2024
Single-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE)
Hanin A, Zhang L, Huttner A, Plu I, Mathon B, Bielle F, Navarro V, Hirsch L, Hafler D. Single-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE). Neurology Neuroimmunology & Neuroinflammation 2024, 11: e200259. PMID: 38810181, PMCID: PMC11139018, DOI: 10.1212/nxi.0000000000200259.Peer-Reviewed Original ResearchConceptsNew-onset refractory status epilepticusTemporal lobe epilepsyGABAergic neuronsExcitatory neuronsInfiltrating macrophagesProportion of GABAergic neuronsChronic temporal lobe epilepsyRefractory status epilepticusInhibitory GABAergic neuronsSingle-cell transcriptome analysisDecreased expression of genesDegree of demyelinationImmune disturbancesNeuronal excitabilityImmune dysregulationNew-onsetStatus epilepticusPoor outcomeRefractory epilepsyHealthy childrenMicroglial reactivitySingle-nucleus RNA sequencingNLRP3 inflammasome activationInflammatory responseLobe epilepsy
2021
Hemorrhage Into a Subependymal Giant Cell Astrocytoma in an Adult With Tuberous Sclerosis
Barbiero FJ, Huttner AJ, Fulbright RK, Baehring JM. Hemorrhage Into a Subependymal Giant Cell Astrocytoma in an Adult With Tuberous Sclerosis. The Neurologist 2021, 26: 122-124. PMID: 34190204, DOI: 10.1097/nrl.0000000000000338.Peer-Reviewed Original ResearchConceptsIntracranial hemorrhageMagnetic resonance imaging (MRI) brainSubependymal giant cell astrocytomaCentral nervous system tumorsYoung adultsLife-threatening complicationsGiant cell astrocytomaNervous system tumorsTuberous sclerosis complexForamen of MonroRare genetic disorderGerm-line mutationsUncommon causeHematoma evacuationDiagnostic delaySpontaneous hemorrhageUnusual causeSubependymal nodulesSurveillance imagingSkin changesTumor resectionSystem tumorsAdenoma sebaceumTuberous sclerosisSkin lesionsProtein kinase D1 variant associated with human epilepsy and peripheral nerve hypermyelination
Omer S, Jin SC, Koumangoye R, Robert SM, Duran D, Nelson‐Williams C, Huttner A, DiLuna M, Kahle KT, Delpire E. Protein kinase D1 variant associated with human epilepsy and peripheral nerve hypermyelination. Clinical Genetics 2021, 100: 176-186. PMID: 33904160, DOI: 10.1111/cge.13973.Peer-Reviewed Original ResearchConceptsProtein kinase D1Kainate-induced seizure activityHomozygote micePeripheral nerve diseaseWild-type miceBrain hyperexcitabilityPatient's epilepsyPeripheral neuropathyNerve diseaseSeizure activityHuman epilepsyCotransporter 3Nervous systemProgressive epilepsyHeterozygote miceHuman nervous systemPKD1 variantsMiceEpilepsyInactivating variantPotential targetSignificant increaseNovel roleDiseaseLocomotor behaviorExome sequencing identifies SLIT2 variants in primary CNS lymphoma
Kaulen LD, Erson‐Omay E, Henegariu O, Karschnia P, Huttner A, Günel M, Baehring JM. Exome sequencing identifies SLIT2 variants in primary CNS lymphoma. British Journal Of Haematology 2021, 193: 375-379. PMID: 33481259, DOI: 10.1111/bjh.17319.Peer-Reviewed Original ResearchConceptsPrimary central nervous system lymphomaShorter progression-free survivalCentral nervous system lymphomaRole of SLIT2Primary CNS lymphomaProgression-free survivalLarger validation cohortNervous system lymphomaShorter overall survivalPossible prognostic implicationsWarrants further investigationCNS lymphomaTumor DNA samplesOverall survivalPCNSL patientsSystem lymphomaPrognostic implicationsValidation cohortPCNSL pathogenesisLymphoid malignanciesFunction variantsTumor suppressor geneExome sequencingLuciferase assayLymphomaDual activating FGFR1 mutations in pediatric pilomyxoid astrocytoma
