The emerging research boosting Parkinson’s disease treatment

Parkinson’s disease (PD) is probably the most iconic neurological disorder. It has diverse manifestations, typical of many neurological diseases. PD is a result of brain dopamine deficiency, and its clinical picture is dominated by motor symptoms- tremor, rigidity and bradykinesia (slowing of movements). It however also manifests with a variety of non-motor symptoms which rival the motor symptoms in their impact. PD is responsive to treatment with several oral medications such as levodopa, infusions such as apomorphine, and interventions such as deep brain stimulation (DBS).

unknown-1769656_1280

Regardless of the intervention used, PD is a neurodegenerative disorder that grinds, slowly and steadily, along a chronic progressive course. This often manifests with disabling features such as freezing, hallucinations, and dyskinesias (drug-induced writhing movements). These symptoms creep or barge in unannounced, challenging the wits of the neurologist, and pushing the resolve of patients and their families to the limit. What hope does research offer to smooth the journey for people with PD? Here are my top 7.

1. Increasing evidence for the benefit of exercise

jogging-1529803_1280

OK, not every advance has to be groundbreaking. It is self-evident that exercise is beneficial for many chronic disorders, but proving this has been difficult…until now that is. Researchers, publishing in the journal Movement Disorders, looked at the benefits of exercise on cognitive function in PD, and their verdict is-yes, it works! The study, titled Exercise improves cognition in Parkinson’s disease: The PRET-PD randomized, clinical trial, comes with strings attached- you have to keep at the exercise for 2 years! A review  in the same journal indicates that exercise also improves mood and sleep in PD.

2. Lithium for treatment of dyskinesias

By Dnn87 - Self-photographed, CC BY 3.0, Link
By Dnn87Self-photographed, CC BY 3.0, Link

Dyskinesias are abnormal, fidgety movements that develop as side effects of the drugs used to treat PD. Most people with dyskinesias are not overly concerned about the movements because the alternative, disabling freezing and immobility, is worse. Dyskinesias are however energy-sapping, and are distressing for family members. Amantadine is one drug neurologists add-on to improve dyskinesias, but many people do not tolerate or benefit from this. The suggestion that lithium may help dyskinesias is therefore welcome news. The report comes from a study in mice reported in the journal Brain Research titled The combination of lithium and l-Dopa/Carbidopa reduces MPTP-induced abnormal involuntary movements (AIMs). A long way to go yet, but hope.

3. Transcranial magnetic stimulation (TMS)

By MistyHora at the English language Wikipedia, CC BY-SA 3.0, Link
By MistyHora at the English language Wikipedia, CC BY-SA 3.0, Link

Transcranial magnetic stimulation (TMS) is playing an increasing role in neurology as I discussed in a previous post titled Are magnets transforming neurology? It is almost inevitable therefore that TMS will crop up in attempts to treat PD. And so it has, going by a meta-analysis and systematic review published in JAMA Neurology. The paper is titled Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease. The reviewers passed the judgement that repetitive TMS improves motor symptoms in PD. Perhaps time to invest in TMS!

4. MRI guided focused ultrasound (MRgFUS)

By Frmir - Own work, CC BY-SA 3.0, Link
By FrmirOwn work, CC BY-SA 3.0, Link

MRI guided ultrasound (MRgFUS) is not new to medicine. It is used, for example, in the treatment of solid tumours and uterine fibroids. It is however innovative in the treatment of tremor and dyskinesia in PD. This came to my attention via a press release from University of Maryland titled Metabolic Imaging Center uses new ultrasound technology to target deep structures of the brain. MRgFUS non-invasively transmits ultrasound waves to the globus pallidus, one of the deep brain structures involved in PD. How this works still remains fuzzy to me, but it is exciting enough to generate a lot of research activity with articles such as MRI guided focused ultrasound thalamotomy for moderate-to-severe tremor in Parkinson’s disease in the journal Parkinson’s Disease; and Unilateral magnetic resonance-guided focused ultrasound pallidotomy for Parkinson disease, published in Neurology. Watch out, deep brain stimulation!

