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Acute Disseminated Encephalomyelitis Clinical Presentation

  • Author: J Nicholas Brenton, MD; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
 
Updated: Dec 30, 2015
 

History

Clinically, acute disseminated encephalomyelitis (ADEM) is usually readily distinguishable from multiple sclerosis (MS) by the presence of certain clinical features, including the following:

  • History of preceding infectious illness or immunization, although a clear preceding event may be absent in up to a quarter of patients. [85]
  • Association with constitutional symptoms and signs, such as fever
  • Prominence of cortical signs such as mental status changes and seizures
  • Comparative rarity of posterior column abnormalities, which are common in MS
  • Age younger than 11-12 years in ADEM and age older than 11-12 years in MS

ADEM is more common in the winter months, with most cases occurring between October and March. Typical cases of ADEM arise 1-2 days to several weeks after a childhood infectious illness.

  • There is usually a clearly defined phase of afebrile improvement lasting 2-21 days or more before onset of neurologic findings.
  • Generally, patients have shown partial or complete recovery from the prodromal illness at the time of onset of ADEM.
  • Whether latencies of longer than 21 days implicate a particular febrile illness as the prodrome of ADEM is unclear. Clinical experience suggests that this is possible.
  • Most of the large envelope-bearing viruses that figured prominently in older series of ADEM, of which measles was a particularly virulent example, no longer figure importantly in the etiology of ADEM because these diseases are prevented by vaccination.
  • Most cases encountered now occur in the wake of respiratory or gastrointestinal illness presumed to be of viral etiology, although a specific virus is seldom identified.
  • Documentation of at least 1 fever-free day is especially suggestive of ADEM, although such a hiatus is also found in post-infectious vasculitides.
  • Occasionally, ADEM may occur in the wake of several weeks of fever of unknown origin.
  • Some patients have premonitory pain in the back prior to the development of ADEM-related inflammatory myelitis.
  • Various vaccines have been suggested as the exogenous provocation of cases of ADEM.
    • This remains a controversial subject, although clear evidence exists for the role of the Pasteur rabies vaccine and compelling, although somewhat less conclusive evidence exists for the role of other vaccines.
    • The overall effect of the introduction of vaccinations for measles and other encephalomyelitogenic viruses has been a marked reduction in the number of severe or fatal cases of ADEM.
    • Measles was associated with ADEM in about 1 out of 800 cases, and in many of these cases, ADEM that was often particularly severe. Measles-associated ADEM had a high rate of both morbidity and mortality.
  • A cause-and-effect relationship between a possible prodrome and ADEM is more difficult to establish in cases where longer or very short intervals exist between a possible exogenous stimulus and inflammatory result.
    • Latencies longer than 50 days have been suggested for infections or vaccines but are difficult to prove.[6]
    • Relationships are also difficult to determine when a febrile systemic process is rapidly followed by neurologic deterioration because such cases may represent meningoencephalitis.
      • Approximately 25% of cases lack a clearly-defined prodrome.[47, 58, 85]
      • Some of these cases are possible examples of longer than 20 days of latency from prodrome to ADEM, especially in prepubertal children, with imaging changes suggesting ADEM, with negative CSF immune profile, and with rapid and complete recovery.
      • Another subgroup with poorly-defined prodrome but low risk for recurrence are children or adolescents manifesting subacute-onset syndromes that combine neuropsychiatric abnormalities and movement disorders and imaging changes suggestive of ADEM. The course in these cases, which could be termed Johnson syndrome, is often prolonged or even progressive, improving with high-dose intravenous corticosteroids.

The first signs of ADEM usually include abrupt onset encephalopathy (alteration in consciousness or behavioral change unexplained by fever, systemic illness or postictal symptoms.[59] Rapid-onset encephalopathy is typically associated with multifocal neurologic symptoms.

  • In most cases, the clinical course is rapidly progressive and typically develops over hours to maximum deficits within days (mean of 4.5 days). [85] A minority of cases show continued deterioration of function for periods as long as 4 weeks.
  • Strictly speaking, encephalopathy, unexplained by fever, should be present for a diagnosis of ADEM, though it may not be the presenting sign. A single institution follow-up study (at least 5.5 y for each individual) of 52 young individuals (age range 10 mo to 19 y) who presented with their first bout of an acute central nervous system demyelinating disease included 26 children ultimately diagnosed with MS and 24 diagnosed with ADEM. Encephalopathy was the presenting sign in 42% of those with a follow-up diagnosis of ADEM but none of the individuals with a follow-up diagnosis of MS. [7]
  • Convulsive seizures occur around the onset of ADEM in as many as 35% of cases. [85]
  • Meningismus may be present and has been reported in up to 30% of cases. [63]
  • Although almost any portion of the CNS may be clinically involved, certain systems appear to be particularly prone to dysfunction; thus, the descending white matter motor tracts, optic nerves, and spinal cord are particularly commonly involved.
  • ADEM-associated optic neuritis is typically bilateral, although the onset in a second eye may follow onset in the first by days to months. Bilaterality may provide a degree of reassurance with regard to MS risk as optic neuritis in MS is frequently unilateral. Visual evoked responses may discern abnormalities in a second eye before clinical deterioration in vision is discernible.
    • A wide variety of cranial nerve abnormalities may occur in addition to optic nerve disease.
    • Long tract signs (eg, clonus, increased muscle stretch reflexes, upgoing toes) are present early in as many as 85% of cases.[85]
    • In some instances, reflexes may be lost at the onset. When this is caused by transverse myelitis, the evolution of disease after spinal shock replaces absent reflexes with increased muscle stretch reflexes within a few days or more. A small number of cases manifest loss of reflexes as a sign of associated peripheral nerve disease with ADEM, a condition termed EMRN. Some of these EMRN cases are associated with evidence for acute infection with Epstein-Barr virus.
      • Weakness may be hemiparetic, double hemiparetic, diparetic, or generalized and symmetric. Fairly symmetric leg weakness is seen in many cases of ADEM-related transverse myelitis with associated abnormalities of bowel and bladder function.

