BackgroundLambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic disorder of neuromuscular transmission in which quantal release of acetylcholine (ACh) is impaired, causing a unique set of clinical characteristics, which include proximal muscle weakness, depressed tendon reflexes, posttetanic potentiation, and autonomic changes. The initial presentation can be similar to that of myasthenia gravis (MG), but the progressions of the 2 diseases have some important differences. Lambert-Eaton myasthenic syndrome (LEMS) merupakan sebuah kelainan dari transmisi neuromuscular yang jarang ditemukan, dimana kelainan ini mempengeruhi pelepasan dari acetylcholine(ACh), dan memberikan karekteristik klinis yang unik, yang meliputi kelemahan otot bagian proksimal, penekanan reflex tendon, potensiasi postteanic, dan perubahan autonomy. Presentasi awal dari penyakit ini menyerupai myasthenia gravis (MG), akan tetapi perkembangan dari kedua penyakit ini memiliki perbedaan yang perlu diperhatikan. In 40% of patients with LEMS, cancer is present when the weakness begins or is found later. This is usually a small cell lung cancer (SCLC), although LEMS has also been associated with non-SCLC, lymphosarcoma, malignant thymoma, or carcinoma of the breast, stomach, colon, prostate, bladder, kidney, or gallbladder. Pada 40% pasien dengan LEMS, ditemukan adanya penyakit keganasan, saat keluhan kelemahan otot muncul, atau setelahnya. Keganasan ini biasanya berupa small cell lung cancer (SCLC), akan tetapi dapat pula dikaitkan dengan non-SCLC, lymphosarcoma, malignant thymoma, atau carcinoma dari payudara, lambung, colon, prostat, kandung kemih, ginjal, atau kandung empedu. Clinical manifestations frequently precede cancer identification. In most cases, the cancer is discovered within the first 2 years after onset of LEMS and, in virtually all cases, within 4 years. Manifestasi klinis dari penyakit ini biasanya uncul sebelum penyakit keganasan terdeteksi. Pada kebanyakan kasus dapat muncul dalam waktu 2 tahun sejak onset dari LEMS muncul, dan secara keseluruhan, rata-rata ditemukan setelah 4 tahun dari munculnya gejala. Pathophysiology Physiologic studies of neuromuscular transmission demonstrate that ACh release from the motor nerve terminal is impaired in the LEMS muscle. An autoimmune attack directed against the voltage-gated calcium channels (VGCCs) on the presynaptic motor nerve terminal results in a loss of functional VGCCs at the motor nerve terminals. Dari hasil studi mengenai transmisi neuromuscular , didapatkan bahwa pelepasan ACh dari saraf motor terminal terganggu pada otot dengan LEMS. Reaksi autoimun yang tertuju pada voltage-gated calcium channels (VGCCs) pada presinaptik saraf motor terminal, menghasilkan hilangnya fungsi dari VGCCs pada daerah tersebut. The number of quanta released by a nerve impulse is diminished. However, because presynaptic stores of ACh and the postsynaptic response to ACh remain intact, rapid repetitive stimulation or voluntary activation that aids in the release of quanta will raise the endplate potential above threshold and permit generation of muscle action potential. Hal tersebut akan mengakibatkan beberapa pelepasan quanta yang dihasilkan dari impuls saraf akan menghilang. Akan tetapi karena adanya cadangan ACh pada bagian presinaptik , dan respon terhadap ACh pada bagian postsinaptok tidak terganggu, maka jika mendapatkan stimulasi berulang, atau adanya aktivasi volunteer yang membantu dalam pelepasan kuanta akan meningkatkan potensi endplate di atas ambang batas dan memungkinkan generasi potensial aksi otot. As neuromuscular transmission is completed at additional neuromuscular junctions, a transient increase will occur in the strength of the muscle. Parasympathetic, sympathetic, and enteric neurons are all affected. Clinically, this phenomenon is noted by the appearance of previously absent tendon reflexes following a short period of strong muscle contraction by the patient. Setelah proses ini berlangsung, peningkatan transien terhadap kekuatan otot akan muncul. Neuron parasimpatis, simpatik, dan enterik semuanya akan terpengaruh. Secara klinis, fenomena ini dicatat oleh munculnya refleks tendon yang sebelumnya menghilang, setelah periode singkat kontraksi otot yang kuat oleh pasien. Etiology are normally arranged in regular parallel arrays on the presynaptic muscle membrane. plasma exchange (PEX). Active zone particles (AZPs). the AZPs cluster and decrease in number. disrupting the parallel arrays. memiliki kenaikan kadar serum organ-specific autoantibodies Beberapa bukti lain juga telah dikumpulkan untuk mendukung teori ini. akan mengganggu parallel array. and intravenous immunoglobulin (IVIg) are effective treatments • Patients with LEMS but without cancer frequently have elevated serum levels of organ-specific autoantibodies More direct evidence has been accumulated supporting the autoimmune etiology of LEMS. Ultimately. Such observations included the following: • LEMS is frequently associated with known autoimmune diseases • Prednisone. and contain high concentrations of VGCCs. biasanya diatur dalam parallel arrays pada membran presynaptic otot. dan pemberian immunoglobulin intravena (IVig) • Pasien LEMS yang tidak memiliki keganasan. dan pada akhirnya AZPs akan terbagi menjadi molekul kecil dan berkurang jumlahnya. clinical observations suggested an autoimmune etiology for LEMS. These observations suggest that VGCC antibodies downregulate VGCCs . plasma exchange (PEX). Calcium influx into these cells is inhibited by LEMS IgG. share a number of antigens with peripheral nervous system tissue. Actif zone particles (AZPs) yang mewakili VGCCs. antibodi divalen terhadap cross link VGCC dan kanal kalsium. divalent antibodies against the VGCC cross-link the calcium channels. which represent the VGCCs. Pengamatan berikut meliputi : • LEMS seringkali dikaitkan dengan penyakit autoimun yang telah dikenal • Pengobatan yang efektif didapat dengan memberikan. Dari hasil observasi klinis yang dilakukan selama beberapa tahun diduga etilogi dari LEMS merupaakn reaksi autoimun. SCLC cells originate from neuroectoderm. Antibodies to VGCCs are found in the serum of most LEMS patients. prednisone. Pada pasien dengan LEMS dan pada tikus yang diijeksi dengan immunoglobulin G (IgG) LEMS. In patients with LEMS and in mice injected with LEMS immunoglobulin G (IgG).For many years. Namun. Dari pengamatan ini ditunjukkan bahwa antibodi VGCC mengurangi komponen VGCCs pada LEMS. an antibody response to domain IV of the 1A subunit of P/Q-type VGCCs is more common than in patients who have LEMS with cancer. Epidemiology . Pada pasien dengan LEMS yang menderita SCLC atau keganasan jenis lainnya. dan mengandung konsentrasi tinggi VGCCs. sel kanker mungkin mengandung antigen yang meniru VGCCs dan menginduksi produksi antibodi VGCC. However. respon antibodi terhadap domain IV dari subunit 1A P / Q-jenis VGCCs lebih umum daripada