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Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles Skeletal muscles A subtype of striated muscle, attached by tendons to the skeleton. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles. Muscle Tissue: Histology caused by dysfunction/destruction of acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors at the neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction. Myasthenia gravis presents with fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, ptosis Ptosis Cranial Nerve Palsies, diplopia, dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming "stuck." Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Diagnosis is established based on clinical presentation, detection of antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions, and electrophysiologic studies. Management is aimed at increasing the activity of acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS at the neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction and suppression Suppression Defense Mechanisms of antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions. This disease can be associated with thymomas and thymic hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation, and thymectomy is sometimes indicated. Myasthenia gravis can progress to a life-threatening cholinergic crisis with respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure, but this is preventable with appropriate management. Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas is generally good with treatment, and some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship can achieve a long-term remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches.

Last updated: Dec 5, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Myasthenia gravis (MG) is a chronic autoimmune disorder Autoimmune Disorder Septic Arthritis in which antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions attack the acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (AChR) complex at the neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction.

Epidemiology

  • Annual incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 7–23 cases per million
  • Female-to-male ratio: 3:2
  • Can occur in any age group, but peak incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency observed in women in their 20s and 30s and men in their 50s and 60s
  • Commonly affects women in the postpartum period Postpartum period In females, the period that is shortly after giving birth (parturition). Postpartum Complications
  • 50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship initially present with ocular symptoms and within a year develop generalized symptoms such as weakness or fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia.
  • There has been a dramatic decrease in mortality Mortality All deaths reported in a given population. Measures of Health Status from 75% to 4.5% due to changes in treatment.

Etiology

  • Antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against AChRs:
  • Thymus Thymus A single, unpaired primary lymphoid organ situated in the mediastinum, extending superiorly into the neck to the lower edge of the thyroid gland and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. Lymphatic Drainage System: Anatomy gland:
    • Research Research Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. Conflict of Interest suggests that the thymus Thymus A single, unpaired primary lymphoid organ situated in the mediastinum, extending superiorly into the neck to the lower edge of the thyroid gland and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. Lymphatic Drainage System: Anatomy gland is involved in the maintenance of antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against AChRs.
    • Some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship diagnosed with MG have associated thymomas (10%), and the MG can present as paraneoplastic syndrome secondary to thymomas.
    • 60%–80% have thymic hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation.
  • Antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against lipoprotein-related protein 4:
    • Some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with MG do not have antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against AChRs or MuSK; instead, they develop antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against lipoprotein-related protein 4.
    • This type of MG is called antibody-negative MG.
    • Lipoprotein-related protein 4 is present on the postsynaptic membrane Postsynaptic membrane Synapses and Neurotransmission and induces clustering of AChRs.

Classification and Pathophysiology

Classification

There are 2 main clinical forms of MG:

  • Ocular myasthenia: weakness is limited to the eyelids Eyelids Each of the upper and lower folds of skin which cover the eye when closed. Blepharitis and extraocular muscles and is characterized by ptosis Ptosis Cranial Nerve Palsies and oculomotor paresis Paresis A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. ‘general paresis’ and ‘general paralysis’ may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. Spinal Disk Herniation.
  • Generalized myasthenia:
    • Weakness not only occurs in the ocular muscles but also affects the bulbar, limb, and respiratory muscles.
    • Weakness can be proximal, distal, symmetric, or asymmetric.

In addition, rarer forms of MG exist that primarily affect the pediatric population:

  • Neonatal MGs:
    • A rare condition that occurs when mothers with MG have children who are born with the disorder.
    • Transplacental passage of maternal antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions that attack the neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction
    • Immediate treatment can resolve the condition within 2 months after birth.
  • Congenital Congenital Chorioretinitis myasthenic syndrome:
    • A rare, hereditary form of myasthenia that is present from birth.
    • This syndrome may be the result of rare mutations that affect the neuromuscular transmission.

