Miastenia Gravis

MG
• Afectiune autoimuna a musculaturii striate, cu
patogenie multipla, caracterizata clinic prin
deficit motor declansat de efort si ameliorat de
repaus.

• Patofiziologic: reducerea potentialului de placa

motorie (PPM) necesar pentru a genera
potentialul de actiune (PA) ce determina
cuplajul electro-mecanic (contractia musculara)
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 -> depolarizare locala
= potential de placa motorie (PPM), daca e
suficient de mare -> contractie = PA
 Fiziologia transmiterii sinaptice
• PA -- depinde de A-PPM -- nr. de cuante de
Acy:
- scade la primele stimulari peste 0,1 Hz, apoi N
- creste timp de 30-60 s dupa 10 s de contractie maxima, apoi
scade in 2-5 min (epuizare postactivare)

• Raportul PPM / PA = factor de siguranta ->

fiecare PPM va fi urmat de PA
functionalitatea sinapsei
factor de siguranta variabil (PPM +/- -> PA) = jitter
neuromuscular
 Fiziologia transmiterii sinaptice

Factorul de siguranta depinde de:

– eliberarea cuantelor de Acy

– activitatea Acy-esterazei

– functionalitatea si densitatea R-Acy

– densitatea canalelor Na si arhitectura mb

postsinaptice
Fiziopatologia transmiterii sinaptice
Disfunctionalitatea sinapsei:

- blocaj presinaptic: toxina botulinica, sdr.

miastenic (SMi)

- blocaj sinaptic: inhibitori colinesteraza,

hemicolina (- recaptarea colinei)

- blocaj postsinaptic: curara (R), MG

 Patogenia MG
• Ac anti R-Acy (90%)

• Ac anti MusK = kinaza musculara - in

vitro corelat cu agregarea R

Nu corelatie: niv. Ac - severitatea bolii

 Patogenia MG
Ac - Ig G - 3 mecanisme:

– mediat de complement - corelat cu grd de

distructie a mb postsinaptice

– cresc rata de distructie a R

– blocheaza R( deschiderea canalului de Na) -

deficit sever
 Clinic
Osserman MG Foundation of
• I - forma oculara (15-20%)
America
• II A. forma generalizata
• I Forma oculara - 15% (1/2 =
usoara, lent progresiva, fara
seronegativa)
crize, responsiva la tratament
(30%) Forma generalizata:
B. Forma generalizata medie, • II - usoara:
cu afectare bulbara, fara – a - axial
crize, raspuns mediu la – b - orofaringian +
tratament (25%) respirator
• III forma acuta fulminanta, cu • III - medie: a, b
crize, raspuns prost la
tratament, mortalitate
• IV - severa: a, b
crescuta (15%) • V - protezata respirator si
• IV forma severa (III) cu alimentar
evolutie in 2 ani (10%)
 Diagnostic
• Neostigmina : 1 mg IV 45” ; 3mg i.m 5min
– (+): ameliorare in 1 mm (! SLA, SdrMi)
• Testul cu gheata (hT incetineste degradarea Acy):
– gheata pe pleoapa  5min  ridicare > 50%
• Testul de somn: 30 min  ridicarea pleoapei

• Dozare serica Ac :
– anti R-Acy  + 90%
– anti-striationali (anti-timici)  + intre 20-50 ani
• CT / RMN timus
• EMG
 Diagnostic diferential
ocular patologie nucleara si de TC (incl Horner),
distrofie oculofaringiana, miastenie
congenitala, Graves
bulbar patologie nucleara si de TC, boala neuronului
motor, lez ORL
deficit central, radicular, periferic
lateralizat al
membrelor
extremitate miopatii distale, radiculopatii, neuropatii
distala
tulburare boala neuronului motor, Smi, polimiozita,
respiratorie distrofie miotonica, deficit acid-maltaza
izolata
deficit boala neuronului motor, miopatie paraspinala,
cervical miopatie inflamatorie
 EMG
• Stimularea supramaximala (+ 10-25%)
repetata a nervului periferic determina
activarea maximala a tuturor fibrelor
musculare -> PCUM - Anormal: progresiv
raspund mai putine fibre => decrement +
jitter

