The 9 neurological manifestations of anti MOG antibody disorder

Autoimmune disorders are probably the most proliferative field of neurology. It seems like there is a blazing headline every week announcing a new antibody disease. Many of these antibodies are esoteric, but some shake the foundations of medical practice. Anti-MOG antibody is one of those which requires you to stop and pay attention, and it has significantly affected neurological practice in a very big way.

By Simon Caulton – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=20522656

Perhaps the most important thing about anti-MOG antibody disease is that, like the chameleon, it presents in many guises. For the neurologist therefore, the first thing is to recognise these varied manifestations. Here then is a quick list of the 9 manifestations of anti MOG antibody disorder.

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1. Optic neuritis (ON)

2. Neuromyelitis optica spectrum disorders (NMOSD)

3. Multiple sclerosis (MS)

4. Acute disseminated encephalomyelitis (ADEM)

5. Multiphasic disseminated encephalomyelitis (MDEM)

6. Isolated transverse myelitis (TM)

7. Leukodystrophy-like phenotype

8. Cerebral cortical encephalitis

9. Combined central and peripheral demyelinating syndrome (CCPD)

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

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You can explore anti MOG antibody disorder further in Neurochecklists under the following titles:

Image from page 400 of “Diseases of the nervous system” (1910). Internet Archive Book Images on Flickr. https://www.flickr.com/photos/internetarchivebookimages/14586405720/

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For a detailed review and guidance, check this paper in Journal of Neuroinflammation:

 MOG encephalomyelitis: international recommendations on diagnosis and antibody testing.

By PecatumOwn work, CC BY-SA 4.0, Link

The art of spinning catchy neurology headlines

The Neurology Lounge is always on the lookout for catchy neurology article titles to adorn its shelves. My previous blog post in this quest was The art of spinning catchy titles.

Since then, there have been quite a few brilliant article titles that have caught my fancy. We must acknowledge the wordsmiths who craftily and meticulously think up these magical headlines; they put in a lot of thought to conjure up the right words to use. The look into their crystal balls to predict the best way to play around with the meanings. With a bit of lexical alchemy, they miraculously come up with the titles that make us do a double-take, but do so with a smile. Below are 9 such catchy titles.

Parkinson’s disease: Oh my gut! 

By The original uploader was Arnavaz at French WikipediaThis image is an old version created by Medium69.Cette image est une ancienne version créée par Medium69.Please credit this : William Crochot – http://www.cancer.gov, Public Domain, Link

This title reflects the science suggesting that Parkinson’s disease originates from the gut. This editorial restates the proposition that α-synuclein starts accumulating in the intestines before migrating, up the vagus nerve, ‘in a prion-like fashion’, to the brain.

Patent foramen ovale and migraine: closing the debate

Medical Illustrations by Patrick Lynch, generated for multimedia teaching projects by the Yale University School of Medicine, Center for Advanced Instructional Media, 1987-2000.

Patent foramen ovale (PFO) is a hole in the heart which connects the upper two heart chambers, or atria. It normally closes after birth, but in some people it persists to cause some grief to cardiologists and neurologists. Whether a PFO causes migraine or not is a long standing contentious issue in Neurology. The authors of this study found no link between migraine and (PFO). The title is brilliant, but the tone of finality is probably premature; I guess this debate is far from over.

Migraine and inhibitory system – I can’t hold it!

Human brain on white background. _DJ_ on Flikr. https://www.flickr.com/photos/flamephoenix1991/8376271918

And still on migraine is this headline grabber. A bit on the basic science spectrum, I quote from the abstract to give you a flavour: ‘This review focuses on recent structural and functional neuroimaging studies that investigated the role of subcortical and cortical structures in modulating nociceptive input in migraine, which outlined the presence of an imbalance between inhibitory and excitatory modulation of pain processing in the disease‘. I would rather stick with the punchy headline myself.

On the nose: olfactory disturbances in patients with transient epileptic amnesia

Big Nose Strikes Again. Bazusa on Flikr. https://www.flickr.com/photos/bazusa/260401471

This research paper establishes a link between transient epileptic amnesia (TEA) and impairment of the sense of smell. TEA continues to surprise, and there is indeed quite a lot to chew in the paper.

