Functional (neurologic) recovery following transient focal cerebral ischemia in the rat requires at least 80% of ipsilateral cortical and subcortical integrity

Though many drugs have been proven to reduce ischemia-induced brain damage in animal models, most of them have failed to reach clinical trials or, if not, have not been proven to be efficient in humans suffering stroke. Here, by performing a global analysis of recently published data in eighty nine rats subjected to middle cerebral artery occlusion (MCAO)-induced transient focal cerebral ischemia, we show that the ability of the animals to recover motor function is dependent on and highly correlated to their percentage of healthy cortex (r = 0.973; P < 0.001) and healthy subcortical brain structures (r = 0.916; P < 0.001). In addition, data analysis further reveals that neuroprotection requires preserving at least 80% and 90% of the integrity of the ipsilateral hemispheris subjected to MCAO to provide partial and full functional neurologic recovery, respectively. We suggest that this should be taken into account in preclinical pharmacological studies to estimate the actual potentially clinical interest of drugs developed for neuroprotection as well as to avoid developing further research on drugs that only provide mild to moderate histologic outcome.     

Long-term outcome of schizoaffective and schizophrenic disorders: a comparative study

Summary The long-term outcome of 72 schizoaffective and 97 schizophrenic patients with a mean duration of illness of 25.6 years and 19.6 years respectively was investigated. The outcome was assessed using the WHO Disability Assessment Schedule (WHO/DAS), the Psychological Impairment Rating Schedule (PIRS) (also developed by the WHO), the Global Assessment Scale (GAS), and the Bonn Psychopathological Criteria of Outcome. The outcome of schizoaffective disorders was found to differ from that of schizophrenia in several ways: (a) schizoaffectives achieve a full remission significantly more frequently than schizophrenics (50% vs 10%); (b) the development of so-called characteristic schizophrenic residua is the exception in schizoaffective disorders, but is frequent in schizophrenia; (c) disability, psychological impairment and disturbances of the level of functioning are not only significantly less frequent in schizoaffective disorders but are also less intense than in the schizophrenic group. The factors influencing the outcome of the two disorders are different (see part 11), as are the social consequences (part III).Supported by the German Research Association (Deutsche Forschungsgemeinschaft) grants Ma 915-1/1 and Ma 915-1/2     

Objective Measure of Treatment Outcome in Epilepsy

Summary: Treatment outcome in epilepsy is too often a vague, ill-defined subjective measure. Based on a proposal of Shoffer and Temkin (1987) of "time to kth seizure" as a measure of seizure frequency, we devised the formula: % improvement = 100 - [time to X seizure (i*) * 100]/ [time to X seizure (f*)]. This formula provides an objective measure of treatment outcome and should prove useful in clinical settings and research. We offer examples of practical applications of the formula.     

Evaluation of psychoanalytic psychotherapy outcome

In a public psychotherapy clinic, the outcome of psychoanalytically oriented psychotherapy was investigated in a controlled study. The patients formed a treatment and a non-treatment (with initial evaluation) group, and psychotherapy was evaluated after 4 months of therapy. MMPI, target symptoms, global evaluation and other clinical evaluations were used. A number of aspects of the results are discussed pointing both to the efficacy of psychotherapy and the relative spontaneous improvement of the untreated patient.     

Long-term social functioning after depression treated by psychiatrists: a review

OBJECTIVES: Numerous long-term studies of depression in psychiatric settings have shown a poor clinical outcome but little emphasis has been placed on psychosocial or functional outcome in studies to date. This article reviews published data on long-term social functioning after depression and considers why psychosocial recovery appears delayed compared with clinical recovery. METHODS: Searches were carried out of the databases MEDLINE, PSYCHLIT and EMBASE for articles published from 1980 using keywords relating to social and functional outcomes of unipolar and bipolar depression. Review articles and relevant textbooks were also searched. RESULTS: The few outcome studies published have described long-term functional impairment in the majority of patients but have been limited by methodological shortcomings. Psychosocial impairment tends to persist even after clinical remission from depression. Residual symptomatology after remission from depression may lead to enduring psychosocial impairment, as may subtle neurocognitive deficits. Axis I and II comorbidities predict a poor psychosocial outcome, but episodes of depression do not appear to lead to personality 'scarring'. CONCLUSIONS: Future outcome studies need to focus on longitudinal social functioning. Full functional recovery after an episode of depression should be the goal of treatment as enduring residual symptoms lead to long-term psychosocial impairment.     

