Brain morphometry and estimation of aging brain in subjects with congenital untreated isolated GH deficiency.

PURPOSE: Individuals with isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene have a normal life expectancy and above 50 years of age, similar total cognitive performance, with better attention and executive function than controls. Our objectives were to evaluate their brain morphometry and brain aging using MRI. METHODS: Thirteen IGHD and 14 controls matched by age, sex, and education, were enrolled. Quantitative volumetric data and cortical thickness were obtained by automatic segmentation using Freesurfer software. The volume of each brain region was normalized by the intracranial volume. The difference between the predicted brain age estimated by MRI using a trained neuronal network, and the chronological age, was obtained. p < 0.005 was considered significant and 0.005 < p < 0.05 as a suggestive evidence of difference. RESULTS: In IGHD, most absolute values of cortical thickness and regional brain volumes were similar to controls, but normalized volumes were greater in the white matter in the frontal pole and in the insula bilaterally, and in the gray matter, in the right insula and in left Caudate (p < 0.005 for all comparisons) We also noticed suggestive evidence of a larger volume in IGHD in left thalamus (p = 0.006), right thalamus (p = 0.025), right caudate (p = 0.046) and right putamen (p = 0.013). Predicted brain ages were similar between groups. CONCLUSION: IGHD is primarily associated with similar absolute brain measurements, and a set of larger normalized volumes, and does not appear to alter the process of brain aging.

Medication adherence with denosumab in patients with bone metastases from solid tumors treated in routine clinical settings: a retrospective study.

PURPOSE: To describe (non)adherence with denosumab among patients with solid tumors and bone metastases. METHODS: This retrospective, observational study pooled data from two completed prospective, multicenter cohort studies (X-TREME; Study 240) in adult patients with bone metastases from primary breast, prostate, lung, kidney, or other solid cancer types and administered denosumab 120 mg in routine clinical practice in Germany and Central and Eastern Europe. The studies were conducted between May 2012 and May 2017; pooled analysis was completed in August 2021. Medication adherence was described according to a three-component consensus taxonomy: initiation (first-ever administration ≤ 90 days from bone metastasis diagnosis), implementation (actual vs prescribed dosing; optimal implementation = regular/consistent dosing), and persistence (≤ 60-day gap between administrations at 3, 6, 9, and 12 months). Descriptive analyses were conducted for each cancer type. RESULTS: The analysis included 1748 patients with solid tumors and bone metastases. Adherence with denosumab was generally high across the initiation, implementation, and persistence phases. Most patients experienced timely initiation (from 64.4% [kidney cancer] to 81.2% [breast cancer]) and optimal implementation (from 62.4% [lung cancer] to 72.5% [breast cancer]). The proportion of patients who were persistent with treatment at 6 months ranged from 41.4% (lung cancer) to 77.8% (prostate cancer). CONCLUSIONS: This study revealed variations by cancer type in the initiation, implementation, and persistence of denosumab in patients with solid tumors and bone metastases in routine clinical practice. Further cancer-specific studies are warranted to examine the determinants of (non)adherence with denosumab, and potential ways to improve medication adherence.

Blunted autonomic reactivity to pharmacological panic challenge under long-term escitalopram treatment in healthy men.

BACKGROUND: Central serotonergic pathways influence brain areas involved in vagal cardiovascular regulation and, thereby, influence sympathetic efferent activity. Selective serotonin reuptake inhibitors (SSRIs) affect multiple serotonergic pathways, including central autonomic pathways. However, only a few studies have assessed SSRI-mediated effects on autonomic reactivity in healthy individuals using heart rate variability (HRV). METHODS: The present study assessed the influence of long-term treatment with escitalopram (ESC) on autonomic reactivity to an intravenous application of 50 µg cholecystokinin tetrapeptide (CCK-4) in 30 healthy young men using a double-blind, placebo (PLA)-controlled, randomized, within-subject cross-over design. Main outcome measures were time- and frequency-domain HRV parameters, assessed at both baseline and immediately after CCK-4 application. RESULTS: Results showed substantial effects for the treatment × CCK-4 challenge interaction with respect to heart rate (p < 0.001; pη(2) = 0.499), SDNN (p < 0.001; pη(2) = 576), RMSSD (p = 0.015; pη(2) = 194), NN50% (p = 0.008; pη(2) = 0.224), and LF% (p = 0.014; pη(2) = 0.196), and moderate effects with respect HF% (p = 0.099; pη(2) = 0.094), with PLA subjects showing a higher increase in HR and SDNN and a higher decrease in RMSSD, NN50, LF and HF than subjects in the ESC condition. Thus, ESC treatment significantly blunted the autonomic reactivity to CCK-4. Secondary analysis indicated no effect of the 5-HTTLPR polymorphism on CCK-4-induced autonomic response. CONCLUSIONS: Our results support findings suggesting an effect of SSRI treatment on autonomic regulation and provide evidence that ESC treatment is associated with blunted autonomic reactivity in healthy men.

