Do statins really increase the risk of Parkinson’s disease?

Statins are famous, and their fame lies in their ability to bust cholesterol, the villain in many medical disorders such as heart attack (myocardial infarction) and stroke. Some may add that statins are infamous, and this is partly because of their side effects such as muscle pain. Love them or hate them, we can’t get away from statins…even as the debate rages about their benefits and downsides.

By ChiltepinsterOwn work, CC BY-SA 3.0, Link

It is not surprising therefore that the statin debate will filter into neurology. The sticking point here however has nothing to do with cholesterol busting, but all to do with whether statins increase or reduce the risk of developing Parkinson’s disease (PD). Strange as it may seem, statins and PD have a long history. And a positive one generally, I hasten to add. There is a large body of evidence to suggest a protective effect of statins on PD as reflected in the following studies:

  1. Confounding of the association between statins and Parkinson disease: systematic review and meta-analysis 
  2. Statin therapy prevents the onset of Parkinson disease in patients with diabetes
  3. Statin use and risk of Parkinson’s disease: A meta-analysis 
  4. Statin use and its association with essential tremor and Parkinson’s disease
  5. Statin use and the risk of Parkinson’s disease: an updated meta-analysis
  6. Long-term statin use and the risk of Parkinson’s disease
  7. Discontinuation of statin therapy associated with Parkinson’s disease
Modeling the Molecular Basis of Parkinson’s Disease. Argonne National Laboratory on Flikr https://www.flickr.com/photos/argonne/4192798573

It was therefore with some consternation that a recent study, published in the journal Movement Disorders, really put the cat among the pigeons. The paper is titled:

Statins may facilitate Parkinson’s disease: insight gained from a large, national claims database,

The authors of this paper set out to investigate ‘the controversy surrounding the role of statins in Parkinson’s disease’. In this retrospective analysis of over 2,000 people with PD, and a similar number of control subjects, the authors found that statins significantly increased the risk of developing PD. This is clearly a conclusion looking for a fight!

By Col. Albert S. Evans – internet archives, Public Domain, Link

I must admit I was totally unaware there was any controversy about statins and PD. I was therefore curious to find out what studies are out there fuelling it. Which other trials have bucked the trend and reported an increased risk of PD from statins? And where best to find the answers but in PubMed, the repository of all human knowledge! And I found that there were only a few studies that did not report a protective effect of statins on PD, and these studies concluded, quite reasonably, that they found no relationship between PD and statins. Here are a few of the studies:

  1. Statin adherence and the risk of Parkinson’s disease: A population-based cohort study. 
  2. Use of statins and the risk of Parkinson’s disease: a retrospective case-control study in the UK. 
  3. Statin use and the risk of Parkinson disease: a nested case control study. 

These papers reporting the absence of evidence seem happy to engage in an amicable debate to resolve the question.

By DavidKF1949Own work, CC BY-SA 3.0, Link

One study however stood out like a sore thumb because it positively reported a negative effect of statins on PD (try and work that out!). This 2015 study, also published in Movement Disorders, is titled Statins, plasma cholesterol, and risk of Parkinson’s disease: a prospective study. The paper concludes that “statin use may be associated with a higher PD risk, whereas higher total cholesterol may be associated with lower risk“. Not only are the authors arguing that statins are bad for PD, they are also suggesting that cholesterol is good! This is a paper that was itching for fisticuffs.

By Jan SteenWeb Gallery of Art:   Image  Info about artwork, Public Domain, Link

What is a jobbing neurologist to do? What are the millions of people on statins to do? Whilst awaiting further studies, I will say stay put. Go with the bulk of the evidence! And keep track of The Simvastatin Trial, funded by The Cure Parkinson’s Trust. This trial is looking at the benefit of statins in slowing down PD. And surely, very soon, the science will lead to a resolution of the argument-all you need to do is keep track of everything PD in Neurochecklists.

By Léon Augustin Lhermittehttp://wellcomeimages.org/indexplus/obf_images/fc/7f/643258ab30237374aaea5ac15757.jpgGallery: http://wellcomeimages.org/indexplus/image/L0006244.html, CC BY 4.0, Link

 

More activity on the fringes of gluten neurology

I have dabbled into gluten neurology before with my post gluten neurology-persisting and growing? 

https://pixabay.com/en/wheat-field-wheat-cereals-grain-640960/
https://pixabay.com/en/wheat-field-wheat-cereals-grain-640960/

Prophetic it seems, as I am here forced to revisit the topic because  I came across a few recent interesting reports on the neurology of gluten.

