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/

The art of spinning catchy neurology headlines

The Neurology Lounge is always on the lookout for catchy neurology article titles to adorn its shelves. My previous blog post in this quest was The art of spinning catchy titles.

Since then, there have been quite a few brilliant article titles that have caught my fancy. We must acknowledge the wordsmiths who craftily and meticulously think up these magical headlines; they put in a lot of thought to conjure up the right words to use. The look into their crystal balls to predict the best way to play around with the meanings. With a bit of lexical alchemy, they miraculously come up with the titles that make us do a double-take, but do so with a smile. Below are 9 such catchy titles.

Parkinson’s disease: Oh my gut! 

By The original uploader was Arnavaz at French WikipediaThis image is an old version created by Medium69.Cette image est une ancienne version créée par Medium69.Please credit this : William Crochot – http://www.cancer.gov, Public Domain, Link

This title reflects the science suggesting that Parkinson’s disease originates from the gut. This editorial restates the proposition that α-synuclein starts accumulating in the intestines before migrating, up the vagus nerve, ‘in a prion-like fashion’, to the brain.

Patent foramen ovale and migraine: closing the debate

Medical Illustrations by Patrick Lynch, generated for multimedia teaching projects by the Yale University School of Medicine, Center for Advanced Instructional Media, 1987-2000.

Patent foramen ovale (PFO) is a hole in the heart which connects the upper two heart chambers, or atria. It normally closes after birth, but in some people it persists to cause some grief to cardiologists and neurologists. Whether a PFO causes migraine or not is a long standing contentious issue in Neurology. The authors of this study found no link between migraine and (PFO). The title is brilliant, but the tone of finality is probably premature; I guess this debate is far from over.

Migraine and inhibitory system – I can’t hold it!

Human brain on white background. _DJ_ on Flikr. https://www.flickr.com/photos/flamephoenix1991/8376271918

And still on migraine is this headline grabber. A bit on the basic science spectrum, I quote from the abstract to give you a flavour: ‘This review focuses on recent structural and functional neuroimaging studies that investigated the role of subcortical and cortical structures in modulating nociceptive input in migraine, which outlined the presence of an imbalance between inhibitory and excitatory modulation of pain processing in the disease‘. I would rather stick with the punchy headline myself.

On the nose: olfactory disturbances in patients with transient epileptic amnesia

Big Nose Strikes Again. Bazusa on Flikr. https://www.flickr.com/photos/bazusa/260401471

This research paper establishes a link between transient epileptic amnesia (TEA) and impairment of the sense of smell. TEA continues to surprise, and there is indeed quite a lot to chew in the paper.

Myelitis in neuromyelitis optica spectrum disorder: the long and the short of it

By JasonRobertYoungMDOwn work, CC BY-SA 4.0, Link

This is a clear play on the defining feature of neuromyelitis optica (NMO), a long segment of inflammation in the spinal cord. This is what neurologists call longitudinally extensive transverse myelitis (LETM). This is an excellent editorial, worthy of the headline. It emphasises the point that NMO really has no defining features, not even the presence of the ‘defining’ antibody, anti-aquaporin 4- just ask anti-MOG NMO about this

AEDs after ICH: preventing the prophylaxis

By BobjgalindoOwn work, GFDL, Link

How do you prevent a harmful preventative practice?. By a paper with a title that is pure genius of course. The authors of this paper highlight the persisting, anti-guideline, practice of using prophylactic antiepileptic drugs (AEDs) in people who have had intracerebral haemorrhage (ICH). The paper rhetorically asks if this has ‘become a habit too difficult to break?’ Not going by this catchy headline!

Paralysis lost: a new cause for a common parasomnia?

