The presentation of acute disseminated encephalomyelitis varies greatly from patient to patient. The disease can exhibit only minimal symptoms in some, whereas in others it can lead to life threatening complications such as failure of the respiratory system. It is usually preceded by a prodromal phase with constitutional symptoms indicative of a viral infection. This phase can last from two days for up to four weeks.

Acute disseminated encephalomyelitis is a monophasic disorder, as it most frequently occurs in a single episode in any individual, without progression or recurrence. Nonetheless, reports involving multiple phases as well as recurrences are present in the medical literature, although their significance has not been fully established.

The disease typically begins with constitutional and non-specific symptoms such as headache, fatigue, tiredness, fever, weight loss, irritability as well as nausea and vomiting. It may also be associated with symptoms of altered mental status, including delirium, stupor, confusion and even coma.

Neurological symptoms are not universal but may occur in a subset of patients and depend greatly on the location of the lesions in the central nervous system. Some of the most commonly reported neurological symptoms are hemiplegia, ataxia, involuntary movements, amnesia, cranial nerve palsies, unilateral numbness and slurred speech. Select patients may also develop psychiatric symptoms such as depression and changes in personality. In addition, visual loss can take place if the inflammation affects the optic nerve and result in optic neuritis.
The peripheral nervous system may also be involved. Most cases, nonetheless, have been reported in adults and rarely in children and adolescents. Typical symptoms are pain, weakness and a burning sensation in the extremities and numbness.

Most patients do not develop all of the symptoms mentioned above. Age of patient also usually influences the presentation. Disturbances in the sensory system generally target adults whereas children suffer more commonly from long term fever and headaches. Seizures are likely to occur in both children and adults.

• Fever

  Poor functional outcome was related to initial high Expanded Disability Status Scale score and absence of fever. [ncbi.nlm.nih.gov]

• Fatigue

  He developed general fatigue, fever, drowsiness and difficulty in walking. He had extensive multiple high-intensity lesions in the white matter of the cerebrum and cerebellum, which are typical findings of ADEM. [ncbi.nlm.nih.gov]

  Neurology 68(suppl 2):S7–S12 CrossRef PubMed Google Scholar Krupp LB, Alvarez LA, LaRocca NG et al (1988) Fatigue in multiple sclerosis. [link.springer.com]

  The disease typically begins with constitutional and non-specific symptoms such as headache, fatigue, tiredness, fever, weight loss, irritability as well as nausea and vomiting. [symptoma.com]

  […] damage of the layer of insulation around the nerves ( myelin ) within affected areas. [1] ADEM often follows viral infection, or less often, vaccinations for measles, mumps, or rubella (MMR). [2] Symptoms usually appear rapidly, beginning with fever, fatigue [rarediseases.info.nih.gov]

• Hodgkin Lymphoma

  Central nervous system involvement is an uncommon complication of systemic non-Hodgkin lymphomas. The majority of these cases concern B-cell lymphomas. [ncbi.nlm.nih.gov]

  We report a case of ADEM with a dramatic clinical onset in an autologous peripheral blood stem cell transplant (PBSCT) recipient for non-Hodgkin’s lymphoma who developed the neurologic syndrome 12 days after PBSC reinfusion. [nature.com]

  Uses [ edit ] Mitoxantrone is used to treat certain types of cancer, mostly metastatic breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma. [en.wikipedia.org]

• Developmental Delay

  […] respiratory failure ), or supplemental oxygen requirement of greater than FiO 2 0.5 to maintain oxygen saturation ≥ 92% Neurologic dysfunction Glasgow Coma Score (GCS) ≤ 11, or altered mental status with drop in GCS of 3 or more points in a person with developmental [en.wikipedia.org]

• Hypercapnic Respiratory Failure

  or arterial partial-pressure of carbon dioxide (PaCO 2 ) > 65 torr (20 mmHg ) over baseline PaCO 2 (evidence of hypercapnic respiratory failure ), or supplemental oxygen requirement of greater than FiO 2 0.5 to maintain oxygen saturation ≥ 92% Neurologic [en.wikipedia.org]

