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.

Will these 10 cutting-edge advances boost stroke care?

Stroke is a global beast. It is a scourge of the young and old. It strikes suddenly, maiming and killing with wanton abandon. So much has been achieved in the attempts to tame the monster, and yet victory still seems a far-off mirage. What are in the pipelines, beyond Aspirin and Statins? What may improve the outlook beyond intravenous clot busters and intensive rehabilitation? What is the likely future of stroke care? Here is a countdown of my top 10 cutting-edge stroke advances. 

10. Uric acid therapy

By AbcdKolya (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons
By AbcdKolya (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)%5D, via Wikimedia Commons

Uric acid is a villain as anyone with gout will attest. And yet there have been recent reports of the benefit of this chemical in neurological diseases. I have previously posted on the protective effect of uric acid on Parkinson’s disease (PD). In its further attempt to change its status from sinner to saint, uric acid is creeping into the world of stroke. A recent article in the journal Stroke is titled Uric Acid Therapy Improves Clinical Outcome in Women With Acute Ischemic Stroke. It was used in conjunction with conventional clot busting of course. Uric acid appears to reduce the growth of the infarct-the part of the brain that is irreversible damaged after a stroke. Why is it only women who benefit? Testament to the fact that it is not so easy to redeem a sullied image.

9. Transdermal glyceryl trinitrate (GTN)

"Nitrogylcerin (3D ball-and-stick model)" by Woodenchemist - Own work. Licensed under Public Domain via Commons.
Nitrogylcerin (3D ball-and-stick model)” by WoodenchemistOwn work. Licensed under Public Domain via Commons.

 

Yes, the simple GTN, popular with those who suffer angina.GTN works in angina by dilating (widening) the arteries thereby improving blood flow to the heart. Why can’t the same effect be expected with the narrow or blocked arteries that lead to stroke? Indeed the effect appears to be the same on the brain as it is on the heart as reported in this article in Stroke titled Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke. The authors showed that applying GTN through a skin patch within 6 hours of stroke leads to improved outcomes. This intervention lowers the blood pressure, improves functional outcomes, and improves cognition to boot. To good to be true? Perhaps not.

8. Virtual reality augmented rehabilitation

"AC89-0437-20 a". Con licenza Pubblico dominio tramite Wikimedia Commons.
AC89-0437-20 a“. Con licenza Pubblico dominio tramite Wikimedia Commons.

 

There are many advances aimed at improving limb function after stroke. These include techniques such as constraint-induced movement therapy and mirror therapy. The exciting advance for me however is virtual reality. This came to my attention in an article in Augmented Reality Trends titled Virtual Reality Assists Stroke Patients Regain Limb Movement. It took some sleuthing to track down the scientific paper, published in Journal of Neuroengineering and Rehabilitation. Titled, in typical academic obfuscation, The visual amplification of goal-oriented movements counteracts acquired non-use in hemiparetic stroke patients, it showed the benefit of a virtual reality environment on hand-reaching in 20 stroke patients. The authors conclude that “the amplification of the movement of the paretic limb in a virtual environment promotes the use of the paretic limb in stroke patients”. Long words, small sample size, but big progress.

7. Enhanced endovascular therapy

"Merci L5" by Neilbarman at English Wikipedia. Licensed under CC BY-SA 3.0 via Commons.
Merci L5” by Neilbarman at English Wikipedia. Licensed under CC BY-SA 3.0 via Commons.

 

Conventional stroke treatment now relies on injection of clot busting agents into a vein (intravenous thrombolysis). In some cases the clot busting agent is given through an artery (intra-arterial thrombolysis). The immediate future of stroke however is moving towards actual clot removal or mechanical thrombectomy. There have been several studies showing the effectiveness of this technique. These include the appropriately named ESCAPE, MR RESCUEand MR CLEANThrombectomy makes use of devices called stent retrievers such as MerciTrevo Pro and Solitaire™ FR. The results of these trials are overwhelmingly convincing, and the title of a recent review article in Interventional Neurology says it all: Mechanical Thrombectomy Is Now the Gold Standard for Acute Ischemic Stroke: Implications for Routine Clinical Practice. It is such a significant development that a recent Lancet Neurology article was titled Stroke in 2015: the year of endovascular treatment!

6. Neurostimulation

By http://www.nimh.nih.gov/health/topics/brain-stimulation-therapies/brain-stimulation-therapies.shtml [Public domain], via Wikimedia Commons
By http://www.nimh.nih.gov/health/topics/brain-stimulation-therapies/brain-stimulation-therapies.shtml [Public domain], via Wikimedia Commons

Neurostimulation is having a field day in neurology and I discussed this in my previous post on vagus nerve stimulation. Stroke is going to be no exception. Take this report published in Stroke titled Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke. This paper suggests that combining vagus nerve stimulation (VNS) with standard rehabilitation improves upper limb function after stroke. Another report in Neurology is titled Deep brain stimulation of the dentate nucleus improves cerebellar ataxia after cerebellar stroke

5. Remote ischaemic conditioning (RIC)

Could repeatedly inflating and deflating a blood pressure cuff around the arm reduce the brain damage that occurs following stroke? Strange as it may seem, this is the idea behind remote ischaemic conditioning (RIC). A recent paper in Nature Reviews Neurology titled Remote ischaemic conditioning—a new paradigm of self-protection in the brain explains how this works. It says RIC protects organs by triggering protective chemical pathways in their cells. This is neuroprotection when applies to nervous structures such as the brain. This process has the potential not only to limit the damage caused by stroke, but to also reduce the risk of the stroke recurring. One study that has looked at this process in detail is published in Stroke and is titled Remote ischemic per-conditioning: a novel therapy for acute stroke? 

