Hypoxic-ischemic encephalopathy induced cognitive decline secondary to upper gastrointestinal bleeding: a case report

Hypoxic-ischemic encephalopathy (HIE) occurs more in neonatal and rarely in adults. In adults, HIE is commonly caused by carbon monoxide (CO) poisoning, shock, cardiac arrest, respiratory depression, anesthesia and drug overdose.[1–3] In patients with acute gastrointestinal bleeding, decreased circulating blood supply causes cerebral ischemia and hypoxia, leading to dizziness, syncope and even sudden death. However, these conditions are more common especially in elderly patients with cerebrovascular stenosis, acute massive blood loss, using hemostatic agents, and high-risk factors of cardiovascular and cerebrovascular disease.[4] Here, we reported a middle-aged male patient, who was diagnosed with HIE after upper gastrointestinal bleeding without these high-risk factors.

CASE

A 42-year-old male patient was admitted to the emergency department with a 3-day history of intermittent melena. The patient developed melena three days before with no obvious cause, the amount is unknown, accompanied by dizziness, and then went to the emergency department. During his emergency department visit, he experienced sudden syncope lasting about one minute without foaming at the mouth and limb convulsions. The patient was immediately rushed to the emergency room for treatment. The man had a prior Helicobacter pylori infection, without chronic medical conditions, smoking or alcoholism history, or syncope history. The patient quickly regained consciousness but was accompanied with mild lethargy, indifferent response and poor ability of calculation. Physical examination revealed no abdominal tenderness or rebound pain, as well as an absence of epileptic seizures and hypotonia. Other than a possibly positive right Pussep sign, there were no other neurological abnormalities noted. The patient was hemodynamic stability (blood pressure 99/53 mmHg [1 mmHg=0.133 kPa], heart rate 82 beats/min). Then, laboratory tests, gastroscope and computed tomography (CT) scans were performed.

The laboratory results were as follows: white blood cell count 9.36×10⁹/L (normal range: [3.5–9.5]×10⁹/L), neutrophil count 7.10×10⁹/L (normal range: [1.8–6.3]×10⁹/L), red blood cell count 2.02×10¹²/L (normal range: [4.3–5.8]×10¹²/L), hemoglobin 61 g/L (normal range: 130–175 g/L), hematocrit 17.8% (normal range: 40%–50%); an electrocardiograph (ECG), electrolytes, renal function and blood sugar were normal. The lipid profile showed triglycerides 2.1 mmol/L (normal range: 0.57–1.7 mmol/L).

Abdominal CT showed thickening in the wall of the horizontal part of the duodenum. Head CT excluded intracerebral hemorrhage but could not rule out possible hypoxic-ischemic encephalopathy. Gastroscope confirmed a stage A2 duodenal bulb ulcer with hemorrhage (Forrest IIc), as well as a healing gastric ulcer.

Considering that the man had the cognitive decline symptoms, and his physical examination of the nervous system showed the right Pussep sign is possibly positive, head magnetic resonance imaging (MRI), magnetic resonance angiography (MRA) and cognitive assessment tools were suggested 12 d after the onset of melena.[5,6]

Brain MRI demonstrated multiple lesions with hypo-intensities on T1-weighted images, hyper-intensities on T2-weighted images and diffusion-weighted imaging (DWI) images in the bilateral centrum semiovale, corona radiata area, basal ganglia, left cerebral peduncle, and the splenium of the corpus callosum (Figures 1A–G). MRI showed the typical lesions imaging at bilateral basal ganglia (Figure 2). The above results suggested HIE diagnosis. The cranial MRA indicated cerebral arteriosclerosis changes, but no clear vascular stenosis was observed (Figure 1H). Mini-Mental State Examination (MMSE) scored 26 points, and Montreal cognitive assessment (MoCA) scored 20 points (supplementary Table 1). Electroencephalogram (EEG) is normal. Echocardiography and 24-hour dynamic electrocardiogram showed no abnormalities, which excluded cardiogenic syncope. Considering that rheumatoid immune antibody and thrombolysis protein tests, including protein C and protein S were normal, vasculitis and thrombophilia were excluded.

Figure 1.

Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) performed 12 d after the onset of melena. The high signal intensity was shown on diffusion-weighted imaging (DWI) flair (A–F), and MRI demonstrated the hypo-intensities signal of corpus callosum on T1-weighted images (G). MRA showed no evident vessel stenosis (H).

Figure 2.

MRI showed the typical lesions imaging at bilateral globus pallidus. T2-weighted images showed high signal intensity in the bilateral globus pallidus (B), and DWI flair exhibited a higher and much clear intensity (C), while it was not distinct on T1-weighted images (A). Apparent diffusion coefficient (ADC) maps demonstrated slightly hypointense lesions with high-signal-intensity rims in the corresponding regions (D).

Combined with examination and clinical manifestations, bleeding duodenal ulcer, HIE and vascular cognitive impairment were diagnosed. The patient received a blood transfusion of 2 units of red blood cells (RBC), intravenous proton pump inhibitors (PPIs), butylphthalide improving cognitive, and other treatments. After one-week hospitalization, his condition was stable without re-bleeding and the level of hemoglobin was elevated to 93 g/L. Then he was discharged from the hospital. At follow-up after one month, the patient had returned to normal daily routines. The hemoglobin level was elevated to 107 g/L. However, we re-assessed his cognitive functions by MoCA suggesting an unimproved functional outcome (scored at 20 points).

DISCUSSION

In this article, we reported a case of HIE caused by gastrointestinal bleeding which was highlighted as a decline in memory and cognitive performance. The patient’s diagnosis of HIE is confirmed with clinical signs, MRI findings, and exclusion of other possible diseases. HIE in adult is primarily caused by CO poisoning or post-resuscitation encephalopathy after cardiac arrest.[7] We have diagnosed and treated a large number of patients with gastrointestinal bleeding, some of them were even life-threatening, but rarely encountered patients with HIE induced by gastrointestinal bleeding. In our case, we presume that rapid blood loss may play an important role in secondary brain injury.

PubMed search results revealed limited reporting of patients with HIE resulting from gastrointestinal bleeding in young, healthy individuals. Only four HIE cases in three papers secondary to gastrointestinal hemorrhage were reported (supplementary Table 2).[8–10] Those patients reported shared common grounds: suffering from numerous underlying diseases, such as coronary artery disease, diabetes, and vascular stenosis etc. It appears that underlying disease may play a role in determining the occurrence of cerebral injury after gastrointestinal bleeding. However, our patient was a young male without any underlying disease.

It is difficult to distinguish HIE from multiple cerebral infarction (such as watershed cerebral infarction) in clinic, because both can be induced by low blood volume and have similar MRI manifestations. HIE is typically caused by CO poisoning, hypotension and cardiopulmonary resuscitation that decrease oxygen supplement dramatically, while cerebral infarction is considered as the consequence of artery stenosis or occlusion. Our diagnosis for this patient is based on two reasons. First, the patient’s MRA, echocardiography and other relevant tests ruled out thrombotic/embolic stroke, vascular malformation and cardiac disease. Second, his MRI features are similar to those of the two HIE patients previously reported, which showing abnormal signal in the bilateral pallidum region and no artery stenosis or occlusion.[10]

Intracranial MRI imaging can help explain nervous clinical symptoms in relation to the severity of HIE. According to the mechanism of selective vulnerability,[11] mild to moderate brain ischemic often causes the lesion of the watershed region, and severe HIE usually results in the gray matter structures, involving the basal ganglia (including globus pallidus), cerebral cortex, thalamus, hippocampus and cerebellum.[12] An MRI evaluation of the patient showed multiple higher signals in areas indicative of severe HIE, including the bilateral watershed, basal ganglia, and corpus callosum.

We administered butylphthalide to support the patient’s recovery after discharge; however, his MoCA score remained below normal. A similar HIE case had a delayed comatose despite a positive initial recovery, indicating that the recovery from HIE may take some time.[7] Although one study indicated that butylphthalide might promote cognitive recovery, we still lack reliable treatments to reduce HIE-linked injuries.[13]

In conclusion, we should pay much attention in clinical work that young patients without underlying diseases may have HIE secondary to gastrointestinal bleeding. Further research on prevention and treatment is necessary.