Miastenie2013.pptx

8/19/2019 Miastenie2013.pptx

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Fiziologia transmiterii sinaptice

Sinapsa neuromusculara:• butonul sinaptic: vezicule cu cuante de Acy

• fanta sinaptica: parcursa de Acy -> fixare

pe R sarcolemei -> descompusa de Acy-esteraza in acetat + colina -> recaptata de

axon

• membrana postsinaptica sarcolema!:

fixarea Acy de R specifici -> depolarizarelocala " potential de placa motorie ##M!$

daca e suficient de mare -> contractie " #A


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• PA -- depinde de A-##M -- nr% de cuante de Acy:- scade la primele stimulari peste &$' (z$ apoi )

- creste timp de *&-& s dupa '& s de contractie maxima$ apoi

scade in ,- min epuizare postactivare!

• Raportul ##M . #A " factor de siguranta ->

fiecare ##M va fi urmat de #Afunctionalitatea sinapsei

factor de siguranta variabil ##M +.- -> #A! " /itter

neuromuscular


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Factorul de siguranta depinde de: – eliberarea cuantelor de Acy

– activitatea Acy-esterazei

– functionalitatea si densitatea R-Acy

– densitatea canalelor )a si ar0itectura mb

postsinaptice


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Fiziopatologia transmiterii sinaptice

1isfunctionalitatea sinapsei:

- bloca/ presinaptic: toxina botulinica$ sdr%

miastenic 2Mi!

- bloca/ sinaptic: in0ibitori colinesteraza$

0emicolina - recaptarea colinei!

- bloca/ postsinaptic: curara R!$ MG


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MG

• Afectiune autoimuna a musculaturii striate$

cu patogenie multipla$ caracterizata clinic

prin deficit motor declansat de efort si

ameliorat de repaus%

• #atofiziologic: reducerea potentialului de

placa motorie ##M! necesar pentru a

genera potentialul de actiune #A! ce

determina cupla/ul electro-mecanic

contractia musculara!


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#atogenia MG

• Ac anti R-Acy 3&4!

• Ac anti Mus5 " 6inaza musculara - in

vitro corelat cu agregarea R

Nu corelatie: niv. Ac - severitatea bolii


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#atogenia MG

Ac - 7g G - * mecanisme:

– mediat de complement - corelat cu grd de

distructie a mb postsinaptice

– cresc rata de distructie a R

– bloc0eaza R desc0iderea canalului de )a! -deficit sever


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8linicOsserman

• 7 - forma oculara '-,&4!• 77 A% forma generalizata

usoara$ lent progresiva$ fara

crize$ responsiva la

tratament *&4!

9% Forma generalizatamedie$ cu afectare bulbara$

fara crize$ raspuns mediu la

tratament ,4!

• 777 forma acuta fulminanta$ cu

crize$ raspuns prost latratament$ mortalitate

crescuta '4!

• 7 forma severa 777! cu

evolutie in , ani '&4!

MG Foundation of

America• 7 Forma oculara - '4 '., "

seronegativa!

Forma generalizata:

•

77 - usoara: – a - axial

– b - orofaringian +

respirator

• 777 - medie: a$ b

• 7 - severa: a$ b• - protezata respirator si

alimentar


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1iagnostic

• )eostigmina : ' mg 7→ ;< = *mg i%m →min – +!: ameliorare in ' mm 2?A$ 2drMi!

• @estul cu g0eata 0@ incetineste degradarea Acy!:

– g0eata pe pleoapa→ min→ ridicare > &4

• @estul de somn: *& min→ ridicarea pleoapei

• 1ozare serica Ac :

–

anti R-Acy→

+ 3&4 – anti-striationali anti-timici!→ + intre ,&-& ani

• 8@ . RM) timus

• MG


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1iagnostic diferentialocular patologie nucleara si de TC (incl Horner),

distrofie oculofaringiana, miasteniecongenitala, Graves

bulbar patologie nucleara si de TC, boala neuronului

motor, lez ORL

deficitlateralizat al

membrelor

central, radicular, periferic

extremitate

distala

miopatii distale, radiculopatii, neuropatii

tulburare

respiratorie

izolata

boala neuronului motor, mi, polimiozita,

distrofie miotonica, deficit acid!maltaza

deficit

cervical

boala neuronului motor, miopatie paraspinala,

miopatie inflamatorie


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MG

• 2timularea supramaximala + '&-,4!

repetata a nervului periferic determinaactivarea maximala a tuturor fibrelor

musculare -> #8BM - Anormal: progresiv

raspund mai putine fibre "> decrement +

/itter

• musc0i proximali si faciali: trapez$ deltoid$

anconeu$ biceps$ em tenara . 0ipotenara$

orbiculari$ platisma . culegere cu ac:

variatia A #8BM sugereaza bloca/ultransmiterii . miopatie


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@e0nica MG

Stimulare: – *- (z -> '& (z " decrement #A, -> #A '&-& (z ">

decrement &4 la m )!

