Background

Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic disorder of neuromuscular transmission in which quantal release of acetylcholine (ACh) is impaired, causin a unique set of clinical characteristics, which include pro!imal muscle wea"ness, depressed tendon refle!es, posttetanic potentiation, and autonomic chan es# $he initial presentation can be similar to that of myasthenia ra%is (M&), but the pro ressions of the ' diseases ha%e some important differences# Lambert-Eaton myasthenic syndrome (LEMS) merupa"an sebuah "elainan dari transmisi neuromuscular yan (aran ditemu"an, dimana "elainan ini mempen eruhi pelepasan dari acetylcholine(ACh), dan memberi"an "are"teristi" "linis yan uni", yan meliputi "elemahan otot ba ian pro"simal, pene"anan refle! tendon, potensiasi postteanic, dan perubahan autonomy# )resentasi awal dari penya"it ini menyerupai myasthenia ra%is (M&), a"an tetapi per"emban an dari "edua penya"it ini memili"i perbedaan yan perlu diperhati"an# *n +,- of patients with LEMS, cancer is present when the wea"ness be ins or is found later# $his is usually a small cell lun cancer (SCLC), althou h LEMS has also been associated with non-SCLC, lymphosarcoma, mali nant thymoma, or carcinoma of the breast, stomach, colon, prostate, bladder, "idney, or allbladder# )ada +,- pasien den an LEMS, ditemu"an adanya penya"it "e anasan, saat "eluhan "elemahan otot muncul, atau setelahnya# .e anasan ini biasanya berupa small cell lun cancer (SCLC), a"an tetapi dapat pula di"ait"an den an non-SCLC, lymphosarcoma, mali nant thymoma, atau carcinoma dari payudara, lambun , colon, prostat, "andun "emih, in(al, atau "andun empedu# Clinical manifestations frequently precede cancer identification# *n most cases, the cancer is disco%ered within the first ' years after onset of LEMS and, in %irtually all cases, within + years# Manifestasi "linis dari penya"it ini biasanya uncul sebelum penya"it "e anasan terdete"si# )ada "ebanya"an "asus dapat muncul dalam wa"tu ' tahun se(a" onset dari LEMS muncul, dan secara "eseluruhan, rata-rata ditemu"an setelah + tahun dari munculnya e(ala#

Pathophysiology
)hysiolo ic studies of neuromuscular transmission demonstrate that ACh release from the motor ner%e terminal is impaired in the LEMS muscle# An autoimmune attac" directed a ainst the %olta e- ated calcium channels (/&CCs) on the presynaptic motor ner%e terminal results in a loss of functional /&CCs at the motor ner%e terminals# 0ari hasil studi men enai transmisi neuromuscular , didapat"an bahwa pelepasan ACh dari saraf motor terminal ter an u pada otot den an LEMS# 1ea"si autoimun yan tertu(u pada voltage-gated calcium channels (VGCCs) pada presinapti" saraf motor terminal, men hasil"an hilan nya fun si dari /&CCs pada daerah tersebut# $he number of quanta released by a ner%e impulse is diminished# 2owe%er, because presynaptic stores of ACh and the postsynaptic response to ACh remain intact, rapid repetiti%e stimulation or %oluntary acti%ation that aids in the release of quanta will raise the endplate potential abo%e threshold and permit eneration of muscle action potential# 2al tersebut a"an men a"ibat"an beberapa pelepasan quanta yan dihasil"an dari impuls saraf a"an men hilan # A"an tetapi "arena adanya cadan an ACh pada ba ian presinapti" , dan respon terhadap ACh pada ba ian postsinapto" tida" ter an u, ma"a (i"a mendapat"an stimulasi berulan , atau adanya a"ti%asi %olunteer yan membantu dalam pelepasan "uanta a"an menin "at"an potensi endplate di atas amban batas dan memun "in"an enerasi potensial a"si otot# As neuromuscular transmission is completed at additional neuromuscular (unctions, a transient increase will occur in the stren th of the muscle# )arasympathetic, sympathetic, and enteric neurons are all affected# Clinically, this phenomenon is noted by the appearance of pre%iously absent tendon refle!es followin a short period of stron muscle contraction by the patient# Setelah proses ini berlan sun , penin "atan transien terhadap "e"uatan otot a"an muncul# 3euron parasimpatis, simpati", dan enteri" semuanya a"an terpen aruh# Secara "linis, fenomena ini dicatat oleh munculnya refle"s tendon yan sebelumnya men hilan , setelah periode sin "at "ontra"si otot yan "uat oleh pasien#

Etiology

4or many years, clinical obser%ations su ested an autoimmune etiolo y for LEMS# Such obser%ations included the followin 5 LEMS is frequently associated with "nown autoimmune diseases )rednisone, plasma e!chan e ()E6), and intra%enous immuno lobulin (*/* ) are effecti%e treatments )atients with LEMS but without cancer frequently ha%e ele%ated serum le%els of or an-specific autoantibodies More direct e%idence has been accumulated supportin the autoimmune etiolo y of LEMS# Acti%e 7one particles (A8)s), which represent the /&CCs, are normally arran ed in re ular parallel arrays on the presynaptic muscle membrane# *n patients with LEMS and in mice in(ected with LEMS immuno lobulin & (* &), di%alent antibodies a ainst the /&CC cross-lin" the calcium channels, disruptin the parallel arrays# 9ltimately, the A8)s cluster and decrease in number# 0ari hasil obser%asi "linis yan dila"u"an selama beberapa tahun didu a etilo i dari LEMS merupaa"n rea"si autoimun# )en amatan beri"ut meliputi 5 LEMS serin "ali di"ait"an den an penya"it autoimun yan di"enal telah

)en obatan yan efe"tif didapat den an memberi"an, prednisone, plasma exchange ()E6), dan pemberian immuno lobulin intra%ena (*/i ) )asien LEMS yan tida" memili"i "e anasan, memili"i "enai"an "adar serum organ-specific autoantibodies :eberapa bu"ti lain (u a telah di"umpul"an untu" mendu"un teori ini# Actif zone particles (A8)s) yan mewa"ili /&CCs, biasanya diatur dalam parallel arrays pada membran presynaptic otot# )ada pasien den an LEMS dan pada ti"us yan dii(e"si den an immuno lobulin & (* &) LEMS, antibodi di%alen terhadap cross link /&CC dan "anal "alsium, a"an men an u parallel array, dan pada a"hirnya A8)s a"an terba i men(adi mole"ul "ecil dan ber"uran (umlahnya# SCLC cells ori inate from neuroectoderm, share a number of anti ens with peripheral ner%ous system tissue, and contain hi h concentrations of /&CCs# Calcium influ! into these cells is inhibited by LEMS * &# Antibodies to /&CCs are found in the serum of most LEMS patients# $hese obser%ations su est that /&CC antibodies downre ulate /&CCs

