Post on 12-Jun-2020
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OsteopathicManipula0onintheManagementAutonomic
Neuropathy
JoshuaAlexander,DO,MPHScrippsClinic
Objec0ves
• Differen0atelargefiber,smallfiber,&autonomic,polyneuropathy
• DescribefeaturesofPOTS• Formulatetreatmentforautonomicneuropathyusingosteopathicmanipula0on
Roadmap• BasicPolyneuropathyReview• SmallFiberNeuropathyRefresher• Autonomicneuropathy
– AllofthisistoarguethatOMMhasaroleinmanagementofdysautonomia
• SomeAnatomyofcourse
• Applica0onofosteopathicmanipula0on
Yale.edu
Polyneuropathy• Impairmentofmul0pleperipheralnerves
– Sensory,motor,orautonomic– Small,large,orautonomicfibers
• Smallfibers– Painandtemperaturecarriedonsmallunmyelinatedorthinlymyelinatedfibers
– Symptoms:burningortemperaturechanges• Largefibers
– AalphaandAbetalargefibers–sensory– Agamma–motor– Vibra0on,propriocep0on,touch/2-pointdiscrimina0on,lossofbulk
– Symptoms:0ngling,pinsandneedles
Polyneuropathy
• LargeFiber– Axonal,Demyelina0ng,orMixed– MotorvsSensoryvsMixed
• AutonomicNeuropathycoveredindetaillater– Carriedonunmyelinatedorthinlymyelinatedfibers
• SmallFiberNeuropathyandAutonomicNeuropathyoVenaccompanyeachother– Moreonthisinlessthanaminute
Polyneuropathy
• AnatomicDistribu0on– Typicallylengthdependentaffec0ngthelowerlimbsfirst
– ThinkStockingGlove• Thegloveisusuallynotaffected0llthethelowerlimbsareinvolveduptotheknees
– Therearemanyexcep0ons
• Agoodresourceis:hXps://neuromuscular.wustl.edu
Pathophysiology– Axonaldegenera0on
• mostcommon• “Dyingback”
– Mostdistalpartoftheaxondies– Typicaldistalsymmetricpolyneuropathy– Usuallytoxicormetabolic– Symptoma0c/suppor0ve
– Walleriandegenera0on• Distaldegrada0on• Traumaornerveinfarc0on• Symptoma0c/suppor0ve/0me
– Segmentaldemyelina0on• Axonspared• Nervesheathimpaired• CanbefocalmononeuropathybutmoreoVenseeninimmunemediated/
inflammatorypolyneuropathy• Medicalmanagement
SmallFiber• ThinlymyelinatedAδ
– Mechanoreceptorsandthermoreceptors– Pain– Cold– Preganglionicfibers(ANS)
• UnmyelinatedCfibers– Polymodalreceptors– Nocicep0on–burningpain– Itching– Warm– Maybecold– Postganglionicfibers
• Sweatglands,bloodvessels,heart,etc
SmallFibers
• Sitinthedermis• Exactpathophysiologyoftheirneuropathyisunknown– Autoan0bodiestoneuronalproteins– Inflammatorycytokines– Dermalvasculi0s
SmallFiberNeuropathyDiagnosis• Possible
– Length-dependentsymptoms– LossofPin/temp;allodynia/hyperalgesia
• Probable– Lengthdependent– LossofPin/temp;allodynia/hyperalgesia– NormalNCS
• Definite– Lengthdependentsymptoms– LossofPin/temp;allodynia/hyperalgesia– NormalNCS– Reducedepidermalnervefiberdensityattheankle(SkinBiopsy)OR
abnormalQST(quan0ta0vesensorytes0ng)ThemistocleousAC,RamirezJD,SerraJ,etal.PractNeurol2014;14:368–379.