– te0nici de favorizare a decrementului: stimulare ;- min=stimulare periferica + isc0emie garou pana la @A2!

– posttetanizare ,&-& (z . contractie voluntara max '& s! ">

- facilitare " creste nr fb activate -> apoi stimulare *- (zimediat si la fiecare ' min -> -'& min " epuizarepostfacilitare

- pseudofacilitare " creste A #8BM prin cresterea A fiecarui

#A$ dar aria ramane aceeasi

Masurare: A #8BM: vf-vf . unda negativa

- 1ecrement! " A;. C A'! : A' x '&& " ) D E4


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@ratament MG

• #rofilaxie

• tiologic- absent

• #atogenic- imunosupresive• corticosteroizi

• azatioprina

• 2imptomatic- anticolinesterazice


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Algoritm de tratament


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#atologia musculara


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s oc em ca sta n ng o rozen musc e us ng

m"ofibrillar #T$ase and oxidative enz"me

stains s%o&s two fiber types, type 1 (slo&!red)

and type 2 (fast!&%ite)' T%ese fibers %ave

distinct m"osin isoforms' T"pe fibers are ric%in oxidative enz"mes, mitoc%ondria, m"oglobin

(an ox"gen carrier), and lipid' T%e" are capable

of protracted slo& action and clonic activit"'

T"pe fibers are ric% in gl"cogen and

gl"col"tic enz"mes' T%e" are capable of fast,

po&erful, tonic contraction' *" var"ing t%e pH

of t%e #T$ase preincubation, t"pe fibers can

be furt%er subdivided into a and b' +iber

t"pes are segregated in birds (red and &%itemeat)' n mammals, t"pe , a, and b fibers

are present in all muscles, mixed li-e a

c%ec-erboard' T%eir proportion varies in

different muscles'


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BASIC PATHOLOGICAL CHAG!S

.uscle %as a limite" repertoire of reactions to in/ur"

&%ic% consists basicall"

of atrop%" and m"onecrosis'


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#yopathy (primar" disease of

muscle)to a clinician means a condition &it%!!!proximal &ea-ness,

!!!elevated C0

$$$myopathic !#G cha%&es'

The latter co%sist of low (olta&e a%" short

motor )%it pote%tials ca)se" by "epletio% of

myofibers of the motor )%it'

T%is broad group includes

't%e muscular d"strop%ies

' inflammator" m"opat%ies'


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1'*istrofii m)sc)lare

2'#iopatii i%flamatorii

+'#iopatii e%"ocri%e

,'#iopatii i%")se "e me"icame%te si to-ice .alcool/'#iopatii metabolice

0'#iopatii co%&e%itale

'#iopatii asociate paraliiilor perio"ice


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1istrofia musculara (1.) este un grup de

afectiuni rare ereditare in care fibrele

musculare sunt neobisnuit de predispuse la

leziuni'#)schii, si i% special m)schii scheletici

"e(i% "i% ce i% ce mai slabi' I% sta"iile

a(a%sate "e "istrofie m)sc)lara, tes)t)l

co%3)%cti( i%loc)ieste fibrele m)sc)lare' I%)%ele forme "e "istrofie m)sc)lara s)%t

afectati miocar")l si alti m)schi i%(ol)%tari

4%ete2i5 prec)m si alte or&a%e'

Tip)rile cele mai com)%e "e "istrofie

m)sc)lara par sa fie ca)2ate "e "eficie%ta

&e%etica a )%ei protei%e %)mite "istrofi%a'

) e-ista )% tratame%t pe%tr) "istrofia

m)sc)lara6 me"icatia si terapiile a(a%"

"oar rol)l "e a i%ceti%i e(ol)tia bolii'


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$ROGR232 .4C4L#R 15TRO$H2

.uscular d"strop%ies are &e%etically tra%smitte"

diseases c%aracterized pat%ologicall" b"

degeneration and

loss of m"ofibers and clinicall" b"

inexorabl" progressive &ea-ness and,

man" of t%em, b" elevated C0' T

%e pattern of &ea-ness, tempo of evolution, and

mode of in%eritance var" among different

d"strop%ies'

Over 67 genes causing muscular d"strop%" are

-no&n presentl"'

.uscular d"strop%ies are clinicall" classified into

t%e follo&ing groups


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7acioscap)loh)meral a%" scap)lopero%eal "ystro

Oc)lophary%&eal m)sc)lar "ystrophy

*istal myopathies


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I7LA##ATO89

#9OPATHI!S

I%flammatory myopathies are characteri2e"patholo&ically

by myo%ecrosis a%" mo%o%)clear

i%flammatory i%filtrates a%" cli%ically by

wea:%ess a%" sore%ess of m)scles a%"

ele(ate" C; a%" erythrocyte se"ime%tatio%

rate'

