Botulism

Overview

Definition

Botulism is a rare, neuroparalytic syndrome caused by the 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 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 ( C. botulinum C. 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), resulting in varying degrees of muscle paralysis and distinct clinical syndromes.

Epidemiology

• Approximately 110 cases per year in the US (rare disease)
• Can occur in any age group
• No person-to-person transmission
• C. botulinum C. 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 is found in soil and marine sediments worldwide.
• The most common types are foodborne and infantile botulism. 
• The least common type is adult intestinal toxemia.

Etiology

• Pathogen C. botulinum C. 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:
  • Gram-positive Gram-Positive Penicillins bacillus Bacillus Bacillus are aerobic, spore-forming, gram-positive bacilli. Two pathogenic species are Bacillus anthracis (B. anthracis) and B. cereus. Bacillus
  • Anaerobic, spore-forming 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
  • Found in soil and marine sediments worldwide
  • 4 distinct phenotypes: I–IV
• Botulinum toxin:
  • Neurotoxic protein produced by C. botulinum C. 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
  • Classified into 7 serotypes: A–G
  • A, B, E, and F cause disease in humans.
  • A and B are used commercially and medically.
  • Blocks the release of the neurotransmitter 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 ( ACh ACh 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 (NMJ)
• Conditions favorable for pathogen growth and spore Spore The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Microsporidia/Microsporidiosis formation:
  • Low O₂ or no O₂ (anaerobic conditions)
  • pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance of 7 and above
  • Ideal temperature range: 25℃–37℃
  • Survive in temperatures as low as 4℃ and as high as 100℃

Classification

Infant botulism

• Mode of infection: ingestion of C. botulinum C. 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 spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax
• The toxin is produced in vivo ( 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 germinate in the GI tract).
• Common occurrence in infants < 6 months of age (natural defenses have not yet developed in the intestine)
• The most common product causing infant botulism is raw honey.

Foodborne botulism

• Mode of infection: ingestion of food contaminated with C. botulinum C. 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 toxin
• Commonly found in inadequately canned foods with low-acid content and lightly preserved food products (e.g., fermented, salted, or smoked meat products)
• Dangerous: may infect many people at once who consume food from the same source

Wound botulism

• Mode of infection: Spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax of C. botulinum C. 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 enter an open wound and thrive under anaerobic conditions.
• Rare form of botulism
• Can result from contamination of the wound by soil, gravel, or inappropriately treated open fractures
• Commonly associated with substance use of black tar heroin Heroin A narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of federal regulations, title 21 parts 329. 1, 1308. 11 (1987). Sale is forbidden in the United States by federal statute. Nephrotic Syndrome disorder

Iatrogenic Iatrogenic Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment. Anterior Cord Syndrome botulism

• Mode of infection: botulinum toxin injections for cosmetic or therapeutic/medical purposes (e.g., migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache, contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing, spasticity Spasticity Spinal Disk Herniation)
• Another rare form of botulism
• A highly concentrated preparation of the toxin can cause iatrogenic Iatrogenic Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment. Anterior Cord Syndrome botulism.

Adult intestinal toxemia

• Mode of infection: ingestion of spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax of C. botulinum C. 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
• Least common form of botulism 
• Similar to infantile botulism but occurs in older children and adults with bowel abnormalities or disruption of the normal intestinal flora (e.g., inflammatory bowel disease)

Inhalation botulism

• Does not occur naturally
• Associated with the accidental or intentional release of toxin in aerosols Aerosols Colloids with a gaseous dispersing phase and either liquid (fog) or solid (smoke) dispersed phase; used in fumigation or in inhalation therapy; may contain propellant agents. Coxiella/Q Fever ( bioterrorism Bioterrorism The use of biological agents in terrorism. This includes the malevolent use of bacteria; viruses; or other biological toxins against people, animals; or plants. Anthrax associated botulism)
• Clinical presentation is similar to foodborne botulism.
• A lethal dose is 2 ng/kg of bodyweight.

Pathophysiology

The means of exposure to the toxin will determine the type of botulism; the toxin is not absorbed through intact skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions.

