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

 

7 ominous signs that suggest you need to see a neurologist

Neurologists spend most of their time diagnosing benign conditions which are curable or treatable, or at least people learn to live with. Every now and then we see people with startling symptoms such as coma, convulsions, neck stiffness, or paralysis. These are obviously concerning to patients and their families who have a foreboding of diseases such as meningitis, epilepsy, and stroke. Serious as these disorders are, they at least announce themselves and show their hands. Many other neurological symptoms unfortunately give no hint of the serious diseases that follow in their trail. That is when things get a bit tricky.

Ominous. Ankakay on Flikr. https://www.flickr.com/photos/ankakay/4101391453
Ominous. Ankakay on Flikr. https://www.flickr.com/photos/ankakay/4101391453

What are these seemingly benign symptoms which jolt neurologists out of their blissful complacency? What are these red flag symptoms that pretend they are grey? Here are my 7 deceptively ominous neurological signs everyone should know about.

7. A numb chin

By Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below)Bartleby.com: Gray's Anatomy, Plate 784, Public Domain, https://commons.wikimedia.org/w/index.php?curid=531758
By Henry Vandyke CarterHenry Gray (1918) Anatomy of the Human Body (See “Book” section below)Bartleby.com: Gray’s Anatomy, Plate 784, Public Domain, https://commons.wikimedia.org/w/index.php?curid=531758

This must be the most deceptive sinister symptom in neurology. Not many people will rush to their doctors to complain about a numb chin, but it is a symptom that makes neurologists very nervous. This is because the chin gets its sensory supply from the mandibular branch of the fifth cranial nerve, also called the trigeminal nerve because it has three branches. And neurologists know that, for some bizarre reason, cancers from other parts of the body occasionally send deposits to this nerve. The numb chin syndrome is therefore not to be treated lightly.

6. Muscle twitching

OK, don’t panic yet. We have all experienced this; a flickering of an overused and tired muscle; a twitching of the odd finger; the quivering of the calf muscles in older people. Neurologists call these fasciculations, and they are only a concern if they are persistent, progressive, and widespread. And also usually only if the affected muscles are weak. In such cases neurologists worry that fasciculations are the harbingers of sinister diseases, particularly motor neurone disease (MND), better known in America as amyotrophic lateral sclerosis (ALS) or Lou Gehrig disease. Many people with muscle twitching will however have nothing seriously wrong with them, and many will be shooed out of the consulting room with the label of benign fasciculations syndrome (we love our syndromes, especially when they are benign). There are many other causes of fasciculations, but MND is clearly the most sinister of them all.

5. Transient visual loss

Scott Maxwell on freestockphotos. http://www.freestockphotos.biz/stockphoto/9747
Scott Maxwell on freestockphotos. http://www.freestockphotos.biz/stockphoto/9747

Neurologists often ask people with headache if their vision blurs or disappears for brief periods of time. These visual obscurations are not as dramatic as the visual loss that accompanies minor strokes or transient ischaemic attacks (TIAs). Visual obscurations affect both eyes and last only a few seconds. They are the result of sudden but brief increases in an already elevated pressure in the head. This may occur with relatively benign conditions such as idiopathic intracranial hypertension (IIH), but it may also portend a serious disorder such as a brain tumour.

4. Sudden loss of bowel or bladder control

bubble-1013915_1920

Loss of control down there would surely concern many people, but often not with the urgency it deserves. There are many non-neurological causes of bowel or bladder incontinence, but a sudden onset suggests that it is arising from the nervous system. The worrying diagnoses here are spinal cord compression and spinal cord inflammation (transverse myelitis). These disorders are often associated with other symptoms such as leg stiffness and weakness, but I really wouldn’t wait until these set in before I ask to see a neurologist.

3. Saddle anaesthesia

bicycle-saddle-791704_1920

Whilst we are on the topic of things down there, a related sinister symptom is loss of sensation around the genitals and buttocks, something your doctor will prudently call saddle anaesthesia. This arises when the nerves coming off the lower end of the spinal cord, collectively called the cauda equina, are compressed. The unpalatable condition, cauda equina syndrome (CES), worries neurologists because the compression may be due to a tumour in the spinal canal.

PS: The bicycle saddle is an apt analogy, but if you prefer horse riding, below is an alternative image to soothe your hurt feelings.

 

By BLW - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1956552
By BLW – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1956552

2. A painful droopy eyelid

A droopy eyelid is a deceptively benign symptom which worries neurologists. This symptom, which neurologist prefer to call ptosis, is particularly concerning if it is accompanied by double vision. One worrying disorder which causes ptosis is myasthenia gravis (MG), and this presents with ptosis on both sides. More sinister is ptosis which is present only on one side, particularly if it is painful. This may be caused by brain aneurysms, especially those arising from a weakness of the posterior communicating artery (PCOM) artery. As the aneurysm grows, it presses on the third cranial or oculomotor nerve, one of three nerves that controls the eyeballs and keeps the eyelids open. An aneurysm is literally a time-bomb in the brain as they wield the threat of bursting and causing a catastrophic bleeding around the brain. This makes ptosis an ominous, but also a helpful, neurological symptom.

