It is a truth universally recognised that the heart and the brain are very good friends. In the lay community, it is believed that the brain is the seat of reason and the heart is the seat of emotions and feelings. They might represent vastly different things, without either, one cannot be complete. Fair enough, there are actually brain and heart comic strips denoting responses emanating from the flow of reason, or pure impulse, respectively. They always bring tears of joy to my eyes. This, despite the contradicting truth that the heart is merely the mechanical pump of the body - tirelessly pumping blood, so that it circulates in the body through vessels, big and small. The real seat of emotion is the amygdala, or the wider limbic system, which complements the seat of logic, located in the prefrontal cortex (this is an oversimplification, since there is a wider system called the default mode network responsible for interpretation of others, moralisation, realisation and reflection of self, as well as future projection and reminiscence of the past). All these structures are located in the brain. [1]
(All credits go to the Awkward Yeti Project). The Brain and Heart comics are my favourite medical comics by far. They always make me double over laughing. By the way, I wear glasses so I assume I'm the brainy one (but at the same time, I would sometimes go for the pizza instead of burden myself with lengthy and hefty health advice). Extracted from: https://cdn2.collective-evolution.com/assets/uploads/2016/10/Choice-1024x1024-f22491fa93b99e74d84c1e4d6dcd38b9.png.
However, in physiology and anatomy, the heart and brain are connected via different means. As we can see, the brain is a busy bee. It is the administrator of the body. Without the brain, one cannot survive since there is simply no leader for coordinating the myriads of processes operating across organs and corporeal systems. The brain, as a result receives 12 per cent of systemic cardiac output, even though it only accounts for 2 per cent of total body mass. [2] I use the term 'systemic cardiac output' for the purpose of specificity. There are two circulatory systems, namely the pulmonary circulation (only the lungs) and the systemic circulation (rest of the body). Blood is important as a carrier of numerous materials, including glucose (basically the food of the brain) and oxygen. It also removes waste such as urea, as well as carbon dioxide (not all though). From the great amount of blood directed to the brain, we can deduce that the brain cannot survive effectively without seamless, normal functioning of the heart. Moreover, the brain is supplied by a vast network of blood vessels, which is aptly called the cerebrovascular system. We usually divide it, by reason of convenience, into the anterior and posterior circulations. The anterior circulation includes the notorious internal carotid artery (notorious since once it is occluded, serious ramifications arise). The posterior circulation, the lesser-researched counterpart, includes the posterior cerebral arteries, basilar arteries and vertebral arteries. Apart from rather large vessels (the ones who are given names), the brain is also supplied by loads of 'perforators' and small capillaries which, when occluded, can give rise to small vessel disease.
Figure showing the Circle of Willis (the loop at the upper portion of the picture) and other major cerebral arteries. (Courtesy of Wikipedia)
Magnetic Resonance Angiography (MRA) Scan of the Neck Arteries and the Circle of Willis. Contrast is added to the patient, giving rise to the enhancement. The arteries look fine but it's better to have a close-up of the Circle of Willis to make sure I haven't missed anything. Scan extracted from: https://media.istockphoto.com/photos/neck-artery-mra-picture-id493743280?k=6&m=493743280&s=170667a&w=0&h=9YlXa84t-EEbGmpxeIlFWud1yfKvY8_nmX2wy7d2ovw=.
The Enigma of Stroke
Stroke is a cerebrovascular disease which involves the reduction in blood supply to the brain. To be more specific, such effects have to last for more than 24 hours (anything which is transient and occurs for less than 24 hours is called a transient ischaemic attack, or TIA). This leads to various complications, including permanent neuronal damage, heart complications [5], as well as systemic issues. Some examples include respiratory and swallowing difficulties. The gag reflex can be lost. The patient has problems in talking. All these features originate from irreversible changes of the tissue in the brainstem (also known as a bulbar stroke, where the corticobulbar pathways are affected). Unluckily, microbes are always stalking us and one of the key mechanisms for their removal is purely mechanical - breathing in and out where dancing cilia act as filtering nets, and swallowing these little devils so that they reach the highly acidic environment in the stomach. Moreover, swallowing problems can lead to retching. All these contribute to infectious and inflammatory complications, including pneumonia. They lead to higher mortality.
I deliberately shy away from mention of any particular mechanism which precipitates the reduction in blood supply, since it can be achieved through different ways. It might be, through the simple route, due to a blockade of the vessel (aka ischaemic stroke). Ischaemic stroke can also occur when there is generalised decrease in blood flow. This means we are no longer infatuated with just one single artery - this is essentially a local effect (at least initially). We're saying that the body does not have enough blood/red blood cells in general. This can happen in conditions like anaemia and hypovolaemic shock (decrease in the amount of blood circulating in the body). It might even be because of a problem with the cardiac pump. The heart cannot pump blood effectively. This leads to a decrease in the amount of blood directed to the brain. More is retained in the heart. This is common in conditions like heart failure, and conduction problems (think about atrial fibrillation and heart blocks).
