Mozart and epilepsy: the rhythm beats on

I can’t seem to get away from the theme of Mozart and epilepsy. When I first looked at this, in a blog post titled Mozart and seizures? The links between epilepsy and music, I took the topic rather lightly, more a subscript than a headline you may say. But I have since learnt to take the links between epilepsy and music more seriously. 

By Barbara KrafftThe Bridgeman Art Library, Object 574471, Public Domain, Link

The major trigger for my ‘road to Damascus’ conversion is a 2018 paper titled Study of the Mozart effect in children with epileptic electroencephalograms, published in the journal Seizure. The paper was an eye-opener because it gave a very helpful comprehensive context to the broader beneficial effect of music…not just in epilepsy, but in other neurological disorders such as Parkinson’s disease, dementia and sleep disorders. The authors, Elyza Grylls and colleagues, started on the established premise that Mozart’s music has a beneficial effect on epilepsy. What they wanted to know was if other forms of music have a similar settling effect on epilepsy, or if only Mozart’s music carries the magic touch. The authors therefore played Mozart’s Sonata for two pianos in D major (K448) to 40 children with epilepsy who were undergoing an EEG (electroencephalogram, or electrical brain wave test). They then compared this with the effect of playing other types of music. Remarkably, they found that only Mozart’s Sonata led to a significant reduction in EEG epileptic discharges.

Public Domain, Link

The authors concluded that there was indeed an anti-epileptic effect of Mozart’s music, the so-called  ‘Mozart therapy’. But what is so special about K448? They speculate that it has to do with the structure of Mozart’s music, containing as it does, long periodicities. Interestingly, the music of Yanni, which is similarly structured, has somewhat a similar effect on brain wave activity. On the contrary, and sorry to Beethoven fans, Fur Elise doesn’t have this effect.

By W.J. Baker (held the expired copyright on the photograph) – Library of Congress[1]Contrairement à une erreur fréquemment répandue le buste a été réalisé par Hugo Hagen, non pas à partir du masque mortuaire mais, comme de nombreux autres, d’après le masque réalisé en 1812 par Franz Klein pour un buste qu’il devait réaliser ensuite., Public Domain, Link
So what does the structure of Mozart’s music do to the brain? One suggestion is that Mozart’s music enhances the body’s parasympathetic drive; this reduces the heart rate, and thereby inhibits the brain’s propensity to epileptic seizures. The suppression of this parasympathetic drive is of course the theory behind using vagus nerve stimulation (VNS) to treat drug-resistant epilepsy. For more on VNS, see my previous blog, Vagus nerve stimulation: from neurology and beyond!

By Bionerd – MRI at Charite Mitte, Berlin (used with permission), CC BY 3.0, Link

You have surely wondered by now whether K448 is the only one of Mozart’s compositions to have an anti-epileptic effect. It doesn’t matter if you haven’t, because the authors of another interesting paper have. They titled their study, published in 2018, Mozart’s music in children with drug-refractory epileptic encephalopathies: comparison of two protocols. Published in the journal Epilepsy and Behaviour, the authors, Giangennaro Coppola and colleagues, compared the effect of K448 with a set of his other compositions. Intriguingly they found that the composition set actually had a greater effect in epilepsy than K448…by a wide margin of 70% to 20%! Furthermore, the set was better tolerated by the children; they were less irritable and had a better nighttime sleep quality.   

https://www.publicdomainpictures.net/en/view-image.php?image=76907&picture=dog-amp-child-painting

So, is it all rosy in the garden of music and the brain? No, it’s not! As every rose grows on a thorny tree, so do some forms of music trigger epileptic seizures. This so-called musicogenic epilepsy is well-recognised, and two recent culprits are the music of Sean Paul, discussed in the journal Scientific American , and the music of Ne Yo, explored by NME. Therefore you should craft your playlist wisely.

By CLASSICNEYOOwn work, CC BY-SA 4.0, Link

So, is it time for neurologists to start prescribing music?

Or is it too much of a double-edged sword?

Music is #SimplyIrresistible. Luca Florio on Flickr. https://www.flickr.com/photos/elle_florio/29516744480

What, precisely, is the Alice in Wonderland syndrome?

Alice’s Adventures in Wonderland is a fairy tale that is beyond comparison in its implausible scenarios and outlandish characters. It intrigues and fascinates in equal measure, and it has held generations of children and adults spellbound since its publication in 1865. The fantasy is as fanciful as Lewis Carroll, the pseudonym of the author Charles Lutwidge Dodgson.

