History

Fact Explanation
History of preceding infection Patients can develop acute disseminating encephalitis following measles, smallpox, rubella, mycoplasma, Epstein-Barr virus, Cytomegalovirus, HIV, rotavirus diarrhea and chickenpox infections and less commonly following non-specific upper respiratory tract infections (Influenza A or B). [1,3,4,5]
History of immunization Rabies, diphtheria, tetanus, pertussis, smallpox, measles, japanese B encephalitis, polio, hepatitis B, BCG and influenza vaccines are known to cause acute disseminating encephalitis. [1,3,4,5]
Fever Fever usually appear 4–21 days after the precipitating event and it is often accompanied by malaise and myalgia. [1,3]
Seizures Seizures are common in acute haemorrhagic disseminating encephalomyelitis. [1,3]
Altered mental status Mental status of the patient may vary from lethargy to coma. These neurological symptoms rapidly develop. [1,3]
Headache Headache is often associated with nausea, and vomiting in most of the patients. Headache can be a part of meningismus. [1]
Focal neurological signs Patients can present with hemiparesis, cranial nerve palsies, and paraparesis. [1]
Meningismus [1,3] Signs of meningismus include neck pain, photophobia, and headache.
Movement disorders [1] Affected patients present with ataxia and difficulty in walking. Cerebral ataxia is commonly associated with varicella infection. [6]
Symptoms of optic neuritis Optic neuritis causes acute loss of vision (over hours to days), eye pain, and loss of color vision. Optic neuritis in acute disseminating encephalitis is often bilateral. [1,2]
Facial weakness Facial weakness occurs due to facial nerve lesions. Patients complain of facial asymmetry, difficulty in speaking and closing eyes. [3]
References
  1. GARG R K. Acute disseminated encephalomyelitis. [online] 2003 January, 79(927):11-17 [viewed 13 September 2014] Available from: doi:10.1136/pmj.79.927.11
  2. OSBORNE B. J., VOLPE N. J.. Optic neuritis and risk of MS: Differential diagnosis and management. Cleveland Clinic Journal of Medicine [online] 2009 March, 76(3):181-190 [viewed 13 September 2014] Available from: doi:10.3949/ccjm.76a.07268
  3. DALE R. C.. Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. [online] 2000 December, 123(12):2407-2422 [viewed 13 September 2014] Available from: doi:10.1093/brain/123.12.2407
  4. JAYAKRISHNAN MP, KRISHNAKUMAR P. Clinical profile of acute disseminated encephalomyelitis in children J Pediatr Neurosci [online] 2010, 5(2):111-114 [viewed 13 September 2014] Available from: doi:10.4103/1817-1745.76098
  5. MENGE TIL, HEMMER BERNHARD, NESSLER STEFAN, WIENDL HEINZ, NEUHAUS OLIVER, HARTUNG HANS-PETER, KIESEIER BERND C., STüVE OLAF. Acute Disseminated Encephalomyelitis. Arch Neurol [online] 2005 November [viewed 13 September 2014] Available from: doi:10.1001/archneur.62.11.1673
  6. ALEXANDER M, MURTHY JM. Acute disseminated encephalomyelitis: Treatment guidelines Ann Indian Acad Neurol [online] 2011 Jul, 14(Suppl1):S60-S64 [viewed 13 September 2014] Available from: doi:10.4103/0972-2327.83095
  7. LASSMANN H.. Acute disseminated encephalomyelitis and multiple sclerosis. Brain [online] December, 133(2):317-319 [viewed 15 September 2014] Available from: doi:10.1093/brain/awp342