Myasthenia gravis may also be classified on the basis of the serologic profile of antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions present:

  • Presence of antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against either AChR or MuSK is referred to as seropositive MG:
    • AChR-positive MG:
      • Presents primarily with proximal limb muscle weakness
      • Facial, bulbar, and respiratory weakness may also be present.
      • Present in about 80% of MG cases
      • Present in 30%–40% of ocular MG
      • 20% chance of remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches 
    • MuSK-positive MG:
      • Presents primarily with facial, bulbar, and respiratory weakness
      • No or relatively mild limb weakness
      • Common in younger female patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
      • Present in 30%–40% of MG cases in which AChR antibody is absent
      • Less chance of remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches
  • Absence of either AChR or MuSK antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions in the presence of clinical signs/symptoms is referred to as seronegative MG (15% of cases).

Pathogenesis

  • AChR antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions (produced in the thymus Thymus A single, unpaired primary lymphoid organ situated in the mediastinum, extending superiorly into the neck to the lower edge of the thyroid gland and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. Lymphatic Drainage System: Anatomy):
    • Are IgG1 and IgG3 subtypes and divalent
    • Antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions target AChRs on the postsynaptic membrane Postsynaptic membrane Synapses and Neurotransmission.
    • Antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions activate the classical complement pathway, which in turn activate the membrane attack complex Membrane attack complex A product of complement activation cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target cell membrane and cell lysis. It is formed by the sequential assembly of terminal complement components (complement C5b; complement C6; complement C7; complement C8; and complement C9) into the target membrane. The resultant C5b-8-poly-c9 is the ‘membrane attack complex’ or MAC. Type II Hypersensitivity Reaction (MAC).
    • The reaction is classified as type 2 Type 2 Spinal Muscular Atrophy hypersensitivity reaction (i.e., it causes cytotoxic Cytotoxic Parvovirus B19 injury).
    • MAC causes a calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes influx that damages the postsynaptic membrane Postsynaptic membrane Synapses and Neurotransmission, which in turn damages the AChRs.
  • MuSK antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions:
    • Mostly IgG4 subtype
    • The pathogenesis is not exactly delineated.
  • Effects on neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction:
    • Damage to the AChRs leads to decreased binding of acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS, which in turn impairs signal transduction Transduction The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a gene transfer technique. Bacteriology at the neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction.
    • Decreased response causes failure of muscle contraction, which causes skeletal muscle weakness and fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia.
Myasthenia gravis pathophysiology

Pathophysiology of myasthenia gravis

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Clinical Presentation

General characteristics

  • Myasthenia gravis initially presents as a specific muscle weakness that progresses through the day and worsens with exertion.
  • Around 50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship initially present with ocular symptoms.
  • Fatigability is a hallmark feature, for example:
    • Diplopia onset or worsening after reading for a while
    • Adequate energy/strength at the onset of a task that wanes with time
  • Absence of sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology symptoms/findings
  • Normal deep tendon reflexes Deep Tendon Reflexes Neurological Examination (DTRs)
  • Normal autonomic function

Ocular symptoms

Ptosis in myasthenia gravis

Ptosis Ptosis Cranial Nerve Palsies in a patient with myasthenia gravis

Image: “Myasthenia Gravis” by Posey & Spiller. License: Public Domain

Bulbar symptoms Bulbar Symptoms Botulism

  • Dysarthria Dysarthria Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from cranial nerve diseases; neuromuscular diseases; cerebellar diseases; basal ganglia diseases; brain stem diseases; or diseases of the corticobulbar tracts. The cortical language centers are intact in this condition. Wilson’s Disease
  • Dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia
  • Nasal/hypophonic speech
  • Weak mastication Mastication The act and process of chewing and grinding food in the mouth. Jaw and Temporomandibular Joint: Anatomy
  • Nasal regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)/aspiration

Facial symptoms

  • Facial paralysis
  • Myasthenic sneer/snarling expression: drooping of the corner of the mouth

Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess and limb symptoms

  • Dropped head syndrome: Weakening of the extensor muscles leads to dropping of the head, which in turn causes pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in the posterior neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess muscles owing to an effort to keep the head straight.
  • The proximal muscles are more involved than the distal muscles.
  • The arm Arm The arm, or “upper arm” in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior). Arm: Anatomy muscles are more involved than the leg Leg The lower leg, or just “leg” in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg: Anatomy muscles.

