leukoencephalopathy

see also:

• meningitis
• encephalopathy
• progressive multifocal leukoencephalopathy (PML)
• Herpes simplex virus (HSV)
• EBV / glandular fever / infectious mononucleosis
• encephalitis

• auto-immune demyelination of the central nervous system mainly affecting white matter especially in children and usually triggered by a viral infection in preceding 1-3 weeks
• can be rapidly progressive over hours sometimes with a poor prognosis
• multiple sclerosis (MS) in contrast is a recurrent flair disease rarely causing decreased mental state and mainly affects adults rather than children

• acute disseminated encephalomyelitis (ADEM)
  • aka acute demyelinating encephalomyelitis
  • a rare autoimmune disease (8 per 1,000,000 people per year) marked by a sudden, widespread attack of inflammation in the brain and spinal cord
  • produces multiple inflammatory lesions in the brain and spinal cord, particularly in the white matter
  • it may be one of the possible clinical causes of anti-MOG associated encephalomyelitis
  • unlike MS, ADEM is usually a single event which usually causes decreased conscious state, coma and death (in 5-10%) and occurs usually in children and is marked with rapid fever, although adolescents and adults can get the disease too
  • occurs in all ages, most reported cases are in children and adolescents, with the average age around 5 to 8 years old
  • adults may have a fulminant cause
  • with aggressive Rx, full recovery is seen in 50 to 75% of cases with increase in survival rates up to 70 to 90% with figures including minor residual disability as well
  • average time to recover from ADEM flare-ups is one to six months
  • cause is often a trigger such as from viral infection (eg. EBV / glandular fever / infectious mononucleosis, measles, COVID-19 coronavirus (2019-nCoV / SARS-CoV-2), etc) or, in extraordinarily rare cases, vaccinations or after organ transplantation
    • the only proven vaccine is the Semple form of the rabies vaccine but many other vaccines have been associated with it but at a case study level only
    • risk of developing ADEM from an actual measles infection, is about 1 per 1,000 cases whereas risk of ADEM from measles vaccination is 1 per 100,000
  • symptoms usually begin 1–3 weeks after infection (or vaccination)
    • may have fever, headache, nausea and vomiting, confusion, vision impairment, drowsiness, seizures, coma
    • generally have UMN lesion clinical features and may have hemiparesis, paraparesis, cranial nerve palsies and peripheral neuropathy
    • neurologic features rapidly progress over the course of hours to days
• Weston-Hurst syndrome
  • aka acute hemorrhagic leukoencephalitis
  • a hyperacute and frequently fatal form of ADEM - 2% of ADEM cases
  • less than 100 cases have been reported in the medical literature as of 2006
  • characterized by necrotizing vasculitis of venules and haemorrhage, and oedema
  • 70% mortality with death usually within 1 week
  • most survivors have neurologic deficits but surprisingly some can survive with little deficit considering the degree of white matter that was damaged
  • occasionally associated with ulcerative colitis and Crohn's disease, malaria, sepsis associated with immune complex deposition, methanol poisoning
  • cerebrospinal fluid (CSF) shows pleocytosis associated with normal glucose and increased protein
  • MRI shows extensive T2-weighted and fluid-attenuated inversion recovery (FLAIR) white matter hyperintensities with areas of haemorrhage, significant oedema, and mass effect

• supportive care of airways, etc for the unconscious patient as per usual Mx
• high dose IV steroids is usually recommended
• consideration for plasmapheresis, high doses of intravenous immunoglobulin (IVIg), mitoxantrone and cyclophosphamide