Valuable interaction with cognitive remediation and optimal antipsychotics for recovery in schizophrenia (VICTORY-S): study protocol for an interventional, open-label, randomized comparison of combined treatment with cognitive remediation and lurasidone or paliperidone.

Background: Cognitive impairment, a core feature of schizophrenia, is associated with poor outcomes. Pharmacotherapy and psychosocial treatment, when used alone, have inadequate effect sizes for cognitive impairment, leading to recent interest in combination interventions. A previous study examined the additive effect of cognitive remediation on lurasidone in patients with schizophrenia, which was negative. Although improvement in cognitive function was suggested for lurasidone, it was inconclusive because there was no antipsychotic control in the study. To clarify whether lurasidone has a meaningful impact on cognitive function in combination with cognitive remediation, we use paliperidone as a control antipsychotic in this study. We hypothesize that combination with lurasidone will improve cognitive and social function to a greater extent than paliperidone. Methods: The valuable interaction with cognitive remediation and optimal antipsychotics for recovery in schizophrenia study is a multicenter, interventional, open-label, rater-blind, randomized comparison study, comparing the effect of lurasidone plus cognitive remediation with that of paliperidone plus cognitive remediation in patients with schizophrenia. The Neuropsychological Educational Approach to Remediation (NEAR) is used for cognitive remediation. Eligible patients will be randomized 1:1 to receive lurasidone or paliperidone combined with NEAR (6 weeks antipsychotic alone followed by 24 weeks combination antipsychotic plus NEAR). The primary endpoint is the change from baseline in the tablet-based Brief Assessment of Cognition in Schizophrenia composite T-score at the end of the NEAR combination treatment period. Secondary endpoints will include change from baseline in social function, schizophrenia symptoms, and quality of life at the end of the NEAR combination treatment period. Furthermore, change from baseline to the end of the pharmacotherapy period and change from the end of the pharmacotherapy period to the end of the NEAR combination treatment period will be assessed for all endpoints. Safety will also be evaluated. Discussion: Achievement of adequate cognitive function is central to supporting social function, which is a key treatment goal for patients with schizophrenia. We think this study will fill in the gaps of the previous study and provide useful information regarding treatment decisions for patients with schizophrenia. Clinical trial registration: Japan Registry of Clinical Trials ID, jRCTs031200338.

The Feasibility and Efficacy of Social Cognition and Interaction Training for Outpatients With Schizophrenia in Japan: A Multicenter Randomized Clinical Trial.

Background: Schizophrenia is a disabling illness. Social cognition and interaction training (SCIT) seeks to improve patients' social functioning by alleviating deficits in social cognition. SCIT has shown promise in improving social cognition in patients with schizophrenia, but has not yet been studied in Japan. Design: An assessor-masked, randomized, parallel-group clinical trial was conducted to compare the feasibility and efficacy of SCIT with treatment as usual (TAU). Setting: Participants were recruited from outpatient clinics at the National Center of Neurology and Psychiatry and four other hospitals in Japan. Participants: Seventy-two patients diagnosed with schizophrenia or schizoaffective disorder consented to participate in the trial. Procedure: Participants were randomly allocated to either a SCIT subgroup or a TAU subgroup. SCIT is a manual-based group intervention that is delivered in 20-24-h-long weekly sessions. Groups include two to three clinicians and four to eight patients. Hypotheses: We hypothesized that SCIT would be found to be feasible and that patients who were randomized to receive SCIT would exhibit improvements in social cognition. Results: Data from 32 participants in each subgroup were entered into analyses. The persistence rate in the SCIT subgroup was 88.9%, and the average attendance rate was 87.0%. Intrinsic motivation was significantly higher in the SCIT subgroup than the TAU group during the first half of the program. Mixed effects modeling of various outcome measures revealed no significant interaction between measurement timepoint and group in any measures, including social cognition, neurocognition, symptom severity, and social functioning. In the case of the social cognition measure, significant change was observed only in the SCIT subgroup; however, the interaction between timepoint and group failed to reach significance. In an exploratory subgroup analysis, a shorter duration of illness was found to be associated with significantly better improvement on the social cognition measure in the SCIT subgroup compared with the TAU subgroup. Conclusions: In terms of the primary objective, the relatively low dropout rate observed in the present study suggests that SCIT is feasible and well tolerated by patients with schizophrenia in Japan. This view is also supported by participants' relatively high attendance and intrinsic motivation.

Impaired Interpretation of Others' Behavior is Associated with Difficulties in Recognizing Pragmatic Language in Patients with Schizophrenia.

