2023
Genetic, electrophysiological, and pathological studies on patients with SCN9A‐related pain disorders
Yuan J, Cheng X, Matsuura E, Higuchi Y, Ando M, Hashiguchi A, Yoshimura A, Nakachi R, Mine J, Taketani T, Maeda K, Kawakami S, Kira R, Tanaka S, Kanai K, Dib‐Hajj F, Dib‐Hajj S, Waxman S, Takashima H. Genetic, electrophysiological, and pathological studies on patients with SCN9A‐related pain disorders. Journal Of The Peripheral Nervous System 2023, 28: 597-607. PMID: 37555797, DOI: 10.1111/jns.12590.Peer-Reviewed Original ResearchConceptsParoxysmal extreme pain disorderPainful peripheral neuropathyPain disordersSCN9A mutationsPeripheral neuropathyNovel SCN9A mutationsVoltage-gated sodium channel Nav1.7Sodium channel Nav1.7Steady-state fast inactivationGene panel sequencingPatch-clamp analysisAutonomic neuropathyNeuropathic painSCN9A geneClinical featuresUnderlying pathogenesisPathological studiesPatientsChannel Nav1.7EM phenotypePhenotypic spectrumNeuropathyNav1.7 channelsPatch-clamp systemElectrophysiological analysisGenetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies
Almomani R, Sopacua M, Marchi M, Ślęczkowska M, Lindsey P, de Greef B, Hoeijmakers J, Salvi E, Merkies I, Ferdousi M, Malik R, Ziegler D, Derks K, Boenhof G, Martinelli-Boneschi F, Cazzato D, Lombardi R, Dib-Hajj S, Waxman S, Smeets H, Gerrits M, Faber C, Lauria G, Group O. Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies. International Journal Of Molecular Sciences 2023, 24: 8278. PMID: 37175987, PMCID: PMC10179245, DOI: 10.3390/ijms24098278.Peer-Reviewed Original ResearchConceptsDiabetic peripheral neuropathySmall fiber neuropathyPainless neuropathySFN patientsPainful neuropathyPeripheral neuropathyNeuropathy patientsPainless diabetic peripheral neuropathyPathogenic variantsPersonalized pain treatmentPainful peripheral neuropathyDifferent pathogenic variantsGenetic profilingSodium channel genePotential pathogenic variantsDPN patientsNeuropathic painNociceptive pathwaysPain treatmentNeuropathyPatientsSodium channelsFrequent featureDifferent centersSCN7ATRPA1 rare variants in chronic neuropathic and nociplastic pain patients
Marchi M, Salvi E, Andelic M, Mehmeti E, D'Amato I, Cazzato D, Chiappori F, Lombardi R, Cartelli D, Devigili G, Bella E, Gerrits M, Almomani R, Malik R, Ślęczkowska M, Mazzeo A, Gentile L, Dib-Hajj S, Waxman S, Faber C, Vecchio E, de Tommaso M, Lauria G. TRPA1 rare variants in chronic neuropathic and nociplastic pain patients. Pain 2023, 164: 2048-2059. PMID: 37079850, PMCID: PMC10443199, DOI: 10.1097/j.pain.0000000000002905.Peer-Reviewed Original ResearchConceptsNociplastic painPainful neuropathyPain patientsHealthy controlsRare variantsChronic neuropathic painChronic pain disordersChronic widespread painChronic pain patientsMolecular profilePainless neuropathyNeuropathic painPain disordersWidespread painChronic painPatient's molecular profileIndependent cohortPainPatientsClinical diagnosisDisease riskNeuropathyTRPA1 variantsNew risk genesPain genesIntegrative miRNA–mRNA profiling of human epidermis: unique signature of SCN9A painful neuropathy
Andelic M, Salvi E, Marcuzzo S, Marchi M, Lombardi R, Cartelli D, Cazzato D, Mehmeti E, Gelemanovic A, Paolini M, Pardo C, D'Amato I, Hoeijmakers J, Dib-Hajj S, Waxman S, Faber C, Lauria G. Integrative miRNA–mRNA profiling of human epidermis: unique signature of SCN9A painful neuropathy. Brain 2023, 146: 3049-3062. PMID: 36730021, PMCID: PMC10316770, DOI: 10.1093/brain/awad025.Peer-Reviewed Original ResearchConceptsNeuropathic painPain-related mechanismsCohort of patientsSmall nerve fibersUnmet clinical needPainful neuropathyTargeted molecular profilingNeuropathy painPathophysiological mechanismsAvailable therapiesPreclinical modelsNerve fibersLimited efficacyHealthy individualsPersonalized managementPotential drug candidatesTranslational gapPainClinical needGene targetsPatientsImmunofluorescence assaysMolecular profilingMiR-30 familyProtein expression
2022
Peripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy
