SEZ6L2 Antibody–Associated Cerebellar Ataxia Responsive to Sequential Immunotherapy

ObjectivesSeizure-related 6 homolog like 2 (SEZ6L2) antibody–associated ataxia is an extremely rare disease. Six patients have been reported and none of them improved significantly with immunotherapy. Herein, we present the case of a patient with cerebellar ataxia and SEZ6L2 antibodies who benefited from immunotherapy, which dramatically altered the course of her disease.MethodsWe present a case report of a 73-year-old woman with progressive balance problems. Her condition had rapidly deteriorated in the 2 weeks before the admission to our hospital leading to repeated falls and eventually left her bed-ridden.ResultsShe presented with severe trunk ataxia, bidirectional nystagmus, dysarthric speech, and persistent nausea. With the exception of cerebellar atrophy, extensive imaging studies revealed no pathology. SEZ6L2 antibodies were found in both CSF and serum. Over a period of 9 months, our patient received immunotherapy consisting of steroid pulse therapy, IV immunoglobulin infusions, rituximab, and cyclophosphamide. Consequently, her condition improved markedly, and she was discharged home from the neurologic rehabilitation unit.DiscussionOur case report shows that intense sequential immunotherapy may considerably improve level of functioning in some patients with SEZ6L2 antibody–associated cerebellar ataxia.Classification of EvidenceThis provides Class IV evidence. It is a single observational study without controls.

Instability and Uncertainty Are Critical for Psychotherapy: How the Therapeutic Alliance Opens Us Up

Tschacher and Haken have recently applied a systems-based approach to modeling psychotherapy process in terms of potentially beneficial tendencies toward deterministic as well as chaotic forms of change in the client’s behavioral, cognitive and affective experience during the course of therapy. A chaotic change process refers to a greater exploration of the states that a client can be in, and it may have a potential positive role to play in their development. A distinction is made between on the one hand, specific instances of instability which are due to techniques employed by the therapist, and on the other, a more general instability which is due to the therapeutic relationship, and a key, necessary result of a successful therapeutic alliance. Drawing on Friston’s systems-based model of free energy minimization and predictive coding, it is proposed here that the increase in the instability of a client’s functioning due to therapy can be conceptualized as a reduction in the precisions (certainty) with which the client’s prior beliefs about themselves and their world, are held. It is shown how a good therapeutic alliance (characterized by successful interpersonal synchrony of the sort described by Friston and Frith) results in the emergence of a new hierarchical level in the client’s generative model of themselves and their relationship with the world. The emergence of this new level of functioning permits the reduction of the precisions of the client’s priors, which allows the client to ‘open up’: to experience thoughts, emotions and experiences they did not have before. It is proposed that this process is a necessary precursor to change due to psychotherapy. A good consilience can be found between this approach to understanding the role of the therapeutic alliance, and the role of epistemic trust in psychotherapy as described by Fonagy and Allison. It is suggested that beneficial forms of instability in clients are an underappreciated influence on psychotherapy process, and thoughts about the implications, as well as situations in which instability may not be beneficial (or potentially harmful) for therapy, are considered.

Terapi rasional-emotif perilaku untuk menurunkan tingkat depresi pada wanita

The subject is a college student woman who has changes in functionality in everyday life. Subject has a bad view of herself and tend to like to compare herself with others, especially physical problems. As a result, subject tend to be easily sad, lose interest, often feel tired and sometimes bring up suicidal thoughts. The assessment methods used were clinical interview, observation, and psychological tests, namely the Weschler Adult Intelligence Scale, graphics, Thematic Apperception Test, the Beck Depression Inventory II scale and WHODAS. Subject was diagnosed with major depressive disorder with moderate level of functioning. The intervention used was rational-emotive behavior therapy which was composed of five sessions. This therapy is used with the aim of reducing depression levels through changing irrational beliefs to become more rational. The results of the intervention showed a decrease in the subject's level of depression as indicated by changes in the scores obtained before and after the intervention was given.

Cognitive and functional deficits are associated with white matter abnormalities in two independent cohorts of patients with schizophrenia

