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.

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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

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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.

9 promising advances in the management of traumatic brain injury

Traumatic brain injury (TBI) is simply disheartening. It is particularly devastating because it usually affects young people in their prime, with the consequent personal, social, and economic consequences. This blog has previously touched a little on TBI with the post titled Will Smith and chronic traumatic encephalopathy? This was a light-hearted take on concussion in sports, but traumatic brain injury is nothing but a serious burden. So what are the big brains in white coats doing to take down this colossus? Quite a lot it seems. Here, for a taster, are 9 promising advances in the management of traumatic brain injury.

brain 22. Affen Ajlfe on Flickr. https://www.flickr.com/photos/142299342@N06/32794072623

Better understanding of pathology

An amyloid PET imaging study by Gregory Scott and colleagues, published in the journal Neurology, reported a rather surprising link between the pathology seen in long-term survivors of traumatic brain injury, with the pathology seen in Alzheimers disease (AD). In both conditions, there is an increased burden of β-amyloid () in the brain, produced by damage to the nerve axons. The paper, titled Amyloid pathology and axonal injury after brain trauma, however notes that the pattern of deposition in TBI can be distinguished from the one seen in AD. The big question this finding raises is, does TBI eventually result in AD? The answer remains unclear, and this is discussed in the accompanying editorial titled Amyloid plaques in TBI.

By National Institute on Aging – http://nihseniorhealth.gov/alzheimersdisease/whatisalzheimersdisease/01.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=25038029

Blood tests to detect concussion

The ideal biomarker for any disorder is one which is easy to detect, such as a simple blood test. A headline that screams Blood test may offer new way to detect concussions is therefore bound to attract attention. The benefits of such a test would be legion, especially if the test can reduce the requirement for CT scans which carry the risks of radiation exposure. This is where glial fibrillary acidic protein (GFAP) may be promising. The research is published in the journal, Academic Research Medicine, with a rather convoluted title, Performance of Glial Fibrillary Acidic Protein in Detecting Traumatic Intracranial Lesions on Computed Tomography in Children and Youth With Mild Head Trauma. The premise of the paper is the fact that GFAP is released into the blood stream from the glial cells of the brain soon after brain injury. What the authors therefore did was to take blood samples within 6 hours of TBI in children. And they demonstrated that GFAP levels are significantly higher following head injury, compared to injuries elsewhere in the body. This sounds exciting, but we have to wait and see where it takes us.

Diabetes test. Victor on Flickr. https://www.flickr.com/photos/v1ctor/10871254373

Advanced imaging

Brain Scars Detected in Concussions is the attention-grabbing headline for this one, published in MIT Technology Review. Follow the trail and it leads to the actual scientific paper in the journal Radiology, with a fairly straight-forward title, Findings from Structural MR Imaging in Military Traumatic Brain Injury The authors studied >800 subjects in what is the largest trial of traumatic brain injury in the military. Using high resolution 3T brain magnetic resonance imaging (MRI), they demonstrated that even what is reported as mild brain injury leaves its marks on the brain, usually in the form of white matter hyperintense lesions and pituitary abnormalities. It simply goes to show that nothing is mild when it comes to the brain, the most complex entity in the universe.

Volume rendering of structural MRI scan. Proxy Design on Flickr. https://www.flickr.com/photos/proxyarch/5920559323

Implanted monitoring sensors

Current technologies which monitor patients with traumatic brain injury are, to say the least, cumbersome and very invasive. Imagine if all the tubes and wires could be replaced with microsensors, smaller than grains of rice, implanted in the brain. These would enable close monitoring of critical indices such as temperature and intracranial pressure. And imagine that these tiny sensors just dissolve away when they have done their job, leaving no damage. Now imagine that all this is reality. I came across this one from a CBS News piece titled Tiny implanted sensors monitor brain injuries, then dissolve away. Don’t scoff yet, it is grounded in a scientific paper published in the prestigious journal, Nature, under the title Bioresorbable silicon electronic sensors for the brain. But don’t get too exited yet, this is currently only being trialled in mice.

