Neurogenic pulmonary edema and stunned myocardium following massive hemimedullary ischemic stroke due to vertebral dissection with spontaneous recovery: a case report
Tinh Quang Dang1
, Thang Ba Nguyen1, Tai Ngoc Tran1, Bien Huu Thien Le2
Contributions: (I) Conception and design: TN Tran, TQ Dang; (II) Administrative support: TN Tran, TB Nguyen, TQ Dang; (III) Provision of study materials or patients: TN Tran, TQ Dang, BHT Le; (IV) Collection and assembly of data: TN Tran, TQ Dang; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
Background: Neurogenic pulmonary edema (NPE) usually manifests as an acute respiratory distress syndrome following severe insults of the central nervous system. The condition typically progresses and regresses within the span of a few days. In many cases, there is concomitant neurogenic myocardial injury. While triggering pathologies usually include brainstem encephalitis, subarachnoid hemorrhage and traumatic brain injury, NPE was rarely reported to be present after ischemic stroke. Sympathetic overactivation and massive catecholamine discharge are speculated to be the underlying cause, with medulla oblongata being one of the sympathetic centers with trigger zone for NPE.
Case Description: Here we report a case of a young female with no prior health problem presenting initially with 3-month chronic neck pain of severe intensity and difficulties in head rotation followed by neurological deficits, which deteriorated rapidly into cardiorespiratory failure. At admission, she was monitored in intensive care unit (ICU) on ventilation support [(VAC) mode with a tidal volume of 450 mL, respiratory rate at 15, positive end-expiratory pressure (PEEP) of 5 cmH2O and a fraction of inspired oxygen (FiO2) between 40–60%]. Chest X-ray showed bilateral diffuse opacities suggestive of NPE. Mild hypokinetic cardiomyopathy with transient elevated troponin was also documented. Massive hemisection medullary infarction extending caudally to upper cervical spinal cord was revealed on magnetic resonance imaging (MRI) and correlated with a combined lateral and medial medullary syndrome clinically. Intramural hematoma of the left vertebral artery on T1-weighted fat saturated sequence was consistent with arterial dissection. The patient received supportive treatment including fluid and oxygen therapy and went on to make a full recovery. At 2-month follow-up, she regained her ability to walk unaided and to take oral food intake.
Conclusions: Through this case, discussions about the complex underlying neuro-cardiac mechanism of this very rare complication of medullary stroke are presented. A combined pathogenesis involving both neurogenic pulmonary and cardiogenic components could be more compatible with clinical observations.
Keywords: Neurogenic pulmonary edema (NPE); medullary stroke; vertebral dissection; case report
Received: 29 September 2024; Accepted: 13 March 2025; Published online: 20 May 2025.
doi: 10.21037/jeccm-24-158
Highlight box
Key findings
• This case study highlights neurogenic pulmonary edema (NPE) as one of the uncommon complications of hemimedullary stroke in a young patient who went on to make a full recovery with supportive treatment.
What is known and what is new?
• Hemimedullary stroke is an extremely rare stroke localization and a potential trigger for fulminant neurogenic cardiorespiratory failure, presumably through damage of the anatomic sympathetic center.
• While NPE is classically regarded as non-cardiogenic, the involvement of a cardiogenic mechanism could be present in the same pathogenesis, as demonstrated in this patient.
What is the implication, and what should change now?
• A combined neuro-cardiac NPE model with both neuro-cardiogenic and non-cardiogenic components could be more compatible with the clinical scenario. Future approach should focus on the determination of the dominant component that could help guide therapeutic decision.
Introduction
Neurogenic pulmonary edema (NPE) can be regarded as an uncommon subset of acute respiratory distress syndrome with a distinct neurogenic mechanism (1). Massive sympathetic release into circulation plays a key role in the initiation of fluid accumulation and subsequent lung injury. Resolution occurred in less than 72 hours in the majority of patients (2). Similarly, myocardial stunning can share a common pathophysiological process and have a rapidly reversible course (3). There are still uncertainties regarding the intricate pathogenesis, especially the involvement of a possible cardiogenic component in a case with typical features of NPE. Triggering pathologies frequently include brainstem encephalitis, traumatic brain injury, hemorrhagic stroke, and in a small number of cases, ischemic strokes both in the posterior and anterior circulation (2,4,5). Respiratory compromise due to ischemia of the medullary sympathetic center is a very rare presentation, accounting for less than 3% of all medullary strokes (6). Currently, there are very few reports of well-documented NPE associated with medullary ischemic strokes in the literature.