Sleepwalking. Gareth on Flikr. https://www.flickr.com/photos/trois-tetes/7240877

Parasomnias are diseases that occur during or related to sleep. This headline is for an editorial on a new parasomnia called anti IgLON5 antibody disorder. This is the subject of my previous blog post titled IgLON5: a new antibody disorder for neurologists. The headline writer here is clearly a fan of John Milton. I however struggled to make the connection between the excellent headline and the subject of the paper. I however presume it relates to the ‘loss of sleep paralysis‘ that accompanies many sleep disorders, including the quintessential parasomnia- REM sleep behaviour disorder (RBD). Excellent title anyway.

Hereditary spastic paraplegia: the pace quickens

By Rawlings, Leo – http://media.iwm.org.uk/iwm/mediaLib//150/media-150073/large.jpgThis is photograph Art.IWM ART LD 6040 from the collections of the Imperial War Museums., Public Domain, Link

With a slightly wicked wit, this headline focuses on the slow walking speed of people with hereditary spastic paraplegia (HSP), contrasting this with the increasing research output on the disease. A bit dated I admit, but the paper refers to work which identified the genetic basis of SPG3, one of the commoner HSPs. A lesson in headline writing from the archives you may say.

Cut your losses: spastin mediates branch-specific axon loss

Synapse. Ben Cadet on Flikr. https://www.flickr.com/photos/47814009@N00/2943548161

The headline is brilliant, but the content goes way over my head. It is an editorial on a basic science paper. For the curious and the nerdy, I quote an extract: ‘during synapse elimination in the developing neuromuscular junction, branch-specific microtubule destabilization results in arrested axonal transport and induces axon branch loss. This process is mediated in part by the neurodegeneration-associated, microtubule-severing protein spastin‘. Enough I hear you say. OK, just stick with the headline.

***

Do you have any catchy titles-please drop a comment.

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Migraine and the challenge of white matter lesions in the brain

Neurologists often refer their patients with headache for a brain MRI scan. Quite often the reason for this is to reassure their patients who are worried about a sinister cause for their headache…and the anxiety provoking culprit is usually a brain tumour. The headache is often a migraine which has recently changed in character, or which is defying conventional treatment.

The neurologist is often ambivalent when requesting such scans. On the one hand, she expects the scan to be normal. On the other hand, she can not be certain there is indeed no sinister cause for the headaches. Another thing also bothers the neurologist, beyond the chance of detecting a brain tumour. And this is the ‘risk’ that the brain scan detects ‘incidental’ findings called white matter lesions (WML). Alas, these reassurograms frequently pick up these less sinister, but nevertheless unexplained, findings.

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

White matter lesions are often just age-related, ‘wear and tear’ changes, and they are more common in people with vascular risk factors such as hypertension, smoking and raised cholesterol levels. Neurologists generally believe migraine is also a risk factor for white matter lesions. And there are several studies to support this belief.

An example is a paper by the headache gurus Marcelo Bigal and Richard Lipton, published in the journal Cephalalgia, titled migraine as a risk factor for deep brain lesions and cardiovascular disease. Another is a paper by Kruit and colleagues in the Journal of the American Medical Association (JAMA) titled migraine as a risk factor for subclinical brain lesions. If you are still not convinced, try this article in the Archives of Neurology by Swartz and colleagues, with the unequivocal title-migraine is associated with magnetic resonance imaging white matter abnormalities.

MIGRAINE. aka TMan on Flikr. https://www.flickr.com/photos/rundwolf/331545021
MIGRAINE. aka TMan on Flikr. https://www.flickr.com/photos/rundwolf/331545021

With this strong evidence, neurologists are able to convince themselves there is nothing to these MRI high signal changes in their patients with migraine. No ‘chicken and egg’ philosophical equivocation is entertained. The scans are sometimes discussed at neuroradiology meetings where everybody murmurs ‘migraine white matter lesions’. All doubt dispelled, the neurologist reassures the patient, and hurriedly closes the chapter.

https://pixabay.com/en/book-closed-bookmark-close-section-2159519/

It is therefore with a strong jolt that neurologists read a recent article in the prestigious journal, Brain, greatly upsetting this cosy neurological consensus. In the paper titled migraine with aura and risk of silent brain infarcts and white matter hyperintensities, the authors found no association between migraine and brain white matter lesions. Shocking!