Fomchenko EI, Reeves BC, Sullivan W, Marks AM, Huttner A, Kahle KT, Erson‐Omay E. Dual activating FGFR1 mutations in pediatric pilomyxoid astrocytoma. Molecular Genetics & Genomic Medicine 2021, 9: e1597. PMID: 33448156, PMCID: PMC8077124, DOI: 10.1002/mgg3.1597.Peer-Reviewed Original ResearchConceptsPilomyxoid astrocytomaPediatric patientsVariant allele frequencyHypothalamic/chiasmatic regionPathologic tissue diagnosisTreatment-related morbidityHigh recurrence ratePI3K/mTOR inhibitionYears of ageExome sequencing resultsSimilar time pointsWhole exome sequencing resultsHypothalamic dysfunctionClinical presentationSurgical managementRecurrence rateShorter survivalAggressive subtypeVision lossChiasmatic regionTissue diagnosisPatient tumorsRadiation therapyFGFR inhibitorsFGFR1 mutationsNeuroinvasion of SARS-CoV-2 in human and mouse brain
Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal Of Experimental Medicine 2021, 218: e20202135. PMID: 33433624, PMCID: PMC7808299, DOI: 10.1084/jem.20202135.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Central nervous systemSARS-CoV-2 neuroinvasionImmune cell infiltratesCOVID-19 patientsType I interferon responseMultiple organ systemsCOVID-19I interferon responseHuman brain organoidsNeuroinvasive capacityCNS infectionsCell infiltrateNeuronal infectionPathological featuresCortical neuronsRespiratory diseaseDirect infectionCerebrospinal fluidNervous systemMouse brainInterferon responseOrgan systemsHuman ACE2Infection
2020
Associations of meningioma molecular subgroup and tumor recurrence
Youngblood MW, Miyagishima DF, Jin L, Gupte T, Li C, Duran D, Montejo JD, Zhao A, Sheth A, Tyrtova E, Özduman K, Iacoangeli F, Peyre M, Boetto J, Pease M, Avşar T, Huttner A, Bilguvar K, Kilic T, Pamir MN, Amankulor N, Kalamarides M, Erson-Omay EZ, Günel M, Moliterno J. Associations of meningioma molecular subgroup and tumor recurrence. Neuro-Oncology 2020, 23: 783-794. PMID: 33068421, PMCID: PMC8099468, DOI: 10.1093/neuonc/noaa226.Peer-Reviewed Original ResearchConceptsDivergent clinical coursesMolecular subgroupsClinical courseClinical outcomesProgression-free survivalExtent of resectionKaplan-Meier analysisLong-term outcomesLow-grade tumorsCox proportional hazardsDistinct clinical outcomesPostoperative radiationIndependent predictorsMale sexRecurrence rateSurveillance imagingTumor recurrencePrevious recurrencesClinical prognosticationKi-67Outcome dataAggressive subgroupRecurrenceElevated recurrenceProportional hazardsDifferential expression of the T-cell inhibitor TIGIT in glioblastoma and MS
Lucca LE, Lerner BA, Park C, DeBartolo D, Harnett B, Kumar VP, Ponath G, Raddassi K, Huttner A, Hafler DA, Pitt D. Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS. Neurology Neuroimmunology & Neuroinflammation 2020, 7: e712. PMID: 32269065, PMCID: PMC7188477, DOI: 10.1212/nxi.0000000000000712.Peer-Reviewed Original ResearchConceptsTumor-infiltrating T cellsT cellsPD-1/PD-L1Anti-TIGIT therapyExpression of CD226Expression of TIGITPostmortem CNS tissueLymphocytes of patientsFresh surgical resectionsLigand CD155TIGIT expressionSurgical resectionPD-1PD-L1CNS diseaseHealthy controlsHealthy donorsLymphocytic expressionImmune responseCNS tissueMS lesionsTIGITImmune pathwaysPatientsGlioblastoma multiformeClinical characteristics of fibroblast growth factor receptor 3 antibody‐related polyneuropathy: a retrospective study
