Guillain-Barré Syndrome

Overview

Definition

• Guillain-Barré syndrome ( GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy) is an immune-mediated polyneuropathy Polyneuropathy Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. Polyneuropathy 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. This condition may occur after an infection. 
• Known causative infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease: 
  • Campylobacter jejuni Campylobacter jejuni A species of bacteria that resemble small tightly coiled spirals. Its organisms are known to cause abortion in sheep and fever and enteritis in man and may be associated with enteric diseases of calves, lambs, and other animals. Campylobacter (most commonly identified agent)
  • Cytomegalovirus Cytomegalovirus CMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus
  • Mycoplasma pneumoniae Mycoplasma pneumoniae Short filamentous organism of the genus mycoplasma, which binds firmly to the cells of the respiratory epithelium. It is one of the etiologic agents of non-viral primary atypical pneumonia in man. Mycoplasma
  • Epstein-Barr virus Epstein-Barr Virus Epstein-Barr virus (EBV) is a linear, double-stranded DNA virus belonging to the Herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus
  • Zika virus Zika virus An arbovirus in the flavivirus genus of the family flaviviridae. Originally isolated in the zika forest of uganda it has been introduced to Asia and the americas. Zika Virus Infection
  • Vaccinations (e.g., flu shot)

Epidemiology

• 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: 1–2 cases per 100,000 person-years 
• Most common cause of acute flaccid paralysis Acute flaccid paralysis West Nile Virus 
• Higher prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency among males than among females
• 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 rises with age.

Pathophysiology

• Molecular mimicry Molecular Mimicry The structure of one molecule that imitates or simulates the structure of a different molecule. Rheumatic Fever:
  • Infection triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) normal immune response.
  • Unidentified infectious antigens create autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques that attack gangliosides of the axonal myelin sheath.
  • 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 forms on the surface of Schwann cells.
  • Macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation target myelin.
  • Inflammatory demyelinating polyneuropathy Polyneuropathy Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. Polyneuropathy occurs.
• Motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology axonal neuropathy Neuropathy Leprosy: 
  • 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 bind BIND Hyperbilirubinemia of the Newborn to nodes in the myelinated Myelinated Internuclear Ophthalmoplegia axons Axons Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. Nervous System: Histology are formed. 
  • Depending on the particular node, voltage-gated sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia channels Channels The Cell: Cell Membrane or paranodal myelin may be attacked.
  • This results in failure in nerve conduction and subsequent muscle weakness.

Clinical Presentation

Clinical symptoms vary based on the subtype of GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy. Individuals may have a history of respiratory or GI symptoms 1–4 weeks prior to the appearance of GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy.

Acute inflammatory demyelinating polyneuropathy Polyneuropathy Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. Polyneuropathy (AIDP)

• Most common form of GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy
• Symmetric weakness and paresthesia
• Ascending flaccid paralysis that typically begins in the lower extremities.
• Dysautonomia also commonly appears (in 70% of cases), causing:
  • 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/ constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation 
  • 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/ tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children 
  • Urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium 
  • Horner syndrome Horner syndrome Horner syndrome is a condition resulting from an interruption of the sympathetic innervation of the eyes. The syndrome is usually idiopathic but can be directly caused by head and neck trauma, cerebrovascular disease, or a tumor of the CNS. Horner Syndrome
• Decreased or absent deep tendon reflexes Deep Tendon Reflexes Neurological Examination of the affected limbs 
• Progression is relatively rapid (within 8 weeks) and progressive (without intermittent improvement and relapses).
• Cranial nerve palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies: facial palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies

Acute motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology axonal neuropathy Neuropathy Leprosy (AMAN)

• Most commonly associated with C. jejuni infection
• Deep tendon reflexes Deep Tendon Reflexes Neurological Examination commonly spared
• Sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology nerves not affected
• Other symptoms similar to AIDP

Acute motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology and sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology axonal neuropathy Neuropathy Leprosy (AMSAN)

• Similar to AMAN, but more severe
• Both sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology and motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology fibers affected 
• Marked axonal degeneration

Miller Fisher variant

• One of the major forms of GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy
• Characteristic symptoms:
  • Ophthalmoplegia Ophthalmoplegia Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. Orbital and Preseptal Cellulitis
  • Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia
  • Areflexia Areflexia Duchenne Muscular Dystrophy
  • Only ¼ of cases involve motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology weakness of limbs

Bickerstaff encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis

• 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 stem encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis 
• Symptoms include:
  • Encephalopathy Encephalopathy Hyper-IgM Syndrome 
  • Hyperreflexia 
  • Ophthalmoplegia Ophthalmoplegia Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. Orbital and Preseptal Cellulitis 
  • Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia

