What is the last word on migraine and PFOs?

This is surely one of neurology’s bug bears, the old chestnut. Just when one generation of neurologists thinks it has buried and sealed it in an impervious crypt, it resurrects to haunt the next breed. This cyclical and macabre dance of migraine and PFOs evokes a sense of deja vu every time it comes around. And each spawn of neurologists predictably picks up the gauntlet, answers the call to arms, and sets out to slaughter the ghost of migraines past.

By Lille1982 – Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9682382

But let’s take a step back to basics with some definitions. The foramen ovale is just a ‘hole in the heart‘ between the right and left atria, or upper heart chambers. It is essential in foetal life because it enables circulating blood to bypass the superfluous foetal lungs (apologies to readers across the Atlantic for the superfluous ‘o’!). However, after birth, when blood needs to circulate through the now indispensable lungs, the foramen ovale becomes irrelevant. In most people, the foramen ovale humbly accepts its fate, crawls to a corner, and closes shop. But foramen ovales in some people are recalcitrant; standing their ground, they endure and survive as PFOs.

By DrJanaOfficial – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=50477765

It is not clear how the myth started, but stories of migraine cure following surgical closure of PFO spread rapidly and widely. Very soon, migraineurs where demanding echocardiograms to check if they have PFOs lurking in their tickers. Research trials investigating this issue started as a trickle, and very soon become a flood. But rather than shed light, the conflicting results intensified the darkness. That is, until some indignant and determined neurologists and cardiologists set out to settle the matter once and for all. And the onslaught came in three waves of studies.

MIGRAINE. aka Tman on Flickr. https://www.flickr.com/photos/rundwolf/331545021

The first wave in the attempt to slay the beast of migraine and PFO was a trial published in the journal Headache. Davinia Larrosa and colleagues studied 183 people with migraine and found that, whilst PFOs were larger and more permanent in people with migraine, there was no relationship between patent foramen ovale and migraine frequency.

Migraine spectrum. JoanDragonfly on Flickr. https://www.flickr.com/photos/joandragonfly/26221136058

The second wave was a study published in the European Heart Journal by Heinrich Mattle and colleagues. In their PRIMA trial (Percutaneous Closure of PFO in Migraine with Aura), they blindly allocated or randomized half of their subjects with refractory migraine and PFO to have PFO closure surgery. And their verdict was, PFO closure did nothing to reduce the frequency of migraine.

Open the key to your heart. Maria Eklind on Flickr. https://www.flickr.com/photos/mariaeklind/24659701809

The third wave, launched by Nauman Tariq and colleagues, took a different tack. They carried out a detailed review of practically all the studies that had addressed the subject. Their brilliantly titled paper, “Patent foramen ovale and migraine: closing the debate, reflected their ambition to settle the question once and for all. After an arduous trawl through the literature, and a mind-blowing crunching of statistics, the authors came to the conclusions that “there is no good quality evidence to support a link between migraine and PFO“, and “closure of PFO for migraine prevention does not significantly reduce the intensity and severity of migraine“.

By Patrick J. Lynch, medical illustrator – Patrick J. Lynch, medical illustrator, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1488277

The final word therefore is, leave PFOs alone! But there is a big caveat. There is one situation where PFO is associated with migraine, and that is when it is accompanied by another heart anomaly called an atrial septal aneurysm (ASA). The evidence for this comes from Roel Snijder and colleagues, and the title of their paper says it all: Patent foramen ovale with atrial septal aneurysm is strongly associated with migraine with aura: a large observational study. We already knew that PFO associated with ASA increases the risk of stroke; we can now add to this, the risk of migraine with aura.

By H. Airy – Flatau 1912 “Migrena” monograph after previous publication of H. Airy, Public Domain, https://commons.wikimedia.org/w/index.php?curid=7814450

The debate is now hopefully sealed and settled. But don’t hold your breath for too long: the phantom of migraine and PFO may just rear its hideous head again at a neuroscience centre near you.


The 9 neurological manifestations of anti MOG antibody disorder

Autoimmune disorders are probably the most proliferative field of neurology. It seems like there is a blazing headline every week announcing a new antibody disease. Many of these antibodies are esoteric, but some shake the foundations of medical practice. Anti-MOG antibody is one of those which requires you to stop and pay attention, and it has significantly affected neurological practice in a very big way.

