7 remarkable technologies shaping the future of the brain

The brain is the most enigmatic structure in the universe. But every now and then, the brain malfunctions. And just like Humpty Dumpty, we struggle to put it back together again…at least not to its previous level of complex organisation. But we are remarkably ingenious creatures, obviously because we possess great brains, and we are ever-inventing brilliant schemes to fix the brain (or at least our brains are). And we, or our brains, often conjure up unthinkable technologies (pardon the intended pun!) Over the years this blog has tried to keep up with these improbable schemes, and you can check the veracity of this claim by looking up two of my very old blog posts on this:

6 exciting neuroscience discoveries that will shape neurology

 10 remarkable breakthroughs that will change neurology.

But the developments keep rolling in, so here are 7 remarkable technologies shaping the future of the brain.

Artificial neurones

What if you could just replace your damaged nerves with spare neurones-just as you would replace a faulty spark plug in your car (OK, wrong analogy for many people I know). Well, this may not be a fantasy for too long. This comes from a piece in Popular Science titled Artificial neurones could replace some real ones in your brain. The article says “Swedish researchers have developed a synthetic neuron that is able to communicate chemically with organic neurones, which could change the neural pathways and better treat neurological disorders”. This is just understandable enough for most people and I will go no further. But if you desire the hard science version, with references to biomimetic neurones, (or is it neurons?), you may check out the original study in the journal Biosensors and Bioelectronics ; it does come with a slightly shorter and less convoluted, but totally undecipherable title, An organic electronic biomimetic neuron enables auto-regulated neuromodulation. I will stick to the Popular Science version.

Brain 22. Affen Aljfe on Flickr. https://www.flickr.com/photos/142299342@N06/32794072623 http://www.modup.net/

Bionic memory

One major disorder everyone fears is dementia. The concept of forgetting, not just your experiences but family, friends, and eventually yourself, is frightening. But what if you could rely on an electronic memory. A start in this direction was a report that researchers have built a nano memory cell that mimics the way humans lay down memory. At 10,000 sizes smaller than a human hair, such an external memory will surely prove useful. But just take a breath and imagine what it will be like to be incapable of forgetting! Solomon Shereshevsky on my mind. Some way to go yet. This story is sourced from the website Mashable but the research itself is published in the journal Advanced Functional Materials with the, again, cryptic title Donor‐induced performance tuning of amorphous SrTiO3 memristive nanodevices: multistate resistive switching and mechanical tunability. Stick to the translated version in Mashable.

Artificial-intelligence-503593_1920. Many Wonderful Artists on Flickr. https://www.flickr.com/photos/alansimpsonme/34715802120

Memory implants

Most people do not want extraordinary memories and would just want to access the ones they have laid down. Some of these are however buried so deep in the crypts of their brains, they have become inaccessible. Again, technology may have something to promise them. And this comes in the form of a memory boosting brain implant. This device, developed by US Defence scientists, can detect how we retrieve memory, and predict when this will fail, and kick in to action to save the day. A sort of brain pacemaker you may say. The potential benefit is in head injury, but we can all do with a little help every now and then, when the ‘uhms’ and the ‘aahs’ kick in. This piece comes from Science Alert but the original article is on the website of the Defence Advanced Research Project Agency (DARPA), and it is titled Targeted Electrical Stimulation of the Brain Shows Promise as a Memory Aid. Not a bad one this time.

Machine Learning & Artificial Intelligence. Mike MacKenzie on Flickr. https://www.flickr.com/photos/mikemacmarketing/42271822770 www.vpnsrus.com

Neural prosthetics

Another technology promising to help memory is neural prosthetics. These serve to directly send our short-term memories into long-term storage, bypassing the hippocampus when it is too defective to do the job properly. This comes from a piece in Science Daily titled Scientists to bypass brain damage by re-encoding memories. What the prosthesis does is “to bypass a damaged hippocampal section and provide the next region with the correctly translated memory”. In effect it will make the hippocampus redundant. I’m sure the hippocampus does other things apart from encode memories… but we don’t want to think of that now.

