"Docteur, j'ai mal et des fourmis dans les jambes le soir..." [Doctor, I have pain and pins and needles in my legs at night].

Restless legs syndrome (RLS) is a frequent chronic condition. It causes discomfort in the lower limbs with an urge to move the legs and sometimes paresthesias. It's frequently associated with sleep and mood disorders causing a significant impact on quality of life. There are four clinical criteria to diagnose it. Treatment includes management of reversible factors and if needed symptomatic treatment. Depending on symptoms severity, non-drug measures can be tried. First-line medication treatment should be dopaminergic agonists. Second-line treatments include, anticonvulsivants (gabapentine), benzodiazepine (clonazepam) or opioids based on predominant symptoms. Difficult cases should be referred to a specialist.

Céphalées pharmacorésistantes: nouvelles approches du casse-tête [Drug-resistant headache: is it the end?].

Chronic primary headache often cause significant interference with function and quality of life despite acute and preventive medicines. New treatments are emerging for pharmacologically intractable cluster headache and migraine. Occipital nerve stimulation in chronic cluster headache and botulinum toxin in chronic migraine represent the most promising therapies.

What factors influence long-term antidepressant use in primary care? Findings from the Australian diamond cohort study.

BACKGROUND: Antidepressants are one of the most commonly prescribed drugs in primary care. The rise in use is mostly due to an increasing number of long-term users of antidepressants (LTU AD). Little is known about the factors driving increased long-term use. We examined the socio-demographic, clinical factors and health service use characteristics associated with LTU AD to extend our understanding of the factors that may be driving the increase in antidepressant use. METHODS: Cross-sectional analysis of 789 participants with probable depression (CES-D≥16) recruited from 30 randomly selected Australian general practices to take part in a ten-year cohort study about depression were surveyed about their antidepressant use. RESULTS: 165 (21.0%) participants reported <2 years of antidepressant use and 145 (18.4%) reported ≥2 years of antidepressant use. After adjusting for depression severity, LTU AD was associated with: single (OR 1.56, 95%CI 1.05-2.32) or recurrent episode of depression (3.44, 2.06-5.74); using SSRIs (3.85, 2.03-7.33), sedatives (2.04, 1.29-3.22), or antipsychotics (4.51, 1.67-12.17); functional limitations due to long-term illness (2.81, 1.55-5.08), poor/fair self-rated health (1.57, 1.14-2.15), inability to work (2.49, 1.37-4.53), benefits as main source of income (2.15, 1.33-3.49), GP visits longer than 20min (1.79, 1.17-2.73); rating GP visits as moderately to extremely helpful (2.71, 1.79-4.11), and more self-help practices (1.16, 1.09-1.23). LIMITATIONS: All measures were self-report. Sample may not be representative of culturally different or adolescent populations. Cross-sectional design raises possibility of "confounding by indication". CONCLUSIONS: Long-term antidepressant use is relatively common in primary care. It occurs within the context of complex mental, physical and social morbidities. Whilst most long-term use is associated with a history of recurrent depression there remains a significant opportunity for treatment re-evaluation and timely discontinuation.

Consommation d'alcool et de benzodiozépines au troisième âge [Consumption of alcohol and benzodiazepines in the elderly]

In Switzerland, 9.1% of the general population accept regular consumption of BZD. In 65-74 years age group, 2% of cases display a high-risk alcohol consumption. Moderate risk consumption is present in 5% of cases. For the BZD, the cognitive difficulties settle in an insidious way; for alcohol, the daily consumption of fairly high quantities may lead to cognitive deterioration. At early stages, alcohol abusers show preserved neuropsychological performances. Gradually, the deficits will affect the remaining cognitive functions and become irreversible. This review indicates that the chronic consumption of alcohol and BZD in old age is at the origin of major clinical difficulties that need ad hoc training both for psychiatrists and general practitioners.

EFNS guidelines on cognitive rehabilitation: report of an EFNS task force.