Myelitis in neuromyelitis optica spectrum disorder: the long and the short of it

By JasonRobertYoungMDOwn work, CC BY-SA 4.0, Link

This is a clear play on the defining feature of neuromyelitis optica (NMO), a long segment of inflammation in the spinal cord. This is what neurologists call longitudinally extensive transverse myelitis (LETM). This is an excellent editorial, worthy of the headline. It emphasises the point that NMO really has no defining features, not even the presence of the ‘defining’ antibody, anti-aquaporin 4- just ask anti-MOG NMO about this

AEDs after ICH: preventing the prophylaxis

By BobjgalindoOwn work, GFDL, Link

How do you prevent a harmful preventative practice?. By a paper with a title that is pure genius of course. The authors of this paper highlight the persisting, anti-guideline, practice of using prophylactic antiepileptic drugs (AEDs) in people who have had intracerebral haemorrhage (ICH). The paper rhetorically asks if this has ‘become a habit too difficult to break?’ Not going by this catchy headline!

Paralysis lost: a new cause for a common parasomnia?

Sleepwalking. Gareth on Flikr. https://www.flickr.com/photos/trois-tetes/7240877

Parasomnias are diseases that occur during or related to sleep. This headline is for an editorial on a new parasomnia called anti IgLON5 antibody disorder. This is the subject of my previous blog post titled IgLON5: a new antibody disorder for neurologists. The headline writer here is clearly a fan of John Milton. I however struggled to make the connection between the excellent headline and the subject of the paper. I however presume it relates to the ‘loss of sleep paralysis‘ that accompanies many sleep disorders, including the quintessential parasomnia- REM sleep behaviour disorder (RBD). Excellent title anyway.

Hereditary spastic paraplegia: the pace quickens

By Rawlings, Leo – http://media.iwm.org.uk/iwm/mediaLib//150/media-150073/large.jpgThis is photograph Art.IWM ART LD 6040 from the collections of the Imperial War Museums., Public Domain, Link

With a slightly wicked wit, this headline focuses on the slow walking speed of people with hereditary spastic paraplegia (HSP), contrasting this with the increasing research output on the disease. A bit dated I admit, but the paper refers to work which identified the genetic basis of SPG3, one of the commoner HSPs. A lesson in headline writing from the archives you may say.

Cut your losses: spastin mediates branch-specific axon loss

Synapse. Ben Cadet on Flikr. https://www.flickr.com/photos/47814009@N00/2943548161

The headline is brilliant, but the content goes way over my head. It is an editorial on a basic science paper. For the curious and the nerdy, I quote an extract: ‘during synapse elimination in the developing neuromuscular junction, branch-specific microtubule destabilization results in arrested axonal transport and induces axon branch loss. This process is mediated in part by the neurodegeneration-associated, microtubule-severing protein spastin‘. Enough I hear you say. OK, just stick with the headline.

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Do you have any catchy titles-please drop a comment.

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What are the most iconic neurological disorders?

Neurology is a broad specialty covering a staggering variety of diseases. Some neurological disorders are vanishingly rare, but many are household names, or at least vaguely familiar to most people. These are the diseases which define neurology. Here, in alphabetical order, is my list of the top 60 iconic neurological diseases, with links to previous blog posts where available.

 

1. Alzheimer’s disease

By uncredited - Images from the History of Medicine (NLM) [1], Public Domain, https://commons.wikimedia.org/w/index.php?curid=11648572
By uncredited – Images from the History of Medicine (NLM) [1], Public Domain, https://commons.wikimedia.org/w/index.php?curid=11648572

2. Behcet’s disease

By Republic2011 - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=17715921
By Republic2011Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=17715921

3. Bell’s palsy

By http://wellcomeimages.org/indexplus/obf_images/69/f2/8d6c4130f4264b4b906960cf1f7e.jpgGallery: http://wellcomeimages.org/indexplus/image/M0011440.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36350600
By http://wellcomeimages.org/indexplus/obf_images/69/f2/8d6c4130f4264b4b906960cf1f7e.jpgGallery: http://wellcomeimages.org/indexplus/image/M0011440.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36350600

4. Brachial neuritis

5. Brain tumours

6. Carpal tunnel syndrome

7. Cerebral palsy (CP)

8. Cervical dystonia

9. Charcot Marie Tooth disease (CMT)

By http://wellcomeimages.org/indexplus/obf_images/66/09/4dfa424fe11bb8dc56b2058f04ba.jpgGallery: http://wellcomeimages.org/indexplus/image/V0026141.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36578490
By http://wellcomeimages.org/indexplus/obf_images/66/09/4dfa424fe11bb8dc56b2058f04ba.jpgGallery: http://wellcomeimages.org/indexplus/image/V0026141.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36578490

