1H nuclear magnetic resonance-based metabolic profiling of cerebrospinal fluid to identify metabolic features and markers for tuberculosis meningitis

BackgroundTuberculosis meningitis (TBM) is the most severe form of tuberculosis, and currently lacks efficient diagnostic approaches. Metabolomics has the potential to differentiate patients with TBM from those with other forms of meningitis and meningitis-negative individuals. However, no systemic metabolomics research has compared the cerebrospinal fluid (CSF) of these patients.Methods¹H nuclear magnetic resonance (NMR) was used for CSF metabolic profiling. Principal component analysis and orthogonal signal correction-partial least squares-discriminant analysis (OPLS-DA) were used to screen for important variables. The Human Metabolome Database was used to identify metabolites, and MetaboAnalyst 4.0 was used for pathway analysis and over-representation analysis.ResultsOPLS-DA modeling could distinguish TBM from other forms of meningitis, and several significantly changed metabolites were identified. Additionally, 23, 6, and 21 metabolites were able to differentiate TBM from viral meningitis, bacterial meningitis, and meningitis-negative groups, respectively. Pathway analysis indicated that these metabolites were mainly involved in carbohydrate and amino acid metabolism, and over-representation analysis indicated that some of these pathways were over-represented.ConclusionsThe metabolites identified have the potential to serve as biomarkers for TBM diagnosis, and carbohydrate and amino acid metabolism are perturbed in the CSF of patents with TBM. Metabolomics is a valuable approach for screening TBM biomarkers. With further investigation, the metabolites identified in this study could aid in TBM diagnosis.     

Disruption of learning and long-term retention of prose passages in patients with focal epilepsy

Recent investigations of accelerated long-term forgetting, a condition in which newly acquired memory is normal initially but decays rapidly over days or weeks, indicate that multiple factors might influence whether this phenomenon is seen in patients with epilepsy. Test-based differences such as learning condition or type of memory measure (e.g., recall vs recognition) as well as epilepsy variables (e.g., side, site, or frequency of epileptiform activity) may be important. The present study sought to characterize factors affecting learning and memory for prose passages in patients with focal epilepsy. We enrolled 21 patients with temporal lobe epilepsy, with and without hippocampal lesions, 11 patients with extratemporal epilepsy (ETE), and 29 healthy controls. Two matched passages were used to compare effects of initial learning condition (one exposure versus learning-to-criterion) on subsequent patterns of retention. Recall and recognition were tested at different delays (i.e., immediately, 30 min, 24 h, and 4 days). Regression analyses and one-way ANOVAs indicated that having a left-hemisphere epileptic focus had a negative impact on learning, whilst presence of a hippocampal lesion (irrespective of side) was associated with deterioration in recall for intervals up to 24 h postencoding. Learning condition affected patterns of memory decay in that the ETE group showed significant decline in recall between 24 h and 4 days only when stories were learned to criterion. In contrast with recall, no changes over time were evident in recognition memory, as patients with hippocampal lesions were impaired from 30 min onward. Epilepsy variables other than side and site of epilepsy/lesion did not influence performance. In conclusion, the left hemisphere is involved in learning of prose material, and the hippocampus is involved in the consolidation of this material mainly for the first 24 h. After this, cortical regions outside the hippocampus become important for recall.     

Subjective cognitive complaints versus objective neuropsychological performance in older adults with epilepsy

Memory complaints are common among older adults with epilepsy (OAE), though discrepancy between subjective complaints and objective performance often exists. This study examined how accurately OAE and their informants reported on the participant's cognitive difficulties by comparing ratings of everyday cognition to objective performance. Thirty-seven OAE and 27 older adult controls completed a brief battery of neuropsychological tests, the Beck Depression Inventory, and the Cognitive Difficulties Scale (CDS). Each participant had an informant who completed the CDS. Older adults with epilepsy performed worse than controls on cognitive testing and reported more subjective cognitive complaints. Neither participant- nor informant-reported cognitive complaints were related to performance on any of the neuropsychological tests for either the group with epilepsy or control group, but both were related to greater depressive symptoms. Results suggest that subjective report of cognitive problems by both OAE and their informants may not reliably reflect the extent to which these problems exist.     

Congenital malformations in infants exposed to antiepileptic medications in utero at Boston Medical Center from 2003 to 2010

ObjectiveThe aim of this study was to determine the frequency of association of major congenital malformations in pregnancy in women exposed to antiepileptic drugs (AEDs) in an inner city population.BackgroundApproximately 0.3–0.5% of all pregnancies involve women with epilepsy. The risk of congenital malformations associated with AED therapy has been well documented, ranging from 2 to 10% as compared to a rate of 3% in the general population. However, the risk of these occurring in a higher risk population, such as an inner city tertiary care center, with multiple comorbidities is not as well known.Design/methodsUsing the Boston Medical Center Database between the years 2003 and 2010, a list of all infants born with major congenital malformations (MCMs) to mothers on AEDs was compiled. Major congenital malformations were defined as cleft lip and/or palate, ventricular or atrial septal defect, other cardiac malformations, and urogenital defects. During pregnancy, AED exposure including serum levels, other medication exposures, breakthrough seizure frequency, positive toxicology tests, and other maternal comorbidities were also analyzed.ResultsOf 17,246 live births between 2003 and 2010, 330 of those births demonstrated a MCM (malformation rate of 1.91%). Of those births, 64 mothers had epilepsy and were exposed to AED therapy during pregnancy, accounting for 0.37% of all births during this time period. Overall, three pregnancies in women with epilepsy resulted in a baby with a MCM, accounting for a 4.7% malformation rate in this patient population. In mothers on AEDs for other indications, the MCM rate was slightly higher, 5.0%, and in women on benzodiazepine monotherapy during pregnancy, the rate was quite high, 10.6%.