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

***

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.

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

=========================================================================

PS. These disorders are all covered in neurochecklists

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

How is neurology stamping out the anguish of Duchenne?

Duchenne muscular dystrophy (DMD) is the most familiar of the inherited muscle diseases called muscular dystrophies. DMD is life limiting, but advances in care are enabling children born with this disease to survive well into adulthood. The disease is named after the French neurologist Guillaume Duchenne.

See page for author [CC BY 4.0], via Wikimedia Commons
See page for author [CC BY 4.0], via Wikimedia Commons

The foundation of long survival in DMD is close supervision of breathing and heart functions. DMD however affects much more than these vital functions, and it remains a challenging disease for families and management teams. Thankfully researchers are not resting on their laurels, working ever hard on heart-warming advances. Here are three.

STEROIDS

By Ring0 (Own work) [Public domain], via Wikimedia Commons
By Ring0 (Own work) [Public domain], via Wikimedia Commons
Steroids are now well-established in the treatment of Duchenne muscular dystrophy. What is new however is a better understanding of their benefits in DMD, together with clearer guidance on their use. This is contained in the recent practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy.

Published in the journal Neurology, this document shows how steroids help to improve muscle strength, maintain breathing functions, stabilise ambulation, prevent spinal deterioration (scoliosis), and delay onset of heart disease.

Is there more one could hope for? Yes, a lot more when it comes to genetic diseases.

IDEBENONE

Mitokondria. 140264jd on Flikr. https://www.flickr.com/photos/140264jd/6286783453/in/photostream/
Mitokondria. 140264jd on Flikr. https://www.flickr.com/photos/140264jd/6286783453/in/photostream/

 

Idebenone is not new to neurologists. Researchers at Newcastle have been investigating its vision-preserving effect in the mitochondrial disease called Leber’s hereditary optic neuropathy (LHON). Idebenone is thought to improve the activity of mitochondria, the energy-producing component of all cells. Idebenone has also been investigated in other neurological disorders such as Friedreich’s ataxia.

Perhaps as an indication of its growing importance, researchers have now looked at the effect of Idebenone in people with DMD, and they did this in two separate trials. DELPHI is published in the journal Neuromuscular Disorders as Idebenone as a novel, therapeutic approach for Duchenne muscular dystrophy. The authors reported benefit in both cardiac and respiratory function.

DELOS, the second trial, is published in Lancet Neurology and titled Efficacy of idebenone on respiratory function in patients with Duchenne muscular dystrophy not using glucocorticoids. The authors again reported similar benefits. For a synthesised take, see this useful review in Touch Neurology.

But is this enough for ambitious researchers? Of course not…not when you see the promise of gene editing.

GENE EDITING

Jazz Mouse. Richard Scott on Flikr. https://www.flickr.com/photos/richardmscott/2091183925
Jazz Mouse. Richard Scott on Flikr. https://www.flickr.com/photos/richardmscott/2091183925

 

I first came across this in Eureka Alert which proclaimed: Gene-editing technique successfully stops progression of Duchenne muscular dystrophy. The gene editing, or gene splicing, technique is called CRISPR. The research itself is published in the journal Science as In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy.

The researchers used CRISPR technology to delete exon 23 from the Duchenne gene on the X chromosome. Exon 23 is the site of the fault that makes DMD patients unable to produce the muscle protein called dystrophin. By splicing this exon out, the researchers demonstrated an increase in the production of dystrophin. And this increase was significant enough to lead to an improvement in muscle strength.

OK, its only the humble mouse at the moment, but exon skipping therapy is clearly beckoning.

B0007267 Muscle Fibers. Welcome Images on Flikr. https://www.flickr.com/photos/wellcomeimages/5814145089
B0007267 Muscle Fibers. Welcome Images on Flikr. https://www.flickr.com/photos/wellcomeimages/5814145089

 

 

12 fascinating advances in epilepsy: big data to pacemakers

I recently posted on the role of vagus nerve stimulation (VNS) in epilepsy. Exciting as it is, there are several cutting edge developments in epilepsy that are making VNS ‘old school’. Here is a round-up of 12 such developments

1. Big data to improve epilepsy care

"Scatter plot" by UCRL - Visualizations that have been created with VisIt. at wci.llnl.gov. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:Scatter_plot.jpg#/media/File:Scatter_plot.jpg
“Scatter plot” by UCRL – Visualizations that have been created with VisIt. at wci.llnl.gov. Licensed under Public Domain via Commons – https://commons.wikimedia.org/wiki/File:Scatter_plot.jpg#/media/File:Scatter_plot.jpg

Big Data is spreading its tentacles everywhere and epilepsy is no exception. Take this review in Lancet Neurology for example; titled ‘Epilepsy in 2015: the year of collaborations for big data’, it reviews the impact of big data in five key epilepsy areas such as surgery, effect of epilepsy on pregnancy, and risks if anti-epileptic drugs (AEDs). I was however more impressed by the paper in Neurology titled Predicting frequent ED use by people with epilepsy with health information exchange data‘ which shows how big data may be used to identify frequent emergency department attenders. The authors showed how big data achieves this; the whole aim is to pick out those patients may benefit most from targeted-interventions. The article itself doesn’t mention big data, but the accompanying editorial fortunately does.