Examination

Fact Explanation
Altered mental state Most of the affected patients are irritable, and lethargic. Some may even progress to coma. Altered behavior and personality changes can also be detected. Other neuropsychiatric symptoms include aggression, agitation, auditory hallucinations, catatonic waxy flexibility, delusions, disorganized behaviour, disorganized thinking, disorientation, inappropriate laughter, hostility, irritability, mania, mood lability, mutism and paranoia. [5,6,8]
Language disturbances Language disturbances is commonly seen in children rather adults. Aphasia is a common examination finding. [7,8]
Fever Some patients are febrile. [1,8]
Signs of meningismus Neck stiffness and photophobia can be elicited in some patients. [1,2]
Signs of optic neuritis Patients with optic neuritis can have reduced visual acuity or blindness, double vision and visual field defects. [1,8,9]
Ophthalmoplegia [2] Demyelination of the third, fourth and sixth cranial nerves leads to ophthalmoplegia. [4]
Signs of facial nerve palsy Facial nerve is the commonest cranial nerve that is involved. Upper motor type of facial nerve palsy leads to reduced power of orbicularis oculi (reduced force of eye closure), muscles of mastication (deviation of mouth towards the side of lesion) and platysma sparing the function of occipitofrontalis muscle. [3,9]
Palatal palsy Demyelination of the vagus nerve causes palatal palsy. The patient finds it difficult to raise the palate with open mouth. [9]
Hemiparesis Upper motor type lesions produce increased muscle tone, increased tendon reflexes, extensor plantar response and positive ankle clonus. [1]
Ataxia Cerebral ataxia can be detected especially in patients with a recent history of varicella infection. [5]
References
  1. GARG R K. Acute disseminated encephalomyelitis. [online] 2003 January, 79(927):11-17 [viewed 13 September 2014] Available from: doi:10.1136/pmj.79.927.11
  2. DALE R. C.. Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. [online] 2000 December, 123(12):2407-2422 [viewed 13 September 2014] Available from: doi:10.1093/brain/123.12.2407
  3. ALSUHAIBANI AH. Facial Nerve Palsy: Providing Eye Comfort and Cosmesis Middle East Afr J Ophthalmol [online] 2010, 17(2):142-147 [viewed 13 September 2014] Available from: doi:10.4103/0974-9233.63078
  4. THURTELL M. J., HALMAGYI G. M.. Complete Ophthalmoplegia: An Unusual Sign of Bilateral Paramedian Midbrain-Thalamic Infarction. Stroke [online] December, 39(4):1355-1357 [viewed 13 September 2014] Available from: doi:10.1161/STROKEAHA.107.504761
  5. KRISHNAKUMAR P, JAYAKRISHNAN MP, DEVARAJAN E. Acute disseminated encephalomyelitis presenting as depressive episode Indian J Psychiatry [online] 2011, 53(4):367-369 [viewed 15 September 2014] Available from: doi:10.4103/0019-5545.91913
  6. KODADHALA VIJAY, DEVULAPALLI SARAVANA, KURUKUMBI MOHANKUMAR, JAYAM-TROUTH ANNAPURNI. A Rare Sequela of Acute Disseminated Encephalomyelitis. Case Reports in Neurological Medicine [online] 2014 December, 2014:1-5 [viewed 15 September 2014] Available from: doi:10.1155/2014/291380
  7. PANICKER JN, NAGARAJA D, KOVOOR JME, SUBBAKRISHNA DK. Descriptive study of acute disseminated encephalomyelitis and evaluation of functional outcome predictors. J Postgrad Med [online] 2010 December [viewed 15 September 2014] Available from: doi:10.4103/0022-3859.62425
  8. DI COSTANZO M, CAMARCA ME, COLELLA MG, BUTTARO G, ELEFANTE A, CANANI RB. Acute disseminated encephalomyelitis presenting as fever of unknown origin: case report BMC Pediatr [online] :103 [viewed 15 September 2014] Available from: doi:10.1186/1471-2431-11-103
  9. JAYAKRISHNAN MP, KRISHNAKUMAR P. Clinical profile of acute disseminated encephalomyelitis in children J Pediatr Neurosci [online] 2010, 5(2):111-114 [viewed 15 September 2014] Available from: doi:10.4103/1817-1745.76098

