Therapeutic hypnosis in a child with a written language disorder.

Children with Attentional Deficit Hyperactivity Disorder (ADHD) frequently have low self-awareness and attentional deficits on which therapeutic hypnosis can have a positive impact. Here we investigated the contribution of therapeutic hypnosis in the treatment of written language disorders in a child with ADHD. This study is a Single-Case Experimental Design (SCED) using repeated measures. The participant is 11 years old. We assessed reading performance and verbal fluency for four weeks before starting the intervention, as well as during the therapeutic window when four hypnosis sessions were administered over an 8-week timeframe. We assessed written language through a regular and irregular word reading test, a spelling choice test, a phonological analysis test, and a fast serial naming test pre- and post-intervention. We assessed attention and self-esteem pre- and post-intervention. The patient's scores on text reading improved during the intervention compared to the baseline (p = .028). Reading fluency improved, but the pre-post comparison did not reach statistical significance. A progression in scores and response times in phonological tests was observed, with the participant moving from pathological scores in the pre-intervention to normative scores in the post-intervention. Attention and self-esteem significantly improved after the treatment (p = .031, and p = .002 respectively). These results indicate that hypnosis-based therapy might be beneficial to children with specific written language disorders. If these results are confirmed in future studies, therapeutic hypnosis may become part of the recommendations for treatment of ADHD.

Antitumoral effect of local injection of TLR-9 agonist emulsified in Lipiodol with systemic anti-PD-1 in a murine model of colorectal carcinoma.

Introduction: Local treatments of cancer, including transarterial chemoembolization, could enhance responses to systemic immune checkpoint inhibitors such as anti-PD-1 antibodies. Lipiodol, a radiopaque oil, is widely used for transarterial chemoembolization as a tumor-targeting drug carrier and could be used in emulsion with immunomodulators. This study aimed at evaluating the antitumoral effect of intra-tumoral injection of Lipiodol-immunomodulator emulsions combined with systemic anti-PD-1 therapy in a murine model of colorectal carcinoma. Method: Mice (male BALB/c) with anti-PD-1-resistant subcutaneous CT26 tumors were injected with immunomodulators, emulsified or not with Lipiodol (N=10-12/group). Results: The TLR-9 agonist CpG displayed antitumor effects, while Poly I:C and QS21 did not. The Lipiodol-CpG emulsion appeared to be stable and maintained CpG within tumors for a longer time. Repeated intra-tumoral injections, combined with anti-PD-1, induced responses towards the tumor as well as to a distant metastatic-like nodule. This treatment was associated with an increase in proliferative CD8+ T cells and of IFN-γ expression, a decrease in proliferative regulatory T cells but also, surprisingly, an increase in myeloid derived suppressor cells. Conclusions: Local administration of CpG emulsified with Lipiodol led to an effective antitumoral effect when combined to systemic anti-PD-1 therapy. Lipiodol, apart from its radiopaque properties, is an efficient drug-delivery system. The formulated oil-in-water emulsion allows efficient loading and control release of CpG, which induces favorable immune modifications in this murine tumor model.

Long-term Gadolinium Retention in the Healthy Rat Brain: Comparison between Gadopiclenol, Gadobutrol, and Gadodiamide.

