Why is neuromyelitis optica (NMO) endlessly surprising neurology?

Neuromyelitis optica (NMO) may be seen as the rarer and more mysterious cousin of multiple sclerosis (MS). It is characterised by a long segment of inflammation in the spinal cord, and this occurs almost simultaneously with inflammation of the optic nerves. Unlike MS, there is usually no involvement of the brain. NMO is also  known as Devic disease, after the French neurologist Eugène Devic.

Optic Nerve Side View. Francisco Bengoa on Flikr. https://www.flickr.com/photos/frecuenciamedicafb/7404373800
Optic Nerve Side View. Francisco Bengoa on Flikr. https://www.flickr.com/photos/frecuenciamedicafb/7404373800

 

NMO has had a very chequered history, refusing to be tied down, and defying all attempts at pigeon-holing. It has thrown up surprises over the decades, from its humble beginnings as a possible variant of multiple sclerosis, to its current complex status as an independent entity. It marks its territory by sprinkling anti aquaporin 4, its presumed causative antibody. We however now know that NMO doesn’t respect any of its defining features, even the presence of  aquaporin 4. The International consensus diagnostic criteria for neuromyelitis optica spectrum disorders confirms this. The experts struggled to pin it down … couldn’t…gave in… and took the easy way out: they developed a wider construct to accommodate it all, calling this neuromyelitis spectrum disorders (NMOSD).

Optic Nerve Front View. Francisco Bengoa on Flikr. https://www.flickr.com/photos/frecuenciamedicafb/7404373518/in/photostream/
Optic Nerve Front View. Francisco Bengoa on Flikr. https://www.flickr.com/photos/frecuenciamedicafb/7404373518/in/photostream/

 

Why is NMO such an enigma? Because neurologists are never satisfied with the superficial. We like digging deeper, unearthing the hidden. And the longer neurologist study NMO, the more unusual the syndrome turns out to be. No wonder NMO now also encompasses patients with cerebral, diencephalic, and brainstem lesions. How more intriguing can it get? Here are 6 surprising reports about NMO.

1. Spinal movement disorders

Spinal movement disorders are not run-of-the-mill in neurology. Myoclonus is probably the closest we get to see. A recent report in Movement Disorders (where else) enlightens us that spinal movement disorders in NMO are not infrequent (pardon the double negative, but it’s so convenient sometimes). The authors classify these disorders into five: tonic spasmsfocal dystonia; spinal myoclonus, spontaneous clonus, and tremors. The paper cautions that NMO may present first with spinal movement disorders, and these are often ‘overlooked, mislabeled, or under-treated’.

2. Impaired sense of smell

Just when you thought only neurodegenerative diseases present with an impaired sense of smell, an article turns up in Journal of Neurology titled Olfactory dysfunction in neuromyelitis optica spectrum disorders. The authors of the paper found that slightly more than half of the 49 subjects with NMO had olfactory dysfunction. Bring out the UPSIT.

3. Abortions

It appears that women who get pregnant after they are diagnosed with NMO are at a higher risk of abortions. This is from a piece in Neurology, a poster rather than a paper, titled Pregnancy outcome in aquaporin-4 positive neuromyelitis optica spectrum disorder. To complicate things, the women run the risk of pre-eclampsia if they also have other autoimmune diseases.

BIO 120 Lab Spinal Cord 031. djneight on Flikr. http://bit.ly/1p7S6pe
BIO 120 Lab Spinal Cord 031. djneight on Flikr. http://bit.ly/1p7S6pe

4. Unusual NMO differential diagnoses

The hallmark of NMO is the longitudinally extensive transverse myelitis (LETM), inflammation of the spinal cord at least 3 vertebral segments long. There are however many other diseases that present with LETM-see this review article in Nature Reviews Neurology which lists diseases that may manifest with LETM. Spoiler alert-it’s not open access! A recent piece in Neurology further extended the list (pardon the puns) with a case of MELAS presenting with LETM. MELAS is a mitochondrial disease that is more notorious for being a stroke mimic. Not to be outdone, JAMA Neurology had a case of nitrous oxide myelopathy with LETM.  Last word however to Neurology, LETM may be seen in CLIPPERS.

By Simon Caulton - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=29451273
By Simon CaultonOwn work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=29451273

5. Genetic pointer to relapse after treatment

It is no news that the monoclonal antibody, Rituximab, is an effective treatment for NMO. What is news is the report of a genetic marker of poor responsiveness to treatment with Rituximab. Researchers publishing in JAMA Neurology report that the fragment c gamma receptor 3A (FCGR3A) polymorphism increases the risk of relapse on treatment. Why on earth did they check for that specific polymorphism? I didn’t have access to the full article to find out…if you have the answer please let us know.

6. Escalation of treatment improves outcome

Sadly the outcome of NMO is not as good as one would hope. Relapses are common after remission, and these are not always amenable to treatment. A recent article however raised the spirits by showing that recalcitrant relapses may respond to escalation of the treatment level. The authors carried out a large scale trial published in Annals of Neurology titled Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses. With escalation of treatment, raising the bar a notch higher, remission is achieved in many cases. There is therefore no place for pulling any punches when it comes to NMO.

The phenotype of neuromyelitis optica will no doubt evolve further. Please leave a comment on any unusual sightings.

 

2 thoughts on “Why is neuromyelitis optica (NMO) endlessly surprising neurology?

  1. My fiancé was diagnosed with NMO in January 2016 … The progression of the disease has been rapid … He has had several attacks and is currently in a coma with lesions in his brain and on a respirator … We want to know do these lesions cause permanent brain damage ? Although he is not resposive he still has some brain activity … because this disease is so evasive and most hospitals have not seen this disease hands on we don’t want to make any bad moves … please we need some specialist advice !!

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    1. I am sorry for the unfortunate situation. Most neurology departments are capable of managing NMO and liaise with experts in bigger centers. I am sue this is the case here but you may wish to discuss with your neurologist options of treatment and prognosis. I wish him the best outcome

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