Perceptual properties of obsessive thoughts are associated with low insight in obsessive-compulsive disorder.

Obsessions are traditionally defined as bothersome and repetitive thoughts that the patient is unable to resist. Preliminary evidence suggests that in a subgroup of patients with obsessive-compulsive disorder (OCD), obsessions are experienced as partially perceptual. The present study explored the frequency of perceptually laden obsessions and their relationship with illness insight and depression. Twenty-six patients with OCD were administered the newly developed Sensory Properties of Obsessions Questionnaire. Participants were asked to endorse on a 5-point Likert scale whether their obsessions were associated with perceptual features. Participants showed moderate symptom severity. A total of 73% affirmed that their obsessions contained perceptual features. The predominant perceptual channels were visual, tactile, and somatic (i.e., bodily sensations). The extent of perceptual aspects associated with obsessions was strongly correlated with lack of insight (Yale-Brown Obsessive-Compulsive Scale item 11) but not depression severity. The present study suggests that obsessive thoughts are frequently accompanied by perceptual sensations, which concurs with models assuming a continuum between hallucinations and intrusions. Apparently, the more "real" or authentic the obsessive thought is experienced, the less the afflicted person is able to dismiss its content as fully irrational or absurd.

Cognitive performance during senescence in untreated congenital isolated GH deficiency.

Individuals with untreated isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene from Itabaianinha Brazil have increased insulin sensitivity, normal life expectancy, and an extended health span, i.e. the period of life free from disabilities. We hypothesize that their prolonged health span is accompanied by a delayed cognitive decline in senescence. To test this hypothesis, we have administered the Literacy-Independent Cognitive Assessment (LICA) to 15 IGHD individuals aged over 50 years and 15 controls matched by age, sex, years of education, and percentage of illiteracy. All individuals were negative for HIV and syphilis serology, and there were no differences in serum levels of folate, vitamin B12 and TSH between the two groups, while free T4 was higher in the IGHD group. IGHD subjects had a higher total LICA score than controls, 215 (22.7) vs 204.2 (18.1), without reaching statistical significance. Scores of memory, visuoconstruction, language and calculation were similar between the two groups, with better attention (9.5 (1.4) vs 8.3 (1.1), P = 0.01) and executive function (38.3 (4.8) vs 35.1 (2.5), P = 0.03) scores in IGHD. MANCOVA revealed that group (but no age) had a significant effect on the LICA variables (partial eta squared of 0.455, power of 0.812, P = 0.02). This effect is verified on attention (partial eta squared 0.216, power of 0.749, P = 0.01) and executive function (partial eta squared 0.154, power of 0.570, P = 0.03. In conclusion, IGHD in senescence is associated with similar total cognitive performance but better attention and executive function than controls.

No effects of antidepressants on negative symptoms in schizophrenia.

Negative symptoms are common in schizophrenia, but often difficult to differentiate from depression. They are associated with long-term impairment and do not respond well to current treatment approaches. Even though antidepressants are commonly prescribed in schizophrenia, their beneficial effect is still under debate. In the present study, we aimed to investigate the effect of serotonergic versus noradrenergic antidepressant add-on therapy on negative symptoms in schizophrenia. Fifty-eight patients with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and with predominant negative symptoms were randomized in a double-blind design to add-on treatment with citalopram, reboxetine, or placebo for 4 weeks. Analysis of covariance with repeated-measures design was used to compare improvement between treatment groups in scores of the Positive and Negative Syndrome Scale and the Hamilton Rating Scale for Depression. A χ² test was used to compare responder rates between treatment groups. Repeated-measures analysis of covariance revealed no differences between treatment groups over time (treatment × time, not statistically significant) for Positive and Negative Syndrome Scale subscales. Although a subgroup analysis in subjects fulfilling the criteria for minor depression was suggestive of higher responder rates in the citalopram group compared with reboxetine, the results did not reach significance level. Our findings do not support a beneficial effect of adjunctive antidepressant treatment on negative symptoms in schizophrenia. However, depressive symptoms are reduced in patients with minor depression by citalopram but not reboxetine, which is in line with previous findings.

