Diabetes and the Nervous System

602 Pages·2014·91.36 MB·English

by  Douglas W. Zochodne and Rayaz A. Malik (Eds.)

HANDBOOK OF CLINICAL
NEUROLOGY
Series Editors
MICHAEL J. AMINOFF, FRANC¸OIS BOLLER, AND DICK F. SWAAB
VOLUME 126
EDINBURGH LONDON NEW YORK OXFORD PHILADELPHIA
ST LOUIS SYDNEY TORONTO 2014
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Availabletitles
Vol.79,Thehumanhypothalamus:basicandclinicalaspects,PartI,D.F.SwaabISBN9780444513571
Vol.80,Thehumanhypothalamus:basicandclinicalaspects,PartII,D.F.SwaabISBN9780444514905
Vol.81,Pain,F.CerveroandT.S.Jensen,eds.ISBN9780444519016
Vol.82,Motorneuronedisordersandrelateddiseases,A.A.EisenandP.J.Shaw,eds.ISBN9780444518941
Vol.83,Parkinson’sdiseaseandrelateddisorders,PartI,W.C.KollerandE.Melamed,eds.ISBN9780444519009
Vol.84,Parkinson’sdiseaseandrelateddisorders,PartII,W.C.KollerandE.Melamed,eds.ISBN9780444528933
Vol.85,HIV/AIDSandthenervoussystem,P.PortegiesandJ.Berger,eds.ISBN9780444520104
Vol.86,Myopathies,F.L.MastagliaandD.HiltonJones,eds.ISBN9780444518996
Vol.87,Malformationsofthenervoussystem,H.B.SarnatandP.Curatolo,eds.ISBN9780444518965
Vol.88,Neuropsychologyandbehaviouralneurology,G.GoldenbergandB.C.Miller,eds.ISBN9780444518972
Vol.89,Dementias,C.DuyckaertsandI.Litvan,eds.ISBN9780444518989
Vol.90,Disordersofconsciousness,G.B.YoungandE.F.M.Wijdicks,eds.ISBN9780444518958
Vol.91,Neuromuscularjunctiondisorders,A.G.Engel,ed.ISBN9780444520081
Vol.92,Stroke–PartI:Basicandepidemiologicalaspects,M.Fisher,ed.ISBN9780444520036
Vol.93,Stroke–PartII:Clinicalmanifestationsandpathogenesis,M.Fisher,ed.ISBN9780444520043
Vol.94,Stroke–PartIII:Investigationsandmanagement,M.Fisher,ed.ISBN9780444520050
Vol.95,Historyofneurology,S.Finger,F.BollerandK.L.Tyler,eds.ISBN9780444520081
Vol.96,Bacterialinfectionsofthecentralnervoussystem,K.L.RoosandA.R.Tunkel,eds.ISBN9780444520159
Vol.97,Headache,G.NappiandM.A.Moskowitz,eds.ISBN9780444521392
Vol.98,SleepdisordersPartI,P.MontagnaandS.Chokroverty,eds.ISBN9780444520067
Vol.99,SleepdisordersPartII,P.MontagnaandS.Chokroverty,eds.ISBN9780444520074
Vol.100,Hyperkineticmovementdisorders,W.J.WeinerandE.Tolosa,eds.ISBN9780444520142
Vol.101,Musculardystrophies,A.AmatoandR.C.Griggs,eds.ISBN9780080450315
Vol.102,Neuro-ophthalmology,C.KennardandR.J.Leigh,eds.ISBN9780444529039
Vol.103,Ataxicdisorders,S.H.SubramonyandA.Durr,eds.ISBN9780444518927
Vol.104,Neuro-oncologyPartI,W.GrisoldandR.Sofietti,eds.ISBN9780444521385
Vol.105,Neuro-oncologyPartII,W.GrisoldandR.Sofietti,eds.ISBN9780444535023