Respiratory symptoms

  • Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
  • Weak breathing
  • Respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure: rare but serious cause of morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status (< 1%)

Cholinergic crisis

  • Life-threatening acute exacerbation of symptoms of MG
  • Myasthenia crisis presents as:
    • Buildup of saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy that causes drooling Drooling Peritonsillar Abscess
    • Jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint: Anatomy or tongue Tongue The tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy weakness
    • Dysarthria Dysarthria Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from cranial nerve diseases; neuromuscular diseases; cerebellar diseases; basal ganglia diseases; brain stem diseases; or diseases of the corticobulbar tracts. The cortical language centers are intact in this condition. Wilson’s Disease
    • Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea/labored breathing/shallow breathing
    • Respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure due to weakness in the diaphragmatic and intercostal muscles Intercostal Muscles Respiratory muscles that arise from the lower border of one rib and insert into the upper border of the adjoining rib, and contract during inspiration or respiration. Chest Wall: Anatomy
  • Seen in around 15%–20% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with MG
  • Mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing is often required.

Aggravating factors for disease exacerbation

  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
  • Stress or exertion
  • Infection
  • Irregularity in taking MG medication
  • Sudden or inappropriate tapering of immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants
  • Medications:
    • Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers)
    • Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers
    • Phenytoin Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. First-Generation Anticonvulsant Drugs
    • Quinidine Quinidine An optical isomer of quinine, extracted from the bark of the cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potentials, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission. Class 1 Antiarrhythmic Drugs (Sodium Channel Blockers) 
    • Lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly
    • Aminoglycosides Aminoglycosides Aminoglycosides are a class of antibiotics including gentamicin, tobramycin, amikacin, neomycin, plazomicin, and streptomycin. The class binds the 30S ribosomal subunit to inhibit bacterial protein synthesis. Unlike other medications with a similar mechanism of action, aminoglycosides are bactericidal. Aminoglycosides
    • Ketamine Ketamine A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (n-methyl-d-aspartate receptors) and may interact with sigma receptors. Intravenous Anesthetics
    • Lidocaine Lidocaine A local anesthetic and cardiac depressant used as an antiarrhythmic agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. Local Anesthetics
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care and the postpartum period Postpartum period In females, the period that is shortly after giving birth (parturition). Postpartum Complications
  • Menstruation Menstruation The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle, premenstrual syndrome Premenstrual Syndrome A combination of distressing physical, psychologic, or behavioral changes that occur during the luteal phase of the menstrual cycle. Symptoms of pms are diverse (such as pain, water-retention, anxiety, cravings, and depression) and they diminish markedly 2 or 3 days after the initiation of menses. Premenstrual Dysphoric Disorder
  • Progression of chronic conditions (cardiac/renal/ autoimmune diseases Autoimmune diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. Selective IgA Deficiency)

Diagnosis

Serologic tests

  • Serum detection of antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against AChRs:
    • Performed with prominent objective weakness
    • Highly specific: around 80% in generalized MG and 30%–40% in ocular myasthenia
  • 3 variations of AChR antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions:
    • Binding antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions:
      • Activate complement → loss of AChRs
      • Sensitivity is high.
      • False positives are rare.
    • Modulating antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions:
      • Causes antigenic modulation → receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors endocytosis Endocytosis Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. The Cell: Cell Membrane
      • 2%–4% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with negative binding antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions will have modulating antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions.
      • 73% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with thymoma Thymoma A neoplasm originating from thymic tissue, usually benign, and frequently encapsulated. Although it is occasionally invasive, metastases are extremely rare. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant. Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin’s disease (previously termed granulomatous thymoma), should not be regarded as thymoma. Primary Lymphatic Organs and MG will have modulating antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions.
    • Blocking antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions:
      • Act as a competitive antagonist at the AChR
      • Present in 50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with generalized MG and 30% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with ocular MG
      • < 1% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have only blocking antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions (without detectable binding or modulating antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions).
  • Other antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions tested are:
    • Anti-MuSK antibody
    • Anti– striated muscle Striated muscle One of two types of muscle in the body, characterized by the array of bands observed under microscope. Striated muscles can be divided into two subtypes: the cardiac muscle and the skeletal muscle. Muscle Tissue: Histology antibody (present in 80% of thymomatous MG)
    • Anti–lipoprotein-related protein 4 antibody
    • Anti-agrin antibody
  • Antinuclear antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions and rheumatoid factor Rheumatoid factor Antibodies found in adult rheumatoid arthritis patients that are directed against gamma-chain immunoglobulins. Autoimmune Hepatitis are tested to rule out systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus.

