Long-Term Functional Outcome Following Left Hemispherotomy in Adults and Pediatric Participants with Fmri Analysis.

Background and Objective: Hemispherotomy surgery in adults is shrouded in doubts regarding the functional outcome. The age at surgery alone should not be the deciding factor for surgery. Language paradigms were used in functional magnetic resonance imaging (fMRI) to confirm the role played by the age at the onset of seizures to predict the postoperative functional outcome. The objective of the study was to formulate an optimal strategy for patient selection for the left-sided hemispherotomy in adults, based on functional outcome analysis. Materials and Methods: A retrospective analysis of 20 participants (age at surgery 1-26 years) who underwent left hemispherotomy (over a 5-year period) was conducted. The language and motor functional assessments of 18 participants (13 pediatric and five adult participants; attrition of participants- two) were recorded at presentation and during follow-up visits. After approval was obtained from the Institutional Ethics Committee, 13 cooperative participants (eight pediatric and five adult participants) underwent language fMRI. Motor fMRI with both active and passive paradigms was done in 16 participants. Results: All 18 participants with a mean follow-up of 24 months had class I seizure-free outcome. Of these 18, five were adults (mean age = 21 years, range: 18-22 years) and 13 were in the pediatric age group (mean age = 8 years, range: 2-15 years). Postoperatively, four adults retained both verbal fluency and language comprehension at a mean follow-up period of 38 months (range: 24-48 months). Their pre- and post-op language fMRI showed word generation and regional activations for semantic comprehension in the right hemisphere. The motor area activations were seen in the right hemisphere in two and in the left hemisphere in two participants. Among the pediatric participants, four (group I [n = 4/13]) who had good language outcome showed activations in the right hemisphere. In two participants (group II [n = 2/13]) who deteriorated postoperatively, the activations were in the left hemisphere. Five participants (group III [n = 5/13]) who retained the telegraphic language postoperatively had bilateral activations of semantic comprehension areas in fMRI. All 13 pediatric participants had motor area activations seen in the left hemisphere, similar to controls. Conclusion: Left hemispherotomy can be advised to adults with comparably good postoperative language and motor outcome as in the pediatric age group, provided the weakness is acquired perinatally or below the age of 7 years. The fMRI is a valuable tool to aid in patient selection.

Development and Evaluation of a Working Memory Intervention Kit in Children with Epilepsy in Low-Resource Settings.

OBJECTIVES: In this pilot study, the authors developed and evaluated a working memory intervention (WMI) using a combination of mobile phone-based application and an activity booklet, among children with idiopathic generalized epilepsy. METHODS: Pre- and post-intervention cognitive evaluation at 8 wk included: subtests comprising working memory index from Wechsler Intelligence Scale-IV, color cancellation task for sustained attention, and parent's rating from the Conners' ADHD/DSM-IV Scales of the Conners' Rating Scales-Revised. RESULTS: Fourteen children completed the intervention; one was lost to follow-up. Significant improvement in most working memory parameters occurred at 8 wk: digit span [scaled scores: median 7 (IQR 4-9) to 12 (IQR 9-14.25); p = 0.001]; letter-number sequencing [scaled scores: median 9 (IQR 5-10) to 11.5 (IQR 6.75-13); p = 0.03]; WMI [median 14 (IQR 9-18) to 22 (IQR 16.75-27); p = 0.001] and sustained attention [time for cancellation test improved from 95 (72-117) to 85 (63-98) s; p = 0.001]. CONCLUSION: This indigenous WMI was feasible and efficacious in improving working memory deficits in CWE in low-resource settings.

EslB Is Required for Cell Wall Biosynthesis and Modification in Listeria monocytogenes.

