Thursday, 29 March 2012

c-MAF transcription factor and touch

Level: 3+

Wende et al. The transcription factor c-Maf controls touch receptor development and function. Science. 2012 Mar 16;335(6074):1373-6.

The sense of touch relies on detection of mechanical stimuli by specialized mechanosensory neurons.  This study shows that the transcription factor c-Maf/c-MAF is crucial for mechanosensory function in mice and humans. The development and function of several rapidly adapting mechanoreceptor types are disrupted in c-Maf mutant mice. In particular, Pacinian corpuscles, a type of mechanoreceptor specialized to detect high-frequency vibrations, are severely atrophied. In line with this, sensitivity to high-frequency vibration is reduced in humans carrying a dominant mutation in the c-MAF gene. This work identifies a key transcription factor specifying development and function of mechanoreceptors and their end organs.

"In humans, dominant c-MAF mutations are associated with ocular developmental abnormalities and cataracts, but their effects on mechanosensation have not been examined. Encouraged by our results in mice, we tested touch sensitivity in a family comprising four carriers of the dominant Arg288→Pro288 (R288P) c-MAF mutation. This mutation in the auxiliary DNA binding domain interferes with c-MAF–dependent transcriptional activation but does not eliminate c-MAF function and represents one of three known cataract-causing point mutations in c-MAF. To assess the function of Meissner and Pacinian corpuscles, we tested vibrotactile acuity over a wide range of frequencies (5 to 240 Hz). Pacinian corpuscles are essential for the detection of small-amplitude high-frequency vibrations. We observed a large increase in the vibration amplitude required to elicit responses in c-MAF mutant carriers at high but not low frequencies. Tactile spatial acuity, that is, the ability to distinguish grids of different spacing, is thought to depend on hair follicle afferents/Meissner corpuscles/Merkel cell-neurite complexes and was not significantly changed. Thus, the R288P c-MAF mutation interferes with normal vibration detection in humans."

Additional reading:  Pacinian corpuscles

Integrative Approaches to Developing Therapeutics for Neurodegenerative Diseases

Young Life Scientists' Symposium
24th August 2012. Cardiff, UK

Neurodegenerative Diseases, such as Alzheimer’s Disease, Parkinson’s Disease and Huntington’s Disease, are becoming increasingly common in our ageing population. Young and early-career researchers all over the country are dedicating their work to understanding and combating these devastating diseases .Integrating our knowledge from every approach is the next step towards fully understanding and treating these diseases.

The focus of this unique symposium is to integrate ALL approaches to researching neurodegenerative diseases, with an overall aim to informing the development of therapeutics. All PhD students and early-career Post-Docs from every school working on neurodegenerative disease are welcome to attend. Researchers based in Psychology, Pharmacy, Physiology, Neuroscience, Biology, Biochemistry, Genetics, Behavioural Neuroscience, Medicine, Physiotherapy, Imaging and the Social Sciences are all encouraged to attend and share their work.

For more information about this symposium and to register, please visit our website: 

Wednesday, 28 March 2012

Evolutionary medicine: prehistoric proteins

Level: 3+

For those interested in the molecular cogs that underpin evolution this article is a must:

This work shows that evolution also relies on random events; I would be very interested to see this type of work done on ion channels. 

Tuesday, 27 March 2012

Seminar: antisense approaches as a therapy for muscular dystrophy

Wednesday 28th March 2012, 13:15 – 14:15
Perrin Lecture Theatre, 4 Newark Street, Whitechapel
Lunch will be provided
University College London  

“Antisense approaches as a therapy for muscular dystrophy”

Professor Muntoni graduated in Medicine in Italy in 1984 and obtained his specialization in Child Neurology and Psychiatry in 1989. Since 1993 he has worked in London, initially as a Lecturer (1993); Senior Lecturer (1994); Reader (1996) and Professor of Paediatric Neurology at the Hammersmith Hospital, Imperial College. In 2007 he moved the clinical, pathology and academic group from Imperial College to UCL Institute of Child Health and Great Ormond Street Hospital for Children. He is director of the Dubowitz Neuromuscular Centre, leading national and international centre for the diagnosis, management, treatment and experimental research therapy development in childhood neuromuscular disorders. The Centre has very close clinical and academic links with the adult neuromuscular centre at the Institute of Neurology, also at UCL.


1) Cirak S et al. Exon skipping and dystrophin restoration in Duchenne Muscular Dystrophy patients after systemic phosphorodiamidate morpholino oligomer treatment. The Lancet, 2011;378:595-605.
2) Cirak S et al .Restoration of the Dystrophin-associated Glycoprotein Complex After Exon Skipping Therapy in Duchenne Muscular Dystrophy. Mol Ther. 2011 Nov 15
3) Anthony K et al. Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials. Brain. 2011 Dec;134(Pt 12):3544-56.
4) Kinali M et al. Local Restoration of Dystrophin Expression in Duchenne Muscular Dystrophy: A Single Blind, Placebo-controlled Dose Escalation Study Using Morpholino Antisense Oligomer AVI-4658. Lancet Neurol. 2009 8(10):918-28.
Coordinator: Professor Dean Nizetic

Making connections - the human connectome project

Level: 3+

You may be interested in the flowing news feature: 

Jon Bardin. Making Connections. Nature 2012;483:394-6.

