Amnestic syndrome of the medial temporal type identifies prodromal AD: a longitudinal study.

International audienceOBJECTIVE: To compare the power of tests assessing different cognitive domains for the identification of prodromal Alzheimer disease (AD) among patients with mild cognitive impairment (MCI). BACKGROUND: Given the early involvement of the medial temporal lobe, a precocious and specific pattern of memory disorders might be expected for the identification of prodromal AD. METHODS: A total of 251 patients with MCI were tested at baseline by a standardized neuropsychological battery, which included the Free and Cued Selective Recall Reminding Test (FCSRT) for verbal episodic memory; the Benton Visual Retention Test for visual memory; the Deno 100 and verbal fluency for language; a serial digit learning test and the double task of Baddeley for working memory; Wechsler Adult Intelligence Scale (WAIS) similarities for conceptual elaboration; and the Stroop test, the Trail Making test, and the WAIS digit symbol test for executive functions. The patients were followed at 6-month intervals for up to 3 years in order to identify those who converted to AD vs those who remained stable over time. Statistical analyses were based on receiver operating characteristic curve and Cox proportional hazards models. RESULTS: A total of 59 subjects converted to AD dementia. The most sensitive and specific test for diagnosis of prodromal AD was the FCSRT. Significant cutoff for the diagnosis was 17/48 for free recall, 40/48 for total recall, and below 71% for index of sensitivity of cueing (% of efficacy of semantic cues for retrieval). CONCLUSIONS: The amnestic syndrome of the medial temporal type, defined by the Free and Cued Selective Recall Reminding Test, is able to distinguish patients at an early stage of Alzheimer disease from mild cognitive impairment non-converters

Assessment of Bowel Preparation Using Low-Volume Sulphate-Based Preparations in Comparison with Macrogols: A Multicenter, Randomized, Comparative Clinical Study of the 3rd Phase

Oral sulphate solution (OSS: sodium sulphate, potassium sulphate and magnesium sulphate) is a low-volume osmotic agent for cleansing the intestines.Aim: in a multicentre, prospective, randomized, 3rd phase study with two parallel groups, the effectiveness, safety and tolerability of OSS was evaluated in comparison with Macrogol 4000 with electrolytes (a reference preparation for bowel cleansing in Russia) in adult patients who were scheduled for routine diagnostic colonoscopy.Methods. This study was conducted in three Russian research centres during the March–December, 2015 period. Men and women over the age of 18 scheduled to undergo routine diagnostic colonoscopy were randomly assigned either to the OSS group or to the Macrogol group with a fractional use mode before the colonoscopy. The colonoscopy researchers were not aware of which preparation had been taken by the patients. Anonymized video records were centrally analysed by three experts. The primary end point was the proportion of patients with a successful bowel preparation for colonoscopy ≥6 points, as determined by the Boston Bowel Preparation Scale of quality assessment (BBPS scale).Results. 296 patients were randomized in the study (147 patients were treated with OSS, 149 patients received Macrogol); 294 participants were included in the Intention to Treat population (ITT-population), and 274 participants were included in the population of patients who completed the study according to the protocol (Per-Protocol; PP-population) (139 patients received OSS, 135 patients received Macrogol). The proportion of patients with a successful bowel preparation (BBPS ≥6 scores) was high in both groups (OSS [PP-population]: 97.2 % (95 % confidence interval [CI] 89.5–99.3), Macrogol [PP-population]: 97.7 % (95 % CI: 90.7–99.4)). The corrected difference between the groups was -0.5 % (95 % CI: -4.2–3.3), thereby demonstrating “no less effective” of OSS as compared to Macrogol. Compliance with the drug use regime was higher in the OSS group than in the Macrogol group (95.7 % versus 82.3 %, respectively, p-value = 0.0011, ITT-population).The most common symptom reported in patients was nausea (27.9 % in the OSS group and 12.9 % in the Macrogol group). The proportion of patients who developed nausea was significantly higher in the OSS group than in the Macrogol group (25.2 % compared with 10.2 % when taking the first dose of the preparation (p = 0.0008) and 19.7 % compared with 6.8 % when taking the second dose of the preparation (p = 0.0016)). Differences in other symptoms (bloating, abdominal pain or abdominal discomfort) between the groups were not significant, with the severity of symptoms being generally mild. The safety profile of the investigated preparations in patients with inflammatory bowel disease (IBD) in remission did not differ from that in the general patient population.The differences in terms of secondary endpoints were not identified, including BBPS assessment for different sections of the colon, the level of polyp detection, the duration and completeness of colonoscopy, and the investigator’s satisfaction with the procedure. The analysis by subgroups also did not reveal any significant differences.Conclusion. In this study, the “not less effectiveness” of the sulphate solution was demonstrated as compared to Macrogol in a fractional use mode. Both preparations were well tolerated. Despite the higher incidence of nausea in the OSS group, the patients showed significantly higher compliance with the OSS mode as compared to that of Macrogol.This study is registered with the ClinicalTrials.gov Registry of Clinical Trials, No. NCT02321462

