Massive gastric perforation in a patient with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes: A case report

Abstract

BACKGROUND

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a rare genetic disorder that is defined clinically by stroke-like episodes, encephalopathy, manifestations of mitochondrial dysfunction. MELAS concurrent with gastrointestinal perforation is rare, and concurrent with massive gastric perforation is extremely rare.

CASE SUMMARY

A 51-years-old woman was admitted to our department for treatment from the gastrointestinal sequelae of MELAS syndrome. She presented with complaints of abdominal pain accompanied by paroxysmal lumbar pain and nausea with vomiting. She underwent a whole abdominal computed tomography scan in the emergency department, which indicated gastrointestinal perforation. This resulted in emergent surgery at which a massive perforation of the stomach was identified. The patient underwent repair of a gastric rupture and received further treatment in the intensive care unit postoperatively.

CONCLUSION

MELAS concurrent with massive gastric perforation is extremely rare, but clinicians should be vigilant about the rare but potentially devastating gastrointestinal consequences of mitochondrial diseases in MELAS patients.

Key Words: Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes; Gastrointestinal perforation; Gastric perforation; Massive gastric perforation; Case report

Core Tip: Massive gastric perforation is an exceptionally rare but life-threatening gastrointestinal complication of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). MELAS concurrent with gastrointestinal perforation is rare, and concurrent with massive gastric perforation is extremely rare. This case highlights that acute abdominal pain in MELAS patients may signal catastrophic perforation requiring urgent imaging and surgical intervention. Early recognition and multidisciplinary management are essential to reduce morbidity and improve outcomes.

INTRODUCTION

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a rare multisystem genetic disorder ascribed to defects in mitochondrial function[1]. The most common mutation in MELAS patients is m.3243A>G, which occurs in the MT-TL1 gene, encoding mitochondrial tRNA Leu (UUR). This mutation represents the most common mutation type for this disease[2]. Although the incidence of MELAS varies across different regions worldwide, its overall prevalence remains very low, making the disease extremely rare[3,4]. The main clinical features of MELAS include varying degrees of cognitive impairment and dementia, lactic acidosis, stroke and transient ischemic attacks, hearing loss, gastrointestinal motility disorders, and physical development delay[5]. However, gastrointestinal perforation in MELAS is rare, with only a handful of case reports documented[6]. The occurrence of a massive gastric perforation in this context is exceptionally rare, and no relevant case reports have been identified to date. Here we report a case of MELAS concurrent with massive gastric perforation.

CASE PRESENTATION

Chief complaints

A 51-year-old woman presented with acute abdominal pain, accompanied by paroxysmal lumbar pain, nausea, and vomiting.

History of present illness

The patient was diagnosed with MELAS 6 months prior to this admission after presenting to the Department of Neurology with psychiatric abnormalities. Brain magnetic resonance imaging showed hyperintense signals in the cortical and subcortical regions of the left temporo-occipital lobe, with a lesion distribution that did not correspond to vascular territories, consistent with features of mitochondrial encephalomyopathy. Next-generation sequencing (NGS) of peripheral blood revealed a mitochondrial DNA (mtDNA) m.3243A>G point mutation (mutation rate 11.6%), confirming the diagnosis of MELAS syndrome. Six months after the diagnosis, she was brought to the emergency department complaining of abdominal pain, accompanied by paroxysmal lumbar pain and nausea with vomiting. The abdominal pain progressively worsened. An emergent whole abdominal computed tomography (CT) scan revealed air infiltrating the retroperitoneum and signs suggestive of gastrointestinal perforation.

History of past illness

The patient had MELAS syndrome with gastrointestinal complications, manifested by recurrent abdominal discomfort such as abdominal distension. She also had a 10-year history of diabetes. She had undergone surgical resection for right lower lobe granulomatous pneumonia three years previously.

Personal and family history

The patient denied any family history of MELAS or gastric perforation.

Physical examination

On physical examination, the vital signs were as follows: Body temperature, 37 °C; blood pressure, 80/56 mmHg; heart rate, 142 beats per min; respiratory rate, 26 breaths per min. Furthermore, the abdomen was rigid with diffuse tenderness and peritonitic signs on palpation.

