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

Medicine is as much defined by diseases as by the people who named them. Neurology particularly has a proud history of eponymous disorders which I discussed in my other neurology blog, Neurochecklists Updates, with the title 45 neurological disorders with unusual EPONYMS in neurochecklists. In many cases, it is a no brainer that Benjamin Duchenne described Duchenne muscular dystrophy, Charle’s Bell is linked to Bell’s palsy, Guido Werdnig and Johann Hoffmann have Werdnig-Hoffmann disease named after them. Similarly, Sergei Korsakoff described Korsakoff’s psychosis, Adolf Wellenberg defined Wellenberg’s syndrome, and it is Augusta Dejerine Klumpke who discerned Klumpke’s paralysis. The same applies to neurological clinical signs, with Moritz Romberg and Romberg’s sign, Henreich Rinne and Rinne’s test, Joseph Babinski and Babinski sign, and Joseph Brudzinski with Brudzinki’s sign.

Yes, it could become rather tiresome. But not when it comes to diseases which, for some reason, never had any names attached to them. Whilst we can celebrate Huntington, Alzheimer, Parkinson, and Friedreich, who defined narcolepsy and delirium tremens? This blog is therefore a chance to celebrate the lesser known history of neurology, and to inject some fairness into the name game. Here then are 25 non-eponymous neurological diseases and the people who discovered, fully described, or named them.

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Amyotrophic lateral sclerosis (ALS)

Jean-Martin Charcot

Készítette: Unidentified photographerhttp://resource.nlm.nih.gov/101425121, Közkincs, Hivatkozás

Aphantasia

Francis Galton (and Adam Zeman)

By Eveleen Myers (née Tennant) – http://www.npg.org.uk/collections/search/portrait/mw127193, Public Domain, Link

Chronic inflammatory demyelinating polyneuropathy (CIDP)

Peter J Dyck

By Dr. Jana – http://docjana.com/#/saltatory ; https://www.patreon.com/posts/4374048, CC BY 4.0, Link

Corticobasal degeneration (CBD)

WRG Gibb, PJ Luthert, C David Marsden

https://upload.wikimedia.org/wikipedia/commons/c/cd/ProteineTau.jpg

Epilepsy

Hippocrates

Hippocrates. Eden, Janine and Jim on Flickr. https://www.flickr.com/photos/edenpictures/8278213840

Essential tremor

Pietro Burresi

By UndescribedOwn work, CC BY-SA 4.0, Link

Frontotemporal dementia (FTD)

Arnold Pick

By Unknown authorhttp://www.uic.edu/depts/mcne/founders/page0073.html, Public Domain, Link

Inclusion body myositis (IBM)

E J Yunis and F J Samaha

CC BY-SA 3.0, Link

Meningitis

Vladimir Kernig and Jozef Brudzinski

By A. F. Dressler – Festschrift zum 70. Geburtstag Dr. Woldemar Kernig’s: Von Verehrern und Schülern herausgegeben als Festnummer der St. Petersburger medicinischen Wochenschrift St. Petersburger medizinische Wochenschrift, Bd. 35, Nr. 45. (1910), Public Domain, Link

Migraine

Aretaeus of Cappadocia

By Cesaree01Own work, CC BY-SA 4.0, Link

Multiple sclerosis (MS)

Jean-Martin Charcot

Journal.pone.0057573.g005http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057573#pone-0057573-g005. Licensed under CC BY 2.5 via Wikimedia Commons.

