Determining the neurocognitive profile of children with tuberous sclerosis complex within the Western Cape region of South Africa.

BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystem genetic disorder associated with a wide spectrum of cognitive impairments that can often result in impaired academic, social and adaptive functioning. However, studies investigating TSC have found it difficult to determine whether TSC is associated with a distinct cognitive phenotype and more specifically which aspects of functioning are impaired. Furthermore, children with TSC living in low-income and middle-income countries, like South Africa, experience additional burdens due to low socio-economic status, high mortality rates and poor access to health care and education. Hence, the clinical population of South Africa may vary considerably from those populations from high-income countries discussed in the literature. METHODS: A comprehensive neuropsychological battery composed of internationally recognised measures examining attention, working memory, language comprehension, learning and memory, areas of executive function and general intellectual functioning was administered to 17 children clinically diagnosed with TSC. RESULTS: The exploration of descriptive data indicated generalised cognitive difficulties in most cognitive domains, aside from memory. With only two participants performing in the average to above-average ranges, the rest of the sample showed poor verbal comprehension, perceptual reasoning, working memory, processing speed, disinhibition, and problems with spatial planning, problem solving, frustration tolerance, set shifting and maintaining a set of rules. Furthermore, correlational findings indicated several associations between socio-demographic and cognitive variables. CONCLUSIONS: Importantly, this is the first study to comprehensively examine multiple domains of neurocognitive functioning in a low-resource setting sample of children with TSC. Current study findings showed that children with TSC have generalised impairments across several cognitive domains, rather than domain-specific impairments. Therefore, although examining individual aspects of cognition, such as those found in previous literature, is important, this approach is limiting. With a comprehensive assessment, including understanding the associations between domains, appropriate and directed support can be provided to ensure all aspects of development are addressed and considered.

Release of angiotensins in paraventricular nucleus of rat in response to physiological and chemical stimuli.

The brain angiotensin (ANG II and III) system is known to play an important role in the central control of cardiovascular function and body water homeostasis. A number of components of the angiotensin system including active peptides, precursors, synthetic enzymes, and receptors have been localized to specific brain nuclei including the paraventricular nucleus (PVN) of the hypothalamus. We and others have hypothesized that the PVN is a major integrative hub of the central angiotensin system receiving angiotensinergic input from central detectors (circumventricular organs) and sending efferents to higher brain and spinal cord centers. Implicit in this idea is that angiotensins, like all neurotransmitters, should be releasable with appropriate chemical and physiological stimuli. Therefore we examined the ability of water deprivation or direct infusion of either 65 mM K+ or 80 microM veratridine to stimulate the release of angiotensins from the PVN of the rat. Using push-pull cannulas to perfuse the PVN and radioimmunoassay (RIA) to analyze the superfusate for immunoreactive angiotensins, we established that 24 h of water deprivation resulted in an approximate 5-fold increase in the angiotensin release rate, whereas 48-h deprivation produced a dramatic 492-fold increase in release. Direct infusion of 65 mM K+ into the PVN was unable to stimulate angiotensin release, but 80 microM veratridine elicited a sevenfold increase in the angiotensin release rate. High-performance liquid chromatographic separation and RIA analysis of veratridine- and water deprivation-stimulated angiotensin release demonstrated that 93.4% of the releasable angiotensin coeluted with ANG III, whereas only 6.8% eluted with authentic ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)