Here we describe a unique case of young stroke patient with lesion locating in the territory of both medial and lateral medulla oblongata, who developed transient but fulminant life-threatening respiratory failure and hypotension. Other differential diagnosis were excluded by a comprehensive workup. Cardiopulmonary function assessments were compatible with NPE associated with a mild reversible stress-induced cardiomyopathy. A combined mechanism with both neuro-cardiac and neuro-pulmonary pathway could be evoked. Vertebral artery dissection was eventually identified to be the etiology of her stroke. We present this case in accordance with the CARE reporting checklist (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-158/rc).
Case presentation
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
A young female in her late 20s was transferred to the Emergency Department of University Medical Center Ho Chi Minh City due to cardiorespiratory failure. There was no prior health problem except for occasional recreational substance use and a 3-month chronic neck pain of severe intensity with difficulties in head-turning movements. Recent history consisted of an abrupt-onset intense vertigo described as “veering-to-the-left” sensation with nausea when she sat behind her friend on a motorbike. There was no report of immediate substance use prior to this event. She was then taken home to rest and was later found unresponsive on her bed and taken to hospital. Severe hypotension at 70/40 mmHg and respiratory failure were present at admission. She was intubated and norepinephrine was administered to stabilize her arterial pressure (starting dose 0.1 mcg/kg/min). Arterial blood gas showed a severely reduced partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) (P/F) ratio of 113. She was transferred 7 hours after onset for further management and investigation.
At admission, she was monitored in intensive care unit (ICU) on ventilation support [volume-assisted controlled (VAC) mode with a tidal volume of 450 mL, respiratory rate at 15, positive end-expiratory pressure (PEEP) of 5 cmH2O and a FiO2 between 40–60%]. Her level of consciousness was preserved with spontaneous eye opening and meaningful motor response. Bilateral fine crackles were noted during auscultation. Initial chest X-ray revealed bilateral diffuse pulmonary opacity affecting peripheral and hilar regions equally (Figure 1); 12-lead electrocardiogram revealed a sinus tachycardia without any specific changes in ST-T waves. Pulmonary computed topography angiography showed patchy non-gravitational diffuse infiltrates and no sign of pulmonary embolism or aspiration (Figure 1). Viral and bacterial panels were negative in sputum sample. Screening tests for substance use were also negative (Table 1). Echocardiography revealed a slightly reduced ejection fraction at 39% with mild diffuse hypokinesis of the left ventricle. After discussion, coronarography was performed and ruled out any relevant obstructive coronaropathy (Figure 2).
Table 1
| Laboratory tests | Results | Reference value |
|---|---|---|
| Toxicology screening (urine) | ||
| Opioid (heroin, morphin, …), amphetamine, barbiturate, cocaine, methamphetamine, phencyclidine, tricyclic anti-depressant | Negative | Negative |
| Toxicology screening (serum) | ||
| Acetaminophen, amlodipine, amiodarone, amitriptyline, amphetamine, atropine, alprazolam, bromazepam, caffeine, carbamazepine, carbofuran, carbosulfan, chlorpheniramine, chlorpromazine, chlorpyrifos, clozapine, codeine, celecoxib, dextromethrophan, diazepam, domperidone, EPN, felodipine, fenobucarb, flurazepam, fluoxetine, gliclazide, haloperidol, imipramine, ketamine, lidocaine, loperamide, levomepromazine, methylenedioxymethamphetamine, malathion, methadone, methamphetamine, metoprolol, metronidazole, midazolam, morphine, nifedipin, olanzapine, omeprazole, pantoprazole, phenytoin, prazepam, prednisolone, primidone, ranitidine, ritodrine, strychnine, sertraline, tetrahydropalmatine, theophylline, tramadol, XLR-11, zopiclone | Negative | Negative |
| Microbiology (sputum) | ||
| Viral panel (influenza A; influenza B; respiratory syncytial virus A; respiratory syncytial virus B; flu A-H1; flu A-H1N1) | Negative | Negative |
| COVID-19 screening test | Negative | Negative |
| Bacterial panel (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, H. influenzae, S. pneumoniae, Bordetella pertussis, Bordetella parapertussis) | Negative | Negative |
| Hematology, biochemistry and young stroke workup | ||
| White blood cells (G/L) | 16.3 | 4–10 |
| Neutrophils (%) | 82.8 | 45–75 |
| Lymphocytes (%) | 10.1 | 20–35 |
| Hemoglobin (G/L) | 132 | 120–175 |
| Platelets (G/L) | 517 | 150–450 |
| C-reactive protein (mg/L) | <1 | <5 |
| Sodium (mmol/L) | 137 | 136–146 |
| Potassium (mmol/L) | 3.56 | 3.4–5.1 |
| Creatinine (μmol/L) | 62.87 | 0.66–1.09 |
| Estimated glomerular filtration rate (CKD-EPI 2021) (mL/h/1.73 m2) | 118 | – |
| Pro-calcitonin (ng/mL) | 0.15 | <0.5 |
| Anti-beta2 glycoprotein antibodies IgM/IgG (U/L) | Negative | Negative: <20.0 |
| Anti-cardiolipin antibodies IgM/IgG | Negative | S/CO <0.8 |
| Anti-phospholipid antibodies IgM/IgG (U/mL) | Negative | <12 |
| Lupus anticoagulant | Negative | Negative |
| Anti-nuclear antibodies | Negative | <0.8 |
| Anti-dsDNA (IU/mL) | Negative | <25 |
CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; COVID-19, coronavirus disease 2019; EPN, ethyl p-nitrophenyl phenylphosphorothioate; IgG/IgM, immunoglobulin G/M; S/CO, signal to cut-off ratio.
