9 promising advances in the management of traumatic brain injury

Traumatic brain injury (TBI) is simply disheartening. It is particularly devastating because it usually affects young people in their prime, with the consequent personal, social, and economic consequences. This blog has previously touched a little on TBI with the post titled Will Smith and chronic traumatic encephalopathy? This was a light-hearted take on concussion in sports, but traumatic brain injury is nothing but a serious burden. So what are the big brains in white coats doing to take down this colossus? Quite a lot it seems. Here, for a taster, are 9 promising advances in the management of traumatic brain injury.

brain 22. Affen Ajlfe on Flickr. https://www.flickr.com/photos/142299342@N06/32794072623

Better understanding of pathology

An amyloid PET imaging study by Gregory Scott and colleagues, published in the journal Neurology, reported a rather surprising link between the pathology seen in long-term survivors of traumatic brain injury, with the pathology seen in Alzheimers disease (AD). In both conditions, there is an increased burden of β-amyloid () in the brain, produced by damage to the nerve axons. The paper, titled Amyloid pathology and axonal injury after brain trauma, however notes that the pattern of deposition in TBI can be distinguished from the one seen in AD. The big question this finding raises is, does TBI eventually result in AD? The answer remains unclear, and this is discussed in the accompanying editorial titled Amyloid plaques in TBI.

By National Institute on Aging – http://nihseniorhealth.gov/alzheimersdisease/whatisalzheimersdisease/01.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=25038029

Blood tests to detect concussion

The ideal biomarker for any disorder is one which is easy to detect, such as a simple blood test. A headline that screams Blood test may offer new way to detect concussions is therefore bound to attract attention. The benefits of such a test would be legion, especially if the test can reduce the requirement for CT scans which carry the risks of radiation exposure. This is where glial fibrillary acidic protein (GFAP) may be promising. The research is published in the journal, Academic Research Medicine, with a rather convoluted title, Performance of Glial Fibrillary Acidic Protein in Detecting Traumatic Intracranial Lesions on Computed Tomography in Children and Youth With Mild Head Trauma. The premise of the paper is the fact that GFAP is released into the blood stream from the glial cells of the brain soon after brain injury. What the authors therefore did was to take blood samples within 6 hours of TBI in children. And they demonstrated that GFAP levels are significantly higher following head injury, compared to injuries elsewhere in the body. This sounds exciting, but we have to wait and see where it takes us.

Diabetes test. Victor on Flickr. https://www.flickr.com/photos/v1ctor/10871254373

Advanced imaging

Brain Scars Detected in Concussions is the attention-grabbing headline for this one, published in MIT Technology Review. Follow the trail and it leads to the actual scientific paper in the journal Radiology, with a fairly straight-forward title, Findings from Structural MR Imaging in Military Traumatic Brain Injury The authors studied >800 subjects in what is the largest trial of traumatic brain injury in the military. Using high resolution 3T brain magnetic resonance imaging (MRI), they demonstrated that even what is reported as mild brain injury leaves its marks on the brain, usually in the form of white matter hyperintense lesions and pituitary abnormalities. It simply goes to show that nothing is mild when it comes to the brain, the most complex entity in the universe.

Volume rendering of structural MRI scan. Proxy Design on Flickr. https://www.flickr.com/photos/proxyarch/5920559323

Implanted monitoring sensors

Current technologies which monitor patients with traumatic brain injury are, to say the least, cumbersome and very invasive. Imagine if all the tubes and wires could be replaced with microsensors, smaller than grains of rice, implanted in the brain. These would enable close monitoring of critical indices such as temperature and intracranial pressure. And imagine that these tiny sensors just dissolve away when they have done their job, leaving no damage. Now imagine that all this is reality. I came across this one from a CBS News piece titled Tiny implanted sensors monitor brain injuries, then dissolve away. Don’t scoff yet, it is grounded in a scientific paper published in the prestigious journal, Nature, under the title Bioresorbable silicon electronic sensors for the brain. But don’t get too exited yet, this is currently only being trialled in mice.