Exposure can occur through the following mechanisms:

• Ingestion of preformed toxin
• Inhalation of preformed toxin
• Production of toxin by C. botulinum C. 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 in the GI tract
• Production of toxin by C. botulinum C. 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 in devitalized tissue at the site of a wound
• Exposure to the toxin by injection for cosmetic or therapeutic/medical purposes

Mechanism of pathogenesis:

• Botulinum toxin is activated by proteolytic cleavage in the circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment and transported to the neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction (NMJ).
• Botulinum toxin exists in the circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment as a polymer of a light chain and a heavy chain.
• The heavy chain of the toxin binds to 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 on the presynaptic neuron Presynaptic neuron Synapses and Neurotransmission and enters the presynaptic neuron Presynaptic neuron Synapses and Neurotransmission via receptor-mediated endocytosis Endocytosis Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. The Cell: Cell Membrane.
• Once inside the endocytotic vesicles Vesicles Female Genitourinary Examination of the presynaptic neuron Presynaptic neuron Synapses and Neurotransmission, the light chain of the toxin crosses the membrane of the endocytotic vesicle Vesicle Primary Skin Lesions and enters the cytoplasm.
• Once in the cytoplasm, the light chain binds SNARE/SNAP proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis, which are involved in the release of ACh ACh 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 from the presynaptic vesicles Vesicles Female Genitourinary Examination where it is stored.
• The inhibition of ACh ACh 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 release prevents ACh ACh 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 from binding to the ACh ACh 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, which halts muscle contraction and leads to weakness/paralysis.

Clinical Presentation

General characteristics

The classic presentation of botulism includes symmetric cranial nerve palsies Cranial Nerve Palsies Cranial nerve palsy is a congenital or acquired dysfunction of 1 or more cranial nerves that will, in turn, lead to focal neurologic abnormalities in movement or autonomic dysfunction of its territory. Head/neck trauma, mass effect, infectious processes, and ischemia/infarction are among the many etiologies for these dysfunctions. Diagnosis is initially clinical and supported by diagnostic aids. Management includes both symptomatic measures and interventions aimed at correcting the underlying cause. Cranial Nerve Palsies and descending paralysis. The 5 key features of botulism include: 

1. 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
2. Symmetric neurologic deficits Neurologic Deficits High-Risk Headaches: symmetric, descending flaccid paralysis of voluntary muscles (begins as proximal muscle weakness Proximal Muscle Weakness Lambert-Eaton Myasthenic Syndrome and progresses distally)
3. Intact sensorium and mental status
4. Normal or slow heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology and normal blood pressure
5. No sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology deficits (except blurred vision Blurred Vision Retinal Detachment)

Cranial neuropathies are common in all types of botulism. The classic presentation includes the “4 Ds” (bulbar symptoms):

1. Diplopia: The 1st clinical symptom/sign is often extraocular involvement.
2. Dysarthria
3. Dysphonia
4. Dysphagia

Botulism does present with autonomic findings:

• Pupillary (dilated, fixed pupils)
• Reduced salivation
• Reduced lacrimation
• Paralytic ileus Paralytic ileus Small Bowel Obstruction/severe 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
• Gastric dilatation
• 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 distention/ urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium
• Orthostatic hypotension Orthostatic hypotension A significant drop in blood pressure after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm hg decrease in systolic pressure or a 10-mm hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include dizziness, blurred vision, and syncope. Hypotension

Infant botulism

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period: 3–30 days after spore Spore The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Microsporidia/Microsporidiosis entry
• Commonly occurs in infants < 6 months of age
• 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: often the 1st sign
• Drooling Drooling Peritonsillar Abscess
• Weak cry
• Irritability
• Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
• Floppy baby syndrome:
  • Bilateral ptosis Ptosis Cranial Nerve Palsies
  • Loss of head control, floppy movements/ hypotonia Hypotonia Duchenne Muscular Dystrophy
  • General weakness/ lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia
  • Poor feeding (weak sucking)

Foodborne botulism

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period: 12–36 hours after toxin consumption
• Prodromal symptoms:
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, 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, and abdominal cramps Cramps Ion Channel Myopathy
  • Initial 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 (direct toxin effect in GI endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology) progresses to 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 (as systemic NMJ manifestations dominate).
• Dry mouth
• Difficulty swallowing Swallowing The act of taking solids and liquids into the gastrointestinal tract through the mouth and throat. Gastrointestinal Motility or speaking 
• Symmetric facial weakness
• Blurred vision Blurred Vision Retinal Detachment
• Cranial neuropathies Neuropathies Chédiak-Higashi Syndrome
• Difficulty breathing

