Non-ketotic hyperglycemic seizure

Non-ketotic hyperglycaemic seizures are one of the neurological complications of non-ketotic hyperglycaemia, along with non-ketotic hyperosmolar coma and non-ketotic hyperglycaemic hemichorea. 

Epidemiology

Seizures in the context of non-ketotic hyperglycaemia are most frequently reported in middle-age to elderly patients with type 2 diabetes mellitus, with one relatively large study reporting an average age of 61 years without any significant gender predilection ¹. It has been reported that up to 25% of patients with non-ketotic hyperglycaemia develop seizures ¹. Interestingly, seizures are comparatively very rare in ketotic hyperglycaemia (or diabetic ketoacidosis) ¹.

Clinical presentation

Seizures are seen in early stages of non-ketotic hyperglycaemia, usually days before coma manifests ^1-5. Most commonly the seizures are focal motor seizures, with a temporal lobe focus, and are often recurrent (epilepsia partialis continua or partial status epilepticus), however focal seizures with an occipital lobe focus have also been reported ^1-5. Symptoms usually resolve upon normalisation of glucose levels ^1-5. 

Pathology

The exact underlying pathophysiology of seizures in non-ketotic hyperglycaemia remains unclear ⁴. Although there are many hypotheses, it is likely that the pathogenesis is multi-factorial, considering ⁴:

• an acidic pH is required for gamma-aminobutyric acid (GABA) synthesis from glutamic acid, and because ketoacidosis does not occur in non-ketotic hyperglycaemia there theoretically could be a decrease in GABA ⁴
• patients with type 2 diabetes mellitus, and thus at risk of developing non-ketotic hyperglycaemia, are more likely to have underlying structural and vascular anomalies which may contribute to a higher risk of seizures ⁴
• patients are often hyponatraemic at presentation which is a known risk factor for developing seizures ⁴

Radiographic features

CT

CT of the brain is often normal throughout the presentation, however regions of decreased density have been reported rarely in the literature ¹. 

MRI

MRI of the brain is the modality of choice for assessing possible non-ketotic hyperglycaemic seizures and demonstrates many features at the epileptogenic focus which would otherwise be atypical and unexpected for a patient with seizures ^6-8.

Generally, patients with non-ketotic hyperglycaemic seizures have T2-weighted subcortical regions of hypointensity often with no accompanying anomalies on T1-weighted images or DWI ^6-8. Imaging findings gradually resolve after glycaemia correction, however evolution of mild atrophy in the region of the epileptogenic focus has been reported ⁶.

This is in stark contrast to classical expected MR findings of seizures (see status epilepticus), which include regions of T2-weighted hyperintensitieshyperintensity and high diffusion signal on DWI, without any significant long-term sequelae ^6,9,10.

It is unclear exactly why there is this difference between the imaging features of non-ketotic hyperglycaemic seizures and other seizures, althoughhowever it has been postulated that perhaps excitotoxic cell damage due to seizure-related excessive synaptic activity in patients with non-ketotic hyperglycaemia may unusually result in the development of excessive free radicals (including iron) which may contribute to cerebral subcortical injury, a process that does not occur without hyperglycaemia ^6-8.

Treatment and prognosis

Management is through normalisation of glucose levels ¹¹.