(Meta)cognitive beliefs in posttraumatic stress disorder following forced displacement at the end of the Second World War in older adults and their offspring.

INTRODUCTION: The aim of the present study was to investigate (meta)cognitive beliefs related to posttraumatic stress disorder (PTSD) in a sample of individuals displaced as children at the end of the Second World War as well as transgenerational effects of trauma and PTSD on the offspring. METHODS: Displaced individuals with (n=20) and without PTSD (n=24) and nondisplaced healthy controls (n=11), as well as one of their adult offspring, were assessed with the Metacognitions Questionnaire (MCQ-30). Older adults, formerly displaced in childhood, were additionally assessed with the Posttraumatic Cognitions Inventory (PTCI). RESULTS: Dysfunctional beliefs (MCQ-30, PTCI) were particularly pronounced in formerly displaced individuals with PTSD, but not in the offspring generation. CONCLUSIONS: The findings suggest that in an aging group of displaced individuals with PTSD dysfunctional beliefs are associated with the disorder. Bias modification may help to attenuate symptomatology. No evidence was found for a transgenerational effect.

Copeptin response to panic provocation with CO2 in healthy adults.

Repeated panic attacks are the core symptom of panic disorder and severely stressful for patients. Additional to the psychological response, the physiological symptoms are an important aspect of the experienced panic. However, data on the extent of hypothalamic-pituitary-adrenal (HPA)-axis activation during panic attacks is inconsistent. Therefore, in the present study, we aimed at investigating the stress-axis activity in more detail by including Copeptin (CoP) as a stable surrogate parameter for the vasopressinergic hypothalamic activity during experimentally induced panic attacks in healthy adults (N = 21). During a placebo-controlled panic challenge with 35% CO2 compared to normal air inhalation, we measured CoP and the peripheral effector hormones Adrenocorticotropic Releasing Hormone (ACTH) and cortisol in plasma along with the psychological response to panic anxiety. We analyzed hormonal secretion patterns, their correlations and individual panic ratings over time and explored differences between female and male participants. We found a significant CO2-induced increase of CoP plasma levels and psychological panic symptoms after CO2-administration, while no positive correlations of CoP levels with the peripheral HPA-axis hormones and with panic symptoms were present. No differences between female and male participants concerning their psychological response nor their baseline CoP levels, the release of CoP or its increase during the experiment were found. CoP could be a sensitive indicator for an organism's physiologic acute hypothalamic response during stress and panic attacks.

Sex differences of salivary cortisol secretion in patients with major depression.

Depression is associated with increased cortisol secretion and occurs more often in women than in men. Thus, it has been hypothesized that differences in cortisol secretion might, in part, be responsible for the greater risk of developing depression in women. However, only few studies have examined sex differences in baseline cortisol secretion in depressed patients and healthy controls. We examined sex effects on cortisol secretion in 52 medication-free patients with major depression (37 women, 15 men, mean ± SD age 35 ± 11 years, Hamilton Depression Scale mean score 27 ± 5) and 50 healthy age- and sex-matched control subjects. Salivary cortisol concentrations were measured at 8:00, 12:00, 16:00, and 22:00 h. Repeated measures analysis of covariance revealed a group × sex interaction (p = 0.05). Post hoc tests revealed higher cortisol concentrations in depressed compared to healthy men [F(1;29) = 7.5, p = 0.01]. No differences were found between depressed and non-depressed women. Our results do not support the hypothesis that differences in cortisol secretion between depressed and non-depressed subjects are more pronounced in women than in men. Study characteristics and methods as well as sex-specific confounding variables such as menstrual cycle, menopause and the use of oral contraceptives may account for inconclusive results across studies.