10. Chronic inflammatory demyelinating polyneuropathy (CIDP)

11. Cluster headache

12. Creutzfeldt-Jakob disease (CJD)

By Unknown - http://www.sammlungen.hu-berlin.de/dokumente/11727/, Public Domain, https://commons.wikimedia.org/w/index.php?curid=4008658
By Unknownhttp://www.sammlungen.hu-berlin.de/dokumente/11727/, Public Domain, https://commons.wikimedia.org/w/index.php?curid=4008658

13. Duchenne muscular dystrophy (DMD)

By G._Duchenne.jpg: unknown/anonymousderivative work: PawełMM (talk) - G._Duchenne.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9701531
By G._Duchenne.jpg: unknown/anonymousderivative work: PawełMM (talk) – G._Duchenne.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9701531

14. Encephalitis

15. Epilepsy

16. Essential tremor

17. Friedreich’s ataxia

By Unknown - http://www.uic.edu/depts/mcne/founders/page0035.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3960759
By Unknownhttp://www.uic.edu/depts/mcne/founders/page0035.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3960759

18. Frontotemporal dementia (FTD)

19. Guillain-Barre syndrome (GBS)

By Anonymous - Ouvrage : L'informateur des aliénistes et des neurologistes, Paris : Delarue, 1923, Public Domain, https://commons.wikimedia.org/w/index.php?curid=28242077
By Anonymous – Ouvrage : L’informateur des aliénistes et des neurologistes, Paris : Delarue, 1923, Public Domain, https://commons.wikimedia.org/w/index.php?curid=28242077

20. Hashimoto encephalopathy

21. Hemifacial spasm

22. Horner’s syndrome

By Unknown - http://ihm.nlm.nih.gov/images/B15207, Public Domain, https://commons.wikimedia.org/w/index.php?curid=19265414
By Unknownhttp://ihm.nlm.nih.gov/images/B15207, Public Domain, https://commons.wikimedia.org/w/index.php?curid=19265414

23. Huntington’s disease (HD)

https://en.wikipedia.org/wiki/George_Huntington#/media/File:George_Huntington.jpg
https://en.wikipedia.org/wiki/George_Huntington#/media/File:George_Huntington.jpg

24. Idiopathic intracranial hypertension (IIH)

25. Inclusion body myositis (IBM)

26. Kennedy disease

27. Korsakoff’s psychosis

28. Lambert-Eaton myasthenic syndrome (LEMS)

29. Leber’s optic neuropathy (LHON)

30. McArdles disease

31. Meningitis

32. Migraine

33. Miller-Fisher syndrome (MFS)

By J3D3 - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=34315507
By J3D3Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=34315507

34. Motor neurone disease (MND)

35. Multiple sclerosis (MS)

36. Multiple system atrophy (MSA)

37. Myasthenia gravis (MG)

38. Myotonic dystrophy

39. Narcolepsy

40. Neurofibromatosis (NF)

41. Neuromyelitis optica (NMO)

42. Neurosarcoidosis

43. Neurosyphilis

44. Parkinson’s disease (PD)

45. Peripheral neuropathy (PN)

46. Peroneal neuropathy

47. Progressive supranuclear palsy (PSP)

48. Rabies

49. Restless legs syndrome (RLS)

50. Spinal muscular atrophy (SMA)

51. Stiff person syndrome (SPS)

52. Stroke

53. Subarachnoid haemorrhage (SAH)

54. Tension-type headache (TTH)

55. Tetanus

56. Transient global amnesia (TGA)

57. Trigeminal neuralgia

58. Tuberous sclerosis

59. Wernicke’s encephalopathy

By J.F. Lehmann, Muenchen - IHM, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9679254
By J.F. Lehmann, Muenchen – IHM, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9679254

60. Wilson’s disease

By Carl Vandyk (1851–1931) - [No authors listed] (July 1937). "S. A. Kinnier Wilson". Br J Ophthalmol 21 (7): 396–97. PMC: 1142821., Public Domain, https://commons.wikimedia.org/w/index.php?curid=11384670
By Carl Vandyk (1851–1931) – [No authors listed] (July 1937). “S. A. Kinnier Wilson“. Br J Ophthalmol 21 (7): 396–97. PMC: 1142821., Public Domain, https://commons.wikimedia.org/w/index.php?curid=11384670

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The Neurology Lounge has a way to go to address all these diseases, but they are all fully covered in neurochecklists. In a future post, I will look at the rare end of the neurological spectrum and list the 75 strangest and most exotic neurological disorders.

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.