The emerging links between Alzheimer’s disease and infections

Alzheimer’s disease (AD) is one of the most fearsome and recalcitrant scourges of neurology. We think we know a lot about it; after all it has been a quite a while since Alois Alzheimer described amyloid plaques and neurofibrillary tangles in his index patient, Frau Deter. But the more neuroscientists study the disease, the murkier the field looks. For example, we are still not quite sure what the plaques and tangles really signify; for all we know, they may just be innocent bystanders, powerless by-products of a neurodegenerative process that defies understanding. We have accumulated an endlessly long list of AD risk factors, but we have singularly been unable to point a finger at the cause of AD.

By National Institute on Aging –, Public Domain, Link

This elusive void may however be a void no longer, if what superficially appears to be an outlandish theory turns out to be correct. And the theory is that AD is caused by infection! Just take a deep breathe, and allow yourself the space to make a giant leap of imagination. My attention was first drawn to the infective hypothesis of AD by a headline in Scientific American screaming Controversial New Push to Tie Microbes to Alzheimer’s Disease. The obvious key word here of course is controversial: is it possible that AD, this quintessential neurodegenerative disease, is…just another chronic infection?

Alzheomer’s at the microscopic level. Oak Ridge National Laboratory on Flickr.

To find the original source of the story, the trail of bread crumbs led to an editorial published in the Journal of Alzheimer’s Disease in 2016, plainly titled Microbes and Alzheimer’s Disease. But this is not a run-of-the-mill editorial at all because it was written by 33 senior scientists and clinicians from a dozen countries. And their reason for an alternative theory of AD is simple: amyloid, the long-suspected culprit for decades, has failed to live up to its billing. They point  out that amyloid exists harmlessly in the brains of many older people who never go on to develop dementia. They also cite studies which demonstrate that treating amyloid, by immunological means, does not improve the state of people suffering from AD. Amyloid, in other words, is not such a bad guy after all. But all the while we have been setting traps to ensnare it, the microbial villains have been running amok, having a field day.

Автор: own work – adapted from using PyMOL, Суспільне надбання (Public Domain), Посилання

But why should microbes succeed where amyloid, the ubiquitous protein, has woefully failed? The editorial gave 8 good reasons to argue that the infection theory is better than the amyloid hypothesis. One reason is that the brains of people with AD are often riddled with inflammation, a characteristic feature of infections. Another reason is the observation that AD can be transferred to primates when they are inoculated with the brain tissue of someone with AD.

194 001 001. US Department of Energy on Flickr.

It may be hard to swallow, but if you are still maintaining your imaginative leap, just spare a thought for the microbes that are on the line-up of competing suspects. Take your pick, from helicobacter pylori to fungal infections, from spirochetes such as Lyme neuroborreliosis to chlamydia, from cytomegalovirus (CMV) to polymicrobial infections. But of all the potential suspects, one stands head and shoulders above the rest (no fungal pun intended-honest).

E. coli bacteria. NIAID on Flickr.

And the culprit with the most number of index fingers pointing at it is herpes simplex virus type 1 (HSV1). The editorial tells us that there have been about 100 publications, by different groups, demonstrating that HSV1 is a ‘major factor‘ in the causation of AD. Some of these studies have shown that people with AD have immunological signs of significant HSV infection in their blood. The editorial goes further to review the possible mechanisms by which HSV1 may cause AD; one of these is the possibility that the virus lowers the risk of AD in people who possess the APOE ɛ4 allele genetic liability.

Von Thomas Splettstoesser ( – Eigenes Werk, CC BY-SA 4.0, Link

Just when you are getting your head round the idea, the infection theory takes a very sinister turn. And this relates to the perverse modus operandi of the microbes. The authors tell us that the microbes first gain access to the brains of their victims when they (the victims) were much younger. Like sleeper cells in their ghoulish crypts, the microbes hibernate, biding their time until their victims get older, and their immunity declines. The microbes then awaken, and like malevolent zombies, set out to wreak gory mayhem and cataclysmic destruction. And they do this either by causing direct damage to the brain, or indirectly by inducing inflammation.

