Neurological soft signs and structural network changes: a longitudinal analysis in first-episode schizophrenia.

BACKGROUND: Neurological soft signs (NSS) are often reported in patients with schizophrenia and may vary with psychopathological symptoms during the course of disease. Many cross-sectional neuroimaging studies have shown that NSS are associated with disturbed network connectivity in schizophrenia. However, it remains unclear how these associations change over time during the course of disorder. METHODS: In present study, 20 patients with first-episode schizophrenia and 20 controls underwent baseline structural magnetic resonance imaging (MRI) scan and at one-year follow-up. Structural network characteristics of patients and controls were analyzed using graph theoretical approach based on MRI data. NSS were assessed using the Heidelberg scale. RESULTS: At baseline, patients demonstrated significant changes of the local network properties mainly involving regions of the cortical-subcortical-cerebellar circuits compared to healthy controls. For further analysis, the whole patient group was dichotomized into a NSS-persisting and NSS-decreasing subgroup. After one-year follow-up, the NSS-persisting subgroup showed decreased betweenness in right inferior opercular frontal cortex, left superior medial frontal cortex, left superior temporal cortex, right putamen and cerebellum vermis and increased betweenness in right lingual cortex. However, the NSS-decreasing subgroup exhibited only localized changes in right middle temporal cortex, right insula and right fusiform with decreased betweenness, and in left lingual cortex with increased betweenness. CONCLUSIONS: These findings provide evidence for brain network reorganization subsequent to clinical disease manifestation in patients with first-episode schizophrenia, and support the hypothesis that persisting NSS refer to progressive brain network abnormalities in patients with schizophrenia. Therefore, NSS could help to establish a better prognosis in first-episode schizophrenia patients.

Assessing capacity to consent to treatment with cholinesterase inhibitors in dementia using a specific and standardized version of the MacArthur Competence Assessment Tool (MacCAT-T).

BACKGROUND: The use of assessment tools has been shown to improve the inter-rater reliability of capacity assessments. However, instrument-based capacity assessments of people with dementia face challenges. In dementia research, measuring capacity with instruments like the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) mostly employ hypothetical treatment vignettes that can overwhelm the abstraction capabilities of people with dementia and are thus not always suitable for this target group. The primary aim of this study was to provide a standardized real informed consent paradigm that enables the dementia-specific properties of capacity to consent to treatment in people with dementia to be identified in a real informed consent process that is both externally valid and ethically justifiable. METHODS: The sample consisted of 53 people with mild to moderate dementia and a group of 133 people without cognitive impairment. Rather than using a hypothetical treatment vignette, we used a standardized version of the MacCAT-T to assess capacity to consent to treatment with cholinesterase inhibitors in people with dementia. Inter-rater reliability, item statistics, and psychometric properties were also investigated. RESULTS: Intraclass correlations (ICCs) (0.951-0.990) indicated high inter-rater reliability of the standardized real informed consent paradigm. In the dementia group, performance on different items of the MacCAT-T varied. Most people with dementia were able to express a treatment choice, and were aware of the need to take a tablet. Further information on the course of the disorder and the benefits and risks of the treatment were less understood, as was comparative reasoning regarding treatment alternatives. CONCLUSION: The standardized real informed consent paradigm enabled us to detect dementia-specific characteristics of patients' capacity to consent to treatment with cholinesterase inhibitors. In order to determine suitable enhanced consent procedures for this treatment, we recommend the consideration of MacCAT-T results on an item level. People with dementia seem to understand only basic information. Our data indicate that one useful strategy to enhance capacity to consent is to reduce attention and memory demands as far as possible.

Cerebrospinal fluid concentrations of functionally important amino acids and metabolic compounds in patients with mild cognitive impairment and Alzheimer's disease.

Cerebrospinal fluid (CSF) biomarkers play an important role in the differential diagnosis of neurodegenerative diseases such as Alzheimer's disease (AD) and its postulated precursor stage mild cognitive impairment (MCI). While CSF tau protein, phospho-tau protein and beta-amyloid have become part of the diagnostic process in clinical routine, the importance of several other biomarkers remains quite unclear. Among these, amino acids and metabolic compounds have been studied in clinical conditions mostly other than AD and, to our knowledge, never in MCI. In patients with AD (n = 14) and MCI (n = 13) we now determined CSF levels of 36 different amino acids and metabolic compounds by high-performance liquid chromatography. We found that 8 out of 36 amino acids (urea, threonine, glutamate, citrulline, alpha-aminobutyric acid, ornithine, ammonia and arginine) were significantly elevated in the CSF of patients with AD compared to those with MCI. As most of these amino acids and metabolic compounds are functionally important for brain-specific metabolic processes, neurotransmitter pathways or compensatory mechanisms, our findings might reflect these changes occurring within the brain of patients with MCI and those who developed manifest AD.

