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Myasthenia gravis: A study from India

Author: Singhal, B; Bhatia, Nisha; Umesh, T; Menon, Suresh
Publication info: Neurology India 56! "#ul$Se% &''()* !5&$5
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Abstract: Bac-ground* .e %resent the findings from the largest hos%ital$/ased studies on myasthenia gra0is
from India, using data collected o0er a %eriod of 1! years from the Neurology De%artment in a tertiary referral
center in India 2/3ecti0es* To study the clinical %resentation, age at onset, gender distri/ution, serological
status and thymic %athology in %atients 4ith myasthenia gra0is Materials and Methods* 5 retros%ecti0e study
4as carried out using records of %atients 4ith myasthenia gra0is from the years 1665 to &''( 7esults* 2f (11
%atients, (!6 "611 males and &&5 females) had ac8uired myasthenia "myasthenia gra0is) and fi0e congenital
myasthenia The median age at onset 4as 1( years "males 5! years and females !1 years) The %ea- age at
onset for males 4as in the si9th and se0enth decade and in females, in the third decade T4o hundred and
t4enty$t4o "&6!1:) %atients had ocular and 616 ";!6(:) generali<ed myasthenia Serological studies 4ere
done in &(1 %atients 4ith myasthenia gra0is for 5cetylcholine rece%tor "5ch7) anti/odies of 4hich &!( "(1;':)
4ere sero%ositi0e The most common histo%athology 4as thymoma and the second most common 4as thymic
hy%er%lasia =onclusion* Myasthenia gra0is in our study 4as more common in males "M*> of &;'*1) There 4as
a single %ea- of age at onset "males si9th to se0enth decade; females third decade) The higher %re0alence of
thymomas in this series is in all %ro/a/ility related to selection /ias as %atients 4ith thymic enlargement or more
se0ere disease under4ent thymectomy Thymoma 4as more common in males; hy%er%lasia in females
Full text: Introduction
Myasthenia gra0is is a %otentially serious /ut treata/le autoimmune disease affecting the
neuromuscular 3unction of the s-eletal muscle It is characteri<ed /y 4ea-ness and fatiga/ility of the 0oluntary
muscles and is, in most %atients, caused /y auto anti/odies against the muscle nicotinic acetylcholine rece%tors
"5ch7) ?1@ There is a lac- of e%idemiological data from India .e %resent findings from our data "collected o0er
1! years from 1665$&''() from a single tertiary referral center in India
Materials and Methods
5ll the %atients included in the study 4ere cases of myasthenia diagnosed on clinical /asis and
res%onse to cholinesterase inhi/itors "edro%honium or neostigmine) =hest A$ray 4as done in all %atients
Blectro%hysiology, serology, =om%uted Tomogra%hy "=T)CMagnetic 7esonance Imaging "M7I) of chest 4ere
done 4hen these /ecame a0aila/le The data 4as analy<ed retros%ecti0ely 4ith res%ect to gender, age at
onset, Myasthenia Dra0is >oundation of 5merica "MD>5) classification and results of in0estigations including
serology, electro%hysiology, and histo%athology of thymectomy s%ecimens 5ll the %atients included in the study
4ere e0aluated and treated /y one of the authors o0er a %eriod of 1! years
Electrophysiological studies
7e%etiti0e ner0e stimulation "7NS) 4as done at slo4 rates at &$! E< to loo- for decremental res%onses
in rested and %ost e9ercised muscles at a lim/ tem%erature of !! ' = The %atients 4ere off the cholinesterase
inhi/itor medication for &1 hours /efore the test 5/ductor digiti minimi, e9tensor indicis, deltoid, tra%e<ius,
nasalis, or/icularis oculi and masseter muscles 4ere e9amined using standard techni8ues as descri/ed ?&@