Profile of health-related quality of life in Nigerian stroke survivors

Background and purpose:  No study using a stroke-specific measure has been previously conducted to determine the profile of health-related quality of life (HRQOL) in Nigerian stroke patients. Such a study is pre-requisite to planning of patient-centered rehabilitative care aimed at maximizing HRQOL improvement. Our objectives were to develop and validate a stroke-specific HRQOL measure, and determine the profile of HRQOL using it.
Methods:  The HRQOL in stroke patients (HRQOLISP) questionnaire was developed and administered to 100 stroke patients and a control group of 100 age- and gender-matched healthy adults. The Stroke Levity Score (SLS) and modified Rankin Scale (mRS) were applied to measure stroke severity and disability respectively.
Results:  The HRQOLISP surpassed the Nunnaly's criterion for reliability and was able to discriminate between stroke (HRQOLsum = 73.5 ± 9.1) and normal subjects (HRQOLsum = 84.4 ± 6.9, P  = 0.002). It differentiated strokes of various severities in the physical dimension (physical, psychological, cognitive and social domains). SLS and mRS correlated only to the domains in the physical dimension.
Conclusion:  The HRQOLISP demonstrated good content, construct and discriminant validity and internal consistency reliability. Stroke had a multifaceted effect on HRQOL, which was more pronounced in the physical dimension.     

Selective outcome reporting across psychopharmacotherapy randomized controlled trials

ObjectiveSelective reporting impairs the valid interpretation of trials and leads to bias with regards to the clinical evidence. We aimed to examine factors associated with selective reporting in psychopharmacotherapy trials and thus enable solutions to prevent such selective reporting in the future.MethodsWe retrieved all registry records of trials investigating medication for depressive, bipolar and psychotic disorders. Multivariate logistic regression was performed with selective reporting as outcome, and funding source, psychiatric disorder, year of study start date, participating centers, and anticipated sample size as explanatory variables, after testing for multicollinearity. Adjusted odds ratios (AOR) were calculated. Two‐sided Fisher exact test was used to compare the proportions of newly added positive primary outcomes with the proportions of positive results in the overall group of primary outcomes.ResultsOf 151 included trials (N = 94,303 participants), 21 (14%) showed irregularities between registered and published primary outcomes. Higher odds of such irregularities were associated with non‐industry‐funded RCTs (AOR 5.3; p = 0.014) and trials investigating major depressive disorder (AOR 12.7; p = 0.024) or schizophrenia (AOR 14.5; p = 0.016; Table 1).ConclusionWe demonstrate discrepancies between trial registrations and publications across RCTs investigating debilitating psychiatric disorders, especially in non‐industry funded RCTs.     

Clinical heterogeneity of juvenile myoclonic epilepsy: Follow-up after an interval of more than 20 years

PurposeThe view that juvenile myoclonic epilepsy (JME) is a uniform and life-long disorder is currently being challenged. The aim of this study was to assess the seizure and psychosocial outcome of JME at least 20 years after onset.MethodsIn 1992, 42 patients with JME were identified. In 2012, 37 agreed to a semi-structured interview. In the remaining five, only medical records were available.ResultsOf 40 patients with known seizure outcome, 21 were in remission for >5 years. Seven were off antiepileptic drugs (AEDs), four being seizure free for >10 years. Myoclonic seizures (MC) evolving to generalized tonic–clonic seizures (GTC) were associated with seizure persistence (p = 0.013), whereas >1 year between MC and GTC onset was associated with a trend to GTC remission (p = 0.069). Of 19 patients with uncontrolled seizures, eight experienced remission with second generation AEDs.Favorable psychosocial outcome by interview was found in a third, whereas another third had psychiatric comorbidity, seven with substance or alcohol abuse. Psychosocial and seizure outcome did not correlate.ConclusionThis study corroborates the heterogeneity of JME in terms of seizure and psychosocial outcome, but without a clear association between the two. It confirms that seizure control may persist after AED withdrawal in some and supports MC evolving to GTC as a predictor of seizure persistence. Moreover, it suggests that newer broad spectrum AEDs may improve the prognosis of JME; their impact should be focus of prospective studies.     

Stroke unit versus neurology ward

Abstract. Introduction: Few studies have tested the hypothesis of whether the beneficial effect of Stroke Units (SUs) can be reproduced in routine clinical practice and whether SU are also superior to neurological wards [NWs]. We aimed to compare the outcomes of patients of a newly implemented SU to the outcomes of patients hospitalized in a NW. Methods: We made a before-after comparison of 352 SUs and 352 NWs patients after adjusting for case-mixes by the multivariate method. Subgroup analyses were also performed to evaluate which patient groups benefit the most. In-hospital case-fatality, proportion of independent patients at discharge, length of hospital stay (LOHS), medical complication rate were the main outcome measures. Results: Adjusted in-hospital case fatality was significantly reduced in the SUs (OR: 0.44, 95 % CI: 0.26–0.76; p = 0.003). The proportion of independent patients at discharge and patients having medical complications was not different. Length of hospital stay was shorter in SU patients (13.76 days vs. 16.72 days, p = 0.003). Treatment in the SUs decreased case fatality in many subgroups [men, elderly, early admitted, severe stroke, co-morbidity present and ischemic stroke groups]. Discussion: The results of randomized trials in favor of SUs can be reproduced in routine clinical practice. The benefit of SU care seems to be more apparent with advancing age and increasing stroke severity. Stroke Unit seems to be a better alternative to an experienced NW.     