Multiple system atrophy (MSA)

Milton Shy and Glen Drager

By Kenneth J. Nichols,Brandon Chen, Maria B. Tomas, and Christopher J. Palestro – Kenneth J. Nichols et al. 2018. Interpreting 123I–ioflupane dopamine transporter scans using hybrid scores., CC BY 4.0, Link

Myasthenia gravis (MG)

Samuel Wilks

By Unknown authorhttp://ihm.nlm.nih.gov/images/B25782, Public Domain, Link 

Myotonic dystrophy

Hans Gustav Wilhelm Steinert

By Unknown author – reprinted in [1], Public Domain, Link 

Neurofibromatosis

Friedreich Daniel von Recklighausen

By Unknown authorIHM, Public Domain, Link 

Narcolepsy

Jean-Baptiste-Edouard Gélineau

https://upload.wikimedia.org/wikipedia/commons/7/74/Jean_Baptiste_Edouard_G%C3%A9lineau.jpg

Poliomyelitis

Michael Underwood

By Manuel Almagro RivasOwn work, CC BY-SA 4.0, Link

Progressive supranuclear palsy (PSP)

John Steele, John Richardson, and Jerzy Olszewski

By Dr Laughlin Dawes – radpod.org, CC BY 3.0, Link

Restless legs syndrome (RLS)

Karl Axel Ekbom

By Peter McDermott, CC BY-SA 2.0, Link

Stiff person syndrome (SPS)

Frederick Moersch and Henry Woltmann

By PecatumOwn work, CC BY-SA 4.0, Link

Synesthesia

Georg Sachs and Gustav Feschner

Synaesthesia. aka Tman on Flickr. https://www.flickr.com/photos/rundwolf/7001467111/

Stroke

Hippocrates

By editShazia Mirza and Sankalp GokhaleSee also source article for additional image creators. – editShazia Mirza and Sankalp Gokhale (2016-07-25). Neuroimaging in Acute Stroke.Attribution 4.0 International (CC BY 4.0), CC BY 4.0, Link

Tabes dorsalis

Moritz Romberg

By https://wellcomeimages.org/indexplus/obf_images/39/1d/edecf5a530781f5c10603a50fa35.jpghttps://wellcomecollection.org/works/gctr3stg CC-BY-4.0, CC BY 4.0, Link

Trigeminal neuralgia

John Fothergill

By Gilbert Stuarthttp://www.pafa.org/Museum/The-Collection-Greenfield-American-Art-Resource/Tour-the-Collection/Category/Collection-Detail/985/mkey–1923/, Public Domain, Link

Tuberous sclerosis

Désiré-Magloire Bourneville

By Unknown author – Bibliothèque Interuniversitaire de Médecine – http://www.bium.univ-paris5.fr/images/banque/zoom/CIPB0452.jpg, Public Domain, Link

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Reunion of neurologists at the Salpêtrière hospital. Photograph, 1926 https://commons.wikimedia.org/w/index.php?curid=36322408

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Let us then celebrate the pioneers…

Eponymous and anonymous alike

10 more catchy titles from the recent neurology literature

The case for testing serum neurofilament light protein in MS

I am yet to request serum neurofilament light protein (NfL) in my practice. I am not sure yet why I should, but until now I confess I really haven’t looked for a reason to do so. I however know that some MSologists now tick it, along with other blood tests, when they investigate people they suspect may have multiple sclerosis (MS). NfL are proteins that are released by damaged neurones. Should I be requesting NfL in my clinical practice? I sniffed around to find the case for testing serum NfL, and below is what I found.

By GerryShaw – Standard tissue culture and immunofluorescencePreviously published: Unpublished, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=26518273

Many studies have looked at the value of NfL in MS. One such very well-planned study that addresses many of my questions is that by Guili Disanto and colleagues, published in the journal Annals of Neurology in 2017. In the paper, titled Serum Neurofilament light: a biomarker of neuronal damage in multiple sclerosis, the authors studied >380 people with MS and >150 healthy controls, and report four important findings.

By GerryShaw – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17500647
  1. The levels of NfL in serum strongly correlate with the levels in cerebrospinal fluid (CSF) of people with MS.
  2. People with more active and more severe MS had higher levels of NfL.
  3. People with MS on disease modifying treatment (DMT) had lower NfL levels than those who were not on treatment.
  4. In people with MS who had their serum NfL tested serially over time, the level of NfL predicted those who will develop frequent relapses or progressive MS.

The authors concluded, with enough justification I think, that serum NfL is a “sensitive and clinically meaningful blood biomarker to monitor tissue damage and the effects of therapies in MS“.

