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~I y:~th'~l,iil gl'l'IviS ;Iud myasthenk-

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IS1~N 07S-0-1fJ-f)73S61-0
(hardcover ~elk. paper]
I. Engel, :\Itdre\v,
l J Series: C<JO!(!IIIj)or':uy flt~lIr(llog\' sertcs : 8.1, OOGtJ-9446
r1>NI,..~1: t. ~'Iya::;tl\cn.l;, t;I'~1\1:<. Z. Neuromuscular juucrion Dlseascs. \\lJ (;()7(i9N \',3120.12/\"):;
LC clussiiication not as....i~ncd
r;16.7'442-- clc23
20 J I ()3!i;().,

5?'t51

Tlle science of utc..heine is a rapidl)' c}I<lllgillg field, As new research uud ("lini(''<llexperience broaden OUT knowledge.
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9.57654321
Prtnte c! ;11 rbe lJuile<t St;Ite":.;{)f t\n,(-ril.::l

011:l(:id-frc(~ p;_lpcr

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Contents

1. THE ANATO~"YAND ~lOLECULAR ARClIITECTURE OF THE

NEUROi\fUSCULAR JUNCTION

A",lrew C. Engel
BASIC CONCEPTS

THE INNERVATION OF ~'IUSCLE

TI-IE PHESYNAPTIC HECION

:3

THE NEHVE TERMINAl.

4
Ciant Synaptic Vesicles Coated Vesicles Dense-core \"esicles Small Clear ,syr,al)tic
Vesicles \lr>si<:\J);.lr r\(.~I) Uptake Synaptic Vesicle J'()O)s Synaptic Vesicles Move to and Dock
:It tlu': :\ctiVi; Zones Exocytotio ~tn(!hjlle,'}' SN,\B,I!: Compb-x I>rillliflg (If Docked S)rulll'tic
vesicles e S)l1<~I)t<.)t:lglllit)-l St(:'IYsin Exocytosis Other Proteins ~1()(JuJalin.gExocytosis Pre':'l';'ptic
Cytoskeletal CC)IYIPC')I)<:lIt:. The Active Zone uud the! \.'(lltagf;-GAtl-:(1 Cal. Channels \'ollag(~-gat{'"'t1K'"

Channels of the Presynaptic Membrane Endocytotic Events and the Formation of Ne....v S}/(l<'l>ticVesicles

TIlE SYNAPTIC SPACE

15

S)'Jll.lllticBasal Lamina ... \s.~'n!lnetl'ic I\Ch

THE POSTSYNAPT[C HEGION

(~oUagen .XlII S)'l'<ll)tic I..nminins

16

The junctional Folds und Thelr Cytoskeletal Components .... \Chl~s on the junctional Folds
"11(' Sall.trati"'g Disk Model (If Ncurornusculur Trensnussiou R-.:gllh\!i()u (If IJI(' Distribution
and Subunit Composition of !\C'hll The Postsynaptic Cytoskeleton The J unctional
Snrcoplasu :\Chl~ Synthesis und Dogrndsrion
SICNALING MECI-IANISMSArTIIE
NEUHOMUSCULAHJUNCTIOK
25
:\grin, ~'luSK, and LI~r>4 1)()k~7and Its Downstream Activators Crk. Crk ..L, and Tid.l
TIl(:: NetJregtditl/}\ (lIt\ Sign(,Jillg r'atll\\'il)'

2. ELECTlIODIACNOS(S
C. Mtcbel ttarper
INTHODUC-rfON

on j\IYASTHENICDlSOH])HS

3,

37

STANDAHD MOTOR NEHVE COKDUCTION STUDIES

I~CI)(:l.itlvCC(UI)P(.)\II)(1 Muscle

J\(~I'iOI)

38

Potent ials

HEPETITIV!': KI::HYE STIMUI.ATION STUDIES 3~)

"J~I,eSl.,Jet)' ~'t'l.lrginof Nouromusculnr Trausuussiou Pseudofacthtatton "S. True Facilitation Drug
Elfects > Choice of Muscles and Stimulation Sites Troublesboouog Techntc ..tl Problems> Special
Considerntious in lnfants and Y()ung Children what Constitutes <\1) Adequate Repetitive Stimulation
Examlnotiou?
IX

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Contents

NEEDLE

ELECl'ROMYOGHAPII Y 46

The Properties of' Motor Unit Potentials ~'IUl' Changes Observed in Myasthenic
Disorders
Singlc:-I"i1:)(:r lO:I.(;(;trO'tl}'()gr~'l)h}'

