Health-related quality of life associated with nocturnal leg cramps in primary care: a mixed methods study.

BACKGROUND: Although nocturnal leg cramps are common, little research is available about their impact on quality of life. This mixed-methods study explored the impact of nocturnal leg cramps on health-related quality of life (HRQoL). METHODS: The study included primary care patients (>50 years) who reported suffering from nocturnal leg cramps (2016-2017). In the quantitative phase, patients completed a questionnaire about their HRQoL (SF-36) and the frequency of their cramps, and we computed the SF-36 scores. Then, we conducted a qualitative study using semi-structured interviews with patients with various levels of HRQol to explore their perception of the impact of cramps on their lives. RESULTS: A total of 114 patients (49%) agreed to participate in the quantitative study (mean age: 71, women: 62%) and 15 patients were included in the qualitative study (mean age: 69, women: 67%). The number of cramps in the previous week was low (mean: 1.6 (SD 1.5)). The SF-36 mean physical and mental summary scores were 43 and 50, respectively, and the domain scores were similar to a comparative general population. Whilst some patients reported little interference with their daily lives, others reported a major decrease in their HRQoL. SF-36 scores were not sufficient to describe the cramp-related impairment, as patients from all levels of SF-36 scores reported major impacts of NLC in the interviews. CONCLUSIONS: Some patients describe a specific impact of cramps on their lives, regardless of their HRQoL. These patients should be the target of future intervention trials.

Procedural learning and retention of audio-verbal temporal sequence is altered in children with developmental coordination disorder but cortical thickness matters.

Rhythmic abilities are impaired in developmental coordination disorder (DCD) but learning deficit of procedural skills implying temporal sequence is still unclear. Current contradictory results suggest that procedural learning deficits in DCD highly depend on learning conditions. The present study proposes to test the role of sensory modality of stimulations (visual or auditory) on synchronization, learning, and retention of temporal verbal sequences in children with and without DCD. We postulated a deficit in learning particularly with auditory stimulations, in association with atypical cortical thickness of three regions of interesting: sensorimotor, frontal and parietal regions. Thirty children with and without DCD (a) performed a synchronization task to a regular temporal sequence and (b) practiced and recalled a novel non-regular temporal sequences with auditory and visual modalities. They also had a magnetic resonance imaging to measure their cortical thickness. Results suggested that children with DCD presented a general deficit in synchronization of a regular temporal verbal sequence irrespective of the sensory modality, but a specific deficit in learning and retention of auditory non-regular verbal temporal sequence. Stability of audio-verbal synchronization during practice correlated with cortical thickness of the sensorimotor cortex. For the first time, our results suggest that synchronization deficits in DCD are not limited to manual tasks. This deficit persists despite repeated exposition and practice of an auditory temporal sequence, which suggests a possible alteration in audio-verbal coupling in DCD. On the contrary, control of temporal parameters with visual stimuli seems to be less affected, which opens perspectives for clinical practice.

Brain Gray Matter MRI Morphometry for Neuroprognostication After Cardiac Arrest.

OBJECTIVES: We hypothesize that the combined use of MRI cortical thickness measurement and subcortical gray matter volumetry could provide an early and accurate in vivo assessment of the structural impact of cardiac arrest and therefore could be used for long-term neuroprognostication in this setting. DESIGN: Prospective cohort study. SETTING: Five Intensive Critical Care Units affiliated to the University in Toulouse (France), Paris (France), Clermont-Ferrand (France), Liège (Belgium), and Monza (Italy). PATIENTS: High-resolution anatomical T1-weighted images were acquired in 126 anoxic coma patients ("learning" sample) 16 ± 8 days after cardiac arrest and 70 matched controls. An additional sample of 18 anoxic coma patients, recruited in Toulouse, was used to test predictive model generalization ("test" sample). All patients were followed up 1 year after cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cortical thickness was computed on the whole cortical ribbon, and deep gray matter volumetry was performed after automatic segmentation. Brain morphometric data were employed to create multivariate predictive models using learning machine techniques. Patients displayed significantly extensive cortical and subcortical brain volumes atrophy compared with controls. The accuracy of a predictive classifier, encompassing cortical and subcortical components, has a significant discriminative power (learning area under the curve = 0.87; test area under the curve = 0.96). The anatomical regions which volume changes were significantly related to patient's outcome were frontal cortex, posterior cingulate cortex, thalamus, putamen, pallidum, caudate, hippocampus, and brain stem. CONCLUSIONS: These findings are consistent with the hypothesis of pathologic disruption of a striatopallidal-thalamo-cortical mesocircuit induced by cardiac arrest and pave the way for the use of combined brain quantitative morphometry in this setting.

