Acute disseminated encephalomyelitis
Encyclopedia
Acute disseminated encephalomyelitis (ADEM) is an immune mediated disease
of the brain
. It usually occurs following a viral infection
but may appear following vaccination
, bacteria
l or parasitic
infection, or even appear spontaneously. As it involves autoimmune demyelination, it is similar to multiple sclerosis
, and is considered part of the Multiple sclerosis borderline diseases. The incidence rate is about 8 per 1,000,000 people per year. Although it occurs in all ages, most reported cases are in children and adolescents
, with the average age around 5 to 8 years old. The mortality rate may be as high as 5%, full recovery is seen in 50 to 75% of cases, while up to 70 to 90% recover with some minor residual disability. The average time to recover is one to six months.
ADEM produces multiple inflammatory
lesion
s in the brain and spinal cord
, particularly in the white matter
. Usually these are found in the subcortical and central white matter and cortical gray-white junction of both cerebral hemispheres, cerebellum
, brainstem, and spinal cord, but periventricular white matter and gray matter of the cortex
, thalami and basal ganglia
may also be involved.
When the patient suffers more than one demyelinating episode, it is called Recurrent disseminated encephalomyelitis or Multiphasic disseminated encephalomyelitis(MDEM).
, enterovirus
, measles
, mumps
, rubella
, varicella zoster, Epstein Barr virus, cytomegalovirus
, herpes simplex virus
, hepatitis A
, and coxsackievirus
; while the bacterial infections include Mycoplasma pneumoniae
, Borrelia burgdorferi
, Leptospira
, and beta-hemolytic Streptococci. The only vaccine proven to induce ADEM is the Semple form of the rabies
vaccine, but hepatitis B, pertussis
, diphtheria
, measles, mumps, rubella, pneumococcus, varicella, influenza, Japanese encephalitis
, and polio vaccines have all been implicated. In rare cases, ADEM seems to follow from organ transplant
ation. The risk of ADEM from measles vaccination is about 1 to 2 per million, which is far lower than the risk of developing ADEM from an actual measles infection, which is about 1 per 1000 for measles (and 1 per 5000 for rubella). Measles infection also appears to lead to worse ADEM outcomes than cases associated with measles immunization. Some vaccines, later shown to have been contaminated with host animal CNS
tissue, have ADEM incident rates as high as 1 in 600.
, headache
, drowsiness, seizures and coma
. Although initially the symptoms are usually mild, they worsen rapidly over the course of hours to days, with the average time to maximum severity being about four and a half days. Additional symptoms include hemiparesis, paraparesis, and cranial nerve palsies.
s, such as methylprednisolone
or dexamethasone
, followed by 3–6 weeks of gradually lower oral doses of prednisolone
. Patients treated with methylprednisolone have shown better outcomes than those treated with dexamethasone. Oral tapers of less than three weeks duration show a higher chance of relapsing, and tend to show poorer outcomes. Other antiinflamatory and immunosuppressive therapies have been reported to show beneficial effect, such as plasmapheresis
, high doses of intravenous immunoglobulin (IVIg), mitoxantrone
and cyclophosphamide
. These are considered alternative therapies, used when corticosteroids cannot be used, or fail to show an effect.
There is some evidence to suggest that patients may respond to a combination of methylprednisolone and immunoglobulins if they fail to respond to either separately
In a study of 16 children with ADEM, 10 recovered completely after high-dose methylprednisolone, one severe case that failed to respond to steroids recovered completely after IVIg; the five most severe cases -with ADAM and severe peripheral neuropathy
- were treated with combined high-dose methylprednisolone and immunoglobulin, two remained paraplegic, one had motor and cognitive handicaps, and two recovered. A recent review of IVIg treatment of ADEM (of which the previous study formed the bulk of the cases) found that 70% of children showed complete recovery after treatment with IVIg, or IVIg plus corticosteroids. A study of IVIg treatment in adults with ADEM showed that IVIg seems more effective in treating sensory and motor disturbances, while steroids seem more effective in treating impairments of cognition, consciousness and rigor. This same study found one subject, a 71-year-old man who had not responded to steroids, that responded to a IVIg treatment 58 days after disease onset.
