Пациент с диагностикой дисфории по признаку пола с множественным склерозом после кардиомиопатии такотсубо и вентральной аритмии: доклад по делу и систематический обзор литературы.

Introduction

Takotsubo cardiomyopathy is a reversible myocardial disorder that does not correspond to the vascular supply area of the heart. Its name is derived from the shape of the Japanese takotsubo , or octopus pot. It was considered to be more prevalent among postmenopausal Asian women and was associated with physical or emotional stress and was also known as “stress-induced cardiomyopathy” ( 1 ). In recent years, a connection between intracranial lesions, including stroke, multiple sclerosis (MS), and takotsubo cardiomyopathy, has been reported. In particular, cases of brainstem lesions in MS and takotsubo cardiomyopathy have been reported.

We herein report the case of a patient with severe headaches and ventricular tachycardia, who was subsequently diagnosed with takotsubo cardiomyopathy and MS. We systematically reviewed the previous literature on the association between MS and takotsubo cardiomyopathy, with a special focus on the disease patterns of MS and the presentation of takotsubo cardiomyopathy.

Case Report

A previously healthy 34-year-old transgender woman of Caucasian ethnicity on a trip to Japan presented to the emergency department with a headache and dyspnea, which had persisted for several hours. She was in acute distress, which precluded detailed medical interviews. A physical examination revealed tachypnea and tachycardia, with a blood pressure of 193/123 mmHg and a pulse oxygen saturation of 91% in ambient air. Electrocardiography (ECG) revealed polymorphic ventricular tachycardia with a heart rate of 117 beats/min ( Fig. 1A ). Given the preserved hemodynamics and polymorphism, magnesium sulfate was intravenously administered based on the current guidelines ( 2 ), and sinus rhythm was subsequently restored. An immediate arterial blood gas analysis revealed respiratory alkalosis, and blood tests demonstrated leukocytosis with a white blood cell count of 10,800 /μL, hypokalemia with a serum potassium level of 2.7 mEq/L, and elevated N-terminal pro-B-type natriuretic peptide (731.9 pg/mL), while other parameters remained within normal ranges ( Table 1 ). An additional ECG showed ST elevation in the aVR, diffuse ST depression in the other leads, and QT prolongation ( Fig. 1B ). Head computed tomography revealed no intracranial bleeding or low-density areas. Chest radiography revealed pulmonary edema. Transthoracic echocardiography (TTE) showed severe basal segment hypokinesis ( Fig. 2 ). Her cardiac troponin T level at 1 h increased to 0.011 μg/L. Therefore, we performed an emergency coronary angiography, which revealed intact coronary arteries. She was diagnosed with a basal variant of takotsubo cardiomyopathy (also referred to as reverse takotsubo cardiomyopathy) and was started on supportive treatment with diuretics for 3 days.

On the third day, the patient reported experiencing right-sided facial weakness and subsequently underwent a comprehensive history assessment and neurological examination. She stated that in the 5 days leading up to admission, she sequentially experienced right-sided hearing loss, right-sided facial hypoesthesia, dizziness, severe headache, and left upper extremity hypoesthesia. A neurological examination revealed gaze-directional nystagmus; decreased pain and temperature sensation on the right side of the face; right-sided facial palsy; right-sided hearing loss; and decreased pain and temperature sensation on the left side of the body. Brain magnetic resonance imaging (MRI) revealed hyperintense lesions on the right side of the pontomedullary junction, around the right middle cerebellar peduncle, in the right centrum semiovale, and in the bilateral periventricular and subcortical white matter on fluid-attenuated inversion recovery (FLAIR) images ( Fig. 3 ). Lesions in the right middle cerebellar peduncle and pontomedullary junction exhibited gadolinium enhancement, while others did not, suggesting the dissemination of lesions in time. A cerebrospinal fluid (CSF) analysis revealed a normal total protein level of 40 mg/dL, normal nucleated cell count of 3 /μL, a high IgG index of 1.22, and the presence of an oligoclonal band. The serum anti-aquaporin-4-antibody test results were negative ( Table 1 ). Cervical and thoracic spine MRI showed no spinal cord lesions. She was diagnosed with MS based on the 2017 McDonald criteria ( 3 ), and treatment with intravenous methylprednisolone (1 g/day for 3 days) was initiated when her neurological symptoms remained stable. On the ninth day, given the stable clinical course and improvement in ST changes on ECG ( Fig. 1C ) and basal segment movement on TTE, the patient was discharged and transported by air to her home country on the same day. Upon returning to her hometown, a local neurologist assumed responsibility for her care and her symptoms improved eight months after discharge.