Kovvuru S, Cardenas Y, Huttner A, Nowak R, Roy B. Clinical characteristics of fibroblast growth factor receptor 3 antibody‐related polyneuropathy: a retrospective study. European Journal Of Neurology 2020, 27: 1310-1318. PMID: 32068339, DOI: 10.1111/ene.14180.Peer-Reviewed Original ResearchConceptsChronic inflammatory neuropathiesInflammatory neuropathiesSensory neuropathyFGFR3 antibodiesDistal lower extremity weaknessIntravenous immunoglobulin responseLower extremity paresthesiasCommon presenting symptomLower extremity weaknessRetrospective chart reviewPure sensory neuropathyHistory of cancerDistal sensationMotor findingsPresenting symptomChart reviewClinical characteristicsDemyelinating featuresNerve biopsySymptom onsetUnsteady gaitClinical presentationFoot dropRetrospective studyAutoimmune diseasesPrimary dural lymphomas: Clinical presentation, management, and outcome
Karschnia P, Batchelor TT, Jordan JT, Shaw B, Winter SF, Barbiero FJ, Kaulen LD, Thon N, Tonn J, Huttner AJ, Fulbright RK, Loeffler J, Dietrich J, Baehring JM. Primary dural lymphomas: Clinical presentation, management, and outcome. Cancer 2020, 126: 2811-2820. PMID: 32176324, DOI: 10.1002/cncr.32834.Peer-Reviewed Original ResearchConceptsPrimary dural lymphomaPrimary CNS lymphomaNon-Hodgkin lymphomaCNS lymphomaOverall survivalDural lymphomaPrimary central nervous system lymphomaT-cell non-Hodgkin lymphomaB-cell non-Hodgkin lymphomaCentral nervous system lymphomaLarge B-cell lymphomaMedian apparent diffusion coefficient (ADC) valuesAvid contrast enhancementMedian overall survivalCerebrospinal fluid analysisNervous system lymphomaMarginal zone lymphomaB-cell lymphomaExtra-axial massApparent diffusion coefficient (ADC) valuesMassachusetts General HospitalAggressive surgeryMultimodality treatmentSystem lymphomaSystemic involvementMRI-Guided Laser Interstitial Thermal Therapy for Radiation Necrosis in Previously Irradiated Brain Arteriovenous Malformations
Hong CS, Cord BJ, Kundishora AJ, Elsamadicy AA, Beckta JM, Huttner A, Chiang VL, Matouk CC. MRI-Guided Laser Interstitial Thermal Therapy for Radiation Necrosis in Previously Irradiated Brain Arteriovenous Malformations. Practical Radiation Oncology 2020, 10: e298-e303. PMID: 32068154, DOI: 10.1016/j.prro.2020.02.003.Peer-Reviewed Original Research
2019
Clinical Reasoning: Progressive proximal weakness in a 56-year-old man with bone pain
Torabi T, Huttner A, Nowak RJ, Roy B. Clinical Reasoning: Progressive proximal weakness in a 56-year-old man with bone pain. Neurology 2019, 93: 939-944. PMID: 31740511, DOI: 10.1212/wnl.0000000000008535.Peer-Reviewed Original ResearchDiagnosis, DifferentialElectromyographyFrontotemporal DementiaHumansLambert-Eaton Myasthenic SyndromeMaleMiddle AgedMuscle WeaknessMuscular Dystrophies, Limb-GirdleMyositisMyositis, Inclusion BodyOsteitis DeformansPainPolyradiculoneuropathy, Chronic Inflammatory DemyelinatingValosin Containing ProteinDNMT3A co-mutation in an IDH1-mutant glioblastoma
