mTORopathy: an emerging buzzword for neurology

I was recently perplexed with my first case of tuberous sclerosis complex (TSC). I had no idea what treatment, monitoring and surveillance I needed to institute. I quickly checked things up in neurochecklists; I found excellent checklists on the pathology and clinical features, but was disappointed that there were no treatment or monitoring checklists. I quickly hunted down TSC diagnostic criteria and TSC surveillance recommendations and updated neurochecklists. Phew!

By Herbert L. Fred, MD and Hendrik A. van Dijk - http://cnx.org/content/m14895/latest/, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11892420
By Herbert L. Fred, MD and Hendrik A. van Dijk – http://cnx.org/content/m14895/latest/, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11892420

In the process I discovered that TSC features may improve on treatment with a class of drugs called mTOR inhibitors. Highfalutin stuff I said to myself, and thought nothing more of it. I had to reassess my opinion very shortly afterwards when I came across the Association of British Neurologists (ABN) SoundCloud page with ABN President Phil Smith interviewing Ingrid Scheffer on epilepsy genetics.

We have all experienced that disquieting feeling of just learning something new, and then seeing it crop up all over the place. This is what I felt when Ingrid Scheffer casually stated that Tuberous Sclerosis is an mTORopathy. mTOR is big enough to be an ‘opathy‘, and I was completely ignorant of it! And how come I haven’t heard of Ingrid Scheffer before now-serves me right for missing the last ABN conference in Brighton.

I decided to dig a bit deeper and here are 9 things about mTOR I discovered:

1

mTOR stands for mammalian (or mechanistic) target of rapamycin

2

mTOR is a kinase

3

The mTOR pathway is important in regulating cell growth and cell death

4

mTOR has an important role in many disorders (mTORopathies). These include tuberous sclerosis, epilepsy, autism, traumatic brain injury, brain tumours, and dementia

5

Mutations in TSC1 or TSC2 genes cause hyperactivation of the mTOR pathway

6

mTOR inhibitors are under investigation for the treatment of these diverse diseases

7

Sirolimus is the major mTOR inhibitor

By Fvasconcellos - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1549073
By FvasconcellosOwn work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1549073

8

The DEPDC5 gene regulates mTOR inhibition.

9

The DEPDC5 gene is mutated in many neurological disorders such as familial focal epilepsies, focal cortical dysplasia, and epileptic spasms. These constitute DEPDC5 motoropathies.

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Enough information to tickle the little grey cells but if you want to dig deeper than you may follow these links:

How will neurology checklists unlock excellent practice?

Launching neurochecklists

After 5 years of data gathering and sorting, neurochecklists launches today. This is a web-based application which covers the spectrum of neurological practice. I was prompted by Atul Gawande‘s call to physicians to develop checklist-driven medicine, as I discussed in my previous blog post, What is the value of checklists in medical practice? Conceived in libraries and coffee shops, lay-bys and terminals, neurochecklists is the culmination of a vision to commit the whole of neurology to checklists.

 

Neurochecklists image

 

What exactly is neurochecklists?

Neurochecklists is a comprehensive and easy-to-search database consisting of thousands of checklists. It is conceived as a mobile resource to aid all cadres of medical professionals. It has 18 categories, each consisting of chapters divided into topics. All checklists are brief and divided into sub-checklists as required. Users may explore topics either through the search boxes available on all webpages, or via the Index. Each checklist is fully referenced, and all articles are hyperlinked to their PubMed abstracts, and books to their Amazon.com page.

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How can neurochecklists help neurological practice?

1. By quickly checking up a topic in the clinic or on a ward round

And you haven't been to your doctor because? Alex Proimos on Flikr. https://www.flickr.com/photos/proimos/6870109454
And you haven’t been to your doctor because? Alex Proimos on Flikr. https://www.flickr.com/photos/proimos/6870109454

2. By helping the preparation of presentations or teachings

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3. By making reading for examinations and researching a topic easier

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4. By complementing the search for relevant and up-to-date references

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5. Facilitating neurology discussions with patients 

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What exactly does neurochecklists contain?

