Hypoglycemic Encephalopathy Caused by Overdose of Metformin in an Adolescent

Hypoglycemic Encephalopathy Caused by Overdose of Metformin in an Adolescent

Hypoglycemic encephalopathy is an acute brain dysfunction resulting from hypoglycemia, characterized by complex and sometimes atypical clinical manifestations that can lead to misdiagnosis. This article presents a detailed case study of hypoglycemic encephalopathy in a 14-year-old adolescent caused by an overdose of metformin during a suicide attempt.

Case Presentation

On May 4th, 2019, a 14-year-old girl was found unconscious by her family, exhibiting symptoms such as hanging eyes, urinary incontinence, and stiff limbs. She was immediately taken to the emergency department of Hebei General Hospital. Initial cerebral computed tomography (CT) revealed low density in the right hemisphere, with narrowing or disappearance of sulci and an unclear gray matter margin. Cerebral diffusion-weighted imaging (DWI) indicated a high probability of acute cerebral infarction in the right frontal, temporal, parietal, and occipital lobes, as well as the splenium of the corpus callosum. Cerebral magnetic resonance angiography (MRA) showed an irregular edge of the blood flow signal in the right middle cerebral artery, suggesting the possibility of endarteritis.

Laboratory tests revealed a white blood cell count of 22.16 x 10^9 cells/L and a neutrophil ratio of 87.30%. The initial blood glucose level was 4.01 mmol/L. Despite administering anti-infection and consciousness-promoting medications, the patient’s consciousness did not improve. On the second day, she was admitted to the neurology department, where she remained comatose but responded to painful stimuli. Babinski signs were negative bilaterally, and the Kernig sign was positive. The patient had a history of a respiratory infection eight days prior, but her family denied any history of birth injury, trauma, toxic or drug exposure, or other diseases. The primary diagnosis was “causes of unconsciousness to be identified: central nervous system infection or acute cerebral infarction.”

Further investigation revealed a critically low blood glucose level of 0.03 mmol/L upon admission. The patient’s family disclosed that she was sensitive and introverted, had recently quarreled with her mother, and had access to metformin, glyburide, and insulin at home due to her mother’s diabetes. A toxicologic analysis confirmed a metformin concentration of 25.4 mg/L, significantly higher than the therapeutic dose of less than 15 mg/L. The final diagnosis was hypoglycemic encephalopathy caused by excessive ingestion of metformin.

Treatment and Follow-Up

The patient was treated with measures to correct hypoglycemia, decrease cranial pressure, and provide nutritional support. However, her consciousness did not improve. A follow-up cerebral DWI on May 5th, 2019, showed abnormal signals in the bilateral cerebral hemispheres, with a larger range of abnormalities than observed at admission. On May 8th, 2019, the patient was transferred to a higher-level hospital for further treatment. As of June 18th, 2019, she remained in a coma. Cerebral fluid attenuated inversion recovery (FLAIR) imaging revealed brain necrosis in the bilateral hemispheres, and cerebral MRA showed decreased branches of the bilateral anterior, middle, and posterior cerebral arteries.

Pathophysiology and Imaging Features

Hypoglycemic encephalopathy can result from various causes, including the unreasonable use of drugs, excessive endogenous insulin secretion, sepsis, alcoholism, liver and kidney failure, and unexplained endocrine diseases. A blood glucose level below 2.3 mmol/L can lead to coma, and a coma lasting more than six hours can cause irreversible damage to nerve cells. The pathophysiological mechanism involves decreased serum glucose levels promoting cellular energy depletion in neurons, leading to the failure of membrane ionic pumps and the loss of membrane ion homeostasis. This results in a shift of water from the extracellular space into the intracellular space.

Cerebral MRI features of hypoglycemic encephalopathy include:

1. Common involvement of the cerebral cortex, hippocampus, basal ganglia, and corpus callosum, with sparing of the cerebellum, brainstem, and thalamus due to higher glucose transporter activity and adenosine triphosphate levels in these regions.
2. Cortical lesions that do not conform to a specific cerebral arterial distribution.
3. Hyperintensity on DWI and FLAIR, slight hyperintensity on T2-weighted imaging, and slight hypointensity on T1-weighted imaging. DWI is crucial for early diagnosis.
4. Brain imaging that is not always diffuse or bilateral, potentially due to metabolic asymmetry between the left and right hemispheres, with the right hemisphere being more susceptible.
5. Hypoglycemia-induced cerebrovascular disease, characterized by swelling of capillary endothelial cells and capillary cavity narrowing, causing circulatory disturbance.

Clinical Implications and Management

Immediate intravenous glucose administration is essential to quickly and effectively correct hypoglycemia. Blood glucose levels should be repeatedly monitored to maintain them within the normal range. Studies suggest that hypoglycemic brain neuronal death is not solely due to fuel deprivation but is induced by neuronal nicotinamide adenine dinucleotide phosphate oxidase activation during glucose reperfusion. Therefore, therapeutic hyperglycemia should be avoided.

In this case, the patient’s initial blood glucose level of 4.01 mmol/L was within the physiological range, but subsequent measurements revealed a critically low level of 0.03 mmol/L. Stress reactions can increase epinephrine, adrenaline, and glucagon, promoting liver glycogen decomposition and reactively elevating blood glucose levels. For comatose patients, blood glucose should be measured repeatedly to avoid delayed diagnosis and treatment of hypoglycemic encephalopathy.

Hypoglycemic encephalopathy often involves the cerebral cortex, basal ganglia, and corpus callosum. In clinical practice, if lesions occur in these areas and do not conform to a specific cerebral arterial distribution, the possibility of hypoglycemic encephalopathy should be considered. In elderly patients, this condition is often caused by the overuse of glucose-lowering medications. However, in adolescents, the possibility of drug or poison ingestion for suicide should be considered.

Conclusion

This case highlights the severe consequences of hypoglycemic encephalopathy caused by an overdose of metformin in an adolescent. Early diagnosis and prompt treatment are crucial to prevent irreversible brain damage. Repeated blood glucose monitoring and awareness of the clinical and imaging features of hypoglycemic encephalopathy are essential for accurate diagnosis and effective management.

doi.org/10.1097/CM9.0000000000000584

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