or EDSS
), average time to recover is one to six months. The mortality rate may be as high as 5%. Poorer outcomes are associated with unresponsiveness to steroid therapy, unusually severe neurological symptoms, or sudden onset. Children tend to have more favorable outcomes than adults, and cases presenting without fevers tend to have poorer outcomes. The latter effect may be due to either protective effects of fever, or that diagnosis and treatment is sought more rapidly when fever is present.
and hemiparesis
.
below age norms in at least one cognitive domain, such as complex attention (one child), short-term memory (one child) and internalizing behaviour/affect
(two children). Group means for each cognitive domain were all within one standard deviation of age norms, demonstrating that, as a group, they were normal. These deficits were less severe than those seen in similar aged children with a diagnosis of MS.
Another study compared nineteen children with a history of ADEM, of which 10 were five years of age or younger at the time (average age 3.8 years old, tested an average of 3.9 years later) and nine were older (mean age 7.7y at time of ADEM, tested an average of 2.2 years later) to nineteen matched controls. Scores on IQ tests and educational achievement were lower for the young onset ADEM group (average IQ 90) compared to the late onset (average IQ 100) and control groups (average IQ 106), while the late onset ADEM children scored lower on verbal processing speed. Again, all groups means were within one standard deviation of the controls, meaning that while effects were statistically reliable, the children were as a whole, still within the normal range. There were also more behavioural problems in the early onset group, although there is some suggestion that this may be due, at least in part, to the stress of hospitalization at a young age.
to constitute a spectrum, differing only in chronicity, severity, and clinical course, while others consider them discretely different diseases.
Problems for differential diagnosis increase due to the lack of agreement for a definition of Multiple Sclerosis. For some people MS should be considered a clinical entity based in inflammatory lesions separated in time and space. As some cases of ADEM satisfy these conditions, they should be considered inside the MS spectrum. Using a pathological definition instead, they would be apart (plaques in the white matter in MS are sharply delineated, while the inflammation in ADEM is widely disseminated and ill-defined).
of venules and hemorrhage, and edema. Death is common in the first week and overall mortality is about 70%, but increasing evidence points to favorable outcomes after aggressive treatment with corticosteroids, immunoglobulins, cyclophosphamide, and plasma exchange. About 70% of survivors show residual neurological deficits, but some survivors have shown surprisingly little deficit considering the magnitude of the white matter affected.
This disease has been occasionally associated with ulcerative colitis and Crohn's disease, septicemia associated with immune complex deposition, methanol poisoning, and other underlying conditions.
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
of the brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
. It usually occurs following a viral infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
but may appear following vaccination
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
, bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l or parasitic
Parasitism
Parasitism is a type of symbiotic relationship between organisms of different species where one organism, the parasite, benefits at the expense of the other, the host. Traditionally parasite referred to organisms with lifestages that needed more than one host . These are now called macroparasites...
infection, or even appear spontaneously. As it involves autoimmune demyelination, it is similar to multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
, and is considered part of the Multiple sclerosis borderline diseases. The incidence rate is about 8 per 1,000,000 people per year. Although it occurs in all ages, most reported cases are in children and adolescents
Adolescence
Adolescence is a transitional stage of physical and mental human development generally occurring between puberty and legal adulthood , but largely characterized as beginning and ending with the teenage stage...
, with the average age around 5 to 8 years old. The mortality rate may be as high as 5%, full recovery is seen in 50 to 75% of cases, while up to 70 to 90% recover with some minor residual disability. The average time to recover is one to six months.
ADEM produces multiple inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
lesion
Lesion
A lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...
s in the brain and spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
, particularly in the white matter
White matter
White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
. Usually these are found in the subcortical and central white matter and cortical gray-white junction of both cerebral hemispheres, cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
, brainstem, and spinal cord, but periventricular white matter and gray matter of the cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
, thalami and basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
may also be involved.
When the patient suffers more than one demyelinating episode, it is called Recurrent disseminated encephalomyelitis or Multiphasic disseminated encephalomyelitis(MDEM).