Neurochecklists is extensive, covering all the core neurological subspecialties:

  • Disorders of Cranial Nerves
  • Disorders of Cognition
  • Disorders of Consciousness
  • Neurological Infections and Toxicity
  • Epilepsy
  • Parkinsonism
  • Non-Parkinsonian Movement Disorders
  • Headache Disorders
  • Neuroinflammatory Disorders
  • Anterior Horn Cell Disorders
  • Peripheral Nerve and Radicular Disorders
  • Neuromuscular Junction and Muscle Diseases
  • Stroke
  • Nervous System Tumours
  • Spinal Cord Disorders
  • Autoimmune and Metabolic Disorders
Binaural-beat-digital-drug. Digitalbob8 on Flikr. https://www.flickr.com/photos/44568283@N02/4098316274
Binaural-beat-digital-drug. Digitalbob8 on Flikr. https://www.flickr.com/photos/44568283@N02/4098316274

Neurochecklists also addresses the range of allied neurological specialities such as:

  • Neurophysiology
  • Neurosurgery
  • Neuroradiology
  • Neuropsychiatry
  • Neuroophthalmology
  • Neurootology
  • Pain Disorders
  • General medicine
  • Surgery
  • Pregnancy

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These diseases are all reviewed from diverse perspectives:

  • Epidemiology
  • Genetics
  • Pathology
  • Clinical Features
  • Investigations 
  • Treatment
Human brain illustrated with millions of small nerves. Ars Electronica on Flikr. https://www.flickr.com/photos/arselectronica/13994747444
Human brain illustrated with millions of small nerves. Ars Electronica on Flikr. https://www.flickr.com/photos/arselectronica/13994747444

 

How reliable are neurochecklists?

In developing neurochecklistsI took into consideration the challenges of such a project as discussed in my previous blog, What are the obstacles to creating reliable neurology checklists? Neurochecklists has also gone through a beta-testing stage, and the feedback has influenced the final version. This is however the beginning of the journey to maintain and improve the database. This on-going challenge will require feedback from users which will be invaluable in advancing the app to higher levels.

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What will it cost to access neurochecklists?

Neurochecklists comes with two levels of access. There is a free version which entitles users to 15 free searches a month. There is therefore no excuse not to have a neurochecklists account! To get the maximum benefit of neurochecklists, a premium account is required, and this comes at the equivalent cost of a coffee and cake a month, and even less with an annual subscription.

 

Cake and coffee. Jeremey keith on Flikr. https://www.flickr.com/photos/adactio/4925134798
Cake and coffee. Jeremey keith on Flikr. https://www.flickr.com/photos/adactio/4925134798

 

The reason for paid subscriptions is to help offset the heavy financial cost of app development and future improvement and enhancement plans. One such plan is to develop android and ios platforms. I am however open to suggestions to make this a completely free resource.

 

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Who helped to develop neurochecklists?

Neurochecklists is the result of a collaborative effort in many ways. My wife Zainab has been invaluable in encouraging and supporting me throughout the journey. To Jafaru Dori for invaluable guidance, support and connections. To the bright young men at Studio 14, Stephen, Tobi and Timi for their great imagination and passion for the project. My gratitude to my work colleagues and the hundreds of social media friends who share so much knowledge, much of which has found its way into neurochecklists. And finally my apologies to Aminah, Safiyyah, Ja’far, and Maryam for not having their dad’s full attention for so long. Hopefully it’s been worth the while.

Feedback checklist. AJ Cann on Flikr. https://www.flickr.com/photos/ajc1/9568156463
Feedback checklist. AJ Cann on Flikr. https://www.flickr.com/photos/ajc1/9568156463

How to get to neurochecklists?

If you have so far resisted the dozen opportunities to click on neurochecklists, go on now and click on the image or text below to check it out! Don’t forget to leave your feedback.

Neurochecklists image

  neurochecklists

 

Imagine you have just suffered a devastating stroke!

Imagine you have just had a stroke!

Devastating,  distressing, life changing.

By Bhernandez from miami - stressed and worried, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=11438423
By Bhernandez from miami – stressed and worried, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=11438423

Imagine you are stuck in a wheelchair,

Helpless and speechless.

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Now imagine you are transported back in time,

6 months before your stroke

Antique clock face with hands. Cindy Schultz on Flikr. https://www.flickr.com/photos/29008389@N03/5937058272
Antique clock face with hands. Cindy Schultz on Flikr. https://www.flickr.com/photos/29008389@N03/5937058272

You see your physically able self,

Master of your faculties,

Enjoying all the ‘good things’ of life.

By http://wellcomeimages.org/indexplus/obf_images/4c/82/72258f7d55d449942e63cf26072d.jpgGallery: http://wellcomeimages.org/indexplus/image/V0019565.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36528051
By http://wellcomeimages.org/indexplus/obf_images/4c/82/72258f7d55d449942e63cf26072d.jpgGallery: http://wellcomeimages.org/indexplus/image/V0019565.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36528051

Now feel the regret,

That you did nothing to prevent the stroke,

The sudden event that stole your dreams and aspirations.