5. Nasal mucosal grafting

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

What a great thing, the blood-brain barrier, protecting the brain from all the bugs and toxins running amok in the bloodstream. This iron-clad fence unfortunately also effectively keeps out, or limits the entrance of, many beneficial drugs which need to get to the brain to act. As with all borders however, there are always people ready to break through, without leaving any tracks behind. And the people in this case are neurosurgeons who have successfully bypassed the blood brain barrier, and safely ‘transported’ PD drugs in to the brain. They did this by removing a portion of the blood brain barrier of mice, and replaced it with a piece of the tissue which lines the inside of the nose, a procedure called nasal mucosal grafting. They then delivered glial derived neurotrophic factor (GDNF), a protein that treats PD in mice, across the graft. The neurosurgeons explained all this in their paper titled Heterotopic mucosal grafting enables the delivery of therapeutic neuropeptides across the blood brain barrier. You may however prefer the simpler version from the Boston Business Journal (can you believe it!) titled A new way to treat Parkinson’s disease may be through your nose. It will however take time before human trials of nasal mucosal grafting…this is science after all, not science fiction!

6. Fetal stem cell transplantation

Marmoset embryonic stem cells forming neurons. NIH Image gallery on Flikr. https://www.flickr.com/photos/nihgov/27406746806
Marmoset embryonic stem cells forming neurons. NIH Image gallery on Flikr. https://www.flickr.com/photos/nihgov/27406746806

It doesn’t seem too long ago when all ethical hell broke loose because some scientists were transplanting fetal tissue into human brains. I thought the clamour had put this procedure into the locker, never to be resurrected. Apparently not; fetal stem cell transplantation (SCT) is back, reminiscent of Arnold Schwarzenegger in the Terminator films. Learn more of this comeback in this piece from New Scientist titled Fetal cells injected into a man’s brain to cure his Parkinson’s. The work is from Roger Barker‘s team at the University of Cambridge, and they are planning a big study into this named TRANSNEURO. Watch this space

7. Pluripotent stem cell transplantation

By Judyta Dulnik - Own work, CC BY-SA 4.0, Link
By Judyta DulnikOwn work, CC BY-SA 4.0, Link

The future of stem cell transplantation probably lies with pluripotent, rather than fetal cells. The idea is to induce skin cells, called fibroblasts, to transform into dopamine-producing cells. Fibroblasts can do this because they are pluripotent cells; that is they are capable of becoming whatever type of cells you want, so long as you know the magic words. In this case, the words are likely to be the transcription factors Mash1, Nurr1 and Lmx1a. Beatsopen sesame‘, and surely less controversial than fetal cells. Researchers are taking this procedure very seriously indeed, setting out ground rules in articles such as Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. This was published in the journal Nature, but you may prefer the easier read in New Scientist titled Brain cells made from skin could treat Parkinson’s. But don’t get too excited…pluripotent stem cell transplantation is barely at the starting line yet.

 

Eu Sou. jeronimo sanz on Flikr. https://www.flickr.com/photos/jeronimooo/12069638595
Eu Sou. jeronimo sanz on Flikr. https://www.flickr.com/photos/jeronimooo/12069638595

There is so much more going on in the field of Parkinson’s disease to cover in one blog post. I will review neuroprotection in Parkinson’s disease in a coming post. In the meantime, here are links to 12 interesting articles and reviews on the future of PD:

_________________________________________________________________________

neurochecklists-image

Masitinib, a breakthrough drug shattering neurology boundaries

In the process of writing a blog post on the research findings altering neurological practice, my sight fell on the drug, Masitinib. I was completely unaware of this tyrosine kinase inhibitor, one of the promising drugs in the fight against multiple sclerosis (MS). We are likely to hear a lot more about Masitinib in MS in the coming months.