Outcome measures in MMN revisited: further improvement needed

The objectives of this study were to provide an overview of the outcome measures (OMs) applied in clinical trials in multifocal motor neuropathy (MMN) and to determine the responsiveness of a core set of selected OMs as part of the peripheral neuropathy outcome measures standardization (PeriNomS) study. The following OMs were serially applied in 26 patients with newly diagnosed or relapsing MMN, receiving intravenous immunoglobulin (assessments: T0/T3/T12 months): 14 muscle pairs MRC (Medical Research Council) scale, the Neuropathy Impairment Scale motor‐subset, a self‐evaluation scale, grip strength, and MMN‐RODS© (Rasch‐built overall disability scale). All data, except the grip strength, were subjected to Rasch analyses before determining responsiveness. For grip strength, responsiveness was examined using a combined anchor‐ (SF‐36 question‐2) and distribution‐based (½ × SD) minimum clinically important difference (MCID) techniques, determining the proportion of patients exceeding both the identified cut‐offs. For the remaining scales, the magnitude of change for each patient on each scale was determined using the MCID related to the individual SE (responder definition: MCID‐SE ≥ 1.96). Overall, a great assortment of measures has been used in MMN trials with different responsiveness definitions. For the selected OMs, responsiveness was poor and only seen in one fourth to one third of the patients, the grip strength being more responsive. Despite the efforts taken to standardize outcome assessment, further clinimetric responsiveness studies are needed in MMN.     

Outcome of reactive psychosis: a prospective study from India

In a prospective study, 22 patients diagnosed to have "Reactive Psychosis" were followed-up for 6 months. Clinical and social recovery was seen in 16 cases, three patients had relapsed, and in three patients the diagnosis of "Reactive Psychosis" was changed to either major depressive disorder or schizophrenia. The results of the study suggest that "Reactive Psychosis" has good outcome and stability of diagnosis over a short period of time.     

The relation between outcome expectation,therapeutic alliance,and outcome among depressed patients in group cognitive-behavioral therapy

Objective: Although patients’ expectation for improvement correlates with their treatment outcome, there remains limited information regarding the mechanisms through which outcome expectation influences outcome. Although several studies have revealed alliance as a mediator of the expectancy-outcome relation, most have focused on individual psychotherapy only. More research is needed examining mediators, including alliance quality, of the outcome expectation-outcome relation in group therapy. Method: This study focused on such associative chains among 91 depressed outpatients who completed 10 weeks of group cognitive-behavioral therapy. We conducted simple and multiple mediation analyses, accounting for the nested data structure. Results: As predicted, we found: (i) The relations between baseline outcome expectation and both posttreatment anxiety and depression were mediated by alliance quality; (ii) the early therapy outcome expectation-posttreatment anxiety relation was mediated by mid-treatment alliance; (iii) the relation between early alliance and posttreatment interpersonal problems was mediated by during-therapy outcome expectation; and (iv) the relation between baseline outcome expectation and posttreatment interpersonal problems was mediated by two variables acting in turn, early alliance and during-therapy outcome expectation. All other tested models were not significant. Conclusions: Results suggest that bidirectional relations between outcome expectation and alliance, with both directions influencing outcome. Clinical and empirical implications are discussed.     

Dissociable regulation of instrumental action within mouse prefrontal cortex

Evaluation of the behavioral 'costs', such as effort expenditure relative to the benefits of obtaining reward, is a major determinant of goal-directed action. Neuroimaging evidence suggests that the human medial orbitofrontal cortex (mOFC) is involved in this calculation and thereby guides goal-directed and choice behavior, but this region's functional significance in rodents is unknown despite extensive work characterizing the role of the lateral OFC in cue-related response inhibition processes. We first tested mice with mOFC lesions in an instrumental reversal task lacking discrete cues signaling reinforcement; here, animals were required to shift responding based on the location of the reinforced aperture within the chamber. Mice with mOFC lesions acquired the reversal but failed to inhibit responding on the previously reinforced aperture, while mice with prelimbic prefrontal cortex lesions were unaffected. When tested on a progressive ratio schedule of reinforcement, mice with prelimbic cortical lesions were unable to maintain responding, resulting in declining response levels. Mice with mOFC lesions, by contrast, escalated responding. Neither lesion affected sensitivity to satiety-specific outcome devaluation or non-reinforcement (i.e. extinction), and neither had effects when placed after animals were trained on a progressive ratio response schedule. Lesions of the ventral hippocampus, which projects to the mOFC, resulted in similar response patterns, while lateral OFC and dorsal hippocampus lesions resulted in response acquisition, though not inhibition, deficits in an instrumental reversal. Our findings thus selectively implicate the rodent mOFC in braking reinforced goal-directed action when reinforcement requires the acquisition of novel response contingencies.     

