An athletic 26-year-old woman was admitted to the emergency department of a Swiss secondary-level care hospital for new-onset numbness in the lower limbs. Initial neurological examination showed lower limb hypoesthesia up to the tenth dorsal level. Spinal magnetic resonance imaging (MRI) showed a T2 lesion at D12 level without contrast enhancement. Cerebral MRI revealed multiple demyelinating lesions, three of which were located in the brainstem (: Cerebral magnetic resonance imaging (T2-flair) performed at day one showing three demyelinating in the brainstem). A lumbar puncture was performed and showed IgG oligoclonal bands with no other abnormality. Urinary pregnancy test was negative. At the time of her admission, apart from the neurological symptoms, she was asymptomatic and in a stable hemodynamic condition. During the course of the night, she was woken up by sudden unbearable holo-cranial pulsatile headache associated with hypertension, with systolic values up to 220 mmHg. She quickly developed chest pain, dyspnea and oxygen saturation dropped to 70% in ambient air. Initial arterial blood gases showed severe hypoxemia, with an oxygen partial pressure of 42 mmHg and lactic acidosis with a pH of 7.30 (N: 7.37–7.45) and an arterial lactate level of 5.3 mmol/L (N < 2.0 mmol/L). An ECG showed ST-segment depression in the inferior (II-III-aVF) and precordial (V3 through V6) leads (: Electrocardiogram performed at day 1 revealing ST-segment depression in the inferior (II-III-aVF) and precordial (V3 through V6) leads). QTc time was measured at 400 ms. Serum high sensitivity (hs) T-troponins were elevated to 438 ng/L (N < 14 ng/L) and D-Dimers were measured at 20818 µg/L (N < 500 µg/L), without NT-proBNP elevation (value: 58 ng/L). Hematological testing was relevant for important leukocytosis of 23.2 G/l (N: 4–10 G/L) with 76% of segmented neutrophils as well as hemoconcentration with a hemoglobin level of 176 g/L (N: 120–157 g/L) and a hematocrit value of 0.52 L/L (N: 0.35–0.47 L/L). However, there was no evidence of active infection with a CRP level below the threshold of 5 mg/L and the absence of fever. The clinical condition worsened thereafter, with acute respiratory failure and hemodynamic instability, with sinus tachycardia (heart rate up to 150/min), requiring a transfer to the intensive care unit for urgent orotracheal intubation. During orotracheal intubation, blood pressure plummeted to a nadir of 59/44 mmHg, requiring aminergic support. Chest radiograph revealed acute pulmonary edema. Initial evaluation with TTE was suggestive of cardiogenic shock with an estimated LVEF of 15 to 20%. Because of the severity of the situation and the young age of the patient, a transfer to the academic tertiary care hospital was decided. Upon arrival, a total-body-CT was performed to rule out intracranial bleeding, pulmonary embolism, and an infectious or neoplastic process. TTE was repeated on day one and was relevant for severe LV dysfunction (LVEF of 24%), and findings suggestive of reverse TTS, with basal and mid-ventricular segments akinesia and a spared apical contractility (: Transthoracic echocardiography performed at day one, showing a severely reduced left ventricular ejection fraction (24%) with basal and midventricular segments akinesia, and preserved apical contraction. There was no significant valvulopathy and right ventricular function was normal. Panel A: Diastole, Panel B: Systole). In the absence of localized wall motion abnormalities matching the territory of a coronary artery, and considering the young age of the patient, with no known personal or familial cardiovascular risk factors, coronary angiography was not performed as the probability of coronary artery disease was considered very low. Hs troponin T levels rose to a peak of 1,894 ng/L on day one, with a subsequent decrease. The clinical situation rapidly improved and the patient was extubated on day two. On day four, a cardiac MRI was performed, showing an improvement of the LVEF to 46%. Horizontal long-axis, color-coded images from T2-mapping revealed hyperintensity in the basal and mid-ventricular segments of the left ventricle that confirmed the presence of regional circumferential myocardial oedema (: cardiac MRI images from T2-mapping revealing myocardial oedema in four, three and two-chamber views), as well as the absence of late gadolinium enhancement (supporting the idea that there was no irreversible myocardial injury) (). Based on these observations, two diagnostic hypotheses were put forward: reverse TTS or an inflammatory cardiomyopathy. However, regarding the latter hypothesis, the Lake Louise criteria were not fulfilled (), reason why reverse TTS was considered the most likely diagnosis, despite the patient having an InterTak Diagnostic Score of only 46 (25 points for female gender, 12 points for no ST-segment depression and 9 points for the acute neurological trigger), meaning a 9.8% probability of TTS (). On day two, cerebral and spinal MRI was repeated but showed no difference in the number of demyelinating lesions. On the basis of neurological clinical examination, MRI and lumbar puncture results, the diagnosis of MS was made by the neurology team, according to the 2017 revised McDonald criteria, as MRI demonstrated dissemination in space and the presence of cerebrospinal fluid-specific oligoclonal bands demonstrated dissemination in time (). In the absence of any evidence for active infection, she was started on high-doses of intravenous corticoid therapy for 5 days for the treatment of MS, as per guidelines (), with an excellent clinical response. The neurological symptoms progressively disappeared and at day nine the patient became completely asymptomatic. A subsequent TTE on day ten showed normalization of the LVEF to 63%, as well as the disappearance of the segmental wall motion abnormalities. The patient was discharged on day twelve without any treatment. Because of a rapid full cardiac function recovery, the hypothesis of an inflammatory cardiomyopathy as well as spontaneous coronary artery dissection was ruled out, confirmed by the follow-up cardiac MRI performed at three months, which showed the complete resolution of ventricular dysfunction. All these elements were in favor of a final diagnosis of reverse TTS triggered by brainstem lesions of MS (: absence of irreversible tissue injury (late gadolinium enhancement) in four, three and two-chamber views) ().