By Simon Caulton – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=20522656

Perhaps the most important thing about anti-MOG antibody disease is that, like the chameleon, it presents in many guises. For the neurologist therefore, the first thing is to recognise these varied manifestations. Here then is a quick list of the 9 manifestations of anti MOG antibody disorder.


1. Optic neuritis (ON)

2. Neuromyelitis optica spectrum disorders (NMOSD)

3. Multiple sclerosis (MS)

4. Acute disseminated encephalomyelitis (ADEM)

5. Multiphasic disseminated encephalomyelitis (MDEM)

6. Isolated transverse myelitis (TM)

7. Leukodystrophy-like phenotype

8. Cerebral cortical encephalitis

9. Combined central and peripheral demyelinating syndrome (CCPD)


Optic Nerve Side View. Francisco Bengoa on Flikr. https://www.flickr.com/photos/frecuenciamedicafb/7404373800


You can explore anti MOG antibody disorder further in Neurochecklists under the following titles:

Image from page 400 of “Diseases of the nervous system” (1910). Internet Archive Book Images on Flickr. https://www.flickr.com/photos/internetarchivebookimages/14586405720/


For a detailed review and guidance, check this paper in Journal of Neuroinflammation:

 MOG encephalomyelitis: international recommendations on diagnosis and antibody testing.

By PecatumOwn work, CC BY-SA 4.0, Link

What are the pitfalls and perils of intracranial pressure?

Crudely speaking, the nervous system is made up of two parts. The peripheral nervous system, composed of nerves and muscles, is rather robust and roams free, exposed to the elements. On the other hand, the central nervous system, consisting of the brain and spinal cord, is delicate and fragile. It is therefore protectively cocooned in a rigid skull and a hardy vertebral skeleton. But even this tough fortress isn’t secure enough for these dainty neurones; they are, after all, the command and control system for the whole body. Therefore, to further insulate them from the physical and physiological perturbations that continuously threaten them, nature has further sequestered them within a very exquisitely regulated irrigation system, the cerebrospinal fluid (CSF).

Internet Archive book Images on Flickr. https://www.flickr.com/photos/internetarchivebookimages/14769907251/

The CSF is actually a fine filtrate of the blood that flows in the arteries. The sieve is the very forbidding blood-brain barrier (BBB) which turns away all the blood cells, and carefully sets a target on how much protein and glucose to let in. The pressure within the CSF is also very finely tuned, not too high…and not too low; that is how the neurones like it.


By Dr. Johannes Sobotta – Atlas and Text-book of Human Anatomy Volume III Vascular System, Lymphatic system, Nervous system and Sense Organs, Public Domain, https://commons.wikimedia.org/w/index.php?curid=29135482


Alas, as with all systems, the CSF is vulnerable to external miscreants; infections such as meningitis,  encephalitis, and brain abscesses which cause brain swelling or cerebral edema. The CSF is also largely defenceless to internal insurgents, fifth columnists, such as a brain tumours, haematomas (bleeds), and cerebral vein thrombosis (venous clots). The smooth flow of the CSF may also be obstructed, resulting in hydrocephalus or enlargement of the brain’s ventricular system. In all these circumstances, the intracranial pressure is often elevated, a situation aptly dubbed intracranial hypertension. Very often, intracranial hypertension may occur without any obvious cause, and this condition is referred to as idiopathic intracranial hypertension (IIH). Because IIH threatens vision, neurologists have abandoned its old and misleading name, benign intracranial hypertension (BIH).

By BruceBlaus. When using this image in external sources it can be cited as:Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014“. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436. – Own work, CC BY 3.0, Link

Intracranial hypertension is no walk in the park as it portends disaster, whatever its cause. As it is a  potentially fatal state, the early warning signs are drilled into all doctors in medical school…when their brains are still malleable. These red flag features are severe headache, impaired consciousness, progressive visual loss, dilated or blown pupils, papilledema (swelling of the optic nerve head), and neck stiffness. The standard operating procedure for intracranial hypertension is to deflate the pressure as quickly as possible, by hook or by crook. This may be medical, with infusions such as mannitol, or surgical, with procedures such as decompressive craniectomy (removal of part of the skull). The terminal stage of intracranial hypertension, the most ominous neurological emergency, is cerebral herniation: this is the catastrophic compression of the brainstem into the narrow and tight spinal canal: a physical state that is incompatible with life.

