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Cardiovascular Complications and Physiological Insights in Guillain-Barré Syndrome: An Integrative Review

Updated: Mar 27


Harpriya Khela1, Linh Huynh2, Taylor Patten3, Caroline Kaufman4, Moshe Shalom4



1Royal College of Surgeons in Ireland, Dublin, Ireland

2Kansas College of Osteopathic Medicine, Kansas, USA

3Arizona College of Osteopathic Medicine, Arizona, USA

4Tel Aviv University Sackler Faculty of Medicine, Tel Aviv, Israel


This study investigates a potential link between Guillain-Barré syndrome (GBS) and cardiomyopathy, with a specific focus on takotsubo cardiomyopathy. GBS, an autoimmune disorder causing acute paralysis, is characterized by autoantibodies attacking the peripheral nervous system. The article posits a relationship between GBS and cardiomyopathy, particularly in the context of sympathetic and vagal neural impulses, proposing that imbalances may contribute to the onset of both conditions, especially in aging hearts. Notably, cardiovascular complications, including takotsubo cardiomyopathy, are observed in GBS patients post-treatment. The research emphasizes the need for clinicians to be vigilant about this potential correlation, urging proactive monitoring through regular echocardiography. The study concludes by highlighting the significance of early intervention in GBS cases to mitigate fatalities, emphasizing the role of healthcare professionals in recognizing and managing the cardiovascular implications of GBS.


Guillain-Barré syndrome (GBS) is an autoimmune and post-infectious immune disease characterized by autoantibodies which attack the peripheral nervous system and ultimately lead to acute paralysis (1, 3, 8). Every year, approximately 100,000 people develop GBS  in the world (1). The symptomatology of GBS involves progressive ascending motor weakness originating in legs, cardiac arrhythmias, instability in blood pressure, and urinary retention (2). The mortality rate for patients with GBS is 3 to 10% (3). In addition, 20% of patients do not resume walking after 6 months (3). Notably, 25% of GBS patients show lack of respiratory sufficiency after developing the disorder (5).

Researchers have observed that individuals with GBS  have activated macrophages, T cells, and serum bodies targeting gangliosides (4). However, more research needs to be conducted on its significance (4). Some of the current effective treatments include intravenous immunoglobulin (IVIG) and plasma exchange (5). Despite high recovery rates, approximately 80%, for patients who received intensive treatment for GBS, many of these patients continue to suffer from persistent muscle weakness after developing the disorder. (6).

In addition to the musculoskeletal sequela of GBS,  individuals with GBS may develop cardiovascular complications (23).  Common cardiovascular complications developed include abnormal electrocardiographic (ECG) findings, hypertension, labile hypertension, tachycardia, bradycardia, and fluctuating heart rate (23). In a study on heart rate variabilities in patients (HRV) with GBS, researchers found that those with GBS have reduced low-frequency HRV, high-frequency HRV, and the total power spectral density of HRV, in comparison to the control group (24). Therefore, clinicians should be mindful and attentive to the relationship between GBS and cardiac conditions, as GBS may have clinical significance in the cardiovascular system. (23), (24).

In addition to the aforementioned cardiac complications associated with GBS, cardiomyopathy development post GBS treatment has been seen and poses another area of focus. Cardiomyopathy can be classified into two main categories: primary and secondary cardiomyopathy (7). Primary cardiomyopathy can be further broken down into genetic, mixed, or acquired (7). Secondary cardiomyopathy includes dilated, hypertrophic, and restrictive patterns (7). Commonly acquired cardiomyopathies include peripartum and stress-induced cardiomyopathy, such as takotsubo cardiomyopathy (7). Takotsubo cardiomyopathy can be identified by an inflated left ventricle (8). The pathogenesis of  takotsubo cardiomyopathy can be explained by the surge of catecholamines in the blood, due to emotional and physical stress (9).

Several case reports noted an association between GBS and takotsubo cardiomyopathy (10). It was seen that patients  with Guillain-Barre syndrome may develop takotsubo cardiomyopathy after treatment (11). Therefore, it is recommended to conduct regular echocardiography for patients with GBS, even though patients may not show symptoms of takotsubo cardiomyopathy. Clinicians should pay attention to the possibility of patients with GBS developing cardiomyopathy.


