Lower Motor Neurons Motor Neuron Disorders Neuropathy · Lower Motor Neurons Motor Neuron Disorders...
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Transcript of Lower Motor Neurons Motor Neuron Disorders Neuropathy · Lower Motor Neurons Motor Neuron Disorders...
LowerMotorNeuronsMotorNeuronDisorders
NeuropathyNicholasJ.Silvestri,M.D.
AssistantProfessorofClinicalNeurology
Outline
• Motorneurons– Upperandlower
• Motorneurondisorders– Anteriorhorncelldiseases
• Peripheralnervedisorders– Nerveroot– Plexus– Nerve
MotorNeurons
• Uppermotorneurons:Cellbodiesinmotorcortex,axonsdescenddownthroughinternalcapsule,brainstem,andspinalcordtosynapseon…
MotorNeurons
• Lowermotorneurons:Cellbodiesareanteriorhorncells,axonsexitventralroots,joindorsalrootsatintervertebralforamenandtravelthroughnervestomuscles
Phenomenology• Uppermotorneuronsigns:
– Weaknessandslownessofmovement– Increasedtone(spasticity)– Hyperreflexia– Upgoingtoes(Babinski’ssign)
• Lowermotorneuronsigns:– Weakness– Decreasedtone– Hyporeflexia– Muscleatrophy– Fasciculationsandcramps
MotorNeuronDisorders
• Spinalmuscularatrophy• Amyotrophiclateralsclerosis
SpinalMuscularAtrophy
• TypeI(Werdnig-Hoffman)– Onsetbefore6monthsofage
• TypeII– Onsetbetween6and18monthsofage
• TypeIII(Kugelberg-Welander)– Onsetafter18monthsofage
• TypeIV– Adult-onset,thirdtofourthdecade
SpinalMuscularAtrophy
• Autosomalrecessiveinheritance• DuetohomozygousdeletionorpointmutationofSMN1geneonchromosome5
• SeverityofphenotyperelatedtonumberofSMN2copies
• Treatmentforalltypesislargelysupportive• Nusinersen approvedDec2016• GenetherapyinPhaseItrials
SpinalMuscularAtrophy
• SMAI:Werdnig-HoffmanDisease– Incidence4-10/100,000–Manifestsinfirst6monthsoflife– Hypotoniawithgeneralized(thoughproximallypredominant)weakness,tonguefasciculations,abdominalbreathing,weakcry,poorsuck
– Neversit– Only8%ofindividualsreachageof10years
SpinalMuscularAtrophy
• SMAII:Intermediateform– Onsetbetween6– 18monthsofage– Childcansitindependentlybutneverwalks– OtherwisesymptomsmimicSMAI– Posturalhandtremor– Pronetokyphoscoliosisandjointcontractures– Two-thirdsofindividualssurvivetoageof25years
SpinalMuscularAtophy
• SMAIII:Kugelberg-WelanderDisease– Onsetafter18monthsofage–Willsitandwalkbutneverrun– 40%stillwalkingat40yearsofage– Posturalhandtremor– Lifeexpectancynottypicallyaffected
AmyotrophicLateralSclerosis
• Neurodegenerativedisordercharacterizedbylossofmotorneuronsinthespinalcord,brainstem,andmotorcortex– Clinically,leadstoacombinationofUMNandLMNsymptomsandsigns
• Incidenceroughly1-2.5/100,000• Etiologyunknownandprogressionofthediseaseisrelentlessresultingindeath– 10%casesfamilial,e.g.C9orf72,SOD1mutations
TheIronHorse
ALS- Presentation
• 2/3patientswithlimb-onsetofsymptoms– Weaknessandwastingofdistallimbmusculature– Fasciculationsandcramps– Lackofsensorysymptoms
• 1/3patientswithbulbar-onsetofsymptoms– Dysphagia,dysarthria,dysphonia,chewingdifficulty
• Mostpatientseventuallydeveloprespiratorymuscleweakness– Dyspnea,orthopnea,signsofCO2retention– MostdeathsfromALSareduetorespiratoryfailure
ALS-Treatment• Riluzole:NMDAreceptorantagonist• Edaverone:Approvedlate2017– reducesoxidativestress
• Nutrition• Physicalandoccupationaltherapy• Speechandswallowingtherapy• Respiratorymanagement• Managementofsymptoms– Spasticity– Siallorhea
ALS- Prognosis
• Mediansurvivalfromtimeofdiseaseonsetrangesfrom24to36monthslookingatdatafromseveralstudiesofthenaturalhistoryofALS
• Mediansurvivalfromtimeofdiagnosisrangesfrom14to21monthsinthesamestudies
• 3yearsurvivalfromonsetroughly40%• 5yearsurvivalfromonsetroughly25%
OtherDisordersoftheAnteriorHornCell
