The 25 most popular Neurology Lounge blog posts of 2020

As we have done for the last five years, I am taking stock of my neurology blogging activities over last 12 months. A sort of reckoning, it enables me to list the blog posts that have attracted the most attention, and to quietly reflect on why some did not blaze a trail.

Bamboo Keyboard and Mouse! Wicker Paradise on Flickr. https://www.flickr.com/photos/wicker-furniture/14786175336

With almost 40,000 visitors, and more than 50,000 views, 2020 has been the busiest so far in the Lounge, outstripping every year since 2015 when I launched the blog. Whilst a lot of the footfall has been to blogs I posted in 2020, I must admit that the golden oldies are attracting more visits than the newbies, making up the top 7 most viewed posts this year. Talk about blossoming with age!

By Cortega9Own work, CC BY-SA 3.0, Link

Enough reflection then, here are the 20 most popular Neurology Lounge blog posts of 2020

 

20.

5 exciting developments in the management of Wilson’s disease

19.

On the seizure-detecting instincts of pets

18.

Migraine and the challenge of white matter lesions in the brain

17.

What is so distinctive about anti-MUSK myasthenia gravis?

16.

The 7 most hazardous occupations to the nervous system

15.

3 exciting emerging interventional treatments for Parkinson’s disease

14.

Monumental breakthroughs in the history of neuroscience

13.

10 more catchy titles from the recent neurology literature

12.

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

11.

What are the most controversial questions in neurology?

Tier10-Digital-Content-marketing-wheel cropped. DigitalRalph on Flickr. https://www.flickr.com/photos/ralphpaglia/8316453191
10.

Which are the most useful neurological applications?

9.

7 remarkable patients who determined the course of neuroscience

8.

25 non-eponymous neurological disorders… and the names behind them

7.

15 more creative and catchy neurology headlines for 2019

6.

7 ominous signs that suggest you need to see a neurologist

5.

Outstanding neurology video channels and sites

4.

10 bizarre things neurologists do to their patients

3.

18 most insightful and profound quotations about the brain

2.

The 13 most dreadful neurological disorders…and the groups standing up to them

1.

Are these the all-time most influential Neurologists?

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There are more exciting blog posts planned for 2021…what may turn out to be a turning point for The Neurology Lounge. So stay tuned!

12 catchy neurology headlines to cast out a year of infamy

2020 was characterised by horror of epidemic proportions. Spawned in 2019, COVID did not attain plague status until 2020. Unfurling its envelope, and baring its spikes, it struck with ruthless efficiency. But the chilling terror it unleashed was not enough to freeze the ink of neurologists. With flowing prose and radiant captions, neurological penmanship flourished in defiance of SARS-CoV-2. So, as we say goodbye to a year we can’t wait to forget, let us take a moment to marvel at the outstanding neurology titles of the last 12 months. Here then are 12 catchy neurology headlines to cast out a year of infamy.

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What are the most important neurological questions of 2020?

It is the season again for reflecting over the most important neurology papers published in the year. Because we keep a keen eye on the relevant journals and neurology headlines, we are well-placed at Neurochecklists to pinpoint those papers which asked the most pressing neurological questions, and either answered them, or pointed to where the wind […]

What are the most important neurological questions of 2020? — Neurochecklists Blog

Should unruptured brain AVMs be left alone?

Medical management with interventional therapy versus medical management alone for unruptured brain arteriovenous malformations (ARUBA): final follow-up of a multicentre, non-blinded, randomised controlled trial. Mohr JP, Overbey JR, Hartmann A, et al. Lancet Neurol 2020; 19:573-581. Abstract Background In A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA), randomisation was halted at a mean follow-up […]

Should unruptured brain AVMs be left alone? — Neurochecklists Blog

What are the risk factors for progression of radiologically isolated syndrome?

Radiologically isolated syndrome: 10-year risk estimate of a clinical event. Lebrun-Frenay C, Kantarci O, Siva A, et al. Ann Neurol 2020 (Online ahead of print). Abstract Objective We have previously identified male sex, younger age, and the presence of spinal cord lesions as independent factors that increase the 5-year risk for evolution from radiologically isolated […]

What are the risk factors for progression of radiologically isolated syndrome? — Neurochecklists Blog

The appendix in Parkinson’s disease: hero or villain?

The brain-gut axis has become a well-recognised cliche, and for very good reasons. Possessing an  almost independent and complex nervous system, the gut is considered to be the ‘second brain‘. The gut of course coordinates things hand-in-hand with the brain with which it communicates via the vagus nerve; through this it not only determines our body balance or homeostasis, but also rules our emotions and guides our decision-making. But some scientists are beginning to think that the brain-gut axis, or more appropriately the gut-brain axis, has a dark side, and this is the simple idea that ‘very bad things‘ in the gut can smuggle their way into the brain by latching on to the vagus nerve. The gut-brain axis may therefore be the seditious agent of neurological ruin by acting as a Trojan horse which surreptitiously jumps over the brain’s elaborate defensive big wall.