pada pasien yang memiliki LEMS dengan kanker. antibodi VGCC mungkin diproduksi sebagai bagian dari keadaan autoimun. Pada pasien dengan LEMS tanpa keganasan. Masuknya kalsium ke dalam sel dihambat oleh IgG LEMS. cancer cells presumably contain antigens that mimic VGCCs and induce production of VGCC antibodies. Pada pasien yang memiliki LEMS tanpa kanker. In patients with LEMS who have SCLC or other cancer. yang juga berbagi sejumlah antigen dengan jaringan sistem saraf perifer. In patients with LEMS but no cancer. Kadar antibodi VGCC tidak berkaitan dengan tingkat keparahan penyakit pada pasien dengan LEMS. All patients with LEMS who have associated SCLC have a history of longterm smoking. Only half of patients with autoimmune LEMS are long-term smokers. level antibodi akan menurun pada pasien jika penyakit membaik setelah terapi kanker atau pemberian imunosupresi. antibody levels do fall in individual patients if the disease improves after cancer therapy or immunosuppression. In patients who have LEMS without cancer.in LEMS. Semua pasien dengan LEMS yang terkait dengan SCLC memiliki riwayat merokok jangka panjang. Sel SCLC berasal dari neuroectoderm. VGCC antibodies are probably produced as part of a more general autoimmune state. Tetapi hanya setengah dari pasien dengan autoimun LEMS adalah perokok jangka panjang. Antibodi terhadap VGCCs ditemukan dalam sejumlah besar serum pasien LEMS. VGCC antibody levels do not correlate with disease severity among patients with LEMS. kidney. prostat. Insidensi yang pasti terhadap LEMS masih belum diketahui. lymphosarcoma. Yang termasuk jenis tersebut adalah non-SCLC. Age. maka jumlah keseluruhan dari prevalensi LEMS diperkirakan akan lebih tinggi. prostate. karsinoma sel basal. there are approximately 400 cases in the United States at any given time. basal cell carcinoma. The overwhelming majority of cancers associated with LEMS are SCLC. gallbladder. dan lymphoma Hodgkin.and sex-related demographics LEMS usually begins in later adulthood and is primarily a disease of middle-aged and older people. Namun. Diperkirakan 3% pasien dengn SCLS memiliki LEMS. stomach. leukemia. Namun. lymphoproliferative disorders such as Castleman syndrome. colon. dan karena LEMS sendiri kadang sulit terdiagnosis pada kebanyakan pasien. lymphosarcoma. perut. many different malignancies may be involved. ada sekitar 400 kasus di Amerika Serikat pada waktu tertentu. Prevalensi SCLC adalah 5 kasus per satu juta penduduk di Amerika Serika. perkiraan ini tidak memperhitungkan jumlah pasien dengan terhindarkan yang tidak memiliki SCLC atau keganasan lain yang dapat diidentifikasi. The most common age for the appearance . neuroendocrine carcinomas. dan rektum. kandung kemih. and rectum. ginjal. kandung empedu. keganasan lain mungkin juga terlibat. Because only 50-70% of patients with LEMS have an identifiable cancer and because LEMS goes undiagnosed in many patients. usus besar. cancers of the breast. malignant thymoma. Mayoritas kanker yang berhubungan dengan LEMS adalah SCLC. Karena hanya 50-70% pasien dengan LEMS yang teridentifikasi memiliki kanker. and Hodgkin lymphoma. bladder. A partial list includes non-SCLC. The prevalence of SCLC is 5 cases per million population in the United States. the true total prevalence of LEMS may be considerably higher. However. karsinoma neuroendokrin. this estimate does not take into account the number of patients with LEMS who do not have SCLC or any other identifiable malignancy. However. gangguan lymphoproliferative seperti sindrom Castleman. Menurut sebuah perkiraan. An estimated 3% of patients with SCLC have LEMS.United States statistics The true incidence of LEMS is unknown. leukemia. According to one estimate. kanker payudara. thymoma ganas. LEMS occurred in males more frequently than females. laporan saat ini mencatat frekuensi hampir sama pada pria dan wanita. setidaknya telah ada 7 anak dengan usia kurang dari 17 tahun dilaporkan memiliki LEMS. Masalah utama yang ditimbulkan oleh LEMS adalah kelemahan yang progresif yang berpengaruh terhadap aktivitas sehari-hari dan mempengaruhi kualitas kehidupan. In most patients. LEMS lebih sering terjadi pada pria daripada wanita. Pada kebanyakan pasien. the presence and severity of any associated autoimmune disease. In earlier reports. Usia yang paling umum untuk munculnya gejala adalah 60 tahun. dengan rasio hampir 2:1. Prognosis The prognosis is often difficult to assess. Dalam laporan sebelumnya. patients with rapidly progressive symptoms usually have more severe disease. It is rare in children. LEMS biasanya dimulai di masa dewasa akhir dan merupakan penyakit pada orang paruh baya dan orang tua. Namun. Maximum severity usually becomes established within several months of symptom onset. pasien dengan gejala yang progresif biasanya memiliki penyakit yang lebih parah. LEMS sepertinya tidak mempengeruhi system respirasi secara signifikan seperti yang ditunjukan oleh MG. The main problem created by LEMS is the progressive weakness that affects everyday activities and general quality of life. However. Tingkat keparahan maksimal dari penyakit ini . kelemahan yang timbul tidak berpengaruh berat pada otot-otot organ vital. and the severity and distribution of weakness. Hal ini jarang terjadi pada anak-anak. dan tingkat keparahan serta distribusi dari kelemahan otot. LEMS does not seem to affect the respiratory system as significantly as MG does.of symptoms is 60 years. It is largely determined by the presence and type of any underlying cancer. Prognosis dari penyakit ini masih sulit untuk ditentukan. at least 7 children younger than 17 years are reported to have had LEMS. weakness does not severely affect vital muscles. namun. however. Karena hal ini dipengaruhi juga oleh. current reports note almost equal frequency in men and women. kehadiran dan keparahan dari penyakit autoimun yang diderita. In addition. ada tidaknya dan jenis kanker yang nyertai. Sebagai tambahan. by a ratio of almost 2:1. Pasien SCLC yang memiliki LEMS mungkin memiliki respon imun yang lebih baik terhadap sel kanker. karena kelangsungan waktu hidup yang sangat singkat pada penderita SCLC. yang dapat meningkatkan angka survival. A more rapid clinical course is more frequent in patients with SCLC-LEMS. . kematian sering dihasilkan oleh penyakit keganasan. Because LEMS may lead to early detection of SCLC. Patients with SCLC who develop LEMS possibly have a more effective immunologic response to the cancer. In most cases. This association is important in overall morbidity. death often results from the underlying malignancy. Asosiasi ini adalah penting dalam angka morbiditas keseluruhan. However.4-diaminopyridine (DAP) may help to relieve symptoms partially. Eventually. seperti 3. prognosis SCLC pada pasien dengan SCLC-LEMS lebih baik ketimbang pasien SCLC tanpa LEMS. Without treatment. since there is a very short survival time with SCLC. dan mempengaruhi transmisi