Neurocritical Care

, Volume 29, Issue 3, pp 508–511 | Cite as

Medulla Oblongata Hemorrhage and Reverse Takotsubo Cardiomyopathy

  • Kevin T. Gobeske
  • Maurice E. Sarano
  • Jennifer E. Fugate
  • Eelco F. WijdicksEmail author
Practical Pearl



Acute brain injury with strong surges of adrenergic outflow has resulted in takotsubo cardiomyopathy, but there are surprisingly few reports of takotsubo cardiomyopathy after intracranial hemorrhage, and none have been described from hemorrhage within the brainstem.


We describe a patient with reverse and reversible cardiomyopathy following a hemorrhage in the lateral medulla oblongata. While it is limited in size, the location of the hemorrhage caused acute systolic failure with left ventricular ejection fraction of 27% and vasopressor requirement for cardiogenic shock and pulmonary edema. There was full recovery after 7 days.


Detailed case report.


Hemorrhage into medulla oblongata pressor centers may result in acute, reversible, stress-induced cardiomyopathy, affirming the adrenergic origin of this condition.


Takotsubo cardiomyopathy Intracranial hemorrhage Medulla oblongata Neurogenic cardiac injury 

A 56-year-old woman with a history of tobacco use and a prior cervical injury from a motor vehicle accident collapsed after a coughing fit. She was brought urgently to our emergency department, where she was found to have right-sided facial paralysis, hemiplegia, diplopia, dysarthria, dysphonia, and difficulty clearing oral secretions. Her systolic blood pressure on arrival relaxed from the 160 to 120 mmHg but her heart rate remained near 100 beats per minute. An EKG showed possible left ventricular enlargement and equivocal ST segment changes.

CT of the brain showed a small but longitudinally extensive hemorrhage within the right posterior lateral medulla, extending to the lower pons and cervical spinal cord (Fig. 1a). CT angiogram showed a cluster of abnormal vessels around the right C1–2 neural foramen with intradural extension (Fig. 1b).
Fig. 1

Imaging studies showed the presence of a hemorrhage in the medial medulla. a CT scans show the acute hemorrhage in coronal view at the level of the ventrolateral medulla. b CT angiography shows a C1–2 right-sided dural arteriovenous fistula with associated aneurysm that was the source of the hemorrhage. c MRI GRE axial section shows hemorrhage extending superiorly to the hypoglossal nucleus and nucleus tractus solitarius sympathetic center. d Cerebral digital subtraction angiogram shows the associated aneurysm that was the likely source of the bleed

Upon arrival in our neurosciences ICU, the motor and sensory components of her neurologic examination remained unchanged, but her cough, had further worsened making it more difficult to handle secretions. Out of concern for impending respiratory failure and in preparation for catheter-based cerebral angiography, she was intubated using a rapid-sequence protocol with fentanyl, propofol, and rocuronium.

An MRI more precisely characterized the location of the hemorrhage and surrounding edema (Fig. 1c). Cerebral angiography confirmed the presence of an arteriovenous fistula at the C1–2 and C2–3 levels (Fig. 1d). Filling occurred predominantly from a C1–2 muscular branch of the right vertebral artery, with additional supply from small branches of the left vertebral artery at C1–2 and C2–3. A minor contribution also came from the anterior spinal artery, associated with a 2-mm unruptured aneurysm at the C1 level. Venous drainage proceeded via the cervical epidural plexus and right posterior cervical vein, without any deep or intradural drainage seen. There were no complications during the procedure, but her blood pressure did have a notable but very transient drop during initiation of additional anesthesia.

Concern for the development of neurogenic cardiac dysfunction prompted further workup and early initiation of inotropic support. An EKG demonstrated normal sinus rhythm, with evidence of mild left-sided enlargement, low anterior forces, and non-specific ST segment changes (Fig. 2a). Plain film chest radiography revealed borderline cardiomegaly, atelectasis, and diffuse patchy pulmonary infiltrates that raised concern for new heart failure and pulmonary edema (Fig. 2b). Serial troponin levels were elevated at 0.34, 0.59, 0.70, and 0.59 ng/ml. Transthoracic echocardiography showed dilatation of the inferior vena cava without inspiratory collapse, minor right ventricular enlargement, and a marked pattern of basal greater-than-apical circumferential hypokinesis, with an ejection fraction of 27% (Fig. 3). This provided the diagnosis of reverse takotsubo cardiomyopathy.
Fig. 2

Screening EKG and chest X-ray provided the first evidence of stress-related ventricular dysfunction. a Electrocardiogram showed mild left-sided enlargement, low anterior forces, and non-specific ST segment and T-wave changes. b Chest radiography shows early pulmonary edema, atelectasis, diffuse patchy infiltrates, and borderline cardiomegaly

Fig. 3

Transthoracic echocardiography in the four-chamber view in transverse planes shows left ventricular circumference at the end of systole and diastole. Sections through the apex show effective contraction at the end of systole compared with diastole, as noted by the arrowheads. Sections through the basal and mid-regions show no contraction between systole and diastole, confirming the basal pattern of circumferential hypokinesis or reverse takotsubo cardiomyopathy

Follow-up echocardiograms, EKGs, and chest X-rays showed full resolution of the syndrome within 7 days. She was extubated on hospital day 9, although her dysarthria and dysphagia persisted. The aneurysm associated with the AV fistula was coiled successfully, and she was able to leave the neurosciences ICU on hospital day 11 for ongoing rehabilitation.