By Marvin 101Own work, CC BY-SA 3.0, Link

Parkinson’s disease (PD) is perhaps the most illustrative example of the consequence of the treacherous behaviour of the gut-brain axis. Some researchers are now convinced that PD actually starts in the gut and, like an undesirable hitchhiker, fastens itself on the vagus nerve as it meanders its way up to the brain. This migration hypothesis is not a fanciful notion but an idea founded on sound facts. For example, take the observation that the guts of people with PD are riddled with α-synuclein, the misfolded protein that is thought to cause PD by disabling the basal ganglia. The story, according to researchers, is that α-synuclein first accumulates in the gut and, feeling cramped, seeks greener pastures. It therefore propagates up the vagus nerve, in ‘prion-like‘ fashion, to get to the brain. Further support for this theory is the observation that people who have had their vagus nerves resected (that’s another story) have a much lower risk of developing PD.

By Niubrad at the English Wikipedia, CC BY-SA 3.0, Link

That’s just as well you may say, but where does the appendix come into all this? I admit the so-called vermiform or worm-like appendix is not a structure that readily comes to mind when one thinks of the gut-brain axis. Apart from being the seat of the dreaded appendicitis, it was considered to be just a useless appendage, nature’s trick on anatomists and physiologists. As diminutive as it may be however, it is part of the gut, and as it turns out, it is heavily laden with α-synuclein in people with PD. Furthermore, it has been shown that people who have had an appendicectomy, or appendectomy if you prefer, have a much lower risk of developing PD. We know this because of researchers such as Bryan Killinger and colleagues who, in their paper titled The vermiform appendix impacts the risk of developing Parkinson’s disease, published in the journal Science Translational Medicine in 2018, found that “early removal of the appendix is associated with a reduced risk of developing PD”. And it all comes down to the powerful immune surveillance function of the appendix which, it seems, mops up all sorts of threats that find their way into our guts. You may say that the appendix is punching way beyond its weight class.

Appendectomy. msafari2425 on Flickr. https://www.flickr.com/photos/msafari/6020024188

As happens to all beautiful theories, they often come up against some immovable objections….and there are quite a few raised eyebrows at the appendix-PD hypothesis. For one, many studies have just not been able to confirm it. For example, take this paper published in the journal Movement Disorders in 2018, titled Appendectomy and risk of Parkinson’s disease in two large prospective cohorts of men and women; the authors disappointingly found little or no evidence for the association between having an appendectomy and the risk of developing Parkinson’s disease. Another paper published in the same journal in 2016, titled Appendectomy and risk of Parkinson’s disease: A nationwide cohort study with more than 10 years of follow‐up, further upturned the applecart because the authors found that having an appendectomy actually increased the risk of developing PD. Another paper from a 2017 issue of the Journal of Parkinson’s Disease was succinctly brutal in shooting down the appendix-PD connection with its title: Appendectomy history is not related to Parkinson’s disease. Even more damning to the “appendectomy is good against PD” theory is this 2019 study whose blazing headline is Parkinson’s disease is more prevalent in patients with appendectomies. Just when you were beginning to feel good about having your appendix removed all those year ago!

http://www.actaneurocomms.org/content/1/1/2., CC BY 2.5, Link

By Mikael Häggström, B jonasOwn work CC0, Link

 

25 updated practical neurology checklists

This is just a quick blog post to let you know of some of our recently revised checklists Alemtuzumab neurological complications Anti MOG antibody disease treatment Cavernomas clinical features Cenobamate Cerebral amyloid angiopathy related inflammation (CAA-ri) *** CIDP clinical features Cluster headache acute treatment Dravet syndrome management Duchenne muscular dystrophy genetic treatments Functional neurological disorders […]

25 updated practical neurology checklists — Neurochecklists Blog

What is the place of magnesium in the treatment of migraine?

Magnesium is a rather understated metal which however plays such a significant role in health. This should not be surprising as it is the eighth most common metal in the Earth’s crust, and the fourth most abundant mineral in the human body. Explaining why magnesium is so central to health, Uwe Gröber and colleagues, in their paper titled Magnesium in prevention and therapy, point out that this underrated element is a cofactor in more than 300 enzyme systems which regulate such diverse biochemical reactions ranging from protein synthesis to neuromuscular transmission.

