The use of the driving function in the analysis of endplate current kinetics

The time course of transmitter release at the neuromuscular junction is non-instantaneous and is more prolonged for nerve-evoked endplate currents (EPCs) than for miniature endplate currents (MEPCs). This creates difficulties in the interpretation of the effects of ion channel blocking drugs which greatly increase the rate of EPC decay, resulting in a substantial number of channels being blocked during the EPC rising phase. Apparent changes in peak current and in the EPC/MEPC peak current ratio can be erroneously interpreted as receptor block or effects on quantal content. A method is described for a more precise assessment of receptor block or quantal content in the presence of ion channel block, by calculation of the EPC driving function. The driving function is a measure of the rate of opening of the ion channels in response to transmitter release, and is independent of ion channel block effects. Simulated EPCs with the same decay rate can be created from the driving functions of EPCs in control and in the presence of the drug. The peak current of such EPCs can be compared to reveal any additional receptor block or quantal content effects independent of a drug's ion channel blocking effects.     

La relevancia del tiempo en la epilepsia parcial continua

IntroductionTiming is one of the most important modifiable prognostic factors in the management of status epilepticus. Epilepsia partialis continua (EPC) is a status epilepticus subtype of highly variable, occasionally prolonged, duration. The aim of this study was to analyze the relationship between EPC duration and outcomes.MethodsWe performed an observational prospective study of all patients with EPC admitted to our tertiary hospital between 1 September 2017 and 1 September 2018.ResultsThe sample included 10 patients, of whom 9 were women; median age was 74 years. The most frequent aetiology was cerebrovascular disease (n = 6). EPC onset occurred outside the hospital in 5 patients, with a median time to hospital admission of 4 hours. The median time to treatment onset for all patients was 12.3 hours. The median time from treatment onset to EPC control was 30 hours; time from treatment onset to EPC control showed a strong positive correlation with TT (Spearman's rho = 0.88). Six patients presented hyperglycaemia at onset; this was positively correlated with time from treatment onset to EPC control (rho = 0.71). All 6 patients with hyperglycaemia presented a brain injury explaining the EPC episode.ConclusionsDelays were observed in different phases of EPC management, which was related to longer duration of the episode. Glycaemia was also related to episode duration, probably acting as a triggering factor rather than as the aetiology.     

Vagus nerve stimulation in refractory epilepsy: New indications and outcome assessment

Although vagus nerve stimulation (VNS) is an effective alternative option for patients with refractory epilepsy unsuitable for conventional resective surgery, predictors of a better control of seizure frequency and severity are still unavailable. This prospective study reports on 39 patients, including 4 children affected by epilepsia partialis continua (EPC), who underwent VNS for refractory epilepsy. The overall seizure frequency outcome was classified into three groups according to reduction rate: ≥ 75%, ≥ 50%, and < 50%. Engel and McHugh classifications were also used. The median follow-up period was 36 months. A seizure reduction rate ≥ 50% or EPC improvement was observed in 74% of the patients. Twenty-one out of 35 cases (60%) resulted in Engel classes II and III. Outcome, as defined by the McHugh scale, showed a responder rate of 71%.These results suggest that younger patient age and focal or multifocal epilepsy are related to a better seizure control and cognitive outcome. Vagus nerve stimulation could also be considered as an effective procedure in severe conditions, such as drug-refractory EPC.     

Predictors of outcomes and refractoriness in status epilepticus: A prospective study

