Lambert–Eaton myasthenic syndrome (LEMS) is a rare
autoimmune
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...
disorder characterized by
muscle weakness
Muscle weakness is a lack of muscle strength. Its causes are many and can be divided into conditions that have either true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, includi ...
of the limbs.
Around 60% of those with LEMS have an underlying
malignancy
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
, most commonly
small-cell lung cancer
Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell car ...
; it is therefore regarded as a
paraneoplastic syndrome
A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of a tumor in the body (usually a cancerous one), specifically due to the production of chemical signaling molecules (such as hormones or cytokines) by ...
(a condition that arises as a result of cancer elsewhere in the body).
[ It is the result of ]antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
against presynaptic voltage-gated calcium channels
Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permeabili ...
, and likely other nerve terminal proteins, in the neuromuscular junction
A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber.
It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction.
Muscles require innervation to ...
(the connection between nerve
A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system.
A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
s and the muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
that they supply).[ The diagnosis is usually confirmed with ]electromyography
Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph to produce a record called an electromyogram. An electromyog ...
and blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose test or a cholester ...
s; these also distinguish it from myasthenia gravis
Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, dro ...
, a related autoimmune neuromuscular disease.[
If the disease is associated with cancer, direct treatment of the cancer often relieves the symptoms of LEMS. Other treatments often used are ]steroids
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
, azathioprine
Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, ...
, which suppress the immune system, intravenous immunoglobulin
Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin or NHIG) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory dem ...
, which outcompetes autoreactive antibody for Fc receptors, and pyridostigmine
Pyridostigmine is a medication used to treat myasthenia gravis and underactive bladder. It is also used together with atropine to end the effects of neuromuscular blocking medication of the non-depolarizing type. It is typically given by mouth ...
and 3,4-diaminopyridine
Amifampridine is used as a drug, predominantly in the treatment of a number of rare muscle diseases. The free base form of the drug has been used to treat congenital myasthenic syndromes and Lambert–Eaton myasthenic syndrome (LEMS) through com ...
, which enhance the neuromuscular transmission. Occasionally, plasma exchange
Plasmapheresis (from the Greek πλάσμα, ''plasma'', something molded, and ἀφαίρεσις ''aphairesis'', taking away) is the removal, treatment, and return or exchange of blood plasma or components thereof from and to the blood circulati ...
is required to remove the antibodies.[
The condition affects about 3.4 per million people.] LEMS usually occurs in people over 40 years of age, but may occur at any age.
Signs and symptoms
The weakness from LEMS typically involves the muscles of the proximal arms and legs (the muscles closer to the trunk). In contrast to myasthenia gravis
Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, dro ...
, the weakness affects the legs more than the arms. This leads to difficulties climbing stairs and rising from a sitting position. Weakness is often relieved temporarily after exertion or physical exercise
Exercise is a body activity that enhances or maintains physical fitness and overall health and wellness.
It is performed for various reasons, to aid growth and improve strength, develop muscles and the cardiovascular system, hone athletic ...
. High temperatures can worsen the symptoms. Weakness of the bulbar muscles (muscles of the mouth and throat) is occasionally encountered.[ Weakness of the ]eye muscles
The extraocular muscles (extrinsic ocular muscles), are the seven extrinsic muscles of the human eye. Six of the extraocular muscles, the four recti muscles, and the superior and inferior oblique muscles, control movement of the eye and the oth ...
is uncommon. Some may have double vision
Diplopia is the simultaneous perception of two images of a single object that may be displaced horizontally or vertically in relation to each other. Also called double vision, it is a loss of visual focus under regular conditions, and is often v ...
, drooping of the eyelids and difficulty swallowing
Dysphagia is difficulty in swallowing. Although classified under " symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right.
It may be a sensation that suggests difficulty in the passage of solids or liqu ...
,[ but generally only together with leg weakness; this too distinguishes LEMS from myasthenia gravis, in which eye signs are much more common.] In the advanced stages of the disease, weakness of the respiratory muscles
The muscles of respiration are the muscles that contribute to inhalation and exhalation, by aiding in the expansion and contraction of the thoracic cavity. The diaphragm and, to a lesser extent, the intercostal muscles drive respiration during q ...
may occur. Some may also experience problems with coordination
Coordination may refer to:
* Coordination (linguistics), a compound grammatical construction
* Coordination complex, consisting of a central atom or ion and a surrounding array of bound molecules or ions
* Coordination number or ligancy of a centr ...