Vol.106,Neurobiologyofpsychiatricdisorders,T.SchlaepferandC.B.Nemeroff,eds.ISBN9780444520029
Vol.107,EpilepsyPartI,H.StefanandW.H.Theodore,eds.ISBN9780444528988
Vol.108,EpilepsyPartII,H.StefanandW.H.Theodore,eds.ISBN9780444528995
Vol.109,Spinalcordinjury,J.VerhaagenandJ.W.McDonaldIII,eds.ISBN9780444521378
Vol.110,Neurologicalrehabilitation,M.BarnesandD.C.Good,eds.ISBN9780444529015
Vol.111,PediatricneurologyPartI,O.Dulac,M.LassondeandH.B.Sarnat,eds.ISBN9780444528919
Vol.112,PediatricneurologyPartII,O.Dulac,M.LassondeandH.B.Sarnat,eds.ISBN9780444529107
Vol.113,PediatricneurologyPartIII,O.Dulac,M.LassondeandH.B.Sarnat,eds.ISBN9780444595652
Vol. 114, Neuroparasitology and tropical neurology, H.H. Garcia, H.B. Tanowitz and O.H. Del Brutto, eds. ISBN
9780444534903
Vol.115,Peripheralnervedisorders,G.SaidandC.Krarup,eds.ISBN9780444529022
Vol.116,Brainstimulation,A.M.LozanoandM.Hallett,eds.ISBN9780444534972
Vol.117,Autonomicnervoussystem,R.M.BuijsandD.F.Swaab,eds.ISBN9780444534910
Vol.118,Ethicalandlegalissuesinneurology,J.L.BernatandH.R.Beresford,eds.ISBN9780444535016
Vol.119,NeurologicaspectsofsystemicdiseasePartI,J.BillerandJ.M.Ferro,eds.ISBN9780702040863
Vol.120,NeurologicaspectsofsystemicdiseasePartII,J.BillerandJ.M.Ferro,eds.ISBN9780702040870
Vol.121,NeurologicaspectsofsystemicdiseasePartIII,J.BillerandJ.M.Ferro,eds.ISBN9780702040887
vi AVAILABLETITLES(Continued)
Vol.122,Multiplesclerosisandrelateddisorders,D.S.Goodin,ed.ISBN9780444520012
Vol.123,Neurovirology,A.C.TselisandJ.Booss,eds.ISBN9780444534880
Vol.124,Clinicalneuroendocrinology,E.Fliers,M.KorbonitsandJ.A.Romijn,eds.ISBN9780444596024
Vol.125,Alcoholandthenervoussystem,E.V.SullivanandA.Pfefferbaum,eds.ISBN9780444626196
Foreword
Diabetesmellitusisamajorandworldwidecauseofprematureillnessanddeath,anditsglobalprevalencecontinuesto
increase,probablyrelatedatleastinparttoincreasingobesityanddiminishedphysicalactivity.Bysomeestimates,in
theUnitedStatesitsprevalenceamongadultsisalmost13%,anditaccountsforalmost14%ofhealthcareexpenditure,
becauseofcomplicationssuchasstroke,peripheralneuropathy,myocardialinfarction,andkidneyandoculardisease.
Fortunately,themostcommonvariety–type2diabetes–canbedetectedatanearlyorpreclinicalstage,andtreatment
canavertcomplicationsandinfluencethelong-termoutcome.
Withthesepointsinmind,weareparticularlypleasedtoincludeavolumeondiabetesinthepresentseriesofthe
HandbookofClinicalNeurology.ItisavailablebothinprintandalsoinanelectronicformatonElsevier’sScience
Directwebsite,whichfacilitatesaccessandsearchesfortopicsofparticularinterest.
