Saturday, 21 November 2015

A new type of Antibody induced demyelination

Di Pauli F, Höftberger R, Reindl M, Beer R, Rhomberg P, Schanda K, Sato D, Fujihara K, Lassmann H, Schmutzhard E, Berger T. Fulminant demyelinating encephalomyelitis: Insights from antibody studies and neuropathology. Neurol Neuroimmunol Neuroinflamm. 2015;2(6):e175.

OBJECTIVES:Antibodies to myelin oligodendrocyte glycoprotein (MOG) are detectable in inflammatory demyelinating CNS diseases, and MOG antibody-associated diseases seem to have a better prognosis despite occasionally severe presentations.
METHODS: We report the case of a 71-year-old patient with acute visual and gait disturbance that dramatically worsened to bilateral amaurosis, tetraplegia, and respiratory insufficiency within a few days.
RESULTS: MRI showed multiple progressive cerebral and spinal lesions with diffusion restriction (including both optic nerves) and marginal contrast enhancement. Routine blood and CSF measures including oligoclonal bands were normal. At disease onset, MOG immunoglobulin G was detected (serum titre 1:1,280, corresponding CSF titer was 1:20) and remained positive in patient serum. Aquaporin-4 antibodies were absent at disease onset but seroconverted to positive at week 9. In addition, CSF glial fibrillary acid protein and myelin basic protein levels were very high at onset but decreased during disease course. After 4 months, the patient died despite immunomodulatory treatment. Post-mortem neuropathologic examination revealed an acute multiple sclerosis (MS) defined by multiple demyelinating lesions with a pronounced destructive component and loss of astrocytes. Lesion pattern of optic chiasm met MS pattern II characterized by antibody and complement-mediated demyelination.
CONCLUSION The case with the clinical presentation of an acute demyelinating encephalomyelitis with predominant optic and spinal involvement, absent oligoclonal bands, a histopathology of acute MS pattern II and development of aquaporin-4 antibodies extends the spectrum of MOG antibody-associated encephalomyelitis. Although, MOG antibodies are suspected to indicate a favorable prognosis, fulminant disease courses are possible and warrant an aggressive immunotherapy.

There are mice that have all T cells reactive to MOG and they get optic neuritis and sub clinical spinal cord disease when they have antibodies to MOG and they get full blown EAE with clinical disease due to spinal cord disease. There are a group of people with Neuromyelitis optica (NMO) that have anti-MOG antibodies and in this case there is a person who had antibodies and converted to produce aquaporin 4 anti-astrocyte antibodies that are characteristic of NMO, this person sadly died. The authors conclude that aggressive immuotherapy is warranted but the question remains what is the most effective treatment for NMO as it behaves differently to MS. Should we even write about NMO although it was once called Devic's MS.

4 comments:

  1. I met some people with NMO have not yet met any man with NMO, only women, anti aquaporin 4 positive and negative oligloconais bands ... What is the prognosis of NMO with treatment using mycophenolate mofetil?

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  2. The fact you've met several people with NMO is remarkable given this is a rare disease! Indeed NMO is generally more prevalent in women. Due to low prevalence and incidence it is notoriously difficult to get dependable figures on treatment effect, but MMF and Azathioprine are both commonly used long term strategies. Where available and affordable Rituximab is now often used with good success, though - again - no phase III trial evidence. A number of trials are underway (https://clinicaltrials.gov/ct2/results?term=nmo&pg=1), and dare I say the word, somebody filed Cladribine for NMO earlier this year (http://www.google.com/patents/WO2015114315A1?cl=en).

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  3. Docs then the Ministry of Health in Brazil "not good" with data management. With exactly 01 years and 08 making monitoring for MS ever met about 10, 12 patients with NMO in my town. All with negative oligloconais bands and anti-aquaporin 4 antibody positive ... Some are stable treatment with azathioprine base, while others need the mycophenolate ... I have not read about epidemiological studies of NMO in Brazil ...

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