Scopolamine effects on functional brain connectivity : a pharmacological model of Alzheimer's disease

Scopolamine administration may be considered as a psychopharmacological model of Alzheimer's disease (AD). Here, we studied a group of healthy elderly under scopolamine to test whether it elicits similar changes in brain connectivity as those observed in AD, thereby verifying a possible model of AD impairment. We did it by testing healthy elderly subjects in two experimental conditions: glycopyrrolate (placebo) and scopolamine administration. We then analyzed magnetoencephalographic (MEG) data corresponding to both conditions in resting-state with eyes closed. This analysis was performed in source space by combining a nonlinear frequency band-specific measure of functional connectivity (phase locking value, PLV) with network analysis methods. Under scopolamine, functional connectivity between several brain areas was significantly reduced as compared to placebo, in most frequency bands analyzed. Besides, regarding the two complex network indices studied (clustering and shortest path length), clustering significantly decreased in the alpha band while shortest path length significantly increased also in alpha band both after scopolamine administration. Overall our findings indicate that both PLV and graph analysis are suitable tools to measure brain connectivity changes induced by scopolamine, which causes alterations in brain connectivity apparently similar to those reported in AD.Peer reviewe

Noninvasive prediction of shunt operation outcome in idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by gait disturbance, cognitive deterioration and urinary incontinence in elderly individuals. These symptoms can be improved by shunt operation in some but not all patients. Therefore, discovering predictive factors for the surgical outcome is of great clinical importance. We used normalized power variance (NPV) of electroencephalography (EEG) waves, a sensitive measure of the instability of cortical electrical activity, and found significantly higher NPV in beta frequency band at the right fronto-temporo-occipital electrodes (Fp2, T4 and O2) in shunt responders compared to non-responders. By utilizing these differences, we were able to correctly identify responders and non-responders to shunt operation with a positive predictive value of 80% and a negative predictive value of 88%. Our findings indicate that NPV can be useful in noninvasively predicting the clinical outcome of shunt operation in patients with iNPH

Coping style and quality of life in patients with epilepsy: a cross-sectional study

Having epilepsy has a large impact on one's well-being, but often seizure frequency and severity do not explain self-reported quality of life. We hypothesized that one's personal coping style is more important. In this study, 105 patients attending the outpatient neurological clinic at the University Medical Centre in Utrecht, the Netherlands, with a diagnosis of partial epilepsy, aged 17–80 years, completed questionnaires. Demographic information, disease characteristics, health-related quality of life (HRQoL), and coping styles were obtained by postal-validated HRQoL questionnaires: the EQ5D and RAND-36 and the Utrecht Coping List. A passive coping style explained 45% of the variance in the mental component of HRQoL and was more important than ‘objective’ seizure-related measures. Confounders such as employment, gender, and side-effects of treatment explained another 6%. Passive coping style also influenced the physical component of the HRQoL, but here seizure-related factors predominated. Overall, epilepsy patients showed a more avoiding coping style, and female patients a less active coping style and more reassuring thoughts, compared to the Dutch population. The personal coping style of patients appears to be more important than seizure-related measures in predicting mental aspects of quality of life. Coping style characteristics rather than disease characteristics should guide clinical decision-making in patients with epilepsy. Further studies should investigate the effect on HRQoL of behavioral interventions to improve coping

Impact of a pharmaceutical care programme on health-related quality of life among women with epilepsy: a randomised controlled trial (IPHIWWE study)

This paper was presented in part at the II Congreso Colombiano de Atención Farmacéutica, Medellín, Colombia, September 27, 2013.Background: Epilepsy is a complex chronic disorder which affects health-related quality of life (HRQOL), especially in women. Pharmaceutical care (PC) allows direct intervention between the pharmacist, the patient and the other healthcare team members to optimise treatments in order to reduce negative outcomes related to medication and contribute to improving HRQOL. The aim of the study was to establish the impact of the application of a pharmaceutical care programme on the HRQOL of women with epilepsy.Methods: This study is a pragmatic randomised controlled trial involving women with epilepsy (WWE) over 18 years of age. The intervention group (IG) received a pharmaceutical care programme consisting of medication review follow-up according to Dáder’s method, health education and therapeutic drug monitoring of anticonvulsants. The impact was assessed by changes in seizure frequency, in the self-administered questionnaires (the QOLIE-31, Liverpool AEP, CES-D, Haynes-Sackett test and Moriski-Green test) and between the first interview and the one at the end of six months of follow-up. A Student’s t-test was performed to compare the final QOLIE-31 score between groups and a paired Student’s t-test was used to determine the change in each group between the start and the end of follow-up.Results: One hundred eighty-two WWE entered the study and 144 (79.1%) completed it. The t-test for comparing the final QOLIE-31 scores between groups yielded a t = −2.166 and confidence interval (CI) (95%): −10.125; −0.4625, p-value =0.0319. The change (Δ) in the QOLIE-31 score for the IG was 12.45 points (p-value <0.001) and for the control group it was 2.61 (p-value =0.072). With 10.7 as the minimally important change we found a relative risk of 2.17 (CI: 1.37; 3.43) and a number needed to treat (NNT) of 3.5.Conclusions: The study demonstrated that the application of a pharmaceutical care programme significantly improves HRQOL in WWE. The NNT we found allows a recommendation to implement the PC programme for the additional benefit that would be obtained in patients’ HRQOL.This study was funded by a competitive investigator grant award from the Universidad Nacional de Colombia (Colombia) - Research Division of Bogotá (ref: 202010011419 Quipu Code)