Culture rat hippocampal neuron. ZEISS Microscopy on Flickr. https://www.flickr.com/photos/zeissmicro/24327909026

The strong correlation between cerebrospinal fluid (CSF) and serum NfL was also confirmed by a study published in the journal Neurology, by Lenka Novakova and colleagues titled Monitoring disease activity in multiple sclerosis using serum neurofilament light protein. As the title indicates, they discovered that serum NfL is as good as CSF NfL in monitoring the progression of MS.

Neuron. NICHD on Flickr. https://www.flickr.com/photos/nichd/21086076575

The observation that NfL predicts the course of MS is supported by many other studies, such as the one by Kristin Varhaug and colleagues in the journal Neurology Neuroimmunology and  Neuroinflammation whose title is also self-explanatory: Neurofilament light chain predicts disease activity in relapsing-remitting MS. A more recent paper, also published in Neurology, further reinforces the benefit of serum NfL in disease course prediction. It is titled Blood neurofilament light chain as a biomarker of MS disease activity and treatment response. In this paper, Jehns Kuhle and colleagues practically confirm all the above stated benefits of NfL, concluding that “our results support the utility of blood NfL as an easily accessible biomarker of disease evolution and treatment response”.

“Neuron” by Roxy Paine. Christopher Neugebauer on Flickr. https://www.flickr.com/photos/chrisjrn/4745660322

As for long term outcome, the 10 year follow up study by Alok Bahn and colleagues, published in the Multiple Sclerosis Journal in 2018, is most informative. In their paper titled Neurofilaments and 10-year follow-up in multiple sclerosis, the authors noted that “CSF levels of NfL at the time of diagnosis seems to be an early predictive biomarker of long-term clinical outcome and conversion from RRMS to SPMS”. Further support for the long term prognostic value of serum NfL comes from a paper published in 2018 in the journal Brain titled Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis. The authors, Christian Barro and colleagues, studied more than 250 people with MS and concluded that “the higher the serum neurofilament light chain percentile level, the more pronounced was future brain and cervical spinal volume loss“.

Nervous Tissue: Spinal Cord Motor Neuron. Berkshire Community College on Flickr. https://www.flickr.com/photos/146824358@N03/41850849912/in/album-72157666241437517/

It is pertinent to note that the MS sphere is not the only one in which NfL is making waves. It has been found to be elevated in many other disorders such as motor neurone disease (MND), multiple system atrophy (MSA), hereditary spastic paraplegia (HSP), stroke, active small vessel disease, and peripheral neuropathy (PN). With these disclaimers in place, it may just be time to start ticking that NfL box.

 

By GerryShaw – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17502311

 

Are parasites the simple solution to the problem of MS?

In medicine, microbes are notorious for causing disease. In neurology particularly, infection is the direct cause of serious diseases such as meningitis and encephalitis. Infections may also act as  catalysts for neurological disorders, for example when they trigger Guillain Barre syndrome (GBS). Infection is therefore a villain, a scoundrel to be apprehended and disarmed whenever it rears its head. But this picture may not hold true when it comes to multiple sclerosis (MS) where a contrary story is emerging, a narrative which holds infection as the hero, the daredevil that will save the day. The premise is simple: MS has very little presence in the regions of the world where infections reign supreme. Just look at any world prevalence map of MS to be convinced.

By MS_Risk_no_legend.svg: *MS_Risk.svg: Dekoderderivative work: Faigl.ladislav (talk)derivative work: Gabby8228 (talk) – MS_Risk_no_legend.svg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=15917004

How strong is this inverse relationship between infection and MS? It all boils down to the so-called hygeine hypothesis of autoimmune diseases. This suggests that the human immune system becomes dysregulated when it is not primed by infections, and this dysregulation results in autoimmune disorders. This point was strongly argued by Aakanksha Dixit and colleagues in their paper published in the International Journal of Molecular Science, titled Novel Therapeutics for Multiple Sclerosis Designed by Parasitic Worms. They contend that the relationship between parasitic infections and autoimmune diseases is “most compelling“, going on to assert that helminthic infections “may be the protective environmental factor against the development of MS”.