• Progressivebulbarpalsy• Progressivemuscularatrophy• Kennedy’sdisease(x-linkedspinalmuscularbulbaratrophy)
• Infectiousetiologies– Poliovirus,enteroviruses,WestNilevirus,HIV
NerveRoot
• Degenerativediseaseofthespine• Discherniation• Inflammatoryorinfectious• Neoplastic
Radiculopathy
Radiculopathy
• Neckorbackpainusuallypresent• Painandmildsensorylossindistributionofnerveroot(dermatomalpattern)
• Weaknessrareduetomyotomaloverlapofmuscleinnervation
• Treatmenteithersurgicalorconservative• Mostcasesareself-limitedbutmayrecurwithtime
Plexus
CausesofPlexopathy
• Trauma– Birthtrauma
• Erb’spalsy:uppertrunkinjury• Klumpke’spalsy:lowertrunkinjury
• Inflammatory/Autoimmune– Parsonage-Turnersyndrome
• Neoplasticinvasion(lung,lymphatic,breast)• Radiationexposure• Structuralanomalies
Nerve
• Mononeuropathies• Polyneuropathies
Mononeuropathies
• Strictlydefinedasinjurytoasinglenerve• Commonexamples:
– Bell’spalsy(CNVII)– Carpaltunnelsyndrome(medianneuropathyatthewrist)– Ulnarneuropathyattheelbow– Saturdaynightpalsy(radialneuropathyatthespiralgroove)
– Commonperonealneuropathyatthefibularneck
Bell’sPalsy
• Annualincidence13-34cases/100,000population
• Norace,gender,orgeographicprediliction– Riskisthreetimesgreaterduringpregnancy(particularlyfirsttrimester)andfirstpost-partumweek
• Idiopathic,thoughmostcommonlythoughttobecausedbyHSV-1activation/infection– Otherviralinfections:VZV,CMV,EBV,etc
Bell’sPalsy
Polyneuropathy
• Typesoffibersinvolved:– Sensory
• Smallfibers(Adelta,Cfibers)• Largefibers
– Motor– Autonomic
• Smallfibers
• Pathophysiology– Axonal– Demyelinating
CausesofPolyneuropathy• AxonalNeuropathies
– Diabetesmellitus/dysglycemia– Amyloidosisorplasmacelldyscrasias– Vasculitis,e.g.polyarteritisnodosa,Churg-Strausssyndrome– Paraneoplastic– Nutritional,e.g.vitaminB1,B6,B12,Edeficiency– Infectious,e.g.viral(especiallyHIV)– Secondarytotoxins,e.g.arsenic,lead,thallium– Secondarytometabolicdisturbances,e.g.liverfailure,uremia,sepsis– Secondarytomedications,e.g.chemotherapeuticagents,antibiotics– Hereditary(Charcot-Marie-Toothdiseasetype2)– Immune-mediated,e.g.axonalvariantsofAIDPalsoknownasAMANand
AMSAN,alsoSjogren’sandothercollagenvasculardiseases– Idiopathic
CausesofPolyneuropathy
• Demyelinatingneuropathies– Immune-mediated:Guillain-BarreSyndrome(AIDP),CIDP(chronicinflammatorydemyelinatingpolyneuropathy)
– Hereditary:e.g.Charcot-Marie-Toothdiseasetypes1,3,and4
– Paraneoplastic:MGUS(IgM),hematologicmalignancies
– Infectious:diphtheria
Guillain-BarreSyndrome(AIDP)
• MostcommoncauseofacuteweaknessinWesterncountries
• Incidence:0.6to1.9/100,000population• Antecedentillness
– Viralsyndrome(URI,gastroenteritis)precedesillnessinabout2/3ofcases,typically1-3weeksbeforedevelopmentofneurologicalsymptoms
• Fairlyrapidlyprogressiveascendingweaknessandsensorysymptoms
Guillain-BarreSyndrome(AIDP)
• Motorsymptoms(weakness)usuallypredominateoversensorysymptoms
• Areflexiaonexamination• AlbuminocytologicdissociationinCSF– Nowhitebloodcells,elevatedprotein
• EMGandnerveconductionstudiesdemonstrateademyelinatingneuropathy
Guillain-BarreSyndrome(AIDP)
• Treatment– IVIgorplasmapheresis– Respiratorymanagement– Treatmentofdysautonomia– Physicalandoccupationaltherapy
Guillain-BarreSyndrome(AIDP)
• Course– Symptomsprogressoverthefirst1to2weeksinmostpatients
– 95%ofpatientsreachtheirnadirby4weeks– Plateauphasefor1to4weeks– Improvementensues,howeverratevariableanddependentonseverityofsymptomsatnadir(usuallyover2-12months)
– Relapsesin2to10%– CIDPin2%
Guillain-BarreSyndrome(AIDP)
• Prognosis–Majorityofpatients(80%)havenoorminorsequelae
– Permanentdisablingsymptomsin5-10%–Mortality<5%