Amours et neurologie

Introduction

Love is a complex emotional state which is difficult to define. Considering anthropological studies, this feeling can now be divided into three distinct behaviors: lust, attraction for a specific partner and conjugal or filial attachment.

State of art

For each, recent findings have contributed to identify specific neuronal networks which are interconnected as shown by common activation of limbic and paralimbic systems. A major role of arginine/vasopressin and oxytocin has also been pointed out for mate choice and attachment promotion. In the field of neurology, studies about pathologies of love are sparse and mainly focused on sexual disorders. Pathologies of attachment like autism and borderline personality are beginning to be identified.

Perspectives

Future investigations would yield a better understanding of this complex emotional state and a better detection of new pathologies related to a major affective disability.

Conclusion

Neurosciences have contributed to highlight mechanisms involved in love.     

Anticoagulant effects of an antidiabetic drug on monocytes in vitro

Introduction

Monocyte- and microparticle (MP)-associated tissue factor (TF) is upregulated in diabetes. Lipopolysaccharide (LPS) induces expression of TF and alternatively spliced TF (asTF) and increases MP release from monocytes. Using LPS-stimulated TF-bearing human monocytes, we examined whether glibenclamide, a sulfonylurea used to treat diabetes type 2, might possess anticoagulant properties.

Methods

We studied the effects of glibenclamide on cell- and supernatant-associated procoagulant activity (Factor Xa-generating assay and clot formation assay), on expression of TF and asTF (flow cytometry, RT-qPCR, western blot) and on cell viability and MP release (flow cytometry).

Results

Glibenclamide dose-dependently decreased procoagulant activity of cells and supernatants. The reduction in cellular procoagulant activity coincided with reduced expression of TF and asTF in cells, whereas cell viability remained almost unchanged. The glibenclamide-induced reduction in procoagulant activity of supernatants appeared to be associated with a decreased number of released MPs.

Conclusions

Reduction of monocyte- and supernatant-associated procoagulant activity by glibenclamide is associated with decreased expression of TF and asTF and possibly with a reduced MP number. Our data indicate that glibenclamide reduces the prothrombotic state in LPS-stimulated monocytes in vitro. Glibenclamide might therefore also have an anticoagulant effect in vivo, but this needs to be further evaluated.     

Voxelwise meta-analysis of gray matter reduction in major depressive disorder

Background

Voxel-based morphometry (VBM) has been widely used in studies of major depressive disorder (MDD) and has provided cumulative evidence of gray matter abnormalities in patients relative to controls. Thus we performed a meta-analysis to integrate the reported studies to determine the consistent gray matter alterations in MDD.

Methods

A systematic search was conducted to identify VBM studies which contrasted MDD patients against a comparison group. The coordinates of gray matter change across studies were meta-analyzed using the activation likelihood estimation (ALE) method hybridized with the rank-based Genome Scan Meta-Analysis (GSMA) to quantitatively estimate regional gray matter reductions in MDD.

Results

A total of 20 VBM studies comparing 543 major depressive patients with 750 healthy control subjects were included. Consistent gray matter reductions in all MDD patients relative to healthy controls were identified in the bilateral anterior cingulate cortex (ACC), right middle and inferior frontal gyrus, right hippocampus and left thalamus.

Conclusions

Meta-analysis of all primary VBM studies indicates that significant gray matter reductions in MDD are localized in a distributed neural network which includes frontal, limbic and thalamic regions. Future studies will benefit from the use of a longitudinal approach to examine anatomical and functional abnormalities within this network and their relationship to clinical profile, particularly in first-episode and drug-naive MDD patients.     

Disrupted regional homogeneity in treatment-resistant depression: a resting-state fMRI study

Background

Using a newly developed regional homogeneity (ReHo) approach, we were to explore the features of brain activity in patients with treatment-resistant depression (TRD) in resting state, and further to examine the relationship between abnormal brain activity in TRD patients and specific symptom factors derived from ratings on the Hamilton Rating Scale for Depression (HRSD).

Methods

24 patients with TRD and 19 gender-, age-, and education-matched healthy subjects participated in the fMRI scans.

