Pediatric myxopapillary ependymoma treated with subtotal resection and radiation therapy: a case report and review of the literature.

STUDY DESIGN: Case report and review of the literature. OBJECTIVES: Myxopapillary ependymoma (MPE) is a relatively rare glioma that develops from the spinal part of the filum terminale, usually in adulthood. While it is generally benign, MPE can disseminate intraspinally, and this malignant behavior requires a multidisciplinary response with surgery and radiotherapy. We report here a case of MPE occurring in the lumbosacral spine area of an 8-year-old boy. SETTING: Japan, Tokyo. METHODS: We report here a case of MPE, treated with subtotal surgical resection followed by craniospinal irradiation (CSI), in an 8-year-old boy. The patient was referred to our hospital with a 6-month history of severe pain in the lower back and legs, paralysis of the legs and dysuria. Magnetic resonance imaging images showed a large tumor that filled the entire spinal canal below L1. After subtotal resection of the tumor, the pathological findings established a diagnosis of MPE. Since the tumor had perforated its capsule, increasing the risk of intraspinal dissemination, the patient underwent radiotherapy and CSI after surgery. RESULTS: Magnetic resonance images obtained 3 years after the surgery did not show any recurrence of MPE. CONCLUSION: Although tumor resection followed by CSI can be considered an effective strategy for treating a child with MPE, long-term follow-up is necessary to ensure early detection of any local recurrence or dissemination of the tumor, or of post-radiotherapy scoliosis.

Transplantation of human neural stem cells for spinal cord injury in primates.

Recent studies have shown that delayed transplantation of neural stem/progenitor cells (NSPCs) into the injured spinal cord can promote functional recovery in adult rats. Preclinical studies using nonhuman primates, however, are necessary before NSPCs can be used in clinical trials to treat human patients with spinal cord injury (SCI). Cervical contusion SCIs were induced in 10 adult common marmosets using a stereotaxic device. Nine days after injury, in vitro-expanded human NSPCs were transplanted into the spinal cord of five randomly selected animals, and the other sham-operated control animals received culture medium alone. Motor functions were evaluated through measurements of bar grip power and spontaneous motor activity, and temporal changes in the intramedullary signals were monitored by magnetic resonance imaging. Eight weeks after transplantation, all animals were sacrificed. Histologic analysis revealed that the grafted human NSPCs survived and differentiated into neurons, astrocytes, and oligodendrocytes, and that the cavities were smaller than those in sham-operated control animals. The bar grip power and the spontaneous motor activity of the transplanted animals were significantly higher than those of sham-operated control animals. These findings show that NSPC transplantation was effective for SCI in primates and suggest that human NSPC transplantation could be a feasible treatment for human SCI.

Establishment of graded spinal cord injury model in a nonhuman primate: the common marmoset.

Most previous studies on spinal cord injury (SCI) have used rodent models. Direct extrapolation of the results obtained in rodents to clinical cases is difficult, however, because of neurofunctional and anatomic differences between rodents and primates. In the present study, the development of histopathologic changes and functional deficits were assessed quantitatively after mild, moderate, and severe spinal cord contusive injuries in common marmosets. Contusive SCI was induced by dropping one of three different weights (15, 17, or 20 g) at the C5 level from a height of 50 mm. Serial magnetic resonance images showed significant differences in the intramedullary T1 low signal and T2 high signal areas among the three groups. Quantitative histologic analyses revealed that the number of motor neurons, the myelinated areas, and the amounts of corticospinal tract fibers decreased significantly as the injury increased in severity. Motor functions were evaluated using the following tests: original behavioral scoring scale, measurements of spontaneous motor activity, bar grip test, and cage-climbing test. Significant differences in all test results were observed among the three groups. Spontaneous motor activities at 10 weeks after injury were closely correlated with the residual myelinated area at the lesion epicenter. The establishment of a reliable nonhuman primate model for SCI with objective functional evaluation methods should become an essential tool for future SCI treatment studies. Quantitative behavioral and histopathologic analyses enabled three distinct grades of injury severity (15-g, 17-g, and 20-g groups) to be characterized with heavier weights producing more serious injuries, and relatively constant behavioral and histopathologic outcomes.