Clinical tests

  • Ice-pack test:
    • Principle: Lower temperatures improve neuromuscular transmission.
    • Procedure: Bag filled with ice is placed on the closed eyelid for 2 minutes, after which the bag is removed to assess the extent of ptosis Ptosis Cranial Nerve Palsies.
    • Inference: Improvement in ptosis Ptosis Cranial Nerve Palsies after 1-minute application is a positive result.
    • Sensitivity is around 80%.
  • Edrophonium/tensilon test:
    • This test is used only in areas where edrophonium is available. This test is currently not used in the United States, as the drug is not available.
    • Only used in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with obvious ptosis Ptosis Cranial Nerve Palsies or ophthalmoparesis
    • Principle: Edrophonium chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes is an acetylcholinesterase (AChE) inhibitor with a rapid onset and short duration of action.
    • Procedure:
      • An initial test dose of 2 mg is given, followed by another dose of 2 mg every 60 seconds until a response is elicited.
      • The maximum dose given is 10 mg.
    • Inference: Improvement in ptosis Ptosis Cranial Nerve Palsies is a positive result.

Electrodiagnostic tests

  • Nerve conduction velocity:
  • Single-fiber electromyography Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Becker Muscular Dystrophy (EMG):
    • This test measures the electrical activity of the impulses between the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and the muscle.
    • Small needles are inserted around the eyes, forehead Forehead The part of the face above the eyes. Melasma, and arms.
    • Disruption of signal transduction Transduction The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a gene transfer technique. Bacteriology (also known as “jitter”): present in > 90% MG cases

Imaging

MRI or CT of the chest is done to rule out the possibility of a thymoma Thymoma A neoplasm originating from thymic tissue, usually benign, and frequently encapsulated. Although it is occasionally invasive, metastases are extremely rare. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant. Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin’s disease (previously termed granulomatous thymoma), should not be regarded as thymoma. Primary Lymphatic Organs.

Ct thymoma

CT scan showing a large thymoma Thymoma A neoplasm originating from thymic tissue, usually benign, and frequently encapsulated. Although it is occasionally invasive, metastases are extremely rare. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant. Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin’s disease (previously termed granulomatous thymoma), should not be regarded as thymoma. Primary Lymphatic Organs

Image: “Association between thymoma Thymoma A neoplasm originating from thymic tissue, usually benign, and frequently encapsulated. Although it is occasionally invasive, metastases are extremely rare. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant. Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin’s disease (previously termed granulomatous thymoma), should not be regarded as thymoma. Primary Lymphatic Organs and persistent hypothermia Hypothermia Hypothermia can be defined as a drop in the core body temperature below 35°C (95°F) and is classified into mild, moderate, severe, and profound forms based on the degree of temperature decrease. Hypothermia: a case report” by Johns RH, Reinhardt AK AK Actinic keratosis (AK) is a precancerous skin lesion that affects sun-exposed areas. The condition presents as small, non-tender macules/papules with a characteristic sandpaper-like texture that can become erythematous scaly plaques. Actinic Keratosis. License: CC BY 2.0

Management

Pharmacotherapy

Acetylcholinesterase inhibitors:

  • Useful for mild and moderate forms of MG
  • Increase the amount of acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS available by preventing its breakdown
  • The most commonly used drug is pyridostigmine Pyridostigmine A cholinesterase inhibitor with a slightly longer duration of action than neostigmine. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants. Cholinomimetic Drugs, an oral AChE inhibitor.
  • Usually combined with the immunosuppressive agents:
    • In generalized MG
    • In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship symptomatic even after being on pyridostigmine Pyridostigmine A cholinesterase inhibitor with a slightly longer duration of action than neostigmine. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants. Cholinomimetic Drugs therapy
  • Adverse effects (muscarinic):
    • Abdominal cramps Cramps Ion Channel Myopathy
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
    • Bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias
    • Increased salivation
    • Increased bronchial secretions

Chronic immunosuppressive drugs Immunosuppressive drugs Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-cells or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. Organ Transplantation:

  • Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids:
    • The most common glucocorticoid used is prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants.
    • Transient worsening of symptoms is a common adverse effect of glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids; hence, an initial dose-escalation regimen is considered.
    • After the required dose is achieved, the dose is kept constant for a while and gradual tapering of the drug is considered to avoid a relapse Relapse Relapsing Fever.
    • Adverse effects:
      • Weight gain
      • Easy bruising Easy bruising Chédiak-Higashi Syndrome
      • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
      • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
      • Osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis 
    • Monitoring:
      • Appropriate diet, calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes and vitamin supplementation
      • Periodic measurement of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types density
      • Routine monitoring of blood pressure and serum glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance
      • Yearly cataract Cataract Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). Neurofibromatosis Type 2 and glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma test
      • Pneumocystis pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia prophylaxis Prophylaxis Cephalosporins in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship on a higher dosage Dosage Dosage Calculation of prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants
  • Nonsteroidal immunosuppressive drugs Immunosuppressive drugs Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-cells or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. Organ Transplantation:
    • Azathioprine Azathioprine An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the fourth annual report on carcinogens, this substance has been listed as a known carcinogen. Immunosuppressants:
      • Purine analog that inhibits the synthesis Synthesis Polymerase Chain Reaction (PCR) of nucleic acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance
      • Interferes with T- and B-cell proliferation
      • Lowers AChR antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions 
    • Mycophenolate Mycophenolate Immunosuppressants mofetil: inhibits lymphocyte proliferation by blocking purine synthesis Synthesis Polymerase Chain Reaction (PCR) 
    • Tacrolimus Tacrolimus A macrolide isolated from the culture broth of a strain of streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. Immunosuppressants:
      • Inhibits calcineurin Calcineurin A calcium and calmodulin-dependent serine/threonine protein phosphatase that is composed of the calcineurin a catalytic subunit and the calcineurin B regulatory subunit. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones; myosin light chain; and the regulatory subunits of camp-dependent protein kinases. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes. Vitiligo and the production of IL-2 
      • Inhibits T-lymphocyte–dependent immune response
      • Adverse effects:
        • Hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus
        • Hypomagnesemia Hypomagnesemia A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. Electrolytes
        • Tremors
        • Paresthesia
    • Cyclosporin:
      • Action is similar to that of tacrolimus Tacrolimus A macrolide isolated from the culture broth of a strain of streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. Immunosuppressants
      • Adverse effects: nephrotoxicity Nephrotoxicity Glycopeptides and hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension

IV immune therapy

  • Plasmapheresis Plasmapheresis Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. Stevens-Johnson Syndrome:
    • Removes AChR or MuSK antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions from the circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment
    • Plasmapheresis Plasmapheresis Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. Stevens-Johnson Syndrome is considered only in an emergency such as dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia or respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure, as it is associated with adverse effects and is expensive.
    • Adverse effects observed are:
      • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
      • Infection
      • Thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus
    • Contraindicated in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
    • 1 session/day × 5 days
    • Onset of action: 3–10 days
    • Duration of action: 3–6 weeks
  • IV immunoglobulin Iv Immunoglobulin Dermatomyositis ( IVIG IVIG Dermatomyositis):
    • IV immunoglobulin Iv Immunoglobulin Dermatomyositis is also a treatment option considered only when there is an emergency, especially if respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure is the presenting symptom.
    • IV infusion of donor immunoglobulin can modulate the immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs and reduce the effects of autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques (can be performed through a peripheral IV).
    • Less effective in mild or moderate MG
    • Adverse effects:
      • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
      • Chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever
      • Dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome)
      • Fluid retention
      • Thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus
      • Anaphylaxis Anaphylaxis An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. Type I Hypersensitivity Reaction
      • Aseptic meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
      • Acute renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
    • Contraindicated in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
    • 0.4 g/kg/day × 5 days
    • Onset of action: 14 days
    • Duration of action: 30 days
  • Monoclonal antibodies Monoclonal antibodies Antibodies produced by a single clone of cells. Ebolavirus and Marburgvirus:
    • Rituximab Rituximab A murine-derived monoclonal antibody and antineoplastic agent that binds specifically to the cd20 antigen and is used in the treatment of leukemia; lymphoma and rheumatoid arthritis. Immunosuppressants: effective in the treatment of MuSK MG
    • Eculizumab:
      • Monoclonal antibody directed toward complement 5
      • Effective in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with generalized MG who are AchR antibody–positive 