By Doc. RNDr. Josef Reischig, CSc. – Archiv autora, CC BY 3.0, Link

To support the hygiene theory of MS, that helminthic infections play a role in banishing MS, three levels of evidence are offered.

  1. The prevalence of MS steadily increases when the frequency of infections in a community is reduces.
  2. People with MS who also have helminthic infections have fewer relapses and slower disease progression.
  3. MS patients who are treated for their helminthic infections develop more relapses and have a more active disease course
Diversity and prevalence of gastrointestinal parasites in seven non-human primates of the Taï National Park, Côte d’Ivoire. Parasite, 2015, 22, 1.doi:10.1051/parasite/2015001, CC BY 4.0, Link

Toxoplasma gondii, the cause of toxoplasmosis, is perhaps the major parasite investigated in relation to MS. Asli Koskderelioglu and colleagues, for example, reported that exposure to T.gondii is less frequent in people with MS than in healthy control subjects. In their 2017 paper titled Is Toxoplasma gondii infection protective against multiple sclerosis risk?, published in Multiple Sclerosis and Related Disorders, they found that MS subjects who have higher toxoplasma antibody levels experience fewer relapses and less severe disease courses. This finding is corroborated by a 2015 paper in the Journal of Neuroimmunology titled Toxoplasma gondii seropositivity is negatively associated with multiple sclerosis.

CC BY 4.0, Link

Neurologists are however very cynical people, and they never believe what single trials tell them. After all, many microbes, such as Ebstein Barr virus (EBV), are touted as MS risk factors. For the sceptical neurologist, only systematic reviews and meta-analyses will do; these are the stuff of our dreams, the essence of our daily existence. So it is with a huge cheer that neurologists welcomed a 2018 systematic review and meta-analysis published in the Journal of Neuroimmunology and titled Is toxoplasma gondii playing a positive role in multiple sclerosis risk? The paper poured very cold water on the beautiful hygiene hypothesis. Whilst the authors, Reza Saberi and colleagues, confirmed that MS subjects had a lower risk of exposure to T. gondii, they found no relationship between this parasite and the development of MS. Wither a theory when it hits the reality of cold statistical analysis.

Cloudburst. Liz West on Flickr. https://www.flickr.com/photos/calliope/28825267500

Notwithstanding the systematic review, the helminth hypothesis marches on. It has even reached the stage of therapeutic trials where, as distasteful as it sounds, subjects ingest parasites by mouth! And the fancied parasite is not Toxoplasma gondii but Trichuris suis ova (TSO). It all began with a small observational trial in 10 people which proved that TSO is safe and well-tolerated (phew), but it had no value whatsoever in treating MS. Not discouraged, the hypothesis entered the slightly larger HINT 2 trial; this again confirmed good tolerability in 16 subjects, but any benefit in reversing MS was questionable. Undeterred, the hypothesis has gone for a bigger study in the form of the TRIOMS trial. This is a randomized, placebo-controlled study of 50 people with MS or clinically isolated syndrome (CIS) in which subjects will be ingesting 2,500 Trichuris suis eggs every two weeks. We wait with bated breaths for the results.

By Universidad de Córdoba – http://www.uco.es/dptos/zoologia/zoolobiolo_archivos/practicas/practica_4/practica4_botton.htm, Public Domain, Link

Before leaving this subject, we must know that helminths are not the only game in town; they have strong competition from their cousins, bacteria. And the standout character in this arena is Helicobacter pylori. We learnt this from a study published in 2015 in the Journal of Neurology Neurosurgery and Psychiatry. Titled Helicobacter pylori infection as a protective factor against multiple sclerosis risk in females, the paper reported that people with MS were less likely than controls to have been exposed to H. pylori. Two meta-analyses have also reviewed the relationship of H. pylori and MS, arguing strongly that, in Western countries, there is an inverse relationship between H pylori and MS. And they assert that H. pylori may be protective against MS. If it feels like déjà vu, it is.