Prescribing for inpatients with schizophrenia: an international multi-center comparative study.

BACKGROUND: This study compares prescription practices for acute inpatients with schizophrenia among six academic departments located in China, Japan, Hungary, and the U.S. METHODS: Prescription data for a sample of 429 inpatients from six academic departments were collected on a randomly chosen census day. All patients met criteria for schizophrenia according to DSM-IV and had a length of illness of at least two years. RESULTS: While patients at the different centers varied in their demographic and clinical characteristics, i. e., age, sex, and length of illness, a great variation in prescription patterns for antipsychotic and other psychotropic drugs among centers was observed even within the same country for all the variables studied (i. e., number and dose antipsychotics, atypical and depot antipsychotics, other psychotropic drugs, multiple antipsychotics, and daily dose) except antidepressant use. In most cases these differences persisted even after adjusting for demographic and clinical characteristics (age, sex, and length of illness) of the subjects. Antipsychotics were usually prescribed in divided daily doses in combination with one or more other psychotropic drugs, including anticholinergics, anticonvulsants, benzodiazepines, and non-benzodiazepine hypnotics. Anticholinergic use was more common with typical antipsychotics. Rates of atypical antipsychotic drug use were lowest in the Japanese center. The Japanese center had by far the highest mean daily dose of antipsychotics. CONCLUSIONS: The results indicate that prescription patterns in different centers do not follow any specific guidelines for the treatment of schizophrenia. The results also confirm previous findings that prescribing practices for schizophrenia vary greatly among centers and countries. A common prescribing pattern found was the use of atypical antipsychotic drugs in combination with psychotropic drugs, such as anticholinergics, hypnotics, anticonvulsants, and benzodiazepines, administered in multiple daily doses.

Voxel-based analysis of MRI reveals anterior cingulate gray-matter volume reduction in posttraumatic stress disorder due to terrorism.

MRI studies using the manual tracing method have shown a smaller-than-normal hippocampal volume in patients with posttraumatic stress disorder (PTSD). However, these studies have yielded inconsistent results, and brain structures other than the hippocampus have not been well investigated. A recently developed, fully automated method called voxel-based morphometry enables an exploration of structural changes throughout the brain by applying statistical parametric mapping to high-resolution MRI. Here we first used this technology in patients with PTSD. Participants were 9 victims of the Tokyo subway sarin attack with PTSD and 16 matched victims of the same traumatic event without PTSD. The voxel-based morphometry showed a significant gray-matter volume reduction in the left anterior cingulate cortex (ACC) in trauma survivors with PTSD compared with those without PTSD. The severity of the disorder was negatively correlated with the gray-matter volume of the left ACC in PTSD subjects. There were no significant differences in other gray-matter regions or any of the white-matter regions between two groups. The present study demonstrates evidence for structural abnormalities of ACC in patients with PTSD. Together with previous functional neuroimaging studies showing a dysfunction of this region, the present findings provide further support for the important role of ACC, which is pivotally involved in attention, emotional regulation, and conditioned fear, in the pathology of PTSD.

1H-MR spectroscopy and gray matter volume of the anterior cingulate cortex in schizophrenia.

Schizophrenic and normal control subjects were examined using both H-magnetic resonance spectroscopy (MRS) and structural MR imaging, in order to accurately assess the partial volume within the spectroscopic volume of interest (VOI) in the anterior cingulate cortex. The gray matter volume within VOI correlated positively with the N-acetyl-aspartate (NAA) to choline (Cho) ratio in schizophrenics only, not in controls. Schizophrenic patients had a reduced NAA/Cho ratio and an elevated Cho/creatine ratio compared to controls after the partial volume effect was eliminated. There was a significant negative correlation between the NAA/Cho ratio and the severity of blunted affect symptom in schizophrenics. These results provide further support to the idea that the measures of H-MRS indicate not only neuronal loss but also neuronal dysfunction in schizophrenia.