Microbes. Quin Dombrowski on Flickr.

You can now descend form your giant imaginative leap and start to wonder: if AD is indeed caused by microbes, what can we do about it? ‘Tis time for some down-to-earth deep thinking.

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.

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 –, Public Domain,

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.

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.

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,

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.

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.

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,

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,


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.

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

Putting cerebral malaria in the powerful spotlight

The blogosphere is a crowded place. To stand out from the pack, a lot of bustling and hustling takes place. Medical blogging is not exempt from this melee. However, in the zeal to put blog posts in the limelight, the blogger may inadvertently fixate on high profile diseases, the ones that seem to readily covet the headlines. In this way, deadlier but less ‘celebrity’ maladies are left to simmer and fester below the radar. To avoid falling into this trap, this blog endeavours, (every now and then), to shine a light on these clandestine infirmities. These are the plagues which profit by virtue of their anonymity. It is no surprise that many of these disorders are tropical diseases, and there is no sweltering equatorial beast more sinister than the ague. It is therefore in the interest of fairness and balance that we are putting cerebral malaria in the powerful spotlight.

Malaria in peripheral blood. Ed Uthman on Flickr.

Malaria is a beast because it is endemic in many developing countries. The epidemiological map below gives a flavour of which countries receive the brunt of the miasm.

Von S. Jähnichen and, CC BY-SA 3.0, Link

Just like other parasitic infections, malaria undertakes a tortuous life cycle. It appears that it is in the nature of these scroungers to beguile and hoodwink their way to the human bloodstream. Scurrying and scampering, they transit from mosquito to man. It is to the credit of malaria-busters such as Ronald Ross that their deceptive course, pictured below, was revealed.

Life cycle of the malaria parasite. NIAID on Flickr.

And a nasty monster is malaria. The different malaria species are transmitted by the female Anopheles mosquito (please don’t ask why). Finding warm veins irresistible, she sates her bloodthirsty cravings whilst  unknowingly transmitting the malaria buggers called sporozoites. Once they get to the liver, these transform into insatiable merozoites which are tasked with one hatchet job: detect, invade and destroy innocent hardworking red blood cells. OK, I admit that’s three hatchet jobs.

By NIAID – Malaria Parasite Connecting to Human Red Blood Cell, CC BY 2.0,

The plasmodium species vivax, ovale, and malariae can all wreak atrocious havoc, but it is falciparum that poses the greatest threat to the nervous system. This is partly because falciparum can make its host cells sticky, and in the brain, these sticky cells adhere tightly to the walls of blood vessels. This is how falciparum evades detection by the immune system, and how it escapes destruction by drugs. The sticky cells eventually clog up the cerebral circulation, resulting in the infamous malarial vasculopathy. Left untreated, cerebral malaria is sadly invariably fatal.

By Content Providers(s): CDC/James GathanyProvider Email: jdg1@cdc.govPhoto Credit: James Gathany – CDC, Public Domain,

Cerebral malaria has diverse manifestations, and the most devastating include retinopathy, rigidity, ataxia (poor balance), subarachnoid haemorrhage, psychosis, hemiparesis, epilepsy, behavioural abnormalities, and coma. And this is over and above what malaria does to the other organs. The run down is very scary indeed; from anaemia to pulmonary edema, from hypoglycaemia (low glucose) to hyponatraemia (low sodium); from metabolic acidosis to hyperpyrexia (high fever), from disseminated intravascular coagulation (DIC) to adult respiratory distress syndrome (ARDS). Heartbreaking.

Malaria-infected red blood cell. NIH Image Gallery on Flickr.

The investigations of cerebral malaria range from the humble blood film to brain imagingTreatments include artemisinin derivatives and cinchona alkaloids. A malaria vaccine remains a dream, but not a far-off one; the RTS,S/AS01 vaccine is a promising candidate. Until this aspiration is achieved, the best hope against cerebral malaria remains prevention. The solutions are simple: basic sanitation, public education, and poverty alleviation. But the implementation seems to defy the wits of the great and the good. A lot of work remains to be done.