in LEMS# Sel SCLC berasal dari neuroectoderm, yan (u a berba i se(umlah anti en den an (arin an sistem saraf perifer, dan men andun "onsentrasi tin i /&CCs# Masu"nya "alsium "e dalam sel dihambat oleh * & LEMS# Antibodi terhadap /&CCs ditemu"an dalam se(umlah besar serum pasien LEMS# 0ari pen amatan ini ditun(u""an bahwa antibodi /&CC men uran i "omponen /&CCs pada LEMS# *n patients with LEMS who ha%e SCLC or other cancer, cancer cells presumably contain anti ens that mimic /&CCs and induce production of /&CC antibodies# *n patients with LEMS but no cancer, /&CC antibodies are probably produced as part of a more eneral autoimmune state# *n patients who ha%e LEMS without cancer, an antibody response to domain */ of the ;A subunit of )<=-type /&CCs is more common than in patients who ha%e LEMS with cancer# )ada pasien den an LEMS yan menderita SCLC atau "e anasan (enis lainnya, sel "an"er mun "in men andun anti en yan meniru /&CCs dan men indu"si produ"si antibodi /&CC# )ada pasien den an LEMS tanpa "e anasan, antibodi /&CC mun "in diprodu"si seba ai ba ian dari "eadaan autoimun# )ada pasien yan memili"i LEMS tanpa "an"er, respon antibodi terhadap domain */ dari subunit ;A ) < =-(enis /&CCs lebih umum daripada pada pasien yan memili"i LEMS den an "an"er# /&CC antibody le%els do not correlate with disease se%erity amon patients with LEMS# 2owe%er, antibody le%els do fall in indi%idual patients if the disease impro%es after cancer therapy or immunosuppression# .adar antibodi /&CC tida" ber"aitan den an tin "at "eparahan penya"it pada pasien den an LEMS# 3amun, le%el antibodi a"an menurun pada pasien (i"a penya"it membai" setelah terapi "an"er atau pemberian imunosupresi# All patients with LEMS who ha%e associated SCLC ha%e a history of lon term smo"in # >nly half of patients with autoimmune LEMS are lon -term smo"ers# Semua pasien den an LEMS yan ter"ait den an SCLC memili"i riwayat mero"o" (an "a pan(an # $etapi hanya seten ah dari pasien den an autoimun LEMS adalah pero"o" (an "a pan(an #

Epidemiology

United States statistics $he true incidence of LEMS is un"nown# An estimated ?- of patients with SCLC ha%e LEMS# $he pre%alence of SCLC is @ cases per million population in the 9nited States# :ecause only @,-A,- of patients with LEMS ha%e an identifiable cancer and because LEMS oes undia nosed in many patients, the true total pre%alence of LEMS may be considerably hi her# *nsidensi yan pasti terhadap LEMS masih belum di"etahui# 0iper"ira"an ?- pasien den n SCLS memili"i LEMS# )re%alensi SCLC adalah @ "asus per satu (uta pendudu" di Ameri"a Seri"a# .arena hanya @,-A,- pasien den an LEMS yan teridentifi"asi memili"i "an"er, dan "arena LEMS sendiri "adan sulit terdia nosis pada "ebanya"an pasien, ma"a (umlah "eseluruhan dari pre%alensi LEMS diper"ira"an a"an lebih tin i# $he o%erwhelmin ma(ority of cancers associated with LEMS are SCLC# 2owe%er, many different mali nancies may be in%ol%ed# A partial list includes non-SCLCB neuroendocrine carcinomasB lymphosarcomaB mali nant thymomaB cancers of the breast, stomach, colon, prostate, bladder, "idney, allbladder, and rectumB basal cell carcinomaB leu"emiaB lymphoproliferati%e disorders such as Castleman syndromeB and 2od "in lymphoma# Mayoritas "an"er yan berhubun an den an LEMS adalah SCLC# 3amun, "e anasan lain mun "in (u a terlibat# Can termasu" (enis tersebut adalah non-SCLC, "arsinoma neuroendo"rin, lymphosarcoma, thymoma anas, "an"er payudara, perut, usus besar, prostat, "andun "emih, in(al, "andun empedu, dan re"tum, "arsinoma sel basal, leu"emia, an uan lymphoproliferati%e seperti sindrom Castleman, dan lymphoma 2od "in# Accordin to one estimate, there are appro!imately +,, cases in the 9nited States at any i%en time# 2owe%er, this estimate does not ta"e into account the number of patients with LEMS who do not ha%e SCLC or any other identifiable mali nancy# Menurut sebuah per"iraan, ada se"itar +,, "asus di Ameri"a Seri"at pada wa"tu tertentu# 3amun, per"iraan ini tida" memperhitun "an (umlah pasien den an terhindar"an yan tida" memili"i SCLC atau "e anasan lain yan dapat diidentifi"asi# Age- and sex-related demographics LEMS usually be ins in later adulthood and is primarily a disease of middle-a ed and older people# $he most common a e for the appearance

of symptoms is D, years# *t is rare in childrenB howe%er, at least A children youn er than ;A years are reported to ha%e had LEMS# *n earlier reports, LEMS occurred in males more frequently than females, by a ratio of almost '5;# 2owe%er, current reports note almost equal frequency in men and women# LEMS biasanya dimulai di masa dewasa a"hir dan merupa"an penya"it pada oran paruh baya dan oran tua# 9sia yan palin umum untu" munculnya e(ala adalah D, tahun# 2al ini (aran ter(adi pada ana"-ana", namun, setida"nya telah ada A ana" den an usia "uran dari ;A tahun dilapor"an memili"i LEMS# 0alam laporan sebelumnya, LEMS lebih serin ter(adi pada pria daripada wanita, den an rasio hampir '5;# 3amun, laporan saat ini mencatat fre"uensi hampir sama pada pria dan wanita#

Prognosis
$he pro nosis is often difficult to assess# *t is lar ely determined by the presence and type of any underlyin cancer, the presence and se%erity of any associated autoimmune disease, and the se%erity and distribution of wea"ness# *n addition, patients with rapidly pro ressi%e symptoms usually ha%e more se%ere disease# )ro nosis dari penya"it ini masih sulit untu" ditentu"an# .arena hal ini dipen aruhi (u a oleh, ada tida"nya dan (enis "an"er yan nyertai, "ehadiran dan "eparahan dari penya"it autoimun yan diderita, dan tin "at "eparahan serta distribusi dari "elemahan otot# Seba ai tambahan, pasien den an e(ala yan pro resif biasanya memili"i penya"it yan lebih parah# $he main problem created by LEMS is the pro ressi%e wea"ness that affects e%eryday acti%ities and eneral quality of life# LEMS does not seem to affect the respiratory system as si nificantly as M& does# *n most patients, wea"ness does not se%erely affect %ital muscles# Ma!imum se%erity usually becomes established within se%eral months of symptom onset# Masalah utama yan ditimbul"an oleh LEMS adalah "elemahan yan pro resif yan berpen aruh terhadap a"ti%itas sehari-hari dan mempen aruhi "ualitas "ehidupan# LEMS sepertinya tida" mempen eruhi system respirasi secara si nifi"an seperti yan ditun(u"an oleh M&# )ada "ebanya"an pasien, "elemahan yan timbul tida" berpen aruh berat pada otot-otot or an %ital# $in "at "eparahan ma"simal dari penya"it ini