Illustration of the various possibilities under each category of vasculitides (extracted from: https://www.researchgate.net/profile/Maurizio_Salvadori/publication/324088680/figure/fig1/AS:609531780423680@1522335109453/Distribution-of-vessel-involvement-by-large-vessel-vasculitis-medium-vessel-vasculitis.png)
ECG showing atrial fibrillation (another potent cause of stroke in virtue of cardio-embolism) which features no P waves (at least no visible ones). The QRS Complexes are irregularly irregular. This means that the rhythm is abnormal. In many cases, even if it is abnormal, there's a set pattern of abnormality. In atrial fibrillation, it is basically a mess and the atria can do whatever they want. That's why the intervals between QRS complexes are always different. Patients with atrial fibrillation are likely to have a heart rate hitting over 170 beats per minute. This ECG is extracted from: https://drsvenkatesan.files.wordpress.com/2008/10/af.jpg.
Alternatively, it can be due to excessive bleeding. Some may get confused by this. If there is too much blood (aka haemorrhagic stroke), what harm is it going to cause since this is what the brain wants. Well, the answer to this rests in the purpose of the blood. The blood is a carrier. It is not, standing alone, an important thing for the brain. If anything, the platelets in blood are lethal to the brain once they form clots. The brain benefits from the blood performing its functions. Hence, once the blood accumulates at a particular portion of the brain, immobile and static, it is not working anymore. The brain benefits nothing from its presence. Instead, the accumulation leads to a mass which pushes the brain. With progressive accumulation, it can lead to a space-occupying effect, therefore pushing the brain downwards since the skull is like a hard box, one that the brain finds itself subpar to in terms of strength. The mass is retained through the gradual actualisation of coagulation processes, leading to haematoma formation. It is not in purely liquid form anymore. Moreover, with a deficit over one part of the brain, there comes a caveat. Other parts of the brain are also affected - the chief of all is lowered blood supply. this especially affects watershed regions, the name given for regions which are 'leftovers' or 'frontiers' in terms of cerebral arterial territories. They are the most vulnerable to lowered blood supply and are subjected to the highest risk of infarction.
Diagrams showing examples of the watershed regions of the brain (left: coronal cross-section, right: axial cross-section); A - watershed region between the anterior cerebral artery (ACA) and middle cerebral artery (MCA); B - watershed region between the MCA and posterior cerebral artery (PCA). Diagram extracted from: https://classconnection.s3.amazonaws.com/771/flashcards/1361771/png/water_shead1337202792303.png.
Diagram (Axial cross-section) showing the cerebrovascular territories of the brain (by Professor Frank Gaillard, Radiopaedia). The lateral lenticulostriate arteries are perforating vessels (very small vessels which cannot be visualised through MRA) emanating from the M1 section of the MCA. If the basal ganglia are affected, then M1 can be deduced to be affected as well. If they are spared, the occlusion may be at M2 instead (from personal experience, anything beyond M2 is pretty difficult to detect, depending on the strength of the MRI machine).
Diagram showing normal brain tissue, penumbra and infarcted tissue. Extracted from: https://i2.wp.com/neupsykey.com/wp-content/uploads/2019/05/00161.jpeg?w=960.
From the above diagram, we can see that the penumbra is an area of 'salvageable damage'. When the brain tissue experiences a prolonged decrease, or even absence of blood supply, things start to change. I'm referring to deep cellular changes, including the increase in production of a substance called lactic acid. It is produced in virtue of a little process called anaerobic respiration, since oxygen is absent and the more effective 'aerobic respiration' cannot be carried out. Respiration is essential for every cell since it synthesises energy to make sure enzymatic processes are carried out. Lactic acid is, naturally put, toxic. Mitochondrial dysfunction and the increase in reactive oxygen species (ROS) are also mechanisms leading to cellular injury. Note that these cells are still, technically, surviving. Once they're dead, grouped together, we call the region an infarct. It would be irreversible since. But then, if it's only injured, there is still a chance of reversal. If treatment is administered promptly to restore the blood supply, this bit of the brain can still be revitalised. Actually, beyond the penumbra, there is also the oligaemia (not shown in the diagram above). It affects the nearby tissue of the penumbra. Oligaemic tissue is affected by the decrease in perfusion (supply of blood) as well. However, only minor cellular changes have been recorded and they're not seriously injured. Expanding from the oligaemia is normal brain tissue.