By Maral10Own work, Public Domain, Link

With such an important physiological function, it is alarming that the body can very easily run out of magnesium. But this is exactly what Gröber and colleagues demonstrated in their paper, which was incidentally published in the journal, Nutrients, in 2015; they showed that magnesium deficiency can result from a myriad of medical disorders such as alcoholism, malabsorption, endocrine disorders, chronic kidney diseases, and dialysis, or from the use of drugs such as antibiotics, chemotherapeutic agents, diuretics, and proton pump inhibitors.

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Because of its diverse and important role, magnesium deficiency doesn’t lie down quietly in the corner and mope; rather it screams out in many tongues. Low magnesium therefore presents with symptoms such as lethargy, vomiting, fatigue, cramps, tremor, carpopedal spasm, tetany, seizures, and cardiac arrhythmias. Even more astonishing is the list of disorders that may be triggered by magnesium deficiency, from asthma, diabetes, hypertension, and osteoporosis, to stroke, attention deficit hyperactivity disorder (ADHD), Alzheimer’s disease, of all things, and of course migraine. Obstetricians will of course remind us of the indispensability of magnesium for eclampsia.

By LeiemOwn work, CC BY-SA 4.0, Link

With the foregoing in the background, it is easy to understand why researchers have thoroughly investigated the possible place of magnesium in the treatment of migraine. Exploring its prophylactic role, for example, Hsiao-Yean Chiu and colleagues touted the virtues of magnesium in their paper titled Effects of intravenous and oral magnesium on reducing migraine: a meta-analysis of randomized controlled trials. Publishing in the journal Pain Physician in 2016, the authors reviewed 10 key studies, with a combined number of 789 subjects, which assessed the ability of magnesium to prevent migraine, and they concluded that “oral magnesium significantly alleviated the frequency and intensity of migraine“. The authors felt confident enough in their findings to recommend oral magnesium as a part of a “multimodal approach to reduce migraine”.

By KulmalukkoOwn work, CC BY-SA 3.0, Link

Even more authoritative about the role of magnesium in migraine prophylaxis is the conclusion of the systematic review published in the journal Headache in 2017 titled Magnesium in migraine prophylaxis-is there an evidence-based rationale? a systematic review. The authors, Alexander von Luckner and Franz Riederer, found grade C, or possibly effective, evidence in support of the preventative role of magnesium in migraine. Going further, Charly Gaul and colleagues, publishing in the Journal of Headache and Pain in 2015, reported that adding riboflavin and coenzyme Q10 significantly increased the beneficial effect of magnesium.

Magnesium. fdecomite on Flickr. https://www.flickr.com/photos/fdecomite/6257573610

There is however a dampener to the celebrity status of magnesium in the migraine prophylaxis saga:  some reports simply found insufficient evidence for it. One such paper, published in the journal Cephalalgia in 2014 is titled An evidence-based review of oral magnesium supplementation in the preventive treatment of migraine. The authors, Levi Teigen and Christopher Boesy, reviewed 16 relevant studies and concluded that “the strength of evidence supporting oral magnesium supplementation is limited at this time“. But even then, they appreciate that absence of evidence is not the evidence of absence. They therefore did not dismiss the potential benefit of magnesium in migraine, and had no objection to migraineurs supplementing their dietary magnesium intake. As this paper was published in 2014, a lot has clearly passed under the bridge since then.

By Ben MillsOwn work, Public Domain, Link

Magnesium in the acute treatment of migraine has also been under scrutiny, and one such searchlight was shone by Hsiao-Yean Chiu and colleagues in their paper cited above. After reviewing 11 relevant studies comprising 948 subjects, they found that “intravenous magnesium significantly relieved acute migraine“. It is reassuring that two older papers also came to the same conclusion; the first, by ME Bigal and colleagues, was published in the journal Cephalalgia in 2002, and the second, by Şeref Demirkaya and colleagues, is reported in the journal Headache in 2004. Both papers revealed that 1000mg of magnesium sulfate intravenously was effective in aborting acute migraine attacks, especially if the attacks are associated with auras. Furthermore, writing in the journal Clinical Neurology and Neurosurgery in 2019, Fanny Xu and colleagues found that magnesium is effective even in status migrainosus, the most pernicious form of acute migraine.

By LoethlinOwn work, CC BY-SA 4.0, Link

But, as you guessed, the verdict on the benefit of magnesium in acute migraine is far from unanimous. For example, Y Cete and colleagues, publishing their case series of emergency department patients in the journal Cephalagia in 2005, reported that magnesium is no better than placebo for acute migraine. Furthermore, Hyun Choi and Nandita Parmar in their meta-analysis, published in the European Journal of Emergency Medicine in 2014, said intravenous magnesium “failed to demonstrate a beneficial effect” in acute migraine. Arpad Pardutz and Laszlo Vecsei, commenting in the Journal of Neural Transmission in 2012, even discouraged the use of magnesium because there are more effective treatment options.