biasanya a"an timbul dalam beberapa bulan setelah onset pertama muncul# *n most cases, therapy with a ents such as ?,+-diaminopyridine (0A)) may help to relie%e symptoms partially, but usually symptoms pro ress o%er time# Eithout treatment, wea"ness and dysfunction do not usually %ary# E!ceptions are durin periods of e!acerbation induced by intercurrent illness or by medications that impair neuromuscular transmission# )ada "ebanya"an "asus, a en terapi, seperti ?,+-diaminopyridine (0A)) dapat membantu mereda"an e(ala secara parsial, tetapi e(ala biasa nya tetap bertambah berat seirin ber(alannya wa"tu# $anpa pen obatan, "elemahan dan disfun si, biasanya tida" a"an terlalu ber%ariasi, hanya sa(a ada pen ecualian, "eti"a memasu"i periode e"saserbasi yan dipicu oleh penya"it penyerta atau pen obatan yan diberi"an, dan mempen aruhi transmisi neuromuscular# E%entually, the wea"ness caused by LEMS can ha%e profound consequences# 2owe%er, death often results from the underlyin mali nancy# $he dia nosis of LEMS frequently heralds cancer# $his association is important in o%erall morbidity, since there is a %ery short sur%i%al time with SCLC# )ada a"hirnya, "elemahan yan disebab"an oleh LEMS dapat menimbul"an "onse"uensi besar# 3amun, "ematian serin dihasil"an oleh penya"it "e anasan# 0ia nosis LEMS biasanya mendahului penya"it "e anasan penyertanya# Asosiasi ini adalah pentin dalam an "a morbiditas "eseluruhan, "arena "elan sun an wa"tu hidup yan san at sin "at pada penderita SCLC# :ecause LEMS may lead to early detection of SCLC, pro nosis of SCLC in patients with SCLC-LEMS is better than in SCLC without LEMS# )atients with SCLC who de%elop LEMS possibly ha%e a more effecti%e immunolo ic response to the cancer, which results in impro%ed sur%i%al# A more rapid clinical course is more frequent in patients with SCLC-LEMS# .arena LEMS dapat men(adi pertanda awal dari SCLC, pro nosis SCLC pada pasien den an SCLC-LEMS lebih bai" "etimban pasien SCLC tanpa LEMS# )asien SCLC yan memili"i LEMS mun "in memili"i respon imun yan lebih bai" terhadap sel "an"er, yan dapat menin "at"an an "a sur%i%al#

Ehen LEMS has been symptomatic for at least ' years and no underlyin cancer has been demonstrated, the LEMS was probably caused by an autoimmune process# At that point, pro nosis is determined by se%erity of dysfunction and the presence and se%erity of other autoimmune conditions# .eti"a e(ala simptomati" LEMS telah muncul setida"nya selama ' tahun, dan tida" ada "an"er penyerta, dapat di"ata"an bahwa penya"it ini mun "in disebab"an oleh proses autoimun# )ada titi" ini, pro nosis ditentu"an berdasar"an dari "eparahan disfun si, dan "ehadiran serta "eparahan dari penya"it autoimun penyertanya# Proceed to Clinical Presentation

History
Symptoms of Lambert-Eaton myasthenic syndrome (LEMS) usually be in insidiously and pro ress slowly# Many patients ha%e symptoms for months or years before the dia nosis is made# Eea"ness is the ma(or symptom# Eea" muscles may ache and are occasionally tender# )ro!imal muscles are more affected than distal musclesB lower e!tremity muscles are affected predominantly# )atients typically ha%e difficulty risin from a chair, climbin stairs, and wal"in # *ncreased temperatures from fe%er or the en%ironment may worsen the wea"ness# )atients may e!perience transient worsenin after hot baths and showers or durin systemic illnesses# $he oropharyn eal and ocular muscles are mildly affected in about one quarter of cases of LEMS, with symptoms that may include ptosis, diplopia, and dysarthria, but they are usually not affected to the same e!tent or se%erity as in myasthenia ra%is (M&)# 0ifferentiation between the ' diseases may be difficult# A study e!aminin the locali7ation of the initial muscle wea"ness and at the time of ma!imum se%erity in M& and LEMS patients found that patients with M& had initial muscle wea"ness in%ol%in the e!traocular muscles (@F-) and bulbar muscles ('F-)#G;H Con%ersely, LEMS patients ne%er presented initially with ocular wea"nessB @- presented with bulbar wea"ness, and F@- presented with limb wea"ness# *n fact, almost all LEMS patients with oculobulbar or pro!imal upper e!tremity wea"ness also ha%e pro!imal lower e!tremity wea"ness# *n contrast, a si nificant portion of patients with M& ne%er pro ress past

wea"ness in the e!traocular muscles# At the point of ma!imum wea"ness, '@- of patients with M& had purely ocular in%ol%ement, and there were no patients with LEMS who had only ocular in%ol%ement#G;H 1espiratory muscles are not usually affected# Ehen respiratory muscle function often is in%ol%ed, the in%ol%ement is usually not as se%ere as with M&# 2owe%er, rare cases of se%ere respiratory compromise or respiratory failure ha%e been reported in patients with LEMS# Acute respiratory compromise is the most si nificant complication of LEMS and the only one that is rele%ant in the emer ency settin # *t is usually of iatro enic ori in# Most patients ha%e a dry mouth, which frequently precedes other symptoms of LEMS# (Many do not mention this unless specifically questioned#) Many patients report an unpleasant metallic taste# Some patients ha%e other manifestations of autonomic dysfunction, includin impotence in males and postural hypotension# LEMS may be disco%ered first when prolon ed paralysis follows the use of neuromuscular bloc"in a ents durin sur ery# E!acerbation of wea"ness has been described after administration of amino lycoside or fluoroquinolone antibiotics, ma nesium, calcium channel bloc"ers, and iodinated intra%enous contrast a ents# Cancer and LEMS Cancer is present or subsequently disco%ered in @,-A,- of patients with LEMS# *n the case of lun cancer, the clinical symptoms of LEMS may precede detection of the underlyin disease# Symptoms of the underlyin cancer, as well as the I:J symptoms of cancer, may be present# Smo"in and a e at onset are ma(or ris" factors for cancer in patients with LEMS# 0uration of symptoms is also a factor# *f a tumor is not found within the first ' years after symptom onset, cancer is unli"ely# 4or e!ample, a patient youn er than @, years at onset who does not ha%e a tumor disco%ered after ' years of close follow-up is unli"ely to ha%e an underlyin cancer# >n the other hand, a lon -term smo"er with LEMS onset after a e @, years probably has underlyin lun cancer#

