Keeping up with the latest practical guidelines in neurology

Neurologists breathe guidelines. And they churn them out at a breathtaking pace. It is extremely difficult keeping up with what’s in, what’s out, and what’s back in again! Often the new guidelines add nothing new, or the important points are buried in sheafs of text justifying the guidelines.

But we can’t get away from them. How then do neurologists keep up, short of becoming paranoid? By becoming obsessive! In developing neurochecklists I had no idea keeping up with the guidelines would be a challenging task because they are released in quick succession. I have looked back to see which are the latest practical guidelines, released in the last 12 months or so. Here they are by disease… but be quick before the guideline-masters revise them…again!

Epilepsy

The American Academy of Neurology (AAN) and the American Epilepsy Society published their 1st seizure management guidelines in Neurology. Among the key recommendations are to inform patients of a 2-year recurrence risk of 21-45%, and that a nocturnal seizure is among the usual culprits that increase the risk. The vexing question of whether to treat a 1st unprovoked seizure remains that-vexing.

Not to be outdone, the International League Against Epilepsy (ILAE) released it’s evidence-based guidelines and recommendations for the management of infantile seizures. Published in Epilepsia in late 2015, it shows that Levetiracetam is tops for both focal and generalised seizures. It also confirmed the  hard-earned place of Stiripentol alongside Valproate and Clobazam for Dravet syndrome. It is open access so well-worth a detailed look.

 

Duchenne muscular dystrophy (DMD)

Steroids are now standard treatment in Duchenne’s muscular dystrophy (DMD). A recent practice guideline update on corticosteroids in Duchenne’s highlights this, and it also indicates the strength of evidence for the different benefits. There is Level B evidence that steroids improve strength and lung function, and Level C for  delaying scoliosis and cardiomyopathy. Enough to encourage any doubters out there.

Facio-scapulo-humeral muscular dystrophy (FSHD)

Not one I thought had guidelines, but this FSHD diagnosis and management guidelines turned out to be quite useful. The guidelines address four key areas-diagnosis, predictors of severity, surveillance for complications, and treatment. And if you like flow charts, there is an excellent one here. A lot of helpful tips here for example, subjects with large D4Z4 gene deletions are more prone to earlier and more severe disability, and these patients should be reviewed by a retinal specialist.

Multiple sclerosis (MS) 

Multiple sclerosis (MS) is one of the most shifty conditions when it comes to guidelines, both diagnostic and management. Take the latest NICE MS guidelines, 39 pages long. All sensible stuff mind you, with time-restricted targets such as 6 weeks for a post-diagnosis follow-up, and 2 weeks to treat a relapse. Mind you, just to keep neurologists on their toes!

MS diagnosis and follow up is often the game of counting lesions on MRI scans. The question of what to count, and when to do so, is addressed in the recent MAGNIMS MS consensus guidelines. More recommendations than guidelines, these did not challenge the sacrosanct MacDonald criteria for dissemination in time, but tinker with dissemination in place. They suggest, for example, that optic nerve lesions be counted. The MAGNIMS consensus guidelines on the use of MRI goes on to stipulate when and how to count lesions throughout the course of MS. Not an easy bedtime read.

Not far behind MAGNIMS, the Association of British Neurologists (ABN) released their revised 2015 guidelines for prescribing disease-modifying treatments in MS. The guidelines classify DMT’s by efficacyAlemtuzumab and Natalizumab triumphing here. We also learn which DMTs to use in different patient groups.

Finally, Neurology published guidelines on rehabilitation in MS. Unfortunately there are quite a few qualifying ‘possibles‘ and ‘probables‘ which water down the strength of most of the recommendations. But what else do we have to go by?

Chronic inflammatory demyelinating polyneuropathy (CIDP)

The Journal of Neurology, Neurosurgery and Psychiatry (JNNP) published a review of CIDP in February 2015. It covers everything ”from bench to bedside”, but heavily skewed towards the former. It confirms that CIDP is a “spectrum of related conditions”, great news for splitters, and disappointing for lumpers. I personally struggle with the concepts of sensory and focal CIDP, have never diagnosed CANOMAD, but never tire of listening to Michael Lunn on VEGF, or be fascinated by the links between CIDP and POEMS syndrome. The review, an editors choice, is open access, and is backed by the authority of Richard Hughes; you really have no choice but to read it!

Unruptured intracranial aneurysms

The America Stroke Association (ASA) published new guidelines on management of unruptured aneurysms in a June 2015 issue of Stroke. It gives a comprehensive review of cerebral aneurysms, addressing the “presentation, natural history, epidemiology, risk factors, screening, diagnosis, imaging and outcomes from surgical and endovascular treatment“. It also suffices for a review article. Some recommendations are easily overlooked such as counsel against smoking and monitor for hypertension (evidence level B). Some important recommendations however have weak evidence, for example surveillance imaging after endovascular treatment (evidence level C).

