What strange things about IBM leave neurologists puzzled?

Inclusion body myositis (IBM) is classified as an inflammatory muscle disease. It however stands out from all other muscle diseases, inflammatory or not. IBM has quite unique, and often unexplained, characteristics. These features mark it out as an enigma, and the mystery deepens the more neurologists research it.

Puzzled. andy.brandon50 on Flikr. https://www.flickr.com/photos/54027476@N07/4999919941
Puzzled. andy.brandon50 on Flikr. https://www.flickr.com/photos/54027476@N07/4999919941

IBM continues to throw up new and challenging riddles for neurologists, and here are my 6 puzzling things about IBM.

6. Unique muscle distribution

Muscle diseases in adults almost always start in the upper or proximal parts of the limbs. IBM however bucks the trend with a specific predilection for muscles of the middle part of the limbs, the knee extensors in the legs, and the long finger flexors in the arms. This unique pattern of muscle involvement results in a characteristic or pathognomonic clinical picture of IBM: marked wasting of the muscles of the forearms, and of the quadriceps. People with IBM therefore complain of a weak grip, and a tendency to fall. The reason for this unique muscle specificity has me dumbfounded.

5. Unusual muscle biopsy features

By Jensflorian - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11763608
By JensflorianOwn work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11763608

 

The classical inflammatory muscle diseases are polymyositis (PM) and dermatomyositis (DM), and the inflammation in these conditions is easily detected on muscle biopsy. This is however not the case with IBM which shows very little inflammation, and this paucity of inflammation underlies IBM’s unresponsiveness to anti-inflammatory treatment with steroids. IBM muscle biopsy specimens however show typical eosinophilic cytoplasmic inclusions and rimmed vacuoles. The unwary neuropathologist however easily misses these specific but elusive landmarks, making IBM notoriously difficult to diagnose, or worse still, easily misdiagnosed as PM or DM.

4. Association with strange bedfellows

IBM is typically an isolated disease, preferring to roam in solitude. Or so I thought until I came across a paper in Neurology which introduced me to the concept of multisystem proteinopathy. This is the association of IBM with Paget’s disease of the bone (PDP), motor neurone disease (MND), or frontotemporal dementia (FTD). Why IBM should associate with these strange and unrelated diseases leaves me totally baffled.

3. Genetic underpinnings

jeans for genes. susan on Flikr. https://www.flickr.com/photos/certified_su/3803103894
jeans for genes. susan on Flikr. https://www.flickr.com/photos/certified_su/3803103894

 

Neurologists like to keep the geneticists busy with every disease they study, and IBM is no exception. It is not clear exactly when, how or why neurologists went gene-hunting in a condition that is typically sporadic. But hunt they did, and their perseverance paid off; we now know that IBM may also be hereditary or familial. And the genetic spectrum of IBM continues to grow. Take this paper in Neurology Genetics which reports two families with abnormalities in the hnRNPA1 gene. Another genetic association of IBM is GNE. To muddy things up a bit more, IBM has been linked to HLA-DRB1*03. Why any disease should decide to have sporadic and genetic forms leaves me very befuddled.

2. Association with hepatitis C virus (HCV)

By HCV_pictures.png: Maria Teresa Catanese, Martina Kopp, Kunihiro Uryu , and Charles Ricederivative work: TimVickers (talk) - HCV_pictures.png, Public Domain, https://commons.wikimedia.org/w/index.php?curid=10903740
By HCV_pictures.png: Maria Teresa Catanese, Martina Kopp, Kunihiro Uryu , and Charles Ricederivative work: TimVickers (talk) – HCV_pictures.png, Public Domain, https://commons.wikimedia.org/w/index.php?curid=10903740

 

Just when you start adjusting your mindset to a disease that may be genetic, sporadic and inflammatory, the neurologists do it again. This time in cahoots with the infectious disease specialists. They ask you once more to adjust your mindset, and see IBM as a possible fallout of a viral invasion, the culprit here being hepatitis C virus (HCV). Writing in Neurology, the authors boldly suggest a possible pathomechanistic link between the 2 conditions. Mindset tuning in progress.

