2024
Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus
Bertino F, Mukherjee D, Bonora M, Bagowski C, Nardelli J, Metani L, Venturini D, Chianese D, Santander N, Salaroglio I, Hentschel A, Quarta E, Genova T, McKinney A, Allocco A, Fiorito V, Petrillo S, Ammirata G, De Giorgio F, Dennis E, Allington G, Maier F, Shoukier M, Gloning K, Munaron L, Mussano F, Salsano E, Pareyson D, di Rocco M, Altruda F, Panagiotakos G, Kahle K, Gressens P, Riganti C, Pinton P, Roos A, Arnold T, Tolosano E, Chiabrando D. Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus. Cell Reports Medicine 2024, 5: 101647. PMID: 39019006, PMCID: PMC11293339, DOI: 10.1016/j.xcrm.2024.101647.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusCalcium handlingNeural progenitor cellsMitochondrial calcium handlingMouse neural progenitor cellsFLVCR1 geneMitochondrial calcium levelsVentricular dilatationLive birthsCalcium levelsProgenitor cellsClinical challengeVentricle enlargementPathogenetic mechanismsSevere formCortical neurogenesisNeural progenitorsFLVCR1aMitochondria-associated membranesHydrocephalusMiceFLVCR1CH genesMolecular mechanismsMetabolic activityPathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics
DeSpenza T, Singh A, Allington G, Zhao S, Lee J, Kiziltug E, Prina M, Desmet N, Dang H, Fields J, Nelson-Williams C, Zhang J, Mekbib K, Dennis E, Mehta N, Duy P, Shimelis H, Walsh L, Marlier A, Deniz E, Lake E, Constable R, Hoffman E, Lifton R, Gulledge A, Fiering S, Moreno-De-Luca A, Haider S, Alper S, Jin S, Kahle K, Luikart B. Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2314702121. PMID: 38916997, PMCID: PMC11228466, DOI: 10.1073/pnas.2314702121.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusCerebral ventriculomegalyPathogenic variantsPrefrontal pyramidal neuronsGenetic subsets of patientsDevelopment of ventriculomegalyRadial gliaSubsets of patientsHigh-frequency firingNeuronal connectivityHeterozygous germline variantsAutism spectrum disorderVentricular-subventricular zoneMicrotubule dynamicsImpaired spermatogenesisCSF shuntingExcitatory driveMicrotubule-severing ATPasePyramidal neuronsDisrupt neuronal connectivityGermline variantsVentriculomegalyCSF homeostasisDisrupt microtubule dynamicsPlanar cell polarityPaediatric hydrocephalus
Kahle K, Klinge P, Koschnitzky J, Kulkarni A, MacAulay N, Robinson S, Schiff S, Strahle J. Paediatric hydrocephalus. Nature Reviews Disease Primers 2024, 10: 35. PMID: 38755194, DOI: 10.1038/s41572-024-00519-9.Peer-Reviewed Original ResearchConceptsSymptoms of elevated intracranial pressureCerebrospinal fluidCentral nervous system infectionChoroid plexus cauterizationEndoscopic third ventriculostomyNervous system infectionNonsurgical treatment strategiesElevated intracranial pressureLong-term outcomesNeural tube defectsCSF-brain interfaceFetal hydrocephalusUtero treatmentAcquired hydrocephalusCSF secretionSurgical closureCSF shuntingHead circumferenceThird ventriculostomyCongenital hydrocephalusAssociated with blockageGene mutationsCerebral ventricleTreatment strategiesCSF pathwaysThe 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 injuryPathwayUtility of cortical tissue analysis in normal pressure hydrocephalus
Greenberg A, Mekbib K, Mehta N, Kiziltug E, Duy P, Smith H, Junkkari A, Leinonen V, Hyman B, Chan D, Curry W, Arnold S, Barker F, Frosch M, Kahle K. Utility of cortical tissue analysis in normal pressure hydrocephalus. Cerebral Cortex 2024, 34: bhae001. PMID: 38275188, PMCID: PMC10839843, DOI: 10.1093/cercor/bhae001.Peer-Reviewed Original ResearchConceptsIdiopathic normal pressure hydrocephalus patientsNormal pressure hydrocephalus patientsCerebrospinal fluid shuntsNormal pressure hydrocephalusIdiopathic normal pressure hydrocephalusHydrocephalus patientsPressure hydrocephalusOriginal patient cohortCortical pathologyRisks of treatmentPrognostic adjunctClinical improvementTissue analysisNegative pathologyShunt outcomeClinical outcomesPatient cohortUnfavorable outcomePooled analysisSystematic reviewOriginal cohortPooled statisticsLiving patientsConfounding diagnosesPatients
2023
Neurosurgery elucidates somatic mutations
Maury E, Walsh C, Kahle K. Neurosurgery elucidates somatic mutations. Science 2023, 382: 1360-1362. PMID: 38127765, DOI: 10.1126/science.adj2244.Peer-Reviewed Original Research