Systematic Literature Review

A literature search was conducted in both the PubMed and Embase databases (up to August 2023) using the following search terms:

PubMed search terms: [“multiple sclerosis” (MeSH Terms) OR “multiple sclerosis” (Title/Abstract)] AND [(“pulmonary edema” (MeSH Terms) OR “pulmonary edema” (Title/Abstract) OR “pulmonary oedema” (Title/Abstract)) OR (“heart failure” (MeSH Terms) OR “heart failure” (Title/Abstract) OR “cardiac failure” (Title/Abstract)) OR (“shock, cardiogenic” (MeSH Terms) OR “cardiogenic shock” (Title/Abstract)) OR (“death, sudden, cardiac” (MeSH Terms) OR “sudden death” (Title/Abstract) OR “sudden cardiac death” (Title/Abstract)) OR (“heart arrest” (MeSH Terms) OR “cardiac arrest” (Title/Abstract) OR “heart arrest” (Title/Abstract)) OR (“ventricular fibrillation” (MeSH Terms) OR “ventricular fibrillation” (Title/Abstract) OR “tachycardia, ventricular” (MeSH Terms) OR “ventricular tachycardia” (Title/Abstract)) OR (“ventricular dysfunction” (MeSH Terms) OR “ventricular dysfunction” (Title/Abstract) OR “systolic dysfunction” (Title/Abstract)) OR (“cardiomyopathies” (MeSH Terms) OR “cardiomyopath*” (Title/Abstract)) OR “takotsubo*” (Text Word)].

Embase search terms: [(‘multiple sclerosis'/mj OR ‘multiple sclerosis': ti, ab, kw) AND ((‘lung edema'/exp OR ‘lung edema': ti, ab, kw OR ‘lung edema': ti, ab, kw OR ‘pulmonary edema': ti, ab, kw OR ‘pulmonary edema': ti, ab, kw) OR (‘heart failure'/exp OR ‘heart failure': ti, ab, kw OR ‘cardiac failure': ti, ab, kw OR ‘ventricular dysfunction': ti, ab, kw OR ‘cardiogenic shock': ti, ab, kw OR ‘systolic dysfunction': ti, ab, kw OR cardiomyopath*: ti, ab, kw OR takotsubo*: ti, ab, kw OR ‘cardiomyopathy'/exp) OR (‘ventricular fibrillation*': ti, ab, kw OR ‘ventricular tachy*': ti, ab, kw OR ‘heart ventricle fibrillation'/de OR ‘heart ventricle tachycardia'/exp OR (sudden NEXT/2 death): ti, ab, kw)) AND ((article)/lim OR (review)/lim)) NOT ((‘multiple sclerosis'/mj OR ‘multiple sclerosis': ti, ab, kw) AND ((‘lung edema'/exp OR ‘lung edema': ti, ab, kw OR ‘lung edema': ti, ab, kw OR ‘pulmonary edema': ti, ab, kw OR ‘pulmonary edema': ti, ab, kw) OR (‘heart failure'/exp OR ‘heart failure': ti, ab, kw OR ‘cardiac failure': ti, ab, kw OR ‘ventricular dysfunction': ti, ab, kw OR ‘cardiogenic shock': ti, ab, kw OR ‘systolic dysfunction': ti, ab, kw OR cardiomyopath*: ti, ab, kw OR takotsubo*: ti, ab, kw OR ‘cardiomyopathy'/exp) OR (‘ventricular fibrillation*': ti, ab, kw OR ‘ventricular tachy*': ti, ab, kw OR ‘heart ventricle fibrillation'/de OR ‘heart ventricle tachycardia'/exp OR (sudden NEXT/2 death): ti, ab, kw)) AND ((article)/lim OR (review)/lim) AND ((medline)/lim OR (preprint)/lim OR (pubmed-not-medline)/lim))

We retrieved 375 and 196 articles from the PubMed and Embase databases, respectively. Two investigators independently reviewed the titles and abstracts of the database records, retrieved the full text for eligibility assessment, and extracted data from these cases ( Fig. 4 ). Of the screened records, 51 articles were eligible for full-text review and 16 met the inclusion criteria. References in the retrieved articles were also searched, but no additional case reports of interest were identified. The clinical characteristics of the 20 cases reported in 16 publications, including our case, are summarized in Table 2 .

