Adrien Julian

Restless Legs Syndrome and Pregnancy: Follow-Up of Pregnant Women before and after Delivery

Aims: To describe the frequency of restless legs syndrome (RLS) in a French population of randomly selected women during their third trimester of pregnancy and its evolution up to 3 months after delivery and to identify potential factors associated with the improvement of RLS after delivery. Methods: A cross-sectional questionnaire survey. Results: 186 pregnant women living in a French town were included. 32% of women were affected by RLS during the third trimester of their pregnancy. Multiple pregnancies and iron intake during pregnancy were significantly associated with RLS during the third trimester. RLS disappeared after delivery among 64.8% of the women, and by less than 2 weeks after delivery in half of them. This improvement after delivery was not associated with the number of previous pregnancies, the RLS severity and iron intake during pregnancy, peridural anaesthesia, caesarean section, delivery complications, newborn weight, breastfeeding, dopaminergic agent intake after delivery, and with the absence of RLS before pregnancy. Conclusions: RLS affects one third of pregnant women during their third trimester and usually improves after delivery. Although there is no allowed treatment, most of the time only counselling and iron status assessment should be provided.

Restless legs syndrome and pregnancy: a questionnaire study in the Poitiers District, France.

Aims: To perform a large and detailed epidemiologic study on restless legs syndrome (RLS) during pregnancy in a European country. Methods: A cross-sectional questionnaire survey. The questionnaire was distributed by the medical staff in different outpatient waiting rooms (obstetrics and gynecology department of the university hospital, obstetrics and gynecology department of a private clinic, private midwives, private obstetrician-gynecologists, radiological centers before fetal ultrasound examination and general practitioners) in a French town and its surrounding area (200,000 inhabitants): A woman was considered affected if she met the International RLS Study Group criteria for RLS diagnosis. Results: 1,022 pregnant women living in a French town were included. 24% of women were affected by RLS during their pregnancy. The disease was strongly related to the third trimester of pregnancy and had a significant impact on sleep leading to severe nocturnal and diurnal consequences with a high consumption of sleep medication. Conclusions: RLS affects one quarter of pregnant women, essentially during the third trimester and represents an important public health issue with sleep medication intake.

Alzheimer disease: From biomarkers to diagnosis

The discovery of biomarkers, considered as surrogate markers of the underlying pathological changes, led an international work group (IWG) to propose a new conceptual framework for AD in 2007 Dubois et al. (2007). According to the IWG, AD is now defined as a dual clinico-biological entity that can be recognized in vivo, prior to the onset of the dementia syndrome, on the basis of: i) a specific core clinical phenotype comprised of an amnestic syndrome of the hippocampal type and ii) supportive evidence from biomarkers reflecting the location or the nature of Alzheimer-type changes. Therefore, AD is diagnosed with the same criteria throughout all symptomatic phases of the disease based on the biologically-based approach to diagnosis independent of clinical expression of disease severity. The definitions were further clarified in 2010 (Dubois et al., 2010). Although the new criteria are proposed for research purposes, we encourage expert centres with adequate resources to begin to use the proposed algorithm in order to move the field forward and facilitate translation into clinical practice.

Management and therapeutic perspectives in amyotrophic lateral sclerosis

ABSTRACT Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder affecting both upper and lower motor neurons. Despite much research and effort, no clear insights into a unifying hypothesis for the pathogenesis has so far emerged for this disease. Areas covered: We review the main pathophysiological hypotheses and the potential therapeutic targets in ALS, as well as the management of these patients (in order to improve their survival and quality of life). Expert commentary: ALS is a complex neurodegenerative disease, these days considered as a multisystem disorder with predominant motor symptoms (and various clinical forms). Further comprehension of the pathophysiology of this disease is required, although pathophysiological mechanisms (such as TDP-43) show promise in the search for new therapies. There is still no curative treatment for ALS, but the emergence of multidisciplinary specialized ALS clinics has increased both the quality of life and the survival of these patients.

Inflammatory Stress on Autophagy in Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease during 24 Months of Follow-Up.

Recent findings indicate that microglia in Alzheimer’s disease (AD) is senescent whereas peripheral blood mononuclear cells (PBMCs) could infiltrate the brain to phagocyte amyloid deposits. However, the molecular mechanisms involved in the amyloid peptide clearance remain unknown. Autophagy is a physiological degradation of proteins and organelles and can be controlled by pro-inflammatory cytokines. The purpose of this study was to evaluate the impact of inflammation on autophagy in PBMCs from AD patients at baseline, 12 and 24 months of follow-up. Furthermore, PBMCs from healthy patients were also included and treated with 20 μM amyloid peptide 1–42 to mimic AD environment. For each patient, PBMCs were stimulated with the mitogenic factor, phytohaemagglutin (PHA), and treated with either 1 μM C16 as an anti-inflammatory drug or its vehicle. Autophagic markers (Beclin-1, p62/sequestosome 1 and microtubule-associated protein-light chain 3: LC3) were quantified by western blot and cytokines (Interleukin (IL)-1β, Tumor necrosis Factor (TNF)-α and IL-6) by Luminex X-MAP® technology. Beclin-1 and TNF-α levels were inversely correlated in AD PBMCs at 12 months post-inclusion. In addition, Beclin-1 and p62 increased in the low inflammatory environment induced by C16. Only LC3-I levels were inversely correlated with cognitive decline at baseline. For the first time, this study describes longitudinal changes in autophagic markers in PBMCs of AD patients under an inflammatory environment. Inflammation would induce autophagy in the PBMCs of AD patients while an anti-inflammatory environment could inhibit their autophagic response. However, this positive response could be altered in a highly aggressive environment.