Assessment of Bowel Preparation Using Low-Volume Sulphate-Based Preparations in Comparison with Macrogols: A Multicenter, Randomized, Comparative Clinical Study of the 3rd Phase

Oral sulphate solution (OSS: sodium sulphate, potassium sulphate and magnesium sulphate) is a low-volume osmotic agent for cleansing the intestines.Aim: in a multicentre, prospective, randomized, 3rd phase study with two parallel groups, the effectiveness, safety and tolerability of OSS was evaluated in comparison with Macrogol 4000 with electrolytes (a reference preparation for bowel cleansing in Russia) in adult patients who were scheduled for routine diagnostic colonoscopy.Methods. This study was conducted in three Russian research centres during the March–December, 2015 period. Men and women over the age of 18 scheduled to undergo routine diagnostic colonoscopy were randomly assigned either to the OSS group or to the Macrogol group with a fractional use mode before the colonoscopy. The colonoscopy researchers were not aware of which preparation had been taken by the patients. Anonymized video records were centrally analysed by three experts. The primary end point was the proportion of patients with a successful bowel preparation for colonoscopy ≥6 points, as determined by the Boston Bowel Preparation Scale of quality assessment (BBPS scale).Results. 296 patients were randomized in the study (147 patients were treated with OSS, 149 patients received Macrogol); 294 participants were included in the Intention to Treat population (ITT-population), and 274 participants were included in the population of patients who completed the study according to the protocol (Per-Protocol; PP-population) (139 patients received OSS, 135 patients received Macrogol). The proportion of patients with a successful bowel preparation (BBPS ≥6 scores) was high in both groups (OSS [PP-population]: 97.2 % (95 % confidence interval [CI] 89.5–99.3), Macrogol [PP-population]: 97.7 % (95 % CI: 90.7–99.4)). The corrected difference between the groups was -0.5 % (95 % CI: -4.2–3.3), thereby demonstrating “no less effective” of OSS as compared to Macrogol. Compliance with the drug use regime was higher in the OSS group than in the Macrogol group (95.7 % versus 82.3 %, respectively, p-value = 0.0011, ITT-population).The most common symptom reported in patients was nausea (27.9 % in the OSS group and 12.9 % in the Macrogol group). The proportion of patients who developed nausea was significantly higher in the OSS group than in the Macrogol group (25.2 % compared with 10.2 % when taking the first dose of the preparation (p = 0.0008) and 19.7 % compared with 6.8 % when taking the second dose of the preparation (p = 0.0016)). Differences in other symptoms (bloating, abdominal pain or abdominal discomfort) between the groups were not significant, with the severity of symptoms being generally mild. The safety profile of the investigated preparations in patients with inflammatory bowel disease (IBD) in remission did not differ from that in the general patient population.The differences in terms of secondary endpoints were not identified, including BBPS assessment for different sections of the colon, the level of polyp detection, the duration and completeness of colonoscopy, and the investigator’s satisfaction with the procedure. The analysis by subgroups also did not reveal any significant differences.Conclusion. In this study, the “not less effectiveness” of the sulphate solution was demonstrated as compared to Macrogol in a fractional use mode. Both preparations were well tolerated. Despite the higher incidence of nausea in the OSS group, the patients showed significantly higher compliance with the OSS mode as compared to that of Macrogol.This study is registered with the ClinicalTrials.gov Registry of Clinical Trials, No. NCT02321462