Wound botulism

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period difficult to estimate (timing of exposure usually uncertain)
• Symptoms are similar to foodborne botulism, except prodromal symptoms are absent.
• Wound botulism presents with 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 leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus in around 50% of cases; other forms of botulism do not typically present with a 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
• Difficulty swallowing Swallowing The act of taking solids and liquids into the gastrointestinal tract through the mouth and throat. Gastrointestinal Motility or speaking
• Symmetric facial weakness
• Blurred or double vision Vision Ophthalmic Exam
• Ptosis Ptosis Cranial Nerve Palsies
• Difficulty breathing
• Descending paralysis
• Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation at the site of the wound

Iatrogenic Iatrogenic Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment. Anterior Cord Syndrome botulism

• After injection of botulinum toxin for cosmetic or therapeutic/medical purposes
• Ptosis Ptosis Cranial Nerve Palsies
• Difficulty speaking
• Paralysis of face
• Thick and weak 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
• Reduced gag reflex Gag Reflex Cranial Nerve Palsies

Adult intestinal toxemia

• Similar to infant botulism but occurs in older children and adults 
• 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
• Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
• Lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia
• Descending paralysis 
• Ptosis Ptosis Cranial Nerve Palsies

Inhalation botulism

• Symptoms are similar to foodborne botulism.
• Can develop early and quickly progress to 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
• 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 
• Dry mouth
• Difficulty swallowing Swallowing The act of taking solids and liquids into the gastrointestinal tract through the mouth and throat. Gastrointestinal Motility or speaking 
• Symmetric facial weakness
• Blurred vision Blurred Vision Retinal Detachment
• Cranial neuropathies Neuropathies Chédiak-Higashi Syndrome
• Difficulty breathing

Diagnosis

History

• Consumption of canned foods
• Symptoms similar in individuals with similar exposure
• History of injectable drug use disorder
• History of cosmetic/medical use of botulinum toxin
• Acute onset of floppy baby syndrome symptoms
• History of honey consumption in babies

Physical examination

• Acute onset of symptoms of cranial neuropathy Neuropathy Leprosy 
• Symmetric descending weakness
• 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
• Alert and conscious patient with neurologic symptoms

Confirmation of diagnosis

• Isolation of C. botulinum C. 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 from stool, wound specimen, or food source
• ELISA ELISA An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. St. Louis Encephalitis Virus or 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) detection of toxin in serum, stool, vomit, or food source
• Other tests:
  • MRI or CT: to rule out other reasons for neurologic symptoms (e.g., stroke)
  • CSF exam: to rule out 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 
  • Electromyography Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Becker Muscular Dystrophy (EMG): for suspected infant botulism 
  • Tensilon test:
    • To rule out 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
    • Not conducted at present (unavailable in the US) because of a high occurrence of false positive False positive An FP test result indicates that a person has the disease when they do not. Epidemiological Values of Diagnostic Tests results

Management

A detailed clinical history and diagnosis are important in botulism, as the tests take time. If a case history is highly suggestive of botulism, treatment should not be delayed.

General approach

• Hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
• Monitor for signs 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:
  • Pulse oximetry
  • Spirometry Spirometry Measurement of volume of air inhaled or exhaled by the lung. Pulmonary Function Tests
  • Arterial blood gas Arterial blood gas Respiratory Alkalosis measurement
  • If inadequate/worsening upper airway Airway ABCDE Assessment competency, or in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a vital capacity Vital capacity The volume of air that is exhaled by a maximal expiration following a maximal inspiration. Ventilation: Mechanics of Breathing < 30%, prompt intubation Intubation Peritonsillar Abscess is indicated.
• For supportive care, provide nasogastric feeding in small amounts to prevent aspiration.
• Administration of antitoxin

Antitoxin

Antitoxin is the mainstay of botulism treatment. Two major forms are available in the United States:

Heptavalent botulinum antitoxin:

• Equine serum heptavalent antitoxin: contains 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 7 types of botulinum toxin 
• Binds to circulating neurotoxins and prevents NMJ binding
• The antitoxin cannot reverse paralysis but can prevent paralysis progression. 
• Antitoxin administration within 24 hours of the onset of symptoms is preferred.
• Dosing considerations:
  • Adults: 1 vial
  • Children 1–17 years of age: 20%–100% of the adult dose
  • Infants < 1 year of age: 10% of the adult dose
• 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 is an adverse effect ( skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions testing before administration is not recommended by the CDC).