Thevolumecomprises36chaptersdividedintothreesections.Thefirst,whichcontains16chapters,discussesthe
clinicalimpactofdiabetesonthenervoussystem.Althoughthefocusismainlyontheperipheralnervoussystem,there
arechaptersonstroke,cognitivedisorders,infections,sexualdysfunction,andpsychosocialissues,aswellasamore
generalchapterthatincludesdiscussionofsomeofthemajormetaboliccomplicationsofdiabetes.Thesecondsection
contains seven chapters on diagnostic and therapeutic approaches to the neurological complications of diabetes,
includingelectrophysiologic,pathologic,andimagingstudies.Inafinalsection,variousfundamentalstudiesconcern-
ingtheneurologicdisturbancesindiabetesarediscussed.
ThevolumehasbeenablyeditedbyProfessorDouglasZochodneoftheUniversityofAlberta,whohasmademany
personal contributions to the field of experimental diabetic neuropathy and peripheral nerve regeneration, and by
Professor Rayaz A. Malik of the University of Manchester, England and Weill Cornell Medical College in Qatar,
Doha,Qatar, whoworksondiabeticneuropathy andcardiomyopathy inboth animal models and atatranslational
levelinpatients.Theyhaveassembledanexcellentteamofcontributors,andwearegratefultothemallforcreating
suchavaluableresource.Havingreadandcommentedoneachofthechaptersinourcapacityasserieseditors,weare
confidentthatbothcliniciansandresearchersalikewillfindmuchtoappealtotheminthevolume.
Asalways,itisapleasuretothankElsevier,ourpublishers–andinparticularMicaHaley,MichaelParkinson,and
KristiAnderson–fortheirassistanceinthedevelopmentandproductionofthisvolume.
MichaelJ.Aminoff
Franc¸oisBoller
DickF.Swaab
Preface
Withthecurrentepidemicofobesityanddiabetes,theprevalenceandconsequencesofdiabeticneuropathyaresetto
increaseinboththedevelopedandthedevelopingworld.Theprevalenceofdiabeticneuropathyrangesfrom50%to
90%andmanifestsaspainfuldiabeticneuropathyinabout20%,erectiledysfunctioninabout40%,andfootulcer-
ationin about 25%ofdiabetic patients.TherearecurrentlynoFDA approved therapies to prevent orrepair nerve
damage,andonlythreeapprovedtherapiesforpainfuldiabeticneuropathyandanumberofnewtherapiesforerectile
dysfunction. Given that approximately 33% of the direct costs for treatment of diabetes and its complications are
attributedtodiabeticneuropathyandfootulceration,thisdemandsfurtherinvestmentforresearchinthisarea.
Moderncentralandperipheralneuroimagingtechniqueshavesignificantlyimprovedourabilitytodiagnoseand
monitortheprogressionofdiabeticneuropathy.Furthermore,molecularbiologyandtheomicsplatformtechnologies
haverevealednovelpathwaysforthedevelopmentandtreatmentofdiabeticneuropathy.However,thetranslational
impactofthesediscoverieswillonlyberealizedwhenoptimalsurrogateend-pointshavebeendeployedinclinicaltrials
ofdiabeticneuropathy.
Thisbookisdividedinthreemajorsections,andsetsthescenebypresentingthemajorsensory,motor,andauto-
nomicmanifestationsofdiabeticneuropathyaswellasthecomplicationsofdiabetesthatinvolvethecentralnervous
system.Aconsiderationofalternativepathologiesaffectingthenervoussystemofdiabeticpatientsprovidesamore
holisticviewoftheneurologicmanifestationsinthesepatients.Chaptersonexperimentalobservationsexplorethe
variedmechanisticpathwaysandnoveltherapiesfordiabeticneuropathy.Furthersectionsdealwithnoveldiagnostic
andtherapeuticstrategiestoprovideclinicalinsightsintothemanagementofdiabeticneuropathyandotherneurologic
complicationsofdiabetes.
Wehaveendeavoredtoprovideanaccessiblebutcomprehensiveandup-to-dateresourceonclinical,experimental
andtranslationalaspectsofdiabeticneuropathyforneurologists,diabetologists,andindeedanyotherhealthprofes-
sionalswhotakecareofdiabeticpatients.WebelievethatthisvolumeoftheHandbookofNeurologywilltherefore
benefitthemanyinvestigatorsandclinicalpractitionersworkinginthefieldofdiabeticneuropathyaswellasthemany
patientswhosufferfromthisdevastatingdisease.
