Delayed identification and diagnosis of Huntington\u27s disease due to psychiatric symptoms

Huntington\u27s disease (HD) is a progressive neurodegenerative illness that affects 2-9/100.000 of the general population. The usual onset is at around age 35-40 years, but there were cases with onset above 55 years. The disease manifests clinically with many neurological and psychiatric symptoms, leading in advanced phases to dementia, but cognitive symptoms are frequently present much earlier in the disease course. HD is caused by an expanded polyglutamine stretch in the N-terminal part of a 350 kDa protein called huntingtin (HTT). This stretch is encoded by a trinucleotide CAG repetition in exon 1 of HTT. An expansion of greater than 36 repeats results in HD. The number of repeats is inversely correlated with the age of onset of motor symptoms, and disease onset during childhood or adolescence is associated with more than 60 CAG repeats. Mood disturbances may be one of the earliest symptoms of HD and may precede the onset of the motor pheno-type for almost 10 years. Neuropsychiatric symptoms may delay the appropriate diagnosis of HD and have major implications for disease management, prognosis and quality of life for patients and families. This case study is about a 58 years old female patient with late identification of Huntington\u27s disease after two admissions to psychiatric inpatient units, for the treatment of behavioral disturbances

Molecular MRI of Inflammation in Atherosclerosis

Inflammatory activity in atherosclerotic plaque is a risk factor for plaque rupture and atherothrombosis and may direct interventional therapy. Inflammatory activity can be evaluated at the (sub)cellular level using in vivo molecular MRI. This paper reviews recent progress in contrast-enhanced molecular MRI to visualize atherosclerotic plaque inflammation. Various MRI contrast agents, among others ultra-small particles of iron oxide, low-molecular-weight Gd-chelates, micelles, liposomes, and perfluorocarbon emulsions, have been used for in vivo visualization of various inflammation-related targets, such as macrophages, oxidized LDL, endothelial cell expression, plaque neovasculature, MMPs, apoptosis, and activated platelets/thrombus. An enzyme-activatable magnetic resonance contrast agent has been developed to study myeloperoxidase activity in inflamed plaques. Agents creating contrast based on the chemical exchange saturation transfer mechanism were used for thrombus imaging. Transfer of these molecular MRI techniques to the clinic will critically depend on the safety profiles of these newly developed magnetic resonance contrast agents

Molecular imaging of inflammation and intraplaque vasa vasorum: A step forward to identification of vulnerable plaques?

Current developments in cardiovascular biology and imaging enable the noninvasive molecular evaluation of atherosclerotic vascular disease. Intraplaque neovascularization sprouting from the adventitial vasa vasorum has been identified as an independent predictor of intraplaque hemorrhage and plaque rupture. These intraplaque vasa vasorum result from angiogenesis, most likely under influence of hypoxic and inflammatory stimuli. Several molecular imaging techniques are currently available. Most experience has been obtained with molecular imaging using positron emission tomography and single photon emission computed tomography. Recently, the development of targeted contrast agents has allowed molecular imaging with magnetic resonance imaging, ultrasound and computed tomography. The present review discusses the use of these molecular imaging techniques to identify inflammation and intraplaque vasa vasorum to identify vulnerable atherosclerotic plaques at risk of rupture and thrombosis. The available literature on molecular imaging techniques and molecular targets associated with inflammation and angiogenesis is discussed, and the clinical applications of molecular cardiovascular imaging and the use of molecular techniques for local drug delivery are addressed

ADMISSION TO THE PSYCHIATRIC EMERGENCY SERVICES OF PATIENTS WITH ALCOHOL-RELATED MENTAL DISORDER

Abstract

Schizophrenia relapse after stopping olanzapine treatment during pregnancy: a case report

Women with schizophrenia have a high risk for symptom exacerbation or relapse during pregnancy and thereafter. Relapses are more frequent when antipsychotics are discontinued. This paper describes the case of a 28-year old woman with schizophrenia who continued treatment with olanzapine during the first trimester. Olanzapine, a second-generation antipsychotic, was administered at a therapeutic dose from week 1 of gestation until week 13 when she reported the pregnancy to her psychiatrist. Despite the psychiatrist\u27s recommendation to continue treatment, the patient stopped olanzapine at 20 weeks. She was hospitalized at week 36 for a schizophrenia relapse and was transferred to the obstetrics department where she gave birth by Cesarean section to a normal child. This case is important, illustrating the perils of unplanned pregnancy during antipsychotic treatment and abrupt discontinuation. Ultimately, clinical decisions should be made on a case-by-case basis, weighing the risks to the mother in terms of symptom exacerbation and relapse if antipsychotic treatment is discontinued, and the potential risk to the fetus regarding possible teratogenic effects of continued antipsychotic treatment

Sudden unexpected death in schizophrenia: Autopsy findings in psychiatric inpatients