Cardiomyopathy types & general pathophysiology

Cardiomyopathy is a heart disease that affects the heart muscle (25).  Hypertrophic cardiomyography is the most common cardiomyopathy, in addition to the most common cause of sudden cardiac death (SCD) in young individuals (12),(13). One in every 500 individuals develop hypertrophic cardiomyopathy in the world (12).  Hypertrophic cardiomyopathy is caused by genetic mutations encoding sarcomeric proteins (13). Hypertrophic cardiomyopathy often leads to heart failure due to left ventricular flow obstruction (LVOT) (14). Ventricular myectomy surgery is often used to widen the left ventricle outflow tract (14). Due to the genetic basis of hypertrophic cardiomyopathy, gene therapy strategies can be used to relieve the symptoms (15).

In contrast to hypertrophic cardiomyopathy, patients with dilated cardiomyopathy have a dilated left ventricle, which makes it difficult for the heart to effectively pump blood throughout the body (16). Patients with dilated cardiomyopathy may have either one or two impaired ventricles (20). The cause of dilated cardiomyopathy is often due to autosomal dominant genetic inheritance or various inflammatory disorders (16), (18). Inflammatory disorders leading to cardiomyopathy are often due to medications, alcohol, or illicit drugs (16),(17),(19). Some of the common treatments for dilated cardiomyography are medication and device therapy (17). Beta blockers, such as metoprolol, carvedilol and bisoprolol, show significant efficacy in managing cardiomyopathy (19).

Patients with restrictive cardiomyopathy have a nondilated ventricle, which results in diastolic dysfunction (21). The cause of restrictive cardiomyopathy may be from genetic or acquired predisposition, disease, or both (21). Similarly to hypertrophic cardiomyopathy, inherited restrictive cardiomyopathy is due to sarcomeric, non-sarcomeric and sarcomeric-associated  protein mutations (22).


In this review paper, we will discuss cardiovascular physiologic dysfunction due to pathologic processes induced by GBS. The goal of this review is to draw attention to the relationship between cardiovascular complications and GBS, with the aim of streamlining earlier monitoring, intervention, treatment, and ultimately improved patient outcomes.


 Cardiovascular and Nervous System Physiology


As the cardiac conduction system matures from infancy to adulthood, it experiences developmental changes that impact cardiac innervation. Specifically, PGP (protein gene product 9.5) , DBH (dopamine b-hydroxylase) , TH (tyrosine hydroxylase), and AChE (acetylcholinesterase) innervation of the cardiac conduction system undergo change(d).  In both the young and adult heart, the density of autonomic innervation is greatest in the sinus node and decreases gradually through the atrioventricular node and bundle branches (d). In an infant’s heart, only acetylcholinesterase positive nerves are found in the sinus and atrioventricular nodes (d). With aging, such conduction tissues lose their cholinesterase content(d). This suggests that the cardiac conduction system matures from sympathetic dominance to both sympathetic and parasympathetic dominance seen in adulthood (d). Thus, age-related changes in the cardiac conduction system impact the autonomic cardiac function.


Optimal cardiac responses to sympathetic nerve stimulation is crucial to cardiac function. With natural aging, changes occur in cardiac electrophysiology, including β-adrenergic receptor responsiveness and sympathetic fiber neurodegeneration (c). In particular, in aged hearts, increased sympathetic nerve stimulation causes minimal change in heart rate, action protection duration, and Ca2+ parameters (c). Such aged hearts are less responsive to physiological sympathetic nerve stimulation [c]. However, the Ca2+ and action potential changes with sympathetic nerve stimulation in the aged heart need to be researched further [c].


In terms of β-adrenergic responsiveness (% change from baseline with isotonic solution), it is decreased in aged hearts (c). This is seen as circulating ISO results in a slower heart rate response (c). Specifically, in aged atria, the sinoatrial node’s β-adrenergic responsiveness is decreased (c).

In aged ventricles, sympathetic nerve density and norepinephrine concentration are reduced. As a result, the decreased responsiveness to sympathetic nerve stimulation may be due to nerve degeneration [c].  In contrast, the atrial norepinephrine content is similar in aged and young hearts, which suggests that atrial sympathetic nerve density may be preserved with age. Subsequently, the decreased responsiveness to sympathetic nerve stimulation in the atria may be due to decreased β-adrenergic responsiveness [c]. In contrast, since the ventricles of an aged heart contain reduced norepinephrine content, the decreased responsiveness to sympathetic nerve stimulation at these sites may be due to nerve degeneration [c]. This suggests that aged hearts are less responsive to physiological sympathetic nerve stimulation.