Background Safety concerns caused by gadolinium retention call for the development of high-relaxivity gadolinium-based contrast agents (GBCAs) allowing minimal dosing. Purpose To investigate brain gadolinium retention in healthy rats after exposure to gadopiclenol (Elucirem, Guerbet; macrocyclic GBCA) compared with gadobutrol (Gadovist or Gadavist, Bayer; macrocyclic GBCA) and gadodiamide (Omniscan, GE Healthcare; linear GBCA) over 1 year. Materials and Methods In this study conducted between May 2018 and April 2020, 9-week-old healthy Sprague Dawley rats received five injections of either gadopiclenol, gadobutrol, or gadodiamide (2.4 mmol of gadolinium per kilogram of body weight for each), or saline (control animals) over a period of 5 weeks. Rats were randomly assigned to different groups (six female and six male rats per group). MRI examinations were performed before euthanasia at 1, 3, 5, or 12 months after the last injection. Brains were sampled to determine the total gadolinium content via inductively coupled plasma mass spectrometry (ICP-MS), to characterize gadolinium species with size exclusion chromatography (SEC)-ICP-MS, and to perform elemental mapping with laser ablation (LA)-ICP-MS. Mann-Whitney tests were performed on pairwise comparisons of the same time points. Results For both macrocyclic agents, no T1 signal hyperintensities were observed in the cerebellum, and approximately 80% of gadolinium washout was found between 1 month (gadobutrol, 0.30 nmol/g; gadopiclenol, 0.37 nmol/g) and 12 months (gadobutrol, 0.062 nmol/g; gadopiclenol, 0.078 nmol/g). After 12 months, only low-molecular-weight gadolinium species were detected in the soluble fraction. Gadodiamide led to significantly higher gadolinium concentrations after 1 month in the cerebellum (gadodiamide, 2.65 nmol/g; P < .001 vs both macrocyclics) combined with only 15% washout after 12 months (gadodiamide, 2.25 nmol/g) and with gadolinium detected bound to macromolecules. Elemental bioimaging enabled visualization of gadolinium deposition patterns colocalized with iron. Conclusion Gadopiclenol and gadobutrol demonstrated similar in vivo distribution and washout of gadolinium in the healthy rat brain, markedly differing from gadodiamide up to 12 months after the last injection. © RSNA, 2022 Online supplemental material is available for this article.

Pitolisant, a wake-promoting agent devoid of psychostimulant properties: Preclinical comparison with amphetamine, modafinil, and solriamfetol.

Several therapeutic options are currently available to treat excessive daytime sleepiness (EDS) in patients suffering from narcolepsy or obstructive sleep apnea. However, there are no comparisons between the various wake-promoting agents in terms of mechanism of action, efficacy, or safety. The goal of this study was to compare amphetamine, modafinil, solriamfetol, and pitolisant at their known primary pharmacological targets, histamine H3 receptors (H3R), dopamine, norepinephrine, and serotonin transporters, and in various in vivo preclinical models in relation to neurochemistry, locomotion, behavioral sensitization, and food intake. Results confirmed that the primary pharmacological effect of amphetamine, modafinil, and solriamfetol was to increase central dopamine neurotransmission, in part by inhibiting its transporter. Furthermore, solriamfetol increased levels of extracellular dopamine in the nucleus accumbens, and decreased the 3,4-dihydroxyphenyl acetic acid (DOPAC)/DA ratio in the striatum, as reported for modafinil and amphetamine. All these compounds produced hyperlocomotion, behavioral sensitization, and hypophagia, which are common features of psychostimulants and of compounds with abuse potential. In contrast, pitolisant, a selective and potent H3R antagonist/inverse agonist that promotes wakefulness, had no effect on striatal dopamine, locomotion, or food intake. In addition, pitolisant, devoid of behavioral sensitization by itself, attenuated the hyperlocomotion induced by either modafinil or solriamfetol. Therefore, pitolisant presents biochemical, neurochemical, and behavioral profiles different from those of amphetamine and other psychostimulants such as modafinil or solriamfetol. In conclusion, pitolisant is a differentiated therapeutic option, when compared with psychostimulants, for the treatment of EDS, as this agent does not show any amphetamine-like properties within in vivo preclinical models.

[Mindfulness meditation for family caregivers]. / La méditation de pleine conscience pour les aidants familiaux.

A significant proportion of elderly people suffering from neurodegenerative pathologies are cared for by an informal caregiver. From the earliest stages of the disease, the psychological and behavioural disorders of patients constitute stress and anxiety factors for their caregivers. Mindfulness meditation has proven its usefulness in the management of anxiety. A study proposes caregiver management based on a mindfulness meditation program.