Heart's Desire and Mechanisms of Stroke
The heart's desire is certainly to fulfil its niche, like any organ in any organism. However, this can get quite tricky. There are many causes of ischaemic stroke (in this article, I think it's easier to talk about ischaemic stroke instead of haemorrhagic stroke, since that would entail an entirely separate discussion, including hypertension). Chief of all are two: thrombosis and embolism. It's all a classical plumbing issue. Atherosclerosis, involving thrombosis, is the leading cause of progressive and chronic arterial occlusion. It is gradual since it starts off as a little bit of fat deposited in the vessel wall. Minute by minute, day by day, this fatty substance grows as inflammatory processes occur. Macrophages, agents of the immune system, engulf the fat as they enter the vascular walls. T lymphocytes are also prevalent. Smooth muscle cells proliferate from the encouragement of the growth factors produced by foam cells. Blood clots are also formed due to the aggregation of platelets following injuries to the vascular wall. The injuries originate from more turbulent blood flow, hence more violent frictional forces between the blood and the 'new' vessel wall, as the width of the vessel lumen is narrowed. Sooner or later, an atheroma (or atheromatous plaque) is formed and obstructs the vessel wall to progressive degrees of intrusiveness. Serious effects are reached when the 50 per cent threshold is reached. More severe effects arise when it gets more serious.
Diagrams illustrating the stages of atherosclerosis - note the progressiveness of the narrowing of the luminal width of the artery. The diagram is extracted from: http://1.bp.blogspot.com/-5EQzLJF4oEQ/VYXMCf_zIoI/AAAAAAAAGQk/-vNKqQDRoaY/s1600/atherosclerosis.gif.
Other circumstances culminating in thrombosis, which means the aggregation of platelets and fibrin (formation of clots), include inflammation stemming from sources other than lipids. This includes classical autoimmune diseases such as systemic lupus erythematosus and a wide range of vasculitides under the International Chapel Hill Criteria*. Vasculitides are essentially autoimmune diseases which involve the vessels. They can be divided into three major categories: large vessels, medium-sized vessels and small vessels. The most prominent of which include giant cell arteritis which commonly affects the superficial temporal artery, polyarteritis nodosa (medium-sized arteries affected) and granulomatosis with polyangiitis (also known as Wegener's granulomatosis; actually this name is the old one but remains affectionate). Such autoimmune conditions lead to the development of immune complexes, attacking self-tissue. This leads to injury and the initiation of the coagulation cascade. Thrombi are formed gradually. Rarer so, we have infections of the vessels that do exactly the same thing, whereby inflammation follows as microbes intrude into the relative tranquility of the vascular walls. Preponderant of which are endarteritis obliterans (tuberculosis), HBV (Hepatitis B) and Streptococcal species (beta-haemolytic).
What about embolism? Embolism is one of the various consequences following atherosclerosis. As there is increased friction between the plaque and the blood, there is a higher chance for part of the plaque to detach itself from the vessel wall. Such small bits of the plaque travel up and down the circulatory system. However, it all depends on the circumstances. If the atherosclerosis occurs at a relatively large vessel, then you're in bad luck. Even the segregated snippet is large enough to stuff the smaller vessels of the cerebrovascular system. We need to remember that as we go up the brain through the neck, vessels get smaller (in more formal terms, the vessel calibre decreases). In this case, the embolus originates from a vessel. However, there are also cases where the embolus arises from the heart, as well shall see later.
Embolism can also occur in some other cases. There is a scenario where the vessel wall, comprising normally three layers (from innermost to outermost: tunica intima, tunica media and tunica adventitia), breaks down. Alternatively, it can be inherently weak, as seen in patients with connective tissue diseases such as Marfan Syndrome and Ehlers-Danlos Syndrome. In such circumstances, there is separation of the layers. It is called 'dissection'. There are thus two ways for blood to travel - (1) along the vessel as usual, or (2) through the 'false' lumen. Obviously, route (2) is a dead-end. As blood always does, it clots when it accumulates and is not moving. This leads to a nidus for embolism - essentially, it is a factory which fires out little missiles to the brain (I use the metaphorical missile to describe emboli because that's just so accurate).
Diagram showing aortic dissection - essentially taking the concept I explained to the extreme since the aorta is the largest artery in the body. This diagram is extracted from: http://upload.medbullets.com/topic/120030/images/09122017vldcardianaorticdissectionmmedits.jpg.
Ultrasound Scan for Carotid Dissection (heed the separation of the walls, especially the lower wall). For anyone struggling with the concept of dissection, this is the perfect picture. We need to know that blood is always flowing (normally). Coagulation does not occur straight away. It does take time. The old blood settling in the false lumen (the blood contained in the artificial pouch originating from the segregated vascular wall layers) coagulates at differing rates. This process is spiced up with the 'wow' factor that new blood keeps crashing in. It depends on the calibre of the vessel and the extent of vascular narrowing. The clots can get detached from frictional forces and travel out of the false lumen, off to the fresh new world. Back to the case of carotid dissection, since the carotid arteries are very close to the brain, there is very high chance of stroke. (Image Courtesy of Wikipedia)
One might ask - how is all this associated with the heart? Exactly- as I mentioned, an embolus can arise from the heart. This is why I want to demonstrate the tight coupling between the brain and the heart using a case study.