2. Better epilepsy monitoring devices

"EEG Recording Cap" by Chris Hope - http://www.flickr.com/photos/tim_uk/8135755109/. Licensed under CC BY 2.0 via Commons - https://commons.wikimedia.org/wiki/File:EEG_Recording_Cap.jpg#/media/File:EEG_Recording_Cap.jpg
“EEG Recording Cap” by Chris Hope – http://www.flickr.com/photos/tim_uk/8135755109/. Licensed under CC BY 2.0 via Commons – https://commons.wikimedia.org/wiki/File:EEG_Recording_Cap.jpg#/media/File:EEG_Recording_Cap.jpg

 

The management of epilepsy is very dependent on the accurate assessment of each patient’s day-to-day event pattern. In the simplest form, this is by a seizure diary. Seizures, the abnormal electrical brain activity that result in epilepsy, do not always manifest as recognisable events. Furthermore, many abnormal movements and behaviours do not necessarily arise from seizures. The neurologist therefore often recommends some form of prolonged brain activity monitoring to sort out what is actually happening. This is often done with procedures such as ambulatory electroencephalogram (EEG) and video EEG telemetry. These are all inconvenient and may only be used for a limited period. It is therefore reassuring that there are better techniques on the way. This press release from the World Federation of Neurology titled New epilepsy monitoring devices offer alternatives to inpatient video EEG lists ‘an array’ of devices such as the Brain Sentinel® System and the EEG PatchTM. These go further than just identifying the seizure activity; they allow patients to monitor clinical and subclinical seizure activity in the everyday home environment and get advance warning before a seizure strikes‘. What could be better for people with epilepsy?

3. Precision medicines for epilepsy

 

Drug firms 'creating ills for every pill' by Publik15 on Flikr. https://www.flickr.com/photos/publik15/3415531899
Drug firms ‘creating ills for every pill’ by Publik15 on Flikr. https://www.flickr.com/photos/publik15/3415531899

Epilepsy is a disease with several types and subtypes, and many genetic forms. Treating epilepsy therefore requires a close fit (no pun intended) of the disease type to its treatment. This is however a difficult task because many epilepsies are poorly defined, and the activity of anti-epileptic drugs (AEDs) are poorly understood. Whilst there are general principles of action of AEDs, these may not apply to individual patients. Herein then lies the promise of precision medicines which, making use of the patient’s genetic makeup or genome, offer a better match of AEDs to individuals. It is still early days but the course is being charted; the EpiPM Consortium recently published ‘A roadmap to precision medicines in the epilepsies‘ in Lancet Neurology.

4. Better prediction of SUDEP

"Ventricular fibrillation" by Jer5150 - Own work. Licensed under CC BY-SA 3.0 via Commons - https://commons.wikimedia.org/wiki/File:Ventricular_fibrillation.png#/media/File:Ventricular_fibrillation.png
“Ventricular fibrillation” by Jer5150 – Own work. Licensed under CC BY-SA 3.0 via Commons – https://commons.wikimedia.org/wiki/File:Ventricular_fibrillation.png#/media/File:Ventricular_fibrillation.png

 

Sudden unexpected death in epilepsy (SUDEP) is a nightmare. It strikes out of the blues, shocking families and neurologists alike. How to predict and prevent this phenomenon is a holy grail in epilepsy care. It is therefore gratifying news in a recent article in the journal Brain that there is a potential SUDEP imaging biomarker. The authors of the paper, titled Structural imaging biomarkers of sudden unexpected death in epilepsyreport that the magnetic resonance imaging (MRI) scans of people at risk of SUDEP show characteristic signs. The main feature is a larger grey matter volume in the right hippocampus and amygdala. The rest of the story is more tricky to understand and involves impaired oxygen regulation leading to the abnormal heart rhythms that presumably cause SUDEP. OK, just take it that this is a potential biomarker to risk-stratify patients for SUDEP!