neuromuscular. The diagnosis of LEMS frequently heralds cancer. agen terapi. biasanya tidak akan terlalu bervariasi. Diagnosis LEMS biasanya mendahului penyakit keganasan penyertanya. Karena LEMS dapat menjadi pertanda awal dari SCLC. but usually symptoms progress over time. ketika memasuki periode eksaserbasi yang dipicu oleh penyakit penyerta atau pengobatan yang diberikan. hanya saja ada pengecualian. Pada akhirnya.biasanya akan timbul dalam beberapa bulan setelah onset pertama muncul. Pada kebanyakan kasus. kelemahan yang disebabkan oleh LEMS dapat menimbulkan konsekuensi besar. prognosis of SCLC in patients with SCLC-LEMS is better than in SCLC without LEMS. which results in improved survival. tetapi gejala biasa nya tetap bertambah berat seiring berjalannya waktu. Tanpa pengobatan. Exceptions are during periods of exacerbation induced by intercurrent illness or by medications that impair neuromuscular transmission. therapy with agents such as 3. Namun.4-diaminopyridine (DAP) dapat membantu meredakan gejala secara parsial. the weakness caused by LEMS can have profound consequences. weakness and dysfunction do not usually vary. kelemahan dan disfungsi. Many patients have symptoms for months or years before the diagnosis is made. with symptoms that may include ptosis. and 95% presented with limb weakness. Weakness is the major symptom. prognosis ditentukan berdasarkan dari keparahan disfungsi. The oropharyngeal and ocular muscles are mildly affected in about one quarter of cases of LEMS. dan kehadiran serta keparahan dari penyakit autoimun penyertanya. dan tidak ada kanker penyerta. Weak muscles may ache and are occasionally tender. and dysarthria. Proximal muscles are more affected than distal muscles. Differentiation between the 2 diseases may be difficult. Ketika gejala simptomatik LEMS telah muncul setidaknya selama 2 tahun. diplopia. In fact.[1] Conversely. Proceed to Clinical Presentation History Symptoms of Lambert-Eaton myasthenic syndrome (LEMS) usually begin insidiously and progress slowly. but they are usually not affected to the same extent or severity as in myasthenia gravis (MG). At that point. Pada titik ini. lower extremity muscles are affected predominantly. almost all LEMS patients with oculobulbar or proximal upper extremity weakness also have proximal lower extremity weakness. In contrast. 5% presented with bulbar weakness. Increased temperatures from fever or the environment may worsen the weakness. Patients may experience transient worsening after hot baths and showers or during systemic illnesses. and walking. A study examining the localization of the initial muscle weakness and at the time of maximum severity in MG and LEMS patients found that patients with MG had initial muscle weakness involving the extraocular muscles (59%) and bulbar muscles (29%). dapat dikatakan bahwa penyakit ini mungkin disebabkan oleh proses autoimun. LEMS patients never presented initially with ocular weakness. Patients typically have difficulty rising from a chair. prognosis is determined by severity of dysfunction and the presence and severity of other autoimmune conditions. climbing stairs. a significant portion of patients with MG never progress past . the LEMS was probably caused by an autoimmune process.When LEMS has been symptomatic for at least 2 years and no underlying cancer has been demonstrated. Exacerbation of weakness has been described after administration of aminoglycoside or fluoroquinolone antibiotics. On the other hand. Symptoms of the underlying cancer. Acute respiratory compromise is the most significant complication of LEMS and the only one that is relevant in the emergency setting. rare cases of severe respiratory compromise or respiratory failure have been reported in patients with LEMS. may be present. LEMS may be discovered first when prolonged paralysis follows the use of neuromuscular blocking agents during surgery. Sensory examination is normal unless a coincident peripheral neuropathy . and there were no patients with LEMS who had only ocular involvement.[1] Respiratory muscles are not usually affected. including impotence in males and postural hypotension. Cancer and LEMS Cancer is present or subsequently discovered in 50-70% of patients with LEMS. cancer is unlikely. 25% of patients with MG had purely ocular involvement. as well as the “B” symptoms of cancer. However. The degree of weakness is usually mild. In the case of lung cancer. producing a waddling gait and difficulty elevating the arms. Most patients have a dry mouth. (Many do not mention this unless specifically questioned. the involvement is usually not as severe as with MG.weakness in the extraocular muscles. and iodinated intravenous contrast agents. which frequently precedes other symptoms of LEMS. a long-term smoker with LEMS onset after age 50 years probably has underlying lung cancer. calcium channel blockers. Physical Examination Strength is usually reduced in proximal muscles of the legs and arms. a patient younger than 50 years at onset who does not have a tumor discovered after 2 years of close follow-up is unlikely to have an underlying cancer. Duration of symptoms is also a factor. magnesium. When respiratory muscle function often is involved. If a tumor is not found within the first 2 years after symptom onset. It is usually of iatrogenic origin.) Many patients report an unpleasant metallic taste. Smoking and age at onset are major risk factors for cancer in patients with LEMS. Some patients have other manifestations of autonomic dysfunction. At the point of maximum weakness. compared with that reported by the patient. For example. the clinical symptoms of LEMS may precede detection of the underlying disease. or skin. however. In some patients. It can also occur in the proximal muscles of patients with MG. usually mild. repeated testing of many separate muscle groups may differentiate the 2 diseases. urinary retention. or dysarthria is present. strength may improve after exercise and then weaken as activity is sustained. Clinical manifestations of underlying malignancy (eg. Constipation. sweating. postural hypotension.is present. pupillary constriction. or respiratory muscle weakness may be present. Reflexes usually are reduced or absent in LEMS. An increase in reflex activity after contraction is a hallmark of LEMS. common in diseases of the anterior horn cell. Most patients have a dry mouth. Occasionally. are absent. difficulty chewing. Some degree of eyelid ptosis or diplopia. such as amyotrophic lateral sclerosis (ALS). cachexia) may be present. dysphagia. eyes. which is not uncommon in patients with underlying cancer. This phenomenon is demonstrable in approximately half of all patients with LEMS. Fasciculations. is found in 25% of patients. Diagnostic Considerations Other conditions to be considered in the diagnosis of Lambert-Eaton myasthenic syndrome (LEMS) include the following: • • • • • • • • • • Anemia