Illustration of valvular thrombotic deposits in the heart. These predispose the patient to much higher risk to cardio-embolism. The diagram is extracted from: https://i1.wp.com/neupsykey.com/wp-content/uploads/2017/06/A316005_1_En_12_Fig7_HTML.gif?fit=540%2C412&ssl=1.
The Case:
Georgina** is a 35-year old woman who has presented with high fever, chest pain and shortness of breath for the past few days. She is taken to the A&E by a friend, although she has exhibited clear attempts in escaping. She is in notable pain and appears fatigued and thin (I hesitate to use the term 'cachexic' since it is usually applied to patients with cancer).
Patient Profile:
Georgina Walker - 35 years old, G0P0, Pre-menopausal;
(a) CHIEF COMPLAINT(S) & FEATURES:
High fever (self-reported) (measured at 39.1 degrees Celsius upon admission) - the patient reports of feverishness for the past three days, with no perceived variation in condition (this is important since swinging fevers can occur in infectious contexts, such as malaria);
Chest Pain - located over the central aspect of the chest, which does not radiate (this is crucial since many conditions, including acute myocardial infarction, may feature pain radiation); persistent in nature, rather than episodic, which has lasted for the last few days; no recorded past episodes of comparable chest pain; dull in quality and graded 6/10 on the Visual Analogue Scale (severity); not improved by any identifiable factor; exacerbated by breathing and movements;
Shortness of Breath - lasted throughout the past few days, persistent and exacerbated by exertions. Exertion-related shortness of breath is typically related to the heart. However, we're apt not to jump to conclusions right now. There is neither exacerbation nor improvement with postural changes. The patient does not suffer from poor sleep in virtue of this issue. (postural changes and nocturnal shortness of breath are related to heart failure; we are concerned about acute heart failure). The problem is severe to the extent that normal daily activities are affected, including walking up stairs and continuously for (roughly) one hundred steps.
Associated Symptoms: Palpitations (unknown onset, persistent in nature), Dizziness (as subjectively felt by the patient and objectively seen by us, where the patient's gait is substantially affected), Malaise (as mentioned before), Fatigue, Anorexia, and night sweats. The patient has no other anaemic symptoms, no coryzal or other respiratory symptoms. Review of systems returns nothing remarkable.
(b) PAST MEDICAL, SURGICAL AND OBSTETRIC/GYNAECOLOGICAL HISTORY:
The patient's medical records cannot be found from the system. It transpires that she is not on the GP register. We therefore gather information by both physical examination (aka our own observations since surgical scars can be observed in many cases) and history-taking, relying on the good faith of the patient (assuming that she doesn't lie to us just to leave the hospital).
3 times of Opioid overdose (all having occurred three months ago, when the patient was living in Spain) (treated successfully with naloxone);
Chlamydia infection (recurrent);
No relevant surgical history. Most importantly, there is no known history of prosthetic valve replacement, and prior cardiovascular disease.
There is no known diabetes mellitus and immunodeficiency syndromes (including HIV) in this patient;
Obstetric and gynaecological history are unknown.
(c) FAMILY HISTORY: It cannot be obtained since the patient refuses to tell us anything.
(d) AUTOIMMUNE HISTORY: Unremarkable.
(e) DRUG HISTORY: no known drug allergies, no chronic medication as prescribed; after multiple medical cautions, the patient confesses that she is a chronic recreational, intravenous drug user and has been so for the past eight years.
(f) SEXUAL HISTORY (flagged due to history of recurrent chlamydia): sexually active, multiple sex partners; no protection used during sexual intercourse; although the patient denies any prior diagnosis of HIV, due to the patient's sexual history, we feel that we need to conduct relevant testing.
(g) SOCIAL HISTORY:
Heavy drinker and smoker, both having lasted for over ten years;
Living with 4 other friends in a one-bedroom flat in Brixton;
No recent travel history and co-habitants not having reported similar symptoms;
Feeling persistently depressed, with evidence of self-harm reported by the triage nurse (multiple, longitudinal scars, as well as pin-prick wounds scattered across the medial processes of the forearms, and soleal lines of the lower limbs).
(i) DIETARY HISTORY: Under-nourished, according to the descriptions of the patient.
Physical Examination:
We have decided to perform the following physical examinations - (a) general, (b) respiratory, and (c) cardiovascular. Without further ado, here are the findings.
(a) General Examination:
Thin and systemically unwell, respiratory rate > 24 breaths per minute, heart rate > 110 beats per minute (tachycardia), blood pressure (averaged): 130 / 90 mmHg; unremarkable urinalysis results and reduced urinary output (in the course of observation); pulse oximetry - 98% oxygen saturation;
Notable shortness of breath (dyspnoea); Janeway lesions can be observed over the digits of both hands. Pin-prick wounds and scars present not only in upper and lower limbs, but also above the clavicles.