5. Out-of-hospital status epilepsy injections

 

By AngelHM (Own work) [CC BY-SA 4.0 (http://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons
By AngelHM (Own work) [CC BY-SA 4.0 (http://creativecommons.org/licenses/by-sa/4.0)%5D, via Wikimedia Commons

A generalised tonic-clonic (or grand mal) seizure often self-terminates within 5 minutes. It may however be prolonged, or occur repeatedly, and this is called status epilepsy or status epilepticus. Out-of-hospital care to terminate status epilepticus often involves the use of buccal Midazolam or, thankfully fading into history, rectal Diazepam. The most effective short-term treatment is however intravenous Lorazepam, but this may only be administered in hospital. Is there something as effective as intravenous Lorazepam which could be administered by paramedics in the community? You guessed it, there probably is. A recent trial published in the New England Journal of Medicine (NEJM) shows that pre-hospital intramuscular Midazolam delivered by paramedics is effective. There are safety issues to sort out but this development promises to avert brain damage that may result from prolonged convulsions. Neuroscience News offers a simplified version of this study.

6. Optogenetics to improve arousal during a seizure

Optogenetics is the use of light to control cell activity in living tissues. I previously listed this in my previous post as one of 10 remarkable breakthroughs that will change neurology. A recent paper in the journal Epilepsia showed how optogenetics may improve epilepsy. Published under the rather unwieldy title Optogenetic stimulation of cholinergic brainstem neurons during focal limbic seizures…., the authors report the application of optogenetics to stimulate subcortical brainstem cells during a focal epileptic seizure. The story is rather complicated but this technique somehow causes inhibition of the cortical cells that generate seizures. A lot of the physiology remains to be sorted, but hey, its shining a light on a difficult problem!

7. 3D electroencephalography (3D-EEG)

 

"Spike-waves". Licensed under CC BY-SA 2.0 via Commons - https://commons.wikimedia.org/wiki/File:Spike-waves.png#/media/File:Spike-waves.png
“Spike-waves”. Licensed under CC BY-SA 2.0 via Commons – https://commons.wikimedia.org/wiki/File:Spike-waves.png#/media/File:Spike-waves.png

The electroencephalogram (EEG) is an indispensable tool in the diagnosis of epilepsy. It helps, amongst other things, to localise the site of a seizure discharge, and to classify the epilepsy type. It is however a rather insensitive tool for planning epilepsy surgery compared to imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) scans which are far better. 3D EEG is however set to make its mark in this area if a recent paper in Epilepsia fulfils its promise. Titled ‘The diagnostic utility of 3D electroencephalography source imaging in pediatric epilepsy surgery‘, the authors show that 3-D EEG is comparable to PET and SPECT in planning epilepsy surgery; and it is also cheaper and less risky.

8. Neurotransmitter imaging of epilepsy

By courtesy of Massachusetts General Hospital and Draper Labs [Public domain], via Wikimedia Commons
By courtesy of Massachusetts General Hospital and Draper Labs [Public domain], via Wikimedia Commons

Epilepsy surgery relies on accurate mapping of the seizure focus. Current techniques are however still suboptimal and scientists are exploring better ways of doing this. One promising field is neurotransmitter-based imaging, and the main neurotransmitter here is glutamate. This MRI technique called glutamate chemical exchange saturation transfer (GluCEST) promises to identify seizure foci that are otherwise difficult to detect. You may read the technical aspects in the original paper in Science Translational Medicine, or go for the layman’s version in Neuroscience News.

An extension of glutamate imaging uses PET scans and relies on imaging NMDA, one type of glutamate receptor. This technique is reported in the Journal of Neurology, Neurosurgery and Psychiatry (JNNP) in an article titled NMDA receptor binding in focal epilepsies. The principle behind NMDA imaging is the knowledge that NMDA receptor ion channels are overactive in epilepsy. Isn’t it nice when science follows first principles!

9. Better mapping of seizure focus

"MRI Location Hippocampus up." by Amber Rieder, Jenna Traynor - Own work. Licensed under CC0 via Commons - https://commons.wikimedia.org/wiki/File:MRI_Location_Hippocampus_up..png#/media/File:MRI_Location_Hippocampus_up..png
“MRI Location Hippocampus up.” by Amber Rieder, Jenna Traynor – Own work. Licensed under CC0 via Commons – https://commons.wikimedia.org/wiki/File:MRI_Location_Hippocampus_up..png#/media/File:MRI_Location_Hippocampus_up..png

Surgery is a very useful tool in treatment of drug-resistant epilepsy. Epilepsy surgery is however not universally successful because localisation of the seizure focus is often imprecise. One promising way to improve the localisation of the seizure focus is to map the changes in oxygen levels that occur in the brain during an epileptic seizure. A paper in the JNNP reports that this is feasible with the use of simultaneous EEG (electroencephalography) and fMRI (functional magnetic resonance imaging). It’s all rather complicated stuff and I recommend this version from the Epilepsy Society which offers an excellently simplified summary. 

