Cerebrogenic cardiopathy

Hypereosinophilic Syndrome (HES) is a condition related to helminthiasis, allergies, vasculitis, adverse reactions to drugs or malignant neoplasms. We report a case of a boy, 7 years old, presenting abdominal pain, vomiting, tachidispnea and leukocytosis with predominance of eosinophils. Bone marrow biopsy revealed intense granulocytic hypercellularity characterized by eosinophilia, as well as immature lymphoid cells in the interstitium, associated with trabecular bone infiltration. The immunohistochemical study revealed positivity for CD79a and TDT. Peripheral blood flow cytometry demonstrated 6.5% of lymphoid blasts. The diagnosis was Lymphoproliferative Disease associated with Hypereosinophilia: Acute Lymphoblastic Leukemia. The association presented is infrequent and its aggressiveness is determined by the physiological limitations imposed by the damages secondary to eosinophilia. Correspondence to: Stephen Oppenheimer, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore MD, USA; E-mail: soppenh@hotmail.com Received: August 13, 2017; Accepted: September 15, 2017; Published: September 18, 2017 Introduction Following Schiff’s discovery in 1875 of heart rate changes on motor cortex stimulation, responses were also elicited from the frontal lobes, subcallosal gyrus, septal area, temporal pole, and cingulate gyrus [1]. Subsequently, ECG changes were produced on feline sigmoid, anterior Sylvian and extosylvian gyri stimulation [1]. In 1926 Burdenko reported that midbrain lesioning in dogs generated scattered subendocardial hemorrhages, and focal myocyte disintegration [1]. In 1933, Neuberger identified similar post-mortem changes (subsequently termed myocytolysis) in seizure patients [1]. Recently specific cardiac representation was demonstrated within the insular cortex. In the human, the insula lies within the Sylvian fissure beneath the frontoparietal operculum and the superficial temporal plane (Figure 1) occupying 2% of the total cortical area. It is a site of visceral and autonomic representation. Cardiac accelerator or decelerator effects identified on rat insular stimulation [2] are mediated by sympathetic or parasympathetic neural tone changes without adrenal involvement [2,3]. Additionally, human right anterior insular cortex stimulation elicits cardiac acceleration alone or accompanied by a pressor response, whereas left anterior insular stimulation, results in cardiac deceleration alone or accompanied by a depressor response [4]. Lesions confined to the right posterior insula increase heart rate and blood pressure, whereas left insular lesions, increase baroreceptor gain [5] indicating that the right insula regulates cardiac and vascular sympathetic tone, and the left, cardiac parasympathetic function. Furthermore, rat insular stimulation generates PR and QT prolongation, ST depression, QRS broadening, succeeded (with continuing stimulation) by ventricular bigeminy, progressive bradycardia, complete heart block and finally asystole [6] with myocytolysis apparent on autopsy (Figure 2). These features suggest sympathetic and parasympathetic coactivation, with sympathetic effects exerted on the ventricular myocardium, altering the characteristics of repolarization and producing myocytolysis, and parasympathetic activation suppressing the SA node and implementing a permissive effect on ventricular automaticity. Further lateralization effects were shown in a murine model where left (but not right) insular lesions significantly decreased myocardial contractility and were accompanied by myocytolysis [7], with a direct inverse relationship between insular lesion volume and contractility reduction. The first clinical reports [8] documented an association between acute subarachnoid hemorrhage (SAH) QT prolongation and tall peaked or inverted T waves (Figure 3) mimicked by changing left ventricular endocardial temperature. Autopsy detailed cardiac pathology like that reported earlier by Neuberger. Termed “myocytolysis”, the changes are seen in conditions where increased sympathetic tone predominates [9,10]. The histopathological spectrum was subsequently amplified to include focal areas of myocardial necrosis and inflammatory response scattered throughout the ventricle, but especially in the bundle of His (Figure 4); these are not centered on blood vessels but on nerves. Regarding cerebrogenic ECG findings and confirming their non-ischemic origin, Kono et al. [11] separated SAH patients Figure 1. Human Insular Anatomy: The overlying opercula have been retracted exposing the five principal insular gyri; of is the orbitofrontal operculum; ofp is the frontoparietal operculum; ot is the temporal operculum; scia, circular insular sulcus-anterior; scii, circular insular sulcus inferior; scis, circular insular sulcus superior. Oppenheimer S (2017) Cerebrogenic cardiopathy Volume 1(2): 2-11 Blood Heart Circ, 2017 doi: 10.15761/BHC.1000112 Stroke QT prolongation, ST elevation/depression, and U waves are specifically associated with acute SAH or intracerebral hemorrhage, but also (with lesser incidence) after ischemic stroke [12]. Comparing pre-stroke with admission ECG, new onset cardiac repolarization changes were identified in 74% compared with 14% of controls. There was no relationship to potassium levels or stroke occurring in the embolic setting of an acute myocardial infarction; 8% showed new onset ventricular fibrillation, although since this was derived from isolated ECG and not Holter data, it likely underestimates the incidence. Recently, ventricular arrhythmias were reported in 22% patients admitted without cardiac history and suffering their first stroke (a confounding issue clearly relates to the shared risk factors for stroke and cardiac ischemia) [13]. These were more common when comparison was made with TIA patients (sharing the same risk factors for cardiac ischemia) and especially so in those with right hemisphere stroke. Additionally, since the arrhythmias disappeared within 2 weeks a probable association occurred with the stroke itself rather than an underlying cardiac cause. Peaked or inverted T waves, ST segment elevation/depression were identified in 24% of acute ischemic strokes [14] with ectopy more frequently encountered compared with controls. This persisted when excluding patients with cardiac history or previous stroke. Regarding repolarization inhomogeneity, QT dispersion is increased after acute stroke compared to age-matched hospitalized controls, both groups without history or clinical evidence of cardiac disease [15]. Since this was noted only within 24 hours of stroke onset, it strengthens the association and interestingly, was noted specifically with insular infarcts [16]. Further insular association arises from the linkage between right insular stroke and AV block, QTc prolongation, T wave inversion and ventricular ectopy, (these not observed with strokes in other locations) and with increased mortality at 3 months [17,18]. Myocytolysis frequent after SAH also occurs after ischemic stroke (Smith cited in 2), albeit less frequently. Treating SAH patients with propranolol and phentolamine [10] abolished ECG repolarization changes and myocytolysis, this implicating cerebrallyderived sympathetic dysregulation in the etiology. These post-mortem observations have a pre-mortem expression in cardiac enzyme into two groups: those with and those without repolarization changes, all lacking cardiac history. On angiography, the coronary arteries of those with ECG changes were completely normal. Abildskov et al. (cited in 1) proposed that cerebrally-related changes primarily affect cardiac repolarization and since they are mimicked by stellate ganglion stimulation are of sympathetic origin.