Gray matter characteristics associated with trait anxiety in older adults are moderated by depression.

BACKGROUND: Structural gray matter characteristics of anxiety remain unclear. The aim of this study was to assess the influence of current depressive symptoms and history of depression on the gray matter characteristics of trait anxiety. METHODS: Structural magnetic resonance imaging (MRI) data from 393 individuals aged 65 years or older were used. Regions of interest (ROIs) included the amygdala, anterior cingulate cortex (ACC), insula, orbitofrontal cortex (OFC), and temporal cortex. Trait anxiety was measured by the State-Trait Anxiety Inventory (STAI). Depression and depressive symptoms were measured using DSM-IV criteria and the Center for Epidemiological Studies Depression Scale (CESD). RESULTS: After adjustments for sociodemographics and health-related variables, anxiety had a significant influence on the gray matter characteristics in all cortical ROIs. First, in participants without depression antecedents, higher trait anxiety was associated with a larger cortical thickness in all cortical ROIs. Second, in participants with a previous history of depression, higher trait anxiety was associated with a smaller cortical thickness in all cortical ROIs. CONCLUSIONS: These results suggest that anxiety is related to cortical thickness differently in healthy older adults and in older adults with psychiatric antecedents. Anxiety associated with thinner cortical areas could reflect symptoms of a specific type of depression or a vulnerability to develop depression.

Rheumatoid Arthritis Associated With Anti-Signal Recognition Particle Immune-Mediated Necrotizing Myopathy: A Case Report.

Immune-mediated necrotizing myopathy (IMNM) is a rare subtype of idiopathic inflammatory myopathy that is characterized by severe subacute proximal weakness, myofiber necrosis, and significantly elevated serum creatine kinase. Anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme-A reductase autoantibodies have been found in about two-thirds of patients with IMNM. This myopathy is usually idiopathic and there is a scarce literature concerning its association with connective tissue diseases. Herein, we report an unusual case of a young woman who presented with both rheumatoid arthritis and severe anti-SRP IMNM. Thankfully to a therapeutic protocol combining rituximab and cyclophosphamide, an important improvement was achieved, and notably no serious side effect was observed.

Validation of a model of itch induction for brain positron emission tomography studies using histamine iontophoresis.

Skin-brain signalling in itch reactions has been demonstrated with neuroimaging techniques showing specific brain activation. With positron emission tomography (PET), the itch model used must be adapted to technical and practical constraints. The technique of itch induction by histamine iontophoresis enables modulation of the sensation via the electrical charge applied. This itch model was validated on normal forearm skin of 56 subjects, with itch visual analogue scores peaking to approximately 1.0 cm after 3-4 min, falling to 0.2 cm at 15 min, with no influence of sex, zone, or order. Subsequently, the model was used in a PET study on 14 male volunteers, comparing histamine with physiological saline (control). The results show that the brain is able to discriminate these two conditions, with activated areas similar to those described previously, with, in addition, the anterior cingulate cortex and the insula being positively correlated with the intensity of the sensation.

Sleep deprivation and Modafinil affect cortical sources of resting state electroencephalographic rhythms in healthy young adults.

OBJECTIVE: It has been reported that sleep deprivation affects the neurophysiological mechanisms underpinning the vigilance. Here, we tested the following hypotheses in the PharmaCog project (www.pharmacog.org): (i) sleep deprivation may alter posterior cortical delta and alpha sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms in healthy young adults; (ii) after the sleep deprivation, a vigilance enhancer may recover those rsEEG source markers. METHODS: rsEEG data were recorded in 36 healthy young adults before (Pre-sleep deprivation) and after (Post-sleep deprivation) one night of sleep deprivation. In the Post-sleep deprivation, these data were collected after a single dose of PLACEBO or MODAFINIL. rsEEG cortical sources were estimated by eLORETA freeware. RESULTS: In the PLACEBO condition, the sleep deprivation induced an increase and a decrease in posterior delta (2-4 Hz) and alpha (8-13 Hz) source activities, respectively. In the MODAFINIL condition, the vigilance enhancer partially recovered those source activities. CONCLUSIONS: The present results suggest that posterior delta and alpha source activities may be both related to the regulation of human brain arousal and vigilance in quiet wakefulness. SIGNIFICANCE: Future research in healthy young adults may use this methodology to preselect new symptomatic drug candidates designed to normalize brain arousal and vigilance in seniors with dementia.