Botulism Cachexia Hypocalcemia Hypokalemia Hypomagnesemia Hyponatremia Hypothyroidism and myxedema coma Paraneoplastic neuropathy Tick paralysis Differential Diagnoses • Acute Inflammatory Demyelinating Polyradiculoneuropathy • Amyotrophic Lateral Sclerosis (ALS) in Physical Medicine and Rehabilitation . They can frequently be provoked or increased by having the patient actively contract the muscle group in question for 10 seconds prior to reflex testing or by repeatedly tapping the muscles. Reports suggest that SOX1. however. because the diagnosis is not made in the emergency department (ED). The sensitivity and specificity of the VGCC antibody assay are affected by the source of the antigen and the specific laboratory measuring the antibody. very few tests are of importance in regard to Lambert-Eaton myasthenic syndrome (LEMS). an immunogenic tumor antigen in SCLC. those with systemic lupus erythematosus or rheumatoid arthritis). and in some patients who do not have LEMS but have high levels of circulating immunoglobulins (eg. more specific tests are ordered as indicated (see below). Antibody Assays Voltage-gated calcium channel antibodies Antibodies to voltage-gated calcium channels (VGCCs) have been reported in 75-100% of LEMS patients who have small cell lung cancer (SCLC) and in 50-90% of LEMS patients who do not have underlying cancer. in up to 25% of patients with lung cancer without LEMS.[2] . These basic tests would include the following: • Complete blood count • Basic chemistry • Pulse oximetry Other.• • • • • • • • Chronic Inflammatory Demyelinating Polyradiculoneuropathy Dermatomyositis Inclusion Body Myositis Multiple Sclerosis Myasthenia Gravis Polymyalgia Rheumatica in Emergency Medicine Polymyositis Spinal Muscular Atrophy Proceed to Workup Approach Considerations In the emergency setting. It would be reasonable. They are also found in fewer than 5% of patients with myasthenia gravis (MG). may play a role in identifying LEMS patients with lung cancer. to consider basic tests in any patient with cancer who reports weakness and dry mouth. to 5-Hz RNS. and fall during 1. Compound muscle action potentials (CMAPs) recorded with surface electrodes are usually small.[3] Repetitive Nerve Stimulation Studies Repetitive nerve stimulation (RNS) studies confirm the diagnosis of LEMS by demonstrating characteristic findings (see the image below). The only true methods of differentiating MG from LEMS are the detection of AChR antibodies and the presence of underlying malignancy. periodic reassessment thereafter is indicated. diagnostic imaging (eg. radiography. .Acetylcholine receptor antibodies ACh receptor (AChR) antibodies are most commonly associated with myasthenia gravis (MG) and are occasionally found in low titers in LEMS. bronchoscopy. bronchoscopy should be performed. If imaging findings are negative in a patient with a substantial risk of having lung cancer. Titulaer et al screened for tumors using various methods (CT. positron emission tomography (PET) scanning should be considered. Screening strategies may help to detect SCLC in patients with newly diagnosed LEMS and therefore offer a better approach to treatment. If both imaging and bronchoscopy results are initially negative and risk factors for lung cancer are present. In a large cohort study. or mediastinoscopy) and found that CT of the thorax detected 93% of the tumors. Imaging Studies and Bronchoscopy SCLC is the malignancy most frequently associated with LEMS. often less than 10% of normal. If all imaging study results are negative in such patients. computed tomography [CT] or magnetic resonance imaging [MRI]) of the chest for cancer detection should be performed.18 F-fluorodeoxyglucose PET (FDG-PET). In all adult patients with LEMS. immediately after voluntary activation of muscle for 10 seconds.Characteristic responses to repetitive nerve stimulation in patient with Lambert-Eaton myasthenic syndrome. (B) Responses as in A. then increases and ultimately becomes more than twice initial value. the CMAP increases in size (ie. During stimulation at 20-50 Hz. This finding is not specific to LEMS and can be seen in MG and other neuromuscular diseases. In virtually all patients with LEMS. A similar increase in CMAP size is seen immediately after the patient voluntarily contracts the muscle maximally for several seconds (see the image below). Amplitude of initial response is less than normal. facilitation) and characteristically becomes at least twice the size of the initial response. (C) Responses in hand muscle elicited by 20-Hz stimulation of nerve for 10 seconds. . increasing almost 10 times after activation. Compound muscle action potentials elicited from hand muscle before and immediately after maximal voluntary activation of muscle for 10 seconds. Amplitude is small initially. a decremental response to lowfrequency nerve stimulation is observed in the hand muscles. falls further during first few stimuli. and response is decremental. Response amplitude is less than normal initially. Amplitude has increased. (A) Responses elicited from hand muscle by stimulation of nerve at 3 Hz. which vary in shape during voluntary activation. When LEMS is mild. Edrophonium (Tensilon) Test Testing with edrophonium (Tensilon) may be performed to help differentiate LEMS from MG. Single-fiber electromyography The jitter and blocking measured by single-fiber EMG is increased markedly in LEMS. such testing is highly subjective. jitter and blocking decrease as the firing rate increases. frequently out of proportion to the severity of weakness. However. the electromyography (EMG) findings may resemble those of MG. Because jitter and blocking may also decrease at higher firing rates in some endplates of patients with MG. the patient almost certainly has LEMS. One helpful feature is that in LEMS. Electromyography Needle electromyography Conventional needle EMG in LEMS demonstrates markedly unstable motor unit action potentials. Facilitation greater than 50% in any muscle suggests LEMS. including normal CMAP amplitudes. If facilitation is greater than 100% in most muscles tested or greater than 400% in any muscle. but rarely is the . This finding is also nonspecific and is commonly observed in other neuromuscular diseases. the patient still may have LEMS. This pattern is not seen in all endplates or in all patients with LEMS. Facilitation greater than 100% is seen in some but not all muscles (or in all patients) with LEMS. In many endplates. The test may produce an improvement in strength. the EMG findings are usually more severe than the clinical findings would suggest. these findings might also be observed in MG. decremental response to RNS at low rates. If facilitation is less than 50% in all muscles tested. especially if weakness has been present for only a short time or the patient has been partially treated. and it is of little value in the diagnosis of LEMS in the