By Rick Fairhurst and Jordan Zuspann, National Institute of Allergy and Infectious Diseases, National Institutes of Health –, Public Domain,

Why not check out the following related posts in our other blog, Neurochecklists Updates:

The 8 most parasitic infestations of the nervous system


The 7 most ruthless bacterial infections of the nervous system


The 7 most devastating viral neurological infections


The 20 most viewed posts on The Neurology Lounge in 2018

With almost 25,000 visitors…

and almost 35,000 post views…

the highest since this blog launched…

It appears The Neurology Lounge has had a busy year.


Two bloggers. Mike Licht on Flikr.

But compared to the previous whirlwind years

2018 was a relatively blog-quiet year.

Dominated by older posts

And a sprinkling of new ones.


John Meynard Keynes blogging. Mike Licht on Flikr.

This is neither because of a flagging spirit

nor a waning passion.

 Neurochecklists, my other task-master…

Demanded more and more of my time.



Revising, refining, retuning…

Simplifying, clarifying, edifying

In pursuit of the ideal neurology database.

As that task is now nearly done

2019 beckons back to the blogging arena.


Blogging when the children have gone to bed. Mike Licht on Flikr.

But just before looking forward

In this season of looking backward

Let’s spare some time to take account.

How did the old expositions fare?

How did the new compositions rank?


Number-04. StefanSzczelkun on Flickr.

Here are your top 20 most viewed blog posts of 2018


20. Advances in the management of giant cell arteritis

19. mTORopathy: an emerging buzzword for neurology


Stay in touch with The Neurology Lounge in 2019

By User:S SeppOwn work, CC BY-SA 3.0,

What do neurology information seekers really want?

A few months ago, Neurochecklists set out to discover how people go about searching for neurology information. We therefore carried out an online survey of neurology information users. We asked 10 critical questions about the who, what, wherewhy, and how of neurology information quest.


We asked these question specifically to guide a major Neurochecklists upgrade. This knowledge is, after all, critical for a website which has set out to be the best source of clear, concise, and comprehensive neurology information. But we needed help to know what really matters to people when they go foraging for neurology. What do they really want, and how do they go about satisfying their need?

Search Key. GotCredit on Flickr.


The response we got was heart-warming; about 190 people answered our online questions. Below are the questions along with the insights we gained from the answers.

Q&A. on Flickr.


Who searches for neurology information?

More than 50% of our responders were consultant neurologists, and about 15% were medical consultantsNeurology trainees constituted about 7%. The range of users is however quite broad, including nurses, surgeons, medical students, and patients! See the breakdown in the pie chart below:

Insight: There are diverse neurology information seekers!

How often do we forage for neurology information?

Neurology information is in high demand, with >50% of responders seeking information at least once a day, and >80% at least once a week. Below is the breakdown:

Insight: There is a huge craving for neurology information!

Where do we go when we need neurology information?

Online websites are by far the most popular source of quick neurology information, accounting for >50% of responses. This is followed by journals which account for just over 25% of responses. Very few responders access textbooks, handbooks, downloadable apps or online videos. Below is the breakdown:

Insight: Neurology source information is now mainly online

Where are we when we most crave neurology information?

In a question which allowed multiple answers, the clinic was by far the most common setting for looking up neurology information. We however also have a strong urge for neurology on the ward, and at home! Below is the breakdown:

Insight: The need for neurology information has no boundaries

Why do we access neurology information?

The most frequent reasons responders access neurology information were to answer clinical questions and for personal study. Other reasons were to aid discussions with patients, and to look for relevant references.

Insight: the checklist approach is the best solution

What devices do we use to access neurology information?

In another multiple answer question, responders most often use their phones to access online neurology information. Laptops and desktops are also favoured, but tablets much less so.

Insight: neurology information must be device-compatible

What features do we most favour in an online neurology database?

We asked what features responders most desire in an online neurology database, and the front-runners here are accuracy and currency of information, followed by conciseness, adequacy, ease of navigation, and link to references.