Decrement of greater than 1': in the /aseline to %ea- am%litudes /et4een first and fourth res%onses 4as
considered significant .hen no decrement 4as o/tained from the muscle at rest, a one minute 0oluntary
e9ercise 4as gi0en and 7NS re%eated after t4o and four minute
The distal com%ound muscle action %otential 4as recorded and 4hen found to /e am/iguous; a 1' sec
%ost e9ercise res%onse 4as recorded to rule out any increment due to a %resyna%tic neuromuscular
transmission defect =oncentric needle electromyogra%hy e9amination 4as done in some %atients to rule out
any %rimary muscle disease or anterior horn cell lesion Single fi/er electromyogra%hic studies 4ere not done
Antibody assays
The 5ch7 anti/odies 4ere measured /y a standard radioimmunoassay method 4ith human 1&5 I$5ch7
as antigen and using 5ch7 7I5$-its "DFD Git, Deselschaft, Dermany) Titers less than '&5 nanomoles %er liter
"nmolesCl) 4ere considered negati0e, 0alues /et4een '&5 to '1' nanomoles %er liter 4ere considered
/orderline and titers greater than '1' nanomoles %er liter 4ere considered %ositi0e Serological studies for auto
anti/odies to the rece%tor tyrosine -inase MuSG in seronegati0e %atients 4ere not a0aila/le and hence not
done
Thymectomy
In the initial years of the study, %rior to the a0aila/ility of the =T scan and M7I, a routine chest A$7ay
4as done to detect thymic enlargement for all %atients In later years, =T scan andCor M7I of chest 4ere done
to detect thymic enlargement
De%ending on the si<e of the thymus, transcer0ical or transternal thymectomy 4as done Indications for
thymectomy 4ere thymic enlargement or tumor documented on radiology In non$thymomatous %atients, the
indications 4ere se0ere and %rogressi0e generali<ed disease 4ith su/o%timal res%onse to anticholinesterase
drugs and no ma3or contraindications to surgery
Results
Age at onset and sex distribution
2f the (11 %atients, (!6 %atients had ac8uired myasthenia 2f these, 611 4ere males and &&5 4ere
females The M*> ratio 4as &;'*1 The median age at onset 4as 1( years "Inter8uartile range !&$61 years); in
males it 4as 5! years "Inter8uartile range !6$61 years) and in females !1 years "Inter8uartile range &1$16
years) The mean age at onset 4as 166 years, "males$51 years, females$!56 years), "7ange &$61 years)
There 4ere fi0e %atients 4ith congenital myasthenia "three males and t4o females) The age of onset in four
%atients 4as /et4een one to eight years and one %atient had onset at 11 years 2f the t4o %atients 4here
genetic studies 4ere done, one %atient had mutation in the B%silon su/unit of the muscle 5ch7 5nother %atient
4ith lim/ girdle %resentation 4as found to ha0e missense mutation N((G in the gene encoding 7a%syn Three
%atients "including a si/ %air) had a %ositi0e family history
In the ac8uired grou%, the %ea- age at onset for males 4as in the si9th and se0enth decade 4ith 1!(
"&&5(:) in the si9th decade and 1!5 "&&'6:) %atients in the se0enth decade In females, the disease
%resented early 4ith a %ea- age at onset in the third decade 4ith 6; "&6;;:) %atients ?>igure 1@
MFA classification
The (!6 %atients 4ith ac8uired myasthenia 4ere retros%ecti0ely classified according to the Myasthenia
Dra0is >oundation of 5merica "MD>5) classification ?>igure &@ 4hen first seen T4o hundred and t4enty
"&6!1:) %atients had ocular myasthenia "=lass I) and 616 ";!6(:) had generali<ed myasthenia 2f the
%atients 4ith generali<ed myasthenia 1&1 "5'!6 :) /elonged to =lass II, 115 "1;!1 :) to =lass III and !6
"16; :) to =lass IH of the MD>5 =lassification Ble0en "1!&:) %atients in the %resent series %resented 4ith
res%iratory muscle 4ea-ness re8uiring intu/ation "=lass H)