Ślęczkowska M, Almomani R, Marchi M, Salvi E, de Greef B, Sopacua M, Hoeijmakers J, Lindsey P, Waxman S, Lauria G, Faber C, Smeets H, Gerrits M. Peripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy. International Journal Of Molecular Sciences 2022, 23: 14095. PMID: 36430572, PMCID: PMC9696564, DOI: 10.3390/ijms232214095.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyNeuropathic painIon channel genesPainful small fiber neuropathyPain score VASPathogenic heterozygous variantGenetic variantsIon channelsCohort studyDiabetic neuropathySevere painDifferent etiologiesPainPatientsVoltage-gated sodium ion channelsHeterozygous variantsNeuropathySodium ion channelsGene screeningGeneration sequencingPrevious findingsSuch variantsEtiologySCN1BVariants
2018
Pharmacological Reversal of a Pain Phenotype in iPSC-Derived Sensory Neurons and Patients with Inherited Erythromelalgia
Cao L, McDonnell A, Nitzsche A, Alexandrou A, Saintot P, Loucif A, Brown A, Young G, Mis M, Randall A, Waxman S, Stanley P, Kirby S, Tarabar S, Gutteridge A, Butt R, McKernan R, Whiting P, Ali Z, Bilsland J, Stevens E. Pharmacological Reversal of a Pain Phenotype in iPSC-Derived Sensory Neurons and Patients with Inherited Erythromelalgia. 2018, 225-246. DOI: 10.7551/mitpress/10310.003.0027.Peer-Reviewed Original ResearchA novel gain-of-function Nav1.7 mutation in a carbamazepine-responsive patient with adult-onset painful peripheral neuropathy
Adi T, Estacion M, Schulman BR, Vernino S, Dib-Hajj S, Waxman S. A novel gain-of-function Nav1.7 mutation in a carbamazepine-responsive patient with adult-onset painful peripheral neuropathy. Molecular Pain 2018, 14: 1744806918815007. PMID: 30392441, PMCID: PMC6856981, DOI: 10.1177/1744806918815007.Peer-Reviewed Original ResearchConceptsPainful peripheral neuropathyDorsal root gangliaPeripheral neuropathyUse-dependent inhibitionDRG neuronsPain disordersM variantFunction Nav1.7 mutationsMulti-electrode array recordingsSympathetic ganglion neuronsCommon pain disordersVoltage-clamp recordingsVoltage-gated sodium channel NaRare MendelianNav1.7 mutationGanglion neuronsSodium channel NaTrigeminal ganglionRoot gangliaNeonatal ratsPatientsNeuropathyMutant channelsFunction variantsNeurons
2017
COL6A5 variants in familial neuropathic chronic itch
Martinelli-Boneschi F, Colombi M, Castori M, Devigili G, Eleopra R, Malik RA, Ritelli M, Zoppi N, Dordoni C, Sorosina M, Grammatico P, Fadavi H, Gerrits MM, Almomani R, Faber CG, Merkies IS, Toniolo D, Network F, Cocca M, Doglioni C, Waxman S, Dib-Hajj S, Taiana M, Sassone J, Lombardi R, Cazzato D, Zauli A, Santoro S, Marchi M, Lauria G. COL6A5 variants in familial neuropathic chronic itch. Brain 2017, 140: 555-567. PMID: 28073787, DOI: 10.1093/brain/aww343.Peer-Reviewed Original ResearchConceptsChronic itchSmall fiber neuropathyJHS/EDS-HT patientsJoint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility typeNew candidate therapeutic targetsIntraepidermal nerve fiber densityEhlers-Danlos syndrome hypermobility typeEDS-HT patientsNonsense variantNerve fiber densitySkin of patientsCandidate therapeutic targetUnrelated sporadic patientsWhole-exome sequencingItch reliefNeuropathic itchDiabetic patientsHypermobility typeSomatosensory pathwaysHealthy controlsSkin biopsiesSide effectsTherapeutic targetPatientsSporadic patients
2016
Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia
Cao L, McDonnell A, Nitzsche A, Alexandrou A, Saintot PP, Loucif AJ, Brown AR, Young G, Mis M, Randall A, Waxman SG, Stanley P, Kirby S, Tarabar S, Gutteridge A, Butt R, McKernan RM, Whiting P, Ali Z, Bilsland J, Stevens EB. Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia. Science Translational Medicine 2016, 8: 335ra56. PMID: 27099175, DOI: 10.1126/scitranslmed.aad7653.Peer-Reviewed Original ResearchConceptsSensory neuronsPain conditionsSodium channelsClinical phenotypeSensory neuronal activityChronic pain conditionsHeat-induced painPeripheral nervous systemUnmet clinical needSodium channel Nav1.7Nav1.7 sodium channelNav1.7 blockersPharmacological reversalPain phenotypesExtreme painNeuronal activityHeat stimuliNervous systemChannel Nav1.7PainClinical needPatientsAberrant responsesSensory conditionsInduced pluripotent stem cell line