The radial pulses are strong and equal bilaterally. They are also of normal rhythm. There is no collapsing pulse (indicative of aortic regurgitation).
No Osler Nodes and Splinter Haemorrhages can be seen. There is no finger clubbing. Unremarkable results for lymph node exam. The patient also has no pallor, jaundice or peripheral oedema.
It is noted that Janeway Lesions, Osler Nodes, Splinter Haemorrhages and Roth Spots are cardinal signs of infective endocarditis. They are caused by the embolisation of infective material adherent to the valvular structures of the heart, and/or the dispersion of immune complexes. Janeway Lesions usually occur in acute cases, whereas the other two, subacute (later in the game, usually measured in weeks). Roth Spots cannot be observed otherwise than using an ophthalmoscope.
Clinical Picture showing Osler Nodes in the digits. Osler Nodes and Janeway Lesions are very similar morphologically. Key differences include (1) location, where Osler Nodes are usually found at the digits and Janeway Lesions, the palms and plantar aspect of the feet; (2) tenderness. Osler Nodes are traditionally tender, whereas Janeway Lesions, not tender. This can be traced back to the fact that Osler Nodes are formed from immune complexes, entailing inflammation which triggers responses from nerve endings. Janeway Lesions are non-tender in virtue of the fact that they are microabscesses originating from septic embolism. The picture is extracted from: http://www.anesthesia.webservices.utoronto.ca/Assets/Anesthesia+Digital+Assets/Anesthesia/Anesthesia+Digital+Assets/Asset+A-M/Janeways+Lesions.jpg.
Clinical Picture showing Roth Spot. This is attained via the use of an ophthalmoscope. The picture is extracted from: http://2.bp.blogspot.com/-qjP6qEqOhG0/UDdxBPSI9qI/AAAAAAAAAAw/NdOSPWP_Qk0/s400/roth%2Bspot.gif.
Clinical Picture showing Splinter Haemorrhages, which usually arise in subacute endocarditis (not necessarily infective, since autoimmune endocarditis such as that led by lupus, can also lead to embolism; what differs remains the composition of the embolus). The picture is extracted from: https://healthjade.com/wp-content/uploads/2019/03/splinter_hemorrhages.jpg.
(b) Respiratory Examination:
Shortness of Breath evident;
Equal expansion on both sides of the chest wall;
No chest wall deformities, nor are there any observable scars or abnormal pulsations or masses;
The apex is not deviated and is located over the intersection between the mid-clavicular line and 5th intercostal space. It is strongly felt. This is significant as it indicates that the heart size should be fine. There are several possibilities which might explain its not being felt (sometimes this list is crucial where heart failure remains a palpable possibility): excessive body fat (exact reverse in this patient), situs inversus/dextrocardia (where things are all in reverse), cardiac tamponade (too much fluid in the outer covering of the heart which limits its expansion);
The trachea is not deviated;
No abnormalities with regard to breath sounds and fremitus (vocal); This is true for both the anterior and posterior chest walls.
No sacral oedema.
(c) Cardiovascular Examination:
JVP Examination: nothing remarkable, where the height of the pulse is roughly 4 inches (thus not suggestive of heart failure, or any issues pertinent to the efficacy of the contractile pump);
No heaves and no thrills (at least I cannot feel any thrills, even if expected);
There is no radio-femoral delay (which can be due to aortic coarctation). There is no radio-radial delay (which can be due to peripheral artery disease, or Takayasu's arteritis).
There is no discrepancy between the radial pulse and the apical beat.
First and Second heart sounds present in all auscultation areas. Second heart sounds for the mitral and aortic regions are louder than those of the other regions (pulmonic, tricuspid). There are no extra heart sounds in all auscultation regions.
There is a pansystolic murmur heard over the mitral region which radiates towards the left lateral chest wall. No murmurs can be heard elsewhere.
We have gained a lot of information from taking the patient's history and having performed the relevant physical examinations. Now, we have to decide on a list of working diagnoses to direct our use of investigations. What are the most likely possibilities?
Top suspicion: INFECTIVE ENDOCARDITIS
The first step is to identify the system at fault. It is unlikely that it is a respiratory issue, since the results of the respiratory examination are largely normal. I turn our attention to the cardiovascular system. I've considered several possibilities, including infective endocarditis, non-infective endocarditis (which basically refers to a non-infective, inflammatory process, pointing towards things like Liebman-Sack's Endocarditis originating from systemic lupus erythematosus and scleroderma [though considerably rare]), myocarditis (inflammation of the heart muscle) and ischaemic heart disease.
However, myocarditis is unlikely since the main theory of its pathophysiology remains the combination between a viral infection (usually Coxsackie Virus) and immunological mechanisms, where the myocytes in the myocardium (muscle layer of heart) are affected. Myocarditis is usually preceded by a viral prodrome of 2-3 weeks that is not observed in this patient. Ischaemic heart disease also does not fit in the picture, seeing that the patient has high fever and constitutional symptoms (more indicative of an infectious disease). There is also no known history of hypertension and family history of coronary heart disease in this patient.