Helicobacter pylori. AJC21 on Flickr. https://www.flickr.com/photos/ajc1/6946417103

We have surely not heard the last of bugs and MS. However, for now, the foundations of the hygiene theory are a bit shaky, and the future rather hazy.

By Doc. RNDr. Josef Reischig, CSc. – Archiv autora, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=17268274

 

The 9 neurological manifestations of anti MOG antibody disorder

Autoimmune disorders are probably the most proliferative field of neurology. It seems like there is a blazing headline every week announcing a new antibody disease. Many of these antibodies are esoteric, but some shake the foundations of medical practice. Anti-MOG antibody is one of those which requires you to stop and pay attention, and it has significantly affected neurological practice in a very big way.

By Simon Caulton – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=20522656

Perhaps the most important thing about anti-MOG antibody disease is that, like the chameleon, it presents in many guises. For the neurologist therefore, the first thing is to recognise these varied manifestations. Here then is a quick list of the 9 manifestations of anti MOG antibody disorder.

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1. Optic neuritis (ON)

2. Neuromyelitis optica spectrum disorders (NMOSD)

3. Multiple sclerosis (MS)

4. Acute disseminated encephalomyelitis (ADEM)

5. Multiphasic disseminated encephalomyelitis (MDEM)

6. Isolated transverse myelitis (TM)

7. Leukodystrophy-like phenotype

8. Cerebral cortical encephalitis

9. Combined central and peripheral demyelinating syndrome (CCPD)

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Optic Nerve Side View. Francisco Bengoa on Flikr. https://www.flickr.com/photos/frecuenciamedicafb/7404373800

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You can explore anti MOG antibody disorder further in Neurochecklists under the following titles:

Image from page 400 of “Diseases of the nervous system” (1910). Internet Archive Book Images on Flickr. https://www.flickr.com/photos/internetarchivebookimages/14586405720/

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For a detailed review and guidance, check this paper in Journal of Neuroinflammation:

 MOG encephalomyelitis: international recommendations on diagnosis and antibody testing.

By PecatumOwn work, CC BY-SA 4.0, Link

A few more catchy titles from the world of neurology

Here we go again. Neurologists can’t seem to stop spinning them, and we can’t help weaving them into blog posts. If you are late to the game, you may catch up with our previous catchy titles:

The art of spinning catchy titles
The art of spinning catchy neurology headlines
A few more catchy neurology article titles to start the year
15 more creative and catchy neurology headlines for 2019

Now that you are up-to-date, here are 10 more catchy neurology article titles to make your day: 

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Optic neuritis in the diagnosis of MS: more than meets the eye

This article looks at a common symptom of multiple sclerosis (MS), and makes the strong case that we need to do more to diagnose optic neuritis. And it is a very catchy way to make the point.

Optic nerve fron view. Francisco Bengoa on Flickr. https://www.flickr.com/photos/frecuenciamedicafb/7404373518/

The many faces of oral-facial-digital syndrome

This is not something neurologists often come across, but it comes close enough to the specialty. Oral-facial-digital-syndrome is typified by facial deformities, but more importantly, the title makes it clear that it is a syndrome with diverse subtypes. A catchy title for a rare disorder, and this paper reveals all.

Ben Eine – The Strangest Week. Bob Bob on Flickr. https://www.flickr.com/photos/bobaliciouslondon/5196843736

The new concussion in sport guidelines are here. But how do we get them out there?

Not all catchy titles are convoluted. This one is simple but yet very inspired. It refers to the 2016 Consensus Statement on Concussion in Sport. As for all guidelines, it is all well and good to develop them, but a herculean task to get anyone to take notice. It is therefore very ingenious to use a catchy editorial to do the job.

By shgmom56 on Flickr – Originally posted to Flickr as “DSC02769”, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=4231521

The great escape: a neuropsychological study of psychogenic amnesia

This is just a case report of fugue state, but it comes with a great title. The perspective of psychological amnesia as an escape is appropriate, and to the point.