By Zeldj - Own work, CC BY-SA 4.0, Link
By ZeldjOwn work, CC BY-SA 4.0, Link

Masitinib is however not flexing its muscles just in neuro-inflammation. On the contrary, it is seeking laurels far afield, in the realm of neuro-degeneration. I was indeed pleasantly surprised to find that researchers are studying the impact of Masitinib on two other horrible scourges of neurology. The first report I came across is the favourable outcome of a phase 3 trial of Masitinib in motor neurone disease (MND) or amyotrophic lateral sclerosis (ALS). The drug reportedly ‘reached its primary objectives‘ of efficacy and safety. In this trial, Masitinib was used as an add-on to Riluzole, the established MND drug. It’s all jolly collaborative at this stage, but who knows what threat Masitinib will pose to Riluzole in future! You may read a bit more on Masitinib and MND in this piece from Journal of Neuroinflammation.

By Capilano1 - Own work, CC BY-SA 4.0, Link
By Capilano1Own work, CC BY-SA 4.0, Link

The second report I came across is the potential of Masitinib in the treatment of Alzheimer’s disease (AD). This is at the phase 2 trial stage, and already showing very good outcomes in people with mild to moderate AD. Masitinib was used as an add-on drug to the conventional AD medications Memantine, Donepezil, Galantamine and Rivastigmine. These drugs can therefore rest comfortably on their thrones…at least for now! You can read a bit more on Masitinib and AD in this article from Expert Review of Neurotherapeutics.

Alzheimer's Disease. Hamza Butt on Flikr. https://www.flickr.com/photos/141735806@N08/28007367952
Alzheimer’s Disease. Hamza Butt on Flikr. https://www.flickr.com/photos/141735806@N08/28007367952

The question however remains, why should one drug work well on such disparate diseases? I know, this feels like deja vu coming shortly after my last blog post titled Alzheimers disease and its promising links with diabetes. In that post I looked at the promise of the diabetes drug, Liraglutide, in the treatment of Alzheimers disease. I have however also reviewed this type of cross-boundary activity of drugs in my older posts, Will riluzole really be good for cerebellar ataxia? and old drugs, new roles? Perhaps Masitinib is another pointer that, as we precisely define the cause of diseases, they will turn out to be merely different manifestations of the same pathology. Food for thought.

Benjah-bmm27 assumed. Own work assumed (based on copyright claims). Public Domain, Link
Benjah-bmm27 assumed. Own work assumed (based on copyright claims). Public Domain, Link

 

As I said, this wasn’t the post I set out to write. So watch out for my next blog post, the major research outcomes altering neurological practice.

_________________________________________________________________________

Neurochecklists image

Alzheimers disease and its promising links with diabetes

In the excellent book, The Innovators Prescription, the authors predict that precision medicine will replace intuitive medicine, and diseases will be defined by their underlying metabolic mechanisms, and not by the organs they affect, or the symptoms they produce. Clayton Christensen and colleagues argue that this precise definition of diseases will lead to more effective treatments. But they also show that precision medicine will show that many different diseases actually share the same underlying metabolic derangements. Many disparate diseases will therefore turn out to be just mere manifestations of the same metabolic disease.

Precision Medicine Conference at Harvard. Isaac Kohane on Flikr. https://www.flickr.com/photos/52786697@N00/16892093678
Precision Medicine Conference at Harvard. Isaac Kohane on Flikr. https://www.flickr.com/photos/52786697@N00/16892093678

A clear indication that precision medicine will blur the boundaries between diseases is the recent suggestion that the anti-diabetes drug Liraglutide may help to treat Alzheimer’s disease (AD). Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist which is effective in type 2 diabetes, a condition which is worlds apart from Alzheimer’s disease. So far removed from each other, it would be easy to dismiss any links as tenuous. But the headlines were emphatic: Drug used to treat diabetes could cure Alzheimer’s, and Diabetes drug could influence brain activity in Alzheimer’s. 

diabetes-1326964_1280

It is however no hype: there is evidence that Liraglutide may benefit people with Alzheimer’s disease. Trials in animal have shown that Liraglutide promotes neuronal survival, learning and memory, and reduces neuroinflammation and amyloid plaque formation. One such study is titled Prophylactic liraglutide treatment prevents amyloid plaque deposition, chronic inflammation and memory impairment in APP/PS1 mice. Beyond animals, small human trials have shown that Liraglutide improves brain glucose metabolism in Alzheimer’s disease.

beta-amyloid-plaques. vestque on Flikr. https://www.flickr.com/photos/35049835@N00/16867428955
beta-amyloid-plaques. vestque on Flikr. https://www.flickr.com/photos/35049835@N00/16867428955

Why should Liraglutide work so well in both diabetes and Alzheimer’s, diseases with apparently different pathologies? The answer lies in insulin resistance, the underlying mechanism of type 2 of diabetes; there is now evidence that insulin resistance contributes to dementia. If this is the case, Liraglutide, by improving glucose metabolism, could potentially treat both diabetes and Alzheimer’s disease.