Artificial Intelligence – Resembling Human Brain. Deepak Pal on Flikr. https://www.flickr.com/photos/158301585@N08/43267970922

Thought-evoked movements

Imagine being able to move a robotic limb by just thinking about it. No, not telepathy, but with your brain wired to the limb. This is what a prosthetic technology promises for people with brain damage who are unable to move. The prosthetic is implanted in the part of the brain that initiates our intention to move. The source for this story comes from USC News, and it is titled Neural prosthetic device yields fluid motions by robotic arm. In the example cited in the piece, the surgeons “implanted a pair of small electrode arrays in two parts of the posterior parietal cortex-one that controls reach and another that controls grasp“. You have to see the robotic arm in action. Sci-fi is becoming reality in a brain lab near you soon.

3D Brain Sculpture STL model. Misanthropic one on Flikr. https://www.flickr.com/photos/22902505@N05/14780918556

Behavioural remote control

Press a button and alter behaviour. Exciting and scary at the same time. But this is what chemogenetics promises, or threatens, depending on your point of view. This one comes from a piece on the website Neuroscience News titled Chemogenetics technique turns mouse behaviour on and off. The technique “achieves remote control by introducing a synthetic brain chemical messenger system that integrates with the workings of naturally-occurring systems”. ‘Integrate’ feels a tad extreme, almost like being assimilated by the Borg. But I suppose it will be no worse than the antipsychotics and sedatives we currently use to control the behaviour of people with schizophrenia and addictive disorders. It surely looks like it has potential, at least in mice for now.

artificial-intelligence-2167835_1280. Many Wonderful Artisits on Flickr. https://www.flickr.com/photos/alansimpsonme/34752491210

Cognitive enhancement

This technology goes beyond just increasing the ability to preserve or retrieve memory. It sets out to make the brain smarter. This piece comes from The Atlantic and is titled Why cognitive enhancement is in your future (and your past). The technology is transcranial direct current stimulation (TDCS) of the deeper reaches of the brain, using electrodes to send small and painless electrical currents. The currents are thought to increase neuroplasticity, and this enables neurons (or perhaps neurones?) to form the connections necessary for learning.

Brains. Neil Conway on Flickr. https://www.flickr.com/photos/neilconway/3792906411

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It is mind-boggling enough just thinking that people out there are thinking of stuff like these! But it is equally reassuring that the future of the brain is bright.

Mozart and epilepsy: the rhythm beats on

I can’t seem to get away from the theme of Mozart and epilepsy. When I first looked at this, in a blog post titled Mozart and seizures? The links between epilepsy and music, I took the topic rather lightly, more a subscript than a headline you may say. But I have since learnt to take the links between epilepsy and music more seriously. 

By Barbara KrafftThe Bridgeman Art Library, Object 574471, Public Domain, Link

The major trigger for my ‘road to Damascus’ conversion is a 2018 paper titled Study of the Mozart effect in children with epileptic electroencephalograms, published in the journal Seizure. The paper was an eye-opener because it gave a very helpful comprehensive context to the broader beneficial effect of music…not just in epilepsy, but in other neurological disorders such as Parkinson’s disease, dementia and sleep disorders. The authors, Elyza Grylls and colleagues, started on the established premise that Mozart’s music has a beneficial effect on epilepsy. What they wanted to know was if other forms of music have a similar settling effect on epilepsy, or if only Mozart’s music carries the magic touch. The authors therefore played Mozart’s Sonata for two pianos in D major (K448) to 40 children with epilepsy who were undergoing an EEG (electroencephalogram, or electrical brain wave test). They then compared this with the effect of playing other types of music. Remarkably, they found that only Mozart’s Sonata led to a significant reduction in EEG epileptic discharges.

Public Domain, Link

The authors concluded that there was indeed an anti-epileptic effect of Mozart’s music, the so-called  ‘Mozart therapy’. But what is so special about K448? They speculate that it has to do with the structure of Mozart’s music, containing as it does, long periodicities. Interestingly, the music of Yanni, which is similarly structured, has somewhat a similar effect on brain wave activity. On the contrary, and sorry to Beethoven fans, Fur Elise doesn’t have this effect.