Fomchenko EI, Erson-Omay EZ, Zhao A, Bindra RS, Huttner A, Fulbright RK, Moliterno J. DNMT3A co-mutation in an IDH1-mutant glioblastoma. Molecular Case Studies 2019, 5: a004119. PMID: 31371348, PMCID: PMC6672028, DOI: 10.1101/mcs.a004119.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkers, TumorBrain NeoplasmsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3ADNA Modification MethylasesEpigenesis, GeneticGene Expression ProfilingGene Expression Regulation, NeoplasticGlioblastomaGliomaHumansIsocitrate DehydrogenaseMaleMutationMutation, MissensePromoter Regions, GeneticConceptsIDH1-mutant glioblastomaEpigenetic controlHistone modificationsTranscriptional regulationDNA methylationExpression profilesGlioblastoma biologySomatic mutationsDe novoMutationsMutant glioblastomasTumor landscapeMutational profileTargeted therapeutic approachesGlioblastomaImportant roleMethylationDNMT3ABiologyGliomagenesisMissenseRegulationNovoPrimary brain tumorsTherapeutic approachesPrognostic markers for immunodeficiency-associated primary central nervous system lymphoma
Kaulen LD, Galluzzo D, Hui P, Barbiero F, Karschnia P, Huttner A, Fulbright R, Baehring JM. Prognostic markers for immunodeficiency-associated primary central nervous system lymphoma. Journal Of Neuro-Oncology 2019, 144: 107-115. PMID: 31190317, DOI: 10.1007/s11060-019-03208-w.Peer-Reviewed Original ResearchConceptsPrimary central nervous system lymphomaDiffusion-weighted imaging patternsMagnetic resonance imagingCentral nervous system lymphomaNervous system lymphomaSystem lymphomaPeripheral enhancementDWI patternsPCNSL casesImaging featuresPrognostic markerHuman immunodeficiency virus (HIV) infectionKaplan-Meier survival analysisDiffuse large B-cell lymphomaYale-New Haven HospitalLarge B-cell lymphomaMedian overall survivalImmunodeficiency virus infectionPredictors of survivalSolid organ transplantationImmunoglobulin heavy chain gene rearrangementPeripheral contrast enhancementLog-rank testMajor risk factorHeavy chain gene rearrangement
2017
Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage
Chang CF, Goods BA, Askenase MH, Hammond MD, Renfroe SC, Steinschneider AF, Landreneau MJ, Ai Y, Beatty HE, da Costa LHA, Mack M, Sheth KN, Greer DM, Huttner A, Coman D, Hyder F, Ghosh S, Rothlin CV, Love JC, Sansing LH. Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage. Journal Of Clinical Investigation 2017, 128: 607-624. PMID: 29251628, PMCID: PMC5785262, DOI: 10.1172/jci95612.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAxl Receptor Tyrosine KinaseBrain InjuriesCerebral HemorrhageC-Mer Tyrosine KinaseErythrocytesHematomaHumansImmunity, InnateInflammationMacrophagesMaleMiceMice, Inbred C57BLMice, TransgenicPhagocytosisPhenotypeProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSolubilityTreatment OutcomeConceptsMonocyte-derived macrophagesIntracerebral hemorrhageEryptotic erythrocytesNeurological recoveryHematoma clearanceExperimental intracerebral hemorrhageReceptor tyrosine kinase AXLHuman monocyte-derived macrophagesTyrosine kinase AXLICH onsetFunctional outcomeBrain injuryTissue injurySoluble AxlDynamic phenotypic changesAlternative activationPhenotypic changesMacrophage phenotypeIron depositionMurine brainMacrophage responseRestorative functionEfferocytosisMacrophagesEngulfment of erythrocytesDisappearing Leukoencephalopathy
Chan AM, Huttner A, Baehring J. Disappearing Leukoencephalopathy. Clinical Neuroradiology 2017, 28: 455-459. PMID: 29196778, DOI: 10.1007/s00062-017-0650-4.Peer-Reviewed Original ResearchA p190BRhoGAP mutation and prolonged RhoB activation in fatal systemic capillary leak syndrome