Some ADEM presentations are fulminant.

  • Fulminant ADEM is more likely to manifest in children younger than 3 years, with rapid evolution of a low state of function and demonstration of severe edema on neuroimaging. Such cases have become uncommon with widespread vaccination against childhood illnesses.
  • Transverse myelitis (TM) may begin rapidly and be associated with severe edema, usually in the cervical region. ADEM-related TM must be distinguished from TM associated with MS, vascular accidents, and directly infectious conditions, including enterovirus. It must also be distinguished from neuromyelitis optica (NMO), which may present with TM in isolation. NMO is a condition for which a biological marker (anti-AQP4 IgG in serum and/or CSF) has been identified.
    • Child/adolescent NMO represents approximately 5% of cases of NMO. Onset is a median range of 10-14 y and the vast majority of these patients are girls or young women. The median number of spinal levels involved is 10 vertebral segments.[72] Motor signs are usually more prominent than sensory signs. CNS lesions may be demonstrated on scans and mental status changes may be noted.
  • Acute administration of very high-dose intravenous corticosteroids may possibly close the blood-brain barrier and subtend the development of edema, which may, in these fulminant cases, account for the high risk for permanent morbidity.

There are unusual presentations for possible ADEM that have uncertain classification. More literature is supporting a continuum of acute demyelinating diseases in childhood and adulthood.

  • Cases of pediatric patients diagnosed with neuromyelitis optica presenting with a clinical and radiographic evidence of ADEM have been reported. [73, 74, 76]
  • Cases of patients with anti-NMDA receptor encephalitis and ADEM-like lesions on MRI have also been reported. [77, 75]
  • Additionally, pediatric cases of ADEM followed by recurrent or monophasic optic neuritis have been described. [78]
  • Young children may manifest a rapidly progressive demyelinating illness that may be fatal within days to weeks and is almost universally associated with profound permanent psychomotor deficits in those who survive. Brain images differ from those typical of juvenile MS and may demonstrate confluent symmetric areas (butterfly pattern) of bright signal abnormality on T2-weighted sequences.
    • Fulminant presentation with lesions showing significant degrees of ring enhancement after contrast administration may also be found.
    • Malignant brain edema may be present, manifested by sulcal and ventricular effacement.
  • Some patients with the large tumor-like lesions, acute MS, or Schilder disease presentations during childhood or adolescence do remarkably well as compared to adults with similar presentations.
  • The classification of rare severe infantile cases, exhibiting features suggesting either severe acute MS or hyperacute ADEM, remains in doubt.
    • Nonetheless, pathological confirmation that some of these cases are MS has been published,[79] and hyperacute adult cases with similar clinical and radiographic manifestations have been reported.[81]
    • Some of these cases display more generalized T2-weighted abnormalities on MRI and may represent cases of what has been referred to as acute toxic encephalopathy.
    • Emphasizing that scan results do not reliably distinguish every case of MS from ADEM is important, but in most cases, reliable inferences may be drawn. Extensive white matter involvement may be found in young infants that some would label as MS[80] while others would label it hyperacute ADEM.
  • Rarely, childhood, adolescent, or adult MS manifests as large unilateral or multiple tumor-like mass lesions that may appear cystic and may impart mass effects (albeit atypically and, if present, unexpectedly mildly). The lesions are steroid responsive and may recur in other locations, such as the contralateral paraventricular white matter.
    • These lesions may represent an intermediate entity between MS and ADEM. Other differential considerations are neoplasm, systemic lupus erythematosus (SLE) and other vasculitic illnesses, progressive multifocal leukoencephalomyelitis, and Schilder myelinoclastic diffuse sclerosis.
    • Schilder disease (diffuse sclerosis) is sometimes considered an MS variant, and the uncertain diagnostic status is beyond the scope of this review. Detailed discussion of that entity is available in the Neurology section of the Medscape Reference journal.

