Overview

Acute disseminated encephalomyelitis (ADEM) is an acute neurologic deficit caused by an autoimmune attack on the brain 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 that leads to multifocal demyelination.

Pediatric ADEM

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

• A polyfocal neurological event with a suspected demyelinating and inflammatory cause
• Unexplained encephalopathy
• Abnormal findings in brain MRI during the acute phase
• MRI findings: large, poorly demarcated lesions involving the white matter 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 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 and spring (October to March)
• Children < 10 years of age account for 80% of cases.
• Mean age: 5–8 years
• Affects adults 18–82 years of age
• Incidence 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 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
  • 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 Rubella (also known as German measles or three-day measles) is caused by a single-stranded, positive-sense RNA virus of the Togaviridae family. Rubella only infects humans and spreads prenatally via vertical transmission or postnatally via droplet contact. Congenital rubella is associated with a classic triad of symptoms: cataracts, cardiac defects, and deafness. Infection in children and adults may be mild and present with constitutional symptoms along with a viral exanthem. 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 & 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
  • 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 Rabies is a diseases caused by the infection of the Rabies virus, a single-stranded, negative-sense RNA virus. It is most often transmitted to humans through the bite of an infected animal. This life-threatening disease affects the CNS, resulting in severe neurologic manifestations. Rabies Virus vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. 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, and rubella (MMR) 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) 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 A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination

Pathophysiology

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

• Molecular mimicry theory: environmental trigger → cell-mediated or antibody response → cross-reaction with myelin autoantigens (myelin basic protein, myelin oligodendrocyte protein, proteolipid protein) → autoantibodies against myelin → demyelination
• Inflammatory response: circulating immune complexes → 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, motor 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
• 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 (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)
• 25% of affected individuals lack a clearly defined prodrome.
• 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 with initial prodrome
• Initial prodrome followed by an afebrile period lasting 2–21 days
• Headache
• Vomiting
• Seizures/status epilepticus (35% of cases)
• Abrupt onset of behavioral changes (encephalopathy) in 42% of cases
• Confusion
• Fatigue
• Persistent irritability in infants
• Hallucinations
• Language disorders
• Psychiatric abnormalities

Physical examination findings:

• Lethargy
• Weakness (75% of affected individuals):
  • Generalized or symmetric
  • Hemiparesis (inability to move 1 side of the body)
  • Double hemiparesis (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):
  • Spasticity
  • Slowing of rapid alternating movements
  • Hyperreflexia
• Meningeal (Kernig or Brudzinski) signs in 30% of affected individuals
• Neuralgic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
• Optic neuritis:
  • Usually bilateral
  • Vision loss
• Cranial nerve abnormalities (23%–89% of cases)
• Ataxia (28%–65% of cases):
  • Appendicular (affecting arms and legs) with nystagmus
  • Generalized ataxia 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 of the CNS
• Symptoms:
  • Meningismus
  • Headache
  • Seizures
  • Multifocal and asymmetric neurologic deficits
  • 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

Acute disseminated encephalomyelitis with peripheral 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. General Structure of the Nervous System involvement:

• A rare variant primarily seen in adults
• Development of peripheral 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. General Structure of the Nervous System symptoms in addition to classic CNS symptoms:
  • Distal limb paresthesia
  • Muscle atrophy

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 Basal Ganglia Basal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia, thalamus Thalamus The thalamus is a large, ovoid structure in the dorsal part of the diencephalon that is located between the cerebral cortex and midbrain. It consists of several interconnected nuclei of grey matter separated by the laminae of white matter. The thalamus is the main conductor of information that passes between the cerebral cortex and the periphery, spinal cord, or brain stem. Thalamus, and cortex
    • Multiple lesions are typically visible.
    • 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
    • Indistinct or “smudged” margins
• CT: focal or multifocal regions of white matter damage
• CSF:
  • Abnormalities in 50%–80% of affected individuals
  • Lymphocytic pleocytosis
  • Elevated protein (< 70 mg/dL)
  • Elevated myelin basic protein: a sign of demyelination
  • Oligoclonal bands (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
• EEG:
  • Focal or generalized slowing of activity
  • Disturbed sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep pattern
  • A lumbar puncture can be normal or may show pleocytosis.

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 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
    • Encephalopathy
    • Meningismus
    • 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 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 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 (IVIGs)
  • Plasma exchange
  • Cyclophosphamide

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:
  • 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 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

• 60%–80% of affected individuals recover completely.
• Recovery period: 1–2 months
• Mortality: < 2%
• Residual focal neurologic deficits: 4%–30% of cases

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, mycoplasma infection, immunizations (most commonly after administration of influenza vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. 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. Overview of the Cranial Nerves. Deep tendon reflexes appear diminished on exam. Pain is common and autonomic dysfunction may occur leading to cardiac arrhythmia, urinary retention, or gastroparesis. 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 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 parenchyma resulting in neurological dysfunction. Multiple viruses including herpesviruses, cytomegalovirus, EBV, enteroviruses, and measles virus Measles Virus Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae and the genus Morbillivirus. It is highly contagious and spreads only among humans by respiratory droplets or direct-contact transmission from an infected person. Measles Virus 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, 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.
• Multiple sclerosis: a demyelinating disorder affecting the white matter and characterized by distinct episodes of waxing and waning neurologic deficits. Multiple sclerosis predominantly affects women and individuals of Caucasian descent. The common presenting symptoms include unilateral vision impairment, cranial nerve deficits, ophthalmoplegia, ataxia, nystagmus, spasticity, 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. 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 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, or optic nerve. Analysis of CSF will show oligoclonal bands and mildly elevated protein. Treatment is with high-dose IV steroids 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.