Insight: Neurochecklists is on the right track


We wish to extend our thanks to everybody who took part in the survey, including the many who attempted it after the closing date! We have taken all the responses on board, and we have been working night and day to provide an enhanced Neurochecklists. Watch out for our next blog post to find out the changes we will be launching soon. Neurology seekers, watch this space!

By AnsonloboOwn work, CC BY-SA 4.0, Link

8 things we now know about the toxicity of gadolinium to the brain

When it comes to imaging the nervous system, nothing but an MRI will do for the fastidious neurologist. CT has its uses, such as in detecting acute intracranial bleeding, but it lacks the sophistication to detect or differentiate between less glaring abnormalities. It also comes with a hefty radiation dose. MRI on the other hand, relying on powerful magnetic fields, is a ‘cleaner’ technology.

SLEIC 6. Penn State on Flickr.

MRI scans on their own are however often insufficient to sate the craving of the neurologist for precision. A plain MRI scan, for example, will not tell if a multiple sclerosis lesion is old or new, and it may fail to detect subtle but significant lesions such as low grade brain tumours or lymphoma. Many lesions on routine MRI scan are also ill-defined and non-specific, and could pass for abscesses, vasculitis, inflammation or just small vessel disease (wear and tear) changes.

The Brain. I has it. Deradrian on Flickr.

To silence the niggling doubts, the neurologist often requests an MRI scan with contrast. The idea is to use a dye to separate the wheat from the chaff, the active lesions from the silent ones. This works because sinister lesions have a bad and dangerous habit of disrupting the blood brain barrier. All such insurgencies across the hallowed BBB is sacrilege, a sign that something serious is afoot, (or is it underfoot?). Contrast dyes, on the other hand, are adept at detecting these breaches, traversing them, and staining the sinister lesion in the process. This stain appears on the MRI scan as contrast enhancement. MRI with contrast is therefore invaluable, and a positive study is a call to arms.

By © Nevit Dilmen, CC BY-SA 3.0, Link

Without any doubt, gadolinium is the favoured dye for contrast MRI scans. Gadolinium (Gd) is a lanthanide rare earth metal and it is one of the heavier elements of the periodic table with atomic number 64. It is named after the thrice-knighted Finnish chemist Johan Gadolin, who also discovered the first rare earth metal, yttrium.

Periodic table model. Canada Science and technology Museum on Flickr.

We know a lot about some of the risks of injecting gadolinium into the body, such as its tendency to accumulate in people with kidney impairment (who cannot excrete it efficiently). We also know that it may cross the placenta to damage the developing baby. These are however hazards with simple and straight-forward solutions: avoid gadolinium in pregnancy, and don’t use it in people with poor renal function.

By Hi-Res Images ofChemical Elements –, CC BY 3.0, Link

Much more challenging is the problem of gadolinium deposition in the brain of people with normal renal function. This is concerning because it is unpredictable, and because it has the potential to compromise brain structure and function. This blog has previously asked the question, “Is gadolinium toxic?“. The question remains unanswered, and regulatory agencies are still studying the data to provide guidance to doctors. Patient groups on the other hand have been up in arms, as one would expect, impatiently waiting for answers. What then is the state of play with gadolinium? Should neurologists and their patients really be worried? Below are 8 things we now know about gadolinium and its potential brain toxicity.

By Peo at the Danish language Wikipedia, CC BY-SA 3.0, Link


1. Gadolinium deposition is related to its insolubility at physiological pH

The toxic potential of gadolinium is thought to be the result of its insolubility at physiological pH. Furthermore, gadolinium competes against calcium, an element fundamental to cellular existence. This competition is obviously detrimental to the body.

064 Gadolinium-Periodic Table of Elements. Science Activism on Flickr.

2. The less stable gadolinium agents are the most toxic

There are two forms of gadolinium based contrast agents (GBCAs): the less stable linear GBCAs, and the more stable macrocyclic GBCAs. The linear GBCAs are more toxic, of which Gadodiamide (Omniscan) stands out. Other linear agents are gadobenate dimeglumine (MultiHance), gadopentetate dimeglumine (Magnevist), gadoversetamide (OptiMARK), gadoxetate (Eovist), and gadofosveset (Ablavar). The macrocyclic GBCAs, even though safer, are not entirely blameless. They include gadobuterol (Gadavist), gadoterate meglumine (Dotarem), and gadoteridol (ProHance). Therefore, choose your ‘gad’ wisely.