DouglasW.Zochodne,MD,PhD
RayazA.Malik,MBChB,PhD
Contributors
U.Alam A.J.M.Boulton
CentreforEndocrinologyandDiabetes,Institute DepartmentofMedicine,UniversityofManchester;
ofHumanDevelopment,CentralManchester DiabetesCentre,ManchesterRoyalInfirmary,
UniversityHospitalsNHSFoundationTrust, Manchester,UKandDiabetesResearchInstitute,
Manchester,UK UniversityofMiami,FL,USA
V.Bril
H.Andersen
DivisionofNeurology,DepartmentofMedicine,
DepartmentofNeurology,AarhusUniversityHospital,
UniversityHealthNetwork,UniversityofToronto,
Aarhus,Denmark
Toronto,Canada
C.S.Andreassen
B.Calabek
DepartmentofOtorhinolaryngologyandHead
NeurologischeAbetilung,KaiserFranzJosefSpital,
andNeckSurgery,AarhusUniversityHospital,
Vienna,Austria
Aarhus,Denmark
N.A.Calcutt
T.G.Arnason DepartmentofPathology,UniversityofCaliforniaSan
DepartmentofAnatomyandCellBiologyand Diego,LaJolla,CA,USA
DepartmentofMedicine,DivisionofEndocrinology
andMetabolism,UniversityofSaskatchewan, B.Callaghan
Saskatoon,Canada DepartmentofNeurology,UniversityofMichigan,Ann
Arbor,MI,USA
O.Asghar
CentreforEndocrinologyandDiabetes, M.Cortez
InstituteofHumanDevelopment,CentralManchester ImagingandNeurosciencesCenter,UniversityofUtah,
UniversityHospitalsNHSFoundationTrust, SaltLakeCity,UT,USA
Manchester,UK
A.M.Demchuk
DepartmentofClinicalNeurosciencesandRadiology,
S.Azmi
FoothillsMedicalCentre,Calgary,Alberta,Canada
CentreforEndocrinologyandDiabetes,Institute
ofHumanDevelopment,CentralManchester
T.Didangelos
UniversityHospitalsNHSFoundationTrust,
1stPropedeuticDepartmentofInternalMedicine,
Manchester,UK
MedicalSchool,AristotleUniversityofThessaloniki,
“AHEPA”Hospital,Greece
S.Bal
DepartmentofClinicalNeurosciencesandRadiology,
J.Doupis
FoothillsMedicalCentre,Calgary,Alberta,Canada
InternalMedicineandDiabetesDepartment,Salamis
NavalHospital,Salamis,Greece
G.J.Biessels
DepartmentofNeurology,RudolfMagnusInstituteof P.J.Dyck
Neurosciences,UniversityMedicalCenterUtrecht,The PeripheralNeuropathyResearchLaboratory,Mayo
Netherlands Clinic,Rochester,MN,USA
xii CONTRIBUTORS
P.J.B.Dyck A.Kalsbeek
DepartmentofNeurologyandPeripheralNeuropathy DepartmentofEndocrinologyandMetabolism,
ResearchLaboratory,MayoClinicRochester, AcademicMedicalCenter,UniversityofAmsterdam,
Rochester,MN,USA Amsterdam,TheNetherlands
G.Ebenezer P.Kempler
CutaneousNerveLaboratory,JohnsHopkinsUniversity FirstDepartmentofInternalMedicine,Semmelweis
SchoolofMedicine,Baltimore,MD,USA University,Budapest,Hungary
E.L.Feldman P.S.Koekkoek
DepartmentofNeurology,UniversityofMichigan,Ann JuliusCenterforHealthSciencesandPrimaryCare,
Arbor,MI,USA UniversityMedicalCenterUtrecht,Utrecht,The
Netherlands
P.Fernyhough
R.S.Laughlin
DepartmentofPharmacologyandTherapeutics,
DepartmentofNeurology,MayoClinicRochester,