2015
Contactin-1 and Neurofascin-155/-186 Are Not Targets of Auto-Antibodies in Multifocal Motor Neuropathy
Doppler K, Appeltshauser L, Krämer HH, Ng JK, Meinl E, Villmann C, Brophy P, Dib-Hajj SD, Waxman SG, Weishaupt A, Sommer C. Contactin-1 and Neurofascin-155/-186 Are Not Targets of Auto-Antibodies in Multifocal Motor Neuropathy. PLOS ONE 2015, 10: e0134274. PMID: 26218529, PMCID: PMC4517860, DOI: 10.1371/journal.pone.0134274.Peer-Reviewed Original ResearchConceptsMultifocal motor neuropathyMotor neuropathyContactin-1Neurofascin 155Multifocal motor neuropathy patientsChronic inflammatory demyelinating polyneuropathyInflammatory demyelinating polyneuropathySubgroup of patientsNeurofascin-186Enzyme-linked immunosorbentHuman embryonic kidney 293 cellsDemyelinating polyneuropathyAuto antibodiesEmbryonic kidney 293 cellsMuscle weaknessNeuropathy patientsPatient seraConduction blockParanodal proteinsNeuropathyPatientsKidney 293 cellsIgMSerumDifferent assaysDe novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy
Blanchard MG, Willemsen MH, Walker JB, Dib-Hajj SD, Waxman SG, Jongmans M, Kleefstra T, van de Warrenburg BP, Praamstra P, Nicolai J, Yntema HG, Bindels R, Meisler MH, Kamsteeg EJ. De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy. Journal Of Medical Genetics 2015, 52: 330. PMID: 25725044, PMCID: PMC4413743, DOI: 10.1136/jmedgenet-2014-102813.Peer-Reviewed Original ResearchConceptsClinical exome sequencingClinical featuresEarly-infantile epileptic encephalopathy type 13Intellectual disabilityVoltage-gated sodium channel Nav1.6De novo SCN8A mutationFunction mutationsExome sequencingSodium channel Nav1.6Variable clinical featuresGenotype-phenotype correlationSCN8A mutationsChannel Nav1.6Hyperpolarising shiftMutant sodium channelsPatientsDe novoHeterozygous lossSodium channelsElectrophysiological analysisClinical interpretationType 13DisabilitySeizuresWildtype channel
2013
A new Nav1.7 mutation in an erythromelalgia patient
Estacion M, Yang Y, Dib-Hajj SD, Tyrrell L, Lin Z, Yang Y, Waxman SG. A new Nav1.7 mutation in an erythromelalgia patient. Biochemical And Biophysical Research Communications 2013, 432: 99-104. PMID: 23376079, DOI: 10.1016/j.bbrc.2013.01.079.Peer-Reviewed Original ResearchConceptsMutations of Nav1.7Voltage-gated sodium channel Nav1.7Year old patientSodium channel Nav1.7Voltage-clamp studiesErythromelalgia patientsOlder patientsDRG neuronsNav1.7 mutationPainful disordersFunction missense mutationsChannel Nav1.7Neuron firingPatientsRamp stimuliExon 20Channel biophysical propertiesControl allelesNav1.7Missense mutationsBiophysical propertiesMutations
2012
Gain-of-function Nav1.8 mutations in painful neuropathy
Faber CG, Lauria G, Merkies IS, Cheng X, Han C, Ahn HS, Persson AK, Hoeijmakers JG, Gerrits MM, Pierro T, Lombardi R, Kapetis D, Dib-Hajj SD, Waxman SG. Gain-of-function Nav1.8 mutations in painful neuropathy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 19444-19449. PMID: 23115331, PMCID: PMC3511073, DOI: 10.1073/pnas.1216080109.Peer-Reviewed Original ResearchConceptsPainful peripheral neuropathySmall fiber neuropathyPainful neuropathyPeripheral neuropathyPainful small fiber neuropathyDorsal root ganglion neuronsSodium channelsApparent underlying causePeripheral nerve axonsDRG neuronsGanglion neuronsNeuropathyNerve axonsUnderlying causeFunction variantsCurrent clampPatientsPotential pathogenicityNeuronsMutationsHyperexcitabilityAxonsResponse
2010
Sodium channel expression and function in multiple sclerosis
