Pathophysiology (Myasthenia Gravis)...pdf

Myasthenia gravis

1. Pathophysiology
presentation on
Myasthenia gravis
Prepared By:-
Pradip Patel
Shivcharan Mandal
Sukesh Kumar Yadav

2. Myasthenia gravis
Myasthenia gravis is an autoimmunedisorder affecting about 1 in
10,000 population and it is more common in women.
Thisisconditioncharacterizedbyprogressivefatigableweakness,
particularlyoftheocular,neck,facialandbulbarmuscle.
Thisisduetotheinabilityofneuromuscularjunctiontotransmit
impulsesfromnervetothemuscle.
Itisseriousandsometimesafetaldisease.
Ocularmyastheniaismorecommoninmales,involvesweakness
ofeyemusclesandeyelids,andmayincludeswallowing
difficultiesandslurredspeech.

3. Causes of Myasthenia gravis
Myastheniagravisisanautoimmunedisease.
Thebodydevelopsantibodiesagainstitsownacetylcholine
receptors.
Theseantibodiesdestroytheacetylcholinereceptorsorbindsonit.
Sothoughtheacetylcholinereleaseisnormal,itcannotact
becauseofdestructionofreceptorsoroccupiedofreceptors.And
cannotshowtheireffect.
This results in weakness and easy fatigability on repeated activity,
with recovery after rest.
The eyelid, external ocular, facial and pharyngeal muscles are
generally involved first.

4. pathophysiology

5. Due to auto-immune response
Development of auto-antibodies
Antibodies attack Acetylcholine (Ach) receptors
at the motor end plate
Act against the nicotinic acetylcholine receptor
Impaired the ability of acetylcholine to bind on
receptors
Resulting in voluntary muscle weakness that escalates with
continued activity

6. Symptoms of Myasthenia gravis
Becauseofthedefectiveneuromuscularactivity,themuscular
contractionisveryslowandweak.
Whenrepeatedcontractionsofmusclesareattemptedbythe
patientsfatigueoccursquickly.
Thecardinalsymptomsis
•Fatigueweaknessofmuscles.
•Movementisinitiallystrongbutrapidlyweakensasmusclesuse
continues.
•Weaknessofoculomotormusclesmaymimicacentraleye
movementdisorder.
•Weaknessofchewing,swallowing,speakingorlimbmovements.
Insevereconditionsthereisparalysisofmuscles.Thepatientdies
mostlyduetotheparalysisofrespiratorymuscles.

7. Fluctuation weakness increasing through the day and relieved
by rest.
The major Sings and Symptoms are:
Diplopia : Double vision-Single object seen as two
Ptosis : Dropping of the eyelids or moving out of place
Snarling Expression
Dysphagia : Difficulty in swallowing
Nasal speech
Proximal limb weakness, rarely distal
Respiratory muscle weakness

9. Types of Myasthenia gravis
Neonatal:In12%ofthepregnancieswithamotherwithMyasthenia
gravis,shepassestheantibodiestotheinfantthroughtheplacenta,
causingneonatalMyastheniagravis.
Thesymptomswillstartinthefirsttwodaysanddisappearwithinafew
weeksafterbirth.Withthemother,itisnotuncommonforthesymptomsto
evenimproveduringpregnancy,buttheymightworsenafterlabor.
Congenital:Childrenofhealthymothercanveryrarely,develop
myastheniasymptomsbeginningatbirth,Congenitalmyasthenia
syndromeorCMS.Otherthanmyastheniagravis,CMSisnotcausedbyan
autoimmuneprocess,butduetosynapticmalformation,whichinturn
causedbygeneticmutations.ThusCMSisahereditarydisease.Morethan
11differentmutationshavebeenidentified,andtheinheritancepatternis
typicallyautosomalrecessive.
Juvenile:Myastheniaoccurringinchildhood,butaftertheperipartum
period.

10. Classification of Myasthenia gravis
ClassI:Anyeyemuscleweakness,possibleptosis,noother
evidenceofmuscleweakness
ClassII:Eyemuscleweaknessofanyseverity,mildweaknessof
othermuscles.
ClassIII:Eyemuscleweaknessofanyseverity,moderate
weaknessofothermuscles.
ClassIV:Eyemuscleweaknessofanyseverity,severeweakness
ofothermuscles.
ClassV:Intubationneededtomaintainairway

11. Diagnosis
Physical examination
Blood tests
Neurophysiology
Edrophonium test
Imaging techniques
Pulmonary function tests

12. Physical examination

13. BloodTests
DetectionofAcetylcholinereceptorantibodies.
•Sensitivityof80-96%
•50%ofpatientswithonlyoculardiseasemaylackinthese
antibodies
Antibodiesagainstvoltagegatedcalciumchannelstodifferentiate
fromofLambert-EatonMyastheniaSyndrome(LEMS).
Neurophysiology
Repetitivenervestimulationtest.
electromyography

14. Imaging
ChestX-Ray
•Detectionofthymoma.
•Todetectlungcancerforalternativediagnosis
i.e.Lambert-EatonSyndrome.
CT-Scan
MRIScan
PulmonaryFunctionTests
ForcedVitalCapacityismonitoredtodetectanygraduallossof
respiratoryfunctions.
Negativeinspiratoryforceisusefultodetectadequacyofventilation.

15. Management and Treatment
Theprinciplesoftreatmentare:-
•Tomaximizetheactivityofacetylcholineatremainingreceptors
intheneuromuscularjunctions.
•Tolimitorabolishtheimmunologicalattackormotorendplates.
Themostcommonlyusedanticholinesterasedrugispyridostigmine
whichisgivenorallyinadosageof30-120mg,actionstartin30-60
minutes&effectlasts4-6hours.
(Cautionforcholinergiccrises.)

16. Immunologicaltreatmentofmyastheniagravis:
Thymectomy:Thesurgicalremovalofthymus.
Plasmaexchange:Plasmapheresis
•Filterouttheantibodiesfromblood
•Effectlastsonlyforfewweeks.
Intravenousimmunoglobulin:
•Providesbodywithantibodies
•Bindstocirculatingantibodies
Corticosteroidtreatment:
•Significanceimprovementisoftenseenafteradecreased
antibodytiterwhichisusually1-4months
Immunosuppressanttreatment:
Azathioprine:2.5mg/kgdaily,(otherareCyclosporine,Mycophenolate)

17. Behavior Modifications
Diet
•Thickened liquids are preferred, when dysphagia arises to
contract the ear of aspiration.
•Asparagus should be taken as it contains steroid-like substance
Activity
•Patients should be as active as possible but should take rest in
between.
•Yoga exercises to stretch the weakened muscles should be done.
•This not only strengthens the muscles but also provides oxygen &
removes carbon dioxide from them.

18. Reference
1.A text book of BIOCHEMISTRY, PATHOLOGY & MICROBIOLOGY
By BirendraKumar Yadav & DhanBahadur Bohara
2. Essential of MEDICAL PHARMACOLOGY
By KD Tripathi
3. Images from Internet

19. ANY
QUESTIONS ?

20. Thank You