Tetanus (Clinical)

Overview

Definition^[1,2,5,6]

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 is a nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification disorder caused by the bacterium Clostridium tetani Clostridium tetani The cause of tetanus in humans and domestic animals. It is a common inhabitant of human and horse intestines as well as soil. Two components make up its potent exotoxin activity, a neurotoxin and a hemolytic toxin. Tetanus.

Etiology^[1,2,5,6]

• Pathogen: Clostridium tetani Clostridium tetani The cause of tetanus in humans and domestic animals. It is a common inhabitant of human and horse intestines as well as soil. Two components make up its potent exotoxin activity, a neurotoxin and a hemolytic toxin. Tetanus:
  • 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
  • Spore-forming, obligate anaerobe
    • Spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax are extremely resistant to heat Heat Inflammation (can survive a temperature of 120°C for 10–15 minutes).
    • Spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax are relatively resistant to chemical agents.
  • 10 serotypes have been identified.
  • All 10 of the serotypes contain 2 common toxins: tetanolysin and tetanospasmin tetanospasmin Protein synthesized by Clostridium tetani as a single chain of ~150 kda with 35% sequence identity to botulinum toxin that is cleaved to a light and a heavy chain that are linked by a single disulfide bond. Tetanolysin is the hemolytic and tetanospasmin is the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal convulsions. Clostridia
• Toxins:
  • Tetanolysin causes local tissue destruction but is not relevant to the pathogenesis of 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.
  • Tetanospasmin tetanospasmin Protein synthesized by Clostridium tetani as a single chain of ~150 kda with 35% sequence identity to botulinum toxin that is cleaved to a light and a heavy chain that are linked by a single disulfide bond. Tetanolysin is the hemolytic and tetanospasmin is the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal convulsions. Clostridia is a potent neurotoxin (exotoxin) that causes clinical 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.
    • Lethal dose: 2.5 mg/kg
• Habitat:
  • Soil
  • Freshwater
  • Marine sediments
  • Intestinal tract of humans and animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic
  • Spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax can be airborne.

Epidemiology^[1,2,5,6]

• 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 is low in resource-rich countries (primarily because of vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination programs)
• Can occur in any age group, but neonates are the age group at the highest risk.
  • Neonatal tetanus Neonatal Tetanus Tetanus is extremely dangerous; it has a mortality Mortality All deaths reported in a given population. Measures of Health Status rate of nearly 100%.
  • Occurs mainly in developing countries with unclean delivery techniques and poor postnatal hygiene
  • The WHO estimates that there were over 34,000 infant deaths from neonatal tetanus Neonatal Tetanus Tetanus in 2015; however, this is still a 96% reduction from the late 1980s.^[9]
• Most cases of 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 occur in countries where there is a lack of immunization.
• Elderly individuals are also at risk because of reduced immunity.
• Spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax of C. tetani C. tetani The cause of tetanus in humans and domestic animals. It is a common inhabitant of human and horse intestines as well as soil. Two components make up its potent exotoxin activity, a neurotoxin and a hemolytic toxin. Clostridia are present in the soil irrespective of geographical location.

Mode of infection^[2,3,5,6]

• Through contaminated wounds (most common)
• Complication of IV drug use
• Through the middle ear Middle ear The space and structures directly internal to the tympanic membrane and external to the inner ear (labyrinth). Its major components include the auditory ossicles and the eustachian tube that connects the cavity of middle ear (tympanic cavity) to the upper part of the throat. Acute Otitis Media ( cephalic tetanus Cephalic Tetanus Tetanus)
• Through the umbilical stump Umbilical Stump Staphylococcal Scalded Skin Syndrome (SSSS) ( neonatal tetanus Neonatal Tetanus Tetanus)
• Risk factors for developing 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:
  • Burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns
  • Surgical wounds
  • IV drug use
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
  • Immunosuppression

Pathophysiology

Types^[2]

• Generalized tetanus Generalized Tetanus Tetanus: most common (> 80% of cases)^[2] and severe form
• Local tetanus Local Tetanus Tetanus: mild form with symptoms that develop only near the infected wound
• Cephalic tetanus Cephalic Tetanus Tetanus: rare but fatal infection that usually enters through the middle ear Middle ear The space and structures directly internal to the tympanic membrane and external to the inner ear (labyrinth). Its major components include the auditory ossicles and the eustachian tube that connects the cavity of middle ear (tympanic cavity) to the upper part of the throat. Acute Otitis Media
• Neonatal tetanus Neonatal Tetanus Tetanus: due to infection of the umbilical stump Umbilical Stump Staphylococcal Scalded Skin Syndrome (SSSS)