A similar physiological response occurs following a myocardial infarction, irrespective of age (b), (c).  A myocardial infarction results in the loss of cardiac sympathetic nerve fibers. The loss of such nerves is a strong predictor for the development of ventricular arrhythmias and cardiac death (b). Similarly, aged hearts are more susceptible to pacing-induced arrhythmias (b).

 Following the loss of cardiac sympathetic nerve fibers in the case of myocardial infarction, the application of dopamine beta-hydroxylase antibody conjugated to saporin, DBH-Sap (anti-DBH-Sap) produces a regional cardiac hypoinnervation of approximately a 50% reduction in healthy epicardial sympathetic fibers (b). These hypoinnervated hearts are sensitive to circulating isoproterenol, resulting in varying action potential duration, regional diastolic Ca2+ elevation, and muted heart rate (b). This suggests that the loss of cardiac sympathetic nerve fibers results in cardiac hypoinnervation.


The parasympathetic stimulation of the heart can be manipulated to control chronotropic and dromotropic effects in a diseased heart (g). As part of the parasympathetic conduction system, cardiac parasympathetic nerves run in conjunction with the superior vena cava (g). These parasympathetic nerves accumulate epicardially, besides the coronary sinus (g). When these nerves are stimulated with 20 Hz, via a multipolar electrode catheter placed in the superior vena cava, the sinus rate decreases and the antegrade Wenckebach period prolongs (g). However, with increasing parasympathetic voltage stimulation in the coronary sinus, a graded-response prolongation of the antegrade Wenckebach interval occurs (g). Prior to such parasympathetic nerve stimulation, negative chronotropic and dromotropic effects begin and , and then stop with the termination of stimulation (g). Thus, within the atrial refractory period, parasympathetic efferent nerve stimulation of the cardiac system induces reversible negative chronotropic and dromotropic effects. Therefore, parasympathetic stimulation may be of value in ventricular rate slowing during tachycardic atrial fibrillation seen in heart failure, and subsequently cardiomyopathy. However, further research is required.

Intracardiac electrophysiology

The epivascular cardiac system influences cardiac function (a). With epivascular cardiac plexus stimulation to the right pulmonary artery, there is an increase in left ventricle contractility, but no increase in heart rate (a). Between the right pulmonary artery and ascending aorta, there are epivascular sites that produce optimal cardiac stimulatory responses (a). However, epivascular cardiac plexus stimulation in cardiomyopathy requires more research.


The aging heart is less responsive to physiological sympathetic nerve stimulation, corresponding to dysautonomia symptoms. Studies have shown that dysautonomia, failures of the sympathetic and/or parasympathetic system, can be found in 75% of GBS patients (a) . However, further research is required to establish a direct correlation between aging and the subsequent development of GBS.  With increased age, the heart becomes progressively less responsive to systemic autonomic innervation, resulting in function failure (a). More research is required to demonstrate a correlation between the development of cardiomyopathy and age-related dysautonomia.


Given that the incidence of both cardiomyopathy and GBS increase with age, and that with increased age the heart becomes progressively less responsive to autonomic innervation, clinicians should be cognizant of the potential correlation between the development of GBS and cardiomyopathy.

GBS Pathophysiology

The pathophysiology behind GBS is not clearly elucidated to clinicians and researchers, despite the many attempts to determine the precise disease mechanism (b.) However, GBS is hypothesized to result from an unequal distribution of sympathetic and vagal neural impulses, in which there is excess sympathetic fiber activity. (a). The mechanism leading to autonomic instability in GBS is autoimmune in nature, with the majority of negative consequences seen in the peripheral nervous system (b). Triggers of this aberrant autoimmune response may be vaccination or infection, in which anti-ganglioside antibodies target axons (b). Transmission from preganglionic sympathetic fibers that are responsible for vasomotor and sudomotor activity, efferent cardiac parasympathetic fibers, and afferent fibers originating from baroreceptors, are thought to be involved in GBS pathogenesis (a). Another hypothesis is that a dramatic increase in catecholamine levels resulting from afferent conduction block, may cause posterior reversible encephalopathy syndrome, syndrome of inappropriate antidiuretic hormone secretion, and excess release of renin (a).