• Nausea

  a neurological condition that is marked by inflammation of the brain and spinal cord, is of sudden onset with variable symptoms (such as fever, headache, nausea, lethargy, weakness and seizures), and is thought to be the result of an immune response [merriam-webster.com]

  […] of insulation around the nerves ( myelin ) within affected areas. [1] ADEM often follows viral infection, or less often, vaccinations for measles, mumps, or rubella (MMR). [2] Symptoms usually appear rapidly, beginning with fever, fatigue, headache, nausea [rarediseases.info.nih.gov]

  The symptoms of ADEM appear rapidly, beginning with encephalitis-like symptoms such as fever, fatigue, headache, nausea and vomiting, and in the most severe cases, seizures and coma. [ninds.nih.gov]

  Other symptoms may include: nausea and vomiting headache confusion weakness ataxia (unsteady walk) sensory changes, including numbness or tingling optic neuritis (trouble with vision) seizures The location of the inflammation (swelling) within the brain [childrenshospital.org]

  They are weakness, loss of vision, lack of balance, incontinence, loss of speech and memory, fever, headaches, nausea, vomiting, irritability, confusion, drowsiness, which may progress to coma. Seizures are common. [doctorstrizhak.com]

• Hypertension

  At times, a fulminant form of ADEM with intracranial hypertension may occur heralded by increasing drowsiness or somnolence. [hoajonline.com]

  Although there has been literature documenting autonomic dysreflexia and hypertensive emergency in 2 pediatric cases of ADEM, to our knowledge there has not been a case detailing paroxysmal sympathetic hyperactivity in an adult patient with ADEM. [ncbi.nlm.nih.gov]

  […] that might have similar symptoms: neurosarcoidosis, vasculitis due to other autoimmune disease, progressive multifocal leukoencephalopathy (PML, infection caused by JC virus), CNS Lymphoma, posterior reversible encephalopathy syndrome due to severe hypertension [doctorstrizhak.com]

• Photophobia

  Other early symptoms are reduced night vision, photophobia and red eyes. Many patients with optic neuritis may lose some of their color vision in the affected eye (especially red ), with colors appearing subtly washed out compared to the other eye. [en.wikipedia.org]

  Meningismus (ie, nuchal rigidity, photophobia/phonophobia) c. CSF pleocytosis (>5 white blood cells/mm 3 ) d. Presence of focal neurologic deficit e. Electroencephalography findings consistent with encephalitis f.  [dx.doi.org]

• Muscular Atrophy

  Bruising Telangiectasia Striae Leukocytosis Thromboembolism Psychological dependence Vertebral collapse Oesophageal ulcer Seizures Hypertriglyceridaemia Intracranial hypertension (long-term treatment) Facial plethora Hypokalaemia Hypocalcaemia Muscular [en.wikipedia.org]

• Euphoria

  Therapeutic doses may cause a feeling of artificial well-being ("steroid euphoria"). [17] The neuropsychiatric effects are partly mediated by sensitization of the body to the actions of adrenaline. [en.wikipedia.org]

  […] bilateral blindness, neuropathic bladder R (0.2) – – + – – – – R (0.8) – – – – – – + R (1.7) – + – – – – – R (5.0) – + – – + (BON) – – 6, M A – – – – – – + 7.0 RRMS ↓ VA 6/12 R (6.0) – – – – + (BON) – – 11, M A – – + + – – + 1.3 RRMS Cerebellar ataxia, euphoria [dx.doi.org]

• Incontinence

  […] describe a previously healthy 10-year-old boy with acute disseminated encephalomyelitis associated with acute acquired Toxoplasma gondii infection, the symptoms of which initially began with nuchal stiffness, difficulty in walking, and urinary and stool incontinence [ncbi.nlm.nih.gov]