Pathophysiology^[1,2,6]

Inoculation:

• C. tetani C. tetani The cause of tetanus in humans and domestic animals. It is a common inhabitant of human and horse intestines as well as soil. Two components make up its potent exotoxin activity, a neurotoxin and a hemolytic toxin. Clostridia has little invasive power.
• Spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax usually enter the organism through contaminated wounds.
• Not every inoculation will result in infection.
• Spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax germinate under anaerobic conditions: wound ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage, tissue necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage, devitalized tissue
• Average incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period is 7–10 days (can last from 1 to 60 days).
  • In general, the further the inoculation/injury site is from the CNS, the longer the incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period.^[2]
  • Shorter incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus periods are associated with more severe disease
• Neonatal tetanus Neonatal Tetanus Tetanus usually presents with a shorter incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period (5–7 days after birth).

Pathogenesis:

• Exotoxins Exotoxins Toxins produced, especially by bacterial or fungal cells, and released into the culture medium or environment. Bacteriology ( tetanospasmin tetanospasmin Protein synthesized by Clostridium tetani as a single chain of ~150 kda with 35% sequence identity to botulinum toxin that is cleaved to a light and a heavy chain that are linked by a single disulfide bond. Tetanolysin is the hemolytic and tetanospasmin is the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal convulsions. Clostridia and tetanolysin) are produced by germinated 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.
• Tetanolysin may play a role in local tissue destruction, but tetanospasmin tetanospasmin Protein synthesized by Clostridium tetani as a single chain of ~150 kda with 35% sequence identity to botulinum toxin that is cleaved to a light and a heavy chain that are linked by a single disulfide bond. Tetanolysin is the hemolytic and tetanospasmin is the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal convulsions. Clostridia is responsible for the neurologic symptoms.
• Tetanospasmin tetanospasmin Protein synthesized by Clostridium tetani as a single chain of ~150 kda with 35% sequence identity to botulinum toxin that is cleaved to a light and a heavy chain that are linked by a single disulfide bond. Tetanolysin is the hemolytic and tetanospasmin is the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal convulsions. Clostridia is released into the blood and enters the presynaptic terminals of the neuromuscular end plate of motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology.
• Inhibit release of GABA GABA The most common inhibitory neurotransmitter in the central nervous system. Receptors and Neurotransmitters of the CNS and glycine Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Synthesis of Nonessential Amino Acids (inhibitory neurotransmitters)
  • A lack of inhibitory neurotransmitters causes a continuous excitatory state of the motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neuron → spastic paralysis
  • Continuous unopposed muscle activity can lead to bone fractures Bone fractures Breaks in bones. Bones: Remodeling and Healing and muscle tears.
• Toxin travels to the CNS^[2] via retrograde axonal transport, where it also blocks GABA GABA The most common inhibitory neurotransmitter in the central nervous system. Receptors and Neurotransmitters of the CNS and glycine Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Synthesis of Nonessential Amino Acids release, which may result in:
  • 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
  • Autonomic instability Autonomic instability Rabies Virus
  • Increased muscle tone Muscle tone The state of activity or tension of a muscle beyond that related to its physical properties, that is, its active resistance to stretch. In skeletal muscle, tonus is dependent upon efferent innervation. Skeletal Muscle Contraction

Clinical Presentation and Diagnosis

Clinical presentation^[1,2,6]

Generalized tetanus Generalized Tetanus Tetanus:

Generalized tetanus Generalized Tetanus Tetanus is the most common and severe clinical form of 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.

