MRI ischemic and hemorrhagic lesions in arterial and venous territories characterize central nervous system intravascular lymphoma in dogs.

Intravascular lymphoma (IVL) is characterized by the proliferation of large malignant lymphocytes within the lumen of blood vessels. This retrospective, multi-center, case series study aimed to describe the MRI features of confirmed central nervous system IVL in dogs and compare them with histopathological findings. Medical record databases from seven veterinary centers were searched for cases of histologically confirmed IVL. Dogs were included if an MRI was performed. The MRI studies and histopathology samples were reviewed to compare the MRI changes with the histopathological findings. Twelve dogs met the inclusion criteria (12 brains and three spinal cords). Imaging of the brains revealed multifocal T2-weighted/FLAIR hyperintense and T1-weighted iso-hypointense lesions, with variable contrast enhancement; areas of abnormal diffusion both in arterial and venous territories in diffusion-weighted imaging; and meningeal enhancement. On gradient echo images (GRE), the changes comprised tubular susceptibility artifacts, consistent with the "susceptibility vessel sign", and additional variably sized/shaped intraparenchymal susceptibility artifacts. Spinal cord lesions presented as fusiform T2-weighted hyperintensities with scattered susceptibility artifacts on GRE and variable parenchymal and meningeal contrast enhancement. On histopathology, subarachnoid hemorrhages and neuroparenchymal areas of edema and necrosis, with or without hemorrhage, indicating ischemic and hemorrhagic infarctions, were found. These lesions were concurrent with severely dilated meningeal and parenchymal arteries and veins plugged by neoplastic lymphocytes and fibrin. Due to the unique angiocentric distribution of IVL, ischemic and hemorrhagic infarcts of variable chronicity affecting both the arterial and venous territories associated with thrombi formation can be detected on MRI.

Can MRI differentiate between ring-enhancing gliomas and intra-axial abscesses?

Gliomas of the brain may appear as expansile ring-enhancing masses in MRI studies, mimicking the appearance of intra-axial abscesses. The aims of this study were to compare the MRI features of ring-enhancing gliomas and intra-axial brain abscesses in dogs and cats and to identify the characteristics that might help differentiate them. For this multicenter, retrospective, and observational study, the inclusion criteria were as follows: (a) a definitive diagnosis of glioma or abscess based on cytological or histopathological examination following CSF collection or surgical biopsy/necropsy, respectively; (b) MRI study performed with a high- or low-field MRI scanner, including a same plane T1W pre- and postcontrast, a T2W and a T2 FLAIR sequence in at least one plane. If available, delayed T1W postcontrast, T2*W GE, DWI/ADC, and SWI sequences were also evaluated. Sixteen patients were diagnosed with ring-enhancing gliomas, and 15 were diagnosed with intra-axial abscesses. A homogenous signal on T1W (P = 0.049) and T2W (P = 0.042) sequences, a T2W (P = 0.005) or T2*W GE (P = 0.046) peripheral hypointense halo, and an even enhancing capsule (P = 0.002) were significantly associated with brain abscesses. A progressive central enhancement on delayed T1W postcontrast sequences was correlated with ring-enhancing gliomas (P = 0.009). The combination of the following features was suggestive of brain abscess: homogeneous T1W or T2W signal intensity, a T2W or T2*W GE peripheral hypointense halo and an evenly enhancing capsule. Central progression of enhancement on delayed T1W postcontrast sequences was suggestive of glioma.

Renal ultrasonographic abnormalities are associated with low glomerular filtration rate calculated by scintigraphy in dogs.