  They are weakness, loss of vision, lack of balance, incontinence, loss of speech and memory, fever, headaches, nausea, vomiting, irritability, confusion, drowsiness, which may progress to coma. Seizures are common. [doctorstrizhak.com]

  Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead. [en.wikipedia.org]

• Headache

  Patients with acute disseminated encephalomyelitis frequently suffer from seizures, disturbances of consciousness, fever, and headaches, and occasionally there are focal signs and symptoms. [ncbi.nlm.nih.gov]

  Symptoms, which vary among individuals, may include headache, delirium, lethargy, coma, seizures, stiff neck, fever, ataxia, optic neuritis, transverse myelitis, vomiting, and weight loss. [web.archive.org]

• Meningism

  unspecified G01 Meningitis in bacterial diseases classified elsewhere G02 Meningitis in other infectious and parasitic diseases classified elsewhere G03 Meningitis due to other and unspecified causes G03.0 Nonpyogenic meningitis G03.1 Chronic meningitis [icd10data.com]

  ADEM in children has a polysymptomatic presentation that includes encephalopathy, fever and meningeal signs. In adults, encephalopathy is less frequent and the clinical presentation is usually dominated by long tract involvement. [ncbi.nlm.nih.gov]

• Ataxia

  Ataxia was the most common presenting feature, occurring in 20 patients (65%). MRI findings were variable, but lesions were most commonly seen bilaterally and asymmetrically in the frontal and parietal lobes. [ncbi.nlm.nih.gov]

  […] in some ataxias. [en.wikipedia.org]

• Confusion

  The meningoencephalitic presentation may include meningism, impaired consciousness (occasionally leading to coma), seizures and confusion, or behavioral disturbances. [ncbi.nlm.nih.gov]

  Clinical manifestations include confusion, somnolence, fever, nuchal rigidity, and involuntary movements. The illness may progress to coma and eventually be fatal. [icd10data.com]

  […] with ADEM The bottom line Several key factors in ADEM distinguish it from MS, including sudden fever, confusion, and possibly even coma. [healthline.com]

  Typical symptoms of ADEM such as fever, headache and confusion, are not usually seen in people with MS. MRIs are helpful when distinguishing ADEM from MS. Most children with MS are treated with ongoing medication to prevent attacks. [childrenshospital.org]

• Altered Mental Status

  She developed altered mental status, left facial paralysis, left paresis, and experienced three episodes of ON. She was treated with rituximab and azathioprine (AZA) as prevention for recurrent ON. [ncbi.nlm.nih.gov]

  We identified 3 persons with probable or suspected encephalitis after smallpox vaccination, with cerebral inflammation evidenced by altered mental status and pleocytosis. [dx.doi.org]

  It may also be associated with symptoms of altered mental status, including delirium, stupor, confusion and even coma. [symptoma.com]

  It is characterized by hyperthermia, muscle rigidity, altered mental status, and increased serum creatine kinase [ 2 ]. [karger.com]

Although ADEM was first described almost 250 years ago, diagnostic criteria are still not well defined. History is the cornerstone for diagnosis. Recent efforts have attempted to provide objective criteria to facilitate diagnosis and they include: neurologic findings indicative of central nervous system disseminated disease, history of an infection that may also be completely asymptomatic, absence of recurrence or progression and absence of concurrent infections or metabolic disease. In practice, it is difficult to conclusively establish a history of infection, as ADEM can present sometimes more than a month after the initial infection. Thus, it is commonly diagnosed after other diseases and conditions are excluded.

