Clin Auton Res DOI 10.1007/s10286-015-0284-z
CASE REPORT
Transient global amnesia and broken heart syndrome: two faces of one pathology Silvio Quick1 • Uwe Speiser1 • Nicole Richter2 • Akram Youssef1 • Nadine Waessnig1 Ruth H. Strasser1 • Karim Ibrahim1
•
Received: 29 September 2014 / Accepted: 17 December 2014 Ó Springer-Verlag Berlin Heidelberg 2015
Abstract We present a case of a 57-year-old female patient with transient global amnesia, who later developed broken heart syndrome also known as takotsubo cardiomyopathy. The present case underlines that co-occurrence of both pathologies might still be an underrecognized clinical problem. Keywords Transient global amnesia Broken heart syndrome Takotsubo cardiomyopathy
Case presentation A 57-year-old woman was rushed to the emergency department by her grandson because of symptoms of confusion and forgetfulness. 2 h before, on the day of admission, he found her confused, disoriented, and asking ‘‘bizarre questions’’. A careful neurological examination was completely normal without evidence of visual, motor, or somato-sensory system dysfunction except for the patient’s disorientation to time, place, and events. Extensive clinical neuropsychological evaluation of higher cortical functions was performed during the initial episode. Questions referring to autobiographical and public
S. Quick and U. Speiser contributed equally to this work. & Silvio Quick [email protected] 1
Heart Centre, Technische Universita¨t Dresden, University Hospital, Dresden, Germany
2
Department of Neurology, Technische Universita¨t Dresden, University Hospital, Dresden, Germany
events revealed a retrograde amnesia of several months. Anterograde amnesia was also tested with the Berlin Amnesia Test (BAT), which showed a severe anterograde memory deficit for verbal and non-verbal material [1]. Except for her memory, all other clinically evaluated higher cortical functions were normal. Cranial computed tomography and electroencephalography revealed no abnormalities. During the cardiovascular examination, the patient complained about typical symptoms of angina pectoris. The electrocardiography showed a dual chamber pacing with T-wave inversion without any evidence of ST segment elevation acute myocardial infarction. Laboratory investigations revealed elevated cardiac biomarkers: troponin T 102 ng/l (normal level, \4 ng/l), and serum creatine kinase MB-fraction total value 0.49 lmol/s l (normal level, \0.41 lmol/s l). Therefore, the patient was referred to the cardiology ICU for further diagnosis and therapy. Echocardiography showed biventricular apical and mid-ventricular akinesia with preserved wall motion of the left and right ventricular base resulting in a mild to moderate reduced left and right ventricular ejection fraction (supplemental data). Furthermore, on Doppler imaging a moderate biventricular diastolic dysfunction with elevated right ventricular systolic pressure of 40 mmHg and reduced systolic waveform of the hepatic vein flow signal was obvious. This led to an increased venous congestion with jugular venous distension on clinical examination. A diagnosis of acute coronary syndrome (ACS) was hypothesized, but an immediate cardiac catheterization excluded coronary artery disease. Ventriculography revealed pronounced wall motion abnormalities with apical ballooning and left ventricular (LV) dysfunction (Fig. 1a,
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Clin Auton Res
Discussion
Fig. 1 Left ventriculograms during a end-diastole and b end-systole show typical apical ballooning wall motion abnormality except for the left ventricular base, which is hyperdynamic
b). The imaging results and clinical presentation supported the diagnosis of takotsubo cardiomyopathy (TTC) according to the criteria proposed by the Mayo Clinic. The Japanese word takotsubo translates to ‘‘octopus pot’’, resembling the shape of the left ventricle during systole on imaging studies. The patient returned to her baseline normal neurologic state over the course of a 24-h hospitalized observation period and has not had any further recurrences. Satisfying the criteria of Hodges, the patient was diagnosed with transient global amnesia (TGA) [2]. Furthermore, left and right ventricular function completely recovered in the follow-up TTE. After the patient’s recovery, we completed a thorough medical history. She mentioned that she was suffering from high levels of stress and anxiety because her only son died 2 weeks before in a car accident.