(ataxia
Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...
).
Three-quarters of people with LEMS also have disruption of the autonomic nervous system
The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the peripheral nervous system that supplies viscera, internal organs, smooth muscle and glands. The autonomic nervous system is a control ...
. This may be experienced as a dry mouth
Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause.
This symptom is very common and is often seen as a side eff ...
, constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
, blurred vision
Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details.
Temporary blurred vision may involve dry eyes, eye infections, alcohol poisoning, hypoglycemia, or low blood pressure. ...
, impaired sweating
Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals.
Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distr ...
, and orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...
(falls in blood pressure on standing, potentially leading to blackouts). Some report a metallic taste in the mouth.[
On ]neurological examination
A neurological examination is the assessment of sensory neuron and motor responses, especially reflexes, to determine whether the nervous system is impaired. This typically includes a physical examination and a review of the patient's medical hist ...
, the weakness demonstrated with normal testing of power is often less severe than would be expected on the basis of the symptoms. Strength improves further with repeated testing, e.g. improvement of power on repeated hand grip (a phenomenon known as " Lambert's sign"). At rest, reflex
In biology, a reflex, or reflex action, is an involuntary, unplanned sequence or action and nearly instantaneous response to a stimulus.
Reflexes are found with varying levels of complexity in organisms with a nervous system. A reflex occurs ...
es are typically reduced; with muscle use, reflex strength increases. This is a characteristic feature of LEMS. The pupillary light reflex
The pupillary light reflex (PLR) or photopupillary reflex is a reflex that controls the diameter of the pupil, in response to the intensity (luminance) of light that falls on the retinal ganglion cells of the retina in the back of the eye, there ...
may be sluggish.[
In LEMS associated with lung cancer, most have no suggestive symptoms of cancer at the time, such as ]cough
A cough is a sudden expulsion of air through the large breathing passages that can help clear them of fluids, irritants, foreign particles and microbes. As a protective reflex, coughing can be repetitive with the cough reflex following three pha ...
, coughing blood, and unintentional weight loss
Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other con ...
.[ LEMS associated with lung cancer may be more severe.][
]
Causes
LEMS is often associated with lung cancer (50–70%), specifically small-cell carcinoma
Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell ca ...
,[ making LEMS a paraneoplastic syndrome.][ Of the people with small-cell lung cancer, 1–3% have LEMS.][ In most of these cases, LEMS is the first symptom of the lung cancer, and it is otherwise ]asymptomatic
In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered asy ...
.[
LEMS may also be associated with ]endocrine disease
Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology.
Types of disease
Broadly speaking, endocrine disorders may be subdivided into three groups:
# Endocrin ...
s, such as hypothyroidism
Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...
(an underactive thyroid gland
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobe (anatomy), lobes. The lower two thirds of the lobes are connected by a thin band of Connective tissue, tissue cal ...
) or diabetes mellitus type 1
Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar f ...
.[ ]Myasthenia gravis
Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, dro ...
, too, may happen in the presence of tumors (thymoma
A thymoma is a tumor originating from the epithelial cells of the thymus that is considered a rare malignancy. Thymomas are frequently associated with neuromuscular disorders such as myasthenia gravis; thymoma is found in 20% of patients with mya ...
, a tumor of the thymus
The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...
in the chest); people with MG without a tumor and people with LEMS without a tumor have similar genetic variations that seem to predispose them to these diseases.[ ]HLA-DR3
HLA-DR3 is composed of the HLA-DR17 and HLA-DR18 split 'antigens' serotypes. DR3 is a component gene-allele of the AH8.1 haplotype in Northern and Western Europeans. Genes between B8 and DR3 on this haplotype are frequently associated with autoi ...
- B8 (an HLA subtype), in particular, seems to predispose to LEMS.[
]
Mechanism
In normal neuromuscular function, a nerve impulse
An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, c ...
is carried down the axon
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...
(the long projection of a nerve cell
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. No ...
) from the spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...
. At the nerve ending in the neuromuscular junction
A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber.
It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction.
Muscles require innervation to ...
, where the impulse is transferred to the muscle cell, the nerve impulse leads to the opening of voltage-gated calcium channels
Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permeabili ...
(VGCC), the influx of calcium ions into the nerve terminal, and the calcium-dependent triggering of synaptic vesicle fusion with plasma membrane. These synaptic vesicles contain acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
, which is released into the synaptic cleft and stimulates the acetylcholine receptor
An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.