Recurrence may occur during the taper of corticosteroid therapy initiated for ADEM. This phenomenon is not thought to represent a second or independent bout of illness; it usually responds to increasing the corticosteroid dosage and prolonging the ensuing taper.

The appearance of small new lesions on MRI within a month of presentation must also be interpreted with caution, and this may be seen in ADEM.

Although long tapers are sometimes required and more than one taper-related worsening occurs in a small number of patients, recovery is achieved within 2-12 months without further recurrence.

A rare subgroup of patients exists who cannot be weaned entirely from anti-inflammatory therapy. Most of the 8 examples one of the authors (RSR) has encountered were in boys, and the onset of illness usually occurred at age 2-6 years.

  • Mental status changes, visual disturbance, and pyramidal weakness are typical findings; seizures occur in most cases.
  • Imaging changes resemble those found in cases of typical ADEM (ie, multiple plaques at the grey-white junction and in deep white matter), a feature that distinguishes these cases from chronic cases considered a manifestation of Schilder disease.
  • The CSF immune profile remains normal despite recurrences, although myelin basic protein may be elevated.
  • The neurologic abnormalities in this group improve significantly with intravenous methylprednisolone treatment (20 mg/kg/d for 3 successive doses) followed by oral methylprednisolone (2 mg/kg/d) with slow taper to achieve alternate-day dosing.
  • Trouble is encountered during the taper, each patient having a particular threshold for recurrence. In most of the authors' cases, this threshold is encountered when the daily methylprednisolone dose is lowered to approximately 12-14 mg every other day.
  • The neurologic worsening responds to higher corticosteroid doses, but this threshold effect cannot be overcome, and steroid therapy has been continued in these patients for periods as long as 8 years.
  • Although prolonged daily steroid therapy is generally well tolerated, osteopenia may develop, and one of the authors' patients developed vertebral compression fractures.

In 2007, the International Pediatric Multiple Sclerosis Study Group (IPMSSG) proposed operational definitions for the pediatric acquired demyelinating diseases (including ADEM) in attempts to improve consistency in terminology for clinical and research purposes. These guidelines were revised in 2013 and are outlined below.[59]

  • The criteria requires that a child must meet all of the following to be accurately classified as pediatric ADEM:
    • A first, polyfocal clinical CNS event with presumed inflammatory demyelinating cause
    • Encephalopathy that cannot be explained by fever
    • No new clinical and MRI findings emerge 3 months or more after onset
    • Brain MRI is abnormal during the acute phase
    • Typical findings on brain MRI (discussed below) that include diffuse, poorly demarcated large lesions involving the cerebral white matter; T1 hypointense lesions of the white matter are rare; deep gray matter lesions may be present.

Recurrent ADEM was previously defined as a new event of ADEM with a recurrence of the initial symptoms and signs 3 or more months after the first ADEM event. Based upon the 2013 consensus criteria from IPMSSG,[59] this entity is now included under the entity known as multiphasic ADEM.

Multiphasic ADEM

  • Individuals who have experienced typical ADEM are at risk for recurrence. As many as 10% of children with an initial diagnosis of ADEM experience another ADEM attack, typically within the first 2-8 years after the initial attack. [85]
  • Included under the entity of “multiphasic ADEM” are new events of ADEM 3 months or more after the initial attack that can be associated with new or re-emergence of prior clinical and/or MRI findings. [59]
    • Relapsing disease that follows a second ADEM attack is, by definition, no longer consistent with a diagnosis of multiphasic ADEM. Typically, these cases represent a chronic neuro-inflammatory disorder (such as MS or NMO).[59]
Next

Physical

Irritability and lethargy are common first signs of acute disseminated encephalomyelitis (ADEM). Fever returns and headache is present in up to half of cases.[47, 63, 58] Meningismus is also detected in approximately one third of cases.[47, 63] Over the course of minutes to weeks, multifocal neurologic abnormalities develop. The interval from onset of symptoms to maximum deficit is varied but is typically seen at a mean of 4-7 days.[47, 58, 85] Among the most common abnormalities are long tract signs, acute hemiparesis, cranial nerve abnormalities (including visual loss), ataxia, and mental status abnormalities. Mental status disturbances include lethargy, fatigue, confusion, irritability, obtundation, and coma. Focal or generalized seizures occur as an early sign in a minority of cases.

Weakness (roughly 75% of cases) is more commonly discerned than sensory defects. The combinations of these signs may suggest cortical, subcortical, brainstem, cranial nerve, or spinal cord localization. Long tract signs develop in more than half of all cases. Cranial nerve palsies (including vision loss) are found in a wide range of cases (23-89%) of childhood ADEM.[58, 54, 47, 63, 71, 85] Mental or psychiatric disturbances, seizures, and cranial nerve palsies are significantly less common in adolescents or adults with a first or second bout of MS and in many adults with an illness labeled ADEM. Sensory changes may be underappreciated in young children; however, posterior column deficits and hemisensory changes are possibly much less common than in adult cases of ADEM or in early bouts of adolescent or adult MS. Band or girdle dysesthesia or Lhermitte’s sign are seldom if ever found in cases of childhood ADEM.

