Achieve Mastery of Medical Concepts

Study for medical school and boards with Lecturio

Acute Disseminated Encephalomyelitis (ADEM)

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated, inflammatory, monophasic, demyelinating condition that affects the white matter White Matter The region of central nervous system that appears lighter in color than the other type, gray matter. It mainly consists of myelinated nerve fibers and contains few neuronal cell bodies or dendrites. Brown-Séquard Syndrome of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy. As a rapidly progressive post-infectious encephalomyelitis, ADEM is characterized by demyelination Demyelination Multiple Sclerosis in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy as a result of 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 following infection or immunization.

Last updated: Oct 6, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Acute disseminated encephalomyelitis (ADEM) is an acute neurologic deficit caused by an autoimmune attack on the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy that leads to multifocal Multifocal Retinoblastoma demyelination Demyelination Multiple Sclerosis.

Pediatric ADEM

All of the following criteria must be met MET Preoperative Care for a diagnosis of pediatric ADEM:

  • A polyfocal neurological event with a suspected demyelinating and inflammatory cause
  • Unexplained encephalopathy Encephalopathy Hyper-IgM Syndrome
  • Abnormal findings in 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 MRI during the acute phase Acute phase Short Bowel Syndrome
  • MRI findings: large, poorly demarcated lesions involving the white matter White Matter The region of central nervous system that appears lighter in color than the other type, gray matter. It mainly consists of myelinated nerve fibers and contains few neuronal cell bodies or dendrites. Brown-Séquard Syndrome and with possible gray matter Gray matter Region of central nervous system that appears darker in color than the other type, white matter. It is composed of neuronal cell bodies; neuropil; glial cells and capillaries but few myelinated nerve fibers. Cerebral Cortex: Anatomy involvement
  • No new changes on MRI ≥ 3 months after onset

Adult ADEM

There are no set diagnostic criteria for adult ADEM.

Epidemiology and Etiology

Epidemiology

  • Peaks in winter Winter Pityriasis Rosea and spring (October to March)
  • Children < 10 years of age account for 80% of cases.
  • Mean Mean Mean is the sum of all measurements in a data set divided by the number of measurements in that data set. Measures of Central Tendency and Dispersion age: 5–8 years
  • Affects adults 18–82 years of age
  • 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 in males > females (1.3:1)
  • No predilection for race
  • Affects 0.4 in 100,000 individuals per year in the US

Etiology

The etiology of ADEM is not well understood, but there seems to be a consistent postinfectious and postvaccinal pattern in cases.

  • Multiple viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology have been associated with ADEM:
    • Influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza
    • EBV EBV Epstein-barr virus (EBV) is a linear, double-stranded DNA virus belonging to the herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus
    • Cytomegalovirus Cytomegalovirus CMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus
    • Varicella
    • Measles Measles Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus: prior to vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination programs
    • Mumps Mumps Mumps is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. Mumps is typically a disease of childhood, which manifests initially with fever, muscle pain, headache, poor appetite, and a general feeling of malaise, and is classically followed by parotitis. Mumps Virus/Mumps
    • Rubella Rubella An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus
    • HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 and 2
    • Human herpesvirus 6
    • Hepatitis A Hepatitis A Hepatitis A is caused by the hepatitis A virus (HAV), a nonenveloped virus of the Picornaviridae family with single-stranded RNA. HAV causes an acute, highly contagious hepatitis with unspecific prodromal symptoms such as fever and malaise followed by jaundice and elevated liver transaminases. Hepatitis A Virus
    • HIV HIV Anti-HIV Drugs
    • Mycoplasma Mycoplasma Mycoplasma is a species of pleomorphic bacteria that lack a cell wall, which makes them difficult to target with conventional antibiotics and causes them to not gram stain well. Mycoplasma bacteria commonly target the respiratory and urogenital epithelium. Mycoplasma pneumoniae (M. pneumoniae), the causative agent of atypical or “walking” pneumonia. Mycoplasma pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Post-immunization causes:
    • Rabies Rabies Acute viral CNS infection affecting mammals, including humans. It is caused by rabies virus and usually spread by contamination with virus-laden saliva of bites inflicted by rabid animals. Important animal vectors include the dog, cat, bat, fox, raccoon, skunk, and wolf. Rabies Virus 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
    • Measles Measles Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus, mumps Mumps Mumps is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. Mumps is typically a disease of childhood, which manifests initially with fever, muscle pain, headache, poor appetite, and a general feeling of malaise, and is classically followed by parotitis. Mumps Virus/Mumps, and rubella Rubella An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus ( MMR MMR A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the base pair mismatch and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. Lynch syndrome) combined vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination
    • Diphtheria Diphtheria Diphtheria is an infectious disease caused by Corynebacterium diphtheriae that most often results in respiratory disease with membranous inflammation of the pharynx, sore throat, fever, swollen glands, and weakness. The hallmark sign is a sheet of thick, gray material covering the back of the throat. Diphtheria 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–acellular pertussis Pertussis Pertussis, or whooping cough, is a potentially life-threatening highly contagious bacterial infection of the respiratory tract caused by Bordetella pertussis. The disease has 3 clinical stages, the second and third of which are characterized by an intense paroxysmal cough, an inspiratory whoop, and post-tussive vomiting. Pertussis (Whooping Cough) ( DTaP DTaP Combined vaccines consisting of diphtheria toxoid; tetanus toxoid; and an acellular form of pertussis vaccine. At least five different purified antigens of b. Pertussis have been used in various combinations in these vaccines. Bordetella) combined vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination
    • Influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza 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

