Intellectual decline in children with moyamoya and sickle cell anaemia.

Intelligence is reported to decline after onset of moyamoya in Japanese populations, but there is less evidence for this in Western populations where the condition may be secondary to stroke and sickle cell anaemia (SCA). Preoperative longitudinal IQ data were obtained from 15 children (seven males, eight females) who developed moyamoya syndrome (MMS) following a stroke (six with SCA, nine without SCA), and 19 controls (10 males, nine females; nine healthy control participants, 10 with SCA). At baseline assessment (Time 1) median age of patients was 7 years 6 months (range 3y 7mo to 12y 5mo); median age of controls was 6 years 3 months (range 4y to 11y 6mo). At follow-up (Time 2), ages were 11 years 8 months (range 3y 7mo to 12y 5mo) and 12 years 8 months (range 6y 4mo to 16y 8mo) in patients and controls respectively. Median duration of follow-up for the patient group was 3 years (range 7 to 10y) and in controls, 4 years 1 month (range 1 to 10y). In children with SCA, Verbal and Performance IQs (VIQ and PIQ) were significantly lower than in controls at Time 1; there was an additional independent statistically significant reduction in PIQ associated with MMS (p=0.004). Although there were further significant reductions in IQ by the second assessment for patients with MMS compared with controls, IQ did not differ significantly between groups with and without SCA. While the reduction in IQ attributed to SCA does not appear to become more marked with increasing age, the difference between those with and without MMS is associated with increasing effect over time.

Low plasma taurine and later neurodevelopment.

Dietary taurine intake may explain the benefits of both breast milk and preterm formula to neurodevelopment. Low plasma neonatal taurine was associated with lower scores on the Bayley mental development index at 18 months and the WISC-R arithmetic subtest at 7 years. Currently it is not mandatory to add taurine to infant formulas.

Brain morphometry and IQ measurements in preterm children.

Although IQ is thought to remain relatively stable in the normal population, a decline in IQ has been noted in children born preterm. It is not clear, however, to what extent the inclusion of children with clear neurological damage has influenced these findings. We examined IQ scores obtained in childhood and then again in adolescence from a group of children born at 30 weeks gestation or less who had been classified as neurologically normal at 7.5-8 years. They showed a significant decline in mean IQ scores over time. MRI scans obtained from a subset of children at adolescence were read as normal in approximately 50% of cases and, in the others, there were no consistent relationships between radiological abnormalities and IQ results. Such children can, however, have relatively subtle brain abnormalities that are not seen on conventional MRI, and we hypothesized that these would be related to declines in IQ. Voxel-based morphometry (VBM) analyses of the MRI scans revealed that absolute IQ scores were related to areas in both the parietal and temporal lobes. The analyses also showed that frontal and temporal lobe regions were associated with the decline in VIQ, while occipital and temporal lobe regions (including the hippocampi) were associated with the decline in PIQ. Hippocampal volume measurements were consistent with the VBM findings. We concluded that preterm children are at risk of declining IQ over time even if they have not suffered obvious neurological damage and that the decline is associated with specific neural regions. Whether this is true of children born at >30 weeks gestation and what other factors predispose to this decline have yet to be determined.

Developmental amnesia and its relationship to degree of hippocampal atrophy.

Two groups of adolescents, one born preterm and one with a diagnosis of developmental amnesia, were compared with age-matched normal controls on measures of hippocampal volume and memory function. Relative to control values, the preterm group values showed a mean bilateral reduction in hippocampal volume of 8-9% (ranging to 23%), whereas the developmental amnesic group values showed a reduction of 40% (ranging from 27% to 56%). Despite equivalent IQ and immediate memory scores in the two study groups, there were marked differences between them on a wide variety of verbal and visual delayed memory tasks. Consistent with their diagnosis, the developmental amnesic group was impaired relative to both other groups on nearly all delayed memory measures. The preterm group, by contrast, was significantly impaired relative to the controls on only a few memory measures, i.e., route following and prospective memory. We suggest that early hippocampal pathology leads to the disabling memory impairments associated with developmental amnesia when the volume of this structure is reduced below normal by approximately 20-30% on each side. Whether this is a sufficient condition for the disorder or whether abnormality in other brain regions is also necessary remains to be determined.