Voxel-based assessments of treatment effects on longitudinal brain changes in the Multidomain Alzheimer Preventive Trial cohort.

The Multidomain Alzheimer Preventive Trial was designed to assess the effect of omega-3 supplementation and multidomain intervention on cognitive decline of subjects with subjective memory complaint. In terms of cognitive testing, no significant effect was found. In this paper, we evaluate the effect of the interventions on the brain morphological changes. Subjects with magnetic resonance imaging acquisitions at baseline and at 36 months were included (N = 376). Morphological changes were characterized by volume measurements and nonlinear deformation. The multidomain intervention was associated with a significant effect on the 3-year brain morphological changes in the deformation-based approach. Differences were mainly located in the left periventricular area next to the temporoparietal junction. These changes were associated with better cognitive performance and mood/behavior stabilization. No effect of the omega-3 supplementation was observed. This result suggests a possible effect on cognition, not yet observable after 3 years. We argue that neuroimaging could help define whether early intervention strategies are effective to delay cognitive decline and dementia.

Recommendations for the Nonpharmacological Treatment of Apathy in Brain Disorders.

Apathy is a common neuropsychiatric syndrome observed across many neurocognitive and psychiatric disorders. Although there are currently no definitive standard therapies for the treatment of apathy, nonpharmacological treatment (NPT) is often considered to be at the forefront of clinical management. However, guidelines on how to select, prescribe, and administer NPT in clinical practice are lacking. Furthermore, although new Information and Communication Technologies (ICT) are beginning to be employed in NPT, their role is still unclear. The objective of the present work is to provide recommendations for the use of NPT for apathy, and to discuss the role of ICT in this domain, based on opinions gathered from experts in the field. The expert panel included 20 researchers and healthcare professionals working on brain disorders and apathy. Following a standard Delphi methodology, experts answered questions via several rounds of web-surveys, and then discussed the results in a plenary meeting. The experts suggested that NPT are useful to consider as therapy for people presenting with different neurocognitive and psychiatric diseases at all stages, with evidence of apathy across domains. The presence of a therapist and/or a caregiver is important in delivering NPT effectively, but parts of the treatment may be performed by the patient alone. NPT can be delivered both in clinical settings and at home. However, while remote treatment delivery may be cost and time-effective, it should be considered with caution, and tailored based on the patient's cognitive and physical profile and living conditions.

[Techniques from EMDR Psychotherapy : a tool against disruptive psycho-behavioural disorders?] / Techniques issues de la psychothérapie EMDR : un outil contre les troubles psycho-comportementaux ?

Behavioural disorders in residential care facilities for dependent seniors are particularly common in residents with Alzheimer's and related diseases. Verbal agitation is one of the most disruptive behavioural disorders. The use of techniques from Eye Movement Desensitisation and Reprocessing therapy in gerontology, its applications and research perspectives may be illustrated.

Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial.

BACKGROUND: No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline. METHODS: The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT00672685). FINDINGS: 1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0·093 (95% CI 0·001 to 0·184; adjusted p=0·142) for the combined intervention group, 0·079 (-0·012 to 0·170; 0·179) for the multidomain intervention plus placebo group, and 0·011 (-0·081 to 0·103; 0·812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events. INTERPRETATION: The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings. FUNDING: French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.

Synthesis and evaluation of a 2-benzothiazolylphenylmethyl ether class of histamine H4 receptor antagonists.

Synthesis and biological evaluation of a new class of histamine H4 receptor ligands, distinct from the previously reported chemotypes, are described. A virtual screening of our corporate compound collection identified a hit with an undesired dual H3R/H4R activity. Chemical exploration led to the discovery of a more potent and selective 2-benzothiazolylphenylmethyl ether lead compound.