The two subtypes of GBS include acute inflammatory demyelinating neuropathy (AIDP), and acute motor axonal neuropathy (AMAN) (i). In AMAN, it has been discovered that IgG antiganglioside antibodies that bind antigens on the axolemma, as well as complement, first result in nerve block and then axonal destruction (i, j). These IgG autoantibodies can be found in the serum of approximately half of GBS patients early in their disease, as a result of a previous Campylobacter jejuni infection or another bacterial agent with antigens that emulate gangliosides (k). The final product of the complement cascade, the membrane attack complex (C5b-9), may result in axonal degeneration as well (i). In AIDP, complement activation and the formation of the membrane attack complex are thought to attack the membranes of Schwann cells, resulting in demyelination (i). Previous studies demonstrate evidence of damage to the peripheral nerves due to complement (i). Additionally, diminished creatine kinase activity and lower levels of creatine have been found in each of the GBS variants, indicating that defective mitochondria may be part of the mechanism (b).

IgG acts as a proinflammatory agent in the pathogenesis of GBS due to infections or autoimmunity (k). When compared to non-diseased patients of the same age and sex, GBS patients were found to have decreased levels of galactosylation of both IgG1 and IgG2, in addition to decreased levels of sialylation of IgG2 (k). These serum levels, prior to the initiation of therapy, demonstrate a pro-inflammatory state for these patients (k). Persistence of these low levels following the acute phase of their illness, may indicate a negative clinical prognosis for these patients (k).

Additionally, elevated glucose levels and ketone bodies, specifically acetoacetate, have been found in GBS patients’ blood and cerebrospinal fluid (b). Considering the cerebrospinal fluid is in direct contact with the nerves and myelin sheath that are destructed in the pathogenic autoimmune response in GBS, this finding can be critical in developing further hypotheses (b). Patients with hyperglycemia and elevated cerebrospinal fluid glucose levels were found to have a greater degree of disability, both throughout their hospitalization and at the time of discharge, than those with normal HbA1C(e).

T-cell immunoglobulin and mucin-3 (TIM-3) is a molecule often found on the surface of Th1 cells, and less frequently expressed on natural killer cells and monocytes (l). The hypothesized mechanism behind TIM-3 and its ligand is Th1 cell inhibition, resulting in less IFN-γ secretion and consequently, peripheral tolerance (l). Decreased expression of TIM-3 has been a contributing factor for GBS and other autoimmune diseases (l). Compared with their healthy counterparts, GBS patients were found to have higher IFN-γ and IL-17 levels in their serum due to this decreased expression, as well as increased Th17 cells in the peripheral circulation (l). One proposed mechanism is that when IL-17 binds to its receptor on the sheath of peripheral nerves, it releasesproinflammatory mediators which may be the cause of neurotoxicity (l).

Another proposed pathologic mechanism behind GBS is the role of mannose-binding lectin activating complement (MBL) (m). Increased serum levels of MBL were found in GBS patients, which has been shown to result in a greater extent of neuronal damage and severity of disease than those with less dramatic increases in MBL (m). This finding further elucidates the previously known mechanism of cross-reactivity of antibodies from past infection. (m)

Patients have also been found to have hypertrophied cervical spinal and peripheral nerves early on in the disease process of GBS. (c) Augmentation of the vagus nerve has also been found in GBS patients via ultrasound. (c) However, this finding is even more pronounced in GBS patients who are displaying autonomic instability. (c) The peripheral nerves are resistant to the shrinkage that is seen in the cervical spinal nerves and vagus nerves after six months. (c) The degree of hypertrophy in the C6 spinal nerve is positively correlated with the quantity of protein present in the cerebrospinal fluid at that level. (c) Hypertrophy of vagus nerve has been shown to remain in GBS patients whose dysautonomia has persisted, which may be a result of either continued inflammation or Wallerian degeneration (c)

When attempting to elucidate the mechanism behind the inferior to superior progression in paralysis in GBS patients, the inflammation present in the roots of spinal nerves, as well as ventral rami, could be notable, pathological hallmarks to consider. (f) These findings have been demonstrated within the first ten days of the clinical manifestations of GBS. (f) This nerve root inflammation could cause alterations in the structural integrity of the blood-brain barrier, permitting IgG anti-ganglioside antibodies to affect inhibitory interneurons in the medulla, resulting in lower motor neuron disinhibition. (g, j)