A 15-day course of donepezil modulates spectral EEG dynamics related to target auditory stimuli in young, healthy adult volunteers.

OBJECTIVE: To identify possible electroencephalographic (EEG) markers of donepezil's effect on cortical activity in young, healthy adult volunteers at the group level. METHODS: Thirty subjects were administered a daily dose of either 5mg donepezil or placebo for 15days in a double-blind, randomized, cross-over trial. The electroencephalogram during an auditory oddball paradigm was recorded from 58 scalp electrodes. Current source density (CSD) transformations were applied to EEG epochs. The event-related potential (ERP), inter-trial coherence (ITC: the phase consistency of the EEG spectrum) and event-related spectral perturbation (ERSP: the EEG power spectrum relative to the baseline) were calculated for the target (oddball) stimuli. RESULTS: The donepezil and placebo conditions differed in terms of the changes in delta/theta/alpha/beta ITC and ERSP in various regions of the scalp (especially the frontal electrodes) but not in terms of latency and amplitude of the P300-ERP component. CONCLUSION: Our results suggest that ITC and ERSP analyses can provide EEG markers of donepezil's effects in young, healthy, adult volunteers at a group level. SIGNIFICANCE: Novel EEG markers could be useful to assess the therapeutic potential of drug candidates in Alzheimer's disease in healthy volunteers prior to the initiation of Phase II/III clinical studies in patients.

Cortical imaging on a head template: a simulation study using a resistor mesh model (RMM).

The T1 head template model used in Statistical Parametric Mapping Version 2000 (SPM2), was segmented into five layers (scalp, skull, CSF, grey and white matter) and implemented in 2 mm voxels. We designed a resistor mesh model (RMM), based on the finite volume method (FVM) to simulate the electrical properties of this head model along the three axes for each voxel. Then, we introduced four dipoles of high eccentricity (about 0.8) in this RMM, separately and simultaneously, to compute the potentials for two sets of conductivities. We used the direct cortical imaging technique (CIT) to recover the simulated dipoles, using 60 or 107 electrodes and with or without addition of Gaussian white noise (GWN). The use of realistic conductivities gave better CIT results than standard conductivities, lowering the blurring effect on scalp potentials and displaying more accurate position areas when CIT was applied to single dipoles. Simultaneous dipoles were less accurately localized, but good qualitative and stable quantitative results were obtained up to 5% noise level for 107 electrodes and up to 10% noise level for 60 electrodes, showing that a compromise must be found to optimize both the number of electrodes and the noise level. With the RMM defined in 2 mm voxels, the standard 128-electrode cap and 5% noise appears to be the upper limit providing reliable source positions when direct CIT is used. The admittance matrix defining the RMM is easy to modify so as to adapt to different conductivities. The next step will be the adaptation of individual real head T2 images to the RMM template and the introduction of anisotropy using diffusion imaging (DI).

N270 sensitivity to conflict strength and working memory: A combined ERP and sLORETA study.

The event-related potential N270 component is known to be an electrophysiological marker of the supramodal conflict processing. However little is know about the factors that may modulate its amplitude. In particular, among all studies that have investigated the N270, little or no control of the conflict strength and of the load in working memory have been done leaving a lack in the understanding of this component. We designed a spatial audiovisual conflict task with simultaneous target and cross-modal distractor to evaluate the N270 sensitivity to the conflict strength (i.e., visual target with auditory distractor or auditory target with visual distractor) and the load in working memory (goal task maintenance with frequent change in the target modality). In a first session, participants had to focus on one modality for the target position to be considered (left-hand or right-hand) while the distractor could be at the same side (compatible) or at opposite side (incompatible). In a second session, we used the same set of stimuli as in the first session with an additional distinct auditory signal that clued the participants to frequently switch between the auditory and the visual targets. We found that (1) reaction times and N270 amplitudes for conflicting situations were larger within the auditory target condition compared to the visual one, (2) the increase in target maintenance effort led to equivalent increase of both reaction times and N270 amplitudes within all conditions and (3) the right dorsolateral prefrontal cortex current density was higher for both conflicting and active maintenance of the target situations. These results provide new evidence that the N270 component is an electrophysiological marker of the supramodal conflict processing that is sensitive to the conflict strength and that conflict processing and active maintenance of the task goal are two functions of a common executive attention system.