By Ambika S., Arjundas D., Noronha V. – https://openi.nlm.nih.gov/detailedresult.php?img=2859586_AIAN-13-37-g001&query=papilledema&it=xg&req=4&npos=2, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=47658492

As with all waves, intracranial pressure also has its lows, and it is a no-brainer that neurologists call this intracranial hypotension. This is not as hazardous as intracranial hypertension, but it is worthy of respect in view of its devastating morbidity. The usual cause, and again no prizes for guessing this, is a leak. The puncture in this case is often iatrogenic, in other words, the whodunnit is the doctor. This may be deliberate, such as when the doctor attempts to remove some CSF to test, via a procedure called a  lumbar puncture (LP). It may also be accidental, such as when your friendly anaesthetist performs an epidural to relieve pain. In both situations, the dura protecting the CSF is perforated, causing spinal fluid leakage. This manifests as postural or orthostatic headache; by definition, this is a headache that sets in within 15 minutes of standing up, and resolves within 15 minutes of lying down flat. The treatment in such cases is strict bed rest, drinking loads of fluids, including caffeinated drinks, and waiting for the dura to heal itself…usually within one week. If this does not happen, then an intravenous caffeine infusion may be required. An epidural blood patch may also be carried out, again by your friendly anaesthetist, who squirts a little of the victims blood around the site of the leak, to, well, ‘patch it up’. In extremis, surgery may be needed to seal the leak, but this is way beyond my pay grade.

By Paul Anthony Stewart – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=75808444

Intracranial hypotension may however develop without any apparent cause, and this is called spontaneous intracranial hypotension (SIH). The causes of SIH include unpredictable dural tears, ruptured meningeal diveticuli (outpouchings of the dura), and direct CSF-venous fistulae (don’t ask!) There are a variety of risk factors for SIH such as connective tissue diseases and bariatric surgery. It is very helpful that SIH leaves characteristic tell-tale clues on brain MRI scans, and these include subdural hygroma (plain fluid collections under the dura); subdural haematoma (blood under the dura); meningeal enhancement with contrast dye; engorgement of the pons and pituitary; and the interesting dinosaur tail sign on fat suppression T2 MRI (FST2WI). The gold standard test to localise the site of leakage in SIH is radionuclide cisternography. In the absence of this rather sophisticated test, a CT myelogram may be considered. Treatment is similar to that of other forms of intracranial hypotension, but other measures that may be required to seal the leak, including the use of fibrin sealeant.

By Hellerhoff – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18946727

If you have reached the end of this blog post, then you deserve a prize. Four prizes actually: recent interesting reports in the field of SIH to explore:

  1. The use of transorbital ultrasound in making a diagnosis.
  2. Treatment of complicated SIH with intrathecal saline infusion.
  3. SIH complicated by superficial siderosis.
  4. Severe SIH complicated by sagging brain causing causing postural loss of consciousness.
By © Nevit Dilmen, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=45660723



Clipping the wings of cerebral aneurysms: is the pendulum swinging back?

This is a follow up to my previous blog post, What should we really know about cerebral aneurysms? In that post, I discussed the nature and presentations of cerebral aneurysms. In this post I will look at the two major treatments for cerebral aneurysms, exploring their pros and cons, and looking at some emerging challenges to the conventional wisdom. 

By Tiago Etiene QueirozOwn work, CC BY-SA 3.0, Link

The first question to answer regarding treatment of aneurysms is whether they need any treatment at all. In other words, are they best left well alone? In principle, aneurysms that have ruptured require treatment, irrespective of their size. On the other hand, aneurysms that are discovered incidentally, before they rupture, may not need surgical treatment unless they are large (usually 7mm or more in diameter), or they are associated with high-risk features/locations. Low-risk aneurysms that do not require treatment however need long-term surveillance with intermittent brain imaging. To limit the growth of such aneurysms, people harbouring them are advised to stop smoking, and if they have hypertension, to ensure that this is well-controlled.

By Professor Dr. O. Bollinger. – LEHMANN’S MEDICIN. HAND ATLANTEN Atlas und Grundrissder PATHOLOGISCHENANATOMIE 1901, Public Domain, Link

There are two treatment approaches to ruptured aneurysms and high-risk unruptured aneurysms. The first is invasive and neurosurgical; the cranium is opened, the aneurysm located, and a surgical clip is put around its neck, sequestering it from its parent vessel. In this way, with its wing literally clipped, the aneurysm is disarmed, its potential for growth and rupture severely restricted. 

