2022
A neural stem cell paradigm of pediatric hydrocephalus
Duy PQ, Rakic P, Alper SL, Robert SM, Kundishora AJ, Butler WE, Walsh CA, Sestan N, Geschwind DH, Jin SC, Kahle KT. A neural stem cell paradigm of pediatric hydrocephalus. Cerebral Cortex 2022, 33: 4262-4279. PMID: 36097331, PMCID: PMC10110448, DOI: 10.1093/cercor/bhac341.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCerebral VentriclesChildHumansHydrocephalusNeural Stem CellsNeurosurgical ProceduresConceptsPediatric hydrocephalusPrimary treatment strategyOptimal surgical managementDevelopmental brain malformationsAnimal model studiesSurgical managementCerebral ventricleCSF diversionVentricular distentionHydrocephalic childrenTreatment strategiesBrain malformationsNeurodevelopmental disabilitiesGerminal neuroepitheliumHydrocephalusStem cell paradigmNeural stem cell fateRecent human geneticBrain surgeryCSF circulationBrain ventriclesCSF volumeNeuroprogenitor cellsBrain defectsCSF homeostasisImpaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus
Duy PQ, Weise SC, Marini C, Li XJ, Liang D, Dahl PJ, Ma S, Spajic A, Dong W, Juusola J, Kiziltug E, Kundishora AJ, Koundal S, Pedram MZ, Torres-Fernández LA, Händler K, De Domenico E, Becker M, Ulas T, Juranek SA, Cuevas E, Hao LT, Jux B, Sousa AMM, Liu F, Kim SK, Li M, Yang Y, Takeo Y, Duque A, Nelson-Williams C, Ha Y, Selvaganesan K, Robert SM, Singh AK, Allington G, Furey CG, Timberlake AT, Reeves BC, Smith H, Dunbar A, DeSpenza T, Goto J, Marlier A, Moreno-De-Luca A, Yu X, Butler WE, Carter BS, Lake EMR, Constable RT, Rakic P, Lin H, Deniz E, Benveniste H, Malvankar NS, Estrada-Veras JI, Walsh CA, Alper SL, Schultze JL, Paeschke K, Doetzlhofer A, Wulczyn FG, Jin SC, Lifton RP, Sestan N, Kolanus W, Kahle KT. Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus. Nature Neuroscience 2022, 25: 458-473. PMID: 35379995, PMCID: PMC9664907, DOI: 10.1038/s41593-022-01043-3.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusCerebral ventricular dilatationPrimary defectNeuroepithelial cell differentiationRisk genesCerebrospinal fluid homeostasisWhole-exome sequencingNeuroepithelial stem cellsCortical hypoplasiaReduced neurogenesisVentricular dilatationVentricular enlargementCH mutationsPrenatal hydrocephalusDisease heterogeneityBrain surgeryCSF circulationHydrocephalusGenetic subtypesFluid homeostasisNeuroepithelial cellsNovo mutationsBrain transcriptomicsStem cellsCell differentiationBrain ventricles as windows into brain development and disease
Duy PQ, Rakic P, Alper SL, Butler WE, Walsh CA, Sestan N, Geschwind DH, Jin SC, Kahle KT. Brain ventricles as windows into brain development and disease. Neuron 2022, 110: 12-15. PMID: 34990576, PMCID: PMC9212067, DOI: 10.1016/j.neuron.2021.12.009.Peer-Reviewed Original Research
2021
PTEN mutations in autism spectrum disorder and congenital hydrocephalus: developmental pleiotropy and therapeutic targets
DeSpenza T, Carlson M, Panchagnula S, Robert S, Duy PQ, Mermin-Bunnell N, Reeves BC, Kundishora A, Elsamadicy AA, Smith H, Ocken J, Alper SL, Jin SC, Hoffman EJ, Kahle KT. PTEN mutations in autism spectrum disorder and congenital hydrocephalus: developmental pleiotropy and therapeutic targets. Trends In Neurosciences 2021, 44: 961-976. PMID: 34625286, PMCID: PMC8692171, DOI: 10.1016/j.tins.2021.08.007.Peer-Reviewed Original ResearchConceptsDevelopmental pleiotropyPTEN-PI3KMTOR pathwayMolecular pathophysiologyPTEN mutationsMolecular similarityTherapeutic targetCommon underlying mechanismNeurodevelopmental disordersUnderlying mechanismTherapeutic promisePleiotropyBiologyPhenotypicMutationsLimited understandingPathwayCommon neurodevelopmental disorderAutism spectrum disorderSimilarityTargetGenomics of human congenital hydrocephalus