Physical Examination
Stren th is usually reduced in pro!imal muscles of the le s and arms, producin a waddlin ait and difficulty ele%atin the arms# $he de ree of wea"ness is usually mild, compared with that reported by the patient# Sensory e!amination is normal unless a coincident peripheral neuropathy

is present, which is not uncommon in patients with underlyin cancer# Some de ree of eyelid ptosis or diplopia, usually mild, is found in '@- of patients# >ccasionally, difficulty chewin , dyspha ia, or dysarthria is present# Most patients ha%e a dry mouth, eyes, or s"in# Constipation, urinary retention, pupillary constriction, sweatin , postural hypotension, or respiratory muscle wea"ness may be present# Clinical manifestations of underlyin mali nancy (e , cache!ia) may be present# 4asciculations, common in diseases of the anterior horn cell, such as amyotrophic lateral sclerosis (ALS), are absent# *n some patients, stren th may impro%e after e!ercise and then wea"en as acti%ity is sustained# $his phenomenon is demonstrable in appro!imately half of all patients with LEMS# *t can also occur in the pro!imal muscles of patients with M&B howe%er, repeated testin of many separate muscle roups may differentiate the ' diseases# 1efle!es usually are reduced or absent in LEMS# $hey can frequently be pro%o"ed or increased by ha%in the patient acti%ely contract the muscle roup in question for ;, seconds prior to refle! testin or by repeatedly tappin the muscles# An increase in refle! acti%ity after contraction is a hallmar" of LEMS#

iagnostic Considerations
>ther conditions to be considered in the dia nosis of Lambert-Eaton myasthenic syndrome (LEMS) include the followin 5 Anemia :otulism Cache!ia 2ypocalcemia 2ypo"alemia 2ypoma nesemia 2yponatremia 2ypothyroidism and my!edema coma )araneoplastic neuropathy $ic" paralysis

i!!erential

iagnoses

Acute *nflammatory 0emyelinatin )olyradiculoneuropathy Amyotrophic Lateral Sclerosis (ALS) in )hysical Medicine and 1ehabilitation

Chronic *nflammatory 0emyelinatin )olyradiculoneuropathy 0ermatomyositis *nclusion :ody Myositis Multiple Sclerosis Myasthenia &ra%is )olymyal ia 1heumatica in Emer ency Medicine )olymyositis Spinal Muscular Atrophy Proceed to "orkup

Approach Considerations
*n the emer ency settin , %ery few tests are of importance in re ard to Lambert-Eaton myasthenic syndrome (LEMS), because the dia nosis is not made in the emer ency department (E0)# *t would be reasonable, howe%er, to consider basic tests in any patient with cancer who reports wea"ness and dry mouth# $hese basic tests would include the followin 5 Complete blood count :asic chemistry )ulse o!imetry >ther, more specific tests are ordered as indicated (see below)#

Anti#ody Assays
$oltage-gated calcium channel anti#odies Antibodies to %olta e- ated calcium channels (/&CCs) ha%e been reported in A@-;,,- of LEMS patients who ha%e small cell lun cancer (SCLC) and in @,-F,- of LEMS patients who do not ha%e underlyin cancer# $hey are also found in fewer than @- of patients with myasthenia ra%is (M&), in up to '@- of patients with lun cancer without LEMS, and in some patients who do not ha%e LEMS but ha%e hi h le%els of circulatin immuno lobulins (e , those with systemic lupus erythematosus or rheumatoid arthritis)# $he sensiti%ity and specificity of the /&CC antibody assay are affected by the source of the anti en and the specific laboratory measurin the antibody# 1eports su est that S>6;, an immuno enic tumor anti en in SCLC, may play a role in identifyin LEMS patients with lun cancer#G'H

Acetylcholine receptor anti#odies ACh receptor (ACh1) antibodies are most commonly associated with myasthenia ra%is (M&) and are occasionally found in low titers in LEMS# $he only true methods of differentiatin M& from LEMS are the detection of ACh1 antibodies and the presence of underlyin mali nancy#

%maging Studies and Bronchoscopy

SCLC is the mali nancy most frequently associated with LEMS# *n all adult patients with LEMS, dia nostic ima in (e , computed tomo raphy GC$H or ma netic resonance ima in GM1*H) of the chest for cancer detection should be performed# Screenin strate ies may help to detect SCLC in patients with newly dia nosed LEMS and therefore offer a better approach to treatment# *f ima in findin s are ne ati%e in a patient with a substantial ris" of ha%in lun cancer, bronchoscopy should be performed# *f both ima in and bronchoscopy results are initially ne ati%e and ris" factors for lun cancer are present, positron emission tomo raphy ()E$) scannin should be considered# *f all ima in study results are ne ati%e in such patients, periodic reassessment thereafter is indicated# *n a lar e cohort study, $itulaer et al screened for tumors usin %arious methods (C$, radio raphy,;K 4-fluorodeo!y lucose )E$ (40&-)E$), bronchoscopy, or mediastinoscopy) and found that C$ of the thora! detected F?- of the tumors#G?H

&epetiti'e (er'e Stimulation Studies

1epetiti%e ner%e stimulation (13S) studies confirm the dia nosis of LEMS by demonstratin characteristic findin s (see the ima e below)# Compound muscle action potentials (CMA)s) recorded with surface electrodes are usually small, often less than ;,- of normal, and fall durin ;- to @-27 13S#

Characteristic responses to repetiti%e ner%e stimulation in patient with Lambert-Eaton myasthenic syndrome# (A) 1esponses elicited from hand muscle by stimulation of ner%e at ? 27# Amplitude of initial response is less than normal, and response is decremental# (:) 1esponses as in A, immediately after %oluntary acti%ation of muscle for ;, seconds# Amplitude has increased# (C) 1esponses in hand muscle elicited by ',-27 stimulation of ner%e for ;, seconds# 1esponse amplitude is less than normal initially, falls further durin first few stimuli, then increases and ultimately becomes more than twice initial %alue#

0urin stimulation at ',-@, 27, the CMA) increases in si7e (ie, facilitation) and characteristically becomes at least twice the si7e of the initial response# A similar increase in CMA) si7e is seen immediately after the patient %oluntarily contracts the muscle ma!imally for se%eral seconds (see the ima e below)#

Compound muscle action potentials elicited from hand muscle before and immediately after ma!imal %oluntary acti%ation of muscle for ;, seconds# Amplitude is small initially, increasin almost ;, times after acti%ation#

*n %irtually all patients with LEMS, a decremental response to lowfrequency ner%e stimulation is obser%ed in the hand muscles# $his findin is not specific to LEMS and can be seen in M& and other neuromuscular diseases#

*n LEMS, the CMA) amplitude is low in most muscles tested# $his findin is also nonspecific and is commonly obser%ed in other neuromuscular diseases# 4acilitation reater than ;,,- is seen in some but not all muscles (or in all patients) with LEMS# 4acilitation reater than @,- in any muscle su ests LEMS# 2owe%er, these findin s mi ht also be obser%ed in M&# *f facilitation is reater than ;,,- in most muscles tested or reater than +,,- in any muscle, the patient almost certainly has LEMS# *f facilitation is less than @,- in all muscles tested, the patient still may ha%e LEMS, especially if wea"ness has been present for only a short time or the patient has been partially treated# Ehen LEMS is mild, the electromyo raphy (EM&) findin s may resemble those of M&, includin normal CMA) amplitudes, decremental response to 13S at low rates, and little facilitation# >ne helpful feature is that in LEMS, the EM& findin s are usually more se%ere than the clinical findin s would su est# $he opposite is frequently true in M&#