It is hypothesized that the infiltration of inflammatory cells, both around the blood vessels and within the endoneurium, could be an agent in the progression of demyelination at each segmental level. (d) Alterations in the typical structure of venules within spinal nerves has been discovered, taking on a more rhomboid-like shape similar to that of high endothelial venules. (f) This structural change in the early stage of GBS increases the permeability of the venules, resulting in endoneurial edema, which in turn could constrict the circulation within the nerve and lead to ischemia. (f) There have been multiple studies that depicted the pathogenesis of GBS to involve both the larger, myelinated nerve fibers, in addition to the smaller, nociceptive nerve fibers. (d) With utilization of contact heat-evoked potentials, GBS patients who denied paresthesia in their extremities, were found to have deterioration in smaller, myelinated nerve fibers. (d)

Onset of Signs and Symptoms of GBS

Some of the more prevalent signs of dysautonomia in those affected by GBS include tachycardic or bradycardic arrhythmias, unexplained oscillations in blood pressure, urinary retention, and absence of propulsion in the intestine. (a) Early symptoms of GBS include loss of sensation, paresis, paresthesia, and extremity myalgia. (d) Throughout the clinical course of GBS, around 10% of patients will either have exaggerated or normal deep tendon reflexes. (g) This finding should show clinicians that a wide range of qualities of deep tendon reflexes can be seen in GBS. (g) Hyperreflexia or even normal tendon reflexes should not immediately exclude GBS from the differential diagnoses. (g) Additionally, normal tendon reflex findings does not necessarily preclude a more severe case of GBS. (g)

Making the Clinical Diagnosis of GBS

Ensuring the clinical diagnosis of GBS is not missed or excluded erroneously, a thorough history of the patient’s previous infections and vaccinations must be taken, along with a neurological exam, lumbar puncture, electromyographic studies, and  anti-ganglioside antibody levels. (g) Cerebrospinal fluid studies can often report normal findings early in the disease course. (h) However, in some patients, these findings last throughout the disease process and do not necessarily indicate a less severe case of GBS. (h)

Characteristics of Severe GBS Cases

The most severe cases of GBS have been shown to be characterized by dysautonomia and organ dysfunction. (a) Both of these attributes of GBS can be fatal. (a) Studies have illustrated that dysautonomia can be found in 75% of GBS patients experiencing quadriparesis. (a)

Although GBS can affect patients of any age, the incidence of GBS and unfavorable prognosis tends to increase with age. (i,k) Patients shown to have the least galactosylation and sialylation of IgG1 and IgG2 Fc two weeks after presentation, were demonstrated to have the most severe deficits in strength after treatment and worst prognosis. (k) Additionally, patients with low levels of galactosylation and sialylation of IgG1 and IgG2 after treatment, were more likely to require mechanical ventilation than those with higher levels. (k)

Hypotheses of Fatality from GBS

For many years, GBS mortality has been thought to be closely associated with the severity of autonomic dysfunction in patients. (a) Many of these fatalities were attributed to myocardial infarction after profound states of dysautonomia. (a) Other fatalities occurred after hypertensive episodes despite the fact that their paralysis was not widespread. (a) Even with plasmapheresis or immunoglobulin treatment, fatalities due to GBS can still occur due to pulmonary embolism, pneumonia, or cardiac arrhythmias. (i) These conditions are due to such severe muscle weakness in the extremities and respiratory muscles, as well as dysautonomia. (i) With the inability to walk, the patient’s motor neuron function does not fully recover. The long-term sequelae of the nervous system are just a few of the contributing factors to these potentially lethal complications. (I)

Prognosis of GBS can be predicted based on the burden of axonal degeneration early in the disease process. (i) If damage to the axons can be mitigated with treatment early in the course of clinical illness, adequate nerve regeneration and remyelination could occur in the months following the point of maximal severity of symptoms. (i) Another prognostic indicator for GBS correlates with the patient’s response to treatment with intravenous immunoglobulins (IVIg). (k) Those who have a smaller increase in IgG serum levels post-treatment are significantly more likely to have a worse outcome than those with higher increases. (k)