1. Autoimmune pathogenesis

Immune cell detects disease. Welcome Images on Flikr. https://www.flickr.com/photos/wellcomeimages/16233121363/in/photolist-qJsZqP
Immune cell detects disease. Welcome Images on Flikr. https://www.flickr.com/photos/wellcomeimages/16233121363/in/photolist-qJsZqP

 

Just before you lose it all, the neurologists take you gently back to familiar territory, autoimmunity. But even here there are strange undertones. The autoimmune antibody associated with IBM is rather unique, as you have now learnt to expect. The reported association of anti cN-1A and IBM comes from the Annals of the Rheumatic Diseases, letting the neurologist off this time. The authors looked at autoantibodies to cytosolic 5′-nucleotidase 1A in sporadic IBM. The significance of the association is still not clear. One thing is however obvious-neurologists need to start working on the reasons they will give to their immunologists to justify sending off that blood sample for anti cN-1A. I foresee a drawn-out battle!

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These and many other things go to show why IBM is such a conundrum for neurologists. It has the neurologists vigorously scratching their heads, wishing for an enigma cipher machine. In the meantime all they can do is assure their patients of the therapeutic advances in IBM. As with all mysteries however, it shall all be revealed in time… and neurologists and their patients will be all smiles!

smiley. susan on Flikr. https://www.flickr.com/photos/certified_su/3802633000/in/photostream/
smiley. susan on Flikr. https://www.flickr.com/photos/certified_su/3802633000/in/photostream/

 

13 unexpected and unusual reports about Parkinson’s disease

Parkinson’s disease (PD) looms large in neurology. As I try to make sense of developments in this field, I am struck by the large number of curious reports emerging all around it. I thought I had covered this comprehensively in my previous blogs, PD-a few curious things and Bee venom acupuncture for PD. On the contrary it looks like I opened a can of worms. I will therefore give the peculiar and the curious one last heave before proceeding to some conventional blogs I have in the pipeline on PD.  Here then are 13 unusual things about PD.

Appendicectomy may delay the onset of PD

Appendectomy. msafari2425 on Flikr. https://www.flickr.com/photos/msafari/6020024188
Appendectomy. msafari2425 on Flikr. https://www.flickr.com/photos/msafari/6020024188

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People with melanoma may have early PD signs

By Unknown - National Cancer Institute (AV Number: AV-8500-3850; Date Created: 1985; Date Entered: 1/1/2001), http://visualsonline.cancer.gov/details.cfm?imageid=2184, Public Domain, https://commons.wikimedia.org/w/index.php?curid=859342
By Unknown – National Cancer Institute (AV Number: AV-8500-3850; Date Created: 1985; Date Entered: 1/1/2001), http://visualsonline.cancer.gov/details.cfm?imageid=2184, Public Domain, https://commons.wikimedia.org/w/index.php?curid=859342

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PD gives rise to cerebellar atrophy

Cerebellum: the brain's locomotion control center. ZEISS microscopy on Flikr. https://www.flickr.com/photos/zeissmicro/14441559904
Cerebellum: the brain’s locomotion control center. ZEISS microscopy on Flikr. https://www.flickr.com/photos/zeissmicro/14441559904

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PD may give rise to a drunk-like state 

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A light skin pigmentation may increase the risk of PD

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People with red hair may run a higher risk of PD

Feuerrotes Haar. Markus Lütkemeyer on Flikr. https://www.flickr.com/photos/helico/363729534
Feuerrotes Haar. Markus Lütkemeyer on Flikr. https://www.flickr.com/photos/helico/363729534

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Coffee consumption may reduce the risk of dyskinesia in PD 

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Hepatitis C virus is a risk factor for PD

By BruceBlaus - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=44967236
By BruceBlausOwn work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=44967236

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A high cholesterol diet may reduce risk of PD in men 

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Milk intake in midlife may predispose to PD

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Drumming classes improve the quality of life of people with PD

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The GyroGlove reduces tremors in PD

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Focal muscle vibration improves gait in PD

Muscles of the forearm and hand, posterior view. Rob Swatski on Flikr. https://www.flickr.com/photos/rswatski/4769875140
Muscles of the forearm and hand, posterior view. Rob Swatski on Flikr. https://www.flickr.com/photos/rswatski/4769875140

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Do you have any unusual reports about PD? Please leave a comment

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