Differential Diagnoses

Fact Explanation
Multiple sclerosis (MS) MS is also a demyelinating disease affecting the central nervous system. The clinical symptoms of both acute disseminated encephalitis and MS are similar. The differentiating feature is that MS can recur after the first few months of the illness. [1]
Transverse myelitis [1] Patients with transverse myelitis present with rapid-onset, severe paraparesis or quadriparesis. Motor weakness and sensory loss is usually bilateral and manifest over few hours to days. [3]
Optic neuritis [1] Optic neuritis is the inflammation of the optic nerve. This is commoner in females, between 18 and 45 years of age. Acute loss of vision and painful opthalmoplegia are common presentations of the disease. [4]
Cerebellitis [1] Cerebellitis can also manifest after viral infections like chickenpox, Epstein-Barr virus, and HIV. Ataxia, dysarthria, dysmetria, nystagmus, tremor and pendular reflexes can be detected on examination. [5]
Brain stem encephalitis [1] Progressive and symmetrical external ophthalmoplegia and ataxia develop within 4 weeks of illness. Altered level of consciousness or hyperreflexia are other examination findings of brain stem encephalitis. [6]
Viral encephalopathy [1] Viral encephalopathy can occur secondary to Herpes simplex virus type 1 and 2, aenoviruses, influenza A, enteroviruses, poliovirus, measles, mumps, rubella, rabies and arboviruses infections. [7]
Infectious meningoencephalitis Infectious meningoencephalitis present with fever and meningismus. The definitive diagnosis can be made with Gram stain and culture of the cerebrospinal fluid. [2]
Antiphospholipid antibody syndrome (APS) Patients with APS can lead to acute onset of clinical symptoms similar to acute disseminated polyneuritis due to cerebral ischemia. These lesions can be detected by MRI. History of recurrent arterial or venous thrombosis, recurrent miscarriages are suggestive of APS. Presence of anticardiolipin antibodies and lupus anticoagulants aids in making the definitive diagnosis. [2]
References
  1. GARG R K. Acute disseminated encephalomyelitis. [online] 2003 January, 79(927):11-17 [viewed 13 September 2014] Available from: doi:10.1136/pmj.79.927.11
  2. MENGE TIL, HEMMER BERNHARD, NESSLER STEFAN, WIENDL HEINZ, NEUHAUS OLIVER, HARTUNG HANS-PETER, KIESEIER BERND C., STüVE OLAF. Acute Disseminated Encephalomyelitis. Arch Neurol [online] 2005 November [viewed 13 September 2014] Available from: doi:10.1001/archneur.62.11.1673
  3. FROHMAN ELLIOT M., WINGERCHUK DEAN M.. Transverse Myelitis. N Engl J Med [online] 2010 August, 363(6):564-572 [viewed 13 September 2014] Available from: doi:10.1056/NEJMcp1001112
  4. MENON V, SAXENA R, MISRA R, PHULJHELE S. Management of optic neuritis Indian J Ophthalmol [online] 2011, 59(2):117-122 [viewed 13 September 2014] Available from: doi:10.4103/0301-4738.77020
  5. LIU WEN-CHENG, CHIU SHENG-KANG, HSIANG CHIH-WEIM, LIN TE-YU. Acute unilateral cerebellitis, Epstein-Barr virus, and HIV. The Lancet Infectious Diseases [online] 2014 August [viewed 13 September 2014] Available from: doi:10.1016/S1473-3099(14)70824-2
  6. VENKATESHWARA PRASAD KN, VENKATESH KS, DEVI NG. Bickerstaff brainstem encephalitis in pediatrics - A case report J Pediatr Neurosci [online] 2013, 8(3):263-264 [viewed 13 September 2014] Available from: doi:10.4103/1817-1745.123718
  7. KENNEDY P G E. VIRAL ENCEPHALITIS: CAUSES, DIFFERENTIAL DIAGNOSIS, AND MANAGEMENT. Journal of Neurology, Neurosurgery & Psychiatry [online] 2004 March, 75(90001):10i-15 [viewed 13 September 2014] Available from: doi:10.1136/jnnp.2003.034280

Investigations - for Diagnosis

Fact Explanation
Complete blood count Leucocytosis can be detected from the complete blood count. Mild thrombocytosis can be seen in some patients. [2,5]
Cerebrospinal fluid (CSF) full report CSF pressure is increased. Lymphocytic count is raised (as much as 1000/mm3) Polymorphonuclear leucocytosis can be an initial finding. CSF protein is usually less than 1.0 mg/l. Increased amounts of gammaglobulin and IgG and myelin basic protein can also be noted. CSF glucose content is usually normal. Rarely oligoclonal band of IgG may be demonstrated in CSF. [1,2,4]
Electroencephalography (EEG) EEG changes are often non-specific. Frequent slow-wave activity can also be detected in some patients. EEG can even be normal. [1,2]
MRI MRI of brain is more informative than the CT scan which shows patchy areas of white matter lesions. Involvement of the cerebellum and brainstem is more common in children. [1,2,3,4]
CT scan CT scan is usually normal during the initial periods of illness. After about 5 to 14 days CT scan shows, multifocal lesions in the subcortical white matter. [1,2,4]
Brain biopsy This is a very invasive investigation which is rarely done in the presence of diagnostic uncertainty. There is complete loss of myelin with preserved axons of the neurons. Inflammatory infiltrate consists of B and T lymphocytes, plasma cells, eosinophils and macrophages scattered around the small blood vessels. [2]
References
  1. GARG R K. Acute disseminated encephalomyelitis. [online] 2003 January, 79(927):11-17 [viewed 13 September 2014] Available from: doi:10.1136/pmj.79.927.11
  2. DALE R. C.. Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. [online] 2000 December, 123(12):2407-2422 [viewed 13 September 2014] Available from: doi:10.1093/brain/123.12.2407
  3. JAYAKRISHNAN MP, KRISHNAKUMAR P. Clinical profile of acute disseminated encephalomyelitis in children J Pediatr Neurosci [online] 2010, 5(2):111-114 [viewed 13 September 2014] Available from: doi:10.4103/1817-1745.76098
  4. MENGE TIL, HEMMER BERNHARD, NESSLER STEFAN, WIENDL HEINZ, NEUHAUS OLIVER, HARTUNG HANS-PETER, KIESEIER BERND C., STüVE OLAF. Acute Disseminated Encephalomyelitis. Arch Neurol [online] 2005 November [viewed 13 September 2014] Available from: doi:10.1001/archneur.62.11.1673
  5. STAMM B, MOSCHOPULOS M, HUNGERBUEHLER H, GUARNER J, GENRICH GL, ZAKI SR. Neuroinvasion by Mycoplasma pneumoniae in Acute Disseminated Encephalomyelitis Emerg Infect Dis [online] 2008 Apr, 14(4):641-643 [viewed 15 September 2014] Available from: doi:10.3201/eid1404.061366

