Magnetic resonance study of the influence of tissue damage and cortical reorganization on PASAT performance at the earliest stage of multiple sclerosis

We sought to determine the influence of tissue damage and the potential impact of cortical reorganization on the performance to the Paced Auditory Serial Addition Test (PASAT) in patients at the earliest stage of multiple sclerosis (MS). Magnetization transfer ratio (MTR) imaging and functional magnetic resonance imaging (fMRI) experiments using PASAT as paradigm were carried out in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS) compared to 18 controls. MTR histogram analyses showed structural abnormalities in patients involving the normal-appearing white matter (NAWM) but also the gray matter (GM). Mean PASAT scores were significantly lower in the group of patients taken as a whole, and were correlated with the mean NAWM MTR value. No correlation was observed between PASAT scores and GM MTR. However, in the subgroup of patients with normal PASAT performance (n = 9), fMRI showed larger activations in bilateral Brodmann area 45 (BA45) and right BA44 compared to that in controls (n = 18). In these areas with potentially compensatory reorganization, the whole group of patients (n = 18) showed significantly greater activation than controls (n = 18). Activation in the right BA45 was inversely correlated with the mean NAWM MTR and the peak position of GM MTR histograms of patients. This study indicates that even at the earliest stage of MS, cortical reorganization is present inside the executive system of working memory and could tend to limit the determinant functional impact of NAWM injury on the execution of the PASAT.     

Reticulons as markers of neurological diseases: focus on amyotrophic lateral sclerosis

Reticulons (RTNs) are a family of proteins that are primarily associated with the endoplasmic reticulum. In mammals, four genes have been identified and referred as to rtn1, 2, 3 and the neurite outgrowth inhibitor rtn4/nogo. These genes generate multiple isoforms that contain a common C-terminal reticulon homology domain of 150-200 amino-acid residues. The N-terminal regions of RTNs are highly variable, and result from alternative splicing or differential promoter usage. Although widely distributed, the functions of RTNs are still poorly understood. Much interest has been focused on rtn4/nogo because of its activity as a potent inhibitor of axonal growth and repair. In the present study, we update recent knowledge on mammalian RTNs paying special attention to the involvement of these proteins as markers of neurological diseases. We also present recent data concerning RTN expression in amyotrophic lateral sclerosis, a fatal degenerative disorder characterized by loss of upper and lower motor neurons, and muscle atrophy. The rearrangement of RTN expression is regulated not only in suffering skeletal muscle but also preceding the onset of symptoms, and may relate to the disease process.     

A 24-week randomized, double-blind, placebo-controlled study of escitalopram for the prevention of generalized social anxiety disorder

OBJECTIVE: Escitalopram has proven efficacy in the short-term treatment of generalized social anxiety disorder (SAD). The present relapse prevention study investigated relapse rates during a 24-week, randomized, double-blind, placebo-controlled period in patients with generalized SAD who had responded to 12-week open-label treatment with escitalopram. METHOD: A total of 517 patients with a primary diagnosis of generalized SAD (per DSM-IV criteria) and a Liebowitz Social Anxiety Scale (LSAS) total score of > or = 70 received 12 weeks of open-label treatment with flexible doses (10-20 mg/day) of escitalopram. Of these patients, 371 responded (Clinical Global Impressions-Improvement scale [CGI-I] score of 1 or 2) and were randomly assigned to 24 weeks of double-blind treatment with escitalo-pram (10 or 20 mg/day) (N = 190) or placebo (N = 181), continuing with the dose level administered at the end of the open-label period. Relapse was defined as either an increase in LSAS total score of > or = 10 or withdrawal due to lack of efficacy, as judged by the investigator. The study was conducted from January 2001 to June 2002. RESULTS: Survival analysis of relapse and time to relapse showed a significant advantage for escitalopram compared to placebo (log-rank test: p < .001). The risk of relapse was 2.8 times higher for placebo-treated patients than for escitalopram-treated patients (p < .001), resulting in significantly fewer escitalopram-treated patients relapsing (22% vs. 50%), at both doses. Escitalopram was well tolerated during double-blind treatment of generalized SAD, and only 2.6% of the escitalopram-treated patients withdrew because of adverse events. The overall discontinuation rate, excluding relapses, was 13.2% for patients treated with escitalopram and 8.3% for patients treated with placebo. CONCLUSION: Escitalopram was effective and well tolerated in the long-term treatment of generalized SAD.     