Alice in Wonderland. -JvL- on Flickr. https://www.flickr.com/photos/-jvl-/6075178802

As outrageous and as preposterous as it is, the book actually confirms the truism that most works of fiction are grounded in hard reality. In their excellent article, Alice in Wonderland Syndrome: A Historical and Medical Review, Osman Farooq and Edward Fine demonstrated that Alice’s adventures are not a figment of the author’s imagination, but the depiction of his real-life illusory experiences. Lewis Carroll suffered from migraine, and Alice was a perfect incarnation of the visual distortions that accompany this very common and debilitating disorder. Therefore, when lay people read that Alice’s body “had grown too tall or too small”, the stoney-eyed neuroscientists only see macropsia and micropsia, objects appearing larger or smaller than they actually are. When ordinary folks read that “parts of her body were changing shape, size, or relationship to the rest of her body”, the neurologist just sighs and yawns…migraine auras again! What spoilsports they are!

Alice. Danny Pig on Flickr. https://www.flickr.com/photos/dannypigart/114365270

Large and small of course bring to mind another great work of fantastic fiction, Gulliver’s Travels by Jonathan Swift. His Lilliputian and Brobdingnagian hallucinations are in another scale altogether, but did Swift also suffer from migraine? He probably did because the list of artists with probable migraine is fairy long (please don’t miss the intended pun). Some neuroscientist will however pour cold water on the idea that migraineurs are blessed with any creative impulses. Indeed it is not universally accepted that Lewis Crroll suffered from migraine auras. And just when you thought your migraines were worth the suffering! You may read more about art-disease relationships in this excellent article titled Alice in Wonderland Syndrome: A Clinical and Pathophysiological Review.

By Louis Rheadhttp://www.childrensbooksonline.org/Gullivers_Travels/index.htm, Public Domain, Link

But we mustn’t be distracted or derailed from the theme of today, Alice in Wonderland syndrome (AIWS). This fascinating disorder, and a disorder it is according to neurologists, puts us in a circular situation: fiction first mimicked fact to produce Alice, and fact then imitated fiction to produce a real ailment. I know, it all sounds absurd. But what did you expect with this theme!

By RodwOwn work, CC BY-SA 3.0, Link

What then is the cause of these illusory experiences that literally blow the mind? Yung-Ting Kuo and colleagues attribute it all to reduction in blood flow to the visual centers in the brain. And how many disorders may do this? Because this is neurology we are talking about…almost anything. The common culprits however are migraine, epilepsy, LSD, an assortment of  intoxicants, and a menagerie of brain infections. The syndrome has also been reported in a host of psychiatric and organic brain disorders such as Cotard syndrome, Capgras syndrome, depression, and schizophrenia. More worrying however is the association of the syndrome with prescription medications. One such drug is Topiramate, a medicine neurologists prescribe to prevent, among other conditions, migraine! And another, Aripiprazole, is paradoxically an excellent treatment for…hallucinations!

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

As bizarre as Alice’s adventures are, Alice in Wonderland syndrome goes much farther: people with the syndrome experience a wider variety of even more grotesque illusory experiences than Lewis Carroll ever imagined. A recent paper in the journal, Neurology Clinical Practice, shows just how grotesque. Titled Clinical Characteristics of Alice in Wonderland Syndrome in a Cohort with Vestibular Migraine, the authors provide an almost endless list of unusual clinical manifestations of AIWS. The prize must however go the illusion that the brain is coming out of the head! There you go Lewis Carroll, you may eat your mad hat: fact will always be stranger than fiction!

Uh-oh. Josh Connell on Flickr. https://www.flickr.com/photos/yhsoj/4636850643/

Migraine and its strange and surprising associations

By Sasha Wolff from Grand Rapids - Can't Concentrate: 14/365, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=11343038
By Sasha Wolff from Grand Rapids – Can’t Concentrate: 14/365, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=11343038

I am casting my sight on the scourge of millions around the world-migraine. This post is a prelude to a piece I am working on titled How is migraine research soothing the pain of neurology? In doing this, I came across a few curiosities which I thought would do nicely as a separate post. Therefore, before the real stuff, here are 8 strange and surprising migraine associations.