Classification
Like other transmembrane receptors, acetylcholine receptors are classified according ...
s on the muscle. The muscle then contracts.[
In LEMS, antibodies against VGCC, particularly the P/ Q-type VGCC, decrease the amount of calcium that can enter the nerve ending, hence less acetylcholine can be released from the neuromuscular junction. Apart from ]skeletal muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
, the autonomic nervous system also requires acetylcholine neurotransmission; this explains the occurrence of autonomic symptoms in LEMS.[ P/Q voltage-gated calcium channels are also found in the ]cerebellum
The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...
, explaining why some experience problems with coordination.[ The antibodies bind particularly to the part of the receptor known as the "domain III S5–S6 linker peptide".][ Antibodies may also bind other VGCCs.][ Some have antibodies that bind ]synaptotagmin
Synaptotagmins (SYTs) constitute a family of membrane-trafficking proteins that are characterized by an N-terminal transmembrane region (TMR), a variable linker, and two C-terminal C2 domains - C2A and C2B. There are 17 isoforms in the mammalian s ...
, the protein sensor for calcium-regulated vesicle fusion.[ Many people with LEMS, both with and without VGCC antibodies, have detectable antibodies against the M1 subtype of the acetylcholine receptor; their presence may participate in a lack of compensation for the weak calcium influx.][
Apart from the decreased calcium influx, a disruption of active zone vesicle release sites also occurs, which may also be antibody-dependent, since people with LEMS have antibodies to components of these active zones (including voltage-dependent calcium channels). Together, these abnormalities lead to the decrease in muscle contractility. Repeated stimuli over a period of about 10 seconds eventually lead to sufficient delivery of calcium, and an increase in muscle contraction to normal levels, which can be demonstrated using an ]electrodiagnostic medicine
Electrodiagnosis (EDX) is a method of medical diagnosis that obtains information about diseases by passively recording the electrical activity of body parts (that is, their natural electrophysiology) or by measuring their response to external elect ...
study called needle electromyography by increasing amplitude of repeated compound muscle action potential
The compound muscle action potential (CMAP) or compound motor action potential is an electromyography investigation (electrical study of muscle function).
The CMAP idealizes the summation of a group of almost simultaneous action potentials from se ...
s.[
The antibodies found in LEMS associated with lung cancer also bind to calcium channels in the cancer cells, and it is presumed that the antibodies originally develop as a reaction to these cells.][ It has been suggested that the immune reaction to the cancer cells suppresses their growth and improves the prognosis from the cancer.]
Diagnosis
The diagnosis is usually made with nerve conduction study (NCS) and electromyography
Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph to produce a record called an electromyogram. An electromyog ...
(EMG), which is one of the standard tests in the investigation of otherwise unexplained muscle weakness. EMG involves the insertion of small needles into the muscles. NCS involves administering small electrical impulses to the nerves, on the surface of the skin, and measuring the electrical response of the muscle in question. NCS investigation in LEMS primarily involves evaluation of compound motor action potentials (CMAPs) of effected muscles and sometimes EMG single-fiber examination can be used.[
CMAPs show small amplitudes but normal latency and conduction velocities. If repeated impulses are administered (2 per second or 2 Hz), it is normal for CMAP amplitudes to become smaller as the acetylcholine in the motor end plate is depleted. In LEMS, this decrease is larger than observed normally. Eventually, stored acetylcholine is made available, and the amplitudes increase again. In LEMS, this remains insufficient to reach a level sufficient for transmission of an impulse from nerve to muscle; all can be attributed to insufficient calcium in the nerve terminal. A similar pattern is witnessed in myasthenia gravis. In LEMS, in response to exercising the muscle, the CMAP amplitude increases greatly (over 200%, often much more). This also occurs on the administration of a rapid burst of electrical stimuli (20 impulses per second for 10 seconds). This is attributed to the influx of calcium in response to these stimuli.][ On single-fiber examination, features may include increased jitter (seen in other diseases of neuromuscular transmission) and blocking.][
Blood tests may be performed to exclude other causes of muscle disease (elevated ]creatine kinase
Creatine kinase (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme () expressed by various tissues and cell types. CK catalyses the conversion of creatine and uses adenosine triphosphate (ATP) to create phosp ...
may indicate a myositis
Myositis is a rare disease that involves inflammation of the muscles. This can present with a variety of symptoms such as skin involvement (i.e., rashes), muscle weakness, and other organ involvement. Systemic symptoms such as weight loss, fatigue ...