Ataxia is found in 28-65% of childhood ADEM cases,[63, 47, 58, 85] which tends to differ from cases of ACA because it is more commonly appendicular with nystagmus or generalized ataxia than the distinctive gait/trunk ataxia of ACA. Extrapyramidal disorders such as choreoathetosis or dystonia are sometimes observed.

Signs and symptoms found in cases of ADEM:

  • Alteration in personality
  • Abnormal consciousness
  • Ataxia (appendicular more than axial or gait)
  • Cranial nerve palsies
  • Hallucinations
  • Headache
  • Language disturbances
  • Meningeal signs
  • Nystagmus
  • Psychiatric abnormalities
  • Optic neuritis
  • Ophthalmoparesis
  • Seizures, focal or generalized
  • Sensory loss/dysesthesia
  • Visual field deficits
  • Vomiting
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Causes

Acute disseminated encephalomyelitis (ADEM) may develop in the wake of a wide variety of infectious illnesses or immunizations, especially those associated with large envelope-bearing viruses. Among the agents most commonly identified by titer rise suggesting responsibility for the prodromal phase are Ebstein-Barr virus, cytomegalovirus, herpes simplex virus (HSV), and mycoplasma; however, a particular agent is identified only in a minority of ADEM cases.

ADEM is somewhat more common in the colder months of the year, during which these various viral illnesses are more prevalent. Prior to widespread immunization programs, measles was the most common associated illness. Now, most cases occur in the wake of respiratory or gastrointestinal illnesses that are presumed to be of viral etiology; specific viral agents are seldom identified.

The hiatus between onset of viral symptoms and onset of ADEM may range from 2-21 days. The two phases of illness are typically separated by a phase of recovery from fever and other constitutional manifestations of the initial infectious phase of illness. ADEM may possibly arise after intervals as long as 30 or more days after an infectious prodrome. The longer the interval between the presumed prodrome and ADEM, the less certain one can be of the etiologic association. A minority of cases lack a prodromal phase. Establishing the etiologic role of immunizations has proven controversial.

Clear links between the Pasteur rabies vaccine and ADEM have been established. Immunizations less frequently associated with ADEM include pertussis, measles,[8] Japanese B virus, tetanus, influenza, hepatitis B, diphtheria, rubella, pneumococcus, varicella, smallpox, poliomyelitis, and human papillomavirus.[82]

The provocation provided by an infectious agent likely requires participation of other genetic or immuno-experiential factors of the individual in order to give rise to ADEM. These factors likely include genetically or experientially determined aspects of immunoregulation, particularly T-helper cell function. Alves-Leon et al have found that the alleles HLA DQB1*0602, DRB1*1501, and DRB1*1503 confer genetic susceptibility to acute disseminated encephalomyelitis.[9]

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Contributor Information and Disclosures
Author

J Nicholas Brenton, MD Assistant Professor of Pediatrics and Neurology, University of Virginia School of Medicine

J Nicholas Brenton, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Nothing to disclose.

Coauthor(s)

Robert Stanley Rust, Jr, MD, MA Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia School of Medicine; Chair-Elect, Child Neurology Section, American Academy of Neurology

Robert Stanley Rust, Jr, MD, MA is a member of the following medical societies: Child Neurology Society, Society for Pediatric Research, American Headache Society, International Child Neurology Association, American Academy of Neurology, American Epilepsy Society, American Neurological Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Glenn Lopate, MD Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, Phi Beta Kappa

Disclosure: Nothing to disclose.

Chief Editor

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS Professor Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Neuroscience Director, Department of Neurology, Crouse Irving Memorial Hospital

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS is a member of the following medical societies: American College of International Physicians, American Heart Association, American Stroke Association, American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners Institute, National Association of Managed Care Physicians, American College of Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, Royal Society of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Christopher Luzzio, MD Clinical Assistant Professor, Department of Neurology, University of Wisconsin at Madison School of Medicine and Public Health

Christopher Luzzio, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

References
  1. Alper G. Acute disseminated encephalomyelitis. J Child Neurol. 2012 Nov. 27(11):1408-25. [Medline].

  2. Huppke P, Rostasy K, Karenfort M, Huppke B, Seidl R, Leiz S, et al. Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients. Mult Scler. 2012 Nov 5. [Medline].

  3. Ishizu T, Minohara M, Ichiyama T, et al. CSF cytokine and chemokine profiles in acute disseminated encephalomyelitis. J Neuroimmunol. 2006 Jun. 175(1-2):52-8. [Medline].

  4. Franciotta D, Zardini E, Ravaglia S, et al. Cytokines and chemokines in cerebrospinal fluid and serum of adult patients with acute disseminated encephalomyelitis. J Neurol Sci. 2006 Sep 25. 247(2):202-7. [Medline].