Laboratory examinations

Laboratory tests on admission revealed the following findings. Fasting blood glucose was 10.5 mmol/L. Complete blood count showed a white blood cell count of 7.06 × 10⁹/L, hemoglobin 169 g/L, and platelet count 271 × 10⁹/L. Routine urinalysis was showed glycosuria 4+. Liver function tests demonstrated alanine aminotransferase 27.6 U/L, aspartate aminotransferase 111.7 U/L, total bilirubin 13.6 μmol/L, and albumin 34.6 g/L. Renal function tests showed serum creatinine 70 μmol/L and blood urea nitrogen 10.8 mmol/L. Arterial blood gas analysis showed pH 7.162, PaCO₂ 21.1 mmHg, PaO₂ 138.6 mmHg, bicarbonate (HCO₃^-) 7.4 mmol/L, base excess -19.2 mmol/L, and lactate 6.88 mmol/L, indicating metabolic acidosis. Serum lactate dehydrogenase was 357 U/L, and α-hydroxybutyrate dehydrogenase was 264.8 U/L. Creatine kinase was 383.2 U/L, creatine kinase-MB was 42.5 U/L, and high-sensitivity cardiac troponin I was 0.014 ng/mL. Complete blood tests revealed high-sensitivity C-reactive protein level of 98.56 mg/L. Six months ago, NGS of peripheral blood revealed a mtDNA m.3243A>G point mutation (mutation rate 11.6%), confirming the diagnosis of MELAS syndrome.

Imaging examinations

Magnetic resonance spectroscopy (3.0 T) performed 6 months earlier showed patchy abnormal signal lesions in the left temporo-occipital lobe, appearing hypointense on T1-weighted images and hyperintense on T2-weighted and FLAIR sequences, with narrowing of the adjacent sulci. An elevated lactate peak was observed in the left temporal lobe (Figure 1A and B). These findings suggested a recent infarction in the left temporo-occipital lobe and were consistent with mitochondrial encephalomyopathy. Concurrently, cranial CT angiography and cerebral CT perfusion imaging showed no significant abnormalities (Figure 1C and D).

Figure 1 Magnetic resonance spectroscopy, cranial computed tomography angiography and cerebral computed tomography perfusion images. A and B: Magnetic resonance spectroscopy showed patchy abnormal signal lesions in the left temporo-occipital lobe, and an elevated lactate peak was observed in the left temporal lobe; C and D: Cranial computed tomography angiography and cerebral computed tomography perfusion imaging showed no significant abnormalities.

An emergent whole abdominal CT scan (Figure 2A and B) demonstrated perforation of a hollow viscus, with the exact site of perforation undetermined, along with diffuse thickening of the gastric wall. An urgent laparotomy was performed. Postoperative histological examination (Figure 2C) revealed loss of the superficial mucosal layer in the gastric wall tissue, accompanied by suppurative inflammation. Extensive acute and chronic inflammatory cell infiltration was observed throughout the full thickness of the gastric wall, along with areas of necrosis. Concurrently, vascular proliferation was observed, accompanied by vasodilation, congestion, and hemorrhagic changes.

Figure 2 Whole abdominal computed tomography scan findings and postoperative histological examination. A and B: Perforation of a hollow organ, diffuse thickening of the gastric wall; C: Loss of the superficial mucosal layer in the gastric wall tissue, accompanied by suppurative inflammation.

FINAL DIAGNOSIS

Massive gastric perforation in a patient with genetically confirmed MELAS (m.3243A>G).

TREATMENT

An urgent laparotomy was performed revealing a 10 cm laceration extending from the gastric body to the anterior wall of the gastric fundus (Figure 3A). Intraoperatively, copious amounts of chyme were observed within the abdominal cavity, predominantly concentrated in the gastric fundus, splenic fossa, and left subdiaphragmatic region. The surrounding gastric wall exhibited blackened gangrene (Figure 3B), while the remaining gastric wall showed edema covered by purulent coating. Localized intestinal loops and the greater omentum demonstrated marked hyperemia. No perforations were identified in the duodenum, jejunum, ileum, colon, or appendix. Surgical Procedure: Purulent fluid was aspirated, and food debris was removed. The abdominal cavity was irrigated with copious amounts of diluted povidone-iodine and normal saline until clear. Adhesions between the His’s angle gastric wall and diaphragm were dissected to fully expose the perforation site. Necrotic gastric wall at the perforation was excised. The perforation was closed with two layers of continuous full-thickness barbed sutures. The abdominal cavity was repeatedly irrigated with diluted povidone-iodine and saline. A negative pressure drainage tube was placed at the perforation site, exiting through the right upper abdomen. An additional drainage tube was placed in the splenic fossa, exiting through the left upper abdomen.

Figure 3 Intraoperative view. A: A 10 cm laceration extending from the gastric body to the anterior wall of the gastric fundus presented; B: Resected black gangrene surrounding the gastric rupture; C: The gastric rupture was repaired.