Takotsubo Cardiomyopathy and GBS

Takotsubo cardiomyopathy, often called broken heart syndrome, involves transient dysfunction of both the left ventricular wall including either hypokinesis, akinesis, or dyskinesis, as well as possible mobility abnormalities of the wall of the apex of the heart. This dysfunction can occur without a background of coronary artery disease. (2a, 2b, 2f) Although rare, Takotsubo cardiomyopathy has been found to be associated with the acute phase of GBS. (2a, 2b, 2c, 2d, 2e) Features of Takotsubo cardiomyopathy include apical ballooning along with hypokinesia of the left ventricle. (2a, 2f) Potentially fatal  complications of Takotsubo cardiomyopathy include arrhythmias, irreversible damage to the myocardium, mural thrombi, and shock. (2a) The symptomatology of Takotsubo, in the background of GBS, has been known to mimic acute coronary syndrome in the clinical setting. (2a 2,b) Thus, the importance of illustrating the association between GBS and Takotsubo is critical for the early diagnosis and treatment of these patients, so as to not mistake Takotsubo symptoms for pure dysautonomia. (2a, 2c, 2d) In GBS patients, electrocardiography patterns such as inverted T waves, should prompt consideration for the possibility of Takotsubo cardiomyopathy. (2d, 2e) Myocarditis, acute coronary syndrome, and arrhythmias, are just a few of the complications that can occur from the severe dysfunction of the autonomic nervous system seen in GBS. (2b) Distinguishing this cardiac pathology from that of Takotsubo is not easily done in the clinical setting. (2a, 2b) Of fourteen previous case reports in which GBS and Takotsubo cardiomyopathy were found to be associated with one another, twelve of the patients were female. (2c) However,, it is unknown whether females are at an increased risk of Takotsubo cardiomyopathy (2c).

Potential Mechanism Behind the Association of GBS and Takotsubo Cardiomyopathy

Literature has shown that patients with symptoms of autonomic dysfunction from GBS could be at an increased risk for Takotsubo, a neurogenic, reversible stress type of cardiomyopathy. (2a, 2b, 2c, 2d, 2e) While the exact mechanism behind this association has not been clearly elucidated, several mechanisms are thought to be potential contributing factors. (2a, 2c, 2f) It is believed that the consequences of severe autonomic neuropathy, with excess sympathetic input seen in GBS, could cause excess release of catecholamines, leading to a stress response of the myocardium. (2a, 2b, 2c, 2d, 2f) Although it is unknown if this is a local or systemic effect, it is believed that the catecholamines could cause vasospasms of multiple coronary vessels resulting in myocardial necrosis, microscopic alterations of the vasculature, or stunning of the myocardium. (2a, 2d, 2f) Previous case reports have shown dramatic increases in serum catecholamines in acute Takotsubo, with one in particular demonstrating alterations in apical innervation. (2a, 2d, 2f) These elevations in norepinephrine and epinephrine are drastically increased compared to levels in an acute myocardial infarction. (2d, 2f)

Psychological-induced stress from the paralytic effects of GBS could also be a considerable factor.(2a, 2d) The massive release of norepinephrine and epinephrine causes hyperdynamic basal contractility, as well as apical dysfunction in systole. (2b, 2d) However, this particular pathologic mechanism was not found to be substantiated in one known patient withTakotsubo cardiomyopathy as the initial manifestation, prior to the onset of neurological deficits. (2a)

Dysfunctional autonomic tone in two-thirds of GBS patients is thought to affect multiple sets of small nerve fibers. (2c, 2d, 2f) Regulation of vasomotor effects and stimulation of sweat glands by sympathetic nerve fibers, regulation of the myocardium by parasympathetic nerve fibers, and baroreceptor innervation with afferents, are the main fibers thought to be dysfunctional in GBS. (2c) Clinically, dysautonomia manifests as undulations in blood pressure, myocardial infarction, malignant tachyarrhythmias or bradyarrhythmias, chronotropic perturbations, urinary retention, hyperthermia or hypothermia, dysfunction of gastrointestinal tract motility, and abnormalities of the pupils. (2c, 2d, 2e, 2f)

Another case report has demonstrated that the substantial catecholamine release contributing to cardiomyopathy can be caused by hemodynamic instability after the onset of anesthesia. (2d, 2e) This transient Takotsubo cardiomyopathy may also be due to autoimmunity in the myocardium and peripheral nerves. (2d) Reduced blood flow to the myocardium due to increased sympathetic activity could also be a potential mechanism for Takotsubo acutely in GBS. (2d) Increases in circulating epinephrine can cause alterations in signal transduction intracellularly, which decreases inotropicity of the myocardium at the apex due to the concentration of local β-adrenoceptors.  (2d, 2f) It is also paramount to note that with the utilization of MIBG-scintigraphy, transitory sympathetic nerve damage can be detected acutely in patients presenting with GBS and Takotsubo cardiomyopathy. (2f) More research should be done in order to clearly elucidate the mechanism behind the association between GBS and Takotsubo cardiomyopathy.