Kundishora AJ, Singh AK, Allington G, Duy PQ, Ryou J, Alper SL, Jin SC, Kahle KT. Genomics of human congenital hydrocephalus. Child's Nervous System 2021, 37: 3325-3340. PMID: 34232380, DOI: 10.1007/s00381-021-05230-8.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusBrain developmentPoor neurodevelopmental outcomesRecent whole-exome sequencing studiesPost-surgical patientsHuman congenital hydrocephalusPathogenesis of hydrocephalusCerebrospinal fluid accumulationDamaging de novoPrimary pathomechanismEarly brain developmentNeural stem cell growthNeurodevelopmental outcomesOutcome prognosticationHuman brain developmentCSF diversionTreatment stratificationWhole-exome sequencing studiesFluid accumulationBrain ventriclesClinical toolHydrocephalusGenetic counselingDisease mechanismsSubstantial minorityInflammatory hydrocephalus
Robert SM, Reeves BC, Marlier A, Duy PQ, DeSpenza T, Kundishora A, Kiziltug E, Singh A, Allington G, Alper SL, Kahle KT. Inflammatory hydrocephalus. Child's Nervous System 2021, 37: 3341-3353. PMID: 34164718, DOI: 10.1007/s00381-021-05255-z.Peer-Reviewed Original ResearchConceptsPost-infectious hydrocephalusImmune cell profilesCerebrospinal fluid diversion techniquesPotential therapeutic vulnerabilitiesImportant protective responseCSF cytokinesProlong diseaseSustained inflammationHigher complicationsPreventable conditionClinical studiesNeurosurgical disordersReparative inflammationDistinct etiologiesHuman patientsHydrocephalusCell profilesProtective responseTherapeutic vulnerabilitiesPhysical irritantsCommon formInflammationDiversion techniquesDisordersFailure rateIntraventricular CSF Turbulence in Pediatric Communicating Hydrocephalus
Duy PQ, Kahle KT. Intraventricular CSF Turbulence in Pediatric Communicating Hydrocephalus. Neurology 2021, 97: 246-247. PMID: 34031199, PMCID: PMC8589266, DOI: 10.1212/wnl.0000000000012237.Peer-Reviewed Original ResearchConceptsProgressive macrocephalyCSF turbulenceLower extremity motor functionDiffuse cortical atrophyExtremity motor functionMild neurocognitive impairmentCommunicating hydrocephalusVentriculoperitoneal shuntCortical atrophyIntracranial hemorrhagePhysical examinationPostoperative imagingComplete resolutionIntracranial pressureMotor functionHead circumferenceOpen myelomeningoceleNeurocognitive impairmentMild decreaseCSF flowVentriculomegalyMacrocephalyExome Sequencing as a Potential Diagnostic Adjunct in Sporadic Congenital Hydrocephalus
Sullivan W, Reeves BC, Duy PQ, Nelson-Williams C, Dong W, Jin SC, Kahle KT. Exome Sequencing as a Potential Diagnostic Adjunct in Sporadic Congenital Hydrocephalus. JAMA Pediatrics 2021, 175: 310-313. PMID: 33196764, PMCID: PMC7670396, DOI: 10.1001/jamapediatrics.2020.4878.Peer-Reviewed Original Research
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 typesInflammation 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
2019
Trim71/lin-41 Links an Ancient miRNA Pathway to Human Congenital Hydrocephalus
Duy PQ, Furey CG, Kahle KT. Trim71/lin-41 Links an Ancient miRNA Pathway to Human Congenital Hydrocephalus. Trends In Molecular Medicine 2019, 25: 467-469. PMID: 30975633, DOI: 10.1016/j.molmed.2019.03.004.Peer-Reviewed Original Research