Ultrasound provides information on kidney morphology, but studies relating structural and functional abnormalities in chronic kidney disease (CKD) are lacking. The aim of this descriptive cross-sectional study was to compare individual kidney (IK) B-mode ultrasound abnormalities to IK glomerular filtration rate (GFR) estimated by scintigraphy normalized to plasma volume (PV) in dogs, to evaluate if ultrasonographic findings were associated with low IKGFR/PV. Eighty privately owned dogs with and without clinical suspicion of CKD were prospectively enrolled, and kidney ultrasound and IKGFR/PV were evaluated independently. Ultrasound images were assessed retrospectively for subjective abnormalities (shape, cortical, and medullary hyperechogenicity), and kidney size was measured. The normal IKGFR/PV cutoff was derived from dogs in the study group with no history and clinical signs of kidney disease and normal blood and urine results (n = 28) and was 16.84 mL/min/L. Kidneys were categorized into normal, mild, moderate, and severe ultrasound changes according to subjective ultrasound grades. Associations were found between low IKGFR/PV and abnormal kidney shape (P = .0004), cortical hyperechogenicity (P = .0008), medullary hyperechogenicity (P < .0001), and low kidney volume (P = .0092). Apart from the moderate and severe category comparison, IKGFR/PV value significantly decreased with increasing severity of category. The combination of ultrasonographic subjective abnormalities had a high sensitivity (93.8%) and moderate specificity (65.7%) for detecting low IKGFR/PV. Kidneys with normal IKGFR/PV had a low frequency of mild ultrasound changes. Findings indicate kidneys with increasing number and grade of subjective ultrasound abnormalities are more likely to have a lower IKGFR/PV.

Agomelatine Improves Apathy in Frontotemporal Dementia.

BACKGROUND/AIMS: Apathy is the most common initial symptom of frontotemporal dementia (FTD) and has been linked to frontal-subcortical dopaminergic system dysfunction. No pharmacological therapy has been approved for the treatment of apathy, but, on the basis of its physiopathological mechanism, we suspected that increasing prefrontal dopaminergic innervation could improve this disabling symptom. METHODS: We evaluated a group of 24 nondepressed patients with a diagnosis of the behavioral variant of FTD, in order to determine the effectiveness on apathy of agomelatine, an antidepressant with MT1 and MT2 receptor agonism and 5-HT2C receptor antagonism; the latter leads to an increase in prefrontal dopaminergic and noradrenergic tone. To try to tease out the effects of 5-HT2C antagonism on apathy, patients were randomized, using a cross-over design, to receive either agomelatine 50 mg/day or sustained release melatonin 10 mg/day for 10 weeks in a double-blind procedure. At the end of the follow-up period, subjects receiving melatonin switched to agomelatine for the following 10 weeks. RESULTS: Agomelatine, but not melatonin, was associated with a significant reduction of apathy in FTD subjects and of caregiver distress due to patients' apathy. The switch from melatonin to agomelatine was associated with a reduction in apathetic behavior. Agomelatine was well-tolerated by all enrolled subjects. CONCLUSIONS: Our data, albeit preliminary, suggest that agomelatine could represent a novel useful approach to the treatment of apathy in FTD patients.

Souvenaid reduces behavioral deficits and improves social cognition skills in frontotemporal dementia: a proof-of-concept study.

BACKGROUND: Souvenaid™ is a nutraceutical compound thought to positively enhance synaptic function. In line with this mechanism of action, Souvenaid™ has been shown to improve cognitive function in subjects with mild Alzheimer's disease in randomized clinical trials. To date, however, the potential of Souvenaid™ to improve cognitive functioning in subjects with other neurodegenerative conditions also characterized by synaptic loss has not been explored. OBJECTIVE: To evaluate the impact of Souvenaid™ on executive functions, social cognition and behavioral disturbances in subjects with the behavioral variant of frontotemporal dementia (bv-FTD). METHODS: Twenty-six subjects with bv-FTD were enrolled in the study and randomized to Souvenaid™ (125 ml/day) or placebo groups. After 12 weeks, subjects were switched between the two groups. All subjects, blinded to treatment, underwent clinical and cognitive evaluations at enrollment, after 12 weeks and after 24 weeks. RESULTS: Treatment with Souvenaid™ was associated with a significant reduction of behavioral symptoms and an increase in Theory of Mind skills compared to placebo, which both returned to baseline when Souvenaid™ was discontinued. Souvenaid™ did not have an effect on executive functions. CONCLUSIONS: Our results provide evidence of the potential of Souvenaid™ therapy for the treatment of behavioral disturbances and social cognition skills in FTD.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial.