• General malaise Malaise Tick-borne Encephalitis Virus
• Trismus Trismus Spasmodic contraction of the masseter muscle resulting in forceful jaw closure. This may be seen with a variety of diseases, including tetanus, as a complication of radiation therapy, trauma, or in association with neoplastic conditions. Tetanus, or lockjaw Lockjaw Spasmodic contraction of the masseter muscle resulting in forceful jaw closure. This may be seen with a variety of diseases, including tetanus, as a complication of radiation therapy, trauma, or in association with neoplastic conditions. Tetanus (80%):
  • Caused by spasm of the masseter Masseter A masticatory muscle whose action is closing the jaws. Jaw and Temporomandibular Joint: Anatomy muscles, which causes difficulty in opening the mouth and difficulty in mastication Mastication The act and process of chewing and grinding food in the mouth. Jaw and Temporomandibular Joint: Anatomy
  • The most important early symptom; preceded by general malaise Malaise Tick-borne Encephalitis Virus
  • Spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy may be triggered by visual, auditory, and mechanical stimuli.
• Stiffness of the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess
• Risus sardonicus Risus Sardonicus Tetanus, or sardonic smile Sardonic Smile Tetanus:
  • Due to tonic rigidity Rigidity Continuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Megacolon involving muscles of the face Muscles of the Face The facial muscles (also called mimetic muscles) control facial expression and are supplied by the facial nerve. Most of them originate from the skull and attach to the skin around the facial openings, which serve as a method to group or classify them. Facial Muscles: Anatomy
  • Contraction of the frontalis muscles and muscles of the angle of the mouth produces a characteristic grinning expression.
• Opisthotonus Opisthotonus Tetanus:
  • A varying degree of rigidity Rigidity Continuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Megacolon develops in the muscles of the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, back, and trunk.
  • The back is usually arched, and the abdominal wall Abdominal wall The outer margins of the abdomen, extending from the osteocartilaginous thoracic cage to the pelvis. Though its major part is muscular, the abdominal wall consists of at least seven layers: the skin, subcutaneous fat, deep fascia; abdominal muscles, transversalis fascia, extraperitoneal fat, and the parietal peritoneum. Surgical Anatomy of the Abdomen appears broad.
• Rigid abdomen
• Convulsions Convulsions Seizures:
  • Painful, violent, exhausting, reflex spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy that last for 3–4 minutes
  • Develop within 24–72 hours after the initial onset of symptoms
• Laryngeal spasm: causes difficulty breathing
• Esophageal spasm: causes 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
• Urethral spasm: causes urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium
• Autonomic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification overactivity (may be one of the initial presenting symptoms; commonly presents later in the illness):
  • Sweating
  • 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
  • Fevers
  • Cardiovascular complications: labile blood pressure, arrhythmias

Neonatal tetanus Neonatal Tetanus Tetanus: 

• Refusal to feed and difficulty opening the mouth due to trismus Trismus Spasmodic contraction of the masseter muscle resulting in forceful jaw closure. This may be seen with a variety of diseases, including tetanus, as a complication of radiation therapy, trauma, or in association with neoplastic conditions. Tetanus in an infant previously able to feed and cry properly
• Poor sucking
• Irritability
• Grimacing
• Clenched hands and dorsiflexed feet
• Intense rigidity Rigidity Continuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Megacolon and spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy can lead to opisthotonus Opisthotonus Tetanus.

Local tetanus Local Tetanus Tetanus: 

• Tonic contractions/ spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy limited to one body region/extremity
• Will often progress to generalized tetanus Generalized Tetanus Tetanus

Cephalic tetanus Cephalic Tetanus Tetanus: 

• Rare, but frequently fatal
• Trismus Trismus Spasmodic contraction of the masseter muscle resulting in forceful jaw closure. This may be seen with a variety of diseases, including tetanus, as a complication of radiation therapy, trauma, or in association with neoplastic conditions. Tetanus
• Peripheral facial paralysis ( facial nerve Facial nerve The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. The 12 Cranial Nerves: Overview and Functions most commonly involved)/focal cranial neuropathies Neuropathies Chédiak-Higashi Syndrome
• 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
• 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
• Can progress to generalized tetanus Generalized Tetanus Tetanus

Complications^[2,10]

• Fractures: Severe spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy can lead to fractures in the vertebrae and other bones.
• Laryngospasm Laryngospasm Hypoparathyroidism:
  • A brief spasm of the larynx Larynx The larynx, also commonly called the voice box, is a cylindrical space located in the neck at the level of the C3-C6 vertebrae. The major structures forming the framework of the larynx are the thyroid cartilage, cricoid cartilage, and epiglottis. The larynx serves to produce sound (phonation), conducts air to the trachea, and prevents large molecules from reaching the lungs. Larynx: Anatomy, usually lasting 30–60 seconds
  • Laryngospasm Laryngospasm Hypoparathyroidism prevents oxygen from reaching the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy, making breathing difficult.
  • In severe cases, laryngospasm Laryngospasm Hypoparathyroidism leads to asphyxia Asphyxia A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. Drowning and, ultimately, death.
• Aspiration pneumonia Aspiration pneumonia A type of lung inflammation resulting from the aspiration of food, liquid, or gastric contents into the upper respiratory tract. Pneumonia: 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 causes muscle rigidity Muscle rigidity Continuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Motor Neuron Lesions, leading to difficulty in coughing and swallowing Swallowing The act of taking solids and liquids into the gastrointestinal tract through the mouth and throat. Gastrointestinal Motility, which can result in aspiration pneumonia Aspiration pneumonia A type of lung inflammation resulting from the aspiration of food, liquid, or gastric contents into the upper respiratory tract. Pneumonia.
• Acute renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome:
  • Severe muscle spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy associated with 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 can cause rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis.
  • Rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis results in the excretion of myoglobin Myoglobin A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. Rhabdomyolysis in the urine, leading to acute kidney failure.
• Complications of prolonged immobilization Immobilization Delirium:
  • Deep vein thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus and 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
  • Nosocomial 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 