ED. and little facilitation. The opposite is frequently true in MG.In LEMS. the CMAP amplitude is low in most muscles tested. this pattern does not confirm an LEMS diagnosis unless it is dramatic and seen in most muscles. However. If an underlying neoplasm is present (eg. and response to previous treatment. In general. secure intravenous (IV) access. to include immunosuppression and plasmapheresis. the most serious threat to life in these patients is the rare cases of respiratory failure.response in patients with LEMS as noticeable as the typical response in patients with MG. chemotherapy does seem to improve the symptoms of LEMS. myasthenia gravis (MG) must be excluded. Competitive neuromuscular blocking agents. If intubation proves necessary. Patients experiencing acute exacerbations of weakness should be admitted for further testing and therapy that is best completed on an inpatient basis. Medical therapy. In patients with LEMS who do not have cancer. If the diagnosis is in any doubt. treat as in any other patient: initiate supplemental oxygen. such as . aggressive immunotherapy should be considered. Typical treatments for patients with SCLC as the cause of their LEMS would include combination therapy with cisplatin and etoposide. underlying disease(s). before medical therapy begins. life expectancy. if indicated. further workup or therapy for MG should be considered. initial treatment should be aimed at the neoplasm because weakness frequently improves with effective cancer therapy. the use of neuromuscular blocking agents may further exacerbate the weakness and have prolonged effects (see Avoidance of weakness-exacerbating drugs). Initial Management Therapy seldom is started in the emergency department (ED). In the ED setting. No further LEMS treatment may be necessary in some patients. Approach Considerations Individually tailor therapy for Lambert-Eaton myasthenic syndrome (LEMS) on the basis of severity of weakness. small cell lung cancer [SCLC]). In such cases. Through both tumor modulation and its direct immunosuppressive properties. Avoidance of weakness-exacerbating drugs Drugs that compromise neuromuscular transmission frequently exacerbate weakness in LEMS. and intubate. may be indicated (see Pharmacologic Therapy and Plasma Exchange). Therapy is best coordinated with the primary care physician and appropriate consultants. and erythromycin. Initial signs of possible LEMS include prolonged weakness or apnea following administration of neuromuscular blocking agents during anesthesia. quinidine. when the diagnosis of LEMS is confirmed. ciprofloxacin). In such cases. and possibly positron emission tomography (PET) scanning. No further LEMS treatment may be necessary in some patients. Accordingly. Unless absolutely necessary. particularly aminoglycosides. Initial treatment should be aimed at the neoplasm because weakness frequently improves with effective cancer therapy. Extensive surveillance for cancer may not be necessary for such patients. LEMS is usually not the major therapeutic concern: the primary concern is the cancer. especially if evidence of coexisting autoimmune disease is present. procainamide) and beta-adrenergic blocking drugs also worsen myasthenic weakness. If no tumor is found. Immunotherapy of LEMS without effective treatment of the underlying . fluoroquinolones (eg. Exacerbation of LEMS after administration of any of several other agents. Some antibiotics. including magnesium and IV iodinated radiographic contrast agents. perform an extensive search for an underlying malignancy with radiography and computed tomography (CT) of the chest. In general. have an exaggerated and prolonged effect in patients with LEMS. quinine. Some antiarrhythmics (eg. has been reported in isolated cases. a thorough knowledge of their potential deleterious effects is required.d-tubocurarine and pancuronium. periodically search again for occult malignancy. have significant neuromuscular blocking effects. Patients older than 50 years with a history of long-term smoking almost certainly have underlying SCLC. Treatment of Underlying Malignancy In patients with cancer. bronchoscopy. patients with LEMS should be observed for clinical worsening after initiating any new medication. Patients younger than 50 years without history of long-term smoking have a low risk of associated malignancy. avoid drugs that are known to impair neuromuscular transmission. Frequency of these evaluations is determined by the patient’s risk of cancer. A theoretical concern is that the immunosuppression may reduce immunologic suppression of tumor growth. Maximal response may take several weeks. the most frequently used immunosuppressants. improvement. Immunosuppressants should be added for more sustained improvement. Prednisone and azathioprine. can be used alone or in combination. If these treatments are not effective and the patient has relatively mild weakness. A Cochrane review identified only 4 controlled trials of 3. Pharmacologic Therapy and Plasma Exchange Limited data from randomized controlled trials examining different interventions for LEMS are available. aggressive immunotherapy should be considered (see Pharmacologic Therapy and Plasma Exchange).cancer usually produces little or no improvement in strength.[4] All other potential interventions have not been examined in controlled trials. although a theoretical concern exists that immunologic suppression of tumor growth may thereby be reduced in paraneoplastic LEMS. either by increasing the release of ACh (eg. Treatment of the associated cancer may also decrease the weakness and other symptoms. pyridostigmine). The initial pharmacotherapy for LEMS is with agents that increase the transmission of acetylcholine (ACh) across the neuromuscular junction. determine if aggressive immunotherapy is justified. When such therapy is warranted. Improvement may be seen within 1-2 month after initiation of cyclosporine. PEX may be . albeit transitory. PEX produces improvement in many patients with LEMS. Cyclosporine may benefit patients with LEMS who are candidates for immunosuppression but cannot take or do not respond well to azathioprine. with the maximum response usually observed in 3-4 months. DAP[5] ) or by decreasing the action of acetylcholinesterase (eg. plasma exchange (PEX) or high-dose IVIg may be used initially to induce rapid. In patients with LEMS who do not have cancer. Repeated courses of PEX may be necessary to maintain improvement. Response to PEX is often more gradual in patients with LEMS than in those with MG. Improvement is temporary unless the patient is also receiving immunosuppression.4-diaminopyridine (DAP) and a single cross-over study that examined the use of IV immunoglobulin (IVIg) and concluded that there was limited but moderate-to-high-quality evidence to suggest improved muscle strength with these interventions. IVIg. either by increasing the release of ACh or by decreasing the action of acetylcholinesterase. The initial pharmacotherapy for Lambert-Eaton myasthenic syndrome (LEMS) is with agents that increase the transmission of acetylcholine (ACh) across the neuromuscular junction.performed 4-6 times over 7-10 days. also induces clinically significant temporary improvement in many patients. as described in standard protocols. Patients should avoid hot showers or baths. Systemic illness of any sort may cause transient worsening of weakness. The diagnosis of LEMS may be suspected clinically but must be confirmed by electrodiagnostic testing. Potential complications include autonomic instability.