BACKGROUND: Data on therapeutic interventions following deliberate self harm (DSH) in patients with treatment-resistant depression (TRD) are very scant and there is no unanimous consensus on the best pharmacological option for these patients. There is some evidence that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with unipolar affective disorders, however no clear cut results have been found so far. The primary aim of the present study is to assess whether adding lithium to standard therapy is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH. METHODS/DESIGN: We will carry out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode will be allocated to add lithium to current therapy (intervention arm) or not (control arm). Following randomisation, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Suicide completion and acts of DSH during the 12 months of follow-up will constitute the composite primary outcome. To preserve outcome assessor blindness, an independent adjudicating committee, blind to treatment allocation, will anonymously review all outcome events. DISCUSSION: The results of this study should indicate whether lithium treatment is associated with lower risk of completed suicide and DSH in adult patients with treatment resistant unipolar depression, who recently attempted suicide. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

Are postnatal traumatic events an underestimated cause of porencephalic lesions in dogs and cats?

Introduction: Porencephaly is defined as a fluid-filled cavity of variable size in the brain cortex. It is regarded as a congenital condition and is typically considered a developmental or an encephaloclastic defect. Our hypothesis is that postnatal traumatic events in the first few months of life may represent a cause of canine and feline porencephaly that is more common than generally suspected. The aims of this study were to retrospectively investigate porencephaly in a large population of dogs and cats, detect MRI features that might be useful to differentiate postnatal acquired traumatic forms from congenital/perinatal porencephaly, and define the prevalence of seizure activity in porencephalic patients. Materials and methods: This is a double-center, descriptive, retrospective case series. Databases were searched for cases within a 17-year time span that involve dogs and cats with an MRI-based diagnosis of cerebral cavitary lesions. Animals were included if a complete signalment and an exhaustive MRI of the brain were available. Besides the porencephalic lesions, MRIs of the head were reviewed to detect concomitant musculoskeletal abnormalities. Results: Thirty-two cases involving nine cats and twenty-three dogs were selected. Of all the cases, 21.9% were aged six years or older at the time of diagnosis. All patients in which the neuroanatomical localization was available showed clinical signs of a prosencephalic disorder. Epileptic seizures were observed in 71.8% of cases. A single porencephalic cavity was found in 78.1% of cases. The most affected cerebral lobe was the parietal lobe (n = 20). The defects involved both the grey and white matter in 78.1% of cases. Twenty cases showed concomitant musculoskeletal abnormalities overlying the porencephalic cavities. Fourteen of twenty cases showed evidence of fractures, of which thirteen showed depression of the calvarium and twelve masticatory muscle abnormalities. Of these, seven of fourteen had a history consistent with a head trauma in the first period of life. Conclusion: The recognition of skull fractures and muscular abnormalities closely associated with the porencephalic cavity may support a diagnosis of a postnatal traumatic origin of porencephaly. Therefore, this study highlights the importance of evaluating musculoskeletal structures in the MRIs of the heads of porencephalic cases.

Obsessive-compulsive disorder and related disorders: a comprehensive survey.

Our aim was to present a comprehensive, updated survey on obsessive-compulsive disorder (OCD) and obsessive-compulsive related disorders (OCRDs) and their clinical management via literature review, critical analysis and synthesis. Information on OCD and OCRD current nosography, clinical phenomenology and etiology, may lead to a better comprehension of their management. Clinicians should become familiar with the broad spectrum of OCD disorders, since it is a pivotal issue in current clinical psychiatry.

Aripiprazole augmentation in poor insight obsessive-compulsive disorder: a case report.

BACKGROUND: Obsessive-compulsive disorder is associated with a relevant impairment in social and interpersonal functioning and severe disability. This seems to be particularly true for the poor insight subtype, characterised by a lack of consciousness of illness and, consequently, compliance with treatment. Poor responsiveness to serotonergic drugs in poor insight obsessive-compulsive patients may also require an augmentation therapy with atypical antipsychotics. METHODS: We reviewed a case in which a patient with a long history of poor insight obsessive-compulsive disorder was treated with a high dosage of serotonin reuptake inhibitors. RESULTS: The treatment resulted in a poor outcome. This patient was therefore augmentated with aripiprazole. CONCLUSION: Doctors should consider aripiprazole as a possible augmentation strategy for serotonergic poor responder obsessive-compulsive patients, but further research on these subjects is needed.

Radiographic and ultrasonographic findings in a dog with emphysematous pyometra.