Diagnosis^[9,10]

• Diagnosis is made on clinical grounds, as it is difficult to isolate C. tetani C. tetani The cause of tetanus in humans and domestic animals. It is a common inhabitant of human and horse intestines as well as soil. Two components make up its potent exotoxin activity, a neurotoxin and a hemolytic toxin. Clostridia from its original site of entry.
  • Other causes of spastic paralysis should be ruled out (e.g., tetany Tetany A disorder characterized by muscle twitches, cramps, and carpopedal spasm, and when severe, laryngospasm and seizures. This condition is associated with unstable depolarization of axonal membranes, primarily in the peripheral nervous system. Tetany usually results from hypocalcemia or reduced serum levels of magnesium that may be associated with hyperventilation; hypoparathyroidism; rickets; uremia; or other conditions. Hypocalcemia due to hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia).
• History:
  • History of a tetanus-prone injury
  • History of inadequate immunization for 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
  • History of immunosuppression or presence of risk factors
• Physical exam:
  • Presence of characteristic findings
  • “ Spatula test Spatula Test Tetanus”: Touching the back of the throat Throat The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy elicits jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint: Anatomy contraction instead of normal gag reflex Gag Reflex Cranial Nerve Palsies.
• Serum antitoxin level:
  • Not always readily available
  • Level ≥ 0.1 IU/mL makes 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 less likely.

Management

Management may vary depending on practice location. The information presented here is based on the current CDC, UK, and international research Research Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. Conflict of Interest guidelines.

Goals of treatment^[10]

• Maintain the airway Airway ABCDE Assessment.
• Manage autonomic dysfunction Autonomic Dysfunction Anterior Cord Syndrome.
• Control muscle spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy (painful, can lead to airway Airway ABCDE Assessment and esophageal spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy and associated complications).
• Halt toxin production ( 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 and antibiotics).
• Neutralize unbound toxins with immunoglobulins Immunoglobulins 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 (TIG).
• Provide supportive care during prolonged hospitalization Prolonged Hospitalization Surgical Infections (e.g., thromboembolism Thromboembolism Obstruction of a blood vessel (embolism) by a blood clot (thrombus) in the blood stream. Systemic Lupus Erythematosus prophylaxis Prophylaxis Cephalosporins, maintaining nutrition and hydration, physical therapy Physical Therapy Becker Muscular Dystrophy, 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).).

Supportive management^[9,10]

Toxin bound to synaptic endings cannot be neutralized. The effects of toxin can, therefore, last for weeks (until neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology can grow new axonal terminals), and supportive management is required. This generally includes:

• ICU ICU Hospital units providing continuous surveillance and care to acutely ill patients. West Nile Virus admission
• Endotracheal intubation Intubation Peritonsillar Abscess is frequently needed to protect airway Airway ABCDE Assessment.
• Tracheostomy Tracheostomy Surgical formation of an opening into the trachea through the neck, or the opening so created. Laryngomalacia and Tracheomalacia may be needed if prolonged intubation Intubation Peritonsillar Abscess is required.
• Maintenance of hydration
• Enteral feeding to maintain nutrition
• Prophylaxis Prophylaxis Cephalosporins against thromboembolism Thromboembolism Obstruction of a blood vessel (embolism) by a blood clot (thrombus) in the blood stream. Systemic Lupus Erythematosus by the administration of anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants
• Prevention and treatment of secondary 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:
  • Clean all wounds and remove foreign material
  • Debride wounds to remove spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax and necrotic tissue
• Physical therapy Physical Therapy Becker Muscular Dystrophy after the cessation of spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy

Management of toxins

Halting production of toxin:^[9,10]

