How can hyperglycemia (high blood sugar) cause seizures?

Hyperglycemia as a Cause of Seizures

Severe hyperglycemia, particularly in the form of hyperosmolar hyperglycemic state (HHS), can directly cause seizures through multiple mechanisms including hyperosmolality, electrolyte disturbances, and cerebral metabolism alterations.

Pathophysiological Mechanisms

• Hyperosmolar hyperglycemic state (HHS) is characterized by severe hyperglycemia (plasma glucose typically ≥600 mg/dl) and elevated serum osmolality (≥320 mOsm/kg), which can lead to impaired mental status and seizures 1

• The hyperosmolar state causes neuronal dehydration and electrolyte disturbances that lower the seizure threshold in the brain 1, 2

• Non-ketotic hyperglycemia (NKH) is particularly associated with focal seizures, which are often resistant to anticonvulsant treatment but respond well to insulin therapy and rehydration 2, 3

• Seizures may be the first manifestation of hyperglycemia, particularly in previously undiagnosed diabetes 2, 3

Clinical Presentation

• Seizures in hyperglycemia commonly present as:

  • Focal motor seizures with or without secondary generalization (100% in some studies) 3
  • Complex partial seizures with visual hallucinations (25% of cases) 3
  • Epilepsia partialis continua (20% of cases) 3, 2
  • Occipital seizures with visual symptoms 4

• Seizure clustering (multiple seizures in a short period) is significantly more common in patients with diabetic hyperglycemia (63%) compared to non-diabetic seizure patients (38.5%) 5

• Movement disorders can also occur in non-ketotic hyperglycemia, which might be misdiagnosed as primary neurological diseases 6

Risk Factors and Correlations

• Poor glycemic control (HbA1c >9%) significantly increases the risk of seizure recurrence (44.8% vs. 8.3%) and seizure clustering (79.3% vs. 25%) 5

• The frequency and duration of seizures positively correlate with blood glucose levels, serum osmolality, and serum sodium levels 3

• In patients with diabetic hyperglycemia and seizures, those with seizure recurrence have significantly higher HbA1c levels than those without recurrence (11.8% vs. 8.6%) 5

Diagnostic Considerations

• Blood glucose should be measured immediately in all patients presenting with seizures, especially in the elderly or those with risk factors for diabetes 6

• Diagnostic criteria for hyperglycemic hyperosmolar state include:

  • Plasma glucose ≥600 mg/dl
  • Serum osmolality ≥320 mOsm/kg
  • Impaired mental status 1

• EEG findings in hyperglycemic seizures may show focal or generalized slowing (65% of cases) and rapid spikes that are often unilateral during seizures 2

Management

• The primary treatment for hyperglycemia-induced seizures is correction of the underlying hyperglycemia with insulin therapy and rehydration, rather than antiepileptic drugs 2, 3, 6

• Seizures associated with non-ketotic hyperglycemia are often resistant to anticonvulsant treatment but respond well to insulin therapy and rehydration 2

• Isotonic saline should be used for initial fluid replacement to correct dehydration, typically at 15-20 ml/kg/hour in the first hour 7

• Careful monitoring and correction of electrolyte imbalances is essential 1

• Antiepileptic drugs may be needed temporarily in some cases but can often be discontinued after glucose normalization 4, 2

Prognosis

• With proper treatment of hyperglycemia, seizures typically resolve completely within an average of 4 days 2

• Early diagnosis and treatment of hyperglycemia-induced seizures is crucial to prevent progression to more severe hyperosmolarity and coma, which carries a much higher mortality rate 2

• Long-term seizure control is typically good after normalization of blood glucose, with many patients not requiring ongoing antiepileptic medication 4