Background Significant evidence links white matter (WM) microstructural abnormalities to cognitive impairment in schizophrenia (SZ), but the relationship of these abnormalities with functional outcome remains unclear. Methods In two independent cohorts (C1, C2), patients with SZ were divided into two subgroups: patients with higher cognitive performance (SZ-HCP-C1, n = 25; SZ-HCP-C2, n = 24) and patients with lower cognitive performance (SZ-LCP-C1, n = 25; SZ-LCP-C2, n = 24). Healthy controls (HC) were included in both cohorts (HC-C1, n = 52; HC-C2, n = 27). We compared fractional anisotropy (FA) of the whole-brain WM skeleton between the three groups (SZ-LCP, SZ-HCP, HC) by a whole-brain exploratory approach and an atlas-defined WM regions-of-interest approach via tract-based spatial statistics. In addition, we explored whether FA values were associated with Global Assessment of Functioning (GAF) scores in the SZ groups. Results In both cohorts, mean FA values of whole-brain WM skeleton were significantly lower in the SCZ-LCP group than in the SCZ-HCP group. Whereas in C1 the FA of the frontal part of the left inferior fronto-occipital fasciculus (IFOF) was positively correlated with GAF score, in C2 the FA of the temporal part of the left IFOF was positively correlated with GAF score. Conclusions We provide robust evidence for WM microstructural abnormalities in SZ. These abnormalities are more prominent in patients with low cognitive performance and are associated with the level of functioning.

Assessment of Stability Level of Functioning and Development of Business Entities Within the System of Industrial Parks

The need to study the development of business entities in the context of individual categories of industrial parks is connected with different concepts of their development and territorial expansion. The suggested methodological approach to assessment of sustainability level of the business firms functioning in the system of industrial parks includes the following main stages: grouping of industrial parks and the selection of representatives of the groups; rating assessment of stability level of firms functioning in the system of industrial parks; grouping of businesses by the level of sustainability. The technique was tested on data from 150 industrial parks. The results of the implementation of the suggested approach show that more vulnerable positions are typical of businesses operating as part of industrial parks as “greenfield” companies. At the same time, the highest proportion of businesses with a low stability level is typical of developing parks, which indicates the need to expand the range of incentives for these businesses. The most stable cluster of entrepreneurs is business entities of developing parks such as “brownfield” companies. Entrepreneurs operating within developed parks as “brownfield” firms are characterized by a satisfactory level of sustainability. The proportion of entrepreneurial structures with a low stability level remains quite high, which indicates the need to adapt the development strategy of business entities in the system of such structures. The results obtained made it possible to identify the most vulnerable groups to risks, business entities and can be used to form a strategy for their sustainable development in the system of industrial parks.

Adapting to change: Clalit's response to the COVID-19 pandemic

The COVID-19 pandemic is the most significant global health event of the past century. The profound and unexpected changes that it brought about have forced healthcare organizations to make far-reaching adjustments to accommodate the new reality. With the outbreak of the pandemic in Israel and the understanding of its consequences, Clalit Health Services (Clalit), the largest healthcare organization in Israel, rapidly mobilized in order to provide the best response possible from the perspective of both its patients and its employees. In the short term, four designated workgroups were established just days into the pandemic. Their task was to prepare operational work plans to achieve the following goals: providing the best possible treatment for COVID patients; maintaining the level of care for non-COVID patients; protecting healthcare personnel without compromising their competence and level of functioning; and beginning the process of post-crisis planning. In the context of the long term, and with the understanding that the changes in healthcare brought about by the COVID-19 pandemic would be long-lasting and irreversible, and would act as a catalyst in Clalit’s preparations for the future, Clalit has carried out the called-for modifications in its organizational strategy. This was based on the need to shift service and treatment foci from the hospitals to the community and the patient’s home and his cellular device, by means of strengthening Clalit’s strategic abilities to become more proactive, more digital and more home-based. In this article, we present a survey of Clalit’s preparations for the new reality in the short and medium terms, as well as the leveraging of insights gained during the first wave of the pandemic, with goal of revising Clalit’s long-term strategic plan. We conclude and point out the organizational abilities required for optimal response to future large-scale emergencies: The ability to quickly identify the need for change, respond quickly while harnessing the various parts of the organization in order to provide an agile and adaptive response, and facilitate long-term planning activity in parallel to providing an operational response in the short and medium terms.

Evaluating and Enhancing Communication Skills in Four Adolescents with Profound and Multiple Disabilities

<p>Individuals with profound and multiple disability (PMD) experience more than one type of disability, typically severe to profound intellectual disability and significant motoric impairment. These complex impairments negatively affect many aspects of the person’s functioning, such as daily living, academic, and social skills. Persons with PMD will often experience fluctuating levels of awareness, and often have such severe communication deficits that they rely on the use prelinguistic behaviours (PLBs) to communicate. It is often difficult for those working with these individuals to identify preferences and behavioural states indicative of engagement and motivation. As a result, these individuals often experience social isolation and a lower quality of life. The purpose of this research project was to evaluate the overall level of functioning and communicative abilities of four adolescents with PMD and identify instructional procedures that might enhance their natural method of communication, such that they are more readily understood. This was achieved through assessment and intervention based methods. First, the repertoire of forms and functions of specific PLBs in four participants with PMD were identified. Then, circumstances under which behaviours indicative of alertness and engagement were assessed. Next, the author validated the function of specific PLBs used to request the continuation or access to preferred stimuli. Subsequently, three intervention case studies were implemented to strengthen and/or enhance the PLB requesting behaviours of three participants using microswitch technology and individualised instructional strategies. Results suggested that individuals with PMD can and do demonstrate consistent PLBs used to request access to preferred stimuli. Specific PLBs of three participants were strengthened and/or enhanced, with two of these participants able to use a microswitch to activate a speech generating device to produce a communicative request. Implications of these results are discussed in terms of the overall outcomes for each participant and the challenges of implementing a whole communication assessment and intervention approach for this population of learners.</p>