Religiosity, magical ideation, and paranormal beliefs in anxiety disorders and obsessive-compulsive disorder: a cross-sectional study.

The relation between religiosity/spirituality (R/S), personal beliefs, and mental health has been extensively studied. However, concerning anxiety disorders (ADs), empirical evidence is scarce. This study investigated the differences in R/S and magical/paranormal ideation among obsessive-compulsive disorder patients (OCD; n = 49), patients with other ADs (n = 36), and healthy controls (HCs; n = 35). Our results suggest negative religious coping as being the only parameter showing significantly higher scores in OCD and AD participants in comparison with HCs. Negative religious coping reflects negative functional expressions of R/S in stressful situations. Logistic regression also suggested negative religious coping as the strongest predictor of group affiliation to the nonhealthy group. Further results show no significant differences between other R/S, magical, and paranormal ideation traits among groups. This study underlines an important role of negative religious coping in ADs yet does not clearly indicate a specific causality. Religious-sensitive treatment targeting cognitive aspects of negative religious coping are discussed.

Rotating Directional Solidification of Ternary Eutectic Microstructures in Bi-In-Sn: A Phase-Field Study.

For the first time, the experimental processing condition of a rotating directional solidification is simulated in this work, by means of a grand-potential-based phase-field model. To simulate the rotating directional solidification, a new simulation setup with a rotating temperature field is introduced. The newly developed configuration can be beneficent for a more precise study of the ongoing adjustment mechanisms during temperature gradient controlled solidification processes. Ad hoc, the solidification of the ternary eutectic system Bi-In-Sn with three distinct solid phases α,ß,δ is studied in this paper. For this system, accurate in situ observations of both directional and rotating directional solidification experiments exist, which makes the system favorable for the investigation. The two-dimensional simulation studies are performed for both solidification processes, considering the reported 2D patterns in the steady state growth of the bulk samples. The desired αßαδ phase ordering repeat unit is obtained within both simulation types. By considering anisotropy of the interfacial energies, experimentally reported tilted lamellae with respect to normal vectors of the solidification front, as well as predominant role of αß anisotropy in tilting phenomenon, are observed. The results are validated by using the Jackson-Hunt analysis and by comparing with the existing experimental data. The convincing agreements indicate the applicability of the introduced method.

Advances in neuroprotective strategies: potential therapies for intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is associated with higher mortality and morbidity than any other form of stroke. However, there currently are no treatments proven to improve outcomes after ICH, and therefore, new effective therapies are urgently needed. Growing insight into ICH pathophysiology has led to the development of neuroprotective strategies that aim to improve the outcome through reduction of secondary pathologic processes. Many neuroprotectants target molecules or pathways involved in hematoma degradation, inflammation or apoptosis, and have demonstrated potential clinical benefits in experimental settings. We extensively reviewed the current understanding of ICH pathophysiology as well as promising experimental neuroprotective agents with particular focus on their mechanisms of action. Continued advances in ICH knowledge, increased understanding of neuroprotective mechanisms, and improvement in the ability to modulate molecular and pathologic events with multitargeting agents will lead to successful clinical trials and bench-to-bedside translation of neuroprotective strategies.

Effects of chronic posttraumatic stress disorder on metabolic risk, quality of life, and stress hormones in aging former refugee children.

It is still unclear whether the association between traumatic stress and physical disease is mediated by posttraumatic stress disorder (PTSD). Therefore, we examined the long-term consequences of PTSD on cardiovascular risk, stress hormones, and quality of life in a sample of former refugee children who were severely traumatized more than six decades ago. In 25 subjects with chronic PTSD and 25 trauma-controlled subjects, we measured the variables of metabolic syndrome supplemented by the ankle-brachial index and highly sensitive C-reactive protein. Quality of life was assessed using the 36-item Short-Form Health Survey. Cortisol, adrenocorticotropin-releasing hormone (ACTH), and dehydroepiandrosterone (DHEA) were measured using the low-dose-dexamethasone suppression test. In addition, salivary cortisol was assessed at 8:00 a.m., 12:00 p.m., 4:00 p.m., and 8:00 p.m. We found a significant group effect between participants with and without PTSD regarding quality of life but not in any metabolic parameter including the ankle-brachial index or cortisol, ACTH, and DHEA in plasma before and after dexamethasone or salivary cortisol. The postulated association between traumatic stress and physical illness does not appear to be mediated by PTSD in this population. Nevertheless, the search for subgroups of PTSD patients with childhood traumatization leading to different metabolic and endocrine long-term consequences in aging PTSD patients is needed.