α. Migraine and the weather

Texture: Thunder Clouds. Virginia Moerenhout on Flikr. https://www.flickr.com/photos/yndra/4784553320
Texture: Thunder Clouds. Virginia Moerenhout on Flikr. https://www.flickr.com/photos/yndra/4784553320

Some migraineurs know that their migraine attacks are related to changes in the weather. For them therefore, the science is just catching up. This piece from the American Migraine Foundation summarises some recent articles which discuss the weather alterations that may trigger migraine headaches. The fingers are pointing at low barometric pressure, high environmental temperature, strong winds, and…wait for it…> 3hours of sunshine!

β. Migraine and irritable bowel syndrome (IBS)

This is not even officially out yet, but a press release announcing the American Academy of Neurology’s April 2016 meeting whets our appetites. The findings of a study to be unveiled in Vancouver reports that migraine is probably genetically linked to irritable bowel syndrome (IBS). Not only that, the two may also share genetic markers with tension type headache (TTH). And the link is thought to be the serotonin transporter, and the serotonin receptor 2A, gene. The association of migraine and IBS will really put the cat among the pigeons; dealing with migraine alone is hard enough but combine the two and…

γ. Migraine and Parkinson’s disease (PD)

By Marvin 101 - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7533521
By Marvin 101Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7533521

Migraine sufferers will really balk at the scary report of migraine as a risk factor for Parkinson’s disease (PD). This is the conclusion of a research work published in the journal Cephalalgia (really just a fancy word for headache). The authors followed up >40,000 people to see if those with migraine are more likely to develop PD than those without. Curious indeed! I have to confess, whatever the hazard ratios say, that I was not impressed by the difference in numbers developing PD of 148 versus 101.

δ. Migraine and radiotherapy

Varian radiation therapy machine. Dina-Roberts Wakulczyk on Flikr. https://www.flickr.com/photos/littlesister/490643515
Varian radiation therapy machine. Dina-Roberts Wakulczyk on Flikr. https://www.flickr.com/photos/littlesister/490643515

I’m not trying to be smart, but SMART syndrome is real. It is an acronym for Stroke-like migraine attacks after radiation therapy. It is easy for neurologists to miss this condition because it sets in years after the radiation treatment. There is however a clue in the MRI of people with SMART syndrome: cortical thickening and gadolinium enhancement in the area of brain treated with radiation. It’s simple really!

ε. Migraine and raised intracranial pressure

By Jonathan Trobe, M.D. - University of Michigan Kellogg Eye Center - The Eyes Have It, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=16115920
By Jonathan Trobe, M.D. – University of Michigan Kellogg Eye Center – The Eyes Have It, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=16115920

An article in Journal of Neurology reports that many people with unrelenting migraine have raised pressure in the brain (raised intracranial pressure or ICP). The article, titled association of unresponsive chronic migraine and raised intracranial pressure, showed that reducing the pressure by a spinal tap (lumbar puncture) leads to sustained remission of migraine. Neurologists diagnose raised ICP by look into the back of the eye for a sign called papilledema. This article however throws a spanner in the works because >75% of the people with migraine and raised ICP in the study did not have papilledema. What do the headache gurus have to say about this, I wonder?

ζ. Migraine and stroke

Neurologists really haven’t sorted this one out yet. We struggle to give our patients a straightforward answer to their simple question, ‘does migraine cause stroke?‘ This is because the literature on this is all smoke and mirrors, and recent papers do little to clear the air. Take this paper in a recent issue of Neurology titled Age-specific association of migraine with cryptogenic TIA and stroke. The authors could only conclude that there is probably a causal or shared risk, and this only in older people. The accompanying editorial, titled Migraine and cryptogenic stroke: the clot thickens, concludes that there may be a higher risk of stroke in migraineurs, but this is in those with other traditional stroke risk factors in the first place. A shaky association I say, but one not to be dismissed too hastily.

η. Migraine and teeth-grinding

By Mik81 - Photography of author, original description page was here., Public Domain, https://commons.wikimedia.org/w/index.php?curid=2478383
By Mik81 – Photography of author, original description page was here., Public Domain, https://commons.wikimedia.org/w/index.php?curid=2478383

I did say these are strange links. Teeth grinding or bruxism is not something neurologists would give a second thought to, but a review article in Practical Neurology says we should think again. Titled Bruxism in the Neurology Clinic, the review says bruxism is closely linked to migraine, and sleep bruxism is only associated with migraine. There is much more to bruxism and neurology; the authors suggests that bruxism may be a form of oromandibular dystonia, and it may arise from dysregulation in the basal ganglia. Quite a lot to chew! Dentists out there should be very worried-the neurologists are out to expand their territory.