  5. Banwell B, Kennedy J, Sadovnick D, Arnold DL, Magalhaes S, Wambera K, et al. Incidence of acquired demyelination of the CNS in Canadian children. Neurology. 2009 Jan 20. 72(3):232-9. [Medline].

  6. Sacconi S, Salviati L, Merelli E. Acute disseminated encephalomyelitis associated with hepatitis C virus infection. Arch Neurol. 2001 Oct. 58(10):1679-81. [Medline].

  7. Alper G, Heyman R, Wang L. Multiple sclerosis and acute disseminated encephalomyelitis diagnosed in children after long-term follow-up: comparison of presenting features. Dev Med Child Neurol. 2009 Jun. 51(6):480-6. [Medline]. [Full Text].

  8. Chowdhary J, Ashraf SM, Khajuria K. Measles with acute disseminated encephalomyelitis (ADEM). Indian Pediatr. 2009 Jan. 46(1):72-4. [Medline].

  9. Alves-Leon SV, Veluttini-Pimentel ML, Gouveia ME, Malfetano FR, Gaspareto EL, Alvarenga MP, et al. Acute disseminated encephalomyelitis: clinical features, HLA DRB1*1501, HLA DRB1*1503, HLA DQA1*0102, HLA DQB1*0602, and HLA DPA1*0301 allelic association study. Arq Neuropsiquiatr. 2009 Sep. 67(3A):643-51. [Medline].

  10. Rust RS, Dodson WE, Trotter JL. Cerebrospinal fluid IgG in childhood: the establishment of reference values. Ann Neurol. 1988 Apr. 23(4):406-10. [Medline].

  11. Callen DJ, Shroff MM, Branson HM, Li DK, Lotze T, Stephens D, et al. Role of MRI in the differentiation of ADEM from MS in children. Neurology. 2009 Mar 17. 72(11):968-73. [Medline].

  12. Baum PA, Barkovich AJ, Koch TK, Berg BO. Deep gray matter involvement in children with acute disseminated encephalomyelitis. AJNR Am J Neuroradiol. 1994 Aug. 15(7):1275-83. [Medline].

  13. Apak RA, Kose G, Anlar B, et al. Acute disseminated encephalomyelitis in childhood: report of 10 cases. J Child Neurol. 1999 Mar. 14(3):198-201. [Medline].

  14. Kesselring J, Miller DH, Robb SA, Kendall BE, Moseley IF, Kingsley D, et al. Acute disseminated encephalomyelitis. MRI findings and the distinction from multiple sclerosis. Brain. 1990 Apr. 113 ( Pt 2):291-302. [Medline].

  15. van der Meyden CH, de Villiers JF, Middlecote BD, Terblanchè J. Gadolinium ring enhancement and mass effect in acute disseminated encephalomyelitis. Neuroradiology. 1994 Apr. 36(3):221-3. [Medline].

  16. Honkaniemi J, Dastidar P, Kähärä V, Haapasalo H. Delayed MR imaging changes in acute disseminated encephalomyelitis. AJNR Am J Neuroradiol. 2001 Jun-Jul. 22(6):1117-24. [Medline].

  17. Trotter JL, Rust RS. Human cerebrospinal fluid immunology. In: Herndon RM, Brumback RA, eds. The Cerebrospinal Fluid. Boston, Mass:. Kluwer Academic Publishers. 1989:179-226.

  18. Nishikawa M, Ichiyama T, Hayashi T, Ouchi K, Furukawa S. Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis. Pediatr Neurol. 1999 Aug. 21(2):583-6. [Medline].

  19. Stricker RB, Miller RG, Kiprov DD. Role of plasmapheresis in acute disseminated (postinfectious) encephalomyelitis. J Clin Apher. 1992. 7(4):173-9. [Medline].

  20. Kanter DS, Horensky D, Sperling RA, Kaplan JD, Malachowski ME, Churchill WH Jr. Plasmapheresis in fulminant acute disseminated encephalomyelitis. Neurology. 1995 Apr. 45(4):824-7. [Medline].

  21. Sugita K, Suzuki N, Shimizu N, Takanashi J, Ishii M, Niimi N. Involvement of cytokines in N-methyl-N'-nitro-N-nitrosoguanidine-induced plasminogen activator activity in acute disseminated encephalomyelitis and multiple sclerosis lymphocytes. Eur Neurol. 1993. 33(5):358-62. [Medline].

  22. Kuni BJ, Banwell BL, Till C. Cognitive and Behavioral Outcomes in Individuals With a History of Acute Disseminated Encephalomyelitis (ADEM). Dev Neuropsychol. 2012 Nov. 37(8):682-96. [Medline].

  23. Atalar MH. Acute disseminated encephalomyelitis in an adult patient. Magnetic resonance and diffusion-weighted imaging findings. Saudi Med J. 2006 Jan. 27(1):105-8. [Medline].