[6] The frequency of improvement in response to repeated courses of treatment has not been determined. hypercalcemia. the patient’s neurologist or primary care physician should coordinate all tests and procedures ordered on an outpatient basis. Medication Summary Medical therapy is tailored for each patient and might include various combinations of the drugs listed below. IVIG has been shown to have significant results. Treatment of the associated cancer may also decrease the weakness and other . Physical therapy and exercise are important parts of the outpatient regimen to help maintain muscle tone and strength. Long-Term Monitoring Ideally. Most notably.[6] Other appropriate consultations may include an oncologist and a physical medicine specialist. In addition. Weakness of LEMS may be worse when the ambient temperature increases or when the patient is febrile. in addition to pharmacotherapy. and initiation of pharmacotherapy. Therapy is best coordinated with the primary care physician and appropriate consultants. further workup. and bleeding due to depletion of clotting factors. Consultations In patients with chronic weakness. consultation with a neurologist may be indicated for electromyography (EMG). given in a course of 2 g/kg over 2-5 days. many of the medications and therapies that have been shown to produce clinical improvement are not appropriate for the ED. Regonol) Pyridostigmine blocks ACh hydrolysis by cholinesterase. a few patients with mild disease may note some difference. or both in some patients with LEMS. plasma exchange (PEX) or high-dose intravenous immunoglobulin (IVIg) may be used initially to induce rapid. Pyridostigmine is the preferred agent and should be administered for several days before assessing response. but they may provide relief from weakness or dry mouth in some patients. The frequency of improvement in response to repeated courses of treatment has not been determined. can be used alone or in combination.4-diaminopyridine (DAP) have been used. improvement. neuromuscular. albeit transitory. given in a course of 2 g/kg over 2-5 days. resulting in ACh accumulation at synapses and increasing stimulation of cholinergic . autonomic symptoms. with many neurologic effects reported. They act by inhibiting the breakdown of ACh. also induces clinically significant temporary improvement in many patients. Both 4-aminopyridine and 3. however. They usually do not provide a significant improvement. Acetylcholinesterase inhibitors do not usually produce dramatic improvement in LEMS. but 4-aminopyridine is thought to be less effective and is almost twice as toxic. Immunosuppressants should be added for more sustained improvement. aggressive immunotherapy may be warranted. Prednisone and azathioprine. IVIg. If these treatments are not effective and the patient has relatively mild weakness. In such cases. Neuromuscular agents Class Summary Neuromuscular agents produce symptomatic improvement in strength.symptoms. the most frequently used immunosuppressants. which is intended to help compensate for the relative lack of ACh quanta release in LEMS. Aminopyridines block potassium channels in membranes and facilitate chemical synaptic transmission at autonomic. and central synapses. View full drug information Pyridostigmine bromide (Mestinon. Cyclosporine may benefit patients with LEMS who are candidates for immunosuppression but cannot take or do not respond well to azathioprine. In most of the literature. NJ. View full drug information . It inhibits respiration by blocking potassium channels and thus prolonging the nerve terminal action potential. It is in combination with drugs such as 3. Princeton. Immunosuppressants Class Summary If the therapies already described are ineffective. permitting lower doses. Maximal effect may take 2-3 days.4-diaminopyridine that cholinesterase inhibitors may have some slight benefit. improvement is marked. This agent is primarily cited in case reports and has not been studied in randomized trials. the consensus seems to be that monotherapy with a cholinesterase inhibitor is ineffective. This agent is not approved for clinical use in the United States. Guanidine HCl Guanidine is thought to act by increasing free intracellular calcium concentrations through inhibition of mitochondrial respiration. with the potential for more long-term immunosuppression. DAP has been used to improve strength and autonomic function in patients with LEMS. Inc. In the authors' experience.receptors at myoneural junction. In most patients. more aggressive immunotherapy may be indicated. usually with prednisone or azathioprine.4-Diaminopyridine (DAP) For more than 20 years. but it is available on a compassionate-use basis for individual patients. Each dose lasts about 4 hours. in over half of these. Obtain application process information from Jacobus Pharmaceutical Co. Effect begins about 20 minutes after an oral dose. pyridostigmine enhances and prolongs DAP's duration of action. This increases release of ACh after nerve impulses and may decrease rates of repolarization and depolarization of muscle cell membranes. 3. Therapy can take the form of plasma exchange or high-dose IVIg.. and maximum effect of a given dosage may not be observed for 2-3 days. Patients with or without underlying cancer benefit from DAP. >80% of patients with LEMS have significant clinical benefit. 