Results

1.

Compared with healthy controls, decreased ReHo were found in TRD patients in the left insula, superior temporal gyrus, inferior frontal gyrus, lingual gyrus and cerebellum anterior lobe (culmen) (p < 0.05, corrected).

2.

Compared with healthy controls, increased ReHo were found in the left superior temporal gyrus, cerebellum posterior lobe (tuber), cerebellum anterior lobe (culmen), the right cerebellar tonsil and bilateral fusiform gyrus (p < 0.05, corrected).

3.

There was no correlation between the ReHo values in any brain region detected in our study and the patients' age, years of education, illness duration, HRSD total score and its symptom factors.

Limitation

The influence of antidepressants to the brain activity in TRD patients was not fully eliminated.

Conclusions

The pathogenesis of TRD may be attributed to abnormal neural activity in multiple brain regions.     

Delirium in children and adolescents: A systematic review of the literature

Objectives

The purpose of this study was to collate all works relating to delirium and probable delirium in children and adolescents published since 1980.

Methods

A systematic review of the literature in all languages published between 1980 and March 2009 was conducted.

Results

The literature is limited to small case series and case reports including a total of 217 children or adolescents with definite delirium and a further 136 children and adolescents with “probable delirium.” These articles, in addition to unsystematic reviews, overviews, editorials, journal commentaries, and pertinent book chapters, are discussed in relation to prevalence, predisposing and precipitating factors, phenomenology, residual psychopathology, mortality, management, and prevention of delirium in childhood and adolescence.

Conclusions

Delirium is an important but neglected disorder of childhood associated with significant morbidity and high mortality. Current clinical practice for management is based on slim empirical evidence.     

A meta-analysis of whole-brain diffusion tensor imaging studies in bipolar disorder

Objectives

White matter abnormalities are one of the most consistently reported findings in neuroimaging studies of bipolar disorder (BD). We conducted an anatomical likelihood estimation meta-analysis of BD whole-brain diffusion tensor imaging (DTI) studies, with the aim of identifying statistically consistent fractional anisotropy (FA) changes reflecting microstructural modifications to white matter in BD.

Methods

We performed online searches of the PUBMED and EMBASE databases in January 2011. Studies were considered for inclusion if they used diffusion tensor MRI, compared a group of subjects with BD with healthy controls and involved whole-brain white matter analysis of FA. The analyses were conducted in Talairach space, using the activation likelihood estimation technique. We carried out a meta-analysis restricted to studies reporting a lower FA in patients with BD than in healthy controls.

Results

Ten studies were included. We identified two significant clusters of decreased FA on the right side of the brain. The first was located in the right white matter, close to the parahippocampal gyrus. Four of the ten studies included contributed to this cluster. The second cluster was located close to the right anterior and subgenual cingulate cortex. These two clusters of decreased FA in BD are crossed by several white matter tracts.

Conclusions

These two clusters of altered FA may underlie the abnormal emotional processing and altered functional limbic connectivity in BD. Explorations based on DTI-based tractography are required to identify the tracts involved in the pathophysiology of BD.     

Periodontopathogens induce soluble P-selectin release by endothelial cells and platelets

Introduction

Soluble P-selectin plays a pivotal role in inflammation and the development of thrombotic and cardiovascular disease. Accordingly, elevated levels of soluble P-selectin are found in periodontitis and (other forms of) inflammatory diseases. However, the cellular source of soluble P-selectin in periodontitis and the effects of periodontopathogens on P-selectin release are unknown.

Material and Methods

Soluble P-selectin was determined in 26 patients with periodontitis and 19 controls.Furthermore, human endothelial cells and platelets were investigated for their ability to elicit soluble and surface P-selectin in response to periodontopathogens A. actinomycetemcomitans Y4 and P. gingivalis. Moreover surface E-selectin and ICAM-1 expression as well as NFκB translocation in response to these bacteria were determined on endothelial cells as well as the formation of platelet-leukocyte complexes.