By Pixelmaniac pictures (Leave a reply) – Own work, CC0, Link

Why are there such conflicting conclusions about the value of magnesium in acute migraine? One answer may lie in the almost prehistoric observation by Alexander Mauksop and colleagues; writing way back in 1996, in the journal Headache, they suggested that only a subset of migraine sufferers are susceptible to low magnesium levels. The authors go further to argue that low magnesium may be a trigger, not just for migraine, but for tension type headaches and cluster headaches; they therefore recommended that magnesium levels should be assessed in patients presenting with significant headaches, whatever the cause.

By 2×910Own work, CC BY-SA 4.0, Link

In conclusion, the evidence for the use of oral magnesium in migraine prophylaxis justifies its clinical use. The evidence for the use of intravenous magnesium for acute migraine is however less clear-cut, and future studies may help to clarify the ambiguity. In the meantime, it may be worth checking magnesium levels when a migraine attack defies conventional treatment: a top-up might just make the difference. And for the researchers, it may be time to look more closely at precision migraine medicine – it might just help to define those migraine sufferers who will benefit from that magic shot of magnesium.

By Warut RoonguthaiOwn work, CC BY-SA 3.0, Link

The emerging influential role of microglia in neurology

By GerryShawOwn work, CC BY-SA 3.0, Link

The most important clinical fallout of dysfunctional microglia appears to be the emergence of dementia. It is indeed speculated that microglia may hold the key to stopping the notorious Alzheimer’s disease (AD). This is because microglia seem to play a role in eliminating the amyloid plaques which are thought to contribute to the disease process. Experiments suggest that there is excessive microglial activation in AD, and these supercharged microglia destructively eat up’ synapses, the all-important junctions where nerve cells communicate with each other. It is also relevant that microglial activation is particularly prominent in the hippocampus, a structure critical for memory formation. Because synaptic loss is such a key feature of AD, it is hoped that a better understanding of microglial function may lead to therapeutic tools that modulate AD microglial activation.

Microglial cells and photoreceptors. NIH Image Gallery on Flickr. https://www.flickr.com/photos/nihgov/46571706425

Microglial activation also seems to play a role in another prominent neurodegenerative disease, Parkinson’s disease (PD). It is also speculated that microglia are activated in PD as a response to environmental triggers, and the activated microglia cause neuronal damage by producing toxic substances. Because this is presumably an inflammatory process, there is the hope that a better understanding of the process will open up new therapeutic possibilities.

Microglia. NIH Image Gallery on FLickr. https://www.flickr.com/photos/nihgov/42301918151

Another disorder in which microglia may play a pathogenetic role is frontotemporal dementia (FTD) in which chronic microglial activation has been reported. It is significant that the microglial activation is most evident in the frontal cortex as this correlates with the behavioural and speech disorders which characterise FTD. More intriguingly, the activated microglia seem to express the progranulin (PGRN) gene mutations that are known to be associated with FTD. Enough clues one might say.

By Mary AntipovaOwn work, CC BY 4.0, Link

The reach of microglial dysfunction however goes way beyond the big three of AD, PD, and FTD. For example, microglia are acutely activated in traumatic brain injury (TBI), and this may be responsible for the damage that results from this. Microglia also appear to be relevant in cerebrovascular disorders because microglial activation has been reported in ischaemic stroke and in haemorrhagic stroke. And the cherry on top is surely the report that microglia play a role in prion disorders. It may well turn out that neuroscientists are just opening up the microglial can of worms.

Abraçada de microglia Patricia Bogdanov-Cristina Sola-Joel Sampedro- Marta Valeri. Vall d’Hebron Institut de Recerca VHIR on Flickr. https://www.flickr.com/photos/vhir/31615774702

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Want to find out more on microglia? You may want to explore these links:

Review: Microglia in motor neuron disease

Motor cortex transcriptome reveals microglial key events in amyotrophic lateral sclerosis

Which drug reduces the autoimmune risks of alemtuzumab?

Mitigating alemtuzumab-associated autoimmunity in MS: a “whack-a-mole” B-cell depletion strategy Meltzer E, Campbell S, Ehrenfeld B, et al. Neurol Neuroimmunol Neuroinflamm 2020; 7:e868. Abstract Objective To determine whether the punctuated administration of low-dose rituximab, temporally linked to B-cell hyperrepopulation (defined when the return of CD19+ B cells approximates 40%-50% of baseline levels as measured before alemtuzumab […]

Which drug reduces the autoimmune risks of alemtuzumab? — Neurochecklists Blog