4. PHD oxygen sensor inhibition

When oxygen supply to the brain is restricted, as occurs in stroke, the brain detects this using proteins called PHD (prolyl hydroxylase domain). PHD triggers a change in the metabolism of the brain cells, letting them adapt to the new state of limited oxygen supply. Unfortunately this adaptation leads to the production of toxic oxygen radicals which cause some of the brain damage that results from stroke. A recent study has however shown that mice that are deficient in PHD develop less severe strokes than normal mice. It requires no stretch of the imagination to guess that medications which inhibit PHD may lead to less severe stroke outcomes. And this is what the title of the research paper says: Deletion or Inhibition of the Oxygen Sensor PHD1 Protects against Ischemic Stroke via Reprogramming of Neuronal MetabolismA simplified version of the paper is published in News-Medical as Oxygen sensor PHD1 identified as potential target for treatment of ischemic stroke

3. Growth factors 

"NGF Beta 2.5S RCSB 1BET" by RCSB PDB - RCSB PDB. Licensed under CC BY 3.0 via Commons.
NGF Beta 2.5S RCSB 1BET” by RCSB PDB – RCSB PDB. Licensed under CC BY 3.0 via Commons.

 

Recent studies have reported two growth factors with the potential to improve stroke care. The first is growth differentiation factor 10 (GDF10). An article in MNT titled Discovery could lead to drug to enhance recovery from stroke describes GDF10 as a chemical which “signals brain cells to make new connections following a stroke“. The scientific paper is published in Nature Neurology titled GDF10 is a signal for axonal sprouting and functional recovery after stroke. This opens the door for potential drug treatments which will improve recovery after stroke.

The second growth factor is Neurotrophin 3 (NT3). This is one type of nerve growth factor which has been shown, at least in rats, to improve brain function. It however has to be administered within 24 hours of stroke. The report published in Brain is titled Delayed intramuscular human neurotrophin-3 improves recovery in adult and elderly rats after stroke. The authors showed that NT3, injected intramuscularly, triggers the sprouting of new nerve cells. This goes beyond neuroprotection and opens a very exiting field for stroke researchers.

2. Stem cell therapy

By Human_embryonic_stem_cells.png: (Images: Nissim Benvenisty)derivative work: Vojtech.dostal (Human_embryonic_stem_cells.png) [CC BY 2.5 or CC BY 2.5], via Wikimedia Commons
By Human_embryonic_stem_cells.png: (Images: Nissim Benvenisty)derivative work: Vojtech.dostal (Human_embryonic_stem_cells.png) [CC BY 2.5 or CC BY 2.5], via Wikimedia Commons

Stem cell therapy is a very promising field of medicine, with exciting reports coming out almost daily. Most recently is the benefit in multiple sclerosis (MS). Recent reports suggest that Stroke is not lagging too far behind. A recent article in The Guardian describes what appears to be a successful trial of stem cell therapy in 5 people with stroke. A review article in International Journal of Preventative Medicine outlines the different types of approaches to stem cell therapy; these include neural, haematopoetic and mesenchymal stem cells. If you are keen on the technical aspects you may look at the research paper in Stem Cells and Translational Medicine titled Intra-Arterial Immunoselected CD34+ Stem Cells for Acute Ischemic Stroke

1. Brain repair with new nerve cells

Neurones in the brain. Welcome Images on Flikr. https://www.flickr.com/photos/wellcomeimages/19923050858
Neurones in the brain. Welcome Images on Flikr. https://www.flickr.com/photos/wellcomeimages/19923050858

 

A step which goes beyond neuroprotection, growth factors, and stem cells, is the creation of functioning nerve cells (neurones) from the supporting cells of the brain (glial cells). This technique promises to repair the part of the brain damaged by stroke by simply replacing the dead cells with new nerve cells. I came across  this first in an article in The Guardian titled Brain damage could be repaired by creating new nerve cells. The evidence so far is from studies in mice but the prospects for this are very exciting indeed. For the scientific details, the original research is in Stem Cells Report titled Sox2-Mediated Conversion of NG2 Glia into Induced Neurons in the Injured Adult Cerebral Cortex

These are all very impressive developments, hinting at a bright future for stroke care. It is hopefully not far off when a devastating stroke will be a totally reversible event.