Bangalore L, Black J, Carrithers M, Waxman S. Sodium channel expression and function in multiple sclerosis. 2010, 29-43. DOI: 10.1017/cbo9780511781698.005.Peer-Reviewed Original ResearchMultiple sclerosisRecovery of functionSodium channel expressionHealth care advisorsMechanisms of recoveryNeurorehabilitation programChannel expressionSpecific syndromesTherapeutic interventionsCare advisorsClinical rehabilitationEfficient therapySclerosisDisease mechanismsPatientsCliniciansNeurorehabilitationInterventionBasic scienceSocial participationPathophysiologySyndromeTherapyNeuroplasticity
2000
A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation
Bendahhou S, Cummins T, Hahn A, Langlois S, Waxman S, Ptácek L. A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation. Journal Of Clinical Investigation 2000, 106: 431-438. PMID: 10930446, PMCID: PMC314328, DOI: 10.1172/jci9654.Peer-Reviewed Original ResearchConceptsChannel slow inactivationPeriodic paralysisSlow inactivationSodium channel slow inactivationMalignant hyperthermia susceptibilitySkeletal muscle disordersHuman skeletal muscleParalytic attacksMuscle disordersHyperkalemic periodic paralysisSkeletal muscleParalysisDisease-causing mutationsNovel mutationsHyperKPPChannel defectsMolecular determinantsAlpha subunitMutant channelsMutationsDouble mutationInactivationPatientsTransmembrane segments S5
1995
Clivus and cervical spinal osteomyelitis with epidural abscess presenting with multiple cranial neuropathies
Azizi S, Fayad P, Fulbright R, Giroux M, Waxman S. Clivus and cervical spinal osteomyelitis with epidural abscess presenting with multiple cranial neuropathies. Clinical Neurology And Neurosurgery 1995, 97: 239-244. PMID: 7586856, DOI: 10.1016/0303-8467(95)00036-j.Peer-Reviewed Original ResearchConceptsCranial nerve abnormalitiesNerve abnormalitiesTwelfth nerve palsyMultiple cranial neuropathiesElevated CSF proteinHistory of otitisCranial neuropathiesDiabetic menNerve palsyEpidural abscessShoulder painSpinal osteomyelitisLumbar punctureCervical spinePrevertebral spaceEpidural spaceCSF proteinImaging proceduresClivusOsteomyelitisPatientsAbnormalitiesNeckPleocytosisNeuropathy
1991
Lhermitte's sign in a patient with herpes zoster
Vollmer T, Brass L, Waxman S. Lhermitte's sign in a patient with herpes zoster. Journal Of The Neurological Sciences 1991, 106: 153-157. PMID: 1802963, DOI: 10.1016/0022-510x(91)90252-3.Peer-Reviewed Original Research
1988
Evoked potentials in suspected multiple sclerosis: Diagnostic value and prediction of clinical course
Hume A, Waxman S. Evoked potentials in suspected multiple sclerosis: Diagnostic value and prediction of clinical course. Journal Of The Neurological Sciences 1988, 83: 191-210. PMID: 3128646, DOI: 10.1016/0022-510x(88)90068-8.Peer-Reviewed Original ResearchConceptsSilent lesionsMultiple sclerosisOptic neuritisIsolated optic neuritisDefinite multiple sclerosisEP abnormalitiesMS suspectsClinical deteriorationBrainstem auditoryClinical courseVisual EPsChance of deteriorationNeurologic disordersOnly abnormalityNormal EPsPatientsAuditory EPsClinical diagnosisDiagnostic valueLesionsSclerosisNeuritisChronicAbnormalitiesFollowNonpyramidal Motor Systems and Functional Recovery After Damage to the Central Nervous System
Waxman S. Nonpyramidal Motor Systems and Functional Recovery After Damage to the Central Nervous System. Neurorehabilitation And Neural Repair 1988, 2: 1-6. DOI: 10.1177/136140968800200101.Peer-Reviewed Original ResearchLateral corticospinal tractCentral nervous systemCorticospinal tractProximal musculatureNervous systemMotor systemProximal limb musculatureResidual motor functionMotor controlCorticobulbar pathwaysMost patientsDistal musclesCortical lesionsFunctional recoveryBilateral innervationMotor cortexMotor functionMotor neuronsMaintenance of postureClinical observationsUnilateral damageBilateral damagePatientsNeurological diseasesMotor response
1986
Different effects of 4-aminopyridine on sensory and motor fibers: pathogenesis of paresthesias.
Kocsis J, Bowe C, Waxman S. Different effects of 4-aminopyridine on sensory and motor fibers: pathogenesis of paresthesias. Neurology 1986, 36: 117-20. PMID: 3001584, DOI: 10.1212/wnl.36.1.117.Peer-Reviewed Original Research