Regret. Neil Moralee on Flikr. https://www.flickr.com/photos/neilmoralee/13747234805
Regret. Neil Moralee on Flikr. https://www.flickr.com/photos/neilmoralee/13747234805

Now you realise this is a second chance,

After such a close shave,

Imagine the relief.

Phew!. Tibor Miklos on Flikr. https://www.flickr.com/photos/tibormade/3267191528
Phew!. Tibor Miklos on Flikr. https://www.flickr.com/photos/tibormade/3267191528

Imagine the pleasure!

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Now you have a choice to make.

To resume the pleasures you previously indulged in…

Sumptuous Lunch. Nadir Hashmi on Flikr. https://www.flickr.com/photos/nadircruise/5749352648
Sumptuous Lunch. Nadir Hashmi on Flikr. https://www.flickr.com/photos/nadircruise/5749352648

Or recollect the warnings you ignored before,

Which you turned a deaf ear to,

Which are now more valuable than all the gems in the world.

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You wisely decide to turn a new leaf.

Turn page. andy.brandon50 on Flikr. https://www.flickr.com/photos/54027476@N07/4999944659
Turn page. andy.brandon50 on Flikr. https://www.flickr.com/photos/54027476@N07/4999944659

Now make a full list,

Of all the things you should have done,

And could have done,

To prevent the disastrous stroke.

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Now take a hard look at your list,

And start acting on it,

Right now!

JUST DO IT. Paper Fold. the_fafa on Flikr. https://www.flickr.com/photos/32559932@N04/6051955099
JUST DO IT. Paper Fold. the_fafa on Flikr. https://www.flickr.com/photos/32559932@N04/6051955099

_______0_______0_______0_______0_______0_______0_______0____

Get off the couch,

Walk round the block,

Put out that cigarette.

Ashtray. Jocelyn on Flikr. https://www.flickr.com/photos/-jocelyn-/6513335519
Ashtray. Jocelyn on Flikr. https://www.flickr.com/photos/-jocelyn-/6513335519

Switch off the TV

Get on that weighing scale

Check your blood pressure

By www.volganet.ru, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16363865
By www.volganet.ru, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16363865

Cut down internet time,

Cut out the fat and carbs,

Get on the treadmill.

Running on a treadmill. E'Lisa Campbell on Flikr. https://www.flickr.com/photos/eccampbellphotography/5447958713
Running on a treadmill. E’Lisa Campbell on Flikr. https://www.flickr.com/photos/eccampbellphotography/5447958713

Say ‘pass’ to that pint 

Top up with the greens

Invest in a good pair of walking shoes

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Visit a garden or park this weekend

Mow the lawn

 Give up the stressful job

6/52³: Estrés / Stress. Andrés Nieto Porras on Flikr. https://www.flickr.com/photos/anieto2k/27247021692
6/52³: Estrés / Stress. Andrés Nieto Porras on Flikr. https://www.flickr.com/photos/anieto2k/27247021692

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And now you have finally done it!

You have prevented a calamitous stroke.

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It wasn’t that hard after all,

Now you can relax,

And be proud of yourself!

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You may download the powerpoint version of this presentation below:

imagine a stroke

What are the obstacles to creating reliable neurology checklists?

This is a follow up to my previous blog post on the value of checklists in medical practice. That post explored how checklists improve clinical practice and promote patient safety. It also cited Atul Gawande‘s call to Medicine to “seize the opportunity” and produce checklists for all aspects of clinical practice.

Neurology. MV Maverick. https://www.flickr.com/photos/themvmaverick/11396461045
Neurology. MV Maverick. https://www.flickr.com/photos/themvmaverick/11396461045

 

Picking up this gauntlet for neurology comes with peculiar challenges. Here are the 7 hurdles to overcome.

1. The challenge of a diverse specialty

Legume diversity. Global Crop Diversity Trust on Flikr. https://www.flickr.com/photos/croptrust/3594324633
Legume diversity. Global Crop Diversity Trust on Flikr. https://www.flickr.com/photos/croptrust/3594324633

Neurology consists of an astonishing diversity of sub-specialities. Any neurology checklist must exhaustively cover the major neurological categories such as stroke, epilepsy, movement disorders, headache, dementia, neuromuscular diseases, sleep disorders, neuro-inflammation, nervous system tumours, and neurological infections. These topics must be thoroughly covered with emphasis on their clinical features, investigations, and treatments. A useful database must also include rare neurological diseases, of which neurology has quite a few. This is reflected in my previous blog on the most perplexing diseases that excite neurologists.