Public Domain, https://commons.wikimedia.org/w/index.php?curid=190358

Drugs to reduce brain inflammation

What if the inflammation that is set off following traumatic brain injury could be stopped in its tracks? Then a lot of the damage from brain injury could be avoided. Is there a drug that could do this? Well, it seems there is, and it is the humble blood pressure drug Telmisartan. This one came to my attention in Medical News Today, in a piece titled Hypertension drug reduces inflammation from traumatic brain injury. Telmisartan seemingly blocks the production of a pro-inflammatory protein in the liver. By doing this, Telmisartan may effectively mitigate brain damage, but only if it is administered very early after traumatic brain injury. The original paper is published in the prestigious journal, Brain, and it is titled Neurorestoration after traumatic brain injury through angiotensin II receptor blockage. Again, don’t get too warm and fuzzy about this yet; so far, only mice have seen the benefits.

Neural pathways in the brain. NICHD on Flickr. https://www.flickr.com/photos/nichd/16672073333

Treatment of fatigue

Fatigue is a major long-term consequence of traumatic brain injury, impairing the quality of life of affected subjects in a very frustrating way. It therefore goes without saying, (even if it actually has to be said), that any intervention that alleviates the lethargy of TBI will be energising news. And an intervention seems to be looming in the horizon! Researchers writing in the journal, Acta Neurologica Scandinavica, have reported that Methylphenidate significantly improved fatigue in the 20 subjects they studied. Published under the title Long-term treatment with methylphenidate for fatigue after traumatic brain injury, the study is rather small, not enough to make us start dancing the jig yet. The authors have rightly called for larger randomized trials to corroborate their findings, and we are all waiting with bated breaths.

Ritalin. Ian Brown on Flickr. https://www.flickr.com/photos/igb/15713970479

Treatment of behavioural abnormalities

Many survivors of traumatic brain injury are left with behavioural disturbances which are baffling to the victim, and challenging to their families. Unfortunately, many of the drugs used to treat these behaviours are not effective. This is where some brilliant minds come in, with the idea of stimulating blood stem cell production to enhance behavioural recovery. I am not clear what inspired this idea, but the idea has inspired the paper titled Granulocyte colony-stimulating factor promotes behavioral recovery in a mouse model of traumatic brain injury. The authors report that the administration of G‐CSF for 3 days after mild TBI improved the performance of mice in a water maze…within 2 weeks. As the water maze is a test of learning and memory, and not of behaviour, I can only imagine the authors thought-surely only well-behaved mice will bother to take the test. It is however fascinating that G‐CSF treatment actually seems to fix brain damage in TBI, and it does so by stimulating astrocytosis and microgliosis, increasing the expression of neurotrophic factors, and generating new neurons in the hippocampus“. The promise, if translated to humans, should therefore go way beyond water mazes, but we have to wait and see.

By Ryddragyn at English Wikipedia – Transferred from en.wikipedia to Commons., Public Domain, https://commons.wikimedia.org/w/index.php?curid=2148036

Drugs to accelerate recovery

The idea behind using Etanercept to promote recovery from brain injury sound logical. A paper published in the journal, Clinical Drug Investigation, explains that brain injury sets off a chronic lingering inflammation which is driven by tumour necrosis factor (TNF). A TNF inhibitor will therefore be aptly placed to stop the inflammation. What better TNF inhibitor than Eternacept to try out, and what better way to deliver it than directly into the nervous system. And this is what the authors of the paper, titled Immediate neurological recovery following perispinal etanercept years after brain injury, did. And based on their findings, they made some very powerful claims: “a single dose of perispinal etanercept produced an immediate, profound, and sustained improvement in expressive aphasia, speech apraxia, and left hemiparesis in a patient with chronic, intractable, debilitating neurological dysfunction present for more than 3 years after acute brain injury”. A single patient, mind you. Not that I am sceptical by nature, but a larger study confirming this will be very reassuring.