Pathophysiology

The pathophysiology of ADEM is unclear; however, 2 primary theories are proposed:

  • Molecular mimicry Molecular Mimicry The structure of one molecule that imitates or simulates the structure of a different molecule. Rheumatic Fever theory: environmental trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation → cell-mediated or antibody response → cross-reaction with myelin autoantigens (myelin basic protein, myelin oligodendrocyte Oligodendrocyte A class of large neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal (not the same as satellite cells, perineuronal of ganglia) according to their location. They form the insulating myelin sheath of axons in the central nervous system. Nervous System: Histology protein, proteolipid Proteolipid Protein-lipid combinations abundant in brain tissue, but also present in a wide variety of animal and plant tissues. In contrast to lipoproteins, they are insoluble in water, but soluble in a chloroform-methanol mixture. The protein moiety has a high content of hydrophobic amino acids. The associated lipids consist of a mixture of glycerophosphates; cerebrosides; and sulfoglycosphingolipids; while lipoproteins contain phospholipids; cholesterol; and triglycerides. Orthopoxvirus protein) → autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques against myelin → demyelination Demyelination Multiple Sclerosis
  • Inflammatory response: circulating immune complexes Immune complexes The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. C3 Deficiency 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 → increased vascular permeability and CNS congestion
  • Commonly affects the descending white matter White Matter The region of central nervous system that appears lighter in color than the other type, gray matter. It mainly consists of myelinated nerve fibers and contains few neuronal cell bodies or dendrites. Brown-Séquard Syndrome, motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology tracts, optic nerves, and spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy
  • May be a precursor of multiple sclerosis Multiple Sclerosis Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis in children

Clinical Presentation

Classic ADEM

History:

  • Preceding infectious illness or prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache (50%–75% of cases)
  • Onset: 1–2 days to several weeks after known illness or vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination (commonly respiratory or GI 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)
  • 25% of affected individuals lack a clearly defined prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache.
  • Reported mental status changes or 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
  • Rapid progression of symptoms to neurological deficits (hours to days)

Signs and symptoms:

  • 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 with initial prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache
  • Initial prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache followed by an afebrile period Afebrile Period Relapsing Fever lasting 2–21 days
  • 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
  • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • 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/ status epilepticus Status Epilepticus A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition. Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. Seizures (35% of cases)
  • Abrupt onset of behavioral changes ( encephalopathy Encephalopathy Hyper-IgM Syndrome) in 42% of cases
  • Confusion
  • 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
  • Persistent irritability Persistent irritability Disruptive Mood Dysregulation Disorder in infants
  • Hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia
  • Language disorders
  • Psychiatric abnormalities

Physical examination findings:

  • 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
  • Weakness (75% of affected individuals):
    • Generalized or symmetric
    • Hemiparesis Hemiparesis The term hemiparesis refers to mild to moderate weakness involving one side of the body. Epidural Hemorrhage (inability to move 1 side of the body)
    • Double hemiparesis Hemiparesis The term hemiparesis refers to mild to moderate weakness involving one side of the body. Epidural Hemorrhage (both sides of the body are affected)
    • Diparesis (symmetrically opposed parts of the body are affected, e.g., legs)
  • Long-tract (pyramidal) signs (50% of cases):
  • Meningeal (Kernig or Brudzinski) signs in 30% of affected individuals
  • Neuralgic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Optic neuritis Optic neuritis Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis). Cranial Nerve Palsies:
  • Cranial nerve abnormalities (23%–89% of cases)
  • Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia (28%–65% of cases):
    • Appendicular (affecting arms and legs) with 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
    • Generalized ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia is more common.
  • Obtundation
  • Extrapyramidal disorders such as choreoathetosis or dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia
  • Coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma in severe cases

Variants of ADEM

Acute hemorrhagic leukoencephalitis (AHL):

  • Severe, hyperacute form of ADEM
  • Associated with hemorrhagic lesions in the white matter White Matter The region of central nervous system that appears lighter in color than the other type, gray matter. It mainly consists of myelinated nerve fibers and contains few neuronal cell bodies or dendrites. Brown-Séquard Syndrome of the CNS
  • Symptoms:
    • Meningismus Meningismus Subarachnoid Hemorrhage
    • 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
    • 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
    • Multifocal Multifocal Retinoblastoma and asymmetric neurologic deficits Neurologic Deficits High-Risk Headaches
    • Coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
Positive signs in meningitis

Meningismus Meningismus Subarachnoid Hemorrhage
Brudzinski and Kernig signs are positive in the context of any condition that causes 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 (also known as meningismus Meningismus Subarachnoid Hemorrhage). These conditions include 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 as well as acute hemorrhagic leukoencephalitis (AHL).

Image by Lecturio.

Acute disseminated encephalomyelitis with 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 involvement:

  • A rare variant primarily seen in adults
  • Development of 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 symptoms in addition to classic CNS symptoms:
    • Distal limb paresthesia
    • Muscle atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation

Diagnosis

Clinical diagnosis can be confirmed using CNS imaging and lab testing.

  • MRI:
    • Modality of choice
    • Changes include:
      • White matter lesions in the periventricular and subcortical areas
      • Gray matter lesions (more rare) in basal ganglia, thalamus, and cortex
      • Multiple lesions are typically visible.
      • Spotty pattern of inflammation
      • Indistinct or “smudged” margins
  • CT: focal or multifocal Multifocal Retinoblastoma regions of white matter White Matter The region of central nervous system that appears lighter in color than the other type, gray matter. It mainly consists of myelinated nerve fibers and contains few neuronal cell bodies or dendrites. Brown-Séquard Syndrome damage
  • CSF:
    • Abnormalities in 50%–80% of affected individuals
    • Lymphocytic pleocytosis Pleocytosis Tick-borne Encephalitis Virus
    • Elevated protein (< 70 mg/dL)
    • Elevated myelin basic protein: a sign of demyelination Demyelination Multiple Sclerosis
    • Oligoclonal bands Oligoclonal bands Multiple protein bands serving as markers of specific antibodies and detected by electrophoresis of cerebrospinal fluid or serum. The bands are most often seen during inflammatory or immune processes and are found in most patients with multiple sclerosis. Multiple Sclerosis (in children, prognostic of progression to multiple sclerosis Multiple Sclerosis Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis)
  • Blood testing: elevated serum autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques
  • EEG EEG Seizures:
Mri scan of a patient with acute disseminated encephalomyelitis (adem)

A typical MRI of an individual with acute disseminated encephalomyelitis (ADEM): Note the spotty pattern of 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 cerebral parenchyma (black arrows).

Image: “MRI scan of a patient with acute disseminated encephalomyelitis (ADEM)” by Kamate M, Chetal V, Tonape V, Mahantshetti N, Hattiholi V. License: CC BY 2.0, cropped by Lecturio.