Brain lateralization for mismatch response to across- and within-category change of vowels.

Differences in hemispheric predominance between across- and within-category change perception of vowels were assessed using a whole-head magnetoencephalography. The magnetic mismatch responses (MMNm) to pure-tone and vowel within-category changes were significantly predominant in the right hemisphere; on the other hand, vowel across-category MMNm did not differ in power between hemispheres. The results suggest that both hemispheres are symmetrically activated in the preattentive across-category change perception of vowels, while the within-category change of a vowel is analyzed as the change in physical features of the stimuli, thus predominantly activating the right hemisphere. Thus, the relative contribution of the left auditory cortex in the preattentive speech processing may occur only at the level of perception of the vowel across-category change.

Impaired suppression of processing in schizophrenic patients suggested by ERPs obtained in a selective attention task.

In the present study, we focused on the ability of suppression of processing in schizophrenic patients, using event-related potentials (ERPs) recorded during a selective attention task. During the task, subjects were required to focus on one ear, counting deviant stimuli, those deviating in duration from a sequence of standard stimuli. We compared amplitude data of two positive components differing in latency elicited by standard stimuli, which reflect suppression of stimulus processing, between schizophrenic patients and normal controls. Significant between-group differences were obtained specifically in the right ear attended condition, suggesting impaired suppression of processing in schizophrenics mediated in the left hemisphere.

Effects of risperidone on event-related potentials in schizophrenic patients.

In order to examine the effects of risperidone on cognitive impairment in schizophrenia, event-related potentials (ERPs) were recorded before and after switching from conventional neuroleptics to risperidone in schizophrenic patients. ERPs were recorded during two auditory discrimination tasks (an oddball task and a distraction task) in 10 medicated schizophrenic patients during conventional neuroleptic and risperidone treatments. The amplitudes and latencies of N 100 and P300 component were measured in ERPs for target stimuli in the oddball task and in ERPs for target and novel stimuli in the distraction task. Although N 100 amplitude and latency and P 300 amplitude did not change significantly after switching the drug compared to that during conventional neuroleptic treatment, P 300 latency for target stimuli shortened significantly during risperidone treatment in both tasks, accompanied by the shortening of the reaction time in the distraction task. The P 300 latency change did not correlate with the change of the severity of psychopathology. These findings suggest that risperidone may speed the information processing in schizophrenic patients, contributing to the improvement of cognitive functions.

Psychophysiological correlates of social skills deficits in persons with schizophrenia.

Social skill deficits in schizophrenia profoundly affect patients' life-long outcome, although the profile of the underlying cognitive dysfunction still remains a matter of debate. In the present study, we investigated the relationship between social skills and event-related potentials (ERPs) in an auditory selective attention task, in addition to the neurocognitive indices obtained from the degraded-stimulus continuous performance test (CPT) and clinical indices, such as Brief Psychiatric Rating Scale (BRPS) and global assessment of function (GAF) scores. Social skills were assessed using a Japanese version of the structured role play test. Fourteen persons with schizophrenia participated in the study. Non-verbal skills showed a positive correlation with GAF, the performance level, N1 and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Verbal communication skills showed a positive correlation with GAF, the performance level and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Processing skills showed a positive correlation with the performance level and N1 amplitude in the ERP task and a negative correlation with reaction time in the CPT. These findings suggested that the social skill deficits of persons with schizophrenia were related to the vigilance level and controlled stimulus detection processing.

Event-related potentials and thought disorder in schizophrenia.

