La miastenia gravis è una rara malattia autoimmunedelle giunzioni neuromuscolari. La miastenia gravis è caratterizzata da una grande affaticabilità muscolare, rapidamente aumentata dall’esercizio, che sopraggiunge a poussè e interessa la muscolatura estrinseca dell’occhio (ptosi, diplopia), i muscoli pellicciai della faccia (faccia ebete), i muscoli della masticazione, della faringe, della laringe, gli estensori della testa e talvolta i muscoli della respirazione. La mistenia gravis è una rara malattia autoimmune delle giunzioni neuromuscolari.
Qual è la causa?
È un’ alterazione della trasmissione dell’impulso nervoso a livello della giunzione neuromuscolare causata da anticorpi antirecettore colinergico nicotinico. La prima malattia autoimmune di cui si è dimostrata la patogenesi.
Quanto è diffusa la miastenia gravis?
La miastenia gravis è una malattia non molto frequente: l’incidenza è di circa 3-4 casi /milioni di abitanti e la prevalenza è intorno a 30-40/casi milioni di abitanti. Pur essendo rara, deve essere conosciuta dal medico in quanto può essere una malattia ancora oggi mortale. Il sesso femminile è più colpito di quello maschile; l’età di inizio è più frequentemente fra i 20 e i 45 anni. Esiste, poi, un altro picco di incidenza, attorno ai 60-70 anni, che predilige il sesso maschile e la sintomatologia bulbare. Raramente colpisce i bambini sotto i 10 anni o i neonati(miastenia neonatale transitoria) colpiti per passaggio transplacentare degli anticorpi materni. La miastenia venne qualificata come gravis da Jolly nel 1895. La malattia era infatti allora mortale in oltre il 90% dei casi. La mortalità è poi progressivamente scesa fino all’attuale 2-3% grazie ad una serie di intuizioni ed acquisizioni scientifiche, che ne hanno chiarito la patogenesi e migliorato la terapia.
Quali sono i sintomi della miastenia gravis?
La malattia inizia con abnorme stancabilità dei muscoli estrinseci oculari: ptosi palpebrale, strabismo e diplopia. L’interessamento dei muscoli faciali provoca amimia, con tipico “sorriso triste” miastenico a labbra socchiuse.
La sintomatologia presenta:
Fluttuazioni circadiane: gravi alla sera, attenuate o assenti al mattino.
La miastenia può rimanere localizzata ai muscoli oculari (miastenia oculare).
Oppure gradualmente, nel giro di mesi o, più raramente, di anni si generalizza interessando i muscoli degli arti e del tronco (ptosi del capo, difficoltà a tenere il capo sollevato da cuscino, talora anche per pochi secondi, stanchezza delle braccia mentre il paziente si pettina, stanchezza delle gambe dopo pochi gradini di una scala)
I muscoli bulbaricon disturbi della masticazione, deglutizione(con pericolosa disfagia), della fonazione ed i muscoli respiratori (con conseguente insufficienza respiratoria).
La sintomatologia miastenica può presentare un peggioramento transitorio catameniale. Le crisi miasteniche possono essere scatenate da concomitanti malattie infettive (più spesso broncopolminiti ma anche da una banale influenza) dall’anestesia generale, e dalla somministrazione di farmaci.
Diagnosi
Oltre che sulla tipica sintomatologia, la diagnosi di miastenia gravis può basarsi su alcune prove: invitando il paziente a chiudere ed aprire i pugni più volte, si osserva una graduale riduzione dell’energia con cui il movimento è compiuto; analogamente, facendogli salire alcuni gradini di una scala, memtre i primi gradini sono affrontati speditamente, i successivi sono superati sempre con maggiore difficoltà.
Elettromiografia (inserimento di un ago in un muscolo per registrarne l’attività elettrica)
Dosaggio degli anticorpi anti-AChR e anti-MuSK nel sangue.
Indagini radiologiche. Ogni paziente miastenico deve fare una TAC o RMN mediastinica cioè riguardante la zona del torace, dal collo in giù.
La timectomia consiste nell’asportazione chirurgica del timo.
Come si cura la miastenia gravis?
Anticolinesterasici: i primi farmaci da somministrare al paziente miastenico. Si tratta di una terapia sintomatica, quasi sempre efficace, almeno all’esordio della sintomatologia, ma che spesso perde efficacia con il tempo.
Farmaci costicoridei (prednisone): rappresentano gli immunosoppressori di prima scelta. Si tratta però, nel paziente miastenico di una terapia cronica di anni e perciò ricca di importanti effetti collaterali (diabete, osteoporosi, cataratta, psicosi, obesità, ecc..) che va preso in considerazione solo nei pazienti in cui la terapia anticolinesterasica e la timectomia non siano stati in grado di garantire un livello di vita soddisfacente.
Azatioprina: può essere usata come farmaco immunosoppressivo di prima scelta in caso di controindicazione assoluta al prednisone (ad esempio grave diabete).
Altri immunosoppressori: la ciclofosfamide la ciclosporina sono usati raramente per i numerosi effetti collaterali.
Plasmaferesi e immunoglobuline: in gravi casi di miastenia (decorso rapidamente ingravescente, frequenti crisi di acuto peggioramento, condizioni di vita insoddisfacenti con ogni altra terapia), si hanno buoni risultati associando al cortisone e/o ad una dei farmaci immunosoppressori la plasmaferesi.
Timectomia: rappresenta il fulcro della terapia immunosoppressiva della miastenia. E’ ben tollerata e induce una sensibilità di miglioramento nel 75% dei casi e la remissione completa e permanente nel 20-40%. L’ intervento deve essere precoce, in quanto l’asportazione dell’organo deve essere effettuata prima che l’alterazione immunologica venga esportata dal timo nei linfonodi periferici. I risultati sono infatti nettamente migliori se l’intervento viene effettuato entro 6-12 mesi dall’esordio.
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