• Debride wound to lower bacterial counts, remove spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax, and remove necrotic tissue (anaerobic environment) where 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 can replicate.
• Antibiotic therapy:
  • Metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess (best choice):
    • Adults: 500 mg IV every 6–8 hours for 7–10 days
    • Children: 30 mg/kg/day oral or IV divided into 4 doses, daily for 7–10 days (maximum dose, 4,000 mg/day)^[9]
  • Penicillin Penicillin Rheumatic Fever G (best alternative):
    • Adults: 2–4 million units IV every 4–6 hours for 7–10 days
    • Children: 100,000 U/kg/day divided into 4 doses for 7–10 days (maximum dose, 12 million U/day)^[9]
  • Other alternatives:
    • Doxycycline 
    • Cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins if co-infection with another organism is suspected

Neutralization of unbound toxin:^[9,10]

• Human 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 immunoglobulin (TIG):^[9,10]
  • Neutralizes only unbound/circulating toxin (does not affect toxin already bound at the neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction)
  • Dosing/administration: a single dose of TIG 500 units IM:
    • If the inoculation site Inoculation site Yellow Fever Virus/source can be identified, local infiltration of part of the dose directly around the wound is recommended (though efficacy has not been proven)
    • If 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 toxoid Toxoid Preparations of pathogenic organisms or their derivatives made nontoxic and intended for active immunologic prophylaxis. They include deactivated toxins. Anatoxin toxoids are distinct from anatoxins that are tropanes found in cyanobacteria. Vaccination vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination is also being administered, it should be given in a location different from that for TIG.
    • Should be administered as soon as possible after diagnosis
• If TIG is not available, then intravenous immunoglobulin ( IVIG IVIG Dermatomyositis) may be administered.^[9,10]
  • Dosing: 200–400 mg/kg IV
  • Not approved by the US Food and Drug Administration for this use
• In countries where TIG is not readily available, IM equine 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 immunoglobulin can be administered.
• Because of high chances of allergic reaction with equine immunoglobulin, a test dose should be administered.

Control of muscle spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy^[3,7,10]

• Place the patient in a quiet room and avoid unnecessary stimuli.
• Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines:^[7]
  • Diazepam Diazepam A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of gamma-aminobutyric acid activity. Benzodiazepines:
    • Dose: 0.05–0.2 mg/kg IV (typically, 5–30 mg for adults) every 1–4 hours as needed
    • Caution for propylene glycol toxicity Toxicity Dosage Calculation with higher total doses
  • Midazolam Midazolam A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at ph less than 4 and lipid-soluble at physiological pH. Benzodiazepines:
    • Loading dose Loading Dose Dosage Calculation: 0.01–0.05 mg/kg IV (typically, 0.5–4 mg)
    • Infusion dose: 0.02–0.1 mg/kg/hr IV 
    • Caution in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome because active metabolites can cause oversedation
• Alternative agents:
  • Neuromuscular blocking agents: vecuronium Vecuronium Monoquaternary homolog of pancuronium. A non-depolarizing neuromuscular blocking agent with shorter duration of action than pancuronium. Its lack of significant cardiovascular effects and lack of dependence on good kidney function for elimination as well as its short duration of action and easy reversibility provide advantages over, or alternatives to, other established neuromuscular blocking agents. Neuromuscular Blockers, pancuronium Pancuronium A bis-quaternary steroid that is a competitive nicotinic antagonist. As a neuromuscular blocking agent it is more potent than curare but has less effect on the circulatory system and on histamine release. Neuromuscular Blockers
  • Intrathecal baclofen Baclofen A gamma-aminobutyric acid derivative that is a specific agonist of gaba-b receptors. It is used in the treatment of muscle spasticity, especially that due to spinal cord injuries. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. Spasmolytics is used in a few cases.

Management of autonomic dysfunction Autonomic Dysfunction Anterior Cord Syndrome^[3,8,14,15]