OUTCOME AND FOLLOW-UP

Following emergent repair of the massive gastric rupture, the patient was transferred to the surgical intensive care unit (SICU) due to persistent hemodynamic instability and septic shock. On SICU admission, she remained unresponsive after anesthesia and required invasive mechanical ventilation (pressure-control mode). She was in refractory septic shock with severe hypotension (as low as 50/30-57/37 mmHg) and marked tachycardia (150-180 beats/minute), necessitating aggressive fluid resuscitation and high-dose vasopressor support. Broad-spectrum antimicrobial therapy was initiated with imipenem (1 g intravenous injection every 6 hours). Arterial blood gas analysis demonstrated hyperlactatemia (lactate 7.90 mmol/L on admission to the SICU, decreasing to 6.40 mmol/L the following morning) with metabolic derangements requiring ongoing correction of electrolyte and acid–base imbalance. Bedside ultrasound suggested abdominal distension with ascites, and supportive measures were provided accordingly.

During the SICU course, serial testing revealed evidence of myocardial injury (high-sensitivity cardiac troponin I 3.534 ng/mL on postoperative day 1) without ST-segment elevation on electrocardiography, which was considered most consistent with septic shock–related myocardial dysfunction. On postoperative day 4, brain natriuretic peptide was 4309.170 pg/mL, and echocardiography showed diffusely reduced left ventricular systolic function (ejection fraction 37%), consistent with acute decompensated heart failure, levosimendan was administered for inotropic support. Because continuous vasoactive infusion was required, a right subclavian central venous catheter was placed on postoperative day 8, without immediate complications. As of the present (approximately 400 days post-surgery), the patient remains hospitalized in the SICU in a comatose state, receiving ongoing critical care for septic shock and organ dysfunction. No reoperation has been performed to date, and postoperative gastrointestinal complications (e.g., anastomotic leak, intra-abdominal abscess) are under continuous surveillance.

DISCUSSION

MELAS syndrome is a rare maternally inherited mitochondrial disorder caused by pathogenic mtDNA variants[7]. The most common pathogenic variant is m.3243A>G in MT-TL1, which encodes mitochondrial tRNA Leu (UUR) and is central to MELAS and related phenotypes[8,9]. The estimated population prevalence rate of MELAS is 0.96/100000[10]. In our case, the mtDNA m.3243A>G variant was detected by NGS of peripheral blood with a reported mutation rate 11.6%. However, heterogeneity levels vary across different tissues and may decrease in peripheral blood with age, therefore, blood heterogeneity may underestimate the systemic mutation burden compared to urine epithelial cells or muscle tissue. The clinical manifestations of MELAS are diverse, with the main clinical features including varying degrees of cognitive impairment and dementia, lactic acidosis, stroke and transient ischemic attacks, hearing loss, gastrointestinal motility disorders, and physical development delay[5]. Gastrointestinal symptoms are relatively common in patients with MELAS, occurring in up to approximately 66% of patients, including bloating, dysphagia, recurrent vomiting and anorexia, chronic diarrhea and gastrointestinal pseudo-obstruction[11,12]. In contrast, gastrointestinal perforation in patients with MELAS is rare, with only a handful of case reports documenting intestinal perforation as a complication of MELAS and are summed in Table 1[6,13]. To the best of our knowledge, a massive gastric perforation of approximately 10 cm in a patient with genetically confirmed MELAS has not been previously described. Our patient in this case, who carried the mtDNA m.3243A>G variant, developed a large gastric wall laceration requiring emergent surgical repair.

Table 1 Case reports regarding gastrointestinal perforations in mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes patients.

Ref.	Patient’s details	Perforation site	The ending
Hallac et al[6]	56-year-old woman	Colon perforation	The patient died after surgery due to poor general condition
Mima et al[13]	50-year-old man	Duodenum perforation	The patient died of hematemesis and hemorrhagic shock

Causal attribution remains challenging. Although biological plausibility supports a potential association between MELAS and catastrophic gastrointestinal events, a definitive causal relationship cannot be established from a single case. In our patient, the defect margins showed gangrenous necrosis, and no ulcerative tissue was observed grossly at the rupture site. Histopathological examination demonstrated transmural acute and chronic inflammation with necrosis and revealed no malignant tumor cells, supporting a diagnosis of gastric wall laceration rather than ulcer crater-related perforation. The patient also had diabetes mellitus, a common comorbidity in m.3243A>G–related disease, which may contribute to gastrointestinal dysmotility and reduced tissue resilience. Regarding alternative etiologies, the patient denied non-steroidal anti-inflammatory drug use. Helicobacter pylori testing was not performed, which is a limitation of this report. Other precipitating factors should be considered when evaluating perforation (e.g., recent endoscopy, nasogastric tube-related iatrogenic injury, cardiopulmonary resuscitation, trauma, and additional ulcerogenic medications). In this case, the patient denied recent endoscopy, nasogastric tube placement, cardiopulmonary resuscitation, trauma, or use of ulcerogenic medications, and intraoperative exploration and pathology did not support other etiologies. Accordingly, we report this event as a rare and severe gastrointestinal complication occurring in the context of MELAS syndrome.