Human botulinum immunoglobulin (BIG-IV):

• Preferred treatment for infants < 1 year diagnosed with infant botulism
• IV administration
• No serious adverse effects have been reported yet.

Type-specific therapy

• Foodborne botulism: In the absence of ileus Ileus A condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced. Small Bowel Obstruction, laxatives Laxatives Laxatives are medications used to promote defecation. Most often, laxatives are used to treat constipation or for bowel preparation for certain procedures. There are 4 main classes of laxatives: bulk-forming, stimulant, osmotic, and emollient. Laxatives and enemas can be considered to eliminate the toxin and relieve 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.
• Infant botulism: 
  • Administer BIG-IV as soon as possible.
  • Strictly avoid antibiotics in infant botulism. 
• Wound botulism: 
  • Extensive debridement Debridement The removal of foreign material and devitalized or contaminated tissue from or adjacent to a traumatic or infected lesion until surrounding healthy tissue is exposed. Stevens-Johnson Syndrome of the wound is important. 
  • If ≥ 5 years since the last immunization, tetanus Tetanus Tetanus is a bacterial infection caused by Clostridium tetani, a gram-positive obligate anaerobic bacterium commonly found in soil that enters the body through a contaminated wound. C. tetani produces a neurotoxin that blocks the release of inhibitory neurotransmitters and causes prolonged tonic muscle contractions. Tetanus boosters are considered.
  • Penicillin Penicillin Rheumatic Fever G and metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess are the preferred antibiotics for mixed 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.
  • 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, polymyxins, and tetracycline Tetracycline A naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis. Drug-Induced Liver Injury are avoided (may induce neuromuscular blockade Neuromuscular Blockade The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction (neural conduction) is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. Aminoglycosides).

Experimental therapies

• 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 and/or guanidine induce the release of ACh ACh 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 NMJ.
• 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

Physiotherapy Physiotherapy Spinal Stenosis

• Breathing exercises:
  • 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 major cause of death in botulism.
  • Diaphragmatic controlled breathing: maintains the respiratory cycle
  • Pursed lip breathing: improves gas mixing at rest and prevents premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis airway Airway ABCDE Assessment collapse
• Range of motion Range of motion The distance and direction to which a bone joint can be extended. Range of motion is a function of the condition of the joints, muscles, and connective tissues involved. Joint flexibility can be improved through appropriate muscle strength exercises. Examination of the Upper Limbs exercises: keeps the joints moving and retains muscle function 
• Strengthening exercises: maintains function in the muscles

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: an autoimmune neuromuscular disorder characterized by varying degrees of muscle weakness in the arms and legs. Presentation also includes ptosis Ptosis Cranial Nerve Palsies, 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, 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 breathlessness. Diagnosis is through a Tensilon test and specific antibody detection. 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 is managed medically with steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors and surgically by thymectomy Thymectomy Surgical removal of the thymus gland. Myasthenia Gravis. 
• Lambert-Eaton syndrome: an autoimmune neuromuscular syndrome often associated with small cell lung carcinoma. Symptoms include 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, paresthesia, and weakness of muscles, which is temporarily relieved on exertion. Diagnosis includes antibody detection, EMG, X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests, and lung CT. Treatment includes resolving the underlying cause and 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. 
• Guillain-Barré syndrome: a disorder 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. Presentation includes initial paresthesia in the feet and legs with progression to ascending paralysis. Additional symptoms include walking abnormalities, 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, 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, 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, and urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium. Diagnosis is by CSF analysis CSF analysis Meningitis, EMG, and nerve conduction studies. Guillain-Barré syndrome Guillain-Barré syndrome Guillain-Barré syndrome (GBS), once thought to be a single disease process, is a family of immune-mediated polyneuropathies that occur after infections (e.g., with Campylobacter jejuni). 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.
• Stroke: a medical emergency causing damage to 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 due to interrupted blood supply. Presentation includes 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, 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 Disease, blurred vision Blurred Vision Retinal Detachment, facial paralysis, and numbness of the face, arms, and legs. Stroke is diagnosed by physical exam, CT, MRI, cerebral angiogram, or carotid ultrasound. Management depends on the type of stroke (ischemic or hemorrhagic). 
• Tick paralysis: occurs due to injection of toxin by the bite of a tick. Symptoms occur within 2–7 days. Clinical presentation includes initial numbness and weakness in both legs with progression 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). The disease is managed by detecting and removing the tick, cleaning the site of the bite, and monitoring for respiratory distress.