Goal Attainment after Treatment with Abobotulinumtoxina and A Tailored Home Therapy Programme in Children with Upper Limb Spasticity: Descriptive, Exploratory Analysis of A Large Randomized, Controlled StudyA

Objective: This exploratory analysis of a large, randomized, double-blind study (NCT02106351) describes the effect of treatment with abobotulinumtoxinA followed by a tailored home exercises therapy programme in enabling children with upper limb spasticity due to cerebral palsy to achieve their functional goals using goal attainment scaling (GAS). Methods: Children with cerebral palsy and spasticity in ≥ 1 upper limb received up to 4 injection cycles of abobotulinumtoxinA (2 U/kg (cycle 1 only), 8U/kg and 16U/kg) into the elbow and wrist flexors and other upper limb muscles selected to support individual treatment goals. Children followed a home exercises therapy programme, which included stretches and exercises specifically chosen to facilitate goal achievement and engagement in activities. Results: For cycle 1, most children had active function goals set as their primary goal (69.7% vs 19.2% passive function goals). GAS T- scores and goal responder rates at week 16 indicated that most types of primary goal were achieved at least as expected during cycle 1 (all groups). Primary goal GAS T-scores were generally maintained for the first 3 abobotulinumtoxinA treatment cycles. Conclusion: Most children with upper limb spasticity treated with repeat cycles of abobotulinumtoxinA supported by an individualized home exercises therapy programme achieved their functional goals. LAY ABSTRACT Treatment with botulinum toxins (such as abobotulinumtoxinA; aboBoNT-A) is often recommended to treat spasticity of the upper limb to help children with cerebral palsy improve their hand skills. In this large study, children with cerebral palsy were treated with up to 4 aboBoNT-A injection cycles followed by a home exercises programme that was specifically made for each child to help them meet their treatment goals. This study aimed to explore the types of goals the children wanted to achieve with this treatment and the factors that influence goal attainment. Most children in this study had “active function” goals set, including “involving the affected arm more in daily activities” and improving “reaching”, “use of limb as a helping hand” and “grasp and release”. Combined treatment with aboBoNT-A and the exercise programme helped most children achieve their goals, but it was difficult to discern any differences in efficacy between the aboBoNT-A doses used in the study. The authors suggest that the high rates of goal achievement in this study indicate that botulinum toxin should not usually be given without a physiotherapy programme

Dose-Dependent Effects of Abobotulinumtoxina (Dysport®) on Spasticity and Active Movements in Adults With Upper Limb Spasticity: Secondary Analysis of A Phase 3 Study

BACKGROUND: AbobotulinumtoxinA has beneficial effects on spasticity and active movements in hemiparetic adults with upper limb spasticity (ULS). However, evidence-based information on optimal dosing for clinical use is limited. OBJECTIVE: To describe joint-specific dose effects of abobotulinumtoxinA in adults with ULS. DESIGN: Secondary analysis of a phase 3 study (NCT01313299). SETTING: Multicenter, international, double-blind, placebo-controlled clinical trial. PARTICIPANTS: A total of 243 adults with ULS >6 months after stroke or traumatic brain injury, aged 52.8 (13.5) years and 64.3% male, randomized 1:1:1 to receive a single-injection cycle of placebo or abobotulinumtoxinA 500 U or 1000 U (total dose). METHODS: The overall effects of injected doses were assessed in the primary analysis, which showed improvement of angles of catch in finger, wrist, and elbow flexors and of active range of motion against these muscle groups. This secondary analysis was performed at each of the possible doses received by finger, wrist, and elbow flexors to establish possible dose effects. MAIN OUTCOME MEASURES: Angle of arrest (XV1) and angle of catch (XV3) were assessed with the Tardieu Scale, and active range of motion (XA). RESULTS: At each muscle group level (finger, wrist, and elbow flexors) improvements in all outcome measures assessed (XV1, XV3, XA) were observed. In each muscle group, increases in abobotulinumtoxinA dose were associated with greater improvements in XV3 and XA, suggesting a dose-dependent effect. CONCLUSIONS: Previous clinical trials have established the clinical efficacy of abobotulinumtoxinA by total dose only. The wide range of abobotulinumtoxinA doses per muscle groups used in this study allowed observation of dose-dependent improvements in spasticity and active movement. This information provides a basis for future abobotulinumtoxinA dosing recommendations for health care professionals based on treatment objectives and quantitative assessment of spasticity and active range of motion at individual joints. LEVEL OF EVIDENCE: I