The guidelines still advocate screening if there are 2 or more affected first degree family members. (I confess my threshold is lower than this). The extensive list of at-risk conditions for aneurysms include the usual suspects such as adult polycystic kidney disease and fibromuscular dysplasia. New culprits (at least to me) are microcephalic osteodysplastic primordial dwarfism, Noonan syndrome, and α-glucosidase deficiency.

 

CC BY-SA 3.0, https://en.wikipedia.org/w/index.php?curid=36822177
CC BY-SA 3.0, https://en.wikipedia.org/w/index.php?curid=36822177
Stroke 

The American Stroke Association (ASA), along with the American Heart Association (AHA), released their guidelines for the management of spontaneous intracerebral haemorrhage in 2015. There are several additional recommendations to the previous guidelines; these include the recommendation to control hypertension immediately from onset to prevent recurrent haemorrhage.

The ASA/AHA also published their updated guidelines on endovascular stroke therapy in 2015. To to show how important this treatment has become, the debate now is whether to use thrombectomy alone, or after thrombolysis. And the winner is…to use thrombectomy after thrombolysis. The eligibility checklist for endovascular therapy with a stent retriever is thankfully quite short.

Concussion and traumatic brain injury (TBI)

Concussion is a very topical issue, what with Will Smith as Bennett Omalu in the recent movie aptly titled… Concussion. I have previously posted on the effect of celebrities on neurology, but this here is the serious stuff.  Unlike most guidelines, these clinical practice guidelines for concussion/mild traumatic brain injury and persistent symptoms is not open access. Published in Brain Injury, I could only peruse the abstract, and this mentions 93 recommendations! Tempting however is it’s breadth, addressing everything from post-traumatic headache to sleep disturbance; from vestibular to visual dysfunction.

Friedreich's ataxia (FA)

OK, I confess these guideline are from 2014, a bit dated. But how often does one think ‘guidelines’ in the context of Friedreich’s ataxia. Furthermore, this Consensus clinical management guidelines for Friedreich ataxia is open access! Published in Orphanet Journal of Rare Diseases, they are the product of 39 experts, and consist of 146 recommendations! They cover everything from sleep, spasticity, and scoliosis to diabetes, dysphagia, and dysarthria. I bet you don’t enquire about restless legs syndrome (RLS) in your patients with FA!

Motor neurone disease (MND)

And hot off the press are the NICE guidelines on motor neurone disease (MND). One thing to mention is its sheer volume- 319 pages long, and containing 123 recommendations! The guidelines targets every aspect of MND care, and it’s futile trying to master it all. Each specialist can really only pick and choose which aspect is relevant to them. There is a lot of balancing of clinical and economic benefits, and this is reflected by questions such as “what are the most clinically- and cost-effective methods of maintaining nutrition…?” The guidelines address several long-standing issues such as the clinically appropriate timing for placing PEG tubes. Whether they add anything really new is however debatable.

 

Do you have a recent guideline or update to share? Please leave a comment.

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

 

Which are the most useful neurological applications?

It is no exaggeration to say our lives revolve around apps. These handy devices bring knowledge to our fingertips at the tap of the finger, or the click of a mouse . They promise easy access to a world of information, often digested to size. Some offer tools to simplify our practice. Neurology is, or should be, no exception.

Apple Store according to the New York Times. Wolf Gang on Flikr. https://www.flickr.com/photos/wolfgangkuhnle/4163909778
Apple Store according to the New York Times. Wolf Gang on Flikr. https://www.flickr.com/photos/wolfgangkuhnle/4163909778

 

So what are the tools out there making neurological practice easier and handier? What are these practical shortcuts making clinical work more efficient? I browsed the web to and found some useful neurology applications and have grouped them as below.

Clinical management apps

Apps that aid the clinical examination

  • Neuro Toolkit. This is only available for the iphone or ipad. A review on Neurology Times says it is ‘an up-to-date, simple and straightforward app’ that contains medical calculators and clinical scoring scales. It also received a favourable review in Neurology journal.
  • 5-minute Neurology Consult. The blurb on google play says Neurology Consult ‘provides instant access to comprehensive, clinically-oriented, must-have information on all disorders of the nervous system’.
  • Neurology a-pocket cards.
  • Neurology Exam Tools promises a flashlight and tuning fork which should lighten the neurologists tool case but it is not clear how efficiently.
  • Neuro Localizer sounds self-explanatory and is developed by neurologists.
  • Neurology pocket app with explanatory video below:

Apps oriented towards clinical scoring

Patient self-management apps

Rubik apps. Cesar Poyatos on Flikr. https://www.flickr.com/photos/cpoyatos/5791320785
Rubik apps. Cesar Poyatos on Flikr. https://www.flickr.com/photos/cpoyatos/5791320785

Disease-specific apps 

Anatomy apps

Journal apps

Allied neurological specialties apps 

Want to explore further? You may check these links out:

Watch out for Neurochecklists coming soon!