Gluten psychosis

By Vincent van Gogh - bgEuwDxel93-Pg at Google Cultural Institute, zoom level maximum, Public Domain, Link
By Vincent van GoghbgEuwDxel93-Pg at Google Cultural Institute, zoom level maximum, Public Domain, Link

Take this case report from Nutrients titled gluten psychosis: confirmation of a new clinical entity. The article comes with some good references that suggest it will do no harm to check anti-gliadin antibodies in people with unexplained psychosis. I do wonder how one case report would confirm an entity such as gluten psychosis, but there you are.

Gluten-induced visual impairment

By OpenStax College - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, Link
By OpenStax College – Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, Link

The second item is another case report published in Journal of Neurology titled severe, persistent visual impairment associated with occipital calcification and coeliac disease. The subject of the case report has long-standing coeliac disease and visual impairment. Her brain MRI scan showed calcifications in the visual area, evidence the authors claim, of celiac disease causing brain calcifications …..and thereby causing the patients visual loss. Is it just a case of correlation rather than causation? But there you are.

Gluten-induced motor neurone disease (MND)

Multiphoton microscopy of mouse motor neurons. ZEISS microscopy on Flikr. https://www.flickr.com/photos/zeissmicro/12174353194
Multiphoton microscopy of mouse motor neurons. ZEISS microscopy on Flikr. https://www.flickr.com/photos/zeissmicro/12174353194

The third report however pushes credulity to the limits. It is a review in Brain Blogger titled celiac disease and amyotrophic lateral sclerosis-is there a link? To its credit, the piece is heavily referenced; one such reference is from the American Journal of Neuroradiology  titled White Matter Lesions Suggestive of Amyotrophic Lateral Sclerosis Attributed to Celiac Disease. The thought is hard to bear, but there you are.

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By Photograph by Pdeitiker - Transferred from en.wikipedia to Commons., Public Domain, Link
By Photograph by Pdeitiker – Transferred from en.wikipedia to Commons., Public Domain, Link

What are your thoughts on the neurology of gluten? Please leave a comment

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Terminological exactitude: changing the names of established neurological disorders

This is a quick post to highlight changes and proposed changes to some neurological terms. It is not unusual for such changes to occur every now and then. We have, for example, seen benign intracranial hypertension (BIH) changed to idiopathic intracranial hypertension (IIH), and Hallavorden Spatz disease transformed into pantethonate kinase associated neurodegeneration (PKAN).

Names scratched into a wall. Evelyn Simak on Geograph. http://www.geograph.org.uk/photo/4681807
Names scratched into a wall. Evelyn Simak on Geograph. http://www.geograph.org.uk/photo/4681807

One recent important change in neurological terminology, starting tentatively but beginning to take hold, is of nocturnal frontal lobe epilepsy (NFLE) to sleep-related hypermotor epilepsy.

The second is the suggested change from exploding head syndrome to episodic cranial sensory shock. I am not quite sure it will take off, but time will tell!

The third, not too new but surprising non-the-less, is the change from primary dystonia to focal isolated dystonia

Are you aware of any other issues of terminological exactitude? Please leave a comment.

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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.

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Why is chronic Lyme disease so frustrating to neurology?

Lyme disease is a well-known infection. It takes its name from Lyme, Connecticut, where it was first recognised as a distinct disease in 1975. The disease is caused by the infamous Borrelia species which get into humans through tick bites. The transmission typically occurs when the victim is taking a gingerly walk in deer-inhabited forests, usually in the pleasant months of May or June. The tick may leave a signature skin rash, erythema migrans. In the ideal situation, the clear history and a positive Lyme serology test make the diagnosis. A short treatment course with an antibiotic such as doxycycline or ceftriaxone and, hey presto, Lyme disease is cured, totally and permanently. And doctor and patient live happily ever after….