Electromyography
(eedle electromyography Con%entional needle EM& in LEMS demonstrates mar"edly unstable motor unit action potentials, which %ary in shape durin %oluntary acti%ation# Single-!i#er electromyography $he (itter and bloc"in measured by sin le-fiber EM& is increased mar"edly in LEMS, frequently out of proportion to the se%erity of wea"ness# *n many endplates, (itter and bloc"in decrease as the firin rate increases# $his pattern is not seen in all endplates or in all patients with LEMS# :ecause (itter and bloc"in may also decrease at hi her firin rates in some endplates of patients with M&, this pattern does not confirm an LEMS dia nosis unless it is dramatic and seen in most muscles#

Edrophonium )*ensilon+ *est

$estin with edrophonium ($ensilon) may be performed to help differentiate LEMS from M&# 2owe%er, such testin is hi hly sub(ecti%e, and it is of little %alue in the dia nosis of LEMS in the E0# $he test may produce an impro%ement in stren th, but rarely is the

response in patients with LEMS as noticeable as the typical response in patients with M&#

Approach Considerations
*ndi%idually tailor therapy for Lambert-Eaton myasthenic syndrome (LEMS) on the basis of se%erity of wea"ness, underlyin disease(s), life e!pectancy, and response to pre%ious treatment# $herapy is best coordinated with the primary care physician and appropriate consultants# *f an underlyin neoplasm is present (e , small cell lun cancer GSCLCH), initial treatment should be aimed at the neoplasm because wea"ness frequently impro%es with effecti%e cancer therapy# 3o further LEMS treatment may be necessary in some patients# $ypical treatments for patients with SCLC as the cause of their LEMS would include combination therapy with cisplatin and etoposide# $hrou h both tumor modulation and its direct immunosuppressi%e properties, chemotherapy does seem to impro%e the symptoms of LEMS# *n patients with LEMS who do not ha%e cancer, a should be considered# ressi%e immunotherapy

%nitial Management
$herapy seldom is started in the emer ency department (E0)# *n eneral, before medical therapy be ins, myasthenia ra%is (M&) must be e!cluded# *f the dia nosis is in any doubt, further wor"up or therapy for M& should be considered# *n the E0 settin , the most serious threat to life in these patients is the rare cases of respiratory failure# *n such cases, treat as in any other patient5 initiate supplemental o!y enB secure intra%enous (*/) accessB and intubate, if indicated# *f intubation pro%es necessary, the use of neuromuscular bloc"in a ents may further e!acerbate the wea"ness and ha%e prolon ed effects (see A%oidance of wea"ness-e!acerbatin dru s)# )atients e!periencin acute e!acerbations of wea"ness should be admitted for further testin and therapy that is best completed on an inpatient basis# Medical therapy, to include immunosuppression and plasmapheresis, may be indicated (see )harmacolo ic $herapy and )lasma E!chan e)# A'oidance o! ,eakness-exacer#ating drugs 0ru s that compromise neuromuscular transmission frequently e!acerbate wea"ness in LEMS# Competiti%e neuromuscular bloc"in a ents, such as

d-tubocurarine and pancuronium, ha%e an e!a effect in patients with LEMS#

erated and prolon ed

*nitial si ns of possible LEMS include prolon ed wea"ness or apnea followin administration of neuromuscular bloc"in a ents durin anesthesia# Some antibiotics, particularly amino lycosides, fluoroquinolones (e , ciproflo!acin), and erythromycin, ha%e si nificant neuromuscular bloc"in effects# Some antiarrhythmics (e , quinine, quinidine, procainamide) and beta-adrener ic bloc"in dru s also worsen myasthenic wea"ness# E!acerbation of LEMS after administration of any of se%eral other a ents, includin ma nesium and */ iodinated radio raphic contrast a ents, has been reported in isolated cases# *n eneral, patients with LEMS should be obser%ed for clinical worsenin after initiatin any new medication# 9nless absolutely necessary, a%oid dru s that are "nown to impair neuromuscular transmission# *n such cases, a thorou h "nowled e of their potential deleterious effects is required#

*reatment o! Underlying Malignancy

*n patients with cancer, LEMS is usually not the ma(or therapeutic concern5 the primary concern is the cancer# Accordin ly, when the dia nosis of LEMS is confirmed, perform an e!tensi%e search for an underlyin mali nancy with radio raphy and computed tomo raphy (C$) of the chest, bronchoscopy, and possibly positron emission tomo raphy ()E$) scannin # *f no tumor is found, periodically search a ain for occult mali nancy# 4requency of these e%aluations is determined by the patientLs ris" of cancer# )atients youn er than @, years without history of lon -term smo"in ha%e a low ris" of associated mali nancy, especially if e%idence of coe!istin autoimmune disease is present# E!tensi%e sur%eillance for cancer may not be necessary for such patients# )atients older than @, years with a history of lon -term smo"in almost certainly ha%e underlyin SCLC# *nitial treatment should be aimed at the neoplasm because wea"ness frequently impro%es with effecti%e cancer therapy# 3o further LEMS treatment may be necessary in some patients# *mmunotherapy of LEMS without effecti%e treatment of the underlyin

cancer usually produces little or no impro%ement in stren th# A theoretical concern is that the immunosuppression may reduce immunolo ic suppression of tumor rowth# *n patients with LEMS who do not ha%e cancer, a ressi%e immunotherapy should be considered (see )harmacolo ic $herapy and )lasma E!chan e)#

Pharmacologic *herapy and Plasma Exchange

Limited data from randomi7ed controlled trials e!aminin different inter%entions for LEMS are a%ailable# A Cochrane re%iew identified only + controlled trials of ?,+-diaminopyridine (0A)) and a sin le cross-o%er study that e!amined the use of */ immuno lobulin (*/* ) and concluded that there was limited but moderate-to-hi h-quality e%idence to su est impro%ed muscle stren th with these inter%entions#G+H All other potential inter%entions ha%e not been e!amined in controlled trials# $he initial pharmacotherapy for LEMS is with a ents that increase the transmission of acetylcholine (ACh) across the neuromuscular (unction, either by increasin the release of ACh (e , 0A)G@H ) or by decreasin the action of acetylcholinesterase (e , pyridosti mine)# $reatment of the associated cancer may also decrease the wea"ness and other symptoms# *f these treatments are not effecti%e and the patient has relati%ely mild wea"ness, determine if a ressi%e immunotherapy is (ustified# Ehen such therapy is warranted, plasma e!chan e ()E6) or hi h-dose */* may be used initially to induce rapid, albeit transitory, impro%ement# *mmunosuppressants should be added for more sustained impro%ement, althou h a theoretical concern e!ists that immunolo ic suppression of tumor rowth may thereby be reduced in paraneoplastic LEMS# )rednisone and a7athioprine, the most frequently used immunosuppressants, can be used alone or in combination# Cyclosporine may benefit patients with LEMS who are candidates for immunosuppression but cannot ta"e or do not respond well to a7athioprine# *mpro%ement may be seen within ;-' month after initiation of cyclosporine, with the ma!imum response usually obser%ed in ?-+ months# )E6 produces impro%ement in many patients with LEMS# *mpro%ement is temporary unless the patient is also recei%in immunosuppression# 1esponse to )E6 is often more radual in patients with LEMS than in those with M&# Ma!imal response may ta"e se%eral wee"s# 1epeated courses of )E6 may be necessary to maintain impro%ement# )E6 may be

performed +-D times o%er A-;, days, as described in standard protocols# )otential complications include autonomic instability, hypercalcemia, and bleedin due to depletion of clottin factors# */* , i%en in a course of ' <" o%er '-@ days, also induces clinically si nificant temporary impro%ement in many patients#GDH $he frequency of impro%ement in response to repeated courses of treatment has not been determined#