SmallFiberNeuropathyE0ology• Metabolic
– Pre-diabetes/diabetes/abnormalglucosemetabolismorrapidcorrec0on
– VitaminB12deficiency– Dyslipidemia– Hypothyroidism– CKD
• Immune– Sjogren’s– Celiac– Sarcoid– RA– SLE– Vasculi0s– InflammatoryBowelDisease– Paraneoplas0c– MonoclonalGammopathy– Amyloid
• Infec0on– HIV– Hepa00sC– Influenza
• Toxins– ARV– An0bio0cs– Chemotherapy– Flecanide– Sta0n– EtOH– Sta0n– VitaminB6
• PrimaryHereditary– Nav1.7and1.8muta0ons– FamilialAmyloidAngiopathy– Fabry’s– Tangier’s
• PrimaryIdiopathic– IdiopathicSFN– BurningMouthSyndrome
AutonomicNervousSystem
• Sympathe0c• Parasympathe0c• Enteric
Sympathe0c
• Hypothalamustotheintermediolateralgraycellcolumninthespinalcord(1storderefferent)– Somatotopicorganiza0on
• Preganglionicaxonsfromthecordprojecttothepostganglionicneurons(2ndorderefferent)ontheparavertebralsympathe0cgangliaattheirlevel,above,orbelow– 3cervical,10-12thoracic,4lumbarand4-5sacral– Mostarepairedganglia
Sympathe0c
• Superiorcervicalganglion• Middlecervicalganglion• Inferiorcervicalganglion– Inferiorcanfusewiththeupperthoracicganglia
Sympathe0cNervousSystem
• Caudalmostgangliaatthecoccyxformtheunpairedganglionimpar
Sympathe0cNervousSystem
• Fromparavertebralganglionthesympathe0cstravelwithspinalnerves,cranialnerves,orbloodvesselwalltotheirtarget
Parasympathe0c• Brainstemandsacrum• Parasympathe0cpreganglionicneurons
– Eddinger-Westphal(III)inrostralmidbrain– Superiorsalivatoryandlacrimalnuclei(VII)inthepon0netegmentum
– Inferiorsalivatorynucleus(IX)periventriculargray–rostralmedulla
– Nucleusambiguus(X)–medullare2cularforma2onposteriortotheinferiorolivarynucleus• Oropharynx
– DorsalMotorNucleus(X)–flooroftheforthventricle• Thoraxandabdomen
– CNXhasthelargestgroupofparasympathe=cfibersinthebody
NucleusTractusSolitarius• ReceivessensoryinputfromanumberofcranialnervesincludingVagus.
• Caro0dbody,aor0cbodies,SAnodeviathevagus
• Taste,sensa0ontothemiddleear• Receivesinputfromtheheart,lungs,GI,liver,etc
• Thereisalotofvagaltonesetthroughherebecauseofthis
• AutonomicReflexzone
DorsalMotorNucleusX
• PleasereferenceNeXer
ANS• Bidirec0onalconnectedbetweentargetandcentral
autonomicnetwork• CentralAutonomicNetwork(CAN)
– Medialprefrontalcortex– Insularcortex– Centralnucleusoftheamygdala– Hypothalamus– Periaqueductalgray– Parabrachialnuclearcomplex– NucleusAmbiguus– NucleusTractussolitarius
• R.PaulLee,DOdescribesareleaseforthisCAN– Wewillnotdoithere
ANSDysfunc0on
DryMucusmembranesAnhydrosisAbnormalpupilsCons0pa0on/DiarrheaVomi0ngAbdominalpainEarlysa0ety/anorexiaIntes0nalpseudo-obstruc0on
Urinaryreten0onSkincolorchangesAbnormalheartrateOrthostasisErec0ledysfunc0on
E0ology
• Diabetes• Mul0systemAtrophy• Guillain-Barre• Sjogren’sSyndrome• Paraneoplas0c
– Smallcelllungcancer• HIV• Botulism• Chagas(nowintheUS)• Diphtheria• Leprosy• Rabies
• AcuteDysautonomia• Parkinsonism• Neuronalintranuclear
inclusiondisease• Myopathyandexternal
ophthalmoplegia,neuropathy,gastrointes0nalencephalopathy
• Anumberofhereditarycondi0ons
POSTURALORTHOSTATICTACHYCARDIASYNDROME
AutonomicNervousSystem
POTS• Thesepa0entsrangefrommildlyimpairedtobedridden• Theywereusuallynormalproduc0vepeoplebefore
– Thiscanbelostonthemedicalsystem– Inseverecasestheirlivesareusuallydestroyedandtheyjustwanttobenormal
– Labeledpsychiatric– Symptomsconfusedwithanxiety