By Doxepine – Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=6796200

Neuroprotection

And finally, that elusive holy grail of neurological therapeutics, neuroprotection. Well, does it exist? A review of the subject published in the journal, International Journal of Molecular Sciences, paints a rather gloomy picture of the current state of play. Titled Neuroprotective Strategies After Traumatic Brain Injury, it said “despite strong experimental data, more than 30 clinical trials of neuroprotection in TBI patients have failed“. But all is not lost. The authors promise that “recent changes in experimental approach and advances in clinical trial methodology have raised the potential for successful clinical translation”. Another review article, this time in the journal Critical Care, doesn’t offer any more cheery news about the current state of affairs when it says that the “use of these potential interventions in human randomized controlled studies has generally given disappointing results”. But the review, titled Neuroprotection in acute brain injury: an up-to-date review, goes through promising new strategies for neuroprotection following brain injury: these include hyperbaric oxygen, sex hormones, volatile anaesthetic agents, and mesenchymal stromal cells. The authors conclude on a positive note: “despite all the disappointments, there are many new therapeutic possibilities still to be explored and tested”.

brain 59. Affen Ajlfe on Flickr. https://www.flickr.com/photos/142299342@N06/32794069243/

What an optimistic way to end! We are not quite there yet, but these are encouraging steps.

15 more creative and catchy neurology headlines for 2019

Regular visitors to this blog know that we love catchy article titles. It is always heartwarming to see how some authors create imaginative and inventive headlines. This skill involves the ability to play with words, and the capacity to be double-edged. This is why this blog keeps a lookout for fascinating neurology titles. And in line with this tradition, and in no particular order of inventiveness, here are 15 more catchy neurology titles!

By Andrikkos – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=33725735

15. Who do they think we are? Public perceptions of psychiatrists and psychologists

This paper, for some unfathomable reason, set out to ask if the public knows the difference between what psychiatrists and psychologists actually do. And the authors discovered that “there is a lack of clarity in the public mind about our roles”. More worryingly, or reassuringly (depending on your perspective), they also found out that “psychologists were perceived as friendlier and having a better rapport“. Not earth-shattering discoveries, but what a great title!

By Laurens van Lieshout – Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2059674

14. OCT as a window to the MS brain: the view becomes slightly clearer

Optical coherence tomography (OCT) is a cool tool which measures the thickness of the retinal fiber layer (RFL). And it has the habit of popping its head up in many neurological specialties. In this case, the specialty is multiple sclerosis, and the subject is how OCT influences its diagnosis and surveillance. Surely a window into the brain is easier to achieve than one into the soul.

Optical coherence tomography of my retina. Brewbooks on Flickr. https://www.flickr.com/photos/brewbooks/8463332137

13. A little man of some importance 

The homonculus is the grotesque representation of the body on the surface or cortex of the brain. This paper reviews how formidable neurosurgeons such as Wilder Penfield worked out the disproportionate dimensions of this diminutive but influential man. He (always a man for some reason) has giant hands, a super-sized mouth, very small legs, and a miniature trunk. The clever brain doesn’t readily allocate its resources to large body parts that perform no complex functions! But be warned, this article is no light-weight reading!

The Homunculus in Crystal Palace (Moncton). Mark Blevis on Flickr. https://www.flickr.com/photos/electricsky/1298772544

12. Brain-focussed ultrasound: what’s the “FUS” all about? 

This title is a play on words around MR-guided focussed ultrasound surgery (MRgFUS), an emerging technique for treating disorders such as essential tremor and Parkinson’s disease (PD). This review looks at the controversial fuss that this technique has evoked.

By Luis Lima89989 – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19162929

11. The Masks of Identities: Who’s Who? Delusional Misidentification Syndromes

This paper explores the interesting subject of delusional misidentification syndromes (DMSs). The authors argue that few concepts in psychiatry can be as confusing as DMSs. And they did an excellent job of clearing our befuddlement around delusions such as Capgras and Fregoli. Very apt title, very interesting read.

no identity. HaPe-Gera on Flickr. https://www.flickr.com/photos/hape_gera/2929195528

 

10. Waking up to sleeping sickness.

This title belongs to a review of trypanosomiasis, aka sleeping sickness. It is a superb play on words, one that evokes several levels of meaning. It is simple and yet complex at the same time. Great imagination.

https://picryl.com/media/the-sleeping-sickness-gordon-ross

09. Brains and Brawn: Toxoplasma Infections of the Central Nervous System and Skeletal Muscle

This paper discusses two parts of nervous system that are affected by toxoplasmosis. Playing on the symbolic  contradiction between intellect and strength, the authors show how toxoplasmosis is an ecumenical abuser: it metes out the same fate to both brain and brawn.