Her cardiorespiratory condition started to improve significantly in the following days. Low dose norepinephrine (0.15 mcg/kg/min) and dobutamine (0.5 mcg/kg/min) were weaned off within 24 hours and her arterial pressure stabilized afterwards. Arterial blood gas normalized and Troponin T decreased significantly after 48 hours (Table 2). She was successfully extubated at the end of day 2 and transferred to Neurology Ward. Repeat chest X-ray after 3 days showed complete resolution of previous pulmonary opacity (Figure 1). Radiographic Assessment of Lung Edema (RALE) score improved from 12 to 0.
Table 2
| Arterial blood gas parameters | Day 1 (since onset) | Day 2 | Day 3 | Reference values |
|---|---|---|---|---|
| pH | 7.16 | 7.43 | 7.44 | 7.35–7.45 |
| pCO2 (mmHg) | 45 | 32.1 | 30.7 | 35–45 |
| pO2 (mmHg) | 68 | 154.8 | 159.8 | 85–95 |
| HCO3− (mmol/L) | 16 | 20.8 | 20.2 | 18–23 |
| P/F ratio | 113 | 442.3 | 532.6 | ≥400 |
| Troponin-T (ng/L) | 833 | 291 | 88 | <14 |
P/F, PaO2 to fraction of inspired oxygen; PaO2, partial pressure of oxygen.
On clinical examination, we found a left-sided hemimedullary or Reinhold syndrome with left-sided Horner syndrome, hemi-ataxia, torsional-horizontal gaze-evoked nystagmus beating most prominently to the right side, and left tongue palsy (Figure 3). Babinski sign was positive on the right side, suggesting involvement of the left pyramidal tract. Ocular lateropulsion was also found upon eye closing. Full sequence magnetic resonance imaging (MRI) with gadolinium-contrasted angiography revealed a massive hemimedullary infarction (Figure 4). Crescent-shaped hyperintensities on T1 fat-saturated sequence corresponded with a left vertebral artery dissection and were consistent with the preceding neck pain (Figure 5). Other lab workups for young stroke were also returned negative for acquired coagulopathy. Repeat echocardiography after 4 days confirmed the resolution of her left ventricular function with a normalized ejection fraction of 53%.
Supportive treatments including fluid and oxygen therapy were given during her stay in ICU. Antibiotics were discontinued once infectious causes were ruled out. Single antiplatelet and statin were given as secondary prevention treatment. She received rehabilitation therapy on balance, speech and swallowing functions. At 2 weeks, she was discharged with a modified Rankin score of 3. At 2-month follow-up, she regained her ability to walk unaided and to take oral food intake. A graphical timeline of the case evolution is presented in Figure 6.
Discussion
Our case demonstrates an unusual respiratory and hemodynamic complication of medullary stroke. The presence of a rapidly progressing cardiopulmonary failure preceded by localizing neurological symptoms prompts the hypothesis of a neurogenic mechanism. The diagnosis is further supported by the reasonable exclusion of other causes of fulminant cardiorespiratory failure in a young patient such as acute obstructive coronaropathy, pulmonary embolism, viral infection and aspiration. However, due to the reduced ejection fraction of left ventricular and lack of pulmonary capillary wedge pressure to demonstrate pulmonary congestion, one cannot rule out cardiogenic pulmonary edema effectively. Although these two conditions can co-exist, the rapid resolution of pulmonary edema without specific treatment is more suggestive of NPE. Bilateral peripheral non-gravitational distribution of lung infiltrates on chest X-ray are also typical findings associated with NPE (7). The monophasic course of her condition was marked by a rapid deterioration phase followed by an equally fast recovery within the span of 3 days, which is a typical feature mentioned in several papers (1,8).