By Wassily Kandinski – http://www.abcgallery.com/K/kandinsky/kandinsky73.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2174133

When the past is lost: focal retrograde amnesia

Another one on amnesia, and what a great title. It is a report of 13 cases of focal retrograde amnesia, all typified by loss of autobiographical memory. The amnesia is severe enough in some cases “to erase the knowledge of their own identity”.

By scanned by Open Clip Art Library user Johnny Automatic – http://openclipart.org/detail/168137/head-scratcher-by-johnny_automatic, Public Domain, https://commons.wikimedia.org/w/index.php?curid=18732522

What gnaws at the heart and gets on the nerves

This inspired title clearly took some thinking to conjure. It is on the subject of transthyretin-related amyloidosis (ATTR), a hereditary disorder that equally maims the heart and the brain. Typical features are small fiber neuropathy, autonomic neuropathy, and ventricular hypertrophy. And the treatment, incidentally, requires transplanting a third organ, the liver.

Amyloidosis, Node, Congo Red. Ed Uthman on Flickr. https://www.flickr.com/photos/euthman/377559787

Hand up! Yawn and raise your arm

Now here is a title to pique anyone’s neurological curiosity. It is about a peculiar disorder, parakinesia brachialis oscitans. There is really no cat to be let out of the bag here; the paper’s abstract reveals all. In some cases of hemiplegia, the abstract says, yawning is associated with involuntary raising of the paralysed arm”. Read all about it!

By Joseph Ducreux – MQG0zXDvoSnYDg at Google Cultural Institute maximum zoom level, Public Domain, https://commons.wikimedia.org/w/index.php?curid=22178664

A sleep medicine medical school curriculum: time for us to wake up

This simple but catchy title is an excellent play on words. It is clearly about the contrariness of the acts of sleep and waking in one headline. This editorial is more than just a catchy title; it is a strong call to action!

Wake up! Simon Bleasdale on Flickr. https://www.flickr.com/photos/simonbleasdale/9562433956

Burnout in neurology: extinguishing the embers and rekindling the joy in practice

It takes great imagination to come up with a title that contains burnout, embers and kindling. And the result is catchy. Burnout is a serious issue that threatens neurological practice, and this editorial flags the concern very forcefully: “the message for all is clear: medicine must identify the root causes of burnout, and more importantly, put the joy back in medicine. It is time to see the light!

Burnout! Dennis Skley on Flickr. https://www.flickr.com/photos/dskley/14692471997

Warts and all: Fingolimod and unusual HPV-associated lesions

Probably not the catchiest title one could come up with, but it is catchy enough to attract attention. The title refers to fingolimod, the multiple sclerosis drug which predisposes to treatment-resistant warts. Simple verruca is bad enough, but the human papilloma virus (HPV) which causes it happens to trigger more sinister diseases: cervical and anogenital cancer. Therefore, with fingolimod, we must pay attention to warts and all!

Human Papillomavirus (HPV) in Head and Neck Cancer. NIH Image Gallery on Flickr. https://www.flickr.com/photos/nihgov/29990958966

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Do you have any catchy titles up your sleeves? Do leave a comment.

15 more creative and catchy neurology headlines for 2019

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

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

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

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

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

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

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

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

13. A little man of some importance 

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

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

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

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

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

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

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

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

 

10. Waking up to sleeping sickness.

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

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

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

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

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

08. Shedding light on photophobia

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

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

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

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

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

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

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

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

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

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

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

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

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

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

03. Diabetes and Parkinson disease: a sweet spot?

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

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

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

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

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

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

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

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

 

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. https://www.flickr.com/photos/pennstatelive/4946556307

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. https://www.flickr.com/photos/mgdtgd/3507973704

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. https://www.flickr.com/photos/cstmweb/4888243867

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 – http://images-of-elements.com/gadolinium.php, 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

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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. https://www.flickr.com/photos/137789813@N06/22951789105

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. https://www.flickr.com/photos/stefan-szczelkun/3931901057

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. https://www.flickr.com/photos/csb13/4276731632

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).

