What do we know about IDH1/2 mutations so far, and how do we use it?

Whole genome analyses have facilitated the discovery of clinically relevant genetic alterations in a variety of diseases, most notably cancer. A prominent example of this was the discovery of mutations in isocitrate dehydrogenases 1 and 2 (IDH1/2) in a sizeable proportion of gliomas and some other neoplasms. Herein the normal functions of these enzymes, how the mutations alter their catalytic properties, the effects of their d-2-hydroxyglutarate metabolite, technical considerations in diagnostic neuropathology, implications about prognosis and therapeutic considerations, and practical applications and controversies regarding IDH1/2 mutation testing are discussed.     

Postural tachycardia syndrome (POTS) and antiphospholipid syndrome (APS): What do we know so far?

As part of the non-criteria clinical manifestations, postural orthostatic tachycardia syndrome (POTS), a multisystem autonomic dysfunction, can co-exist with antiphospholipid syndrome (APS). Several pieces of evidence hint on the autoimmune basis of POTS, and its possible association with several autoimmune diseases, including APS. Indeed, the evidence exists in the etiologies, symptomatology, and treatment options. Although infections, viral ones in particular, stress, and pregnancy are etiologies to both POTS and APS, the exact pathophysiological connection is still to be studied taking into consideration the activity of cytokines in both diseases. Nevertheless, certain immunomodulatory treatments used for the catastrophic or obstetrical forms of APS, such as intravenous immunoglobulins (IVIG) and steroids, have been also used for the treatment of POTS resistant to classical treatments. Therefore, our review aims to highlight the association between POTS and APS, shedding light on the common etiologies explaining the pathophysiology of the two disorders, the diagnostic approach to POTS as a possible clinical criterion of APS, and the treatment of APS in the context of treating POTS.     

Cannabinoids for epilepsy: What do we know and where do we go?

Over the past decade there has been an increasing interest in using cannabinoids to treat a range of epilepsy syndromes following reports of some remarkable responses in individual patients. The situation is complicated by the fact that these agents do not appear to work via their attachment to endogenous cannabinoid receptors. Their pharmacokinetics are complex, and bioavailability is variable, resulting in difficulty in developing a suitable formulation for oral delivery. Drug interactions also represent another complication in their everyday use. Nevertheless, recent randomized, placebo‐controlled trials with cannabidiol support its efficacy in Dravet and Lennox‐Gastaut syndromes. Further placebo‐controlled studies are underway in adults with focal epilepsy using cannabidivarin. The many unanswered questions in the use of cannabinoids to treat epileptic seizures are briefly summarized in the conclusion.     

Text level reading comprehension in aphasia: What do we know about therapy and what do we need to know?

Background: Reading comprehension difficulties are a common feature of aphasia, affecting the understanding of single words, sentences, paragraphs and extended text. Whilst there have been studies investigating treatment for single word reading, there are a limited number of studies of treatment methods targeting the reading of paragraphs and connected text.

Aims: This paper will describe a series of single case studies, each investigating the effectiveness of a different therapy approach for paragraph level reading comprehension. The studies raise a number of issues regarding the assessment of reading, choice of therapy and measurement of outcome; these will be discussed in relation to the studies and the wider evidence base.

Methods & Procedures: Four people with aphasia were involved in the studies. Participants presented with reading difficulties alongside other language difficulties. Each study involved a single case study, multiple baseline with control task design. Detailed assessment of reading comprehension was completed pre-therapy, post-therapy and at follow-up, approximately 2–4 weeks post-therapy. Participants were also asked about their pre-morbid reading abilities and preferences, their reading difficulties and their views about therapy and its impact.

Outcomes & Results: All participants showed some improvement in the accuracy of reading comprehension but there was extensive variability in the significance of gains, when gains were seen and on which assessments. Post-therapy, three of the four participants read the assessment passages and answered the questions more quickly. All participants reported some positive change in their reading, either in reading ability, reading behaviour or feelings about reading, but again individual variation was evident in the extent and type of change perceived.

Conclusions: These studies raise a number of important issues regarding the assessment of reading, therapy choice and measuring the outcome of therapy. These issues are discussed in relation to current literature, with an aim of informing future research investigating the assessment of, and therapy for, reading comprehension difficulties in people with aphasia. Reading is fundamental to everyday activities and developing the evidence base is of crucial importance in supporting people with aphasia to maximise their reading ability.     

Health behavior changes after a cancer diagnosis: What do we know and where do we go from here?