By زرشکOwn work, CC BY-SA 3.0, Link


3. Gadolinium deposits in favoured sites in the brain

It is now established that gadolinium deposits in three main brain areas. The most favoured site is the dentate nucleus of the cerebellum. Other popular regions are the globus pallidus and the pulvinar. This deposition is, paradoxically, visible on plain T1-weighted MRI scans where it shows as high signal intensity.

By Polygon data were generated by Database Center for Life Science(DBCLS)[2]. – Polygon data are from BodyParts3D[1], CC BY-SA 2.1 jp, Link

4. The risk of deposition depends on the number of injections

The risk of gadolinium deposition in the brain is higher with multiple administrations. Stated another way, and to stretch this paragraph out a bit longer, the more frequently contrast injections are given, the higher the chances gadolinium will stick to the brain. The possible risk threshold is 4 injections of gadolinium. The fewer the better…obviously!

Number-04. StefanSzczelkun on Flickr.

5. Gadolinium also deposits outside the brain

The favoured site of gadolinium deposition outside the brain is the kidney, where it causes nephrogenic systemic fibrosis, a scleroderma-like disorder. This however occurs mostly in people with renal impairment. Gadolinium also deposits in other organs outside the brain including bone, skin, and liver. (Strictly speaking, this item has nothing to do with the brain, but it helped to tot up the number to 8 in the title of this blog post, avoiding the use of the more sinister se7en).

By JudgefloroOwn work, CC BY-SA 4.0, Link

 6. Harm from gadolinium brain deposition has not been established

Whilst we know for sure that gadolinium deposits in the nervous system, harm from deposition has not been definitively established. There are, however, reports that gadolinium deposition may produce muscle and eye symptoms, and chronic pain. There are also reports of cognitive impairment manifesting as reduced verbal fluency.

Words words words. Chris Blakeley on Flickr.

7. Precautions may reduce the risk of gadolinium brain deposition

The current recommendation is not to withhold the appropriate use of gadolinium, but to observe simple precautions. Sensibly, use GBCAs only when absolutely necessary. Also consider preferentially using macrocyclic GBCAs and evaluate the necessity for giving repeated GBCA administrations.


By IntropinOwn work, CC BY-SA 3.0, Link


8. There are emerging ways to avoid gadolinium toxicity

The safest use of gadolinium is not to use it at all. There are some developments in the pipeline to achieve this, although probably not in the very near future. Such developments include manganese based contrast agents such as Mn-PyC3A. A less definitive option is to mitigate the effects of gadolinium by using chelating agents; two such potential agents are nanoparticles and 3,4,3-LI(1,2-HOPO).


Why not get the snapshot view of gadolinium toxicity in the neurochecklist:

Gadolinium-based contrast agent (GBCA) toxicity

…and leave a comment!


MRI scan. NIH Image Gallery on Flikr.

What is so distinctive about anti-MUSK myasthenia gravis?

Myasthenia gravis (MG) is an iconic neurological disorder. It is classical in its presentation, weakness setting in with exertion and improving with rest. This fatigability is demonstrable in the laboratory when repetitive nerve stimulation (RNS) of the muscles results in a progressively decremental response. Clinically, myasthenia gravis is often a benign disorder which restricts itself to the muscles of the eyes: this ocular MG manifests just with droopy eyelids (ptosis) and double vision (diplopia). At the extreme however is generalised MG, a severe and life-threatening condition that justifies its grave appellation

By Posey & Spiller – Posey & Spiller: Fatigue (Ptosis) in a patient with MG (ed. 1904), Public Domain, Link