2. The challenge of multiple associated specialties

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Neurological disorders cut across many diverse allied neurological specialties. Any dependable checklist database must cover these specialised fields which include neurosurgery, neuroradiology, neuroophthalmology, neuropsychiatry, neuropaediatrics, and pain management. It must also include important diseases which straddle neurology and general medicine. These include a long list of cardiovascular, nutritional, endocrine and gastrointestinal disorders. Furthermore, neurologists often have to deal with surgical complications especially in orthopaedics and following transplant surgery. Neurologists are also frequently called upon to attend to neurological problems that are unique to pregnancy. Any practical checklist application must therefore thoroughly address these areas.

Brain Cells Created From Skin Cells in Landmark Study. Day Donaldson on Flikr. https://www.flickr.com/photos/thespeakernews/15656329862
Brain Cells Created From Skin Cells in Landmark Study. Day Donaldson on Flikr. https://www.flickr.com/photos/thespeakernews/15656329862

3. The challenge of reliable content

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It goes without saying that the most important feature of any database is reliable content which alone will engender trust and confidence. A reliable checklist must obtain its material from dependable sources. Neurology is replete with reliable textbooks and reference websites, . Neurology is also bursting at the seams with journals such as Neurology, Brain, the JNNP, and Journal of Neurology, each churning out a bewildering array of neurology guidelines, review articles, ground-breaking studies, and fascinating case reports. The challenge is to keep a regular handle on these sources, sifting through for practical and established material. As important for the user is that any checklist must be fully referenced and hyperlinked to the source material.

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4. The challenge of practical functionality

Any practical checklist database must be available on the move, easily accessible and searchable. In other words, it must be in the form of a mobile application. The app must have a reliable search functionality. More importantly for users is the requirement that the application must serves as a prompt to remember important points across the breadth of neurological practice: history taking, investigations, differential diagnosis, and treatment. For the administrator, the technology must make it easy to update and edit content, keeping the content consistently up-to-date.

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5. The challenge of varied target groups

Toy_balls_with_different_Colors

In developing any form of medical resource, it is a challenge to define the target audience. The primary aim of a neurology checklist application is to ease the challenges medical professionals face in accessing relevant and practical information about neurology in a timely way. This may be on a busy ward round or clinic, but also when researching a topic or preparing a presentation. The core users of a neurology application will therefore clearly be neurologists and neurology trainees.

By SpinningSpark real life identity: SHA-1 commitment ba62ca25da3fee2f8f36c101994f571c151abee7 - Created with Superliminal's Magic Cube 4D, CC BY-SA 3.0, https://en.wikipedia.org/w/index.php?curid=17492843
By SpinningSpark real life identity: SHA-1 commitment ba62ca25da3fee2f8f36c101994f571c151abee7 – Created with Superliminal’s Magic Cube 4D, CC BY-SA 3.0, https://en.wikipedia.org/w/index.php?curid=17492843

In many places however other cadres of medicine cater for people with neurological diseases. Psychiatrists, neurosurgeons, paediatriciansgeneral physicians, obstetricians, ophthalmologists, specialist and general nurses, would likely access the database. Other health care professionals may also find areas of interest such as speech therapists, physiotherapists and occupational therapistsMedical students and researchers also require vast amounts of neurological information, often within restricted time frames.

A Tangle of Different Colours 001. Christina Quinn on Flikr. https://www.flickr.com/photos/chrisser/7909899736
A Tangle of Different Colours 001. Christina Quinn on Flikr. https://www.flickr.com/photos/chrisser/7909899736

6. The challenge of public access

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Specialised medical application are never aimed at non-medically trained people. The reality however is that the general public are closely involved in their care today, seeking reliable information to address their medical concerns. It is inevitable that patients and their families will access the checklist database. For this reason the language must be simple and clear, avoiding any sort of ambiguity.

7. The challenge of resources and pricing

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A checklist application, to be most beneficial, should ideally be free to use. A Wikipedia model would be a model to adapt. But creating a checklist database, with all the features mentioned above, would surely stretch resources in terms of time and funding. There will also be great demands on resources to maintain and enhance it. A balance must be struck between beneficence and realism. Such a balance should have, as with most applications, a free version with sufficient access of some sort, and a premium version with unlimited access. The developer must also be aware that potential users have limited resources to spread round their conflicting demands. Any premium account should be affordable, perhaps not more than the equivalent cost of a cup of coffee and a cake a month.