Results

Plasma levels of soluble P-selectin are significantly elevated in periodontitis and correlate with severity of disease and bacterial infection. Stimulation of endothelial cells with periodontopathogens results in rapid surface expression of P-selectin but does not induce NFκB translocation and subsequent de novo synthesis of P-selectin, E-selectin or ICAM-1. In platelets, bacterial stimulation leads to surface expression of P-selectin and fosters the formation of platelet-leukocyte aggregates within minutes. P-selectin is rapidly shed from the surface of platelets and endothelial cells and results in increased levels of soluble P-selectin.

Conclusions

Periodontopathogens are able to directly cause activation of endothelial cells and platelets within minutes. Given that transient periodontitis-associated bacteremia commonly occurs after tooth brushing or chewing, our data suggest that reduction of periodontopathogens might result in potential cardiovascular benefits.     

Pregnancy affects appraisal of negative life events

Objective

It has been demonstrated that physiological responses to stress are diminished late in pregnancy. This study investigates whether emotional responding is diminished as well by measuring affective responses to specific life events during pregnancy.

Methods

A total of 292 pregnant women reported the occurrence of and affective responses to a range of major life events during gestation. Two analyses were conducted (across events and within events) on these responses to determine whether life events occurring in the first trimester were rated as more stressful than those that occurred in the third trimester.

Results

Both within-event and across-events analyses of responses to life events demonstrated that events occurring early in pregnancy were perceived as more stressful than events occurring later in pregnancy.

Conclusion

Responses to stress and affective state are progressively altered in pregnant women, suggesting that timing of stress exposure during gestation may be critical in determining its impact.     

Psychopathologic, neuropsychological and functional outcome measures during cognitive rehabilitation in schizophrenia: A prospective controlled study in a real-world setting

Background

Cognitive dysfunction has been demonstrated in patients with schizophrenia, and this may affect patients’ functional outcome. The improvement of such dysfunction by means of cognitive remediation interventions has become a relevant target in the care of schizophrenia.

Objective

To assess the effectiveness of the cognitive subprograms of Integrated Psychological Therapy (IPT) on symptomatological, neuropsychological and functional outcome variables and to analyze the relationships between cognitive and functional outcome changes in schizophrenia.

Methods

Thirty-two patients with schizophrenia were assigned to cognitive remediation (IPT-cog) or usual rehabilitative interventions in a naturalistic setting of care. Clinical, neuropsychological and functional outcome variables were assessed at baseline and after 24 weeks of treatment.

Results

The IPT-cog group improved significantly more than the comparison group with respect to psychopathological and functional outcome variables. Moreover, only the IPT-cog group improved significantly in the neuropsychological domains of verbal and working memory, with specific significant correlations between neurocognitive performance and functional outcome changes.

Conclusions

The results of the study confirm the effectiveness of the cognitive remediation component of IPT in schizophrenia, and indicate that some of the changes in functional outcome may be mediated by improvement in specific cognitive domains.     

Is switching antidepressants following early nonresponse more beneficial in acute-phase treatment of depression?: a randomized open-label trial

Rationale

Treatment guidelines for major depressive disorder (MDD) recommend a continuous use of antidepressants for several weeks, while recent meta-analyses indicate that antidepressant efficacy starts to appear within 2 weeks and early treatment nonresponse is a predictor of subsequent nonresponse.

Objectives

We prospectively compared 8-week outcomes between switching antidepressants and maintaining the same antidepressant in early nonresponders, to generate a hypothesis on possible benefits of early switching strategy.

Method

Patients with MDD without any treatment history for the current episode were included. When subjects failed to show an early response (i.e., ≥ 20% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS)) to the initial treatment with sertraline 50 mg at week 2, they were randomly divided into two groups; in the Continuing group, sertraline was titrated at 50-100 mg, whereas sertraline was switched to paroxetine 20-40 mg in the Switching group. A primary outcome measure was a response rate (i.e., ≥ 50% improvement in the MADRS) at week 8.

Results

Among 132 subjects, 41 subjects showed early nonresponse. The Switching group (n = 20) showed a higher rate of responders than the Continuing group (n = 21) (75% vs. 19%: p = 0.002). Further, the Switching group was also superior in the rate of remitters (total score of ≤ 10 in the MADRS) (60% vs. 14%: p = 0.004) and continuous changes in the MADRS (19.0 vs. 7.5: p < 0.001).