By W.J. Baker (held the expired copyright on the photograph) – Library of Congress[1]Contrairement à une erreur fréquemment répandue le buste a été réalisé par Hugo Hagen, non pas à partir du masque mortuaire mais, comme de nombreux autres, d’après le masque réalisé en 1812 par Franz Klein pour un buste qu’il devait réaliser ensuite., Public Domain, Link
So what does the structure of Mozart’s music do to the brain? One suggestion is that Mozart’s music enhances the body’s parasympathetic drive; this reduces the heart rate, and thereby inhibits the brain’s propensity to epileptic seizures. The suppression of this parasympathetic drive is of course the theory behind using vagus nerve stimulation (VNS) to treat drug-resistant epilepsy. For more on VNS, see my previous blog, Vagus nerve stimulation: from neurology and beyond!

By Bionerd – MRI at Charite Mitte, Berlin (used with permission), CC BY 3.0, Link

You have surely wondered by now whether K448 is the only one of Mozart’s compositions to have an anti-epileptic effect. It doesn’t matter if you haven’t, because the authors of another interesting paper have. They titled their study, published in 2018, Mozart’s music in children with drug-refractory epileptic encephalopathies: comparison of two protocols. Published in the journal Epilepsy and Behaviour, the authors, Giangennaro Coppola and colleagues, compared the effect of K448 with a set of his other compositions. Intriguingly they found that the composition set actually had a greater effect in epilepsy than K448…by a wide margin of 70% to 20%! Furthermore, the set was better tolerated by the children; they were less irritable and had a better nighttime sleep quality.   

https://www.publicdomainpictures.net/en/view-image.php?image=76907&picture=dog-amp-child-painting

So, is it all rosy in the garden of music and the brain? No, it’s not! As every rose grows on a thorny tree, so do some forms of music trigger epileptic seizures. This so-called musicogenic epilepsy is well-recognised, and two recent culprits are the music of Sean Paul, discussed in the journal Scientific American , and the music of Ne Yo, explored by NME. Therefore you should craft your playlist wisely.

By CLASSICNEYOOwn work, CC BY-SA 4.0, Link

So, is it time for neurologists to start prescribing music?

Or is it too much of a double-edged sword?

Music is #SimplyIrresistible. Luca Florio on Flickr. https://www.flickr.com/photos/elle_florio/29516744480

A few more catchy neurology article titles to start the year

The Neurology Lounge is addicted to journal articles whose titles show that a lot of thought and attention went into constructing them. I have reviewed some of these in my previous blog posts titled The Art of Spinning Catchy Titles, and The Art of Spinning Catchy Neurology Headlines. To keep the tradition alive, here are a few more recent catchy titles.

Journal Entry. Joel Montes de Oca on Flikr. https://www.flickr.com/photos/joelmontes/4762384399

Stoop to conquer: preventing stroke and dementia together

This comes from an editorial in Lancet Neurology urging a joint approach to preventing stroke and dementia, a strategy the author calls ‘the lowest hanging fruit in the fight against these two greatest threats to the brain’. He argues that ‘at the moment, the fruit might be hanging too low for our gaze, and we are wrongly fixated on the distant future of Alzheimer’s disease treatment. We might have to stoop to conquer‘.

By Gavarni – Le voleur, n°95, 27 août 1858, page 265. Reproduction d’une gravure extraite des Toquades de Paul Gavarni, éditées par Gabriel de Gonet, Paris 1858., Public Domain, Link

Romberg’s test no longer stands up

This opinion piece in Practical Neurology takes a stab at the age-old neurological test of sensory impairment. Subject are asked to stand up and try to maintain their balance with their eyes shut. The author asserts that this, the Romberg’s test, ‘lacks essential specificity’, ‘risks physical injury’, and is ‘redundant’. He argues that there are much better, and safer, ways of testing for sensory ataxia. There goes an interesting test!

By Mikhail KonininFlickr: Meerkat / At the zoo / Novosibirsk / Siberia / 24.07.2012, CC BY 2.0, Link

Dacrystic seizures: a cry for help

This is from a case report of a 69-year old man in the journal Neurology. He presented with unusual crying spells which turned out to be dacrystic (crying) seizures. This case is eventually revealed to be a case of….sorry, no spoilers. Click on the link to find out.

