Chimeric antigen receptor T-cell neuropsychiatric toxicity in acute lymphoblastic leukemia.

Chimeric antigen receptor T cells are used in the treatment of B-cell leukemias. Common chimeric antigen receptor T-cell toxicities can range from mild flu-like symptoms, such as fever and myalgia, to a more striking neuropsychiatric toxicity that can present as discrete neurological symptoms and delirium. We report here two cases of chimeric antigen receptor T-cell neuropsychiatric toxicity, one who presented as a mild delirium and aphasia that resolved without intervention, and one who presented with delirium, seizures, and respiratory insufficiency requiring intensive treatment. The current literature on the treatment and proposed mechanisms of this clinically challenging chimeric antigen receptor T-cell complication is also presented.

Negative symptoms, past and present: a historical perspective and moving to DSM-5.

The diagnosis of schizophrenia includes "positive" and "negative" symptoms. These titles were developed to respectively reflect if the symptoms are additions to normal experiences, such as delusions and hallucinations, or if they refer to the absence or the loss of normal emotional function or behavior. This paper describes the history of the negative symptom concept, from its origins up to the considerations for the DSM-5, including the steps that produced the current conceptualizations. The DSM-5 only includes deficits in emotional expression and avolition as negative symptoms, which can be assessed from interview information. Factor analyses show they encompass most other negative symptom items. In addition to using these negative symptoms in a categorical manner to make a diagnosis, the DSM-5 has quantitative severity ratings of the negative symptoms, along with ratings of delusions, cognitive symptoms, motor symptoms, disorganization, depression and mania. With this approach, the different symptom domains, including negative symptoms, can be measured and tracked over time. Another change in the DSM-5 is the dropping of the schizophrenia subtypes that have been included in earlier volumes, as they were not useful in treatment decisions or prognosis. An intended outcome of these changes in DSM-5 is for clinicians to directly treat the individual psychopathological domains of the disorder for optimizing individual outcomes. Finally, this paper includes descriptions of the negative symptom items from over a dozen different scales.

White matter integrity and lack of insight in schizophrenia and schizoaffective disorder.

OBJECTIVE: Poor insight into illness is commonly associated with schizophrenia and has implications for the clinical outcome of the disease. A better understanding of the neurobiology of these insight deficits may help the development of new treatments targeting insight. Despite the importance of this issue, the neural correlates of insight deficits in schizophrenia remain poorly understood. METHOD: Thirty-six individuals diagnosed with schizophrenia or schizoaffective disorder underwent diffusion tensor imaging (DTI). The subjects were assessed on two dimensions of insight (symptom awareness and attribution of symptoms) using the Scale to Assess Unawareness of Mental Disorder (SUMD). Level of psychosis was assessed with the Positive and Negative Syndrome Scale (PANSS). RESULTS: White matter abnormalities in the right superior frontal gyrus, left middle frontal gyrus, bilateral parahippocampal gyrus, adjacent to the right caudate head, right thalamus, left insula, left lentiform nucleus, left fusiform gyrus, bilateral posterior cingulate, left anterior cingulate, right cingulate gyrus, left lingual gyrus, and bilateral claustrum were associated with symptom unawareness. Misattribution of symptoms was related to deficits in the white matter adjacent to the right lentiform nucleus, left middle temporal gyrus, and the right precuneus. CONCLUSIONS: Impaired insight in schizophrenia implicates a complex neural circuitry: white matter deficits in fronto-temporo brain regions are linked to symptom unawareness; compromised temporal and parietal white matter regions are involved in the misattribution of symptoms. These findings suggest the multidimensional construct of insight has multiple neural determinants.

Avolition and expressive deficits capture negative symptom phenomenology: implications for DSM-5 and schizophrenia research.

The DSM-5 formulation presents an opportunity to refine the negative symptom assessments that are crucial for a schizophrenia diagnosis. This review traces the history of negative symptom constructs in neuropsychiatry from their earliest conceptualizations in the 19th century. It presents the relevant literature for distinguishing between different types of negative symptoms. Although a National Institute of Mental Health consensus initiative proposed that there are five separate negative symptom domains, our review of the individual items demonstrates no more than three negative symptom domains. Indeed, numerous factor analyses of separate negative symptom scales routinely identify only two domains: 1) expressive deficits, which include affective, linguistic and paralinguistic expressions, and 2) avolition for daily life and social activities. We propose that a focus on expressive deficits and avolition will be of optimum utility for diagnosis, treatment-considerations, and research purposes compared to other negative symptom constructs. We recommend that these two domains should be assessed as separate dimensions in the DSM-5 criteria.

Human hippocampal subfields in young adults at 7.0 T: feasibility of imaging.

PURPOSE: To establish an imaging approach to visualize the 100-microm-thick hippocampal neuron-generating dentate granule cell layer (DGCL) consistently within a clinically feasible magnetic resonance (MR) imaging duration and to assess its sensitivity by quantifying the likelihood that it will be detected in healthy young adults. MATERIALS AND METHODS: The study was HIPAA compliant and institutional review board approved. All subjects provided written informed consent. Ten healthy volunteers (five male subjects, five female subjects; mean age, 26 years +/- 6 [standard deviation]) were imaged at 7.0 T by using a 24-element head coil array with three-dimensional T1-weighted MR imaging for anatomic reference, followed by T2*-weighted gradient-echo (echo time, 25 msec; repetition time, 944 msec) imaging at 232-microm in-plane resolution (0.05-mm(3) pixels) in coronal and sagittal slabs (17 sections at 1 mm thick) over the hippocampus in 14 minutes. The entire study took 45 minutes. RESULTS: The DGCL was consistently visible in all 10 enrolled subjects. All larger subfields were visible in excellent detail and contrast in every subject. CONCLUSION: The spatial resolution and tissue contrast at high field strength (7.0 T) MR imaging can be used to consistently reveal hippocampal morphology down to 100-microm subfields within a clinically acceptable imaging duration. This imaging technique might be used to detect cellular disarray and degenerative changes in this sensitive circuit earlier than at 1.5 T or even 3.0 T. (c) RSNA, 2010.