Discrimination of benign and malignant lymph nodes at 7.0T compared to 1.5T magnetic resonance imaging using ultrasmall particles of iron oxide: a feasibility preclinical study.

RATIONALE AND OBJECTIVES: To investigate the feasibility and performance of 7T magnetic resonance imaging compared to 1.5T imaging to discriminate benign (normal and inflammatory changed) from tumor-bearing lymph nodes in rabbits using ultrasmall particles of iron oxide (USPIO)-based contrast agents. MATERIALS AND METHODS: Six New Zealand White rabbits were inoculated with either complete Freund's adjuvant cell suspension (n = 3) to induce reactively enlarged lymph nodes or with VX2 tumor cells to produce metastatic lymph nodes (n = 3). Image acquisition was performed before and 24 hours after bolus injection of an USPIO contrast agent at 1.5T and afterward at 7T using T1-weighted and T2*-weighted sequences. Sensitivities, specificities, and negative and positive predictive values for the detection of lymph node metastases were calculated for both field strengths with histopathology serving as reference standard. Sizes of lymph nodes with no, inflammatory, and malignant changes were compared using a Mann-Whitney U-test. RESULTS: All 24 lymph nodes were detected at 1.5T as well as at 7T. At 1.5T, sensitivity amounted to 0.67, while specificity reached a value of 1. At the higher field strength (7T), imaging was able to reach sensitivity and specificity values of 1. No statistical differences were detected concerning lymph node sizes. CONCLUSIONS: Magnetic resonance lymphography with USPIO contrast agents allows for differentiation of normal and reactively enlarged lymph nodes compared to metastatic nodes. First experiments at 7T show promising results compared to 1.5T, which have to be evaluated in further trials.

Memantine effects measured with the Relevant Outcome Scale for Alzheimer's disease in an open-label, single-arm, multicenter clinical study.

OBJECTIVE: The Relevant Outcome Scale for Alzheimer's disease (ROSA) is a novel, valid, and reliable instrument for multidimensional assessment of Alzheimer's disease (AD) symptoms across all severity stages. The ROSA and four standard instruments -- the Alzheimer's disease Assessment Scale-cognitive (ADAS-cog), Severe Impairment Battery (SIB), Disability Assessment for Dementia (DAD), and the Neuropsychiatric Inventory (NPI) -- were used in an open-label, multicenter, single-arm clinical study to assess treatment-induced changes in cognitive, functional, and behavioral symptoms in patients with AD at different severity stages. METHODS: A total of 451 patients were treated with memantine (initiated at 5 mg/day and up-titrated with 5 mg weekly to a final dose of 20 mg/day) for 12 weeks. The study endpoints comprised changes from baseline in the scores of the ROSA, ADAS-cog, SIB, DAD, and NPI as well as global changes on the Clinical Global Impression of Change (CGI-C). Analyses were performed for the overall population and by AD severity stage (early, middle, late). RESULTS: The ROSA scores increased significantly after a 12-week treatment in all study groups except for early stage. Mean changes in the ADAS-cog score indicated a trend towards worsening in early and middle stages. Non-significant changes were shown by the SIB, NPI, and DAD assessments at week 12. The CGI-C demonstrated 'minimal improvement' or 'no change' for most of the patients. Overall, memantine treatment was safe and well tolerated. CONCLUSION: The results demonstrated the ROSA feasibility in daily practice for assessment of memantine effects over time in patients with moderate and late AD.

Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial.