Causes and antecedent history
Viral infections thought to induce ADEM include influenza virusOrthomyxoviridae
The Orthomyxoviridae are a family of RNA viruses that includes five genera: Influenzavirus A, Influenzavirus B, Influenzavirus C, Isavirus and Thogotovirus. A sixth has recently been described...
, enterovirus
Enterovirus
Enteroviruses are a genus of ssRNA viruses associated with several human and mammalian diseases. Serologic studies have distinguished 66 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes on the...
, measles
Measles
Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
, mumps
Mumps
Mumps is a viral disease of the human species, caused by the mumps virus. Before the development of vaccination and the introduction of a vaccine, it was a common childhood disease worldwide...
, rubella
Rubella
Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...
, varicella zoster, Epstein Barr virus, cytomegalovirus
Cytomegalovirus
Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...
, herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
, hepatitis A
Hepatitis A
Hepatitis A is an acute infectious disease of the liver caused by the hepatitis A virus , an RNA virus, usually spread the fecal-oral route; transmitted person-to-person by ingestion of contaminated food or water or through direct contact with an infectious person...
, and coxsackievirus
Coxsackievirus
Coxsackievirus is a virus that belongs to a family of non enveloped linear positive-sense ssRNA viruses, Picornaviridae and the genus Enterovirus, which also includes poliovirus and echovirus. Enteroviruses are among the most common and important human pathogens and ordinarily its members are...
; while the bacterial infections include Mycoplasma pneumoniae
Mycoplasma pneumoniae
Mycoplasma pneumoniae is a very small bacterium in the class Mollicutes.It causes the disease mycoplasma pneumonia, a form of atypical bacterial pneumonia, and is related to cold agglutinin disease.-Cell wall/Treatment:...
, Borrelia burgdorferi
Borrelia burgdorferi
Borrelia burgdorferi is a species of Gram negative bacteria of the spirochete class of the genus Borrelia. B. burgdorferi is predominant in North America, but also exists in Europe, and is the agent of Lyme disease....
, Leptospira
Leptospira
Leptospira is a genus of spirochaete bacteria, including a small number of pathogenic and saprophytic species...
, and beta-hemolytic Streptococci. The only vaccine proven to induce ADEM is the Semple form of the rabies
Rabies
Rabies is a viral disease that causes acute encephalitis in warm-blooded animals. It is zoonotic , most commonly by a bite from an infected animal. For a human, rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms...
vaccine, but hepatitis B, pertussis
Pertussis
Pertussis, also known as whooping cough , is a highly contagious bacterial disease caused by Bordetella pertussis. Symptoms are initially mild, and then develop into severe coughing fits, which produce the namesake high-pitched "whoop" sound in infected babies and children when they inhale air...
, diphtheria
Diphtheria
Diphtheria is an upper respiratory tract illness caused by Corynebacterium diphtheriae, a facultative anaerobic, Gram-positive bacterium. It is characterized by sore throat, low fever, and an adherent membrane on the tonsils, pharynx, and/or nasal cavity...
, measles, mumps, rubella, pneumococcus, varicella, influenza, Japanese encephalitis
Japanese Encephalitis
Japanese encephalitis —previously known as Japanese B encephalitis to distinguish it from von Economo's A encephalitis—is a disease caused by the mosquito-borne Japanese encephalitis virus. The Japanese encephalitis virus is a virus from the family Flaviviridae. Domestic pigs and wild birds are...
, and polio vaccines have all been implicated. In rare cases, ADEM seems to follow from organ transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
ation. The risk of ADEM from measles vaccination is about 1 to 2 per million, which is far lower than the risk of developing ADEM from an actual measles infection, which is about 1 per 1000 for measles (and 1 per 5000 for rubella). Measles infection also appears to lead to worse ADEM outcomes than cases associated with measles immunization. Some vaccines, later shown to have been contaminated with host animal CNS
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
tissue, have ADEM incident rates as high as 1 in 600.
Presentation
ADEM has an abrupt onset and a monophasic course. Symptoms usually begin 1–3 weeks after infection or vaccination. Major symptoms include feverFever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, drowsiness, seizures and coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
. Although initially the symptoms are usually mild, they worsen rapidly over the course of hours to days, with the average time to maximum severity being about four and a half days. Additional symptoms include hemiparesis, paraparesis, and cranial nerve palsies.