Hemimedullary infarct is an extremely uncommon stroke location, accounting for less than 3% of all medullary strokes (6). The clinical syndrome is caused by a concurrent ischemia of median, paramedian lateral, and dorsal zones of the medulla oblongata, producing a combined Wallenberg and Dejerine syndrome. In theory, the large infarcted area could allow for more extensive damage of medullary structures. In the upper medulla, several trigger areas for NPE have been described with neuronal projections to the sympathetic centers in the cervical spinal cord, which in turn innervates the pulmonary vascular bed (9). In animal model, damage to these connections could result in the formation of NPE (8). Injury to the solitary tract in the ventrolateral medulla can also produce simultaneously pulmonary edema and myocardial damage (8,10).
In the current literature, there were few reports of NPE associated with vertebral dissection, although no patient was seen with a massive hemimedullary lesion (Table 3). All patients presented with significant neck pain and 3 patients had a clear traumatic factor. Lung findings are consistent in the peripheral distribution of lesion in 3 cases with available data (4,5,11). One patient was initially misdiagnosed with myocardial ischemia, while in 3 out of 4 cases, there were elevated markers suggestive of myocardial dysfunction (4,5,12). Repeat echocardiography confirmed resolution of cardiac function in all patients. In two cases, a medullary lesion was radiologically documented, although it could be supposed that medullary involvement should be present based on anatomical basis (5,11). Favorable outcome was seen in all patients, mostly within 24–72 hours after stroke onset.
Table 3
| Cases | Age (years)/gender | Stroke location | Artery affected | Preceding traumatic factor | NPE onset and course | Chest X-ray features | Associated cardiac injury | Reference |
|---|---|---|---|---|---|---|---|---|
| 1 | 38/female | Right cerebellum | Right V4 occlusion, V3 intimal flap | Tennis | 3 hours, improved after 1 day | Mild, patchy peripheral infiltrates | Elevated BNP 3,028 ng/L | (4) |
| 2 | 28/male | Bilateral cerebellum, left occipital lobe | Right V3 stenosis with intimal flap and IMH | Football | Acute, improved after several days | Bilateral patchy peripheral infiltrates | Elevated troponin 1,331 ng/L, mild LV failure, elevated BNP 3,655 ng/L | (5) |
| 3 | 68/female | Left dorsolateral medulla | Left V3–V4 occlusion | Golf | 5.25 hours, improved in 24 hours | Bilateral interstitial edema | – | (11) |
| 4 | 34/male | Right medulla, bilateral cerebellum | Right V2 dissection | – | 2 hours, improved after 1 day | – | Increased MB-fraction of CK at 19% | (12) |
| Our study | 25/female | Left hemi-medulla | Left V3 | – | <2 hours, improved after 3 days | Patchy non-gravitational diffuse infiltrates | Elevated troponin-T, reduced ejection fraction | – |
BNP, B-type natriuretic peptide; CK, creatine kinase; IMH, intramural hematoma; LV, left ventricle; MB, muscle brain; NPE, neurogenic pulmonary edema.
While NPE was traditionally defined as an entity at the other end of the pulmonary edema spectrum and opposite to cardiogenic ones, a multifactorial neuro-cardiac model was proposed suggesting a certain role of neurogenic myocardial dysfunction in the pathogenesis (8). In our patient, there was evidence of both pulmonary and myocardial compromise. On one hand, pulmonary capillary injury secondary to increased hydrostatic pressure and endothelial dysfunction can lead to the formation of transudative leak into the alveolar space (8). One the other hand, neurogenic pump failure due to stress-induced cardiomyopathy or stunned myocardium is another overlapping entity linked to the same sympathetic hyperactivity (3). This neuro-cardiogenic component could be explained by either direct cell injury or due to increased systemic vascular resistance, both of which could result from the causative catecholamine overload (8). The diagnosis requires evidence of reversible myocardial damage and ventricular dysfunction, and exclusion of obstructive coronary disease. Naum et al. described a case with subarachnoid hemorrhage presenting with confirmed NPE and stunned myocardium, the criteria of which can be fully applied to that of our patient (13). A common thread could be the brain-heart-lung interaction where a central nervous system (CNS) injury triggers a massive sympathetic stimulus acting on both systems, resulting in a neurogenic cardiorespiratory failure.