Pharyngeal-cervical-brachial weakness

• Weakness of the oropharyngeal, neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, and shoulder muscles 
• Swallowing Swallowing The act of taking solids and liquids into the gastrointestinal tract through the mouth and throat. Gastrointestinal Motility dysfunction
• Facial weakness
• Lower-extremity strength and reflexes preserved

Paraparesis

• Mild variant
• Isolated weakness of the lower extremities 
• Rare in upper extremities 
• Reduced or absent 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 reflexes 
• Electrodiagnostic studies of upper extremities abnormal in 90%

Diagnosis

General approach

• Initial diagnosis is based on clinical presentation and medical history.
• Features that are unlikely for GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy:
  • Asymmetric pattern of weakness
  • 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/bowel dysfunction at onset
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever at onset 
  • Respiratory dysfunction without limb weakness at onset 
  • Hyperreflexia

Additional workup

• Confirmatory workup:
  • CSF analysis CSF analysis Meningitis: often shows elevated protein with no WBCs
  • Nerve conduction studies: 
    • Serves to distinguish axonal from demyelinating form of neuropathy Neuropathy Leprosy
    • Decreased velocity of conduction 
    • Reduced amplitude in compound muscle action potentials
  • Electromyography Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Becker Muscular Dystrophy:
    • Serves to distinguish from pathology in neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction 
    • Common findings on electromyography Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Becker Muscular Dystrophy include motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology conduction block and temporal dispersion Dispersion Central tendency is a measure of values in a sample that identifies the different central points in the data, often referred to colloquially as “averages.” The most common measurements of central tendency are the mean, median, and mode. Identifying the central value allows other values to be compared to it, showing the spread or cluster of the sample, which is known as the dispersion or distribution. Measures of Central Tendency and Dispersion.
  • Serum IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis 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 to GQ1b: 90% sensitive for Miller Fisher syndrome
• MRI:
  • Not a routine diagnostic tool
  • Can exclude stroke, spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy lesions, malignancy Malignancy Hemothorax, etc ETC The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC). 

Management

Criteria for ICU ICU Hospital units providing continuous surveillance and care to acutely ill patients. West Nile Virus admission

• 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 requiring intubation Intubation Peritonsillar Abscess and 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 
• Airway Airway ABCDE Assessment compromise: 
  • Presents with diminished cough reflex or swallowing Swallowing The act of taking solids and liquids into the gastrointestinal tract through the mouth and throat. Gastrointestinal Motility dysfunction 
  • Intubation Intubation Peritonsillar Abscess and 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
• Autonomic cardiovascular dysfunction:
  • 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
  • Atrioventricular blocks and asystole Asystole No discernible electrical activity, flatline on electrocardiogram (P waves and QRS complexes are not present). Cardiac Arrest

Immunomodulatory therapy

• Started when individuals are unable to ambulate independently or show severe symptoms or rapid progressive weakness.
• 2 major options:
  • Intravenous immunoglobulin ( IVIG IVIG Dermatomyositis)
  • Plasma exchange Plasma exchange Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (ppf), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. Thrombotic Thrombocytopenic Purpura 
  • Both equally effective, with similar risks of complications 
  • Treatment may be repeated; however, plasma exchange Plasma exchange Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (ppf), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. Thrombotic Thrombocytopenic Purpura must not follow IVIG IVIG Dermatomyositis, as it would wash away the immunoglobulin.

Monitoring

• Always monitor for respiratory insufficiency.
• Changes in blood pressure and new-onset arrhythmias may occur.
• To prevent pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism for those with limited mobility
• Psychological distress must be managed early with sufficient education of the individual.
• Physical rehabilitation focusing on improving physical function, 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, and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways is necessary to avoid long-term residual problems of GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy.

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

• Most show significant recovery within 1 year after onset.
• Recurrence is rare; however, those who had GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy are more likely than the general population to get GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy again.
• Mortality Mortality All deaths reported in a given population. Measures of Health Status (estimated 3%–10%) is mostly secondary to cardiovascular/respiratory complications. 