Much attention has been paid to the pragmatic language function in schizophrenia. This study of Japanese patients with schizophrenia examined the relationship between impaired interpretation of the behaviors of other people in social contexts and the ability to recognize metaphor and irony. We assessed 34 patients with schizophrenia and 34 normal subjects using first- and second-order theory of mind tasks, the Metaphor and Sarcasm Scenario Test, and the Dewey Story Test (which tests the ability to judge others' social behaviors). We compared the performance between the groups and analyzed correlations between the tasks. All tasks revealed significant deficits in the patients compared with the controls. In the patient group, metaphor comprehension was correlated with the ability to judge normal behaviors, and irony comprehension was correlated with the ability to judge abnormal behaviors, suggesting that deficits of social cognition in schizophrenia include these two types of factors associated with pragmatic language.

Early Cerebral Circulation Disturbance in Patients Suffering from Severe Traumatic Brain Injury (TBI): A Xenon CT and Perfusion CT Study.

Traumatic brain injury (TBI) is widely known to cause dynamic changes in cerebral blood flow (CBF). Ischemia is a common and deleterious secondary injury following TBI. Detecting early ischemia in TBI patients is important to prevent further advancement and deterioration of the brain tissue. The purpose of this study was to clarify the cerebral circulatory disturbance during the early phase and whether it can be used to predict patient outcome. A total of 90 patients with TBI underwent a xenon-computed tomography (Xe-CT) and subsequently perfusion CT to evaluate the cerebral circulation on days 1-3. We measured CBF using Xe-CT and mean transit time (MTT: the width between two inflection points [maximum upward slope and maximum downward slope from inflow to outflow of the contrast agent]) using perfusion CT and calculated the cerebral blood volume (CBV) using the AZ-7000W98 computer system. The relationships of the hemodynamic parameters CBF, MTT, and CBV to the Glasgow Coma Scale (GCS) score and the Glasgow Outcome Scale (GOS) score were examined. There were no significant differences in CBF, MTT, and CBV among GCS3-4, GCS5-6, and GCS7-8 groups. The patients with a favorable outcome (GR and MD) had significantly higher CBF and lower MTT than those with an unfavorable one (SD, VS, or D). The discriminant analysis of these parameters could predict patient outcome with a probability of 70.6%. During the early phase, CBF reduction and MTT prolongation might influence the clinical outcome of TBI. These parameters are helpful for evaluating the severity of cerebral circulatory disturbance and predicting the outcome of TBI patients.

Development of the Cognitive Test for Severe Dementia.

BACKGROUND/AIMS: Existing cognitive measures for moderate-to-severe dementia have shown floor effects and an inability to assess the remaining cognitive function, especially for profound dementia. METHODS: We constructed the Cognitive Test for Severe Dementia (CTSD), which consists of 13 items covering 7 cognitive domains, and examined its reliability and validity. RESULTS: Cronbach's α in severe dementia participants was 0.896. Interrater and test-retest reliability were 0.961 and 0.969, respectively. The CTSD showed a significant correlation with 3 other measures of cognitive function (Mini-Mental State Examination, Severe Cognitive Impairment Rating Scale, and Hasegawa Dementia Scale-Revised: r values = 0.870-0.922, p values <0.001). While the other measures showed floor effects, the CTSD did not. CONCLUSION: The CTSD was able to sensitively capture the remaining cognitive function in severe dementia patients when compared with other cognitive tests.

[Infected subdural hematoma having a surgery of chronic subdural hematoma 1 year ago:a case report].

We report a case of an infected subdural hematoma that occurred 1 year after burr-hole irrigation for chronic subdural hematoma. A 78-year-old woman who had developed left hemiparesis was admitted to our hospital. A computed tomography(CT)scan revealed the presence of a chronic subdural hematoma in the right hemisphere. Her clinical symptoms improved immediately after emergency burr-hole irrigation, which allowed her discharge from the hospital. One year after the initial surgery, she developed an infection of the urinary tract infection, which led to severe pyelonephritis and septic shock. Treatment of the urological symptoms eliminated the systemic inflammation. One month after the urinary infection, the patient was readmitted to the hospital in a comatose state. A CT scan showed regrowth of a residual subdural hematoma surrounded by a thick capsule, causing a midline shift in the brain. An emergency operation for removal of the subdural hematoma by burr-hole irrigation was performed, and pus was drained from the subdural mass. Microbiological cultures of the abscess revealed the presence of Proteus mirabilis. After surgery, the patient was administered an antibiotic treatment for three weeks and she was discharged with no neurological deficits. Cultures of blood from the septic shock as well as from the abscess both revealed the presence of Proteus mirabilis. Therefore, a diagnosis of infected subdural hematoma, which was caused by hematogenous infection, was made. We conclude that attention should be paid to the risk of infection of the hematoma capsule in subdural hematomas.