609-799-1176 (fax). It temporarily improves strength in many patients with LEMS.. IVIg can be an effective treatment for LEMS. Blood products Class Summary Agents in this category may be used to improve clinical and immunologic aspects of LEMS. blockade of Fc receptors on macrophages. and a possible increase in cerebrospinal fluid (CSF) immunoglobulin (IgG).Prednisone Prednisone is used as an immunosuppressant in the treatment of autoimmune disorders. RNA. downregulation of proinflammatory cytokines. and proteins. These effects may inhibit formation of immune cells. possibly reducing activity of immune system. blockade of the complement cascade. promotion of remyelination. Tempat produksi toksin berbeda untuk tiap bentuk. yaitu yang di tularkankan melalui makanan (bentuk klasik) dan yang ditularkan melalui. The combination of corticosteroid therapy with azathioprine may be more effective than steroid monotherapy. suppression of inducer T and B cells and augmentation of suppressor T cells. Azasan) Azathioprine inhibits mitosis and cellular metabolism by antagonizing purine metabolism and inhibiting synthesis of DNA. Botulisme 1. They may decrease autoantibody production and increase solubilization and removal of immune complexes. Ada 3 bentuk botulisme. including interferon gamma. tetapi semua bentuk memberikan gejala lumpuh layuh yang diakibatkan oleh racun saraf botulinum. View full drug information Intravenous immunoglobulin (IVIg) (Gamunex. Carimune NF) Features of IVIg that may be relevant to efficacy include neutralization of circulating antibodies through anti-idiotypic antibodies. Identifikasi. Botulisme saluran pencernaan diusulkan sebagai identitas penyakit baru dari . Gammagard. View full drug information Azathioprine (Imuran. luka dan saluran pencernaan (bayi dan dewasa). Nama baru secara resmi diterima pada pertengahan tahun 1999. Muntah dan konstipasi atau diare mungkin muncul pada awalnya. CFR di AS 5 £ 10 %. Pemulihan bisa berlangsung beberapa bulan. susah menelan. Gangguan visual (kabur dan dobel). Demam tidak terjadi bila tidak ada komplikasi Infeksi lain. gambaran klinis yang sama terlihat pada saat organisme penyebab mengkontaminasi luka dalam kondisi anaerob.apa yang sebelumnya disebut Botulisme bayi. listlessness. Untuk jenis Botulisme luka. dan akan digunakan secara umum di bab ini sebagai pengganti istilah botulisme bayi. Penyakit ini ditandai dengan gangguan nervus cranialis bilateral akut dan melemahnya anggota tubuh disertai kelumpuhan. tetapi dapat juga menyerang orang dewasa yang mempunyai kelainan anatomi saluran pencernaan serta terjadinya perubahan flora usus. diikuti dengan letargi. tidak nafsu makan. ptosis. hipotonia dan menjurus kepada keadaan lemah secara menyeluruh (floppy baby) dan pada . ini muncul akibat menelan spora Clostridium botulinum kemudian tumbuh berkembang dan memproduksi racun pada usus besar. Gejala-gejala ini bisa meluas berupa layuh simetris pada orang yang waspada akan gejalagejala ini. Sedangkan botulisme saluran pencernaan (bayi) adalah bentuk botulisme yang paling sering terjadi di AS. Gejala klinis khas dimulai dengan konstipasi. disfagia dan mulut kering sering merupakan keluhan pertama. Botulisme saluran pencernaan ini secara spesifik menyerang bayi dibawah 1 tahun. kehilangan kontrol gerakan kepala. Foodborne botulism adalah keracunan berat yang diakibatkan karena menelan racun yang terbentuk di dalam makanan yang terkontaminasi. type B in the eastern states. CFR dari penderita yang dirawat di rumah sakit di AS kurang dari 1 %. Four of the toxins (types A. and rarely F) affect humans. beberapa penelitian menemukan bahwa penyakit ini merupakan penyebab terjadinya 5% sindroma kematian mendadak (Sudden Infant Death Syndrome/SIDS). botulinum elaborates 7 types of antigenically distinct neurotoxins. Diagnosa dari botulisme yang ditularkan melalui makanan ditegakkan dengan menemukan racun botulinum dalam serum. atau dari kultur C. botulinum cairan lambung atau tinja penderita. neurotoxin produced in contaminated food is eaten. E. botulinum toxin has also been developed as a bioweapon. cairan lambung atau makanan yang tercemar. Diagnosis is clinical and by laboratory identification of toxin. Botulisme pada bayi mempunyai spektrum klinis luas. and type E in Alaska and the Great Lakes area (type E is frequently associated with ingestion of fish products). which interfere with release of acetylcholine at peripheral nerve endings. Type A toxin occurs predominantly west of the Mississippi River. Neurotoxin is elaborated in vivo by C. Symptoms are symmetric cranial nerve palsies accompanied by a symmetric descending weakness and flaccid paralysis without sensory deficits.merckmanuals.beberapa kasus. terjadi kesulitan bernapas sampai gagal nafas. botulinum in infected tissue in wound botulism and in the large intestine in infant botulism (see Anaerobic . B. tinja.com/professional/neurologic_disorders/peripher al_nervous_system_and_motor_unit_disorders/disorders_of_neuromuscul ar_transmission. Botulism may occur without infection if toxin is ingested. Treatment is with support and antitoxin. About 50% of food-borne outbreaks in the US are caused by type A toxin. Types A and B are highly poisonous proteins resistant to digestion by GI enzymes. sudah barang tentu penderita tanpa akses ke Rumah Sakit dengan Unit Perawatan Intensif Anak akan terjadi lebih banyak kematian. Type A toxin is used therapeutically to relieve excess muscle activity. Botulism occurs in 3 forms: • Food-borne • Wound • Infant In food-borne botulism. mulai dari sakit ringan dengan onset bertahap hingga kematian mendadak.html Botulism is neuromuscular poisoning due to Clostridium botulinum toxin. Menemukan organisme dari http://www. C. followed by types B and E. and the pulse remains normal or slow unless intercurrent infection develops. patty melt sandwiches) have caused restaurantassociated outbreaks. usually 18 to 36 h after toxin ingestion. foil-wrapped baked potatoes. Sources of infection: Home-canned foods. milk products. on the other hand. In recent years. and cooking food at 80° C for 30 min safeguards against botulism. Dysphagia can lead to aspiration pneumonia. pork. Nausea. are the most common sources. chopped garlic in oil. types A and B cause the rest. and other foods have been involved. inside a refrigerator) and does not require strict anaerobic conditions. and difficulty swallowing. and the sensorium usually remains clear. Pupillary light reflex is diminished or totally lost. beginning with the cranial nerves and followed by descending weakness or paralysis. Muscles of respiration and of the extremities and trunk progressively weaken in a descending pattern. C. Vegetables. There are no sensory disturbances. particularly low-acid foods. Of outbreaks caused by seafood. slurred speech. Toxins. blurred or double vision. Toxin production (especially type E) can occur at temperatures as low as 3° C (ie. are readily destroyed by heat. However. and condiments are the most common vehicles. but commercially prepared foods have been implicated in about 10% of outbreaks.Bacteria: Infant Botulism). Injecting contaminated heroin into a muscle or under the skin (skin popping) is riskiest. and many cases may be caused by ingestion or inhalation of dust or by absorption through the eyes or a break in the skin. Injecting drugs with unsterilized needles can cause wound botulism. . C. type E causes about 50%. fish. and diarrhea frequently precede neurologic symptoms. although the incubation period may vary from 4 h to 8 days. vomiting. Common initial symptoms and signs include dry mouth. botulinum spores are highly heat-resistant and may survive boiling for several hours at 100° C. Neurologic symptoms are characteristically bilateral and symmetric. fruits. abdominal cramps. Symptoms and Signs Food-borne botulism: Symptoms begin abruptly. botulinum spores are common in the environment. poultry. but beef. foods that are not canned (eg. exposure to moist heat at 120° C for 30 min kills the spores. Fever is absent. drooping eyelids. Patients with significant symptoms often have impaired airway reflexes. so if charcoal is used. myasthenia gravis.Constipation is common after neurologic impairment appears. poliomyelitis. the pattern of neuromuscular disturbances and ingestion of a likely food source are important diagnostic clues. which may be located through local health authorities or the Centers for Disease Control and Prevention (CDC). tick paralysis. Wound botulism: Neurologic symptoms appear. it should be given via gastric tube. which is confirmed by demonstrating C. The simultaneous presentation of at least 2 patients who ate the same food simplifies diagnosis. In food-borne botulism. finding toxin in serum or isolating C. Administration of activated charcoal may be helpful. Diagnosis • Toxin assays • Sometimes electromyography Botulism may be confused with Guillain-Barré syndrome. botulinum toxin in suspect food identifies the source. as in food-borne botulism. Major complications include respiratory failure caused by diaphragmatic paralysis and pulmonary infections. In wound botulism. botulinum organisms on anaerobic culture of the wound confirms the diagnosis. but there are no GI symptoms or evidence implicating food as a cause. stroke. and poisoning caused by curare or belladonna alkaloids. A thorough search should be made for breaks in the skin and for skin abscesses caused by self-injection of illegal drugs. Finding C. A history of a traumatic injury or a deep puncture wound in the preceding 2 wk may suggest the diagnosis. Toxin assays are done only by certain laboratories. and the airway should be protected by a cuffed endotracheal tube. Treatment • Supportive care • Equine trivalent antitoxin Anyone known or thought to have been exposed to contaminated food must be carefully observed. botulinum toxin in serum or stool or by isolating the organism from stool. . Electromyography shows characteristic augmented response to rapid repetitive stimulation in most cases. Autoimmune. Respiratory impairment requires management in an ICU. and 8500 IU of antitoxin E. preexisting neurologic impairment cannot be reversed rapidly. Progressive paralysis prevents patients from showing signs of respiratory distress as their vital capacity decreases. All patients who require the antitoxin must be reported to state health authorities or the CDC. Antitoxin should be given as soon as possible after clinical diagnosis and not delayed to await culture results. which may take weeks or months. and avoids the potential infectious and vascular complications inherent in IV alimentation. E) is available from the CDC through state health departments.The greatest threat to life is respiratory impairment and its complications. Patients with wound botulism require wound debridement and parenteral antibiotics such as penicillin or metronidazole SOME TRADE NAMES FLAGYL Click for Drug Monograph . antitoxin may slow or halt further progression. 5500 IU of antitoxin B. Autoimmune. allows the use of breast milk in infants. Antitoxin does not inactivate toxin that is already bound at the neuromuscular junction. (For precautions. Patients should be hospitalized and closely monitored with serial measurements of vital capacity. botulinum from the gut). Improvements in such supportive care have reduced the mortality rate to < 10%. (Ultimate recovery depends on regeneration of nerve endings. for treatment. stimulates intestinal peristalsis (which eliminates C. see Allergic. Antitoxin is less likely to be of benefit if given > 72 h after symptom onset. see Allergic. Because antitoxin is derived from horse serum. and Other Hypersensitivity Disorders: Anaphylaxis. antitoxin can reduce complications and mortality rate. where intubation and mechanical ventilation are readily available. therefore.) However. In the US. the telephone number is 404-639-2206 weekdays and 404-639-2888 for all other times. Antitoxin: Trivalent equine antitoxin (A. botulism equine trivalent antitoxin is given as a single 10-mL dose containing 7500 IU of antitoxin A. In patients with wound botulism. Antitoxin is available only through the CDC. there is a risk of anaphylaxis or serum sickness.) . Nasogastric intubation is the preferred method of alimentation because it simplifies management of calories and fluids. B. and Other Hypersensitivity Disorders: Drug Hypersensitivity . congenital muscular dystrophy. poor muscle tone (floppy baby syndrome). and the oldest was 12 mo. their colonization of the large intestine. infant botulism is not caused by ingestion of a preformed toxin.Prevention Because even minute amounts of C. infants < 12 mo should not be fed honey. spinal muscular atrophy. pooling of oral secretions. and benign congenital hypotonia. all materials suspected of containing toxin require special handling. Toxoids are available for active immunization of people working with C. decreased gag reflex. Correct canning and adequate heating of home-canned food before serving are essential. extraocular muscle palsies. Most cases are idiopathic. The youngest reported patient was 2 wk. which may contain C. Diagnosis Infant botulism may be confused with sepsis. poor suck. beginning with the cranial nerves and proceeding to peripheral and respiratory musculature. Severity varies from mild lethargy and slowed feeding to severe hypotonia and respiratory insufficiency. and an expressionless face. Treatment • Human botulism antitoxin Infants are hospitalized. INFANT BOTULISM Infant botulism results from ingestion of C. botulinum spores. . Canned foods showing evidence of spoilage and swollen or leaking cans should be discarded. thus. Details regarding specimen collection and handling can be obtained from state health departments or the CDC. botulinum toxin or organisms in the stool establishes the diagnosis. Cranial nerve deficits typically include ptosis. Symptoms and Signs Constipation is present initially in 90% of cases and is followed by neuromuscular paralysis. hypothyroidism. Finding C. Unlike food-borne botulism. and supportive care (eg. botulinum spores. Infant botulism occurs most often in infants < 6 mo. and toxin production in vivo. weak cry. although some have been traced to ingestion of honey. botulinum or its toxins. botulinum toxin can cause serious illness. ventilatory support) is given as needed. Treatment is started as soon as the diagnosis is suspected. given slowly. Antibiotics are not given because they may lyse C. The dose is 50 mg/kg IV once. . botulinum in the gut and increase toxin availability.Specific treatment is with human botulism immune globulin. waiting for confirmatory test results is dangerous. The horse serum antitoxin used in adults is not recommended for infants.