We examined the relationship between event-related potentials and thought disorder in schizophrenia. The subjects were 29 chronic schizophrenic patients. Thought disorder was assessed using the Comprehensive Index of Positive Thought Disorder developed by Harrow and colleagues (Harrow and Quinlan, 1985; Marengo et al., 1986). Auditory event-related potentials were recorded during a standard oddball task. The P300 amplitude correlated negatively with the severity of the thought disorder. The P300 amplitude in the patients with thought disorder was significantly smaller than in the patients without thought disorder. These results suggest that a reduction in P300 amplitude is associated with a fundamental impairment of information processing in schizophrenic patients.

Algorithms for the pharmacotherapy psychotic depression.

Psychotic depression is reported and requires different pharmacological treatment from other mood disorders, however, sufficient studies to guide us in selecting successful treatment strategies have not been performed. In this study, algorithm for the treatment of psychotic depression was developed by the Japan Psychopharmacology Algorithm Project. The following three issues are emphasized: (1) risk of suicide; (2) agitation; and (3) oral intake ability. When patients show a high risk of suicide and/or agitation, prompt treatment strategies, such as tricyclic antidepressant (TCA)/neuroleptics therapy or electroconvulsive therapy (ECT), are necessary. If patients show no suicidal risk without agitation, TCA therapy is recommended. ECT is recommended as the first choice when the symptoms are severe or when there is an inability of oral intake.

Questionnaire survey on the prescribing practice of Japanese psychiatrists for mood disorders.

The answers to a questionnaire on the practical prescription in mood disorders from 298 Japanese psychiatrists was obtained. As the first-line treatment, a majority of respondents chose newer tricyclic agents (TCA) or non-TCA for moderate depression and older TCA for severe depression both with and without psychotic features. Combination therapy with antidepressants and anxiolytics was fairly popular in moderate depression, while antidepressant/neuroleptic combination was more common in severe psychotic depression. Sulpiride was the most favored drug for dysthymia. Although lithium was the most popular for bipolar mania, respondents were divided on the treatment of bipolar depression.

Multiple generators in the auditory automatic discrimination process in humans.

To reveal the spatiotemporal characteristics of the auditory automatic discrimination process, mismatch negativity (MMN) generators were assessed with a high-resolution EEG system (128ch) and scalp current density (SCD) analysis. Ten normal volunteers participated in the study. Event-related potentials were recorded during a selective attention task. Sequential SCD mappings revealed that a current sink/source combination in the left temporal regions and a current sink in the right frontotemporal regions appeared around 200 msec irrespective of the ear of stimulation. Moreover, a parietal sink/source combination was demonstrated on the right hemisphere around 240 ms irrespective of the ear of stimulation. These findings demonstrate that the auditory automatic change detection process is, both spatially and temporally, a multiple-generated system.

P300 and disability of daily life in schizophrenia.

1. The relationship between the P300 component of event-related potentials and disability of daily life was examined in schizophrenia. The subjects were 26 chronic schizophrenic patients. 2. Disability of daily life was assessed by using the Life Assessment Scale for Mental Illness (LASMI). 3. Auditory event-related potentials were recorded during a standard oddball task. 3. P300 amplitude correlated negatively with general psychopathology scale of PANSS (r = -0.416) and Work of LASMI (r = -0.417). P300 latency did not correlate with any of PANSS or LASMI score. 4. These results indicate that P300 amplitude can be an index for disability of daily life in schizophrenia.

Electrophysiological evidence for sequential activation of multiple brain regions during the auditory selective attention process in humans.

In an attempt to examine dynamic involvement of multiple brain regions in the auditory selective attention process, negative difference wave (Nd) generators were assessed using a high-resolution EEG system (128ch) and scalp current density (SCD) analysis. Ten normal volunteers participated in the study. Event-related potentials were recorded during a selective attention task. Sequential SCD mappings revealed that current sinks were located in the bilateral temporal regions at 160 ms subsequent to the onset of stimuli, shifting the dipole orientation more tangentially to the scalp at around 220 ms. Moreover, a current sink was demonstrated in the midfrontal region at around 320 ms. These findings confirm that different cortical regions are sequentially involved in the auditory selective attention process.

Algorithm for the treatment of mood disorders in Japan.