10. Personalised epilepsy surgery

"White Matter Connections Obtained with MRI Tractography" by Xavier Gigandet et. al. - Gigandet X, Hagmann P, Kurant M, Cammoun L, Meuli R, et al. (2008) Estimating the Confidence Level of White Matter Connections Obtained with MRI Tractography. PLoS ONE 3(12): e4006. doi:10.1371/journal.pone.0004006. Licensed under CC BY 2.5 via Commons.
White Matter Connections Obtained with MRI Tractography” by Xavier Gigandet et. al. – Gigandet X, Hagmann P, Kurant M, Cammoun L, Meuli R, et al. (2008) Estimating the Confidence Level of White Matter Connections Obtained with MRI Tractography. PLoS ONE 3(12): e4006. doi:10.1371/journal.pone.0004006. Licensed under CC BY 2.5 via Commons.

 

A holy grail of epilepsy (OK, there are many holy grails) is to individualise all types of epilepsy treatment, including surgery. Personalised epilepsy surgery is guided by a simulated model of a patient’s brain neural connections or connectome. This technique is reported in PLOS Computational Biology  under the title Predicting surgery targets in temporal lobe epilepsy through structural connectome based simulations. Why scientists love long windy titles baffles me. Anyway, the authors first acquired a map of their subject’s brain connectivity using an MRI technique called diffusion tensor imaging (DTI). They then applied a computerised model of how a seizure propagates to the connectivity map. In this way they are able to establish a more accurate surgical target. The area that is resected at surgery using this technique produced better outcomes than resection using a standard procedure. Makes sense to me.

11. Endoscopic epilepsy surgery

"Flexibles Endoskop" by de:Benutzer:Kalumet - Own work. Licensed under CC BY-SA 3.0 via Commons - https://commons.wikimedia.org/wiki/File:Flexibles_Endoskop.jpg#/media/File:Flexibles_Endoskop.jpg
“Flexibles Endoskop” by de:Benutzer:Kalumet – Own work. Licensed under CC BY-SA 3.0 via Commons – https://commons.wikimedia.org/wiki/File:Flexibles_Endoskop.jpg#/media/File:Flexibles_Endoskop.jpg

 

Although surgery is a good technique for epilepsy, it is an invasive procedure with attendant risks. Endoscopy, using minimal access to perform great feats, reduces this risk significantly. It is widely practiced in medicine and indeed neurosurgeons use it to relieve raised intracranial pressure in some cases. It is therefore a relief to learn that major epilepsy operations may be performed endoscopically. A recent article in the Journal of Neuroscience titled ‘Endoscopic corpus callosotomy and hemispherectomy reports the effectiveness of endoscopy in epilepsy operations such as corpus callosotomy; a procedure that interrupts the large bundle of nerve fibers that connect the two brain hemispheres. You may read the easy version in Mental Floss.

12. Deep brain stimulation for epilepsy

 

By Shamir R, Noecker A and McIntyre C [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons
By Shamir R, Noecker A and McIntyre C [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)%5D, via Wikimedia Commons

Deep brain stimulation (DBS) is now routine in many neurological diseases such as Parkinson’s disease (PD). Epilepsy has been slow to catch on but this is changing. A recent piece on the Mayo Clinic website peered into the future treatment options for epilepsy and referred to pacemaker-like devices to control the seizure focus. There are many studies showing the feasibility and effectiveness of implantable devices which directly stimulate an epileptic focus to abort a seizure. One such system is Responsive Brain Neurostimulator (RNS® System)It may be counterintuitive but stimulation rather than suppression is the key. A review of Responsive neurostimulation in epilepsy says ‘the strategy is to interfere as early as possible with the accumulation of seizure activity to prematurely abort or even prevent an upcoming seizure’.

"Hippocampus small" by Images are generated by Life Science Databases(LSDB). - from Anatomography, website maintained by Life Science Databases(LSDB).You can get this image through URL below. 次のアドレスからこのファイルで使用している画像を取得できますURL.. Licensed under CC BY-SA 2.1 jp via Commons - https://commons.wikimedia.org/wiki/File:Hippocampus_small.gif#/media/File:Hippocampus_small.gif
“Hippocampus small” by Images are generated by Life Science Databases(LSDB). – from Anatomography, website maintained by Life Science Databases(LSDB).You can get this image through URL below. 次のアドレスからこのファイルで使用している画像を取得できますURL.. Licensed under CC BY-SA 2.1 jp via Commons – https://commons.wikimedia.org/wiki/File:Hippocampus_small.gif#/media/File:Hippocampus_small.gif

The future is bright for epilepsy care-and it can’t come soon enough for the millions of people whose lives are restricted and compromised by this disease.