Survival rates for certain types of cancer have improved over the past few decades. Changing unhealthy behaviors such as smoking, poor diet, and sedentary life-style among individuals who have been diagnosed with cancer may help to reduce cancer treatment sequelae, possibly reduce risk of recurrence for specific types of cancer, and reduce risk for other common diseases such as cardiovascular disease, obesity, and hypertension. This article reports the prevalence of each of these behaviors among those diagnosed with cancer and reviews interventions that have targeted these risk behaviors. There is considerable variation in the type of research questions asked, the methodologic quality of the research, sample sizes, and the outcomes observed across studies focusing on changing the three health risk behaviors. In the final section, we provide guidelines for researchers in developing health behavior interventions for individuals diagnosed with cancer and highlight challenges that should be addressed.     

Treating anxiety disorders in children and adolescents with epilepsy: What do we know?

Children with epilepsy are at significant risk of psychiatric disorders, which can in turn negatively impact social skills development, academic achievement, and quality of life. The most commonly reported psychiatric comorbidities in pediatric epilepsy are ADHD, depression, and anxiety. The prevalence rates of anxiety disorders in pediatric epilepsy range from 5 to 49%, and in the general population, anxiety disorders are the most common psychiatric disorder in childhood. For the purposes of this review, anxiety disorders will be examined in order to 1) examine rates of anxiety disorders in children and adolescents with epilepsy, 2) review treatment options for anxiety disorders in children with epilepsy, and 3) identify future avenues for the development of evidence-based practices for the treatment of anxiety disorders in youth with epilepsy.     

What do we (not) know about the management of blood pressure in acute stroke?

Although it is indisputable that high blood pressure should be treated to prevent a first or a recurrent stroke, the management of high blood pressure in the first hours and days after stroke remains controversial. There is no high-quality evidence from randomized controlled trials to guide treatment in the 80% of patients who have elevated blood pressure during the first days after stroke. Theoretically, there are pros and cons for manipulating blood pressure after onset of stroke. Most treatment guidelines suggest leaving blood pressure untouched based on pathophysiologic principles. Post-hoc analyses from randomized trials, however, suggest that elevated blood pressure is associated with recurrent stroke and higher mortality, even after adjustment for potential confounders. On the other hand, preliminary studies have suggested that voluntarily increasing blood pressure might be beneficial in a selected subgroup of patients. In this overview, we present a summary of recent studies on this topic.     

What do we know about the serotonergic genetic heterogeneity in attention-deficit/hyperactivity and autistic disorders?

BACKGROUND: Shared candidate gene regions point to a link between autistic disorders and attention-deficit/hyperactivity disorder (ADHD). Although they represent nosologically different diagnoses, the disorders do show some shared symptoms, above all inattention. For both disorders, the association with the serotonergic system is a focus of current research. SAMPLING AND METHODS: The current work provides an overview of serotonergic mechanisms in ADHD and autistic disorders as well as the resulting pharmacogenetic approaches. RESULTS: No uniform picture emerges either for ADHD or for autistic disorders. In pharmacogenetic terms, there are some isolated studies on associations between serotonergic mechanisms and pharmacotherapy. For the area of autism, such studies are still lacking. CONCLUSIONS: The presented serotonergic mechanisms show relationships of this polymorphism to ADHD and autistic disorders, but they do not result in a uniform picture. The overlaps can best be explained by a dimensional classification approach. As yet, only a small number of studies on attentional disorders in autism and ADHD using shared samples have been carried out. With regard to diagnostics and therapy, analyses on the etiology of the attentional disorder of ADHD and autism are required.     

What do we know about home education and autism? A thematic synthesis review

BackgroundMainstream education can be difficult for autistic children given the social communication difficulties, highly focused interests and sensory sensitives associated with autism. Educators can still find providing a safe, inclusive and supportive environment for autistic students challenging. Subsequently some parents decide to remove their children from school and home educate. The purpose of this thematic review is to synthesise reported findings on home educating autistic children who have previously attended formal education.MethodPRISMA guidelines informed the review process. Articles included were published in the last 10 years and specific to autistic children being educated at home. Of the 22 articles meeting eligibility for full text review, 10 matched the final inclusion criteria.ResultsFindings related to four main themes emerging from the synthesis: the motivations and reasons that led parents to home educate their autistic children; parents’ experiences of home educating; practices and pedagogical approaches used by parents; and the impact of home education on the outcomes for autistic students. Findings revealed that home education can be a positive experience for families with good academic and social outcomes for autistic children and young people. Limitations of the evidence base are considered.ConclusionAlthough not all parents may be in a position to home educate their children, this review indicates that parents with appropriate educational, financial and social supports have found home educating their autistic child empowering. They report being able to provide flexible, balanced and individualised education leading to positive outcomes.     