• muschi proximali si faciali: trapez, deltoid,

anconeu, biceps, em tenara / hipotenara,
orbiculari, platisma / culegere cu ac:
variatia A PCUM sugereaza blocajul
transmiterii / miopatie
 Tehnica EMG
Stimulare:
– 3-5 Hz -> 10 Hz = decrement PA2 -> PA5 (10-50 Hz =>
decrement 50% la m N)
– tehnici de favorizare a decrementului: stimulare 4-5 min;
stimulare periferica + ischemie (garou pana la TAS)
– posttetanizare (20-50 Hz / contractie voluntara max 10 s) =>
- facilitare = creste nr fb activate -> apoi stimulare 3-5 Hz
imediat si la fiecare 1 min -> 5-10 min = epuizare
postfacilitare
- pseudofacilitare = creste A PCUM prin cresterea A fiecarui
PA, dar aria ramane aceeasi

Masurare: A PCUM: vf-vf / unda negativa

- D(ecrement) = (A4/5 – A1) : A1 x 100 = N < 8%
 Tratament MG
• Profilaxie

• Etiologic- absent

• Patogenic- imunosupresive
• corticosteroizi
• azatioprina

• Simptomatic- anticolinesterazice
Algoritm de tratament
Patologia musculara
BASIC PATHOLOGICAL CHANGES

Muscle has a limited repertoire of

reactions to injury
which consists basically

of atrophy and myonecrosis.

Myopathy (primary disease of
muscle)
to a clinician means a condition with
---proximal weakness,
---elevated CK
---myopathic EMG changes.

The latter consist of low voltage and short

motor unit potentials caused by depletion of
myofibers of the motor unit.

This broad group includes

1.the muscular dystrophies

2. inflammatory myopathies.
1.Distrofii musculare
2.Miopatii inflamatorii
3.Miopatii endocrine
4.Miopatii induse de medicamente si toxice –alcool
5.Miopatii metabolice
6.Miopatii congenitale
7.Miopatii asociate paraliziilor periodice
Distrofia musculara (DM) este un grup de
afectiuni rare ereditare in care fibrele
musculare sunt neobisnuit de predispuse la
leziuni.  
Muschii, si in special muschii scheletici
devin din ce in ce mai slabi. In stadiile
avansate de distrofie musculara, tesutul
conjunctiv inlocuieste fibrele musculare. In
unele forme de distrofie musculara sunt
afectati miocardul si alti muschi involuntari
(netezi) precum si alte organe. 
Tipurile cele mai comune de distrofie
musculara par sa fie cauzate de deficienta
genetica a unei proteine numite distrofina. 
Nu exista un tratament pentru distrofia
musculara; medicatia si terapiile avand
doar rolul de a incetini evolutia bolii.
 PROGRESSIVE MUSCULAR DYSTROPHIES

Muscular dystrophies are genetically transmitted

diseases characterized pathologically by
degeneration and
loss of myofibers and clinically by
inexorably progressive weakness and,
many of them, by elevated CK. T
he pattern of weakness, tempo of evolution, and
mode of inheritance vary among different
dystrophies.
Over 30 genes causing muscular dystrophy are
known presently.
Muscular dystrophies are clinically classified into
the following groups
Facioscapulohumeral and scapuloperoneal dystrophy

Oculopharyngeal muscular dystrophy

Distal myopathies
INFLAMMATORY
MYOPATHIES
Inflammatory myopathies are characterized
pathologically

by myonecrosis and mononuclear

inflammatory infiltrates and clinically by
weakness and soreness of muscles and
elevated CK and erythrocyte sedimentation
rate.