By Roberto Stefini – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=47226273

The other procedure, younger and safer than clipping, is endovascular coiling or coil embolisation. This procedure, performed by an interventional neuroradiologist, involves tunnelling a fine wire or coil through blood vessels until it reaches the aneurysm. The aneurysm space is then filled up with the coil until it is totally obliterated. Unable to fill up with blood or expand, the aneurysm is rendered impotent. Both coiling and clipping however carry a small failure risk, resulting in aneurysm recurrence or re-rupture.

By 77giallo77 – Own work, CC BY-SA 4.0, Link

This is the conventional wisdom of cerebral aneurysm treatment. But there are advocates out there who are pushing the case for clipping over coiling. One reason they put forward is the emerging observation that clipping results in better recovery of function of the third cranial or oculomotor nerve. The oculomotor nerve is critical to the movement of the eye and eyelid, and it is vulnerable to compression by the posterior communicating artery (PCOM) aneurysm. A compressed third cranial nerve results in a droopy eyelid (ptosis) and double vision (diplopia); recovery of function of the oculomotor nerve is therefore an important goal in the treatment of aneurysms.

Автор: Patrick J. Lynch, medical illustrator – Patrick J. Lynch, medical illustrator, CC BY 2.5, Посилання

There are now at least four systematic reviews and/or meta-analyses that show that recovery of the oculomotor nerve function is better achieved by clipping than by coiling. These are:

Another meta-analysis, titled Clinical outcome after surgical clipping or endovascular coiling for cerebral aneurysms, goes further to argue that clipping results in better chances of survival and independent living than coiling. 

By HellerhoffOwn work, CC BY-SA 3.0, Link

These may be the last-gasp attempts of clippers to have one up over coilers, but the consensus still remains dominantly in favour of endovascular coiling. We however need to keep a close eye on this pendulum-it may just swing back unexpectedly.


Why not check out these related blog posts:

How does aspirin influence the rupture risk of cerebral aneurysms?

Is the growth of cerebral aneurysms predictable?

What should we really know about cerebral aneurysms?

Cerebral aneurysms are scary things. It is alarming enough that they exist, but it is more spine-chilling that they enlarge with time. The most infamous aneurysm arises from the posterior communicating artery, the so-called PCOM aneurysm. And it signifies its sinister intent when it gradually enlarges and compresses its vascular neighbour, the third cranial nerve, otherwise known as the oculomotor nerve. A dysfunctional third nerve manifests with a droopy eyelid (ptosis) and double vision (diplopia). The reason for the double vision becomes obvious when the neurologist examines the eyes; one eyeball is out of kilter and is deviated downwards and outwards; it is indeed down and out! The pupil is also very widely dilated (mydriasis). These are among the most worrying red flags in medicine, and a very loud call to arms. Cerebral aneurysms however often wave no flags, red or otherwise. Indeed the most malevolent of them will expand quietly until they reach horrendous proportions, and then, without much ado, just rupture. They are therefore veritable time bombs…just waiting to go off.

By Tiago Etiene Queiroz – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=24418848

Cerebral aneurysm however do not need to reach large proportions to rupture; some just rupture when they feel like. Aneurysms under 7mm in diameter however are less prone to rupture. A rupturing aneurysm presents with very startling symptoms. The most ominous is a sudden onset thunderclap headache (TCH), subjects reporting feeling as if they have been hit on the back of the head with a baseball or cricket bat. It is not quite known what non-sporting patients experience-for some reason they never get aneurysms in neurology textbooks! More universally appropriate, a ruptured aneurysm may manifest as sudden loss of consciousness. Both symptoms result from leakage of blood into the cerebrospinal fluid (CSF) space, a condition known as a subarachnoid haemorrhage (SAH).

By Lipothymia – Anonymised CT scan from my own practice, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=787177

You may breath a small sigh of relief here because the vast majority of people with thunderclap headaches do not have subarachnoid haemorrhage. Unfortunately, every person who presents with a thunderclap headache must be investigated- to exclude (hopefully), or confirm (ruefully), this catastrophic emergency. The first test is a CT head scan which identifies most head bleeds. The relief of a normal scan is however short-lived because some bleeds do not show on the CT. The definitive test to prove the presence or absence of a bleed is less high tech, but more invasive: the humble spinal tap or lumbar puncture (LP). This must however wait for least 12 hours after the onset of headache or blackout. This is the time it takes for the haemoglobin released by the red blood cells to be broken down into bilirubin and oxyhaemoglobin. These breakdown products are readily identified in the biochemistry lab, and they also impart on the spinal fluid a yellow tinge called xanthochromia. The test may be positive up to 2 weeks after the bleed, but the sensitivity declines after this time. A positive xanthochromia test is startling and sets off an aggressive manhunt for an aneurysm-the culprit in most cases. 