By Cumulus z niderlandzkiej Wikipedii, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=3167579
By Cumulus z niderlandzkiej Wikipedii, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=3167579

There are many other causes of ptosis including Horner’s syndrome, so don’t panic yet but get that eyelid checked out if it refuses to straighten out.

 

1. Thunderclap headache

By © Marie-Lan Nguyen / Wikimedia Commons, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=24189896
By © Marie-Lan Nguyen / Wikimedia Commons, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=24189896

thunderclap headache is a symptom that means exactly what it says on the label! Neurologists will ask if the onset felt as if one was hit by a cricket bat. Even though most people have never been so assaulted, almost everyone with thunderclap headache readily agree this is what it feels like. It is such a distressing symptom that it doesn’t strike the afflicted person (pun intended) that their doctors are more concerned about investigating them, then they are in curing their headache. They patient is rushed to the CT scanner, and then subjected to a lumbar puncture. The doctors then heave a huge sigh of relief when the spinal fluid shows no blood or blood products, reassured that the patient has not suffered a subarachnoid haemorrhage (SAH) from a ruptured a brain aneurysm. The patient, who now has just another headache, is left to get to grips with their now, suddenly, very uninteresting symptom. There are many other causes of a thunderclap headache, but a ruptured aneurysm is the most sinister. If you develop a thunderclap headache, don’t wait to see a neurologist…just get to the nearest hospital!

PS: Don’t feel aggrieved if you are across the Pacific; it is also a thunderclap headache if it felt like being hit by a baseball bat!

Baseball bat in sun. Peter Chen on Flikr https://www.flickr.com/photos/34858596@N02/3239696542
Baseball bat in sun. Peter Chen on Flikr https://www.flickr.com/photos/34858596@N02/3239696542

 

Want to check out more ominous signs? Check out Smart handles and red flags in neurological diagnosis by the neurologist Chris Hawkes in Hospital Medicine.

 

6 exciting neuroscience discoveries that will shape neurology

Allan Ajifo on Flikr. https://www.flickr.com/photos/125992663@N02/14601014695
Allan Ajifo on Flikr. https://www.flickr.com/photos/125992663@N02/14601014695

 

The brain is a mystery and that is why neurologists find it fascinating. The more we know, the more it tantalises us with its hidden gems. Great neurologists have waxed lyrical about the ability of the brain to elude all efforts to fully understand it. Santiago Ramon y Cajal for instance says:

“The brain is a world

consisting of a number of unexplored continents

and great stretches of unknown territory” 

Non-neurologists are similarly awed by the brain. Emerson M. Pugh for example says:

“If the human brain were so simple that we could understand it,

we would be so simple that we couldn’t”

Neuroscience and neuroanatomy are at the forefront of exploring this great unknown; the research output from these fields is mind-boggling (pardon the intended pun). But which recent findings are most likely to change neurological practice in the near future? Here are my top 6.

1. Newly discovered brain lymphatic system

"Gray602" by Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below)Bartleby.com: Gray's Anatomy, Plate 602. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:Gray602.png#/media/File:Gray602.png
“Gray602” by Henry Vandyke Carter – Henry Gray (1918) Anatomy of the Human Body (See “Book” section below)Bartleby.com: Gray’s Anatomy, Plate 602. Licensed under Public Domain via Commons – https://commons.wikimedia.org/wiki/File:Gray602.png#/media/File:Gray602.png

A recent report that researchers have discovered a previously unknown lymphatic system in the brain is to say the least shocking. That these lymphatic channels have eluded the sharpest eyes and most focussed microscopes for centuries goes to show how mysterious the brain indeed is. Why has it stayed undiscovered for so long? Apparently because it is tucked behind a major blood vessel! Hiding in plain sight says one review article. The discovery is so important that one article says it will have the scientists rewriting textbooks. 

The finding however raises hope of better treatments for some neurological diseases. Because the lymphatic system is closely linked to the immune system, multiple sclerosis (MS) is one potential beneficiary of this discovery. Because lymphatics also act as drainage systems, there are implications for conditions such as Alzheimer’s Disease (AD). Hopefully this brain lymphatic system could be manipulated to clear the accumulated abnormal proteins that cause AD and other neurodegenerative diseases.

2. Newly discovered brain networks

"White Matter Connections Obtained with MRI Tractography" by Xavier Gigandet et. al. - Gigandet X, Hagmann P, Kurant M, Cammoun L, Meuli R, et al. (2008) Estimating the Confidence Level of White Matter Connections Obtained with MRI Tractography. PLoS ONE 3(12): e4006. doi:10.1371/journal.pone.0004006. Licensed under CC BY 2.5 via Commons - https://commons.wikimedia.org/wiki/File:White_Matter_Connections_Obtained_with_MRI_Tractography.png#/media/File:White_Matter_Connections_Obtained_with_MRI_Tractography.png
“White Matter Connections Obtained with MRI Tractography” by Xavier Gigandet et. al. – Gigandet X, Hagmann P, Kurant M, Cammoun L, Meuli R, et al. (2008) Estimating the Confidence Level of White Matter Connections Obtained with MRI Tractography. PLoS ONE 3(12): e4006. doi:10.1371/journal.pone.0004006. Licensed under CC BY 2.5 via Commons – https://commons.wikimedia.org/wiki/File:White_Matter_Connections_Obtained_with_MRI_Tractography.png#/media/File:White_Matter_Connections_Obtained_with_MRI_Tractography.png