Disorders of language, spatial perception, attention, memory, calculation and praxis are a frequent consequence of acquired brain damage [in particular, stroke and traumatic brain injury (TBI)] and a major determinant of disability. The rehabilitation of aphasia and, more recently, of other cognitive disorders is an important area of neurological rehabilitation. We report here a review of the available evidence about effectiveness of cognitive rehabilitation. Given the limited number and generally low quality of randomized clinical trials (RCTs) in this area of therapeutic intervention, the Task Force considered, besides the available Cochrane reviews, evidence of lower classes which was critically analysed until a consensus was reached. In particular, we considered evidence from small group or single cases studies including an appropriate statistical evaluation of effect sizes. The general conclusion is that there is evidence to award a grade A, B or C recommendation to some forms of cognitive rehabilitation in patients with neuropsychological deficits in the post-acute stage after a focal brain lesion (stroke, TBI). These include aphasia therapy, rehabilitation of unilateral spatial neglect (ULN), attentional training in the post-acute stage after TBI, the use of electronic memory aids in memory disorders, and the treatment of apraxia with compensatory strategies. There is clearly a need for adequately designed studies in this area, which should take into account specific problems such as patient heterogeneity and treatment standardization.

Social dysfunctioning after mild to moderate first-ever stroke at vocational age.

BACKGROUND: With improvements in stroke treatments, the number of patients with dramatic recovery is increasing. However, many of them are still complaining of difficulties in returning to work and every day activities. The aim was to assess work and social dysfunctioning in patients with minor to moderate stroke and explore its contributing factors. METHODS: Consecutive patients were prospectively included at a median 7 months after a first-ever stroke. Scores on the Work and Social Adjustment Scale (WSAS), a generic self-reported scale for assessing social functioning, were correlated with scores on the National Institutes of Health Stroke Scale (NIHSS), activities of daily living, Hospital Anxiety and Depression scale (HAD) and MMSE, Iowa Scale of Personality Changes and return to work at 1 year. RESULTS: Among the 84 included patients (mean age 43.5 years), 57 (68%; 95% CI 57 to 78%) complained of significant perturbation of functioning attributed to stroke. WSAS was highly significantly related to modified Rankin scale, daily living activities, Iowa Scale of Personality Changes and return to work at 1 year. Using ordinal logistic regression, the contributors to WSAS were initial neurological severity (NIHSS at admission), HAD and MMSE. CONCLUSIONS: The study showed that up to 68% of our patients complained of significant work and social dysfunction due to stroke, despite a good clinical outcome. This self-estimation was correlated to external validation criteria, stressing the high burden of stroke from the patient's viewpoint. Moreover, when compared across diseases, social dysfunctioning after mild stroke was as important as in other major disabling diseases.

Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiates.

Drugs of abuse, such as psychostimulants and opiates, are generally considered as exerting their locomotor and rewarding effects through an increased dopaminergic transmission in the nucleus accumbens. Noradrenergic transmission may also be implicated because most psychostimulants increase norepinephrine (NE) release, and numerous studies have indicated interactions between noradrenergic and dopaminergic neurons through alpha1-adrenergic receptors. However, analysis of the effects of psychostimulants after either destruction of noradrenergic neurons or pharmacological blockade of alpha1-adrenergic receptors led to conflicting results. Here we show that the locomotor hyperactivities induced by d-amphetamine (1-3 mg/kg), cocaine (5-20 mg/kg), or morphine (5-10 mg/kg) in mice lacking the alpha1b subtype of adrenergic receptors were dramatically decreased when compared with wild-type littermates. Moreover, behavioral sensitizations induced by d-amphetamine (1-2 mg/kg), cocaine (5-15 mg/kg), or morphine (7.5 mg/kg) were also decreased in knock-out mice when compared with wild-type. Ruling out a neurological deficit in knock-out mice, both strains reacted similarly to novelty, to intraperitoneal saline, or to the administration of scopolamine (1 mg/kg), an anti-muscarinic agent. Finally, rewarding properties could not be observed in knock-out mice in an oral preference test (cocaine and morphine) and conditioned place preference (morphine) paradigm. Because catecholamine tissue levels, autoradiography of D1 and D2 dopaminergic receptors, and of dopamine reuptake sites and locomotor response to a D1 agonist showed that basal dopaminergic transmission was similar in knock-out and wild-type mice, our data indicate a critical role of alpha1b-adrenergic receptors and noradrenergic transmission in the vulnerability to addiction.

Treatment of velopharyngeal insufficiency by autologous fat injection.