ObjectiveThe objective of this study was to determine the predictors of outcomes and refractoriness in status epilepticus (SE).MethodsThis is a prospective study of 59 adult patients with SE who were admitted to the Emergency Department between February 2012 and December 2013. The effects of clinical, demographic, and electrophysiologic features of patients with SE were evaluated. To evaluate outcome in SE, STESS, mSTESS, and EMSE scales were used.ResultsLogistic regression analysis showed that being aged ≥ 65 years (p = 0.02, OR: 17.68, 95% CI: [1.6–198.4]) for the short term and having potentially fatal etiology (p = 0.027, OR: 11.7, 95% CI: [1.3–103]) for the long term were the only independent predictors of poor outcomes; whereas, the presence of periodic epileptiform discharges (PEDs) in EEG was the only independent predictor of refractoriness (p = 0.032, OR: 13.7, 95% CI: [1.3–148.5]). The patients with ≥ 3 Status Epilepticus Severity Score (STESS) did not have poorer outcomes in the short- (p = 0.157) and long term (p = 0.065). There was no difference between patients with 0–2, 3–4, and ≥ 4 mSTESS in the short- and long term in terms of outcome (p = 0.28 and 0.063, respectively). Also, there was no difference between subgroups (convulsive SE [CSE], nonconvulsive SE [NCSE], and epilepsia partialis continua [EPC]) in terms of STESS and mSTESS. When patients with EPC were excluded, both STESS and mSTESS scores of the patients correlated with poorer long-term outcomes (p = 0.025 and 0.017, respectively). The patients with ≥ 64 points in the Epidemiology-based Mortality in SE-Etiology, age, comorbidity, EEG (EMSE-EACE) score and those with ≥ 27 points in EMSE-Etiology, age, comorbidity (EMSE-EAC) score did not have poorer outcomes in the short term (p = 0.06 and 0.274, respectively) while they had significantly poorer outcome in the long term (p < 0.001 and 0.002, respectively). In subgroup analysis, patients with CSE with ≥ 64 points in EMSE-EACE had significantly poorer outcome in the both short- and long term (p = 0.014 and 0.012, respectively), and patients with CSE with ≥ 27 points in EMSE-EAC had significantly poorer outcome in the long term (p = 0.03) but not in the short term (p = 0.186). Outcomes did not correlate with EMSE scores in patients with NCSE and EPC. Status epilepticus was terminated with intravenous (IV) levetiracetam (LEV) in 68.75% of patients and with IV phenytoin (PHT) in 83.3% of patients. No statistically significant difference was found between the two groups in terms of efficacy (p = 0.334).ConclusionBeing aged ≥ 65 years predicts poor short-term outcomes, and having potentially fatal etiology predicts poor long-term outcomes, which highlight the importance of SE treatment management in the elderly. Both STESS and mSTESS are not predictive for poor outcomes in EPC. Excluding patients with EPC, STESS, and mSTESS could predict poor long-term outcomes but not in the short term in SE. Epidemiology-based Mortality in Status Epilepticus score could predict poor outcome in the long term better than STESS and mSTESS. Specifically, EMSE scores correlated with poor outcome in patients with CSE but not with NCSE and EPC. New scales are needed to predict outcome especially in patients with NCSE and EPC. The presence of PEDs in EEG is a predictor of RSE, and EMSE score can also be used to predict RSE. There was no difference in the efficacy of IV LEV and IV PHT in SE. This study is significant for having one of the longest follow-up periods in the literature.     

Effect of the quantal composition, membrane potential and cholinoreceptor density on the temporal flow of the end plate current in the rat under conditions of acetylcholinesterase inhibition]

The factors determining the decay of multiquantal end plate currents (EPC) were studied in the diaphragm muscle of rat by the comparison of EPC and miniature EPC (MEPC) amplitude--temporal characteristics. The decay of EPC (quantal content 25-100) was 1.2 times slower than the decay of MEPC when AChE was active. The AChE inhibition by armine or neostigmine made this difference 10-100 times higher. In most synapses the decay of multiquantal EPC can be approximated by a sum of two or three exponents. It depended on the quantal content and 3-exponential EPC could be transformed in 2-exponential and later to monoexponential ones if increasing concentration of magnesium ions. A slow component of EPCs (but not of MEPC) decay was highly sensitive to concentration of magnesium ions and had 3 times higher dependence of the membrane potential value than that one of MEPC. The irreversible blocking of receptors by alpha-bungarotoxin (alpha-BuTX) accelerated the decay of MEPC but the decay of multiquantal EPC changed in two phases: it was prolonged at the beginning of alpha-BuTX action followed by its acceleration, but never the time of the decay of EPC had achieved the apparent open time of ACh-activated ionic channels. It is suggested that during the multiquantal EPC generation not only the synchronization of opening but the kinetic of ACh-activated channels is changed, probably by blocking of this channels by high concentrations of endogenous ACh.     

