Non-ketotic hyperglycemic seizure

Dr Rohit Sharma et al.

Non-ketotic hyperglycemic seizures are one of the neurological complications of non-ketotic hyperglycemia, along with non-ketotic hyperosmolar coma and non-ketotic hyperglycemic hemichorea

Seizures in the context of non-ketotic hyperglycemia are most frequently reported in middle-aged 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 hyperglycemia develop seizures 1. Interestingly, seizures are comparatively very rare in ketotic hyperglycemia (or diabetic ketoacidosis) 1.

Seizures are seen in the early stages of non-ketotic hyperglycemia, 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 normalization of glucose levels 1-5

The exact underlying pathophysiology of seizures in non-ketotic hyperglycemia 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 hyperglycemia there theoretically could be a decrease in GABA 4
  • patients with type 2 diabetes mellitus, and thus at risk of developing non-ketotic hyperglycemia, are more likely to have underlying structural and vascular anomalies which may contribute to a higher risk of seizures 4
  • patients are often hyponatremic at presentation which is a known risk factor for developing seizures 4

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

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

  • T1: often no anomaly 6-9
  • T2/FLAIR: subcortical regions of hypointensity 6-9
  • DWI: often no anomaly 6-9
  • T1 C+ (Gd): leptomeningeal enhancement has been reported in at least one study 9

Imaging findings gradually resolve after glycemia correction, however the 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 hyperintensity and high diffusion signal on DWI, without any significant long-term sequelae 6,10,11.

It is unclear exactly why there is this difference between the imaging features of non-ketotic hyperglycemic seizures and other seizures, however it has been postulated that perhaps excitotoxic cell damage due to seizure-related excessive synaptic activity in patients with non-ketotic hyperglycemia 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 hyperglycemia 6-8.

Management is through normalization of glucose levels 12

Article information

rID: 55332
Synonyms or Alternate Spellings:
  • Non-ketotic hyperglycaemic seizures
  • Partial status epilepticus associated with nonketotic hyperglycemia
  • Partial status epilepticus associated with non-ketotic hyperglycemia
  • Epilepsia partialis continua associated with nonketotic hyperglycemia
  • Epilepsia partialis continua associated with non-ketotic hyperglycemia
  • Nonketotic hyperglycaemic seizures
  • Non-ketotic hyperosmolar hyperglycaemic seizures
  • Nonketotic hyperosmolar hyperglycaemic seizures
  • Non-ketotic hyperosmolar hyperglycaemic seizure
  • Nonketotic hyperosmolar hyperglycaemic seizures

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Cases and figures

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