Thymectomy

  • Research Research Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. Conflict of Interest suggests that in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who undergo thymectomy when indicated, remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches and decreased drug dependency are observed.
  • Indications are:
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with thymoma Thymoma A neoplasm originating from thymic tissue, usually benign, and frequently encapsulated. Although it is occasionally invasive, metastases are extremely rare. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant. Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin’s disease (previously termed granulomatous thymoma), should not be regarded as thymoma. Primary Lymphatic Organs
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship without thymoma Thymoma A neoplasm originating from thymic tissue, usually benign, and frequently encapsulated. Although it is occasionally invasive, metastases are extremely rare. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant. Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin’s disease (previously termed granulomatous thymoma), should not be regarded as thymoma. Primary Lymphatic Organs:
      • Positive anti-AChR antibody
      • < 60 years of age with generalized MG
  • Thymectomy is not recommended in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with MuSK antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions.

Management of cholinergic crisis

  • Intubation Intubation Peritonsillar Abscess/mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing may be performed electively prior to the development of emergent situations.
  • Cholinesterase Cholinesterase Liver Function Tests inhibitor therapy is stopped temporarily.
  • Rapid therapies include plasmapheresis Plasmapheresis Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. Stevens-Johnson Syndrome and IVIG IVIG Dermatomyositis.
  • Immunosuppressive drugs Immunosuppressive drugs Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-cells or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. Organ Transplantation are started at a moderate to high dose.

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

  • With the development in treatment over the decades, the prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship has significantly improved, and patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship can lead nearly normal lives.
  • Few cases can go into remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches either temporarily or permanently.
  • In 50% of the cases, thymectomy can lead to stable and complete remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches.

