Teaching Case

An unconscious 30 year old female was presented to the emergency department. Toxicology screen was positive for insulin, benzodiazepines and ketamine. Glasgow coma scale remained low for several days and epileptiform abnormalities were seen on electro-encephalogram.

The initial CT brain showed suggestion of subtle brain swelling compared to previous investigations but was otherwise unremarkable. CT perfusion and CT angiography were normal.

MRI of the brain was performed on day 9 consisting of an axial T2 and T1, DWI, 3D FLAIR, post-contrast 3DT1 and SWI. The MRI showed T2 hyperintensity in the basal ganglia, hippocampi and cortical grey matter with cortical swelling (figure 1). Cortical involvement was bilateral and diffuse; the perirolandic and frontal regions were relatively spared. Restricted diffusion was present in the globus pallidus, hippocampi and affected cortical regions (figure 2). The thalami, cerebral white matter and cerebellum were not affected.

The brain has high energy demand [1]. It consumes 20% of the resting body’s oxygen and >50% glucose (about 100-150 g/day). Since the brain cannot store glucose, a steady supply is needed. Hypoglycaemic encephalopathy (HE) results from low glucose levels (e.g. due to insulin overuse, insulinomas, and liver and renal failure). HE results in neuronal dysfunction, cytotoxic and excitotoxic oedema and, ultimately in neuronal necrosis [2]. Brain areas with high energy consumption are most susceptible to hypoglycaemia.

Glucose levels of <2.9 mmol/l predispose for HE. In this case the initial glucose levels were 1.1 mmol/l. Symptoms of HE are non-specific, varying from sweating and pallor in mild HE to coma and seizures in severe HE. Thus clinical history and imaging are important to guide diagnosis and help predict outcome [2,3].

MRI typically shows T2/FLAIR hyperintensity in the cerebral cortex (mainly parieto-occipital and insular), basal ganglia and hippocampi [4]. Additional white matter involvement can occur, mainly in the posterior limb of the internal capsule, corona radiata and splenium. Affected areas show diffusion restriction [4]. The thalami and cerebellum are typically spared. Prognosis depends on the extent of disease. Diffuse cortex and basal ganglia involvement predict a poor outcome, especially if these do not regress on follow up [2,5]. Because of the lack in clinical improvement and the severe damage on the MRI in this case, treatment was discontinued and the patient deceased.

The most important differential considerations are other conditions with diffuse grey matter involvement of which hypoxic ischemic encephalopathy (HIE) is the most common [4]. HIE also shows restricted diffusion in the cortex and basal ganglia. HIE can be differentiated from HE as it shows typical perirolandic and occipital involvement and in severe cases involves the cerebellum and thalami [4]. Creutzfeldt-Jakob disease (CJD) is another disease that gives diffuse cortical diffusion restriction, but CJD also involves the thalami, typically with a ‘hockey stick’ appearance [3]. Seizure related changes also show typical thalamic (pulvinar) involvement with unilateral or bilateral involvement, but also cortex and subcortical white matter and hippocampal involvement. Hepatic encephalopathy may reveal differentiating T1 hyperintensities next to the overlapping T2 hyperintensities in the globus pallidus, subthalamic region, midbrain and diffuse cortical oedema with sparing of the perirolandic and occipital regions.

The final diagnosis is made by combining the clinical history, laboratory confirmation of (severe) hypoglycaemia and typical imaging findings as described above [3].

Written informed patient consent for publication has been obtained.