Immunomodulatory therapy versus surgery for Rasmussen syndrome in early childhood

We examined seizure, cognitive, and motor outcomes in patients with Rasmussen syndrome or Rasmussen encephalitis (RS), after recent initiation of immunomodulatory therapies. Among 53 patients with a diagnosis of RS referred from all over Japan, 49 patients (male 22, female 27) with symptoms and findings characteristic of RS were evaluated. Regular intravenous immunoglobulin (IVIg) therapy was administered at a dose of 100 mg/kg/day, etc. Regular steroid pulse therapy was conducted with methylprednisolone at a dose of 30 mg/kg/day (children) or 1000 mg/day (adults) for 3 days. Tacrolimus was given at an initial dose of 0.1 mg/kg/day (children). Mean onset age was 8.7 ± 10.5 years. Seizure-free rate was 71% after treatment by functional hemispherectomy (FH), and response rate for seizures was 81% by regular steroid pulse therapy, 42% by tacrolimus therapy, and 23% by regular IVIg therapy. Rate of patients with IQ higher than 80 (R80) was 50% by regular steroid pulse therapy, 43% by regular IVIg therapy, 29% by tacrolimus therapy, and 0% by FH. R80 after regular steroid pulse therapy was 100% in patients without MRI lesions, and 37% in those with advanced MRI lesions. Improvement of motor function (paresis) was observed only by immunomodulatory therapy. Motor function was aggravated in 100% of patients treated by FH, 62% by regular IVIg, and 10% by regular steroid pulse therapy. We suggest a new treatment strategy for RS using early immunomodulatory therapy: initiation of regular steroid pulse therapy after early diagnosis indicated by biomarkers, then switching to tacrolimus therapy after several months.     

Developing core sets for persons with bipolar disorder based on the International Classification of Functioning, Disability and Health

INTRODUCTION: Functioning is increasingly being taken into account when assessing the impact of bipolar disorder (BD) on the individual, as well as the effectiveness of treatments. With the International Classification of Functioning, Disability and Health (ICF), we can now rely on a globally agreed-upon framework and system for classifying the typical spectrum of problems in functioning, given the environmental context in which subjects live. ICF Core Sets are subgroups of ICF items selected to capture those aspects of functioning that are most likely to be affected by specific disorders. Within a given disorder, both Brief and Comprehensive Core Sets can be established to serve specific purposes. OBJECTIVE: The aim of this paper is to outline the development process of the ICF Core Sets for BD. METHODS: The final definition of ICF Core Sets for BD will be determined at an ICF Core-Sets Consensus Conference, which will integrate evidence from preliminary studies, namely (a) semi-structured interviews with people with BD in different countries, (b) a Delphi exercise with international experts participating and (c) a cross-sectional study. CONCLUSION: ICF Core Sets are being designed with the goal of providing useful standards for research, clinical practice and teaching. We believe that these ICF Core Sets for BD will stimulate research leading to improved understanding of functioning, disability and health in BD. Such research, we hope, will lead to interventions and accommodations to improve restoration and maintenance of functioning and minimise disability among people with BD throughout the world.     

Proposing the stroke levity scale: a valid, reliable, simple, and time-saving measure of stroke severity

Background and purpose:  National Institutes of Health Stroke Scale (NIHSS) is long and complex. Our objective was to design a valid, reliable, simple, and time-saving stroke severity scale.
Methods:  About 103 and 100 consecutive stroke patients in Berlin (Germany) and Ibadan (Nigeria), respectively were evaluated using the measures listed below. The Stroke Levity Scale (SLS) was calculated as maximum power (0–5) in the dexterous hand + maximum power in the weaker lower limb + mobility score−1(if aphasia present).
Results:  It took less than 2 min to administer the SLS in contrast to 8 min for the NIHSS. The SLS showed significant correlation to the NIHSS ( ρ  = −0.79, P  < 0.0001), the modified Rankin Scale ( ρ  = −0.79, P  < 0.0001), and the health-related quality of life (QOL) in stroke patient's questionnaire ( ρ  = 0.78, P  < 0.0001). It had Cronbach's α of 0.75 (Ibadan) and 0.71 (Berlin). The κ -value for test-retest reliability was 0.77 with P  < 0.0001.
Conclusions:  The SLS is a concise, valid, and reliable stroke impairment scale that can be used routinely to monitor outcome in stroke patients. Because it is brief and simple to apply, non-neurologists can be taught to administer it in addition to QOL and disability scales for stroke survivors without significantly increasing the respondent burden.