Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep.

PURPOSE: To present the long-term follow-up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike-waves during slow wave sleep (CSWS). METHODS: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered. KEY FINDINGS: After a mean duration of follow-up of 15.6 years (range, 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long-term outcome correlated best with duration of CSWS. SIGNIFICANCE: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.

Treatment motivation in adolescents with psychosis or at high risk: Determinants and impact on improvements in symptoms and cognitive functioning, preliminary results.

Abstract Low motivation is frequent in chronic disorders such as psychosis and may limit treatment efficacy. Although some evidence supports this view in adults, few studies so far have focused on adolescents. We assessed the impact of baseline symptoms, cognitive deficits and cognitive treatment characteristics on treatment motivation (TM), and examined whether TM affected treatment outcome. Twenty-eight adolescents with psychotic disorders participated in 16 sessions of computerized cognitive remediation or games. TM was assessed for each session. Lower TM was predicted by more severe symptoms at baseline, and was associated with smaller improvements in symptoms and both cognitive and psychosocial functioning at the end of the intervention. Experiencing success in the treatment exercises enhanced TM in all patients.

The impact of past direct-personal traumatic events on 12-month outcome in first episode psychotic mania: trauma and early psychotic mania.

OBJECTIVE: Past traumatic events have been associated with poorer clinical outcomes in people with bipolar disorder. However, the impact of these events in the early stages of the illness remains unclear. The aim of this study was to investigate whether prior traumatic events were related to poorer outcomes 12 months following a first episode of psychotic mania. METHODS: Traumatic events were retrospectively evaluated from patient files in a sample of 65 participants who had experienced first episode psychotic mania. Participants were aged between 15 and 28 years and were treated at a specialised early psychosis service. Clinical outcomes were measured by a variety of symptomatic and functioning scales at the 12-month time-point. RESULTS: Direct-personal traumatic experiences prior to the onset of psychotic mania were reported by 48% of the sample. Participants with past direct-personal trauma had significantly higher symptoms of mania (p=0.02), depression (p=0.03) and psychopathology (p=0.01) 12 months following their first episode compared to participants without past direct-personal trauma, with medium to large effects observed. After adjusting for baseline scores, differences in global functioning (as measured by the Global Assessment of Functioning scale) were non-significant (p=0.05); however, participants with past direct-personal trauma had significantly poorer social and occupational functioning (p=0.04) at the 12-month assessment with medium effect. CONCLUSIONS: Past direct-personal trauma may predict poorer symptomatic and functional outcomes after first episode psychotic mania. Limitations include that the findings represent individuals treated at a specialist early intervention centre for youth and the retrospective assessment of traumatic events may have been underestimated.

Respiratory symptoms in preterm infants: burden of disease in the first year of life.

OBJECTIVE: While respiratory symptoms in the first year of life are relatively well described for term infants, data for preterm infants are scarce. We aimed to describe the burden of respiratory disease in a group of preterm infants with and without bronchopulmonary dysplasia (BPD) and to assess the association of respiratory symptoms with perinatal, genetic and environmental risk factors. METHODS: Single centre birth cohort study: prospective recording of perinatal risk factors and retrospective assessment of respiratory symptoms during the first year of life by standardised questionnaires. MAIN OUTCOME MEASURES: Cough and wheeze (common symptoms), re-hospitalisation and need for inhalation therapy (severe outcomes). PATIENTS: 126 preterms (median gestational age 28.7 weeks; 78 with, 48 without BPD) hospitalised at the University Children's Hospital of Bern, Switzerland 1999-2006. RESULTS: Cough occurred in 80%, wheeze in 44%, re-hospitalisation in 25% and long term inhalation therapy in wheezers in 13% of the preterm infants. Using logistic regression, the main risk factor for common symptoms was frequent contact with other children. Severe outcomes were associated with maximal peak inspiratory pressure, arterial cord blood pH, APGAR- and CRIB-Score. CONCLUSIONS: Cough in preterm infants is as common as in term infants, whereas wheeze, inhalation therapy and re-hospitalisations occur more often. Severe outcomes are associated with perinatal risk factors. Preterm infants who did not qualify for BPD according to latest guidelines also showed a significant burden of respiratory disease in the first year of life.

Assessing depression outcome in patients with moderate dementia: sensitivity of the HoNOS65+ scale.