Shocked girl. Bixendro on Flikr. https://www.flickr.com/photos/bixentro/6360922151
Shocked girl. Bixendro on Flikr. https://www.flickr.com/photos/bixentro/6360922151

The authors studied female twin pairs aged between 30–60 years. The twins were  identified through the population-based Danish Twin Registry. The authors compared the MRI scans of the subjects with and without migraine, and found no difference in the frequency of white matter changes between the two groups. They proudly, and disconcertingly, declare that ‘we found no evidence of an association between silent brain infarcts, white matter hyperintensities, and migraine with aura‘.

Migraine with aura. Joana Roja on Flikr. https://www.flickr.com/photos/cats_mom/2761999058
Migraine with aura. Joana Roja on Flikr. https://www.flickr.com/photos/cats_mom/2761999058

Oh dear-what do neurologists tell their patients now? I shudder to think!

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What are the most iconic neurological disorders?

Neurology is a broad specialty covering a staggering variety of diseases. Some neurological disorders are vanishingly rare, but many are household names, or at least vaguely familiar to most people. These are the diseases which define neurology. Here, in alphabetical order, is my list of the top 60 iconic neurological diseases, with links to previous blog posts where available.

 

1. Alzheimer’s disease

By uncredited - Images from the History of Medicine (NLM) [1], Public Domain, https://commons.wikimedia.org/w/index.php?curid=11648572
By uncredited – Images from the History of Medicine (NLM) [1], Public Domain, https://commons.wikimedia.org/w/index.php?curid=11648572

2. Behcet’s disease

By Republic2011 - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=17715921
By Republic2011Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=17715921

3. Bell’s palsy

By http://wellcomeimages.org/indexplus/obf_images/69/f2/8d6c4130f4264b4b906960cf1f7e.jpgGallery: http://wellcomeimages.org/indexplus/image/M0011440.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36350600
By http://wellcomeimages.org/indexplus/obf_images/69/f2/8d6c4130f4264b4b906960cf1f7e.jpgGallery: http://wellcomeimages.org/indexplus/image/M0011440.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36350600

4. Brachial neuritis

5. Brain tumours

6. Carpal tunnel syndrome

7. Cerebral palsy (CP)

8. Cervical dystonia

9. Charcot Marie Tooth disease (CMT)

By http://wellcomeimages.org/indexplus/obf_images/66/09/4dfa424fe11bb8dc56b2058f04ba.jpgGallery: http://wellcomeimages.org/indexplus/image/V0026141.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36578490
By http://wellcomeimages.org/indexplus/obf_images/66/09/4dfa424fe11bb8dc56b2058f04ba.jpgGallery: http://wellcomeimages.org/indexplus/image/V0026141.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36578490

10. Chronic inflammatory demyelinating polyneuropathy (CIDP)

11. Cluster headache

12. Creutzfeldt-Jakob disease (CJD)

By Unknown - http://www.sammlungen.hu-berlin.de/dokumente/11727/, Public Domain, https://commons.wikimedia.org/w/index.php?curid=4008658
By Unknownhttp://www.sammlungen.hu-berlin.de/dokumente/11727/, Public Domain, https://commons.wikimedia.org/w/index.php?curid=4008658

13. Duchenne muscular dystrophy (DMD)

By G._Duchenne.jpg: unknown/anonymousderivative work: PawełMM (talk) - G._Duchenne.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9701531
By G._Duchenne.jpg: unknown/anonymousderivative work: PawełMM (talk) – G._Duchenne.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9701531

14. Encephalitis

15. Epilepsy

16. Essential tremor

17. Friedreich’s ataxia

By Unknown - http://www.uic.edu/depts/mcne/founders/page0035.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3960759
By Unknownhttp://www.uic.edu/depts/mcne/founders/page0035.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3960759