The mai% i%flammatory myopathies arepolymyositis, "ermatomyositis, a%" i%cl)sio%

bo"y myositis'


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?ymp0ocyte in

myofiber

#olymyositis

Polymyositis is a cell$me"iate"

a)toimm)%e "isor"er i% which

cytoto-ic T$cells a%" macropha&esi%(a"e a%" "estroy myofibers'

* t iti ff t %ild d


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*ermatomyositis affects c%ildren and

adults' t causes a purple (%eliotrope)

discolorarion of t%e upper e"elids,

edema around t%e e"es and mout%,

s-in ras% on t%e face and over

extensor surfaces of t%e extremities,

muscle pain, &ea-ness and stiffness of muscles'

Contractures,

subcutaneous calcification, intestinalulceration,

and ot%er extramuscular manifestations

are fre8uent in c%ildren'


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ecrotic

capillary1ermatom"ositis

Perifascic)lar

atrophy

The :ey patholo&ical cha%&e of

"ermatomyositis is a (asc)litis which

i%(ol(es e%"omysial a%" perimysial

capillaries a%" arterioles' This (asc)litis

be&i%s with e%"othelial swelli%& a%" isfollowe" by e%"othelial %ecrosis a%"

capillary loss' The (asc)litis is ca)se" by

circ)lati%& a%ti$e%"othelial a%tibo"ies'


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I%cl)sio% bo"y myositis

T%e pat%ological c%anges of ,*. are%ig%l" c%aracteristic' Lig%t

microscop" s%o&s m"ofibers &it%

vacuoles or crac-s some of &%ic% arelined b" basop%ilic granules' T%ese

are best seen in cr"ostat sections

stained &it% modified Gomori

*ermatomyositis a%" polymyositis


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*ermatomyositis a%" polymyositis

4a%" less fre


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Miopatii metabolice

• Afectare metabolism glucidic: – Glicogenoze tip '-!

• Afectare metabolism lipidic

• Afectare mitocondriala: – Asociata si cu alte afectari in special 2)8


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Miopatii congenitale

Afectare

– #roteine structurale

– Aparat contractil al celulei musculare


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2indroame neurologice

paraneoplazice• 1efinitie: grup de boli$ de etiologie necunoscuta ce se petrec exclusiv$ cu o

frecventa inalta in asociere cu debutul unui cancer%

• #ot afecta orice structuta a 2)8 si 2)#%

• 2dr% paraneoplazice reprezinta sub '4 din complicatiile neurologice ale unuicancer%

•

1e obicei asociate unor anumite tipuri de cancer$ antedatand diagnosticulde cancer%

• Anumiti Ac au fost descrisi in sange si ?8R ipoteza autoimuna!---respectivsd paraneoplazic este raspunsul imunologic impotriva antigenelor tumorale$ce sunt gresit directionate catre antigene similare din 2) model ce a fostdovedit pt sdr. miastenic Eaton Lambert !%

• Ac: ---mar6er diag% in anumite sdr% paraneo$

---identifica anumiti pacienti cu aspect clinic necaracteristic pt un anumitsdr% paraneo$

--- suport teoretic pt terapie imunosupresoare%


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2dr% paraneoplazice ale 2)8

• ncefalomielita$

• ncefalita limbica$

• ncefalita bulbara$

• Mielita$

• 1egenerarea cerebeloasa$

• Retinopatie$

• psoclonus-mioclonus$

• 2d de persoana intepenita$

• Mielopatia necrotizanta%


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2dr% paraneoplazice ale 2)#

• )europatia subacuta motorie$

• )europatie subacuta senzitiva$

• )europatie senzitivo-motorie$

• Multineurita si vasculita$

• )europatii autonome$

• )euromiotonia%


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2dr% paraneoplazice ale /onctiunii

neuromusculare si ale musc0ilor • 2dr% miastenic aton ?ambert$

• 1ermatomiozita$

• Miopatia acuta necrotizanta%


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@ratamentul sdr% paraneoplazice

• volutia clinica nu este uniforma$

• Ameliorare spontana: la cativa pacienti cu sd paraneoplazic $ ex cei cu:

encefalomielita. neuropatie senzitiva subacuta cancer #l cu cel mici!$ in sd

mioclonus-opsoclonus asociat meduloblastomului $ in degenerescenta

cerebelara din 9oala (odg6in$ in cazul neuropatiilor senzitivo-motorii acutesau subacute%

• Tratamentul cancerului: greu de apreciat eficienta asupra sd

paraneoplazic%

• Trat imunosupresiv: 82$ plasmafereza$ doze crecute de 7g G iv%

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Miastenie2013.pptx