Patterns of gaze behavior during an eye-tracking measure of joint attention in typically developing children and children with autism spectrum disorder

This study evaluated whether diagnostic classifications or features of ASD were associated with individual differences in children's gaze pattern during an eye-tracking measure of joint attention. The sample included 21 children with ASD (mean age, 7.3 ± 1.5 years) and 24 typically developing children (mean age, 6.8 ± 1.6 years), matched on receptive language abilities. Results revealed no significant group differences on global measures of gaze allocation (total gaze time allocation). However, significant group differences emerged using a measure evaluating a microstructure of children's gaze (duration of first fixation). In addition, individual differences in children's gaze pattern were reliably predicted by parent report measures of children's social abilities. The majority of children in this sample (including all typically developing children and those children with ASD who scored lowest on the SRS Social Awareness subscale) showed significant modulation in eye-gaze between the two experimental conditions. In contrast, children with ASD who also scored the highest on the SRS Social Awareness subscale consistently failed to modulate their eye gaze in accordance with the experimental condition. This failure to flexibly modulate gaze in the context of a joint attention eye-tracking paradigm may reveal children's limited awareness of social cues that may further limit social learning.     

Correlations between interpersonal and cognitive difficulties: Relationship to suicidal ideation in military suicide attempters

BackgroundUnderstanding suicidal ideation may help develop more effective suicide screening and intervention programs. The interpersonal and the cognitive-deficit theories seek to describe the factors leading to suicidal behavior. In the military setting it is common to find over- and under-reporting of suicidal ideation. This study sought to determine the relationship between these two models and determine to what degree their components can indirectly predict suicidal ideation.MethodsSuicide attempters (n = 32) were compared with non-suicidal psychologically treated peers (n = 38) and controls (n = 33), matched for sex and age (mean 19.7 years). Pearson's analysis was used to quantify the relationship between the variables from the two models and hierarchal regression analysis was used to determine the explanation of suicidal ideation variance by these variables.ResultsSuicide attempters have more difficulties in problem-solving, negative emotion regulation and burdensomeness compared with their peers (P < .001). These variables are all closely correlated with each other and to suicide ideation (r > ± 0.5; P < .001). Prior suicide attempt, loneliness and burdensomeness together explain 65% (P < .001) of the variance in suicidal ideation.ConclusionsSuicidal ideation is strongly correlated with components of interpersonal and cognitive difficulties. In addition to assessing current suicidal ideation, clinicians should assess past suicide attempt, loneliness and burdensomeness.     

Multisystem resiliency moderates the major depression–Telomere length association: Findings from the Heart and Soul Study

Major depressive disorder (MDD) has been associated with reduced leukocyte telomere length (LTL). It is not known, however, whether psychosocial and behavioral protective factors moderate this association. In the current study, we examine whether multisystem resiliency – defined by healthy emotion regulation, strong social connections, and health behaviors (sleep and exercise) – predicts LTL and mitigates previously demonstrated associations between depression diagnosis and LTL. LTL was measured, using a quantitative PCR assay, in 954 patients with stable cardiovascular disease in the Heart and Soul Study. In a fully adjusted model, high multisystem resiliency predicted longer LTL (b = 80.00, SE = 27.17, p = .003), whereas each individual factor did not. Multisystem resiliency significantly moderated the MDD-LTL association (p = .02). Specifically, MDD was significantly related to LTL at 1 SD below the mean of multisystem resiliency (b = −142.86, SE = 56.46, p = .01), but not at 1 SD above the mean (b = 49.07, SE = 74.51, p = .51). This study suggests that MDD associations with biological outcomes should be examined within a psychosocial–behavioral context, because this context shapes the nature of the direct relationship. Further research should explore the cognitive, neural, and other physiological pathways through which multisystem resiliency may confer biological benefit.     

