A consecutive case series experience with [18 F] florbetapir PET imaging in an urban dementia center: impact on quality of life, decision making, and disposition.

BACKGROUND: Identification and quantification of fibrillar amyloid in brain using positron emission tomography (PET) imaging and Amyvid™ ([18 F] Amyvid, [18 F] florbetapir, 18 F-AV-45) was recently approved by the US Food and Drug Administration as a clinical tool to estimate brain amyloid burden in patients being evaluated for cognitive impairment or dementia. Imaging with [18 F] florbetapir offers in vivo confirmation of the presence of cerebral amyloidosis and may increase the accuracy of the diagnosis and likely cause of cognitive impairment (CI) or dementia. Most importantly, amyloid imaging may improve certainty of etiology in situations where the differential diagnosis cannot be resolved on the basis of standard clinical and laboratory criteria. RESULTS: A consecutive case series of 30 patients (age 50-89; 16 M/14 F) were clinically evaluated at a cognitive evaluation center of urban dementia center and referred for [18 F] florbetapir PET imaging as part of a comprehensive dementia workup. Evaluation included neurological examination and neuropsychological assessment by dementia experts. [18 F] florbetapir PET scans were read by trained nuclear medicine physicians using the qualitative binary approach. Scans were rated as either positive or negative for the presence of cerebral amyloidosis. In addition to a comprehensive dementia evaluation, post [18 F] florbetapir PET imaging results caused diagnoses to be changed in 10 patients and clarified in 9 patients. Four patients presenting with SCI were negative for amyloidosis. These results show that [18 F] florbetapir PET imaging added diagnostic clarification and discrimination in over half of the patients evaluated. CONCLUSIONS: Amyloid imaging provided novel and essential data that: (1) caused diagnosis to be revised; and/or (2) prevented the initiation of incorrect or suboptimal treatment; and/or (3) avoided inappropriate referral to an anti-amyloid clinical trial.

The neural processing of negative emotion postpartum: a preliminary study of amygdala function in postpartum depression.

While contemporary diagnostic nosology characterizes postpartum depression (PPD) as a specifier of a major depressive disorder (MDD), this classification continues to be questioned. Functional magnetic resonance imaging (fMRI) holds the promise of helping to characterize the neuroanatomical dysfunction associated with dysregulated emotion after childbirth. Twenty postpartum women underwent fMRI in the presence of emotionally valenced stimuli. The observation of relative amygdala non-responsivity in subjects demonstrating greater depression symptomotology stands in contrast to imaging studies of MDD and provides insight into possible phenotypic differences of PPD.

Posterior cortical atrophy: an exemplar for renovating diagnostic formulation in neuropsychiatry.

Neurodegenerative dementias represent among the most clinically and pathologically complex syndromes in neuropsychiatry. Phenomenologically protean, and often initially presenting with subtle subsyndromal characteristics, neurodegenerative behavioral syndromes can manifest with an assortment of cognitive, mood, personality, and comportmental changes, often alloyed with elementary neurologic (e.g., motor) signs. A range of pathogenic mechanisms (e.g., amyloid plaques, Pick bodies, etc) typically underlie corresponding clinical syndromes. However, overlap in both clinical expression and histopathologic comorbidities frequently exist among cortical and subcortical neurodegenerative disorders. Moreover, secondary central nervous system pathologies (e.g., cerebrovascular disease) commonly coexist with neurodegenerative processes, further complicating clinical phenomenology-based nosologic categorization. Evolving insight into the etiologic mechanisms of neurodegenerative dementias, and correspondingly improving potential for intervention, require more precise differentiation among dementia subtypes and comprehensive identification of contemporaneous neurodegenerative processes. Increasing appreciation of this diagnostic complexity is prompting the need for renovation of existing diagnostic schemas. We address these issues by reviewing the atypical dementia type known as posterior cortical atrophy. We then use posterior cortical atrophy as an exemplar for renovating neuropsychiatric diagnostic classification to better account for the layered complexity of clinical and pathologic domains needing to be characterized to accurately and completely diagnose neuropsychiatric disturbances.

Predictors and outcomes of seizures after cardiac surgery: a multivariable analysis of 2,578 patients.