AbobotulinumtoxinA is effective in patients with urinary incontinence due to neurogenic detrusor overactivity regardless of spinal cord injury or multiple sclerosis etiology: Pooled analysis of two phase III randomized studies (CONTENT1 and CONTENT2)

BACKGROUND: Neurogenic detrusor overactivity incontinence (NDOI) is often inadequately managed with oral therapy. OBJECTIVE: To assess efficacy and safety of abobotulinumtoxinA (aboBoNT-A; Dysport®; Ipsen Ltd.) according to etiology of NDOI. DESIGN, SETTING, AND PARTICIPANTS: Two phase III, randomized, double-blind studies (CONTENT1 [NCT02660138] conducted in Asia, Europe and North America; CONTENT2 [NCT02660359] conducted in the Americas, Asia, Europe and Oceania) both included patients with spinal cord injury (SCI) or multiple sclerosis (MS), with inadequately managed NDOI, regularly performing clean intermittent catheterization (CIC). INTERVENTION: Patients in CONTENT1 and CONTENT2 received aboBoNT-A injections 600 U (n = 162)/800 U (n = 161), or placebo (n = 162) into the detrusor muscle.OOUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint: mean change from baseline in number of NDOI episodes/week at Week 6. Secondary endpoints: proportion of patients with no NDOI episodes; incontinence-related quality of life (I-QoL); urodynamic parameters; and time-to-retreatment. Safety was also assessed. Statistical analyses were conducted for pooled populations by etiology (aboBoNT-A doses vs. placebo). RESULTS AND LIMITATIONS: Of 485 randomized patients, 341 (70%) and 144 (30%) had SCI and MS etiologies, respectively. A significant reduction was observed in mean NDOI episodes/week at Week 6 with both aboBoNT-A doses versus placebo in the SCI (all p < 0.001) and MS (all p < 0.01) groups, as well as significant improvements in I-QoL and urodynamic parameters. Median time-to-retreatment was longer in patients with MS (48–62 weeks across doses) than those with SCI (39–44 weeks). Safety data were similar between etiologies. Urinary tract infection was the most frequent adverse event; similar numbers were reported across treatment groups. CONCLUSIONS: AboBoNT-A was well tolerated and significantly improved continence and bladder function, and QoL, in patients with SCI or MS with NDOI performing regular CIC. PATIENT SUMMARY: AboBoNT-A injections improved QoL, symptoms, and bladder function in patients with SCI or MS with bladder muscle overactivity that causes incontinence

Frontal Assessment Battery is a marker of dorsolateral and medial frontal functions: A SPECT study in frontotemporal dementia.

International audienceThe objective of this study is to identify the cerebral regions that are assessed by the Frontal Assessment Battery (FAB). Using SPM voxel-based analysis, we looked for correlations between FAB performance and brain SPECT perfusion in 47 patients with the frontal variant of frontotemporal dementia (fv-FTD) recruited by the French FTD research network, a multicentre initiative of French University hospitals with expertise in the field of dementia. A significant correlation was found between FAB performance and perfusion in the medial and dorsolateral frontal cortex bilaterally, independently of age, gender and MMSE. No correlations were observed with orbital frontal or parietal perfusion, in spite of the presence of hypoperfusion in these areas, or with perfusion of any other cortical or subcortical region. These findings confirm that the FAB is an adequate tool for assessing functions related to the dorsolateral and medial frontal cortex, and is thus useful for the evaluation of diseases associated with frontal dysfunction