Randomized double-blind comparison of cognitive and EEG effects of lacosamide and carbamazepine

Differential effectiveness of antiepileptic drugs (AEDs) is more commonly determined by tolerability than efficacy. Cognitive effects of AEDs can adversely affect tolerability and quality of life. This study evaluated cognitive and EEG effects of lacosamide (LCM) compared with carbamazepine immediate-release (CBZ-IR). A randomized, double-blind, double-dummy, two-period crossover, fixed-dose study in healthy subjects compared neuropsychological and EEG effects of LCM (150 mg, b.i.d.) and CBZ-IR (200 mg, t.i.d.). Testing was conducted at screening, predrug baseline, the end of each treatment period (3-week titration; 3-week maintenance), and the end of each washout period (4 weeks after treatment). A composite Z-score was derived for the primary outcome variable (computerized cognitive tests and traditional neuropsychological measures) and separately for the EEG measures. Other variables included individual computer, neuropsychological, and EEG scores and adverse events (AEs). Subjects included 60 healthy adults (57% female; mean age: 34.4 years [SD: 10.5]); 44 completed both treatments; 41 were per protocol subjects. Carbamazepine immediate-release had worse scores compared with LCM for the primary composite neuropsychological outcome (mean difference = 0.33 [SD: 1.36], p = 0.011) and for the composite EEG score (mean difference = 0.92 [SD: 1.77], p = 0.003). Secondary analyses across the individual variables revealed that CBZ-IR was statistically worse than LCM on 36% (4/11) of the neuropsychological tests (computerized and noncomputerized) and 0% of the four EEG measures; none favored CBZ-IR. Drug-related AEs occurred more with CBZ-IR (49%) than LCM (22%). Lacosamide had fewer untoward neuropsychological and EEG effects and fewer AEs and AE-related discontinuations than CBZ-IR in healthy subjects. Lacosamide exhibits a favorable cognitive profile.     

Comparison between an automatic and a visual scoring method of the chin muscle tone during rapid eye movement sleep

ObjectiveTo compare two different methods, one visual and the other automatic, for the quantification of rapid eye movement (REM) sleep without atonia (RSWA) in the diagnosis of REM sleep behavior disorder (RBD).MethodsSeventy-four RBD patients (mean age, 62.14 ± 9.67 years) and 75 normal controls (mean age, 61.04 ± 12.13 years) underwent one night video-polysomnographic recording. The chin electromyogram (EMG) during REM sleep was analyzed by means of a previously published visual method quantifying the percentage of 30 s epochs scored as tonic (abnormal, ⩾30%) and that of 2 s mini-epochs containing phasic EMG events (abnormal, ⩾15%). For the computer quantitative analysis we used the automatic scoring algorithm known as the atonia index (abnormal, <0.8). The percentage correct classification, sensitivity, specificity, and Cohen kappa were calculated.ResultsThe atonia index correctly classified 82.6% of subjects, similar to the percentage of correct classifications with individual components of the visual analysis (83.2% each for tonic and phasic), and the combined visual parameters (85.9%). The sensitivity and specificity of automatic analysis (84% and 81%) was similar to the combined visual analysis (89% and 83%). The correlation coefficient between the automatic atonia index and the percentage of visual tonic EMG was high (r = −0.886, P < 0.00001), with moderately high correlation with the percentage of phasic EMG (r = −0.690, P < 0.00001). The agreement between atonia index and the visual parameters (individual or combined) was approximately 85% with Cohen’s kappa, ranging from 0.638 to 0.693.ConclusionSensitivity, specificity, and correct classifications were high with both methods. Moreover, there was general agreement between methods, with Cohen’s kappa values in the ‘good’ range. Given the considerable practical advantages of automatic quantification of REM atonia, automatic quantification may be a useful alternative to visual scoring methods in otherwise uncomplicated polysomnograms.     