Management and Complications

Management

  • Immunosuppressive therapy: high dose of IV glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids
  • Empirical antimicrobials:
    • Antiviral Antiviral Antivirals for Hepatitis B coverage in affected individuals with evidence of CNS 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:
      • 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
      • Encephalopathy Encephalopathy Hyper-IgM Syndrome
      • Meningismus Meningismus Subarachnoid Hemorrhage
      • CSF findings suggestive of 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
    • Antibacterial Antibacterial Penicillins coverage only if CSF findings are suggestive of bacterial 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
  • Alternative therapies in individuals with inadequate initial response to glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids:
    • IV immunoglobulins IV immunoglobulins Immunoglobulin preparations used in intravenous infusion, containing primarily immunoglobulin g. They are used to treat a variety of diseases associated with decreased or abnormal immunoglobulin levels including pediatric aids; primary hypergammaglobulinemia; scid; cytomegalovirus infections in transplant recipients, lymphocytic leukemia, chronic; kawasaki syndrome, infection in neonates, and idiopathic thrombocytopenic purpura. DiGeorge Syndrome (IVIGs)
    • Plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products exchange
    • Cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants

Complications

  • Fulminant ADEM:
    • Common prior to widespread vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination
    • Affects children < 3 years of age
    • Severe neurological deficits
    • Severe edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema on imaging
  • Transverse myelitis Myelitis Inflammation of the spinal cord. Relatively common etiologies include infections; autoimmune diseases; spinal cord; and ischemia. Clinical features generally include weakness, sensory loss, localized pain, incontinence, and other signs of autonomic dysfunction. Relapsing Fever:
    • Due to spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy lesions
    • Rapid onset
    • May present with cervical cord edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Multiphasic (recurrent) ADEM:
    • Recurrent episodes > 3 months after the initial episode
    • 10% risk of recurrence
    • 2–8 years following the initial episode
    • May exhibit new or recurring MRI findings
  • Relapsing ADEM:
    • Chronic neuroinflammatory disorder
    • Related to multiple sclerosis Multiple Sclerosis Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis or neuromyalgia optica

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

Differential Diagnosis

  • Guillain–Barré syndrome: an autoimmune attack on the peripheral nerve root that typically affects the myelin sheath. Guillain–Barré syndrome is usually preceded by an acute illness such as 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, mycoplasma Mycoplasma Mycoplasma is a species of pleomorphic bacteria that lack a cell wall, which makes them difficult to target with conventional antibiotics and causes them to not gram stain well. Mycoplasma bacteria commonly target the respiratory and urogenital epithelium. Mycoplasma pneumoniae (M. pneumoniae), the causative agent of atypical or “walking” pneumonia. Mycoplasma infection, immunizations (most commonly after administration of influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza 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), or diarrheal illnesses such as campylobacteriosis. Guillain–Barré syndrome is characterized by an acute onset of symmetric weakness that progresses over a few days with a typical ascending pattern, beginning in the legs and arms and moving upward to affect the cranial nerves Cranial nerves There are 12 pairs of cranial nerves (CNs), which run from the brain to various parts of the head, neck, and trunk. The CNs can be sensory or motor or both. The CNs are named and numbered in Roman numerals according to their location, from the front to the back of the brain. The 12 Cranial Nerves: Overview and Functions. Deep tendon reflexes Deep Tendon Reflexes Neurological Examination appear diminished on exam. Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways is common and autonomic dysfunction Autonomic Dysfunction Anterior Cord Syndrome may occur leading to cardiac arrhythmia, urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium, or gastroparesis Gastroparesis Chronic delayed gastric emptying. Gastroparesis may be caused by motor dysfunction or paralysis of stomach muscles or may be associated with other systemic diseases such as diabetes mellitus. Malabsorption and Maldigestion. 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 may result, for which mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing is necessary. Analysis of CSF will show significantly elevated protein with normal white cell count. Treatment is with IVIGs. Although recovery may take months, 95% of affected individuals will recover.
  • Viral encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis: 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 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 parenchyma resulting in neurological dysfunction. Multiple viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology including herpesviruses, cytomegalovirus Cytomegalovirus CMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus, EBV EBV Epstein-barr virus (EBV) is a linear, double-stranded DNA virus belonging to the herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus, enteroviruses, and measles Measles Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology may cause encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis. Symptoms include 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, confusion, 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 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. Treatment is supportive. Seizure medications may be required to achieve seizure control. Antivirals are not typically used except in specific types of viral encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis such as herpes or CMV 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.
  • Multiple sclerosis Multiple Sclerosis Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis: a demyelinating disorder affecting the white matter White Matter The region of central nervous system that appears lighter in color than the other type, gray matter. It mainly consists of myelinated nerve fibers and contains few neuronal cell bodies or dendrites. Brown-Séquard Syndrome and characterized by distinct episodes of waxing and waning neurologic deficits Neurologic Deficits High-Risk Headaches. Multiple sclerosis Multiple Sclerosis Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis predominantly affects women and individuals of Caucasian descent. The common presenting symptoms include unilateral vision Vision Ophthalmic Exam impairment, cranial nerve deficits, ophthalmoplegia Ophthalmoplegia Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. Orbital and Preseptal Cellulitis, ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia, 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, spasticity Spasticity Spinal Disk Herniation, urinary incontinence Urinary incontinence Urinary incontinence (UI) is involuntary loss of bladder control or unintentional voiding, which represents a hygienic or social problem to the patient. Urinary incontinence is a symptom, a sign, and a disorder. The 5 types of UI include stress, urge, mixed, overflow, and functional. Urinary Incontinence, and a conjugate lateral gaze due to damage to the medial longitudinal fasciculus Medial Longitudinal Fasciculus Internuclear Ophthalmoplegia. The clinical course varies and is typically relapsing and remitting. Symptoms may worsen with changes in temperature. Diagnosis may be confirmed based on MRI findings, which show multiple well-circumscribed, irregular plaques located near the lateral ventricles Lateral ventricles Cavity in each of the cerebral hemispheres derived from the cavity of the embryonic neural tube. They are separated from each other by the septum pellucidum, and each communicates with the third ventricle by the foramen of monro, through which also the choroid plexuses (choroid plexus) of the lateral ventricles become continuous with that of the third ventricle. Ventricular System: Anatomy or in the brainstem, spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy, or optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions. Analysis of CSF will show oligoclonal bands Oligoclonal bands Multiple protein bands serving as markers of specific antibodies and detected by electrophoresis of cerebrospinal fluid or serum. The bands are most often seen during inflammatory or immune processes and are found in most patients with multiple sclerosis. Multiple Sclerosis and mildly elevated protein. Treatment is with high-dose IV 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 for individuals in the acute relapsing stage, beta interferons Interferons Interferon (IFN) is a cytokine with antiviral properties (it interferes with viral infections) and various roles in immunoregulation. The different types are type I IFN (IFN-ɑ and IFN-β), type II IFN (IFN-ɣ), and type III IFN (IFN-ƛ). Interferons to modulate the disease, or 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 in the case of refractory disease.