To date, there is no widely accepted clinical scale to monitor the evolution of depressive symptoms in demented patients. We assessed the sensitivity to treatment of a validated French version of the Health of the Nation Outcome Scale (HoNOS) 65+ compared to five routinely used scales. Thirty elderly inpatients with ICD-10 diagnosis of dementia and depression were evaluated at admission and discharge using paired t-test. Using the Brief Psychiatric Rating Scale (BPRS) "depressive mood" item as gold standard, a receiver operating characteristic curve (ROC) analysis assessed the validity of HoNOS65+F "depressive symptoms" item score changes. Unlike Geriatric Depression Scale, Mini Mental State Examination and Activities of Daily Living scores, BPRS scores decreased and Global Assessment Functioning Scale score increased significantly from admission to discharge. Amongst HoNOS65+F items, "behavioural disturbance", "depressive symptoms", "activities of daily life" and "drug management" items showed highly significant changes between the first and last day of hospitalization. The ROC analysis revealed that changes in the HoNOS65+F "depressive symptoms" item correctly classified 93% of the cases with good sensitivity (0.95) and specificity (0.88) values. These data suggest that the HoNOS65+F "depressive symptoms" item may provide a valid assessment of the evolution of depressive symptoms in demented patients.

Factors associated with favorable drinking outcome 12 months after hospitalization in a prospective cohort study of inpatients with unhealthy alcohol use.

BACKGROUND: Prevalence of unhealthy alcohol use among medical inpatients is high. OBJECTIVE: To characterize the course and outcomes of unhealthy alcohol use, and factors associated with these outcomes. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 287 medical inpatients with unhealthy alcohol use. MAIN MEASURES: At baseline and 12 months later, consumption and alcohol-related consequences were assessed. The outcome of interest was a favorable drinking outcome at 12 months (abstinence or drinking "moderate" amounts without consequences). The independent variables evaluated included demographics, physical/sexual abuse, drug use, depressive symptoms, alcohol dependence, commitment to change (Taking Action), spending time with heavy-drinking friends and receipt of alcohol treatment (after hospitalization). Adjusted regression models were used to evaluate factors associated with a favorable outcome. KEY RESULTS: Thirty-three percent had a favorable drinking outcome 1 year later. Not spending time with heavy-drinking friends [adjusted odds ratio (AOR) 2.14, 95% CI: 1.14-4.00] and receipt of alcohol treatment [AOR (95% CI): 2.16(1.20-3.87)] were associated with a favorable outcome. Compared to the first quartile (lowest level) of Taking Action, subjects in the second, third and highest quartiles had higher odds of a favorable outcome [AOR (95% CI): 3.65 (1.47, 9.02), 3.39 (1.38, 8.31) and 6.76 (2.74, 16.67)]. CONCLUSIONS: Although most medical inpatients with unhealthy alcohol use continue drinking at-risk amounts and/or have alcohol-related consequences, one third are abstinent or drink "moderate" amounts without consequences 1 year later. Not spending time with heavy-drinking friends, receipt of alcohol treatment and commitment to change are associated with this favorable outcome. This can inform efforts to address unhealthy alcohol use among patients who often do not seek specialty treatment.

Hyperhidrosis: a new and often early symptom in Fabry disease. International experience and data from the Fabry Outcome Survey.

Hypohidrosis is a classic feature of Fabry disease; in contrast, hyperhidrosis has only been rarely described. The aim of the study is to characterise the baseline descriptive data on hyperhidrosis (frequency, age at onset, sex ratio and outcome with and without enzyme replacement therapy) in hemizygous male and heterozygous female patients with Fabry disease. We describe case histories of five patients with Fabry disease and hyperhidrosis seen at three different centres. We have also analysed a cohort of 21 paediatric patients in the UK and a large European cohort of patients enrolled in the Fabry Outcome Survey (FOS). Five patients (three female, two male) with hyperhidrosis were originally identified, although each had additional symptoms related to Fabry disease. The age at onset of hyperhidrosis was less than 18 years in four cases. In the cohort of 21 paediatric patients (12 female, nine male), one female had hyperhidrosis; the age at onset of this symptom was 11 years. In the FOS cohort, 66 of 714 patients with Fabry disease had hyperhidrosis (44 of 369 females, 11.9%; 22 of 345 males, 6.4%). The female predominance was observed in seven of nine countries from which data were analysed. Hyperhidrosis is an increasingly recognised feature of the Fabry disease phenotype. It is more prevalent in females than in males and often appears in childhood or adolescence. The efficacy of enzyme replacement therapy on this recently recognised symptom should be assessed.

Gender differences in premorbid, entry, treatment, and outcome characteristics in a treated epidemiological sample of 661 patients with first episode psychosis.