Conclusions

Our preliminary findings suggest that patients with MDD who fail to show early response to an initial antidepressant may derive benefits from the early switching antidepressants in the acute-phase treatment of depression.     

Association of the ZNF804A gene polymorphism rs1344706 with white matter density changes in Chinese schizophrenia

Background

ZNF804A gene polymorphism rs1344706, the first genetic risk variant to achieve genome wide significance for schizophrenia, has been linked to neural functional connectivity. Dysconnectivity of WM may be the primary pathological mechanism of schizophrenia. Association of this variant with regional WM density has not been investigated in schizophrenic patients.

Methods

69 healthy controls and 80 patients with schizophrenia underwent genotyping of rs1344706 SNPs, and were examined for WM density (T1-weighted MRI). The association of rs1344706 with WM changes in schizophrenia patients and healthy controls was analyzed using a full-factorial 2 × 2 analysis of variance.

Results

1. There was an interaction on WM density in the left prefrontal lobe between the rs1344706 genotype and schizophrenic diagnosis, where the risk T allele carriers presented higher WM density in the schizophrenia patients and lower WM density in healthy controls in comparison with the non-risk allele carriers.2. The risk allele was associated with an increased WM density of the bilateral hippocampus in both the patients and the healthy group.

Limitation

The influence of antipsychotics to the white matter in schizophrenic patients was not fully eliminated.

Conclusions

The ZNF804A variant may confer risk for schizophrenia by exerting its effects on the WM in the left prefrontal lobe together with other risk factors for schizophrenia.     

Effects of discontinuation of long-term biperiden use on cognitive function and quality of life in schizophrenia

Background

The high use of long-term antiparkinsonian anticholinergic drugs with antipsychotics has been identified as an important issue in the treatment of schizophrenia in Japan. The aim of this study was to evaluate the effects of gradual discontinuation of biperiden, an anticholinergic drug, on cognitive function and quality of life (QOL) in schizophrenia.

Methods

Thirty-four schizophrenic patients who had received a second-generation antipsychotic (SGA) with concomitant biperiden for at least 3 months were enrolled. Before and 4 weeks after discontinuation of biperiden, the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J) and the Schizophrenia Quality of Life Scale (SQLS-J) were administered. Clinical evaluation also included the Positive and Negative Syndrome Scale (PANSS). To compare the practice effect on BACS-J, 10 chronic patients with schizophrenia were assessed without tapering biperiden.

Results

Biperiden was discontinued safely in most patients, and no emergent extrapyramidal symptoms were observed. Significant improvements were shown in attention, processing speed, and composite score, as measured by the BACS-J without practice effect. In addition, the psychosocial condition score on the SQLS-J and the general psychopathology score on the PANSS significantly improved after biperiden discontinuation.

Conclusion

Discontinuation of long-term biperiden use may be warranted in patients with schizophrenia treated with SGAs, as it may improve cognitive function, subjective QOL, and psychiatric symptoms with no significant adverse effects.     

White matter hyperintensities in affected and unaffected late teenage and early adulthood offspring of bipolar parents: A two-center high-risk study

Background

White matter hyperintensities (WMHs) are among the most replicated neuroimaging findings in bipolar disorder (BD). It is not clear whether these lesions are an artifact of comorbid conditions, or whether they are directly associated with the disorder, or even represent biological risk factor for BD.

Methods

To test whether WMHs meet criteria for an endophenotype of BD, we conducted a high-risk design study and recruited 35 affected, 44 unaffected relatives of bipolar probands (age range 15-30 years), matched by age and sex with 49 healthy controls without any personal or family history of psychiatric disorders. The presence of WMHs was determined from Fluid Attenuated Inversion Recovery (FLAIR) scans acquired on a 1.5 Tesla scanner using a validated semi-quantitative scale.

Results

We found mostly low grade WMHs in all groups. The proportion of WMH-positive subjects was comparable between the unaffected high-risk, affected familial and control groups.