123
The present case study describes a patient with a transient global amnesia and takotsubo cardiomyopathy. To our knowledge, the association of TGA with a stress cardiomyopathy was only described once before [3]. The pathophysiology of both diseases is still not well understood. Although the etiology of TGA remains controversial, there is consensus that the areas involved are the hippocampus and the parahippocampus region. Based on their literature review and study of 142 patients with TGA, Quinette et al. [4] postulated that TGA, as a multifactorial syndrome, may have at least three different causes: a neurotoxic effect on hippocampal function occurring after emotional or physical stress, venous congestion due to insufficient jugular vein valves precipitated by a Valsalva maneuver in men, and spreading depression of cortical activity in younger patients with a history of migraine. Especially in women, episodes are mainly associated with an emotional precipitating event. The trigger factors often involve emotional arousal and anxiety and up to 50 % of TGA patients demonstrate a phobic personality trait. The triggering factors, especially in women, might be the most common features of both diseases, supporting the theory of coincidence. In most patients with stress cardiomyopathy, whereby females comprise over 90 % of reported cases, an acute stressor has been identified resulting in a significant elevation of plasma catecholamines. The precise mechanism in which excessive sympathetic stimulation may result in transient left ventricular dysfunction remains controversial. Abnormal myocardial blood flow due to sympathetically mediated microvascular dysfunction has been suggested and is supported by decreased coronary flow reserve during the acute phase of TTC. An alternative explanation is the direct effect of catecholamines on cardiac myocytes. Lyon et al. postulated that high levels of circulating catecholamines trigger a switch in intracellular signal transmission. This change in signaling is negatively inotropic, and the effect is greatest at the apical myocardium, in which the density of b-adrenoceptors is highest [5]. Potentially, significant elevation of plasma catecholamine levels may also play a role in the pathogenesis of TGA. Saura et al. [6] reported a case of TGA following dobutamine stress echocardiography. However, this assumption remains speculative since no evaluation of catecholamine levels in TGA has ever been performed. On the other hand, a causality of TTC and TGA should also be taken into account. TTC following a neurological disorder is not a rarity. In particular, seizures or acute subarachnoid hemorrhage are
Clin Auton Res
well-known triggers for TTC. The crucial mediator of neurogenic cardiac injury may also be the endogenous release of catecholamines from the myocardial sympathetic nerve. In recent times, more attention has been drawn to the socalled biventricular takotsubo cardiomyopathy, which, along with the impairment of the left ventricular systolic function, also has a right ventricular involvement. An additional systolic RV dysfunction is associated with more severe congestive heart failure, resulting in higher venous pressure and following an elevated jugular vein pressure, one main aspect discussed in TGA pathogenesis. The low prevalence of biventricular TTC may be one reason why TGA does not occur more often in the whole TTC patient population. Finally, the pathophysiology of both TGA and TTC has not been clarified in detail yet, therefore trying to find common mechanisms of pathogenesis or corollary on basis of a single case remains speculative. Both disease manifestations are treated in different medical disciplines (neurology and cardiology). Because of a fundamental lack of awareness concerning these rare entities, they are most probably significantly under-diagnosed in the current diagnostic practice. Thus, it is possible that patients suffering from both TGA and TTC, due to their obvious symptoms of amnesia, are mainly referred to the neurologists. The profound cardiovascular examination, including assessment of cardiac biomarkers or echocardiography, is frequently of secondary importance. However, one should not forget that TTC has been a well-acknowledged acute cardiac problem with considerable morbidity and mortality due to arrhythmia, cardiogenic shock, and ventricular rupture.
Therefore, this diagnosis should not be missed as it needs adequate management and specific therapeutic strategies. A transthoracic echocardiography should be performed when electrocardiographic abnormalities and elevated cardiac biomarkers are present in TGA, even in asymptomatic patients, as this easy paraclinic tool can diagnose an unexpected cardiomyopathy. This case should draw attention to the importance of the coincidence of TGA and TCC. In this regard, neurologists should gain knowledge about this unusual but important entity in the clinical practice.