Discussion

Takotsubo cardiomyopathy associated with central nervous system disease is characterized by basal wall motion abnormalities, occurring more frequently in younger patients than in other takotsubo cardiomyopathy patients ( 1 ).

In this systematic literature review, we identified 16 publications that reported 20 cases (including our case) ( 4 - 19 ). The median age was 30 years (range, 16-69 years) and 15 patients (75%) were female. They presented with headache, gait and trunk ataxia, and sensory and motor disturbances. ECGs were characterized by ST depression in 40% of the cases ( 20 ). Troponin was elevated in all cases. The mean (± standard deviation) left ventricular ejection fraction (LVEF) was 31±11%. Thirteen patients (65%) were diagnosed with the basal variant of takotsubo cardiomyopathy. It has been previously reported that the majority of takotsubo cardiomyopathy cases are of the apical type (82%), while the basal variant accounts for only 2% of all cases ( 21 ). This discrepancy is in line with a previous report in which central nervous system disease-associated takotsubo cardiomyopathy was characterized mostly by basal wall motion abnormalities and occurred more frequently in younger patients in comparison to other takotsubo cardiomyopathies ( 1 ). The reason for the high incidence of the basal type in central nervous system disease-associated takotsubo cardiomyopathy remains unclear and may be associated with lesion involvement in the medulla oblongata. No lethal arrhythmia has been reported, except in the present case ( 22 ). In this case, ventricular tachycardia was attributed to QT prolongation resulting from both takotsubo cardiomyopathy and hyperventilation-induced hypokalemia, as evidenced by the patient's recovery with potassium and magnesium replacement alone.

Brain MRI showed involvement of the medulla oblongata and pontomedullary area in 16 cases (72%). Anatomically, a solitary bundle nucleus is located here and projects into the cardiac vagal plexus. Solitary bundle nuclei are among the vagal nuclei that project to the heart. Their destruction may lead to sympathetic predominance, which is supported by evidence from animal studies ( 23 ). The development of takotsubo cardiomyopathy in MS is likely linked to a surge in catecholamines resulting from lesions involving the medullary solitary bundle nuclei.

The prevalence of MS is higher in individuals with male-to-female gender dysphoria (MtFGD) than in the general population ( 22 ). In the present case, although MtFGD might have contributed to the onset of MS, its interaction with the association between MS and takotsubo cardiomyopathy is unclear due to the lack of literature on such cases.

A recent report from France estimated the complication rate of takotsubo cardiomyopathy in MS as 4.3 per 10,000 patients. Given that the estimated prevalence of MS is 2.3 million people worldwide ( 24 ), it is possible that MS-associated takotsubo cardiomyopathy has been overlooked. Emergency physicians and general practitioners should be aware of this entity because the dramatic presentation of sudden onset chest pain and/or dyspnea may mask neurological findings, as in the current case.

Conclusion

In this report, we reviewed the characteristics of patients with MS and takotsubo cardiomyopathy. Basal type of takotsubo cardiomyopathy was the most common type, and most cases involved the medulla oblongata. Recognition of these associations by physicians, coupled with their active involvement in multidisciplinary approaches, may facilitate the early diagnosis and improve the prognosis of these patients.

The authors state that they have no Conflict of Interest (COI).

Financial Support

Zhehao Dai is supported by a Grant-in-Aid from Japan Society for the Promotion of Science (JSPS) for JSPS fellows (grant number 23KJ0434) and a Grant-in-Aid from Japan Foundation for Applied Enzymology.

Shinya Yamanaka and Mariko Nishihara contributed equally to this work.

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