Public Domain, https://commons.wikimedia.org/w/index.php?curid=190358

Drugs to reduce brain inflammation

What if the inflammation that is set off following traumatic brain injury could be stopped in its tracks? Then a lot of the damage from brain injury could be avoided. Is there a drug that could do this? Well, it seems there is, and it is the humble blood pressure drug Telmisartan. This one came to my attention in Medical News Today, in a piece titled Hypertension drug reduces inflammation from traumatic brain injury. Telmisartan seemingly blocks the production of a pro-inflammatory protein in the liver. By doing this, Telmisartan may effectively mitigate brain damage, but only if it is administered very early after traumatic brain injury. The original paper is published in the prestigious journal, Brain, and it is titled Neurorestoration after traumatic brain injury through angiotensin II receptor blockage. Again, don’t get too warm and fuzzy about this yet; so far, only mice have seen the benefits.

Neural pathways in the brain. NICHD on Flickr. https://www.flickr.com/photos/nichd/16672073333

Treatment of fatigue

Fatigue is a major long-term consequence of traumatic brain injury, impairing the quality of life of affected subjects in a very frustrating way. It therefore goes without saying, (even if it actually has to be said), that any intervention that alleviates the lethargy of TBI will be energising news. And an intervention seems to be looming in the horizon! Researchers writing in the journal, Acta Neurologica Scandinavica, have reported that Methylphenidate significantly improved fatigue in the 20 subjects they studied. Published under the title Long-term treatment with methylphenidate for fatigue after traumatic brain injury, the study is rather small, not enough to make us start dancing the jig yet. The authors have rightly called for larger randomized trials to corroborate their findings, and we are all waiting with bated breaths.

Ritalin. Ian Brown on Flickr. https://www.flickr.com/photos/igb/15713970479

Treatment of behavioural abnormalities

Many survivors of traumatic brain injury are left with behavioural disturbances which are baffling to the victim, and challenging to their families. Unfortunately, many of the drugs used to treat these behaviours are not effective. This is where some brilliant minds come in, with the idea of stimulating blood stem cell production to enhance behavioural recovery. I am not clear what inspired this idea, but the idea has inspired the paper titled Granulocyte colony-stimulating factor promotes behavioral recovery in a mouse model of traumatic brain injury. The authors report that the administration of G‐CSF for 3 days after mild TBI improved the performance of mice in a water maze…within 2 weeks. As the water maze is a test of learning and memory, and not of behaviour, I can only imagine the authors thought-surely only well-behaved mice will bother to take the test. It is however fascinating that G‐CSF treatment actually seems to fix brain damage in TBI, and it does so by stimulating astrocytosis and microgliosis, increasing the expression of neurotrophic factors, and generating new neurons in the hippocampus“. The promise, if translated to humans, should therefore go way beyond water mazes, but we have to wait and see.

By Ryddragyn at English Wikipedia – Transferred from en.wikipedia to Commons., Public Domain, https://commons.wikimedia.org/w/index.php?curid=2148036

Drugs to accelerate recovery

The idea behind using Etanercept to promote recovery from brain injury sound logical. A paper published in the journal, Clinical Drug Investigation, explains that brain injury sets off a chronic lingering inflammation which is driven by tumour necrosis factor (TNF). A TNF inhibitor will therefore be aptly placed to stop the inflammation. What better TNF inhibitor than Eternacept to try out, and what better way to deliver it than directly into the nervous system. And this is what the authors of the paper, titled Immediate neurological recovery following perispinal etanercept years after brain injury, did. And based on their findings, they made some very powerful claims: “a single dose of perispinal etanercept produced an immediate, profound, and sustained improvement in expressive aphasia, speech apraxia, and left hemiparesis in a patient with chronic, intractable, debilitating neurological dysfunction present for more than 3 years after acute brain injury”. A single patient, mind you. Not that I am sceptical by nature, but a larger study confirming this will be very reassuring.