Muffin and coffee. Phil Gyford on Flikr. https://www.flickr.com/photos/philgyford/6534958441
Muffin and coffee. Phil Gyford on Flikr. https://www.flickr.com/photos/philgyford/6534958441 

 

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Is there any neurology checklist application that has taken the above challenges into consideration? This will be revealed in my next blog post, How simple checklists unlock excellent neurological practice?

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What is the value of checklists in medical practice?

Checklists

We all know how important checklists are in our day-to-day lives. We cannot survive the day without a to-do list reminding us of the tasks that make our lives go round. It is clearly not an exaggeration to say we live by the checklist.

Feedback checklist. AJ Cann on Flikr. https://www.flickr.com/photos/ajc1/9568156463
Feedback checklist. AJ Cann on Flikr. https://www.flickr.com/photos/ajc1/9568156463

Airline safety

But checklists perform far more important roles than reminding us to buy the milk, or to pick junior after football practice. Checklists are central to the maintenance of safe practice in many industries. Checklists are best celebrated in aviation where they are indispensable to airline safety.

By Janke - Janke, CC BY 3.0, https://en.wikipedia.org/w/index.php?curid=27079600
By JankeJanke, CC BY 3.0, https://en.wikipedia.org/w/index.php?curid=27079600

The Checklist Manifesto

Despite their recognised value, checklists are not applied widely enough in medicine. One person who has passionately addressed this shortcoming is Atul Gawande in his highly acclaimed book, The Checklist Manifesto. In this book, the author explored the positive impact of checklists based on his own research into surgical safety. His view of checklists is quite instructive, for example when he says:

  • Checklists translate knowledge into a simple, usable, and systematic form
  • Checklists are quick and simple tools aimed to buttress the skills of expert professionals.
  • Good checklists could become as important for doctors and nurses as good stethoscopes
By Courtesy of the John D. and Catherine T. MacArthur Foundation, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=35497665
By Courtesy of the John D. and Catherine T. MacArthur Foundation, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=35497665

 

The WHO surgical safety checklist

Gawande’s major contribution to patient safety is the development of the acclaimed WHO Surgical Safety Checklist. This simple tool is now a key component of surgical operating procedures globally.

WHO Surgical Safety Checklist. John Sloan on Flikr. https://www.flickr.com/photos/johnlsloan/8485508277
WHO Surgical Safety Checklist. John Sloan on Flikr. https://www.flickr.com/photos/johnlsloan/8485508277

 

Gawande’s own experience of using the checklist shows how important this tool is. He says:

  • I have yet to get through a week in surgery without the checklist’s leading us to catch something we would have missed
  • With the checklist in place, we have caught unrecognized drug allergies, equipment problems, confusion about medications, mistakes on labels for biopsy specimens
  • We have made better plans and been better prepared for patients

Beyond the operating room

Atul Gawande made the important observation that checklists have potential applications “beyond the operating room“. He said “…there are hundreds, perhaps thousands, of things doctors do that are as dangerous and prone to error as surgery“. He gave several examples of these such as the evaluation of headache, chest pain, lung nodules and breast lumps. He also pointed to the treatment of heart attacks, strokes, drug overdoses, pneumonias, kidney failures, seizures, and headache.

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Addressing Gawande’s challenge

Gawande appreciates that all medical activities involve risk, uncertainty, and complexity. His simple recommendation is to commit them all to checklists. He urges the medical fraternity to seize the opportunity and do this. Apart from Anaesthesia which is probably ahead of the curve, there are only few medical checklists such as:

By http://wellcomeimages.org/indexplus/obf_images/7e/71/50f93b8f2f172d5b4544ddbe42b6.jpgGallery: http://wellcomeimages.org/indexplus/image/L0040163.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36095194
By http://wellcomeimages.org/indexplus/obf_images/7e/71/50f93b8f2f172d5b4544ddbe42b6.jpgGallery: http://wellcomeimages.org/indexplus/image/L0040163.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36095194

 

Neurology checklists

Gawande’s vision of a checklist-led approach to medicine, encompassing the spectrum of clinical practice, is indeed challenging. As a neurologist who is keen on patient safety, I was intrigued by this perspective, and I wondered if it was possible to commit the whole of neurology to checklists. In taking up the challenge, I imagined a neurology checklist application that is practical, comprehensive, easy to search, evidence-based, and up-to-date. After five years of collecting and distilling articles, reviews and guidelines, and after months of engagement with software developers, the dream is becoming reality. In my next blog post I will describe the outcome of the journey and discuss how simple checklists may unlock excellent neurological practice.

Screen Shot 2016-06-18 at 10.00.30

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/