Ruptured aneurysm of the PICA communicating artery: a case report.

A 47-year-old man presented with a rare aneurysm arising from the posterior inferior cerebellar artery communicating artery (PICA com A), manifesting as subarachnoid with intraventricular hemorrhage. Cerebral angiography showed a defect of the left PICA, and the left PICA region was supplied by a communicating artery formed by the fusion of branches from the right PICA and right vertebral artery. Aneurysms arose in the communicating artery, and a small, unruptured fusiform aneurysm was observed adjacent to a ruptured aneurysm. Trapping was performed for the 2 aneurysms with occipital artery (OA)-PICA bypass. Six cases of aneurysms occurring in this vessel including ours have been reported, and hemodynamic factors and congenital fragility of the arterial wall have been suggested as causative factors. Ours is the first case in which a ruptured aneurysm of this vessel was treated surgically with concurrent vascular reconstruction. If the aneurysm has a shape that is difficult to clip, the affected vessel is difficult to preserve, and collateral blood flow to the affected PICA region is considered insufficient, trapping with OA-PICA bypass is recommended.

[Study of cumulative head injury in high shock avoider rat (THA rat)].

PURPOSE: Small but repeated head trauma, as represented by boxing-related punch-drunk syndrome and dementia pugilistica, occasionally cause dyskinesia and marked brain dysfunction following long-term post-traumatic follow-up, despite the absence of intracranial lesions, such as cerebral contusion and intracranial hemorrhage. We defined this condition as "cumulative head injury." To clarify its mechanism, we conducted an experiment involving appliciation of continuous head trauma of Tokai High Avoider (THA) rats, and examined subsequent marked function/histopathological changes. METHODS: THA rats were divided into 3 categories based on the frequency of impact exposure: a control group (Group A), a group exposed to 1 impact set (Group B), and a group exposed to 3 impact sets (Group C). In each group, histopathological, spontaneous motility, and learning tests were conducted. RESULTS: Histopathologically, no marked tissue destruction was observed in Group B or C. In Group C, the number of GFAP-positive cells were increased in acute-phase specimens of the hippocampus, cerebral cortex, and basilar cortex. With respect to chronic-phase histological changes, the numbers of GFAP-positive cells were increased in the hippocampus and the basilar cortex in Group C; however, these changes were less marked than in the acute stage. A marked function test identified emotional suppression in the acute stage and bimodal learning reduction in the acute to chronic stages in Group C. CONCLUSION: The results of this experiment revealed that the repetition of low-level trauma which did not lead to brain injury as revealed on pathological examination, induced emotional suppression and the bimodal reduction in learning results; further, this disorder exacerbated with an increase in impact frequency. The influence on marked brain function could be verified using a specific experimental system of THA rats. This model may be useful for evaluating the cumulative effects of repeated head trauma.

Brainstem involvement in hypertensive encephalopathy: a report of two cases and literature review.

The cerebral hemispheres show prominent involvement in hypertensive encephalopathy far more frequently than the brainstem. Two patients with severe paroxysmally accelerated hypertension associated with brainstem hyperintensity in T2-weighted magnetic resonance images are presented. Both present hyperintense lesions improved dramatically in appearance after stabilization of blood pressure. Extreme acceleration of hypertension may be essential for breakdown of autoregulation in the brainstem circulation. The marked clinicoradiologic dissociation ruled out major brainstem infarction and made tumor unlikely.

Primary midbrain cystic germinoma mimicking glioma: a case with neuroendoscopic biopsy.

Intracranial germinoma arising primarily in the midbrain is extremely rare. We present the first reported case of cystic midbrain germinoma that lacked evident solid components and mimicked a midbrain glioma. In a 22-year-old man with headache and diplopia, magnetic resonance imaging showed a ring-enhancing lesion in the midbrain. The preoperative diagnosis included brain stem glioma, metastasis, and neuroepithelial cyst. A neuroendoscopic biopsy specimen provided a histologic diagnosis of germinoma. The patient responded well to chemotherapy and radiotherapy. The case illustrates the diagnostic value of neuroendoscopic biopsy in the differential diagnosis of brainstem lesions in adult. The possibilities considered should now include germinoma.