BACKGROUND: Prevention strategies are urgently needed to tackle the growing burden of Alzheimer's disease. We aimed to assess efficacy of long-term use of standardised ginkgo biloba extract for the reduction of incidence of Alzheimer's disease in elderly adults with memory complaints. METHODS: In the randomised, parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we enrolled adults aged 70 years or older who spontaneously reported memory complaints to their primary-care physician in France. We randomly allocated participants in a 1:1 ratio according to a computer-generated sequence to a twice per day dose of 120 mg standardised ginkgo biloba extract (EGb761) or matched placebo. Participants and study investigators and personnel were masked to study group assignment. Participants were followed-up for 5 years by primary-care physicians and in expert memory centres. The primary outcome was conversion to probable Alzheimer's disease in participants who received at least one dose of study drug or placebo, compared by use of the log-rank test. This study is registered with ClinicalTrials.gov, number NCT00276510. FINDINGS: Between March, 2002, and November, 2004, we enrolled and randomly allocated 2854 participants, of whom 1406 received at least one dose of ginkgo biloba extract and 1414 received at least one dose of placebo. By 5 years, 61 participants in the ginkgo group had been diagnosed with probable Alzheimer's disease (1·2 cases per 100 person-years) compared with 73 participants in the placebo group (1·4 cases per 100 person-years; hazard ratio [HR] 0·84, 95% CI 0·60-1·18; p=0·306), but the risk was not proportional over time. Incidence of adverse events was much the same between groups. 76 participants in the ginkgo group died compared with 82 participants in the placebo group (0·94, 0·69-1·28; p=0·68). 65 participants in the ginkgo group had a stroke compared with 60 participants in the placebo group (risk ratio 1·12, 95% CI 0·77-1·63; p=0·57). Incidence of other haemorrhagic or cardiovascular events also did not differ between groups. INTERPRETATION: Long-term use of standardised ginkgo biloba extract in this trial did not reduce the risk of progression to Alzheimer's disease compared with placebo. FUNDING: Ipsen.

Comparison of two different iron oxide-based contrast agents for discrimination of benign and malignant lymph nodes.

OBJECTIVES: The aim of this study was to investigate the performance of 2 different ultrasmall superparamagnetic iron oxide particles-based contrast agents for intravascular magnetic resonance lymphography in normal, inflammatory, and tumor-bearing lymph nodes in rabbits. MATERIALS AND METHODS: Two USPIO agents were assessed: Sinerem and P904 (both Guerbet Research, Aulnay-sous-Bois, France). Signal change of popliteal and paraaortic lymph nodes were studied in VX-2 tumor-bearing rabbits (n = 4) and rabbits in whom complete Freund adjuvant had been applied (n = 6). Image acquisition was performed before and 5 to 120 minutes and 24 hours after bolus injection of Sinerem (n = 5) and P904 (n = 5). Lymph node size was assessed and signal-to-noise ratios of lymph nodes were calculated. The contrast agents were compared regarding nodal signal changes over time. Furthermore, sensitivities, specificities, and negative and positive predictive values were calculated for both contrast agents, with histopathology serving as the standard of reference. RESULTS: No statistically significant size differences were detected between normal, reactively enlarged and tumor-infiltrated lymph nodes. Signal change over time showed greater differences between benign and metastatic lymph nodes for P904 especially at 24 hours after injection, whereas Sinerem showed the highest signal loss in benign nodes. After 24 hours, P904 showed a higher sensitivity (0.75 vs 0.67) and higher specificity (1 vs 0.94) compared with Sinerem. At earlier time points, sensitivity for Sinerem was lower (0.33), whereas for P904, sensitivity at 120 minutes was as good as after 24 hours (0.75). CONCLUSION: Magnetic resonance lymphography with USPIO contrast agents allows for differentiation of reactively enlarged lymph nodes compared with metastatic nodes. P904 yielded higher sensitivity and specificity values, with higher signal differences between benign and malignant enlarged lymph nodes. Furthermore, diagnosis seems to be possible earlier. This agent therefore seems to be a promising tool for staging cancer patient.

The 2008-2012 French Alzheimer plan: description of the national Alzheimer information system.