What Electrophysiology Tells Us About Alzheimer’s Disease::A Window into the Synchronization and Connectivity of Brain Neurons

Electrophysiology provides a real-time readout of neural functions and network capability in different brain states, on temporal (fractions of milliseconds) and spatial (micro, meso, and macro) scales unmet by other methodologies. However, current international guidelines do not endorse the use of electroencephalographic (EEG)/magnetoencephalographic (MEG) biomarkers in clinical trials performed in patients with Alzheimer’s disease (AD), despite a surge in recent validated evidence. This Position Paper of the ISTAART Electrophysiology Professional Interest Area endorses consolidated and translational electrophysiological techniques applied to both experimental animal models of AD and patients, to probe the effects of AD neuropathology (i.e., brain amyloidosis, tauopathy, and neurodegeneration) on neurophysiological mechanisms underpinning neural excitation/inhibition and neurotransmission as well as brain network dynamics, synchronization, and functional connectivity reflecting thalamocortical and cortico-cortical residual capacity. Converging evidence shows relationships between abnormalities in EEG/MEG markers and cognitive deficits in groups of AD patients at different disease stages. The supporting evidence for the application of electrophysiology in AD clinical research as well as drug discovery pathways warrants an international initiative to include the use of EEG/MEG biomarkers in the main multicentric projects planned in AD patients, to produce conclusive findings challenging the present regulatory requirements and guidelines for AD studies

Diagnostic Pitfall of Platypnea-Orthodeoxia Syndrome Caused by Atrial Septal Defect after Right Pneumonectomy

We describe a case of platypnea-orthodeoxia syndrome (POS) due to atrial septal defect (ASD) occurring in the early postoperative course of a right pneumonectomy. Deformation of the atrial septum after right pneumonectomy deviates the blood from the inferior vena cava to ASD during the sitting position creating, a massive right-to-left shunt. Diagnosis can initially be missed by making contrast bubble test through the superior vena cava. The atrial septal defect was then closed using the surgical technique, allowing an instantaneous improvement of hematosis

Resting-state EEG source localization and functional connectivity in schizophrenia-like psychosis of epilepsy

BACKGROUND: It is unclear whether, like in schizophrenia, psychosis-related disruption in connectivity between certain regions, as an index of intrinsic functional disintegration, occurs in schizophrenia-like psychosis of epilepsy (SLPE). In this study, we sought to determine abnormal patterns of resting-state EEG oscillations and functional connectivity in patients with SLPE, compared with nonpsychotic epilepsy patients, and to assess correlations with psychopathological deficits. METHODOLOGY/PRINCIPAL FINDINGS: Resting EEG was recorded in 21 patients with focal epilepsy and SLPE and in 21 clinically-matched non-psychotic epilepsy controls. Source current density and functional connectivity were determined using eLORETA software. For connectivity analysis, a novel nonlinear connectivity measure called "lagged phase synchronization" was used. We found increased theta oscillations in regions involved in the default mode network (DMN), namely the medial and lateral parietal cortex bilaterally in the psychotic patients relative to their nonpsychotic counterparts. In addition, patients with psychosis had increased beta temporo-prefrontal connectivity in the hemisphere with predominant seizure focus. This functional connectivity in temporo-prefrontal circuits correlated with positive symptoms. Additionally, there was increased interhemispheric phase synchronization between the auditory cortex of the affected temporal lobe and the Broca's area correlating with auditory hallucination scores. CONCLUSIONS/SIGNIFICANCE: In addition to dysfunction of parietal regions that are part of the DMN, resting-state disrupted connectivity of the medial temporal cortex with prefrontal areas that are either involved in the DMN or implicated in psychopathological dysfunction may be critical to schizophrenia-like psychosis, especially in individuals with temporal lobe epilepsy. This suggests that DMN deficits might be a core neurobiological feature of the disorder, and that abnormalities in theta oscillations and beta phase synchronization represent the underlying neural activity

Association of cerebrospinal fluid tap-related oscillatory activity and shunt outcome in idiopathic normal-pressure hydrocephalus

BACKGROUND: Idiopathic normal-pressure hydrocephalus (iNPH) is a neuropsychiatric syndrome characterized by the clinical triad of gait disturbance, urinary dysfunction, and cognitive impairment. The aim of the present study was to find specific EEG patterns associated with shunt response in iNPH. METHODS: Twenty five iNPH patients (10 shunt responders and 15 non-responders) were enrolled in this study. We performed current source density (CSD) analysis in several frequency bands (delta: 2-4 Hz, theta: 4-8 Hz, alpha: 8-13 Hz, beta: 13-30 Hz, gamma: 30-60 Hz) using exact Low Resolution Brain Electromagnetic Tomography (eLORETA). CSD distribution was compared between shunt responders and non-responders for each frequency band before and after CSF tap test. RESULTS: Shunt responders showed increased gamma CSD in the left temporal cortex before CSF tapping relative to non-responders. However, after CSF tapping, shunt response was associated with significantly higher CSDs in several frequency bands, specifically theta, alpha, beta and gamma, involving mainly the frontal and temporal areas. Using eLORETA analysis, we were able to identify cortical oscillatory activity before and after CSF tap test related to clinical recovery due to shunt operation in iNPH. CONCLUSION: Our findings support and extend the results of previous studies examining the effects of CSF tap test and shunt operation in patients with iNPH, possibly indicating electrophysiological features of shunt response in this disease. These findings warrant future studies to use EEG for prediction of shunt response in iNPH