HeartBroken-Tears are the Baptism of the Soul. Anil Kumar on Flikr. https://www.flickr.com/photos/87128018@N00/139136870

Game of TOR -the target of rapamycin rules four kingdoms

I am no fan of Game of Thrones, but it is an in-your-face television series which provides the setting for this catchy title. The mechanistic target of rapamycin (mTOR) pathway is underlies the pathology of tuberous sclerosis. It is therefore the target of many therapeutic strategies in the form of mTOR inhibitors. And the 4 kingdoms? You have to read the piece from the New England Journal of Medicine…perhaps after you have watched the TV series!

Stack. Wendy on Flikr. https://www.flickr.com/photos/wenzday01/4332780839

Restless legs syndrome: losing sleep over the placebo response

This editorial, also from Neurology, addresses the disturbing report in the same journal warning of the high placebo response of interventions for restless legs syndrome (RLS). The title couldn’t be more apt. 

By Edvard Munch – The Athenaeum: pic, Public Domain, Link

 


…and some not very catchy titles

Unfortunately many neurology titles are not as catchy as the ones above. Many article titles appear to be half-baked and fall short. Here are a few:

And the prize for the silliest title in neurology must go to this paper in the Journal of Neural Transmission that is simply…unreadable!

What are the new diseases emerging in neurology?

Medical futurists predict that scientific advances will lead to more precise definition of diseases. This will inevitably result in the emergence of more diseases and fewer syndromes. This case is made very eloquently in the book, The Innovators Prescription. Many neurological disorders currently wallow at the intuitive end of medical practice, and their journey towards precision medicine is painfully too slow. Neurology therefore has a great potential for the emergence of new disorders.

https://pixabay.com/en/pie-chart-diagram-statistics-parts-149727/
https://pixabay.com/en/pie-chart-diagram-statistics-parts-149727/

In the ‘good old days’, many diseases were discovered by individual observers working alone, and the diseases were named after them. In this way, famous diseases were named after people such as James Parkinson, Alois Alzheimer, and George Huntington. For diseases discovered by two or three people, it didn’t take a great stretch of the imagination to come up with double-barrelled names such as Guillain-Barre syndrome (GBS) or Lambert-Eaton myasthenic syndrome (LEMS).

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
Today, however, new diseases emerge as a result of advances made by large collaborations, working across continents. These new diseases are named after the pathological appearance or metabolic pathways involved (as it will require an act of genius to create eponymous syndromes to cater for all the scientists and clinicians involved in these multi-centre trials). This is unfortunately why new disorders now have very complex names and acronyms. Take, for examples, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) and chronic relapsing inflammatory optic neuropathy (CRION). It is a sign that we should expect new neurological diseases to be baptised with more descriptive, but tongue-twisting, names.

 

https://pixabay.com/en/letters-a-abc-alphabet-literacy-67046/
https://pixabay.com/en/letters-a-abc-alphabet-literacy-67046/

New disease categories emerge in different ways. One is the emergence of a new disorder from scratch, with no antecedents whatsoever. Such was the case with autoimmune encephalitis, a category which has come from relative obscurity to occupy the centre stage of eminently treatable diseases. I have posted on this previously as What’s evolving at the cutting edge of autoimmune neurology and What are the dreadful autoimmune disorders that plague neurology? Other disease categories form when different diseases merge into a completely new disease category, or when a previously minor diseases mature and stand on their own feet. These are the stuff of my top 8 emerging neurological disorders.

 

By Photo (c)2007 Derek Ramsey (Ram-Man) - Self-photographed, CC BY-SA 2.5, Link
By Photo (c)2007 Derek Ramsey (Ram-Man) – Self-photographed, CC BY-SA 2.5, Link

1. mTORopathy

This huge monster is ‘threatening’ to bring together, under one roof, diverse disorders such as tuberous sclerosis complex, epilepsy, autism, traumatic brain injury, brain tumours, and dementia. You may explore this further in my previous blog post titled mTORopathy: an emerging buzzword for neurology.