References

  1. Anilkumar, A.C., Foris, L.A., Tadi, P. (2021). Acute Disseminated Encephalomyelitis. StatPearls. Treasure Island (FL): StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK430934/ 
  2. Brenton, J.N. (2021). Acute Disseminated Encephalomyelitis: Background, Pathophysiology, Epidemiology. Medscape. Retrieved from https://emedicine.medscape.com/article/1147044-overview 
  3. Johnston, M. (2016). Neurodegenerative disorders of childhood. In Behrman, R.E., Kliegman, R.M., Jenson, H.B. (Eds.). Nelson Textbook of Pediatrics (20th ed.). Elsevier.
  4. Hemingway, C. (2020). Demyelinating disorders of the central nervous system. In Kliegman, R.M., et al. (Eds.), Nelson Textbook of Pediatrics, pp. 3196-3209.e2. Elsevier.
  5. Ryan, M.M. (2020). Guillain-Barré syndrome. In Kliegman, R.M., et al. (Eds.), Nelson Textbook of Pediatrics, pp. 3335-3339.e1. Elsevier.
  6. Kliegman, R.M., et al. (2020). Disorders of neuromuscular transmission and of motor neurons. In Kliegman, R.M., et al. (Eds.), Nelson Textbook of Pediatrics, pp. 3304-3320.e1. Elsevier.

USMLE™ is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). MCAT is a registered trademark of the Association of American Medical Colleges (AAMC). NCLEX®, NCLEX-RN®, and NCLEX-PN® are registered trademarks of the National Council of State Boards of Nursing, Inc (NCSBN®). None of the trademark holders are endorsed by nor affiliated with Lecturio.

Create your free account or log in to continue reading!

Sign up now and get free access to Lecturio with concept pages, medical videos, and questions for your medical education.

User Reviews

¡Hola!

Esta página está disponible en Español.

Details