, and abnormal thyroid function test
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
s may indicate thyrotoxic myopathy). Antibodies against voltage-gated calcium channels can be identified in 85% of people with EMG-confirmed LEMS.[ Once LEMS is diagnosed, investigations such as a ]CT scan
A computed tomography scan (CT scan; formerly called computed axial tomography scan or CAT scan) is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers ...
of the chest are usually performed to identify any possible underlying lung tumors. Around 50–60% of these are discovered immediately after the diagnosis of LEMS. The remainder is diagnosed later, but usually within two years and typically within four years.[ As a result, scans are typically repeated every six months for the first two years after diagnosis.][ While CT of the lungs is usually adequate, a ]positron emission tomography
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...
scan of the body may also be performed to search for an occult tumour, particularly of the lung.
Treatment
If LEMS is caused by an underlying cancer, treatment of the cancer usually leads to resolution of the symptoms.[ Treatment usually consists of ]chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
, with radiation therapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
in those with limited disease.[
]
Immunosuppression
Some evidence supports the use of intravenous immunoglobulin
Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin or NHIG) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory dem ...
(IVIG). Immune suppression tends to be less effective than in other autoimmune diseases. Prednisolone (a glucocorticoid or steroid) suppresses the immune response, and the steroid-sparing agent azathioprine may replace it once therapeutic effect has been achieved. IVIG may be used with a degree of effectiveness. Plasma exchange (or plasmapheresis), the removal of plasma proteins such as antibodies and replacement with normal plasma, may provide improvement in acute severe weakness. Again, plasma exchange is less effective than in other related conditions such as myasthenia gravis, and additional immunosuppressive medication is often needed.[
]
Other
Three other treatment modalities also aim at improving LEMS symptoms, namely pyridostigmine
Pyridostigmine is a medication used to treat myasthenia gravis and underactive bladder. It is also used together with atropine to end the effects of neuromuscular blocking medication of the non-depolarizing type. It is typically given by mouth ...
, 3,4-diaminopyridine
Amifampridine is used as a drug, predominantly in the treatment of a number of rare muscle diseases. The free base form of the drug has been used to treat congenital myasthenic syndromes and Lambert–Eaton myasthenic syndrome (LEMS) through com ...
(amifampridine), and guanidine
Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experie ...
. They work to improve neuromuscular transmission.
Tentative evidence supports 3,4-diaminopyridine] at least for a few weeks.[ The 3,4-diaminopyridine base or the water-soluble 3,4-diaminopyridine phosphate may be used. Both 3,4-diaminopyridine formulations delay the repolarization of nerve terminals after a discharge, thereby allowing more calcium to accumulate in the nerve terminal.][
Pyridostigmine decreases the degradation of acetylcholine after release into the synaptic cleft, and thereby improves muscle contraction. An older agent, guanidine, causes many side effects and is not recommended. 4-Aminopyridine (dalfampridine), an agent related to 3,4-aminopyridine, causes more side effects than 3,4-DAP and is also not recommended.][
]
History
Anderson and colleagues from St Thomas' Hospital
St Thomas' Hospital is a large NHS teaching hospital in Central London, England. It is one of the institutions that compose the King's Health Partners, an academic health science centre. Administratively part of the Guy's and St Thomas' NHS Foun ...
, London, were the first to mention a case with possible clinical findings of LEMS in 1953, but Edward H. Lambert, Lee Eaton, and E.D. Rooke at the Mayo Clinic
The Mayo Clinic () is a nonprofit American academic medical center focused on integrated health care, education, and research. It employs over 4,500 physicians and scientists, along with another 58,400 administrative and allied health staff, ...
were the first physicians to substantially describe the clinical and electrophysiological findings of the disease in 1956. In 1972, the clustering of LEMS with other autoimmune diseases led to the hypothesis that it was caused by autoimmunity. Studies in the 1980s confirmed the autoimmune nature,[ and research in the 1990s demonstrated the link with antibodies against P/Q-type voltage-gated calcium channels.]
References
External links
{{DEFAULTSORT:Lambert-Eaton myasthenic syndrome
Myoneural junction and neuromuscular diseases
Paraneoplastic syndromes
Autoimmune diseases
Syndromes affecting muscles
Channelopathies