A case of logopenic primary progressive aphasia with C9ORF72 expansion and cortical florbetapir binding.

We report the case of a 65-year-old woman, clinically diagnosed with the logopenic variant of primary progressive aphasia (PPA), and carrier of C9ORF72 expansion, despite cerebrospinal fluid biomarkers suggesting Alzheimer's disease (AD). She underwent structural MRI, metabolic PET, and amyloid PET imaging using florbetapir. Comparison with healthy controls revealed widespread hypometabolism, left sided cortical atrophy, and an increased cortical amyloid load. No difference in amyloid binding was found between the patient and predemential AD patients. This case provides evidence of amyloidopathy in a carrier of C9ORF72 expansion exhibiting a clinical profile of the logopenic variant of PPA.

Effects of the audiovisual conflict on auditory early processes.

Auditory alarm misperception is one of the critical events that lead aircraft pilots to an erroneous flying decision. The rarity of these alarms associated with their possible unreliability may play a role in this misperception. In order to investigate this hypothesis, we manipulated both audiovisual conflict and sound rarity in a simplified landing task. Behavioral data and event related potentials (ERPs) of thirteen healthy participants were analyzed. We found that the presentation of a rare auditory signal (i.e., an alarm), incongruent with visual information, led to a smaller amplitude of the auditory N100 (i.e., less negative) compared to the condition in which both signals were congruent. Moreover, the incongruity between the visual information and the rare sound did not significantly affect reaction times, suggesting that the rare sound was neglected. We propose that the lower N100 amplitude reflects an early visual-to-auditory gating that depends on the rarity of the sound. In complex aircraft environments, this early effect might be partly responsible for auditory alarm insensitivity. Our results provide a new basis for future aeronautic studies and the development of countermeasures.

LIMO EEG: a toolbox for hierarchical LInear MOdeling of ElectroEncephaloGraphic data.

Magnetic- and electric-evoked brain responses have traditionally been analyzed by comparing the peaks or mean amplitudes of signals from selected channels and averaged across trials. More recently, tools have been developed to investigate single trial response variability (e.g., EEGLAB) and to test differences between averaged evoked responses over the entire scalp and time dimensions (e.g., SPM, Fieldtrip). LIMO EEG is a Matlab toolbox (EEGLAB compatible) to analyse evoked responses over all space and time dimensions, while accounting for single trial variability using a simple hierarchical linear modelling of the data. In addition, LIMO EEG provides robust parametric tests, therefore providing a new and complementary tool in the analysis of neural evoked responses.

Effects of skull thickness, anisotropy, and inhomogeneity on forward EEG/ERP computations using a spherical three-dimensional resistor mesh model.

Bone thickness, anisotropy, and inhomogeneity have been reported to induce important variations in electroencephalogram (EEG) scalp potentials. To study this effect, we used an original three-dimensional (3-D) resistor mesh model described in spherical coordinates, consisting of 67,464 elements and 22,105 nodes arranged in 36 different concentric layers. After validation of the model by comparison with the analytic solution, potential variations induced by geometric and electrical skull modifications were investigated at the surface in the dipole plane and along the dipole axis, for several eccentricities and bone thicknesses. The resistor mesh permits one to obtain various configurations, as local modifications are introduced very easily. This has allowed several head models to be designed to study the effects of skull properties (thickness, anisotropy, and heterogeneity) on scalp surface potentials. Results show a decrease of potentials in bone, depending on bone thickness, and a very small decrease through the scalp layer. Nevertheless, similar scalp potentials can be obtained using either a thick scalp layer and a thin skull layer, and vice versa. It is thus important to take into account skull and scalp thicknesses, because the drop of potential in bone depends on both. The use of three different layers for skull instead of one leads to small differences in potential values and patterns. In contrast, the introduction of a hole in the skull highly increases the maximum potential value (by a factor of 11.5 in our case), because of the absence of potential drop in the corresponding volume. The inverse solution without any a priori knowledge indicates that the model with the hole gives the largest errors in both position and dipolar moment. Our results indicate that the resistor mesh model can be used as a robust and user-friendly simulation tool in EEG or event-related potentials. It makes it possible to build up real head models directly from anatomic magnetic resonance imaging without tessellation, and is able to take into account head heterogeneities very simply by changing volume elements conductivity. Hum. Brain Mapping 21:84-95, 2004.