  24. Brinar VV. Non-MS recurrent demyelinating illnesses. Clin Neurol Neurosurg. 2004. 106(3):197-210.

  25. Dale RC, Branson JA. Acute disseminated encephalomyelitis or multiple sclerosis: can the initial presentation help in establishing a correct diagnosis?. Arch Dis Child. 2005 Jun. 90(6):636-9. [Medline].

  26. Garg RK. Acute disseminated encephalomyelitis. Postgrad Med J. 2003 Jan. 79(927):11-7. [Medline].

  27. Hahn JS, Siegler DJ, Enzmann D. Intravenous gammaglobulin therapy in recurrent acute disseminated encephalomyelitis. Neurology. 1996 Apr. 46(4):1173-4. [Medline].

  28. Hartel C, Schilling S, Gottschalk S, Sperner J. Multiphasic disseminated encephalomyelitis associated with streptococcal infection. Eur J Paediatr Neurol. 2002. 6(6):327-9. [Medline].

  29. Holtmannspotter M, Inglese M, Rovaris M, et al. A diffusion tensor MRI study of basal ganglia from patients with ADEM. J Neurol Sci. 2003 Jan 15. 206(1):27-30. [Medline].

  30. John L, Khaleeli AA, Larner AJ. Acute disseminated encephalomyelitis: a riddle wrapped in a mystery inside an enigma. Int J Clin Pract. 2003 Apr. 57(3):235-7. [Medline].

  31. Kadhim H, De Prez C, Gazagnes MD, Sebire G. In situ cytokine immune responses in acute disseminated encephalomyelitis: insights into pathophysiologic mechanisms. Hum Pathol. 2003 Mar. 34(3):293-7. [Medline].

  32. Mariotti P, Batocchi AP, Colosimo C,et al. Multiphasic demyelinating disease involving central and peripheral nervous system in a child. Neurology. 2003 Jan 28. 60(2):348-9. [Medline].

  33. Murthy JM. Acute disseminated encephalomyelitis. Neurol India. 2002 Sep. 50(3):238-43. [Medline].

  34. Oksuzler YF, Cakmakci H, Kurul S, et al. Diagnostic value of diffusion-weighted magnetic resonance imaging in pediatric cerebral diseases. Pediatr Neurol. 2005 May. 32(5):325-33. [Medline].

  35. Pena JA, Montiel-Nava C, Hernandez F, et al. [Disseminated acute encephalomyelitis in children]. Rev Neurol. 2002 Jan 16-31. 34(2):163-8. [Medline].

  36. Pradhan S, Gupta RP, Shashank S, Pandey N. Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis. J Neurol Sci. 1999 May 1. 165(1):56-61. [Medline].

  37. Rust RS. Multiple sclerosis, acute disseminated encephalomyelitis, and related conditions. Semin Pediatr Neurol. 2000 Jun. 7(2):66-90. [Medline].

  38. Sakakibara R, Yamanishi T, Uchiyama T, Hattori T. Acute urinary retention due to benign inflammatory nervous diseases. J Neurol. 2006 Aug. 253(8):1103-10. [Medline].

  39. Schwarz S, Mohr A, Knauth M, Wildemann B, Storch-Hagenlocher B. Acute disseminated encephalomyelitis: a follow-up study of 40 adult patients. Neurology. 2001 May 22. 56(10):1313-8. [Medline].

  40. Sunnerhagen KS, Johansson K, Ekholm S. Rehabilitation problems after acute disseminated encephalomyelitis: four cases. J Rehabil Med. 2003 Jan. 35(1):20-5. [Medline].

  41. Tenembaum S, Chamoles N. Acute disseminated encephalomyelitis: a longterm follow-up study of 84 pediatric patients. J Neurol Neurosurg Psychiatr. 1995. 58(4):467-470.

  42. Verbruggen SC, Catsman CE, Naghib S, et al. [Respiratory insufficiency caused by acute disseminated encephalomyelitis in a child]. Ned Tijdschr Geneeskd. 2006 May 20. 150(20):1134-8. [Medline].

  43. Weng WC, Peng SS, Lee WT, et al. Acute disseminated encephalomyelitis in children: one medical center experience. Acta Paediatr Taiwan. 2006 Mar-Apr. 47(2):67-71. [Medline].

  44. Wingerchuk DM. The clinical course of acute disseminated encephalomyelitis. Neurol Res. 2006 Apr. 28(3):341-7. [Medline].

  45. Yapici Z, Eraksoy M. Bilateral demyelinating tumefactive lesions in three children with hemiparesis. J Child Neurol. 2002 Sep. 17(9):655-60. [Medline].

  46. Tenembaum S, Chitnis T, Ness J, Hahn JS. Acute disseminated encephalomyelitis. Neurology. 2007. 68(suppl 2):S23-S36. [Full Text].

  47. Dale RC, de Sousa C, Chong WK, Cox TC, Harding B, Neville BG. Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain. 2000 Dec. 123 Pt 12:2407-22. [Medline].