Rheumatic fever (or rheumatic heart fever, from recurrent rheumatic fever) is also unlikely since there is no evidence that the patient has experienced a recent event of streptococcal infection. Moreover, the patient lacks the symptoms and signs which form the major criteria of the JONES Criteria (diagnostic of rheumatic fever) - polyarthritis, carditis, subcutaneous nodules, erythema marginatum and Sydenham chorea.
All credits go to www.medcomic.com. This is an artistic interpretation of the JONES Criteria, essential for the diagnosis of Rheumatic Fever.
I ardently support the working diagnosis of infective endocarditis in accordance with the following reasons:
Chest Pain, Palpitations, High Fever, (other) Constitutional Symptoms, tachypnoea, tachycardia, reduced urinary output, hypertension --> Infectious likely;
Janeway Lesions present;
Intravenous Drug User (huge risk factor for infective endocarditis);
Repeated events of self-harm (increasing the risk of infective endocarditis);
Mitral Regurgitation (pansystolic murmur and loud S2) --> this can occur if the lesion is located over the mitral valve;
Recurrent chlamydia (and possibly afflicted by other maladies in virtue of sexual history, such as HIV) ---> immunodeficiency.
Infective endocarditis is diagnosed through the Duke Criteria. It remains a top suspicion, not a formal diagnosis. We need to carry out investigations before we can ascertain it. However, at this stage, the patient already matches 3 minor criteria (vascular phenomenon, high fever and intravenous drug user) and 1 (borderline) major criterion (mitral regurgitation - the point is that we don't really know if it's a changing or pre-existing murmur).
The Duke Criteria for diagnosing infective endocarditis - extracted from: https://rebelem.com/wp-content/uploads/2017/11/Modified-Duke-Criteria-from-Cardiology-secrets-Chapter-34-Endocarditis-and-Endocarditis-Prophylaxis.jpg.
An elucidation of the major and minor criteria of Duke Criteria - extracted from: http://rebelem.com/wp-content/uploads/2017/11/Modified-Duke-Criteria-2-Cardiology-secrets-Chapter-34-Endocarditis-and-Endocarditis-Prophylaxis-7.jpg.
Investigations:
We therefore order the following investigations:
Basic Blood Tests: Full Blood Count, CRP, ESR, Liver and Renal Function Tests, U&E, Coagulation Profile (to see about general health status & deterioration to sepsis), Group & Save and Crossmatching (in case the patient requires blood transfusion; there is a high risk of septic shock);
Microbiology: Gram-staining, Blood Cultures (3 blood samples taken in a 3-hour interval); STI Panel (for sexually transmitted infections, covering syphilis, HIV and so forth);
Imaging and Tests: Chest X-Ray (to exclude respiratory pathologies and to check cardiomegaly), ECG, Echocardiography (ECHO) (Transthoracic).
Pregnancy Test - the patient has unprotected sexual intercourse regularly. We better see if there is a pregnancy since this will cause a substantial impact on our clinical decision-making.
I know it sounds tempting to operate on the patient and get a pathological specimen but this is not usually done.
Results:
Leucocytosis, High Urea, High Creatinine, High CRP and ESR, Borderline normal platelet count;
The patient is not pregnant.
Microbiology has successfully cultured Staphylococcus aureus (gram positive cocci). The microbe is a member of the skin flora and is the most commonly found microbe in intravenous drug users. Moreover, the patient is HIV-positive (negative for other types of sexually-transmitted infections).
Chest X-Ray is unremarkable. ECG seems normal (I always use the word 'seem' since my interpretations may deceive me). ECHO shows a mobile lesion over the mitral valve, indicative of abscess formation characteristic of infective endocarditis.
[13] ECHO showing vegetations (the lesion in infective endocarditis) over the mitral valve.
Clinical Picture showing Staphylococcus aureus (3, yellow) cultured on Mannitol-Salt agar. (Courtesy of Wikipeda)
At this stage, we've got two major criteria and three minor criteria. This is sufficient for us to make a definite diagnosis, ready for planning treatment.
As a side note, infective endocarditis can be caused by a wide range of microbes. Aside Staphylococcus aureus, which is the black sheep of the herd (since it is only common in patients who are intravenous drug users), we have Staphylococcus epidermidis. This is a more ubiquitously encountered microbe in patients with prosthetic heart valves. And then, we've got the common favourites such as Streptococcus pyogenes, Streptococcus bovis, Enterococcus faecalis, and the HACEK gang. HACEK is an acronym for five different types of microbes: Haemophilus (a member of the group, Haemophilus influenzae, is commonly vaccinated in children), Aggregatibacter, Cardiobacterium, Eikenella, and Kingella. They are technically not highly infectious and are members of the normal flora. However, when the host's immune system is dysfunctional, they can strike as lethal as a machete. Viridans Streptococci, another diverse gang of microbes, can also cause infective endocarditis. This time, they are related to oral health. They cause a phenomenon called 'transient bacteraemia', meaning that the bacteria get into the blood for brief periods of time. This leads to heightened risk of affliction towards the heart. This is why the execution of dental procedures is preceded by the taking of antibiotic prophylaxis to reduce the risk of infective endocarditis.