ELECTHOD1.AGNOSTJC

FlNDJNGS

IN SPECIFIC

Autoimmune ]\'I)...asthenia Cruvis I....unbert-Eaton

Syndromes

3. THE IM~IUNOPATHOGENESIS

MYASTHENIC DlSOHDERS

Syndrome

Botulism Congenital Myasthenic

OF MYASTHENIA GRAVIS

Re; .. IIaId floJ.1fel,l,

Herr!>",,,! \Vcke,.le, a 11,1Alc;<ClII,I,,,1I1m.<

INTHODUCTION

(;0

JMMUNOLOGICAL
Basic Properties

>

The Intrathymic

l)iffereolhlti()11 ofT Cells

:\ntigen !{e<:ognition by n Cells and Antibodies

O1n(1
Autotmmunity

so

61

PHINCIPLES

of L1C("Us :lIul T Cclls

47

Tolerance

- :\rlligell Recognition by

CC)()l)f$r~'lion ol'B Celts and Helper T (;(,:Jj~

T Cells

MYASTHENIA \V1TH THYM to HYPF.HI'LAS1A

70
Eal'I): Norions on the Role ofthe Thymus in (\IC Intrathymic )"I)roid Cells and r\Chl~ Key
Tenets of vlntrathymic Pnthogenesis'' Introtbymtc Antigell Presentation Th)111icAutoantibody
Producrion Intrathymic C:eJ11)inaJ Centers and B Cells Human _rv(c Thymus Crafted into
SCI D ~'Ii(;p Two-Step Model of' Intrathymic Autosensltization "Promiscuous" Expression of
!\U')IIl)tig(!lls 1)I\'Jt..'t:lnllar)'l"I)',fliC Epithelial Cells Hole or 1{<~b"'llat('I')'
T Cells rrr(;g) Pcssihlc
Role of Viruses
MYASTHEl\I,\
GHJ\V]S \VITIl THYMOMA
74
l~pidel)llolog)' Classification ofThymoms ...... Thymoma Features Associated with ~'Ic;
Autountibodies in Thymoma-Associated t\'IG Pathogenesis of Thymoma-Asscctated i\'IG Models
ofl ...ulcruuec Breakdown if I Tl\MC

B CF.LL IlF.SI'ONSES

TN MYASTHENII\

GRAVIS
78
General Features of :\ntj,.\Chl{ Antibodies Epitopes l{e<:ognized by Anti~t\ChR Autibodies
,1\ III i-St riatioual J\nliI.)I )(lie:-- "'~'IIiSK-p<)sitj\,('" and "SI~r()II(;g<)Livc" ivt}':-..slbonia

>

T CELL HI~:SI'ONSES IN MYASTHENIA

CHAVIS
8.1
AChH.SpedfioT Cells > Antigenic Epitopes Hecognized by AChH.SpedfioT Cells

COOPEHATION
PATHOGENIC

HET\VEEN

SUMMARY

EFFECTS

B CELLS AND T CELLS IN MG

OF THE i\NTI-i\CHR

ANTIBODIES

82
83

84

4. NATURAL HISTORY OF ~1YASTBENJ.AGUAVIS 90

\'la(J.inr.;r Luchanok atl(ZI'ie'llry
TilE

,I.

IUSTOI\Y AND '"NATUHAL"

EP[D~MLOLOCY
ONSET

Ka',I:;,lski

IIISTOHY 01' MYASTIIENTA CHAV1S

90

92

92

OCULAR MYASTHENL<\

9:3

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Contents

XI

GENHALIZED MYASTllNIA GRAVIS \)4

'Time Between Onset and Ceneralized Manifestations Sjl11lS and
Symptoms Exacerbation Remission C<Ulr$I' ~'I(lrl'ilJjty

"

SL'ECFC CLNICAL STUATIONS ~9

t-.llISK~l,,<utJ)enia
Gra\ris Pregnancy Neonatal Mvusthenia Oruvis
.

..

AGE-RELATED

ISSUES FO], MY/ISTI-IENIA GRAVIS

FAMILIAL INCIDENCE
DISORDERS
Thymoma

OF MYASTHENIA GRAVIS

ASSOCIATED

Thyroid Disorders

SUMMARY

\VITH MYASTHENIA

too
101

GR/IVIS

10]

Other Autoimmune Diseases

102

5. TITE DL>\GNOSIS OF MYASTlffiNlA GR>\VIS AND OTHER

DISO){DERS OF NEURO.MUSCULAR TltANSMISSION
lOS
]"'" es F. Howoni.].
INTHODUCTION

AND HISTOIUCAL

BACKGHOUND

l'HESENTATION
109
i'\'[}:~lsllu.:I)iaGr~~\;;s ~\'l(~Caused I)~'Autilxxlies

.L08

CLINICAL

1<)Muscle-Specific Protein

Kinase (i\'luSK-1'.'IG}

PllYSICAL FINDINGS
Ill.
Myasthenia Gravis
}\'luSK-j'vIC
DIFFERENTIAL

113

DIAGNOSIS

Di Ilcrcnt ial l)iaguosiS of I)t()!,js Di ifcrcn I iAI l)i~lgJlo$i!' of J)il}I())in Difl~"rt!lItial

r)jagl'l()~i~

cf'Dysarthria and l)lsl)hagia

Differenrial f)iilgnosis ofIsolated J~esl)iratory!~fllscle

f)iagno~is of 'Aligllc ()ifft;rt;fltinll)i;igl)t)~i~
of ~'Iinlickiftg Disorde-rs

\o\IC:ftkl)t~S:s Diifcrcnfinl

STU DI ES FOH MYASTH ENIA CHAVIS

DIAGNOSTIC

11(;