Sugar Cubes. David Pace on Flikr. https://www.flickr.com/photos/63723146@N08/7164573186
Sugar Cubes. David Pace on Flikr. https://www.flickr.com/photos/63723146@N08/7164573186

To explore this potential further, there is now a large multicentre trial exploring the real benefit of Liraglutide in Alzheimer’s disease. Titled Evaluating Liraglutide in Alzheimer’s Disease or ELAD, it is recruiting people with mild disease, aged between 50-85 years old, and who do not have diabetes. As they say, watch this space!

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

Going back to the subject of precision medicine, why not visit my other blog, The Doctors Bookshelf where I will soon be reviewing The Innovators Prescription

What is the relationship of MND and cancer?

There are many sources of neurology information, as I listed in my previous post titled what are the most reliable neurology reference sources? These sources let us know what is in and what is out; what is breaking and what has gone stale. Keeping on top of the ever-shifting information the journals churn out is challenging, but interesting. This information is the life blood of The Neurology Lounge, and keeps neurochecklists current and reliable.

Reference tracker icon. Berto on Flikr. https://www.flickr.com/photos/bertop/2485992973
Reference tracker icon. Berto on Flikr. https://www.flickr.com/photos/bertop/2485992973

In the task of keeping level with neurological developments, I first go to the journal Neurology, one of the clear leaders of the pack. Check it out on twitter under its handle, @GreenJournal. Browsing through a recent issue, I  was struck by a paper titled Population-based risks for cancer in patients with ALS. The authors of this paper report that people with motor neurone disease (MND) appear to be protected from developing many cancers, including the notorious lung cancer. In contrast, they are at a higher risk of testicular and salivary gland cancer.

cancer-389921_1920

Curious to know more, I looked for previous reports on this topic but I came out not any wiser. Older research have given conflicting results on the links between MND and cancer. Take this paper published in the International Journal of Cancer titled The risk of amyotrophic lateral sclerosis after cancer in U.S. elderly adults: a population-based prospective study. This found no links at all, as did another paper published in Journal of Neurology titled Prior medical conditions and the risk of amyotrophic lateral sclerosis. On the other hand, other researchers found that people with MND were at a higher risk of cancer. An example is this paper titled The association between cancer and amyotrophic lateral sclerosis, published in Cancer Causes and Control. This reported a link between MND and melanoma, and with tongue cancer. The bulk of the research before now however suggests that there is no link. Take this paper published in Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration, and titled Amyotrophic lateral sclerosis and cancer: a register-based study in Sweden; the authors, led by Ammar al Chalabi, sounded an authoritative ring of finality when they said “our results provide no evidence for comorbidity of cancer and ALS“. Before now, that is!

statistics-754120_1920

So, is the latest study bucking the trend? Does MND really protect against some cancers and predispose to others? What does this all mean for people with MND? Or is all this just a quirk of the statistics? Questions, questions. I suspect this paper has just re-opened a can of worms, and more studies will surely follow. And they will refute and confirm the findings in equal measure.

lougehriggoudeycard

For now, MND remains an enigma. You may explore it a bit more in my previous blog posts on the subject…and leave your thoughts behind in the comments box.

_________________________________________________________________________
neurochecklists-image

What is the startling research unsettling the treatment of myasthenia gravis?

The long-term treatment of myasthenia gravis (MG) relies on drugs which suppress the immune system. I listed some of these in my previous post titled How is innovative neurology research energising myasthenia? Steroids are the established first line immune suppressing treatment for MG but because of their many nasty side effects, they cannot be used at effective doses for long periods. This is why neurologists treating MG use so-called steroid-sparing agents to reduce, or eliminate, the need for steroids.