BACKGROUND: Emphysematous pyometra is a rare canine disease characterized by gas-forming bacteria infecting the uterus and causing an accumulation of both gas and infectious exudate in the uterine lumen. While radiological features of emphysematous pyometra have been previously described in dogs, the ultrasonographic appearance has not been reported. CASE PRESENTATION: A 7-year-old intact female Labrador Retriever was presented because of a 1 day history of vomiting, anorexia, mild polyuria/polydipsia and signs of fatigue. On physical examination the dog had a swollen vulva with a sparse amount of yellow discharge. Lateral and ventrodorsal radiographs showed a dilated predominantly gas-filled tubular structure located in the mid and cranial abdomen traversing from left to right and ending dorsally at the level of the 12th thoracic vertebra. A small intestinal ileus was initially suspected. Following the radiographic examination, abdominal ultrasound was performed. In the left mid and caudal abdomen there were two thin-walled gas-containing tubular structures. One had the typical layered appearance of an intestinal wall and represented the descending colon. The second structure had a similar thickness but homogenously hypoechoic wall and contained gas and echogenic fluid in the lumen. By use of several positional changes of the dog aiming to alter the location of the intraluminal gas, the second structure was traced to the right ovary cranially and the uterine body caudally, confirming that the structure was the right uterine horn. A final diagnosis of emphysematous pyometra was made. CONCLUSION: Ultrasound can be used as a non-invasive diagnostic method to differentiate between small intestinal ileus and emphysematous pyometra.

Prevalence and cognitive underpinnings of isolated apathy in young healthy subjects.

BACKGROUND: Apathy is well described in neurodegenerative conditions, however to date there is no evidence of significant isolated apathy in subjects free from other neurological and psychiatric co-morbidites. Identifying isolated apathy in subjects free from neuropsychiatric conditions could contribute to refining current concepts of apathy and reevaluate its nosological classification as an independent clinical syndrome. METHODS: We assessed apathy and perceived quality of life in a group of 2751 adults (age 19-40 years) free from neuropsychiatric or medical conditions. Subjects with and without elevated apathy were compared on measures of depression, self-efficacy, behavioral inhibition, and behavioral activation. RESULTS: Observed prevalence of isolated elevated apathy was 1.45%. Subjects with apathy presented with reduced quality of life and lower behavioral activation compared to apathy-free subjects, while there was no difference between the two groups on measures of depression, self-efficacy, and perceived social skills. LIMITATIONS: The main limitation of this study is the use of self-report questionnaires. CONCLUSIONS: Isolated, ecologically-relevant apathy can be found in adults independently from the presence of subclinical depression or of concurrent medical conditions. Apathy screening should be considered in the evaluation of young non-depressed subjects with reduced perceived quality of life.

Maternal attitudes and attachment styles in mothers of obese children.

This study evaluated categories of attachment style and the maternal attitude toward educational role in a sample of 30 mothers of obese children and a control group of 80 mothers of children of normal weight. All mothers completed the 1994 Attachment Style Questionnaire and the 1958 Parental Attitude Research Instrument. 30 mothers (M age 37.4 yr., range 31 to 54 years; M yr. of education 11.6, range 5 to 18 years) of obese children (range 30 to 60% above normal weight) and a control group of 80 mothers (M age 37.1 yr., range 29 to 52 years; M yr. of schooling 11.4, range 5 to 18 years) of children with normal weight were contacted at the primary school attended by their children and joined the project voluntarily. Age and number of years of education were not significantly different between the two groups of women. There was a significant prevalence of the Insecure Attachment Style in the group of mothers with obese children (66.6%) as compared to the control group of mothers of children of normal weight (38.5%) and significantly higher scores on 6 subscales of the Parental Attitude Research Instrument of Obese compared to Nonobese children. These data indicate that obese children's mothers tend to make the family their exclusive centre of interest. They also tend to dedicate themselves to their children with possessiveness and hyperprotection. They seem to have an insistent requirement of idealisation of their own role as parent and reward expectations that confirm the efficiency of the care they provide their children. Consequently, these findings suggest that in addition to dietetic treatment, it may be important to include a psychological intervention, which involves the mother and aims to modify the relational dynamics between the mother and her obese child.

