Severe hypoglycemia can lead to fatal coma or severe brain damage. Profound hypoglycemia typically affects diabetic patients receiving treatment with oral hypoglycemic agents or insulin as a complication of therapy. Radiologists seldom come across patients with severe hypoglycemia, except in rare instances when abdominal CT is requested to rule out insulinoma as the cause. The clinical cause of the coma is usually known, and the value of MRI of the brain to diagnose hypoglycemia or predict outcome is not backed up by evidence- based studies.

Physicians began to see clusters, however, of nondiabetic men admitted to hospitals across Singapore with severe, unexplained hypoglycemia in February 2008.¹ Several of these patients suffered severe coma and neurological sequelae. At least four subsequently died. This wave coincided with a sudden increase in requests for MRI examinations of coma patients who had severe brain damage.

All patients underwent a series of toxicological tests and were questioned about their drug-taking history. This questioning revealed that their drop in blood sugar was due to consumption of an illegal product sold for sexual enhancement that contained glibenclamide(Drug information on glibenclamide) or glyburide, an oral hypoglycemic agent commonly used for diabetes treatment.

The majority of cases were associated with Power 1 Walnut, an illegal preparation that claims to be an herbal medicine. These preparations had been purchased from unauthorized itinerant peddlers and makeshift stalls. Forensic chemistry tests showed that the supposedly natural tablets were adulterated with glibenclamide and small traces of sildenafil(Drug information on sildenafil), the active ingredient in Viagra.

Most patients who were poisoned by up to five times the total daily recommended dose of glibenclamide were treated successfully in the emergency department without significant sequelae. Eight patients suffered prolonged hypoglycemia and severe complications.^2,3

MRI FINDINGS

Patients were examined on 1.5T and 3T MRI systems using conventional and advanced pulse sequences. Diffusionweighted imaging and T2-weighted MRI showed abnormalities in the hippocampus, cerebral cortex, and basal ganglia, sparing the subcortical white matter and cerebellum (Figure 1). These findings are consistent with previous case reports and animal studies that describe the selective vulnerability of the brain to hypoglycemic damage and characteristic lesion distribution in the cerebral cortex, insular cortex, and hippocampus.

The MRI distribution and appearance of these lesions are not specific, and ischemia, hypoglycemia, and epilepsy may have similar MRI findings. The underlying neurochemistry, time course, and selective neuronal necrosis are, however, fundamentally different and distinct for each of them.⁴

Some patients also had abnormalities in the splenium of the corpus callosum and internal capsules. These may represent a distinctive pattern of limited involvement on diffusion-weighted imaging (Figure 2).^5,6 The abnormalities were not seen on T2-weighted images in some of these reported cases. They may normalize rapidly on follow-up imaging and probably represent fluid movement rather than irreversible cell necrosis. Further follow-up studies may still be needed to better understand the mechanisms of these unusual findings.