Brain vs. Brawn. Yau Hoong Tang on Flickr. https://www.flickr.com/photos/tangyauhoong/4474921735

08. Shedding light on photophobia

A slightly paradoxical title this one. Ponder on it just a little more! And then explore the excellent paper shedding light on a condition that is averse to light.

Photophobia (light sensitivity). Joana Roja on Flickr. https://www.flickr.com/photos/cats_mom/2772386028/

07. No laughing matter: subacute degeneration of the spinal cord due to nitrous oxide inhalation

Nitrous oxide, or laughing gas, is now “the seventh most commonly used recreational drug”. But those who pop it do so oblivious of the risk of subacute combined degeneration. This damage to the upper spinal cord results from nitrous oxide-induced depletion of Vitamin B1 (thiamine). Not a laughing matter at all!

Empty Laughing Gas Canisters. Promo Cymru on Flickr. https://www.flickr.com/photos/promocymru/18957223365

06. To scan or not to scan: DaT is the question

Dopamine transport (DaT) scan is a useful brain imaging tests that helps to support the diagnosis of Parkinson’s disease and other disorders which disrupt the dopamine pathways in the brain. It is particularly helpful in ruling out mimics of Parkinson’s disease such as essential tremor. When to request a DaT scan is however a tricky question in practice. This paper, with its Shakespearean twist, looks at the reliability of DaT scans.

Dopamine. John Lester on Flickr. https://www.flickr.com/photos/pathfinderlinden/211882099

05. TauBI or not TauBI: what was the question?

It should be no surprise if Shakespeare rears his head more than once in this blog post. Not when the wordsmith is such a veritable source of inspiration for those struggling to invent catchy titles. This paper looks at taupathy, a neurodegeneration as tragic as Hamlet. It particularly comments on an unusual taupathy, one induced by traumatic brain injury. Curious.

By Lafayette Photo, London – This image is available from the United States Library of Congress‘s Prints and Photographs divisionunder the digital ID cph.3g06529.This tag does not indicate the copyright status of the attached work. A normal copyright tag is still required. See Commons:Licensing for more information., Public Domain, Link

04. Mind the Brain: Stroke Risk in Young Adults With Coarctation of the Aorta

What better way to call attention to a serious complication than a catchy title like this one. This paper highlights the neurological complications of coarctation of the aorta, a serious congenital cardiovascular disease. And the key concerns here are the risks of stroke and cerebral aneurysms. Cardiologists, mind the brain!

Own work assumed (based on copyright claims)., Public Domain, https://commons.wikimedia.org/w/index.php?curid=803943

03. Diabetes and Parkinson disease: a sweet spot?

This paper reviews the unexpected biochemical links between diabetes and Parkinson’s disease. And this relationship is assuming a rather large dimension. Why, for example, are there so many insulin receptors in the power house of Parkinson’s disease, the substantia nigra? A sweet curiosity.

Insulin bubble. Sprogz on Flickr. https://www.flickr.com/photos/sprogz/5606839532

02. PFO closure for secondary stroke prevention: is the discussion closed?

The foraman ovale is a physiological hole-in-the-heart which should close up once a baby is born. A patent foramen ovale (PFO) results when this hole refuses to shut up. PFOs enable leg clots to traverse the heart and cause strokes in the brain. This paper reviews the evidence that surgically closing PFOs prevents stroke. Common sense says it should, but science demands proof. And the authors assert that they have it all nicely tied up. Hmmm.

By Kjetil Lenes – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=3705964

01. Closure of patent foramen ovale in “cryptogenic” stroke: Has the story come to an end?

Not to be beaten in the catchy title race is another brilliant PFO review article. Why do I feel the answer here is ‘no’? This is science after all.

https://www.flickr.com/photos/fliegender/293340835

 

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

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