Consultations
*n patients with chronic wea"ness, consultation with a neurolo ist may be indicated for electromyo raphy (EM&), further wor"up, and initiation of pharmacotherapy# $he dia nosis of LEMS may be suspected clinically but must be confirmed by electrodia nostic testin # *n addition, many of the medications and therapies that ha%e been shown to produce clinical impro%ement are not appropriate for the E0# Most notably, in addition to pharmacotherapy, */*& has been shown to ha%e si nificant results#GDH >ther appropriate consultations may include an oncolo ist and a physical medicine specialist#

Long-*erm Monitoring
*deally, the patientLs neurolo ist or primary care physician should coordinate all tests and procedures ordered on an outpatient basis# )hysical therapy and e!ercise are important parts of the outpatient re imen to help maintain muscle tone and stren th# Eea"ness of LEMS may be worse when the ambient temperature increases or when the patient is febrile# )atients should a%oid hot showers or baths# Systemic illness of any sort may cause transient worsenin of wea"ness#

Medication Summary
Medical therapy is tailored for each patient and mi ht include %arious combinations of the dru s listed below# $herapy is best coordinated with the primary care physician and appropriate consultants# $he initial pharmacotherapy for Lambert-Eaton myasthenic syndrome (LEMS) is with a ents that increase the transmission of acetylcholine (ACh) across the neuromuscular (unction, either by increasin the release of ACh or by decreasin the action of acetylcholinesterase# $reatment of the associated cancer may also decrease the wea"ness and other

symptoms# *f these treatments are not effecti%e and the patient has relati%ely mild wea"ness, a ressi%e immunotherapy may be warranted# *n such cases, plasma e!chan e ()E6) or hi h-dose intra%enous immuno lobulin (*/* ) may be used initially to induce rapid, albeit transitory, impro%ement# *mmunosuppressants should be added for more sustained impro%ement# )rednisone and a7athioprine, the most frequently used immunosuppressants, can be used alone or in combination# Cyclosporine may benefit patients with LEMS who are candidates for immunosuppression but cannot ta"e or do not respond well to a7athioprine# */* , i%en in a course of ' <" o%er '-@ days, also induces clinically si nificant temporary impro%ement in many patients# $he frequency of impro%ement in response to repeated courses of treatment has not been determined#

(euromuscular agents
Class Summary 3euromuscular a ents produce symptomatic impro%ement in stren th, autonomic symptoms, or both in some patients with LEMS# $hey act by inhibitin the brea"down of ACh, which is intended to help compensate for the relati%e lac" of ACh quanta release in LEMS# $hey usually do not pro%ide a si nificant impro%ementB howe%er, a few patients with mild disease may note some difference# Aminopyridines bloc" potassium channels in membranes and facilitate chemical synaptic transmission at autonomic, neuromuscular, and central synapses# :oth +-aminopyridine and ?,+-diaminopyridine (0A)) ha%e been used, but +-aminopyridine is thou ht to be less effecti%e and is almost twice as to!ic, with many neurolo ic effects reported# Acetylcholinesterase inhibitors do not usually produce dramatic impro%ement in LEMS, but they may pro%ide relief from wea"ness or dry mouth in some patients# )yridosti mine is the preferred a ent and should be administered for se%eral days before assessin response#
/iew full dru information

Pyridostigmine #romide )Mestinon- &egonol+ )yridosti mine bloc"s ACh hydrolysis by cholinesterase, resultin in ACh accumulation at synapses and increasin stimulation of choliner ic

receptors at myoneural (unction# *n most of the literature, the consensus seems to be that monotherapy with a cholinesterase inhibitor is ineffecti%e# *t is in combination with dru s such as ?,+-diaminopyridine that cholinesterase inhibitors may ha%e some sli ht benefit# .-/- iaminopyridine ) AP+ 4or more than ', years, 0A) has been used to impro%e stren th and autonomic function in patients with LEMS# Effect be ins about ', minutes after an oral dose# Each dose lasts about + hours, and ma!imum effect of a i%en dosa e may not be obser%ed for '-? days# )atients with or without underlyin cancer benefit from 0A)# *n the authorsM e!perience, NK,- of patients with LEMS ha%e si nificant clinical benefitB in o%er half of these, impro%ement is mar"ed# $his a ent is not appro%ed for clinical use in the 9nited States, but it is a%ailable on a compassionate-use basis for indi%idual patients# *n most patients, pyridosti mine enhances and prolon s 0A)Ms duration of action, permittin lower doses# >btain application process information from Oacobus )harmaceutical Co#, *nc#, )rinceton, 3O, D,F-AFF-;;AD (fa!)# 0uanidine HCl &uanidine is thou ht to act by increasin free intracellular calcium concentrations throu h inhibition of mitochondrial respiration# *t inhibits respiration by bloc"in potassium channels and thus prolon in the ner%e terminal action potential# $his increases release of ACh after ner%e impulses and may decrease rates of repolari7ation and depolari7ation of muscle cell membranes# *t temporarily impro%es stren th in many patients with LEMS# Ma!imal effect may ta"e '-? days# $his a ent is primarily cited in case reports and has not been studied in randomi7ed trials#

%mmunosuppressants
Class Summary *f the therapies already described are ineffecti%e, more a ressi%e immunotherapy may be indicated# $herapy can ta"e the form of plasma e!chan e or hi h-dose */* , with the potential for more lon -term immunosuppression, usually with prednisone or a7athioprine#
/iew full dru information

Prednisone )rednisone is used as an immunosuppressant in the treatment of autoimmune disorders# $he combination of corticosteroid therapy with a7athioprine may be more effecti%e than steroid monotherapy#
/iew full dru information

A1athioprine )%muran- A1asan+ A7athioprine inhibits mitosis and cellular metabolism by anta oni7in purine metabolism and inhibitin synthesis of 03A, 13A, and proteins# $hese effects may inhibit formation of immune cells, possibly reducin acti%ity of immune system#

Blood products
Class Summary A ents in this cate ory may be used to impro%e clinical and immunolo ic aspects of LEMS# $hey may decrease autoantibody production and increase solubili7ation and remo%al of immune comple!es# */* can be an effecti%e treatment for LEMS#
/iew full dru information

