ranjeva S, Donaldson S, Warf B, Mugamba J, Johnson D, Opio Z, Jayarao B, Kapur V, Poss M, Schiff S. Association of bacteria with hydrocephalus in Ugandan infants. Journal Of Neurosurgery Pediatrics 2011, 7: 73-87. PMID: 21194290, DOI: 10.3171/2010.9.peds10162.Peer-Reviewed Original ResearchConceptsUgandan infantsNeonatal sepsisPostinfectious hydrocephalusMajority of patientsMost patientsRecent infectionPolymerase chain reactionEffective treatmentPatientsPrevention strategiesHydrocephalusInfectionInfantsAcinetobacter speciesChain reactionAssociation of bacteriaBacterial DNAGram-negative bacteriaNegative bacteriaSepsisEnvironmental samplingSyndromeSeason infection