18. Frontotemporal dementia (FTD)

19. Guillain-Barre syndrome (GBS)

By Anonymous - Ouvrage : L'informateur des aliénistes et des neurologistes, Paris : Delarue, 1923, Public Domain, https://commons.wikimedia.org/w/index.php?curid=28242077
By Anonymous – Ouvrage : L’informateur des aliénistes et des neurologistes, Paris : Delarue, 1923, Public Domain, https://commons.wikimedia.org/w/index.php?curid=28242077

20. Hashimoto encephalopathy

21. Hemifacial spasm

22. Horner’s syndrome

By Unknown - http://ihm.nlm.nih.gov/images/B15207, Public Domain, https://commons.wikimedia.org/w/index.php?curid=19265414
By Unknownhttp://ihm.nlm.nih.gov/images/B15207, Public Domain, https://commons.wikimedia.org/w/index.php?curid=19265414

23. Huntington’s disease (HD)

https://en.wikipedia.org/wiki/George_Huntington#/media/File:George_Huntington.jpg
https://en.wikipedia.org/wiki/George_Huntington#/media/File:George_Huntington.jpg

24. Idiopathic intracranial hypertension (IIH)

25. Inclusion body myositis (IBM)

26. Kennedy disease

27. Korsakoff’s psychosis

28. Lambert-Eaton myasthenic syndrome (LEMS)

29. Leber’s optic neuropathy (LHON)

30. McArdles disease

31. Meningitis

32. Migraine

33. Miller-Fisher syndrome (MFS)

By J3D3 - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=34315507
By J3D3Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=34315507

34. Motor neurone disease (MND)

35. Multiple sclerosis (MS)

36. Multiple system atrophy (MSA)

37. Myasthenia gravis (MG)

38. Myotonic dystrophy

39. Narcolepsy

40. Neurofibromatosis (NF)

41. Neuromyelitis optica (NMO)

42. Neurosarcoidosis

43. Neurosyphilis

44. Parkinson’s disease (PD)

45. Peripheral neuropathy (PN)

46. Peroneal neuropathy

47. Progressive supranuclear palsy (PSP)

48. Rabies

49. Restless legs syndrome (RLS)

50. Spinal muscular atrophy (SMA)

51. Stiff person syndrome (SPS)

52. Stroke

53. Subarachnoid haemorrhage (SAH)

54. Tension-type headache (TTH)

55. Tetanus

56. Transient global amnesia (TGA)

57. Trigeminal neuralgia

58. Tuberous sclerosis

59. Wernicke’s encephalopathy

By J.F. Lehmann, Muenchen - IHM, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9679254
By J.F. Lehmann, Muenchen – IHM, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9679254

60. Wilson’s disease

By Carl Vandyk (1851–1931) - [No authors listed] (July 1937). "S. A. Kinnier Wilson". Br J Ophthalmol 21 (7): 396–97. PMC: 1142821., Public Domain, https://commons.wikimedia.org/w/index.php?curid=11384670
By Carl Vandyk (1851–1931) – [No authors listed] (July 1937). “S. A. Kinnier Wilson“. Br J Ophthalmol 21 (7): 396–97. PMC: 1142821., Public Domain, https://commons.wikimedia.org/w/index.php?curid=11384670

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The Neurology Lounge has a way to go to address all these diseases, but they are all fully covered in neurochecklists. In a future post, I will look at the rare end of the neurological spectrum and list the 75 strangest and most exotic neurological disorders.

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

What are the most controversial questions in neurology?

Uncertainty and doubt abound in Neurology. There are many evidence-free areas where experts rub each other the wrong way. These controversies are big and occur in all neurology subspecialties. Controversy-busters have tried for about a decade to iron out these wrinkles on neurology’s face, but the unanswered questions remain. This is why there is a 10th World Congress of Controversies in Neurology (CONy) holding in Lisbon this year.