In France, one of the aims of the current national Alzheimer's disease plan is to collect data from all memory centers (memory units, memory resource and research centers, independent neurologists) throughout the country. Here we describe the French Alzheimer Information System and present a 'snapshot' of the data collected throughout the country during the first year of operation. We analyzed all data transmitted by memory centers between January 2010 and December 2010. Each participating center is required to transmit information on patients to the French National Alzheimer dataBank (BNA). This involves completing a computer file containing 31 variables corresponding to a limited data set on AD (CIMA: Corpus minimum d'information Alzheimer). In 2010, the BNA received data from 320 memory centers relating to 199,113 consultations involving 118,776 patients. An analysis of the data shows that the initial MMSE (Mini Mental State Examination) mean score for patients in France was 16.8 points for Alzheimer's disease, 25.7 points for mild cognitive impairment, and 18.8 points for 'related disorders related disorders. The BNA will provide longitudinal data that can be used to assess the needs of individual local health areas and size specialized care provision in each regional health scheme. By contributing to the BNA, the memory centers enhance their clinical activity and help to advance knowledge in epidemiology and medical research in the important field of Alzheimer's disease and related dementias.

[Treatment of behavioral disorders in Alzheimer's disease]. / Prise en charge des troubles du comportement dans les maladies d'Alzheimer.

Behavioural and psychological symptoms (BPSD) are now known to be frequently associated to cognitive and functional decline in Alzheimer's disease and related disorders. Recommendations for the management of BPSD have been proposed. Non-pharmacological interventions should be the first-line treatment. Anti-dementia agents (cholinesterase inhibitors, memantine) and psychotropic drugs (antipsychotics, antidepressants and anticonvulsivants) could be associated to non-pharmacological interventions only in case of limited response with non pharmacologic approaches. Low-dose antipsychotics should only be prescribed for limited periods of time, in case of psychotic and/or aggressive refractory symptoms.

Monitoring blood-brain barrier status in a rat model of glioma receiving therapy: dual injection of low-molecular-weight and macromolecular MR contrast media.

PURPOSE: To evaluate the sequential injection of a low-molecular-weight (gadoterate meglumine [Gd-DOTA], 0.5 kDa) and a macromolecular (P846, 3.5 kDa) contrast media in monitoring the effect of antitumor therapies (antiangiogenic therapy and/or microbeam radiation therapy [MRT]) on healthy brain tissue and implanted tumors. MATERIALS AND METHODS: Animal use was compliant with official French guidelines and was assessed by the local Internal Evaluation Committee for Animal Welfare and Rights. Eighty male rats bearing 9L gliosarcoma were randomized into four groups: untreated, antiangiogenic (sorafenib) therapy, MRT, and both treatments. Magnetic resonance (MR) imaging was performed 1 day before and 1, 5, and 8 days after the start of the treatment. At all time points, vascular integrity to a macromolecular contrast medium (P846) and, 11 minutes 30 seconds later, to low-molecular-weight contrast medium (Gd-DOTA) was evaluated by using a dynamic contrast material-enhanced MR imaging approach. To quantify vessel wall integrity, areas under the signal intensity curves were computed for each contrast medium. Unpaired t tests and one-way analysis of variance were used for statistical analyses. RESULTS: Tumor vessels receiving antiangiogenic therapy became less permeable to the macromolecular contrast medium, but their permeability to the low-molecular-weight contrast medium remained unchanged. Healthy double-irradiated vessels became permeable to the low-molecular-weight contrast medium but not to the macromolecular contrast medium. CONCLUSION: Antiangiogenic therapy and MRT generate different effects on the extravasation of contrast medium in tumoral and healthy tissues. This study indicates that the use of a low-molecular-weight contrast medium and a macromolecular contrast medium provides complementary information and suggests that the use of two contrast media within the same MR imaging session is feasible.

Management of agitation and aggression associated with Alzheimer disease.