Duloxetine-bupropion combination for treatment-resistant atypical depression: a double-blind, randomized, placebo-controlled trial.

The efficacy, safety, and tolerability of combined bupropion versus placebo using duloxetine as active reference drug, in patients with a DSM-IV diagnosis of major depression with atypical features and a history of treatment resistance, were evaluated in this preliminary six-week study. Patients (n=46) had a baseline Hamilton Depression Scale (HAM-D) ≥14 and were randomly assigned to 150/300 mg/day bupropion vs. placebo, which was added to 60 to 120 mg/day duloxetine depending on baseline depression severity. Atypical features of depression were assessed using the additional eight-item module of the Structured Interview Guide for the HAM-D with the Atypical Depression Supplement. By week 6, only five (21.7%) patients receiving duloxetine+placebo vs. six (26.1%) patients on the bupropion combination achieved response. No significant difference in final HAM-D scores between the two groups was observed between those patients achieving response. The presence of a higher number of atypical features significantly predicted non-response, with the relevant binary logistic regression model correctly classifying 17 out 22 (77.3%) of non-responders [Exp(B)=0.294; p=0.016] vs. 17 out 23 (73.9%) [Exp(B)=0.353; p=0.028] non-responder cases in the "+placebo" and "+bupropion" groups, respectively. In those patients receiving bupropion, treatment-emergent adverse events leading to withdrawal were more common among those receiving lower doses of the combination drug, and no life-threating dangers were noted. Additional studies, including an adequate course of duloxetine trial, are nonetheless aimed to allow a firm conclusion about the usefulness of the combination of duloxetine and bupropion for treatment-resistant cases of major depression with atypical features.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial.

BACKGROUND: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size. METHODS: We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome. RESULTS: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected. CONCLUSIONS: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

Employment status, inflation and suicidal behaviour: an analysis of a stratified sample in Italy.

BACKGROUND: There is abundant empirical evidence of a surplus risk of suicide among the unemployed, although few studies have investigated the influence of economic downturns on suicidal behaviours in an employment status-stratified sample. AIMS: We investigated how economic inflation affected suicidal behaviours according to employment status in Italy from 2001 to 2008. METHODS: Data concerning economically active people were provided by the Italian Institute for Statistical Analysis and by the International Monetary Fund. The association between inflation and completed versus attempted suicide with respect to employment status was investigated in every year and quarter-year of the study time frame. We considered three occupational categories: employed, unemployed who were previously employed and unemployed who had never worked. RESULTS: The unemployed are at higher suicide risk than the employed. Among the PE, a significant association between inflation and suicide attempt was found, whereas no association was reported concerning completed suicides. No association was found between completed and attempted suicides among the employed, the NE and inflation. Completed suicide in females is significantly associated with unemployment in every quarter-year. CONCLUSION: The reported vulnerability to suicidal behaviours among the PE as inflation rises underlines the need of effective support strategies for both genders in times of economic downturns.

Ziprasidone hydrocloride: what role in the management of schizophrenia?

BACKGROUND: Since schizophrenia is considered one of the top ten causes of disease-related disability in the world, the development of second-generation (atypical) antipsychotics (SGAs) has increased the hopes of psychiatrists. SGAs, however, cannot be considered a unique pharmacological class since each SGA has many complex pharmacologic actions, only some of which are shared with other SGAs. Even though manyantipsychotics have similar efficacy on average, prescribers may be able to achieve better than average results by considering differences in selecting a specific drug for a specific patient. Clinicians know that each patient is unique. In order to achieve best outcomes for the individual patient, the better therapy is the therapy tailored for the single patient. OBJECTIVES: With this article, we provide information on a relatively new antipsychotic ziprasidone released in 2001 by Pfizer for the treatment of schizophrenia. Compared with other first line atypical antipsychotics ziprasidone has a unique profile due to potent interaction with serotonergic receptors and lesser action upon α1 adrenergic, H1 and M1 antagonist activities. This paper describes the development of ziprasidone, its unique properties and its metabolically-friendly profile including its receptor binding affinities, pharmacokinetics, CNS activity results of clinical efficacy and relevant clinical trials. Safety, efficacy and patient preference are also examined. The available literature on ziprasidone of the last five years is reviewed.