%ntra'enous immunoglo#ulin )%$%g+ )0amunex- 0ammagard- Carimune (2+ 4eatures of */* that may be rele%ant to efficacy include neutrali7ation of circulatin antibodies throu h anti-idiotypic antibodiesB downre ulation of proinflammatory cyto"ines, includin interferon ammaB bloc"ade of 4c receptors on macropha esB suppression of inducer $ and : cells and au mentation of suppressor $ cellsB bloc"ade of the complement cascadeB promotion of remyelinationB and a possible increase in cerebrospinal fluid (CS4) immuno lobulin (* &)#

Botulisme 1. Identifikasi. Ada 3 bentuk botulisme, yaitu yang di tularkankan melalui makanan (bentuk klasik) dan yang ditularkan melalui, luka dan saluran pencernaan (bayi dan dewasa). Tempat produksi toksin berbeda untuk tiap bentuk, tetapi semua bentuk memberikan gejala lumpu layu yang diakibatkan ole racun saraf botulinum. !otulisme saluran pencernaan diusulkan sebagai identitas penyakit baru dari

apa yang sebelumnya disebut !otulisme bayi. "ama baru secara resmi diterima pada pertenga an ta un 1###, dan akan digunakan secara umum di bab ini sebagai pengganti istila botulisme bayi. $oodborne botulism adala keracunan berat yang diakibatkan karena menelan racun yang terbentuk di dalam makanan yang terkontaminasi. %enyakit ini ditandai dengan gangguan ner&us cranialis bilateral akut dan melema nya anggota tubu disertai

kelumpu an. 'angguan &isual (kabur dan dobel), disfagia dan mulut kering sering merupakan kelu an pertama. 'ejala(gejala ini bisa meluas berupa layu simetris pada orang yang waspada akan gejala( gejala ini. )unta dan konstipasi atau diare mungkin muncul pada awalnya. *emam tidak terjadi bila tidak ada komplikasi Infeksi lain. +$, di A- . / 10 1. %emuli an bisa berlangsung beberapa bulan. 2ntuk jenis !otulisme luka, gambaran klinis yang sama terli at pada saat organisme penyebab mengkontaminasi luka dalam kondisi anaerob. -edangkan botulisme saluran pencernaan (bayi) adala bentuk botulisme yang paling sering terjadi di A-3 ini muncul akibat menelan spora +lostridium botulinum kemudian tumbu berkembang dan memproduksi racun pada usus besar. !otulisme saluran pencernaan ini secara spesifik menyerang bayi dibawa 1 ta un, tetapi dapat juga menyerang orang dewasa yang mempunyai kelainan anatomi saluran pencernaan serta terjadinya peruba an flora usus. 'ejala klinis k as dimulai dengan konstipasi, diikuti

dengan letargi, tidak nafsu makan, listlessness, ptosis, susa menelan, ke ilangan kontrol gerakan kepala, ipotonia dan menjurus kepada keadaan lema secara menyeluru (floppy baby) dan pada

beberapa kasus, terjadi kesulitan bernapas sampai gagal nafas. !otulisme pada bayi mempunyai spektrum klinis luas, mulai dari sakit ringan dengan onset berta ap ingga kematian mendadak3 beberapa penelitian menemukan ba wa penyakit ini merupakan penyebab terjadinya .1 sindroma kematian mendadak (-udden Infant *eat -yndrome4-I*-). +$, dari penderita yang dirawat di ruma sakit di A- kurang dari 1 13 suda barang tentu penderita tanpa akses ke ,uma -akit dengan 2nit %erawatan Intensif Anak akan terjadi lebi banyak kematian. *iagnosa dari botulisme yang ditularkan melalui makanan ditegakkan dengan menemukan racun botulinum dalam serum, tinja, cairan lambung atau makanan yang tercemar3 atau dari kultur +. botulinum cairan lambung atau tinja penderita. )enemukan organisme dari

http !!"""#merckmanuals#com!professional!neurologic$disorders!peripher al$nervous$system$and$motor$unit$disorders!disorders$of$neuromuscul ar$transmission#html %otulism is neuromuscular poisoning due to Clostridium botulinum toxin# %otulism may occur "ithout infection if toxin is ingested# &ymptoms are symmetric cranial nerve palsies accompanied by a symmetric descending "eakness and flaccid paralysis "ithout sensory deficits# 'iagnosis is clinical and by laboratory identification of toxin# (reatment is "ith support and antitoxin# C# botulinum elaborates A types of anti enically distinct neuroto!ins, which interfere with release of acetylcholine at peripheral ner%e endin s# 4our of the to!ins (types A, :, E, and rarely 4) affect humans# $ypes A and : are hi hly poisonous proteins resistant to di estion by &* en7ymes# About @,of food-borne outbrea"s in the 9S are caused by type A to!in, followed by types : and E# $ype A to!in occurs predominantly west of the Mississippi 1i%er, type : in the eastern states, and type E in Alas"a and the &reat La"es area (type E is frequently associated with in estion of fish products)# $ype A to!in is used therapeutically to relie%e e!cess muscle acti%ityB botulinum to!in has also been de%eloped as a bioweapon# :otulism occurs in ? forms5
4ood-borne Eound *nfant

*n food-borne botulism, neuroto!in produced in contaminated food is eaten# 3euroto!in is elaborated in %i%o by C# botulinum in infected tissue in wound botulism and in the lar e intestine in infant botulism (see Anaerobic

:acteria5 *nfant :otulism)#

C# botulinum spores are hi hly heat-resistant and may sur%i%e boilin for se%eral hours at ;,,P C# 2owe%er, e!posure to moist heat at ;',P C for ?, min "ills the spores# $o!ins, on the other hand, are readily destroyed by heat, and coo"in food at K,P C for ?, min safe uards a ainst botulism# $o!in production (especially type E) can occur at temperatures as low as ?P C (ie, inside a refri erator) and does not require strict anaerobic conditions# Sources of infection: 2ome-canned foods, particularly low-acid foods, are the most common sources, but commercially prepared foods ha%e been implicated in about ;,- of outbrea"s# /e etables, fish, fruits, and condiments are the most common %ehicles, but beef, mil" products, por", poultry, and other foods ha%e been in%ol%ed# >f outbrea"s caused by seafood, type E causes about @,-B types A and : cause the rest# *n recent years, foods that are not canned (e , foil-wrapped ba"ed potatoes, chopped arlic in oil, patty melt sandwiches) ha%e caused restaurantassociated outbrea"s# C# botulinum spores are common in the en%ironment, and many cases may be caused by in estion or inhalation of dust or by absorption throu h the eyes or a brea" in the s"in# *n(ectin dru s with unsterili7ed needles can cause wound botulism# *n(ectin contaminated heroin into a muscle or under the s"in (s"in poppin ) is ris"iest# Symptoms and Signs Food-borne botulism: Symptoms be in abruptly, usually ;K to ?D h after to!in in estion, althou h the incubation period may %ary from + h to K days# 3ausea, %omitin , abdominal cramps, and diarrhea frequently precede neurolo ic symptoms# 3eurolo ic symptoms are characteristically bilateral and symmetric, be innin with the cranial ner%es and followed by descendin wea"ness or paralysis# $here are no sensory disturbances, and the sensorium usually remains clear# Common initial symptoms and si ns include dry mouth, blurred or double %ision, droopin eyelids, slurred speech, and difficulty swallowin # )upillary li ht refle! is diminished or totally lost# 0yspha ia can lead to aspiration pneumonia# Muscles of respiration and of the e!tremities and trun" pro ressi%ely wea"en in a descendin pattern# 4e%er is absent, and the pulse remains normal or slow unless intercurrent infection de%elops#