UniversityofManitobaandDivisionof
Rochester,MN,USA
NeurodegenerativeDisorders,StBonifaceHospital
ResearchCentre,Winnipeg,Manitoba,Canada
S.E.LaFleur
DepartmentofEndocrinologyandMetabolism,
E.Fliers
AcademicMedicalCenter,UniversityofAmsterdam,
DepartmentofEndocrinologyandMetabolism,
Amsterdam,TheNetherlands
AcademicMedicalCenter,UniversityofAmsterdam,
Amsterdam,TheNetherlands
C.A.Lee-Kubli
GraduateSchoolofBiomedicalSciences,Sanford-
R.Freeman
BurnhamInstituteforMolecularMedicineand
DepartmentofNeurology,BethIsraelDeaconessMedical
DepartmentofPathology,UniversityofCaliforniaSan
Center,HarvardMedicalSchool,Boston,MA,USA
Diego,LaJolla,CA,USA
J.S.Gonzalez
J.K.Mah
FerkaufGraduateSchoolofPsychology,Yeshiva
DivisionofPediatricNeurology,Departmentof
UniversityandDiabetesResearchCenter,Albert
Pediatrics,CummingSchoolofMedicine,Universityof
EinsteinCollegeofMedicine,Bronx,NY,USA
Calgary,Calgary,Alberta,Canada
M.Goyal
R.A.Malik
DepartmentofClinicalNeurosciencesandRadiology,
CentreforEndocrinologyandDiabetes,Institute
FoothillsMedicalCentre,Calgary,Alberta,Canada
ofHumanDevelopment,CentralManchester
UniversityHospitalsNHSFoundationTrust,
M.Greig
Manchester,UKandWeillCornellMedicalCollegein
DiabetesDepartment,RoyalHallamshireHospital,
Qatar,Doha,Qatar
Sheffield,UK
J.McGavock
M.D.Hill DepartmentofPediatricsandChildHealth,University
StrokeUnit,FoothillsHospital,HotchkissBrainInstitute, ofManitobaandCentreforPhysicalActivityand
UniversityofCalgary,Calgary,Alberta,Canada CardiometabolicHealthinYouth,ManitobaInstituteof
ChildHealth,Winnipeg,Manitoba,Canada
S.Javed
CentreforEndocrinologyandDiabetes,Instituteof A.P.Mizisin
HumanDevelopment,CentralManchesterUniversity DepartmentofPathology,SchoolofMedicine,
HospitalsNHSFoundationTrust,Manchester,UK UniversityofCaliforniaSanDiego,LaJolla,CA,USA
C.A.Jay S.Mohseni
DepartmentofNeurology,UniversityofCalifornia DepartmentofClinicalandExperimentalMedicine,
SanFranciscoandNeurologyService,SanFrancisco DivisionofCellBiology,FacultyofHealthSciences,
GeneralHospital,SanFrancisco,CA,USA Link€opingUniversity,Link€oping,Sweden
CONTRIBUTORS xiii
H.Nukada A.G.Smith
DepartmentofMedicine,UniversityofOtagoMedical DepartmentofNeurologyandDepartmentof
School,Dunedin,NewZealandandNukadaInstitutefor Anesthesiology,UniversityofUtah,SaltLakeCity,UT,
MedicalandBiologicalResearch,Chiba,Japan USA
D.Pacaud B.E.Smith
DivisionofPediatricEndocrinology,Departmentof DepartmentofNeurology,MayoClinic,Scottsdale,AZ,
Pediatrics,CummingSchoolofMedicine,Universityof USA
Calgary,Calgary,Alberta,Canada
E.Smith
N.Papanas DepartmentofClinicalNeurosciencesandRadiology,
SecondDepartmentofInternalMedicine,Democritus FoothillsMedicalCentre,Calgary,Alberta,Canada
