Final day of ANA 2015- Prions center stage

It was the final day of the American Association of Neurology (ANA) conference yesterday and prion diseases took center stage. John Collinge, the only prominent British presence at the conference, set the ball rolling with insights into the potential treatment of CJD with anti-PrP monoclonal antibodies.

"Prion subdomain-colored sec structure" by Cornu (talk) 19:04, 5 June 2009 (UTC) - Own work. Licensed under CC BY 2.5 via Commons.
Prion subdomain-colored sec structure” by Cornu (talk) 19:04, 5 June 2009 (UTC) – Own work. Licensed under CC BY 2.5 via Commons.

 

But it wasn’t the day for traditional prion diseases as speaker after speaker took the stage to claim prion pathology for other neurodegenerative diseases; and not just Parkinson’s disease (PD) or multiple system atrophy MSA. Neil Cashman gave an excellent talk on propagated misfolding (what a buzzword) in SOD1 motor neurone disease (MND) and also hinted at potential treatment with antibodies. Marc Diamond looked at tau prions and how their spread may be tracked by FRET-based biosensor cell assay (a mouthful).

J Paul Taylor looked at the role of RNA binding proteins (RBPs) in several neuodegenerative diseases including MND and frontotemporal dementia (FTD). And yes, these RBPs show prion-like activity.

There was an interesting case-based session on chronic traumatic encephalopathy (CTE). This was led by Jeffrey Kutcher, possibly the foremost authority on this neurodegenerative condition. I learnt that CTE is a post-mortem diagnosis and that in life the diagnosis should be restricted to traumatic encephalopathy syndrome (TES).

"Blausen 0836 Stroke" by Blausen Medical Communications, Inc. - Donated via OTRS, see ticket for details. Licensed under CC BY 3.0 via Wikimedia Commons.
Blausen 0836 Stroke” by Blausen Medical Communications, Inc. – Donated via OTRS, see ticket for details. Licensed under CC BY 3.0 via Wikimedia Commons.

 

The day was rounded up by two excellent debates on stroke treatment. Marc Chimowitz took on Graeme Hankey on the comparative advantages of dual and single antiplatelets for secondary stroke prevention; it was the battle of the lumpers versus the splitters and it was probably a draw. Jeffrey Saver was however the clear winner over Colin Derdeyn by arguing for the combined use of thrombolysis and thrombectomy, rather than thromectomy alone.

 

 

6 buzzwords from day 2 ANA Chicago 2015

Chicago at night
Chicago at night

 

Its day 3 about to start at the American Neurological Association (ANA) annual conference. As a follow up tp my previous posts, this is a quick take on 6 new buzzwords for me from day 2. These are at the cutting edge of neurology

  • Metagenomic deep sequencing. This promises to solve the pervasive problem of undiagnosed encephalitis and meningitis. James Wilson’s talk was heavy; here is a link to an abstract which hopefully simplifies things
  • Neuroprosthesis. The future of re-animation of paralysed limbs after spinal cord injury. Hunter Peckam’s website
  • Brain-machine interface. Krishna Shinoy presentation seems more SciFi than neurology. Harnessing the power of the will to communicate. Here he is explaining things

https://www.youtube.com/embed/I7lmJe_EXEU” target=”_blank”>

 

  • Neurofascin and Contactin-1 antibodies. Just a few more antibodies to muddy the waters of immune-mediated neuropathies. Cutting edge review by Alan Pestronk of NeuroWUSTL fame
  • Sequestosome and Matrin-3 syndromes of adult onset myopathies. No wonder many of our cases go undiagnosed. Margherita Milone‘s talk went slightly over my head but my gut feeling says this is important
  • Mitophagy. Another culprit process contributing to traffiking problems in motor neurone disease. Teepu Siddique was erudite

MS risk factors: the top 6

Before day 2 commences, a quick word on a wonderful symposium on Multiple Sclerosis (MS).