Imaging with MRI and CSF analysis are usually not sufficient to diagnose acute disseminating encephalomyelitis. MRI, in particular, can exclude other diseases that target the white matter, including infectious, vascular, inflammatory and metabolic conditions. Findings on MRI are similar to multiple sclerosis. There will be increased signal on T2 weighted images, increased enhancement after injection with gadolinium as well as abnormalities after FLAIR signal assessment. Nonetheless, unlike multiple sclerosis, ADEM may show less periventricular involvement, a stronger signal and margins that are not well defined and may involve both the thoracic and cervical spinal cord. In fact, findings in the spinal cord can be more useful in differentiating between the two conditions. Lesions in the spinal cord tend to be more diffuse and present in many parts whereas multiple sclerosis is usually characterized by changes that are restricted to the posterior side on both axial and cross-sectional sections. In addition, lesions with ADEM are continuous and affect several levels, unlike those in multiple sclerosis, which are usually limited to only one level of the spinal cord.

Electroencephalography is usually abnormal, although findings are nonspecific and do not necessarily help in establishing the diagnosis. Common abnormalities include discharges characteristic of epilepsy as well as focal slowing.

Cerebrospinal fluid analysis is generally employed to exclude other conditions. Findings with acute demyelinating encephalomyelitis are nonspecific and include elevated proteins and increased numbers of lymphocytes. It may be completely normal. Cultures are also frequently negative.

Treatment aims to decrease and limit inflammation, the main pathophysiological mechanism of the illness. Steroids are the cornerstone of management. High dose methylprednisolone is given for 3 to 5 days, then followed with oral prednisolone for up to 6 weeks. Initial dosage of methylprednisolone is about 10 to 30 mg per kg per day, with a maximum dose of 1 gram per day.

Other options for the treatment of ADEM can also be available. In particular, plasmapheresis and IV immunoglobulin infusion have shown significant benefits in select patients. Usage of both plasmapheresis and IV immunoglobulin is generally reserved for patients who do not respond to corticosteroids or in patients with contraindications to steroids. Guidelines for the management of ADEM have not been defined, and method and treatment of choice in case of non-response to steroids depend on the experience of the neurologist and the general condition of the patient. It should be also noted that, to date, there have been no randomized controlled trials that compared the usage of steroid medication against other options such as plasmapheresis and IV immunoglobulin.

Prognosis of ADEM varies, with complete recovery expected in 50 to 70% of all patients within six months [6]. Nonetheless, death can result and occurs in approximately 5% of all patients [6]. Outlook is generally much more favorable in children than adults and improves with the presence of fever, response to steroids, insidious onset and the absence of severe neurological symptoms [7].

Around 70 to 90% of all patients will exhibit non-significant residual deficits. Furthermore, up to 30% of all patients may suffer from residual motor disabilities that vary considerably in their severity, and can range from clumsiness to hemiparesis [8].

Neurocognitive deficits can also occur and tend to have a predilection for younger patients, although it is unclear if this is caused by the disease itself or hospitalization at a young age, which has been previously shown before to correlate with behavioral problems [9] [10].

The causative factors underlying acute disseminated encephalomyelitis are various but mostly include infections with large and enveloped viruses. There is no single virus responsible for the majority of cases but the most frequently involved viruses are Epstein-Barr virus, herpes simplex virus, cytomegalovirus and mycoplasma. Previously, measles was responsible for the majority of infections but advances in immunization have significantly reduced the association. Nowadays, most cases have been correlated with various gastrointestinal or respiratory viruses but, frequently, no identification of a specific organism is made. The disease tends to be more common in the winter season, possibly because of a greater association with viral illness.

The association between ADEM and vaccination remains uncertain. Nonetheless, the Pasteur rabies vaccine has been strongly linked with the disease. In addition, several other vaccines have been also correlated with acute disseminating encphalomyelitis, although the link is not as strong. These include vaccines for tetanus, poliomyelitis, rubella, pneumococcus, diphteria, hepatitis B, influenza, Japanese B virus, smallpox and varicella [1] [2].

The virus or the vaccine are not the only factors responsible for triggering the disease. Patients may be genetically predisposed and may have abnormal immune reactions to the presence of particular foreign antigens. In fact, helper T-cells have been involved in the disease in addition to certain genetic mutations in the HLA system, such as HLA DQB1*0602, DRB1*1501 and DRB1*1503 [3].