Know any useful apps I’ve missed out? Please leave a comment

 

 

How bright is the future for Alzheimer’s disease?

Alzheimer’s disease (AD) is scary. It is the most prevalent cause of dementia, and the name strikes terror, especially to those with a close family history of the condition. It is disturbing when a person loses the concept of ‘self’. It is devastating when parents fail to recognise their children.

Any progress in finding the cause or the cure for this neurodegenerative disease should therefore be celebrated. Following on my previous post, Alzheimer’s disease: a few curious things, here are my top 10 breakthroughs giving hope for Alzheimer’s disease.

Deep brain stimulation (DBS)

By Andreashorn - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=40251125
By AndreashornOwn work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=40251125

 

I have waxed lyrical on the widening influence of neurostimulation in the context of epilepsy, stroke and vagus nerve stimulation (VNS). I was however taken aback by the potential role of deep brain stimulation (DBS) in dementia. This headline from Alzheimers.net reports the Benefits of Deep Brain Stimulation for Alzheimer’sand refers to a study published in eLife. This doesn’t sound a very ‘peer-reviewed’ source, but the title is scientific enough: Ventromedial prefrontal cortex stimulation enhances memory and hippocampal neurogenesis in the middle-aged rats. I should warn you here that most of the studies in this post involve furry little creatures! The study reports that chronic electrical stimulation of the brain increases the activity of memory-related genes, and this in turn increases the number of memory nerves in the hippocampus. Alzheimers.net puts it bluntly-Using Deep Brain Stimulation to Create New Brain Cells.

Iron-reducing treatments

By Vaccinationist - PubChem, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=43392593
By VaccinationistPubChem, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=43392593

 

Based on a premise that high brain iron levels are related to the pathology in Alzheimer’s disease, researchers have looked at iron reducing therapies. This isn’t a new idea because an article in Lancet from 1991 was titled Intramuscular desferrioxamine in patients with Alzheimer’s disease. This study showed that the progression of Alzheimer’s disease could be slowed down by reducing the iron levels in the brain. New Scientist has brought this therapeutic strategy back into contention in its article titled Iron levels in brain predict when people will get Alzheimer’s. The article tantalisingly refers to a link between high iron levels and ApoE4, a gene associated with Alzheimer’s disease. Watch this space.

Ultrasound therapy

By Unknown - Popular Science Monthly Volume 13, Public Domain, https://commons.wikimedia.org/w/index.php?curid=11085835
By UnknownPopular Science Monthly Volume 13, Public Domain, https://commons.wikimedia.org/w/index.php?curid=11085835

 

New Alzheimer’s treatment fully restores memory function, so blares this headline in Science Alert. It refers to a study in mice which shows that focused therapeutic ultrasound stimulates microglia, the cells responsible for clearing the brain’s waste products. The paper, published in Science Translational Medicine, is titled Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model. The authors report that that by clearing amyloid, this technique restored memory in about 75% of mice models of Alzheimer’s disease. Human trials must surely beckon.

Dampening amyloid production

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12274694
By NephronOwn work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12274694

 

The idea of dampening the production of amyloid comes from the discovery of a new chemical pathway in the brain; I didn’t realise there were any more pathways left to discover! My ignorance was dispelled by this article in MNT titled A newly discovered molecular feedback process may protect the brain against Alzheimer’s. The article discusses WAVE-1, a protein which is central to a pathway involved in ß-amyloid production. How could scientists could suppress this pathway and improve the clearance of ß-amyloid? By somehow enhancing an inhibitory feedback loop thereby reducing WAVE-1 production. The scientific details are published in Nature Medicine titled APP intracellular domain–WAVE1 pathway reduces amyloid-β production

Monoclonal antibodies

B0007277 Monoclonal antibodies Anna Tanczos. Wellcome Images images@wellcome.ac.uk http://images.wellcome.ac.uk
B0007277 Monoclonal antibodies
Anna Tanczos. Wellcome Images
images@wellcome.ac.uk
http://images.wellcome.ac.uk

 

It would be surprising if monoclonal antibodies did not crop up in this post, being the rage in many other diseases. The monoclonal antibody raising hopes in Alzheimer’s disease is Solanezumab. I came across this in Russia Today (yes…RT) in an article titled Alzheimer’s breakthrough? First ever drug found that may slow disease. ‘First ever’ is obviously hype, but there does seem to be some benefit of Solanezumab, even if this is restricted to those with early disease.  The phase 3 trial of Solanezumab, called EXPEDITION 3, will study this effect further. More hope, less hype!