I want to assure you I have no conflict of interest to declare in this blog. My interest is to explore  which questions have plagued this conference over the last 10 years to pick out the most controversial topics in neurology. To do this I reviewed all previous conference programs and focused on the items that were slated for debate. I looked for practical topics that have remained unresolved, or are just emerging. Here are my top controversial neurological questions:

Raccoon argument II. Tambako The Jaguar on Flikr. https://www.flickr.com/photos/tambako/7460999402
Raccoon argument II. Tambako The Jaguar on Flikr. https://www.flickr.com/photos/tambako/7460999402

 

1st CONy 2007 (Berlin, Germany)

  • Clinically isolated syndromes (CIS): To treat or not to treat
  • Is stem cell therapy an imminent treatment in advanced multiple sclerosis (MS)?
  • Vascular cognitive impairment is a misleading concept?
  • Is mild cognitive impairment a misleading concept?

 

2nd CONy 2008 (Athens, Greece)

  • Can physical trauma precipitate multiple sclerosis?
  • Should patients with Parkinson’s disease (PD) be treated in the pre-motor phase?
  • What is the first line therapy for chronic inflammatory demyelinating polyneuropathy (CIDP)?
  • Is intravenous immunoglobulin (IVIg) effective in chronic myasthenia gravis (MG)?
  • Tau or ß-amyloid immunotherapy in Alzheimer’s disease (AD)?
  • Chronic fatigue syndrome is an organic disease and should be treated by neurologists?

 

3rd CONy 2009 (Prague, Czech Republic)

  • Should cerebrospinal fluid (CSF) be tested in every clinically isolated syndrome?
  • Can we prevent multiple sclerosis (MS) by early vitamin D supplementation and EBV vaccination?
  • Does Parkinson’s disease (PD) have a prion-like pathogenesis?
  • Patients with medication overuse headache should be treated only after analgesic withdrawal?

 

 

4th CONy 2010 (Barcelona, Spain)

  • Camptocormia in parkinson’s disease (PD): Is this dystonia or myopathy?
  • Does chronic venous insufficiency play a role in the pathogenesis of multiple sclerosis (MS)?
  • IVIg or immunosuppression for long-term treatment of CIDP?

 

5th CONy 2011 (Beijing, China)

  • Is sporadic Parkinson’s disease etiology predominantly environmental or genetic?
  • Is multiple sclerosis (MS) an inflammatory or a primarily neurodegenerative disease?
  • Are the new multiple sclerosis oral medications superior to conventional therapies?
  • Is bilateral transverse venous sinus stenosis a critical finding in idiopathic intracranial hypertension (IIH)?

 

6th CONy 2012 (Vienna, Austria)

  • Will there ever be a valid biomarker for Alzheimer’s disease (AD)?
  • Is amyloid imaging clinically useful in Alzheimer’s disease (AD)?
  • Do functional syndromes have a neurological substrate?
  • Should blood pressure be lowered immediately after stroke?
  • Migraine is primarily a vascular disorder?

 

 

7th CONy 2013 (Istanbul, Turkey)

  • Is intravenous thrombolysis the definitive treatment for acute large artery stroke?
  • Atrial fibrillation related stroke should be treated only with the new anticoagulants?
  • Is the best treatment for chronic migraine botulinum toxin?
  • IS CGRP the key molecule in migraine?
  • Is chronic cluster headache best treated with sphenopalatine ganglion (SPG) stimulation?
  • When should deep brain stimulation (DBS) be initiated for Parkinson’s disease?
  • Do interferons prevent secondary progressive multiple sclerosis (SPMS)?
  • Is deep brain stimulation (DBS) better than botulinum toxin in primary dystonia?
  • Are present outcome measures relevant for assessing efficacy of disease modifying therapies in multiple sclerosis (MS)?
  • Should radiologically isolated syndromes (RIS) be treated?
  • Does genetic testing have a role in epilepsy management?
  • Should cortical strokes be treated prophylactically against seizures?
  • Should enzyme-inducing antiepileptic drugs (AEDs) be avoided?
  • EEG is usually necessary when diagnosing epilepsy

 

8th CONy 2014 (Berlin, Germany)