Treatment
No controlled clinical trials have been conducted on ADEM treatment, but aggressive treatment aimed at rapidly reducing inflammation of the CNS is standard. The widely accepted first-line treatment is high doses of intravenous corticosteroidCorticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s, such as methylprednisolone
Methylprednisolone
Methylprednisolone is a synthetic glucocorticoid or corticosteroid drug. It is marketed in the USA and Canada under the brand names Medrol and Solu-Medrol. It is also available as a generic drug....
or dexamethasone
Dexamethasone
Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...
, followed by 3–6 weeks of gradually lower oral doses of prednisolone
Prednisolone
Prednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...
. Patients treated with methylprednisolone have shown better outcomes than those treated with dexamethasone. Oral tapers of less than three weeks duration show a higher chance of relapsing, and tend to show poorer outcomes. Other antiinflamatory and immunosuppressive therapies have been reported to show beneficial effect, such as plasmapheresis
Plasmapheresis
Plasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...
, high doses of intravenous immunoglobulin (IVIg), mitoxantrone
Mitoxantrone
Mitoxantrone is an anthracenedione antineoplastic agent.-Uses:It is used in the treatment of certain types of cancer, mostly metastatic breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma...
and cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
. These are considered alternative therapies, used when corticosteroids cannot be used, or fail to show an effect.
There is some evidence to suggest that patients may respond to a combination of methylprednisolone and immunoglobulins if they fail to respond to either separately
In a study of 16 children with ADEM, 10 recovered completely after high-dose methylprednisolone, one severe case that failed to respond to steroids recovered completely after IVIg; the five most severe cases -with ADAM and severe peripheral neuropathy
Peripheral neuropathy
Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....
- were treated with combined high-dose methylprednisolone and immunoglobulin, two remained paraplegic, one had motor and cognitive handicaps, and two recovered. A recent review of IVIg treatment of ADEM (of which the previous study formed the bulk of the cases) found that 70% of children showed complete recovery after treatment with IVIg, or IVIg plus corticosteroids. A study of IVIg treatment in adults with ADEM showed that IVIg seems more effective in treating sensory and motor disturbances, while steroids seem more effective in treating impairments of cognition, consciousness and rigor. This same study found one subject, a 71-year-old man who had not responded to steroids, that responded to a IVIg treatment 58 days after disease onset.
Prognosis
Full recovery is seen in 50 to 70% of cases, ranging to 70 to 90% recovery with some minor residual disability (typically assessed using measures such as mRSModified Rankin Scale
The modified Rankin Scale is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke, and it has become the most widely used clinical outcome measure for stroke clinical trials. It was originally introduced in 1957 by...
or EDSS
Expanded Disability Status Scale
The Kurtzke Expanded Disability Status Scale is a method of quantifying disability in multiple sclerosis.The EDSS quantifies disability in eight Functional Systems and allows neurologists to assign a Functional System Score in each of these....
), average time to recover is one to six months. The mortality rate may be as high as 5%. Poorer outcomes are associated with unresponsiveness to steroid therapy, unusually severe neurological symptoms, or sudden onset. Children tend to have more favorable outcomes than adults, and cases presenting without fevers tend to have poorer outcomes. The latter effect may be due to either protective effects of fever, or that diagnosis and treatment is sought more rapidly when fever is present.
Motor deficits
Residual motor deficits are estimated to remain in about 8 to 30% of cases, the range in severity from mild clumsiness to ataxiaAtaxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
and hemiparesis
Hemiparesis
Hemiparesis is weakness on one side of the body. It is less severe than hemiplegia - the total paralysis of the arm, leg, and trunk on one side of the body. Thus, the patient can move the impaired side of his body, but with reduced muscular strength....
.