FINAL DIAGNOSIS: INFECTIVE ENDOCARDITIS.
The patient is immediately given a 6-week regimen of oxacillin administered intravenously. Supportive therapy, concerning nutrition and supplementary oxygen and anti-pyretics, is also given. Antiretroviral therapy is given since the patient is HIV-positive. This is accompanied by psychological support and counselling. Psychiatric opinion is sought over the patient's self-harm issue.
However, this is not the end of the story.
Oh god.
In the following three days, the patient presents with worsened dizziness and slurring of speech. According to the attending physician (because I'm just a bumblebee and does not check up on the patient all the time), the patient presents with unsteadiness in gait which has worsened very rapidly. The patient is incontinent and has wetted the sheets. The patient experiences issues with swallowing and retches frequently, where it necessitates that a different mode of nutrition is adopted. The patient has progressively worsening deficits in memory and cognition. The patient is disoriented in time and is progressively drowsy and less alert to surroundings.
Fearful of the intimate connection between the heart and brain, as well as the prospect of stroke (these symptoms and signs are very consistent with brainstem stroke). We have done an immediate Brain CT to check if there is anything amiss.
Here is a Brain CT comparable to the one we received from our patient.
[14]
There are two features to be noted here:
Hyperdense basilar artery (the little, shining dot in the centre). This indicates that the basilar artery is obstructed.
The tissue over the brainstem is hypodense to the cortical parenchyma. This is indicative of infarction.
A Brain CT is useful since it identifies any obvious signs of infarction, intracranial haemorrhage, and signs of brain herniation.
We go on to do an MR evaluation. However, shortly after the scans are acquired, the patient falls into a coma and assumes, what we call, a 'decerebrate posture'. I present to you both the MRI findings and what the patient looks like when illustrated.
This diagram shows decorticate and decerebrate posturing respectively. Decorticate posturing occurs when there is midbrain stroke. Decerebrate posturing occurs when there is pontine stroke. The midbrain is a structure located above the pons in the brainstem. As elaboration of decerebrate posturing, we can see that extension of the limbs is the main theme here. The medial reticulospinal tracts gain prominence and they are in control of extensor movements across all four limbs (medial tracts = stimulation; lateral tracts = inhibition). The rubrospinal tract (in control of upper limb flexion) is not functional when the pons falls. It only works when only the midbrain falls - thus in the decorticate posture, the arms are flexed. The corticospinal tracts do not work in both cases. They are responsible for lower limb flexion. Hence, extension forces are always stronger in the lower limbs, in the two cases presented above. Patients who assume such posturing are usually in coma due to the heavy impact on the pathways responsible for consciousness (ARAS = ascending reticular activation system). The diagram is extracted from: https://nursekey.com/wp-content/uploads/2016/12/B9781437717099000134_f013-001-9781437717099.jpg.
The following MR Brain scans are all extracted from Radiopaedia (I really like them). The sequence in question is DWI, which is very sensitive to infarcts. As you can see, the patient has multiple hyperintense lesions (indicative of infarction) over the bilateral pons and the right cerebellum (especially the posterolateral and inferior aspects). For the sake of convenience, scans obtained from other MR sequences are not presented. Rest assured, the ADC findings match those here - this means the findings below are (very likely) not artefacts.
Our hypothesis at this stage is that the patient experiences cardioembolism, where the septic emboli (septic = infectious material) travel from the heart (right from the mitral valvular leaflets) to the brain. Of course, the affected artery in this case is very likely to be the basilar artery. Basilar artery syndrome carries very high mortality, amounting to higher than 85 per cent. In the BASICS Registry [3], 41 per cent of patients had non-fatal strokes and did quite well regardless of the treatment received. Embolism accounts for 30 to 35 per cent of all cases of basilar artery occlusion, whereas 26 to 36 per cent, atherosclerosis. [3]
Illustration of the vascular territories of the Basilar Artery (Courtesy of Geeky Medics), extracted from: https://geekymedics.com/arterial-supply-of-the-brain/. According to [3], the basilar artery is anatomically divided into three portions: proximal (which goes from the vertebral artery junction to the giving out of the anterior inferior cerebellar arteries), middle (all the way to the point which gives out the superior cerebellar arteries), and distal (all the way to the bifurcation of the artery to give posterior cerebellar arteries). Pontine perforators are arteries of small calibre and are much more prone to occlusion by shower emboli.