An instrument to assess patient satisfaction with epilepsy treatment

AimsPatient satisfaction with antiepileptic drugs is an important component in the management of epilepsy. This study aimed to develop a visual analog scale (VAS) to evaluate patient satisfaction with the effectiveness and tolerability of the current antiepileptic treatment and to identify the most appropriate threshold scores of patient dissatisfaction predictive of a decision to change the antiepileptic drugs.MethodsThis observational study was conducted among patients with epilepsy consulting a neurologist in France. Two anonymous questionnaires were used, one for patients and one for neurologists. The patients' questionnaire assessed satisfaction using a four-point Likert scale and a 10-centimeter VAS. The neurologists' questionnaire evaluated whether the neurologist decided to change the current treatment or not. The determination of the threshold scores predictive of patient dissatisfaction correlated with a change of the medication was performed using analyses of receiver operating characteristic curves. Visual analogue scale scores collected from the patient questionnaire were tested against the responses collected from the neurologist questionnaire.ResultsFive hundred eighteen patient questionnaires and five hundred seven neurologist questionnaires were completed. For the satisfaction with effectiveness and tolerability, the mean VAS scores were 6.7 ± 2.8 and 7.0 ± 2.8, respectively and were, respectively, 6.9 ± 1.7 and 7.0 ± 1.6 for patients who declared to be satisfied with their current antiepileptic drugs and were, respectively, 3.4 ± 1.7 and 3.3 ± 1.9 for those who declared to be dissatisfied. The neurologist decided to change the current antiepileptic drugs in 41.1% (n = 208) of the cases principally because of inadequate effectiveness. With respect to the receiver operating characteristic curves, a VAS threshold of 6 would correctly predict the decision to change the current antiepileptic drugs with sensitivity and specificity values over 73% for both effectiveness and tolerability.ConclusionsThe VAS developed in this study can help patients to evaluate their antiepileptic drugs and to facilitate timely treatment modification when the current treatment is unsatisfactory.     

Measuring attitudes towards suicide: Preliminary evaluation of an attitude towards suicide scale

ObjectivesOur study aimed to validate a previously published scale assessing attitudes towards suicide. Factor structure, convergent and discriminant validity, and predictive validity were investigated.MethodAdult German participants (N = 503; mean age = 24.74 years; age range = 18–67 years) anonymously completed a set of questionnaires. An exploratory factor analysis was conducted, and incongruous items were deleted. Subsequently, scale properties of the reduced scale and its construct validity were analyzed. A confirmatory factor analysis was then conducted in an independent sample (N = 266; mean age = 28.77 years; age range = 18–88 years) to further confirm the factor structure of the questionnaire.ResultsParallel analysis indicated a three-factor solution, which was also supported by confirmatory factor analysis: right to commit suicide, interpersonal gesture and resilience. The subscales demonstrated acceptable construct and discriminant validity. Cronbach's α for the subscales ranged from 0.67 to 0.83, explaining 49.70% of the total variance.ConclusionsPositive attitudes towards suicide proved to be predictive of suicide risk status, providing preliminary evidence for the utility of the scale. Future studies aiming to reproduce the factor structure in a more heterogeneous sample are warranted.     

Occurrence of discal and non-discal changes after sequestrectomy alone versus sequestrectomy and implantation of an anulus closure device

Sequestrectomy alone represents a procedure for the treatment of lumbar disc herniation. For selected cases, an anulus closure device (ACD) can be implanted which may result in lower reoperation rates. However, comparative magnetic resonance imaging (MRI) changes and their clinical relevance of both procedures are unclear and have not been reported so far.Clinical and MRI data of patients after limited discectomy with ACD implantation (group ACD; N = 45) and patients after sequestrectomy alone (group S; N = 40) with primary lumbar disc herniation were compared retrospectively. Pain intensity on the visual analogue pain scale (VAS), oswestry disability index (ODI) or the patient satisfaction index (PSI) were collected. Disc signal intensity, Modic type changes, endplate reactions, anular tears and reherniations were investigated using MRI before and <18 months postoperative. Morphologic changes were correlated with clinical outcome.There was no difference in VAS back, VAS leg or ODI/PSI after the operation although group S showed significantly more reherniations in MRI. The overall rate of repeated surgery at the same level was similar with a trend in favour of the ACD group (P = 0.729). Significantly more patients of the ACD group experienced endplate erosions after surgery (P < 0.001). Both groups experienced progression of disc signal intensity, Modic type changes, and anular tears with most MRI signs being without clinical relevance.ACD implantation is associated with a significantly lower reherniation rate in MRI but showed a significantly higher rate of endplate erosions. The structural changes do not appear to be clinically relevant.     