Lysozyme is an important component of the innate immune system. It functions by hydrolyzing the peptidoglycan (PG) layer of bacteria. The human pathogen Listeria monocytogenes is intrinsically lysozyme resistant. The peptidoglycan N-deacetylase PgdA and O-acetyltransferase OatA are two known factors contributing to its lysozyme resistance. Furthermore, it was shown that the absence of components of an ABC transporter, referred to here as EslABC, leads to reduced lysozyme resistance. How its activity is linked to lysozyme resistance is still unknown. To investigate this further, a strain with a deletion in eslB, coding for a membrane component of the ABC transporter, was constructed in L. monocytogenes strain 10403S. The eslB mutant showed a 40-fold reduction in the MIC to lysozyme. Analysis of the PG structure revealed that the eslB mutant produced PG with reduced levels of O-acetylation. Using growth and autolysis assays, we showed that the absence of EslB manifests in a growth defect in media containing high concentrations of sugars and increased endogenous cell lysis. A thinner PG layer produced by the eslB mutant under these growth conditions might explain these phenotypes. Furthermore, the eslB mutant had a noticeable cell division defect and formed elongated cells. Microscopy analysis revealed that an early cell division protein still localized in the eslB mutant, indicating that a downstream process is perturbed. Based on our results, we hypothesize that EslB affects the biosynthesis and modification of the cell wall in L. monocytogenes and is thus important for the maintenance of cell wall integrity.IMPORTANCE The ABC transporter EslABC is associated with the intrinsic lysozyme resistance of Listeria monocytogenes However, the exact role of the transporter in this process and in the physiology of L. monocytogenes is unknown. Using different assays to characterize an eslB deletion strain, we found that the absence of EslB affects not only lysozyme resistance but also endogenous cell lysis, cell wall biosynthesis, cell division, and the ability of the bacterium to grow in media containing high concentrations of sugars. Our results indicate that EslB is, by means of a yet-unknown mechanism, an important determinant for cell wall integrity in L. monocytogenes.

Origins of Metabolic Pathology in Francisella-Infected Drosophila.

The origins and causes of infection pathologies are often not understood. Despite this, the study of infection and immunity relies heavily on the ability to discern between potential sources of pathology. Work in the fruit fly has supported the assumption that mortality resulting from bacterial invasion is largely due to direct host-pathogen interactions, as lower pathogen loads are often associated with reduced pathology, and bacterial load upon death is predictable. However, the mechanisms through which these interactions bring about host death are complex. Here we show that infection with the bacterium Francisella novicida leads to metabolic dysregulation and, using treatment with a bacteriostatic antibiotic, we show that this pathology is the result of direct interaction between host and pathogen. We show that mutants of the immune deficiency immune pathway fail to exhibit similar metabolic dysregulation, supporting the idea that the reallocation of resources for immune-related activities contributes to metabolic dysregulation. Targeted investigation into the cross-talk between immune and metabolic pathways has the potential to illuminate some of this interaction.

A randomized, double blind, sham-controlled trial of repetitive transcranial magnetic stimulation (rTMS) in the treatment of negative symptoms in schizophrenia.

BACKGROUND: Research has implicated hypofrontality in the pathogenesis of Negative symptoms of schizophrenia.These symptoms are often resistant to treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) has been shown to reverse this hypofrontality. Higher frequency rTMS has shown better promise, but so far there has been very little research in this area. OBJECTIVE: We aimed to evaluate the efficacy of high-frequency (20 Hz) unilateral rTMS over the left Dorso-Lateral Pre-frontal Cortex (DLPFC) in the improvement of Negative symptoms in Schizophrenia. METHODS: 100 patients of schizophrenia with predominantly negative symptoms, were enrolled for this randomized, sham-controlled, double-blind trial.Each participant received 20 sessions of rTMS at 20 Hz frequency and 100% motor threshold, via either the active or the sham coil, over 4 weeks. A total of 2000 pulses were imparted in 10 trains per session. Negative symptoms were assessed with the SANS and PANSS. CDSS was used to rule out depressive symptoms. Assessments were carried out at baseline, post-intervention, and 1-month, 2-months, 3-months and 4-months follow ups. RESULTS: The improvement in the negative symptoms (Anhedonia, Alogia, Avolition, Attention impairment) in active group was statistically significant at 0.01 and 0.05 (p-value) as compared to sham group. CONCLUSIONS: These results suggest that high-frequency rTMS may lead to improvement in negative symptoms of schizophrenia. It may be worth considering its use as an adjunct to pharmacological treatment of negative symptoms.