Acute disseminated encephalomyelitis usually develops after a prodromal phase, characterized by fever and other non-specific symptoms of viral illness. The prodromal phase and the period associated with the disease are generally separated by a recovery phase, where symptoms are absent. In some cases, acute disseminated encephalomyelitis can develop after more than 30 days from the end of the prodromal phase. The prodromal phase itself can vary between 2 and 21 days, and that greatly depends on the responsible infectious organism, although some viruses are not associated with any prodrome. In general, the longer the recovery phase, the more difficult it is to determine exactly the responsible etiologic factor.

Most affected patients are either children or adolescents, although the condition occurs in patients in any age. Cases of acute disseminated encephalomyelitis tend to occur more commonly in the winter and spring, usually connected with the seasonal peaks of viral illness [4]. Immunization is a rare cause for acute disseminated encephalomyelitis and is responsible for less than 5% [5].

The pathophysiological mechanisms underlying the disease are still not completely elucidated. ADEM generally results in the demyelination of neurons in the brain. A potential mechanism underlying the disease involves an abnormal inflammatory reaction within the central nervous system that follows an infection or, possibly, an autoimmune disorder. The underlying pathological and histological characteristics are poorly understood, especially because it tends to resolve on its own and biopsies are rarely needed.

The pattern associated with the condition is random and generally closely resembles that of multiple sclerosis. An important difference is that patients usually suffer from only one episode whereas multiple sclerosis is a chronic disease that is either progressive or recurrent.

Because ADEM shares some similarities with autoimmune disorders, it has been thought that risk factors for autoimmune disorders may also contribute to the disease. In particular, a significantly decreased exposure to sunlight and infections in childhood has been associated with a remarkable increase in the incidence of autoimmune disorders in the developed world. Nonetheless, the links with ADEM remain very tenuous.

Immunization against measles has played an important role in limiting cases of ADEM and diseases on a similar spectrum such as acute hemorrhagic leukoencephalitis.

Acute disseminating encephalomyelitis (ADEM) is a demyelinating disease that is thought to occur after acquiring an infectious illness, particularly with viral organisms. The condition has been most strongly associated with measles, mumps, and rubella but is also thought to occur occasionally after immunization. The underlying mechanisms are poorly understood, but scientists hypothesize that a genetic predisposition, in combination with an infection, result in a dysregulated immune response that ultimately attacks the nervous system and leads to demyelination. Patients present with a range of findings, with most cases being preceded by a prodromal phase with nonspecific symptoms such as fever, fatigue, weight loss and headaches. Neurologic abnormalities occur in some patients and vary significantly depending on the location and the extent of the lesions. Diagnosis is established mostly with history, and frequently made by exclusion. Magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analyses are sometimes performed to rule out other diseases and to assess the distribution of the associated lesions. Treatment is with corticosteroids, although intravenous immunoglobulin and plasmapheresis can be beneficial in patients who fail to respond to steroids.

Acute disseminated encephalomyelitis is a disease of the nervous system that most commonly occurs after an infection with a virus or immunization with a vaccine. The mechanisms underlying the condition are still poorly understood, but it is thought that the immune system develops an exaggerated response and attacks the myelin sheath. The latter is a substance that envelops nerve cells to ensure proper transmission of electrical messages within them. Several diseases have been associated with the disease, especially mumps, measles and rubella. Patients present initially with a prodromal viral illness and exhibit nonspecific symptoms such as fever, weight loss and fatigue. Later neurological occurrences can take place and vary greatly from patient to patient. Diagnosis is mostly established with history. MRI and analysis of the cerebrospinal fluid can both aid in the exclusion of other diseases and in the assessment of the extent of the disease. Acute disseminated encephalomyelitis is most commonly treated with corticosteroids.

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