 

"Journal.pone.0057573.g005" by Veela Mehta, Wei Pei, Grant Yang, Suyang Li, Eashwar Swamy, Aaron Boster, Petra Schmalbrock, David Pitt - Mehta V, Pei W, Yang G, Li S, Swamy E, et al. (2013) Iron Is a Sensitive Biomarker for Inflammation in Multiple Sclerosis Lesions. PLoS ONE 8(3): e57573. doi:10.1371/journal.pone.0057573. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057573#pone-0057573-g005. Licensed under CC BY 2.5 via Wikimedia Commons.
Journal.pone.0057573.g005” by Veela Mehta, Wei Pei, Grant Yang, Suyang Li, Eashwar Swamy, Aaron Boster, Petra Schmalbrock, David Pitt – Mehta V, Pei W, Yang G, Li S, Swamy E, et al. (2013) Iron Is a Sensitive Biomarker for Inflammation in Multiple Sclerosis Lesions. PLoS ONE 8(3): e57573. doi:10.1371/journal.pone.0057573. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057573#pone-0057573-g005. Licensed under CC BY 2.5 via Wikimedia Commons.

 

MS epidemiologists and researchers dissected the topic Causes/Triggers of MS. Speakers were David Hafler, Alberto Aschiero, Lisa Barcellos and Larry Steinman. And the top 6 are

  • Genetics
  • Tobacco smoking

 

smoking

  • Vitamin D deficiency

 

milk-33603_1280

 

  • EBV infection
  • Overweight in early age
  • High salt intake

 

salt-653072_1280

 

 

I suggested to David we should only be looking for correlation rather than causation (an idea I picked up from a great book Big Data).


He strongly disagreed! He believes genome wide association studies (GAS) have confirmed the cause for MS. I think the search for a definite cause is probably futile but we define cause flexibly. Alberto made the point that even if all the known risk factors were eliminated, MS will still be very prevalent

 

ANA 2015-Five new things

If you missed my blog on Klotho, you should check it out first before continuing. Below are the other four new things I learnt on the first full day of the American Neurological Association meeting, Chicago 2015:

 

The Magnificent Mile, Chicago
The Magnificent Mile, Chicago
  1. BIN1 is the second commonest monogenic genetic cause of Alzheimer’s disease (AD). And I never even heard of BIN1 before today. Work by Erik Roberson
  2. LINGO 1 is probably the only gene established to be associated with Essential Tremor (ET). Presentation by Ludy Shih
  3. FLAIR* MRI imaging of Multiple Sclerosis (MS) shows either a centripetal or centrifugal pattern of inflammatory lesions with serious implications to prognosis. Work by Daniel Reich of NINDS
  4. Diabetic peripheral neuropathy is a result of the metabolic syndrome; research by Lucy Hinder in mice suggests this is potentially reversible

Klotho, the elixir of life

It’s the American Neurological Association‘s 140th Annual meeting in Chicago this weekend and my first attendance. It is holding at the grand Marriott Hotel on The Magnificent Mile.

Chicago
Chicago

It is a rigorously academic meeting and the highlight for me on the first day is the presentation by the Gross Awardee, Dena Dubal, on the longevity protein Klotho. Heterozygote variants of its gene appears to confer longevity, enhance cognition, and prevent neurodegenerative diseases. It’s almost too good to be true- but her research is practically faultless.

Dena Dubal. Attribution to Christopher Michel on Flikr https://www.flickr.com/photos/cmichel67/18448440110
Dena Dubal. Attribution to Christopher Michel on Flikr https://www.flickr.com/photos/cmichel67/18448440110

‘What happens if one has the homozygote variant?’ she was asked during Q and A. Unfortunately and paradoxically a double dose of the variant results in faster aging!

Her lab’s site has more to say on her research into aging and neuroscience-well worth bookmarking.