  • Is late-onset depression prodromal neurodegeneration?
  • Does Parkinson’s disease begin in the peripheral nervous system?
  • What is the best treatment in advanced Parkinson’s disease?
  • Are most cryptogenic epilepsies immune mediated?
  • Should epilepsy be diagnosed after the first unprovoked seizure?
  • Do anti-epileptic drugs (AEDs) contribute to suicide risk?
  • Should the ketogenic diet be prescribed in adults with epilepsy?
  • Do patients with idiopathic generalized epilepsies require lifelong treatment?
  • Cryptogenic stroke: Immediate anticoagulation or long-term ECG recording?
Southern Chivalry: Argument Vs Clubs. elycefeliz on Flikr. https://www.flickr.com/photos/elycefeliz/6271932825
Southern Chivalry: Argument Vs Clubs. elycefeliz on Flikr. https://www.flickr.com/photos/elycefeliz/6271932825

 

9th CONy 2015 (Budapest, Hungary)

  • Is discontinuation of disease-modifying therapies safe in  long-term stable multiple sclerosis?
  • Is behavioral therapy necessary for the treatment of migraine?
  • Which is the first-line therapy in cases of IIH with bilateral papilledema?
  • Should patients with unruptured arterio-venous malformations (AVM) be referred for intervention?
  • Should survivors of hemorrhagic strokes be restarted on oral anticoagulants?
  • Will stem cell therapy become important in stroke rehabilitation?
  • Do statins cause cognitive impairment?

 

10th CONy 2016 (Lisbon, Portugal)

  • Which should be the first-line therapy for CIDP? Steroids vs. IVIg
  • Should disease-modifying treatment be changed if only imaging findings worsen in multiple sclerosis?
  • Should disease-modifying therapies be stopped when secondary progressive MS develops?
  • Should non-convulsive status epilepsy be treated aggressively?
  • Does traumatic chronic encephalopathy (CTE) exist?
  • Does corticobasal degeneration (CBD) exist as a clinico-pathological entity?
  • Is ß-amyloid still a relevant target in AD therapy?
  • Will electrical stimulation replace medications for the treatment of cluster headache?
  • Carotid dissection: Should anticoagulants be used?
  • Is the ABCD2 grading useful for clinical management of TIA patients?
  • Do COMT inhibitors have a future in treatment of Parkinson’s disease?

 

Debate Energetico. Jumanji Solar on Flikr. https://www.flickr.com/photos/jumanjisolar/5371921203
Debate Energetico. Jumanji Solar on Flikr. https://www.flickr.com/photos/jumanjisolar/5371921203

 

Going through this list, I feel reassured that the experts differ in their answers to these questions? The acknowledgement of uncertainty allows us novices to avoid searching for non-existent black and white answers. It is however also unsettling that I thought some of these questions had been settled long ago. It goes to show that apparently established assumptions are not unshakable?

Do you have the definitive answers to resolve these controversies? Are there important controversies that are missing here? Please leave a comment

 

Are magnets transforming neurological practice?

The armoury of the neurologist is traditionally a cocktail of tablets and injections. The neurosurgeons and neuroradiologists seem to have all the fancy gadgets. This may however be changing with techniques that are gradually creeping into neurological practice. One such technique is transcranial magnetic stimulation (TMS). This is a non-invasive method of stimulating specific parts of the brain using a magnetic field generator or coil.