Several mechanisms may plausibly link MELAS to severe gastrointestinal injury. Retrospective analyses suggest that gastrointestinal dysmotility and gastrointestinal pseudo-obstruction can be prominent in MELAS; for example, Sekino et al[12] reported that approximately 40% of patients with MELAS developed chronic intestinal pseudo-obstruction. Although the mechanisms remain incompletely understood, intermittent failure of energy supply to intestinal smooth muscle or enteric neuronal dysfunction has been proposed[14-18]. Because mitochondrial energy metabolism is essential for cellular homeostasis, mitochondrial dysfunction may predispose gastrointestinal tissues to dysmotility, hypoperfusion, and impaired repair capacity, thereby increasing vulnerability to catastrophic events under extreme physiologic stress.

In our case, direct case-level evidence for an acute pseudo-obstruction episode or marked gastric dilatation immediately preceding perforation is limited. Although the patient reported recurrent gastrointestinal discomfort such as abdominal distension, objective documentation of prior pseudo-obstruction attacks or imaging evidence of significant gastrointestinal dilatation was not available. Therefore, mechanistic statements should be interpreted as hypotheses. We proposed two hypotheses regarding the possible mechanism of MELAS perforation. One possibility is that acute pseudo-obstruction episodes cause pathological changes such as highly gastrointestinal distension and functional impairment, leading to gastric wall necrosis and subsequently inducing gastric perforation. Another possibility is that mitochondrial dysfunction causes sudden and complete collapse of cellular metabolism, resulting in continuous coagulative necrosis of the gastric wall and ultimately leading to gastric perforation.

The correlation between radiologic findings and operative observations also requires clarification. Preoperative abdominal CT demonstrated perforation of a hollow viscus with an undetermined perforation site, accompanied by diffuse thickening of the gastric wall. Exploratory laparotomy revealed a large laceration extending from the gastric body to the anterior wall of the gastric fundus, while no perforations were identified in the duodenum, small intestine, colon, or appendix. After intraoperative exploration excluded other potential sources of perforation, the stomach was confirmed as the site of perforation in this patient.

We performed gastric rupture repair on the patient. No ulcerative tissue was observed at the site of gastric wall disruption, and pathological examination revealed no malignant tumor cells. Therefore, the gastric wall defect was considered to be caused by a laceration rather than an ulcer or other etiologies. Surgical management for a massive gastric defect with necrotic margins is complex and individualized. In this patient, necrotic tissue at the perforation margin was debrided and the laceration was repaired with a two-layer full-thickness closure with adequate drainage. Although the procedure proceeded smoothly, due to the patient's poor physical condition and the fact that mitochondrial energy metabolism disorders affect all somatic cells, the patient was ultimately transferred to the intensive care unit for further treatment following surgery. Given the patient’s profound shock physiology and systemic mitochondrial disease, rapid source control and physiologic stabilization were prioritized. Postoperatively, nasogastric tube decompression was applied, and proton pump inhibitor therapy and nutritional support were implemented as part of standard care to reduce gastric acid-related stress and promote recovery. The postoperative course was complicated by septic shock requiring prolonged intensive care unit support, underscoring the high morbidity associated with catastrophic gastrointestinal events in patients with MELAS syndrome.

It should be noted that visceral involvement in MELAS affects the entire gastrointestinal tract. Although gastrointestinal symptoms are common in MELAS, gastric perforation (particularly massive gastric perforation) appears rare but could be a devastating consequence, requiring vigilant care and close monitoring. Clinicians should maintain a high index of suspicion for severe intra-abdominal complications when MELAS patients present with acute abdominal pain and promptly pursue imaging and multidisciplinary management. Since the pathophysiology of MELAS involves cellular energy deficiency, while there is currently no curative treatment for patients with mtDNA disease, early recognition of symptoms with recommendations about diet and management of comorbidities remain essential to mitigate the risk of devastating outcomes. Healthcare professionals treating patients with the MELAS should be aware of the incidence of gastrointestinal discomfort and should therefore proactively inquire about gastrointestinal symptoms to ensure a timely treatment of these issues.

CONCLUSION

Here we reported a rare case of MELAS syndrome complicated by a massive gastric perforation. Surgical management and postoperative recovery of such cases present significant challenges as there is no curative option for mitochondrial myopathies and their unfavourable prognosis. Therefore, primary care physicians and clinicians treating MELAS should be aware of the potential emergencies associated with this disorder.

ACKNOWLEDGEMENTS

We extend our sincere gratitude to Professor Danling Guo from Shaoxing People’s Hospital for providing the imaging data for this case.