By Ben Mills – Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=13051957

Many people with cerebral aneurysms have a family history of these, or of subarachnoid haemorrhage. Some others may have connective tissue diseases such as Ehler’s Danlos syndrome (EDS), adult polycystic kidney disease (APCKD), or the rare Loeys-Dietz syndrome. This family history is a window of opportunity to screen family members for aneurysms. The screening is usually carried out with a CT angiogram (CTA) or MR angiogram (MRA). People are often not born with aneurysms, but tend to develop them after the age of 20 years. Aneurysm surveillance therefore starts shortly after this age, and many experts advocate repeating the screening test every 5-7 years until the age of 70-80 years.

By Nicholas Zaorsky, M.D. – Nicholas Zaorsky, M.D., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15533196

How are aneurysms treated? This will be the subject of a future blog post so watch this space!


Revealing the invisible rhinoceros: paying attention to adult ADHD

Adult attention deficit hyperactivity disorder (ADHD) is a key psychiatric disorder. It is characterised by some core clinical features which are hyperactivity, inattention, impulsivity, disorganisation, and low stress tolerance. People with ADHD have several life impediments that characterise their day-to-day lives; these include difficulty starting tasks, struggling to prioritise, and failing to pay attention to details. Enduring chaotic lifestyles, they struggle to keep up with their academic, employment, and relationship commitments.

ADHD. Practical Cures on Flickr. https://www.flickr.com/photos/practicalcures/23280349432

For the public and for most physicians, ADHD is recognised only as a childhood disorder. But 10-60% of childhood onset ADHD persist into adulthood. Furthermore, about 4.5% of adults have ADHD. The failure to recognise ADHD as an adult problem therefore means it is easily missed in adult psychiatry and neurology clinics. Referring to this in a review published in the journal Psychiatry (Edgmont), David Feifel labelled adult ADHD as the invisible rhinoceros (you must read the article to understand why it is not the elephant in the room). Concerned that many adults with ADHD are misdiagnosed as suffering with anxiety or depression, he urged psychiatrists to routinely screen for adult ADHD in every adult presenting with these disorders.

Southern White Rhino. William Murphy on flickr. https://www.flickr.com/photos/infomatique/34467891470

The scale of the failure to diagnose adult ADHD was emphasised by Laurence Jerome in a letter to the Canadian Journal of Psychiatry. Titled Adult attention-deficit hyperactivity disorder is hard to diagnose and is undertreated, his letter highlighted the finding of the US ADHD National Comorbidity Survey which concluded that most adults with ADHD have ‘never been assessed or treated’. He argued that this oversight places heavy lifetime burdens on adults with ADHD such as impaired activities of daily living, academic underachievement, poor work record, marital breakdown, and dysfunctional parenting. A great burden indeed, but a preventable and treatable one!

ADHD. Bob on Flickr. https://www.flickr.com/photos/contortyourself/5016270276

How is all this psychiatry relevant to the general neurologist? Well, many manifestations of ADHD are the stuff of the neurology clinic. Cognitive dysfunction for example is prevalent in adult ADHD, and it may present to the neurologist as impaired short term memory, executive dysfunction, impaired verbal learning, and, of course, impaired attention. Sleep related disorders are also frequent in adult ADHD, and these include excessive daytime sleepiness (EDS), restless legs syndrome (RLS), periodic leg movements of sleep (PLMS), and cataplexy. There are also several other neurological co-morbidities of adult ADHD such as epilepsy and learning disability.

ADHD. Jesper Sehested on Flickr. https://www.flickr.com/photos/153278281@N07/38447999522


It is therefore high time for neurologists and psychiatrists to reveal the invisible rhinoceros!

The emerging links between Alzheimer’s disease and infections

Alzheimer’s disease (AD) is one of the most fearsome and recalcitrant scourges of neurology. We think we know a lot about it; after all it has been a quite a while since Alois Alzheimer described amyloid plaques and neurofibrillary tangles in his index patient, Frau Deter. But the more neuroscientists study the disease, the murkier the field looks. For example, we are still not quite sure what the plaques and tangles really signify; for all we know, they may just be innocent bystanders, powerless by-products of a neurodegenerative process that defies understanding. We have accumulated an endlessly long list of AD risk factors, but we have singularly been unable to point a finger at the cause of AD.

