Hypoglycaemia-induced changes in regional brain volume and memory function.

BACKGROUND: Hypoglycaemic events can be a serious complication of insulin therapy in Type 1 diabetes mellitus. Severe hypoglycaemic exposure can lead to episodic memory impairments, including anterograde amnesia. However, relatively little is known regarding the long-term impact of severe hypoglycaemia on brain structure in Type 1 diabetes mellitus. The goals of the present study were to gain a greater understanding of the long-term effects of severe hypoglycaemia exposure on brain structure and the neural correlates of memory impairments in Type 1 diabetes mellitus. CASE REPORT: Regional grey and white matter volume and total white matter lesion volume were quantified in an individual with long-standing hypoglycaemia-induced anterograde amnesia and compared with age- and gender-matched healthy controls. Our patient has significant reductions in grey matter volume in the hippocampus, thalamus and pallidum, and significant reductions in white matter volume in the splenium, isthmus of the cingulate and cerebellum. He also has a significantly larger total white matter lesion volume than controls. CONCLUSION: This case study highlights the potential of hypoglycaemia for permanent deleterious effects on brain structure and memory function. Our results suggest that subcortical grey matter, periventricular white matter and posterior white matter may be most susceptible to injury from hypoglycaemia exposure, and that structural damage to the hippocampus and isthmus of the cingulate may play a central role in hypoglycaemia-induced memory impairments.

Neural correlates of STN DBS-induced cognitive variability in Parkinson disease.

BACKGROUND: Although deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson disease (PD) improves motor function, it has variable effects on working memory (WM) and response inhibition (RI) performance. The purpose of this study was to determine the neural correlates of STN DBS-induced variability in cognitive performance. METHODS: We measured bilateral STN DBS-induced blood flow changes (PET and [(15)O]-water on one day) in the supplementary motor area (SMA), dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and right inferior frontal cortex (rIFC) as well as in exploratory ROIs defined by published meta-analyses. STN DBS-induced WM and RI changes (Spatial Delayed Response and Go-No-Go on the next day) were measured in 24 PD participants. On both days, participants withheld PD medications overnight and conditions (OFF vs. ON) were administered in a counterbalanced, double-blind manner. RESULTS: As predicted, STN DBS-induced DLPFC blood flow change correlated with change in WM, but not RI performance. Furthermore, ACC blood flow change correlated with change in RI but not WM performance. For both relationships, increased blood flow related to decreased cognitive performance in response to STN DBS. Of the exploratory regions, only blood flow changes in DLPFC and ACC were correlated with performance. CONCLUSIONS: These results demonstrate that variability in the effects of STN DBS on cognitive performance relates to STN DBS-induced cortical blood flow changes in DLPFC and ACC. This relationship highlights the need to further understand the factors that mediate the variability in neural and cognitive response to STN DBS.

Unilateral vs. bilateral STN DBS effects on working memory and motor function in Parkinson disease.

Bilateral subthalamic nucleus deep brain stimulation (STN DBS) can reduce working memory while improving motor function in Parkinson disease (PD), but findings are variable. One possible explanation for this variability is that the effects of bilateral STN DBS on working memory function depend in part on functional or disease asymmetry. The goal of this study was to determine the relative contributions of unilateral DBS to the effects seen with bilateral DBS. Motor (Unified Parkinson Disease Rating Scale Part III, UPDRS) and working memory function (Spatial Delayed Response, SDR) were measured in 49 PD patients with bilateral STN DBS while stimulators were Both-off, Left-on, Right-on and Both-on in a randomized, double-blind manner. Patients were off PD medications overnight. Effects of unilateral DBS were compared to effects of bilateral STN DBS. Mean UPDRS and SDR responses to Left-on vs. Right-on conditions did not differ (p>.20). However, improvement in contralateral UPDRS was greater and SDR performance was more impaired by unilateral DBS in the more affected side of the brain than in the less affected side of the brain (p=.008). The effect of unilateral DBS on the more affected side on contralateral UPDRS and SDR responses was equivalent to that of bilateral DBS. These results suggest that motor and working memory function respond to unilateral STN DBS differentially depending on the asymmetry of motor symptoms.

Prevalence of mood disorders and relationship to asthma severity in patients at an inner-city asthma clinic.

BACKGROUND: Depressive symptoms are associated with noncompliance and even sudden death in asthma patients. Some studies suggest that low-income, minority, inner-city asthma patients may be at high risk for asthma-related morbidity and mortality in which depression may be a risk factor. Minimal data are available on the prevalence of depression and other mood disorders in asthma patients. OBJECTIVE: In this pilot study, we examined the prevalence of depression and the association between depression and measures of asthma severity in patients at an inner-city asthma clinic. METHODS: Mood disorders were diagnosed using a diagnostic interview given to patients (N = 44) at asthma clinic visits. Inhaled steroid dose, FEV1 percentage, and asthma severity were also obtained. RESULTS: Eighteen patients (41%) had a lifetime mood disorder but only seven of these patients received pharmacotherapy. Patients with a past mood disorder had significantly higher FEV1 percentage predicted values (P = 0.03) than those without a mood disorder. Trends toward less severe asthma (P = 0.13) and lower inhaled steroid dose (P = 0.13) in patients with a mood disorder history were also found. CONCLUSIONS: The data suggest that mood disorders are common, but often unrecognized and untreated in asthma patients. The data also suggest that mood disorders are not necessarily associated with more severe asthma, at least in the population studied.

Effect of mutagen-induced cell lethality on the dose response of germline mutations.

Molecular tests for mutations require a sample of tissue from which DNA is extracted, to determine the presence or absence of one or more mutations per sample. To ensure mutation fixation each sample must consist of an equal number of cells that have had one or more DNA replications. In an in vivo test, surviving stem cells compensate to give the same number of cells per sample, leaving as the only evidence for stem cell lethality the increase in mutants of clonal origin because the mutant clone developed from a population of fewer stem cells. A problem is that an increase in mutagen dose increases stem cell death, resulting in a decreased number of surviving target cells, thus giving a downward bias of samples with one or more mutations per sample. To compare in vivo tests with molecular tests we will use as a model system the sex-linked recessive lethal (SLRL) test for germ cell mutations in Drosophila melanogaster. Spermatogonia cells in male larvae were exposed to ENU and mutations detected in sperm cells from adults. The same SLRL data were analyzed by two methods: (1) The conventional analysis of SLRL data, in which each mutation of a cluster of mutations of common origin was counted. (2) An analysis was used to simulate a sample for molecular analysis by determining mutations per male with an equal size sample of progeny per male. With this second analysis a correction factor is required based on the change in cluster size of mutants of common origin.