Does education play a role in language reorganization after surgery in drug refractory temporal lobe epilepsy: An fMRI based study?

OBJECTIVES: Patients with drug refractory epilepsy (DRE) and a high level of education may differ in their language recovery after surgery. Our aim was to determine whether there were differences in the extent of improvement and pattern of reorganization of language functions on functional magnetic resonance imaging (fMRI) after surgery to treat refractory temporal lobe epilepsy (TLE) between patients with more than 12 years of formal education versus those with a shorter period of regular schooling. METHODS: After approval by an institutional ethics committee, 60 right-handed, adult patients of left TLE and 20 right-handed, healthy controls were recruited to the study. Multiple aspects of language (Repetition, Naming, Word fluency, Visual word and Comprehension reading) were tested using the Indian Aphasia Battery (IAB) in the Hindi language; fMRI was performed using a standardized Hindi language paradigm (lexical, semantic, syntactic and comprehension components) in both cases and controls, before and after an anterior temporal lobectomy (in cases) with a 1.5T MR Scanner. An array of performance tests of intelligence and the verbal adult intelligence scale (VAIS) were used to measure the Intelligence Quotient (IQ) in Left TLE (LTLE) patients before and after surgery. Language laterality was estimated using the laterality index (LI-toolbox-spm8). Cohen's d test was performed to determine the effect sizes of the differences in the IAB scores, and Pearson's correlation was applied between regional (IFG and STG) activation in controls and TLE patients with more than 12 years of schooling [higher educational status (HES subgroup)] and those with less than 12 years of schooling [lower educational status (LES subgroup)]. RESULTS: At the baseline, clinical testing with IAB showed better scores in controls than in cases. Better scores were observed in subjects with higher levels of education than in those with lower levels of education. An improvement was observed in IQ scores in both the HES and LES groups after ATLR; significant worsening in the abstract ability subtest was noted in the LES group, whereas in the HES group there was an improvement. Blood-oxygen-level dependent (BOLD) activation during language tasks was observed in both cerebral hemispheres in the TLE cases, while it was observed in the traditional left hemispheric language areas in controls. Postoperatively, greater BOLD activation was observed in the left inferior frontal gyri (IFG, r=0.65*; p<0.05), middle frontal gyrus (MFG, r=0.77**; p<0.01) superior temporal gyri (STG, r=0.88* p<0.02) and angular gyrus (AG, r=0.73*; p<0.04) in HES compared to LES subjects. Similarly, LI showed left lateralization of the frontal (LIw=0.77 & 0.71) and temporal (LIw=0.74 & 0.5) regions in controls and the TLE group (post-surgery) compared to the pre-surgery group during language tasks. CONCLUSIONS: Greater improvement in language skills and BOLD activation in the left hemisphere in TLE-patients (after epilepsy surgery) with a high level of education was similar to that of healthy controls, implying that education has an effect on the functional reorganization/recovery of language areas.

Effect of preoperative statin therapy on early postoperative memory impairment after off-pump coronary artery bypass surgery.