By Doxepine – Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=6796200

Neuroprotection

And finally, that elusive holy grail of neurological therapeutics, neuroprotection. Well, does it exist? A review of the subject published in the journal, International Journal of Molecular Sciences, paints a rather gloomy picture of the current state of play. Titled Neuroprotective Strategies After Traumatic Brain Injury, it said “despite strong experimental data, more than 30 clinical trials of neuroprotection in TBI patients have failed“. But all is not lost. The authors promise that “recent changes in experimental approach and advances in clinical trial methodology have raised the potential for successful clinical translation”. Another review article, this time in the journal Critical Care, doesn’t offer any more cheery news about the current state of affairs when it says that the “use of these potential interventions in human randomized controlled studies has generally given disappointing results”. But the review, titled Neuroprotection in acute brain injury: an up-to-date review, goes through promising new strategies for neuroprotection following brain injury: these include hyperbaric oxygen, sex hormones, volatile anaesthetic agents, and mesenchymal stromal cells. The authors conclude on a positive note: “despite all the disappointments, there are many new therapeutic possibilities still to be explored and tested”.

brain 59. Affen Ajlfe on Flickr. https://www.flickr.com/photos/142299342@N06/32794069243/

What an optimistic way to end! We are not quite there yet, but these are encouraging steps.

Putting cerebral malaria in the powerful spotlight

The blogosphere is a crowded place. To stand out from the pack, a lot of bustling and hustling takes place. Medical blogging is not exempt from this melee. However, in the zeal to put blog posts in the limelight, the blogger may inadvertently fixate on high profile diseases, the ones that seem to readily covet the headlines. In this way, deadlier but less ‘celebrity’ maladies are left to simmer and fester below the radar. To avoid falling into this trap, this blog endeavours, (every now and then), to shine a light on these clandestine infirmities. These are the plagues which profit by virtue of their anonymity. It is no surprise that many of these disorders are tropical diseases, and there is no sweltering equatorial beast more sinister than the ague. It is therefore in the interest of fairness and balance that we are putting cerebral malaria in the powerful spotlight.

Malaria in peripheral blood. Ed Uthman on Flickr. https://www.flickr.com/photos/euthman/6289093848

Malaria is a beast because it is endemic in many developing countries. The epidemiological map below gives a flavour of which countries receive the brunt of the miasm.

Von S. Jähnichenhttp://rbm.who.int/wmr2005/html/map1.htm and http://www.dtg.org/uploads/media/Malariakarte-DTG-2005_04.pdf, CC BY-SA 3.0, Link

Just like other parasitic infections, malaria undertakes a tortuous life cycle. It appears that it is in the nature of these scroungers to beguile and hoodwink their way to the human bloodstream. Scurrying and scampering, they transit from mosquito to man. It is to the credit of malaria-busters such as Ronald Ross that their deceptive course, pictured below, was revealed.

Life cycle of the malaria parasite. NIAID on Flickr. https://www.flickr.com/photos/niaid/20771605491

And a nasty monster is malaria. The different malaria species are transmitted by the female Anopheles mosquito (please don’t ask why). Finding warm veins irresistible, she sates her bloodthirsty cravings whilst  unknowingly transmitting the malaria buggers called sporozoites. Once they get to the liver, these transform into insatiable merozoites which are tasked with one hatchet job: detect, invade and destroy innocent hardworking red blood cells. OK, I admit that’s three hatchet jobs.