The main inflammatory myopathies are

polymyositis, dermatomyositis, and inclusion
body myositis.
Dermatomyositis affects children and
adults. It causes a purple (heliotrope)
discolorarion of the upper eyelids,
edema around the eyes and mouth,
skin rash on the face and over
extensor surfaces of the extremities,
muscle pain, weakness and stiffness of
muscles.
Contractures,
subcutaneous calcification, intestinal
ulceration,
and other extramuscular manifestations
are frequent in children.
Dermatomyositis and polymyositis
(and less frequently inclusion body
myositis) are associated with
scleroderma, mixed connective tissue
disease, and cancer. Patients with
polymyositis and dermatomyositis may
have cardiac involvement leading to
arrhythmia and heart failure,
arthralgia, Raynaud phenomenon,
interstitial pneumonitis, and renal
involvement. Some of them have
circulating antibodies to a
macromolecular complex of tRNA
synthetases.
 Miopatii metabolice
• Afectare metabolism glucidic:
– Glicogenoze (tip 1-5)

• Afectare metabolism lipidic

• Afectare mitocondriala:
– Asociata si cu alte afectari in special SNC
 Miopatii congenitale
Afectare

– Proteine structurale

– Aparat contractil al celulei musculare

 Sindroame neurologice
paraneoplazice
• Definitie: grup de boli, de etiologie necunoscuta ce se petrec exclusiv, cu o
frecventa inalta in asociere cu debutul unui cancer.
• Pot afecta orice structuta a SNC si SNP.
• Sdr. paraneoplazice reprezinta sub 1% din complicatiile neurologice ale unui
cancer.
• De obicei asociate unor anumite tipuri de cancer, antedatand diagnosticul
de cancer.
• Anumiti Ac au fost descrisi in sange si LCR (ipoteza autoimuna)---respectiv
sd paraneoplazic este raspunsul imunologic impotriva antigenelor tumorale,
ce sunt gresit directionate catre antigene similare din SN( model ce a fost
dovedit pt sdr. miastenic Eaton Lambert ).
• Ac: ---marker diag. in anumite sdr. paraneo,
---identifica anumiti pacienti cu aspect clinic necaracteristic pt un
anumit sdr. paraneo,
--- suport teoretic pt terapie imunosupresoare.
 Sdr. paraneoplazice ale SNC
• Encefalomielita,
• Encefalita limbica,
• Encefalita bulbara,
• Mielita,
• Degenerarea cerebeloasa,
• Retinopatie,
• Opsoclonus-mioclonus,
• Sd de persoana intepenita,
• Mielopatia necrotizanta.
 Sdr. paraneoplazice ale SNP
• Neuropatia subacuta motorie,
• Neuropatie subacuta senzitiva,
• Neuropatie senzitivo-motorie,
• Multineurita si vasculita,
• Neuropatii autonome,
• Neuromiotonia.
 Sdr. paraneoplazice ale jonctiunii
neuromusculare si ale muschilor
• Sdr. miastenic Eaton Lambert,
• Dermatomiozita,
• Miopatia acuta necrotizanta.
 Sdr.Eaton Lambert (LEMS)
• Slabiciune musculara proximala
• Disautonomie
• Areflexie
• Neuropatie distala senzitiva
• 50-60% asociate SCLC
• Ac anti VGCC 90-95%
• Rar afectare oculara/bulbara
Tratamentul sdr. paraneoplazice
• Evolutia clinica nu este uniforma,

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

encefalomielita/ neuropatie senzitiva subacuta (cancer Pl cu cel mici), in sd
mioclonus-opsoclonus asociat meduloblastomului , in degenerescenta
cerebelara din Boala Hodgkin, in cazul neuropatiilor senzitivo-motorii acute
sau subacute.

• Tratamentul cancerului: greu de apreciat eficienta asupra sd

paraneoplazic.

• Trat imunosupresiv: CS, plasmafereza, doze crecute de Ig G iv.