Myasthenia gravis depletes the energy reserve of muscles, something which is entirely dependent on acetylcholine (ACh), a chemical released at nerve endings. After release, ACh traverses the neuromuscular junction (NMJ) to attach itself to the acetylcholine receptor (AChR), which is comfortably nestled on the surface of the muscle. This binding of chemical to receptor is a significant event, setting sparks flying, and muscles contracting. In myasthenia gravis, this fundamental process is rudely disrupted by the onslaught of acetylcholine receptor antibodies. These aggressive AChR antibodies, produced by the thymus gland in the chest, vent their rage by competitively binding to the receptor, leaving acetylcholine high and dry. Eventually, the rampaging antibodies destroy the receptor in an act of unjustified savagery.

Drosophilia Neuron. NICHD on Flickr.

In tackling myasthenia gravis, it is no wonder that neurologists first have to hunt down the ferocious AChR antibodies. They whisk off an aliquot of serum to a specialist laboratory, but waste no time in planning a counteroffensive, confident that the test will return as positive. The strategy is to boost the level of acetylcholine in the NMJ, tilting the balance in favour of ACh against the antibodies. The tactic is to zealously despatch a prescription for a drug that will block acetylcholine esterase inhibitor, the enzyme which breaks down acetylcholine. The neurologist then closely observes the often dramatic response, one of the most gratifying in clinical medicine; one minute as weak as a kitten, the next minute as strong as an ox. MG is therefore one disorder which debunks the wicked jibe that neurologists know so much…but do so little to make their patients better!

Drosophilia Neuromuscular Junction. NICHD on Flickr.

Unfortunately for the neurologist, every now and then, the AChR antibody test result comes back as negative. In the past, the dumbfounded and befuddled, but nevertheless undaunted neurologist, will march on, battling a diagnosis of antibody-negative MG. Nowadays however, this not a comfortable diagnosis to make because AChR antibody is no longer the only game in town. We now know that there are many other antibodies that are jostling for commanding positions in the anti-myasthenia coalition. These include anti LRP4, cotarctin, titin, agrin, netrin 1, VGKC, and ryanodine. However, the clear frontrunner in this melee is anti-MUSK antibody, responsible for 30-50% of MG in which there are no AChR antibodies.

By PyMol, CC0, Link

Anti MUSK syndrome has many distinguishing features that set it apart from the run-of-the-mill myasthenia gravis. Below are five distinctive markers of anti-MUSK syndrome:

  1. Subjects with anti-MUSK syndrome are typically middle-aged women in their 3rd or 4th decades. This is younger than the usual age of people with AChR MG. Indeed neurologists now recognise typical myasthenia as a disease of older people.
  2. People with anti-MUSK syndrome present with acute and prominent involvement of head and neck muscles. This results in marked swallowing and breathing difficulties. They are therefore at a higher risk of myasthenia crisis.
  3. Single fiber electromyogram (sfEMG), a specific and reliable neurophysiological test of MG, is often normal in anti-MUSK syndrome. This is partly because the limb muscles are usually spared in anti MUSK syndrome.
  4. People with anti-MUSK myasthenia often do not benefit from, nor do they tolerate, the  acetylcholinesterase inhibitors which are used to treat MG. Indeed, these drugs may worsen anti-MUSK syndrome.
  5. Thymectomy, removal of the thymus gland, is not beneficial in people with anti-MUSK syndrome, unlike its usefulness in AChR MG.
Thymus gland 2. RachelHermosillo on Flickr.

All this is just the tip of the evolving myasthenia gravis iceberg. You may explore more of myasthenia in our previous blog posts:

How is innovative neurology research energising myasthenia?

What is the startling research unsettling the treatment of myasthenia gravis?

What is the relationship of pregnancy to myasthenia gravis?

Is Zika virus infection a risk factor for myasthenia gravis?

What does the EMG show in LRP4 myasthenia gravis?

What’s evolving at the cutting-edge of autoimmune neurology?

What are the most iconic neurological disorders?


You may also explore anti-MUSK, and all the other myasthenia gravis subtypes, in neurochecklists. Go on…you know you want to know more!

Antibody lights. Isabelle on Flickr.