Neurocognitive
Patients with demyelinating illnesses, such as MS, have shown cognitive deficits even when there is minimal physical disability. Research suggests that similar effects are seen after ADEM, but that the deficits are less severe than those seen in MS. A study of six children with ADEM (mean age at presentation 7.7 years) were tested for a range of neurocognitive tests after an average of 3.5 years of recovery. All six children performed in the normal range on most tests, including verbal IQ and performance IQ, but performed at least one standard deviationStandard deviation
Standard deviation is a widely used measure of variability or diversity used in statistics and probability theory. It shows how much variation or "dispersion" there is from the average...
below age norms in at least one cognitive domain, such as complex attention (one child), short-term memory (one child) and internalizing behaviour/affect
Affect (psychology)
Affect refers to the experience of feeling or emotion. Affect is a key part of the process of an organism's interaction with stimuli. The word also refers sometimes to affect display, which is "a facial, vocal, or gestural behavior that serves as an indicator of affect" .The affective domain...
(two children). Group means for each cognitive domain were all within one standard deviation of age norms, demonstrating that, as a group, they were normal. These deficits were less severe than those seen in similar aged children with a diagnosis of MS.
Another study compared nineteen children with a history of ADEM, of which 10 were five years of age or younger at the time (average age 3.8 years old, tested an average of 3.9 years later) and nine were older (mean age 7.7y at time of ADEM, tested an average of 2.2 years later) to nineteen matched controls. Scores on IQ tests and educational achievement were lower for the young onset ADEM group (average IQ 90) compared to the late onset (average IQ 100) and control groups (average IQ 106), while the late onset ADEM children scored lower on verbal processing speed. Again, all groups means were within one standard deviation of the controls, meaning that while effects were statistically reliable, the children were as a whole, still within the normal range. There were also more behavioural problems in the early onset group, although there is some suggestion that this may be due, at least in part, to the stress of hospitalization at a young age.
ADEM and multiple sclerosis
While ADEM and MS both involve autoimmune demyelination, they differ in many clinical, genetic, imaging, and histopathological aspects. Some authors consider MS and its borderline formsIdiopathic inflammatory demyelinating diseases
Idiopathic inflammatory demyelinating diseases , sometimes known as borderline forms of multiple sclerosis, is a collection of multiple sclerosis variants, sometimes considered different diseases, but considered by others to form a spectrum differing only in terms of chronicity, severity, and...
to constitute a spectrum, differing only in chronicity, severity, and clinical course, while others consider them discretely different diseases.
Problems for differential diagnosis increase due to the lack of agreement for a definition of Multiple Sclerosis. For some people MS should be considered a clinical entity based in inflammatory lesions separated in time and space. As some cases of ADEM satisfy these conditions, they should be considered inside the MS spectrum. Using a pathological definition instead, they would be apart (plaques in the white matter in MS are sharply delineated, while the inflammation in ADEM is widely disseminated and ill-defined).
Acute hemorrhagic leukoencephalitis
Acute hemorrhagic leukoencephalitis (AHL, or AHLE), also known as acute necrotizing encephalopathy (ANE), acute hemorrhagic encephalomyelitis (AHEM), acute necrotizing hemorrhagic leukoencephalitis (ANHLE), Weston-Hurst syndrome, or Hurst's disease, is a hyperacute and frequently fatal form of ADEM. AHL is relatively rare (less than 100 cases have been reported in the medical literature as of 2006), it is seen in about 2% of ADEM cases, and is characterized by necrotizing vasculitisNecrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
of venules and hemorrhage, and edema. Death is common in the first week and overall mortality is about 70%, but increasing evidence points to favorable outcomes after aggressive treatment with corticosteroids, immunoglobulins, cyclophosphamide, and plasma exchange. About 70% of survivors show residual neurological deficits, but some survivors have shown surprisingly little deficit considering the magnitude of the white matter affected.
This disease has been occasionally associated with ulcerative colitis and Crohn's disease, septicemia associated with immune complex deposition, methanol poisoning, and other underlying conditions.
Experimental allergic encephalomyelitis
Experimental allergic encephalomyelitis (EAE) is an animal model of CNS inflammation and demyelination frequently used to investigate potential MS treatments. An acute monophasic illness, EAE is far more similar to ADEM than MS.External links
- Acute Disseminated Encephalomyelitis (ADEM) at myelitis.org