References 1. Metzler P, Rudolph M, Voshage J, Nickel B (1991) [The concept of amnesia and quantitative assessment of amnesic disorders]. Fortschr Neurol Psychiatr 59:207–215 2. Hodges JR, Warlow CP (1990) Syndromes of transient amnesia: towards a classification. A study of 153 cases. J Neurol Neurosurg Psychiatry 53:834–843 3. Grautoff S, Sitzer M, Weitkamp P, Kahler J (2012) [transient global amnesia and tako-tsubo cardiomyopathy—coincidence or corollary?]. Dtsch Med Wochenschr 137:2256–2259 4. Quinette P, Guillery-Girard B, Dayan J, de la Sayette V, Marquis S, Viader F, Desgranges B, Eustache F (2006) What does transient global amnesia really mean? Review of the literature and thorough study of 142 cases. Brain 129:1640–1658 5. Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE (2008) Stress (takotsubo) cardiomyopathy—a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 5:22–29 6. Saura D, Penafiel P, Morales A, Albert L, Martinez F, de la Morena G, Valdes-Chavarri M (2008) Transient global amnesia after dobutamine—atropine stress echocardiography. Eur J Echocardiogr. 9:567–568
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CASE REPORT
Transient global amnesia and broken heart syndrome: two faces of one pathology Silvio Quick1 • Uwe Speiser1 • Nicole Richter2 • Akram Youssef1 • Nadine Waessnig1 Ruth H. Strasser1 • Karim Ibrahim1
•
Received: 29 September 2014 / Accepted: 17 December 2014 Ó Springer-Verlag Berlin Heidelberg 2015
Abstract We present a case of a 57-year-old female patient with transient global amnesia, who later developed broken heart syndrome also known as takotsubo cardiomyopathy. The present case underlines that co-occurrence of both pathologies might still be an underrecognized clinical problem. Keywords Transient global amnesia Broken heart syndrome Takotsubo cardiomyopathy
Case presentation A 57-year-old woman was rushed to the emergency department by her grandson because of symptoms of confusion and forgetfulness. 2 h before, on the day of admission, he found her confused, disoriented, and asking ‘‘bizarre questions’’. A careful neurological examination was completely normal without evidence of visual, motor, or somato-sensory system dysfunction except for the patient’s disorientation to time, place, and events. Extensive clinical neuropsychological evaluation of higher cortical functions was performed during the initial episode. Questions referring to autobiographical and public
S. Quick and U. Speiser contributed equally to this work. & Silvio Quick [email protected] 1
Heart Centre, Technische Universita¨t Dresden, University Hospital, Dresden, Germany
2
Department of Neurology, Technische Universita¨t Dresden, University Hospital, Dresden, Germany
events revealed a retrograde amnesia of several months. Anterograde amnesia was also tested with the Berlin Amnesia Test (BAT), which showed a severe anterograde memory deficit for verbal and non-verbal material [1]. Except for her memory, all other clinically evaluated higher cortical functions were normal. Cranial computed tomography and electroencephalography revealed no abnormalities. During the cardiovascular examination, the patient complained about typical symptoms of angina pectoris. The electrocardiography showed a dual chamber pacing with T-wave inversion without any evidence of ST segment elevation acute myocardial infarction. Laboratory investigations revealed elevated cardiac biomarkers: troponin T 102 ng/l (normal level, \4 ng/l), and serum creatine kinase MB-fraction total value 0.49 lmol/s l (normal level, \0.41 lmol/s l). Therefore, the patient was referred to the cardiology ICU for further diagnosis and therapy. Echocardiography showed biventricular apical and mid-ventricular akinesia with preserved wall motion of the left and right ventricular base resulting in a mild to moderate reduced left and right ventricular ejection fraction (supplemental data). Furthermore, on Doppler imaging a moderate biventricular diastolic dysfunction with elevated right ventricular systolic pressure of 40 mmHg and reduced systolic waveform of the hepatic vein flow signal was obvious. This led to an increased venous congestion with jugular venous distension on clinical examination. A diagnosis of acute coronary syndrome (ACS) was hypothesized, but an immediate cardiac catheterization excluded coronary artery disease. Ventriculography revealed pronounced wall motion abnormalities with apical ballooning and left ventricular (LV) dysfunction (Fig. 1a,
123
Clin Auton Res
Discussion
Fig. 1 Left ventriculograms during a end-diastole and b end-systole show typical apical ballooning wall motion abnormality except for the left ventricular base, which is hyperdynamic
b). The imaging results and clinical presentation supported the diagnosis of takotsubo cardiomyopathy (TTC) according to the criteria proposed by the Mayo Clinic. The Japanese word takotsubo translates to ‘‘octopus pot’’, resembling the shape of the left ventricle during systole on imaging studies. The patient returned to her baseline normal neurologic state over the course of a 24-h hospitalized observation period and has not had any further recurrences. Satisfying the criteria of Hodges, the patient was diagnosed with transient global amnesia (TGA) [2]. Furthermore, left and right ventricular function completely recovered in the follow-up TTE. After the patient’s recovery, we completed a thorough medical history. She mentioned that she was suffering from high levels of stress and anxiety because her only son died 2 weeks before in a car accident.