"Transcranial magnetic stimulation" by Eric Wassermann, M.D. - Wassermann, Eric. Transcranial Brain Stimulation. Behavioral Neurology Unit. National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States Department of Health and Human Services. Archived from the original on 2013-10-29. Retrieved on 2013-10-29.. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:Transcranial_magnetic_stimulation.jpg#/media/File:Transcranial_magnetic_stimulation.jpg
“Transcranial magnetic stimulation” by Eric Wassermann, M.D. – Wassermann, Eric. Transcranial Brain Stimulation. Behavioral Neurology Unit. National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States Department of Health and Human Services. Archived from the original on 2013-10-29. Retrieved on 2013-10-29.. Licensed under Public Domain via Commons – https://commons.wikimedia.org/wiki/File:Transcranial_magnetic_stimulation.jpg#/media/File:Transcranial_magnetic_stimulation.jpg

 

The classical neurological application of TMS is in the treatment and prevention of migraine. The role of TMS in migraine has been fairly well-studied although the impact on symptoms is modest. There is however enough evidence to convince the National Institute of Health and Care Excellence to issue NICE guidelines on TMS. These, as expected, prescribed hope and caution in equal measure.

A potential application of TMS is in Parkinson’s disease. A recent systematic review and meta-analysis in JAMA Neurology is fairly convincing that TMS improves the motor symptoms of Parkinson’s disease

"Basal ganglia in treatment of Parkinson's" by Mikael Häggström, based on image by Andrew Gillies/User:Anaru - Derivative of File:Basal ganglia circuits.png. Licensed under CC BY-SA 3.0 via Commons - https://commons.wikimedia.org/wiki/File:Basal_ganglia_in_treatment_of_Parkinson%27s.png#/media/File:Basal_ganglia_in_treatment_of_Parkinson%27s.png
“Basal ganglia in treatment of Parkinson’s” by Mikael Häggström, based on image by Andrew Gillies/User:Anaru – Derivative of File:Basal ganglia circuits.png. Licensed under CC BY-SA 3.0 via Commons – https://commons.wikimedia.org/wiki/File:Basal_ganglia_in_treatment_of_Parkinson%27s.png#/media/File:Basal_ganglia_in_treatment_of_Parkinson%27s.png

What of TMS as a cognitive enhancer? I came across the report that TMS may boost memory in Gizmag. OK it’s not a neurology journal but it made a more exciting headline than the original study published in Science  under the elusive title targeted enhancement of cortical-hippocampal brain networks and associative memory. In simple language, TMS may enhance the neural networks in the hippocampus, the brains memory hub. Whilst the study was carried out in people with normal memory, there are implications for cognitive disorders such as Alzheimer’s disease if the potential and promise of TMS are realised.

"Magnet0873" by Newton Henry Black - Newton Henry Black, Harvey N. Davis (1913) Practical Physics, The MacMillan Co., USA, p. 242, fig. 200. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:Magnet0873.png#/media/File:Magnet0873.png
“Magnet0873” by Newton Henry Black – Newton Henry Black, Harvey N. Davis (1913) Practical Physics, The MacMillan Co., USA, p. 242, fig. 200. Licensed under Public Domain via Commons – https://commons.wikimedia.org/wiki/File:Magnet0873.png#/media/File:Magnet0873.png

 

A further surprising application of TMS, potential of course, is in dyslexia. This is an emerging field, still under investigation, but imagine the potential this will unleash! There is a helpful review article in Neuroimmunology and Neuroinflammation which discusses the role of rapid rate TMS in the treatment of dyslexia.

"Dislexia nens" by cuidado infantil - cuidadoinfantil.net. Licensed under CC BY-SA 3.0 via Wikimedia Commons - https://commons.wikimedia.org/wiki/File:Dislexia_nens.jpg#/media/File:Dislexia_nens.jpg
“Dislexia nens” by cuidado infantil – cuidadoinfantil.net. Licensed under CC BY-SA 3.0 via Wikimedia Commons – https://commons.wikimedia.org/wiki/File:Dislexia_nens.jpg#/media/File:Dislexia_nens.jpg

 

We’re not quite there yet but there is hope for the neurological arsenal; who knows, we may soon dispense with all these difficult to swallow pills and cumbersome to deliver injections!

 

Medicine 01 by Taki Steve on Flikr. https://www.flickr.com/photos/13519089@N03/4746653392
Medicine 01 by Taki Steve on Flikr. https://www.flickr.com/photos/13519089@N03/4746653392

Interested in delving deeper into TMS?

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