Merging bubbles. Charlie Reece on Flikr. https://www.flickr.com/photos/charliereece/777487250
Merging bubbles. Charlie Reece on Flikr. https://www.flickr.com/photos/charliereece/777487250

2. IgG4-related autoimmune diseases

This new group of neurological diseases is threatening to disrupt the easy distinction between several neurological disorders such as myasthenia gravis (MG), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and Guillain Barre syndrome (GBS). It even includes the newly described IgLON 5 antibody disorder, something I blogged about as IgLON5: a new antibody disorder for neurologists. You may explore IgG4-related disorders in this paper titled The expanding field of IgG4-mediated neurological autoimmune disorders. 

By Aida Pitarch - Own work, CC BY-SA 4.0, Link
By Aida PitarchOwn work, CC BY-SA 4.0, Link

3. Anti-MOG antibody disorders

Now, neurologists have always known about MOG, mostly as a minor bit player, an extra, so to say. No more, it is now all grown up and matured. And the growth is fast and involves many inflammatory demyelinating disease of the CNS such as fulminant demyelinating encephalomyelitis and multiphasic disseminated encephalomyelitis. How far will it go?

http://thebluediamondgallery.com/a/autoimmune.html
http://thebluediamondgallery.com/a/autoimmune.html

4. Hepatitis E virus related neurological disorders

A field which is spurning new neurological disorders is neurological infections, and Hepatitis E virus (HEV) is in the forefront. We are now increasingly recognising diverse Hepatitis E related neurological disorders. HEV has now been linked to diseases such as Guillain Barre syndrome (GBS) and brachial neuritis. And the foremost researcher in this area is Harry Dalton, a hepatologist working from Cornwall, not far from me! And Harry will be presenting at the next WESAN conference in Exeter in November 2017.

By Transferred from en.wikipedia to Commons.This media comes from the Centers for Disease Control and Prevention's Public Health Image Library (PHIL), with identification number #5605.Note: Not all PHIL images are public domain; be sure to check copyright status and credit authors and content providers.English | Slovenščina | +/−, Public Domain, Link
By Transferred from en.wikipedia to Commons.This media comes from the Centers for Disease Control and Prevention‘s Public Health Image Library (PHIL), with identification number #5605.Note: Not all PHIL images are public domain; be sure to check copyright status and credit authors and content providers.English | Slovenščina | +/−, Public Domain, Link

5. Zika virus

Zika virus is another novel infection with prominent neurological manifestations. We are learning more about it every day, and you may check my previous blog post on this, titled 20 things we now know for certain about the Zika virus.

By Manuel Almagro Rivas - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=47941048
By Manuel Almagro RivasOwn work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=47941048

6. Multisystem proteinopathy

Multisystem proteinopathy is a genetic disorder which affects muscles and bone, in addition to the nervous system. It is associated with Paget’s disease of the bone and inclusion body myositis, with implications for motor neurone disease (MND) and frontotemporal dementia (FTD). Quite a hydra-headed monster it seems, all quite complex, and perhaps one strictly for the experts.

Hydra. Andrew Jian on Flikr. https://www.flickr.com/photos/andrew_jian/475479747
Hydra. Andrew Jian on Flikr. https://www.flickr.com/photos/andrew_jian/475479747

7. GLUT-1 deficiency syndromes

GLUT-1 stands for glucose transporter type 1. Deficiency of GLUT-1 results in impaired transportation of glucose into the brainGLUT-1 deficiency syndrome presents with a variety of neurological features such as dystonia, epilepsy, ataxia, chorea, and a host of epilepsy types. It starts in infancy and is characterised by a low level of glucose and lactic acid in the cerebrospinal fluid. Expect to hear more on this in the near future.

Sugar Cubes. David pacey on Flikr. https://www.flickr.com/photos/63723146@N08/7164573186
Sugar Cubes. David pacey on Flikr. https://www.flickr.com/photos/63723146@N08/7164573186

8. Progressive Solitary Sclerosis

And this is my favourite paradigm shifter. Neurologists often see people with brain inflammatory lesions and struggle to decide if they fulfil the criteria for multiple sclerosis (MS). The current threshold for concern is when there have been two clinical events consistent with inflammation of the nervous system, or their MRI scan shows involvement of at least two different sites of the nervous system. Well, dot counting may soon be over, going by this paper in Neurology titled Progressive solitary sclerosis: gradual motor impairment from a single CNS demyelinating lesion. The authors identified 30 people with progressive clinical impairment arising from a single inflammatory nervous system lesion. The authors were convinced enough to recommend the inclusion of this new entity, progressive solitary sclerosis, in future classifications of inflammatory disorders of the central nervous system. Move over progressive MS, here comes progressive SS. Neurologists will surely have their job cut out for them.