Basic research and model systems in familial dysautonomia: What do we know and what’s next?

Clinical Autonomic Research -     

What do we know about the relationship between source monitoring deficits and executive dysfunction?

In clinical neuropsychology, source monitoring deficits have been classically attributed to executive dysfunction. Nevertheless, in this review we identified only 16 papers that provided statistical data about the relationships between source monitoring and executive processes. Surprisingly, they reported either a total, partial or non-existent relationship between source monitoring and executive tasks. In order to understand and explain these contradictions, we classified the source and executive tasks of the 16 papers according to two well-accepted definitions. Source tasks were classified using the Source Monitoring Framework (Johnson, Hashtroudi, & Lindsay, 1993 ) which specifies reality and external and internal source monitoring. Executive tasks were classified according to the model of Miyake Friedman, Emerson, Witzki, and Howerter (2000) which specifies complex, shifting, updating and inhibition tasks. We found that evaluation of reality and internal source monitoring was limited. Regarding executive functions, there was no assessment of updating and only a limited assessment of shifting and inhibition. Therefore, the relationship between source monitoring and executive functions remains an open question. Our findings point to the need for the simultaneous assessment of source monitoring and executive functions as defined by multidimensional theoretical frameworks. Such investigations would help in understanding the relationship between specific source monitoring deficits and specific executive decline in clinical populations.     

The chance of cure following surgery for drug-resistant temporal lobe epilepsy. What do we know and do we need to revise our expectations?

Although surgery is often seen as a curative treatment for patients with drug-resistant temporal lobe epilepsy, little information is available how many cases can be considered cured after surgery, i.e. are seizure-free for several years without taking antiepileptic drugs (AEDs). In our review, 13 retrospective and five prospective clinical observations published since 1980 provided data on long-term seizure control off AEDs in a total of 1658 patients. No randomized studies were found. Following temporal lobe surgery, approximately one in four adult patients and approximately one in three children or adolescents can currently shown to be seizure-free for 5 years without AEDs (25%, mean of eight studies in adults, 95% CI: 21–30%, and 31%, mean of three studies in children, 95% CI: 20–41%). The rate of seizure control off AEDs seemed to be stable after 2 years of follow-up. However, as 55% of patients free of disabling seizures preferred not to discontinue their medication completely as late as 5 years after surgery, it is impossible to know if they are cured or not. No features predictive of surgical cure were detected except for better cure outcome in children versus adults with hippocampal sclerosis and in patients with typical versus atypical Ammonshorn's sclerosis or tumor in one small study each. In conclusion, the available evidence on seizure outcome off AEDs after temporal lobe surgery is based on non-randomized studies and, in part, data were collected retrospectively. A randomized controlled trial is needed to determine if, in fact only one in three to four patients with temporal lobe epilepsy undergoing surgery can be considered cured.     

Vagus nerve stimulation (VNS) for depression: What do we know now and what should be done next?

Vagus nerve stimulation (VNS) therapy is the first US Food and Drug Administration-approved somatic clinical intervention for treatment-resistant depression (TRD). Long-term open data suggest a sustainable antidepressant response over time. Here we review the clinical data that exist so far and their limitations. We also discuss guidelines that may inform the clinical utilization of this procedure. Further clinical studies, in addition to prospective cost utilization and health economic investigations, are needed to better understand VNS therapy and the impact it holds on TRD care.     

What do we know about dementia?: a survey on knowledge about dementia in the general public of Japan

OBJECTIVE: The importance of early detection of dementia has been highlighted in recent years by the medical and scientific community; however, delays often occur between the recognition of signs or symptoms and a decision by the patient or family to seek professional help. Such delays may be caused by a lack of knowledge about dementia among patients and family members. The aim of this study was to determine the understanding of dementia among the general public. METHODS: We conducted a survey in Japan that asked 11 questions regarding knowledge of 'general' information, 'symptoms', and 'biomedical' issues related to dementia. A quota sampling method was used to select 2,500 participants, 2,115 of who were eligible for the analyses. RESULTS: The average number of correct responses among females was significantly greater than that among the males. A multiple comparisons test demonstrated that middle-aged women were more knowledgeable than younger and older respondents. It was revealed that there was a lack of knowledge on biomedical aspects of dementia, i.e. cause, treatment, and prognosis along with a misunderstanding of dementia as senescence forgetfulness among the general public. CONCLUSIONS: There appeared to be gaps in knowledge on dementia among the general public, which may prevent caregivers from planning upcoming social and financial challenges. Correct information needs to be given by health professionals and care staff. Educational initiatives planned for the general public could be useful, and should target those groups, men and non-middle aged women who have lower knowledge.