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 criteriaand TSC surveillance recommendations and updated neurochecklists. Phew!
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
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
The DEPDC5 gene is mutated in many neurological disorders such as familial focal epilepsies, focal cortical dysplasia, and epileptic spasms. These constitute DEPDC5 motoropathies.
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.
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 theirPubMed abstracts, and books to their Amazon.com page.
How can neurochecklists help neurological practice?
1. By quickly checking up a topic in the clinic or on a ward round
In developing neurochecklists, I 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.
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.
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.
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.
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 promotepatient safety. It also cited Atul Gawande‘s call to Medicine to “seize the opportunity” and produce checklists for all aspects of clinical practice.
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
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.
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.
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.
5. The challenge of varied target groups
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.
In many places however other cadres of medicine cater for people with neurological diseases. Psychiatrists, neurosurgeons, paediatricians, general 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 therapists. Medical students and researchers also require vast amounts of neurological information, often within restricted time frames.
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
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.
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?
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.
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 airlinesafety.
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
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.
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.
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:
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.
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.
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.
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.
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.
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.
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!
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!
An apple a day will never be enough to avoid neurological diseases. For one, the nervous system is extensive, vulnerable from the top of the head to the tips of the toes. For another, the cells that constitute the nervous system are susceptible to an astonishing variety of insults. This explains the diversity and number of neurological diseases, and why medical students and doctors find neurology daunting.
There are many neurological diseases that we can do absolutely nothing to guard against. This is the case with genetic neurological diseases, unless we find a way of choosing our parents wisely! Proven ways of improving our defences include exercising regularly, eating healthily, and stopping smoking; these however have their limitations against many neurological disorders.
But don’t despair, there are measures we can take to shield ourselves against some avoidable neurological conditions. Many of these arise because of activities we engage in, often mindless of their consequences. The list is fairly long, but here are my ‘12 Don’ts of Neurology’ to help avoid a meeting with a neurologist.
1. Don't get angry
Anger is an unpredictable negative emotion which hardly ever serves any useful purpose. If you need a very good reason to keep your cool, know that anger is a recognised trigger of stroke. On balance therefore, it’s not worth blowing a fuse.
Excessive neck extension, as occurs at the hairdresser’s or the chiropractor, could stretch and tear the inner lining of a neck artery. This painful tear is called a dissection and it allows a blood clot to form. What happens next is the serious part; the clot may dislodge and travel up the blood vessel where it blocks blood flow to the brain. The result, understandably, is called the beauty parlor stroke syndrome.
We all do it: sit back and hang one leg over the other knee. Habitual crossed-leg sitting however puts your peroneal nerve at risk of compression where it crosses round the knee to innervate the leg and foot muscles. The result is foot drop. Sitting in the yoga lotus position causes a similar damage, as does prolonged squatting (strawberry pickers foot drop).
The sciatic nerve is the largest peripheral nerve in the body, and it traverses the buttock on its way to innervate most of the lower limb muscles. It is vulnerable to prolonged sitting on hard surfaces, and it’s a no-brainer that this is called toilet-seat neuropathy. You could of course have your toilet seat nicely padded! You may also protect your sciatic nerve by not putting thick wallets and coins in your back pocket.
It is trendy to have a nice six-pack or firm pecs, but this may come at a price. As the muscles get stronger and bulkier, they may compress the nerves which pass through them. Most vulnerable are the thoracodorsal, the suprascapular, and the pectoral nerves. A shrunken pectoral muscle on one side is sure evidence that you have overdone it.
6. Don’t over-do the athletic thing
Athletic sports that involve excessive upper limb movements may stretch and compress the nerves. Particularly vulnerable is the axillary nerve which supplies the muscles you need to lift your arm away from your body. The culprit sports include volleyball, javelin, rock climbing, and rugby.
It’s so convenient to sling a backpack over the shoulder, but it is not benign if you overload it. This is because the heavy weight of a backpack may damage the brachial plexus, the large network of nerves that innervate the upper limb. The resulting limp upper arm is called…you guessed it, rucksack paralysis.
The wrist is the gateway to three important nerves, all vulnerable to compression. External pressure on the wrist particularly picks on the superficial branch of the radial nerve. The resulting handcuff palsy causes pain and tingling over the back of the hand. A similar effect may result from tight wristwatches and bracelets. A good reason to go bare below the elbows.
9. Don’t hold to tightly to your bicycle handlebars
To avoid the so-called cyclists palsy, you must not only choose your machine carefully, but take care when riding. This is to protect your ulnar nerve which traverses the wrist just where the cycle handlebars would compress it. This causes paralysis of many of the small muscles of the hand, sparing only the thumb.
10. Don’t tighten your belt excessively
The victim nerve this time is a branch of the femoral nerve, the second largest nerve of the lower limb. This nerve migrates from the abdomen into the thigh by squeezing just under the belt line. It is vulnerable to compression here, and the result is meralgia paraesthetica. This is a fairly common condition, easily recognised by a combination of pain, tingling, and numbness over a well-demarcated patch on the outer thigh. Wearing skinny jeans is another recognised cause, as are prolonged sitting and weight gain.
Choosing the wrong ski boots may not just mess up your skiing holiday, it could result in compression of the peroneal nerve around the ankle . This causes tingling over the foot …but this may persist long after you have (angrily?) discarded the offending boots.
The nerves vulnerable to the hangman’s noose are the greater auricular nerves. These nerves transmit sensation from the ears; not a major problem if the hanging is successful; if the attempt fails however, be prepared for numb ears in resurrection.