• Especiallysinceitaffectswomenmorethanmen• Theywillsearchforexo0cdiagnoses• TheywillneedalotofhandholdingandTLC• Severecasesmaytakeyearstorecover
– 1yearOMM,1yearPT,thenaddi0onalOMM
POTS-AutonomicNeuropathy• Somees0matesarethat1%ofUSpopula0onhasPOTS• Heartrateincrease≥30bpmwithin10minofupright
postureinadults.Heartrateincreaseof≥40bpmwithin10minisrequiredinadolescentsage12–19years
• Absenceoforthosta0chypotensiondefinedasasustaineddropinbloodpressure≥20/10mmHgwithin3minofuprightposture
• Symptomsoforthosta0cintolerancefor≥6months• Absenceofovertcausesforsinustachycardiasuchasacute
physiologicals0muli,dietaryinfluences,othermedicalcondi0onsandmedica0ons
• Tilttabletestwithorw/osudomotortes0ngandtranscranialdoppler
POTS• Female:Male4:1• Typically13-50yearsold• 13%withfamilyhistory• Heterogeneous(Cardiogenicvsneurogenicvsstructural*)• StartaVeracutestress
– Surgery,viralillness,MVCetc.• Blurryvision,brainfog,cogni0vedysfunc0on,chestpain,
lightheaded,nausea,fa0gue,cons0pa0on,acrocyanosis,sleepabnormali0es,anxious/brainstemfeeling
• Onlyabout30%havesyncope• LookforEhler’sDanlosTypeIII*,MastCellAc0va0onSyndrome,
ChronicFa0gueSyndrome,migraine,fibromyalgia,Sjogren’sandotherautoimmunecondi0ons,GIproblems(bloa0ng,chroniccons0pa0on)
Pathophysiology
• 50%ofPOTSpa0entshavedistalsmallfiberneuropathywithsympathe0cdenerva0on– Pa0entmaynotbeawareoftheneuropathy– Impairedperipheralvascularresistanceinthelegswhenstandingduetobluntednorepinephrinethere• Causesexcessivevenouspoolingà• Sympathe0cac0va0onà• Increaseheartratetomaintainbloodpressure
Pathophysiology
• 50%haveHyperadrenergicstate• Excessiveorthosta0ctachycardia• Mightberelatedtoexcessiveinterleukin-6• Usuallyfromhypovolemiaorpar0alsympathe0cdenerva0on
• Testorthosta0ccatecholamines15minutessupinethen15minutesstanding(okaytoleanagainstawall)
Pathophysiology
• Norepinephrinetransporterdeficiency– Causeslossofsympathe0cac0va0onbydecreasingamountofNEtakenupatthesynapse
– GeneSLC6A2– Tricyclican0depressants,serotonin-norepinephrinereuptakeinhibitors,atomoxe0neimpactNET
Pathophysiology
• Hypovolemia– Lowbloodvolumewithdecreasedredbloodcellcount– 13%deficitinplasmavolumeinPOTS
• Thoughttocauselowerstrokevolumeandcompensatorytachycardia
• Impairedvascularandrenalresponsetohypovolemia– AngiotensinIIlevelsarehighandBPisnormal
• Fluidresponsive– GiveLactatedRingersorisotonicsaline– Oralrehydra0on
• PleasereferenceArnoldetal.Posturaltachcardiasyndrome–diagnosis,physiology,andprognosis.AutonomicNeuroscience:BasicandClinical.2018.hXps://doi.org/10.1016/j.autneu.2018.02.005
• Figures3and4
Pathophysiology
• Immunemediated(somestudiesshow20%)
• An0bodiestoganglionicacetylcholinereceptor
• An0bodiestoalpha1andbetaadrenergicreceptorsandcardiaclipidproteins
• Non-specificmarkers(e.g,ANA)posi0vein25%while31%havesomean0body+
• IgGagainstcardiacproteins– 40iden0fied
POTSassocia=on:• Sjögrensyndrome• Ankylosingspondyli0s• An0phospholipidsyndrome• Behcet'sdisease
Celiacdisease• Chronicimmunedemyelina0ng
polyneuropathy• Inflammatoryboweldisease(Crohnand
ulcera0vecoli0s)• Hashimoto'sthyroidi0s
Mul0plesclerosisNeuromyeli0sop0caRheumatoidarthri0sSarcoidosisSystemiclupuserythematosusJuvenilerheumatoidarthri0sAdultS0ll'sdiseaseUndifferen0atedconnec0ve0ssuedisease
Pathophysiology
• Impairedcerebralautoregula0on• Orthosta0cintolerancedespitenormalbloodpressure– Isthisproblemcentralratherthanperipheral?