 

Parkinson’s disease-a few curious things

Quite a few neurological disorders remain mysteries even when we know so much about them. Parkinson’s diseases (PD) is one of them. Dopamine deficiency is the established final common pathway, but why this deficiency presents in different ways is unclear. PD variants such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and Lewy body disease (LDB) have distinct clinical features to confound any common cause. What then causes dopamine deficiency in the first place?

Substantia nigrai in PD. By Werner CJ., Heyny-von Haussen R., Mall G., Wolf S. [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons
Substantia nigrai in PD. By Werner CJ., Heyny-von Haussen R., Mall G., Wolf S. [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)%5D, via Wikimedia Commons

One link researchers are looking at is the possibility of a pathogen travelling up to the brain from the gut via the vagus nerve. This report from the Annals of Neurology suggests this hypothesis; the researchers found a reduced risk of PD in patients who have had the main trunk of the vagus nerve severed (vagotomy). For more details see a full analysis of the study here.

 

PD PET scan image.By Jens Maus (http://jens-maus.de/) - Own work. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:PET-image.jpg#/media/File:PET-image.jpg
PD PET scan image.By Jens Maus (http://jens-maus.de/) – Own work. Licensed under Public Domain via Commons – https://commons.wikimedia.org/wiki/File:PET-image.jpg#/media/File:PET-image.jpg

 

Clearly we can’t recommend vagotomy to our at-risk PD patients, and neither can we recommend gout! Yes, studies have suggested that PD patients have a low uric acid level, and this predates the disease onset. Another study takes things further to suggest that uric acid is neuroprotective because of its antioxidant effect. This long list of PubMed abstracts shows the proliferating research into uric acid.

 

Uric acid crystals. By cnicholsonpath (Uric acid) [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons
Uric acid crystals. By cnicholsonpath (Uric acid) [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)%5D, via Wikimedia Commons

And finally, again from the Annals of Neurology, is a paper reporting increased creativity in people with PD on dopamine replacement treatment. The study compares people with PD on treatment to control subjects. It is however not clear if the creativity is a feature of PD, or of its treatment.

Just a few curious things

=========================================================================

neurochecklists-image

Gluten neurology-persistent and growing?

Gluten neurology is a controversial issue, to say the least! The heated debates between Sheffield and Nottingham may lie in the fog of history, but the issue simmers just below the surface. Gluten sensitivity, or coeliac disease, is a big time player in other body systems, but its neurological manifestations are clouded in mystery.

Wheat: Gluten-rich "Wheat close-up" by User:Bluemoose - Own work. Licensed under ">CC BY-SA 3.0 via Wikimedia Commons.
Wheat: Gluten-rich
Wheat close-up” by User:BluemooseOwn work. Licensed under CC BY-SA 3.0 via Wikimedia Commons.

 

A lot of papers have ‘confirmed‘ a variety of neurological disorders associated with gluten sensitivity. These include even rare conditions such as progressive ataxia with palatal tremor. Other researchers have however struggled to find any relationship between gluten sensitivity and either ataxia or neuropathy.

Gluten neurology however keeps marching on, and the latest is gluten psychosisA single case report it is, published in Nutrients. And it brings the total number now to …2.

The debate goes on. In the meantime, it may just be prudent to check anti-gliadin antibodies in people with undiagnosed neurological conditions… before they are labelled idiopathic.

By Kurt Stueber - www.biolib.de, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7487
By Kurt Stueber – www.biolib.de, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7487

 

What is the value of celebrity neurology?

It is always headlines when a celebrity comes out with, or dies of, any disease. The disease often gets a boost, its profile raised high. We saw this with the ‘Jade Goody effect‘ which boosted cervical cancer screening. The same occurred with the ‘Angelina Jolie effect‘ which improved the provision of breast cancer services.

Angelina Jolie
Angelina Jolie

The celebrity effect also works in Neurology, although never as successfully as the examples above. Some single-minded neurology celebrities have tackled their diseases head-on, often by funding research. This is the case with the Michael J. Fox Foundation and Parkinson’s disease (PD).