Calculation difficulties in children of very low birthweight: a neural correlate.

Learning difficulties, including problems with numeracy, are common in Western populations. Many children with learning difficulty are survivors of preterm birth. Although some of these children have neurological disabilities, many are neurologically normal, and the latter group provides us with an important opportunity to investigate the neural bases of learning problems. We have conducted a neuroimaging study of adolescent children who had been born preterm at 30 weeks gestation or less, to investigate the relationship between brain structure and a specific difficulty in arithmetic calculation. Using voxel-based morphometry, we have been able to demonstrate that there is an area in the left parietal lobe where children without a deficit in calculation ability have more grey matter than those who do have this deficit. To our knowledge, this is the first report establishing a structural neural correlate of calculation ability in a group of neurologically normal individuals.

Intelligence after stroke in childhood: review of the literature and suggestions for future research.

Review of published clinical and neuropsychologic outcome studies reveals limited information about intellectual functioning after childhood stroke. The extant data are supplemented here by analysis of intelligence quotient (IQ) results obtained from 38 children in an ongoing study of unilateral middle cerebral artery ischemic stroke. Evidence so far indicates that, after stroke, mean IQ falls significantly below the population mean but remains within the average range. There is no significant difference between hemispheric side of injury; the Verbal and Performance IQ lateralization profile widely recognized in adults with unilateral injury is not apparent in younger children, and there is only a trend toward this profile in older children. The effects of a number of other variables, including sex, site of stroke, and longitudinal assessment, are also considered. Although the generally minor effect of stroke on IQ is encouraging, a number of children do require extra help on return to school. Some suggestions for future research are highlighted in order to encourage further consideration of the issues raised here.

Hippocampal volume and everyday memory in children of very low birth weight.

Children born preterm and of very low birth weight have an increased incidence of learning difficulties, but little is known about the specific nature of their cognitive deficits and the underlying neuropathology. We hypothesized that their vulnerability to hypoxic, metabolic, and nutritional insults would lead to reduced hippocampal volumes and to deficits in memory because of the role of the hippocampus in this domain of cognition. Neuropsychological and magnetic resonance imaging methods were used to investigate this hypothesis in adolescents born preterm (< or = 30 wk gestation, n = 11) or full-term (n = 8). The preterm group had significantly smaller hippocampal volumes bilaterally, despite equivalent head size, and showed specific deficits in certain aspects of everyday memory, both on objective testing and as indicated by parental questionnaires. The preterm group also had a specific deficit in numeracy. The reduced hippocampal volumes and deficits in everyday memory have previously been unrecognized, but their prevalence in a group of neurologically normal children is striking.

Lateralization of brain function in childhood revealed by magnetic resonance spectroscopy.

We used proton magnetic resonance spectroscopy (1H MRS) for the assessment of focal brain pathology in 22 right-handed children with a diagnosis of intractable temporal lobe epilepsy, and we related this pathology to cognitive dysfunction. Cognitive assessment was based on measurements of verbal IQ, performance IQ, and the Paired Associate Learning subtest of the Wechsler Memory Scale. Five of the 22 children showed no abnormalities of the temporal lobes on 1H MRS, seven showed unilateral pathology, and 10 showed bilateral abnormalities. We found that left-sided pathology is associated with a loss of verbal cognitive functions, whereas right-sided pathology is associated with a loss of nonverbal functions. These findings are consistent with the pattern of lateralization of brain function that has been observed in adults.

Development of language in six hemispherectomized patients.

The development of language skills in the isolated right hemisphere was investigated by comparing the performance of 3 left hemispherectomized with that of the 3 right hemispherectomized patients and three groups of control subjects on baseline clinical measures of language and on production and judgement of morphological markers. The initial brain insult in the hemispherectomy patients of each group had occurred either during early, middle or late childhood. The left hemispherectomy patients were severely impaired in language processing across all three stages of language development. The consequences of a right hemisphere insult on language development were more restricted, with deleterious effects being apparent only in the case in which the lesion was acquired during early childhood.