Pathophysiology
• Decondi0oning–notsureifthisisprimaryorsecondary
• Aerobicexerciseiscri0cal• Isthehearttoosmall?
StructuralAssocia0ons
• ThoracicOutletSyndrome– Stellateganglioncompression?
• Hypermobility–EhlersDanlostype3– AlsoassociatedwithMastCellAc0va0onSyndrome
• MaybeChiariMalforma0on• Eaglesyndrome– Elongatedstyloid– CompressionofCNX,IX,caro0d
StructuralAssocia0ons
• Medianarcuateligamentsyndrome– intermiXentobstruc0onofceliacorsuperiormesentericarteriesbythemedianarcuateligament• celiacplexuscompression
– postprandialorpost-exer0onalabdominalpain
• Pelvicveinvaricosi0es– Venouspooling
ArolefortheVagusNerveinTreatment?
• Vagalnerves0mula0on– An0-inflammatory– Showntoimproverheumatoidarthri0s,Crohn’s,Sjogrens
• Regularexerciseimprovesvagaltone• An0-inflammatorydiet• Acupuncture• Biofeedback• Musictherapy• Medita0on
Treatment• Agreatcardiologistorautonomicneurologist• Increasedsodiumandfluidintake• Compressionstockings• Aerobicexercise• Isotonicsaline/LactatedRingersinfusions• Betablockers
– Metoprolol– Corlanor
• Alpha1agonist:Midodrine• Florinefinsomecases• L-Dopa,carbidopa• SSRI/SNRI• IVIG/PlasmaExchange/steroids/Rituximab
POTSAddi0onalInforma0on• Arnoldetal.Posturaltachcardiasyndrome–diagnosis,physiology,
andprognosis.AutonomicNeuroscience:BasicandClinical.2018.hXps://doi.org/10.1016/j.autneu.2018.02.005
• VerninoandS0les.Autoimmunityinposturalorthosta0ctachycardiasyndrome:currentunderstanding.AutonomicNeuroscience:BasicandClinical.2018.hXps://doi.org/10.1016/j.autneu.2018.04.005
• Goodman.Evalua0onofposturalorthostasistachycardiasyndrome(POTS).AutonomicNeuroscience:BasicandClinical.2018.hXps://doi.org/10.1016/j.autneu.2018.04.004
• Wellsetal.Posturaltachycardiasyndrome:currentperspec0ves.VascularHealthandRiskManagement.2018:14;1-11.
ISTHEREAROLEFOROMT?POTS
OMTforPOTS• GoodkinandBellew2014describeOMTforPOTS
– 26yearoldfemalewithfa0gue,pre-syncope,heatintolerance,cogni0vedysfunc0on,diffusejointpain,insomnia,jawinjury
– POTSdiagnosed,par0alresponsetoFlorinef,midodrine– Ligamentousar0cularstrain– Osteopathiccranialmanipula0vemedicine– Pre-treatment–couldonlytolerate5minutesinahotshower– Posttreatment–45minutes– Wasabletoreducemidodrineandamphetaminefor8days– Treatedagainandthis0meimprovedfor8weeks– Treateda3rd0me28dayslaterandremainedcontrolledather18monthfollow-up
– JAOANov2014;114:874-877
OMTforPOTS–GIsymptoms• CromeensandGambler2010• 48yearoldmalewithdecadeofpost-prandialabdominalbloa0ng,
cramping,nauseaandvomi0ng,andPOTS,spinepainthroughout• Bythe3rdtreatmentpa0enthadreducedGIsymptoms• 4thTreatmentdecreasedpain• Requiredmaintenancetreatment• SoV0ssue,muscleenergy,ar0culatory,ligamentousar0cular
strain,integratedneuromuscularrelease,ar0culatorytechniques
• OsteopathicFamilyPhysician2010;2:144-147
OSTEOPATHICMANIPULATIONTECHNIQUES
Polyneuropathy
OsteopathicManipula0on
• Largefiberneuropathy– Besttotreattheunderlyingcause– HoweverTreatmentofCSF,epineuralspaceandperineuralspacemightbehelpful
Today’sLabwillfocusonVagusBut…
• AutonomicNeuropathy– LineaAlbarelease