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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. https://www.flickr.com/photos/nihgov/30805879596

What are the promising CSF biomarkers of MND?

The Neurology Lounge strives hard to keep to the straight and narrow path of clinical neurology. But every now and then it takes a peek at what is happening at the cutting edge of neuroscience. And what can be more cutting edge then biomarkers, with their promise of simplifying disease identification, making prompt and accurate diagnosis an effortless task.

Darts. Richard Matthews on Flickr. https://www.flickr.com/photos/richardofengland/6788829651

The quintessential biomarker however remains as elusive as quicksilver. Not that one could tell, going by the rate biomarkers are being spun from the neuroscience mills. Biomarkers are the buzz in many neurological fields, from brain tumours to multiple sclerosis (MS), from Alzheimer’s disease (AD) to Huntington’s disease (HD).

By Muffinator – Own work, CC0, Link

The proliferation of contending biomarkers is however probably highest in the field of motor neurone disease (MND). Is there a holy grail out there to enable the rapid and accurate diagnosis of this relentlessly progressive disease? There is clearly no dearth of substances jostling for prime position in the promised land of MND biomarkers. Below is a shortlist of potential MND CSF biomarkers; just click on any to go to the source!

By Horia Varlan from Bucharest, Romania – Graduated cylinders and beaker filled with chemical compounds, CC BY 2.0, Link

Biomarkers elevated in the cerebrospinal fluid (CSF) 


Ferritin heavy chain (FHC)

Ferritin light chain (FLC)

Interferon g (IFN-g)

MIP 1a

Interleukin 12

Interleukin 15

Interleukin 17

Interleukin 23

Chromogranin A (CgA)

Basic fibroblast growth factor (bFGF)

Tau

Green Coral brain. Sarah Spaulding on Flickr. https://www.flickr.com/photos/visionwithin/61464453/

Neurofilaments

Vascular endothelial growth factor (VEGF)

Chitotriosidase 1 (CHIT 1)

Insulin-like growth factor 1 (IGF 1)

Matric metaloproteinases (MMPs)

Homocysteine

Cystacin C

Monocyte chemotactic protein 1 (MCP 1)

Flt3 ligand

Prostaglandin E2 (PGE2)

Nitrate

Anti-ganglioside antibodies

By Nevit Dilmen (talk) – Own work, CC BY-SA 3.0, Link

Biomarkers reduced in the cerebrospinal fluid (CSF) 


Alpha 1 antitrypsin

Erythropeoitin

Chloride

Angiotensin II

Cytochrome C

Cyclic GMP (cGMP)

Acetylcholine esterase (AChE) activity

 


Why not check out more about MND in Neurochecklists

By © Nevit Dilmen, CC BY-SA 3.0, Link

What is the impact of Vitamin D on the complicated course of MS?

Some general neurologists get away with not having to think too much about multiple sclerosis (MS). This is because they have an ‘MSologist‘ at hand to refer all their patients with ‘demyelination‘. Many general neurologists however care for people with MS because they do not have a ‘fallback guy‘ to do the heavy lifting for them. This therefore makes it imperative for neurologists to keep up with everything about this often disabling and distressing disorder.

MS prevalence map. By AdertOwn work and [1], CC BY-SA 3.0, Link
The management of MS is however very tricky, and it is challenging to get a grip of it all. This is partly because the clinical course is varied, and the diagnostic process tortuous. The patient first goes through an onerous retinue of tests which include an MRI, a lumbar puncture, evoked potentials, and a shedload of blood tests. This is all in a bid to secure the diagnosis and to exclude all possible MS mimics.