Comparison of the clinical profile of Parkinson's disease between Spanish and Cameroonian Cohorts

BackgroundThere are limited data in terms of the clinical profile of Parkinson's disease in sub-Saharan African patients.ObjectiveTo compare the clinical profile and access to standard antiparkinsonian therapies of a Cameroonian cohort of patients with an age, sex, and disease duration-matched Spanish cohort (Longitudinal Study of Parkinson's disease, ELEP).MethodsObservational, cross-sectional design. Demographic data were collected and the following ELEP assessments were applied: Scales for Outcomes in Parkinson's disease (SCOPA) Motor, Autonomic, Cognition, Sleep and Psychosocial; Hoehn and Yahr staging; modified Parkinson Psychosis Rating Scale; Cumulative Illness Rating Scale-Geriatrics; Hospital Anxiety and Depression Scale; pain and fatigue visual analog scales; Zarit, and EuroQoL.Results74 patients with idiopathic Parkinson's disease were included (37 from each country) with a mean age of 64.4 ± 10.5 years old, 70.3% males, and mean disease duration of 5.6 ± 5.9 years. Compared to the Spanish cohort, Cameroonians were intermittently treated, less frequently received dopaminergic agonists (p < 0.001), had a trend for taking lower doses of levodopa (p = 0.06), and were more frequently on anticholinergics (p < 0.0005). Cameroonians were more severely impaired in terms of motor (Hoehn Yahr stage, p = 0.03; SCOPA-Motor, p < 0.001), cognitive status (p < 0.001), anxiety and depression (p < 0.001), psychosis (p = 0.008), somnolence, fatigue and pain (p < 0.001, respectively), caregiver burden (p < 0.0001), and quality of life (p = 0.002). Instead, autonomic, comorbidity, and nocturnal sleep problems were similarly found.ConclusionsLimited and intermittent access to dopaminergic drugs has a negative impact on motor symptoms, nonmotor symptoms and quality of life in patients with Parkinson's disease and their caregivers.     

L’attachement du client au thérapeute en psychothérapie : une revue systématique des études empiriques

Attachment theory describes characteristic patterns of relating to close others and has important implications for psychotherapy. Consistent with Bowlby's (1988) secure base conception of attachment in psychotherapy, several instruments have been developed to measure client attachment to therapist. Despite a large number of studies, no review takes into account all published work. The purpose of this systematic review was to compare different measures of client's attachment to therapist, with different groups of client and in different therapeutic contexts. Medline, Embase, Pubmed, PsycInfo, and Web Of Science were searched to identify studies published between 1995 and 2019 reporting on help-seeking client's attachment to therapist. Twenty-five empirical papers met the inclusion criteria. Meta-analyses were conducted for studies that examined client attachment to therapist subscales (Secure, Avoidant–Fearful, Preoccupied–Merger) as correlates of client-rated working alliance (K = 11, 892 clients), and general adult attachment (K = 11, 752 clients). The results show that the client's secure attachment to therapist is strongly correlated with the therapeutic alliance (mean weighted R = 0,71 [95% CI = 0.62–0.79]), moderately correlated with the results, and negatively correlated with the avoidance (mean weighted r = − 0,12 [IC 95% = − 0.06–− 0.21]) and anxiety dimensions (mean weighted R = − 0,11 [IC 95% = − 0.03–− 0.17]) of adult attachment. With the Avoidant–Fearful style, results go in the opposite direction, negatively correlated with the therapeutic alliance (mean weighted R = − 0.55 [IC 95% = − 0.59–− 0.50]), negatively correlated with the results, and correlated with the avoidance dimension of adult attachment (mean weighted R = 0,16 [IC 95% = 0.09–0.23]). The Preoccupied–Merger style shows weak (positive or negative) to zero correlations. In addition, nine studies looked at some dimensions of the psychotherapy process (e.g., resistance, transference, emotions, self-disclosure, and attitude toward psychotherapy), showing that insecurity of attachment to the therapist (both Avoidant–Fearful style and Preoccupied–Merger style) seem to interfere in one way or another with the development of a productive psychotherapy process. Overall, these results are in line with what was expected. They are consistent with Bowlby's conception of a secure base of attachment in psychotherapy. They showed that dysfunction and maladaptive developmental experience interfere with adult's ability needed to establish secure attachments and that psychotherapy may play the role of what has been previously defined as corrective emotional–or intersubjective–experience. In addition, these results do not seem to vary according to the instruments used. Together, the high correlation with therapeutic alliance and the weak correlation with pretherapy adult attachment confirm the relevance of the client's attachment to therapist as a specific variable related to the process of change in psychotherapy.     