• Releasetheceliacganglionandplexuswhileyouarethere– Correctdysfunc0onoftherespiratoryandpelvicdiaphragm
– CV4,mightneedlotsofthem– TreatANSandstructuralabnormali0es
• Treattheocciput/OA,sacrum,coccyx,– Whenthepa=entishealthyenoughintegratethesystems– Treattheganglionimpars
» Trea0nghandonthesacro-coccygealjunc0onand0pofcoccyx– Treatmidlineofthesacrum– Releasethesympathe0cchainthere
• Trea0ngthevagusnerveanditsnuclei(nextslide)
ForImages
• Pleasereference:NeXer• Blumenfeld:NeuroanatomythroughClinicalCases
VagusNerveAnatomy
• ExitsMedulla– Betweenoliveandinferiorcerebellarpeduncle
• Jugularforamen– Sensoryganglia
• Superiorandinferior• JoinsCNXIbelowtheinferiorsensoryganglion• Descendsthroughthecaro0dsheathposterolateraltocaro0d
• Medialtointernaljugularvein
RightVagus
• Crossesanteriortosubclavianartery• Fatbehindtheinnominatevessels• Entersthoraxrightofthetrachea• Risesbehindthehilumoftherightlung• Coursesmediallytowardesophagus– JoinstheleVvagustoformtheesophagealplexus
LeVVagus
• CrossesanteriortotheleVsubclavianartery• EntersthethoraxbetweentheleVcommoncaro0dandsubclavianarteries
• DescendsonleVsideoftheaor0carch• Behindthephrenicnerve• BehindtherootoftheleVlung• Mediallyanddownwardtoesophagus• Meetsrightvagusàesophagealplexus
Vagus:GastricNerves
• Esophagealplexusgivesrisetotheanteriorandposteriorgastricnerves
• SupplyallabdominalorgansandGItracttothesplenicflexure
• Rightvagusàposteriorgastricplexus– Posterioinferior
• LeVvagusàanteriorgastricplexus– Anterosuperior
Vagus:CeliacNerve
• Rightvagusnerve• Celiacplexus
VagusandtheHeart
• Esophagealplexus– Suppliesposteriorpericardium
• Investsinthedeepcardiacplexus– Anteriortocarina– Inferiorcardiacbranch
• Rightsidefromtrunkofvagusatthetrachea• LeVfromrecurrentlaryngealnerve
CardiacPlexus
• Superficial– Undertheaor0carchanteriortotherightpulmonaryartery
– LeVsympathe0ctrunkandlowersuperiorcervicalcardiacbranchofthevagus
• Deep– Anteriortothecarina,posteriortoaor0carch– Mixofsympathe0cfromtheandparasympathe0cfrominferiorcardiacbranchofvagus
DeepCardiacPlexus
• Rightside– Anteriorandposteriorcoronaryplexus– Rightatrium
• LeVside– Superficialcardiacplexus– LeVatrium– Posteriorcoronaryplexus
Okaylet’streat• Occipitocervicalholdorvault–justbecomfortable–treatbyinten0on,ifyouneedtotreatlocally,
handsanteriorchestwallatthelevelofthecarina(sternalangle)andepigastricareaisfine• DONOTINVADE;DONOTRUSH• Getonthe4thventricle• Moveanteriorandfinddorsalmotornerveofthevagus
– Justlateraltothehypoglossalnucleus–pickonesidetotreatfirstthenbringintheother• BringyouraXen0ontotheesophagealplexus–bridgetothedorsalmotornucleusofthevagus• NowbringyouraXen0ontotheanteriorandposteriorgastricplexus• Bridgeittotheesophagealplexusthenthedorsalmotornucleus• NowbringyouraXen0ontotheceliacplexusanddothesameasabove• BringyouraXen0ontothesuperficialanddeepcardiacplexus– treatandintegratewiththe
esophagealplexus• Nowseethebigpictureandputitalltogether• Nowreleasethenucleustractussolitariusthennucleusambiguus• THISISTOOBIGATREATMENTFORASICKPATIENT
– Treattheindividualcomponentsfirstandover0mestartlinkingthemtogether