MRI scan. NIH Image Galley on Flikr. https://www.flickr.com/photos/nihgov/30805879596

Then comes the head-scratching phase of determining if the patient actually fulfils the diagnostic criteria for MS, or if they just have clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS). To secure the diagnosis of MS, the neurologist turns to the McDonald criteria which stipulate dissemination in time and place of inflammatory events. As simple as this should be, this is no easy task at all. This is because, at different times, the criteria have meant different things to different people. The guidelines have also gone through several painful, and often confusing, iterations. Indeed the McDonald criteria have only recently been re-revised-to the delight of MSologists but the chagrin of the general neurologist!

Steampunk Time and Space Machine. Don Urban on Flikr. https://www.flickr.com/photos/donpezzano/3230179951

Once the diagnosis of relapsing remitting MS (RRMS) is reasonably established, the patient is taken through a guided tour of the ever-expanding available treatment options. These are typically to prevent relapses, but more recently to prevent disease progression as well. People with mild to moderate MS are nudged towards interferons, glatiramer acetate, dimethylfumarate, or terifluonamide. Those with more aggressive disease, on the other hand, are offered a menu of fingolimod, natalizumab, or alemtuzumab. Other newer agents include daclizumab and cladribine. And, just stepping into the arena, there is ocrelizumab for primary progressive (PPMS). Whichever option is chosen, the course of treatment is long, and it is fraught with risks such as infections and immune suppression.

https://pixabay.com/en/syringe-pill-bottle-morphine-small-1884784/

Once the bigger questions have been settled, the neurologist then braces for the ‘minor’ questions her enlightened patients will ask. The easier questions relate to the treatment of symptoms, and some of the most vexing concern the role of Vitamin D deficiency. Such questions include, ‘Is vitamin D deficiency a cause of MS?‘, ‘Do people who are vitamin D deficient experience a worse outcome?‘, and ‘Should patients with MS be on Vitamin D supplementation?‘.

Pandora’s box. Michael Hensman on Flikr. https://www.flickr.com/photos/mycael/3664900435

To attempt to resolve these questions I plunged into some of the literature on Vitamin D and MS. And this is like opening Pandora’s box. Here are some of the things I found.

***

Is MS associated with Vitamin D deficiency?

It therefore appears that there is an association of vitamin D deficiency with MS, but it is far from certain that this is a causative relationship. One hypothesis is that vitamin D deficiency is the outcome, rather than the cause, of MS. The deficiency presumably results becuase the very active immune system in people with MS mops up the body’s Vitamin D. This so-called reverse causation hypothesis asserts that vitamin D deficiency is a consumptive vitaminopathy

Sunshine Falls. Dawn Ellner on Flikr. https://www.flickr.com/photos/naturesdawn/4299041739

Does Vitamin D deficiency worsen MS progression?

There is therefore no single answer to this question, but the emerging consensus is that Vitamin D deficiency adversely affects the course of MS. 

Milk splash experiment. Endre majoros on Flikr. https://www.flickr.com/photos/boneball/24597145866

Should people with MS be on Vitamin D supplementation?

Even if Vitamin D deficiency doesn’t cause MS, the evidence suggests that it negatively influences the course of the disease.

Salmon salad nicoise. Keith McDuffee on Flikr. https://www.flickr.com/photos/gudlyf/3609052894

What to do?

This is the million dollar question eloquently posed by a recent editorial in the journal Neurology titled Preventing multiple sclerosis: to (takevitamin D or not to (takevitamin D? The reasonable consensus is to encourage vitamin D replenishment to prevent MS, starting from preconception. It is also generally agreed that people with MS should be on vitamin D supplementation in the expectation that it will slow the disease activity.

A practical approach to Vitamin D replacement is the Barts MS team vitamin D supplementation recommendation. This is to start with 5,000IU/day vitamin D, and aim for a plasma level of 100-250 nmol/L. Depending on the level, the dose is then adjusted, up or down, to between 2-10,000IU/day. They also advise against giving calcium supplementation unless there is associated osteoporosis.

What is a general neurologist to do? To follow the prevailing trend, and hope it doesn’t change direction too soon!

Vitamin D Pills. Essgee51 on Flikr. https://www.flickr.com/photos/sg51/5224823967