Bursts and oscillations as independent properties of neural activity in the parkinsonian globus pallidus internus

Bursts and oscillatory modulations in firing rate are hallmark features of abnormal neuronal activity in the parkinsonian Globus Pallidus internus (GPi). Although often implicated together in the pathophysiology of parkinsonian signs, little is known about how burst discharges and oscillatory firing (OF) relate to each other. To investigate this question, extracellular single-unit neuronal activity was recorded from 132 GPi cells in 14 Parkinson's disease patients. We found that burst firing was equally prevalent in OF and non-oscillatory firing (NOF) cells (p > 0.5). More than half of the cells were characterized by either aperiodic bursty activity or OF, but not both. OF and NOF cells had statistically-indistinguishable levels of mean burstiness (p = 0.8). Even when bursting and OF co-existed in individual cells, levels of burstiness and oscillatory power were seldom correlated across time. Interestingly, however, the few OF cells with spectral peaks between 8–13 Hz (α-range) were substantially burstier than other cells (p < 0.01) and showed an unique burst morphology and stronger temporal correlations between oscillatory power and burstiness. We conclude that independent mechanisms may underlie the burst discharges and OF typical of most neurons in the parkinsonian GPi.     

One step closer to a global tool for rapid screening of major depression in epilepsy: Validation of the French NDDI-E

ObjectiveDepression in people with epilepsy (PWE) is underdiagnosed and undertreated. The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a screening questionnaire used for detecting major depressive episode (MDE) in PWE, and is already validated in 10 languages. However a version in French, one of the world's widely spoken languages, was, until now, lacking. We aimed to translate and validate the French NDDI-E.MethodsThis study was performed under the auspices of the ILAE. People with epilepsy > 18 years of age were recruited from 2 specialist epilepsy units in Marseille, France. Two native French speakers and 2 native English speakers performed a forward–backward translation. The Mini International Neuropsychiatric Interview (MINI) was performed as the gold standard, and the Center for Epidemiological Studies Depression symptoms index (CES-D) was performed for external validity. Data were compared between PWE with MDE and PWE without MDE using the chi-square test and Student's t-test. Internal structural validity, external validity, and receiver operator characteristics were analyzed.ResultsTesting was performed on 116 PWE: mean age = 40.39 years (SD = 13.83, range: [18–81] years old); 58.6% (68) were women; 87.1% had focal epilepsy. Using the MINI, we found that 33 (28.4%) patients had current MDE and that 15 (12.9%) patients had dysthymia; also, we found that 37 (31.9%) patients presented suicidal ideation and/or behavior. Cronbach's alpha coefficient was 0.838, indicating satisfactory internal consistency. Correlation between the NDDI-E and the CES-D scores was high (r(116) = 0.817, p < 0.0001), indicating good external validity. Receiver operator characteristic analysis showed an area under the curve of 0.958 (95% CI = 0.904–0.986), (p < 0.0001), indicating good capacity of the NDDI-E to detect MDE (defined by MINI). The cutoff for maximal sensitivity and specificity was 15. The mean NDDI-E score in PWE with MDE was 18.27 (SD = 2.28), and the mean NDDI-E score in PWE without MDE was 10.61 (SD = 3.63).SignificanceThis study validated the French NDDI-E, with a cutoff score of 15/24 for MDE, similar to previous studies, and reinforces the NDDI-E as a global tool for detection of MDE.     