Management - General Measures

Fact Explanation
Airway protection Airway protection should be done in patients who are semiconscious or comatosed, to minimize the risk of aspiration of gastric contents. Additionally, insertion of a nasogastric tube will allow free drainage of gastric contents and reduce the risk of aspiration. Tracheal intubation and mechanical ventilation is important in patients with respiratory paralysis. [2]
Antiepileptics Antiepileptics are indicated for the treatment when seizures are present. [2]
Prophylactic anticoagulation Prophylactic anticoagulation with heparin or warfarin is indicated to minimize the risk of deep vein thrombosis. [2]
Maintenance of electrolyte homeostasis This is a common reversible cause for the development of seizures. [2]
Immunization Post infectious acute disseminated encephalitis can be prevented by use of effective vaccines against mumps, measles, rubella, and chickenpox. [1]
Health education Patients with acute disseminated encephalitis usually shows complete resolution within a few days, or over a period of few weeks to months. The necessity of developmental assessment for children and psychological and behavioral therapy should also be told to the patient as they are beneficial for some patients. [1]
References
  1. GARG R K. Acute disseminated encephalomyelitis. [online] 2003 January, 79(927):11-17 [viewed 13 September 2014] Available from: doi:10.1136/pmj.79.927.11
  2. ALEXANDER M, MURTHY JM. Acute disseminated encephalomyelitis: Treatment guidelines Ann Indian Acad Neurol [online] 2011 Jul, 14(Suppl1):S60-S64 [viewed 13 September 2014] Available from: doi:10.4103/0972-2327.83095

Management - Specific Treatments

Fact Explanation
Intravenous corticosteroids [1,2] To reduce the inflammation and suppress immune reaction. Intravenous methyl prednisolone (10–30 mg/kg/day, up to a maximum of 1 g/day) is the first line drug in the treatment of acute disseminated encephalitis. Treatment should be continued for about 3 to 5 days. [3]
Plasmapheresis [1,2] Plasmapheresis is the second line treatment option once the intravenous corticosteroids fail to relieve symptoms. Plasmapheresis helps in removing the circulating autoantibodies. [3]
Intravenous immunoglobulin (IVIg) [1,2] IVIg is given 0.4 gm/kg/day for 5 days. [3]
Cyclophosphamide Cyclophosphamide is used in the treatment of fulminant disease. Acts as an immunosuppressant.[3]
Hypothermia Although less commonly practiced this is also an effective mode of treatment. [3]
References
  1. GARG R K. Acute disseminated encephalomyelitis. [online] 2003 January, 79(927):11-17 [viewed 13 September 2014] Available from: doi:10.1136/pmj.79.927.11
  2. ischemic lesions detectable by MRI may be indistinguishable from those seen with ADEM. A history of recurrent arterial or venous thrombosis, fetal loss, and the detection of specific anticardiolipin antibodies and lupus anticoagulants
  3. ALEXANDER M, MURTHY JM. Acute disseminated encephalomyelitis: Treatment guidelines Ann Indian Acad Neurol [online] 2011 Jul, 14(Suppl1):S60-S64 [viewed 13 September 2014] Available from: doi:10.4103/0972-2327.83095