By National Institute on Aging – http://www.nia.nih.gov/alzheimers/topics/alzheimers-basics, Public Domain, Link

This elusive void may however be a void no longer, if what superficially appears to be an outlandish theory turns out to be correct. And the theory is that AD is caused by infection! Just take a deep breathe, and allow yourself the space to make a giant leap of imagination. My attention was first drawn to the infective hypothesis of AD by a headline in Scientific American screaming Controversial New Push to Tie Microbes to Alzheimer’s Disease. The obvious key word here of course is controversial: is it possible that AD, this quintessential neurodegenerative disease, is…just another chronic infection?

Alzheomer’s at the microscopic level. Oak Ridge National Laboratory on Flickr. https://www.flickr.com/photos/oakridgelab/4071453587

To find the original source of the story, the trail of bread crumbs led to an editorial published in the Journal of Alzheimer’s Disease in 2016, plainly titled Microbes and Alzheimer’s Disease. But this is not a run-of-the-mill editorial at all because it was written by 33 senior scientists and clinicians from a dozen countries. And their reason for an alternative theory of AD is simple: amyloid, the long-suspected culprit for decades, has failed to live up to its billing. They point  out that amyloid exists harmlessly in the brains of many older people who never go on to develop dementia. They also cite studies which demonstrate that treating amyloid, by immunological means, does not improve the state of people suffering from AD. Amyloid, in other words, is not such a bad guy after all. But all the while we have been setting traps to ensnare it, the microbial villains have been running amok, having a field day.

Автор: own work – adapted from http://www.pdb.org/pdb/cgi/explore.cgi?pdbId=1IYT using PyMOL, Суспільне надбання (Public Domain), Посилання

But why should microbes succeed where amyloid, the ubiquitous protein, has woefully failed? The editorial gave 8 good reasons to argue that the infection theory is better than the amyloid hypothesis. One reason is that the brains of people with AD are often riddled with inflammation, a characteristic feature of infections. Another reason is the observation that AD can be transferred to primates when they are inoculated with the brain tissue of someone with AD.

194 001 001. US Department of Energy on Flickr. https://www.flickr.com/photos/departmentofenergy/14534273083

It may be hard to swallow, but if you are still maintaining your imaginative leap, just spare a thought for the microbes that are on the line-up of competing suspects. Take your pick, from helicobacter pylori to fungal infections, from spirochetes such as Lyme neuroborreliosis to chlamydia, from cytomegalovirus (CMV) to polymicrobial infections. But of all the potential suspects, one stands head and shoulders above the rest (no fungal pun intended-honest).

E. coli bacteria. NIAID on Flickr. https://www.flickr.com/photos/niaid/16578744517

And the culprit with the most number of index fingers pointing at it is herpes simplex virus type 1 (HSV1). The editorial tells us that there have been about 100 publications, by different groups, demonstrating that HSV1 is a ‘major factor‘ in the causation of AD. Some of these studies have shown that people with AD have immunological signs of significant HSV infection in their blood. The editorial goes further to review the possible mechanisms by which HSV1 may cause AD; one of these is the possibility that the virus lowers the risk of AD in people who possess the APOE ɛ4 allele genetic liability.

Von Thomas Splettstoesser (www.scistyle.com) – Eigenes Werk, CC BY-SA 4.0, Link

Just when you are getting your head round the idea, the infection theory takes a very sinister turn. And this relates to the perverse modus operandi of the microbes. The authors tell us that the microbes first gain access to the brains of their victims when they (the victims) were much younger. Like sleeper cells in their ghoulish crypts, the microbes hibernate, biding their time until their victims get older, and their immunity declines. The microbes then awaken, and like malevolent zombies, set out to wreak gory mayhem and cataclysmic destruction. And they do this either by causing direct damage to the brain, or indirectly by inducing inflammation.

Microbes. Quin Dombrowski on Flickr. https://www.flickr.com/photos/quinndombrowski/4067633894

You can now descend form your giant imaginative leap and start to wonder: if AD is indeed caused by microbes, what can we do about it? ‘Tis time for some down-to-earth deep thinking.