Immunological findings
Serological studies 4ere done on &(1 %atients 4ith ac8uired myasthenia for 5ch7 anti/odies 2f these,
&!( "(1;':) 4ere sero%ositi0e
Electrophysiology
Blectro%hysiological studies using 7NS 4ere documented for 511 %atients of 4hom !61 ";65&:)
%atients sho4ed a decremental res%onse
Thymectomy and thymic histology
The different ty%es of thymic histology are sho4n in ?>igure !@ T4o hundred and thirteen %atients
"&5!&:) under4ent thymectomy of 4hich 1!5 "6!!(:) 4ere males and ;( "!661:) females The
histo%athology findings 4ere a0aila/le in 1(! thymectomy s%ecimens The most common histo%athology finding
re%orted 4as thymoma in 5( "!166:), of 4hich 1' 4ere from males and 1( from females Thymic hy%er%lasia
4as the ne9t most common histo%athology finding accounting for 5& "&(11:) of 4hich &1 4ere from males and
!1 4ere from females >orty$fi0e s%ecimens sho4ed atro%hic thymus, !; from males and eight from females
The remaining &1 sam%les sho4ed /enign %athology 0arying from cysts to li%omas
!onclusion
Myasthenia gra0is in our study 4as more common in males There 4as a single %ea- of age at onset in
/oth males and females* in males in the si9th to se0enth decade and in females in the third decade 5ch7
anti/odies 4ere %ositi0e in nearly (1: of the %atients 4here it 4as tested 7NS 4as %ositi0e in ;6: of the
%atients The higher %re0alence of thymomas in this series is in all %ro/a/ility due to selection /ias as %atients
4ith thymic enlargement and more se0ere disease under4ent thymectomy Thymomas 4ere more common in
males and thymic hy%er%lasia in females
Ac"no#ledgments
.e are grateful to Dr B G Doyal, Dean, Bom/ay Eos%ital Institute of Medical Sciences for allo4ing us to
use the medical records .e are grateful to Dr Ghushnuma Mansu-hani and Dr Bha0na Doshi for doing the
electro%hysiological studies and late +rofessor #ohn Ne4som$Da0is and Dr D Beeson for genetic studies .e
than- Dr Nemish Shah and Dr +ra-ash +atil for doing the thymectomies
References
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AuthorAffiliation
B Singhal* De%artment of Neurology, Bom/ay Eos%ital Institute of Medical Sciences, Mum/ai $ 1'' '&'
Nisha Bhatia* De%artment of Neurology, Bom/ay Eos%ital Institute of Medical Sciences, Mum/ai $ 1'' '&'
T Umesh* De%artment of Neurology, Gamineni .o-hardt Eos%ital, Eydera/ad
Suresh Menon* De%artment of Neurology, Bom/ay Eos%ital Institute of Medical Sciences, Mum/ai $ 1'' '&'
$ub%ect: Eistology; Tomogra%hy; Studies; +atients; Medical imaging; Males; Eos%itals;
Me$&: 5dolescent, 5dult, 5ge Distri/ution, 5ge >actors, 5ge of 2nset, 5ged, 5ged, (' L o0er, 5nti/odies $$
meta/olism, =hild, =hild, +reschool, Blectro%hysiology $$ methods, >emale, Eumans, India $$ e%idemiology,
Infant, Male, Middle 5ged, Myasthenia Dra0is $$ immunology, Myasthenia Dra0is $$ %hysio%athology, Myasthenia
Dra0is $$ surgery, 7ece%tors, =holinergic $$ immunology, 7etros%ecti0e Studies, Se9 Distri/ution, Thymectomy
$$ methods, Ioung 5dult, Myasthenia Dra0is $$ e%idemiology "ma3or)
$ubstance: 5nti/odies; 7ece%tors, =holinergic;
Publication title: Neurology India
'olume: 56
Issue: !
Pages: !5&$5
(umber of pages: !
Publication year: &''(
Publication date: #ul$Se% &''(
)ear: &''(
Publisher: Med-no4 +u/lications L Media +0t Ftd
Place of publication: Mum/ai
!ountry of publication: India
Publication sub%ect: Medical Sciences$$+sychiatry 5nd Neurology
I$$(: ''&(!((6
$ource type: Scholarly #ournals
*anguage of publication: Bnglish
+ocument type: #ournal 5rticle
Accession number: 1(6;156!
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