Velopharyngeal insufficiency (VPI) is a structural or functional trouble, which causes hypernasal speech. Velopharyngeal flaps, speech therapy and augmentation pharyngoplasty, using different implants, have all been used to address this trouble. We hereby present our results following rhinopharyngeal autologous fat injection in 18 patients with mild velopharyngeal insufficiency (12 soft palate clefts, 4 functional VPI, 2 myopathy). 28 injections were carried out between 2004 and 2007. The degree of hypernasal speech was evaluated pre- and postoperatively by a speech therapist and an ENT specialist and quantified by an acoustic nasometry (Kay Elemetrics). All patients were exhaustively treated with preoperative speech therapy (average, 8 years). The mean value of the nasalance score was 37% preoperatively and 23% postoperatively (p = 0.015). The hypernasality was reduced postoperatively in all patients (1-3 degrees of the Borel-Maisonny score). There were no major complications, two minor complications (one hematoma, one cervical pain). The autologous fat injection is a simple, safe, minimally invasive procedure. It proves to be efficient in cases of mild velopharyngeal insufficiency or after a suboptimal velopharyngoplasty.

Deletion of CREB-Regulated Transcription Coactivator 1 Induces Pathological Aggression, Depression-Related Behaviors, and Neuroplasticity Genes Dysregulation in Mice.

BACKGROUND: Mood disorders are polygenic disorders in which the alteration of several susceptibility genes results in dysfunctional mood regulation. However, the molecular mechanisms underlying their transcriptional dysregulation are still unclear. The transcription factor cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and the neurotrophin brain-derived neurotrophic factor (BDNF) have been implicated in rodent models of depression. We previously provided evidence that Bdnf expression critically rely on a potent CREB coactivator called CREB-regulated transcription coactivator 1 (CRTC1). METHODS: To further evaluate the role of CRTC1 in the brain, we generated a knockout mouse line and analyzed its behavioral and molecular phenotype. RESULTS: We found that mice lacking CRTC1 associate neurobehavioral endophenotypes related to mood disorders. Crtc1(-/-) mice exhibit impulsive aggressiveness, social withdrawal, and decreased sexual motivation, together with increased behavioral despair, anhedonia, and anxiety-related behavior in the novelty-induced hypophagia test. They also present psychomotor retardation as well as increased emotional response to stressful events. Crtc1(-/-) mice have a blunted response to the antidepressant fluoxetine in behavioral despair paradigms, whereas fluoxetine normalizes their aggressiveness and their behavioral response in the novelty-induced hypophagia test. Crtc1(-/-) mice strikingly show, in addition to a reduced dopamine and serotonin turnover in the prefrontal cortex, a concomitant decreased expression of several susceptibility genes involved in neuroplasticity, including Bdnf, its receptor TrkB, the nuclear receptors Nr4a1-3, and several other CREB-regulated genes. CONCLUSIONS: Collectively, these findings support a role for the CRTC1-CREB pathway in mood disorders etiology and behavioral response to antidepressants and identify CRTC1 as an essential coactivator of genes involved in mood regulation.

Acute reversible Charles Bonnet syndrome precipitated by sudden severe anemia.

PURPOSE: To report the sudden onset of reversible Charles Bonnet syndrome precipitated byacute severe anemia. METHODS: The charts of three patients (Usher syndrome, bilateral macular degeneration, and bilateral retinal vein occlusion) with acute Charles Bonnet syndrome in the setting of severe anemia were reviewed. RESULTS: Anemia resulted from bladder surgery, recto-colitis, and severe urinary tract infection. Hemoglobin ranged from 78 to 86 g/L. Decreased visual acuity and formed visual hallucinations (giants, flowers, animals) were present in all three patients. Rapid reversal of Charles Bonnet syndrome and visual acuity improvement followed blood transfusion. CONCLUSIONS: Acute severe anemia can precipitate Charles Bonnet syndrome, which may be reversible by blood transfusion.

Vulnerabilität und psychische Erkrankung

Vulnerability and psychic illness Based on a sample of 1701 college and university students from four different sites in Switzerland, the U.S., and Argentina, this study investigated the interrelationships between insufficient coping skills under chronic stress and impaired general health. We sought to develop standardised means for "early" identification of students at risk of mental health problems, as these students may benefit from "early" interventions before psychiatric symptoms develop and reach clinically relevant thresholds. All students completed two self-report questionnaires: the Coping Strategies Inventory "COPE" and the Zurich Health Questionnaire "ZHQ", with the latter assessing "regular exercises", "consumption behavior", "impaired physical health", "psychosomatic disturbances", and "impaired mental health". This data was subjected to structure analyses based on neural network approaches, using the different study sites' data subsets as independent "learning" and "test" samples. We found two highly stable COPE scales that quantified basic coping behaviour in terms of "activity-passivity" and "defeatism-resilience". The excellent reproducibility across study sites suggested that the new scales characterise socioculturally independent personality traits. Correlation analyses for external validation revealed a close relationship between high scores on the defeatism scale and impaired physical and mental health, hence underlining the scales' clinical relevance. Our results suggested in particular: (1.) the proposed method to be a powerful screening tool for early detection and prevention of psychiatric disorders; (2.) physical activity like regular exercises to play a critical role not only in preventing health problems but also in contributing to early intervention programs.