Differential Diagnosis

  • Eaton–Lambert syndrome: autoimmune neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction syndrome associated with small-cell lung carcinoma: Symptoms include muscle weakness (temporarily relieved on exertion), ptosis Ptosis Cranial Nerve Palsies, dry mouth, bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess and bowel changes, erectile dysfunction Erectile Dysfunction Erectile dysfunction (ED) is defined as the inability to achieve or maintain a penile erection, resulting in difficulty to perform penetrative sexual intercourse. Local penile factors and systemic diseases, including diabetes, cardiac disease, and neurological disorders, can cause ED. Erectile Dysfunction, and paresthesia. Eaton–Lambert syndrome is diagnosed by antibody detection, electromyography Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Becker Muscular Dystrophy, and imaging of lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy. Treatment includes immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants and addressing the malignancy Malignancy Hemothorax.
  • Guillain–Barré syndrome: autoimmune disorder Autoimmune Disorder Septic Arthritis of the peripheral nervous system Peripheral nervous system The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. Nervous System: Anatomy, Structure, and Classification triggered by an acute bacterial or viral infection: Guillain–Barré syndrome presents with initial paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Posterior Cord Syndrome in the feet and legs progressing to ascending paralysis. The syndrome is diagnosed by CSF analysis CSF analysis Meningitis, electromyography Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Becker Muscular Dystrophy, and nerve conduction studies. Guillain–Barré syndrome is managed with plasmapheresis Plasmapheresis Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. Stevens-Johnson Syndrome and immunoglobulin therapy, analgesics, blood thinners, and physiotherapy Physiotherapy Spinal Stenosis.
  • Amyotrophic lateral sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor: group of neurologic disorders that involve neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology associated with voluntary movement: Clinical presentation includes fasciculations Fasciculations Involuntary contraction of the muscle fibers innervated by a motor unit. Fasciculations may be visualized as a muscle twitch or dimpling under the skin, but usually do not generate sufficient force to move a limb. They may represent a benign condition or occur as a manifestation of motor neuron disease or peripheral nervous system diseases. Polyneuropathy, muscle cramps Cramps Ion Channel Myopathy, spasticity Spasticity Spinal Disk Herniation, and dysarthria Dysarthria Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from cranial nerve diseases; neuromuscular diseases; cerebellar diseases; basal ganglia diseases; brain stem diseases; or diseases of the corticobulbar tracts. The cortical language centers are intact in this condition. Wilson’s Disease, which are progressive over time. There is no definitive test, and diagnosis relies heavily on history and physical examination. Treatment includes supportive care, as no cure has been found yet.
  • Botulism Botulism Botulism is a rare, neuroparalytic syndrome caused by Clostridium botulinum (C. botulinum). A fatal neurotoxin (botulinum toxin) is released causing varying degrees of muscle paralysis and distinct clinical syndromes. The most common types of botulism are foodborne and infant. Botulism: foodborne infectious neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction disease caused by the organism Clostridium botulinum Clostridium botulinum A species of anaerobic, gram-positive, rod-shaped bacteria in the family clostridiaceae that produces proteins with characteristic neurotoxicity. It is the etiologic agent of botulism in humans, wild fowl, horses; and cattle. Seven subtypes (sometimes called antigenic types, or strains) exist, each producing a different botulinum toxin (botulinum toxins). The organism and its spores are widely distributed in nature. Clostridia. Clinically, botulism Botulism Botulism is a rare, neuroparalytic syndrome caused by Clostridium botulinum (C. botulinum). A fatal neurotoxin (botulinum toxin) is released causing varying degrees of muscle paralysis and distinct clinical syndromes. The most common types of botulism are foodborne and infant. Botulism presents with ptosis Ptosis Cranial Nerve Palsies, abdominal cramps Cramps Ion Channel Myopathy, symmetric neurologic deficits Neurologic Deficits High-Risk Headaches, diplopia, and blurred vision Blurred Vision Retinal Detachment. Botulism Botulism Botulism is a rare, neuroparalytic syndrome caused by Clostridium botulinum (C. botulinum). A fatal neurotoxin (botulinum toxin) is released causing varying degrees of muscle paralysis and distinct clinical syndromes. The most common types of botulism are foodborne and infant. Botulism is diagnosed by isolation of the organism and detection of toxin in the serum or food source. Botulism Botulism Botulism is a rare, neuroparalytic syndrome caused by Clostridium botulinum (C. botulinum). A fatal neurotoxin (botulinum toxin) is released causing varying degrees of muscle paralysis and distinct clinical syndromes. The most common types of botulism are foodborne and infant. Botulism is treated with botulinum antitoxin Botulinum antitoxin Antiserum given therapeutically in botulism. Botulism, immunoglobulin, and physiotherapy Physiotherapy Spinal Stenosis.
  • Tick paralysis: Tick paralysis is caused by injection of toxin through the bite of a tick. Symptoms occur within 2–7 days after the bite. Clinical presentation includes initial numbness and weakness in both legs that progresses to ascending paralysis and respiratory distress within hours. Deep tendon reflexes Deep Tendon Reflexes Neurological Examination are decreased or absent. Diagnosis is based on symptoms and finding an embedded tick, usually on the scalp. Managed by finding and removing the tick, cleaning the site of the bite, and monitoring for respiratory distress.

References

  1. Mayo Clinic. Myasthenia gravis (2019). https://www.mayoclinic.org/diseases-conditions/myasthenia-gravis/symptoms-causes/syc-20352036
  2. Goldenberg, W.D., Sinert, R.H. (2018). Emergent management of myasthenia gravis. Medscape. https://emedicine.medscape.com/article/793136-overview#a1
  3. Bird, S.J. (2020). Pathogenesis of myasthenia gravis. UpToDate. https://www.uptodate.com/contents/pathogenesis-of-myasthenia-gravis
  4. Bird, S.J. (2019). Clinical manifestations of myasthenia gravis. UpToDate. https://www.uptodate.com/contents/clinical-manifestations-of-myasthenia-gravis
  5. Philips, W.D., Vincent, A. (2016). Pathogenesis of myasthenia gravis. NCBI. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926737/
  6. Jowkar, A., Goldenberg, W.D (2018). Myasthenia gravis. Medscape. https://emedicine.medscape.com/article/1171206-overview#a1
  7. Longo, D. L. Fauci, A. S. Kasper, Hauser, S., Jameson, J. L., Loscalzo, J. (2011). Myasthenia gravis and other diseases of the neuromuscular junction. Harrison’s Principles of Internal medicine. 18th ed. pp. 6813–6824.

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