Little red pills. Jon nagl on Flikr. https://www.flickr.com/photos/jonnagl/2470078845
Little red pills. Jon nagl on Flikr. https://www.flickr.com/photos/jonnagl/2470078845

Azathioprine has the best evidence of effectiveness as a steroid-sparing drug, and it is the acknowledged favourite of neurologists. Azathioprine may however fail or cause unacceptable side effects. It is also unsuitable for people who lack TPMT, the enzyme that breaks it down. It is in these situations that things become slightly tricky for the neurologist.

By NLM - NLM Pillbox, http://pillbox.nlm.nih.gov/assets/large/000040lg.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=14666931
By NLM – NLM Pillbox, http://pillbox.nlm.nih.gov/assets/large/000040lg.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=14666931

In theory, neurologists are spoilt for choice when they can’t use Azathioprine. Methotrexate is my favourite option in such cases because it has an easy weekly dosing regime and it is fairly well-tolerated. Alas, a recent paper in Neurology titled A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis has unsettled me by suggesting that methotrexate is not living up to its top billing. The authors of the paper studied 50 people with myasthenia gravis who were already taking steroids. They put some of them on methotrexate, and the others on placebo. The outcome was surprising; methotrexate did very little to reduce the requirement for steroids, and it did nothing to improve the symptoms of MG.

By Fdardel - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15465576
By Fdardel – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15465576

 

This is clearly disappointing. Whilst waiting for further studies to confirm or refute this finding, I wonder how reliable the other steroid-sparing MG drugs are. How good are mycophenolate, ciclosporin, cyclophosphamide, tacrolimus, and rituximab? What really works in MG? To the rescue comes the International consensus guidance for management of myasthenia gravis, just hot off the press! Alas, the experts who drafted this guidance only compounded my woes. They made many treatment recommendations, but these came with as many caveats. They said the evidence for mycophenolate and tacrolimus in MG is rather thin, and the evidence-based ciclosporine and cyclophosphamide have potentially serious side effects. And they couldn’t agree on how promising rituximab, the new kid on the block, really is.

By Oguenther at de.wikipedia - Own work mit Jmol auf Basis RCSB PDB 2OSL., Public Domain, https://commons.wikimedia.org/w/index.php?curid=15482243
By Oguenther at de.wikipedia – Own work mit Jmol auf Basis RCSB PDB 2OSL., Public Domain, https://commons.wikimedia.org/w/index.php?curid=15482243

We are therefore back to the question, what to do when Azathioprine fails? The experts tell us to stick to the usual suspects, but they urge caution. Perhaps what we need are newer and safer alternatives such as Lefluonamide, so new to the MG arena that it did not get a mention in the expert guidance.

 

 

Are steroids detrimental to survival in brain tumours?

As I update neurochecklists I come across some papers which make me go, ‘really!’ Such studies challenge established theories and threaten conventional practice. Such is the case with a recent paper in Brain titled, unequivocally, Corticosteroids compromise survival in glioblastoma.

By Christaras A - Created myself from anonymized patient MR, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=1247035
By Christaras A – Created myself from anonymized patient MR, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=1247035

Glioblastoma is the worst form of primary brain tumour, and survival is already poor. Treatment is usually palliative with debulking surgery and radiotherapy. Dexamethasone, a corticosteroid, effectively reduces the swelling or oedema that the tumour evokes around it. Corticosteroids are therefore often the first treatment for glioblastoma because they  almost immediately improve symptoms such as reduced consciousness, headache, and visual blurring.

By LHcheM - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18648311
By LHcheMOwn work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18648311

It is, therefore, surprising when a study suggests that corticosteroids cause harm. But this is no ordinary study; it is a classic bench-to-bedside research which looked at patients with glioblastoma, and then devised a mouse model to study the real impact of steroids on the tumour.

By Jensflorian - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11814552
By JensflorianOwn work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11814552

 

The authors show that a ‘ dexamethasone-associated gene expression signature correlated with shorter survival’. They pass the verdict that corticosteroids are detrimental to survival and urge caution when prescribing dexamethasone.

hope-1220981_1920

You may be feeling a bit low after reading. You may, however, lift your spirits by reading my previous posts titled maggots, viruses and lasers: some innovations for brain tumours and calming the rage of brain tumours.

