Case Report: Role of hypoglycemia in seizure aggravation in a case of focal epilepsy: revealing a missing link between diabetes and dementia

Abstract

Aim: While low-frequency electroencephalographic (EEG) activity increases during hypoglycemia, the relationship between hypoglycemia and changes in epileptic activities has not been fully investigated. Recently, the American Clinical Neurophysiology Society's EEG Terminology 2021 defined criteria for Brief Potentially Ictal Rhythmic Discharges (BIRDs) including rhythmic fast activities. We evaluated the association between hypoglycemia and BIRDs.

Methods: Data from a 27-year-old female with focal epilepsy and idiopathic hypoglycemia, who underwent scalp-recorded long-term video-EEG using the International 10-20 system with T1/T2 electrodes, were analyzed. Her anti-neuronal antibody test results were negative. EEG recordings over 6 h were retrospectively evaluated in longitudinal bipolar montages at 15 s per display screen. The number and duration of BIRDs were assessed in each 30 min epoch. Glucose levels were obtained using a flash glucose monitoring system, and the average glucose level for each epoch was calculated using the area under the curve (AUC), measured by pixel-counting software. The relationship between the number and duration of BIRD subtypes and average glucose levels was evaluated using cut-off values of 70, 60, and 50 mg/dL.

Results: During the recording, the EEG showed focal slow activities, epileptic spikes, and BIRDs in the left temporal area, but no clinical or electrographic seizures were observed. The number of evolving BIRDs per epoch was significantly higher during more severe hypoglycemia when the cut-off values were set at 60 mg/dL (2.00 ± 0.71 vs. 0.38 ± 0.70, mean ± SD, p < 0.05, Mann-Whitney U test) and 50 mg/dL (2.33 ± 0.47 vs. 0.44 ± 0.68, p < 0.05). The total duration of definite BIRDs per epoch also showed a statistically significant difference when the cut-off was set at 50 mg/dL (3.15 ± 1.82 vs. 2.10 ± 1.00 s, p < 0.05).

Conclusion: Maintaining glucose levels above 60 mg/dL appears important for the early termination of epileptic rhythmic discharges. Individuals with diabetes are at high risk of Alzheimer's disease (AD), and hippocampal hyperactivity contributes to epileptic seizures, amyloid deposition, and disease progression. Fluctuations in blood glucose levels, including episodes of hypoglycemia, increase the risk of dementia. The present findings suggest a potential causative role of hypoglycemia in AD and propose a precise method to correlate glucose levels with brain activities.

Keywords: Alzheimer’s disease; Brief Potentially Ictal Rhythmic Discharges; electroencephalography; flash glucose monitoring; focal epilepsy; hypoglycemia; long-term video-electroencephalography monitoring; temporal lobe epilepsy.

Figure 1

(A) Left: evolving BIRDs; Right: non-evolving definite BIRDs. Enlarged waveforms at the bottom show the duration of BIRDs. (B) Measurement of average glucose level. Left: raw graph of glucose levels obtained by the flash glucose monitoring system. The gray area indicates glucose levels between 70 and 150 mg/dL, and the pink square shows a 1 h segment. Right: An enlarged image of the 1 h segment showing the measurement of the AUC of a 30 min epoch (pink area). (C) Temporal changes in glucose level (blue line), number of total definite BIRDs (red line), number of evolving BIRDs (red dotted line), and duration of BIRDs (green bars). Error bars indicate standard deviation. (D) Box-and-whisker plots of the number of evolving BIRDs (upper row) and the duration of definite BIRDs (lower row) with cut-off glucose levels of 70, 60, and 50 mg/dL. Boxes represent the median and interquartile range (IQR). Whiskers indicate the maximum and minimum values within 1.5 × IQR, and outliers are shown as dots. Mean values are indicated by crosses. The number of evolving BIRDs was significantly larger in severe hypoglycemia when cut-off values were set at 60 mg/dL (2.00 ± 0.71 vs. 0.38 ± 0.70, mean ± SD) and 50 mg/dL (2.33 ± 0.47 vs. 0.44 ± 0.68) (p < 0.05, Mann–Whitney U test), and the duration of total definite BIRDs showed a significant difference when a cut-off value was set at 50 mg/dL (3.15 ± 1.82 vs. 1.97 ± 0.96 s) (p < 0.05) (pink squares). BIRDs: Brief Potentially Ictal Rhythmic Discharges. AUC, area under the curve.