Schizophrenia is associated with premature mortality and a high rate of sudden, unexpected deaths. Autopsy data are scant, and in studies using death certificates or root cause assessments, a majority of sudden deaths remained unexplained. In the community, post-mortem data indicate that the most common cause of sudden natural death is coronary artery disease. In this study, we used autopsy findings to determine the cause of sudden death in a consecutive cohort of 7189 schizophrenia patients admitted to a free-standing, psychiatric teaching hospital from 1989 to 2013. Medical record review identified 57 patients (0.79%) who died suddenly and unexpectedly during hospitalization. Autopsies were performed in 51 (89.5%) patients (55.9 +/- 9.4 years, male = 56.9%). Autopsy-based causes of sudden death were most commonly cardiovascular disorders (62.8%). Specific causes included myocardial infarction (52.9%), pneumonia (11.8%), airway obstruction (7.8%), myocarditis (5.9%), and dilated cardiomyopathy, hemopericardium, pulmonary embolus, hemorrhagic stroke and brain tumor (2.0% each). The sudden death remained unexplained in 6 (11.8%) patients, 3 of whom had evidence of coronary arteriosclerosis on autopsy. Patients with and without myocardial infarction were similar regarding age, gender, smoking, body mass index and psychotropic treatment (p values \u3e= 0.10). In conclusion, sudden cardiac death occurs at a 0.8% rate in a psychiatric hospital, well above general population rates. Autopsy findings indicate that sudden death in schizophrenia is caused by structural cardiovascular, respiratory and neurological abnormalities, with most cases due to acute myocardial infarction. Early recognition and treatment of coronary artery disease must become a clinical priority for all adults with schizophrenia. (C) 2014 Elsevier B.V. All rights reserved

Effectiveness and safety of rapid clozapine titration in schizophrenia

Objective: Clinical guidelines recommend slow clozapine dose titration in order to decrease the risk of seizures and hypotension. The recommendation may delay adequate control of severe psychotic symptoms. We evaluated the safety and effectiveness of rapid clozapine titration in patients who had been previously exposed to the drug and in patients who received clozapine for the first time after failing to respond to other antipsychotics. Method: Analysis of hospital course of a consecutive cohort of schizophrenia patients (N = 111) who received 25-100 mg of clozapine as needed every 6 h the first treatment day, followed by upward adjustments of 25-100 mg/day. Results: Symptom control was obtained with an average dose of 353 +/- 174 mg/day after 4.1 +/- 3.1 days in the 73 patients previously treated with clozapine. For the 38 patients initially started on other antipsychotics, the average clozapine dose required for symptom control (409 +/- 188 mg/day) was reached after 7.1 +/- 4.8 days. None of the patients had seizures, severe hypotension or other major adverse reactions. Conclusion: In this naturalistic cohort study rapid clozapine titration appeared safe and effective for the treatment of schizophrenia. The results justify controlled clinical trials of this treatment method

Rapid clozapine titration in treatment-refractory bipolar disorder

Background: Clozapine is effective in treatment-refractory bipolar disorder (BD). Guidelines recommend slow titration to prevent seizures, hypotension and myocarditis, but this stance is not supported by comparative data. Objective: To evaluate the safety and effectiveness of rapid clozapine titration in BD. Methods: Analysis of a consecutive cohort of treatment-refractory BD patients with mixed/manic episode admitted on alternate days to one of two units of a psychiatric hospital. On one unit, clozapine was started at 25 mg followed by 25-50 mg as needed every 6 h (maximum 100 mg/day) on clay 1, followed by increases of 25-100 mg/day. On the other unit, clozapine was initiated with 25 mg in day 1, followed by increases of 25-50 mg/day. The primary outcome was the number of days from starting clozapine until readiness for discharge, adjusted in logistic regression for the number of antipsychotics tried during the hospitalization, psychotropic co-treatments and presence of psychotic features. Results: Patients subject to rapid (N = 44) and standard (N = 23) titration were similar in age, gender, smoking status, body mass index, illness severity at baseline and discharge, and highest clozapine dose. Clozapine was discontinued due to hypotension (N = 1) and pneumonia (N = 1) during rapid titration, and for excessive sedation (N = 1) in each titration group. The number of hospital days from starting clozapine until readiness for discharge was 3.8 days shorter in the rapid titration group (12.7 +/- 6.3 vs. 16.5 +/- 5.8, p = 0.0077). Conclusion: Rapid clozapine titration appeared safe and effective for treatment-refractory BD. The potential for shorter hospital stays justifies prospective trials of this method. (C) 2014 Elsevier B.V. All rights reserved

A tripodal ruthenium-gadolinium metallostar as a potential α(v)β(3) integrin specific bimodal imaging contrast agent.

International audienceGd(III)-containing metallostar contrast agents are gaining increased attention, because their architecture allows for a slower tumbling rate, which, in turn, results in larger relaxivities. So far, these metallostars find possible applications as blood pool contrast agents. In this work, the first example of a tissue-selective metallostar contrast agent is described. This RGD-peptide decorated Ru(II)(Gd(III))(3)metallostar is synthesized as an α(v)β(3)-integrin specific contrast agent, with possible applications in the detection of atherosclerotic plaques and tumor angiogenesis. The contrast agent showed a relaxivity of 9.65 s(-1) mM(-1), which represents an increase of 170%, compared to a low-molecular-weight analogue, because of a decreased tumbling rate (τ(R) = 470 ps). The presence of the MLCT band (absorption 375-500 nm, emission 525-850 nm) of the central Ru(II)(Ph-Phen)(3)-based complex grants the metallostar attractive luminescent properties. The (3)MLCT emission is characterized by a quantum yield of 4.69% and a lifetime of 804 ns, which makes it an interesting candidate for time-gated luminescence imaging. The potential application as a selective MRI contrast agent for α(v)β(3)-integrin expressing tissues is shown by an in vitro relaxometric analysis, as well as an in vitroT(1)-weighted MR image