OBJECTIVES: Gender differences in psychotic disorder have been observed in terms of illness onset and course; however, past research has been limited by inconsistencies between studies and the lack of epidemiological representative of samples assessed. Thus, the aim of this study was to elucidate gender differences in a treated epidemiological sample of patients with first episode psychosis (FEP). METHODS: A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics of 661 FEP consecutive patients treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. RESULTS: Prior to onset of psychosis, females were more likely to have a history of suicide attempts (p=.011) and depression (p=.001). At service entry, females were more likely to have depressive symptoms (p=.007). Conversely, males had marked substance use problems that were evident prior to admission (p<.001) and persisted through treatment (p<.001). At service entry, males also experienced more severe psychopathology (p<.001) and lower levels of functioning (GAF, p=.008; unemployment/not studying p=.004; living with family, p=.003). Treatment non-compliance (p<.001) and frequent hospitalisations (p=.047) were also common for males with FEP. At service discharge males had significantly lower levels of functioning (GAF, p=.008; unemployment/not studying p=.040; living with family, p=.001) compared to females with FEP. CONCLUSIONS: Gender differences are evident in illness course of patients with FEP, particularly with respect to past history of psychopathology and functioning at presentation and at service discharge. Strategies to deal with these gender differences need to be considered in early intervention programs.

Rapid fatal outcome from pulmonary arteries compression in transitional cell carcinoma.

Transitional cell carcinoma of the urinary bladder is a malignancy that metastasizes frequently to lymph nodes including the mediastinal lymph nodes. This occurrence may produce symptoms due to compression of adjacent structures such as the superior vena cava syndrome or dysphagia from esophageal compression. We report the case of a 59-year-old man with metastatic transitional cell carcinoma for whom mediastinal lymphadenopathy led to pulmonary artery compression and a rapidly fatal outcome. This rare occurrence has to be distinguished from pulmonary embolism, a much more frequent event in cancer patients, in order that proper and prompt treatment be initiated.

Prediction of functional outcome 18 months after a first psychotic episode: a proton magnetic resonance spectroscopy study.

CONTEXT: Recent magnetic resonance imaging studies have attempted to relate volumetric brain measurements in early schizophrenia to clinical and functional outcome some years later. These studies have generally been negative, perhaps because gray and white matter volumes inaccurately assess the underlying dysfunction that might be predictive of outcome. OBJECTIVE: To investigate the predictive value of frontal and temporal spectroscopy measures for outcome in patients with first-episode psychoses. DESIGN: Left prefrontal cortex and left mediotemporal lobe voxels were assessed using proton magnetic resonance spectroscopy to provide the ratio of N-acetylaspartate (NAA) and choline-containing compounds to creatine and phosphocreatine (Cr) (NAA/Cr ratio). These data were used to predict outcome at 18 months after admission, as assessed by a systematic medical record audit. SETTING: Early psychosis clinic. PARTICIPANTS: Forty-six patients with first-episode psychosis. MAIN OUTCOME MEASURES: We used regression models that included age at imaging and duration of untreated psychosis to predict outcome scores on the Global Assessment of Functioning Scale, Clinical Global Impression scales, and Social and Occupational Functional Assessment Scale, as well as the number of admissions during the treatment period. We then further considered the contributions of premorbid function and baseline level of negative symptoms. RESULTS: The only spectroscopic predictor of outcome was the NAA/Cr ratio in the prefrontal cortex. Low scores on this variable were related to poorer outcome on all measures. In addition, the frontal NAA/Cr ratio explained 17% to 30% of the variance in outcome. CONCLUSIONS: Prefrontal neuronal dysfunction is an inconsistent feature of early psychosis; rather, it is an early marker of poor prognosis across the first years of illness. The extent to which this can be used to guide treatment and whether it predicts outcome some years after first presentation are questions for further research.

Choice of outcome measures in postprandial trials

Comment on: Heinrich H, Goetze O, Menne D, Iten PX, Fruehauf H, Vavricka SR, Schwizer W, Fried M, Fox M. Effect on gastric function and symptoms of drinking wine, black tea, or schnapps with a Swiss cheese fondue: randomised controlled crossover trial. BMJ. 2010 Dec 14;341:c6731. doi: 10.1136/bmj.c6731. PMID 21156747.

Personality traits influence clinical outcome in day hospital-treated elderly depressed patients

OBJECTIVES: Although personality traits are considered significant predictors of both physical and mental health, their specific impact on treatment outcome in elderly patients with depression remains largely unexplored. Impact of personality traits on the evolution of depressive symptoms, quality of life, and perception of clinical progress was assessed in a psychotherapeutic community. DESIGN: A prospective longitudinal study was conducted in 62 elderly outpatients. SETTING: Day hospital treatment as usual combined group and individual therapies, pharmacological treatment, as well as family and network meetings. PARTICIPANTS: Patients presented with major depression or a depressive episode of bipolar disease. MEASUREMENTS: The Geriatric Depression Scale, the Short Form Survey, and the Therapeutic Community Assessment scale were administrated at admission, 3, 6, 12 months, and at discharge. Personality was evaluated with the NEO Five-Factor Personality Inventory. RESULTS: Outcome revealed reduced depression and improved mental quality of life and clinical progress. Higher Geriatric Depression Scale scores were found in individuals with higher levels of Neuroticism (and its Vulnerability facet). Better self-perception of clinical progress was observed in individuals with lower levels of the Depressiveness and Modesty facets and higher openness to action. Improvement in quality of life was predicted by high Positive emotions facet. All these associations remained significant after controlling for age, gender, and treatment length. CONCLUSION: Personality traits may predict clinical outcome in psychotherapeutic hospital day care for elderly patients with depression.