  48. Dale RC. Acute disseminated encephalomyelitis. Semin Pediatr Infect Dis. 2003 Apr. 14(2):90-5. [Medline].

  49. Van Haren K, Tomooka BH, Kidd BA, Banwell B, Bar-Or A, Chitnis T. Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing-remitting multiple sclerosis. Mult Scler. 2013 Nov. 19(13):1726-33. [Medline].

  50. Baumann M, Sahin K, Lechner C, Hennes EM, Schanda K, Mader S. Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein. J Neurol Neurosurg Psychiatry. 2014 Aug 13. [Medline].

  51. Pröbstel AK, Dornmair K, Bittner R, Sperl P, Jenne D, Magalhaes S. Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis. Neurology. 2011 Aug 9. 77(6):580-8. [Medline].

  52. Brilot F, Dale RC, Selter RC, Grummel V, Kalluri SR, Aslam M, et al. Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease. Ann Neurol. 2009 Dec. 66(6):833-42. [Medline].

  53. Di Pauli F, Mader S, Rostasy K, Schanda K, Bajer-Kornek B, Ehling R. Temporal dynamics of anti-MOG antibodies in CNS demyelinating diseases. Clin Immunol. 2011 Mar. 138(3):247-54. [Medline].

  54. Murthy SN, Faden HS, Cohen ME, Bakshi R. Acute disseminated encephalomyelitis in children. Pediatrics. 2002 Aug. 110(2 Pt 1):e21. [Medline].

  55. Leake JA, Albani S, Kao AS, Senac MO, Billman GF, Nespeca MP, et al. Acute disseminated encephalomyelitis in childhood: epidemiologic, clinical and laboratory features. Pediatr Infect Dis J. 2004 Aug. 23(8):756-64. [Medline].

  56. Pohl D, Hennemuth I, von Kries R, Hanefeld F. Paediatric multiple sclerosis and acute disseminated encephalomyelitis in Germany: results of a nationwide survey. Eur J Pediatr. 2007 May. 166(5):405-12. [Medline].

  57. Torisu H, Kira R, Ishizaki Y, Sanefuji M, Yamaguchi Y, Yasumoto S. Clinical study of childhood acute disseminated encephalomyelitis, multiple sclerosis, and acute transverse myelitis in Fukuoka Prefecture, Japan. Brain Dev. 2010 Jun. 32(6):454-62. [Medline].

  58. Hynson JL, Kornberg AJ, Coleman LT, Shield L, Harvey AS, Kean MJ. Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children. Neurology. 2001 May 22. 56(10):1308-12. [Medline].

  59. Krupp LB, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC, et al. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler. 2013 Sep. 19(10):1261-7. [Medline].

  60. Hung KL, Liao HT, Tsai ML. The spectrum of postinfectious encephalomyelitis. Brain Dev. 2001 Mar. 23(1):42-5. [Medline].

  61. Mikaeloff Y, Suissa S, Vallée L, Lubetzki C, Ponsot G, Confavreux C, et al. First episode of acute CNS inflammatory demyelination in childhood: prognostic factors for multiple sclerosis and disability. J Pediatr. 2004 Feb. 144(2):246-52. [Medline].

  62. Idrissova ZhR, Boldyreva MN, Dekonenko EP, Malishev NA, Leontyeva IY, Martinenko IN, et al. Acute disseminated encephalomyelitis in children: clinical features and HLA-DR linkage. Eur J Neurol. 2003 Sep. 10(5):537-46. [Medline].

  63. Anlar B, Basaran C, Kose G, Guven A, Haspolat S, Yakut A, et al. Acute disseminated encephalomyelitis in children: outcome and prognosis. Neuropediatrics. 2003 Aug. 34(4):194-9. [Medline].

  64. Jacobs RK, Anderson VA, Neale JL, Shield LK, Kornberg AJ. Neuropsychological outcome after acute disseminated encephalomyelitis: impact of age at illness onset. Pediatr Neurol. 2004 Sep. 31(3):191-7. [Medline].

  65. Hahn CD, Miles BS, MacGregor DL, Blaser SI, Banwell BL, Hetherington CR. Neurocognitive outcome after acute disseminated encephalomyelitis. Pediatr Neurol. 2003 Aug. 29(2):117-23. [Medline].

  66. Brenton JN, Koenig S, Goldman MD. Vitamin D status and age of onset of demyelinating disease. Multiple Sclerosis and Related Disorders. 2014. [Full Text].

  67. Mowry EM, James JA, Krupp LB, Waubant E. Vitamin D status and antibody levels to common viruses in pediatric-onset multiple sclerosis. Mult Scler. 2011 Jun. 17(6):666-71. [Medline].

  68. Banwell B, Bar-Or A, Arnold DL, Sadovnick D, Narayanan S, McGowan M. Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study. Lancet Neurol. 2011 May. 10(5):436-45. [Medline].

  69. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20. 296(23):2832-8. [Medline].