Boosting the brain’s immune system

B0007277 Monoclonal antibodies Anna Tanczos. Wellcome Images images@wellcome.ac.uk http://images.wellcome.ac.uk
B0007277 Monoclonal antibodies
Anna Tanczos. Wellcome Images
images@wellcome.ac.uk
http://images.wellcome.ac.uk

 

Microglia, the brain’s waste disposal cells, also play a key role in it’s immune system. In this way they protect the brain from damage by ß-amyloid. This immune function is however countered by EP2, a prostaglandin receptor protein found on the surface of the microglia. In other words EP2 functions to restrict the activity of the microglia. Researchers have now shown that the nuisance effect of EP2 could be blocked, as reported in an article titled Prostaglandin signaling suppresses beneficial microglial function in Alzheimer’s disease models, and published in Journal of Clinical Investigation. Enhancing the activity of microglia therefore raises hope for the treatment for Alzheimer’s disease… if it could be translated to humans.

Neurotrophic factors

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

 

What if we could boost the activity of cells that have not yet been affected by Alzheimer’s disease? An experimental drug called J147 might just do that. According to researchers, J147 is a neurotrophic drug which enhances nerve activity in mice. The research, appropriately published in the journal Aging, shows that J147 improves cognitive function in mice which have been modified to age fast. The article is titled A comprehensive multiomics approach toward understanding the relationship between aging and dementia. I personally prefer the headline in Neuroscience News which simply says Experimental Alzheimer’s Drug Slows Clock on Key Aspects of Aging. Too soon to speculate, but could we be talking age reversal here? Perhaps competition for klotho.

Enhancing proteasome activity

By User:KGH - User:KGH, <a href="http://creativecommons.org/licenses/by-sa/3.0/" title="Creative Commons Attribution-Share Alike 3.0">CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=552918
By User:KGHUser:KGH, <a href=”http://creativecommons.org/licenses/by-sa/3.0/&#8221; title=”Creative Commons Attribution-Share Alike 3.0 
“>CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=552918

 

We can’t get too far away from waste clearance in this post. This time it’s a drug called Rolipram which seems to enhance the brains waste disposal system. It does this by increasing the activity of proteasomes. Neuroscience News describes a proteasome as ‘a hollow, cylindrical structure which chews up defective proteins into smaller pieces that can be recycled into new proteins needed by a cell‘. The scientific paper is published in Nature Medicine titled Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling. The authors show that Rolipram also reduces the levels of tau, another toxic product involved in Alzheimer’s disease. For an easier read see the Neuroscience News article titled Slowing Alzheimer’s by Speeding Up Brain’s Waste Disposal.

Gene therapy

There is no getting away from it, and gene therapy had to crop up in this post. And yes, it may have a role in the future of Alzheimer’s disease. Researchers genetically treated 10 Alzheimer’s disease patients using nerve growth factor (NGF) gene, and then waited and waited, …and then studied the brains of the subjects. They reported their findings the Journal of the American Medical Association (JAMA) under the title Nerve Growth Factor Gene Therapy Activation of Neuronal Responses in Alzheimer Disease. The details of the study are rather complicated, but it appears the nerve growth factor treatment triggered nerve growth. Doesn’t sound like rocket science but imagine the potential. I only wished they had used a more straightforward title. I prefer the layman’s version in The Guardian simply titled Gene therapy rescues dying cells in the brains of Alzheimer’s patients. Scientific journals really need better headline writers!

Reprogramming astroglia

A cocktail mixture which transforms the brain’s supporting cells into proper nerve cells? Not science fiction it seems. A group of scientists have developed a mixture which could reprogram glial cells into functional brain cells. I came across this in Neurology Times under the title Transforming Glial Cells. For a change, the original research paper is well headlined; it is published in Cell under the title Small Molecules Efficiently Reprogram Human Astroglial Cells into Functional Neurons. The authors show that the cocktail of nine small molecules do the trick by inhibiting glial pathways and activating neuronal pathways. And this all happens within 8-10 days! Too good to be true? Hopefully not.

 

Looking for more? Here are 13 headlines to further raise the spirits of people with Alzheimer’s disease:

Please share your thoughts

Should neurologists be thinking of Influenza H1N1?