123
The present case study describes a patient with a transient global amnesia and takotsubo cardiomyopathy. To our knowledge, the association of TGA with a stress cardiomyopathy was only described once before [3]. The pathophysiology of both diseases is still not well understood. Although the etiology of TGA remains controversial, there is consensus that the areas involved are the hippocampus and the parahippocampus region. Based on their literature review and study of 142 patients with TGA, Quinette et al. [4] postulated that TGA, as a multifactorial syndrome, may have at least three different causes: a neurotoxic effect on hippocampal function occurring after emotional or physical stress, venous congestion due to insufficient jugular vein valves precipitated by a Valsalva maneuver in men, and spreading depression of cortical activity in younger patients with a history of migraine. Especially in women, episodes are mainly associated with an emotional precipitating event. The trigger factors often involve emotional arousal and anxiety and up to 50 % of TGA patients demonstrate a phobic personality trait. The triggering factors, especially in women, might be the most common features of both diseases, supporting the theory of coincidence. In most patients with stress cardiomyopathy, whereby females comprise over 90 % of reported cases, an acute stressor has been identified resulting in a significant elevation of plasma catecholamines. The precise mechanism in which excessive sympathetic stimulation may result in transient left ventricular dysfunction remains controversial. Abnormal myocardial blood flow due to sympathetically mediated microvascular dysfunction has been suggested and is supported by decreased coronary flow reserve during the acute phase of TTC. An alternative explanation is the direct effect of catecholamines on cardiac myocytes. Lyon et al. postulated that high levels of circulating catecholamines trigger a switch in intracellular signal transmission. This change in signaling is negatively inotropic, and the effect is greatest at the apical myocardium, in which the density of b-adrenoceptors is highest [5]. Potentially, significant elevation of plasma catecholamine levels may also play a role in the pathogenesis of TGA. Saura et al. [6] reported a case of TGA following dobutamine stress echocardiography. However, this assumption remains speculative since no evaluation of catecholamine levels in TGA has ever been performed. On the other hand, a causality of TTC and TGA should also be taken into account. TTC following a neurological disorder is not a rarity. In particular, seizures or acute subarachnoid hemorrhage are
Clin Auton Res
well-known triggers for TTC. The crucial mediator of neurogenic cardiac injury may also be the endogenous release of catecholamines from the myocardial sympathetic nerve. In recent times, more attention has been drawn to the socalled biventricular takotsubo cardiomyopathy, which, along with the impairment of the left ventricular systolic function, also has a right ventricular involvement. An additional systolic RV dysfunction is associated with more severe congestive heart failure, resulting in higher venous pressure and following an elevated jugular vein pressure, one main aspect discussed in TGA pathogenesis. The low prevalence of biventricular TTC may be one reason why TGA does not occur more often in the whole TTC patient population. Finally, the pathophysiology of both TGA and TTC has not been clarified in detail yet, therefore trying to find common mechanisms of pathogenesis or corollary on basis of a single case remains speculative. Both disease manifestations are treated in different medical disciplines (neurology and cardiology). Because of a fundamental lack of awareness concerning these rare entities, they are most probably significantly under-diagnosed in the current diagnostic practice. Thus, it is possible that patients suffering from both TGA and TTC, due to their obvious symptoms of amnesia, are mainly referred to the neurologists. The profound cardiovascular examination, including assessment of cardiac biomarkers or echocardiography, is frequently of secondary importance. However, one should not forget that TTC has been a well-acknowledged acute cardiac problem with considerable morbidity and mortality due to arrhythmia, cardiogenic shock, and ventricular rupture.
Therefore, this diagnosis should not be missed as it needs adequate management and specific therapeutic strategies. A transthoracic echocardiography should be performed when electrocardiographic abnormalities and elevated cardiac biomarkers are present in TGA, even in asymptomatic patients, as this easy paraclinic tool can diagnose an unexpected cardiomyopathy. This case should draw attention to the importance of the coincidence of TGA and TCC. In this regard, neurologists should gain knowledge about this unusual but important entity in the clinical practice.
References 1. Metzler P, Rudolph M, Voshage J, Nickel B (1991) [The concept of amnesia and quantitative assessment of amnesic disorders]. Fortschr Neurol Psychiatr 59:207–215 2. Hodges JR, Warlow CP (1990) Syndromes of transient amnesia: towards a classification. A study of 153 cases. J Neurol Neurosurg Psychiatry 53:834–843 3. Grautoff S, Sitzer M, Weitkamp P, Kahler J (2012) [transient global amnesia and tako-tsubo cardiomyopathy—coincidence or corollary?]. Dtsch Med Wochenschr 137:2256–2259 4. Quinette P, Guillery-Girard B, Dayan J, de la Sayette V, Marquis S, Viader F, Desgranges B, Eustache F (2006) What does transient global amnesia really mean? Review of the literature and thorough study of 142 cases. Brain 129:1640–1658 5. Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE (2008) Stress (takotsubo) cardiomyopathy—a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 5:22–29 6. Saura D, Penafiel P, Morales A, Albert L, Martinez F, de la Morena G, Valdes-Chavarri M (2008) Transient global amnesia after dobutamine—atropine stress echocardiography. Eur J Echocardiogr. 9:567–568
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