Associations between brain structural networks and neurological soft signs in healthy adults.

Neurological soft signs (NSS), as minor neurological deficits, have been identified in several psychiatric disorders, especially in schizophrenia. However, it's unclear how the neuropathological processes of the disease affect NSS related brain morphological changes and whether it is confounded by the use of medication. As NSS also exist in healthy people, the potential confounding effects of psychopathology or medication will be excluded if NSS are investigated in healthy people. Therefore, we applied a novel multivariate approach, source-based morphometry (SBM), to study structural networks in relation to NSS in healthy adults based on structural magnetic resonance imaging (MRI) data. The Heidelberg Scale was applied to evaluate NSS. Using SBM, we constructed structural networks and investigated their associations with NSS in healthy adults. Six grey matter (GM) structural networks were identified. Sensory integration subscores were associated with the cerebellar component and the cortico-basal ganglia-thalamic component. Motor coordination subscores and total NSS scores were associated with the sensorimotor component. The present findings indicated that structural network abnormalities in cerebellar, subcortical and cortical sensorimotor areas contribute to NSS performance in healthy adults.

Cytomegalovirus and schizophrenia.

Several lines of evidence suggest that cytomegalovirus (CMV) may play an aetiological role in schizophrenia. Epidemiologically, both have a worldwide distribution and an increased prevalence in lower socioeconomic groups. Studies have reported that some patients experiencing initial episodes of schizophrenia have increased levels of IgG antibodies against CMV, but not other herpes viruses, in their sera and CSF. Treatment with antipsychotic medications may result in a decrease in CMV antibodies, while treatment with anti-herpes virus and anti-inflammatory medications may reduce symptoms in some individuals with schizophrenia. There is also some overlap in the genes that are thought to operate in CMV infections and schizophrenia. The strongest argument against the role of CMV in schizophrenia is the absence of the traditional CMV neuropathological changes in the brains of individuals with schizophrenia; however, neuropathological studies of CMV have mostly been conducted in immune-compromised individuals. Further studies on CMV and schizophrenia are needed and may lead to improved treatments for schizophrenia.

Effect of donepezil in patients with Alzheimer's disease previously untreated or treated with memantine or nootropic agents in Germany: an observational study.

OBJECTIVE: This open-label, prospective, observational, Post-Marketing Surveillance (PMS) study assessed the efficacy and safety of donepezil in patients who had been switched from therapies currently used in Germany to treat Alzheimer's disease (AD), such as memantine and nootropics, due to insufficient efficacy or poor tolerability. A treatment-naive population was included as a comparator. RESEARCH DESIGN AND METHODS: Patients with AD were treated with donepezil and observed for a period of approximately 3 months. A cognitive assessment was made using the Mini-Mental State Examination (MMSE). Quality of life (QoL) was assessed by the investigators who answered the question 'How did therapy with donepezil influence the QoL of the patient and/or his family over the observation period?' and was graded using three ratings: improved/unchanged/worsened. Adverse events (AEs) were also monitored. RESULTS: A total of 913 patients entered the study (mean +/- SD MMSE score 18.03 +/- 5.34). Efficacy assessments were analyzed for three groups: an overall group of patients who had received any form of prior AD drug therapy (N+ group; n = 709); a subgroup of patients from the N+ group who had received prior memantine therapy only (M+ group; n = 111) and patients who were drug treatment naive (N- group; n = 204). In the evaluable population donepezil improved MMSE scores by 2.21 +/- 3.47 points on average, with similar improvements observed in all three groups. QoL was judged to be improved in at least 70% of patients, again with similar results obtained for all three groups. Donepezil was well tolerated, with 85 of 913 (9.3%) patients reporting AEs. The most common AEs were those typically seen with cholinergic therapies (i.e., diarrhoea, vomiting and nausea). CONCLUSIONS: In this observational PMS study, donepezil was shown to be efficacious and well tolerated in patients who were being insufficiently treated with memantine or nootropic therapy. The magnitude of response was similar to that observed in patients who were previously treatment naive, suggesting prior medication does not effect donepezil's efficacy.

Brain signatures of moral sensitivity in adolescents with early social deprivation.