• Magnesium sulfate Magnesium Sulfate A small colorless crystal used as an anticonvulsant, a cathartic, and an electrolyte replenisher in the treatment of pre-eclampsia and eclampsia. It causes direct inhibition of action potentials in myometrial muscle cells. Excitation and contraction are uncoupled, which decreases the frequency and force of contractions. Laxatives:^[14,15]
  • Mechanisms:
    • Acts as a presynaptic neuromuscular blocker 
    • Reduces neuronal catecholamine release
    • Reduces response to catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones 
  • No consensus on dosing to treat severe 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
  • Most studies suggest a dose between 70 and 80 mg/kg (4 and 5 grams) IV bolus over 5 minutes, followed by an infusion rate of 1–3 g/hr to maintain a serum magnesium Magnesium A metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation. Electrolytes level of 2–4 mmol/L.
  • Monitor patellar reflexes and serum magnesium Magnesium A metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation. Electrolytes level.
• Labetalol Labetalol A salicylamide derivative that is a non-cardioselective blocker of beta-adrenergic receptors and alpha-1 adrenergic receptors. Subarachnoid Hemorrhage:^[8]
  • 0.3–1 mg/kg per dose up to a maximum of 20 mg (given as a slow IV injection) every 10 minutes, up to total maximum dose of 300 mg in a 4–6-hour period; or 
  • 0.4–1 mg/kg/hr IV infusion increasing up to 3 mg/kg/hr, with a total dose of 300 mg every 4–6 hours

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^[6]

• The majority of those affected will recover with appropriate care.
• Shorter incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus periods are associated with more severe disease.
• In resource-limited countries, the case fatality rate Case fatality rate Defined as the number of deaths of individuals with a certain disease or condition divided by the total number of people diagnosed with that same disease or condition over a specific time period. Measures of Health Status is 5%–50%.
• Neonatal tetanus Neonatal Tetanus Tetanus has mortality Mortality All deaths reported in a given population. Measures of Health Status rates of 3%–88%.
• Residual neurologic deficits Neurologic Deficits High-Risk Headaches are common in survivors.

Differential Diagnosis

• Strychnine poisoning: Strychnine is a toxic alkaloid used in pesticides. After ingestion, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with symptoms of muscle spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy, cramping, stiffness, agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus, 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, tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination, mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma, and nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism. Diagnosis is by a thorough history and laboratory assays of blood, urine, and tissue. There is no specific treatment; only supportive management is required.
• Phenothiazine overdose: Phenothiazine is a drug used to treat schizophrenia Schizophrenia Schizophrenia is a chronic mental health disorder characterized by the presence of psychotic symptoms such as delusions or hallucinations. The signs and symptoms of schizophrenia are traditionally separated into 2 groups: positive (delusions, hallucinations, and disorganized speech or behavior) and negative (flat affect, avolition, anhedonia, poor attention, and alogia). Schizophrenia. Symptoms of overdose include deviation of eyes, writhing movements of head and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, drooling Drooling Peritonsillar Abscess, and shallow breathing. Diagnosis is by detailed history and blood and urine analysis. Treatment is by the administration of the anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs agent benztropine Benztropine A centrally active muscarinic antagonist that has been used in the symptomatic treatment of parkinson disease. Benztropine also inhibits the uptake of dopamine. Anticholinergic Drugs.
• Tetany Tetany A disorder characterized by muscle twitches, cramps, and carpopedal spasm, and when severe, laryngospasm and seizures. This condition is associated with unstable depolarization of axonal membranes, primarily in the peripheral nervous system. Tetany usually results from hypocalcemia or reduced serum levels of magnesium that may be associated with hyperventilation; hypoparathyroidism; rickets; uremia; or other conditions. Hypocalcemia: carpopedal spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy, muscle cramps Cramps Ion Channel Myopathy, tremors or spasms Spasms An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. Ion Channel Myopathy of the face, and calf muscles: Tetany Tetany A disorder characterized by muscle twitches, cramps, and carpopedal spasm, and when severe, laryngospasm and seizures. This condition is associated with unstable depolarization of axonal membranes, primarily in the peripheral nervous system. Tetany usually results from hypocalcemia or reduced serum levels of magnesium that may be associated with hyperventilation; hypoparathyroidism; rickets; uremia; or other conditions. Hypocalcemia is caused by hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia secondary to an underlying disorder or deficiency. Diagnosis is by blood analysis and the presence of 2 clinical signs: Chvostek and Trousseau. Treatment is by the administration of calcium gluconate Calcium gluconate The calcium salt of gluconic acid. The compound has a variety of uses, including its use as a calcium replenisher in hypocalcemic states. Hypocalcemia and resolution of the underlying cause.
• 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: an 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 of the meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy commonly caused by bacterial and viral 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: Symptoms include 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, 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, stiff neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, and 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, as well as refusal to feed and irritability in infants. Diagnosis is by blood analysis and spinal tap Spinal Tap Febrile Infant. Treatment includes antibiotics or antiviral Antiviral Antivirals for Hepatitis B therapy and supportive management.