At this stage, we aim to recanalise the basilar artery. In other words, we think that once we've removed the lesion and that the basilar artery is cleared of obstacles, everything will be fine. This is, however, also disturbed by numerous setbacks, since cardioembolism entails 'shower embolism', a phenomenon involving the shooting of various missiles up the brain. The vegetation on the mitral valve serves as a nidus for embolisation. Moreover, judging by the current status of the patient, we're worried that she might not be able to survive an intervention.
Ending:
Well, I haven't even talked about the treatment modalities. Why am I telling you the ending? That's because there's no treatment administered. As we're discussing about the next step, the patient develops cardiac arrest and passes away peacefully. All this happens two hours after we've got the MRI Scans and plan to do intra-arterial thrombolysis to clear the basilar artery.
Concluding Remarks:
In popular culture, the heart and brain are polar opposites - one on intuition, the other on reason. In medicine, both are intrinsically-linked. This strong bond formed between arguably the two most important organs in the body is sufficient to make matters escalate rapidly when one goes wrong. That prompts extra clinical vigilance and alertness. If the underlying heart condition is not resolved, it is very likely that the brain is going to be afflicted. A mistake can cost lives, just like the case of Georgina.
*Refer to: Jennette J, Falk R, Bacon P et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis & Rheumatism. 2012;65(1):1-11. doi:10.1002/art.37715, for more details.
**As you recall, Georgina is the name of my fictional wife. Anyway, this is also a fictional case to illustrate the main points of cardio-embolism.
References and Further Reading:
[1] Mak LE, Minuzzi L, MacQueen G, Hall G, Kennedy SH, Milev R. The Default Mode Network in Healthy Individuals: A Systematic Review and Meta-Analysis. Brain Connect. 2017;7(1):25-33. doi:10.1089/brain.2016.0438.
[2] Meng L, Hou W, Chui J, Han R, Gelb A. Cardiac Output and Cerebral Blood Flow. Anesthesiology. 2015;123(5):1198-1208. doi:10.1097/aln.0000000000000872.
[3] Mattle H, Arnold M, Lindsberg P, Schonewille W, Schroth G. Basilar artery occlusion. The Lancet Neurology. 2011;10(11):1002-1014. doi:10.1016/s1474-4422(11)70229-0.
[4] Crossman A, Neary D, Crossman B. Neuroanatomy: An Illustrated Colour Text. 6th ed. Edinburgh: Elsevier; 2019.
[5] Scheitz J, Nolte C, Doehner W, Hachinski V, Endres M. Stroke–heart syndrome: clinical presentation and underlying mechanisms. The Lancet Neurology. 2018;17(12):1109-1120. doi:10.1016/s1474-4422(18)30336-3.
[6] Ekker M, Boot E, Singhal A et al. Epidemiology, aetiology, and management of ischaemic stroke in young adults. The Lancet Neurology. 2018;17(9):790-801. doi:10.1016/s1474-4422(18)30233-3.
[7] Lee WH, Ko YH, Kim DI, Lee BB, Park JE. Prevalence of foam cells and helper-T cells in atherosclerotic plaques of Korean patients with carotid atheroma. Korean J Intern Med. 2000;15(2):117-121. doi:10.3904/kjim.2000.15.2.117.
[8] Debette S, Leys D. Cervical-artery dissections: predisposing factors, diagnosis, and outcome. The Lancet Neurology. 2009;8(7):668-678. doi:10.1016/s1474-4422(09)70084-5.
[9] Cahill T, Prendergast B. Infective endocarditis. The Lancet. 2016;387(10021):882-893. doi:10.1016/s0140-6736(15)00067-7.
[10] McDonald JR. Acute infective endocarditis. Infect Dis Clin North Am. 2009;23(3):643-664. doi:10.1016/j.idc.2009.04.013.
[11] Lambova S. Cardiac manifestations in systemic sclerosis. World J Cardiol. 2014;6(9):993-1005. doi:10.4330/wjc.v6.i9.993.
[12] Fung G, Luo H, Qiu Y, Yang D, McManus B. Myocarditis. Circ Res. 2016;118(3):496-514. doi:10.1161/circresaha.115.306573.
[13] Evangelista A, Gonzalez-Alujas MT. Echocardiography in infective endocarditis. Heart 2004;90:614-617.
[14] Garg R, Biller J. Neuroimaging Predictors of Clinical Outcome in Acute Basilar Artery Occlusion. Front Neurol. 2017;8. doi:10.3389/fneur.2017.00293.
[15] Belizna C, Hamidou M, Levesque H, Guillevin L, Shoenfeld Y. Infection and vasculitis. Rheumatology. 2008;48(5):475-482. doi:10.1093/rheumatology/kep026.
[16] Bayer A, Bolger A, Taubert K et al. Diagnosis and Management of Infective Endocarditis and Its Complications. Circulation. 1998;98(25):2936-2948. doi:10.1161/01.cir.98.25.2936.
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