UniversityofThrace,Alexandroupolis,Greece
M.V.Solbrig
B.Perkins DepartmentsofInternalMedicine(Neurology)and
DivisionofEndocrinologyandMetabolism,Department MedicalMicrobiology,UniversityofManitoba,
ofMedicine,UniversityHealthNetwork,Universityof Winnipeg,Manitoba,Canada
Toronto,Toronto,Canada
M.Tavakoli
CentreforEndocrinologyandDiabetes,Instituteof
I.N.Petropoulos
HumanDevelopment,CentralManchesterUniversity
CentreforEndocrinologyandDiabetes,Instituteof
HospitalsNHSFoundationTrust,Manchester,UK
HumanDevelopment,CentralManchesterUniversity
HospitalsNHSFoundationTrust,Manchester,UKand
S.Tesfaye
WeillCornellMedicalCollegeinQatar,Doha,Qatar
DiabetesDepartment,RoyalHallamshireHospital,
Sheffield,UK
M.Polydefkis
CutaneousNerveLaboratoryandJohnsHopkins
C.Toth
BayviewEMGLaboratory,JohnsHopkinsUniversity
DepartmentofClinicalNeurosciencesandHotchkiss
SchoolofMedicine,Baltimore,MD,USA
BrainInstitute,UniversityofCalgary,Calgary,Alberta,
Canada
G.E.H.M.Rutten
JuliusCenterforHealthSciencesandPrimaryCare,
T.Va´rkonyi
UniversityMedicalCenterUtrecht,Utrecht,The
FirstDepartmentofInternalMedicine,Universityof
Netherlands
Szeged,Szeged,Hungary
R.E.Schmidt
V.M.K.Verge
DepartmentofPathologyandImmunology,Washington
DepartmentofAnatomyandCellBiologyandCameco
UniversitySchoolofMedicine,SaintLouis,MO,USA
MSNeuroscienceResearchCenter,Universityof
Saskatchewan,SaskatoonCityHospital,Saskatoon,
D.Selvarajah
Canada
DiabetesDepartment,RoyalHallamshireHospital,
Sheffield,UK A.Veves
MicrocirculationLaboratoryandJoslin–BethIsrael
J.E.Shaw DeaconessFootCenter,BethIsraelDeaconessMedical
BakerIDIHeartandDiabetesInstitute,Melbourne, CenterandHarvardMedicalSchool,Boston,MA,USA
Victoria,Australia
L.Vileikyte
A.A.F.Sima DepartmentofMedicine,UniversityofManchester,
DepartmentsofPathologyandNeurology,WayneState Manchester,UK
University,Detroit,MI,USA
A.I.Vinik
J.R.Singleton DiabetesCenterforEndocrineandMetabolicDisorders
DepartmentofNeurology,UniversityofUtah,SaltLake andNeuroendocrineUnit,EasternVirginiaMedical
City,UT,USA School,Norfolk,VA,USA
xiv CONTRIBUTORS
I.D.Wilkinson D.Ziegler
AcademicRadiology,Departmentof InstituteforClinicalDiabetology,GermanDiabetes
CardiovascularScience,RoyalHallamshire CenteratHeinrichHeineUniversity,LeibnizCenter
Hospital,Sheffield,UK forDiabetesResearch;DepartmentofEndocrinology
andDiabetology,UniversityHospital,Düsseldorf,
N.M.Wilson Germany
DepartmentofAnatomyandCellBiology,
UniversityofKansasMedicalCenter, W.Zhang
KansasCity,KS,USA DepartmentofPathology,WayneStateUniversity,
Detroit,MI,USA
D.E.Wright
DepartmentofAnatomyandCellBiology, D.W.Zochodne
UniversityofKansasMedicalCenter,KansasCity, DivisionofNeurology,DepartmentofMedicine,
KS,USA UniversityofAlberta,Edmonton,Alberta,Canada