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

neurochecklists-image

How is migraine research soothing the pain of neurology?

Migraine is a very common medical disorder. 15% of the world’s population have migraine, and 2% have chronic migraine. Most migranuers never need to see a neurologist because they have learnt how to manage their headaches. Neurologists are called in only when the usual treatments fail, often a euphemism for ‘inadequate doses and duration of treatment’.

Migraine. Quinn Dumbrowski on Flikr. https://www.flickr.com/photos/quinnanya/3820597553/in/photostream/
Migraine. Quinn Dumbrowski on Flikr. https://www.flickr.com/photos/quinnanya/3820597553/in/photostream/

Many people with difficult to control migraine however really have just that…difficult to control migraine. And it is the most avid neurologist who doesn’t silently sigh and grunt at referrals which say the patient has tried every migraine treatment, to no avail. And with good reason: the journey for people with chronic migraine is hardly ever smooth-sailing.

By User:S. JähnichenBrain_bulbar_region.svg: Image:Brain human sagittal section.svg by Patrick J. Lynch; Image:Brain bulbar region.PNG by DO11.10; present image by Fvasconcellos. - Brain_bulbar_region.svg, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=6049291
By User:S. JähnichenBrain_bulbar_region.svg: Image:Brain human sagittal section.svg by Patrick J. Lynch; Image:Brain bulbar region.PNG by DO11.10; present image by Fvasconcellos. – Brain_bulbar_region.svg, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=6049291

Why does migraine remain such a pain, and what hope is there to relieve the headache for patients and their neurologists? Here are 8 prospective candidates jostling to soothe the pain.

 

1. The hypoxia hypothesis for migraine triggers

There are probably as many migraine triggers as there are migraine hypotheses. Some of the triggers are curious, as discussed in my previous blog Migraine and its strange and surprising associations. Some researchers think the common link to migraine triggers is low oxygen or hypoxia. Writing in the prestigious journal Brain, they report on Migraine induced by hypoxia: an MRI spectroscopy and angiography study. Sorry, the full paper is locked to non-subscribers, but the abstract is unequivocal: hypoxia induces migraine-like attacks. And the accompanying editorial is agog with the prospects this study opens up with its headline, Hypoxia, a turning point in migraine pathogenesis? Who doesn’t love turning points, especially as the previous turning points can then be conveniently forgotten?

2. Migraine with cranial autonomic symptoms-clarified

Alison Smith on Flikr. https://www.flickr.com/photos/polygrams/232755351/in/photostream/
Alison Smith on Flikr. https://www.flickr.com/photos/polygrams/232755351/in/photostream/

Migraine with unilateral cranial autonomic symptoms is a new construct for most jobbing neurologists (OK I may just be speaking for myself here). Unilateral cranial autonomic symptoms (UAS) refer to one-sided symptoms such as reddening of the eye, blockage or running of the nose, a droopy eyelid, and a small pupil. These features are however classically seen in conditions called trigeminal autonomic cephalalgias (TACS), the main one being cluster headache.

Neurologists often see people with classical migraine but who, in addition, have UAS. The cognitive dissonance this causes the neurologist is relieved by making a diagnosis of cluster migraine. It is therefore important to know that unilateral cranial autonomic symptoms are common in migraine. The authors studied >750 migraine sufferers who also had UAS, and report that it is a severe, one-sided headache. Worse still, it goes on for more than the 72 hours which headache experts have ‘specified’ as the maximum duration for migraine. Naughty, naughty. Hopefully this study will put the final nail in the coffin of cluster migraine-it is Migraine with UAS from now on.