GBS is characterized by autoantibodies attacking the peripheral nervous system, causing progressive peripheral motor weakness and cardiac arrhythmias (1,3,8). GBS is hypothesized to result from an unequal distribution of sympathetic and vagal neural impulses, in which there is excess sympathetic fiber activity.. (a) Transmission from preganglionic sympathetic fibers that are responsible for vasomotor and sudomotor activity, efferent cardiac parasympathetic fibers, and afferent fibers originating from baroreceptors, are thought to be involved in the pathogenesis of GBS (a).

With maturation to the elderly heart, the infant cardiac conduction system transitions from sympathetic dominance to combined sympathetic and parasympathetic dominance (d).

With natural aging, changes occur in cardiac electrophysiology, B-adrenergic receptor responsiveness, and sympathetic fiber neurodegeneration (c). In aged ventricles, sympathetic nerve density and norepinephrine concentration are reduced, leading to decreased responsiveness.  This loss of sympathetic nerve density is also seen following myocardial infarctions, irrespective of age (b). To note, both myocardial infarctions and GBS are associated with nerve degeneration and tissue hypoinnervation, which ultimately can lead to heart failure. Within the atrial refractory period, parasympathetic efferent nerve stimulation of the cardiac system induces reversible negative chronotropic and dromotropic effects. Therefore, parasympathetic stimulation may be of value in slowing the ventricular rate during tachycardic atrial fibrillation seen with heart failure, and subsequently cardiomyopathy (g). However, further research is required. Given that the incidence of both cardiomyopathy and GBS increase with age, and that with increased age the heart becomes progressively less responsive to autonomic innervation, clinicians should put further suspicion into investigating the potential correlation between the development of GBS and cardiomyopathy.

Notably, cardiovascular complications in GBS patients include abnormal ECG findings, hypertension, labile hypertension, tachycardia, bradycardia, and fluctuating heart rate (23). Several case reports noted that many GBS patients developed takotsubo cardiomyopathy, a reversible stress type of cardiomyopathy, after treatment (11). Additionally, takotsubo cardiomyopathy has been found to be associated with the acute phase of GBS (2a, 2b, 2c, 2d, 2e). The symptomatology of Takotsubo, in the background of GBS, has been known to mimic acute coronary syndrome (2a, 2b). Thus, the importance of illustrating the association between GBS and Takotsubo is critical for the early diagnosis and treatment of these patients, as to not mistake Takotsubo symptoms for pure dysautonomia (2a, 2c, 2d).

In GBS patients, presentations on electrocardiography such as inverted T waves, should cause prompt consideration for the possibility of Takotsubo cardiomyopathy (2d, 2e). Regarding potential mechanisms, the consequences of severe autonomic neuropathy with excess sympathetic input seen in GBS could cause excess release of catecholamines, leading to a stress response of the myocardium (2a, 2b, 2c, 2d, 2f). The catecholamines released during stress could cause vasospasms of multiple coronary vessels resulting in myocardial necrosis, microscopic alterations of the vasculature, or catecholamine-induced stunning of the myocardium. (2a, 2d, 2f). Reduced blood flow to the myocardium from increased sympathetic activity could also be a potential mechanism for Takotsubo acutely in GBS (2d). More research should be done in order to clearly elucidate the mechanism behind the association between GBS and Takotsubo cardiomyopathy.  Notably, hypertrophic cardiomyopathy is the most common cardiomyopathy and is the most common cause of sudden death in young individuals (12),(13). This often leads to heart failure, due to left ventricle flow obstruction. Thus, clinicians should pay attention to the possibility of GBS patients developing cardiomyopathy, and subsequent heart failure.

Many GBS fatalities are attributed to myocardial infarction after profound states of dysautonomia (a). Despite plasmapheresis or immunoglobulin treatment, fatalities in GBS patients can still occur due to pulmonary embolism, pneumonia, or cardiac arrhythmias (i). However, early treatment can mitigate axonal damage, allowing for adequate nerve regeneration and remyelination to occur in the months following the point of maximal severity of symptoms (i). This decreases the likelihood for complications, such as cardiomyopathy. Overall, clinicians should be put further insight into investigating the potential correlation between GBS and the development of cardiomyopathy.


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