Michael J Fox
Michael J Fox

The celebrity may support a charity on account of a family member with a condition such as JK Rowling aiding the Multiple Sclerosis Society in Scotland on behalf of her mother who had the disease; unfortunately they eventually fell out.

Most recently we learnt that Robin Williams had Lewy Body disease a variant of Parkinson’s disease, and he probably died from the hallucinations common in this disorder. Will this boost the profile Lewy body diseases? Will it improve research into its risk factors and treatment?

Robin Williams
Robin Williams

Sometimes its a celebrity event that does the trick. The ice bucket challenge raised millions for MND. The celebrity endorsements for the campaign was a boost for those fighting to eliminate the disease. And one of the best clips is of Benedict Cumberbatch-worth a look!

https://www.youtube.com/embed/YOa7ZjxRuKM” target=”_blank”>

But how valuable is a one-off benefit such as this? A lot it seems going by the MND Association feedback-£7m is not to be scoffed at!

On the theme of MND we see the example of a celebrity ‘endorsement’ of a different type. Stephen Hawking, the world-renowned theoretical physicist, has not been particularly bullish in his support of MND but his biopic, The Theory of Everything, has had an interesting effect;

https://www.youtube.com/embed/Salz7uGp72c” target=”_blank”>

A grandfather made a self-diagnosis of MND after watching the film. Talk of celebrity influence!

What of naming nerve cells after celebrities? Yes indeed. Heard of the Jennifer Aniston neuron? Neuroscientists have discovered that individual nerve cells learn to recocgnise specific faces, and Jennifer’s was a face they used in their trials. A lot of good it has done for her, but a clever way for neuroscience to embed their lesson in our minds; a very good use of celebrity.

By Angela George, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=6044960
By Angela George, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=6044960

Which other celebrities with neurological diseases have raised the profile of their condition, or influenced it, in any way at all? The subject for a blog sequel!

_________________________________________________________________________

neurochecklists-image

Bee venom acupuncture for PD?

 

Yes you heard it right-potential benefit from bee venom acupuncture in Parkinson’s disease (PD). What next you may say? But breathe easy, its from a study form the Journal of Alternative and Complementary Medicine. The treatment, in addition to conventional PD treatment, shows significant improvements in gait speed, PDQL score, and activities of daily living.

 

 

I am not sure I will be in a hurry to send my patients for this unconventional treatment based on a this open labelled, prospective, uncontrolled study of 11 subjects.

_________________________________________________________________________

neurochecklists-image

Head transplant, anyone?

Coming near you soon, a maverick performing human head transplantation. The idea of head transplantation has a long history. Performing it in humans however is a different kettle of fish.The present day advocate is an Italian neurosergeon Sergio Canavero. He has passionately championed the idea and you should listen to him here at a TED talk.

https://www.youtube.com/embed/FmGm_VVklvo” target=”_blank”>

His attempts have however not convinced the American Neurosurgeons who rebuffed his attempts to involve them. Who would be the guinea pig for Dr Canavero! There is already a patient waiting eagerly, and these journalists discuss the layman’s view of the patient’s perspective.

https://www.youtube.com/embed/pJOQx6XNh-Y” target=”_blank”>

 

A pacesetter or a crank? Too early to pass judgment but history shows that the scientific establishment repeatedly resists ground-breaking progress: remember in-vitro fertilization, antibiotics for peptic ulcer etc? I recently reviewed two books on my other blog, thedoctorsbookshelf.com, and both books, The Rise and Fall of Modern Medicine and Bad Medicine, cite several examples of this type of institutional conservatism. Reassuringly not everyone is dismissing him and some are already talking the ethics of head transplantation.

Canevaro on the other hand seems to have done his homework well. Gauging by this paper which reviews the planned protocol he is taking the matter seriously. And this newspaper article suggests a team will be set to go in 2017!

We have to watch this space.

_________________________________________________________________________

neurochecklists-image