Agitation and aggression are frequently occurring and distressing behavioral and psychological symptoms of dementia (BPSD). These symptoms are disturbing for individuals with Alzheimer disease, commonly confer risk to the patient and others, and present a major management challenge for clinicians. The most widely prescribed pharmacological treatments for these symptoms-atypical antipsychotics-have a modest but significant beneficial effect in the short-term treatment (over 6-12 weeks) of aggression but limited benefits in longer term therapy. Benefits are less well established for other symptoms of agitation. In addition, concerns are growing over the potential for serious adverse outcomes with these treatments, including stroke and death. A detailed consideration of other pharmacological and nonpharmacological approaches to agitation and aggression in patients with Alzheimer disease is, therefore, imperative. This article reviews the increasing evidence in support of psychological interventions or alternative therapies (such as aromatherapy) as a first-line management strategy for agitation, as well as the potential pharmacological alternatives to atypical antipsychotics-preliminary evidence for memantine, carbamazepine, and citalopram is encouraging.

Dark lumen magnetic resonance colonography in a rodent polyp model: initial experience and demonstration of feasibility.

PURPOSE: We sought to assess dark lumen magnetic resonance (MR) colonography for the detection of colon polyps in a rodent model with histology as the gold standard. MATERIAL AND METHODS: Fourteen male Wistar rats were subjected to carcinogenic N-methyl-N'-nitro-N-nitrosoguanidine at the age of 4 months to induce colon neoplasms. MR imaging was performed after a time interval of 1 year. Preparation and data acquisition was performed with the animals under full anesthesia. After a body-warm saline enema images were acquired on a clinical 1.5-T whole-body MR system using a standard extremity coil. Plain and contrast-enhanced (0.3 mmol/kg; Gd-DOTA; Dotarem, Guerbet, France) 3-dimensional T1-weighted gradient recall echo images were acquired. Two radiologists analyzed the MR data sets in consensus for lesion depiction. Contrast uptake in colonic wall and polyps was quantitatively assessed by signal-to-noise ratio and contrast-to-noise ratio measurements and compared using a Wilcoxon-Mann-Whitney U test with statistical significance at a P value < 0.05. Finally, all animals were killed, and the MR imaging results were compared with pathologic findings. Sensitivity and specificity were calculated. RESULTS: By pathology, a total of 15 polyps were found in 9 of 14 rats. MR colonography detected 13 of 15 polyps measuring between 4 and 11 mm (mean 7 +/- 0.6 mm) in 8 of 9 animals, resulting in a sensitivity and specificity of 0.87 and 1.0, respectively. Compared with the precontrast data, all polyps showed a statistically significant increase in signal-to-noise ratio (78.2 +/- 6.3 to 167.4 +/- 17.7) and contrast-to-noise ratio (45.4 +/- 5.2 to 124.6 +/- 11.2). CONCLUSION: MR colonography with a dark colon lumen and a bright, contrast-enhanced colon wall appears well suited for the detection of colonic lesions in a rodent model.

Effect of subthalamic nucleus stimulation on obsessive-compulsive disorder in a patient with Parkinson disease. Case report.

The authors report on a patient with Parkinson disease (PD) and severe obsessive-compulsive disorder (OCD), in whom bilateral stimulation of the subthalamic nucleus (STN) was used to treat both PD and OCD symptoms. This 49-year-old man had displayed symptoms of PD for 13 years. Progressively, his motor disability became severe despite optimal medical treatment. In parallel, he suffered severe OCD for 16 years, with obsessions of accumulation and compulsions of gathering and rubbing that lasted more than 8 hours per day. Bilateral high-frequency STN stimulation was performed to treat motor disability. After surgery (at 1-year follow up), motor and OCD symptoms were dramatically improved. The pre- and postoperative Yale-Brown Obsessive-Compulsive Scale scores were 32 and 1, respectively. No additional antiparkinsonian drugs were administered. This case and other recent reports indicate that OCD symptoms can be improved by deep brain stimulation, a finding that opens new perspectives in the surgical treatment of severe and medically intractable OCD.