Infection VIH et personnes âgées [HIV infection and the elderly].

HIV infection is becoming a chronic disease, due to decreased mortality induced by the introduction of combined antiviral treatments. The HIV positive population is aging progressively. HIV infection in the elderly has certain specificities, including a late initial diagnosis, a less marked immune response to treatment and the potential association of multiple comorbidities associated with HIV infection and aging. These factors may affect the quality of life of elderly patients and ultimately lead to increased functional dependence. Screening and specific treatment of comorbidities associated with HIV and aging are particularly recommended.

Partial Cricotracheal Resection in Children: Potential Pitfalls and Avoidance of Complications.

OBJECTIVES: To delineate the various factors contributing to failure or delay in decannulation after partial cricotracheal resection (PCTR) in children. STUDY DESIGN: Case series. SETTING: Academic tertiary medical center. SUBJECTS AND METHODS: A retrospective case review of 100 children who underwent PCTR between 1978 and 2008 for severe subglottic stenosis using an ongoing database. RESULTS: Ninety of 100 (90%) patients were decannulated. Six patients needed secondary tracheostomy. The results of the preoperative evaluation showed grade II stenosis in four patients, grade III in 64 patients, and grade IV in 32 patients. The overall decannulation rate was 100 percent in grade II, 95 percent in grade III, and 78 percent in grade IV stenosis. Fourteen (14%) patients required revision open surgery. The most common cause of revision surgery was posterior glottic stenosis. Partial anastomotic dehiscence was seen in four patients. Delayed decannulation (>1 year) occurred in nine patients. Overall mortality rate in the whole series was 6 percent. No deaths were directly related to the surgery. No iatrogenic recurrent laryngeal nerve injury was present in the entire series. CONCLUSION: Comorbidities and associated syndromes should be addressed before PCTR is planned to improve the final postoperative outcome in terms of decannulation. Perioperative morbidity due to anastomotic dehiscence, to a certain extent, can be avoided by intraoperative judgment in the selection of double-stage surgery when more than five tracheal rings need to be resected. Subglottic stenosis with glottic involvement continues to pose a difficult challenge to pediatric otolaryngologists, often necessitating revision procedures.

Case-control analysis of paternal age and trisomic anomalies.

OBJECTIVES: To determine whether older paternal age increases the risk of fathering a pregnancy with Patau (trisomy 13), Edwards (trisomy 18), Klinefelter (XXY) or XYY syndrome. DESIGN: Case-control: cases with each of these syndromes were matched to four controls with Down syndrome from within the same congenital anomaly register and with maternal age within 6 months. SETTING: Data from 22 EUROCAT congenital anomaly registers in 12 European countries. PARTICIPANTS: Diagnoses with observed or (for terminations) predicted year of birth from 1980 to 2005, comprising live births, fetal deaths with gestational age ≥ 20 weeks and terminations after prenatal diagnosis of the anomaly. Data include 374 cases of Patau syndrome, 929 of Edwards syndrome, 295 of Klinefelter syndrome, 28 of XYY syndrome and 5627 controls with Down syndrome. MAIN OUTCOME MEASURES: Odds ratio (OR) associated with a 10-year increase in paternal age for each anomaly was estimated using conditional logistic regression. Results were adjusted to take account of the estimated association of paternal age with Down syndrome (1.11; 95% CI 1.01 to 1.23). RESULTS: The OR for Patau syndrome was 1.10 (95% CI 0.83 to 1.45); for Edwards syndrome, 1.15 (0.96 to 1.38); for Klinefelter syndrome, 1.35 (1.02 to 1.79); and for XYY syndrome, 1.99 (0.75 to 5.26). CONCLUSIONS: There was a statistically significant increase in the odds of Klinefelter syndrome with increasing paternal age. The larger positive associations of Klinefelter and XYY syndromes with paternal age compared with Patau and Edwards syndromes are consistent with the greater percentage of these sex chromosome anomalies being of paternal origin.