"The network, dubbed the 'connectome', is a web of nerve-fibre bundles that criss-cross the brain in their thousands and form the bulk of the brain's white matter. It relays signals between specialized regions devoted to functions such as sight, hearing, motion and memory, and ties them together into a system that perceives, decides and acts as a unified whole...."

The Human Connectome Project is an a initiative to map this network!

Saturday, 24 March 2012

Case study: horizontal diplopia

A 32-year woman presents with horizontal double vision on looking to the left. It is noted that her right eye fails to adduct and that there is nystagmus in the left eye. The remainder of her neurological examination is normal except for bilaterally upgoing plantar responses, i.e. bilaterally positive Babinski responses.

Level 1
What is the differential diagnosis?
Describe the neuroanatomy of horizontal eye movements?
Why does she not have a 3rd nerve palsy?
What is the significance of the the upgoing plantar responses?

Level 2
What investigations would you do?

Level 3
Why does she have nystagmus in the abducting left eye?
What happens to convergence?

Monday, 19 March 2012

The split brain: left brain vs. right brain

Level 3

When I was in high school I read the first edition of "Left brain right brain" which is now in its 5th edition. This is one of the books that kindled my interest in neuroscience and was a fascinating read. Last week's Nature has a news feature on this topic, which I recommend you read:

David Wolman. The split brain: A tale of two halves. Nature 2012;483:260-263.

The article discusses the seminal observations made on studying patients who had their corpus callosums cut to control epilepsy. This procedure has now been abandoned and the patients who had this procedure done are now old; research on this cohort is coming to an end.  However, the insights from studying these patients have been seminal; for example blind-sight, responding to stimuli that are are not conciosuly perceived and a large number of the disconnection syndromes. 

The following is a figure that summarises the experimental paradigm that is used to study the split brain patients.

Similalry, you may want to catch the last weeks Horizon, "Out of control", on the BBC iPlayer. A lot of what is discussed in this episode is relevant to the split brain; for example blind-sight is discussed in detail. 

Wednesday, 14 March 2012

Evolutionary neurology: depth perception

Level 3+

Jumping spiders jump long distances to catch their prey. This require accurate depth perception. Nagata and colleagues show that jumping spiders use a process called image defocus, which allows depth perception through the comparison of a unfocused image to a focused image within the same eye. A single layer within the spider's eye that could not focus green light nevertheless contained a green sensitive pigment; therefore this layer always receives an unfocused image, while other layers receive images in focus. Spiders are accurate jumpers in green light, but jump short of their target in red light.  

Please see original article and perspective:

Nagata et al. Depth Perception from Image Defocus in a Jumping Spider. Science 27 January 2012: 469-471.

Herberstein & Kemp. A Clearer View from Fuzzy Images. Science 27 January 2012: Vol. 335 no. 6067 pp. 409-410 

"Why is this relevant to neurology? It is an example of convergent evolution; i.e. nature has invented the means of assessing depth several times; it is obviously an important trait. Man mainly uses binocular vision to judge depth; the physical phenomenon is parallax.

Some questions to make you think:
  1. How does someone with uniocular vision or an amblyopic eye judge depth? 
  2. What symptoms would someone with a lack of depth perception complain of?
  3. Is it an important sensory attribute? 
  4. What are the DVLA rules in relation to driving regulations concerning impaired depth perception? 
All these questions should be relevant to someone studying neurology."

Monday, 12 March 2012

Assessing vertigo

Level 1

Benign paroxysmal positional vertigo or BPPV is the most common vestibular problem in adulthood. Patients will present with vertigo - the sensation of either the room or their head spinning - typically worse on head movements. They (or a significant other) may have noticed nystagmus and this can provoke referral to many different specialities. See this YouTube video for common presentations and the underlying pathology:

We each have two sets of semi-circular canals. The diagram to the left shows a schematic diagram of one. The three canals are oriented at 90 degrees to each other, providing information about head movement in any axis. For more information on the anatomy, see the following YouTube video:

The Hallpike manoeuvre (or Dix-Hallpike Test) is a simple and useful addition the arsenal of clinical tests for many clinicians, including Neurologists, ENT surgeons, GPs, Geriatricians and A&E doctors. We would encourage medical students to learn about it. A Hallpike manoeuvre is positive when it provokes nystagmus (as witnessed by the examiner) and vertigo (as felt by the patient) - this is strongly suggestive that the underlying diagnosis is BPPV.

The manoeuvre was first described in M. R. Dix and C. S. Hallpike: The pathology, symptomatology and diagnosis of certain common disorders of the vestibular system. The Annals of Otology, Rhinology and Laryngology, December 1952, 61 (4): 987-1016. For more modern guidance on the details of the test, see The British Society of Audiology's guidance.

The importance of the test is all the more apparent as a positive test indicates the presence of posterior canal BPPV; negating the need for further cli tests and offering the potential for an easy treatment in the form of the Epley manoeuvre:

For one more video covering the Hallpike and Epley, click here