Every now and then neurologists come across patients with what appears to be ‘straightforward’ viral encephalitis but who do not respond to conventional treatment. These treatments are usually according to established guidelines such as the ABN/BIAN guidelines, the IDS Guidelines. What to do when the patient isn’t responding is however very challenging.

Journal of Neuroinfectious Diseases (ssshh…the JNNP declined it) has just published our case report of such a patient who turned out to have H1N1 influenza encephalopathy. This experience suggests we should consider an autoimmune cause in such cases, especially if the spinal fluid does not show any viruses.

3D model of influenza virus
3D model of influenza virus

 

It’s only a single patient but with an excellent outcome and valuable insights (I would say so wouldn’t I!). It was rather fortuitous as her treatment with IVIg was on the assumption she had anti NMDA antibody encephalitis. Its not always in the science as the viral serology subsequently showed!

Is your interest piqued enough? OK, here is the link (and its open access):

H1N1 Associated Encephalopathy in an Adult: Response to Intravenous Immunoglobulin Supporting an Autoimmune Pathogenesis

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?

Which are the most reliable neurology reference sources?

Neurology is huge. It consists of diverse subspecialties, each covering several distinct diseases. Neurology is also a rapidly advancing field with cutting-edge diagnostic processes and novel therapeutic approaches. Neurological practice, therefore, depends on reliable and up-to-date resources.

"Interior view of Stockholm Public Library" by Marcus Hansson from Göteborg, Sweden - The best days are not planned. Licensed under CC BY 2.0 via Wikimedia Commons.
Interior view of Stockholm Public Library” by Marcus Hansson from Göteborg, Sweden – The best days are not planned. Licensed under CC BY 2.0 via Wikimedia Commons.

 

I have previously posted on the proven all-time outstanding neurology textbooks, the most helpful and practical neurology guidelines, and the top all-time neurology review articles. These are all very useful, but all struggle keep up with the rapidly evolving progress in neurology; these resources become obsolete very quickly, and updates often go through laborious and slow processes. Neurologists therefore need reliable sources that keep up with new knowledge, and make sense of all the information ‘out there’. What are these dependable neurology reference sites?  Here is a selection.

Neurology-specific reference sites

  1. The NINDS Disorder Index is a library of all neurological disorders listed alphabetically. All sections have information on current research, and provide links to involved organisations. It is an extensive resource, but you would expect this from the world-renown National Association of Neurological Disorders and Stroke.
  2. MedLink Neurology is an extensive resource for a wide variety of neurological diseases. Content requires paid registration. Articles cite references linked to PubMed and indicate the date they were last updated.

General medical sites with neurology sections

  1. Uptodate has a neurology section with a good search function but needs a subscription. It is text intensive.
  2. Medscape has a very good and extensive neurology section listed alphabetically, and it is free!
  3. BMJ Best Practice also lists neurology topics alphabetically but requires access
  4. BMJ Neurology resources page has a few important neurology links
  5. The Cochrane Library is searchable using neurology as search terms; as far as I can see, most if not all, contents are free
  6. Scholarpedia appears to be a growing site with a helpful neuroscience section worth keeping an eye on.
  7. Medline is the go-to resource for current articles on everything medical. It is however difficult to confirm which articles are relevant or reliable
  8. Trip Database is another huge searchable resource including neurology

Specialty-specific neurology reference sites

  1. The Neuromuscular Disease Centre of Washington University has a detailed database of neuromuscular diseases
  2. Brain Infections UK is a useful site for updates on neurological infections but has a research-focus
  3. Radiopaedia is, as expected, an image-intensive site. It is useful because neurologists need to keep on top of the subtle neuro-radiological features of the diseases they treat. And its free.
  4. PsychCentral is a useful resource for mental health diseases, but you should go straight to the resources directory.

Neurology Guidelines resources

  1. American Academy of Neurology (AAN) guidelines is a reliable site for guidelines covering the broad range of neurology
  2. NICE guidelines are the authoritative benchmark for medical practice in the UK and there is extensive coverage of the major neurological conditions
  3. SIGN guidelines are the equivalent of the NICE guidelines in Scotland
  4. Guidelines Central has an extensive library of guidelines and this link is to neurology section

 

Neurochecklists

For the future, neurochecklists is now live. Learn more about it in my blog post What is the secret of neurochecklists?  Check it out and leave some feedback:

Neurochecklists web-Banner

Looking for more? The Queen Square Library resources page of University College London (UCL) Queen Square Library has several helpful links.

 

Any thoughts or suggestions? Please leave a comment.