Evaluating and Enhancing Communication Skills in Four Adolescents with Profound and Multiple Disabilities

<p>Individuals with profound and multiple disability (PMD) experience more than one type of disability, typically severe to profound intellectual disability and significant motoric impairment. These complex impairments negatively affect many aspects of the person’s functioning, such as daily living, academic, and social skills. Persons with PMD will often experience fluctuating levels of awareness, and often have such severe communication deficits that they rely on the use prelinguistic behaviours (PLBs) to communicate. It is often difficult for those working with these individuals to identify preferences and behavioural states indicative of engagement and motivation. As a result, these individuals often experience social isolation and a lower quality of life. The purpose of this research project was to evaluate the overall level of functioning and communicative abilities of four adolescents with PMD and identify instructional procedures that might enhance their natural method of communication, such that they are more readily understood. This was achieved through assessment and intervention based methods. First, the repertoire of forms and functions of specific PLBs in four participants with PMD were identified. Then, circumstances under which behaviours indicative of alertness and engagement were assessed. Next, the author validated the function of specific PLBs used to request the continuation or access to preferred stimuli. Subsequently, three intervention case studies were implemented to strengthen and/or enhance the PLB requesting behaviours of three participants using microswitch technology and individualised instructional strategies. Results suggested that individuals with PMD can and do demonstrate consistent PLBs used to request access to preferred stimuli. Specific PLBs of three participants were strengthened and/or enhanced, with two of these participants able to use a microswitch to activate a speech generating device to produce a communicative request. Implications of these results are discussed in terms of the overall outcomes for each participant and the challenges of implementing a whole communication assessment and intervention approach for this population of learners.</p>

Momentary Manifestations of Negative Symptoms as Predictors of Clinical Outcomes in People at High Risk for Psychosis: Experience Sampling Study

Background Negative symptoms occur in individuals at ultrahigh risk (UHR) for psychosis. Although there is evidence that observer ratings of negative symptoms are associated with level of functioning, the predictive value of subjective experience in daily life for individuals at UHR has not been studied yet. Objective This study therefore aims to investigate the predictive value of momentary manifestations of negative symptoms for clinical outcomes in individuals at UHR. Methods Experience sampling methodology was used to measure momentary manifestations of negative symptoms (blunted affective experience, lack of social drive, anhedonia, and social anhedonia) in the daily lives of 79 individuals at UHR. Clinical outcomes (level of functioning, illness severity, UHR status, and transition status) were assessed at baseline and at 1- and 2-year follow-ups. Results Lack of social drive, operationalized as greater experienced pleasantness of being alone, was associated with poorer functioning at the 2-year follow-up (b=−4.62, P=.01). Higher levels of anhedonia were associated with poorer functioning at the 1-year follow-up (b=5.61, P=.02). Higher levels of social anhedonia were associated with poorer functioning (eg, disability subscale: b=6.36, P=.006) and greater illness severity (b=−0.38, P=.045) at the 1-year follow-up. In exploratory analyses, there was evidence that individuals with greater variability of positive affect (used as a measure of blunted affective experience) experienced a shorter time to remission from UHR status at follow-up (hazard ratio=4.93, P=.005). Conclusions Targeting negative symptoms in individuals at UHR may help to predict clinical outcomes and may be a promising target for interventions in the early stages of psychosis.

“Maybe No One Is Really Crazy, but Everyone Is Just a Little Bit Mad”: Framing Experiences of Living with Madness in the TED Talk

This article explores the victimizing experiences of individuals with mental illness using grounded inductive qualitative research methods, by extracting themes from 15 first-hand accounts of living with mental illness delivered on the TED Talks media platform. Emergent themes included (1) victimizing effects of the illness including the effects of medication and the effects of stigma, (2) normalcy, (3) the importance of help-seeking in the process of overcoming obstacles presented by mental health issues, and (4) victimization by others. We conclude that the speakers in our sample, even though they reflect an extraordinary level of functioning, still view themselves as what Becker (1991 [1963]) describes as outsiders, acting as moral entrepreneurs, crusading to normalize madness through a variety of strategies.