Minimum duration of actigraphy-defined nocturnal awakenings necessary for morning recall

BackgroundHealthy adults awaken between each sleep cycle approximately 5 times each night but generally do not remember all of these awakenings in the morning. A rule of thumb has arisen in the sleep field that approximately 5 min of continuous wakefulness are required to form a memory for an awakening. However, few studies have examined memory for these sleep-wake transitions and none have done so in the home, while participants follow their normal routine.MethodsSelf-report and actigraphy were used in the participant’s home environment to determine the minimum duration of an awakening necessary for morning recall for each of the 39 healthy adults.ResultsRecall thresholds ranged from 30 to 600 s with a mean of 259 s (4 min 19 s) and were negatively associated with sleep efficiency but not significantly associated with total sleep time, age, income, or education. There also was a sex by cohabitation interaction, with single men having lower thresholds than single women and cohabiting participants, which was explained by higher sleep efficiency in noncohabitating men. Large individual differences suggest that many factors may influence recall threshold.ConclusionsOur preliminary study is the first to calculate the duration of wakefulness necessary for morning recall of nocturnal awakenings and the first to use a field-based design, allowing for the study of habitual sleep patterns at the participant’s home. Further study is needed to explore if recall thresholds calculated using actigraphy can be validated against polysomnography (PSG) or be used to guide potential treatments.     

Evaluating the effects of amantadin,modafinil and acetyl-l-carnitine on fatigue in multiple sclerosis – result of a pilot randomized,blind study

ObjectiveFatigue affects more than 60% of multiple sclerosis (MS) patients and is one of the most troublesome symptoms of the disease. Current treatment options for MS fatigue include amantadine, modafinil and acetyl-l-carnitine (ALCAR). The aim of our study was to compare efficacy of amantadine, modafinil and ALCAR with placebo in patients with MS.MethodsPatients with MS and a disability level ≤5.5 on the Kurtzke Expanded Disability Status Scale (EDSS) and fatigue were included in the study. Patients were assigned to a one month treatment with either amantadine 200 mg, ALCAR 2 g, modafinil 200 mg or placebo. Efficacy of the treatment was evaluated by using the modified fatigue impact scale (MFIS).ResultsSixty patients were included in the study (39 females). The mean age of patients was 38 ± 6.7 years and the mean disease duration was 6.6 ± 1.2 years. Contrast analysis showed significantly lower mean MFIS score after one month in patients on amantadine compared to placebo (mean difference = 17.3, p = 0.001). There was also a trend of a lower MFIS score in ALCAR group in comparison to placebo (mean difference = 12.4, p = 0.05, with Keppel-corrected alpha of 0.046). The quality of life measured as SF 36 – PCS and SF 36 – MCS proved to be significantly influenced by treatment.ConclusionOne month treatment with amantadine improved fatigue in patients with relapsing-remitting MS as evaluated by MFIS. No or only a trend of improvement was seen in patients treated with modafinil or ALCAR, respectively.     

Effects of nidus microarchitecture on cerebral arteriovenous malformation hemodynamics

Intranidal vessel geometry and organization underlying flow within cerebral arteriovenous malformations (AVM) is poorly understood. We examine the relationship between intranidal vessel characteristics and AVM flow. Records of patients with AVM evaluated at our institution between 2007 and 2013 were retrospectively reviewed. Patients were included if surgical specimens were available and flows were obtained before treatment using quantitative magnetic resonance angiography. Intranidal vessels were identified and the diameter and cross-sectional area of each vessel were measured from digitized images of specimen slides. The relationship between vessel diameter, vessel cross-sectional area, AVM volume, and AVM flow was assessed. Twenty-nine patients were included. Mean total number of vessels per specimen was 133. Mean total AVM flow was 340 ± 276 mL/min. Mean vessel diameter ranged from 0.18–2.37 mm and mean vessel cross-sectional area ranged from 0.09–9.46 mm². Linear regression analysis showed that total flow is significantly associated with larger AVM volume (R² = 0.28, P = 0.007), but not with number of vessels per section of the specimen (P = 0.20) or mean vessel diameter (P = 0.92). Exponential regression analysis demonstrated that AVM flow is significantly correlated to the sum of the cross-sectional vessel areas within each specimen (R² = 0.16, P = 0.05). Total AVM flow is significantly related to sum of the cross-sectional areas of all vessels within each nidus, rather than to total number of vessels or mean nidal vessel diameter. This finding suggests that the sum of the cross-sectional areas of intranidal vessels likely determines the resistance to flow within a cerebral AVM.