Experimental panic provocation in healthy man-a translational role in anti-panic drug development?

Experimental neurochemical provocation of panic attacks in susceptible human subjects has considerably expanded our knowledge of the pathophysiology and psychopharmacology of panic disorder. Some panicogens also elicit short-lived panic-like states in healthy man. This offers the opportunity to assess the anti-panic action of drugs in proof-of-concept studies. However, from current data it is still unclear whether experimental panic in healthy man is a valid translational model. Most such studies in healthy volunteers have been performed using a cholecystokinin tetrapeptide (CCK-4) challenge. While CCK-4 panic was blocked by alprazolam pretreatment, escitalopram showed negative results in healthy man. Preliminary findings on novel investigational drugs and a few problematic results will be reviewed. Small sample sizes in many panic provocation studies, lack of dose-response aspects, and still-insufficient knowledge about the biological underpinning of experimental and spontaneous panic limit the interpretation of existing findings and should inspire further research.

[Long-term consequences of flight and expulsion in former refugee children]. / Langzeitfolgen von in der Kindheit am Ende des II. Weltkrieges erlebter Flucht und Vertreibung.

Little is known about long-term consequences of flight and expulsion during childhood. The aim of this study was to interview aging former refugee children about their recollection of traumatic experiences and to screen for full and partial posttraumatic stress disorder (PTSD) and their differential impact on today's quality of life and mental health. In 502 participants from the former German eastern territories who were displaced as children at the end of World War II (at the age of 5-12 years) we examined traumatic experiences, posttraumatic stress symptoms (PDS), comorbid symptoms (SCL-90-R), depressive symptoms (BDI) and quality of life (SF-36). 31.5% participants reported posttraumatic stress symptoms indicating current full PTSD, and 33.7% fulfilled the criteria of a current partial PTSD. Participants with full and partial PTSD reported a significantly reduced quality of life, often depressive and comorbid symptoms and were compromised in their well-being compared to participants without PTSD. The study demonstrates the long-term consequences of flight and expulsion during childhood in aging former refugee children more than 60 years later. Posttraumatic stress symptoms play a prominent role for quality of life and well-being in this population.

Childhood Maltreatment in Individuals With Schizophrenia Spectrum Disorders: The Impact of Cut-Off Scores on Prevalence Rates.

Childhood maltreatment is a common phenomenon in various psychiatric disorders. Accordingly, patients with disorders from the schizophrenia spectrum (SSD) appear to have high prevalence rates of childhood maltreatment. However, the interpretation and comparability of prevalence rates is impeded by methodological weaknesses and differences such as measures and thresholds used in previous studies. Therefore, we aimed to provide and compare systematically captured data on prevalence rates of all common types of childhood maltreatment in patients with SSD using a standardized and well-established questionnaire and the most frequently used thresholds. The sample consisted of 48 patients with a primary diagnosis of SSD. 58.3-77.1% of the sample experienced at least one type of childhood maltreatment. Prevalence rates for physical abuse, physical neglect, and emotional abuse were dependent on the thresholds used, while equal rates were found for emotional neglect and sexual abuse. Physical neglect (46-67%), and emotional abuse (44-48%) were most commonly reported, followed by emotional neglect (38%), physical abuse (25-38%), and sexual abuse (25%). Additionally, high levels of peer victimization were reported by SSD patients. It appears that childhood maltreatment is a common phenomenon in SSD, even though methodological details, especially cut-off scores, have a substantial impact on the prevalence rates that are determined. Therefore, the methodology of studies should be closely examined when drawing conclusions from presented prevalence rates.

Atrial natriuretic peptide (ANP) as an endogenous anxiolytic in patients with heart failure? - No replication of previous results showing an inverse association of anxiety and plasma ANP parameters.