In order to establish algorithms for mood disorders in Japan, over 300 psychiatrists completed a questionnaire. They were asked to recommend various drug treatments for particular cases. The order in which the drugs were recommended was taken into consideration. References were made to the randomized double blind study conducted by the working group. Evidence was ranked according to its probability, with the addition of case reports and medical opinions, since conclusions derived from the randomized double blind study alone did not give a full representation. Japanese documentation was referred to as much as possible in order to represent Japanese characteristics. Algorithms were made for eight subtypes; acute mania, bipolar depression, mild or moderate, severe major depression, psychotic depression, rapid cycling bipolar disorder, dysthymic disorder and major depression with advanced cancer. Major depression and bipolar disorder algorithms are discussed in this paper. Clinical psychopharmacological evidence in Japan was insufficient to generate these algorithms for mood disorders. These algorithms may need revision according to future advances in clinical psychopharmacology. (Int J Psych Clin Pract 1999; 3: 277-285).

P3a of event-related potential in chronic methamphetamine dependence.

To investigate the psychophysiological features of methamphetamine (MAP) dependence, we recorded auditory event-related potentials (ERPs) in 15 patients with MAP dependence and in 15 age-matched normal controls. ERPs were recorded during a standard oddball task and a read task similar to those employed by Squires et al. (Squires NK, Squires KC, Hillyard SA [1975] Two varieties of long-latency positive waves evoked by unpredictable auditory stimuli in man. Electroenceph Clin Neurophysiol 38:387-401). The patients with MAP dependence showed reduced P3a amplitude and area in the read task and delayed P3b latency with normal P3b amplitude and area in the oddball task. These results suggest that central noradrenergic dysregulation may persist after the remission of acute psychotic symptoms in MAP psychosis and that chronic MAP dependence would produce impairment of the frontal cortex.

Decreased plasma cortisol level during alprazolam treatment of panic disorder: a case report.

1. Changes in the plasma cortisol level were reported in a male patient with panic disorder during the period of low-dose alprazolam treatment (mean 0.62 +/- 0.15 mg/day) compared with during the period of high-dose period (mean 1.08 +/- 0.28 mg/day). 2. The plasma cortisol level was significantly higher in the low-dose period (mean 13.90 +/- 3.35 micrograms/ml) than in the high-dose period (mean 9.06 +/- 2.75 micrograms/ml) although, paradoxically, the panic attack frequency was significantly lower in the low-dose period (mean 1.35 +/- 0.29/day) than in the high-dose period (mean 2.09 +/- 0.66/day). 3. Thus, the decreased plasma cortisol level during alprazolam treatment of panic disorder was suggested to be caused not by symptom alleviation due to alprazolam but by alprazolam administration itself.

Event-related potentials during a selective attention task with short interstimulus intervals in patients with schizophrenia.

OBJECTIVE: To study selective attention in schizophrenia by examining event-related potentials during a dichotic listening task with short interstimulus intervals (ISIs). DESIGN: Prospective study. PARTICIPANTS: Twelve patients with schizophrenia in remission and 12 age-matched controls with no history of psychiatric or neurological illness. INTERVENTIONS: Participants were asked to push a button in response to target stimuli in either ear. OUTCOME MEASURES: Reaction time, correct response rate and results of electroencephalography recorded at 3 regions: mean segmental amplitudes between 0 and 200 ms and between 200 and 400 ms after stimuli and processing negativity (Nd), measured by the negative area during these periods. RESULTS: Distinct slow-positive potentials for unattended stimuli, which were elicited in a task with long ISIs in a previous report, did not emerge in either group in this study. Although the 2 groups did not differ significantly in terms of Nd area, in the controls the mean segmental amplitude for attended standard stimuli was significantly greater than that in the patients with schizophrenia. CONCLUSIONS: Impairment of selective attention in patients with schizophrenia is related to a lack of ability to focus attention on attended task-relevant stimuli during a selective attention task with short ISI.