Solitary tree at Sunset. epcp on Flikr. https://www.flickr.com/photos/epcprince/3418260382
Solitary tree at Sunset. epcp on Flikr. https://www.flickr.com/photos/epcprince/3418260382

Do you have any suggestions of emerging neurological disorders? Please leave a comment

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PS. These disorders are all covered in neurochecklists

screen-shot-2016-12-19-at-18-32-39

What are the prospects of stamping out Huntington’s disease?

Huntington’s disease (HD) is, without doubt, one of the most dreaded neurological disorders. It is named after George Huntington, but the first description is probably by Charles Oscar Waters in 1842. It is dominantly inherited, each child carrying a 50% chance of acquiring the faulty gene. The genetics is slightly tricky because HD is also a tricnucleotide repeat expansion disorder, similar to some other neurological diseases such as Friedreich’s ataxia (FA), Kennedy disease, myotonic dystrophyspinocerebellar ataxia (SCA), and oculopharyngeal muscular dystrophy (OPMD). In these diseases, a section of the genetic code duplicates itself repeatedly, producing abnormally long segments; worse still, these segments get longer which each transmission down the family line. This is called genetic anticipation, and it leads to later generations of the family developing the disease at an earlier age, and manifesting it more severely.

By Zephyris from en.wikipedia.org, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2118354
By Zephyris from en.wikipedia.org, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2118354

HD is not a nice disease. It is accompanied by chorea, probably the most distressing abnormal movement to torment the human body. This is a continuous, writhing muscle activity which involves all the body, and generating very grotesque and painful postures. As if this wasn’t enough, dementia eventually sets in, as does almost every other neurological symptom one could imagine. HD is a problem neurology needs to solve. And thankfully there is some activity in that direction. Here are 4 recent hope-raising developments.

1. Gene silencing with ISIS-HTTRx

RNA molecules. NIH Image Gallery on Flikr. https://www.flickr.com/photos/nihgov/24148252722
RNA molecules. NIH Image Gallery on Flikr. https://www.flickr.com/photos/nihgov/24148252722

The manufacturers of ISIS-HTTRx must surely be rueing the unfortunate choice of name for their gene silencing drug. But they will take comfort in its promise to crush HD. It is the first trial of a new drug for HD, and it is touted as probably ‘one of the most important developments since the gene for Huntington’s disease was discovered‘. ISIS-HTTRx neutralises huntingtin, the toxic product which accumulates in, and damages, the nerves of people with HD. The only snag…it has to be delivered directly into the spinal fluid. I’m sure an oral tablet will eventually follow, but ISIS-HTTRx is still a long way off; it has to be tested in human volunteers first. One eye then on Sarah Tabrizi, the trial lead, and the other eye on the drug’s name; ISIS pharmaceuticals is now IONIS.

2. Suppressing Huntingtin by enhancing PPAR-δ

By Emw - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8820973
By EmwOwn work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8820973

PPAR-δ stands for peroxisome proliferator-activated receptor delta, and it is a good guy. Researchers have shown that enhancing the activity of PPAR-δ in mouse models of HD has a beneficial effect on mitochondrial function, motor activity, neurodegeneration, and survivalHuntingtin, the infamous bad protein in HD, suppresses PPAR-δ activity. But the wily researchers found a way to reverse this suppression by using an agent called KD3010. They announced their findings in Nature Medicine under the refreshingly self-explanatory title, PPAR-δ is repressed in Huntington’s disease, is required for normal neuronal function and can be targeted therapeutically. (OK, it could be a little shorter). The question now is whether this can be translated to humans. We don’t have too long to wait to find out because the Food and Drug Administration (FDA) has just approved KD3010 human trials