By NIAID – Malaria Parasite Connecting to Human Red Blood Cell, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=62117171

The plasmodium species vivax, ovale, and malariae can all wreak atrocious havoc, but it is falciparum that poses the greatest threat to the nervous system. This is partly because falciparum can make its host cells sticky, and in the brain, these sticky cells adhere tightly to the walls of blood vessels. This is how falciparum evades detection by the immune system, and how it escapes destruction by drugs. The sticky cells eventually clog up the cerebral circulation, resulting in the infamous malarial vasculopathy. Left untreated, cerebral malaria is sadly invariably fatal.

By Content Providers(s): CDC/James GathanyProvider Email: jdg1@cdc.govPhoto Credit: James Gathany – CDC http://phil.cdc.gov/PHIL_Images/09262002/00008/A.gambiae.1354.p_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=745600

Cerebral malaria has diverse manifestations, and the most devastating include retinopathy, rigidity, ataxia (poor balance), subarachnoid haemorrhage, psychosis, hemiparesis, epilepsy, behavioural abnormalities, and coma. And this is over and above what malaria does to the other organs. The run down is very scary indeed; from anaemia to pulmonary edema, from hypoglycaemia (low glucose) to hyponatraemia (low sodium); from metabolic acidosis to hyperpyrexia (high fever), from disseminated intravascular coagulation (DIC) to adult respiratory distress syndrome (ARDS). Heartbreaking.

Malaria-infected red blood cell. NIH Image Gallery on Flickr. https://www.flickr.com/photos/nihgov/26834372607

The investigations of cerebral malaria range from the humble blood film to brain imagingTreatments include artemisinin derivatives and cinchona alkaloids. A malaria vaccine remains a dream, but not a far-off one; the RTS,S/AS01 vaccine is a promising candidate. Until this aspiration is achieved, the best hope against cerebral malaria remains prevention. The solutions are simple: basic sanitation, public education, and poverty alleviation. But the implementation seems to defy the wits of the great and the good. A lot of work remains to be done.

By Rick Fairhurst and Jordan Zuspann, National Institute of Allergy and Infectious Diseases, National Institutes of Health – https://www.flickr.com/photos/nihgov/25534997493/in/photolist-EUrx8t-CvR53a-B3Ad52-ydGygr-wZzPff-C5BN5H, Public Domain, https://commons.wikimedia.org/w/index.php?curid=49182050

Why not check out the following related posts in our other blog, Neurochecklists Updates:

The 8 most parasitic infestations of the nervous system

 

The 7 most ruthless bacterial infections of the nervous system

 

The 7 most devastating viral neurological infections

 

The 20 most viewed posts on The Neurology Lounge in 2018

With almost 25,000 visitors…

and almost 35,000 post views…

the highest since this blog launched…

It appears The Neurology Lounge has had a busy year.

 

Two bloggers. Mike Licht on Flikr. https://www.flickr.com/photos/notionscapital/2744489459

But compared to the previous whirlwind years

2018 was a relatively blog-quiet year.

Dominated by older posts

And a sprinkling of new ones.

 

John Meynard Keynes blogging. Mike Licht on Flikr. https://www.flickr.com/photos/notionscapital/7276886256

This is neither because of a flagging spirit

nor a waning passion.

 Neurochecklists, my other task-master…

Demanded more and more of my time.

 

 

Revising, refining, retuning…

Simplifying, clarifying, edifying

In pursuit of the ideal neurology database.

As that task is now nearly done

2019 beckons back to the blogging arena.

 

Blogging when the children have gone to bed. Mike Licht on Flikr. https://www.flickr.com/photos/notionscapital/8479881057

But just before looking forward

In this season of looking backward

Let’s spare some time to take account.

How did the old expositions fare?

How did the new compositions rank?

 

Number-04. StefanSzczelkun on Flickr. https://www.flickr.com/photos/stefan-szczelkun/3931901057

Here are your top 20 most viewed blog posts of 2018

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20. Advances in the management of giant cell arteritis

19. mTORopathy: an emerging buzzword for neurology

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Stay in touch with The Neurology Lounge in 2019

By User:S SeppOwn work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2949887