 

The brain’s extensive connections is one of its enduring and fascinating mysteries. The winding fibers and tracts, meandering and looping around each other, demonstrate the brain’s complexity. As soon as we think we have grasped it all, along comes a discovery that causes a paradigm shift. This is illustrated by the report of the discovery of a new brain network involved in memory processing. This Parietal Memory Network (PMN), in the brain’s left hemisphere, responds differentially to new and to old information. This may have relevance for cognitive disorders such as Alzheimer’s Disease (AD). For the more technical details of the network, the paper is published in the journal Trends in Cognitive Neuroscience.

3. Newly discovered brain connection

Synapse by Peter Morgan on Flikr. https://www.flickr.com/photos/moogan/5997439279
Synapse by Peter Morgan on Flikr. https://www.flickr.com/photos/moogan/5997439279

 

In a similar vein is the discovery of previously unknown brain fiber tracts called the vertical occipital fasciculus (VOF). This new ‘brain corridor‘ is involved in visual processing. The research paper, published in the Proceedings of the National Academy of Science (PNAS), says the VOF is important in the perception of words and faces, amongst other things, and is ‘involved in the control of eye movements, attention, and motion perception. The main benefit of this finding is the improvement of our understanding of how the brain learns to read.

4. Newly discovered brain activity in deep coma

By Wojder (Own work(own work by uploader)) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 4.0-3.0-2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/4.0-3.0-2.5-2.0-1.0)], via Wikimedia Commons
By Wojder (Own work(own work by uploader)) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 4.0-3.0-2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/4.0-3.0-2.5-2.0-1.0)%5D, via Wikimedia Commons

The common assumption that the electrical activity of the comatose brain flatlines on the electroencephalogram (EEG) now appears to be a misconception. This is according to a report of the discovery of a previously unknown electrical brain activity in deep coma suggests. One journal reported this as the discovery of life after brain death!

These electrical waves, seen in deep coma, are called Nu complexes. They are well-described in the original paper in PLoS One. This finding will alter our definition of brain death which relies very much on the absence of organised brain electrical activity. Another implication is for patients whose medical conditions require that they are put into a coma; this finding will potentially guide the anaesthetist to apply the best form of induced coma. 

5. Newly discovered brain cell type 

 

I thought I learnt all the different types brain cells or neurones that exist when I was in medical school. The mysterious brain however has a joker at every corner. The report of the discovery of a new type of neurone should come as a surprise, but by now we have learnt not to be shocked by new brain discoveries. The strange thing about these cells, found in the hippocampus of the the brains of mice, is that they have direct connections between their axons (the single long tail) and their dendrites (the smaller hair like projections). This connection by-passes the nerve body; this direct connection enhances the strength of the signals the cell generates. The reason for this peculiarity is not clear but, because the hippocampus is the seat of memory, I guess there are implications for cognitive disorders.

6. Newly discovered brain repair enhancers

We know that the brain repairs itself (neuroplasticity), and that brain fibers make new connections even if this occurs very slowly. What is new is that these processes can be enhanced or accelerated by external agents. Two interesting substances recently reported are psilocybin and curry. Yes, healing mushrooms and spices!

It appears that Psilocybin (psychedelic mushrooms) can establish stable connections between parts of the brain which do not normally communicate well. The research on this is published under the title ‘Homological Scaffolds of Brain Functional Networks‘. The paper describes how psilocybin helps in nerve re-wiring with the potential implications for the treatment of depression and addiction. A bit paradoxical, using an addictive substance to treat addiction; but hey, this is the brain we are talking about!

"Curcuma longa roots" by Simon A. Eugster - Own work. Licensed under CC BY-SA 3.0 via Commons - https://commons.wikimedia.org/wiki/File:Curcuma_longa_roots.jpg#/media/File:Curcuma_longa_roots.jpg
“Curcuma longa roots” by Simon A. Eugster – Own work. Licensed under CC BY-SA 3.0 via Commons – https://commons.wikimedia.org/wiki/File:Curcuma_longa_roots.jpg#/media/File:Curcuma_longa_roots.jpg

 

Curry on the other hand contains tumeric which contains tumerone. Tumerone has now been shown to help with nerve growth repair, and it does this by causing proliferation of brain nerve cells. The research itself is titled ‘Aromatic-tumerone induces neural stem cell proliferation in vitro and in vivo‘. It is a study in rats, but are human brains very different? Potential beneficiaries are all the neurodegenerative diseases which neurologists have singularly failed to reverse.

Enough food for thought,  but if you want to keep up with neuroscience findings, here are the most popular neuroscience blogs.

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