By USDA photo by Scott Bauer - Image Number: K5437-3.http://www.ars.usda.gov/is/graphics/photos/may01/k5437-3.htm, Public Domain, https://commons.wikimedia.org/w/index.php?curid=245466
By USDA photo by Scott Bauer – Image Number: K5437-3.http://www.ars.usda.gov/is/graphics/photos/may01/k5437-3.htm, Public Domain, https://commons.wikimedia.org/w/index.php?curid=245466

The above scenario, unfortunately, only plays out on planet Utopia. On planet earth, things are rarely that straightforward. In reality, the story is often vague and devoid of ticks, deer, and forests. The Lyme blood test is often ambiguous and frequently misleading. And in many cases, the antibiotic only partially improves the symptoms. The end result is a frustrated patient and a baffled doctor. Several Google searches after and the patient is convinced they have chronic Lyme disease, and demanding extended courses of antibiotic treatment. Several PubMed searches later, the doctor finds no scientific evidence to support prolonged antibiotic use, and refuses to acquiesce (apologies to Captain Barbossa). A vicious pantomime then follows.

tick-1271763_1280

Neurologists tango with Lyme disease in the form of neuroborelliosis. This form of Lyme disease is a nightmare for neurologists because of the varied ways it may present. This was highlighted by a recent excellent review in the American Journal of Neuroradiology titled Lyme Neuroborreliosis: Manifestations of a Rapidly Emerging Zoonosis. These manifestations include a painful lymphocytic meningoradiculitis, cranial nerve palsies, meningoencephalitis, encephalomyelitis, and transverse myelitis. Then there is the nebulous concept of chronic Lyme neuroborreliosis, something the authors say is ‘a focus of ongoing conjecture and controversy‘. They, however, jumped into this minefield and proposed a set of diagnostic criteria which include characteristic symptoms, specific serum antibodies, spinal fluid inflammation, and spinal fluid antibody production. On Utopia, you might add.

By Centers for Disease Control and Prevention (NIH) - Centers for Disease Control and Prevention (NIH), Public Domain, https://commons.wikimedia.org/w/index.php?curid=29608423
By Centers for Disease Control and Prevention (NIH) – Centers for Disease Control and Prevention (NIH), Public Domain, https://commons.wikimedia.org/w/index.php?curid=29608423

To resolve the tricky question, a group of researchers carried out a systematic review of 44 clinical trials that had reported on chronic Lyme neuroborreliosis. They published their findings in the Journal of Neurology under the title Prevalence and spectrum of residual symptoms in Lyme neuroborreliosis after pharmacological treatment: a systematic review. The authors found that, in those studies that were rigorously carried out, there was very little evidence of chronic Lyme disease. They concluded that chronic Lyme disease may just be ‘an artifact of unspecific case definitions in single studies‘.

By Photo Credit:Content Providers(s): CDC - This media comes from the Centers for Disease Control and Prevention's Public Health Image Library (PHIL), with identification number #6631.Note: Not all PHIL images are public domain; be sure to check copyright status and credit authors and content providers.English | Slovenščina | +/−Cropped and uploaded originally to (http://en.wikipedia.org/wiki/Image:Borrelia_image.jpg), Public Domain, https://commons.wikimedia.org/w/index.php?curid=4393667
By Photo Credit:Content Providers(s): CDC – This media comes from the Centers for Disease Control and Prevention‘s Public Health Image Library (PHIL), with identification number #6631.Note: Not all PHIL images are public domain; be sure to check copyright status and credit authors and content providers.English | Slovenščina | +/−Cropped and uploaded originally to (http://en.wikipedia.org/wiki/Image:Borrelia_image.jpg), Public Domain, https://commons.wikimedia.org/w/index.php?curid=4393667

This conclusion is supported by another study in the same journal titled Quality of life, fatigue, depression and cognitive impairment in Lyme neuroborreliosis. This study discovered that patients who were adequately treated for Lyme neuroborreliosis hardly ever developed persisting symptoms.

By Childe Hassam - http://www.the-athenaeum.org/art/full.php?ID=19897, Public Domain, https://commons.wikimedia.org/w/index.php?curid=10199778
By Childe Hassam – http://www.the-athenaeum.org/art/full.php?ID=19897, Public Domain, https://commons.wikimedia.org/w/index.php?curid=10199778

I guess this will not be the end of the story with chronic Lyme disease, but research is shedding light on a very controversial subject. Nirvana soon?

Whilst on the subject, you may want to check out these articles that open up another potential can of worms, intracranial hypertension in Lyme neuroborreliosis.

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

 

Gluten neurology-persistent and growing?

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

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

 

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

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

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

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