Conclusion

White matter hyperintensities did not meet criteria for an endophenotype of BD. Bipolar disorder in young subjects without comorbid conditions was not associated with increased rate of WMHs.     

Place de l’IRM dans l’orientation diagnostique et le suivi des maladies métaboliques : intérêt des nouvelles techniques

Introduction

Conventional MRI allows diagnostic and prognosis approaches for patients with suspected metabolic disease.

Background

Bilateral and symmetrical abnormalities are the most suggestive aspects. Signal characteristics (intensity, difference of signal on various sequences), lesion extension and location provide important etiological information. Non-conventional MRI techniques are particularly interesting for pathophysiology. Different MRI modalities offer promising techniques for monitoring treatments and patient follow-up.

Conclusion

Combining different MRI modalities can contribute to the diagnosis and help improve understanding of the pathogenic mechanisms of adult metabolic diseases; they offer promising options for the prognosis and treatment follow-up.     

Has the incidence of deep vein thrombosis in patients undergoing total hip/knee arthroplasty changed over time? A systematic review of randomized controlled trials

Background

There is a perception in the orthopaedic and thromboembolism community that the incidence of deep vein thrombosis (DVT) has decreased in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA).

Objectives

To assess the incidence of DVT with warfarin thromboprophylaxis over time in patients undergoing elective TKA or THA.

Methods

The MEDLINE, EMBASE, and Cochrane Library databases were searched to October 2006, supplemented by a manual search of reference lists. Two reviewers independently extracted data on study characteristics, quality and the frequency of total, symptomatic and proximal DVT.

Results

Fourteen studies (4,423 patients) were included. Total and proximal DVT after TKA declined over time (r = − 0.75, p = 0.031; r = − 0.86, p = 0.007 respectively). Total and proximal DVT after THA did not change. The risk of developing DVT after TKA was significantly higher than after THA (OR 1.85, 95% CI 1.6 - 2.14; p < 0.0001). The risk of developing symptomatic DVT after THA was significantly higher than after TKA (OR 2.18, 95% CI 1.11 - 4.27; p = 0.012).

Conclusions

The incidence of DVT in patients undergoing elective TKA appears to have declined in patients receiving warfarin thromboprophylaxis.     

Predictors of treatment outcome after cognitive behavior therapy and antispasmodic treatment for patients with irritable bowel syndrome in primary care

Objective

To examine predictors of treatment outcome in IBS-patients who participated in a randomized controlled trial in primary care, where 149 irritable bowel syndrome (IBS) patients were randomized to mebeverine hydrochloride (n=77) or mebeverine+cognitive behavior therapy (CBT) (n=72). CBT offered additional benefit over mebeverine alone.

Methods

Regression analyses were used to identify predictors of work and social adjustment 12 months after treatment ended. The intervention groups were analyzed separately in order to look at the separate effects in each group.

Results

Lower levels of psychological distress (anxiety and depression) at baseline predicted a good outcome in the mebeverine group [β=0.388 (95% CI: 0.065-0.936), P=.025] but not in the mebeverine+CBT group. In the adjusted model for the mebeverine+CBT group less adaptive IBS related behavioral coping predicted a good outcome [β=0.285 (95% CI: 0.002-0.210), P=.045].

Conclusion

Different factors are associated with outcome depending on the treatment received. At assessment clinicians should assess patients coping styles and may want to consider recommending CBT to those patients with IBS in primary care who are engaging in unhelpful coping behavior.     

Static and pulsatile intracranial pressure in idiopathic intracranial hypertension

Objective

The aim of this observational study was to characterize the static and pulsatile intracranial pressure (ICP) in conservatively (medically) treated idiopathic intracranial hypertension (IIH) patients in need of shunt surgery, and also in patients with chronic daily headache (CDH) without visual disturbances.

Methods

The material includes 14 IIH patients and 7 CDH patients in whom ICP was monitored continuously over-night. Static ICP was characterized by mean ICP, pulsatile ICP was characterized by the wave amplitude, rise time, and rise time coefficient.