Edrophonium "rest Antibody Tests Elecrrodiagnosric Testing Ocular ("';ooling()(e.rlack

Test) Comparison of DhtgJl(.)sli(.:. Tec.:)Ju.i(]I.ICS Other Diag"f)stic.:

(l. 'fH.EHAPY OF ~IYASTllliNIA CHAVIS

Dttniel. 8. Drachman
INTHOOUCTTON

I'ATHOGEKSIS

Tests

130

130

1:30

OF MG

luuuuuc Patlt<.gC1'lc~i~ of ~\'JC

onrci

N OF MG

1.3.1

THEATMENTOFMG

132-

Prelimtnaries

Treatment StJ'illegies

THEATING

~1G IN SPECIAL SITUATIONS

or

145

Ocular )'<I)Iil$(h('lIia ~"lftnllg:(,I"(1(:1)1" Associated Conditions Co-morhidifics

()rug Interactions

'>regual)(:), and Neonatal ~,tC Myasthenic Crisis

FUTURE
The

PROSPECTS

PUl'H(lc)X of

FOH TREATMENT

I)i (lienll) ill ()I)tffil)ii"lg Approval

CONCLUSIONS

(")1'

OF ~fG

148

!\,tC Treatments

150

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XII

Contents

7. THE LA~tllElIT-EATON .MYASTHENiC SYNDlIOl\lE

Vern C.[uei "nd, Donald. 8, Sanders

(If STORY

1.5(;

CLIKICAL

FEATUHES

156

J5i

S),IIIIII()lIl!'> I'lIylii<':lIl fllI(ling~

CANCER-ASSOCIATE!)
NON-CANCER

L,I~MS (CA-LE:MS)

157

ASS()CIATE;,I) OR AUTOIMMUr\E:

EI'IL)EM IOLOGY

LEMS (NCA-LEMS)

151>

159

PATHOPHYSIOLOGY
ELECTHODIAGNOSTIC

AND IMMUNOPATHOLOGY

l5!)

FI:-1DINGS

16l
Repetitive Nerve Stimulation Testing Needle ElectTolll)'ogr,lph)' (E;v[G) Si,ngJ(::.fll)er
1~1C!<:I'l"on)y()gl'<)I)lly Electl'()IYI~f(lgl'al)lljc

Qnantitation

SEHOLOGICAL TESTING
l65
\loll'lge.g~ll(.~(,1
Calcium Channel Autihodies SOXl
OTH EH TESTS

1136

DIFFEHENTJAL

l)J;\GNOSlS

MGn,ElvIS OVERLAP
TREATMENT
Cancer

;\Jlcib('ldic.::!'

l66

167
lmmunotherapy

AGENTS THAT MAY \VOHSEN LEMS

SUMMARY

severity

)67

Svmptomatic Treatment

PROGNOSIS

(If

168

169
169

8. CONGENITAL MYASTHEN(C SYl'il)RO,MES

173
Atl(irelV C. E1lgel, Xin-l\'I;,lg Sl1e'/t, K;,tji ()It,'IO, and Stecel. "At. Siue
A EHIEF HISTORY OF THE CONGENITAL

MYASTHENIC

SYNDHOMES

173

MECHANISMS COMPROMISING
THE SAFETY ~IARGIN OF
NEUROMUSCULAR
TRANSMISSION
li4
THE CLASSIF1CATION
THE INVESTIGATION
Clintcnl ()tISCI'Vilt-iUI)S

OF CONGENITAL
OF CONGENITAL

l\!J()tl)hc)i(I!,.,)'

MYASTHENIC SYNDROMES

li11

MYASTHENIC SYNDHOlvlES

),74

'C'>J.((~l)gl 13iYI(ling: Sites })cr Endplate

In vitro

Electrophysiology Studies Molecular Cenetic Studies

PRESYNAPTIC CMS 181

C]I.ISCaused by DcJ(;<.:I~in Choline

(Ch!\'r} J)~ltllJit)1(If S)~flilllli<:Vesicles :'IIUJ

Reduced Quantol Release Congenital Myasthenic Syndrome llesemblfng tile Lambert-Eaton
j\l.'t>tyltr:'lllsf(ra$(

Svndrouu-

SYr\AIYfIC BASAJ/LAMINA-ASSOCIATI!:D
eMS
lilt)
Endplate Acetylcholinesterase Deficiency Defects il) p2.L.~\lninin

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