Constipation is common after neurolo ic impairment appears# Ma(or complications include respiratory failure caused by diaphra matic paralysis and pulmonary infections# Wound botulism: 3eurolo ic symptoms appear, as in food-borne botulism, but there are no &* symptoms or e%idence implicatin food as a cause# A history of a traumatic in(ury or a deep puncture wound in the precedin ' w" may su est the dia nosis# A thorou h search should be made for brea"s in the s"in and for s"in abscesses caused by self-in(ection of ille al dru s# iagnosis
$o!in assays Sometimes electromyo raphy

:otulism may be confused with &uillain-:arrQ syndrome, poliomyelitis, stro"e, myasthenia ra%is, tic" paralysis, and poisonin caused by curare or belladonna al"aloids# Electromyo raphy shows characteristic au mented response to rapid repetiti%e stimulation in most cases# *n !ood-#orne #otulism, the pattern of neuromuscular disturbances and in estion of a li"ely food source are important dia nostic clues# $he simultaneous presentation of at least ' patients who ate the same food simplifies dia nosis, which is confirmed by demonstratin C# botulinum to!in in serum or stool or by isolatin the or anism from stool# 4indin C# botulinum to!in in suspect food identifies the source# *n ,ound #otulism, findin to!in in serum or isolatin C# botulinum or anisms on anaerobic culture of the wound confirms the dia nosis# $o!in assays are done only by certain laboratories, which may be located throu h local health authorities or the Centers for 0isease Control and )re%ention (C0C)# *reatment
Supporti%e care Equine tri%alent antito!in

Anyone "nown or thou ht to ha%e been e!posed to contaminated food must be carefully obser%ed# Administration of acti%ated charcoal may be helpful# )atients with si nificant symptoms often ha%e impaired airway refle!es, so if charcoal is used, it should be i%en %ia astric tube, and the airway should be protected by a cuffed endotracheal tube#

$he reatest threat to life is respiratory impairment and its complications# )atients should be hospitali7ed and closely monitored with serial measurements of %ital capacity# )ro ressi%e paralysis pre%ents patients from showin si ns of respiratory distress as their %ital capacity decreases# 1espiratory impairment requires mana ement in an *C9, where intubation and mechanical %entilation are readily a%ailable# *mpro%ements in such supporti%e care ha%e reduced the mortality rate to R ;,-# 3aso astric intubation is the preferred method of alimentation because it simplifies mana ement of calories and fluids, stimulates intestinal peristalsis (which eliminates C# botulinum from the ut), allows the use of breast mil" in infants, and a%oids the potential infectious and %ascular complications inherent in */ alimentation# )atients with wound botulism require wound debridement and parenteral antibiotics such as penicillin or metronida7ole
S>ME $1A0E 3AMES 4LA&CL
Clic" for 0ru Mono raph

# Antitoxin: $ri%alent equine antito!in (A, :, E) is a%ailable from the C0C throu h state health departments# Antito!in does not inacti%ate to!in that is already bound at the neuromuscular (unctionB therefore, pree!istin neurolo ic impairment cannot be re%ersed rapidly# (9ltimate reco%ery depends on re eneration of ner%e endin s, which may ta"e wee"s or months#) 2owe%er, antito!in may slow or halt further pro ression# *n patients with wound botulism, antito!in can reduce complications and mortality rate# Antito!in should be i%en as soon as possible after clinical dia nosis and not delayed to await culture results# Antito!in is less li"ely to be of benefit if i%en N A' h after symptom onset# *n the 9S, botulism equine tri%alent antito!in is i%en as a sin le ;,-mL dose containin A@,, *9 of antito!in A, @@,, *9 of antito!in :, and K@,, *9 of antito!in E# All patients who require the antito!in must be reported to state health authorities or the C0C# Antito!in is a%ailable only throu h the C0C, the telephone number is +,+-D?F-'',D wee"days and +,+-D?F-'KKK for all other times# :ecause antito!in is deri%ed from horse serum, there is a ris" of anaphyla!is or serum sic"ness# (4or precautions, see Aller ic, Autoimmune, and >ther 2ypersensiti%ity 0isorders5 0ru 2ypersensiti%ity B for treatment, see Aller ic, Autoimmune, and >ther 2ypersensiti%ity 0isorders5 Anaphyla!is#)

Pre'ention :ecause e%en minute amounts of C# botulinum to!in can cause serious illness, all materials suspected of containin to!in require special handlin # $o!oids are a%ailable for acti%e immuni7ation of people wor"in with C# botulinum or its to!ins# 0etails re ardin specimen collection and handlin can be obtained from state health departments or the C0C# Correct cannin and adequate heatin of home-canned food before ser%in are essential# Canned foods showin e%idence of spoila e and swollen or lea"in cans should be discarded# %(2A(* B3*UL%SM )nfant botulism results from ingestion of C# botulinum spores* their colonization of the large intestine* and toxin production in vivo# *nfant botulism occurs most often in infants R D mo# $he youn est reported patient was ' w", and the oldest was ;' mo# 9nli"e food-borne botulism, infant botulism is not caused by in estion of a preformed to!in# Most cases are idiopathic, althou h some ha%e been traced to in estion of honey, which may contain C# botulinum sporesB thus, infants R ;' mo should not be fed honey# Symptoms and Signs Constipation is present initially in F,- of cases and is followed by neuromuscular paralysis, be innin with the cranial ner%es and proceedin to peripheral and respiratory musculature# Cranial ner%e deficits typically include ptosis, e!traocular muscle palsies, wea" cry, poor suc", decreased a refle!, poolin of oral secretions, poor muscle tone (floppy baby syndrome), and an e!pressionless face# Se%erity %aries from mild lethar y and slowed feedin to se%ere hypotonia and respiratory insufficiency# iagnosis *nfant botulism may be confused with sepsis, con enital muscular dystrophy, spinal muscular atrophy, hypothyroidism, and beni n con enital hypotonia# 4indin C# botulinum to!in or or anisms in the stool establishes the dia nosis# *reatment
2uman botulism antito!in

*nfants are hospitali7ed, and supporti%e care (e , %entilatory support) is i%en as needed#

Specific treatment is with human botulism immune lobulin# $reatment is started as soon as the dia nosis is suspectedB waitin for confirmatory test results is dan erous# $he dose is @, m <" */ once, i%en slowly# $he horse serum antito!in used in adults is not recommended for infants# Antibiotics are not i%en because they may lyse C# botulinum in the ut and increase to!in a%ailability#