Results

In the IIH group all 14 had headache and visual disturbances. Mean ICP was high (>15 mmHg) in only 7 patients (50%), while mean ICP wave amplitude was high (≥4 mmHg) in all 14 (100%). All IIH patients were shunted and improved clinically thereafter (i.e., relief from visual disturbances and/or headache). None in the CDH group had high mean ICP or mean ICP wave amplitude, and none were shunted.

Conclusions

In this cohort of 14 conservatively treated IIH patients with lasting and shunt-responsive headache and visual disturbances, the mean ICP wave amplitude was elevated (≥4 mmHg) in all patients despite normal mean ICP (<15 mmHg) in 7 patients (all but one on medication). Therefore, the pulsatile ICP may be more relevant than the static ICP in the diagnostic setting for patients with IIH. Further prospective standardized approaches are warranted.     

Acute panicogenic, anxiogenic and dissociative effects of carbon dioxide inhalation in patients with post-traumatic stress disorder (PTSD)

Background

Increased anxiety and panic to inhalation of carbon dioxide (CO₂) has been described in patients with anxiety disorders, especially panic disorder, compared to healthy subjects. Post-traumatic stress disorder (PTSD) has been hypothesised to resemble panic disorder and is currently classified as an anxiety disorder in DSM-IV. However, there are only very few data available about the sensitivity of patients with PTSD to CO₂.

Methods

In 10 patients with PTSD, 10 sex- and age-matched healthy subjects and 8 patients with panic disorder we assessed anxiety, panic, dissociative and PTSD symptoms before and after a single vital capacity inhalation of 35% CO₂.

Results

Patients with PTSD showed an increased anxiety, panic and dissociative reaction to the inhalation of 35% CO₂ compared to healthy participants. PTSD subjects’ responses were indistinguishable from those of panic patients. Additionally, PTSD-typical symptoms like post-traumatic flashbacks were provoked in patients with PTSD after the inhalation of CO₂.

Conclusions

In our sample, PTSD was associated with an increased CO₂ reactivity, pointing to an increased susceptibility of PTSD patients to CO₂ challenge.     

Progressive paraparesis with sensorineural deafness and leukoencephalopathy revealing neurobrucellosis

Introduction

Brucellosis is a rare disease with variable neurological and imaging manifestations.

Case report

A 54-year-old woman presented with progressive paraparesis and sensorineural hearing loss over 18 months. The presence of diffuse white matter changes on brain magnetic resonance imaging (MRI) and cerebrospinal fluid findings led to the diagnosis of neurobrucellosis. Spinal MRI did not show any lesion that could explain the paraparesis that was finally attributed to the leukoencephalopathic lesions. The patient improved clinically after three months of antibiotic treatment but no significant changes were noticed on brain imaging.

Discussion and conclusion

Neurobrucellosis is a treatable disease which should be discussed when a patient presents with the triade progressive paraparesis, sensorineural hearing loss and leukoencephalopathy on MRI. Outcome can be favorable if adapted treatment is given early.     

Adolescent depressive symptoms and smoking behavior: The gender-specific role of weight concern and dieting

Objective

Increased weight concern and dieting are associated with both depression and smoking among adolescents, particularly girls. This cross-sectional study examined the gender-specific role of weight concerns and dieting on the adolescent depression-smoking association.

Methods

Participants were 2051 adolescents (1056 boys and 995 girls) from seven high schools in the Netherlands who filled out questionnaires on smoking, depression, and weight constructs and of whom weight and height were measured.

Results

Logistic regression analyses showed that for girls, but not for boys, the depression-smoking association disappeared after controlling for weight concerns and dieting.

Conclusion

Our findings indicate that weight concerns and dieting are important factors to consider in the depression-smoking initiation relation for girls, but not for boys. This suggests that smoking prevention programs for depressed girls might be enhanced by challenging the idea of smoking as a diet strategy and incorporating a focus on healthy weight regulation. However, before setting up a prevention trial, future prospective studies should first examine why and how weight concerns and dieting are important factors in the depression-smoking initiation relation among girls, also in conjunction with other established risk factors such as parental and peer smoking.