Differential Diagnosis

• Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis: 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 Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. 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 Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis, 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 on the basis of 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. 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 Thymectomy Surgical removal of the thymus gland. Myasthenia Gravis is sometimes indicated. The disease can progress to a life-threatening cholinergic crisis Cholinergic Crisis Myasthenia Gravis 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 individuals can achieve long-term remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches.
• Rabies Rabies Acute viral CNS infection affecting mammals, including humans. It is caused by rabies virus and usually spread by contamination with virus-laden saliva of bites inflicted by rabid animals. Important animal vectors include the dog, cat, bat, fox, raccoon, skunk, and wolf. Rabies Virus: infectious disease caused by a single-stranded, negative-sense RNA Negative-sense RNA RNA viruses that have their genetic material encoded in the form of single-stranded, negative-sense RNA. Unlike retroviruses they do not employ DNA intermediates in their life-cycle. Respiratory Syncytial Virus virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology. This bullet-shaped Bullet-shaped Rabies Virus virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology belongs to the family Rhabdoviridae Rhabdoviridae A family of bullet-shaped viruses of the order mononegavirales, infecting vertebrates, arthropods, protozoa, and plants. Genera include vesiculovirus; lyssavirus; ephemerovirus; novirhabdovirus; cytorhabdovirus; and nucleorhabdovirus. Rabies Virus and the genus Lyssavirus Lyssavirus A genus of the family rhabdoviridae that includes rabies virus and other rabies-like viruses. Rabies Virus. Rabies Rabies Acute viral CNS infection affecting mammals, including humans. It is caused by rabies virus and usually spread by contamination with virus-laden saliva of bites inflicted by rabid animals. Important animal vectors include the dog, cat, bat, fox, raccoon, skunk, and wolf. Rabies Virus is a preventable disease most often transmitted to humans through the bite of an infected animal (e.g., bats, raccoons, skunks, and foxes). This life-threatening disease affects the CNS, resulting in severe neurologic manifestations. There are 5 stages of the disease in humans: incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus, prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache, acute neurologic period Acute neurologic period Rabies Virus, coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma, and death. The diagnosis is made with antibody, antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination, or viral RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure detection in a tissue biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma specimen, serum, CSF, and 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. There is no effective treatment for symptomatic disease, so prevention with human rabies Rabies Acute viral CNS infection affecting mammals, including humans. It is caused by rabies virus and usually spread by contamination with virus-laden saliva of bites inflicted by rabid animals. Important animal vectors include the dog, cat, bat, fox, raccoon, skunk, and wolf. Rabies Virus immunoglobulin and vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination is the mainstay of management.
• Progressive multifocal Multifocal Retinoblastoma leukoencephalopathy ( PML PML An opportunistic viral infection of the central nervous system associated with conditions that impair cell-mediated immunity (e.g., acquired immunodeficiency syndrome and other immunologic deficiency syndromes; hematologic neoplasms; immunosuppression; and collagen diseases). The causative organism is JC polyomavirus (JC virus) which primarily affects oligodendrocytes, resulting in multiple areas of demyelination. Clinical manifestations include dementia; ataxia; visual disturbances; and other focal neurologic deficits, generally progressing to a vegetative state within 6 months. JC Virus and BK Virus): demyelinating disease of the CNS caused by polyomavirus JC virus JC Virus JC virus (JCV) is a small, nonenveloped, single-stranded DNA virus belonging to the Polyomaviridae family, which are ubiquitous in the human population. While the primary infection is usually asymptomatic, the infection leads to lifelong latency in the kidneys and lymphoid organs. JC Virus and BK Virus, which causes disease only among those who are immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis. Presentation is with cognitive impairments, ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia, aphasia Aphasia A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. Ischemic Stroke, or other symptoms depending on the location of the lesion. Progressive multifocal Multifocal Retinoblastoma leukoencephalopathy is diagnosed with 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 imaging, CT, or MRI, which show nonenhancing white matter White Matter The region of central nervous system that appears lighter in color than the other type, gray matter. It mainly consists of myelinated nerve fibers and contains few neuronal cell bodies or dendrites. Brown-Séquard Syndrome lesions and with CSF analysis CSF analysis Meningitis with PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) testing positive for the virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology. Management is supportive and aims to reverse the cause of immunosuppression. 
• 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: rare neuroparalytic syndrome caused by 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, which releases a fatal neurotoxin ( botulinum toxin Botulinum toxin Toxic proteins produced from the species Clostridium botulinum. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon endocytosis into presynaptic nerve endings. Once inside the cell the botulinum toxin light chain cleaves specific snare proteins which are essential for secretion of acetylcholine by synaptic vesicles. This inhibition of acetylcholine release results in muscular paralysis. Botulism) causing varying degrees of muscle paralysis and distinct clinical syndromes. The 2 most common types are foodborne and infant botulism Infant Botulism Botulism. 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 symmetric descending flaccid paralysis, blurred vision Blurred Vision Retinal Detachment, and 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 and is characterized by intact sensorium, normal heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology and blood pressure, absence of fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, and absence of sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology deficits. Diagnosis is made on clinical grounds and can be confirmed by the isolation of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology or toxins from stool, wound specimens, or food sources. The approach to managing a case of 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 should include prompt management of 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, administration of antitoxin, and supportive care for paralysis.