Global acute neurologic injuries, such as aneurysmal subarachnoid hemorrhage, status epilepticus, and large strokes, are recognized neurogenic causes of takotsubo cardiomyopathy [1, 2, 3, 4]. After numerous reports in the literature, there is growing support that system-level injuries disrupting cortical–diencephalic–brainstem networks can alter sympathetic outflow and catecholamine surges to the heart [3, 4, 5, 6, 7]. Aneurysmal subarachnoid hemorrhage is the most frequent neurogenic cause of takotsubo cardiomyopathy; diffuse involvement of basal forebrain, third and fourth ventricles, and peri-mesencephalic regions can further increase the risk [2, 3, 4, 8]. Status epilepticus is the second most common neurogenic trigger for takotsubo cardiomyopathy [2, 3, 4, 9]. This also demonstrates that network or system dysfunction, and not necessarily gross pathologic injury, is sufficient to initiate stress ventricular dysfunction. Ischemic stroke and traumatic brain injury are also associated with the development of takotsubo syndrome, especially for diffusely damaged lesions damage or those involving the right insular regions with known function in sympathetic and cardiac regulation [1, 2, 3, 4, 5, 6]. Larger intraparenchymal hemorrhages involving similar locations or spreading into the ventricles may also trigger catecholamine dysregulation and neurogenic cardiomyopathy [10, 11, 12, 13].

Compared to acute global CNS injuries, spatially isolated lesions are less common causes of takotsubo cardiomyopathy. Scattered cases reported after cerebellar hemorrhage typically also involve the fourth ventricle and cerebellar outflow tracts [13, 14, 15, 16, 17, 18]. A few cases likewise are reported following brainstem lesions due to demyelinating disease or infection [19, 20, 21]. Interestingly, the proportion of reverse subtype takotsubo syndrome (basal rather than apical hypokinesis) appears to be relatively higher when neurogenic stress cardiac dysfunction is triggered by posterior lesions than by the more typical supratentorial injuries. In our review of the literature, three out of five cases showed the reverse pattern of reversible injury, compared with less than 10–20% of injuries above the hindbrain [2, 14, 15, 16, 17, 18]. Non-neurogenic causes of takotsubo syndrome likewise are unlikely to cause the reverse pattern of regional hypokinesis. Yet there is no difference in the proposed mechanism of pathogenesis at the level of the coronary microvasculature for typical or reverse takotsubo cardiomyopathy [22, 23, 24, 25].

Our patient’s case supports the hypothesis that neurogenic cardiac injury is triggered by even small lesions of medullary or spinal sympathetic outflow centers. Thus, the development of stress-related cardiac injury should be considered following such injuries, especially in higher risks, such as older–middle-aged, or postmenopausal patients.

Takotsubo cardiomyopathy is recognized clinically by ST segment changes in EKG, unexplained hypotension, non-specific cardiac arrhythmias, and elevated BNP and troponin levels. Echocardiograms show impaired ventricular function and circumferential hypokinesis not fitting a single vascular territory, typically with ballooning around the apex. Myocardial injury is thought to stem from intramyocardial calcium overload or an ischemic reperfusion phenomenon. The clinical course can vary notably with some patients requiring only observation and others requiring intensive care with vasopressors and inotropes. Outcomes depend upon the recognizing and managing ventricular failure, with all-cause fatality of 6% per patient-year and a recurrence rate of 2% demonstrated in one large patient registry.

This case also demonstrates the role of medullary centers for cardiovascular regulation in the generation of takotsubo cardiomyopathy. Cortical–limbic–diencephalic networks interconnect with brainstem and spinal centers including the nucleus tractus solitarius (NTS), caudal ventrolateral medulla, and rostral ventrolateral medulla [26, 27]. In our patient, hemorrhage impaired the function of the NTS to relay appropriate signals to parasympathetic preganglionic neurons, thalamus, and hypothalamus, as well as to mediate the gag reflex. Injury to NTS and the adjacent hypoglossal nucleus also explain her dysphonia and loss of palatal elevation and oral secretion control. The inferior portion of the bleed also involves the caudal ventrolateral medulla, resulting in loss of inhibitory projections to the rostral ventrolateral medulla, and thereby increasing sympathetic catecholaminergic output. The combination of impaired NTS gating of inputs to the network and altered ventrolateral medullary control of sympathetic outputs may create a labile system, with fluctuating surges of catecholamine activity to the heart.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Kevin T. Gobeske
    • 1
  • Maurice E. Sarano
    • 2
  • Jennifer E. Fugate
    • 1
  • Eelco F. Wijdicks
    • 1
    Email author
  1. 1.Division of Critical Care Neurology, Division of Neurocritical Care, Department of NeurologyMayo ClinicRochesterUSA
  2. 2.Division of Cardiology, Department of MedicineMayo ClinicRochesterUSA

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