BACKGROUND: Limited data exist regarding the epidemiology and prognosis of seizures in adults after cardiac surgery. The aim of this study was to define preoperative predictors of seizures and impact on postoperative outcomes. METHODS: A prospective database of 2,578 consecutive adults who underwent cardiac surgery at a single institution between April 2007 and December 2009 was retrospectively analyzed to determine risk factors for postoperative seizures and prognostic impact. No patient received tranexamic acid or aprotinin. RESULTS: Seizures occurred in 31 patients (1%) at a median of 2 days postoperatively (1 patient had a preoperative diagnosis of seizure disorder). Seizures were classified as generalized tonic-clonic (71%), simple/complex partial (26%), or status epilepticus (3%). Incidence differed according to procedure (coronary bypass 0.1%, isolated valve 1%, valve/coronary bypass 3%, aorta 5%; p <0.001). Patients who experienced seizures had nearly a fivefold higher operative mortality than patients who did not (29% versus 6%, p <0.001). Head computed tomography was performed in 26 patients (84%), of whom ischemic strokes were identified in 14 cases (53%). These were embolic in 9 patients (34%), and watershed in 3 (12%). Hemorrhagic strokes were observed in 2 patients (8%). The occurrence of a new postoperative stroke in seizure patients did not significantly increase the likelihood of in-hospital death. Thirteen patients (41%) were discharged without neurologic deficit. Multivariable logistic regression analysis identified three risk factors for seizure: deep hypothermic circulatory arrest, aortic calcification or atheroma, and critical preoperative state. CONCLUSIONS: Seizures in adults after cardiac surgery are strong independent predictors of permanent neurologic deficit and increased operative mortality. Early head computed tomography may be indicated to identify treatable pathology.

The impact of socioeconomic status on the neural substrates associated with pleasure.

Low socio-economic status (SES) is associated with increased morbidity and premature mortality. Because tonic adversity relates to a diminished ability to experience pleasure, we hypothesized that subjects living in poverty would show diminished neural responsivity to positive stimuli in regions associated with positive experience and reward. Visual images were presented to twenty-two subjects in the context of a EPI-BOLD fMRI paradigm. Significant differences in neural responses between SES groups to poverty vs. neutral images were assessed, examining group, condition, and interaction effects. The data suggest that persons living in low-SES have neural experiences consistent with diminished interest in things generally enjoyed and point toward a possible explanation for the relationship between socioeconomic inequalities and mood disorders, such as depression, by SES.

Mood disorders in patients with epilepsy: epidemiology and management.

Patients with epilepsy are at high risk for depression because of an incompletely understood combination of factors that may be both psychosocial and neurological. Interictal depression in patients with epilepsy is an undertreated condition, in part because of concern regarding drug interactions and the risk of exacerbating seizures with antidepressant treatment. Bipolar disorder is not described as occurring with a higher than expected frequency in the population with epilepsy, but high rates of depression and suicide are well recognised, highlighting the need for more emphasis on antidepressive treatment in this group of at-risk patients. Neurological factors, including site and lateralisation of seizure focus, may be important for the development of depression, with left-sided seizure foci having a higher association with depressive symptoms. Forced normalisation may be a factor in the paradoxical onset of depression in patients with epilepsy whose seizures suddenly become well controlled by anti-seizure treatment. Lowering of folic acid levels by some antiepileptic drugs (AEDs) may also influence the expression of depression in patients with epilepsy. New AEDs continue to emerge as beneficial treatments themselves for mood disorders, with lamotrigine, gabapentin and, to a lesser extent, topiramate having clinical trials data to support their use in patients with bipolar disease. Similar positive data are available for vagal nerve stimulation. Mood effects of AEDs can be complicated, however, as many of these drugs (e.g. tiagabine) have also been reported to cause depression as an adverse effect. Electroconvulsive therapy in depressed patients with epilepsy requires special consideration. The selective serotonin reuptake inhibitors (SSRIs) and antidepressants that act at multiple receptors (e.g. nefazodone, venlafaxine) are the most appropriate treatments for depressed patients with epilepsy. Among these agents, citalopram has a low risk of interactions with AEDs. Bupropion, clomipramine and maprotiline are associated with a greater risk of seizures compared with other antidepressants and consequently should be used with caution in the treatment of depression in patients with epilepsy.