Current view and perspectives in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), identified as a distinct clinical entity by Charcot since the end of the nineteenth century, is a devastating and fatal neurodegenerative disorder that affects motor neurons in the brain, brainstem and spinal cord. Survival of patients with ALS is associated with several factors such as clinical phenotype, age at onset, gender, early presence of respiratory failure, weight loss and treatment with Riluzole (the only disease-modifying drug approved for this disease). Nowadays, there is still no curative treatment for ALS: palliative care and symptomatic treatment are therefore essential components in the management of these patients. Nevertheless, the scientific knowledge in the field of ALS motor neuron degeneration is growing, with the prospect of new treatments. Based on this physiopathological knowledge, several new therapeutic targets are being studied, involving various mechanisms such as excitotoxicity, neuroinflammation, mitochondrial dysfunction, oxidative stress, RNA metabolism and other attractive concepts. Moreover, it is also important to identify reliable biomarkers that will be essential components for future therapeutic development and study design in ALS. In this review, we present the main recent advances and promising therapeutics and biomarkers in the field of ALS.

Peripheral Blood Mononuclear Cells of Alzheimer's Disease Patients Control CCL4 and CXCL10 Levels in a Human Blood Brain Barrier Model

BACKGROUND Alzheimers disease (AD) is accompanied by a neuroinflammation triggering chemoattractant signals towards peripheral blood mononuclear cells (PBMCs), which in turn could reduce amyloid plaques after transmigration through the blood brain barrier (BBB). But the chemotactic environment remains unclear. OBJECTIVE To analyze five chemokines known to be involved in AD in three different cellular models to better understand the cellular and molecular interactions in the BBB. METHOD Chemokines (CCL-2, 4 and 5, CXCL10 and CX3CL1) were measured in isolated cells, a BBB model without PBMCs (H4 and hCMEC/D3 cells, a neuroglioma and human endothelial cells, respectively) and in a complete BBB model with PBMCs from AD patients at a moderate stage. In one set of experiments, H4 cells were treated with Aβ42. RESULTS CCL2 and CCL5 significantly increased in hCMEC/D3 and H4 cells in the complete BBB model. In turn, the rate of CCL2 increased in PBMCs whereas for CCL5, it decreased. CXCL10 increased in all cellular actors in the complete BBB model, compared to isolated cells. For CCL4, PBMCs induced a robust increase in H4 and hCMEC/D3. In turn, the level of CCL4 decreased in PBMCs. Furthermore, PBMCs triggered a significant increase in CX3CL1 in hCMEC/D3. Surprisingly, no effect of Aβ42 was observed in the complete BBB model. CONCLUSION These findings highlight the interest of a BBB model in order to explore chemokine production. For the first time, results showed that PBMCs from patients with AD can control the production of CCL4 and CXCL10 in a human BBB model.

Long-term outcome of basilar stenosis in Erdheim-Chester disease: A case report.

Background:Erdheim–Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis. This inflammatory myeloid neoplasm is frequently complicated by neurological symptoms, but stroke is an exceptional manifestation of this disease. Methods:We report the case of a 59-year-old woman who presented a vertebrobasilar stroke secondary to infiltration and severe stenosis of the basilar artery, improved after interferon-alpha therapy. We performed a review of the relevant literature and reported the few other cases described. Results:With our patient, we have found only 7 observations of cerebrovascular disorder in ECD. Most of them had supravascular arteries involvement. Conclusion:Stroke is a rare treatable and potentially reversible complication of ECD. The pathophysiological processes explaining stroke in this disease are uncertain, but periarterial stenosis of cerebral arteries may be a mechanism.

Differential chemokine expression under the control of peripheral blood mononuclear cells issued from Alzheimer’s patients in a human blood brain barrier model

Growing evidence highlights the peripheral blood mononuclear cells (PBMCs) role and the chemokine involvement in the Alzheimer’s disease (AD) physiopathology. However, few data are available about the impact of AD PBMCs in the chemokine signature in a brain with AD phenotype. Therefore, this study analyzed the chemokine levels in a human blood brain barrier model. A human endothelial cell line from the immortalized cerebral microvascular endothelial cell line (hCMEC/D3) and a human glioblastoma U-87 MG cell line, both with no AD phenotype were used while PBMCs came from AD at mild or moderate stage and control patients. PBMCs from moderate AD patients decreased CCL2 and CCL5 levels in endothelial, and also CXCL10 in abluminal compartments and in PBMCs compared to PBMCs from mild AD patients. The CX3CL1 expression increased in endothelial and abluminal compartments with PBMCs from mild AD patients compared to controls. AD PBMCs can convert the chemokine signature towards that found in AD brain, targeting some chemokines as new biomarkers in AD.

Blood Inflammatory Mediators and Cognitive Decline in Alzheimer’s Disease: A Two Years Longitudinal Study

Peripheral inflammatory processes are involved in Alzheimers disease (AD). We aimed to determine whether plasma inflammatory mediator levels at diagnosis are associated with cognitive decline through a 2-year follow-up in AD patients. Patients (n = 109, mean age 79.44 (6.82) years) were included at diagnosis with MMSE scores between 16 and 25, with C-reactive protein <10 mg/L, and without any acute or chronic inflammation status. Plasma IL-1β, IL-6, TNF-α, and CCL5 were measured using Luminex X-MAP technology at baseline, and after one year and two years of follow-up. The mean values of IL-1β, IL-6, TNF-α, and CCL5 at diagnosis were 0.3, 1.94, 6.57, and 69,615.81 pg/mL, respectively. Mean cognitive decline in MMSE was 3.35 points. No correlation between plasmatic value of IL-1β, IL-6, TNF-α, or CCL5 at diagnosis and cognitive decline during the two years of follow-up was found. Cognitive decline in AD does not appear to be predictable by the tested inflammatory mediators.