  70. Mikaeloff Y, Caridade G, Husson B, Suissa S, Tardieu M. Acute disseminated encephalomyelitis cohort study: prognostic factors for relapse. Eur J Paediatr Neurol. 2007 Mar. 11(2):90-5. [Medline].

  71. McKeon A, Lennon VA, Lotze T, Tenenbaum S, Ness JM, Rensel M, et al. CNS aquaporin-4 autoimmunity in children. Neurology. 2008 Jul 8. 71(2):93-100. [Medline].

  72. Saiki S, Ueno Y, Moritani T, Sato T, Sekine T, Kawajiri S. Extensive hemispheric lesions with radiological evidence of blood-brain barrier integrity in a patient with neuromyelitis optica. J Neurol Sci. 2009 Sep 15. 284(1-2):217-9. [Medline].

  73. Eichel R, Meiner Z, Abramsky O, Gotkine M. Acute disseminating encephalomyelitis in neuromyelitis optica: closing the floodgates. Arch Neurol. 2008 Feb. 65(2):267-71. [Medline].

  74. Kaneko K, Sato DK, Misu T, Kurosawa K, Nakashima I, Fujihara K. Anti-N-methyl-D-aspartate receptor encephalitis with multiphasic demyelination. Ann Neurol. 2014 Sep. 76(3):462-4. [Medline].

  75. Okumura A, Nakazawa M, Igarashi A, Abe S, Ikeno M, Nakahara E, et al. Anti-aquaporin 4 antibody-positive acute disseminated encephalomyelitis. Brain Dev. 2014 May 16. [Medline].

  76. Titulaer MJ, Höftberger R, Iizuka T, Leypoldt F, McCracken L, Cellucci T, et al. Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis. Ann Neurol. 2014 Mar. 75(3):411-28. [Medline]. [Full Text].

  77. Huppke P, Rostasy K, Karenfort M, Huppke B, Seidl R, Leiz S, et al. Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients. Mult Scler. 2013 Jun. 19(7):941-6. [Medline].

  78. Shaw CM, Alvord EC Jr. Multiple sclerosis beginning in infancy. J Child Neurol. 1987 Oct. 2(4):252-6. [Medline].

  79. Maeda Y, Kitamoto I, Kurokawa T, Ueda K, Hasuo K, Fujioka K. Infantile multiple sclerosis with extensive white matter lesions. Pediatr Neurol. 1989 Sep-Oct. 5(5):317-9. [Medline].

  80. Vliegenthart WE, Sanders EA, Bruyn GW, Vielvoye GJ. An unusual CT-scan appearance in multiple sclerosis. J Neurol Sci. 1985 Nov. 71(1):129-34. [Medline].

  81. Noorbakhsh F, Johnson RT, Emery D, Power C. Acute disseminated encephalomyelitis: clinical and pathogenesis features. Neurol Clin. 2008 Aug. 26(3):759-80, ix. [Medline].

  82. Cohen SR, Brooks BR, Herndon RM, McKhann GM. A diagnostic index of active demyelination: myelin basic protein in cerebrospinal fluid. Ann Neurol. 1980 Jul. 8(1):25-31. [Medline].

  83. Höllinger P, Sturzenegger M, Mathis J, Schroth G, Hess CW. Acute disseminated encephalomyelitis in adults: a reappraisal of clinical, CSF, EEG, and MRI findings. J Neurol. 2002 Mar. 249(3):320-9. [Medline].

  84. Tenembaum S, Chamoles N, Fejerman N. Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients. Neurology. 2002 Oct 22. 59(8):1224-31. [Medline].

  85. Kleiman M, Brunquell P. Acute disseminated encephalomyelitis: response to intravenous immunoglobulin. J Child Neurol. 1995 Nov. 10(6):481-3. [Medline].

  86. Keegan M, Pineda AA, McClelland RL, Darby CH, Rodriguez M, Weinshenker BG. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology. 2002 Jan 8. 58(1):143-6. [Medline].

  87. Rust RS, Mathisen J, Prensky AL, et al. Acute disseminatedencephalomyelitis (ADE) and childhood multiple sclerosis(MS). Ann Neurol. 1989. 26:467.

 
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Fatal ADEM-related transverse myelitis in a 13-month-old. This is an image of the MIDBRAIN NOT OF THE CERVICAL CORD RECOMMEND ELIMINATING THIS and ADD AN IMAGE OF THE CERVICAL CORD AFFECTED BY ADEM-RELATED TANSVERSE MYELITIS
Typical childhood ADEM in 7-year-old. Note tendency to involve gray-white junction, the fact that the lesion margins are less well defined than typical MS plaques, and that the deep white matter lesions are not oriented perpendicularly to the ventricular surface as is typical in MS.
Typical adolescent multiple sclerosis findings on MRI. Note the tendency of lesions to exhibit sharp margins, to be elongated, to occur in deep white matter or corpus callosum sparing the cortical gray-white junction, and to be oriented perpendicularly to the ventricular surface.
 
 
 
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