OBJECTIVE: An acute anxiolytic-like effect of atrial natriuretic peptide (ANP) has been demonstrated in several preclinical and clinical studies. In a so far singular study (Herrmann-Lingen et al., 2003), patients with congestive heart failure, who pathognomonicly display increased plasma ANP, showed a significant inverse association of anxiety symptoms and pro-ANP levels, giving rise to speculations about ANP as an endogenous anxiolytic. We tried to replicate and extend this preliminary finding. METHODS: In 56 patients suffering from heart failure with reduced left ventricular ejection fraction we measured ANP, mid-regional pro-ANP (MR-proANP) and cyclic guanosine monophosphate (cGMP) as plasma parameters of ANP functioning and characterized anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS) and in addition the State Trait Anxiety Inventory (STAI) for state anxiety. Spearman rank correlation coefficients were calculated. RESULTS: None of our plasma ANP parameters showed a significant association with anxiety symptoms as per HADS ratings. The same picture emerged with STAI state anxiety. ANP, MR-proANP and cGMP significantly correlated with each other. CONCLUSION: In another sample of patients with heart failure we were unable to replicate previous and preliminary cross-sectional findings of low anxiety in subjects with high plasma pro-ANP. Direct measurement of effector hormone ANP and its second messenger as well did not support our hypothesis. Chronically elevated ANP in heart failure might attenuate its potential anxiolytic effects. Longitudinal studies experimentally increasing ANP levels in anxious heart failure patients are needed to test if this approach has clinical psychotropic utility.

[Implementation of Continuity of Care in Everyday Care - A Comparison Between two Psychiatric Hospitals]. / Umsetzung von Behandlungskontinuität im Versorgungsalltag ­ ein Vergleich zwischen zwei psychiatrischen Kliniken 1.

OBJECTIVE: The rigid separation of outpatient and inpatient care in the German health care system prevents continuity of care, although it has been shown to be of great importance for psychiatric patients. This study analyzes continuity of care of a model hospital with a global treatment budget according to §â€Š64b SGB V and constant treatment staff across all settings in comparison to a control hospital with regular financing without such a team. METHODS: In a prospective cohort study with a 20-month observation period, we collected data on continuity of care of 220 model and 215 control clinic patients. RESULTS: The model clinic achieved significant higher continuity of care than the control clinic, both during inpatient treatment at the time of recruitment and across all settings during the observation period. CONCLUSION: A global treatment budget can create the necessary conditions for more flexible psychiatric care and better implementation of continuity of care.

Decreased recognition of negative affect after selective serotonin reuptake inhibition is dependent on genotype.

Selective serotonin reuptake inhibitors (SSRIs) are known to influence the information processing of emotional material in depressed patients and healthy controls. The functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been shown to interact with the effectiveness of serotonin reuptake inhibitors. It is not known whether 5-HTTLPR has an influence on emotional processing in healthy controls. We report first data with long-term SSRI administration after genetic characterization of 5-HTTLPR in a randomized, double-blind, placebo-controlled, crossover design. In 30 healthy controls, 15 homozygous for the long and 15 for the short allele of 5-HTTLPR, emotionally valent images were used to elicit positive or negative emotions. We found a diminished perception of sad and fearful information under SSRI which was significant in the long allele group. These findings emphasize the importance of genetic variance in emotion processing research.

Clinical grading scales in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) carries higher risk of long-term disability and mortality than any other form of stroke. Despite greater understanding of ICH pathophysiology, treatment options for this devastating condition remain limited. Moreover, a lack of a standard, universally accepted clinical grading scale for ICH has contributed to variations in management protocols and clinical trial designs. Grading scales are essential for standardized assessment and communication among physicians, selecting optimized treatment regiments, and designing effective clinical trials. There currently exist a number of ICH grading scales and prognostic models that have been developed for mortality and/or functional outcome, particularly 30 days after the ICH onset. Numerous reliable scales have been externally validated in heterogeneous populations. We extensively reviewed the inherent strengths and limitations of all the existing clinical ICH grading scales based on their development and validation methodology. For all ICH grading scales, we carefully observed study design and the definition and timing of outcome assessment to elucidate inconsistencies in grading scale derivation and application. Ultimately, we call for an expansive, prospective, multi-center clinical outcome study to clearly define all aspects of ICH, establish ideal grading scales, and standardized management protocols to enable the identification of novel and effective therapies in ICH.