Comparison of regional cerebral perfusion, EEG and cognitive functions in type 1 diabetic children with and without severe hypoglycaemia

Abstract

Mild abnormal findings in brain perfusion, the EEG and in cognitive processing are common in children with type 1 diabetes, but these abnormalities are not associated with previous severe hypoglycaemia.We studied the effect of diabetes on long-term brain function by comparing two age-matched groups of normally developed prepubertal type 1 diabetes children (age 5.6-11.9 years, diabetes duration 1.8-9.6 years). Of the 20 patients, 10 had experienced severe hypoglycaemia leading to unconsciousness and/or convulsions. All patients were in normal school or preschool. Their mean HbA1c ± SD was 8.4±1.7% (reference range 4.0%-6.2%). For every patient, we performed within 1 month (1) cerebral blood flow detected by single-photon emission tomography (SPECT) without anaesthesia, (2) brain electrical activity detected by 8-channel EEG, and (3) cognitive function evaluated by comprehensive neuropsychological assessment. The blood glucose level of the patients was measured before each study session to avoid hypoglycaemia.In the SPECT analysis, transaxial slices were reconstructed at three levels: canto-meatal line (CM) +36 mm, 48 mm, and 64 mm. Six symmetrical cortical regions of interest (ROI) were drawn on each hemisphere and labelled from the frontal to the occipital as ROIs 1 to 6 [3]. The average radioactivity of each region and hemisphere was measured and the left-right index was calculated for each ROI and hemisphere (2 · (left-right)/(left + right)), where left and right represent the average radioactivities of two symmetrical ROIs in each hemisphere. Data from the literature were used for normal cerebral blood flow [1]. EEGs were analysed visually and semiquantitatively and scored 0-5 according to amount of background slowing, paroxysmality, and focal abnormalities.Intelligence was assessed with The Wechsler Intelligence Scale for Children-Revised (WISC-R) [4] or Wechsler Preschool and Primary Scale of IntelligenceRevised (WPPSI-R) [5]. Cognitive functions were evaluated with The Developmental Neuropsychological Assessment (NEPSY) [2] in five domains (Table 1). Of the 30 NEPSY tests, 16 were administered.The left-right indexes in SPECT were tested both between the groups and against zero with the Student t-test. According to power-analysis, the number of subjects in each group was sufficient to detect a difference of 0.05 in the left-right index. Fisher's exact test was used for comparison of EEGs. The Student t-test and the v 2 test were used to determine group differences in the neuropsychological study. P values <0.05 were considered significant.The left-right index of the hemispheres in both groups was negative. These results differ from those of normal children, in whom the left cerebral blood flow values are significantly higher than the right values [1]. The left-right index of the hemispheres of the two groups did not differ from each other. However, the hypoglycaemic patients had significantly more ROIs where the left-right index exceeded the average +2SD than did the other patients (9 versus 2, the number o...

Effect of verbal task complexity in a working memory paradigm in patients with type 1 diabetes. A fMRI study

“…Multiple studies have shown that children and adults diagnosed with T1D usually achieve lower scores than their peers in different neuropsychological tests [2–9, 15, 38]. Our patients had significantly lower IQs than the control group.…”

“…Cognitive impairments in T1D in both adults and children are reported in the areas of psychomotor speed, memory, processing speed, verbal ability, learning, attention and executive functions, including working memory [2–9]. A meta-analysis reported that patients with T1D decline in mental processing speed and mental flexibility, while the other cognitive functions seem to be spared [10].…”

The Effect of Recurrent Severe Hypoglycemia on Cognitive Performance in Children With Type 1 Diabetes

“…These 9 studies were, therefore, excluded from meta-analysis. Final meta-analysis included the 12 studies 1, [8][9][10]14,15,[25][26][27][28][29][30] summarized in Table 1. These studies are heterogeneous with respect to cognitive domains.…”

“…Refs. : General intelligence ¼(1, 8, 10, 14, 15, 27, 28, 30), Learning ¼ (8-10, 14, 15, 26, 29, 30), Memory ¼ (1, 8-10, 15, 25, 26, 28, 29, 30), Verbal fluency/language ¼ (1,10,14,15,29,30). Numbers in parenthesis showed sample size.…”

Regional Brain Volume Differences Associated With Hyperglycemia and Severe Hypoglycemia in Youth With Type 1 Diabetes

“…At least three neuropathological case studies also described more extensive damage in the left than in the right hemisphere with severe hypoglycemia (18,23,24). Additionally, in a single photon emission computed tomography (SPECT) study, children with diabetes had abnormal left-right blood flow ratios, suggestive of left hemisphere dysfunction (25). Interestingly, in the default system, this same region has a greater response to cognitive challenge on the left than on the right side (22).…”