Treatment of the triggering factor (i.e., elevated intracranial pressure) depends on the underlying etiologies. In our case, treatment of ischemic stroke attributable to vertebral artery dissection was secondary prevention and rehabilitation. No reperfusion therapy was given considering her late presentation beyond the thrombolytic window. Aspirin is the antithrombotic agent of choice per European guideline with treatment duration ranging from 3–6 months (14). The determination of the predominant component in NPE pathogenesis, neuro-cardiogenic or non-cardiogenic, could have therapeutic implications and help guide more specific treatment decision regarding fluid balance in the acute clinical setting. Catecholamine dosing could be helpful although it was not tested in our patient. Alpha-adrenergic blocker like phentolamine was also reported to be effective in a case study (15). In most cases, management revolves around supportive care and ventilation support in wait of its transient nature.
There are several limitations regarding our paper. Data about the initial phase before hospitalization was not available, thus the presence of a preceding elevated blood pressure due to increased systemic vascular resistance could not be confirmed. The scarcity of this complex pathology makes it difficult to find enough patients to make statistically meaningful interpretation. The lack of well-defined markers for the diagnosis of NPE or neurogenic cardiopulmonary failure could also contribute to the under-recognition of this entity. Future studies are needed to provide more insights into this issue.
Conclusions
Hemimedullary stroke is an exceptional trigger for neurogenic cardiorespiratory failure. NPE should be considered in patients presenting with fulminant pulmonary edema preceded by localizing neurological deficits. Clinical observation suggests that NPE and stunned myocardium share a common pathophysiological process.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-158/rc
Peer Review File: Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-158/prf
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-158/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
References
- Busl KM, Bleck TP. Neurogenic Pulmonary Edema. Crit Care Med 2015;43:1710-5. [Crossref] [PubMed]
- Finsterer J. Neurological Perspectives of Neurogenic Pulmonary Edema. Eur Neurol 2019;81:94-102. [Crossref] [PubMed]
- Gherasim L, Nistor R. Neurogenic Stunned Myocardium as Part of Stress Cardiomyopathy. Maedica (Bucur) 2022;17:902-10. [Crossref] [PubMed]
- Aljishi M, Jayathissa S. Neurogenic pulmonary oedema secondary to vertebral artery dissection while playing tennis. BMJ Case Rep 2018;2018:bcr2017221753. [Crossref] [PubMed]
- Bonello M, Pullicino R, Larner AJ. Acute pulmonary oedema: not always cardiogenic. J R Coll Physicians Edinb 2017;47:57-9. [Crossref] [PubMed]
- Kameda W, Kawanami T, Kurita K, et al. Lateral and medial medullary infarction: a comparative analysis of 214 patients. Stroke 2004;35:694-9. [Crossref] [PubMed]
- Milne EN, Pistolesi M, Miniati M, et al. The radiologic distinction of cardiogenic and noncardiogenic edema. AJR Am J Roentgenol 1985;144:879-94. [Crossref] [PubMed]
- Davison DL, Terek M, Chawla LS. Neurogenic pulmonary edema. Crit Care 2012;16:212. [Crossref] [PubMed]
- Colice GL. Neurogenic pulmonary edema. Clin Chest Med 1985;6:473-89. [Crossref] [PubMed]
- Nayate A, Moore SA, Weiss R, et al. Cardiac damage after lesions of the nucleus tractus solitarii. Am J Physiol Regul Integr Comp Physiol 2009;296:R272-9. [Crossref] [PubMed]
- Raja HM, Herwadkar AV, Paroutoglou K, et al. Neurogenic pulmonary oedema complicating a lateral medullary infarct. BMJ Case Rep 2018;2018:bcr2018225437. [Crossref] [PubMed]
- L'e Orme RM, McGrath NM, Rankin RJ, et al. Extracranial vertebral artery dissection presenting as neurogenic pulmonary oedema. Aust N Z J Med 1999;29:824-5. [Crossref] [PubMed]
- Naum R, Filatov A, Alusma-Hibbert K, et al. Pulmonary Edema and Stunned Myocardium in Subarachnoid Hemorrhage. Cureus 2020;12:e7746. [Crossref] [PubMed]
- Debette S, Mazighi M, Bijlenga P, et al. ESO guideline for the management of extracranial and intracranial artery dissection. Eur Stroke J 2021;6:XXXIX-LXXXVIII. [Crossref] [PubMed]
- Davison DL, Chawla LS, Selassie L, et al. Neurogenic pulmonary edema: successful treatment with IV phentolamine. Chest 2012;141:793-5. [Crossref] [PubMed]
Cite this article as: Dang TQ, Nguyen TB, Tran TN, Le BHT. Neurogenic pulmonary edema and stunned myocardium following massive hemimedullary ischemic stroke due to vertebral dissection with spontaneous recovery: a case report. J Emerg Crit Care Med 2025;9:24.