Night-time and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients

BACKGROUND: In newly diagnosed apnoeic patients without a history of hypertension, clinical hypertension is underdiagnosed in at least 40% of the cases. An increase in diastolic blood pressure is the most frequent pattern encountered. OBJECTIVE: To assess clinic and 24-h blood pressure, baroreflex sensitivity and left ventricular mass for identifying the prevalence, the type and the consequences of hypertension in newly diagnosed apnoeic patients. PATIENTS AND METHODS: Fifty-nine unselected patients (age = 48 +/- 12 years, body mass index = 28.1 +/- 4.5 kg/m2) referred to a university hospital sleep laboratory for symptoms suggesting obstructive sleep apnoea were included. Diagnosis of apnoea was accepted when respiratory disturbance index was > or = 15/h of sleep. Blood pressure was considered as normal by their general practitioner and all of them were free of any medication for hypertension. Echocardiography, 24-hour ambulatory blood pressure monitoring and assessment of the baroreflex sensitivity were performed. RESULTS: Forty-two percent of the apnoeic patients demonstrated a clinical hypertension, 34 subjects (58%) had a daytime hypertension, and 45 patients (76%) had a night-time hypertension, using 24-h monitoring. All the daytime hypertensives also had night-time hypertension. Forty-seven of the 59 patients (80%) were hypertensive either in the clinic or using 24-h recording. Diastolic and systolo-diastolic hypertension were the prominent types of hypertension observed both by clinic or ambulatory measurements. Respiratory disturbance index was significantly higher in apnoeic patients suffering isolated diastolic hypertension than in the normotensives (50.9 +/- 26.5/h versus 36.0 +/- 12.3/h, respectively; P = 0.02). The prevalence rate of left ventricular hypertrophy was high (between 15 and 20%) and occurred independently of associated hypertension. Baroreflex sensitivity was altered whatever the type of hypertension and decreased with the severity of obstructive sleep apnoea. CONCLUSION: Hypertension is hugely underdiagnosed in apnoeic patients unknown to be hypertensive. Use of 24-h blood pressure monitoring allowed the diagnosis of twice as much hypertension than did clinical measurement. Even at the beginning of their history of hypertension, apnoeic patients exhibited chronic adaptations of their cardiovascular system, as shown by early changes in baroreflex sensitivity and an increased prevalence of left ventricular hypertrophy.     

High incidence of myocardial ischemia during postpartum hemorrhage

BACKGROUND: Postpartum hemorrhage remains a major cause of global maternal morbidity and mortality, even in developed countries, despite the use of intensive care units. This study sought to (1) assess whether myocardial ischemia could be associated with and even aggravate hemorrhagic shock in young parturients admitted for postpartum hemorrhage, and (2) identify the independent risk factors for myocardial ischemia. METHODS: On their referral to the intensive care unit, a multidisciplinary team managed parturients with severe postpartum hemorrhage. Ventilation, transfusion, catecholamines, surgery, or angiography with uterine embolization were provided as clinically indicated. Plasma cardiac troponin I levels were used as a surrogate marker of acute myocardial injury and electrocardiograms of myocardial ischemia. RESULTS: A total of 55 parturients were referred with severe postpartum hemorrhage, all in hemorrhagic shock. Twenty-eight parturients (51%) had elevated serum levels of cardiac troponin I (9.4 microg/l [3.7-26.6 microg/l]), which were associated with electrocardiographic signs of ischemia and deteriorated myocardial contractility and correlated with the severity of hemorrhagic shock. Indeed, multivariate analysis identified low systolic and diastolic arterial blood pressure (< 88 and < 50 mmHg, respectively) and increased heart rate (> 115 beats/min) as independent predictors of myocardial injury. In addition, all patients who were given catecholamines also had elevated cardiac troponin I levels. CONCLUSIONS: These results suggest that treatment of postpartum hemorrhage-induced hemorrhagic shock should be coupled with concomitant prevention of myocardial ischemia, even in young parturients.     

The effects of prolonged ambulation on labor with epidural analgesia

Ambulation during labor is becoming more popular, although its impact on the progress of labor and on pain intensity remains unclear. We wondered whether prolonged ambulation with epidural analgesia had a possible effect on duration of labor and pain. In this prospective, randomized trial, 61 parturients with uncomplicated term pregnancies were allocated to be recumbent (n = 31) or to ambulate (n = 30). Epidural analgesia was provided with intermittent administrations of 0.08% bupivacaine-epinephrine plus 1 microg/mL of sufentanil. Of the 30 women assigned to the ambulatory group, 25 actually walked. Their ambulating time was 64 +/- 34 min (mean +/- SD), i.e., 29% +/- 16% of the first stage. There were no differences between the two groups in the length of labor and in pain visual analog scale scores. However, the ambulatory group received smaller doses of bupivacaine (6.4 +/- 2.2 mg/h versus 8.4 +/- 3.6 mg/h; P = 0.01) and of oxytocin (6.0 +/- 3.7 mUI/min versus 10.2 +/- 8.8 mUI/min; P < 0.05). A greater ability to void was also found in the ambulatory group (P < 0.01). Although the duration of labor and pain relief was unchanged, these findings support that ambulation during labor may be advantageous. IMPLICATIONS: This study compared the duration of labor and pain relief between parturients receiving epidural analgesia who were ambulated or were recumbent. Whereas walking had no impact on either duration of labor or pain relief, it was associated with a reduction in both bupivacaine and oxytocin requirements.