Impact of stressful life event on the global functioning outcome after an assertive community treatment

Background: Assertive community treatment (ACT) was reported to be an effective treatment to improve global functioning of ultra-high risk (UHR) adolescents. However, the infl uence of stressful life event (SLE) was not extensively studied which represent our objective. Method: The SLE (encompassing adoption, migration, family member's deceased, sexual or physical abuse, etc.) of 20 UHR adolescents, treated with an ACT model, were rated. 10 adolescents having 0 to 1 SLE (mainly parents' divorce; low SLE group) were compared 10 adolescents with 2 to 5 SLE (high SLE group). The adolescents were assessed at baseline and after treatment with the Health of Nation Outcome Scale for Children and Adolescents (HoNOSCA). The HoNOSCA allowed rating different diffi culties such as behavior, symptoms, disorders and social. Results: First, results on the whole sample indicated signifi cant improvement after ACT (compared to baseline) on the total (P = .04), symptoms (P = .025) and social (P = .009) scores of the HoNOSCA. Second, the improvement on the HoNOSCA's score of the high SLE group were signifi cantly higher for the total (P = .016), symptoms (P = .019) and behavior (P = .033) scores compared to the low SLE group. Discussion/Conclusion: Globally, ACT seems to be an appropriate treatment to enhance global functioning and more specifi cally the social and symptoms diffi culties of UHR adolescents. Additionally, UHR adolescents with a high numbers of SLE were observed to have a better benefi t of the ACT on global, symptoms and behavioral diffi culties.

Unusual association of diseases/symptoms: Encephalitis with herpes simplex-2 in the cerebrospinal fluid and anti-RI (ANNA-2) antibodies: an infectious or a paraneoplastic syndrome?

We report on a 70-year-old woman with partial complex status epilepticus who was initially diagnosed with herpes simplex-2 (HSV-2) encephalitis, based on brain magnetic resonance imaging (MRI) findings, cerebrospinal fluid (CSF) lymphocytic pleocytosis and HSV-2 DNA detection by polymerase chain reaction (PCR) in the CSF, but without improvement on intravenous acyclovir. Anti-Ri antibodies were positive and computed tomography (CT) investigations revealed a small cell carcinoma at biopsy suggesting paraneoplastic encephalitis. The outcome was unfavourable and the autopsy showed typical features of paraneoplastic encephalitis but no evidence of viral inclusions. This case report is interesting because: (1) it is the first report of an autopsy proven paraneoplastic widespread encephalitis with anti-Ri antibodies; (2) despite a positive HSV-2 PCR in the CSF, there was no sign of herpetic infections of the nervous system; and (3) it illustrates the fact that if paraneoplastic antibodies are usually good markers of the underlying tumour, they are not always predictive of neurological deficits.

The impact of insight in a first-episode mania with psychosis population on outcome at 18 months.

BACKGROUND: To explore whether poor initial insight during a first episode of mania with psychotic features was predictive of poor psychosocial and clinical outcomes at 18 months. METHODS: Secondary analysis was performed on data collected during an 8-week RCT comparing the efficacy of olanzapine versus chlorpromazine as an adjunct to lithium, and at 18-month follow-up. 74 participants were divided into three groups (no insight, partial insight, and full insight) according to the insight item from the Young Mania Rating Scale (YMRS). Differences between these three groups were examined at baseline and at 18 months on measures of symptoms (YMRS, HAMD-21, and CGI-S), and social and occupational functioning (SOFAS). Baseline differences between the three groups were determined using general linear models and chi-squared analyses. Group differences from baseline to 18-month follow-up were determined using repeated measures general linear models. RESULTS: At baseline there were significant differences between the three insight groups in terms of mania and functioning, but at 18 months all groups had improved significantly in terms of psychopathology, mania, depression and social and occupational functioning. There were no significant differences between the three groups at study completion with respect to these domains. LIMITATIONS: The study was limited by the lack of availability of a more detailed rating scale for insight, and it did not account for the duration of untreated psychosis (DUI). CONCLUSIONS: Poor initial insight during a first episode of mania with psychotic features does not predict poor clinical and psychosocial outcome at 18 months.