θ. Migraine and hiccups

Try this Flikr. Bart on Flikr. https://www.flickr.com/photos/cayusa/3029282000
Try this Flikr. Bart on Flikr. https://www.flickr.com/photos/cayusa/3029282000

And finally a report which links migraine and hiccups. Again from Cephalalgia, this is a case series of people with migraine who report hiccups as aura of migraine. Strange and surprising indeed!

migraine aura 2 - when it's light and shimmery. Joanna Roja on Flikr. https://www.flickr.com/photos/cats_mom/2758240218
migraine aura 2 – when it’s light and shimmery. Joanna Roja on Flikr. https://www.flickr.com/photos/cats_mom/2758240218

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Alzheimer’s disease: a few curious things

This is a prelude to my upcoming post, How Bright is the Future for Alzheimer’s Disease? In writing that post I came across a few curious reports about Alzheimer’s disease. I thought these reports were not ground-breaking enough to impact on the future of Alzheimer’s disease. They were however all interesting and thought I should share them.

How does your sleep posture increase your risk of Alzheimer’s disease?

By by Reggaeman - photo by Reggaeman, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1042279
By by Reggaeman – photo by Reggaeman, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1042279

 

Could sleeping on your side help to prevent Alzheimer’s disease? So suggests a study published in Journal of Neuroscience titled The Effect of Body Posture on Brain Glymphatic Transport. What on earth is the glymphatic system!? Wikipedia says it’s a functional waste clearance pathway for the mammalian central nervous system. The authors showed that rats lying on their side cleared brain waste better than if when lying on their backs or fronts. And this waste includes β amyloid, one culprit behind Alzheimer’s disease. If only things were this simple. But just so you know, I now sleep on my side!

Which fatigue-banishing medication may improve Alzheimer’s disease?

This is how to take an exam. Dan Tentler on Flikr. https://www.flickr.com/photos/vissago/3593809008
This is how to take an exam. Dan Tentler on Flikr. https://www.flickr.com/photos/vissago/3593809008

 

Still in slumber-mode, a recent article suggests that the medication, Modafinil, improves cognition. Modafinil is a drug familiar to neurologists who use it to treat conditions typified by excessive sleep, as in narcolepsy. It is also an alerting drug which improves fatigue in conditions such as multiple sclerosis (MS). The article is a systematic review of the evidence on the effect of Modafinil on cognition. It is published in the journal, European Neuropsychopharmacology under the title Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects. Curious, but I don’t see neurologists prescribing this for Alzheimer’s disease anytime soon.

Which fruit juice should you drink to protect yourself from Alzheimer’s disease?

This may seem like a newspaper headline but it is a scientific research published in European Journal of Nutrition titled Consumption of anthocyanin-rich cherry juice for 12 weeks improves memory and cognition in older adults with mild-to-moderate dementia. In the study, 49 people with mild to moderate dementia were given anthocyanin-rich cherry juice over 12 weeks. The authors reported that cherry juice significantly improved verbal fluency, and both long- and short-term memory. Cherry juice is supposedly rich in anthocyanin, a flavonoid, and this is a cognitive enhancer. I wouldn’t run out and stock on cherry juice yet: the number of participants in the study was small, and the duration of the study too small, to make any conclusions. But a curious finding none-the-less.

Which bugs are linked to Alzheimer’s disease?

This is probably the most curious of the questions. The headline from Scientific Reports says Different Brain Regions are Infected with Fungi in Alzheimer’s Disease. The authors of the report show that the brains of people with Alzheimer’s disease, unlike the brains of control subjects, are infiltrated with fungi. If you didn’t have a reason to keep away from fungi before, now you have a curious one.

Brain Aging. Kalvicio de las Nieves on Flikr. https://www.flickr.com/photos/118316968@N08/19444505382
Brain Aging. Kalvicio de las Nieves on Flikr. https://www.flickr.com/photos/118316968@N08/19444505382

 

For the more ground-breaking stuff, watch out for my next post titled How Bright is the Future for Alzheimer’s Disease?