3. Persistent migraine aura or visual snow?

By Googleaseerch at the English language Wikipedia, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=3359664
By Googleaseerch at the English language Wikipedia, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=3359664

I admit I didn’t know persistent migraine aura (PMA) even existed before now. It is migraine aura lasting more than a week, and it has two subtypes-persistent primary visual disturbance (PPVD) and typical aura (TA). Digging deeper, I found that PMA could easily be confused with something called visual snow. Another new one for me. An article in Brain titled ‘Visual snow’ – a disorder distinct from persistent migraine aura makes the differences clear. With its co-author no less than the headache authority Peter Goadsby, go on and read all about it-its open access after all. For a simplified read, try this piece in About Health titled Why Visual Snow Syndrome is Not a Migraine Variant. Another small step to making the right diagnosis.

4. Monoclonal antibodies for migraine

monoclonal-antibody-services.jpg. 元永利 on Flikr. https://www.flickr.com/photos/linsc/4628425031/in/dateposted/
monoclonal-antibody-services.jpg. 元永利 on Flikr. https://www.flickr.com/photos/linsc/4628425031/in/dateposted/

Neurologists have a long list of interventions for migraine. The treatments range from Triptans to Topiramate, from Propranolol to Pizotifen. But the long list of interventions is no comfort for the equally long list of dissatisfied chronic migraine sufferers. Perhaps what we need are newer and better drugs. And monoclonal antibodies are in the frontline here. Take TEV-48125 and AMG 334  both reported in Lancet Neurology. These are monoclonal antibodies against the calcitonin gene receptor peptide (CGRP) receptor. The articles are classical illustrations of bench-to-bedside neurology, treatment following where the hypothesis leads. The hypothesis in this case stipulates that the CGRP system is central to the pathology in migraine, and CGRP may be a migraine biomarker. TEV-48125 and AMG 334 are entering phase 3 trial stages. And we can’t wait, what with both treatments having a unique 4-weekly subcutaneous injection regime! AMG 334, also known as erenumab, has passed phase 3 trials with good results.

5. Statins and Vitamin D: new tricks for old dogs

Statins are very old dogs in medicine, and their classical trick is to lower cholesterol levels. They are however very adaptive, these statins. They have edged into secondary stroke prevention, and they are now trying to muscle into migraine prevention. But for migraine they are planning a double act with Vitamin D. The cat was let out of the bag by Annals of Neurology in an article titled Simvastatin and vitamin D for migraine prevention: A randomized, controlled trial. There were only 57 study subjects but the results are encouraging; >25% of the study subjects reported a >50% reduction in migraine days; only 3% of those not on the magic combination showed this type of improvement. Note here that neurologists never promise you 100% reduction in your migraine days. Clever, clever.

6. Memantine-another old dog

Another old dog looking for new tricks is Memantine. This is a drug which usually gets its accolades in the fields of dementia and eye movement disorders. It is however not getting the appreciation it thinks it rightly deserves, and it is seeking a wider audience. And is there a wider audience than in the migraine arena? Memantine made its grand migraine debut through the journal Headache in an article titled  Memantine for Prophylactic Treatment of Migraine Without Aura. It may turn out to be a damp squid because the researchers only compared it to placebo. But guess its unique selling point… its potential safety in pregnancy. We have to wait and see what the migraine arena masters think of this.

7. Transcranial magnetic stimulation (TMS):old tricks for a new dog 

Away with old dogs, and welcome back more new dogs. One is transcranial electrical stimulation (TMS) which now has the blessing of the UK National Institute of Clinical and Health Excellence (NICE) for migraine treatment and prevention. See my previous blog, Are magnets transforming neurological practice, for more on TMS.

8. Peripheral nerve stimulation

Another new dog is reported in Neurology with the self-explanatory title: Migraine prevention with a supraorbital transcutaneous stimulator. Nerve stimulation is of course an old trick in migraine, but the supraorbital nerve is a new target. This article from Pain Physician gives a detailed review of peripheral nerve stimulation and migraine.

 

Migraine Aura Kaleidoscope. Joana Roja on Flikr. https://www.flickr.com/photos/cats_mom/2988669345/in/photostream/
Migraine Aura Kaleidoscope. Joana Roja on Flikr. https://www.flickr.com/photos/cats_mom/2988669345/in/photostream/

 

Migraine remains challenging to neurologists and distressing for their patients. Perhaps we can now dispense hope along with prescriptions.

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

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