CONTEXT: Frequent incidence of early postoperative memory impairment (POMI) after cardiac surgery remains a concern because of associated morbidity, impaired quality of life, and increased health care cost. AIM: To assess the effect of preoperative statin therapy on POMI in patients undergoing off-pump coronary artery bypass (OPCAB) surgery. SETTING AND DESIGN: Prospective observational study in a tertiary level hospital. METHODS: Sixty patients aged 45-65 years undergoing OPCAB surgery were allocated into two groups of 30 each. Group A patients were receiving statin and Group B patients were not receiving statins. All patients underwent memory function assessment preoperatively after admission to hospital and on the 6 th postoperative day using postgraduate institute memory scale. STATISTICAL ANALYSIS: Appropriate tests were applied with SPSS 20 to compare both groups. The value P < 0.05 was considered statistically significant. Multiple regression analysis was performed with confounding factors to determine the effect on memory impairment. RESULTS: Patients in Group A showed significant postoperative deterioration in 6 of the 10 functions and in Group B showed deterioration in 9 of 10 functions tested compared to preoperative scores. Intergroup comparison detected less POMI in Group A compared to Group B and was statistically significant in 8 memory functions. Multiple regression analysis detected statin as an independent factor in preventing memory impairment. CONCLUSIONS: Preoperative statin therapy attenuates the early POMI in patients undergoing OPCAB. Future long-term studies will define the efficacy of statin on POMI.

Mapping of cognitive functions in chronic intractable epilepsy: Role of fMRI.

BACKGROUND: Functional magnetic resonance imaging (fMRI), a non-invasive technique with high spatial resolution and blood oxygen level dependent (BOLD) contrast, has been applied to localize and map cognitive functions in the clinical condition of chronic intractable epilepsy. PURPOSE: fMRI was used to map the language and memory network in patients of chronic intractable epilepsy pre- and post-surgery. MATERIALS AND METHODS: After obtaining approval from the institutional ethics committee, six patients with intractable epilepsy with an equal number of age-matched controls were recruited in the study. A 1.5 T MR scanner with 12-channel head coil, integrated with audio-visual fMRI accessories was used. Echo planar imaging sequence was used for BOLD studies. There were two sessions in TLE (pre- and post-surgery). RESULTS: In TLE patients, BOLD activation increased post-surgery in comparison of pre-surgery in inferior frontal gyrus (IFG), middle frontal gyrus (MFG), and superior temporal gyrus (STG), during semantic lexical, judgment, comprehension, and semantic memory tasks. CONCLUSION: Functional MRI is useful to study the basic concepts related to language and memory lateralization in TLE and guide surgeons for preservation of important brain areas during ATLR. This will help in understanding future directions for the diagnosis and treatment of such disease.

Health-related quality of life using QOLIE-31: before and after epilepsy surgery a prospective study at a tertiary care center.

BACKGROUND: Outcome following epilepsy surgery has traditionally been measured in terms of relief of seizures. However, changes in health-related quality of life (HRQOL) after surgery for intractable epilepsy are also important to document. There are no studies on the Indian population which assess the outcome of epilepsy surgery in terms of HRQOL. MATERIALS AND METHODS: We conducted a prospective study on the patients undergoing epilepsy surgery for intractable seizures, between February 2004 and May 2006 at our center. All patients cleared for epilepsy surgery by the epilepsy surgery team were taken up for study. All patients RESULTS: Thirty-six patients satisfying the inclusion/exclusion criteria were included in the analysis. Twenty-nine of these (Group 1) had good seizure outcome (Engel 1 and 2), while seven patients (Group 2) had poor seizure outcome (Engel 3 and 4) at six months. Overall, 77% of all study patients were completely seizure-free at follow-up. There was no baseline difference in the seven domains of QOLIE-31 between the two groups. There was very significant improvement (P value>0.005 using paired sample T test) in all the domains of QOLIE-31 in the good outcome group after surgery. Health-related quality of life improvement was seen in all the domains in the poor outcome group also, however, it was statistically significant only for the following parameters: seizure worry, overall QOL, emotional wellbeing, energy fatigue and social functioning domains. Improvement in seizure worry, overall QOL, emotional wellbeing and social functioning was significantly more in Group 1 as compared to Group 2. CONCLUSION: Complete seizure-free state after surgery is associated with very significant improvement in HRQOL parameters. Several, but not all parameters of HRQOL as assessed by QOLIE-31, improved after surgery even in the poor seizure outcome group. The improvement in domains of seizure worry, overall QOL, emotional wellbeing and social functioning is significantly more in those patients in whom complete seizure-free state is achieved.