3. Removing cholesterol by boosting CYP46A1

By Jynto (talk) - Own workThis chemical image was created with Discovery Studio Visualizer., CC0, https://commons.wikimedia.org/w/index.php?curid=37702275
By Jynto (talk) – Own workThis chemical image was created with Discovery Studio Visualizer., CC0, https://commons.wikimedia.org/w/index.php?curid=37702275

CYP46A1 is an enzyme which regulates the breakdown of cholesterol. And what has cholesterol got to do with HD? Well…wait for this…cholesterol accumulates in the nerve cells of people with HD, and may contribute to nerve damage. The good news is that CYP46A1 helps to get rid of cholesterol, and some researchers postulate that medicines which enhance the activity of CYP46A1 will improve HD. This all comes from a paper in the journal Brain titled CYP46A1, the rate-limiting enzyme for cholesterol degradation, is neuroprotective in Huntington’s disease. We are still at the proof of concept stages, but it will help if the CYP46A1-enhancing drugs come as handy pills! 

4. Controlling chorea with deutetrabenazine

By (bencbartlett (talk)) - I (bencbartlett (talk)) created this work entirely by myself., CC BY-SA 3.0, https://en.wikipedia.org/w/index.php?curid=27611647
By (bencbartlett (talk)) – I (bencbartlett (talk)) created this work entirely by myself., CC BY-SA 3.0, https://en.wikipedia.org/w/index.php?curid=27611647

Neurologists are familiar with tetrabenazine, the best treatment for chorea. And Star Trek fans are familiar with the heavy hydrogen atom, deuterium. Put the two together and, voila, you get deutetrabenazine (SD809). The heavy hydrogen of deuterium makes deutetrabenazine a more stable drug. This should make it last longer in the body, and also cause less side effects. Considering that the adverse effects of tetrabenazine include depression and parkinsonism, this is not an insignificant advantage (pardon the double negative…I couldn’t help it).

How well does deutetrabenazine translate to clinical practice? Sufficiently well enough it seems, going by the trial published in JAMA Neurology titled Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease. The authors compared the drug to placebo and showed that deutetrabenazine effectively improved chorea at 12 weeks. It is not surprising that the trial compared deutetrabenazine to placebo rather than the existing alternative; head-to-head drug trials are as rare as hen’s teeth in medicine (I wonder why that is). Anyway, deutetrabenazine may be coming to a pharmacy near you soon…we hope. 

Hope. Sign pointing to the village of Hope, Derbyshire UK. Paul Sifter on Flikr. https://www.flickr.com/photos/polsifter/4047982682
Hope. Sign pointing to the village of Hope, Derbyshire UK. Paul Sifter on Flikr. https://www.flickr.com/photos/polsifter/4047982682

There is still a long way to go yet, but each  small step is a glimmer of hope for a neurodegenerative disease such as HD.

Remember, you can have everything HD at your fingertips with neurochecklists (and pardon the shameless pitch).

Addendum

Shortly after posting this blog I came across these articles on HD prospects

  • From Huntington’s Disease News comes Pridopidine. One more to add to the hope for neuroprotection against HD.
  • From the Hazard Gazette comes SIRT2 as a future treatment target for HD

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

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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.

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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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IgLON5: a new antibody disorder for neurologists

IgLON5 antibody syndrome first came to my attention in a paper from Lancet Neurology titled A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5. A passing phenomenon I thought, but added it to neurochecklists anyway.

Antibody by Gentaur (Gentaur) [Public domain], via Wikimedia Commons
Antibody by Gentaur (Gentaur) [Public domain], via Wikimedia Commons

I then came across another paper in Neurology 2015 expanding the phenotype titled Sleep disorder, chorea, and dementia associated with IgLON5 antibodies. And another paper from Journal of Immunology practically established this as a real, and not a phantom, phenomenon. The paper is titled Chorea and parkinsonism associated with autoantibodies to IgLON5 and responsive to immunotherapy.

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So what is IgLON5? Well its a neuronal cell adhesion protein. Naturally. The key features of the syndrome are:

  • Parasomnia
  • Sleep-related breathing problems
  • Rapid eye movement (REM) sleep behaviour disorder
  • Chorea
  • Dementia
  • Parkinsonism

We are surely going to hear more of this antibody syndrome. Watch this space!

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