Pierce RW, Merola J, Lavik JP, Kluger MS, Huttner A, Khokha MK, Pober JS. A p190BRhoGAP mutation and prolonged RhoB activation in fatal systemic capillary leak syndrome. Journal Of Experimental Medicine 2017, 214: 3497-3505. PMID: 29097442, PMCID: PMC5716031, DOI: 10.1084/jem.20162143.Peer-Reviewed Original ResearchConceptsTumor necrosis factorSystemic capillary leakDermal microvascular endothelial cellsMicrovascular endothelial cellsPatient-derived endothelial cellsEndothelial cellsCapillary leakNormal human dermal microvascular endothelial cellsSystemic capillary leak syndromeBarrier functionCapillary leak syndromeHuman dermal microvascular endothelial cellsTransendothelial electrical resistanceEC barrier functionNormal endothelial cellsLeak syndromeCritical illnessFatal casesNecrosis factorBarrier recoverySiRNA knockdownEC culturesRhoB activationGreater increaseJunctional proteinsLong-term outcomes of tissue-based ACTH-antibody assay-guided transsphenoidal resection of pituitary adenomas in Cushing disease.
Erfe JM, Perry A, McClaskey J, Inzucchi SE, James WS, Eid T, Bronen RA, Mahajan A, Huttner A, Santos F, Spencer D. Long-term outcomes of tissue-based ACTH-antibody assay-guided transsphenoidal resection of pituitary adenomas in Cushing disease. Journal Of Neurosurgery 2017, 129: 629-641. PMID: 29027854, DOI: 10.3171/2017.3.jns162245.Peer-Reviewed Original ResearchConceptsTranssphenoidal resectionMRI studiesCushing's diseaseCortisol levelsLong-term corticosteroid therapyUrinary free cortisol levelsLong-term disease remissionLong-term patient outcomesResults Fourteen patientsLong-term outcomesPostoperative MRI studiesSurgical tumor samplesFree cortisol levelsPreoperative MRI studiesPrecise tumor localizationACTH antibodiesPituitary microCorticosteroid therapyStudy patientsDisease remissionFourteen patientsRemission rateRetrospective reviewTreatment failureCure rateMulticentric Chordoma
Jones JR, Huttner A, Malhotra A. Multicentric Chordoma. Clinical Neuroradiology 2017, 28: 283-288. PMID: 28766007, DOI: 10.1007/s00062-017-0610-z.Peer-Reviewed Original ResearchSOX2 immunity and tissue resident memory in children and young adults with glioma
Vasquez JC, Huttner A, Zhang L, Marks A, Chan A, Baehring JM, Kahle KT, Dhodapkar KM. SOX2 immunity and tissue resident memory in children and young adults with glioma. Journal Of Neuro-Oncology 2017, 134: 41-53. PMID: 28620836, PMCID: PMC7906294, DOI: 10.1007/s11060-017-2515-8.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsAntigen-Presenting CellsB7-H1 AntigenBrain NeoplasmsCell ProliferationChildChild, PreschoolCytokinesFemaleFlow CytometryGliomaHumansInfantMaleMyeloid CellsProgrammed Cell Death 1 ReceptorReceptors, ImmunologicRNA, Small InterferingSOXB1 Transcription FactorsT-LymphocytesTransfectionYoung AdultConceptsPediatric glial tumorsGlial tumorsT cellsExpression of SOX2Inhibitory checkpointsCD8/CD4 T cellsTissue-resident memory phenotypeTumor-infiltrating immune cellsTumor-infiltrating T cellsTumor cellsYoung adultsResident memory phenotypeTissue-resident memoryAnti-tumor immunityT cell immunityCD4 T cellsNatural killer cellsGlial tumor cellsNew antigenic targetsSingle-cell mass cytometryHigh mutation burdenStem cell antigenGlioma initiating cellsImmune checkpointsPD-1