The present study examined neural responses associated with moral sensitivity in adolescents with a background of early social deprivation. Using high-density electroencephalography (hdEEG), brain activity was measured during an intentional inference task, which assesses rapid moral decision-making regarding intentional or unintentional harm to people and objects. We compared the responses to this task in a socially deprived group (DG) with that of a control group (CG). The event-related potentials (ERPs) results showed atypical early and late frontal cortical markers associated with attribution of intentionality during moral decision-making in DG (especially regarding intentional harm to people). The source space of the hdEEG showed reduced activity for DG compared with CG in the right prefrontal cortex, bilaterally in the ventromedial prefrontal cortex (vmPFC), and right insula. Moreover, the reduced response in vmPFC for DG was predicted by higher rates of externalizing problems. These findings demonstrate the importance of the social environment in early moral development, supporting a prefrontal maturation model of social deprivation.

Insular networks for emotional processing and social cognition: comparison of two case reports with either cortical or subcortical involvement.

INTRODUCTION: The processing of the emotion of disgust is attributed to the insular cortex (IC), which is also responsible for social emotions and higher-cognitive functions. We distinguish the role of the IC from its connections in regard to these functions through the assessment of emotions and social cognition in a double case report. These subjects were very rare cases that included a focal IC lesion and a subcortical focal stroke affecting the connections of the IC with frontotemporal areas. MATERIALS & METHODS: Both patients and a sample of 10 matched controls underwent neuropsychological and affective screening questionnaires, a battery of multimodal basic emotion recognition tests, an emotional inference disambiguation task using social contextual clues, an empathy task and a theory of mind task. RESULTS: The insular lesion (IL) patient showed no impairments in emotion recognition and social emotions and presented with a pattern of delayed reaction times (RTs) in a subset of both groups of tasks. The subcortical lesion (SL) patient was impaired in multimodal aversive emotion recognition, including disgust, and exhibited delayed RTs and a heterogeneous pattern of impairments in subtasks of empathy and in the contextual inference of emotions. CONCLUSIONS: Our results suggest that IC related networks, and not the IC itself, are related to negative emotional processing and social emotions. We discuss these results with respect to theoretical approaches of insular involvement in emotional and social processing and propose that IC connectivity with frontotemporal and subcortical regions might be relevant for contextual emotional processing and social cognition.

Evaluation of disk position and prevalence of internal derangement, in a sample of the elderly, by gadolinium-enhanced magnetic resonance imaging.

OBJECTIVES: To assess disk position and the prevalence of disk displacement (DD) in a sample of the elderly by use of contrast agent-enhanced magnetic resonance imaging (MRI). STUDY DESIGN: Thirty subjects (73-75 years old) were drawn from a representative sample and examined clinically. The position and contours of the temporomandibular disk was assessed by using gadolinium-enhanced MR images which were evaluated by 2 independent raters. Statistical assessment was performed by using descriptive statistics and nonparametric tests. RESULTS: Agreement between raters with respect to disk position was excellent. The MRI showed that 8 subjects (27%; 2 men, 6 women) had DD. CONCLUSION: Gadolinum-enhanced MRI showed that DD is common in the elderly (27%) and that DD occurs more frequently in women than in men. In women without DD the disk is positioned more anteriorly than in men.

12 years' experience with intraoperative radiotherapy (IORT) of malignant gliomas.

BACKGROUND: Even after surgery and radiotherapy, malignant gliomas still have a poor prognosis. The authors report on their experience with IORT in 71 patients. PATIENTS AND METHODS: From May 1992 to February 2004, 71 patients with malignant gliomas were treated with IORT. 26 patients suffered from grade III gliomas, 45 patients from glioblastomas (GBM). IORT was carried out using a standard electron tube and 9- to 18-MeV electrons. 52/71 patients who were primarily treated received 20 Gy IORT + 60 Gy postoperative radiotherapy, 19/71 patients with recurrences only received IORT (20-25 Gy). RESULTS: The complication rates were 1.4% for wound infections and 5.6% for hemorrhage. Median disease-specific survival amounted to 14.9 months (gliomas III) and 14.2 months (GBM). The 2-year survival rates amounted to 26.9% (gliomas III) and 6.8% (GBM; p = 0.0296). Total versus subtotal resection had no significant influence on survival (p = 0.0741), nor had age, sex, tumor site, performance status, size, primary versus recurrence, and radiation dose. A comparison to a conventionally treated patient group did not show a significant survival improvement. 3 months after treatment, initial symptoms had improved in 59% (hemiparesis), 50% (aphasia), 50% (hemianopsia), and 60% (convulsions). CONCLUSION: IORT has been shown to be feasible; perioperative complication rates were not increased. Survival was generally not improved compared to a historical control group. Recurrences achieved the same survival as primary tumors, and GBM also had a slightly increased survival, thus being possible indications for IORT.